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Morphological and molecular characterization of Nepalese Common Bean (Phaseolus vulgaris L.) Landraces

Nepalese common bean landraces constitute valuable yet underexplored genetic reservoirs for crop improvement. However, integrated morphological and molecular characterization of this germplasm remains limited. This experiment was conducted at 2023 and 2024 to evaluate the morphological and molecular traits of 58 Nepalese common bean landraces collected from 21 districts of the Nepal via an augmented block design. Twenty-three quantitative and twenty-four qualitative traits were measured and analyzed via descriptive and multivariate methods. The Shannon-Weaver diversity indices (H’) ranged from 0.085–0.99 for qualitative traits and 0.46–0.92 for quantitative traits. The five principal components (PCs) explained 70.86% of the total phenotypic variation, with two PCs explaining 46.27% of the variation. Phenotypic cluster analysis grouped the 58 accessions into 5 distinct groups. Molecular analysis via 15 SSR markers revealed 38 alleles, with an average of 3.16 alleles per marker. The PIC value ranged from 0.16 to 0.46. The genotypic dendrogram grouped the 58 landraces into 3 clusters. The first two molecular principal coordinates accounted for 43.27% of the variation among the accessions. The analysis of molecular variance revealed a maximum variation of 93% within the population and only 7% variation among the populations. Population structure analysis revealed three genetic clusters, with most accessions showing admixture with moderate heterozygosity and a high fixation index. The accessions NGRCO4168 and NGRCO9516 were identified as promising accessions for traits including days to 50% flowering, days to 50% fruiting, maturity, and yield (t/ha). These accessions should be further evaluated across diverse environments to assess their stability and adaptability. Additionally, expanded SSR or SNP analyses integrated with phenotypic data could facilitate marker–trait association studies aimed at identifying genomic regions linked to key agronomic traits.

Verbascoside triggers apoptosis and ferroptosis in NSCLC by targeting BCAT2

Background The treatment of non-small cell lung cancer (NSCLC) has challenges such as drug resistance and recurrence. Concurrently, the induction of apoptosis and ferroptosis is a promising therapeutic strategy. This study aimed to investigate whether the natural product, verbascoside, induces apoptosis and ferroptosis in NSCLC cells by targeting BCAT2. Methods Bioinformatic analysis was used to predict the potential targets of verbascosides. Stable cell lines with BCAT2 knockdown and overexpression were constructed. The effects of verbascoside on NSCLC were evaluated in vitro and using a mouse xenograft model. Results Bioinformatics screening and molecular docking identified BCAT2 as a potential target of verbascoside, with a significantly stronger binding energy (−7.8 kcal/mol) than another candidate, PARP1. In vitro and in vivo experiments confirmed that BCAT2 knockdown significantly inhibited NSCLC cell viability, induced apoptosis and ferroptosis, and induced mitochondrial damage. Conversely, BCAT2 overexpression produced opposite effects. Verbascoside treatment inhibited BCAT2 expression in a concentration-dependent manner, recapitulating the apoptotic, ferroptotic, and mitochondrial damage phenotypes induced by BCAT2 knockdown; however, BCAT2 overexpression significantly reversed these effects of verbascoside. In an animal model, treatment with verbascoside significantly suppressed tumor growth and activated apoptosis and ferroptosis in tumor tissues by downregulating BCAT2. Conclusions Verbascoside can induce apoptosis and ferroptosis in NSCLC by directly targeting and inhibiting BCAT2, leading to mitochondrial dysfunction. This finding not only reveals BCAT2 as a novel target of verbascoside but also confirms its ability to induce apoptosis and ferroptosis in NSCLC cells.

