bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal changes in blood biomarkers associated with sleep apnoea severity: a retrospective cohort study in Finland
Authors: Hellen Mira , Ruoranen Toni , Toppila-Salmi Sanna , Vasankari Tuula , Kreivi Hanna-Riikka , Mattila Tiina , Ollila Hanna M , Strausz Satu
Published: February 2025

Introduction

Obstructive sleep apnoea (OSA) is a common sleep disorder associated with breathing interruptions during sleep, often leading to oxygen level drops and sleep disturbances. OSA is known to impact various physiological parameters, including haematological and lipid profiles. This study aims to investigate the effect of continuous positive airway pressure (CPAP) therapy on laboratory values in patients with OSA.

Methods

A retrospective study was conducted using data from Finland’s largest hospital district, including 30 722 adult OSA patients treated between 2005 and 2020. A text search algorithm was implemented within the patient chart data to extract the apnoea-hypopnoea index (AHI) and the usage of CPAP therapy, along with identifying patients who had declined treatment. Haematological and metabolic laboratory values were collected 3 years before and after the first OSA diagnosis. Analysis of covariance was employed to compare parameter variations across severity levels, adjusted for age, sex and body mass index (BMI). T-test for repeated measurements was used to analyse the differences between data, 3 years prior and 3 years after the first OSA diagnosis.

Results

The study of 30 722 OSA patients showed varying severity levels: 14.8% mild, 32.6% moderate and 52.6% severe, with an average diagnosis age of 55.0 years and a mean BMI of 32.4. The most clinically significant changes were observed in lipid profile markers, with improvements in cholesterol and low-density lipoprotein (LDL) levels (p value<0.05), measured before CPAP treatment initiation and after the treatment began. Conversely, glucose levels increased during the follow-up period. Similarly, haematocrit and haemoglobin decreased significantly after initiation of the CPAP treatment. In sex-specific analyses, significant improvements in cholesterol and LDL levels were found in both sexes. Triglyceride levels improved in male patients, in contrast with female participants, whose triglyceride levels increased during the follow-up period.

Conclusions

CPAP therapy significantly improves cholesterol and LDL levels in both sexes and reduces haematocrit and haemoglobin levels. This study highlights the systemic effects of OSA and underscores the importance of evaluating haematological and lipid profiles in OSA management.
Health valuation protocol for dual discrete choice experiment (dual-DCE) surveys to estimate the effects of different scenarios and attributes on main effects
Authors: Craig Benjamin Matthew
Published: February 2025

Introduction

A typical health preference study conducts a single discrete choice experiment (DCE). For example, a health valuation study may elicit preferences on an individual’s health-related quality of life along five EQ-5D-5L attributes (Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression). Using this protocol, researchers can conduct a dual-DCE survey (ie, with two different full-block DCEs completed sequentially). To demonstrate this protocol, we will conduct 12 dual-DCE surveys in two waves and estimate the effects of different scenarios and descriptive systems on main effects (ie, incremental differences in value between levels).

Methods and analysis

Each of the two DCEs in a dual-DCE survey equates to a stand-alone health valuation study. To demonstrate this protocol, each is an EQ-5D-5L valuation study, including d-efficient blocks of 15 kaizen tasks and 5 paired comparisons. In wave 1 (six surveys, 1000 US adults each), the two DCEs will differ by scenario (1-year episodes ending in recovery or death or no duration/ending described). In wave 2 (six surveys, 200 US adults each), the two DCEs will include the same 5 EQ-5D-5L attributes but differ by the number of additional attributes related to cognition: none, one composite attribute (memory/concentration) and two component attributes (memory, concentration). For each DCE, we will estimate a conditional logit model and test for differences in value using cluster bootstrap techniques. We hypothesise that the values will differ by scenarios and systems. As secondary analyses, we assess the effects of sampling, scenario/system order and DCE order.

Ethics and dissemination

The independent review board (IRB) at Advarra determined that this research project (Pro00080475; 11 July 2024) is exempt from IRB oversight based on the Department of Health and Human Services regulations found at 45 CFR 46.104(d)(2). Furthermore, the IRB determined that the project is not subject to requirements for continuing review. To disseminate our findings, we will prepare multiple manuscripts for publication in peer-reviewed journals and present highlights at scientific meetings, such as the EuroQol Plenary Meeting, International Academy of Health Preference Research and ISPOR.
Exploring the relationship between different modes of transportation and levels of physical activity among senior high school students of the University of Santo Tomas: a cross-sectional study protocol
Authors: Manlapaz Donald , Sicat Zyra Mae , Engbino April Alexandra , Cervo Nyl Eiller Israel , Daquiz Jamil , Leung Dathan Nevin , Luciano Iana Mikhela , Wee Arianne Ysabelle
Published: February 2025

Introduction

Rapid changes in technology, communication and transportation prompted challenges in achieving the recommended level of physical activity. Although the students are returning for in-campus classes to promote more interaction and socialisation, the youth still fall short of living up to the desired level of physical activity. The mode of transportation plays a pivotal role in physical activity, yet its relationship is poorly elucidated. The aim of the study is to explore the relationship between the types of transportation and the level of physical activity among senior high school students aged 16–18 from the University of Santo Tomas.

