Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (938)

Search Parameters:
Keywords = provenance trials

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
16 pages, 1169 KiB  
Review
Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma
by Romeo Gabriel Mihaila and Samuel B. Todor
J. Clin. Med. 2025, 14(15), 5534; https://doi.org/10.3390/jcm14155534 - 6 Aug 2025
Abstract
T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and [...] Read more.
T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article
(This article belongs to the Special Issue Immunotherapy of Hematological Malignancies: The State of the Art)
Show Figures

Figure 1

14 pages, 5479 KiB  
Article
Assessment of Three Provenances of Juglans neotropica Diels to Identify Optimal Seed Sources in the Northern Ecuadorian Andes
by Jorge-Luis Ramírez-López, Mario Añazco, Hugo Vallejos, Carlos Arcos and Kelly Estrada
Int. J. Plant Biol. 2025, 16(3), 87; https://doi.org/10.3390/ijpb16030087 (registering DOI) - 6 Aug 2025
Abstract
Identifying optimal seed sources is critical for the propagation and restoration of Juglans neotropica Diels in the northern Ecuadorian Andes, where populations are declining due to habitat loss and overexploitation. This study evaluated the seed quality and germination performance of Juglans neotropica from [...] Read more.
Identifying optimal seed sources is critical for the propagation and restoration of Juglans neotropica Diels in the northern Ecuadorian Andes, where populations are declining due to habitat loss and overexploitation. This study evaluated the seed quality and germination performance of Juglans neotropica from three ecologically distinct provenances: a natural regeneration site (Cuyuja), a pure plantation (Natabuela), and an agroforestry system (Pimampiro). Five phenotypically superior trees were selected from each site, and germination was assessed under controlled nursery conditions over a 150-day period using a completely randomized design. Initial viability tests confirmed the physiological integrity of the seeds across all provenances. Germination onset ranged from day 55 to day 73, with significant differences in germination percentage, speed, and uniformity. The agroforestry provenance showed the highest germination rate (69%) and superior performance in all physiological indices, while natural regeneration had the lowest (15%). Post-trial viability assessments indicated that a substantial proportion of non-germinated seeds from Cuyuja remained dormant or deteriorated. These findings underscore the role of agroforestry systems in enhancing seed physiological quality and support their prioritization for large-scale propagation and ecological restoration initiatives involving Juglans neotropica. Full article
(This article belongs to the Section Plant Reproduction)
Show Figures

Graphical abstract

26 pages, 9773 KiB  
Review
A Narrative Review of the Clinical Applications of Echocardiography in Right Heart Failure
by North J. Noelck, Heather A. Perry, Phyllis L. Talley and D. Elizabeth Le
J. Clin. Med. 2025, 14(15), 5505; https://doi.org/10.3390/jcm14155505 - 5 Aug 2025
Abstract
Background/Objectives: Historically, echocardiographic imaging of the right heart has been challenging because its abnormal geometry is not conducive to reproducible anatomical and functional assessment. With the development of advanced echocardiographic techniques, it is now possible to complete an integrated assessment of the right [...] Read more.
Background/Objectives: Historically, echocardiographic imaging of the right heart has been challenging because its abnormal geometry is not conducive to reproducible anatomical and functional assessment. With the development of advanced echocardiographic techniques, it is now possible to complete an integrated assessment of the right heart that has fewer assumptions, resulting in increased accuracy and precision. Echocardiography continues to be the first-line imaging modality for diagnostic analysis and the management of acute and chronic right heart failure because of its portability, versatility, and affordability compared to cardiac computed tomography, magnetic resonance imaging, nuclear scintigraphy, and positron emission tomography. Virtually all echocardiographic parameters have been well-validated and have demonstrated prognostic significance. The goal of this narrative review of the echocardiographic parameters of the right heart chambers and hemodynamic alterations associated with right ventricular dysfunction is to present information that must be acquired during each examination to deliver a comprehensive assessment of the right heart and to discuss their clinical significance in right heart failure. Methods: Using a literature search in the PubMed database from 1985 to 2025 and the Cochrane database, which included but was not limited to terminology that are descriptive of right heart anatomy and function, disease states involving acute and chronic right heart failure and pulmonary hypertension, and the application of conventional and advanced echocardiographic modalities that strive to elucidate the pathophysiology of right heart failure, we reviewed randomized control trials, observational retrospective and prospective cohort studies, societal guidelines, and systematic review articles. Conclusions: In addition to the conventional 2-dimensional echocardiography and color, spectral, and tissue Doppler measurements, a contemporary echocardiographic assessment of a patient with suspected or proven right heart failure must include 3-dimensional echocardiographic-derived measurements, speckle-tracking echocardiography strain analysis, and hemodynamics parameters to not only characterize the right heart anatomy but to also determine the underlying pathophysiology of right heart failure. Complete and point-of-care echocardiography is available in virtually all clinical settings for routine care, but this imaging tool is particularly indispensable in the emergency department, intensive care units, and operating room, where it can provide an immediate assessment of right ventricular function and associated hemodynamic changes to assist with real-time management decisions. Full article
(This article belongs to the Special Issue Cardiac Imaging in the Diagnosis and Management of Heart Failure)
Show Figures

