bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-prescription antibiotic use and its predictors among children in low- and middle-income countries: a systematic review and meta-analysis
Authors: Zewdie Segenet , Kassa Assefa Andargie , Yayehrad Ashagrachew Tewabe , Bizuneh Mekonnen Melkie , Ayenew Wondim , Zewudie Melkamu , Mulat Selomie , Bitew Bayih Endalew , Zewudie Serkalem , Meharie Birhanu Geta , Tesfaye Tegenu Chanie , Zerga Aregash Abebayehu , Ayele Fanos Yeshanew , Toleha Husein Nurahmed , Workineh Birhanu Demeke , Bayked Ewunetie Mekashaw 
Published: December 2024

AbstractGlobally antibiotics are among the most commonly used drugs. Non-prescription use of antibiotics is a major factor for the emergence and spread of antimicrobial resistance one of the top global public health and development threats. This systematic review and meta-analysis aim to assess non-prescription antibiotic use and predictors among children in Low and middle-income countries.A comprehensive search of electronic databases was conducted from PubMed, Scopus and HINARI to identify primary studies published between 2000 and 2024. Observational studies conducted among children ≤ 18 years old and published in English language were included in the review. After screening, the studies were assessed using Joanna Briggs Institute (JBI) critical appraisal tool and data were extracted using a checklist. Heterogeneity was assessed using forest plot, Chocran’s Q Test and I2. The random effects meta-analysis model was employed to pool the prevalence of non-prescription antibiotic use among children in low-and middle-income countries. Sub-group analysis and meta-regression were performed to identify the sources of heterogeneity. Publication bias was assessed using funnel plots with Egger’s test.The review was conducted among 32 cross-sectional studies with a sample size of 80,133 participants. The pooled prevalence of non-prescription antibiotic use among children in low-and middle-income countries was 38.86% (95% CI 34.32, 43.40; P < 0.0001) with high heterogeneity (I2 = 99.38%, p < 0.001). The prevalence of non-prescribed antibiotic use among studies conducted in upper middle-income countries (30.85% (24.49%, 37.21%)) was low when compared to studies conducted in LMICs (44.00% (37.72%, 52.09%). Penicillin was the most often antibiotic class used without prescription, while upper respiratory infections were the most prevalent illness/symptoms that prompted non-prescription antibiotic use.The pooled prevalence of non-prescription antibiotic use among children in low-and middle-income countries is high indicating that two out of five children used non-prescribed antibiotics. This review is important for international organizations, ministry of health of the low-and middle- income countries, regulatory bodies and researchers.
GenomeDelta: detecting recent transposable element invasions without repeat library
Authors: Pianezza Riccardo , Haider Anna , Kofler Robert 
Published: December 2024

Abstract
We present GenomeDelta, a novel tool for identifying sample-specific sequences, such as recent transposable element (TE) invasions, without requiring a repeat library. GenomeDelta compares high-quality assemblies with short-read data to detect sequences absent from the short reads. It is applicable to both model and non-model organisms and can identify recent TE invasions, spatially heterogeneous sequences, viral insertions, and hotizontal gene transfers. GenomeDelta was validated with simulated and real data and used to discover three recent TE invasions in Drosophila melanogaster and a novel TE with geographic variation in Zymoseptoria tritici.
STABLE trial of spectacle provision and driving safety among myopic motorcycle users in Vietnam: study protocol for a stepped-wedge, cluster randomised trial
Authors: Le Vinh Chi , To Kien Gia , Le Van Dat , Nguyen Le , MacKenzie Graeme , Sigwadhi Lovemore Nyasha , Piyasena Prabhath , Tran Mai , Chan Ving Fai , Khanna Rohit C. , Clarke Mike , Lohfeld Lynne , Dickey Heather , Azuara-Blanco Augusto , Mettla Asha Latha , Rayasam Sridevi , Doan Han Thi Ngoc , Van Do Dung , Le Phuoc Hong , Klauer Charlie , Hanowski Richard , Bowden Zeb , Murphy Lynn , Thompson Joanne , McMullan Susan , McDowell Cliona , Narayanan Raja , Little Julie-Anne , Ha Huong Thu , Yoon Sangchul , Goel Rahul , Luong Lan , Nguyen Xuan , Congdon Nathan 
Published: December 2024

Abstract
Background
Traffic crashes are the leading cause of death globally for people aged 5–29 years, with 90% of mortality occurring in low- and middle-income countries (LMICs). The STABLE (Slashing Two-wheeled Accidents by Leveraging Eyecare) trial was designed to determine whether providing spectacles could reduce risk among young myopic motorcycle users in Vietnam.

