Oxaliplatin is widely used in the treatment of gastric and gastro-oesophageal junction cancer. However, oxaliplatin-induced nausea and vomiting often complicate treatment and negatively affect patients’ quality of life. The current standard antiemetic regimen—dexamethasone (DEX) plus palonosetron—offers only limited efficacy, benefiting approximately 70% of patients, and is associated with steroid-related adverse effects, including insomnia and gastrointestinal bleeding. Consequently, there is a clear clinical need for effective DEX-free antiemetic regimens. This study aims to evaluate the efficacy and safety of megestrol acetate versus DEX in preventing oxaliplatin-induced nausea and vomiting in patients with gastric or gastro-oesophageal junction cancer.
This is an investigator-led, multicentre, randomised-controlled, open-label, phase III, non-inferiority trial. Chemotherapy-naïve patients scheduled to receive oxaliplatin-based chemotherapy are randomly (1:1) assigned to receive either megestrol acetate (megestrol acetate group) or DEX (DEX group) in combination with palonosetron. The primary endpoint is the complete response (CR; no vomiting and no rescue therapy) rate during the first 120 hours following the initiation of chemotherapy (0–120 hours). Secondary endpoints include the following indicators: CR rate in acute period (0–24 hours), CR rate in delayed period (24–120 hours), time to treatment failure, frequency of salvage medication use, nausea, anorexia, adverse events and quality of life.
The study will evaluate the efficacy and safety of megestrol acetate compared with DEX for prevention of oxaliplatin-induced nausea and vomiting in patients with gastric or gastro-oesophageal junction cancer. If proven effective, the results might inform future antiemetic strategies in the long term to (1) provide a novel DEX-free antiemetic treatment for prevention of moderate-emetogenic chemotherapy, (2) reduce DEX-related adverse effects and improve quality of life in patients with gastric or gastro-oesophageal junction cancer and (3) support the potential incorporation of megestrol acetate into standard antiemetic medications.
The study protocol is conducted in accordance with the Declaration of Helsinki and approved by the Certified Review Board of West China Hospital, Sichuan University (Ethics Approval No 1116/2023). The results of this study will be disseminated via presentations at national and international scientific conferences and publication in peer-reviewed journals.
ChiCTR2300075943.
To assess the level of alarm fatigue among intensive care unit (ICU), cardiac care unit (CCU) and emergency room (ER) nurses, identify associated demographic and occupational factors, determine the most frequent sources of alarms and evaluate nurses’ psychological reactions to alarms.
A cross-sectional, descriptive–analytical study.
ICUs, CCUs and ERs of six public teaching hospitals affiliated with Tehran and Kashan Universities of Medical Sciences in Iran.
Using a multistage stratified random sampling method, 285 nurses were approached, of whom 260 completed and returned the questionnaires (response rate: 91%). Participants were registered nurses with at least a bachelor’s degree or higher and 3 months of experience in ICUs, CCUs or ERs.
The primary outcome was the level of alarm fatigue measured using the validated Nurses’ Alarm Fatigue Questionnaire. Secondary outcomes included factors associated with alarm fatigue and nurses’ reported psychological responses to frequent alarms.
The mean score of alarm fatigue was 26.4±7.9, indicating a moderate level. After adjusting for confounders and hospital-level clustering using multivariable mixed-effects regression, higher monthly income was significantly associated with lower alarm fatigue (β=–0.15, p=0.03), and nurses working rotational shifts reported significantly higher fatigue compared with those with fixed shifts (β=0.18, p=0.02). Other demographic and occupational factors were not significant. Reported psychological reactions to alarms included indifference (14%), irritability (18%) and anxiety/stress (15%).
ICU, CCU and ER nurses experience a moderate level of alarm fatigue, with income and shift type as independent associated factors. The association between income and alarm fatigue may reflect the role of financial stress as an additional job demand that compounds the burden of frequent alarms, particularly in contexts where low base salaries lead nurses to rely on overtime and multiple shifts. These findings underscore the need for targeted managerial and educational interventions, including shift schedule optimisation and attention to workload-related stressors, alongside alarm prioritisation strategies. Due to the cross-sectional design, causal inferences cannot be drawn.
To develop and user-test a patient decision aid for people diagnosed with degenerative cervical myelopathy and who are considering surgery.
Mixed-methods study describing the development of a patient decision aid.
A draft decision aid was developed by a multidisciplinary steering group (including study authors with degenerative cervical myelopathy, health professionals and researchers) informed by the best available evidence, authorship consensus and existing patient decision aids.