Figure 1

24 pages, 6639 KiB  
Article
CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept
by Frits C. de Beer and Harry W. M. Steinbusch
Anatomia 2025, 4(3), 12; https://doi.org/10.3390/anatomia4030012 - 1 Aug 2025
Viewed by 99
Abstract
Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells [...] Read more.
Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells and their effective medical applications has intensified research into spinal cord regeneration. However, despite these advances, the impact of clinical trials involving spinal cord-injured (SCI) patients remains disappointingly low. Long-distance regeneration has yet to be proven. Methods: Our study involved a microsurgical dorsal myelotomy in fetal rats. The development of pioneering long primary afferent axons during early gestation was examined long after birth. Results: A single cut triggered the intrinsic ability of the dorsal root ganglion (DRG) neurons to reprogram. Susceptibility to hypoxia caused the axons to stop developing. However, the residual axonal outgrowth sheds light on the intriguing temporal and spatial events that reveal long-distance CNS regeneration. The altered phenotypes displayed axons of varying lengths and different features, which remained visible throughout life. The previously designed developmental blueprint was crucial for interpreting these enigmatic features. Conclusions: This research into immaturity enabled the exploration of the previously impenetrable domain of early life and the identification of a potential missing link in CNS regeneration research. Central axon regeneration appeared to occur much faster than is generally believed. The paradigm provides a challenging approach for exhaustive intrauterine reprogramming. When the results demonstrate pre-clinical effectiveness in CNS regeneration research, the transformational impact may ultimately lead to improved outcomes for patients with spinal cord injuries. Full article
(This article belongs to the Special Issue From Anatomy to Clinical Neurosciences)
Show Figures

