Life | Editor’s choice Articles

11 pages, 2968 KiB

Open AccessEditor’s ChoiceArticle

Physiological and Transcriptome Analysis Revealed the Effect of ABA on Promoting Persimmon Fruit Postharvest Deastringency

by Han Zhou, Jiao-Jiao Nie, Meng-Lin Ren, Yu-Duan Ding, Ya-Xiu Xu and Qing-Gang Zhu

Life 2025, 15(7), 1027; https://doi.org/10.3390/life15071027 - 27 Jun 2025

Viewed by 332

Abstract

Persimmon (Diospyros kaki Thunb.) fruit can accumulate proanthocyanidins (tannins) during development, which causes astringency and affects consumption. The hormone abscisic acid (ABA) has been reported to play a key role in fruit ripening and softening. However, the effect of ABA on postharvest [...] Read more.

Persimmon (Diospyros kaki Thunb.) fruit can accumulate proanthocyanidins (tannins) during development, which causes astringency and affects consumption. The hormone abscisic acid (ABA) has been reported to play a key role in fruit ripening and softening. However, the effect of ABA on postharvest persimmon fruit deastringency remains unclear. In this study, we found that 300 mg/L ABA treatment could decrease the content of soluble tannins, thus leading removal of persimmon fruit astringency. The contents of acetaldehyde and ethanol did not increase during the storage time, indicating that ABA treatment-promoted persimmon fruit deastringency was not due to the acetaldehyde interaction with soluble tannins. Furthermore, the transcriptome analysis showed that 6713 differentially expressed genes (DEGs) were identified, and the WGCNA (weighted gene co-expression network analysis) showed that one module, which comprises 575 DEGs, significantly correlated with the contents of soluble and resoluble tannins. The analysis based on the carbohydrate metabolism pathway indicated that 37 differentially expressed structural genes involved in acetaldehyde metabolism were upregulated by ABA. Real-time quantitative PCR showed that the previously reported key genes, including structural genes and transcription factors, were all upregulated by ABA treatment. The obtained results indicate that ABA treatment, promoting persimmon fruit astringency removal, may occur through gel polymerization of cell wall materials with soluble tannins. Full article

(This article belongs to the Special Issue Postharvest Softening, Flavor and Quality of Fruits: Molecular Mechanisms and Regulatory Approaches)

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20 pages, 864 KiB

Open AccessEditor’s ChoiceReview

Refractory Nausea and Vomiting Due to Central Nervous System Injury: A Focused Review

by Stefan Stoica, Christopher Hogge and Brett James Theeler

Life 2025, 15(7), 1021; https://doi.org/10.3390/life15071021 - 27 Jun 2025

Viewed by 903

Abstract

The area postrema (AP) is a circumventricular organ (CVO) at the base of the fourth ventricle. It has a crucial role in regulating nausea and vomiting due to its unique blood–brain barrier (BBB)-permeability and extensive neural connectivity. Here, we present two cases of [...] Read more.

The area postrema (AP) is a circumventricular organ (CVO) at the base of the fourth ventricle. It has a crucial role in regulating nausea and vomiting due to its unique blood–brain barrier (BBB)-permeability and extensive neural connectivity. Here, we present two cases of area postrema syndrome (APS), a rare condition of intractable nausea and vomiting resulting from direct AP injury. Our cases each occurred in the context of infratentorial neoplasms or their treatment. Using these cases as a framework, we review the literature on central emetic pathways and propose a treatment algorithm for managing refractory nausea and vomiting of central origin. We also highlight other targets beyond conventional serotonergic, dopaminergic, or histaminergic blockade and their roles in central hyperemesis. Our literature review suggests that APS is due to the disruption of the baseline inhibitory tone of outgoing AP signals. When other options fail, our algorithm culminates in the off-label use of combined serotonergic and neurokinin-1 blockade, which is otherwise used to manage chemotherapy-induced nausea and vomiting (CINV). We believe multimodal CNS receptor blockade is efficacious in APS because it addresses the underlying central neural dysregulation, rather than solely targeting peripheral emetic triggers. Full article

(This article belongs to the Section Physiology and Pathology)

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17 pages, 4596 KiB

Open AccessEditor’s ChoiceArticle

OsMYBR1, a 1R-MYB Family Transcription Factor Regulates Starch Biosynthesis in Rice Endosperm

by Kunyong Huang, Long Chen, Guiai Jiao, Zheyan Ruan, Xinwei Li, Shaoqing Tang, Peisong Hu and Xiangjin Wei

Life 2025, 15(6), 962; https://doi.org/10.3390/life15060962 - 16 Jun 2025

Viewed by 595

Abstract

Starch is the primary component of the endosperm and plays a crucial role in rice quality. Although the enzymes involved in starch synthesis have been extensively studied, the transcription factors that regulate these enzymes remain largely unknown. Here, we identified a MYB family [...] Read more.

Starch is the primary component of the endosperm and plays a crucial role in rice quality. Although the enzymes involved in starch synthesis have been extensively studied, the transcription factors that regulate these enzymes remain largely unknown. Here, we identified a MYB family transcription factor, OsMYBR1, that regulates starch biosynthesis in rice. OsMYBR1 is highly expressed during endosperm development. Mutations of OsMYBR1 result in reduced grain thickness and a decrease in 1000-grain weight. The endosperm of osmybr1 mutants exhibit rounded and loosely packed starch granules, decreased amylose content, altered fine structure of amylopectin, and modified physicochemical properties. The analysis of RT-qPCR showed that the expression of several starch-synthesis enzyme-coding genes (SSEGs), including OsGBSSⅠ, OsAGPL1, OsAGPL2, OsBEⅡb, OsISA1, PHOL, and OsSSⅢa, is altered in osmybr1 mutants. Further experiments indicated that OsMYBR1 directly binds to the promoters of OsGBSSⅠ, OsAGPL1, OsAGPL2, OsISA1, OsBEⅡb, and PHOL, resulting in an increase in the expression of OsGBSSⅠ but a decrease in the expression of OsAGPL2, OsISA1, and OsSSⅢa. In contrast, OsMYBR1-overexpressing endosperm appears normal, with starch granule morphology, increased amylopectin content, and improved alkali spreading value, indicating enhanced rice eating and cooking quality (ECQ). These findings suggest that the overexpression of OsMYBR1 could be a promising strategy for improving rice ECQ. Full article

(This article belongs to the Special Issue Recent Advances in Crop Genetics and Breeding)

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13 pages, 7555 KiB

Open AccessEditor’s ChoiceArticle

Healed Perforated Corneal Ulcers in Human

by Yasser Helmy Mohamed, Masafumi Uematsu, Mao Kusano, Keiji Suzuki and Akio Oishi

Life 2025, 15(6), 939; https://doi.org/10.3390/life15060939 - 11 Jun 2025

Viewed by 505

Abstract

This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half [...] Read more.

This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half was fixed in 10% formaldehyde for immunofluorescence (IF) examination. TEM identified layered structures with two cell types (polygonal and elongated) connected by gap or adherent junctions during early stage of healing. Both apoptotic and mitotic changes were found in both types of cells. There were no endothelial cells or Descemet’s membrane (DM) present in early stage of healing. During the intermediate stage, the healed area comprised three layers: epithelium, Bowman’s layer, and stroma, with an increase in stromal collagen. Later, adjacent endothelial cells crept in, forming DM and completing the cornea’s 5-layer structure. IF examinations revealed that vimentin⁺ and α-smooth muscle actin (αSMA)⁺ myofibroblasts gathered around the damaged site. Proliferating cell nuclear antigen⁺ cells, which indicated cell proliferation, were found in both cells. Anti-phospho-histone H2AX antibodies were found in some epithelial cells. CK14-positive cells were only found in superficial polygonal cells. Corneal wound healing is a complex process that includes apoptosis, cell migration, mitosis, differentiation, and extracellular matrix remodeling. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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17 pages, 1926 KiB

Open AccessEditor’s ChoiceArticle

Patterns of Variation and Coordination in Shoot Traits Across Four Branching Orders of Larix principis-rupprechtii

by Yang Yu, Huayong Zhang, Zhongyu Wang and Zhao Liu

Life 2025, 15(6), 927; https://doi.org/10.3390/life15060927 - 9 Jun 2025

Viewed by 405

Abstract

Intraspecific variation in functional traits can more accurately quantify plant responses to environmental changes and resource competition, while the plant economic spectrum provides a fundamental framework for understanding trait variation along environmental gradients. As the structural units of the aboveground branching system in [...] Read more.

Intraspecific variation in functional traits can more accurately quantify plant responses to environmental changes and resource competition, while the plant economic spectrum provides a fundamental framework for understanding trait variation along environmental gradients. As the structural units of the aboveground branching system in woody plants, it remains unclear whether shoots exhibit a universal whole-plant economic spectrum and whether branch order significantly affects the patterns of trait variation and coordination. We collected 1551 shoots of Larix principis-rupprechtii to examine the patterns of trait variation and coordination from different branch orders to the whole-plant level. From the perspective of the plant economic spectrum, five functional traits were selected to represent the trade-off between structural and nutrient investment: the stem diameter (SD), stem length (SL), stem dry mass (SDM), specific stem length (SSL), and stem tissue density (STD). From different branch orders to the whole-plant level, allocation played a relatively more important role, and the patterns of pairwise trait correlations and trade-offs along the resource economic axis were consistent. Branch order did not strongly influence the correlations and degree of coordination within the shoot economic spectrum, as the whole-plant shoot economic spectrum was evident within each branch order. Our results support the hypothesis that the coordinated economic spectrum across branch orders forms an integrated whole-plant economic spectrum representing a “conservative–collaborative” resource management strategy. This strategy is robust to recent evolutionary changes (such as genotypic variation and even differences among shoots within the same species) as well as to variation across different branch orders. Full article

(This article belongs to the Section Plant Science)

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31 pages, 1898 KiB

Open AccessEditor’s ChoiceReview

Traumatic Brain Injury: Novel Experimental Approaches and Treatment Possibilities

by Kristina Pilipović, Tamara Janković, Jelena Rajič Bumber, Andrej Belančić and Jasenka Mršić-Pelčić

Life 2025, 15(6), 884; https://doi.org/10.3390/life15060884 - 30 May 2025

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Abstract

Traumatic brain injury (TBI) remains a critical global health issue with limited effective treatments. Traditional care of TBI patients focuses on stabilization and symptom management without regenerating damaged brain tissue. In this review, we analyze the current state of treatment of TBI, with [...] Read more.

Traumatic brain injury (TBI) remains a critical global health issue with limited effective treatments. Traditional care of TBI patients focuses on stabilization and symptom management without regenerating damaged brain tissue. In this review, we analyze the current state of treatment of TBI, with focus on novel therapeutic approaches aimed at reducing secondary brain injury and promoting recovery. There are few innovative strategies that break away from the traditional, biological target-focused treatment approaches. Precision medicine includes personalized treatments based on biomarkers, genetics, advanced imaging, and artificial intelligence tools for prognosis and monitoring. Stem cell therapies are used to repair tissue, regulate immune responses, and support neural regeneration, with ongoing development in gene-enhanced approaches. Nanomedicine uses nanomaterials for targeted drug delivery, neuroprotection, and diagnostics by crossing the blood–brain barrier. Brain–machine interfaces enable brain-device communication to restore lost motor or neurological functions, while virtual rehabilitation and neuromodulation use virtual and augmented reality as well as brain stimulation techniques to improve rehabilitation outcomes. While these approaches show great potential, most are still in development and require more clinical testing to confirm safety and effectiveness. The future of TBI therapy looks promising, with innovative strategies likely to transform care. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI))

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17 pages, 3648 KiB

Open AccessEditor’s ChoiceArticle

Placental Pathology and Placental Growth Factor (PlGF)/Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1) Pathway Expression Evaluation in Fetal Congenital Heart Defects

by Alexandru Cristian Bolunduț, Ximena Maria Mureșan, Rada Teodora Suflețel, Lavinia Patricia Mocan, Simina Pîrv, Sergiu Șușman and Carmen Mihaela Mihu

Life 2025, 15(6), 837; https://doi.org/10.3390/life15060837 - 22 May 2025

Viewed by 698

Abstract

The heart and placenta have simultaneous embryologic development, the interactions between the two organs representing the heart–placental axis. They both share key developmental pathways, one of which involves the placental growth factor (PlGF) and its receptor, vascular endothelial growth factor receptor-1 (VEGFR-1). The [...] Read more.

