Men with obesity infrequently engage with weight management services. To determine: (1) percentage weight loss at 12 and 24 months for text messages with or without financial incentives compared to control; (2) secondary outcomes; (3) cost-effectiveness; (4) moderators of effectiveness and (5) participant and stakeholder perspectives. Assessor-blinded randomised controlled trial. United Kingdom National Health Service perspective cost-effectiveness over 24 months and modelled lifetime horizon. Mixed-methods process evaluation. Five hundred and eighty-five men with body mass index ≥ 30 kg/m2 enrolled (July 2021-May 2022) in Belfast, Bristol and Glasgow; final follow-up June 2024. Random allocation to 12 months of behavioural text messages plus financial incentives (N = 196), same texts alone (N = 194) or 12-month waiting list control group offered 3 months of texts between 12 and 15 months (N = 195). A £400 financial incentive was lost if weight loss targets were not met. Weight change as a percentage of baseline weight at 12 and 24 months comparing control with (1) texts with financial incentives and (2) texts alone. Of 585 men (mean age 51 years; mean weight: 119 kg), 227 (39%) lived in lower socioeconomic areas, 146 (25%) reported a mental health condition and 253 (40%) had multiple long-term conditions. Follow-up was completed by 426 (73%) at 12 months and 377 (64%) at 24 months. At 12 months, mean percentage weight changes (standard deviation) were -4.8% (6.1) (-5.7 kg), -2.7% (6.3) (-3.0 kg), and - 1.3% (5.5) (-1.5 kg) for the incentives, text-only, and control groups, respectively. Compared to control, weight loss was significantly greater with incentives [-3.2% (97.5% confidence interval -4.6 to -1.9; p < 0.001)] but not texts alone (-1.4%; confidence interval -2.9 to 0.0; p = 0.053). At 24 months, changes were -3.9% (-4.6 kg), -2.6% (-3.1 kg), and -2.2% (-2.6 kg), no significant between-group differences. Intervention costs were £243 for texts with incentives, £110 for texts alone. There were no significant differences between 24-month costs and quality-adjusted life-years. Long-term modelling found texts with incentives versus control were: quality-adjusted life-year difference (95% confidence interval): 0.02 (0.007 to 0.029); cost difference: £176 (£43; £311); incremental cost-effectiveness ratio: £9748 (£7705 to £11,791). For texts alone versus control: quality-adjusted life-year difference: 0.03 (0.015 to 0.037); cost difference: £16.5 (-£117; £152); incremental cost-effectiveness ratio: £628 (-£5914 to £5384). There were no moderator effects for socioeconomic, health or well-being status for either comparison versus control. The texts with incentives group had a higher engagement in weight goal setting, food changes, self-weighing, confidence, satisfaction and quality of life compared to the control. Generalisability to women, diverse ethnic groups and people with low literacy is uncertain. Not generalisable to people with no mobile phone access. Retention was lowest in the text messages alone group. Texts with financial incentives have a modest but important effect to 12 months with clinically relevant weight loss maintenance to 24 months, are cost-effective and equally effective regardless of socioeconomic or health characteristics. Implementation, adapt for women, other cultures and longer-term follow-up. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR129703. The Game of Stones study aimed to help men lose weight and keep it off for at least 2 years. Five hundred and eighty-five men living with obesity across the United Kingdom were split into three groups by chance: supportive text messages for 1 year and opportunity to get money for weight loss the same text messages alone for 1 year neither for 1 year, then text messages for 3 months. The first two groups received the same daily text messages about changing weight-related behaviours. Group 1 was told at the start that £400 had been put aside for them and that money would be lost if weight targets were missed. The targets were 5% weight loss at 3 months, 10% at 6 months and maintaining that 10% loss at 12 months. Money was then paid to the men after being weighed at 12 months. Every man was asked questions about their health, well-being and experiences of being in the study. After 1 year, the men in group 1 lost the most weight (5%, 5.7 kg). The men in group 2 lost some weight (3%, 3.0 kg) but not as much as the first group. The men in group 3 lost the smallest amount of weight (1%, 1.5 kg). On average, men in group 1 received £128 for meeting weight loss targets. One year after the 12-month measures, men in groups 1 and 2 had gained back some weight. Men in group 3 lost a bit more weight between year 1 and 2. Weight loss was similar whether or not men had long-term health conditions, disability, mental health issues or lived in the most deprived areas. This study showed that Game of Stones was a popular, low-cost and modestly effective way of helping men to lose weight.
