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Search Results (295)

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Keywords = confirmation/evidence distinction

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16 pages, 5435 KB  
Article
Genetic Mechanism of Geothermal Water in Typical Structural Belts from the Altay and Tianshan to the Kunlun Mountains in Xinjiang: Evidence from Hydrogeochemistry and δ2H–δ18O Isotopes
by Dongqiang Hu, Yanjun Li, Zhilon Qi, Xinghua Qi and Changqiang Ma
Water 2025, 17(20), 2946; https://doi.org/10.3390/w17202946 (registering DOI) - 13 Oct 2025
Abstract
This study investigates geothermal waters in the Xinjiang region through hydrogeochemical methods, including cluster analysis, ionic ratios, and isotopic analysis. Cluster analysis categorized the geothermal water samples into three distinct groups (G1, G2, and G3). The predominant hydrochemical facies are SO4-HCO [...] Read more.
This study investigates geothermal waters in the Xinjiang region through hydrogeochemical methods, including cluster analysis, ionic ratios, and isotopic analysis. Cluster analysis categorized the geothermal water samples into three distinct groups (G1, G2, and G3). The predominant hydrochemical facies are SO4-HCO3-Na, SO4-Cl-Na, and Cl-Na types, whose formation is controlled by multiple factors. Evidence from molar ratios of major ions suggests that geothermal waters in Group G1 are predominantly governed by water–rock interactions, whereas Groups G2 and G3 are mainly influenced by evaporative concentration. Hydrogen and oxygen isotopic signatures confirm that meteoric water serves as the primary recharge source for these geothermal waters. The spatial correlation between regional tectonic features and most geothermal discharge points demonstrates a consistent relationship between geothermal water occurrence and structural distribution in Xinjiang. Additionally, a conceptual circulation model is proposed wherein meteoric water undergoes deep circulation following local recharge, ascends along fault zones under tectonic pressure, and mixes with shallow groundwater. This research primarily elucidates the hydrogeochemical characteristics and recharge mechanisms of geothermal resources in Xinjiang, thereby providing a scientific basis for their future development and utilization. Full article
(This article belongs to the Special Issue Groundwater Thermal Monitoring and Modeling)
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30 pages, 20586 KB  
Article
A Shallow Water Case of Ordovician Marine Red Beds (South China): Evidence from Sedimentary Structures and Response to the Kwangsian Orogeny
by Liangjun Wu, Xiqiang Quan, Yuanhai Zhang, Pujun Wang and Chao Huang
Geosciences 2025, 15(10), 394; https://doi.org/10.3390/geosciences15100394 (registering DOI) - 12 Oct 2025
Abstract
Ordovician marine red beds (OMRBs) are widely developed along the margins of Gondwana and represent distinctive limestone facies. These red beds are known for their diverse sedimentary structures and have been described by scholars as the “fashionable facies” in geological history. However, their [...] Read more.
Ordovician marine red beds (OMRBs) are widely developed along the margins of Gondwana and represent distinctive limestone facies. These red beds are known for their diverse sedimentary structures and have been described by scholars as the “fashionable facies” in geological history. However, their characteristics and classification remain controversial. Multiple hypotheses about their origin have also hindered a clear understanding of these strata. Therefore, this study focuses on the Xiangxi area (South China) and presents a detailed analysis of the sedimentary structures of marine red beds, building on previous research on OMRBs in South China. Based on genetic features, we divide the most debated “nodule-like” and “cracked” structures—previously identified by earlier researchers—into ten subtypes. Three key genetic end-members are identified among these subtypes: breccia, patch, and argillaceous band. Detailed studies using microslab analysis, scanning electron microscopy, geochemistry, and paleontology were carried out on these three end-members. The results confirm that the Ordovician marine red beds were mainly deposited in a shallow marine environment, with the red coloration primarily derived from continental sources. As the sea level rose, the color of the red beds lightened, and the dominant sedimentary structures shifted from breccia end-members to argillaceous band end-members. Additionally, this study identified a vertically penetrating argillaceous band controlled by syndepositional compressive stress, which may be linked to NW-directed compression from the Kwangsian Orogeny. Evidence from tectonic styles, biofacies migration, and chronostratigraphy supports this hypothesis. Full article
(This article belongs to the Section Sedimentology, Stratigraphy and Palaeontology)
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22 pages, 703 KB  
Systematic Review
Current Perspectives on Non-Metastatic Male Breast Cancer: Genetics, Biology, and Treatment Advances: A Systematic Review
by Kathleen Melan, Pierre Loap and Youlia Kirova
Cancers 2025, 17(19), 3270; https://doi.org/10.3390/cancers17193270 - 9 Oct 2025
Viewed by 247
Abstract
Background/Objectives: Male breast cancer (MBC) is a rare malignancy representing less than 1% of all breast cancer cases, with rising incidence worldwide. Current treatment strategies largely rely on extrapolation from female breast cancer, despite clear biological and clinical distinctions. This review aims to [...] Read more.