The heart and placenta have simultaneous embryologic development, the interactions between the two organs representing the heart–placental axis. They both share key developmental pathways, one of which involves the placental growth factor (PlGF) and its receptor, vascular endothelial growth factor receptor-1 (VEGFR-1). The aim of this study was to evaluate the placental pathology and the expression patterns of PlGF and VEGFR-1 in pregnancies with fetuses with congenital heart defects (CHDs). We analyzed placental gross and microscopic alterations between placentas from pregnancies with CHD fetuses and pregnancies with structurally normal heart fetuses. We also performed the immunohistochemical (IHC) assessment of the placental expression of PlGF and VEGFR-1 in the two groups. We discovered significant gross placental abnormalities in pregnancies with CHD fetuses, including a shorter umbilical cord, marginal or velamentous umbilical cord insertion, and a lower fetal-to-placental weight ratio. Also, 88.2% of the placentas in the CHD group displayed microscopic pathologic aspects. We demonstrated significant placental immunostaining for PlGF and VEGFR-1 in the syncytiotrophoblast and decidual cells compared to villous endothelial cells. We identified a lower placental IHC expression of PlGF in pregnancies with CHD fetuses compared to controls but no differences in the placental immunostaining pattern for VEGFR-1 between the two groups. Our study uncovered a potential role played by the PlGF/VEGFR-1 pathway in the development of CHDs through placental-mediated mechanisms. Full article

(This article belongs to the Special Issue From Stem Cells to Embryos, Congenital Anomalies and Epidemiology)

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13 pages, 2602 KiB

Open AccessEditor’s ChoiceArticle

Retinal Phosphenes Induced by Transorbital Electrical Stimulation: Influence of Light Adaptation, Electrode Montage, and View Direction

by Alexander Hunold, Daniela Ortega, Stefanie Freitag, Dietmar Link, Andrea Antal, Sascha Klee and Jens Haueisen

Life 2025, 15(5), 820; https://doi.org/10.3390/life15050820 - 21 May 2025

Viewed by 2363

Abstract

In this study, the perception of phosphenes was used as a surrogate identifier for stimulation sites for use in retinal-degenerative diseases. We aimed to investigate the influence of adaptation, electrode montage, and direction of view on electrically induced phosphenes. We developed a practical [...] Read more.

In this study, the perception of phosphenes was used as a surrogate identifier for stimulation sites for use in retinal-degenerative diseases. We aimed to investigate the influence of adaptation, electrode montage, and direction of view on electrically induced phosphenes. We developed a practical methodology to assess non-invasive ocular electrical stimulation, addressing specific areas in the retina. Phosphene thresholds were identified under light and dark adaptation for non-invasive transorbital electrical stimulation. The location and extent characterized the morphology of electrically induced retinal phosphenes for five directions of view and for seven electrode montages in 62 participants. Our results indicated the lowest phosphene thresholds under light adaptation. Cumulative charts of phosphenes visualized the location of phosphene hot spots and their focality for the investigated directions of view and electrode montages. Under consistent light adaptation, we found changes in electrode montage generated stronger changes in the phosphenes’ morphology and distribution. Adjusting the electrodes in the orbital vicinity was more effective than changing the direction of view to shift the phosphene hot spot location to a pathological region to induce neuronal activity there. In this study, we established the first practical methodology to adapt non-invasive transorbital electrical stimulation to address specific areas in the retina. Full article

(This article belongs to the Special Issue Technical Innovations in Transcranial Electrical Stimulation)

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15 pages, 1552 KiB

Open AccessEditor’s ChoiceArticle

Cognitive Slowing, Dysfunction in Verbal Working Memory, Divided Attention and Response Inhibition in Post COVID-19 Condition in Young Adults

by Johanna Takács, Darina Deák, Beáta Seregély and Akos Koller

Life 2025, 15(5), 821; https://doi.org/10.3390/life15050821 - 21 May 2025

Cited by 1 | Viewed by 9991

Abstract

After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive [...] Read more.

After COVID-19 infection, about 30% of people have clinically persisting symptoms, characterized as Post COVID-19 Condition (PCC). One of the most reported symptoms in PCC is cognitive dysfunction, yet there are only a few studies investigating long-term effects on different domains of cognitive function. A total of 107 young adults, university students aged 18–34 years, participated. In total, 68.2% had contracted SARS-CoV-2; 21.9% showed PCC. Three groups were compared: no-C19 (COVID-19-negative controls), C19 (COVID-19-recovered without PCC) and PCC. Attention and executive function were measured with the Vienna Test System (Schuhfried^®, Mödling, Austria). In verbal working memory, the PCC group had a significantly lower performance with a moderate effect. The rate of below-average performance was higher in PCC (56.2%) compared to no-C19 (20.6%) and C19 (15.8%). In divided attention and response inhibition, PCC also showed lower performance, 62.5% and 37.5%, respectively, than no-C19 and C19. The co-occurrence of decreased cognitive functions was pronounced in PCC. The present study revealed significant long-lasting cognitive dysfunction in PCC in young adults, two years after COVID-19 infection. Verbal working memory was significantly impaired, and a lower performance was found in divided attention and response inhibition. In addition, there was an increased reaction time in most cognitive tasks, demonstrating cognitive slowing in young people with PCC. Full article

(This article belongs to the Section Medical Research)

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32 pages, 3117 KiB

Open AccessEditor’s ChoiceSystematic Review

Cardiac Manifestations and Emerging Biomarkers in Multisystem Inflammatory Syndrome in Children (MIS-C): A Systematic Review and Meta-Analysis

by Diana-Andreea Ciortea, Mădălina Nicoleta Matei, Mihaela Debita, Ancuța Lupu, Mirela Mătăsaru, Gabriela Isabela Verga (Răuță) and Silvia Fotea

Life 2025, 15(5), 805; https://doi.org/10.3390/life15050805 - 19 May 2025

Viewed by 897

Abstract

Background: Cardiac involvement is a key prognostic factor in multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition that typically occurs 2–6 weeks after SARS-CoV-2 infection and is characterized by fever, systemic inflammation, and multiorgan involvement. Biomarkers may aid in [...] Read more.

Background: Cardiac involvement is a key prognostic factor in multisystem inflammatory syndrome in children (MIS-C), a rare but serious inflammatory condition that typically occurs 2–6 weeks after SARS-CoV-2 infection and is characterized by fever, systemic inflammation, and multiorgan involvement. Biomarkers may aid in early detection, severity assessment, and treatment stratification. Objective: To evaluate the diagnostic utility of established and emerging serum biomarkers in MIS-C, with an emphasis on cardiac dysfunction and disease severity. Methods: A systematic search was conducted in PubMed, Scopus, and Web of Science up to April 2025. Eligible studies included pediatric MIS-C cases with reported serum biomarkers. Meta-analyses were performed for NT-proBNP and troponin using random-effects models. Descriptive profiling was applied to emerging biomarkers. Subgroup comparisons were explored between severe and moderate MIS-C. Quality assessment followed the Newcastle–Ottawa Scale, and publication bias was assessed via funnel plots and Egger’s test. Results: A total of 67 studies were included, comprising >4000 pediatric MIS-C cases. NT-proBNP and troponin were consistently elevated (pooled means: 9697 pg/mL and 0.384 ng/mL, respectively), with a low risk of publication bias. Emerging biomarkers such as CXCL9, angiopoietin-2, and vitamin D revealed high inter-study variability but potential prognostic value. Subgroup analyses for selected studies (n = 5) suggested higher biomarker levels in severe MIS-C. Conclusions: NT-proBNP and troponin are robust indicators of cardiac injury in MIS-C. Emerging biomarkers show promise but require validation. Future studies should include copeptin and adopt standardized reporting to refine biomarker-guided management. Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Pathology)

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21 pages, 613 KiB

Open AccessEditor’s ChoiceReview

Three-Dimensional Bioprinting Techniques in Skin Regeneration: Current Insights and Future Perspectives

by Anna Barbara Di Stefano, Valentina Urrata, Kim Schilders, Mara Franza, Simona Di Leo, Francesco Moschella, Adriana Cordova and Francesca Toia

Life 2025, 15(5), 787; https://doi.org/10.3390/life15050787 - 15 May 2025

Cited by 2 | Viewed by 1625

Abstract

Skin is composed of three layers: the epidermis, dermis, and hypodermis. It is enriched with skin appendages, including hair follicles, sweat glands, and sebaceous glands, which play essential roles in regulating fluid exchange, controlling body temperature, and providing protection against pathogens. Currently, skin [...] Read more.

Skin is composed of three layers: the epidermis, dermis, and hypodermis. It is enriched with skin appendages, including hair follicles, sweat glands, and sebaceous glands, which play essential roles in regulating fluid exchange, controlling body temperature, and providing protection against pathogens. Currently, skin regeneration treatments rely on transplantations. However, this approach has several disadvantages, including hemostasis at the recipient site, limitations in donor area closure, increased graft contraction, and hypertrophic scarring. Recent advancements in three-dimensional (3D) bioprinting technologies have enabled the fabrication of structures that closely mimic native tissues, with the aim of enhancing tissue regeneration. Bioprinting offers several advantages, such as high reproducibility, precision, and the ability to create complex geometries. The most promising bioinks combine excellent biocompatibility and biodegradability, with mechanical and rheological stability. This review highlights the most recent and innovative studies on 3D-printed bioinks in the field of skin tissue engineering. In particular, considering the growing interest in the regenerative potential of exosomes, we discuss cutting-edge research involving exosome-loaded bioinks and their potential to support skin regeneration and repair. Full article

(This article belongs to the Special Issue Mechanism, Diagnostic and Therapeutic Novelties in Dermatology: 3rd Edition)

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40 pages, 1730 KiB

Open AccessEditor’s ChoiceReview

Integrative Strategies for Preventing and Managing Metabolic Syndrome: The Impact of Exercise and Diet on Oxidative Stress Reduction—A Review

by Ana Onu, Daniela-Marilena Trofin, Andrei Tutu, Ilie Onu, Anca-Irina Galaction, Dragos-Petrica Sardaru, Dan Trofin, Cristiana Amalia Onita, Daniel-Andrei Iordan and Daniela-Viorelia Matei

Life 2025, 15(5), 757; https://doi.org/10.3390/life15050757 - 8 May 2025

Cited by 4 | Viewed by 2667

Abstract

Metabolic syndrome (MetS) is characterized by central obesity, insulin resistance, hypertension, dyslipidemia, and chronic inflammation, significantly increasing the risk of cardiovascular disease and type 2 diabetes. Effective management of MetS is critical, with exercise being a key intervention. This review analyzed the effects [...] Read more.

