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Hoy — Marzo 6th 2026Tus fuentes RSS

Disaggregating innovation for sustainable development in ASEAN: Panel evidence on the moderating role of government effectiveness

by Pureheart Ogheneogaga Irikefe, Mohammad Falahat, Ahmad Danial Zainudin, Ihtisham Ullah, Nohman Khan, Bernard Ojonugwa Anthony

With progress toward the 2030 Agenda faltering, many see innovation as a key to sustainable development. The Association of Southeast Asian Nations (ASEAN) bloc represents a unique opportunity to examine how innovation capabilities drive sustainability in diverse economic and developmental contexts. Using panel data for ASEAN countries from 2011 to 2022, this study breaks down innovation into the seven pillars of the Global Innovation Index (GII) and investigates their impact on the Sustainable Development Goal (SDG) Index; with the objective of identifying which GII pillars most strongly predict SDG, while examining the moderating role of government effectiveness and controlling the impacts of gross national income per capita and foreign direct investment. Fixed effects models were used to analyse the data and supplemented by Driscoll-Kraay standard errors, addressing unobserved heterogeneity and cross-sectional dependence. Results reveal that only Institutions and Infrastructure pillars exert a consistently positive impact on SDG performance. In contrast, Creative Outputs have a negative impact. Importantly, Government Effectiveness reverses the negative impact of Creative Outputs, so that this pillar becomes positive for SDG achievement, without significant moderation of the other six GII pillars when controlling for year effects. In conclusion, these findings contest the efficacy of universal innovation policies and underscore the imperative for nuanced, context‑specific ones. It is recommended that ASEAN governments prioritize institutional and infrastructural investments and develop tailored regulatory frameworks, such as green intellectual property regimes and digital economy standards, to harness the creative economy for inclusive, sustainable growth by explicitly integrating innovation strategies with governance reforms.

Revisiting the associations between cooking oils and survival among older people in China: A nationwide, community-based, prospective cohort study

by Kexin Wang, Chao Ban, Liming Zhao, Haiyan Ruan, Ziqiong Wang, Yi Zheng, Sen He

Background

The study aimed to investigate the associations between cooking oils and survival outcomes in a nationwide, community-based, prospective cohort study of older adults in China.

Methods

A total of 5372 older participants (median age: 85.0, inter-quartile range [IQR] age: 77.0–93.0; male: 46.1%) from the 2014 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2014 were included, with follow-up until 2018. The exposure was cooking oils, including vegetable oils and lard, and outcomes were overall survival (OS) and disease-specific survival (i.e., cardiovascular disease [CVD]-specific survival and non-CVD-specific survival). Accelerated failure time (AFT) models were used to analyze the associations between cooking oils and study outcomes.

Results

During a median follow-up of 3.5 years (IQR: 2.4–4.2 years), 2064 (38.4%) deaths were recorded, including 433 CVD deaths, 1229 non-CVD deaths, and 402 deaths with unknown causes. Kaplan-Meier analysis revealed cooking with lard was associated a higher CVD-specific survival probability than vegetable oils (93.9% vs. 88.2%, log-rank p  Conclusions

Cooking with lard was associated with significantly longer CVD- specific survival compared to vegetable oils among older adults in China.

Multidrug resistance patterns and carbapenemase production among Gram-negative bacteria causing healthcare-associated infections in hospitalized patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia

by Kindu Alem, Mucheye Gizachew, Mulat Dagnew, Worku Ferede, Solomon Belay, Baye Gelaw, Feleke Moges

Background

Klebsiella pneumoniae, Acinetobacter species, and Pseudomonas aeruginosa are priority pathogens identified by the World Health Organization that have emerged as major causes of healthcare-associated infections. Their increasing resistance to multiple antimicrobial agents poses significant challenges to clinical management and infection control efforts.

Objective

This study aimed to determine the prevalence, associated risk factors, antimicrobial resistance patterns, and carbapenemase production of K. pneumoniae, Acinetobacter spp., and P. aeruginosa among hospitalized patients with suspected bloodstream, urinary tract, and surgical site healthcare-associated infections at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

Methods

A hospital-based cross-sectional study was conducted from August 2024 to June 2025 among 477 patients suspected of bloodstream, urinary tract, or surgical site healthcare-associated infections. Socio-demographic and clinical data were collected using a semi-structured questionnaire. Blood, urine, and wound/pus specimens were aseptically collected and inoculated on MacConkey, blood, and cysteine lactose electrolyte-deficient agar following standard microbiological techniques. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method on Mueller-Hinton agar according to Clinical and Laboratory Standards Institute guidelines. Data were analyzed using SPSS version 27. Bivariate and multivariate logistic regression analyzes were used to identify factors associated with healthcare-associated infections. P value  Results

Among the 477 patients, 118 (24.7%) developed healthcare-associated infections caused by K. pneumoniae, Acinetobacter spp., and P. aeruginosa, with culture positivity rates of 14.9%, 4.8%, and 5%, respectively. Significant associated factors included age under five (AOR = 13.260, p K. pneumoniae, 69.6% of Acinetobacter spp., and 58.3% of P. aeruginosa isolates. Carbapenemase production occurred in 92%, 77.8%, and 57.1% of these carbapenem-resistant isolates, respectively. Amikacin, meropenem, and ciprofloxacin were the most effective antimicrobials, whereas chloramphenicol was effective only against K. pneumoniae.