Figure 1

17 pages, 706 KiB  
Article
A Multicenter Pilot Randomized Trial of a Lifestyle Intervention to Prevent Type 2 Diabetes in High-Risk Individuals
by Raira Pagano, Thatiane Lopes Valentim Di Paschoale Ostolin, Danielle Cristina Fonseca, Aline Marcadenti, Ana Paula Perillo Ferreira Carvalho, Bernardete Weber, Carla Daltro, Enilda Lara, Fernanda Carneiro Marinho Noleto, Josefina Bressan, Jussara Carnevale de Almeida, Malaine Morais Alves Machado, Marcelo Macedo Rogero, Olivia Garbin Koller, Rita de Cássia Santos Soares, Sônia Lopes Pinto, Viviane Sahade, Cleyton Zanardo de Oliveira, Guilherme William Marcelino, Camila Martins Trevisan and Angela Cristine Bersch-Ferreiraadd Show full author list remove Hide full author list
Nutrients 2025, 17(15), 2518; https://doi.org/10.3390/nu17152518 - 31 Jul 2025
Viewed by 186
Abstract
Background: Type 2 diabetes (T2D) is a growing public health concern, particularly in low- and middle-income countries. Although prediabetes is a major risk factor for T2D, it remains largely underdiagnosed and untreated. Structured lifestyle interventions have proven effective in preventing diabetes, but their [...] Read more.
Background: Type 2 diabetes (T2D) is a growing public health concern, particularly in low- and middle-income countries. Although prediabetes is a major risk factor for T2D, it remains largely underdiagnosed and untreated. Structured lifestyle interventions have proven effective in preventing diabetes, but their feasibility within the Brazilian public health system remains unclear. Methods: This multicenter pilot randomized controlled trial assessed the feasibility of a culturally adapted lifestyle intervention (PROVEN-DIA) across the five regions of Brazil. A total of 220 adults at high risk for T2D were randomized to an intervention group or a control group (usual care) and followed for three months. Both groups received similar educational content on healthy eating and physical activity, but the intervention group participated in a structured and personalized lifestyle program with regular follow-up sessions. The primary outcome was adherence to dietary recommendations, assessed using the BALANCE Index—a validated dietary score (range: 0–40) based on the Brazilian Cardioprotective Diet that classifies foods into color-coded groups according to nutritional quality—along with engagement in moderate-to-vigorous physical activity (MVPA). Secondary outcomes included diet quality (DQIR), anthropometric and metabolic parameters. Results: Feasibility was demonstrated by a 93.2% retention rate (n = 205). There was no significant difference in the primary outcome (simultaneous improvement in diet and MVPA). However, the PROVEN-DIA group exhibited significantly greater improvements in diet quality, with a 2.8-point increase in the BALANCE Index (vs. 0.5 in the control, p = 0.03), and a significant improvement in the DQIR (p < 0.001). No significant differences between groups were observed in MVPA, HbA1C, glycaemia, or body weight. Conclusions: The PROVEN-DIA intervention proved feasible within the Brazilian public health context, resulting in significant improvements in dietary quality among individuals at high risk for T2D. A larger trial with longer follow-up is warranted to evaluate its effectiveness in preventing the progression to diabetes. However, to enhance physical activity outcomes, specific adaptations and targeted strategies may be required to better support participant engagement in exercise. Full article
Show Figures

Figure 1

12 pages, 402 KiB  
Article
SBRT in the Very Elderly: A Viable Option for Pulmonary Oligometastases?
by Samuel M. Vorbach, Meinhard Nevinny-Stickel, Ute Ganswindt and Thomas Seppi
Cancers 2025, 17(15), 2512; https://doi.org/10.3390/cancers17152512 - 30 Jul 2025
Viewed by 389
Abstract
Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in [...] Read more.
Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article
(This article belongs to the Special Issue Treatment Outcomes in Older Adults with Cancer)
Show Figures

Figure 1

19 pages, 371 KiB  
Review
Plant Extracts and Natural Compounds for the Treatment of Urinary Tract Infections in Women: Mechanisms, Efficacy, and Therapeutic Potential
by Ya-Ting Hsu, Hsien-Chang Wu, Chung-Che Tsai, Yao-Chou Tsai and Chan-Yen Kuo
Curr. Issues Mol. Biol. 2025, 47(8), 591; https://doi.org/10.3390/cimb47080591 - 25 Jul 2025
Viewed by 515
Abstract
Urinary tract infections (UTIs) are among the most prevalent bacterial infections in women, with high recurrence rates and growing concerns over antimicrobial resistance. The need for alternative or adjunctive therapies has spurred interest in plant-based treatments, which offer antimicrobial, anti-inflammatory, antioxidant, and immune-modulatory [...] Read more.
Urinary tract infections (UTIs) are among the most prevalent bacterial infections in women, with high recurrence rates and growing concerns over antimicrobial resistance. The need for alternative or adjunctive therapies has spurred interest in plant-based treatments, which offer antimicrobial, anti-inflammatory, antioxidant, and immune-modulatory benefits. This review summarizes the mechanisms of action, clinical efficacy, and therapeutic potential of various medicinal plants and natural compounds for preventing and treating UTIs in women. Notable candidates include cranberry, bearberry, pomegranate, green tea, and other phytochemicals with proven anti-adhesive and biofilm-disrupting properties. Evidence from clinical trials and meta-analyses supports the role of cranberry natural products and traditional herbal medicines (THMs) in reducing UTI recurrence, especially when combined with antibiotics. Notably, A-type proanthocyanidins in cranberry and arbutin in bearberry are key bioactive compounds that exhibit potent anti-adhesive and biofilm-disrupting properties, offering promising adjunctive strategies for preventing recurrent urinary tract infections. Additionally, emerging therapies, such as platelet-rich plasma (PRP), show promise in restoring bladder function and reducing infection in women with lower urinary tract dysfunction. Overall, plant-based strategies represent a valuable and well-tolerated complement to conventional therapies and warrant further investigation through high-quality clinical trials to validate their efficacy, safety, and role in personalized UTI management. Full article
(This article belongs to the Special Issue Role of Natural Products in Inflammatory Diseases)
Show Figures