Metabolic syndrome (MetS) is characterized by central obesity, insulin resistance, hypertension, dyslipidemia, and chronic inflammation, significantly increasing the risk of cardiovascular disease and type 2 diabetes. Effective management of MetS is critical, with exercise being a key intervention. This review analyzed the effects of different exercise intensities—low, moderate, and high-intensity interval training (HIIT)—on metabolic health, oxidative stress (OS), inflammation, and cardiovascular function. A search of Medline, PEDro, and EBSCO identified 2251 articles, with 159 studies published between 1999 and 2025 included after screening. Low-intensity exercise improved insulin sensitivity, reduced OS markers (e.g., MDA, 8-OHdG), and enhanced antioxidant enzyme activity. Moderate-intensity exercise showed similar benefits with notable reductions in inflammatory markers (e.g., IL-1β, TNF-α). HIIT promoted fat loss and improved metabolic markers but temporarily increased OS and inflammation. Dietary strategies also play a critical role. The Mediterranean diet and Dietary Approaches to Stop Hypertension (DASH) diets are well established, emphasizing nutrient-dense foods like unsaturated fats and fiber to reduce inflammation and manage weight. The ketogenic diet (KD), a high-fat, low-carbohydrate approach, has recently gained attention for its metabolic benefits. KD induces ketosis, improving insulin sensitivity, reducing triglycerides, and enhancing fat oxidation. Studies show KD effectively reduces body weight and glucose levels, though long-term adherence and nutrient deficiencies remain challenges. Intermittent fasting also showed potential benefits, though effects on glucose metabolism were inconsistent. This review underscores the need for tailored approaches combining exercise, diet, and fasting to optimize MetS outcomes, offering integrative strategies for prevention and management. Full article

(This article belongs to the Special Issue Diet and Vascular Disease)

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18 pages, 11122 KiB

Open AccessEditor’s ChoiceArticle

Serotonin Signaling and Macrophage Subsets in Goldfish Gills: Unraveling the Neuroimmune Network for Gill Homeostasis

by Manal T. Hussein, Giacomo Zaccone, Marco Albano, Alessio Alesci, Sebastian Marino, Rasha Alonaizan and Doaa M. Mokhtar

Life 2025, 15(5), 751; https://doi.org/10.3390/life15050751 - 7 May 2025

Cited by 1 | Viewed by 619

Abstract

Goldfish (Carassius auratus) gills function as both respiratory and immune-regulatory organs, integrating neuroendocrine and immune responses to environmental stimuli. This study explores the spatial organization and interaction of neuroendocrine cells (NECs) and immune cells within goldfish gills using confocal immunohistochemistry and [...] Read more.

Goldfish (Carassius auratus) gills function as both respiratory and immune-regulatory organs, integrating neuroendocrine and immune responses to environmental stimuli. This study explores the spatial organization and interaction of neuroendocrine cells (NECs) and immune cells within goldfish gills using confocal immunohistochemistry and transmission electron microscopy. NECs, identified near blood capillaries and nerve fibers, highlight their role in environmental sensing and physiological regulation. These cells express serotonin (5-HT), a neurotransmitter critical for neuroimmune communication. Two distinct macrophage subsets were observed: iNOS-positive macrophages, concentrated in the basal epithelium, suggest a pro-inflammatory role, whereas 5-HT-positive macrophages, dispersed in the subepithelium, likely contribute to immune modulation. The co-localization of MHC-II and CD68 in macrophages further supports an active antigen-processing system in the gills. Ultrastructural analysis revealed diverse immune cells, including rodlet cells, telocytes, and lymphocytes, within the gill epithelium. Telocytes formed intricate networks with immune cells, highlighting their role in immune coordination and tissue homeostasis. These findings provide new insights into the neuroimmune interactions in fish gills, contributing to a broader understanding of aquatic immune systems and environmental adaptability. Full article

(This article belongs to the Special Issue Feature Papers in Animal Science: 4th Edition)

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18 pages, 2231 KiB

Open AccessEditor’s ChoiceArticle

Predicting the S. cerevisiae Gene Expression Score by a Machine Learning Classifier

by Piotr H. Pawłowski and Piotr Zielenkiewicz

Life 2025, 15(5), 723; https://doi.org/10.3390/life15050723 - 29 Apr 2025

Viewed by 602

Abstract

The topic of this work is gene expression and its score according to various factors analyzed globally using machine learning techniques. The expression score (ES) of genes characterizes their activity and, thus, their importance for cellular processes. This may depend on many different [...] Read more.

The topic of this work is gene expression and its score according to various factors analyzed globally using machine learning techniques. The expression score (ES) of genes characterizes their activity and, thus, their importance for cellular processes. This may depend on many different factors (attributes). To find the most important classifier, a machine learning classifier (random forest) was selected, trained, and optimized on the Waikato Environment for Knowledge Analysis WEKA platform, resulting in the most accurate attribute-dependent prediction of the ES of Saccharomyces cerevisiae genes. In this way, data from the Saccharomyces Genome Database (SGD), presenting ES values corresponding to a wide spectrum of attributes, were used, revised, classified, and balanced, and the significance of the considered attributes was evaluated. In this way, the novel random forest model indicates the most important attributes determining classes of low, moderate, and high ES. They cover both the experimental conditions and the genetic, physical, statistical, and logistic features. During validation, the obtained model could classify the instances of a primary unknown test set with a correctness of 84.1%. Full article

(This article belongs to the Section Microbiology)

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14 pages, 2599 KiB

Open AccessEditor’s ChoiceArticle

Immune Escape and Drug Resistance Mutations in Patients with Hepatitis B Virus Infection: Clinical and Epidemiological Implications

by Maria Antonia De Francesco, Franco Gargiulo, Francesca Dello Iaco, Laert Zeneli, Serena Zaltron, Giorgio Tiecco, Simone Pellizzeri, Emanuele Focà, Arnaldo Caruso and Eugenia Quiros-Roldan

Life 2025, 15(4), 672; https://doi.org/10.3390/life15040672 - 20 Apr 2025

Viewed by 847

Abstract

Hepatitis B virus (HBV) genetic variability, shaped by high mutation rates and selective pressures, complicates its management and increases the emergence of drug-resistant and immune-escape variants. This study aims to analyze immune escape mutations (IEMs) and drug resistance mutations (DRMs) in patients with [...] Read more.

Hepatitis B virus (HBV) genetic variability, shaped by high mutation rates and selective pressures, complicates its management and increases the emergence of drug-resistant and immune-escape variants. This study aims to analyze immune escape mutations (IEMs) and drug resistance mutations (DRMs) in patients with HBV infection exposed to antiviral therapies and exhibiting detectable plasma HBV viremia. This monocentric retrospective real-life study was carried out at the ASST Spedali Civili di Brescia, Italy, from 2015 to 2023. A total of 102 consecutive patients with detectable serum HBV-DNA exposed to at least one NA and for whom a drug resistance assay was available were included in our study. HBV sequences were amplified, sequenced, and analyzed for mutations using Geno2pheno and Stanford University tools. Phylogenetic analysis and statistical regression were performed to confirm genotypes and identify mutation patterns and associated risk factors. Our study shows a 38.2% prevalence of DRMs, with M204I/V (95%) and L180M (64%) being the most common, and a 43% prevalence of IEMs, primarily in the major hydrophilic region. Genotype D3 exhibited a higher mutation burden than other genotypes. Significant associations were found between HBsAb presence and increased IEM burden, while HBeAg was protective against DRMs. Atypical serological profiles were observed in 18.6% of patients, including cases of HBV reactivation under immunosuppressive therapy. This study highlights the high prevalence of IEMs and DRMs in a real-world setting, particularly among HBV genotype D3 carriers. These findings underscore the importance of mutation surveillance to guide therapeutic strategies, vaccine design, and public health policies to address the challenges posed by HBV genetic variability. Full article

(This article belongs to the Section Epidemiology)

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18 pages, 2490 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Three DNA Isolation Methods and Two Sequencing Techniques for the Study of the Human Microbiota

by Julio Plaza-Díaz, Mariana F. Fernández, Federico García, Natalia Chueca, Luis Fontana and Ana I. Álvarez-Mercado

Life 2025, 15(4), 599; https://doi.org/10.3390/life15040599 - 4 Apr 2025

Viewed by 953

Abstract

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of female death. Altered interactions between the host and the gut microbiota appear to play an influential role in carcinogenesis. Several studies have shown different signatures of the [...] Read more.

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of female death. Altered interactions between the host and the gut microbiota appear to play an influential role in carcinogenesis. Several studies have shown different signatures of the gut microbiota in patients with breast cancer compared to healthy women. Currently, there is disagreement regarding the different DNA isolation and sequencing methodologies for studies on the human microbiota, given that they can influence the interpretation of the results obtained. The goal of this work was to compare (1) three different DNA extraction strategies to minimize the impact of human DNA, and (2) two sequencing strategies (16S rRNA and shotgun) to identify discrepancies in microbiome results. We made use of breast tissue and fecal samples from both healthy women and breast cancer patients who participated in the MICROMA study (reference NCT03885648). DNA was isolated by means of mechanical lysis, trypsin, or saponin. The amount of eukaryotic DNA isolated using the trypsin and saponin methods was lower compared to the mechanical lysis method (mechanical lysis, 89.11 ± 2.32%; trypsin method, 82.63 ± 1.23%; saponin method, 80.53 ± 4.09%). In samples with a predominance of prokaryotic cells, such as feces, 16S rRNA sequencing was the most advantageous approach. For other tissues, which are expected to have a more complex microbial composition, the need for an in-depth evaluation of the multifactorial interaction between the various components of the microbiota makes shotgun sequencing the most appropriate method. As for the three extraction methods evaluated, when sequencing samples other than stool, the trypsin method is the most convenient. For fecal samples, where contamination by host DNA is low, no prior treatment is necessary. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

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13 pages, 1363 KiB

Open AccessEditor’s ChoiceArticle

The Effects of the COVID-19 Pandemic on Trends and Types of Pediatric Burn Injuries: Lessons from a National Burn Center and the Role of Strategic Resource Allocation

by Raluca Tatar, Dan Mircea Enescu, Doina Iulia Nacea, Gabriela Viorela Nițescu, Andreea Lescaie, Mihaela Pertea, Petruța Mitrache and Laura Sorina Diaconu

Life 2025, 15(4), 544; https://doi.org/10.3390/life15040544 - 26 Mar 2025

Viewed by 587

Abstract

The COVID-19 pandemic had a huge global impact on healthcare systems that affected all medical services, including burn care facilities. This paper analyzes the effects of this medical crisis on pediatric burn injuries by comparing patient data from 2019 (pre-pandemic) and 2020 (during [...] Read more.