Background/Objectives: Male breast cancer (MBC) is a rare malignancy representing less than 1% of all breast cancer cases, with rising incidence worldwide. Current treatment strategies largely rely on extrapolation from female breast cancer, despite clear biological and clinical distinctions. This review aims to summarize current knowledge on non-metastatic MBC, with a particular focus on genetic predisposition, tumor biology, and recent therapeutic advances. Methods: A systematic literature search was conducted using PubMed and PMC databases to identify clinical trials, observational studies and systematic reviews related to MBC published up to 1st June, 2025. Studies were selected for their relevance to genetic and molecular features, as well as treatment outcomes in non-metastatic disease. Results: Fifty-one studies were included in the review. Findings confirm the predominance of hormone receptor–positive tumors in MBC and underscore the central role of BRCA2 mutations. Germline mutations in BRCA2 and BRCA1 were reported in approximately 1 and 2% of male cases, respectively. Additional germline alterations were identified in PALB2, CHEK2, and other DNA repair genes. Comparative analyses of surgical approaches showed no significant difference in survival between breast-conserving surgery and mastectomy. Postmastectomy radiotherapy improved overall survival compared to surgery alone. Adjuvant tamoxifen therapy was independently associated with significant survival benefits, although adherence remains a challenge. Conclusions: MBC is a biologically distinct and molecularly heterogeneous disease. Breast-conserving surgery appears safe and effective in selected patients. Adjuvant radiotherapy and tamoxifen confer clear survival advantages. The lack of male-specific clinical trials remains a major limitation in optimizing evidence-based care for MBC. Full article
(This article belongs to the Section Cancer Therapy)
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21 pages, 8591 KB  
Article
Simulation of Compaction Process of Tight Sandstone in Xiashihezi Formation, North Ordos Basin: Insights from SEM, EDS and MIP
by Hongxiang Jin, Feiyang Wang, Chong Han, Chunpu Wang, Yi Wu and Yang Hu
Processes 2025, 13(10), 3191; https://doi.org/10.3390/pr13103191 - 8 Oct 2025
Viewed by 223
Abstract
The Permian Xiashihezi Formation in the Ordos Basin is a typical tight sandstone gas reservoir, which is characterized by low porosity and strong heterogeneity. Diagenesis plays a crucial role in controlling reservoir quality. However, the multiple phases and types of diagenetic processes throughout [...] Read more.
The Permian Xiashihezi Formation in the Ordos Basin is a typical tight sandstone gas reservoir, which is characterized by low porosity and strong heterogeneity. Diagenesis plays a crucial role in controlling reservoir quality. However, the multiple phases and types of diagenetic processes throughout geological history make the compaction mechanisms highly complex. This study employed a high-temperature and high-pressure diagenesis simulation system to conduct geological simulation experiments. Typical reservoir samples from the 2nd Member of the Permian Xiashihezi Formation were selected for these simulations. The experiments replicated the diagenetic evolution of the reservoirs under various temperature, pressure, and fluid conditions, successfully reproducing the diagenetic sequences. The diagenetic sequence included early-stage porosity reduction through compaction, early carbonate cementation, quartz overgrowth, chlorite rim formation, feldspar dissolution, and late-stage illite and quartz cementation. Mechanical compaction is the primary factor reducing reservoir porosity, exhibiting a distinct four-stage porosity reduction pattern: (1) continuous burial stage (>4000 m); (2) stagnation stage of burial (3900 m–4100 m); (3) the secondary continuous burial stage (>5000 m); (4) tectonic uplift stage (3600 m). The experiments confirmed that the formation of various authigenic minerals is strictly controlled by temperature, pressure, and fluid chemistry. Chlorite rims formed in an alkaline environment enriched with Fe2+ and Mg2+ (simulated temperatures of 280–295 °C), effectively inhibiting quartz overgrowth. Illite appeared at higher temperatures (>300 °C) in platy or fibrous forms. Feldspar dissolution was noticeable upon injection of acidic fluids (simulated organic acids), providing material for authigenic quartz and kaolinite. The key mineral composition significantly impacts reservoir diagenesis. The dissolution released Mg2+ and Fe2+ ions, crucial for forming early chlorite rims in the overlying sandstones, confirming the importance of inter-strata interactions in “source-facies coupling.” Through physical simulation methods, this study deepened the understanding of the diagenetic evolution and compaction mechanisms of tight sandstones. This provides significant experimental evidence and theoretical support for predicting “sweet spot” reservoirs in the area. Full article
(This article belongs to the Topic Exploitation and Underground Storage of Oil and Gas)
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43 pages, 5132 KB  
Article
Multi-Technique Flavoromics for Identifying Key Differential Volatile Compounds Underlying Sensory Profiles in Lager Beers
by Yiyuan Chen, He Huang, Ruiyang Yin, Xiuli He, Liyun Guo, Yumei Song, Dongrui Zhao, Jinyuan Sun, Jinchen Li, Mingquan Huang and Baoguo Sun
Foods 2025, 14(19), 3428; https://doi.org/10.3390/foods14193428 - 5 Oct 2025
Viewed by 390
Abstract
In this study, inter-brand variations in volatile flavor compound profiles of four lager beers were systematically investigated by integrating sensory evaluation with GC-MS, GC×GC-TOF-MS, and GC-O-MS. A total of 594 volatile compounds were identified, of which 71 with odor activity values (OAV) ≥ [...] Read more.