Graphical abstract

14 pages, 5085 KiB  
Communication
Development and Validation of a Histologic Respiratory Index (HRI) in Poultry
by Tamer A. Sharafeldin, Mohamed Selim, Noreen Bashir and Sunil K. Mor
Pathogens 2025, 14(8), 727; https://doi.org/10.3390/pathogens14080727 - 23 Jul 2025
Viewed by 327
Abstract
Respiratory viral diseases infecting poultry lead to variable lesions in the respiratory organs, including nasal sinuses, trachea, lungs, and air sacs. Additional involvement of eyelids/conjunctiva was reported. The distribution and the intensity of lesions depend on multiple factors, including virulence, the host’s immunity, [...] Read more.
Respiratory viral diseases infecting poultry lead to variable lesions in the respiratory organs, including nasal sinuses, trachea, lungs, and air sacs. Additional involvement of eyelids/conjunctiva was reported. The distribution and the intensity of lesions depend on multiple factors, including virulence, the host’s immunity, and secondary or concurrent infections. It may be challenging to detect remarkable lesions during experimental infections conducted in a controlled environment because some viruses fail to produce the intense lesions seen in field cases. This creates a challenge in developing a reliable model to study pathogenicity or vaccine efficacy experimentally. The development of the proposed histologic respiratory index (HRI) aims to help monitor the least microscopic changes that can be scored, thereby creating an objective and accurate grading of lesions in experimentally infected birds. HRI scores the changes in eyelids/conjunctiva and respiratory mucosa, including hyperplasia, metaplasia, inflammatory cellular infiltration in the submucosa, including lymphocytes and heterophils, and vascular changes (vasculitis) in nasal sinuses, trachea, and lungs. The score was validated in birds infected experimentally with avian metapneumovirus (aMPV) and low pathogenic avian influenza (LPAI-H4N6). The HRI reliably graded higher scores in the respiratory organs of experimentally infected birds compared with non-infected control ones. The HRI is the first of its type with poultry viral respiratory pathogens and it was initially proven to be a reliable in pathogenicity and vaccine trials of certain poultry respiratory viral diseases. Full article
(This article belongs to the Section Viral Pathogens)
Show Figures

Figure 1

14 pages, 1388 KiB  
Article
The Impact of Different Agricultural Practices on Nematode Biodiversity on Tomato- and Lettuce-Growing Periods Across Two Consecutive Years
by Giada d’Errico and Silvia Landi
Diversity 2025, 17(8), 501; https://doi.org/10.3390/d17080501 - 22 Jul 2025
Viewed by 265
Abstract
Protecting the soil ecosystem’s functioning is one of the main goals of recent regulations of chemicals. It is important to take soil biodiversity into account when designing cropping systems and measuring their impacts. Our main objective was to evaluate the effects of an [...] Read more.
Protecting the soil ecosystem’s functioning is one of the main goals of recent regulations of chemicals. It is important to take soil biodiversity into account when designing cropping systems and measuring their impacts. Our main objective was to evaluate the effects of an organic amendment on soil nematode biodiversity compared to two years of fumigation. The plot-trial was conducted on tomato and lettuce plants under greenhouse, and free-living nematodes were used as bio-indicators of soil health. Treatments included a soil fumigant (applied once or twice over time), water control, and an organic substance. Soil samplings were carried out to determine the Meloidogyne incognita reproduction factor and the soil nematode community analysis using soil biological indicators. Data showed that soil fumigation clearly made the soil increasingly dependent on chemicals. Furthermore, fumigants suppressed pests and pathogens as well as their natural antagonists, causing a lack of biodiversity. While soils treated with organic matter respond slowly to stressors, they are progressively more suppressive thanks to biodiversity enrichment. Nematodes have proven to be useful indicators of the soil biota in response to biotic or abiotic disturbances. Their species richness and functional diversity make them valid bioindicators of soil management impact. Full article
(This article belongs to the Special Issue Distribution, Biodiversity, and Ecology of Nematodes)
Show Figures