ObjectiveTo evaluate whether early variability in mean corpuscular volume (MCV) during the first five days of intensive care unit stay is associated with in-hospital mortality in critically ill patients.MethodsWe retrospectively studied all adult patients treated on intensive care units (ICU) at the University Medical Center Mannheim between 2018 and 2022 with more than one MCV measurement within the first five days, including at least one on the day of admission. The primary endpoint was in-hospital mortality. MCV variation, expressed as the coefficient of variation (CV), was analyzed using generalized additive models, multivariable logistic and Cox regression.ResultsAmong 5,327 patients (median age 66 years, 38.9% female, mortality 28.3%), median MCV variation was 1.86% (IQR 1.15-2.74%). Patients with high variation (CV >2.5%) showed higher mortality rates (34.7% vs. 20.1%, p<0.0001). In a baseline-adjusted model, this association remained significant (OR 1.65, 95% CI 1.46-1.87, p<0.001). By contrast, baseline MCV at admission showed a univariat association with mortality but was not independently associated with mortality after multivariate adjustment (OR 1.02, 95% CI 0.98-1.06, p=0.31). Determinants of high variation (>2.5%) included elevated CRP, transfusion volume, respiratory disease, and fluid balance disturbances. In a second, severity-adjusted model including lactate, mean arterial pressure, and fluid balance, the previously observed association between high MCV variation and mortality was no longer significant (adjusted OR 1.16, p = 0.57, CI: 0.84-1.59).ConclusionsEarly variation in MCV during the initial five days after ICU admission is associated with in-hospital mortality in unadjusted analyses. However, this relationship is not independent of established clinical severity markers, suggesting that MCV variability reflects disease severity. Nonetheless, MCV variation may serve as a readily accessible adjunctive marker of physiological instability in critically ill patients, meriting further investigation.
Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for pseudomyxoma peritonei (PMP), and complete cytoreduction remains essential for prognosis. While gastrectomy has traditionally represented a major threshold of surgical aggressiveness, the functional impact of increasingly extensive perigastric dissection is not well defined. We retrospectively analyzed 110 consecutive patients who underwent CRS and HIPEC for appendiceal PMP between 2016 and 2024. Perigastric procedures were categorized into five Gastric Cytoreductive Levels (GCLs) based on the extent of vascular sacrifice. Postoperative gastrointestinal recovery was compared among stomach-preserving procedures (GCL1-4), whereas morbidity and oncologic outcomes were evaluated across all five groups. Independent predictors of delayed oral refeeding were assessed through multivariable logistic regression, and a predictive nomogram was developed. Gastrointestinal recovery worsened with increasing extent of stomach-preserving perigastric dissection. Patients in GCL4 experienced delayed oral intake, longer dependence on parenteral nutrition, and prolonged hospitalization compared with those undergoing less extensive procedures; nasogastric tube removal was also delayed. Major morbidity, 30 day mortality, and long-term survival were similar across all groups. Female sex, longer operative duration, and GCL4 independently predicted delayed oral refeeding. The nomogram demonstrated good discrimination and calibration. Increasingly extensive perigastric cytoreduction is associated with impaired postoperative gastric recovery while maintaining acceptable morbidity and oncologic outcomes. The predictive nomogram-although exploratory-may help to anticipate postoperative nutritional needs and support tailored recovery strategies after extensive CRS and HIPEC for PMP.
In this study, latent profile analysis (LPA) was used to identify naturally occurring patterns or profiles of maladaptive and adaptive perfectionism, impulsivity, and disordered eating (DE) in early adolescence (111 boys, 138 girls; M age = 13.6 years). Profile membership at age 13 was used to examine disordered eating patterns assessed at ages 11 and 12, providing insights into how symptoms had developed prior to profile formation. Using LPA, we identified five profiles: (1) high functioning (2), maladaptively impulsive (3), anxious-avoidant (4), maladaptively perfectionistic, and (5) maladaptively impulsive-perfectionistic. The maladaptively perfectionistic profile showed the highest levels of dieting, preoccupation with food, and body concerns as well as perceived sociocultural pressure to be thin, followed by the maladaptively impulsive-perfectionistic profile. Analyses of earlier DE patterns indicated that the anxious-avoidant profile consistently showed the lowest BMI and highest perceived pressure to eat, both at age 13 and at earlier assessment points, suggesting possible feeding-related difficulties. The findings confirm that maladaptive and adaptive perfectionism, impulsivity, and BMI are jointly associated with the development of DE in early adolescence, demonstrating that considering these traits together yields greater explanatory value than focusing on any single factor alone. While identifying general risk factors is essential, differentiating personality-based profiles of vulnerable adolescents may be particularly valuable for targeted early prevention. This study examined how perfectionism and impulsivity are linked to disordered eating in early adolescence. We studied 249 boys and girls aged 13 to 14 and also looked at their eating patterns from ages 11 to 12. We identified naturally occurring groups of adolescents based on their levels of perfectionism, impulsivity, and disordered eating, and found five distinct profiles that differed in their eating-related attitudes and behaviors. Among the profiles found, adolescents with high perfectionism showed the strongest signs of restrictive eating, preoccupation with food, and concerns about their body. Another group had low body weight and reported feeling pressure from others to eat, suggesting feeding-related challenges. Some of these differences were already evident at ages 11–12, suggesting that these patterns were present across early adolescence. These findings highlight that young people can experience disordered eating in different ways. Recognising such patterns may help identify those at greater risk and improve early prevention and support.