The COVID-19 pandemic had a huge global impact on healthcare systems that affected all medical services, including burn care facilities. This paper analyzes the effects of this medical crisis on pediatric burn injuries by comparing patient data from 2019 (pre-pandemic) and 2020 (during the pandemic) at a national burn center in Romania. The study included, overall, 676 patients, out of which 412 were admitted in 2019. In 2020, the admissions decreased by 35.9% (n = 264). However, moderate and severe burns remained constant and burn severity increased in 2020, with a larger total body surface area affected on average. Surgical management rates and hospital stay duration increased in 2020 from 18% to 39% and from 7 days to 11 days, respectively. Admissions to the intensive care unit and mortality rates remained similar between 2019 and 2020. Scalds were the leading cause of burns in both years; however, in 2020, they affected a larger total body surface area. Contact burns decreased significantly in 2020 from 10.9% to 5.2%, likely due to reduced outdoor activities. The concomitant presence of SARS-CoV-2 infection and burn injuries did not have a negative impact on complication rates, surgical management approaches, or duration of hospitalization. These findings emphasize the need to preserve dedicated burn care human and material resources during global health crises in order to offer access to the best quality of care, thus ensuring optimal patient outcomes, regardless of fluctuations in admission rates. Full article

(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)

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17 pages, 2959 KiB

Open AccessEditor’s ChoiceArticle

Non-Invasive Spectroscopic Determination of the Skin and Blood Carotenoids of Term and Preterm Infants in the First Month of Life and the Influence of Free Radical-Mediated Diseases

by Hanne Lademann, Maxim E. Darvin, Anna Häfke, Jürgen Lademann, Laura Wagner, Jan Däbritz and Dirk M. Olbertz

Life 2025, 15(4), 534; https://doi.org/10.3390/life15040534 - 24 Mar 2025

Viewed by 706

Abstract

Postpartum adaptation causes an increased formation of free radicals (FRs) in the organism, which can lead to development of various FR-mediated diseases (FRMDs) in the newborn. The present study investigates the kinetics of skin and blood carotenoid antioxidants in term and preterm infants [...] Read more.

Postpartum adaptation causes an increased formation of free radicals (FRs) in the organism, which can lead to development of various FR-mediated diseases (FRMDs) in the newborn. The present study investigates the kinetics of skin and blood carotenoid antioxidants in term and preterm infants and the influence of FRMD. In the first phase, a diffuse reflectance spectroscopy-based scanner was validated for non-invasive measurements of skin carotenoids in term infants (thenar eminence) by correlation with blood carotenoids via reflection spectroscopy. In the second phase, the skin and blood carotenoids of 22 term and 13 preterm infants with and without FRMD were assessed from birth until discharge. It could be shown that the scanner reliably assessed carotenoids in the infants’ skin. The term and preterm infants showed similar kinetics of skin carotenoids, which increased and entered a plateau after 3–4 days. In our cohort, FRMD did not have a significant influence on skin carotenoid concentration. This was due to immature sweat glands and an insufficient excretion of carotenoids. Skin carotenoids seem to be unavailable, suggesting that they may have to be supplemented in infants with FRMD. Blood carotenoid concentrations tended to be lower in preterm infants and infants with FRMD compared to healthy term infants. Full article

(This article belongs to the Special Issue Current Research on Dermatology: Pathology, Clinical Manifestation, Investigation and Therapy: 2nd Edition)

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15 pages, 3194 KiB

Open AccessEditor’s ChoiceReview

Neural Mechanisms of Cognitive Behavioral Therapy Efficacy in Anxiety Disorders: A Scoping Review of fMRI-Based Studies That Tested the Dual Model

by Judith Domínguez-Pérez, Wenceslao Peñate-Castro and Francisco Luis Rivero-Pérez

Life 2025, 15(3), 493; https://doi.org/10.3390/life15030493 - 18 Mar 2025

Cited by 1 | Viewed by 2960

Abstract

Anxiety disorders are common mental health conditions characterized by excessive fear and anxiety. Cognitive behavioral therapy (CBT) has demonstrated efficacy, yet the possible neurobiological mechanisms underpinning its effects remain debated. The dual-route model offers a potential explanation by suggesting that CBT increases activation [...] Read more.

Anxiety disorders are common mental health conditions characterized by excessive fear and anxiety. Cognitive behavioral therapy (CBT) has demonstrated efficacy, yet the possible neurobiological mechanisms underpinning its effects remain debated. The dual-route model offers a potential explanation by suggesting that CBT increases activation in the brain areas responsible for emotion regulation while decreasing activation in limbic areas. This scoping review examined possible neurobiological mechanisms supporting CBT’s efficacy in anxiety disorders by exclusively reviewing studies that utilized functional magnetic resonance imaging (fMRI). The included studies published since 2018 focused on adult samples that received CBT for anxiety disorders, with pre- or post-treatment fMRI data. The data extraction followed a standardized process, with key variables, such as the study design, population, and neuroimaging findings, systematically charted. While the dual-route model explains key aspects of CBT’s neurobiological effects, the findings suggest the need for expansion to incorporate areas such as the precuneus, particularly in specific phobias and social anxiety disorder. Further research is required to refine this model and explore additional mechanisms underlying CBT’s efficacy. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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37 pages, 4776 KiB

Open AccessEditor’s ChoiceReview

Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches

by Olga Adriana Caliman-Sturdza, Roxana Gheorghita and Andrei Lobiuc

Life 2025, 15(3), 439; https://doi.org/10.3390/life15030439 - 11 Mar 2025

Cited by 4 | Viewed by 5472

Abstract

The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. [...] Read more.

The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual’s quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients’ quality of life. Full article

(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)

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25 pages, 1535 KiB

Open AccessEditor’s ChoiceReview

Traumatic Brain Injury and Artificial Intelligence: Shaping the Future of Neurorehabilitation—A Review

by Seun Orenuga, Philip Jordache, Daniel Mirzai, Tyler Monteros, Ernesto Gonzalez, Ahmed Madkoor, Rahim Hirani, Raj K. Tiwari and Mill Etienne

Life 2025, 15(3), 424; https://doi.org/10.3390/life15030424 - 7 Mar 2025

Cited by 4 | Viewed by 7119

Abstract

Traumatic brain injury (TBI) is a leading cause of disability and death globally, presenting significant challenges for diagnosis, prognosis, and treatment. As healthcare technology advances, artificial intelligence (AI) has emerged as a promising tool in enhancing TBI rehabilitation outcomes. This literature review explores [...] Read more.

Traumatic brain injury (TBI) is a leading cause of disability and death globally, presenting significant challenges for diagnosis, prognosis, and treatment. As healthcare technology advances, artificial intelligence (AI) has emerged as a promising tool in enhancing TBI rehabilitation outcomes. This literature review explores the current and potential applications of AI in TBI management, focusing on AI’s role in diagnostic tools, neuroimaging, prognostic modeling, and rehabilitation programs. AI-driven algorithms have demonstrated high accuracy in predicting mortality, functional outcomes, and personalized rehabilitation strategies based on patient data. AI models have been developed to predict in-hospital mortality of TBI patients up to an accuracy of 95.6%. Furthermore, AI enhances neuroimaging by detecting subtle abnormalities that may be missed by human radiologists, expediting diagnosis and treatment decisions. Despite these advances, ethical considerations, including biases in AI algorithms and data generalizability, pose challenges that must be addressed to optimize AI’s implementation in clinical settings. This review highlights key clinical trials and future research directions, emphasizing AI’s transformative potential in improving patient care, rehabilitation, and long-term outcomes for TBI patients. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI))

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20 pages, 615 KiB

Open AccessEditor’s ChoiceSystematic Review

Factors Associated with Post-COVID Cardiac Conditions and Potential Prognostic Factors: A Systematic Review

by Lidian Franci Batalha Santa Maria, Josicélia Estrela Tuy Batista, Virginia Kagure Wachira, Wenderval Borges Carvalho Junior, Alexandre Anderson de Sousa Munhoz Soares, Isis Polianna Silva Ferreira de Carvalho and Henry Maia Peixoto

Life 2025, 15(3), 388; https://doi.org/10.3390/life15030388 - 28 Feb 2025

Cited by 1 | Viewed by 1456

Abstract

Cardiac conditions are a significant category of post-COVID conditions. The objective of this study was to synthesise the evidence on the factors associated with the development of post-COVID cardiac conditions, the frequency of clinical outcomes in affected patients, and the potential prognostic factors. [...] Read more.

Cardiac conditions are a significant category of post-COVID conditions. The objective of this study was to synthesise the evidence on the factors associated with the development of post-COVID cardiac conditions, the frequency of clinical outcomes in affected patients, and the potential prognostic factors. A systematic review was conducted using the databases EBSCOhost, MEDLINE via PubMed, BVS, and Embase, covering studies from 2019 to December 2023. A total of 8343 articles were identified, and seven met the eligibility criteria for data extraction. The protective effect of vaccination stood out among the associated factors, showing a reduced risk of developing post-COVID cardiac conditions. Conversely, COVID-19 reinfections were associated with an increased risk of cardiovascular outcomes. Regarding the main outcomes in these patients, most recovered, although some cases persisted beyond 200 days of follow-up. The study included in the analysis of prognostic factors reported that the four children who did not recover by the end of the study were between two and five years old and had gastrointestinal symptoms during the illness. The COVID-19 vaccination regimen reduces the risk of developing post-COVID cardiac conditions. Public health policies promoting immunisation should be encouraged to prevent SARS-CoV-2 infections and reinfections. Full article

(This article belongs to the Collection COVID-19 and Life)

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15 pages, 773 KiB

Open AccessEditor’s ChoiceArticle

The Role of the Subcostal Transversus Abdominis Plane Block in Facilitating Operating Room Extubation After Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Propensity Score-Matching Analysis

by Jaewon Huh and Min Suk Chae

Life 2025, 15(2), 297; https://doi.org/10.3390/life15020297 - 14 Feb 2025

Cited by 1 | Viewed by 952

Abstract

Background: Effective pain management is essential to early extubation and recovery in living donor liver transplantation (LDLT). The subcostal transversus abdominis plane (TAP) block has emerged as a potential strategy to address postoperative pain while reducing opioid consumption. This study evaluated the effectiveness [...] Read more.

Background: Effective pain management is essential to early extubation and recovery in living donor liver transplantation (LDLT). The subcostal transversus abdominis plane (TAP) block has emerged as a potential strategy to address postoperative pain while reducing opioid consumption. This study evaluated the effectiveness of the TAP block in facilitating early extubation in the OR and examined its impact on re-intubation rates, postoperative fentanyl requirements, and pain intensity upon ICU admission to determine its role in perioperative pain management. Methods: This retrospective cohort study included adult patients who underwent LDLT for hepatocellular carcinoma within the Milan criteria. Propensity score matching was performed to compare outcomes between patients who received the subcostal TAP block and those who did not. The primary outcome was the rate of successful extubation in the operating room (OR). Secondary outcomes included re-intubation rates, postoperative fentanyl requirements, and peak numeric rating scale (NRS) pain scores upon ICU admission. Results: The subcostal TAP block was associated with a significantly higher rate of successful OR extubation compared with no TAP block. Multivariable analysis revealed that the TAP block independently increased the likelihood of successful extubation. Patients receiving the TAP block required less fentanyl for pain management and demonstrated lower peak NRS pain scores upon ICU admission. No complications related to the TAP block were observed, underscoring its safety in this high-risk population. Conclusions: The subcostal TAP block facilitates early OR extubation by effectively managing postoperative pain and reducing opioid requirements, promoting smoother recovery without increasing adverse events. These findings support its inclusion in multimodal analgesia protocols for optimizing perioperative outcomes in LDLT patients. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations)

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25 pages, 331 KiB

Open AccessEditor’s ChoiceReview

Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication

by Ana Borrajo

Life 2025, 15(2), 276; https://doi.org/10.3390/life15020276 - 11 Feb 2025

Cited by 2 | Viewed by 6278

Abstract

Recent advances in virology, particularly in the study of HIV-1, have significantly progressed the pursuit of a definitive cure for the disease. Emerging therapeutic strategies encompass innovative gene-editing technologies, immune-modulatory interventions, and next-generation antiretroviral agents. Efforts to eliminate or control viral reservoirs have [...] Read more.

