bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methodological report of a cross-sectional survey of abortion-related knowledge, attitudes and practices amongst health professionals in Britain, strategies adopted and lessons learned: evidence from the SACHA Study
Authors: French R. S. , Palmer M. J. , McCarthy O. , Salaria N. , Meiksin R. , Shawe J. , Lewandowska M. , Scott R. , Wellings K. ,   the SACHA Study Team, Aronsson A. , Baraitser P. , Cameron S. , Free C. , Keogh L. , Lohr P. A. , Murphy C. , Norman W. V. , Reiter J. , Sheldon S. , Wong G. 
Published: December 2024

Abstract
Background
Most surveys examining health professionals’ knowledge, attitudes and practices around abortion have used convenience samples and have targeted doctors. Our goal in the SACHA Study, drawing on evidence-based strategies to maximise response rates, was to achieve a representative sample of a wider range of health professionals, working in general practice, maternity services, pharmacies, sexual and reproductive health (SRH) clinics and specialist abortion services in Britain, to explore the knowledge, attitudes and experience of abortion care and views on future models of delivery.

Methods
A cross-sectional questionnaire-based survey of midwives, doctors, nurses and pharmacists in England, Scotland and Wales was undertaken between November, 2021 and July, 2022. We used a stratified cluster sampling approach to select a random sample of sites and all eligible staff within those services were asked to respond to the survey. Evidence-based strategies to maximise completion rates were adopted, including postal delivery of the one-page questionnaire with personal letter of invitation and a stamped address envelope for return, inclusion of an unconditional voucher and follow-up.

Results
Overall, 147 of the 314 (46.8%) health service sites randomly selected took part in the survey. Reasons for non-participation included local Research and Development (R&D) Department non-response, lack of resources or insufficient time to support or approve the study, lack of interest in or perceived relevance of the topic and insufficient capacity to take part, exacerbated by work demands during the COVID epidemic. Of the 1370 questionnaires sent to eligible identified participants within these services, 771 were completed and returned (56.3%). At the service level the highest proportion of returns was from SRH clinics (81.0%) and the lowest from general practice (32.4%). In relation to profession, returns were highest amongst midwives (69.6%) and lowest amongst pharmacists (36.5%).

Conclusions
Obtaining information about health professional knowledge, attitudes and practices is key to guide service development and policy and to identify gaps in training and service provision in abortion. Despite our attempts to gain a representative sample of health professionals, the challenges we experienced limited the representativeness of the sample, despite the use of an evidence-based strategy.
Patient characteristics and healthcare use for high-cost patients with musculoskeletal disorders in Norway: a cohort study
Authors: Amundsen Olav , Moger Tron Anders , Holte Jon Helgheim , Haavaag Silje Bjørnsen , Bragstad Line Kildal , Hellesø Ragnhild , Tjerbo Trond , Vøllestad Nina Køpke 
Published: December 2024

Abstract
Background
A high proportion of healthcare costs can be attributed to musculoskeletal disorders (MSDs). A small proportion of patients account for most of the costs, and there is increasing focus on addressing service overuse and high costs. We aimed to estimate healthcare use contributing to high costs over a five-year period at the individual level and to examine if healthcare use for high-cost patients is in accordance with guidelines and recommendations. These findings contribute to the understanding of healthcare use for high-cost patients and help in planning future MSD-care.

Methods
This study combined Norwegian registries on healthcare use, diagnoses, demographic, and socioeconomic factors. Patients (≥ 18 years) were included by their first MSD-contact in 2013–2015. We analysed healthcare use during the subsequent five years. Descriptive statistics were used to compare high-cost (≥ 95th percentile) and non-high-cost patients. Total healthcare contacts and costs for high-cost patients were examined stratified by number of hospitalisations and surgical treatments. Healthcare use of General Practitioners (GPs), physiotherapy, chiropractor and Physical Medicine and Rehabilitation physicians prior to the first hospitalisation or surgical treatment for a non-traumatic MSD was registered.