Methods
This investigator-masked, stepped-wedge, cluster randomised naturalistic driving trial will recruit 625 students aged 18–23 years, driving ≥ 50 km/week, with ≥ 1-year driving experience and using motorcycles as their primary means of transport, in 25 clusters of 25 students in Ho Chi Minh City, Vietnam. Motorcycles of consenting students who have failed self-testing on the WHOeyes app will be fitted with Data Acquisition Systems (DAS) with video cameras and accelerometers. Video clips (± 30 s) of events flagged by the accelerometer will be reviewed for crash and near-crash events per 1000 km driven (main outcome). Five clusters of 25 students will be randomly selected every 12 weeks to undergo ocular examination and an estimated 40% of these will have bilateral spherical equivalent < − 0.5 D, and better-eye presenting distance visual acuity < 6/12, correctable bilaterally to ≥ 6/7.5. They will be given free distance spectacles and their driving data before receiving spectacles will be analysed as the control condition and subsequent data as the intervention condition. Secondary outcomes include visual function, cost-effectiveness and self-reported crash events.

Discussion
STABLE will be the first randomised trial of vision interventions and driving safety in a LMIC.

Trial registration
ClinicalTrials.gov, NCT05466955. Initial registration: 20 July 2022, most recent update: 9 July 2024.
Perceived barriers and facilitators of staff recruiting participants to a randomised controlled trial of a community rehabilitation intervention following hip fracture
Authors: Harvey Kathryn , Ralph Penelope , Spencer Llinos Haf , Doungsong Kodchawan , Morrison Val , Lemmey Andrew , Golding-Day Miriam , Dodd Susanna , Hardwick Ben , Dorkenoo Shanaz , Hennessey Sophie , Williams Nefyn 
Published: December 2024

Abstract
Background

Randomised controlled trials (RCTs) often struggle with recruitment and many need extensions which leads to delayed implementation of effective interventions. Recruitment to complex intervention trials have similar difficulties. Alongside this, the COVID-19 pandemic had a major impact upon trial recruitment. Research has shown that many other recruitment issues can be anticipated, for example overestimating target population prevalence; however, a range of factors may play a role. The aim of this study is to investigate facilitators and barriers to recruitment from the perspective of the recruiter.

Methods
Fracture in the Elderly Multidisciplinary Rehabilitation – phase III (FEMuR III) was a RCT of a complex intervention post-surgery for hip fracture in patients over 60 years old. A process evaluation was undertaken, and semi-structured interviews were conducted with seven recruiters between November 2022 and March 2023 to identify barriers and facilitators to recruitment. A thematic analysis was undertaken in NVIVO (Version 12) using a critical realist perspective.

Results
The trial took place mostly during the COVID-19 pandemic, and the unique impact of this on reported barriers is considered. A key finding included recruiter reluctance to approach patients that they felt would not benefit from the trial due to other factors (e.g. comorbidities or complex living situations). A possible barrier to recruiting carers appeared to be that family members did not relate to the label of ‘carer’ and so did not take part. Facilitators included recruiters approaching patients with other clinical or research staff. This approach, which included tailored initial information on the trial, reduced participant stress by increasing patient familiarity with recruiting staff and allowing staff time to develop relationships with patients.

Conclusion
This paper identifies barriers and facilitators of recruitment to FEMuR III with six broad themes for both barriers and facilitators identified in the qualitative data synthesis. The impact of the COVID-19 pandemic was the main, but not sole, barrier to recruitment. Key findings concern reluctance to approach some eligible patients, the label of ‘carer’, the involvement of clinical staff and patient preference for trial group. Strategies to identify and overcome recruitment problems are highlighted and should be implemented and evaluated in further RCTs of complex interventions.