Recent advances in virology, particularly in the study of HIV-1, have significantly progressed the pursuit of a definitive cure for the disease. Emerging therapeutic strategies encompass innovative gene-editing technologies, immune-modulatory interventions, and next-generation antiretroviral agents. Efforts to eliminate or control viral reservoirs have also gained momentum, with the aim of achieving durable viral remission without the continuous requirement for antiretroviral therapy. Despite these promising developments, critical challenges persist in bridging the gap between laboratory findings and clinical implementation. This review provides a comprehensive analysis of recent breakthroughs, ongoing clinical trials, and the barriers that must be addressed to translate these advancements into effective treatments, emphasizing the multifaceted approaches being pursued to achieve a curative solution for HIV-1 infection. Full article

(This article belongs to the Special Issue Emerging Knowledge on Human Immunodeficiency Virus)

29 pages, 398 KiB

Open AccessEditor’s ChoiceArticle

Extracting Knowledge from Machine Learning Models to Diagnose Breast Cancer

by José Manuel Martínez-Ramírez, Cristobal Carmona, María Jesús Ramírez-Expósito and José Manuel Martínez-Martos

Life 2025, 15(2), 211; https://doi.org/10.3390/life15020211 - 31 Jan 2025

Viewed by 1324

Abstract

This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but [...] Read more.

This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but also provide insights into the factors driving predictions, addressing the need for trustworthy AI in healthcare. Several classification models were evaluated, including OneR, JRIP, the FURIA, J48, the ADTree, and the Random Forest, all of which are known for their explainability. The dataset included a variety of biomarkers, such as electrolytes, metal ions, marker proteins, enzymes, lipid profiles, peptide hormones, steroid hormones, and hormone receptors. The Random Forest model achieved the highest accuracy at 99.401%, followed closely by JRIP, the FURIA, and the ADTree at 98.802%. OneR and J48 achieved 98.204% accuracy. Notably, the models identified oxytocin as a key predictive biomarker, with most models featuring it in their rules. Other significant parameters included GnRH,

β

-endorphin, vasopressin, IRAP, and APB, as well as factors like iron, cholinesterase, the total protein, progesterone, 5-nucleotidase, and the BMI, which are considered clinically relevant to breast cancer pathogenesis. This study discusses the roles of the identified parameters in cancer development, thus underscoring the potential of explainable machine learning models for enhancing early breast cancer diagnosis by focusing on explainability and the use of serum biomarkers.The combination of both can lead to improved early detection and personalized treatments, emphasizing the potential of these methods in clinical settings. The identified markers also provide additional research and therapeutic targets for breast cancer pathogenesis and a deep understanding of their interactions, advancing personalized approaches to breast cancer management. Full article

(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)

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15 pages, 1153 KiB

Open AccessEditor’s ChoiceReview

Use of Live Biopreservatives and Bacteriophages to Enhance the Safety of Meat Products

by Cristina Rodríguez-Marca, Cristina Domenech-Coca, Miho Nakamura, Nàdia Ortega-Olivé and Pere Puigbò

Life 2025, 15(2), 197; https://doi.org/10.3390/life15020197 - 28 Jan 2025

Cited by 1 | Viewed by 1912

Abstract

Critical health considerations for both raw and processed meats include addressing bacterial spoilage and ensuring safety. Nitrites and nitrates are widely used in the meat industry to enhance color and flavor and extend shelf life. However, health concerns linked to their use make [...] Read more.

Critical health considerations for both raw and processed meats include addressing bacterial spoilage and ensuring safety. Nitrites and nitrates are widely used in the meat industry to enhance color and flavor and extend shelf life. However, health concerns linked to their use make reducing nitrites and nitrates in meat production a significant challenge with potential benefits for both the food industry and consumer health. This challenge has been addressed with the use of biopreservatives, i.e., substances extracted from natural sources or produced by fermentation that can enhance food quality and safety. In this article, we assess the use of live biopreservatives (LBs), defined here as microorganisms that produce antimicrobial substances that can be used to preserve and extend the shelf life of food. Moreover, the potential synergistic effects of LBs with bacteriophages and biodegradable food packaging for meat is also explored. This innovative combination offers a comprehensive approach to meat preservation, enhancing both microbial control and sustainability. Overall, the inclusion of LBs extends the shelf life of meat products through bacteriostatic mechanisms, whereas bacteriophages offer direct (lytic) action against pathogens. Enhancing meat preservation and safety with mixed microbe-mediated strategies requires deeper empirical and theoretical insights and further revision of laws and ethical considerations. Full article

(This article belongs to the Special Issue Antimicrobial Innovations)

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24 pages, 2805 KiB

Open AccessEditor’s ChoiceArticle

Dairy Wastewaters to Promote Mixotrophic Metabolism in Limnospira (Spirulina) platensis: Effect on Biomass Composition, Phycocyanin Content, and Fatty Acid Methyl Ester Profile

by Luca Baraldi, Luca Usai, Serenella Torre, Giacomo Fais, Mattia Casula, Debora Dessi, Paola Nieri, Alessandro Concas and Giovanni Antonio Lutzu

Life 2025, 15(2), 184; https://doi.org/10.3390/life15020184 - 26 Jan 2025

Cited by 4 | Viewed by 2103

Abstract

This study explores the mixotrophic cultivation of Limnospira platensis using dairy byproducts, specifically scotta whey (SW), buttermilk wastewater (BMW), and dairy wastewater (DWW), to promote biomass production and enhance the composition of bioactive compounds. By assessing various concentrations (1%, 2%, and 4% v [...] Read more.

This study explores the mixotrophic cultivation of Limnospira platensis using dairy byproducts, specifically scotta whey (SW), buttermilk wastewater (BMW), and dairy wastewater (DWW), to promote biomass production and enhance the composition of bioactive compounds. By assessing various concentrations (1%, 2%, and 4% v v⁻¹) of these byproducts in a modified growth medium, this study aims to evaluate their effect on L. platensis growth, phycocyanin (C-PC) content, and fatty acid methyl ester (FAME) profiles. The results show that the optimal biomass production was achieved with 2% scotta and dairy wastewater, reaching maximum concentrations of 3.30 g L⁻¹ and 3.19 g L⁻¹, respectively. Mixotrophic cultivation led to increased C-PC yields, especially in buttermilk and dairy wastewater treatments, highlighting the potential for producing valuable pigments. Additionally, the FAME profiles indicated minimal changes compared to the control, with oleic and γ-linolenic acids being dominant in mixotrophic conditions. These findings support the viability of utilizing dairy byproducts for sustainable L. platensis cultivation, contributing to a circular bioeconomy while producing bioactive compounds of nutritional and commercial interest. Full article

(This article belongs to the Special Issue Algae—a Step Forward in the Sustainability of Resources: 2nd Edition)

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13 pages, 1131 KiB

Open AccessEditor’s ChoiceArticle

Divergent Patterns of Metabolite Expression in Red Seaweeds (Devaleraea mollis and Palmaria hecatensis) Following Nitrate and Ammonium Supplementation

by Schery Umanzor, Jae Woo Jung, Muriel Dittrich, Jang K. Kim, Patrick Tomco, Zachary C. Redman and Monica Brandhuber

Life 2025, 15(2), 143; https://doi.org/10.3390/life15020143 - 21 Jan 2025

Cited by 1 | Viewed by 1344

Abstract

This study explores species-specific metabolic responses to different nitrogen-rich formulations in Devaleraea mollis and Palmaria hecatensis, highlighting distinct adaptive strategies. We evaluated the effects of Von Stosch Enrichment (VSE, nitrate-only), F/2 (nitrate-only), and Jack’s Special (JS, nitrate and ammonium) on metabolic profiles. [...] Read more.

This study explores species-specific metabolic responses to different nitrogen-rich formulations in Devaleraea mollis and Palmaria hecatensis, highlighting distinct adaptive strategies. We evaluated the effects of Von Stosch Enrichment (VSE, nitrate-only), F/2 (nitrate-only), and Jack’s Special (JS, nitrate and ammonium) on metabolic profiles. D. mollis exhibited elevated energy storage and growth-related metabolites, with JS enhancing creatine production for energy storage and regeneration, alongside increased DNA/RNA synthesis and cell division activity. This suggests D. mollis prioritizes rapid growth and energy demands, supporting broader ecological adaptability. Conversely, P. hecatensis showed higher expression of metabolites linked to amino acid metabolism and protein synthesis, indicating a focus on efficient nitrogen use for protein production, likely advantageous in low-light, high-turbidity conditions. Nitrogen sources significantly influence amino acid metabolism, with JS promoting broader amino acid production and VSE and F/2 stimulating specific metabolites. These species-specific metabolic patterns underscore the flexibility of D. mollis in energy use versus adaptations of P. hecatensis to protein synthesis pathways. These findings highlight species-specific nutrient formulations as essential for optimizing seaweed growth and metabolic traits in aquaculture. Full article

(This article belongs to the Special Issue Algae—a Step Forward in the Sustainability of Resources: 2nd Edition)

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27 pages, 856 KiB

Open AccessEditor’s ChoiceReview

Alzheimer’s Disease and Porphyromonas gingivalis: Exploring the Links

by Ivana Shawkatova, Vladimira Durmanova and Juraj Javor

Life 2025, 15(1), 96; https://doi.org/10.3390/life15010096 - 14 Jan 2025

Cited by 6 | Viewed by 6128

Abstract

Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer’s disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a [...] Read more.

Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer’s disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting P. gingivalis to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood–brain barrier disruption, neuroinflammation, and neuronal damage. P. gingivalis-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting P. gingivalis virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into P. gingivalis-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management. Full article

(This article belongs to the Special Issue Alzheimer’s Disease: Recent Developments in Pathogenesis, Diagnosis, and Therapy)

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15 pages, 3560 KiB

Open AccessEditor’s ChoiceArticle

Gut Microbiota Regulates the Homeostasis of Dendritic Epidermal T Cells

by Jinwoo Chung, Joo-Chan Lee, Hanna Oh, Yesung Kim, Suin Lim, Chanu Lee, Yoon-Gyu Shim, Eun-Chong Bang and Jea-Hyun Baek

Life 2024, 14(12), 1695; https://doi.org/10.3390/life14121695 - 21 Dec 2024

Viewed by 1279

Abstract

Dendritic epidermal T cells (DETCs) are a γδ T cell subset residing in the skin epidermis. Although they have been known for decades, the fate of DETCs has largely remained enigmatic. Recent studies have highlighted the relationship between the gut microbiome and γδ [...] Read more.

Dendritic epidermal T cells (DETCs) are a γδ T cell subset residing in the skin epidermis. Although they have been known for decades, the fate of DETCs has largely remained enigmatic. Recent studies have highlighted the relationship between the gut microbiome and γδ T cells in various epithelial and non-epithelial tissues, such as the small intestine, lung, liver, gingiva, and testis. While the skin microbiota has been shown to impact skin γδ T cells, a direct relationship between the gut microbiota and DETCs remains unexplored. In this study, we investigated whether DETCs are regulated by the gut microbiota in the steady-state skin epidermis. We examined the occurrence of DETCs in Balb/c mice, which have a skin epidermis barely populated with DETCs, compared to C57BL/6 mice, under different housing conditions. Our findings reveal that local skin inflammation markedly increases DETC numbers in the ear epidermis of Balb/c mice and that DETCs are activated by environmental factors. Furthermore, an investigation of the gut microbiota under different housing conditions revealed distinct microbial compositions and functional profiles. Taken together, these results suggest a strong connection between DETCs and gut microbiota. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

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12 pages, 2269 KiB

Open AccessEditor’s ChoiceArticle

Immunomodulatory Properties of Multi-Strain Postbiotics on Human CD14⁺ Monocytes

by Kyle D. Roberts, Sadia Ahmed, Erin San Valentin, Luca Di Martino, Thomas S. McCormick and Mahmoud A. Ghannoum

Life 2024, 14(12), 1673; https://doi.org/10.3390/life14121673 - 17 Dec 2024

Cited by 2 | Viewed by 1684

Abstract

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of [...] Read more.