Conclusion

This study showed high prevalence of multidrug resistance and carbapenemase production among K. pneumoniae, Acinetobacter spp., and P. aeruginosa in the study area, highlighting the urgent need to strengthen infection prevention and control measures and to promote antimicrobial stewardship programs.

The Nottingham recovery from COVID-19 research platform (NoRCoRP): Functional, clinical and patient-reported outcomes in adults referred to a post-COVID respiratory service

by Malik Hamrouni, Ayushman Gupta, Sophie Middleton, Sabrina Prosper, Theresa Harvey-Dunstan, Joanne Porte, Tricia M. McKeever, Ian P. Hall, Charlotte E. Bolton

Aims

To characterise symptoms, function and patient-reported outcome measures (PROMs), and identify associated factors in adults with persisting respiratory symptoms post-COVID.

Methods

Cross-sectional analysis of 210 non-hospitalised adults referred to a post-COVID respiratory clinic (December 2020-July 2024) who consented to research. Assessments included demographics, symptoms, lung function, chest CT, and several PROMs: MRC dyspnoea score, Nijmegen Questionnaire score (NQ), Hospital Anxiety and Depression Scale, Chalder Fatigue Scale, Short Physical Performance Battery (SPPB) and Fried Frailty Index. Multivariate logistic regression examined key exposure-outcome associations.

Results

Among participants (mean age 49.4 years; 68% female; median 13.3 months since COVID-19 diagnosis), 95% reported shortness of breath, 54% had clinically significant breathlessness (MRC ≥ 3), 68% had an NQ score (>23) consistent with dysregulated breathing, 32% had a low SPPB score ( Conclusion

In non-hospitalised patients with persistent respiratory symptoms post-COVID, dysregulated breathing, deconditioning and psychological distress were key factors linked with symptom burden. These findings suggest a multidisciplinary approach should be considered to optimise recovery.

Detection of spike protein in term placentas of COVID-19 vaccinated and/or SARS-CoV-2 infected women

by Catharina Bartmann, Vanessa Schmidt, Michael Mörz, Michael Schwab, Monika Rehn, Bettina Blau-Schneider, Achim Wöckel, Ulrike Kämmerer

Introduction

COVID-19 (Corona Virus Induced Disease-19) caused by the SARS-CoV-2 coronavirus can be a serious in pregnancy. Therefore, vaccination with modRNA vaccines was recommended depending on the immunity status for women of reproductive age and pregnant women since 2022. However, there are only preliminary data on transplacental transmission of the virus and modRNA from genetic vaccines so far.

Methods

The study population included 106 women who have given birth at the Department of Obstetrics and Gynecology, University Hospital of Würzburg during November 2020 to October 2022. In addition to medical data and vaccination history, immunohistochemical examination of the placenta was performed with antibodies against SARS-CoV-2 spike and nucleocapsid proteins. RNAscope in situ Hybridization was used to show RNA detection in positive placental tissues as a proof of concept.

Results

Altogether, 87% of participants received at least one vaccine dose against SARS-CoV-2 and 56 women (42 vaccinated, 14 not vaccinated) contracted COVID-19. In total, 31 placentas were found positive for the spike protein. Spike positive cells were predominantly Hofbauer cells and trophoblasts. In three cases of vaccinated and then infected woman, an additional nucleocapsid staining was detected, but there was no significant difference in staining pattern in correlation to the vaccine/COVID-19 status. Interestingly, we did not find viral RNA in the investigated samples, but we could show a positive in situ Hybridization of BNT162b2 and S-encoding mRNA-1273 in two individual samples.

Discussion

The spike protein of SARS-CoV-2 has been be detected in placental Hofbauer and Trophoblast cells as well as villous endothelia after infection and vaccination indicating a possible transplacental transfer or uptake. These findings may suggest a potential for transplacental transfer or cellular uptake; however, the extent, mechanisms, and clinical significance of this phenomenon remain to be fully understood.Clinical trial registration: DRKS00022506.