Results
High-cost patients were responsible for 61% of all costs. Ninety-four percent of their costs were related to hospital treatment. Ninety-nine percent of high-cost patients had at least one hospitalisation or surgical procedure. Out of the high-cost patients, 44% had one registered hospitalisation or surgical procedure, 52% had two to four and 4% had five or more. Approximately 30–50% of patients had seen any healthcare personnel delivering conservative treatment other than GPs the year prior to their first hospitalisation/surgical treatment for a non-traumatic MSD.

Conclusion
Most healthcare costs were concentrated among a small proportion of patients. In contrast to guidelines and recommendations, less than half had been to a healthcare service focused on conservative management prior to their first hospitalisation or surgical treatment for a non-traumatic MSD. This could indicate that there is room for improvement in management of patients before hospitalisation and surgical treatment, and that ensuring sufficient capacity for conservative care and rehabilitation can be beneficial for reducing overall costs.
The human Dicer helicase domain is capable of ATP hydrolysis and single-stranded nucleic acid binding
Authors: Ciechanowska Kinga , Szczepanska Agnieszka , Szpotkowski Kamil , Wojcik Klaudia , Urbanowicz Anna , Kurzynska-Kokorniak Anna 
Published: December 2024

Abstract
Background
Vertebrates have one Dicer ortholog that generates both microRNAs (miRNAs) and small interfering RNAs (siRNAs), in contrast to the multiple Dicer-like proteins found in flies and plants. Here, we focus on the functions of the human Dicer (hDicer) helicase domain. The helicase domain of hDicer is known to recognize pre-miRNA substrates through interactions with their apical loop regions. Besides interacting with canonical substrates, the hDicer helicase domain has also been suggested to bind many different cellular RNAs; however, a comprehensive study of the biochemical activities and substrate specificity of the hDicer helicase domain towards different nucleic acids has yet to be undertaken.

Results
Here, we reveal that full-length hDicer, through its helicase domain, hydrolyzes ATP. The ATPase activity of hDicer can only be observed under low-turnover conditions. To the best of our knowledge, this is the first time this activity has been reported for vertebrate Dicers. We also show that the hDicer helicase domain binds single- but not double-stranded RNAs and DNAs and that this binding activity presumably is not nucleotide-dependent. Moreover, the hDicer helicase domain may influence the structure of the RNA to which it binds.

Conclusions
Preservation of ATPase activity by hDicer suggests that this enzyme performs many more functions in the cell than is currently assumed. Our findings open new avenues for future studies aimed at defining the cellular activities of hDicer that may be associated with these newly described biochemical properties: ATP hydrolysis and single-stranded nucleic acid binding activities.
The burden and clinical trajectory of immune checkpoint inhibitor-induced endocrinopathies: an 8-year experience
Authors: Ata Fateen , Khan Adeel Ahmad , Algorani Emad , Alsharafi Amr Faisal Musaed , Shdid Reham Abo , Nofal Mohammad , Ibrahim Ayman R. , Abdullah Loai , Annan Khalil Youssef El , Al-Bkoor Tareq Emad Hawash , Rasul Kakil Ibrahim , Elhadd Tarik , Surchi Haval 
Published: December 2024

Abstract
Background
Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancer patients, but the emergence of ICI-related endocrinopathies (IREs) has introduced new clinical challenges. Despite worldwide recognition of these adverse effects, data from the Middle East is scarce.

Methods
This retrospective-observational study included adult cancer patients who received at least one dose of ICI between January 2015 and January 2023. Descriptive statistics and multivariable regression (MVR) models were applied to delineate the incidence and clinical impact of IREs.

Results
The median age of 649 included patients was 55 years, with male preponderance (70.7%). The incidence of IREs was 26.7%, dominated by primary hypothyroidism (62.4%), insulin deficiency (15%), and primary hyperthyroidism (13.9%). Pembrolizumab (62%) was the most utilized ICI among the study cohort, followed by nivolumab (23.7%), atezolizumab (12.5%), durvalumab (0.9%), avelumab (0.6%) and ipilimumab (0.1%). The mortality rates in the cohort and the IRE subgroup were 43.4% and 42.2%. MVR revealed age (OR 1.02, 95% CI (1.003–1.03), P = 0.02), pre-ICI white-cell (WBC) count (OR 0.94, 95% CI (0.89–0.99), P = 0.04), pembrolizumab (OR 2.6, 95% CI (1.05–6.3), P = 0.04), and nivolumab use (OR 2.6, 95% CI (1.04–6.6), P = 0.04) as significant predictors of IREs. After MVR, factors influencing mortality in the subgroup with IREs included a higher age (OR 1.1, 95% CI 1.04–1.2, P = 0.001) and platelet-to-lymphocyte ratio (OR 1.004, 95% CI 0.7–1.4, P = 0.006).