Methods and analysis

This will be an observational, cross-sectional, analytical study design. Participants’ demographics and anthropometric measurements such as height, weight and hip and waist circumferences will be collected. To measure the variables of interest, the International Physical Activity Questionnaire and Global Physical Activity Questionnaire will be used. Descriptive statistics will be used to characterise the samples using frequency, mean, median and SD, while inferential statistics such as analysis of variance for comparison and Pearson’s and Spearman for correlation will be used. All analysis will be done using IBM Statistical Packages for Social Sciences V.23 with the significant level set at alpha 0.05.

Ethics and dissemination

Ethical approval was obtained from the University of Santo Tomas—College of Rehabilitation Sciences Ethics Review Committee with the protocol number SI-2023–029. The study will comply with the principles of the Declaration of Helsinki, Ethical Guidelines on Health-Related Social Research of the Philippine Health Research Ethics Board and the Data Privacy Act 2012. All results, regardless of outcome, whether positive or negative, will be accessible through publication and by reporting to the participant through email and other relevant authorities.
Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised controlled trial (PROSPECTOR studies)
Authors: Ng Irvin , James Fiona , Copaescu Ana , Vogrin Sara , Mitri Elise , Rose Morgan , Sullivan Richard , Lane Michael , Legg Amy , Godsell Jack , Fernando Suran , Garvey Lene Heise , Sabato Vito , Li Philip , Peter Jonathan Grant , Trubiano Jason
Published: February 2025

Introduction

Penicillin allergy labels (PALs) are reported in 1 in 10 hospitalised patients globally and associated with inferior patient, hospital and microbiological outcomes; however, the majority are incorrect and should be removed. Direct oral penicillin challenge has been demonstrated to be a safe and effective method for the removal of PALs. However, the question of whether a single dose is sufficient to ascertain true allergy status remains unanswered, with some studies suggesting that extended challenges of 3 or more days are superior for the exclusion of delayed immune reactions. The aim of the PROSPECTOR studies was to determine the feasibility (PROSPECTOR-1) of a definitive trial (PROSPECTOR-2) to evaluate the safety and effectiveness of prolonged oral challenge (ie, 5 days) versus single-dose oral challenge in patients with a delayed or unknown penicillin allergy phenotype (PROSPECTOR-2).

Methods and analysis

A pair of double-blind two-arm parallel placebo-controlled trials will be undertaken—PROlonged versusSingle dose inPEnicillin oralChallengeTesting double-blind parallel group randomised placebo-cOntrolled tRial (PROSPECTOR Studies). Patients with a reported delayed or unknown timing penicillin allergy who have passed a supervised single-dose oral amoxicillin challenge (with or without prior skin testing/single or split dose) will be recruited. Informed patient consent will be granted for sites to recruit patients and collect routine clinical data. PROSPECTOR-1 will assess the safety and feasibility of a placebo-controlled trial for single-dose amoxicillin challenge versus 5-day prolonged oral challenge. PROSPECTOR-2 will assess the superiority of the 5-day prolonged oral challenge compared with single-dose amoxicillin challenge in excluding a delayed immune reaction. PROSPECTOR-2 will commence immediately post completion of PROSPECTOR-1 in a vanguard design, with adjustments to the projected sample size for superiority made following completion of PROSPECTOR-1. PROSPECTOR-2 will commence recruitment immediately following closure of PROSPECTOR-1; however, data from each trial will be analysed separately.

Ethics and dissemination

These studies were reviewed and approved by the Austin Health Human Research Ethics Committee (PROSPECTOR-1: HREC/99740/Austin-2023 and PROSPECTOR-2: HREC/109785/Austin-2024). The results will be published in peer-reviewed journals and presented at relevant conferences.

Trial registration number

PROSPECTOR-1: ACTRN12623001242617 and PROSPECTOR-2: ACTRN12624001107516.
Availability, prices and affordability of self-monitoring blood glucose devices: surveys in six low-income and middle-income countries
Authors: Ewen Margaret , Lepeska Molly , Abdraimova Aida , Besançon Stéphane , Cham Nguyen Thi Phuong , Dunganova Asel , Nguemeni Moise , Oldfield Lachlan , Tenorio-Mucha Janeth , Ramadaniati Hesty Utami , Vetter Beatrice , Beran David
Published: February 2025

Introduction

Accessing glucose meters, test strips, lancets and continuous/flash glucose monitoring devices for self-monitoring blood glucose (SMBG) is crucial for the management of diabetes. Yet little is known about access to SMBG devices in low-income and middle-income countries.

Methods

In 2022/2023, facility-based surveys were undertaken in selected regions and sectors in Fiji, Indonesia, Kyrgyzstan, Mali, Peru and Vietnam. Availability and patient prices were collected in public sector outlets (hospital dispensaries/clinics) and private pharmacies in the community by in-person visits (except in Mali where it was collected by phone). Data were also collected in medical device shops (Vietnam), online marketplaces (Indonesia) and online from device manufacturers.

Availability was assessed as the percentage of outlets with the device in stock on the day of data collection. Median prices were calculated and reported in US dollars (US$). Affordability was assessed as the number of days’ wages needed by the lowest-paid unskilled government worker to purchase each device. The affordability of self-monitoring was then compared with that of insulin.