Genomic epidemiology of Group B Streptococcus colonization among pregnant women in Japan, 2021–2023

Group B Streptococcus (GBS) colonization in pregnant women is a major risk factor for neonatal diseases; however, molecular epidemiological studies on GBS in Japan remain limited. We characterized 219 GBS isolates recovered from vaginal screening cultures at a general hospital in Osaka Prefecture, Japan between 2021 and 2023. Capsular type, clonal complex/sequence type (CC/ST), virulence factors (pilus islands, Alp family, Srr1/Srr2, and HvgA), and antimicrobial resistance determinants were analyzed using whole-genome sequencing. The predominant lineages were CC19 (27.9%), CC23 (21.9%), and CC1 (21.0%), whereas the hypervirulent CC17 lineage accounted for only 5.5% of isolates. Capsular type Ia, III, and V comprised >60% of the isolates. PI-1/PI-2a (58.0%) was the predominant pilus profile, and rib (35.2%) was the most frequent Alp family gene. The hypervirulence-associated markers hvgA and srr2 were confined to capsular types III/CC17 and IV/CC452. All isolates were susceptible to β-lactams and vancomycin, whereas resistance to macrolides, clindamycin, and levofloxacin was observed at varying frequencies. These findings provide a pre-vaccine molecular baseline for maternal GBS carriage in Japan and highlight srr2 -positive CC452 as a potential emerging lineage of concern.

T-Cell Engager–Mediated HLA Antibody Depletion before Kidney Transplantation

Prevalence and anatomical distribution of incidental and actionable findings on CBCT scans for implant planning

Objectives To determine the prevalence and anatomical distribution of incidental (IF) and actionable findings (AF) on cone-beam computed tomography (CBCT) scans obtained for dental implant planning, and to evaluate their associations with patient demographics and imaging parameters. Materials and Methods This retrospective observational study included all consecutive CBCT scans obtained for implant planning (n = 368). A structured, zone-based evaluation protocol was applied, systematically assessing four anatomical regions: (1) cranium and paranasal sinuses, (2) zygomaticomaxillary/orbital complex including the temporomandibular joint, (3) maxillomandibular region, and (4) structures inferior to the mandible. IF were defined as findings unrelated to the implant planning site, and AF were classified based on the oral and maxillofacial radiologist recommendations for further evaluation, referral, or management rather than confirmed clinical outcomes. Associations between IF, AF, CBCT field of view (FOV), age, and sex were analyzed using univariate and multivariable methods. Results IF were observed in 257 patients (69.8%) and AF in 199 (54.1%). IF prevalence increased from 50% in patients ≤40 years to 78.8% in those >70 years, and was higher in males than females (76.2% vs. 64.5%; p  = 0.01). In univariate analyses, AF were not significantly associated with sex (p = .97) or age (p = .25). However, patients >70 years had higher odds of AF in multivariable analysis, although the overall model was not statistically significant. Zone 2 findings were more common in females than males (21.5% vs. 7.1%; p  < 0.001). IF were most common in medium FOV scans (72.2%), whereas AF did not vary by FOV ( p  = .94). The most prevalent findings involved the maxillary sinus (35.1%), cervical spine (27.4%), tonsils (15.8%), TMJ (11.7%), and vasculature (8.4%). Conclusions IF and findings classified as AF based on OMR recommendations were highly prevalent in CBCT scans obtained for implant planning. Approximately half of the scans presented AF (54%). These findings were distributed across multiple anatomical zones and were associated with age and sex, while AF showed no association with FOV.

Products That Pose Health Risks — Can Litigation Protect Us When Government Fails?