Conclusions
This first extensive Middle Eastern and South Asian cohort reported a higher-than-previously known incidence of IREs. Hypothyroidism, insulin deficiency, and hyperthyroidism were the commonest IREs, with pembrolizumab being the commonest ICI. IRE development was associated with higher age, a low WBC count, pembrolizumab, and nivolumab use. The development of IREs did not seem to influence mortality. Further research on IREs is imperative to optimize management guidelines in the era of precision medicine.
Incidence, risk factors, and epidemiological trends of tracheal cancer: a global analysis
Authors: Huang Junjie , Chen Mingtao , Zhang Lin , Lin Xu , Lucero-Prisno Don Eliseo , Zhong Claire Chenwen , Xu Wanghong , Zheng Zhi-Jie , Withers Mellissa , Wong Martin C. S. ,   N. C. D. Global Health Working Group,   Association of Pacific Rim Universities (APRU)
Published: December 2024

Abstract
Background
Tracheal cancer is a rare malignancy with limited research but high mortality rates. This study aims to analyse recent data to understand the global burden, trends, and risk factors for tracheal cancer, facilitating improved prevention and treatment strategies.

Methods
We conducted a study on tracheal cancer using data from the Global Cancer Observatory and the Cancer Incidence in Five Continents databases. We collected information on the incidence of tracheal cancer, risk factors, and the Human Development Index (HDI) at the country level. The univariate linear regression was used to explore the relationship between tracheal cancer and the various risk factors. We utilised joinpoint regression analysis to calculate the Average Annual Percentage Change (AAPC) in tracheal cancer incidence.

Results
The global age-standardised rate of incidence of tracheal cancer was 2.9 per 10 million (3,472 cases in total) in 2022, with the highest regional incidence observed in Central and Eastern Europe (ASR = 9.0) and the highest national incidence in Hungary (12.5). Higher incidence was found among the males (3.8) than females (2.0); among the older adults aged 50-74 (11.9) than the younger population aged 15-49 (1.2). A higher tracheal cancer incidence ratio was associated with higher levels of smoking, alcohol drinking, diabetes, lipid disorders, and HDI. Despite the overall decreasing trends for all population groups (highest decrease in Thailand; AAPC: -15.06, 95% CI: -21.76 to -7.78, p = 0.002), there was an increase in some female populations (highest increase in Colombia, AAPC: 19.28, 95% CI: 16.48 to 22.15, p < 0.001) and younger populations (highest increase in Ireland; AAPC: 29.84, 95% CI: 25.74 to 34.06, p < 0.001).

Conclusion
This study provides a comprehensive analysis of tracheal cancer, focusing on risk factors and population-level trends. There has been an overall decreasing trend in the incidence of tracheal cancer, particularly among males and older adults, while the decline is less pronounced in females and younger individuals. Further research is needed to explore the underlying drivers of these epidemiological trends.
The plasma lipidome varies with the severity of metabolic dysfunction-associated steatotic liver disease
Authors: Heymann Clément J. F. , Mak Anne Linde , Holleboom Adriaan G. , Verheij Joanne , Shiri-Sverdlov Ronit , van Mil Saskia W. C. , Tushuizen Maarten E. , Koek Ger H. , Grefhorst Aldo 
Published: December 2024

Abstract
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics. We aimed to explore whether the plasma lipidome and its variations can serve as a biomarker for MASLD stages.

Methods
We investigated the plasma lipidome of 7 MASLD-free subjects and 32 individuals with MASLD, of whom 11 had MASH based on biopsy scoring.