Patient-participants and health professional-participants who manage people with degenerative cervical myelopathy were recruited through social media and the steering group’s research and practice network. Quantitative questionnaires were used to gather baseline data, descriptive feedback, refine the decision aid and assess its acceptability. Qualitative semi-structured interviews were conducted online to gather feedback on the decision aid and were analysed using reflexive thematic analysis.
We conducted 32 interviews: 19 patient-participants and 13 health professional-participants who manage people with degenerative cervical myelopathy (neurosurgeons, neurologists, physiotherapists, orthopaedic surgeons, general practitioners, rehabilitation and pain specialists and consultant occupational physicians and chiropractors). Participants were from 10 countries (Australia, Canada, Cyprus, Germany, Ireland, New Zealand, Sweden, Switzerland, United Kingdom and USA). Most participants rated the decision aid’s acceptability as good-to-excellent and agreed with most aspects of the decision aid (eg, defining degenerative cervical myelopathy, management recommendations, potential benefits and harms, questions to consider asking a health professional).
Our patient decision aid was rated as an acceptable tool by both health professional-participants who treat degenerative cervical myelopathy and patient-participants with lived experience of degenerative cervical myelopathy. This decision aid can be used by clinicians and people with degenerative cervical myelopathy to help with shared decision making following a diagnosis of degenerative cervical myelopathy. A study testing the potential benefits of this decision aid in a clinical setting is recommended.
Language-concordant care, or healthcare in one’s preferred language, is important both for health equity and for improving health outcomes. Linguistic minorities, like Francophones in Ontario, Canada, are at risk of poorer clinical outcomes if they receive non-language-concordant primary care. However, common ratio-based access measures can provide misleading views of minorities’ actual access levels. This cross-sectional geospatial study demonstrates a new way to measure primary care access using average travel time to the nearest five English- and French-speaking family physicians. We also introduce the concept of primary care access fragility, where a region’s primary care access may depend on one or a few local family physicians. Our research question is: are there differences in travel burden and access fragility for census subdivisions (CSDs) across language (English/French), rurality (urban/rural) and region (north/south) in the province of Ontario, Canada?
We conducted a cross-sectional geospatial analysis to estimate English-language and French-language primary care travel burdens and access fragility in Ontario, Canada. We used population and boundary data from Statistics Canada’s 2021 census, road-network data from OpenStreetMaps, and family physician practice locations and language abilities from the College of Physicians and Surgeons of Ontario. We measured travel burden using Valhalla, an open-source road-network analysis platform.
We conducted our analysis for Ontario, Canada’s 577 CSDs, which correspond roughly to municipalities and with populations ranging from 5 inhabitants in Rainy Lake 17B to a high of 2 794 356 in Toronto.
Using public data from January 2026, we identified 15 762 family physicians practising in Ontario, of whom 11.0% reported speaking French. Patient data were obtained from the most recent 2021 census.
Our first primary outcome measures were CSD-level mean travel time to the nearest five English-speaking family physicians, and CSD-level mean travel time to the nearest five French-speaking family physicians, which we compared to explore regional inequities in travel burden. Our secondary outcome measures were based on a novel notion of the travel burden component of ‘primary care access fragility’. This metric indicates how dependent a region’s access is on a small number of local physicians and is defined as the difference between the CSD-level mean travel time to the nearest one physician and to the nearest five physicians. As the difference in travel times grows, so too does access fragility.
Median differences in French-language and English-language travel burdens were strongly significant across rurality, regions and overall (median difference 13.4 min, p
Compared with the general public, Ontario’s French-speakers face higher travel burdens to language-concordant family physicians and higher access fragility, especially in rural and northern regions. Our results are of interest to policymakers and health-system planners, and our methods are applicable to other populations and regions.
To develop and evaluate an explainable machine learning framework enhanced with synthetic data generation to predict unplanned 30-day hospital readmissions among patients with chronic obstructive pulmonary disease (COPD), heart failure (HF) and type 2 diabetes mellitus (T2DM), and to identify key clinical and social predictors of readmission.
A retrospective cohort study using electronic health record data incorporating both structured variables and information extracted from unstructured clinical notes. Synthetic data were generated using advanced resampling and deep learning-based techniques to address outcome imbalance and improve model training.
Intensive care unit and general ward admissions at a single tertiary academic medical centre included in the MIMIC-IV (Medical Information Mart for Intensive Care IV) database.
Adult patients (≥18 years) were admitted with a primary diagnosis of COPD (n=14 050), HF (n=7097) or T2DM (n=12 735) between 2008 and 2019, with complete 30-day follow-up and no in-hospital mortality during the index admission.