Current clinical practices in pediatric audiology among audiologists in India

Objective Evidence-based practice is central to audiology; however, adherence to best-practice guidelines varies, particularly in pediatric settings. This study explored current pediatric audiology practices among audiologists in India. Methods A cross-sectional survey was conducted using an adapted version of the American Board of Audiology’s Pediatric Audiology Clinical Practice Analysis Survey modified for the Indian context. The survey was distributed electronically via email using contact information available with Rehabilitation Council of India (RCI). Eligible participants held at least a bachelor’s degree in Audiology and Speech-Language Pathology and had a minimum of one year of clinical experience. Participation was voluntary, informed consent was obtained, and confidentiality of responses was ensured. Descriptive statistical analyses were performed. Scale content validity index was calculated to assess content validity of the questionnaire. Results A total of 130 audiologists participated, representing a predominantly early-career workforce (mean experience = 4.92 ± 5.41 years). Core pediatric audiology procedures were widely practiced. Newborn hearing screening was considered very important by 66.2% of participants, while 35.4% performed it several times daily. Tympanometry was rated very important by 61.5%, with 40% performing it several times daily. Counselling-related practices were strongly emphasized, with 68.5% rating explanation of test results as very important and 48.5% performing it several times daily. In contrast, advanced procedures demonstrated lower utilization. Cortical evoked potentials were not performed by 35.4% of participants, vestibular assessments by 43.1%, cochlear implant programming by 45.4%, and bone conduction device management by 57.7%. Conclusions Indian audiologists consistently provide essential pediatric audiology services; however, gaps persist in specialized diagnostics and rehabilitation. Enhancing infrastructure, professional training, and adherence to evidence-based guidelines is necessary to strengthen pediatric audiological care in India.

Precision Intensification in Metastatic Prostate Cancer

You “can’t get away from the social”: Individual, relational, and contextual influences on mental health and substance use-related help-seeking among people in contact with the criminal justice system

Rationale People in contact with the criminal justice system outside institutional settings have high levels of mental health and substance use problems, contributing to adverse outcomes. Help-seeking behaviour is an important component of optimising access to effective treatment and support that is under-explored in this population. Empirical investigation into the influences on help-seeking for stigmatised health conditions is needed to inform efforts to facilitate help-seeking. Aim This study established the individual, relational, and contextual influences on help-seeking for mental health and substance use problems among people in contact with the criminal justice system living in the community, and examined the applicability of existing models and frameworks for understanding help-seeking behaviour in this population. Methods We applied framework analysis to qualitative data from a mixed-methods social network analysis study. Our framework drew on help-seeking behaviour and healthcare access models to determine initial categories for help-seeking influences (desire, ability, and context). Results Help-seeking was confirmed to result from an interaction between ‘desire to seek help’, ‘ability to seek help’, and ‘help-seeking context’. We show that help-seeking is not an individual behaviour, but strongly affected by relational influences that operate between individuals, across social networks, and via cultural norms. High levels of criminal justice involvement, and mental health and substance use problems in the social networks of people in contact with the criminal justice system shape these influences. Conclusions and implications Optimising help-seeking for mental health and substance use problems among people in contact with the criminal justice system living in the community requires critical engagement with, and application of, existing models to ensure sufficient appreciation of relational and contextual influences. Research is needed to develop and test multi-level policy/practice interventions that go beyond individual factors.

Pulsatile Liver in Severe Tricuspid Regurgitation

Radiographic legal age estimation based on third molar development using Machine-learning algorithms

Background Age assessment plays an important role in forensic sciences to aid in criminal or civil matters. Third molars continue developing during the legal age of adulthood. Dental age estimation based on radiographic examination is an operator-dependent procedure. The aim was to test the performance of supervised machine learning (SML) to classify individuals according to the threshold of 18 years using the third molar index (I3m). Methods Panoramic radiographs (n = 597) of 52% males and 48% females between 13 and 26 years were used. Three Convolutional Neural Networks were compared to segment the third molar. Several machine learning algorithms were tested with a 10-fold cross-validation approach to identify the best age classification algorithm. The SML age estimation model was compared to the expert. Results Attention U-Net achieved the highest segmentation scores, and the k-nearest neighbors (KNN) showed the best scores of classification algorithms. The SML (KNN) scored sensitivity = 77.77%, specificity = 96%, and AUC = 0.87 in males. In females, sensitivity = 77.4%, specificity = 86.7%, and AUC = 0.82. The expert scores were: sensitivity = 70.4%, specificity = 100%, AUC = 0.85 for male, and for female: sensitivity = 54.8%, specificity = 93.3%, AUC = 0.74. Conclusion SML classified males and females below and above the legal age with high accuracy compared to manual methods. The presented work suggests that AI, using pixel-level analysis, can detect subtle cues beyond human perception. This signals a possible departure from traditional age estimation indices.

PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer

Determinants of parental traditional medicine use for children during COVID-19 in Dire Dawa city administration, Eastern Ethiopia, 2023/24: Mixed community based cross-sectional study design

Introduction Globally, 85% of the population uses traditional medicine. Ethiopia is a country with various traditional medicinal practices. However, various studies also reported traditional medicine used in children by their parents has had adverse outcomes and hospitalized them with complications. Various studies had also reported that traditional medicine use was high during COVID-19. Despite the fact that, children are particularly vulnerable population, limited studies exists regarding the prevalence, types, and determinants of parental TM use during COVID-19. In addition the existing studies were also confined to quantitative methods. Therefore, this study uses a mixed study design to explore indigenous methods of traditional medicine knowledge acquisition, preservation, preparation, storage, and dosage of herbs; barriers of disclosure; and prevalence of concomitant use. Methods A community-based concurrent mixed study design was conducted among 941 randomly selected parents from Dec 01/2023 to March 01/2024. The data was cleaned, coded, and entered in Epi-Data version 4.6 and transferred to Stata version 14.1 for analysis. Finally, an AOR with a 95% CI was computed, and variables with a p-value < 0.05 in the multivariable analysis were taken as significant factors. The qualitative data was collected from 16 selected key informants by in-depth face-to-face interviews and analyzed by using thematic analysis. Result The prevalence of parental TM use for children was 87.6%. Sibling relation to child (AOR: 0.45, 95% CI, 0.01–0.77), religion (AOR: 0.11, 95% CI, 0.04–0.29), parental TM use for themselves (AOR: 6.55, 95% CI, 1.67–25.69), easy accessibility (AOR: 2.72, 95% CI, 1.16–6.40), safety & efficacy (AOR: 4.53, 95% CI, 2.3–13.61), and TM skill in the family (AOR: 0.47, 95% CI, 0.19–0.84) were determinants of TM utilization. Lack of awareness, misperception of TM, lack of trust in HCP and negative judgment from HCP were the main-barriers for non-disclosure of TM use. Conclusion This result indicated traditional medicine use was high; nearly 9 out of 10 parents had used TM for their children during COVID-19. There was high concomitant utilization (90.6%) and high non-disclosure rate (98.1%) of traditional medicine use to health workers. Hence, it is better to give priority to strengthening the implementation of TM policy and manage accordingly.

Redefining Early Relapse in Multiple Myeloma — Time to Change the Rules

Acid-activated chitosan-modified Iranian bentonite for adsorption of Cu(II) and Zn(II) from water; A green and sustainable water treatment approach

This study evaluates the adsorption performance of an Iranian bentonite modified through two routes: activation with HNO 3 followed by calcination at 500 °C yielding NWF adsorbent and activation with HCl followed by chitosan intercalation to obtain HWF adsorbent. Batch experiments assessed Cu 2+ and Zn 2+ removal from aqueous solutions under varying pH, contact time (5–45 min), sorbent dosage (10–150 mg), initial concentration (20–200 mg/L), and temperatures (20–45°C). Atomic Absorption Spectroscopy was used to evaluate heavy metal concentrations. Nonlinear isotherm fitting showed that the Langmuir model described the data well with high mass normalized capacities under the low-dose condition. Freundlich fits indicated favorable adsorption on heterogeneous surfaces. Kinetics followed the pseudo-second-order model (R² = 0.996–0.998), could be described by chemisorption and in case of NWF, faster uptake (higher k 2 ) achieved. Optimal adsorption performance occurred at a pH of approximately 6–7, achieving equilibrium capacities ( q e ) as high as 99.0 mg/g and blank tests at pH ≥ 8 minimized contributions from metal hydroxide precipitation. Thermodynamic analysis has been carried out to confirm spontaneous and endothermic adsorption in temptatures ranged from 20–45°C. X-ray Diffraction, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscopy corroborated successful modification and enhanced site accessibility. The results of this study showed that acid-activated and chitosan-modified bentonites are low-cost, effective, and sustainable sorbents for Cu 2+ and Zn 2+ removal from water, with practical relevance to wastewater treatment.

Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy

From manual counting to YOLO: Using computer vision to automate large-scale fecundity assays in C. elegans

Fecundity measurements play a crucial role in life history research, providing insights into reproductive fitness, population dynamics, and environmental responses. In the model nematode Caenorhabditis elegans , fecundity assays are widely used to study development, aging, and genetic or environmental influences on reproduction. C. elegans hermaphrodites have large numbers of offspring (>100), so manual counting of viable offspring is time-consuming and susceptible to human error. Automated counting methods have the potential to enhance throughput, accuracy, and precision in data collection. We applied computer vision to 9972 images of broods from individual C. elegans hermaphrodites from several strains under multiple treatments to capture variation in fecundity. We trained models using You Only Look Once (YOLO) versions v8 to v11 (large and extra-large variants) to detect and count viable offspring, then compared the model results to estimates from manual counting. The best-performing model, YOLO v11-L, detected offspring with high accuracy after fine-tuning, achieving 92.6% recall and 94.9% precision. Manual counts differed from verified ground-truth counts by an average of 2.16 offspring per image, compared to 0.9 for the trained computer vision model. In addition, we detected significant effects of counter identity, experimental block, and their interaction on manual counts. Computer vision counts were not affected by these biases and outperformed manual counting in both speed, consistency, and accuracy. We demonstrate that computer vision can be a powerful tool for fecundity assays in C. elegans and provide a pipeline for applying this approach to new image sets. More broadly, applying computer vision to digital collections can advance ecological and evolutionary research by accelerating the study of fitness and life history. In practice, this reduces months of manual counting to about 2 hours on a consumer GPU, lowering barriers to large-scale fecundity assays.

Phase 2b Trial of a Na _V 1.8 Inhibitor for Acute Pain

Growing up without violence (GWV): Results of a cluster randomised trial of a school-based intervention preventing adolescent sexual abuse and exploitation in Brazil

Introduction Child sexual abuse and exploitation (CSAE) are pervasive problems that significantly affect the health of children and adolescents. This paper presents the results of a cluster randomised controlled trial (cRCT) evaluating a school-based intervention designed to prevent CSAE in Brazil through education. Methods We conducted a two-arm cRCT with parallel assignment in two Brazilian municipalities. Sixty schools were randomly allocated to intervention and control arms (30 per group) using stratified randomisation based on municipality and school type (municipal and state-run). We invited 50 randomly selected students, aged 12–17, from each school to complete surveys at baseline and endline. Teachers enrolled in GWV training completed an implementation questionnaire. Our primary analysis focused on a cross-sectional comparison of students’ CSAE risk knowledge between control and intervention schools. Results We found no statistically significant difference in adolescents’ CSAE risk knowledge between the study arms (adjusted mean difference: 0.02, 95% CI −0.19 to 0.23, p = 0.87). There was borderline evidence of interaction by gender, with a greater difference in knowledge scores among girls (p = 0.032). No significant association was found between the number of GWV components implemented and knowledge scores. Discussion Several factors may contribute to this result: the intervention might not have been implemented with sufficient fidelity or intensity, the true effect of GWV could be minimal and below the study's detection threshold, the intervention may have influenced outcomes that were not measured, or the intervention may simply lack effectiveness. Further rigorous evaluations and implementation studies are essential to ensure that resources are directed toward effective strategies. Trial registration The American Economic Association’s registry for randomised controlled trials (AEA RCT Registry). RCT ID: AEARCTR-0011299, https://www.socialscienceregistry.org/trials/11299

Iptacopan in IgA Nephropathy — Final 24-Month Data