Results

SMBG devices were not generally provided to individuals for self-testing by governments in Fiji, Indonesia, Kyrgyzstan and Peru. Public sector availability ranged from 0% to 57% (meters) and 0% to 53% (strips). In private pharmacies, availability was 31% to 100% (meters) and 39% to 100% (strips). Some large regional variations were seen within countries. Median prices for one meter ranged from US$15.62 to US$35.18. For one strip, median prices ranged from US$0.27 to US$0.56. Continuous/flash glucose monitoring devices were only found online at US$88–US$107 per sensor. Between 1.5 and 10.9 days’ wages were needed to purchase 1 meter, and 1.0–12.8 days’ wages for 50 strips. Online purchases of 1-month supply of continuous/flash device sensors required 15–65 days’ wages. The cost of self-testing exceeded the cost of human insulin vials/syringes. However, analogue prefilled pens/pen needles were often higher priced than the cost of self-testing.

Conclusion

Poor availability and high prices were found for SMBG devices which can impact diabetes management. Prices of meters, test strips and sensors were unaffordable. Pricing for these essential tools requires further investigation including cost of goods sold; government procurement prices and volumes; and price components in supply chains. Accessing SMBG devices must not be considered in isolation to accessing insulin. Governments need to include SMBG devices in their package of essential diabetes services. They must also support ongoing monitoring to ensure people are accessing SMBG devices.
Cultural adaptation and reliability of the Turkish version of the Children’s Assessment of Participation with Hands scale in children with physical disabilities
Authors: Cetin Sebahat Yaprak , Tonak Hasan Atacan , Kaya Kara Ozgun , Senol Hande , Kara Koray
Published: February 2025

Background

The ‘Children’s Assessment of Participation with Hands (CAP-H)’ scale is a parent report questionnaire that can be used to measure participation in life situations that require hand use for children with disabilities. The aim of this study was to examine the reliability of a Turkish version of the CAP-H scale in order to evaluate the hand participation of children with physical disabilities and compare them with typically developing children.

Methods

Evaluation was made of a total of 182 physically disabled children (8.53±3.94 years) and 90 typically developing children (9.40±3.04 years). The CAP-H scale was used to evaluate children’s hand participation, compare with typically developing children and to examine the reliability of the Turkish version. Cronbach’s alpha and intraclass correlation coefficients (ICCs) were evaluated for internal consistency and test–retest reliability, respectively.

Results

Cronbach’s alpha value used for all subscores was found to be excellent in all domains for internal consistency (Cronbach’s α: 0.84–1). According to the test–retest reliability, it was found to be perfectly reliable in all domains (ICC: 0.81–1). There was a significant difference in all items of CAP-H (p=0.00) except for participation in self-care, frequency of recreational activities and frequency of educational domain in favour of typically developing children.

Conclusions

The results of this study demonstrated that the Turkish translation of CAP-H is a reliable evaluation for children’s participation in life requiring hand use. In addition, hand participation of children with physical disabilities is lower compared with typically developing children.
Characterising airway inflammation in Aboriginal and Torres Strait Islander and non-Aboriginal and Torres Strait Islander adults with asthma and COPD
Authors: Young Nick , Chen Winnie , Chatterjee Shimul , Gelzinnis Scott , Latheef Aishath Lam’aan , Simpson Jodie , Wark Peter A B
Published: February 2025

Objective

To examine airway inflammatory cell profiles in Indigenous Australian adults with asthma and chronic obstructive pulmonary disease (COPD).

Design/setting

A retrospective, cross-sectional study on data from a tertiary referral respiratory outpatient clinic.

Participants

Indigenous (n=23) and non-Indigenous (n=71) adults were matched according to diagnosis, gender and age to the ratio of 1:3.

Main outcome measures

Participants were defined by self-determined identification as Indigenous (Aboriginal) or non-Indigenous. A relevant history was taken, and lung function was measured by spirometry. In those with a diagnosis of asthma, symptom control was assessed by the Asthma Control Questionnaire, six items (ACQ6). In those with a diagnosis of COPD, symptoms were assessed by the COPD assessment test (CAT). Airway cell counts were obtained in all groups from bronchial lavage (BL) cell count.

Results

Lung function and inhaled corticosteroid dose were similar between groups. Current smoking was three times more common in Indigenous people (35%) compared with non-Indigenous people (12%, p=0.009). In participants with asthma, ACQ6 scores were similar between Indigenous and non-Indigenous participants with asthma. In those with COPD, Indigenous participants had significantly higher total CAT scores as well as scores for cough and sputum with a score indicating a high impact on quality of life (CAT score ≥14, 85%–25%, p=0.017). There was no difference in BL cell differential counts.

Conclusions

Indigenous people with COPD had higher smoking rates, worsened CAT scores and more symptoms of cough and sputum production. There were no differences between the groups in airway inflammation, but neutrophilic inflammation was associated with poorly-controlled asthma.
Prospective analysis of injury demographics, distribution, severity and risk factors in adolescent climbers
Authors: Schöffl Volker Rainer , Schöffl Isabelle , Jones Gareth , Klinder Annett , Küpper Thomas , Gunselmann Lukas , Simon Michael , Moser Othmar , Bayer Thomas , Lutter Chris
Published: February 2025

Objective

This study aims to prospectively analyse current demographics, distribution and severity of climbing injuries in adolescents. We hypothesised that the injury distribution of adolescent climbers would differ from adults, as presented in the literature and that primary periphyseal stress injuries of the finger (PPSI) will be very common and correlate with training hours and climbing level.

Methods

We performed a prospective single-centre injury surveillance of all adolescent (<18 years of age) climbers who presented between 2017 and 2020. A standard questionnaire, including questions for medical history, injury and training data and an examination protocol, was conducted in all patients. Injuries were graded, and risk factors, anthropometric specifics and stages of development were analysed. Injury epidemiology of adolescents was then compared with adults as presented in the literature.