The primary outcome was unplanned all-cause hospital readmission within 30-days of discharge. Predictors were drawn from six domains, including demographics, comorbidities, clinical acuity, therapies, behavioural factors and care continuity. Predictive performance was evaluated using multiple machine learning methods and fivefold cross-validation, with model interpretability assessed using established goal and local explanation approaches.
Ensemble-based machine learning models demonstrated the strongest predictive performance across all three disease cohorts. Key predictors of readmission included higher illness severity, greater comorbidity burden, medication non-adherence, gaps in preventive care and limited social support. Models incorporating synthetic data augmentation showed improved discrimination compared with models trained on original data alone.
An explainable synthetic-data driven framework incorporating clinical, behavioural and social data can support prediction of 30-day readmissions among patients with common chronic conditions using routinely available electronic health record data.
Overweight and obesity are a growing global public health problem. Eating behaviours of adults and children are largely influenced by the home food environment (HFE). The lack of access to nutritious food in homes contributes to unhealthy dietary habits and, consequently, overweight and obesity among adults and children, as well as chronic diseases associated with poor diets. The present systematic review aims to identify existing HFE and household food security interventions and to determine the effects of these interventions in improving the availability of healthy food in the home, household access to food, diet quality and nutritional status of adults.
This systematic review protocol was developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols guidelines. Electronic databases including PubMed, Web of Science, Scopus, Science Direct and CINAHL (EBSCOhost) will be searched for relevant articles using keywords and MeSH terms. Risk of bias will be assessed using the adapted Cochrane effective practice and organisation of Care risk of bias tool for studies with a separate control group and Risk of Bias in non-randomised studies of interventions. The overall strength of the evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Two reviewers will independently screen the identified records and assess the eligible full texts for inclusion. Any discrepancies will be resolved through consensus or consultation with a third reviewer. Where sufficient homogeneous data are available, subgroup analysis will be conducted to explore heterogeneity. A thematic synthesis will be performed for qualitative studies.
This study has a systematic review and meta-analysis design, which will assess published data and does not require ethical approval. Findings of the systematic review will be disseminated through peer-reviewed publications and conference presentations.
CRD420251030896.
Poststroke motor dysfunction places a heavy burden on individuals and society. Virtual reality (VR) offers enhanced motor skill transfer and active rehabilitation by overcoming the scenario-specific constraints of conventional therapies. Validating the efficacy of VR rehabilitation could lead to scalable and cost-effective solutions, potentially enabling home-based rehabilitation. However, the widespread clinical application remains constrained by the lack of rehabilitation-specific VR and multidimensional quantitative assessments. The aim of this study was to investigate the multidimensional effects and neural mechanisms of VR rehabilitation in poststroke motor recovery.
This study is a prospective, randomised, controlled clinical trial protocol designed to evaluate the effects of multisensory VR training on motor dysfunction in patients who had a stroke using multidimensional assessments. The trial consists of a baseline assessment, a 4-week intervention period and an endpoint assessment. A total of 40 patients who had a stroke will be randomly allocated in a 1:1 ratio to either a VR combined with treadmill group or a treadmill-only group. The primary outcome measure is the Fugl-Meyer Assessment of Lower Extremity score, while secondary outcomes include three-dimensional gait analysis, the Berg Balance Scale score, the activities of daily living score and functional near-infrared spectroscopy results. Safety will be evaluated by monitoring the incidence of adverse events. This study aims to determine whether VR rehabilitation offers superior efficacy in improving motor function in patients who had a stroke by using a multidimensional assessment approach, including neural coupling function, muscle movement mechanics and clinical performance. The findings will provide robust, high-quality evidence to support the broader application of VR in clinical practice.
The trial was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (2022–155). This study protocol was registered with the clinicaltrials.gov (NCT06275516). The results will be published in a peer-reviewed journal or presented at a conference.
Sub-Saharan Africa (SSA) continues to be the hub of the global HIV/AIDS pandemic, globally. Despite several attempts to meet their HIV prevention needs, men continue to have high rates of HIV infection. Pre-exposure prophylaxis (PrEP) is an effective treatment that, when taken as prescribed, can be very efficient in preventing and reducing the risk of HIV acquisition. HIV self-testing (HIVST) has been demonstrated to be acceptable among men in SSA. As such, this review aims to explore the existing literature on the integration of PrEP dispensing with HIVST among men in SSA.