Results
Compared with the MASLD-free subjects, individuals with MASLD had higher plasma concentrations of sphingolipids, glycerolipids, and glycerophospholipids. Only plasma concentrations of ceramide-1-phosphate C1P(d45:1) and phosphatidylcholine PC(O-36:3), PC(O-38:3), and PC(36:2) differed significantly between presence of MASH in individuals with MASLD. Of these lipids, the first three have a very low relative plasma abundance, thus only PC(36:2) might serve as a biomarker with higher plasma concentrations in MASLD individuals without MASH compared to those with MASH.

Conclusions
Plasma lipids hold promise as biomarkers of MASLD stages, whereas plasma PC(36:2) concentrations would be able to distinguish individuals with MASH from those with MASLD without MASH.
Lessons from an intervention study on the sustainability of after-school comprehensive sexuality education in Zambia: the perspectives of teachers, health workers and guardians
Authors: Svanemyr Joar , Zulu Joseph Mumba , Munsaka Ecloss , Sandøy Ingvild Fossgard 
Published: December 2024

Abstract
Background
Comprehensive sexuality education (CSE) has been introduced in many sub-Saharan African countries, but limited political interest and insufficient funding have resulted in many CSE initiatives being dependent on donor funding or non-governmental organisations (NGOs) supporting its implementation. This has created concerns about the sustainability of the programmes. The objective of this study was to explore factors affecting the sustainability of CSE delivered through a youth club organized after school hours in Zambia.

Methods
We interviewed teachers and community health workers (CHWs) who had implemented CSE as part of an after-school youth club set up as part of a cluster randomized controlled trial. The trial evaluated the effectiveness of economic support for adolescent girls, CSE and community dialogue meetings on adolescent childbearing. Teachers and CHWs in 63 schools were trained to facilitate the CSE youth clubs, and they were given economic incentives during the trial´s two-year intervention period to organize meetings every fortnight. Two years after the external support for the youth clubs ended, we conducted qualitative interviews with the facilitators in 15 of the 63 schools, interviews with some head teachers, and focus group discussions with guardians of adolescent girls.

Results
Whereas CHWs were generally supportive of teaching adolescents about contraception, some of the teachers stressed that abstinence was the most effective method to avoid pregnancy and diseases. The respondents’ diverging points of view did not affect their willingness to continue teaching CSE, including contraception. However, the youth club meetings were only continued in a few schools after the external support period ended. This was attributed to transfers of trained teachers and a lack of training among the remaining staff; lapse of moral support, resources and incentives; limited involvement of the school management in the CSE initiative; and attention shifting to other projects.

Conclusion
To ensure the sustainability of CSE initiatives for adolescents, emphasis should be placed on training several teachers in each school, and continued moral support and encouragement also appeared essential.
Trial registration: ISRCTN (ISRCTN12727868).
Knockout of AMPA receptor binding protein Neuron-specific gene 2 (NSG2) enhances associative learning and cognitive flexibility
Authors: Zimmerman Amber J. , Serrano-Rodriguez Antonio , Sun Melody , Wilson Sandy J. , Linsenbardt David N. , Brigman Jonathan L. , Weick Jason P. 
Published: December 2024

AbstractThe vast majority of gene mutations and/or gene knockouts result in either no observable changes, or significant deficits in molecular, cellular, or organismal function. However, in a small number of cases, mutant animal models display enhancements in specific behaviors such as learning and memory. To date, most gene deletions shown to enhance cognitive ability generally affect a limited number of pathways such as NMDA receptor- and translation-dependent plasticity, or GABA receptor- and potassium channel-mediated inhibition. While endolysosomal trafficking of AMPA receptors is a critical mediator of synaptic plasticity, mutations in genes that affect AMPAR trafficking either have no effect or are deleterious for synaptic plasticity, learning and memory. NSG2 is one of the three-member family of Neuron-specific genes (NSG1-3), which have been shown to regulate endolysosomal trafficking of a number of proteins critical for neuronal function, including AMPAR subunits (GluA1-2). Based on these findings and the largely universal expression throughout mammalian brain, we predicted that genetic knockout of NSG2 would result in significant impairments across multiple behavioral modalities including motor, affective, and learning/memory paradigms. However, in the current study we show that loss of NSG2 had highly selective effects on associative learning and memory, leaving motor and affective behaviors intact. For instance, NSG2 KO animals performed equivalent to wild-type C57Bl/6n mice on rotarod and Catwalk motor tasks, and did not display alterations in anxiety-like behavior on open field and elevated zero maze tasks. However, NSG2 KO animals demonstrated enhanced recall in the Morris water maze, accelerated reversal learning in a touch-screen task, and accelerated acquisition and enhanced recall on a Trace Fear Conditioning task. Together, these data point to a specific involvement of NSG2 on multiple types of associative learning, and expand the repertoire of pathways that can be targeted for cognitive enhancement.
Dynamic changes in the hippocampal neuronal circuits activity following acute stress revealed by miniature fluorescence microscopy imaging
Authors: Gerasimov Evgenii , Pchitskaya Ekaterina , Vlasova Olga , Bezprozvanny Ilya 
Published: December 2024