Results

137 independent climbing-related injuries were found in 95 patients. Injury onset was acute in 67 (48.9%) and chronic in 70 (51.8%). Forty-one injuries (29.9%) occurred during bouldering, 18 (13.1%) during lead climbing, 2 (1.5%) in speed climbing and 1 (0.7%) while training on the campus board. Average International Climbing and Mountaineering Federation injury score was 1.5±0.5 (range 0–3). Females had more training hours (p=0.004), more campus board use (p=0.004) and more acute injuries than males (p<0.001). 82% of the injuries affected the upper extremity and the most frequent injury was PPSI (45.3% of all injuries). Finger injuries were significantly more common in males than in females (p<0.05). The injury distribution in adolescent climbers differed significantly from adults (p<0.001).

Conclusions

Injured adolescent climbers had mostly chronic injuries affecting the upper extremity, with almost half of the injuries being PPSIs of the fingers. Further preventive measures targeting this type of injury need to be identified. Reducing the use of the finger crimp grip, monitoring the load, ensuring adequate recovery and targeted education appear to be crucial.
Time-loss and recurrence rate of lateral ankle sprains in male professional football players depending on the severity grade: do we trivialise LAS?
Authors: Flore Zacharias , Hambly Karen , De Coninck Kyra , Welsch Götz
Published: February 2025

Objectives

Lateral ankle sprains (LAS) are among the most common injuries in professional football (soccer). Despite this, the severity and possible long-term consequences of LAS remain trivialised. This multicentre observational study in German elite football provides insights into time-loss and recurrence rates after LAS. Time-loss and recurrence rates are outcome measures vital for the future evaluation of rehabilitation protocols.

Methods

798 male football players representing 34 teams from 13 professional German football clubs participated in this study during the 2021–2022 season, followed by a 12-month follow-up period. Data collection and reporting were carried out in accordance with the UEFA recommendations for the standardised collection of data on football injuries. Time-loss, recurrence rate and standardised severity grades (I–III) after LAS were recorded for professionals, U23, U19 and U17, respectively.

Results

A total of 187 ankle injuries were reported, with 115 out of the total being analysed. The overall time-loss was 29.89 days, with significant differences between youth elite players and professionals (32.96 vs 15.53 days lost; p<0.001). Professional players demonstrated the shortest time-loss in all LAS injury grades. Time-loss decreased with advancing age (R2=0.03,F(1, 106)=3.16, p=0.078). Grade I LAS’s time-loss differs significantly from grades II and III (p<0.001). A recurrent LAS was recorded in 34 players. The overall LAS recurrence rate was 25.6%.

Conclusion

This study provides data on time-loss and recurrence, which serve as reference values for future evaluation of rehabilitation concepts after LAS in elite football players.
Small bowel imaging in Crohn’s disease with a special focus on obesity, pregnancy and postsurgical assessment
Authors: Kaazan Patricia , Charabaty Aline , Yong Shaanan , Andrews Jane M , Pathi Ramon , Heilbronn Leonie K , Segal Jonathan P , Pellino Gianluca , Novak Kerri L , Rayner Christopher K , Barras Christen D
Published: February 2025

Crohn’s disease (CD) is an immune-mediated, multisystem inflammatory disorder characterised by discontinuous transmural, sometimes granulomatous, inflammation of the gastrointestinal tract. Although it can occur anywhere in the gastrointestinal tract, it has a 70% predilection for the terminal ileum. Ileocolonoscopy with biopsy remains the gold standard for initial diagnosis and assessment of CD activity but has several limitations, including invasiveness, risk of complications and cost. With a shifting focus towards treatment targets including transmural healing, non-invasive imaging modalities are being used increasingly to assess the small bowel, particularly the terminal ileum. CT enterography, magnetic resonance enterography and gastrointestinal ultrasound are widely used for small bowel imaging in clinical practice and have relatively good sensitivity and specificity. Obesity is a growing problem for patients with CD and is associated with limitations in medical imaging. Equally, cross-sectional imaging in pregnant and postsurgical patients with CD has its own challenges. In this article, we review small bowel imaging in CD with a special focus on obesity, pregnancy and postsurgical assessment.
RNA-based therapies in liver metabolic diseases
Authors: Fontanellas Antonio , Berraondo Pedro , Urigo Francesco , Jericó Daniel , Martini Paolo G V , Pastor Fernando , Avila Matias A
Published: February 2025