We will systematically search bibliometric databases, including PubMed/MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature Plus, Sociological Abstracts, ProQuest Dissertations and Theses global. Our review will be guided by the Arskey and O’Malley framework and Levac et al. The review results will be reported using the preferred reporting items for systematic reviews and meta-analysis: extension for scoping reviews guidelines. To assess the methodological quality of the included articles, the mixed methods appraisal tool version 2018 will be used. We will use NVivo software (V.11) to synthesise data from the included studies using a thematic approach.
Ethical approval is not required, as this review uses publicly available data. Findings will be disseminated through peer-reviewed publication, conference presentations and engagement with key stakeholders in HIV prevention and treatment across SSA.
by Navdeep Kaur, Marcus V. Merfa, Alexandra K. Kahn, Rodrigo P. P. Almeida, Leonardo De La Fuente
Xylella fastidiosa (Xf) is an insect-transmitted, xylem-limited bacterial plant pathogen that infects hundreds of plant species. This pathogen causes bacterial leaf scorch in southern highbush blueberry (Vaccinium corymbosum interspecific hybrids) in the southeastern United States, a disease that has not yet been reported elsewhere. Previously, a comparative genomic analysis of Xf and ancestral host species identified evolutionary events of gene gain and loss related to host range specificity. Here, by using a similar workflow, we identified two loci that are significantly found in blueberry-infecting strains. Locus_1088 included a hypothetical protein and a small part of the N-terminus of an orphan RelE toxin, while Locus_2741 was annotated as a hypothetical protein. Using a protocol based on natural competence, mutants were generated in three Xf subsp. multiplex strains from blueberry. Less biofilm, more planktonic growth, and increased twitching motility as compared to its wild-type (WT) were observed for the strain LA-Y3C_1088 mutant. In blueberry virulence assays, the LA-Y3C_1088 mutant caused significantly more severe symptoms than LA-Y3C_WT, whereas no significant differences were observed for other mutated strains. Interestingly the mutation of Locus_1088 additionally disrupted a toxin (part of a toxin-antitoxin system) that is likely responsible for the phenotypic changes observed. However, because the two independent mutants were not generated, we could not determine whether the phenotype resulted from disruption of hypothetical protein or the toxin. Additionally, since the coffee-isolated but never tested in blueberry Xf subsp. fastidiosa strain CFBP8073 was found to encode the two blueberry-associated loci studied here, its virulence was assessed in blueberry. This strain caused severe symptoms comparable to the control strain AlmaEm3 from blueberry. Due to the complexity of understanding host specificity in Xf, any advance in identifying genetic markers for host specificity in this devastating pathogen could greatly improve management of Xf worldwide.by Meirong Shan, Qian Guo, Ruofei Li, Ni Li, Yanhua Fu, Huanyu Qi, Ge Zhang, Qian Wang, Xingli Xu, Jinchuan Lai
Hypertension is one of the main causes of cardiovascular diseases worldwide, affecting over one billion people. Although aliskiren offers a valuable option for inhibiting the renin-angiotensin system, its safety profile in the real world remains insufficiently explored, especially for rare or under-recognized adverse events (AEs), which have not been fully clarified. Therefore, leveraging large-scale post-marketing surveillance data is crucial for identifying rare AEs and guiding safer clinical practice. This study aims to elucidate pharmacovigilance signals associated with aliskiren (an antihypertensive drug) by systematically analyzing the characteristics of adverse events (AEs) from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and WHO-VigiAccess database, which provides a reliable scientific basis for clinical practice and regulatory decision-making. We conducted a retrospective quantitative analysis of aliskiren-related AE reports from the aforementioned two databases, employing the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) algorithms for signal detection. The results indicate that there were 5,596 and 5,549 aliskiren-related reports in the FAERS and WHO-VigiAccess databases, respectively. The median duration of these AEs during the observation period was 62 days, with an interquartile range (IQR) of 7–282 days. In both databases, signals for aliskiren were distributed across 28 System Organ Classes (SOCs), among which