Characterising the vector role of a species is critical to understand and quantify host-vector-pathogen interactions. This role has to be assessed for each suspected vector species, but also at the population level. Indeed, different populations of the same species can exhibit biological and ecological variability that can amplify or limit their epidemiological role in transmitting pathogens to human and/or animal populations. In this work, we characterise the spatio-temporal dynamics of two major viruses of veterinary interest (bluetongue virus [BTV] and epizootic hemorrhagic disease virus [EHDV]) in the five species of Culicoides (Diptera: Ceratopogonidae) present in Reunion Island, located in the Indian Ocean. Our aim is to quantify the infection rates of the two viruses in field-collected Culicoides over a 2-year period. A total of 33,358 individuals comprising 11,504 pools were molecularly screened to detect the presence of both viruses. Our work applied an original statistical approach based on the use of Bayesian inference and showed that all five Culicoides species could be involved in the transmission of the two viruses with different levels of infection. EHDV circulated within Culicoides populations for only 4 months over the study period, while BTV circulated within the same populations throughout the entire 2-year period. We hypothesized that although both viruses are transmitted by the same Culicoides species, they exhibit distinct epidemiological patterns: BTV displays enzootic circulation in Reunion Island, whereas EHDV shows an epizootic pattern. La caractérisation du rôle vectoriel d'une espèce est essentielle pour comprendre et quantifier les interactions hôte‐vecteur‐pathogène. Ce rôle doit être évalué pour chaque espèce suspectée d'être vectrice, mais aussi au niveau de la population. En effet, différentes populations d'une même espèce peuvent présenter une variabilité biologique et écologique susceptible d'amplifier ou de limiter leur rôle épidémiologique dans la transmission d'agents pathogènes aux populations humaines et/ou animales. Dans ce travail, nous caractérisons la dynamique spatio‐temporelle de deux virus majeurs d'intérêt vétérinaire (le virus de la fièvre catarrhale ovine [FCO] et le virus de la maladie hémorragique épizootique [MHE]) chez les cinq espèces de Culicoides (Diptera: Ceratopogonidae) présentes sur l'île de La Réunion, située dans l'océan Indien. Notre objectif est de quantifier les taux d'infection des deux virus chez les Culicoides collectés sur le terrain sur une période de deux ans. Au total, 33 358 individus comprenant 11 504 pools ont été soumis à un dépistage moléculaire afin de détecter la présence des deux virus. Notre travail a appliqué une approche statistique originale basée sur l'utilisation de l'inférence bayésienne et a montré que les cinq espèces de Culicoides pouvaient être impliquées dans la transmission des deux virus avec différents niveaux d'infection. La MHE n'a circulé au sein des populations de Culicoides que pendant quatre mois au cours de la période d'étude, tandis que le BTV a circulé au sein des mêmes populations pendant toute la période de deux ans. Nous avons émis l'hypothèse que, bien que les deux virus soient transmis par la même espèce de Culicoides, ils présentent des schémas épidémiologiques distincts: la FCO présente une circulation enzootique à La Réunion, tandis que la MHE présente un schéma épizootique.
Operating room nurses (ORNs) are at high risk for compassion fatigue (CF), which significantly impairs individuals' well-being, undermines the stability of the nursing workforce, and jeopardizes patients' safety. The study aimed to analyze the prevalence and symptom characteristics of CF among ORNs, construct and compare predictive models using machine learning, and determine the relative contribution of distinct features to the models. This is a multi-center cross-sectional study. The questionnaires used in the study included a sociodemographic questionnaire, the Professional Quality of Life Scale (ProQoL), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Pittsburgh Sleep Quality Index (PSQI). LASSO regression was used to select critical variables, and predictive models such as decision tree, logistic regression, random forest, SVM, and XGBoost were constructed and compared. SHapley Additive exPlanation (SHAP) were drawn to show the contribution of each feature to the models. SPSS version 26.0 and R software version 4.4.0 were used for statistical analyses. In this study, a total of 1024 ORNs from 20 cities across China were recruited. According to ProQoL, 326 (31.8%) reported severe CF, 311 (30.4%) moderate CF, and the remaining 387 (37.8%) no or mild CF. Among the three dimensions, the incidence of secondary traumatic stress was most common (95.4%), followed by low compassion satisfaction (61.3%) and burnout (35.0%). In five machine learning-based predictive models, the RF model stood out with the highest AUC at 0.851 (95%CI: 0.795-0.907) in testing set. Following closely, the XGBoost model showed favorable efficacy with the AUC at 0.824 (95%CI: 0.769-0.879) in testing set, outperforming the remaining algorithms. The results of the two SHAP plots (RF and XGBoost) were consistent: depression, anxiety, self-mental health training, sleep quality, and length of service emerged as the five most significant contributors to the models. This study identified severe CF among ORNs, and the most serious symptom was secondary traumatic stress. The RF model exhibited the best performance in identifying high-level CF among ORNs, and SHAP improved the interpretability of the model. The findings of this study could help medical managers and researchers better understand CF and provide timely interventions for ORNs. Not applicable.