Enhanced lung volumes and pressures in traditional wind instrument musicians: The case of the Mejwez

by Mohammad Z. Darabseh, Aseel Aburub, Ragad Alkaraki, Abdullah Saber Alshammari, Yazan Almansi, Ghaith Dalalah, Csaba Melczer, Pongrác Ács

To evaluate pulmonary function and respiratory muscle strength in Mejwez players compared to predicted norms, and to assess the influence of smoking behaviours on these outcomes. A cross-sectional study was conducted involving adult Mejwez players. Spirometric parameters (forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), and FEV₁/FVC) and respiratory pressures (maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP)) were measured and compared to predicted values. Multiple linear regression was used to assess the impact of smoking behaviours on respiratory outcomes. Mejwez players demonstrated significantly higher FEV₁ (+0.38 L, p 
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Integrating sequence-based GWAS and comparative genomic analysis reveals conservation and species-specificity of putative functional variants influencing tail length and tail abnormalities in pigs and sheep

by Xuying Zhang, Johanna Mainzer, Isabella Giambra, Tong Yin, Petra Engel, Hannah Hümmelchen, Henrik Wagner, Axel Wehrend, Christiane Egerer, Katharina Gerhards, Gerald Reiner, Sven König

Long tails trigger tail biting in pigs and increase the risk of flystrike infections in sheep. Tail docking has been a common management practice in both species for decades, but increasingly conflicts with legal animal welfare guidelines. Sustainable solutions require breeding strategies targeting shorter tails. In consequence, the aims were to conduct whole-genome sequencing (WGS)-based genome-wide association studies (GWAS) and comparative genomic analyses (CGA) to explore functional elements influencing tail traits. Phenotypically divergent experimental populations of pigs and sheep were established through unified selection and mating experiments. Tail traits included tail length (TL) measured at birth, and tail abnormalities (TA) assessed radiographically at 14 weeks of age. WGS-based GWAS identified a significant locus on SSC18 in pigs and suggestive loci for TL in both species, which, together with previously reported loci for TA, were further analyzed by CGA. The genomic windows of the significant locus on SSC18 in pigs and the TL GWAS locus on OAR4 in sheep were found to be conserved, harboring six common genes with predicted functional variants. These variants were jointly associated with TL (Plm) in both species in linear regression models adjusted for sex, age of the dam, body length, and body weight. In other GWAS locus windows (±1 Mb), species-specific TL candidate genes were identified in sheep (HOXB13, MUC5B, EPB41L3, MTCL1, PIEZO2, MPPE1, and LOXHD1) and in pigs (KNL1, DISP2, SPRED1, TGFB2, and HAND1), each harboring associated putative functional variants. For TA, sheep-specific candidates (PGM2, LRRC66, CRACD, LOC105601916, and SH2D4B) and pig-specific candidates (MYOT, TMCO6, and PCDHAC2) were revealed using logistic regression models (Pglm). GO analyses of candidate genes predicted shared biological processes between sheep and pigs, whereas pathway analyses indicated that common carbohydrate metabolism pathways, along with species-specific immune and inflammatory signaling, and pig-specific TGF-β signaling and endochondral ossification, may contribute to tail length variation and abnormalities. These findings provided deeper insights into the genetic basis of differential embryonic tail morphogenesis and perinatal tail development across species.

COVID-19 knowledge, attitudes, and practices among people vulnerable to HIV in Uganda: A cross-sectional cohort analysis

by Job Kasule, Julius L. Tonzel, Natalie Burns, Tyler Hamby, Roger Ying, Grace Mirembe, Immaculate Nakabuye, Hannah Kibuuka, Margaret Yacovone, Betty Mwesigwa, Trevor A. Crowell, for the Multinational Observational Cohort of HIV and other Infections (MOCHI) Study Group

Background

People with behavioral vulnerability to HIV face barriers to healthcare engagement that may impede uptake of non-pharmaceutical and other interventions to prevent COVID-19. Understanding COVID-19 knowledge, attitudes, and practices in this population can inform disease prevention efforts during future pandemics.

Materials and methods

From October 2022 to September 2024, we enrolled participants aged 14–55 years without HIV who endorsed recent sexually transmitted infection, injection drug use, transactional sex, condomless sex, and/or anal sex with male partners. At enrollment, we collected socio-behavioral data, including assessments of COVID-19 knowledge, attitudes, and practices. Robust Poisson regression with purposeful variable selection was used to estimate prevalence ratios with 95% confidence intervals for factors associated with COVID-19 preventive practices.

Results

Among 418 participants, 228 (56.9%) were female, the median age was 21 years (interquartile range 19−24), and 362 (84.9%) reported sex work. Knowledge about SARS-CoV-2 transmission routes was high (95.4%) but lower for the consequences of genetic variants (48.5%−69.7%) and possibility for asymptomatic infection or transmission (66.7%−80.8%). Handwashing was practiced by 90.8% of participants in the preceding month, whereas mask-wearing (76.5%), avoiding symptomatic people (73.7%), and any history of COVID-19 vaccination (46.9%) were less prevalent. Males were more likely to report avoiding symptomatic people (adjusted prevalence ratio 1.16 [95% confidence interval 1.03–1.31]) and COVID-19 vaccination (1.30 [1.05–1.60]). Enrollment during the BQ.1/BQ.1.1 Omicron wave was associated with less mask-wearing (0.81 [0.67–0.99]) but more vaccination (1.59 [1.29–1.95]).