RNA-based therapeutics have rapidly emerged over the past decade, offering a new class of medicines that differ significantly from conventional drugs. These therapies can be programmed to target or restore defective genes, allowing for more personalised treatments and reducing side effects. Notably, RNA therapies have made significant progress in the treatment of genetic liver diseases, exemplified by small interfering RNA treatments for hereditary transthyretin amyloidosis, which use liver-targeting strategies such as GalNAc conjugation to improve efficacy and safety. RNA-based gene-editing technologies, such as base editor and prime editor clustered regularly interspaced short palindromic repeats systems, also show promise with their ability to minimise genomic rearrangements and cancer risk. While RNA therapies offer high precision, challenges remain in optimising delivery methods and ensuring long-term safety and efficacy. Lipid nanoparticle-mRNA therapeutics, particularly for protein replacement in rare diseases, have gained support from preclinical successes. Compared with viral gene therapies, mRNA therapies present a safer profile with reduced risks of genomic integration and oncogene activation. However, clinical trials, especially for rare diseases, face limitations such as small sample sizes and short observation periods. Further preclinical studies, including non-human primates, will be essential for refining trial designs. Despite their potential, the high costs of RNA therapies pose a challenge that will require cost–utility models to guide pricing and accessibility. Here, we discuss the fundamental aspects of RNA-based therapeutics and showcase the most relevant preclinical and clinical developments in genetic liver metabolic diseases.
Multicentre randomised controlled trial of a self-assembling haemostatic gel to prevent delayed bleeding following endoscopic mucosal resection (PURPLE Trial)
Authors: Drews Jan , Zachäus Markus , Kleemann Tobias , Schirra Jörg , Cahyadi Oscar , Möschler Oliver , Schulze Christian , Steinbrück Ingo , Wedi Edris , Pech Oliver , Weismüller Tobias J , Küllmer Armin , Abdelhafez Mohamed , Wedemeyer Jochen , Beyna Torsten , Riedel Julian , Halm Ulrich Paul , Güther Carola , Vasapolli Riccardo , Torres Reyes Christian , Quast Daniel R , Bachmann Oliver , Dedonaki Erini , Ulrich Jörg , Marchuk Inna , Frahm Christina , Steffen Tanja , Wohlmuth Peter , Bunde Torsten , Geßler Nele , von Hahn Thomas
Published: February 2025

Background

Prophylactic application of a haemostatic gel to the resection field may be an easy way to prevent delayed bleeding, a frequent complication after endoscopic mucosal resection (EMR).

Objective

We aimed to evaluate if the prophylactic application of a haemostatic gel to the resection field directly after EMR can reduce the rate of clinically significant delayed bleeding events.

Design

We conducted a prospective randomised trial of patients undergoing hot-snare EMR of flat lesions in the duodenum (≥10 mm) and colorectum (≥20 mm) at 15 German centres. Prophylactic clip closure was not allowed, but selective clipping or coagulation could be used prior to randomisation to treat intraprocedural bleeding or for prophylactic closure of visible vessels. Patients were randomised to haemostatic gel application or no prophylaxis. The primary endpoint was delayed bleeding within 30 days.

Results

The trial was stopped early due to futility after an interim analysis. The primary endpoint was analysed in 232 patients (208 colorectal, 26 duodenal). Both groups were comparable in age, sex, comorbidities and lesion characteristics. Preventive measures, such as selective clipping or coagulation, were applied prior to randomisation in 51.9% of cases, with no difference between groups. Delayed bleeding occurred in 14 cases (11.7%; 95% CI 7.1% to 18.6%) after Purastat and in 7 cases (6.3%; 95% CI 3.1% to 12.3%) in the control group (p=0.227), with no difference between colorectal and duodenal subgroups.

Conclusion

The application of a haemostatic gel following EMR of large flat lesions in the duodenum and colorectum does not reduce the rate of delayed bleeding.
Explosive Ordnance Risk Education boosts interpersonal discussion to increase safe behavioural intentions in Afghanistan
Authors: Paskuj Benedek , Zaki Mahdi , Zsila Ágnes , Bailey Nicola , Orosz Gábor
Published: February 2025

Background

Explosive remnants of war claim more than three lives every day in Afghanistan. This study evaluates the impact of BBC Media Action Afghanistan’s Explosive Ordnance Risk Education project in raising public awareness and promoting safe behaviours regarding explosive ordnances in Afghanistan. The project deployed a multimedia approach to reach a mass audience, including a radio discussion show, public service announcements on TV and radio, social media content and playing content on intercity buses.

Methods

A panel study with 400 participants from high-risk provinces assessed knowledge, discussion and behavioural intentions related to explosives before and after a mass media intervention. In the broadcast period, the research unobtrusively monitored the dosage of exposure to the media content.

Results

Findings from the panel study indicated a significant increase in discussions about explosive risks and safer behavioural interventions (e.g. avoiding and reporting explosive ordnances) post intervention.

Conclusion

The results constitute one of the first pieces of systematically collected evidence on media and communication’s potential in explosive risk education by facilitating interpersonal discussion and in turn change of behavioural intentions in areas contaminated by explosive ordnances and remnants of war.
Mechanisms of paediatric injury: an 11-year review of injury trends from the National Trauma Data Bank
Authors: Tomas Carissa , Kallies Kara , Levas Michael , deRoon-Cassini Terri , Cassidy Laura , Flynn-O’Brien Katherine
Published: February 2025

Background/purpose

Unintentional injuries are the leading cause of death among children and adolescents. The objective of this study was to describe temporal trends of paediatric traumatic injury over an 11-year period by mechanism of injury (MOI), age, sex, race and ethnicity, injury severity and hospital discharge disposition.

Methods

The National Trauma Data Bank was queried to identify paediatric patients (1–17 years old) injured from 2012 to 2022. Two-sided non-parametric Mann-Kendall trend tests were used to evaluate temporal trends of MOI for all patients and within demographic groups.

Results/outcomes

Over the 11-year period, 1 092 308 injury records met study inclusion criteria and had complete demographic and MOI data. Across all patients, there was a significant increase in bites and stings, cut/pierce injuries and firearm injuries, whereas there were decreasing trends in pedestrian and other blunt injuries over time. There was a significant increase in injury over time for Black, Hispanic or Latino, and Pacific Islander patients and those 5–9 years old. The MOIs with the highest injury severity and in-hospital mortality were firearm, pedestrian and motor vehicle transportation occupant injuries.