The effects of hydroxychloroquine (HCQ) dose based on actual body weight (ABW) on systemic lupus erythematosus (SLE) remain unclear. We investigated the effects of HCQ dose based on ABW of patients with SLE. Patients were classified into ≥5 mg/kg ABW (high dose [HD]) and <5 mg/kg ABW (low dose [LD]) groups. Patient backgrounds were adjusted using inverse probability of treatment weighting method. The discontinuation rate owing to adverse events of overall cohort (group 1) was evaluated. Subgroups with a disease duration ≥1 year (group 2) and without additional immunosuppressive agents and biologics after HCQ initiation (group 3) were compared with evaluate flare-rates, prednisolone dose, and serological data. Among 182 patients in group 1, 60 (33%) comprised the HD group. Five-year discontinuation rates were 18.9% and 13.6% in the HD and LD groups, respectively (p= 0.314). Three-year flare-free rates in HD groups were higher than those in LD group: 75.0% (HD) vs 60.7% (LD) (p= 0.239) in group 2, and 79.2% (HD) vs 57.8% (LD) (p= 0.141) in group 3. In group 3, each 0.2 mg/kg increase in the HCQ dose reduced flares (hazard ratio, 0.91; 95% confidence interval: 0.84-0.99). No clear differences in efficacy and safety were observed between the HD and LD groups; however, a higher HCQ dose was associated with a reduced flare risk. Our findings suggest that a lower HCQ dose may be associated with a higher flare risk in patients with SLE, highlighting the importance of HCQ dose based on ABW.
In 2019, Ethiopia introduced the National Medical Licensing Examination (NMLE) to standardize medical competence, enhance accountability in education, and ensure patient safety. The effectiveness of such high-stakes exams is significantly influenced by the perceptions of key stakeholders, including medical students, faculty, and school deans. This study investigates their views on the relevance and impact of the NMLE. A qualitative descriptive study was conducted with a stratified sample of public and private medical schools. We conducted eight key informant interviews (KIIs) with deans and eleven focus group discussions (FGDs); five with medical faculty and six with graduating medical students. Interviews and FGDs were audio-recorded, transcribed verbatim, coded, and analysed thematically. Data were coded in MAXQDA24 using pre-identified themes and open coding to include newly identified themes. Three main themes and eighteen subthemes were identified. The NMLE was generally recognized as an important tool for establishing minimum competencies, standardizing medical education, and building public trust, particularly among faculty and deans. However, students expressed concerns about redundancy with other assessments and relying solely on knowledge-based assessments. Faculty and deans acknowledged the exam's role in quality assurance and institutional benchmarking but highlighted design flaws and a lack of practical assessments. While faculty expressed trust in the exam's intent, students expressed scepticism due to perceived imposition and transparency issues. The exam encouraged learning and prompted curricular changes, but also resulted in significant anxiety, stress, and a delayed entry into the workforce. Students felt their institutions provided inadequate support. There is strong consensus among study participants on the need for reform on the exam: adding a practical component, applying a stepwise assessment model, reducing redundancy, and improving transparency. While the NMLE is recognised for promoting educational quality, ensuring minimum competence and safeguarding patient safety, it is considered inadequate for fully assessing physician competence and redundant with other assessments. The findings highlight gaps between policy intent and implementation, which require collaborative dialogue among stakeholders to co-create meaningful improvements in the assessment and ensure effective policy implementation.