investigations, cardiac disorders, renal and urinary disorders, vascular disorders, and metabolism and nutrition disorders exhibited significant signals based on specific criteria applied across the four algorithms. A total of 607 preferred terms (PTs) with significant disproportionality signals were detected using the four algorithms, including potential AEs not previously well-documented, such as palpitations, myalgia, proteinuria, muscular weakness, pulmonary edema, and pollakiuria. This study not only confirms the known adverse reactions of aliskiren but also uncovers new potential risks, highlighting the importance of strengthening drug safety monitoring to enhance therapeutic efficacy and reduce the risk of adverse reactions. It provides valuable safety insights for physicians considering the use of aliskiren in the management of primary hypertension.by Mingming Pan, Yanhua Shen, Jiayu Wu, Chaonan Liu, Meihong Zhu, Zhengyu Zhou
This study aimed to investigate the therapeutic effects of ELASEM®Flex and ELASEM®ProFlex, two eggshell membrane (EM) products, on sodium iodoacetate (MIA)-induced osteoarthritis (OA) in rats. An OA model was established by a single intra-articular injection of MIA into the knee joint. After modeling, rats were administered diclofenac sodium, ELASEM®Flex, and ELASEM®ProFlex by gavage daily for 4 consecutive weeks. During the experiment, food intake, water intake, body weight, and plantar mechanical pain threshold (MPT) of rats were measured weekly. Serum levels of TNF-α, COX-2, IL-1β, and CTX-II were assessed at weeks 2 and 4. After 4 weeks, knee joints were harvested for histopathological examination (HE staining and Safranin-O fast green staining). Results indicated that knee joints of OA rats showed significant swelling, which was alleviated to varying degrees in all treatment groups. Both ELASEM®Flex and ELASEM®ProFlex significantly increased the MPT (P ®Flex and ELASEM®ProFlex can exert preventive and reparative effects on knee OA in rats by alleviating arthritis pain, inhibiting inflammatory factor expression, reducing type II collagen degradation, and promoting chondrocyte proliferation.by Sudim Sharma, Anjali Neupane, Dikshya Kandel, Pratibha Chalisay, Sabina Marasini, Budhi Setiawan, Deepak Chandra Bajracharya, Shyam Raj Upreti, Leela Khanal, Haruko Yokote, Chahana Singh, Kshitij Karki
BackgroundHome-Based Records (HBRs) are personal health documents intended to improve continuity of care and caregiver engagement across reproductive, maternal, newborn, and child health (RMNCH) services. In Nepal, both standalone (sHBR) and integrated (iHBR) models are implemented, yet comparative evidence on their utilization and implementation challenges is limited. This study examined utilization patterns and system-level barriers associated with sHBR in Madhesh Province and iHBR in Koshi Province.
MethodsWe conducted a comparative qualitative study with descriptive quantitative profiling between May 17 and August 27, 2024. A total of 100 semi-structured in-depth interviews were completed with caregivers, health workers, Female Community Health Volunteers, and program managers across two provinces. The study applied “kuragraphy,” an ethnographic approach integrating interviews and field observations to construct contextual case narratives. Socio-demographic data were analyzed descriptively using the statistical package for the social Sciences (SPSS). Informed by the Human Centered Design (HCD) approach, the qualitative data were thematically analyzed in Excel using the Journey to Health and Immunization (JTHI) framework.
ResultsCaregivers widely perceived HBRs as essential documents, primarily for immunization tracking and future service access. The iHBR was viewed as more comprehensive and user-friendly, particularly due to its illustrations, which improved comprehension among low-literacy users. However, understanding remained limited among illiterate and marginalized populations. Family involvement in record management was minimal and largely confined to mothers. Implementation barriers included inadequate training – particularly for iHBR use, limited decision-making authority among frontline health workers, incomplete documentation of non-immunization components, poor material quality of sHBR, and concerns regarding the sustainability of donor-supported iHBR initiatives.
ConclusionHBR utilization in Nepal is shaped by caregiver literacy, gender dynamics, and health-system readiness. Strengthening training, supportive supervision, user-centered design, and sustainable supply mechanisms will be essential to optimize HBR effectiveness and support equitable RMNCH service delivery.