Conclusions

Though a few MOIs increased for all paediatric patients in the study period, disparities persist for several specific populations. As such, injury prevention strategies should be tailored based on age, sex and race or ethnicity, and relevant education and resources should be provided to both children and their adult guardians. Future research should consider additional socioeconomic and community-based characteristics.
Targeted delivery of CCL3 reprograms macrophage antigen presentation and enhances the efficacy of immune checkpoint blockade therapy in hepatocellular carcinoma
Authors: Liu Muqi , Li Linzhe , Cao Lu , Li Wei , Gu Xingshi , Yang Min , Wu Di , Li Yanan , Deng Yao , Zhang Juan , Yang Cejun , Liang Qi , Liu Huaping , Rong Pengfei , Ma Xiaoqian , Wang Wei
Published: February 2025

Background

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, especially in advanced stages where limited treatment options result in poor prognosis. The immunosuppressive tumor immune microenvironment (TIME), characterized by low immune cell infiltration and exhaustion, limits immunotherapy efficacy. To address this, our study investigates the role of C-C motif chemokine ligand 3 (CCL3) in modulating the HCC TIME.

Methods

We analyzed CCL3 expression in human HCC samples from The Cancer Genome Atlas database, focusing on its correlation with inflammatory gene signatures and immune cell infiltration. High-dimensional single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence were used to investigate CCL3’s effects on macrophage function and T cell activation. The biological impact of CCL3 on macrophages was assessed using co-culture systems, confocal imaging, metabolite detection, and inhibition assays. Preclinical HCC models and ex vivo tumor fragment assays further explored how CCL3 modulates immune responses and enhances immune checkpoint blockade efficacy.

Results

Our study shows that CCL3 is suppressed in the tumor microenvironment and positively correlates with immune infiltration and inflammatory responses. Targeted liver delivery of rAAV-Ccl3 reprograms the immune microenvironment in HCC, promoting immune cell recruitment and tertiary lymphoid structure formation, thus suppressing tumor growth via immune engagement. Through scRNA-seq, flow cytometry, and multiplex immunofluorescence, we found that CCL3 enhances macrophage antigen uptake and activates cytotoxic T cells. In vivo and in vitro experiments confirmed that CCL3 facilitates T cell infiltration and upregulates MHC II expression on macrophages, enhancing antigen presentation. The CCL3-CCR5 pathway also boosts macrophage metabolism, increasing lysosomal activity and antigen uptake, thereby strengthening adaptive immune responses and increasing sensitivity to immune checkpoint blockade therapies in preclinical models.

Conclusions

This study highlights the pivotal role of CCL3 in reshaping the TIME and enhancing antitumor immunity in HCC. By promoting immune cell recruitment and enhancing antigen presentation, CCL3 demonstrates significant potential to improve the efficacy of immunotherapy, particularly in combination with immune checkpoint inhibitors. Targeting CCL3 may help to overcome the immunosuppressive TIME in HCC and improve patient outcomes.
Association of single and multiple cardiometabolic diseases with atrial fibrillation: a prospective cohort study
Authors: Peng Qunyong , Ma Tianqi , Gao Ming , Wang Xuerui , Pan Wei
Published: February 2025

Background

Individual cardiometabolic diseases (CMDs) increase atrial fibrillation (AF) risk; however, whether multiple CMDs exert a cumulative effect on AF risk remains unclear. Our objective was to examine the link between coexisting CMDs and AF, as well as their cumulative impact.

Methods

This UK Biobank-based prospective cohort study included data from participants with information related to CMDs and AF. The assessment of CMDs and AF was based on participants’ self-reported medical histories and electronic health records. Cox proportional hazard regression models were employed to analyse the link between the number of CMDs and AF and to determine the cumulative effect of multiple CMDs. Further, we performed stratified analyses and adjusted for confounding factors.

Results

The study included 308 916 participants. The risk of AF was substantially associated with varying numbers of CMDs after multivariable adjustment in comparison to the reference group (all p<0.001). In the fully adjusted model, participants with 1, 2 and ≥3 CMDs exhibited elevated risks of 54% (HR: 1.54, 95% CI 1.48 to 1.59), 104% (HR: 2.04, 95% CI 1.94 to 2.15) and 212% (HR: 3.12, 95% CI 2.87 to 3.38), respectively. A significant cumulative dose-response relationship was noted between the number of CMDs and AF risk (HR: 1.45, 95% CI 1.42 to 1.48, p<0.001). A consistent dose-dependent cumulative relationship was observed in both stratified and sensitivity analyses.

Conclusions

Multiple CMDs increased AF risk and exhibited a significant cumulative effect based on the number of CMDs.
Efficacy of cardiac myosin inhibitors mavacamten and aficamten in hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomised controlled trials
Authors: Aman Ayesha , Akram Arfa , Akram Bisma , Maham Momina , Bokhari Masooma Zainab , Akram Aleena , Akram Sania , Yaqub Furqan
Published: February 2025

Background

Unlike other suggested therapies, myosin inhibitors have been shown to change the course of hypertrophic cardiomyopathy by altering the contractile mechanics of cardiomyocytes. This meta-analysis sought to determine the efficacy of mavacamten and aficamten in hypertrophic cardiomyopathy.

Methods

The online databases were searched from inception to July 2024, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, ClinicalTrials.gov. The meta-analytical data were pooled using risk ratios (RRs) with 95% CI, standard mean difference (SMD) and SE.