Estimands can help to clarify the research questions being addressed in randomised trials. Because the choice of estimand can affect how relevant trial results are to patients and other stakeholders, such as clinicians or policymakers, it is important for them to be involved in these decisions. However, there are barriers to having these conversations. For instance, discussions around how intercurrent events (post-randomisation events which affect the interpretation or existence of the outcome) should be addressed in the estimand definition typically involve complex concepts as well as technical language. We aimed to provide tools that could facilitate conversations between researchers and patients and other stakeholders about the choice of intercurrent event strategy for estimands. We developed three tools: (i) a video explaining the concept of an estimand and the five different ways that intercurrent events can be incorporated into the estimand definition; (ii) an infographic outlining these five strategies; and (iii) an editable PowerPoint slide which can be completed with trial-specific details to facilitate conversations around choice of estimand for a particular trial. Each tool was produced through collaboration between researchers and public partners. This involved (i) an initial meeting between researchers and public partners to discuss the aims of the tool; (ii) a draft of the tool being prepared by the research team; (iii) public partners providing feedback; and (iv) the research team updating and finalising the tool. These resources can help to start conversations between the trial team and patients and other stakeholders about the best choice of estimand and intercurrent event strategies for a randomised trial. The video and infographic-which explain estimands and intercurrent events with reference to imagined examples-can be sent to stakeholders in advance of a consultation, or presented in the meeting itself. It is important that a member of the trial team is available to answer questions or clarify concepts following this. The editable slide can be completed by the trial team with the specific details of their trial, and then shown to patients or other stakeholders during the meeting to facilitate discussion around which intercurrent event strategy is most relevant for the trial. An example of a completed editable slide is also provided for an example weight loss trial. We developed three tools to help researchers to have conversations with patients and other stakeholders about estimands, and how intercurrent events should be incorporated into the target estimand for a randomised trial. Further work to evaluate the tools in real-world settings across different stakeholder groups could help to validate the tools and reveal any further refinements necessary to improve their utility.
Although laparoscopy continues to be the predominant minimally invasive approach in most emergency settings, the advantages of robotics, well established in elective surgery, are currently being explored in selected scenarios and specialized centres. A systematic review was conducted using PubMed, Cochrane Library and Scopus databases until January 2025. Primary outcome was safety and feasibility of robotics in emergency colorectal surgery. Secondary endpoints included perioperative and postoperative outcomes. Fifteen articles were included with a total of 46 robotic emergency colorectal surgical procedures. Most were performed in a tertiary centre with a da Vinci system. Most common procedures were robotic right hemicolectomy for colon cancer and sigmoid colectomy for acute diverticulitis. Mean operating time for robotic right hemicolectomy was 134 min for benign cases and 241 ± 7 min for malignant cases; robotic sigmoid colectomy showed a mean operating time of 171 ± 3 min. No intraoperative complications were recorded. One case required conversion. Intracorporeal anastomosis was performed in most cases (n = 13). Mean length of stay was 5 days. No Clavien-Dindo grade ≥ 3 complications, reoperation or readmission were reported. Five complete mesocolic excisions (CMEs) were performed. Pathology outcomes were available for four CMEs: showing R0 resection with a mean lymph node harvest of 54 ± 13. In four CMEs, the involved team included an on-call robotic colorectal surgeon and an experience theatre team including experienced anaesthetist in robotic procedures. Robotics in emergency settings is feasible and safe but requires additional training and dedicated teams for optimal outcomes.
Tumor-associated high endothelial venules (TA-HEVs) mediate lymphocyte trafficking into tumors and modulate the tumor microenvironment, with reported effects on clinical outcomes. However, reports have described discordant associations across cancers and microenvironmental contexts. Studies on state-specific, pan-cancer analyses of TA-HEV function remain limited. We integrated publicly available single-cell RNA sequencing datasets from 11 cancer types. Functional features of TA-HEVs were inferred by pathway enrichment and single-cell gene-set scoring for pathway gene sets. State-specific programs were applied to The Cancer Genome Atlas dataset to assess their clinical impact. We constructed a comprehensive atlas of tumor-associated endothelial cells and identified TA-HEV subclusters. Five TA-HEV subclusters were grouped into two functional states: inflammatory and stress-metabolic. The inflammatory TA-HEVs were enriched for innate immune stimulation, cytokine/chemokine signaling, and MHC class II antigen presentation, whereas the stress-metabolic TA-HEVs were characterized by the unfolded protein response, heat shock pathways, oxidative phosphorylation, and ATP biosynthesis. Across cancers, the stress-metabolic TA-HEV state was generally associated with worse prognosis, while the inflammatory TA-HEV state showed context-dependent associations. Together, these findings define TA-HEVs as a heterogeneous endothelial population comprising distinct functional states with divergent clinical associations, providing a pan-cancer framework for interpreting TA-HEV signals in tumor biology.