by Julia Drespling, Steffen Heelemann, Selina Strathmeyer, Heike Kühn, Bianca Schwarz, Lars Mundhenk
Equine asthma is a chronic, non-infectious inflammatory disease of the lower airways in horses, classified as mild to moderate (MEA) or severe (SEA). Its pathogenesis is not fully understood and is influenced by environmental and seasonal factors. In this cross-sectional study, seasonal effects on the bronchoalveolar lavage fluid (BALF) metabolome were investigated in asthmatic and non-asthmatic horses. The metabolome of 230 BALF samples from horses across different seasons, classified as cytologically unremarkable (CUA), MEA, or SEA, was analyzed using proton nuclear magnetic resonance spectroscopy (1H-NMR). Principal component analysis was performed for each season, and metabolite profiles were statistically compared between seasons within each group. Altered metabolites were subjected to pathway enrichment analysis using the FELLA R package. Asthmatic horses showed significant seasonal changes in metabolite concentrations between warm and cold seasons, whereas only trends were observed in CUA horses. Pathway analysis indicated enrichment of cholesterol metabolism across all groups. The mTOR signaling pathway was only enriched in SEA horses. Several metabolites—including valine, taurine and carnitine —were altered during the transition from winter to spring in asthmatic horses. These findings indicate that the winter to spring transition significantly modulates the airway metabolome in asthmatic horses, particularly in SEA-affected animals.by Tadgh Connery, Sofija Kukulite, Conor Farrell, Rosa Horgan, Karen Barry, Megan Doyle, Annalisa Setti, Mike Murphy
BackgroundDeath anxiety is fast becoming recognised as a transdiagnostic construct across myriad mental health conditions. Though existing clinical treatments of death anxiety, such as Cognitive Behaviour Therapy type interventions, have been shown to be effective, Terror Management Theory (TMT) proposes self-esteem as a protective factor against death anxiety by endowing individuals with a feeling of significance in life and helping them to process the nature of death and its inevitability. Despite the centrality of self-esteem to TMT, however, extant research examining its relationship with death anxiety has yet to be synthesised. The current study aims to systematically review peer-reviewed, quantitative research examining the association between death anxiety and self-esteem and, where possible, to test the strength of these associations through meta-analysis.
MethodA systematic search of quantitative and mixed-methods studies will be conducted across six databases: MEDLINE; PsycINFO; PubMed; Web of Science; CINAHL and; EMBASE. Google Scholar will also be searched and the first 200 records by relevance will be screened for eligibility. Searches will be conducted by TC, and records will be screened by TC, SK, CF, RH and KB, so that each record is screened for eligibility by at least two authors. Data extraction and quality assessment, using the Joanna Briggs Inventory Risk of Bias tools, will be performed by TC, SK, CF, RH and KB, so that each record is assessed by at least two authors, with doubts and discrepancies being resolved through discussion with AS and MM. A narrative synthesis of relevant data will be presented and, where sufficient data are available, meta-analysis will be conducted using the MAJOR extension for Jamovi to establish an overall effect size for the association between death anxiety and self-esteem. Should sufficient data be available, demographic factors, such as gender and age, and clinical population status (clinical vs. non-clinical population) will be examined as moderators of the effect. This protocol was developed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and has been registered in PROSPERO (CRD42024591775).
DiscussionThe current review will systematically examine the relationship between death anxiety and self-esteem. Should sufficient data be available, an overall effect size of the relationship will be generated. By better understanding how death anxiety is related to self-esteem, and by establishing the size and significance of the relationship will aid firstly in systematically validating TMT and, secondly, identify whether self-esteem may be targeted in future death anxiety interventions to reduce death anxiety and improve individuals’ overall mental health.
by Jocshan Loaiza-Moss, Michael Leitges
Cancer remains a leading cause of mortality worldwide and a significant barrier to improving quality of life across all populations. The protein kinase D family, including PRKD3, has been demonstrated to play a crucial role in cancer development through its involvement in regulating key cellular processes. Although growing evidence highlights the role of PRKD3 in the tumorigenesis of certain cancers, a comprehensive pan-cancer analysis of PRKD3 remains unavailable. To address this, we performed an integrative pan-cancer analysis of PRKD3 using multi-omics datasets from The Cancer Genome Atlas, the Genotype-Tissue Expression project, and cBioPortal. We examined PRKD3 expression, copy number variation, mutation, and DNA methylation, and evaluated their associations with clinicopathological features, patient survival, and diagnostic potential across 33 cancer types. Immune relevance was further assessed through correlations with immune infiltration, checkpoint gene expression, and immunotherapy response-related genomic biomarkers. Our results revealed that PRKD3 expression was highly heterogeneous, showing significant