In this study, inter-brand variations in volatile flavor compound profiles of four lager beers were systematically investigated by integrating sensory evaluation with GC-MS, GC×GC-TOF-MS, and GC-O-MS. A total of 594 volatile compounds were identified, of which 71 with odor activity values (OAV) ≥ 1 were found to contribute directly to aroma expression. Additionally, 59 compounds with taste activity values (TAV) ≥ 1 were identified and may also contribute to taste perception. Furthermore, 53 aroma-active compounds were confirmed through GC-O-MS, providing additional evidence for their sensory contribution. Partial least squares discriminant analysis (PLS-DA), correlation analysis, and flavor addition experiments revealed brand-specific differential flavor compounds. Ultimately, twenty key differential flavor compounds, encompassing esters, alcohols, aromatic compounds, acids, lactones, and others, were confirmed to contribute to fruity, floral, burnt, and sweet notes. Phenethyl alcohol, with concentrations varying from 1377.1 mg/L in QD to 3297.5 mg/L in HR, showed a more than 2.4-fold difference across brands and was strongly associated with fruity (r = 0.553) and floral (r = 0.564) aroma. These compounds acted in combination to shape distinct aroma profiles. This study provides a molecular-level basis for understanding lager beer flavor and offers practical guidance for targeted flavor modulation in brewing. Full article
(This article belongs to the Special Issue Sensory Detection and Analysis in Food Industry)
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20 pages, 3734 KB  
Systematic Review
One Health in Coastal and Marine Contexts: A Critical Bibliometric Analysis Across Environmental, Animal, and Human Health Dimensions
by Alexandra Ioannou, Evmorfia Bataka, Nikolaos Kokosis, Charalambos Billinis and Chrysi Laspidou
Int. J. Environ. Res. Public Health 2025, 22(10), 1523; https://doi.org/10.3390/ijerph22101523 - 4 Oct 2025
Viewed by 425
Abstract
Coastal ecosystems sustain biodiversity, food resources, and human livelihoods, yet are increasingly exposed to climate change, pollution, and anthropogenic stressors. These pressures affect not only ecosystem integrity but also human health, highlighting the urgency of adopting the One Health framework. While One Health [...] Read more.
Coastal ecosystems sustain biodiversity, food resources, and human livelihoods, yet are increasingly exposed to climate change, pollution, and anthropogenic stressors. These pressures affect not only ecosystem integrity but also human health, highlighting the urgency of adopting the One Health framework. While One Health has gained global prominence, its systematic application in coastal and marine governance remains limited. This study provides the first bibliometric review of One Health research in coastal and marine contexts, analyzing 154 publications from Scopus (2003–2025) using Bibliometrix under PRISMA-S guidelines. Scientific output was minimal until 2015 but accelerated after 2020, peaking at 37 publications in 2024. Less than 20% of studies explicitly integrated all three One Health dimensions. Research has largely centered on environmental monitoring and aquaculture health, with antimicrobial resistance, climate–health linkages, and integrated coastal indicators underexplored. Keyword mapping revealed two distinct yet connected clusters: a biomedical cluster emphasizing antibiotics, resistance, and microbiology, and an environmental cluster focusing on pollution, ecosystems, and zoonotic risks. Outputs are geographically concentrated in high-income countries, particularly the USA, Brazil, and the UK, while contributions from low- and middle-income coastal regions remain scarce. These findings confirm both the rapid growth and the fragmentation of One Health scholarship in coastal contexts. By identifying gaps, trends, and collaboration patterns, this study builds an evidence base for embedding One Health in coastal monitoring, climate adaptation, and governance, advancing multiple United Nations’s Sustainable Development Goals. Full article
(This article belongs to the Special Issue Implications of Climate Change and One Health Approach)
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17 pages, 935 KB  
Systematic Review
Potential Genetic Intersections Between ADHD and Alzheimer’s Disease: A Systematic Review
by Riccardo Borgonovo, Lisa M. Nespoli, Martino Ceroni, Lisa M. Arnaud, Lucia Morellini, Marianna Lissi and Leonardo Sacco
NeuroSci 2025, 6(4), 97; https://doi.org/10.3390/neurosci6040097 - 1 Oct 2025
Viewed by 354
Abstract
Background: attention-deficit/hyperactivity disorder (ADHD) and Alzheimer’s disease (AD) are distinct neurological conditions that may share genetic and molecular underpinnings. ADHD, a neurodevelopmental disorder, affects approximately 5% of children and 3% of adults globally, while AD, a neurodegenerative disorder, is the leading cause of [...] Read more.