Gut microbiota (GM) has been increasingly implicated in cancer development through immune modulation, metabolic regulation, and systemic inflammatory pathways. Although observational studies have suggested a potential link between GM dysbiosis and bladder cancer (BC), these findings remain susceptible to confounding and reverse causation. To our knowledge, few studies have applied a Mendelian randomisation (MR) framework to systematically evaluate the gut-bladder axis from a genetic perspective. We performed a two-sample MR analysis to examine associations between genetically predicted GM composition and BC risk. Genetic instruments for 119 GM taxa were obtained from the MiBioGen consortium. Summary-level genetic association data for BC were derived from the UK Biobank. The inverse variance weighted (IVW) method was used as the primary analytical approach, complemented by Mendelian randomisation-Egger regression (MR-Egger) and weighted median methods. Sensitivity analyses were conducted to assess heterogeneity and horizontal pleiotropy. Instrumental variants were further mapped to host genes to perform exploratory functional annotation and pathway enrichment analyses. In the primary IVW analysis, five GM taxa demonstrated nominal associations with BC risk. Higher genetically predicted abundance of Oscillibacter (OR = 0.706, 95% CI: 0.564-0.883) and Oscillospira (OR = 0.668, 95% CI: 0.490-0.910) was associated with lower risk, whereas Lachnospiraceae (FCS020 group) was associated with increased risk (OR = 1.406, 95% CI: 1.070-1.847). However, none of the associations remained statistically significant after Bonferroni correction for multiple testing. Sensitivity analyses revealed no evidence of significant heterogeneity or directional pleiotropy, and estimates were broadly consistent across MR methods. In this MR study, we identified nominal associations between genetically predicted GM composition and BC risk. As none of the findings remained statistically significant after correction for multiple testing, these results should be interpreted with caution. Further replication in independent cohorts and mechanistic investigations into the role of candidate taxa are warranted to clarify the potential involvement of the gut-bladder axis in bladder carcinogenesis.
Phytochrome-interacting factors (PIFs) are central bHLH transcription factors that link light perception to developmental programs and stress response. Although PIFs have been characterized in several model and crop species, their family composition and potential roles in broomcorn millet remain unknown. Based on the AJ08 reference genome, publicly available transcriptome datasets, and resequencing variants from 516 accessions, we conducted an integrated analysis combining genome-wide identification, comparative genomics, expression profiling, RT-qPCR validation, and haplotype analysis. We identified 15 PmPIF genes that were unevenly distributed across 11 chromosomes and could be classified into four phylogenetic groups (Groups 1-4). All PmPIF proteins harbored a conserved bHLH domain and were predicted to localize in the nucleus; secondary structure prediction indicated that α-helices and random coils were predominant. Promoter analyses revealed abundant cis-acting elements related to light responsiveness, phytohormone signaling, and stress responses. Expression analyses under contrasting photoperiod treatments showed pronounced divergence among PmPIF members, with PmPIF5 consistently showing differential expression across multiple comparisons. KEGG enrichment implicated PmPIF5 in the circadian rhythm-plant pathway, and correlation analyses revealed significant associations between PmPIF5 and several light signaling-related genes, including PRR73, UVR8, GHD7, and COL13. Population-level haplotype analysis of PmPIF5 detected five haplotypes among the 516 accessions, with Hap1 being the predominant haplotype (74.42%). This study provides a comprehensive resource for the PmPIF gene family in broomcorn millet and suggests that PmPIF5 is a promising candidate gene involved in photoperiod-related regulation. These findings lay the foundation for functional validation and support molecular breeding for photoperiod adaptation in broomcorn millet.
Little is known about compliance with intravitreal anti-vascular endothelial growth factor (VEGF) therapy for the treatment of macular and retinovascular diseases among Nigerians and Africans. The objective of this study is to measure compliance to 3 or more and 6 or more intravitreal anti-VEGF injections for common macular and retinovascular diseases in Nigerian clinics and evaluate the impact on visual outcomes. Retrospective multicenter chart review of 622 eyes/ 528 patients diagnosed with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusions (RVOs), including branch, central, and hemiretinal (BRVO, CRVO, and HRVO), and non-AMD Choroidal Neovascular Membrane (CNVM) from five clinics (urban, semi-urban, and rural), collecting demographics, diagnosis, injection type/number, pre-/post-BCVA (converted to LogMAR), and follow-up. Treatments were intravitreal Bevacizumab (Avastin), Ranibizumab (Patizra), and Aflibercept (Eylea). Definitions of compliance: compliant; ≥3 injections (standard loading), also ≥ 6 injections. For all 622 eyes, presenting BCVA: 1.21 ± 0.84 and the final BCVA: 0.91 ± 0.80 (P = < 0.001). Overall compliance with ≥ 3 injections was 47.5%, and with ≥ 6 injections, 10.1%. Compliance to ≥ 3 injections by diagnosis was as follows: AMD 50.4%, Non-AMD CNVM 58.2%, BRVO 44.8%, CRVO 44.0%, HRVO 46.7%, DME 40.6%. Age (P = 0.264) and sex (P = 0.870) did not affect compliance to ≥ 3 injections. Clinic location significantly influenced compliance with ≥ 3 injections (P = 0.000), but not with 6 injections (P = 0.173). The highest rates of compliance with ≥ 3 injections were observed in urban tertiary centers. Injection type and cost were not significant factors (P = 0.36). Eyes with ≥ 3 injections achieved better vision (≥ 6/18) across all diagnoses; the most notable improvements were in non-AMD CNVM (+ 41.4%) and BRVO (+ 35%). Statistically significant LogMAR improvements were seen in CRVO (p = 0.049) and DME (p = 0.043). Postoperative endophthalmitis occurred in 2/622 eyes (0.0032) (both Avastin); no other serious adverse event was recorded. Real-world compliance is significantly lower than ideal. Urban and tertiary clinics show better adherence. Receiving the recommended loading doses is associated with improved visual outcomes for most diagnoses. Understanding the reasons for non-compliance, using a prospective approach, and addressing them will improve treatment outcomes for more Nigerian and presumably African patients receiving anti-VEGF drugs.