upregulation in liver cancer, gastric cancer, and adrenocortical carcinoma, and downregulation in others. Elevated expression was consistently associated with poor prognosis and increased stromal, neutrophil, and cancer-associated fibroblast infiltration in adrenocortical carcinoma, liver cancer, and stomach cancer, whereas paradoxical associations with favorable outcomes were observed in kidney clear cell carcinoma. PRKD3 expression also correlated with immune checkpoint molecules including PD-1, PD-L1, and CTLA-4, supporting an immunosuppressive role, while context-dependent associations with TMB and MSI highlighted its potential influence on tumor immunogenicity and responsiveness to immune checkpoint blockade. Collectively, these findings identify PRKD3 as a potential context-dependent modulator of tumor biology, prognosis, and immune interactions, underscoring its potential as a biomarker of diagnostic, prognostic, and therapeutic relevance in precision oncology.by Tomoo Hidaka, Takeyasu Kakamu, Hideaki Kasuga, Yuko Suzuki, Toshihiro Terui, Shizuka Kawamoto, Tatsuya Sato
Municipal government officials (MGOs) have played key roles in managing decontamination project of radioactive materials in the aftermath of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. However, the subjective distress experienced by MGOs during the decontamination project, mainly stemming from challenges in coordination with the national government, is not yet fully documented. The purpose of this study is to descriptively understand the nature and causes of subjective distress among MGOs and to make an exploratory conceptual model of the process through which such subjective distress becomes manifest. Narratives from three MGOs were collected through interviews and subjected to qualitative analysis using the Steps for Coding and Theorisation method. For the first purpose, the results indicate that inconsistencies in national reconstruction and decontamination designs impose substantial burdens at the operational level; these burdens are further amplified by inadequate management by national authorities, and subjective distress emerges through a breakdown of trust among national government officials, municipalities, and residents. For the second purpose, an exploratory conceptual model explaining the progression toward subjective distress through the following four stages was created: the emergence of distrust and adversarial orientations toward the national government, the dilemma of occupying an intermediate position, the erosion of ties with residents, and the threat to professional pride. Overall, through experiences such as questioning the national government’s reconstruction policies, enduring the psychological burden of occupying an intermediate position, and witnessing a breakdown in trust with residents, MGOs may find their professional pride undermined; consequently, subjective distress, manifesting as a profound sense of emptiness, may arise. As MGOs are likely to stand at the frontline of managing post-radiation-disaster reconstruction and decontamination efforts, it is essential to develop protective measures for their mental health from both macro-level, organisational perspectives and micro-level, occupational and psychological perspectives.by Aino Kitayama, Yu-Tai Liu, Ai Shibata, Sayaka Kurosawa, Koichiro Oka
BackgroundChronic musculoskeletal pain is a significant symptom among workers. 24-hour movement behaviours comprising sleep, sedentary behaviour, light-intensity physical activity, and moderate-to-vigorous-intensity physical activity are associated factors. However, the relationships between these behaviours and workers’ chronic musculoskeletal pain, considering the interrelationship between the behaviours, are still unclear. This study aimed to investigate the associations of 24-hour movement behaviours with workers’ low-back and neck/shoulder pain.
MethodsIn 2023, cross-sectional survey was conducted targeting adults who registered for a Japanese Internet survey system. Time for 24-hour movement behaviours and other demographic characteristics (age, gender, marital status, education, household income, height, weight, smoking, alcohol, chronic disease, work hours, and job activity) were self-reported. The intensity of low-back and neck/shoulder pain was evaluated using the numerical rating scale and a score of ≥4 was considered as moderate-to-severe pain. Compositional logistic regression and isotemporal substitution were performed to examine the associations of 24-hour movement behaviours and time reallocations between the behaviours with moderate-to-severe low-back and neck/shoulder pain, adjusted for all the demographic variables.
Results1,665 full-time workers (women: 35.8%, mean age: 42.1 ± 10.2 years) were analysed. Increased sleep and decreased light-intensity or moderate-to-vigorous-intensity physical activity were associated with lower odds of moderate-to-severe low-back (adjusted odds ratio [AOR] = 0.54, 95% confidence interval [CI] = 0.40–0.72; 1.45, 1.25–1.69; 1.17, 1.06–1.30, respectively) and neck/shoulder pain (AOR = 0.60, 95% CI = 0.45–0.80; 1.37, 1.19–1.60; 1.12, 1.01–1.24, respectively). Reallocating sleep from the other behaviours was associated with decreased probabilities of low-back and neck/shoulder pain, whereas replacing sedentary behaviour or light-intensity physical activity with more intense activity was associated with increased probabilities. However, the results of moderate-to-vigorous-intensity physical activity reallocation were no longer significant when restricted to complete cases.