Results

A total of 6 randomised controlled trials with 826 hypertrophic cardiomyopathy patients (mean age±SD up to 59.8±14.2 years in intervention vs 60.9±10.5 years in placebo) were included in our study. Of these, 443 received a cardiac myosin inhibitor and 383 received a placebo. The resting left ventricular outflow tract (LVOT) gradient between the two groups was considerably improved by cardiac myosin inhibitors (MD −57.27; 95% CI −63.05 to −51.49). Significant differences were also observed in the post-Valsalva LVOT gradient between the two groups (MD −55.86; 95% CI −65.55 to −46.18). Significantly decreased left ventricle ejection fraction (LVEF) was also seen (MD −4.74; 95% CI −7.22 to −2.26). The New York Health Association (NYHA) class improvement between the two groups also changed significantly (RR 2.21; 95% CI 1.75 to 2.80). Cardiac myosin inhibitors also caused significant improvement in the Kansas City Cardiomyopathy Questionnaire in a Clinical Summary Score between the two groups (MD 7.71; 95% CI 5.37 to 10.05) and significant reduction in the N-terminal pro-B-type natriuretic peptide (SMD −13.27; 95% CI −17.51 to −9.03) and the cardiac troponin I (SMD −11.90; 95% CI −15.07 to −8.72).

Conclusion

According to our meta-analysis, cardiac myosin inhibitors significantly improve the resting and post-Valsalva LVOT gradient, reduce the LVEF and improve the NYHA class and cardiac biomarkers when compared with the placebo.

PROSPERO registration number

CRD52024586161.
Targeting the IL-17A pathway for therapy in early-stage tendinopathy
Authors: Millar Neal L , McInnes Iain B , Kolbinger Frank , Raulf Friedrich , Akbar Moeed , Li Yufei , Beckmann Nicolau , Accart Nathalie , Leupin Olivier , Calonder Claudio , Schieker Matthias , Kneissel Michaela , Bruns Christian , Siegel Richard M , Weber Eckhard
Published: February 2025

Objectives

Tendinopathy is a frequent clinical problem and represents an extraordinary health economic and socioeconomic burden with high unmet medical needs. Recent clinical evidence suggests blockade of interleukin 17A (IL-17A) for tendinopathy therapy. The present preclinical study elucidates the biological mechanisms of IL-17A pathway stimulation and blockade in tendinopathy.

Methods

We explored whether IL-17A and other IL-17 family members are differentially expressed in biopsies of healthy, early-stage and late-stage tendinopathic human rotator cuff tendons using RT-qPCR. IL-17 pathway signature genes in healthy human tendon-derived cells were identified following IL-17A stimulation using AmpliSeq RNA. The molecular, structural and functional consequences of IL-17A pathway stimulation were explored in healthy human tendon-derived cells and in a rat tendon fascicle model ex vivo. The effects of IL-17A pathway blockade were investigated in a rat model of rotator cuff tendinopathy in vivo.

Results

We provide evidence of differential expression of IL-17A mRNA (IL17A) versus other IL-17 family members in human rotator cuff early-stage tendinopathy. In human tendon-derived cells, stimulation with IL-17A induced the expression of the selected IL-17A pathway signature genesNFKBIZ, ZC3H12A, CXCL1, IL6, MMP3. Expression was inhibited by IL-17A blockade. In the rat ex vivo and in vivo models, IL-17A blockade alleviated inflammatory immune effector release, tendon structural degeneration, tendon inflammation and impaired tendon function.

Conclusion

Our data provide evidence that IL-17A is a key contributor to the pathogenesis of tendinopathy by promoting tendon inflammation and degeneration and that IL-17A blockade may represent a potential therapy in early-stage tendinopathy.
Continued nintedanib in patients with systemic sclerosis-associated interstitial lung disease: 3-year data from SENSCIS-ON
Authors: Allanore Yannick , Vonk Madelon C , Distler Oliver , Azuma Arata , Mayes Maureen D , James Alexandra , Kohlbrenner Veronika , Alves Margarida , Khanna Dinesh , Highland Kristin B
Published: February 2025

Objective

We assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.

Methods

Adverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON (‘continued nintedanib’ group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug–drug interaction study and then received nintedanib in SENSCIS-ON (‘initiated nintedanib’ group).

Results

The continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised 247 patients (231 from SENSCIS). Diarrhoea was the most frequent adverse event, reported in 152 (77.2%) and 183 (74.1%) patients in the continued nintedanib and initiated nintedanib groups, respectively. Among patients in the continued and initiated nintedanib groups, respectively, 53 (26.9%) and 148 (59.9%) had ≥1 dose reduction, 72 (36.5%) and 131 (53.0%) had ≥1 treatment interruption and 29 (14.7%) and 72 (29.1%) had adverse events that led to treatment discontinuation. Mean (SE) changes in FVC (mL) at week 148 were −189.1 (29.5) in the continued nintedanib group and −126.4 (26.4) in the initiated nintedanib group.

Conclusion

The safety profile of nintedanib over 148 weeks of SENSCIS-ON was consistent with that reported in SENSCIS. Changes in FVC during SENSCIS and SENSCIS-ON supported a continued effect of nintedanib on slowing the decline in lung function, but showed continued progression of SSc-ILD.
Incidence of rheumatoid arthritis in Austria: a prospective population-based cohort study in a federal province
Authors: Puchner Rudolf , Sautner Judith , Ritschl Valentin , Pieringer Herwig , Alkin Alois , Balcar Lorenz , Rammer Yvonne , Schumacher Sabine , Stamm Tanja A
Published: February 2025

Objective

When it comes to prospective studies on the incidence of rheumatoid arthritis (RA), the Norfolk study from 1994 is still frequently cited as prospective incidence data by many countries lacking comprehensive RA registries, including Austria. The aim of this study was, therefore, to gather robust data on the incidence of RA among Austrian adults for the first time.