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of postbiotics (cell wall components and secreted metabolites derived from live organisms) to regulate host immunity. In the present study, we tested postbiotics comprising single strains of bacteria and yeast (Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, Saccharomyces cerevisiae var. boulardii 16mxg) as well as combinations of multiple strains for their ability to stimulate cytokine production by human CD14⁺ monocytes. We quantified cytokine gene and protein expression levels in monocytes following stimulation with postbiotics. Both heat-killed L. acidophilus and L. rhamnosus stimulated naïve monocytes without significant differences between them. Heat-killed S. boulardii stimulated less cytokine production compared to postbiotic bacteria at the same concentration. Interestingly, the addition of heat-killed yeast to heat-killed L. acidophilus and L. rhamnosus resulted in an enhancement of immune stimulation. Thus, heat-killed postbiotics have immune-modulating potential, particularly when bacteria and yeast are combined. This approach may hold promise for developing targeted interventions that can be fine-tuned to modulate host immune response with beneficial health impact. Full article

(This article belongs to the Section Microbiology)

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14 pages, 261 KiB

Open AccessEditor’s ChoiceArticle

Learning Curve of First-Trimester Detailed Cardiovascular Ultrasound Screening by Moderately Experienced Obstetricians in 3509 Consecutive Unselected Pregnancies with Fetal Follow-Up

by Tibor Elekes, Gyula Csermely, Krisztina Kádár, László Molnár, Gábor Keszthelyi, Andrea Hozsdora, Miklós Vizer, Marianna Török, Petra Merkely and Szabolcs Várbíró

Life 2024, 14(12), 1632; https://doi.org/10.3390/life14121632 - 9 Dec 2024

Viewed by 1423

Abstract

Our primary objective was to assess the effectiveness of detailed cardiovascular ultrasound screening during the first trimester, which was performed by obstetricians with intermediate experience. We collected first-trimester fetal cardiac screening data from an unselected pregnant population at RMC-Fetal Medicine Center during a [...] Read more.

Our primary objective was to assess the effectiveness of detailed cardiovascular ultrasound screening during the first trimester, which was performed by obstetricians with intermediate experience. We collected first-trimester fetal cardiac screening data from an unselected pregnant population at RMC-Fetal Medicine Center during a study period spanning from 1 January 2010, to 31 January 2015, in order to analyze our learning curve. A pediatric cardiologist performed a follow-up assessment in cases where the examining obstetrician determined that the fetal cardiac screening results were abnormal or high-risk. Overall, 42 (0.88%) congenital heart abnormalities were discovered prenatally out of 4769 fetuses from 4602 pregnant women who had at least one first-trimester cardiac ultrasonography screening. In total, 89.2% of the major congenital heart abnormalities (27 of 28) in the following fetuses were discovered (or at least highly suspected) at the first-trimester screening and subsequent fetal echocardiography by the pediatric cardiology specialist. Of these, 96.4% were diagnosed prenatally. According to our results, the effectiveness of first-trimester fetal cardiovascular ultrasound screening conducted by moderately experienced obstetricians in an unselected (’routine’) pregnant population may reach as high as 90% in terms of major congenital heart defects, provided that equipment, quality assurance, and motivation are appropriate. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: Go From Bench to Bedside)

15 pages, 5384 KiB

Open AccessEditor’s ChoiceArticle

Intrauterine Growth Restriction Alters Postnatal Hippocampal Dentate Gyrus Neuron and Microglia Morphology and Cytokine/Chemokine Milieu in Mice

by Frank A. Strnad, Ashley S. Brown, Matthew Wieben, Emilio Cortes-Sanchez, Megan E. Williams and Camille M. Fung

Life 2024, 14(12), 1627; https://doi.org/10.3390/life14121627 - 9 Dec 2024

Viewed by 1296

Abstract

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown [...] Read more.

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown that UPI causes premature embryonic hippocampal dentate gyrus (DG) neurogenesis in IUGR offspring. The DG is a brain region that receives the first cortical information for memory formation. In the current study, we examined the postnatal DG neuron morphology one month after delivery (P28) using recombinant adeno-associated viral labeling of neurons. We also examined DG microglia’s morphology using immunofluorescent histochemistry and defined the hippocampal cytokine/chemokine milieu using Luminex xMAP technology. We found that IUGR preserved the principal dendrite lengths but decreased the dendritic branching and volume of DG neurons. IUGR augmented DG microglial number and cell size. Lastly, IUGR altered the hippocampal cytokine/chemokine profile in a sex-specific manner. We conclude that the prematurely-generated neuronal progenitors develop abnormal morphologies postnatally in a cell-autonomous manner. Microglia appear to modulate neuronal morphology by interacting with dendrites amidst a complex cytokine/chemokine environment that could ultimately lead to adult learning and memory deficits in our mouse model. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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14 pages, 1412 KiB

Open AccessEditor’s ChoiceReview

Regulation of Plant Growth and Development by Melatonin

by Dawei Shi, Lejia Zhao, Ruijia Zhang and Qiaofeng Song

Life 2024, 14(12), 1606; https://doi.org/10.3390/life14121606 - 4 Dec 2024

Cited by 3 | Viewed by 1919

Abstract

Melatonin is a naturally occurring chemical with pleiotropic effects in various species. In plants, melatonin is associated with a variety of plant physiological processes, including plant growth and development, stress responses, etc. Thus, melatonin may hold promise for improving crop yields and agricultural [...] Read more.

Melatonin is a naturally occurring chemical with pleiotropic effects in various species. In plants, melatonin is associated with a variety of plant physiological processes, including plant growth and development, stress responses, etc. Thus, melatonin may hold promise for improving crop yields and agricultural sustainability. This review describes the biosynthetic mode of melatonin and its properties and summarizes its functions in growth, development, and reproduction. In addition, the role of melatonin in plants facing various stressful environments is elaborated upon, and its relationship with other phytohormones is summarized. Through this review, we recognize the problems and challenges facing melatonin research and propose some feasible solutions. Full article

(This article belongs to the Special Issue Plant Adaptation Mechanisms to Abiotic Stresses)

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9 pages, 438 KiB

Open AccessEditor’s ChoiceArticle

Effect of Continuous Intake of Lactobacillus salivarius WB21 on Tissues Surrounding Implants: A Double-Blind Randomized Clinical Trial

by Yusuke Taniguchi, Nao Suzuki, Kae Kakura, Kazunari Tanabe, Ryutaro Ito, Tadahiro Kashiwamura, Akie Fujimoto, Marie Naito, Masahiro Yoneda, Takashi Hanioka and Hirofumi Kido

Life 2024, 14(12), 1532; https://doi.org/10.3390/life14121532 - 22 Nov 2024

Viewed by 2581

Abstract

Objective: This study aimed to improve the health of peri-implant tissues through continuous intake of Lactobacillus salivarius WB21 (LSWB21) tablets. Methods: A double-blind, randomized controlled trial was conducted with 23 maintenance patients who had generally healthy oral peri-implant tissues. Participants were divided into [...] Read more.

Objective: This study aimed to improve the health of peri-implant tissues through continuous intake of Lactobacillus salivarius WB21 (LSWB21) tablets. Methods: A double-blind, randomized controlled trial was conducted with 23 maintenance patients who had generally healthy oral peri-implant tissues. Participants were divided into a test group (n = 12) receiving LSWB21 tablets and a control group (n = 11) receiving placebos. All patients took one tablet three times daily for 2 months. Evaluation measures included modified Gingival Index (mGI), modified Plaque Index (mPI), modified Bleeding Index (mBI), salivary secretory IgA, and oral symptoms assessed at baseline, 1 month, and 2 months. Results: After 2 months, significant improvements in the mGI, mPI, and mBI were observed in the test group; significant improvement in the mPI was observed in the control group. Changes in the mGI over 2 months significantly differed between the groups (p = 0.038), and multiple regression analysis confirmed the effectiveness of LSWB21 in reducing the mGI (p = 0.034). Subjective symptoms such as bad breath in the test group and tongue symptoms in the control group also significantly improved. Conclusion: Continuous intake of LSWB21 may be beneficial for stabilizing peri-implant tissue. Trial registration: UMIN000039392 (UMIN-CTR). Full article

(This article belongs to the Section Medical Research)

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14 pages, 603 KiB

Open AccessEditor’s ChoiceReview

Extremophiles and Extremophilic Behaviour—New Insights and Perspectives

by George N. Angelakis, Chrysianna Psarologaki, Stergios Pirintsos and Kiriakos Kotzabasis

Life 2024, 14(11), 1425; https://doi.org/10.3390/life14111425 - 5 Nov 2024

Cited by 4 | Viewed by 4761

Abstract

Extremophiles, throughout evolutionary time, have evolved a plethora of unique strategies to overcome hardships associated with the environments they are found in. Modifying their genome, showing a bias towards certain amino acids, redesigning their proteins, and enhancing their membranes and other organelles with [...] Read more.

Extremophiles, throughout evolutionary time, have evolved a plethora of unique strategies to overcome hardships associated with the environments they are found in. Modifying their genome, showing a bias towards certain amino acids, redesigning their proteins, and enhancing their membranes and other organelles with specialised chemical compounds are only some of those strategies. Scientists can utilise such attributes of theirs for a plethora of biotechnological and astrobiological applications. Moreover, the rigorous study of such microorganisms regarding their evolution and ecological niche can offer deep insight into science’s most paramount inquiries such as how life originated on Earth and whether we are alone in the universe. The intensification of studies involving extremophiles in the future can prove to be highly beneficial for humanity, even potentially ameliorating modern problems such as those related to climate change while also expanding our knowledge about the complex biochemical reactions that ultimately resulted in life as we know it today. Full article

(This article belongs to the Special Issue Extremophiles Breakthrough: Hot Topics and Current Issues in Their Isolation, Identification and Biotechnological Applications)

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19 pages, 1172 KiB

Open AccessEditor’s ChoiceReview

Unlocking the Potential of Circulating miRNAs as Biomarkers in Glioblastoma

by Sanika Suvarnapathaki, Antolin Serrano-Farias, Jonathan C. Dudley, Chetan Bettegowda and Jordina Rincon-Torroella

Life 2024, 14(10), 1312; https://doi.org/10.3390/life14101312 - 16 Oct 2024

Cited by 1 | Viewed by 4296

Abstract

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant [...] Read more.

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant current diagnostic constraints and limited therapeutic strategies. MiRNA dysregulation is present in GBM. The intricate involvement of miRNAs in altering cell proliferation, invasion, and immune escape makes them prospective candidates for identifying and monitoring GBM diagnosis and response to treatment. These miRNAs could play a dual role, acting as both potential diagnostic markers and targets for therapy. By modulating the activity of various oncogenic and tumor-suppressive proteins, miRNAs create opportunities for precision medicine and targeted therapies in GBM. This review centers on the critical role and function of circulating miRNA biomarkers in GBM diagnosis and treatment. It highlights their significance in providing insights into disease progression, aiding in early diagnosis, and potential use as targets for novel therapeutic interventions. Ultimately, the study of miRNA would contribute to improving patient outcomes in the challenging landscape of GBM management. Full article

(This article belongs to the Special Issue Novel Approaches to Early Cancer Detection)

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12 pages, 1598 KiB

Open AccessEditor’s ChoiceArticle

Therapy for Dupuytren’s Disease: Collagenase Therapy—A Long-Term Follow-Up Study

by Nikolaus Wachtel, Francesca Romana Dingler, Tim Nürnberger, Felix Hubertus Vollbach, Nicholas Moellhoff, Riccardo Giunta and Wolfram Demmer

Life 2024, 14(10), 1275; https://doi.org/10.3390/life14101275 - 8 Oct 2024

Cited by 1 | Viewed by 1813

Abstract

Background: Dupuytren’s disease (DD) is a systemic connective tissue disorder of the palm. It particularly affects men of Northern European or Caucasian origin over the age of 55. In addition to the classical surgical therapy via limited fasciectomy, Dupuytren’s contracture can also be [...] Read more.