Graphical abstract

20 pages, 2290 KiB  
Article
Use of Bacillus pretiosus and Pseudomonas agronomica for the Synthesis of a Valorized Water Waste Treatment Plant Waste as a Biofertilizer Intended for Quercus pyrenaica L. Fertigation
by Diana Penalba-Iglesias, Marina Robas-Mora, Daniel González-Reguero, Vanesa M. Fernández-Pastrana, Agustín Probanza and Pedro A. Jiménez-Gómez
Biology 2025, 14(7), 902; https://doi.org/10.3390/biology14070902 - 21 Jul 2025
Viewed by 278
Abstract
The loss of hectares of forest areas has become a global issue that has worsened over recent years due to unsustainable human activities. In a context of limited availability of productive land, it is urgent to adopt efficient strategies to recover the affected [...] Read more.
The loss of hectares of forest areas has become a global issue that has worsened over recent years due to unsustainable human activities. In a context of limited availability of productive land, it is urgent to adopt efficient strategies to recover the affected natural areas. Actions based on a circular economy, such as the use of organic chemical matrices recovered from water waste treatment plant waste, have proven to be effective. In this regard, the addition of plant growth-promoting bacteria (PGPB), such as Bacillus pretiosus and Pseudomonas agronomica, can contribute to the chemical treatment, favoring the recovery of soils, accelerating the recovery of vegetation cover, and inducing an increase in biodiversity. In this research, the effect of bio-fertigation under controlled laboratory conditions in Quercus pyrenaica is evaluated. After a thirty-six-week trial, the biometric and nutritional parameters of the plants were harvested and measured, and the diversity and composition of the metagenomes of their rhizospheres were evaluated. As well, the cenoantibiogram and the metabolic diversity were measured. The results showed that the use of these biofertilizers increased the variables related to plant production, quality of plant composition as an indirect means of their resilience, as well as an increase in rhizospheric microbial diversity and a reduction in their MIC resistance to the most widely used antibiotics. For all these reasons, the use of the biofertilizer result of the combination of WWTP waste, Bacillus pretiosus, and Pseudomonas agronomica is postulated as an environmentally friendly strategy that can contribute to the recovery of potential oak forest areas. Full article
(This article belongs to the Collection Plant Growth-Promoting Bacteria: Mechanisms and Applications)
Show Figures