Background: attention-deficit/hyperactivity disorder (ADHD) and Alzheimer’s disease (AD) are distinct neurological conditions that may share genetic and molecular underpinnings. ADHD, a neurodevelopmental disorder, affects approximately 5% of children and 3% of adults globally, while AD, a neurodegenerative disorder, is the leading cause of dementia in older adults. Emerging evidence suggests potential overlapping contributors, including pathways related to synaptic plasticity, neuroinflammation, and oxidative stress. Methods: this systematic review investigated potential genetic predispositions linking Attention-Deficit/Hyperactivity Disorder (ADHD) and Alzheimer’s Disease (AD). Following PRISMA guidelines, a search was conducted in Web of Science, Embase, PsycINFO, and PubMed using keywords related to ADHD, AD, and genetic factors. Studies included were original human studies utilizing genetic analyses and ADHD polygenic risk scores (PRS), with AD confirmed using established diagnostic criteria. Exclusion criteria comprised non-original studies, animal research, and articles not addressing genetic links between ADHD and AD. Screening was conducted with Rayyan software, assessing relevance based on titles, abstracts, and full texts. Results:. The search identified 1450 records, of which 1092 were screened after duplicates were removed. Following exclusions, two studies met inclusion criteria. One study analyzed ADHD-PRS in 212 cognitively unimpaired older adults using amyloid-beta (Aβ) PET imaging and tau biomarkers. The findings revealed that ADHD-PRS was associated with progressive cognitive decline, increased tau pathology, and frontoparietal atrophy in Aβ-positive individuals, suggesting that ADHD genetic liability may exacerbate AD pathology. Another study assessed ADHD-PRS in a cohort of 10,645 Swedish twins, examining its association with 16 somatic conditions. The results showed modest risk increases for cardiometabolic, autoimmune, and neurological conditions, with mediation effects through BMI, education, tobacco use, and alcohol misuse, but no direct link between ADHD-PRS and dementia. Discussion and conclusion: this review highlights preliminary but conflicting evidence for a genetic intersection between ADHD and AD. One study suggests that ADHD genetic liability may exacerbate AD-related pathology in Aβ-positive individuals, whereas another large registry-based study finds no direct link to dementia, with associations largely mediated by lifestyle factors. The potential ADHD–AD relationship is likely complex and context-dependent, influenced by biomarker status and environmental confounders. Longitudinal studies integrating genetics, biomarkers, and detailed lifestyle data are needed to clarify this relationship. Full article
25 pages, 720 KB  
Review
Management Strategy for Non-Responsive and Refractory Celiac Disease in Adults: A Review Article
by A. Al-Toma
J. Clin. Med. 2025, 14(19), 6934; https://doi.org/10.3390/jcm14196934 - 30 Sep 2025
Viewed by 412
Abstract
Background/Objectives: A substantial number of adults with celiac disease (CeD) experience ongoing symptoms despite consuming a gluten-free diet (GFD), a condition labelled as non-responsive CeD (NRCD). However, many experts contest the term, viewing NRCD not as a distinct entity, but as a clinical [...] Read more.