Discussion

We observed variable COVID-19 knowledge and attitudes among Ugandan adolescents and adults with little impact on COVID-19 preventive practices. Efforts to address suboptimal uptake of disease preventive practices during this and future disease outbreaks will require more than just improving knowledge.

Simulation of phased alerting of community first responders for cardiac arrest

by Pieter L. van den Berg, Shane G. Henderson, Hemeng Li, Bridget Dicker, Caroline J. Jagtenberg

Background

Community First Responders (CFRs) are commonly used for out-of-hospital cardiac arrests, and advanced systems send so-called phased alerts: notifications with built-in time delays. The policy that defines these delays affects both response times and volunteer fatigue.

Methods

We compare alert policies by Monte Carlo Simulation, estimating patient survival, coverage, number of alerts and redundant CFR arrivals. In the simulation, acceptance probabilities and response delays are bootstrapped from 29,307 rows of historical data covering all GoodSAM alerts in New Zealand between 1-12-2017 and 30-11-2020. We simulate distances between the patient and CFRs by assuming that CFRs are located uniformly at random in a 1-km circle around the patient, for different CFR densities. Our simulated CFRs travel with a distance-dependent speed that was estimated by linear regression on observed speeds among those responders in the above-mentioned data set that eventually reached the patient.

Results

The alerting policy has a large impact on the four metrics above, and the best choice depends on volunteer density. For each volunteer density, we are able to identify a policy that improves GoodSAM New Zealand’s current policy on all four metrics. For example, when there are 30 volunteers within 1 km from the patient, sending out alerts to 7 volunteers and replacing each volunteer that rejects by a new one, is expected to save 10 additional lives per year compared to the current policy, without increasing volunteer fatigue. Our results also shed light on polices that would improve one metric while worsening another, for example, when there are 10 volunteers within 1 km from the patient, dispatching them all immediately increases our survival estimate by 11% compared to the current policy, with the downside of also increasing the redundant arrivals by 137%.

Conclusions

Monte Carlo simulation can help CFR system managers identify a good policy before implementing it in practice. We recommend balancing survival and volunteer fatigue, aiming to ultimately further improve a CFR system’s effectiveness.

Protocol for a systematic review and meta-analysis of pharmacological and non-pharmacological interventions for chronic pain management in chronic kidney disease

by Chi Peng Chan, Babaniji Omosule, Courtney Lightfoot, Ellesha A. Smith, Ffion Curtis, James O. Burton, Paul Gardner, Sarah Jasat, Sherna F. Adenwalla, Jyoti Baharani, Daniel S. March

Background

Chronic pain affects up to 60% of people with chronic kidney disease (CKD), yet remains under-recognised and under-treated. Pain management in this population is complicated by altered drug pharmacokinetics, polypharmacy, and the potential nephrotoxicity of conventional analgesics. Despite the high prevalence and significant impact on quality of life, evidence-based guidance specific to pain management in CKD remains limited.

Objectives

This systematic review aims to evaluate the effectiveness and safety of both pharmacological and non-pharmacological interventions in reducing chronic pain intensity among people with CKD on dialysis, not on dialysis, and kidney transplant recipients, across all stages of CKD.

Methods

The primary outcome is the effectiveness of interventions in reducing chronic pain intensity as assessed by pain assessment tools. We will conduct a comprehensive search of MEDLINE, Embase, CINAHL, Web of Science, and ClinicalTrials.gov from their inception to the present date to identify studies for chronic pain management in people living with CKD. Study screening will be conducted independently by two reviewers. One reviewer will extract data from each study, with a second reviewer cross-checking for accuracy and completeness. Data will be extracted on study characteristics, participant demographics, intervention components, pain outcomes, and adverse events. The certainty of evidence will be evaluated independently by two reviewers using the GRADE approach. Where applicable, data will be combined in meta-analyses using random-effects models. Additionally, a network meta-analysis will be performed if enough studies are available.

Expected results

This review will synthesise the current evidence for pain management strategies in CKD, by evaluating effectiveness of interventions among people receiving different renal replacement therapy modalities with varying pain and disease phenotypes. Findings will highlight the comparative effectiveness of various interventions while considering their safety profiles specific to the CKD context. The review will identify gaps in the literature and provide recommendations for clinical practice and future research.