ConclusionsConsidering the interrelationship of 24-hour movement behaviours, sleep was favourably associated with workers’ low-back and neck/shoulder pain.
by Napapat Sitthikitpanya, Alissara Reungsang
The increasing occurrence of microplastics (MPs) in organic waste streams raises concerns about their impact on anaerobic digestion (AD). This study examined the effect of polypropylene MPs (PP-MPs) on methane production during AD of food waste for 150 days under batch conditions. PP-MPs were added at 10–300 mg g-1 total solids (TS), covering reported MP levels in food waste and food packaging materials and extending to worst-case scenarios. Methane yields ranged from 310.2 to 324.4 mL CH4 g-1 volatile solids (VS) across treatments versus 334.3 ± 5.2 mL CH4 g-1 VS in the control, with no significant differences (p = 0.634). Kinetic modeling confirmed no consistent inhibitory trends. FTIR and SEM analyses indicated minor surface oxidation and cracking on PP-MPs, while the polymer backbone remained intact, suggesting only superficial aging. These results provide critical assurance for waste-to-energy facilities processing plastic-contaminated organic waste streams. Although PP-MPs do not impair AD performance, their persistence and potential fragmentation pose environmental risks. These findings provide critical insight into the resilience of AD systems and emphasize the need for strategies to mitigate secondary MP formation in biogas production from contaminated waste streams.by Makiko Sasaki, Mamoru Tanaka, Akihiro Nomoto, Ryusei Yamasaki, Tomokazu Yoshimura, Shigenobu Yano, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka
Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.by Verner N. Orish, Renosten E. Tetteh, David Adzah, Chinecherem A. Ndiokwelu, Emmanuel A. Allotey, Evans A. Yeboah, Sylvester Y. Lokpo, Kenneth Ablordey, Duneeh R. Vikpebah, Ekene K. Nwaefuna, Precious K. Kwadzokpui, Noble D. Dika, Elom Y. Dzefi, Kokou H. Amegan-Aho, Aninagyei Enoch, Senyo Tagboto
BackgroundToxoplasma gondii (T. gondii) is a successful protozoan parasite infecting up to a third of the human population. It has varied transmission routes including ingestion of food and water contaminated by cat feces containing oocysts of the parasite and ingestion of bradyzoites in poorly cooked meat. Blood transfusion is another possible route of transmission especially among people with medical conditions requiring blood transfusion, such as those with sickle cell disease (SCD). This study aimed at finding out the prevalence of T. gondii infection and the association of blood transfusion among patients with SCD.
MethodThis study was a cross-sectional study involving SCD patients attending the SCD clinic at the Ho Teaching Hospital in the Volta Region of Ghana. Questionnaire administration was employed to obtain sociodemographic information, cat ownership, consumption of poorly cooked meat, as well as blood transfusion history. A blood sample was collected and anti-T. gondii IgG and IgM were detected using Rapid Diagnostic Test (RDT), while Enzyme-linked Immunosorbent Assay (ELISA) was used as the gold standard and reference. Seropositivity was defined as either positive for IgG, IgM or both. Data was analyzed using SPSS version 23, with frequency distribution done for the sociodemographic variables and the prevalence of RDT and ELISA anti-T. gondii IgG and IgM. Pearson Chi-square analysis was performed to find any significant association between diagnosis of T. gondii infection with sociodemographic variables and blood transfusion. Logistic regression analysis was performed to investigate the odds of seropositivity (ELISA) with sociodemographic variables and blood transfusion.
ResultsA total of 156 SCD patients participated in this study of which 124 (79.5%) and 32(20.5%) were HbSS and HbSC respectively. Among the study participants, 105 (67.3%) had a history of blood transfusion. A total of 60 (38.5%) and 83 (53.2%) patients were positive for RDT and ELISA respectively. No significant association was seen between T. gondii diagnosis and cat ownership (RDT,20[37.7%], p = 0.891; ELISA, 27[50.9%], p = 0.673) and consumption of poorly cooked meat (RDT,37[41.6%],p = 0.370;ELISA,53[59.6%], p = 0.211). However there was a significant association between T. gondii diagnosis and age, with seropositive results predominantly seen among older patients (≥20 years) (RDT, 38[52.1%], p = 0.002; ELISA 49 [67.1%, p = 0.002]. Blood transfusion had a significant association with T.gondii diagnosis (RDT, p = 0.003; ELISA, p = 0.001). A total of 66 (62.9%) of SCD patients who had history of blood transfusion tested positive for ELISA and they had 3 times the odds of testing positive for ELISA (adjusted OR 3.14[95% CI 1.50–6.58]; p = 0.002).
ConclusionThe prevalence of T. gondii infection was higher by ELISA (53.0%) than by rapid diagnostic testing (RDT) (38.5%), and sickle cell disease patients with a transfusion history had higher odds of seropositivity. These findings highlight the need to strengthen transfusion safety protocols and consider screening strategies for T. gondii among high-risk populations such as patients with sickle cell disease. Also, there is the need for longitudinal research to help elucidate the true contribution of blood transfusion transmission of T. gondii since a cross-sectional study, causality could not be established.