Background/Objectives: A substantial number of adults with celiac disease (CeD) experience ongoing symptoms despite consuming a gluten-free diet (GFD), a condition labelled as non-responsive CeD (NRCD). However, many experts contest the term, viewing NRCD not as a distinct entity, but as a clinical prompt to identify a specific underlying cause. A minority develop refractory CeD (RCD), a severe complication with persistent villous atrophy, after beginning a diet excluding gluten exposure. This review synthesizes evidence to provide a practical, stepwise algorithm for managing these complex patients. Methods: A narrative review was conducted based on a targeted literature search of major databases seeking studies on adults with NRCD or RCD, focusing on diagnostic and therapeutic strategies. Results: The most frequent cause of NRCD is inadvertent gluten ingestion. Objective and systematic assessment, including expert dietitian evaluation and testing with gluten immunogenic peptides (GIPs) in stool or urine GIP testing, is essential before the investigation seeking to exclude or establish RCD. This is a critical step for evaluating adherence beyond the patient self-report. The management of confirmed RCD hinges on precise subtyping via duodenal biopsy with immunophenotyping. While RCD type I (RCD-I) typically responds to budesonide, RCD type II (RCD-II) carries a high risk of lymphoma and necessitates aggressive therapies in specialized centers. Conclusions: This review underscores the necessity of a structured, hierarchical diagnostic approach in distinguishing persistent gluten exposure from true RCD. The integration of GIP testing and specialist dietitian review is a cornerstone of modern management. The findings highlight significant evidence gaps, particularly for RCD-II, and aim to guide clinical practice and inform future research towards standardized protocols. Full article
(This article belongs to the Special Issue Future Trends in the Diagnosis and Management of Celiac Disease)
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13 pages, 354 KB  
Systematic Review
Applications of Artificial Intelligence in Alpha-1 Antitrypsin Deficiency: A Systematic Review from a Respiratory Medicine Perspective
by Manuel Casal-Guisande, Laura Villar-Aguilar, Alberto Fernández-Villar, Esmeralda García-Rodríguez, Ana Casal and María Torres-Durán
Medicina 2025, 61(10), 1768; https://doi.org/10.3390/medicina61101768 - 30 Sep 2025
Viewed by 228
Abstract
Background and Objectives: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema, and with liver involvement through a distinct toxic gain-of-function mechanism. Despite its clinical relevance, AATD remains [...] Read more.
Background and Objectives: Alpha-1 antitrypsin deficiency (AATD) is a rare genetic condition associated with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and emphysema, and with liver involvement through a distinct toxic gain-of-function mechanism. Despite its clinical relevance, AATD remains underdiagnosed and exhibits marked phenotypic heterogeneity. Artificial intelligence (AI) has shown growing potential in respiratory medicine, yet its application to AATD is still limited. This systematic review synthesizes the clinical evidence on AI in AATD, primarily in the respiratory domain and, where available, in hepatic outcomes. Materials and Methods: We conducted a PRISMA-guided search (PubMed, Web of Science, IEEE Xplore) for original, peer-reviewed articles (January 2014–September 2025) applying AI to detection, classification, stratification, or prediction tasks in AATD. Results: Six studies met eligibility criteria. Supervised models (e.g., XGBoost, penalized regression, Transformer-based architectures) and one unsupervised approach were identified. Applications included screening in COPD populations, prediction of emphysema progression from CT, proteomic modeling of lung function, identification of clinical subgroups, and prediction of clinical outcomes in AATD-associated liver disease. External validation and genotype diversity remained limited across studies. Conclusions: Although AI shows promise in improving detection, prognosis, and patient stratification in AATD across both respiratory and hepatic manifestations, the current evidence remains limited. Broader, multicenter validation in genotype-diverse cohorts is required to confirm its clinical utility and support the implementation of precision medicine in AATD. Full article
(This article belongs to the Section Pulmonology)
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16 pages, 1865 KB  
Article
Correlations of Tinel and Phalen Signs with Nerve Conduction Study Test Results in a Randomly Chosen Population of Patients with Carpal Tunnel Syndrome
by Katarzyna Kaczmarek, Jędrzej Pepliński, Anna Kaczmarek, Dariusz Andrzejuk, Kacper Andruszkiewicz, Alicja Wysocka, Matylda Witkowska and Juliusz Huber
NeuroSci 2025, 6(4), 94; https://doi.org/10.3390/neurosci6040094 - 28 Sep 2025
Viewed by 322
Abstract
Background: The consequences of median nerve compression at the carpal tunnel level require a precise diagnostic evaluation before a frequently applied surgical intervention. Positive Tinel or Phalen signs are not always related to abnormal results in electroneurographic examinations of sensory and motor nerve [...] Read more.