Significance

This review seeks to deliver a thorough evaluation of pain management strategies for people living with CKD. This systematic review is supported by the UK Kidney Association (UKKA), and findings will inform the upcoming UKKA guideline on symptoms management in people with CKD, alongside the other symptoms including itch, fatigue, and gastrointestinal symptoms. This review will aid clinicians in making well-informed decisions regarding pain management strategies, ensuring a balance between effectiveness and the specific risks associated with CKD.

Exploring the relationship between mental health and urban green space soundscapes: A scoping review

by Elham Ahmadi, Sophia Baierl, Stephan Voss, Ida Asenkerschbaumer, Ursula Berndt, Leonie Bernhard, Anita Hennig, Anna-Lena Würfele, Michaela Coenen

Urban soundscapes, particularly those experienced in green spaces, have been increasingly recognized as factors that influence human mental health. This scoping review explores the existing literature on soundscapes within urban green spaces and their associated mental health outcomes. It aims to classify the methodologies used in this domain, identify mental health outcomes related to urban green space soundscapes, and examine specific soundscape elements and their correlations with mental health. A systematic search of peer-reviewed studies was conducted. After screening titles, abstracts, and full texts, 22 studies met the inclusion criteria. Diverse methodological approaches were identified, with an emphasis on quantitative multi-method designs. Commonly studied mental health outcomes include stress reduction, mood enhancement, perceived restorativeness, and cognitive restoration. Standardized psychometric tools, such as the Perceived Stress Scale (PSS-14), Positive and Negative Affect Schedule (PANAS) and Perceived Restorativeness Soundscape Scale (PRSS) are frequently used as outcome measures. Natural soundscape elements such as birdsong, water sounds, and rustling leaves had a positive association with relaxation and perceived mental restoration throughout all studies, while mechanical sounds, such as traffic noise were linked to adverse mental health outcomes. These findings highlight that natural soundscapes in urban green spaces have a potential positive relationship with mental health by reducing stress and enhancing mood. However, the cross-sectional design and methodological heterogeneity of the included studies limit causal interpretation. Future research should explore multi-sensory experiences and examine soundscapes in diverse urban contexts to provide more robust insights into their relationship with mental health. The practical implications suggest that urban planners should prioritize integrating natural sound elements into urban areas to improve mental health. The study protocol of this scoping review had been registered at OSF (osf.io/4r7gd).

Computational frameworks for automated detection and quantification of paroxysmal sympathetic hyperactivity among traumatic brain injury patients

by Xiangxiang Kong, Lujie Karen Chen, Sancharee Hom Chowdhurry, Ryan B. Felix, Shiming Yang, Peter Hu, Neeraj Badjatia, Jamie Erin Podell

Paroxysmal sympathetic hyperactivity (PSH) is a syndrome that occurs in a large subset of critically ill traumatic brain injury (TBI) patients and is associated with complications and poor recovery. PSH is defined by recurrent episodic vital sign elevations in the appropriate clinical context. However, standard diagnostic criteria rely heavily on subjective judgment, leading to challenges and delays in recognition, monitoring, and management. The objective of this study was to develop automated PSH detection and quantification tools that exclusively utilize objective bedside continuous vital sign data. Using a cohort of 221 critically ill acute TBI patients with at least 14 days of continuous physiologic data (of which 107 were clinically diagnosed with PSH) we developed a high-resolution clinical feature scale based on established PSH-Assessment Measure criteria and two artificial intelligence-based episode detection models including an expert system approach and a machine learning model approach, using a clinician-annotated case example as ground truth. For the episode detection methods, PSH was quantified as the number, duration, and overall temporal burden of detected episodes. To evaluate performance, we compared quantifications across PSH cases and controls and explored precision and recall. All three methods demonstrated initial face validity to delineate PSH cases from non-PSH TBI controls. Future optimization and implementation of the described computational frameworks with real-time patient data could improve the standard monitoring and management of this challenging clinical syndrome.

“The system is a bit broken…” a qualitative exploration of barriers in the pathway for diagnosing Developmental Coordination Disorder

by Lucy H. Eddy, Nat K. Merrick, Cara E. Staniforth, Jade L. Jukes, Liam J. B. Hill, Mark Mon-Williams, Farid Bardid, Rebecca Murray

Background

Approximately 5% of children are affected by a neurodevelopmental disorder of their sensorimotor skills. DSM-V and ICD-10, the two most widely used diagnostic systems, define this diagnostically as ‘Developmental Coordination Disorder’ (DCD) or ‘Specific Developmental Disorder of Motor Function’ (SDDMF), respectively. A diagnosis of DCD has been found to have a detrimental impact on a range of outcomes (e.g., health and education). It is therefore crucial that these children receive timely intervention. This is reliant, however, on effective assessment and support pathways. Research has shown there is great parental dissatisfaction, but there has been limited research exploring a clinical and education perspective. This study therefore aimed to understand barriers and facilitators for clinical and education practitioners in the pathway in a diverse district in the UK (Bradford).