Methods

All Upper Austrian rheumatologists reported newly diagnosed RA patients with symptom onset between 2016 and 2018, together with demographic data, laboratory and radiographic results. Cases still unclear at the end of 2018 were tracked in an extended observation period until 2023.

Results

In total, 701 RA cases were reported. 583 complete patient datasets were analysed. In all 551 individuals with a mean age of 60.2 (±14.2) years, 359 (65.2%) being females, the diagnosis of RA was ascertained clinically by a rheumatologist, optionally applying RA-classification criteria. Across all 3 years, the annual RA incidence rate was 14.9/100 000 (95% CI 12.9 to 17.3), ranging from 20.0/100 000 (95% CI 17.6 to 22.7) in 2016 to 13.5/100 000 (95% CI 11.5 to 15.7) in 2017 and 11.3/100 000 (95% CI 9.5 to 13.3) in 2018. The incidence was highest in individuals >65 years (21.6/100 000, 95% CI 16.4 to 27.9). Women had a higher RA incidence (18.1/100 000, 95% CI 14.9 to 21.7) than men (10.4/100 000, 95% CI 8.0 to 13.3).

Conclusions

This study provided prospective population-based data on the incidence of RA in Austrian adults for the first time. Incidence rates were comparable with other European countries. Compared with the Norfolk study, we found lower rates in both genders, more pronounced in females, however.
Religious practices and quality of life in palliative care: insights from Tanzania
Authors: Sokoine Sonia Nada Edward , Kilonzo Gad , Ahmed Nadia , Sawe Kelvin Furanaeli
Published: February 2025

Objective

To explore the role of religious practices in palliative care and their impact on the quality of life among inpatients at Ocean Road Cancer Institute.

Methods

A quantitative cross-sectional study was conducted, using structured surveys to gather data from 150 inpatients receiving palliative care. The WHO Quality of Life-BREF (WHOQOL-BREF) tool was used to measure quality of life, alongside data on the usage of religious practices.

Results

The findings reveal that most of the participants (90%) expressed a need for religious practices, predominantly prayer. Notably, access to these practices positively correlated with improved perceptions of well-being, despite a considerable portion of patients reporting a poor quality of life (84.7%).

Conclusion

The study’s findings highlight the importance of incorporating religious practices into palliative care, particularly in low-resource settings like Tanzania, to provide culturally sensitive, holistic support for patients with cancer.
Experimental investigations on seepage erosion-interface shear behavior of suction caisson in sandy seabed
Authors: Zhang Yaru , Wang Lizhong , Rui Shengjie , Xu Mengtao , Guo Zhen
Published: February 2025

To evaluate the seepage erosion during the installation of suction caissons, this study developed a seepage erosion-interface shear test system to simulate the erosion phenomena. First, a parametric analysis was conducted to systematically investigate the effects of main factors (consolidation pressure, particle size distribution, inhomogeneous pressure) on sand erosion characterization, vertical deformation, seepage characterization, as well as the interface strength of suction caisson. Following this, interface shear tests were performed to compare and analyze the changes in caisson-sand interface strength before and after soil erosion. It is indicated that the soil erodibility initially increases and then decreases when increasing fine particles. Seepage channels form first at the bottom and become dominant near the caisson wall, enhancing the sand hydraulic conductivity. In addition, the soil inside the caisson is less stable under smaller consolidation pressure. After the erosion, changes in sand particle distributions significantly reduce the caisson-sand interface strength with the maximum reduction of approximately 50%. This study emphasizes the influence of seepage erosion on caisson in-service capacity, which needs more attention in practice.
Cecal Microbiome in Broiler Chicken Related to Antimicrobial Feeding and Bird’s Sex
Authors: Mak Philip , Yin Xianhua , Clairmont Lindsey , Bean-Hodgins Lisa , Kiarie Elijah , Tang Joshua , Lepp Dion , Diarra Moussa
Published: February 2025

This study investigated the cecal microbiome of broilers raised under specific antimicrobial feeding programs (AFPs). A total of 2,304-day-old Ross-708 male (M, n=1,152) and female (F, n=1,152) chicks were distributed into 48 floor pens which were allocated to one of three AFPs: Conventional (CON), raised without medically important antibiotics (RWMIA), and raised without antibiotics (RWA). At 28 (D28) and 41 (D41) days of age, cecal contents were collected for culture dependent and independent analyses. At both 28 and 41 days, Enterococcus was more abundant in RWA-raised broilers than other groups with the most abundance of this bacterium being found in female birds (P < 0.05). At D41, the most abundant Eimeria tenella counts was observed in RWA-raised broiler ceca (P < 0.05). Sex effects were observed on the abundances of four of the 248 identified antimicrobial resistance genes (ARGs) while abundances of 10 were modulated by AFPs (P <0.05). Ceca of females birds showed more tssB than males, and ceca of RWMIA-raised birds contained the highest abundance of chuY genes regardless of sex. This study showed that in a specific feeding program, cecal resistome can be affected by chicken’s sex contributing to understand the AMR related to the AMU.