Background: The consequences of median nerve compression at the carpal tunnel level require a precise diagnostic evaluation before a frequently applied surgical intervention. Positive Tinel or Phalen signs are not always related to abnormal results in electroneurographic examinations of sensory and motor nerve fibers, which are intended to confirm final diagnoses, thereby confusing both surgeons and neurophysiologists. In the face of contradictory data, this study aims to reinvestigate these correlations in a randomly chosen population of patients with a primary diagnosis of carpal tunnel syndrome (CTS). Methods: Seventy-five randomly chosen patients with clinically detected CTS underwent neurophysiological studies of median nerve sensory (SNAP) and motor (CMAP) fibers conduction at the wrist. Both the median and ulnar nerves were assessed to reduce the risk of misinterpretation related to anatomical variations. Results: This study provides evidence on the relatively high utility of Phalen’s test in the early clinical detection of CTS within a general population of patients, whose positive results moderately correlate (rho = −0.327) with abnormalities in amplitudes rather than the distal latency parameters of SNAP recordings. The axonal injury type is more distinct than slowing-down impulses at the wrist following compression of the sensory nerve fibers in the early course of CTS. Positive Tinel’s test results are useful in diagnosing CTS patients with advanced axonal and demyelinating changes in the motor fibers at the wrist, which weakly correlate with prolonged latency and decreased amplitude in SNAP recordings (rho = −0.214 and rho = −0.235, respectively), but not with abnormalities in recordings of both amplitudes and latencies in CMAP electroneurography. Conclusions: The correlations between clinical signs and neurophysiological findings in CTS indicate that provocative tests, such as Phalen’s and Tinel’s, have limited diagnostic value, demonstrating only weak-to-moderate associations with neural conduction parameters. A positive Tinel’s sign should be regarded mainly as a marker of severe or chronic sensory impairment, often accompanied by motor fibers involvement in advanced pathological stages, rather than as an indicator of motor damage alone. Nerve conduction studies remain essential for confirming CTS, assessing its severity, and guiding treatment decisions, including surgical qualification. The presented correlation of clinical and functional neurophysiological results in CTS diagnosis allows us not only to specify the source and severity of the pathology of the median nerve fibers but also may influence the personalization of physiotherapeutic and surgical treatments. Full article
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20 pages, 420 KB  
Review
Immunotherapy-Induced Complete Response in dMMR Rectal Cancer—A Surgical Dilemma?
by Panagiotis Loufopoulos, Konstantinos Perivoliotis, Danai Chatziathanasiou, Maximos Frountzas, Anisha Sukha, Abdullah Alrebdi, Mohammad Mahmoud Rajab Eddama, Christos Kontovounisios, Shengyang Qiu, Paris Tekkis and Shahnawaz Rasheed
Cancers 2025, 17(19), 3153; https://doi.org/10.3390/cancers17193153 - 28 Sep 2025
Viewed by 549
Abstract
Background: Deficient mismatch repair rectal cancer represents approximately 10% of rectal malignancies and demonstrates exceptional responsiveness to immune checkpoint inhibitors, achieving unprecedented complete response rates approaching 100%. This creates a novel clinical dilemma: should patients achieving complete response undergo standard surgical resection or [...] Read more.
Background: Deficient mismatch repair rectal cancer represents approximately 10% of rectal malignancies and demonstrates exceptional responsiveness to immune checkpoint inhibitors, achieving unprecedented complete response rates approaching 100%. This creates a novel clinical dilemma: should patients achieving complete response undergo standard surgical resection or pursue organ preservation through watch-and-wait management? Methods: We conducted a comprehensive literature review of clinical trials and retrospective studies published through 2025, focusing on response assessment strategies, decision-making frameworks, oncological outcomes, and quality of life assessments. Results: Landmark studies demonstrated remarkable efficacy with dostarlimab achieving 100% clinical complete response, while surgical cohorts achieved 68–92% pathological complete response rates. Response assessment challenges included pseudoprogression and pseudoresidue phenomena that complicated conventional imaging interpretation and required specialised multimodal evaluation protocols. Comparative analyses suggest equivalent oncological outcomes between surgical and non-surgical approaches in complete responders, achieving 100% disease-free survival at 2–3 years across multiple studies. The watch-and-wait approach offered significant advantages by preserving organ integrity and avoiding surgical morbidity, including permanent colostomy (15.4%) and perioperative complications (19.3%). Conversely, surgical management provided distinct benefits through definitive tissue confirmation and anxiety relief from intensive surveillance requirements and potential recurrence concerns. Conclusions: The surgery versus watch-and-wait dilemma represents a choice between equally effective oncological approaches with different quality of life implications. Evidence supports individualised decision-making weighing functional preservation benefits against patient preferences and institutional capabilities in this evolving therapeutic landscape. Full article
(This article belongs to the Special Issue Surgical Treatment of Abdominal Tumors)
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23 pages, 2800 KB  
Article
Genome-Driven Insights into Lactococcus sp. KTH0-1S Highlights Its Biotechnological Potential as a Cell Factory
by Nisit Watthanasakphuban, Hind Abibi, Nuttakan Nitayapat, Phitsanu Pinmanee, Chollachai Klaysubun, Nattarika Chaichana, Komwit Surachat and Suttipun Keawsompong
Biology 2025, 14(10), 1323; https://doi.org/10.3390/biology14101323 - 25 Sep 2025
Viewed by 384
Abstract
The safety, genetic distinctiveness, and functional capabilities of Lactococcus sp. KTH0-1S, a strain isolated from Thai fermented shrimp (Kung-Som), were investigated to assess its potential as a next-generation probiotic and microbial cell factory. Whole-genome sequencing and multilocus sequence typing (MLST) analysis revealed that [...] Read more.