AbstractCoordinated activity of neuronal ensembles is a basis for information processing in the brain. Recent development of miniscope imaging technology enabled recordings of neuronal circuits activity in vivo in freely behaving animals. Acute stress is believed to affect various hippocampal functions, especially memory. In the current study, we utilized miniscope imaging to investigate the hippocampal neuronal circuits properties in a mouse as function of time and immediately in response to an acute stress, induced by passive restraint, 3 h and 10 days after. Comprehensive quantitative analysis of network activity changes at the neuronal ensembles level revealed highly stable neuronal activity parameters, which exhibited a rapid and robust shift in response to acute stress stimulation. This shift was accompanied by the restructuring of the pairwise-correlated neuronal pairs. Remarkably, we discovered that ensembles activity characteristics returned to the initial state following recovery period, demonstrating hippocampal homeostatic stability at the neuronal circuits level. Obtained results provide an evidence about hippocampal neuronal ensembles activity in response to acute stress over time.
Parvovirus B19 infection in children: a comprehensive review of clinical manifestations and management
Authors: Bloise Silvia , Cocchi Enrico , Mambelli Lorenzo , Radice Caterina , Marchetti Federico 
Published: December 2024

AbstractParvovirus B19 (B19V) is a significant pathogen responsible for a wide range of clinical manifestations, particularly in children and pregnant women. While B19V is most commonly recognized as the cause of Fifth disease, a mild erythematous illness in children, its clinical impact extends far beyond this condition. B19V can lead to severe complications, including transient aplastic crisis in individuals with chronic hemolytic anemias, arthralgia, and more severe joint diseases. During pregnancy, B19V infection poses serious risks, such as spontaneous abortion, non-immune hydrops fetalis, and fetal anemia, particularly when infection occurs between 9 and 20 weeks of gestation. Moreover, B19V is associated with a variety of organ system involvements, including cardiac, neurological, hepatic, and renal complications. These manifestations can range from mild to life-threatening, necessitating a broad spectrum of therapeutic approaches, including symptomatic care, immunoglobulins, corticosteroids, and supportive therapies. Despite the significant clinical burden posed by B19V, no specific antiviral treatment or vaccine is currently available, making early recognition and prompt management crucial for improving patient outcomes. This review provides a comprehensive overview of the diverse clinical presentations of B19V infection, with a focus on pediatric and pregnancy-related complications. It underscores the need for ongoing research into targeted therapies and highlights the importance of vigilant clinical management to mitigate the severe consequences of this pervasive virus.
EpiGePT: a pretrained transformer-based language model for context-specific human epigenomics
Authors: Gao Zijing , Liu Qiao , Zeng Wanwen , Jiang Rui , Wong Wing Hung 
Published: December 2024

AbstractThe inherent similarities between natural language and biological sequences have inspired the use of large language models in genomics, but current models struggle to incorporate chromatin interactions or predict in unseen cellular contexts. To address this, we propose EpiGePT, a transformer-based model designed for predicting context-specific human epigenomic signals. By incorporating transcription factor activities and 3D genome interactions, EpiGePT outperforms existing methods in epigenomic signal prediction tasks, especially in cell-type-specific long-range interaction predictions and genetic variant impacts, advancing our understanding of gene regulation. A free online prediction service is available at http://health.tsinghua.edu.cn/epigept.