Methods

Semi-structured interviews were completed with stakeholders across the pathway to identify barriers and facilitators to assessing, diagnosing, and supporting children with sensorimotor skill difficulties. Theoretical thematic analysis aligned to the Capability, Opportunity, Motivation model of Behaviour change (COM-B) was used to analyse the qualitative data.

Results

Interviews revealed many barriers in the DCD pathway related to capability (confusing terminology, inconsistent knowledge, inappropriate referrals), opportunity (resource constraints, DCD being considered low priority, and disconnected services), and motivation (overlapping job roles, a desire to consider those with difficulties not eligible for a diagnosis). No facilitators were consistently identified across interviews.

Conclusion

Families face multiple barriers to obtaining a diagnosis for their child through existing clinical pathways for assessment and support. These findings are unlikely to be unique to Bradford, due to international research highlighting these issues via parental interviews. These findings therefore may reflect challenges both nationally and internationally within DCD pathways. There is an urgent need for: (i) clear communication across different services (with consistency in terminology), and (ii) a more collaborative and integrated approach to assessment, diagnosis, and support in order to help these children thrive.

Exploratory study on the impact of <i>Ganoderma australe</i> extract on gut microbiota and immune gene expression in honey bees exposed to <i>Vairimorpha ceranae</i>

by Sarah Zuern, Bella Romero, Carlos Spichiger, Leandro Ortiz, Alejandro Jerez, Esteban Basoalto, Max Emil Schön, Sigisfredo Garnica

The microsporidium Vairimorpha (Nosema) ceranae is an emerging threat to honey bees (Apis mellifera), known to disrupt gut microbiota and suppress immune responses, potentially contributing to colony losses. Fungal extracts have recently gained interest as sources of bioactive compounds with antimicrobial and immunomodulatory potential. In this study, we explored the effects of different dietary supplements—sugar syrup, HiveAlive™, and a novel Ganoderma australe extract (GanoBee)—on gut bacterial composition and immune-related gene expression in honey bees subjected to experimental exposure to V. ceranae 1 x 104 spores per bee. The GanoBee diet altered the gut microbiota, notably reducing the relative abundance of Rhizobiaceae (Bartonella apis) and increasing Frischella compared to other treatments. While alpha diversity was not significantly affected by diet or exposure to V. ceranae, beta diversity differed significantly in bees fed with GanoBee. Additionally, the expression of the antimicrobial peptide genes abaecin and hymenoptaecin was elevated in both exposed and unexposed bees fed with GanoBee, depending on the sampling day. However, the establishment of V. ceranae infection appeared limited, likely due to low spore viability, and mortality in control bees was higher than expected. The low Vairimorpha ceranae infection levels observed in this study are likely attributable to reduced spore viability caused by storage conditions and/or suboptimal environmental conditions within the laboratory cages. Post hoc analyses indicated that the high viscosity of GanoBee-supplemented diets likely contributed to the elevated bee mortality observed, underscoring a critical limitation of the experimental design related to diet formulation and delivery method. These physical factors complicate the interpretation of treatment efficacy and highlight the importance of optimizing feeding protocols to avoid confounding effects. Despite these constraints, GanoBee demonstrated promising potential as a modulator of gut microbiota composition and immune-related gene expression, supporting the need for further research under improved and carefully controlled experimental conditions.

Methodological review of the design, objectives and sample size of Research for Patient Benefit (RfPB) applications that use an external randomised controlled pilot trial design: A protocol

by Claire L. Chan, Saskia Eddy, Jennie Hejdenberg, Ben Morgan, Heather M. Morgan, Gillian Lancaster, Clare Robinson, Sandra M. Eldridge

Background

The National Institute for Health and Care Research accepts applications for pilot and feasibility studies to their Research for Patient Benefit (RfPB) programme. There has been limited work describing the design practices of these applications and funding status. Knowing some of the qualities which may contribute towards a pilot or feasibility study application successfully gaining funding could help researchers improve the quality of their applications. Therefore, this study describes the protocol for a review looking at the characteristics of funded and non-funded external pilot trial applications. In particular, the primary objective is to describe the planned sample size and sample size justifications.

Methods

The study will be conducted on 100 applications from Competition 31–37 with a randomised feasibility design, identified and given access to us by RfPB where the lead applicant has consented. We will screen these applications to identify the external pilot trials, first looking through the titles and then the full text. Following this, we will extract data on information such as medical area, study design, objective(s), sample size, sample size justification, and funding outcome stage one and two. Validation will be performed on 20% of the data extracted; discrepancies will be resolved by discussion or a third reviewer will decide if there is no consensus. We will use descriptive statistics to summarise quantitative data, and will analyse qualitative data using thematic analysis. Findings will be summarised through discussion with the project contributors to produce a reader-friendly guidance document.