Trial registration
ISRCTN28376407. November 23, 2018.
The role of healthcare professionals’ communication in trial participation decisions: a qualitative investigation of recruitment consultations and patient interviews across three RCTs
Authors: Farrar Nicola , Elliott Daisy , Jepson Marcus , Young Bridget , Donovan Jenny L. , Conefrey Carmel , Realpe Alba X. , Mills Nicola , Wade Julia , Lim Eric , Stein Robert C. , Caskey Fergus J. , Rooshenas Leila 
Published: December 2024

Abstract
Background
Although the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients’ participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions.

Methods
Three pragmatic UK-based multicentre RCTs were purposively sampled to provide contrasting clinical specialities. Data collection was integrated into each RCT, including audio-recordings of patient recruitment consultations and interviews with patients. Where possible, consultation audio-recordings were linked to interviews to explore how information communicated by recruiters was interpreted and used by patients during their decision-making. Data were analysed thematically, using the constant comparison approach.

Results
Twenty audio-recorded recruitment consultations were obtained across the 3 RCTs, combined with 42 interviews with patients who had consented to or declined RCT participation. Consultation and interview data were ‘linked’ for 17 individual patients. Throughout the patient’s clinical pathway, HCPs (both those involved in the RCT and not) influenced patients’ perceptions of treatment need and benefit by indicating that they preferred a particular treatment option for the patient as an individual. Whilst patients valued and were influenced by information conveyed by HCPs, they also drew on support from other sources and ultimately framed RCT participation decisions as their own. Patients’ willingness to be randomised hinged on perceptions of whether they stood to benefit from a particular treatment and the availability of those treatments outside of the trial.

Conclusion
This study supports the need for training and support for healthcare professionals involved throughout the clinical pathway of patients eligible for RCTs, as all healthcare professionals who interact with patients have the potential to influence their perceptions of treatments being compared in the trial.

Trial registration
OPTIMA ISRCTN42400492. Prospectively registered on 26 June 2012.
Prepare for Kidney Care ISRCTN17133653. Prospectively registered on 31 May 2017.
MARS 2 ISRCTN44351742. Retrospectively registered on 5 September 2018.
Reliability of wing morphometrics for species identification of human-biting black flies (Diptera: Simuliidae) in Thailand
Authors: Aupalee Kittipat , Srisuka Wichai , Limsopatham Kwankamol , Sanit Sangob , Takaoka Hiroyuki , Saeung Atiporn 
Published: December 2024

Abstract
Background
Fast and reliable species identification of black flies is essential for research proposes and effective vector control. Besides traditional identification based on morphology, which is usually supplemented with molecular methods, geometric morphometrics (GM) has emerged as a promising tool for identification. Despite its potential, no specific GM techniques have been established for the identification of black fly species.

Methods
Adult female black flies collected using human bait, as well as those reared from pupae, were used in this study. Here, landmark-based GM analysis of wings was assessed for the first time to identify human-biting black fly species in Thailand, comparing this approach with the standard morphological identification method and DNA barcoding based on the mitochondrial cytochrome c oxidase subunit I (COI) gene. To explore genetic relationships between species, maximum likelihood (ML) and neighbor-joining (NJ) phylogenetic trees were built. Additionally, three different methods of species delimitation, i.e., assemble species by automatic partitioning (ASAP), generalized mixed yule coalescent (GMYC), and single Poisson tree processes (PTP), were utilized to identify the morphologically defined species. The effectiveness of a COI barcode in identifying black fly species was further examined through the best match (BM) and best close match (BCM) methods.

Results
Seven black fly species, namely Simulium tenebrosum Takaoka, Srisuka & Saeung, 2018 (complex), S. doipuiense Takaoka & Choochote, 2005 (complex), S. nigrogilvum Summers, 1911, S. nodosum Puri, 1933, S. asakoae Takaoka & Davies, 1995, S. chamlongi Takaoka & Suzuki, 1984, and S. umphangense Takaoka, Srisuka & Saeung, 2017 were morphologically identified. Compared with the standard method, the GM analysis based on wing shape showed high success in separating species, achieving an overall accuracy rate of 88.54%. On the other hand, DNA barcoding surpassed wing GM for species identification with a correct identification rate of 98.57%. Species delimitation analyses confirmed the validity of most nominal species, with an exception for S. tenebrosum complex and S. doipuiense complex, being delimited as a single species. Moreover, the analyses unveiled hidden diversity within S. asakoae, indicating the possible existence of up to four putative species.