Background: Dupuytren’s disease (DD) is a systemic connective tissue disorder of the palm. It particularly affects men of Northern European or Caucasian origin over the age of 55. In addition to the classical surgical therapy via limited fasciectomy, Dupuytren’s contracture can also be treated minimally invasively. A relatively new treatment method is the use of collagenase injections (Xiapex) to reduce the contracture of the fingers. The data regarding the long-term success of this therapy are currently limited. Methods: In this monocentric retrospective study, we examined 35 patients who were treated with collagenase (Xiapex) for Dupuytren’s contracture in the long fingers. Following the manufacturer’s recommendations, the injection was administered intralesionally, and the cord was ruptured through the passive extension of the finger under local anesthesia with Mepivacain the following day. The clinical follow-up examination was conducted after an average of 5.7 years. The stages of Dupuytren’s disease were documented using the Tubiana classification. Additionally, parameters of finger extension ability, differentiated by metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints, as well as patient-specific risk parameters, were evaluated Results: The long-term results of collagenase therapy after an average of 5.7 years showed a significant improvement in the contracture of the affected fingers. In the MCP joints, the flexion contracture decreased from 42° to 17° (p ≤ 0.001), and in the PIP joints, it decreased from 56° to 33° (p ≤ 0.001). The primary recurrence rate was 11% for the MCP joints and 19% for the PIP joints, respectively. The analysis of risk factors showed a significant risk for worse long-term outcomes in patients with diabetes and those with nicotine abuse. Conclusions: Collagenase therapy for Dupuytren’s disease achieved significant long-term improvements in contracture in both MCP and PIP joints. In accordance with general risk factors for DD, patients with diabetes and those with nicotine abuse are at risk of worse long-term outcomes. Overall, it is a time-saving, low-risk, and straightforward technique for treating the disabling contracture component of this disease. Full article

(This article belongs to the Special Issue Novel Approaches in Plastic and Reconstructive Surgery to Improve Quality of Life)

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12 pages, 965 KiB

Open AccessEditor’s ChoiceArticle

Different ECLS Pump Configurations for Temporary Right Ventricular Assist Device in LVAD Patients: A Retrospective Case–Control Study

by Dragan Opacic, Christian Klüß, Darko Radakovic, Georges El-Hachem, Tobias Becker, Markus Rudloff, Volker Lauenroth, Marcus-André Deutsch, Claudio Velasquez-Silva, Henrik Fox, René Schramm, Michiel Morshuis, Jan F. Gummert and Sebastian V. Rojas

Life 2024, 14(10), 1274; https://doi.org/10.3390/life14101274 - 7 Oct 2024

Cited by 1 | Viewed by 2081

Abstract

Background: Acute right ventricular failure is a critical complication after left ventricular assist device (LVAD) implantation, often managed with a temporary paracorporeal right ventricular assist device (RVAD). This study examined three extracorporeal life support (ECLS) systems regarding mortality, bleeding complications, and intensive care [...] Read more.

Background: Acute right ventricular failure is a critical complication after left ventricular assist device (LVAD) implantation, often managed with a temporary paracorporeal right ventricular assist device (RVAD). This study examined three extracorporeal life support (ECLS) systems regarding mortality, bleeding complications, and intensive care unit (ICU) stay duration. Methods: This monocentric, retrospective case–control study included all patients receiving LVAD with paracorporeal RVAD between 2009 and 2020. Three patient groups were formed: Centrimag^TM (A), Cardiohelp^TM (B), and Deltastream^TM (C). Results: A total of 245 patients were included. Preoperative parameters were similar between the Centrimag^TM and Deltastream^TM groups, but Cardiohelp^TM patients had worse Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Scores (A: 1.7 ± 0.8, B: 1.36 ± 0.5, C: 1.9 ± 0.9; p < 0.05). In-hospital death rates were A: 61 (41.8%), B: 15 (32.6%), C: 29 (54.7%); p < 0.05, and reoperation due to bleeding rates were A: 32 (21.9%), B: 8 (17.4%), C: 25 (47.2%); p < 0.05, with the Deltastream^TM group showing the highest rates. This group also had increased thrombocyte consumption and prolonged ICU stays. Conclusions: Temporary RVADs lead to bleeding complications, affecting patient outcomes. The Deltastream^TM group had significantly higher bleeding complications, likely due to high pump revolution rates and thrombocyte decline. Due to the study’s retrospective nature and complex patient profiles, these interesting findings should be validated in future studies. Full article

(This article belongs to the Section Medical Research)

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11 pages, 246 KiB

Open AccessEditor’s ChoiceArticle

Association of Loneliness with Functional and Cognitive Status in Minor and Major Neurocognitive Disorders

by Maria Claudia Moretti, Iris Bonfitto, Luciano Nieddu, Ivana Leccisotti, Savino Dimalta, Giovanni Moniello, Madia Lozupone, Antonello Bellomo, Francesco Panza, Carlo Avolio and Mario Altamura

Life 2024, 14(10), 1216; https://doi.org/10.3390/life14101216 - 24 Sep 2024

Cited by 1 | Viewed by 2032

Abstract

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive [...] Read more.

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n = 42) and major NCD (n = 164) through DSM-5 criteria on 206 participants aged > 65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (β = −1.05, p < 0.0001) and minor NCD (β = −0.06, p < 0.01). In the fully adjusted multivariate regression model (sex–age–education–multimorbidity–depressive symptoms–antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (β = 0.09, p < 0.001). The effect of loneliness on IADL (β = −0.26, p < 0.0001) and ADL (β = −0.24, p < 0.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL: β = 0.26, p < 0.0001; ADL: β = 0.05, p = 0.01). Minor NCD displayed different levels of MMSE (β = 6.68, p < 0.001) but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD. Full article

(This article belongs to the Special Issue Alzheimer's Disease: From Pathogenesis to Therapy)

22 pages, 10840 KiB

Open AccessEditor’s ChoiceArticle

Murine Retina Outer Plexiform Layer Development and Transcriptome Analysis of Pre-Synapses in Photoreceptors

by Soo-Young Kim, Christine Haewon Park, Bo-Hyun Moon and Gail K. Seabold

Life 2024, 14(9), 1103; https://doi.org/10.3390/life14091103 - 2 Sep 2024

Cited by 2 | Viewed by 2435

Abstract

Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited [...] Read more.

Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited knowledge about rod versus (vs.) cone synapse development and the associated genes. The transcription factor neural retina leucine zipper (NRL) determines the rod vs. cone photoreceptor cell fate and is critical for rod differentiation. Nrl knockout mice fail to form rods, generating all cone or S-cone-like (SCL) photoreceptors in the retina, whereas ectopic expression of Nrl using a cone-rod homeobox (Crx) promoter (CrxpNrl) forms all rods. Here, we examined rod and cone pre-synapse development, including axonal elongation, terminal shaping, and synaptic lamination in the outer plexiform layer (OPL) in the presence or absence of Nrl. We show that NRL loss and knockdown result in delayed OPL maturation and plasticity with aberrant dendrites of bipolar neurons. The integrated analyses of the transcriptome in developing rods and SCLs with NRL CUT&RUN and synaptic gene ontology analyses identified G protein subunit beta (Gnb) 1 and p21 (RAC1) activated kinase 5 (Pak5 or Pak7) transcripts were upregulated in developing rods and down-regulated in developing SCLs. Notably, Gnb1 and Gnb5 are rod dominant, and Gnb3 is enriched in cones. NRL binds to the genes of Gnb1, Gnb3, and Gnb5. NRL also regulates pre-synapse ribbon genes, and their expression is altered in rods and SCLs. Our study of histological and gene analyses provides new insights into the morphogenesis of photoreceptor pre-synapse development and regulation of associated genes in the developing retina. Full article

(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)

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10 pages, 3046 KiB

Open AccessEditor’s ChoiceArticle

Screening and Validation of Leaf Width-Related Genes in Inbred Maize Lines

by Shi Lu, Qi Wang, Junqi Yin, Shubo Zheng, Tingting Gao, Xudong Zhou, Jianxin Zhang, Yuexian Xing, Yingjie Ma, Min Wang, Delong Zhou, Ming Lu, Wenguo Liu, Piwu Wang and Zhijun Zhang

Life 2024, 14(9), 1057; https://doi.org/10.3390/life14091057 - 23 Aug 2024

Viewed by 1339

Abstract

Leaf width is a key determinant of planting density and photosynthetic efficiency. In an effort to determine which genes regulate maize plant leaf width, we performed a genome-wide association study (GWAS) of 1.49 × 106 single nucleotide polymorphisms (SNPs) in 80 sequenced backbone [...] Read more.

Leaf width is a key determinant of planting density and photosynthetic efficiency. In an effort to determine which genes regulate maize plant leaf width, we performed a genome-wide association study (GWAS) of 1.49 × 106 single nucleotide polymorphisms (SNPs) in 80 sequenced backbone inbred maize lines in Jilin Province, China, based upon phenotypic leaf width data from two years. In total, 14 SNPs were identified as being significantly related to leaf width (p < 0.000001), with these SNPs being located on chromosomes 1, 2, 3, 5, 6, 7, 8, and 9. A total of five candidate genes were identified within a mean linkage disequilibrium (LD) distance of 9.7 kb, with a significant SNP being identified within the Zm00001d044327 candidate gene. RNA was then isolated from 12 different inbred maize lines from this GWAS study cohort and was used to conduct qPCR analyses which revealed significant differences in Zm00001d044327 expression among strains exhibiting significant differences in leaf width. Based on an assessment of EMS mutant lines harboring a conserved amino acid stop mutation and two non-synonymous mutations in Zm00001d044327 that exhibited a narrow leaf width, these data suggested that Zm00001d044327 is a key regulator of maize leaf width. Full article

(This article belongs to the Section Plant Science)

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17 pages, 4891 KiB

Open AccessEditor’s ChoiceArticle

TMEM9B Regulates Endosomal ClC-3 and ClC-4 Transporters

by Margherita Festa, Maria Antonietta Coppola, Elena Angeli, Abraham Tettey-Matey, Alice Giusto, Irene Mazza, Elena Gatta, Raffaella Barbieri, Alessandra Picollo, Paola Gavazzo, Michael Pusch, Cristiana Picco and Francesca Sbrana

Life 2024, 14(8), 1034; https://doi.org/10.3390/life14081034 - 20 Aug 2024

Cited by 3 | Viewed by 4669

Abstract

The nine-member CLC gene family of Cl⁻ chloride-transporting membrane proteins is divided into plasma membrane-localized Cl⁻ channels and endo-/lysosomal Cl⁻/H⁺ antiporters. Accessory proteins have been identified for ClC-K and ClC-2 channels and for the lysosomal ClC-7, but not [...] Read more.