Discussion

This work will provide a more complete picture of RfPB external randomised pilot and feasibility trials. The findings will assist researchers when planning their pilot trials, and could help improve the quality of submitted applications.

Protocol Registration

Open Science Framework protocol registration DOI: https://doi.org/10.17605/OSF.IO/PYKVG.

Real-world clinical effectiveness of trimethoprim–sulfamethoxazole for primary prophylaxis of pneumocystis pneumonia in non-hodgkin lymphoma patients treated with rituximab

by Patcharaporn Charoenrit, Pimjai Niparuck, Porpon Rotjanapan

There are no definitive clinical practice guidelines regarding the necessity and dosage of trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in individuals undergoing rituximab therapy. This retrospective study evaluated the effectiveness and safety of various TMP–SMX prophylactic dosing regimens over a 1-year period in 690 patients with non-Hodgkin lymphoma treated with rituximab at a university hospital in Thailand from 2013 to 2022. Out of these patients, 622 (90.1%) received TMP/SMX, with a mean duration of prophylaxis of 265.7 days (SD 85.66). The overall incidence of PJP was 1% (7 patients), which was significantly higher in the non-prophylaxis group (5.8%, 4 patients) compared to the prophylaxis group (0.6%, 3 patients). No cases of PJP occurred among those receiving standard prophylaxis or a single-strength tablet every other day, three times a week. However, instances in the prophylaxis cohort were reported in patients who took two single-strength tablets twice daily, twice a week. Prophylaxis resulted in a significant reduction in the one-year incidence of PJP, with a hazard ratio of 0.105 (95% CI: 0.023–0.469). Mild adverse reactions were noted in 3.05% of patients, all of whom recovered. These findings suggest that TMP/SMX prophylaxis was associated with a lower incidence of PJP and was well tolerated. Future studies should explore optimal dosing strategies while considering patient selection bias and concurrent immunosuppressive therapy.

Pragmatic, open-label, multicentre, randomised controlled trial to guide initial therapy for immune checkpoint inhibitor-induced inflammatory arthritis comparing standard of care (prednisolone) to adalimumab without glucocorticoids: REACT trial protocol

Por: Fisher · B. A. · Rowe · A. · Hodson · C. · Wilkhu · M. · Williams · E. · Turner · E. · Allard · A. · Blake · T. · Bombardieri · M. · Cope · A. P. · Dubey · S. · Mankia · K. · Malley · T. · Moore · O. · Payne · M. · Plummer · R. · Tilby · M. · Tillett · T. · Wong · E. · Wu · Y. · Filer · A. · Pra
Introduction

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.

A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.

Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.

Methods and analysis

REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).

The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.

Ethics and dissemination

The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

Trial registration number

ISRCTN18217497.

Mapping the evidence on dietary acculturation post-migration among Indian immigrants in Australia, Canada, New Zealand and the UK: a scoping review protocol

Por: Bachani Singh · S. · George · M. S. · Upton · P. · Knight-Agarwal · C. R.
Introduction

Indian immigrants experience significant dietary acculturation post-migration, shifting from traditional diets to more westernised eating patterns influenced by socioeconomic and environmental factors. This transition, often marked by increased processed food consumption and reduced intake of traditional staples, contributes to elevated risks of obesity and type 2 diabetes. Despite the growing Indian diaspora in Australia, Canada, New Zealand and the UK, the evidence on their dietary acculturation remains limited.

Methods and analysis

This review will adopt the Joanna Briggs Institute (JBI) methodology for scoping reviews. A three-step search strategy will be applied across databases including MEDLINE (via PubMed), CINAHL, Scopus and Web of Science. Google Scholar will be used as a supplementary search tool to identify additional relevant studies. The search will include peer-reviewed studies and grey literature published in English between 1 January 2000 and 22 May 2025. First-generation Indian immigrants of all ages will be included, while second-generation immigrants, refugee populations and studies linked to non-communicable disease interventions will be excluded. Screening will be conducted in Covidence by two independent reviewers, with discrepancies resolved by a third reviewer. Data will be extracted using a standard JBI tool, charted in tabular form, and synthesised narratively and thematically.

Ethics and dissemination

As this review will use published and publicly available data, formal ethics approval is not required. Findings will be disseminated through peer-reviewed publication, conference presentations and community engagement.

From mother to child: a protocol paper on the longitudinal effects of a perinatal intervention on maternal self-efficacy and emotion regulation and child outcomes

Por: Montreuil · T. · Skinner · J. · Humez · L. · Gratton · C. · Herba · C. M. · Cote · S. M.
Introduction

Parental psychological challenges and poor well-being are key factors in shaping both the quality of parent-child interactions and child development. Specifically, maternal psychological distress is a central determinant of child development. Elevated levels of distress in mothers are associated with poorer child cognitive, behavioural and social-emotional outcomes, with effects persisting into adolescence and adulthood. While this highlights the critical importance of early prevention and intervention efforts to support parents, postpartum mental healthcare remains limited, despite ongoing and evident needs.