The safety, genetic distinctiveness, and functional capabilities of Lactococcus sp. KTH0-1S, a strain isolated from Thai fermented shrimp (Kung-Som), were investigated to assess its potential as a next-generation probiotic and microbial cell factory. Whole-genome sequencing and multilocus sequence typing (MLST) analysis revealed that Lactococcus sp. KTH0-1S is a novel, phylogenetically distinct strain within the Lactococcus genus. Comprehensive in silico safety evaluation confirmed the absence of antimicrobial resistance genes and major virulence factors, supporting its suitability for food-grade applications. The genome encodes multiple probiotic-relevant traits, including stress tolerance (e.g., dnaK, clpP), adhesion and biofilm formation (e.g., gapA, luxS, glf2), and nutrient acquisition genes, enabling adaptation to gastrointestinal and fermentation environments. Notably, Lactococcus sp. KTH0-1S harbors a chromosomally encoded nisin Z biosynthesis gene cluster with auto-induction capability, providing a self-regulated and stable alternative to conventional plasmid-based NICE systems in Lactococcus lactis. The strain also exhibits nisin immunity, allowing tolerance to high nisin concentrations, thus supporting robust protein production. Genomic evidence and phenotypic assays confirmed a functional respiration metabolism activated by heme supplementation, enhancing biomass yield and culture stability. Furthermore, the presence of diverse CAZyme families (GHs, GTs, CEs) enables utilization of various carbohydrate substrates, including lignocellulosic and starchy agro-industrial residues. These properties collectively underscore Lactococcus sp. KTH0-1S as a safe, stable, and metabolically versatile candidate for probiotic applications and as a cost-effective, food-grade expression host for biotechnological production. Full article
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17 pages, 5715 KB  
Article
Spatiotemporal Characteristics of Oxygen Content in the Vegetation Growing Season of Qinghai Province Based on Vertical Gradients
by Ziqian Zhang, Weidong Ma, Fenggui Liu, Zemin Zhi and Wenjing Xu
Appl. Sci. 2025, 15(18), 10301; https://doi.org/10.3390/app151810301 - 22 Sep 2025
Viewed by 426
Abstract
To reveal the spatiotemporal variations in near-surface oxygen content during the growing season across different altitudinal gradients in Qinghai Province and to deepen the understanding of oxygen cycling in plateau ecosystems, this study analyzed daily observations from 12 monitoring stations spanning three elevation [...] Read more.
To reveal the spatiotemporal variations in near-surface oxygen content during the growing season across different altitudinal gradients in Qinghai Province and to deepen the understanding of oxygen cycling in plateau ecosystems, this study analyzed daily observations from 12 monitoring stations spanning three elevation ranges (1500–2500 m, 2500–3500 m, and 3500–4500 m) during the 2022–2023 growing seasons (March–July). The Mann–Kendall test was employed to detect temporal trends, variability indices such as standard deviation and coefficient of variation were used to quantify fluctuation intensity, Kernel density estimation (KDE) was applied to characterize distributional features, and the Kruskal–Wallis test was conducted to assess statistical significance. The results indicate that: (1) oxygen content showed a significant increasing trend at all three altitudinal gradients, with the strongest rise at low elevations and the weakest at high elevations; (2) fluctuation intensity exhibited clear spatial heterogeneity, with the most pronounced variability in summer at low elevations, a distinct peak in June at mid-elevations, and overall stability at high elevations; and (3) KDE analysis revealed a broader distribution and higher frequency of extreme oxygen values at low elevations, while mid- and high-elevations displayed more concentrated distributions. Both the Kruskal–Wallis test and post hoc comparisons confirmed highly significant differences among the three elevation ranges. These findings demonstrate that elevation is a key factor influencing the spatiotemporal distribution of near-surface oxygen content during the growing season in Qinghai Province. Differences are not only evident in absolute oxygen levels but also in fluctuation intensity and distributional characteristics. This study provides empirical evidence for understanding oxygen variability mechanisms on the plateau and offers theoretical and practical references for ecological management and health risk prevention in high-altitude regions. Full article
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21 pages, 10257 KB  
Article
Assessing Recent Changes in the Contribution of Rainfall and Air Temperature Effects to Mean Flow and Runoff in Two Slovenian–Croatian Basins Using MLR and MLLR
by Ognjen Bonacci, Ana Žaknić-Ćatović and Tanja Roje-Bonacci
Water 2025, 17(18), 2787; https://doi.org/10.3390/w17182787 - 22 Sep 2025
Viewed by 512
Abstract
This study investigates the recent changes in the relationship between annual precipitation, mean annual air temperature, mean annual river discharge, and annual runoff coefficients in two small, neighboring continental catchments in Slovenia and Croatia: the Sutla/Sotla and Krapina River basins. Analyses of discharge, [...] Read more.