Figure 1

24 pages, 31371 KiB  
Article
Ultrasound Phenotype-Based Approach to Treatment Choice in Osteoarthritis
by Rositsa Karalilova, Velichka Popova, Konstantin Batalov, Dimitar Kolev, Lyatif Kodzhaahmed, Dimitrina Petrova-Stoyankova, Nikola Tepeliev, Tsvetelina Kostova, Lili Mekenyan and Zguro Batalov
Life 2025, 15(7), 1140; https://doi.org/10.3390/life15071140 - 19 Jul 2025
Viewed by 353
Abstract
Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost [...] Read more.
Introduction/Objectives: Osteoarthritis (OA) is a chronic systemic disease that affects the entire array of joint structures. It is one of the most common chronic, socially significant diseases, associated with a decline in the quality of life of patients and constantly increasing the cost of treatment. Clinical trial outcomes are largely inconclusive, and OA remains one of the few musculoskeletal diseases without an established disease-modifying therapy. One potential explanation is the use of ineffective tools for OA classification, patient stratification, and the assessment of disease progression. There is growing interest in musculoskeletal ultrasonography (MSK US), as it enables the dynamic visualization of the examined structures and gives information about both inflammatory and structural changes that have occurred. Determining the leading ultrasound phenotype, which depends on the most damaged tissue at a given time (bone, cartilage, synovial membrane, joint capsule, ligaments, tendons, menisci, etc.), can rationalize therapy use by selecting patients more suitable for specific treatments. This article aims to evaluate and summarize the potential of MSK US in the process of determining the clinical phenotype of OA and to emphasize the importance of this imaging modality in evaluating further therapeutic strategies. Method: A single-center prospective study conducted in the period of September 2023–June 2024 enrolled 259 consecutive patients with proven OA. The statistical program Minitab version 22.2.1 (2025) was used to analyze the data. The predominant and secondary phenotypes were tabulated for each OA localization and were presented numerically and as relative proportions (%). The rate of the most frequently occurring phenotypes was compared against that of the less frequent ones through paired z-tests. The initially acceptable type I error was set at 5%; it was further adjusted for the number of comparisons (Bonferroni). Results: The most frequent and predominant US phenotype for patients with knee OA was intra-articular effusion (n = 47, 37.90%). It was significantly higher compared to the rest of the US phenotypes: synovial proliferation (n = 22, 17.70%; p < 0.001), cartilage destruction (n = 26, 21%; p = 0.001), altered subchondral bone (n = 8, 6.50%; p < 0.001), extra-articular soft tissue changes (n = 12, 9.70%; p < 0.001), crystal deposits (n = 6, 4.8%; p < 0.001), and post-traumatic (n = 3, 2.40%; p < 0.001). The most common US phenotype for hip OA was altered subchondral bone (n = 32, 47.1%), with significant differences from intra-articular effusion (n = 12, 17.60%; p = 0.001), synovial proliferation (n = 5, 7.40; p = 0.001), cartilage destruction (n = 12, 17.60%; p = 0.001), extra-articular soft tissue changes (n = 3, 4.40%; p = 0.001), crystal deposits (n = 3, 4.40%; p = 0.001), and post-traumatic (n = 0). Altered subchondral bone was also the leading US phenotype for hand OA (n = 31, 55.40%), with significant differences compared to intra-articular effusion (n = 1, 1.80%; p < 0.001), synovial proliferation (n = 7, 12.50%; p < 0.001), cartilage destruction (n = 11, 19.60%; p < 0.001), extra-articular soft tissue changes (n = 2, 3.60%; p < 0.001), crystal deposits (n = 3, 5.40%; p < 0.001), and post-traumatic (n = 1, 1.80%, p < 0.001). For shoulder OA, extra-articular soft tissue changes were the most frequent (n = 8, 46.20%), followed by post-traumatic (n = 4, 30.70%), as the rate of both phenotypes was significantly higher compared to that of intra-articular effusion (n = 0), synovial proliferation (n = 0), cartilage destruction (n = 1, 7.70%; p = 0.003), and crystal deposits (n = 0). Conclusions: The therapeutic approach for OA is a dynamic and intricate process, for which the type of affected joint and the underlying pathogenetic mechanism at a specific stage of the disease’s evolution is essential. MSK US is one of the options for the clinical phenotyping of OA. Some of the suggested ultrasound subtypes may serve as the rationale for selecting a particular treatment. Full article
Show Figures

Figure 1

17 pages, 3681 KiB  
Article
Sensitivity of Pancreatic Cancer Cell Lines to Clinically Approved FAK Inhibitors: Enhanced Cytotoxicity Through Combination with Oncolytic Coxsackievirus B3
by Anja Geisler, Babette Dieringer, Leslie Elsner, Maxim Girod, Sophie Van Linthout, Jens Kurreck and Henry Fechner
Int. J. Mol. Sci. 2025, 26(14), 6877; https://doi.org/10.3390/ijms26146877 - 17 Jul 2025
Viewed by 280
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by a dense desmoplastic stroma and a highly immunosuppressive tumor microenvironment (TME). The focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is considered a critical regulator of various cellular processes involved in cancer [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by a dense desmoplastic stroma and a highly immunosuppressive tumor microenvironment (TME). The focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is considered a critical regulator of various cellular processes involved in cancer development. FAK inhibitors (FAKi) have proven to be promising therapeutics for cancer treatment including for pancreatic cancer. As monotherapy, however, FAKi showed only a modest effect in clinical studies. In this study, we investigated the cytotoxicity of six FAKi (Defactinib, CEP-37440, VS-4718, VS-6062, Ifebemtinib and GSK2256098) used in clinical trials on five pancreatic tumor cell lines. We further examined whether their anti-tumor activity can be enhanced by combination with the oncolytic coxsackievirus B3 (CVB3) strain PD-H. IC50 analyses identified Defactinib and CEP-37440 as the most potent inhibitors of tumor cell growth. VS-4718, VS-6062, and Ifebemtinib showed slightly lower activity, while GSK2256098 was largely ineffective. The combination of Defactinib, CEP-37440, VS-4718, and VS-6062 with PD-H resulted in varying effects on cytotoxicity, depending on the cell line and the specific FAKi, ranging from no enhancement to a pronounced increase. Using the Chou–Talalay method, we determined combination indices (CI), revealing synergistic, additive, but also antagonistic interactions between the respective FAKi and PD-H. Considering both oncolytic efficacy and the CI, the greatest enhancement in oncolytic activity was achieved when VS-4718 or CEP-37440 was combined with PD-H. These findings indicate that co-treatment with PD-H can potentiate the therapeutic activity of the selected FAKi and may represent a novel strategy to improve treatment outcomes in PDAC. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapies of Pancreatic Cancer: 2nd Edition)
Show Figures