Methods and analysis

This protocol outlines a 2-year longitudinal follow-up study investigating the impact of a secondary perinatal programme (ie, Toi, Moi, Bébé), completed by mothers during pregnancy, and its impact on children’s cognitive and social-emotional functioning at 24 and 48 months. Further, the study aims to explore whether maternal self-efficacy and emotion regulation may serve as potential mediators or moderators of the relationship between programme participation and child development outcomes. The research aims to leverage the Toi, Moi, Bébé programme, by recruiting mother-child dyads (n=250) in which the mothers participated in the programme during pregnancy. Mothers were randomly assigned to complete the parenting well-being intervention either independently or with added telephone support. Participants who consent will be invited to take part in a two-wave follow-up at 24 months (T1) and 48 months postpartum (T2). At both time points, mothers will complete demographic questionnaires and standardised measures assessing maternal well-being (Generalised Anxiety Disorder-7, Edinburgh Postnatal Depression Scale and Perceived Stress Scale), child cognitive functioning (Ages and Stages Questionnaire-3 and MacArthur-Bates Communicative Development Inventory), child social-emotional functioning (Ages and Stages Questionnaire, Social Emotional—second Edition-2 and Child Behaviour Checklist for Ages 1.5–5), maternal emotion regulation (Cognitive Emotion Regulation Questionnaire) and maternal self-efficacy (Parental Cognitions and Conduct Towards the Infant Scale & Me as a Parent Scale). Parents’ perceptions of their parenting experience will be measured using the Parental Reflective Functioning Questionnaire. Mother-child interaction, parenting quality and cognitive stimulation in the home environment will be measured using a brief virtual interview (StimQ2-Toddler) and a naturalistic observation assessment (Parenting Interactions with Children: Checklist of Observations Linked to Outcomes). Using RStudio, linear mixed models will be used to assess the impact of the intervention (online intervention only vs only with telephone support) on child cognitive and social-emotional development at T1 and T2. In parallel, separate models will be conducted to examine associations between maternal emotion regulation and self-efficacy on the child development outcomes at the same timepoints. Exploratory analyses will be conducted to examine potential moderating effects of child sex and group assignment on the associations between maternal emotion regulation and self-efficacy and child developmental (cognitive and socioemotional) outcomes, using causal inference models.

Ethics and dissemination

The current study has been registered, reviewed and approved (MP-37-2025-10894) by the Research Institute of the McGill University Health Centre Research Ethics Board. Findings from this research will be disseminated through peer-reviewed open access publications, and presentations at national and international conferences.

Trial registration number

NCT05110456.

Effectiveness and cost-effectiveness of a 9 week multi-component cycling programme versus an existing single cycling training session: protocol for the Cycle Nation Communities randomised controlled trial

Por: Lawlor · E. R. · Gabler Trisotti · M. F. · McIntosh · E. · McConnachie · A. · Gill · J. M. R. · Gray · C. M.
Introduction

Cycling can be beneficial for health, well-being and the environment; however, cycling participation in the UK remains low. Effective and cost-effective strategies are needed to support people in the community to increase cycling. The Cycle Nation Communities randomised controlled trial (RCT) will evaluate whether a 9 week multi-component cycling programme (Cycle Nation) is more effective and cost-effective than an existing national cycle training session on cycling participation, transport use and health and well-being.

Methods and analysis

This pragmatic, single-blinded, two-arm RCT will recruit ≥268 adults who cycle infrequently. Participants will be randomised to the 9 week multi-component individual/social-level group-based Cycle Nation programme or an existing national standard single group-based cycle training session. Both arms will be delivered by community-based cycling organisations in Glasgow. Participants will complete self-reported measurements at baseline, 12 weeks and 12 months. The primary outcome is the proportion of participants cycling at least weekly at 12 months. Secondary outcomes include proportion of participants cycling at least weekly at 12 weeks; change in weekly number of rides and minutes of cycling and use of private car, taxi, public transport and walking at 12 weeks and 12 months; change in motivation, perceptions of cycling safety, confidence to cycle, self-esteem, vitality, health-related quality of life and perceived general physical health at 12 weeks and 12 months. A within-trial economic evaluation from a National Health Service/personal social service and a broader societal perspective will be undertaken. Pending within-trial results, a long-term model may be developed. An embedded process evaluation will use participant and facilitator interviews, participant acceptability questionnaires, facilitator delivery proforma and session observations.

Ethics and dissemination

Ethical approval has been obtained from the University of Glasgow Medical, Veterinary and Life Sciences Ethics Committee (11 April 25). Findings will be published in peer-reviewed journals and communicated to stakeholders and the public.

Trial registration number

NCT07005674.

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