This study investigates the recent changes in the relationship between annual precipitation, mean annual air temperature, mean annual river discharge, and annual runoff coefficients in two small, neighboring continental catchments in Slovenia and Croatia: the Sutla/Sotla and Krapina River basins. Analyses of discharge, precipitation, and temperature time series were conducted on an annual scale using simple linear regression, multiple linear regression (MLR), and multiple log-linear regression (MLLR). Despite their geographical proximity and similar climatic conditions, the two basins exhibit markedly different runoff coefficients. Lower values observed in the Krapina River at Kupljenovo likely reflect gentle slopes, permeable soils, dense vegetation, and significant infiltration losses, while higher runoff coefficients at the Sutla River near Rakovec suggest more rapid surface runoff, reduced infiltration, and potentially distinct land use. In both basins, a pronounced rise in mean annual air temperatures has been evident since 1992, followed approximately eight years later by a sharp decline in mean annual flows and annual runoff coefficients. Our results show that the influence of air temperature on both discharge and runoff coefficients has become significantly stronger in recent decades, especially since the year 2000, contributing to a notable decline in mean annual discharges as well as annual runoff coefficients. Mean annual discharges have decreased by 19% in the Sutla and 15% in the Krapina basin, coinciding with temperature increases. Regression analyses confirm that air temperature has become a dominant negative predictor of discharge and runoff, with its influence intensifying over the past two decades. The runoff coefficient declined from 0.483 to 0.394 in the Sutla basin and from 0.325 to 0.270 in the Krapina basin during the same period. These findings highlight the importance of catchment-specific assessments for understanding and managing the localized impacts of climate change on hydrological processes. However, future work should incorporate evaporation as a key variable to better attribute the observed runoff reductions. Full article
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Article
Indirect Modeling of Post-Prandial Intestinal Lymphatic Uptake of Halofantrine Using PBPK Approaches: Limitations and Implications
by Malaz Yousef, Farag E. S. Mosa, Khaled H. Barakat, Neal M. Davies and Raimar Löbenberg
Pharmaceutics 2025, 17(9), 1228; https://doi.org/10.3390/pharmaceutics17091228 - 22 Sep 2025
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Abstract
Background/Objectives: Despite the recognized importance and distinctive characteristics of the intestinal lymphatic pathway in drug absorption, its pharmacokinetic modeling remains largely unexplored. This study aimed to address this gap by developing a physiologically based pharmacokinetic model (PBPK) to represent the oral lymphatic uptake [...] Read more.
Background/Objectives: Despite the recognized importance and distinctive characteristics of the intestinal lymphatic pathway in drug absorption, its pharmacokinetic modeling remains largely unexplored. This study aimed to address this gap by developing a physiologically based pharmacokinetic model (PBPK) to represent the oral lymphatic uptake of halofantrine following a fatty meal. Methods: Using GastroPlus™ 9.8.3 and published literature data, halofantrine absorption, distribution, metabolism, and elimination in both fasting and fed states were modeled. As the used software does not directly simulate intestinal lymphatic transport, lymphatic involvement in the fed state was examined indirectly through parameter adjustments such as first-pass metabolism, pKa-driven solubility changes, and bile-salt-mediated solubilization, with the aid of molecular dynamics simulations under post-prandial pH. Results: The pharmacokinetic models revealed a reduction in the first-pass effect of halofantrine in the fed state compared to that in the fasting state. While adjustments in metabolism kinetics sufficed for constructing a representative PBPK model in the fasting state, capturing the fed-state profile required both modifications to metabolism kinetics and other parameters related to the structural rearrangements of halofantrine driven by the changes in intestinal pH following food intake. These changes were confirmed using molecular dynamics simulations of halofantrine in pHs reflecting the post-prandial conditions. Conclusions: This study underscores the need for further exploration and direct modeling of intestinal lymphatic uptake via PBPK models, highlighting its underexplored status in simulation algorithms. Moreover, the importance of integrating representative physicochemical factors for drugs, particularly in post-prandial conditions or lipid formulations, is evident. Overall, these findings contribute to advancing predictive regulatory and developmental considerations in drug development using post hoc analyses. Full article
(This article belongs to the Special Issue In Silico Pharmacokinetic and Pharmacodynamic (PK-PD) Modeling)
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