The nine-member CLC gene family of Cl⁻ chloride-transporting membrane proteins is divided into plasma membrane-localized Cl⁻ channels and endo-/lysosomal Cl⁻/H⁺ antiporters. Accessory proteins have been identified for ClC-K and ClC-2 channels and for the lysosomal ClC-7, but not the other CLCs. Here, we identified TMEM9 Domain Family Member B (TMEM9B), a single-span type I transmembrane protein of unknown function, to strongly interact with the neuronal endosomal ClC-3 and ClC-4 transporters. Co-expression of TMEM9B with ClC-3 or ClC-4 dramatically reduced transporter activity in Xenopus oocytes and transfected HEK cells. For ClC-3, TMEM9B also induced a slow component in the kinetics of the activation time course, suggesting direct interaction. Currents mediated by ClC-7 were hardly affected by TMEM9B, and ClC-1 currents were only slightly reduced, demonstrating specific interaction with ClC-3 and ClC-4. We obtained strong evidence for direct interaction by detecting significant Förster Resonance Energy Transfer (FRET), exploiting fluorescence lifetime microscopy-based (FLIM-FRET) techniques between TMEM9B and ClC-3 and ClC-4, but hardly any FRET with ClC-1 or ClC-7. The discovery of TMEM9B as a novel interaction partner of ClC-3 and ClC-4 might have important implications for the physiological role of these transporters in neuronal endosomal homeostasis and for a better understanding of the pathological mechanisms in CLCN3- and CLCN4-related pathological conditions. Full article

(This article belongs to the Special Issue Ion Channels and Neurological Disease: 2nd Edition)

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14 pages, 1032 KiB

Open AccessEditor’s ChoiceReview

The Role of Brassinosteroids in Plant Cold Stress Response

by Zhiqi He, Mengdi Zhou, Xiaojie Feng, Qinghua Di, Di Meng, Xianchang Yu, Yan Yan, Mintao Sun and Yansu Li

Life 2024, 14(8), 1015; https://doi.org/10.3390/life14081015 - 15 Aug 2024

Cited by 5 | Viewed by 2139

Abstract

Temperature affects plant growth and geographical distribution. Cold stress occurs when temperatures fall below the physiologically optimal range for plants, causing permanent and irreversible damage to plant growth, development, and production. Brassinosteroids (BRs) are steroid hormones that play an important role in plant [...] Read more.

Temperature affects plant growth and geographical distribution. Cold stress occurs when temperatures fall below the physiologically optimal range for plants, causing permanent and irreversible damage to plant growth, development, and production. Brassinosteroids (BRs) are steroid hormones that play an important role in plant growth and various stress responses. Recent studies have shown that low temperatures affect BR biosynthesis in many plant species and that BR signaling is involved in the regulation of plant tolerance to low temperatures, both in the CBF-dependent and CBF-independent pathways. These two regulatory pathways correspond to transient and acclimation responses of low temperature, respectively. The crosstalk between BRs and other hormones is a significant factor in low-temperature tolerance. We provide an overview of recent developments in our knowledge of BRs’ function in plant responses to cold stress and how they interact with other plant hormones in this review. Full article

(This article belongs to the Special Issue Plant Biotic and Abiotic Stresses 2024)

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25 pages, 444 KiB

Open AccessEditor’s ChoiceReview

Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment

by Marina Mattar, Florence Umutoni, Marwa A. Hassan, M. Wambui Wamburu, Reagan Turner, James S. Patton, Xin Chen and Wei Lei

Life 2024, 14(8), 991; https://doi.org/10.3390/life14080991 - 9 Aug 2024

Cited by 16 | Viewed by 10581

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology of CIPN is not completely understood; however, it is believed that chemotherapies induce peripheral neuropathy via directly damaging mitochondria, impairing the function of ion channels, triggering immunological mechanisms, and disrupting microtubules. The treatment of CIPN is a medical challenge, and there are no approved pharmacological options. Currently, duloxetine and other antidepressants, antioxidant, anti-inflammatory, and ion-channel targeted therapies are commonly used in clinics to relieve the symptoms of CIPN. Several other types of drugs, such as cannabinoids, sigma−1 receptor antagonists, and nicotinamides ribose, are being evaluated in preclinical and clinical studies. This paper summarizes the information related to the physiology of CIPN and medicines that could be used for treating this condition. Full article

(This article belongs to the Special Issue Conservative Management of Chronic Disease)

13 pages, 1051 KiB

Open AccessEditor’s ChoiceArticle

Leveraging Electronic Health Records to Predict the Risk of Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation

by Elena Bischoff and Nikola Kirilov

Life 2024, 14(8), 987; https://doi.org/10.3390/life14080987 - 8 Aug 2024

Viewed by 1127

Abstract

Background: The objective of this study is to assess the electronic health records (EHRs), which are potential risk factors for acute kidney injury (AKI) after allogenic hematopoietic cell transplantation (allo-HCT), and to propose a basic dataset and score for the calculation of HCT-acute [...] Read more.

Background: The objective of this study is to assess the electronic health records (EHRs), which are potential risk factors for acute kidney injury (AKI) after allogenic hematopoietic cell transplantation (allo-HCT), and to propose a basic dataset and score for the calculation of HCT-acute kidney injury risk (HCT-AKIR). Methods: We undertook a retrospective analysis of the EHRs of 312 patients. Pre- and post-transplant factors were assessed, recognizing the following structured entries: laboratory data, encounters, medication, imaging studies, diagnoses, and procedures. Composite variables were used to create patient groups by combining two or more multivariate significant risk factors for AKI. The EHRs dataset and HCT-AKIR score were created based on the multivariate analysis of the composite variables. Results: A multivariate analysis showed that previous CKD and once-impaired pre-transplant kidney function, sepsis, imaging procedures with contrast media, and cumulative length of intensive care unit stay after transplantation were significant risk factors. A new unit-weighted composite score based on the combination of significant risk factors contained in common EHR resources was proposed. Conclusions: Using our novel HCT-AKIR score calculated from the basic EHR dataset could be an easy way to increase awareness of post-transplant AKI and provide risk stratification. Full article

(This article belongs to the Section Epidemiology)

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12 pages, 3309 KiB

Open AccessEditor’s ChoiceArticle

A Cross-Sectional Analysis of Interventional Clinical Trials in High-Grade Glioma Therapy

by Angelo Angione, Jonathan Patterson, Ebrar Akca, Jessica Xu, Emily Xu, Vanessa Raab, Omar Elghawy, Adam A. Barsouk and Jonathan H. Sussman

Life 2024, 14(8), 926; https://doi.org/10.3390/life14080926 - 24 Jul 2024

Cited by 2 | Viewed by 1553

Abstract

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and [...] Read more.

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status. Full article

(This article belongs to the Special Issue Cancer Epidemiology, Survival, and Disparities: Past, Present, and Future)

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20 pages, 2787 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism Spectrum Disorder

by John P. Jones III, Lauren Williamson, Zacharoula Konsoula, Rachel Anderson, Kathryn J. Reissner and William Parker

Life 2024, 14(8), 918; https://doi.org/10.3390/life14080918 - 23 Jul 2024

Cited by 2 | Viewed by 3413

Abstract

More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant [...] Read more.

More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in silico methods to create an ideal (virtual) population of 120,000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal dataset shows little to no risk of acetaminophen use if the cofactors that create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors that impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in the analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD. Full article

(This article belongs to the Section Pharmaceutical Science)

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15 pages, 768 KiB

Open AccessEditor’s ChoiceArticle

Sensitization to Lanolin in North-Eastern Italy, 1997–2021: Prevalence, Risk Factors and the Impact of Occupation

by Luca Cegolon, Francesca Larese Filon and on behalf of the North-East Research Group on Contact Dermatitis

Life 2024, 14(8), 916; https://doi.org/10.3390/life14080916 - 23 Jul 2024

Cited by 5 | Viewed by 1918

Abstract

Background: Direct skin contact with items containing lanolin can induce sensitization and development of contact dermatitis (CD). This multi-centric study investigated prevalence of lanolin sensitization among 30,269 outpatients from North-Eastern Italy patch tested during 1997–2021. Methods: European baseline and extended Triveneto [...] Read more.

Background: Direct skin contact with items containing lanolin can induce sensitization and development of contact dermatitis (CD). This multi-centric study investigated prevalence of lanolin sensitization among 30,269 outpatients from North-Eastern Italy patch tested during 1997–2021. Methods: European baseline and extended Triveneto series were applied on the upper part of patients’ back and removed after 48 h. Risk factors for lanolin sensitization were investigated by multiple logistic regression analysis, reporting adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Results. Overall lanolin patch test positive ratio (PTPR) was 1.64% (=501/30,629), with variability over time and by research center. The body area most frequently affected by CD were hands (36.32%), followed by face (19.52%) and legs (8.09%), with a lanolin PTPR of 1.68%, 1.37% and 3.07%, respectively. Prevalence of occupational CD was 8.24%, and 1.83% patients with occupational CD patch tested positive against lanolin. Lanolin sensitization was significantly higher in males (aOR = 1.34; 95%CI: 1.08; 1.65) and among patients with leg CD aged 49–60 years (aOR = 2.34; 95%CI: 1.20; 4.57) or older than 60 (aOR = 4.21; 95%CI: 2.59; 6.85). Sub-group analysis confirmed the significantly higher sensitization rate of older patients with leg CD, with much stronger effect size in females 61+ years old (aOR = 5.33; 95%CI 2.87; 9.89) than males in the same age group (aOR = 2.92; 95%CI: 1.34; 6.39). Moreover, female house painters were more likely to test positive to lanolin. Conclusions: The variability of lanolin PTPR over time and by research center endorsed the ongoing debate on the relevance of the respective skin reaction. Clinicians assessing patients with dermatitis should collect information on potential risk factors for lanolin sensitization, particularly use of skin care products containing the hapten. Occupational exposure to lanolin-containing varnishes should also be considered. Full article

(This article belongs to the Section Epidemiology)

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25 pages, 501 KiB

Open AccessEditor’s ChoiceSystematic Review

Mobile Application Applied for Cognitive Rehabilitation: A Systematic Review

by Su-Min Cha

Life 2024, 14(7), 891; https://doi.org/10.3390/life14070891 - 18 Jul 2024

Cited by 4 | Viewed by 4438

Abstract

The COVID-19 pandemic has increased the demand for home rehabilitation services, leading to the development and rising demand for cognitive rehabilitation apps. However, a comprehensive analysis of the content and effectiveness of these apps is needed. This study systematically reviewed and analyzed the [...] Read more.

The COVID-19 pandemic has increased the demand for home rehabilitation services, leading to the development and rising demand for cognitive rehabilitation apps. However, a comprehensive analysis of the content and effectiveness of these apps is needed. This study systematically reviewed and analyzed the literature on mobile apps for cognitive rehabilitation. One researcher and an external expert conducted the study selection, data extraction, and quality assessment following the PRISMA Checklist 2020 guidelines. Our review of 18 studies identified 8 randomized controlled trials (RCTs) (44.44%) of high quality and 10 non-RCT studies (55.56%) of moderate quality. Overall, 16 of the 18 studies (88.88%) demonstrated positive clinical implications for cognitive function after using cognitive rehabilitation apps. Eight studies showed a correlation between app use and improved cognitive function, and four highlighted the potential for cognitive function evaluation through apps. All studies employed various occupational therapy (OT) intervention approaches, with prevention being the most common (100%), followed by establishment and restoration (83.33%), maintenance (77.77%), and creation and promotion (38.88%). This study clinically validates the effectiveness of cognitive rehabilitation mobile applications from an occupational therapy perspective. Full article

(This article belongs to the Section Medical Research)

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