Advance care planning and respect for patient autonomy are central concerns in contemporary medical ethics, particularly for patients whose decision-making capacity may be impaired. This study aimed to examine and identify ethical challenges in judicial judgments in Japan relating to these patients. We conducted a retrospective observational study of Japanese civil court judgments using Westlaw Japan. We systematically identified judgments addressing physicians' duties of explanation or informed consent for patients with impaired decision-making capacity. Cases were limited to judgments rendered after May 2007, following publication of the national Guidelines on the Decision-Making Process for Medical Care and Care at the End of Life in Japan. We evaluated five items: (1) substantive consideration of patients' wishes and values; (2) individualized assessment of decision-making capacity and underlying conditions; (3) whether family members' wishes were treated merely as surrogate consent; (4) whether a repeated, dialogical decision-making process involving family members and healthcare or care teams was described; and (5) whether advance directives or similar written documents were referenced. Each item was coded dichotomously. We assessed inter-rater agreement between researchers using agreement rates and Cohen's κ statistics. Of 116 identified judgments, 10 civil cases met the inclusion criteria. Patients had a mean age of 79.5 years, and all cases involved impaired decision-making capacity due to conditions such as dementia. Courts explicitly attempted to respect or infer patients' wishes in two cases. Consideration of decision-making capacity and its medical assessment was noted in two cases. In two cases, courts treated family members' wishes as sources for inferring the patient's presumed wishes rather than as surrogate consent. A repeated, dialogical decision-making process was described in four cases. No judgment referred to advance directives. Inter-rater agreement was high for all items. The civil court judgments analyzed in this study for patients with impaired decision-making capacity did not sufficiently reflect principles emphasized in ethical guidelines in Japan. This highlights an important challenge in clinical practice and medico-legal evaluation in Japan and underscores the need for future empirical research to evaluate the implementation of advance care planning in clinical practice.
To assess whether ChatGPT can autonomously generate and select "human touch" elements (anecdotes, beliefs, and old sayings) and produce writing comparable to human-authored manuscripts. A disagreement letter was composed and then tasked ChatGPT-5 with writing a new disagreement letter. The model was instructed to select suitable anecdotes from a candidate list and generate new ones. Both letters were compared. Eight experienced researchers independently assessed whether the letters were appealing. ChatGPT was able to select appropriate elements from the candidate list and, importantly, generate new ones. The human-generated letter was found to be more appealing by five of eight reviewers, and the ChatGPT-generated letter by three reviewers. None of the researchers reported that they found the use of human touch inappropriate or disruptive. Conclusion Although a single case was studied, these findings may help inform reflection on the use of LLMs in medical writing.
Bovine respiratory disease (BRD) remains a major economic and animal health concern in cattle production, exacerbated by rising antimicrobial resistance and limited vaccine efficacy. Endolysins, phage-derived peptidoglycan hydrolases, have emerged as promising alternatives to antibiotics, but their activity against gram-negative bacteria is hindered by the outer membrane (OM) barrier. In this study, we identified five distinct prophage-derived endolysins from Mannheimia haemolytica and successfully expressed two (185 and 587AP2) along with their engineered polycationic nanopeptide (PCNP) fusions (PCNP-185 and PCNP-587AP2). All four recombinant proteins demonstrated muralytic activity, with original endolysins exhibiting higher enzymatic efficiency. However, PCNP-fused variants showed superior antibacterial effects as compared to those without. Especially, PCNP-185 achieved the most consistent multi-log10 reductions of up to 4.5 in bacterial counts across M. haemolytica serotypes, particularly when combined with EDTA which increased permeability of the OM. These findings highlight the synergistic potential of engineered endolysins and EDTA in overcoming the gram-negative barrier. Additionally, selecting an appropriate buffer was found crucial to rule out the effect of buffers on antibacterial activity of endolysins. To our knowledge, this is the first report of engineering and evaluating prophage-derived endolysins against M. haemolytica, underscoring their promise as innovative therapeutics for BRD. KEY POINTS: • Prophage endolysins are potent antibacterials with engineering potential. • Chelator synergy boosts endolysin efficacy; buffer choice is critical. • Endolysins hold strong promise as next-generation therapeutic agents against multi-drug-resistant M. haemolytica causing bovine respiratory disease.