Conclusions
This study highlights the potential of wing GM as a promising and reliable complementary tool for species identification of human-biting black flies in Thailand.

Graphical Abstract
Sequencing confirms Anopheles stephensi distribution across southern Yemen
Authors: Baheshm Yasser A. , Zayed Alia , Awash Abdullah A. , Follis Madison , Terreri Payton , Samake Jeanne N. , Aljasari Adel , Harwood James F. , Lenhart Audrey , Zohdy Sarah , Al-Eryani Samira M. , Carter Tamar E. 
Published: December 2024

Abstract
The invasion of Anopheles stephensi in Africa warrants investigation of neighboring countries. In this study, genetic analysis was applied to determine the status of An. stephensi in southern Yemen. Cytochrome c oxidase subunit I (COI) and internal transcribed spacer 2 (ITS2) were sequenced in An. stephensi collected in Dar Sa’ad (Aden City), Tuban, Rodoom, Al Mukalla, and Sayhut, and phylogenetic analysis confirmed An. stephensi identity. Our analyses revealed that the ITS2 sequences were identical in all An. stephensi, while COI analysis revealed two haplotypes, one previously reported in northern Horn of Africa and one identified in this study for the first time. Overall, these findings revealed low levels of mitochondrial DNA diversity, which is consistent with a more recent population introduction in parts of southern Yemen relative to the Horn of Africa. Further, whole genomic analysis is needed to elucidate the original connection with invasive populations of An. stephensi in the Horn of Africa.

Graphical Abstract
Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo
Authors: Wang Lu , Zhai Bintao , Wang Chen , Elsheikha Hany M. , Guo Haiting , Zheng Xiao-Nan , Zhou Chun‑Xue , Zhu Xing-Quan 
Published: December 2024

Abstract
Background
Toxoplasma gondii is an obligate protozoan parasite capable of infecting a wide range of warm-blooded animals and humans. Current treatment options, primarily pyrimethamine and sulfadiazine, have limitations, such as high recurrence rates, long treatment durations, and limited effectiveness against T. gondii. There is an unmet need for novel, safe, low-toxicity, and highly effective treatments. This study aimed to evaluate the anti-T. gondii effects of glabridin, a natural compound derived from the roots of a widely used medicinal plant.

Methods
The cytotoxicity of glabridin in Vero cells was assessed using a CCK-8 cell viability assay. Quantitative polymerase chain reaction (qPCR) targeting the Tg-529 gene was developed to quantify T. gondii and assess the inhibitory effects of glabridin on parasite proliferation. Ultrastructural changes in T. gondii after treatment were examined using electron microscopy. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were examined to assess the effects of glabridin on ROS levels and ΔΨm in T. gondii tachyzoites. Additionally, metabolomics and transcriptomics analyses were conducted to investigate the mechanisms underlying glabridin’s anti-T. gondii effects.

Results
Glabridin exhibited low toxicity to host cells and effectively inhibited T. gondii invasion and proliferation in vitro in a time-dependent manner. Glabridin-treated tachyzoites exhibited significant structural alterations, along with increased ROS production and a reduction in ΔΨm. Metabolomic analysis indicated that glabridin significantly affected amino acid metabolism pathways in T. gondii. In vivo, glabridin treatment significantly improved survival rates in T. gondii-infected BALB/c mice at a dosage of 100 mg/kg.

Conclusions
This study demonstrates that glabridin has potent anti-T. gondii effects in vitro and in vivo, likely through disruption of amino acid metabolism in the parasite. These findings highlight glabridin’s potential as a promising therapeutic agent for toxoplasmosis.