Figure 1

20 pages, 2609 KiB  
Article
Priming ‘Santa Isabel’ Pea (Pisum sativum L.) Seeds with NaCl and H2O2 as a Strategy to Promote Germination
by Javier Giovanni Álvarez-Herrera, Julián Stiven Lozano and Oscar Humberto Alvarado-Sanabria
Seeds 2025, 4(3), 34; https://doi.org/10.3390/seeds4030034 - 17 Jul 2025
Viewed by 244
Abstract
Peas possess significant nutritional properties due to their high protein levels, carbohydrates, fiber, and vitamins. Increased climate variability can lead to water stress in crops like peas. Therefore, priming plants through seed priming is a technique that has proven effective as a pre-conditioning [...] Read more.
Peas possess significant nutritional properties due to their high protein levels, carbohydrates, fiber, and vitamins. Increased climate variability can lead to water stress in crops like peas. Therefore, priming plants through seed priming is a technique that has proven effective as a pre-conditioning method for plants to cope with more severe future stresses. Different doses and soaking times of ‘Santa Isabel’ pea seeds in NaCl and H2O2 were evaluated to enhance and promote germination. Two experiments were conducted under controlled conditions (average temperature 15.8 °C) through a completely randomized design with a 4 × 3 factorial arrangement, comprising 12 treatments in each trial. In the first trial, NaCl doses (0, 50, 100, or 150 mM) and the soaking time of the seeds in NaCl (12, 24, or 36 h) were examined. In the second trial, H2O2 doses (0, 20, 40, or 60 mM) were tested with the same imbibition times. The 50 mM NaCl dose at 24 h demonstrated the best values for germination rate index, mean germination time, germination rate (GR), and germination potential (GP). Seed imbibition for 24 h in NaCl, as well as in H2O2, is the ideal time to achieve the best GR and GP. The dry mass of leaf and stipule recorded the highest values with a 60 mM dose of H2O2 and 24 h of imbibition. An application of 150 mM NaCl resulted in the highest values of germinated seed dry mass, while causing lower dry mass in roots, stems, leaves, and stipules; however, it maintained similar total dry mass values. Full article
Show Figures