Lactobacillaceae have shown promise with their potential to outcompete pathogens and restore a healthy microbial balance in otitis externa (OE). This study aimed to evaluate the presence of viable Lactobacillaceae over time and in vitro ability to inhibit growth of common OE pathogens. Fifteen healthy dogs were enrolled and randomised into five groups (n = 3 per group) to receive six probiotic ear drops containing live Lactiplantibacillus plantarum YUN-V2.0 and Lacticaseibacillus rhamnosus YUN-S1.0. Ear swabs were taken 24, 48, 72, 96 h and 7 days post single application for culturing. For pathogen inhibition, clinical isolates of Pseudomonas aeruginosa, Staphylococcus pseudintermedius and Malassezia pachydermatis were tested against the probiotic ear drop and antimicrobial disks of florfenicol 30 μg, gentamicin 30 μg, marbofloxacin 5 μg, miconazole 10 μg, neomycin 120 μg and terbinafine 1.5 μg. A relatively basal low abundance of commensal and Lactobacillaceae micro-organisms was detected (1.34 × 103 colony-forming units [cfu]/mL). At 24 h post-application, Lactobacillaceae increased significantly (2.3 × 106 cfu/mL; p < 0.001), and remained above 105 cfu/mL at 1 week post-application (1.6 × 105 cfu/mL). Lactobacilli demonstrated better growth inhibition of P. aeruginosa than gentamicin and marbofloxacin, and of S. pseudintermedius than gentamicin, neomycin and marbofloxacin. For M. pachydermatis similar growth inhibition versus miconazole and terbinafine was observed. These results suggest that probiotic strains exhibit excellent retention and can inhibit the growth of S. pseudintermedius, P. aeruginosa, and M. pachydermatis.
The juice sac granulation of citrus fruits is a biological disorder that commonly occurs during the stages of growth, mature, and post-harvest, which severely affects the quality and reduces consumer acceptance of fruits. To explore the correlation between granulation and both external morphological characteristics and internal quality characteristics, 11 external and internal quality characteristics of Guanxi honey pomelo were collected and systematically analyzed by principal component analysis and linear regression. Then seven external quality characteristics and one critical characteristics, GR% were applied in machine learning modeling. The results indicated that several characteristics such as single fruit weight, single fruit volume, longitudinal diameter, and transverse diameter showed positive correlations with juice sac granulation rate (GR%), and were subsequently incorporated into classification model development. Among the five models evaluated, support vector machine demonstrated superior performance with a precision and recall rate of 100.00% and 100.00%, respectively, verifying its favorable accuracy and robustness. This research combined traditional statistical approaches with modern computational techniques, offering a reliable screening solution for juice sac granulation degree of Guanxi honey pomelo, which provided potential applicability in citrus processing industries and a theoretical foundation for non-destructive quality assessment.
This study evaluates the utility of the Diffusion-Tensor Imaging Analysis along the Perivascular Space (DTI-ALPS) index as an imaging marker for neuromyelitis optica spectrum disorder (NMOSD). We investigated its correlation with disease duration, clinical severity, and its specificity relative to a Multiple Sclerosis (MS) cohort. We conducted a cross-sectional study involving patients with NMOSD (n = 21), RRMS (n = 42), and healthy controls (n = 34). DTI-ALPS values were calculated from 3T MRI data using a standardized automated pipeline. Correlations between DTI-ALPS and clinical metrics-including the Expanded Disability Status Scale (EDSS) and disease duration-were analyzed. Comparisons were performed between all three groups to assess the index's ability to differentiate neuroinflammatory pathologies. NMOSD and MS patients demonstrated significantly lower DTI-ALPS values compared to controls (PCON.NMOSD < 1.03 × 10- 7 and PCON, MS < 4.03 × 10- 5, respectively). However, no significant difference was observed between the NMOSD and MS cohorts (PNMOSD, MS = 0,241). In the NMOSD group, a significant negative correlation was found between DTI-ALPS and EDSS (R = -0.462, P = 0.011), whereas no such association was observed in the MS cohort (R = -0.035, P = 0.772). Furthermore, disease duration strongly correlated with the ALPS index (R = -0.799, P = 0.013), with patients exceeding five years of disease showing a more pronounced decline in perivascular diffusivity. The DTI-ALPS index is a sensitive marker for capturing cumulative neuroinflammatory and neurodegenerative changes in NMOSD. Interestingly, the correlation with clinical disability was unique to the NMOSD group, suggesting that the index may track disease progression differently across demyelinating pathologies. While the index successfully differentiates patients from healthy individuals, the comparable values found in the MS cohort suggest that DTI-ALPS reflects a common pathway of image biomarker for glymphatic or microstructural impairment across demyelinating diseases rather than NMOSD-specific pathology. These findings support its use as a rapid, complementary metric for monitoring disease progression at a group level.