Graphical abstract
Role of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritis
Authors: dos Santos Gilson Goncalves , Jiménez-Andrade Juan Miguel , Muñoz-Islas Enriqueta , Candanedo-Quiroz Mariana E. , Cardenas Andrea Gonzalez , Drummond Bronwen , Pham Peter , Stilson Gwendalynn , Hsu Chao-Chin , Delay Lauriane , Navia-Pelaez Juliana M. , Lemes Julia Paes , Miller Yury I. , Yaksh Tony L. , Corr Maripat 
Published: December 2024

Abstract
Background
In the murine K/BxN serum transfer rheumatoid arthritis (RA) model, tactile allodynia persists after resolution of inflammation in male and partially in female wild type (WT) mice, which is absent in Toll-like receptor (TLR)4 deficient animals. We assessed the role of TLR4 on allodynia, bone remodeling and afferent sprouting in this model of arthritis.

Methods
K/BxN sera were injected into male and female mice with conditional or stable TLR4 deletion and controls. Paw swelling was scored and allodynia assessed by von Frey filaments. At day 28, synovial neural fibers were visualized with confocal microscopy and bone density assayed with microCT. Microglial activity and TLR4 dimerization in spinal cords were examined by immunofluorescence and flow cytometry.

Results
In the synovium, K/BxN injected WT male and female mice showed robust increases in calcitonin gene related-peptide (CGRP+), tyrosine hydroxylase (TH)+ and GAP43+ nerve fibers. Trabecular bone density by microCT was significantly decreased in K/BxN WT female but not in WT male mice. The number of osteoclasts increased in both sexes of WT mice, but not in Tlr4-/- K/BxN mice. We used conditional strains with Cre drivers for monocytes/osteoclasts (lysozyme M), microglia (Tmem119 and Cx3CR1), astrocytes (GFAP) and sensory neurons (advillin) for Tlr4f/f disruption. All strains developed similar arthritis scores after K/BxN serum injection with the exception being the Tlr4Tmem119 mice which showed a reduction. Both sexes of Tlr4Lyz2, Tlr4Tmem119 and Tlr4Cx3cr1 mice displayed a partial reversal of the chronic pain phenotype but not in Tlr4Avil, and Tlr4Gfap mice. WT K/BxN male mice showed increases in spinal Iba1, but not GFAP, compared to Tlr4-/- male mice. To determine whether spinal TLR4 was indeed activated in the K/BxN mice, flow cytometry of lumbar spinal cords of WT K/BxN male mice was performed and revealed that TLR4 in microglia cells (CD11b+ /TMEM119+) demonstrated dimerization (e.g. activation) and a characteristic increase in lipid rafts.

Conclusion
These results demonstrated a complex chronic allodynia phenotype associated with TLR4 in microglia and monocytic cell lineages, and a parallel spinal TLR4 activation. However, TLR4 is dispensable for the development of peripheral nerve sprouting in this model.
Sex differentially affects pro-inflammatory cell subsets in adipose tissue depots in a diet induced obesity model
Authors: Schuetz Lisa T. , Duran Gayel , Baeten Paulien , Lintsen Daphne , Hermans Doryssa , Chenine Sarah , Verreycken Janne , Vanmierlo Tim , Wouters Kristiaan , Broux Bieke 
Published: December 2024

AbstractObesity is a growing pandemic that increases the risk for cardiovascular diseases, type 2 diabetes, and particularly in women also the risk of cancer and neurodegenerative disorders such as dementia and multiple sclerosis. Preclinical studies on obesity focus on male mice as they gain bodyweight faster and show a clear pro-inflammatory phenotype. Here, using male and female mice, we induced obesity by feeding a high fat diet (HFD), and compared adipose tissue (AT) inflammation at the same adiposity stage (% AT/bodyweight) between both sexes. Doing so, we identified that female mice show an increase in the number of pro-inflammatory immune cells in the visceral AT at a lower adiposity stage than male mice, but the effect of HFD is diminished with higher adiposity. Interestingly, only female mice showed an increase in immune cells in the subcutaneous AT after HFD feeding. Nonetheless, we found that pro-inflammatory cytokines in blood plasma mirror the inflammatory stage of the visceral AT in both male and female mice. Uniquely in male mice, myeloid cells in the visceral AT showed a higher inflammasome activation upon HFD. In summary, we showed that adiposity differentially affects immune cells in fat depots based on sex.