Figure 1

43 pages, 4357 KiB  
Systematic Review
Vitamin D’s Impact on Cancer Incidence and Mortality: A Systematic Review
by Sunil J. Wimalawansa
Nutrients 2025, 17(14), 2333; https://doi.org/10.3390/nu17142333 - 16 Jul 2025
Viewed by 1534
Abstract
Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This [...] Read more.
Background/Objectives: Adequate vitamin D levels are essential for various physiological functions, including cell growth, immune modulation, metabolic regulation, DNA repair, and overall health span. Despite its proven cost-effectiveness, widespread deficiency persists due to inadequate supplementation and limited sunlight exposure. Methods: This systematic review (SR) examines the relationship between vitamin D and the reduction of cancer risk and mortality, and the mechanisms involved in cancer prevention. This SR followed the PRISMA and PICOS guidelines and synthesized evidence from relevant studies. Results: Beyond genomic actions via calcitriol [1,25(OH)2D]-receptor interactions, vitamin D exerts cancer-protective effects through mitigating inflammation, autocrine, paracrine, and membrane signaling. The findings reveal a strong inverse relationship between serum 25(OH)D levels and the incidence, metastasis, and mortality of several cancer types, including colon, gastric, rectal, breast, endometrial, bladder, esophageal, gallbladder, ovarian, pancreatic, renal, vulvar cancers, and both Hodgkin’s and non-Hodgkin’s lymphomas. While 25(OH)D levels of around 20 ng/mL suffice for musculoskeletal health, maintaining levels above 40 ng/mL (100 nmol/L: range, 40–80 ng/mL) significantly lowers cancer risks and mortality. Conclusions: While many observational studies support vitamin D’s protective role in incidents and deaths from cancer, some recent mega-RCTs have failed to demonstrate this. The latter is primarily due to critical study design flaws, like recruiting vitamin D sufficient subjects, inadequate dosing, short durations, and biased designs in nutrient supplementation studies. Consequently, conclusions from these cannot be relied upon. Well-designed, adequately powered clinical trials using appropriate methodologies, sufficient vitamin D3 doses, and extended durations consistently demonstrate that proper supplementation significantly reduces cancer risk and markedly lowers cancer mortality. Full article
Show Figures

Figure 1

11 pages, 224 KiB  
Article
Randomized Trial of Midazolam Plus Meperidine Versus Midazolam Plus Fentanyl Versus Placebo for Colonoscopic Sedation
by Miltiadis K. Moutzoukis, Ioannis V. Mitselos, Nikoletta Karavasili, Vasileios Theopistos, Alexandros Skamnelos, Dimitrios Sigounas, Varvara Pantazi, Panagiota Moschou and Dimitrios K. Christodoulou
Gastrointest. Disord. 2025, 7(3), 46; https://doi.org/10.3390/gidisord7030046 - 11 Jul 2025
Viewed by 241
Abstract
Objective: A combination of midazolam and opioid is usually used to achieve conscious sedation and analgesia during colonoscopy, but many patients may tolerate the procedure well without any sedation. This randomized trial aimed to compare the efficacy and recovery time of 3 different [...] Read more.
Objective: A combination of midazolam and opioid is usually used to achieve conscious sedation and analgesia during colonoscopy, but many patients may tolerate the procedure well without any sedation. This randomized trial aimed to compare the efficacy and recovery time of 3 different regimens consisting of (a) midazolam plus meperidine (b) midazolam plus fentanyl and (c) placebo. The endoscopists’ and patients’ satisfaction was assessed by an appropriate questionnaire. Methods: A total 248 consecutive, unselected patients attending outpatient colonoscopy at a University Hospital were enrolled with informed consent and were randomized to receive (a) midazolam with meperidine [group A] (b) midazolam with fentanyl [group B] or (c) placebo [group C]. Data for procedure times, perceived patient’s discomfort (using a relative patient questionnaire) and physician’s satisfaction from the procedure were collected. Patients and all endoscopy staff directly involved with the procedure except the research nurse were blinded to the regimens used. Results: The mean age of the patients was 58 ± 15 years (range 19–85 years) and 130 were males. The completion rate and time to reach cecum did not differ among the three groups. The recovery time was significantly shorter in group C (placebo, 10.4 ± 2.9 min) compared to the other groups (p < 0.000), but it was also shorter in group B (midazolam plus fentanyl, 43.0 ± 9.3 min) compared to group A (midazolam plus pethidine, 50.1 ± 9.0 min) (p = 0.001). Patients of group B (midazolam plus fentanyl) experienced less pain and discomfort than patients of group A (midazolam plus meperidine) (p = 0.02) and patients of group A experienced less pain than patients of group C (placebo). Many more patients in group B were extremely or very satisfied by the procedure(86.7%) compared to group A (59.7%) and group C (44.5%) (p = 0.001). Adverse events were mild in all groups and slightly less in group B. Conclusions: Sedation with midazolam and fentanyl was more effective, better tolerated and led to slightly faster recovery time than sedation with midazolam and meperidine. According to our findings and the literature, the most appropriate regimen for conscious sedation during colonoscopy is the combination of midazolam and fentanyl. However, both sedation regimens were proven to be effective and safe and even a significant proportion of unsedated patients could tolerate the procedure fairly well. Full article
Back to TopTop