bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive atlas of nuclear sequences of mitochondrial origin (NUMT) inserted into the pig genome
Authors: Bolner Matteo , Bovo Samuele , Ballan Mohamad , Schiavo Giuseppina , Taurisano Valeria , Ribani Anisa , Bertolini Francesca , Fontanesi Luca 
Published: September 2024

Abstract
Background
The integration of nuclear mitochondrial DNA (mtDNA) into the mammalian genomes is an ongoing, yet rare evolutionary process that produces nuclear sequences of mitochondrial origin (NUMT). In this study, we identified and analysed NUMT inserted into the pig (Sus scrofa) genome and in the genomes of a few other Suinae species. First, we constructed a comparative distribution map of NUMT in the Sscrofa11.1 reference genome and in 22 other assembled S. scrofa genomes (from Asian and European pig breeds and populations), as well as the assembled genomes of the Visayan warty pig (Sus cebifrons) and warthog (Phacochoerus africanus). We then analysed a total of 485 whole genome sequencing datasets, from different breeds, populations, or Sus species, to discover polymorphic NUMT (inserted/deleted in the pig genome). The insertion age was inferred based on the presence or absence of orthologous NUMT in the genomes of different species, taking into account their evolutionary divergence. Additionally, the age of the NUMT was calculated based on sequence degradation compared to the authentic mtDNA sequence. We also validated a selected set of representative NUMT via PCR amplification.

Results
We have constructed an atlas of 418 NUMT regions, 70 of which were not present in any assembled genomes. We identified ancient NUMT regions (older than 55 million years ago, Mya) and NUMT that appeared at different time points along the Suinae evolutionary lineage. We identified very recent polymorphic NUMT (private to S. scrofa, with < 1 Mya), and more ancient polymorphic NUMT (3.5–10 Mya) present in various Sus species. These latest polymorphic NUMT regions, which segregate in European and Asian pig breeds and populations, are likely the results of interspecies admixture within the Sus genus.

Conclusions
This study provided a first comprehensive analysis of NUMT present in the Sus scrofa genome, comparing them to NUMT found in other species within the order Cetartiodactyla. The NUMT-based evolutionary window that we reconstructed from NUMT integration ages could be useful to better understand the micro-evolutionary events that shaped the modern pig genome and enriched the genetic diversity of this species.
“Do they think I’m good enough?”: General practitioners’ experiences when treating doctor-patients
Authors: Hutton Claire J. , Kay Margaret , Round Penny , Barton Chris 
Published: September 2024

Abstract
Background
When doctors seek medical care, there is evidence that the treating doctor can struggle to provide optimal treatment. Guidelines state that doctor-patients should be treated like any other patient, but this is challenging for the treating doctor. This study set out to explore both the positive experiences general practitioners (GPs) have when caring for doctor-patients, and the challenges they confront. It sought to identify whether GPs believe they treat doctor-patients differently to other patients and if so, in what ways, for what reasons, and how this impacts their provision of care. The study also aimed to develop a model that makes sense of GPs’ experiences when caring for a patient who is also a medical doctor.

Method
Qualitative in-depth interviews with 26 GPs were carried out, with analysis of de-identified transcripts using pragmatic grounded theory. Evolving understandings were used to develop a model to make sense of GPs’ experiences caring for their doctor-patients.

Results
The core aspects of GPs’ experiences of treating fellow doctors centred around concepts of respect and collegiality. These play a central role in mediating how a treating doctor experiences a consultation with a doctor-patient, influencing the quality of care provided. GPs shared that the use of medical language (and assumptions about the doctor-patient’s knowledge/behaviours), testing, the exploration of sensitive issues, and the degree of shared decision-making were areas where their treatment might vary when treating a doctor-patient. Treating doctors often experience anxiety about errors and the likely scrutiny from the medical, and wider community. The decision to treat the doctor-patient differently was driven by a desire to maintain a sense of collegiality, to not offend, to meet their doctor-patient’s expectations, and to appear competent.

Conclusion
The professional socialisation of doctors, with its emphasis on collegiality and respect, plays a significant role in the dynamics of the therapeutic relationship when a doctor treats a doctor-patient. Current guidelines make little reference to these dynamics with the over-simplified ‘keep it normal’ recommendations. Treating doctors need evidence-informed training to navigate these challenges and ensure they can effectively deliver quality care to their doctor-patients.
Exploring the trend of age-standardized mortality rates from cardiovascular disease in Malaysia: a joinpoint analysis (2010–2021)
Authors: Hasani Wan Shakira Rodzlan , Musa Kamarul Imran , Cheng Kueh Yee , Dass Sarat Chandra 
Published: September 2024

Abstract
Introduction
Cardiovascular disease (CVD) is a major health concern worldwide, particularly in low- and middle-income countries. The COVID-19 pandemic that emerged in late 2019 may have had an impact on the trend of CVD mortality. This study aimed to investigate the trend and changes in CVD mortality rates in Malaysia, using age-standardized mortality rates (ASMR) from 2010 to 2021.

Methods
The Malaysian population and mortality data from 2010 to 2021 were obtained from the Department of Statistics Malaysia (DOSM). ASMRs from CVD per 100,000 population were calculated based on the World Health Organization (2000–2025) standard population using the direct method. The ASMRs were computed based on sex, age groups (including premature mortality age, 30–69 years), and CVD types. The annual percent change (APC) and average annual percent change (AAPC) of the ASMR with corresponding 95% confidence intervals (95% CI) were estimated from joinpoint regression model using the Joinpoint Regression Program, Version 4.9.1.0.

Results
Throughout the study period (2010–2021), ASMRs for CVD exhibited an increase from 93.1 to 147.0 per 100,000, with an AAPC of 3.6% (95% CI: 2.1 to 5.2). The substantial increase was observed between 2015 and 2018 (APC 12.6%, 95% CI: 5.4%, 20.3%), with significant changes in both sexes, and age groups 50–69, 70 years and over, and 30–69 (premature mortality age). Notably, the ASMR trend remained consistently high in the premature mortality age group across other age groups, with males experiencing higher rates than females. No significant changes were detected before or after the COVID-19 pandemic (between 2019 and 2021), except for females who died from IHD (10.3% increase) and those aged 0–4 (25.2% decrease).

Conclusion
Overall, our analysis highlights the persistently high burden of CVD mortality in Malaysia, particularly among the premature mortality age group. These findings underscore the importance of continued efforts to address CVD risk factors and implement effective prevention and management strategies. Further research is needed to fully understand the impact of the COVID-19 pandemic on CVD mortality rates and to inform targeted interventions to reduce the burden of CVD in Malaysia.
Uncovering the relationship between trace element exposure, cognitive function, and dietary inflammation index in elderly americans from the National Health and Nutrition Examination Survey 2011–2014
Authors: Tang Chunlan , Shen Min , Hong Hang 
Published: September 2024

Abstract
Background
The consequences of trace element exposure on cognitive function in elderly adults have been recognized as primarily attributed to the inflammatory response. It is noteworthy that diet can either exacerbate or reduce the inflammatory response. Despite this, there have been limited studies about the effects of diet on the relationship between trace element exposure and cognitive function.

Methods
A cross-sectional study utilized data from the 2011–2014 NHANES survey to explore the association between trace element exposure and cognitive function in elderly adults. The study enrolled 1726 participants, and generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression (WQS), and quantile g-computation regression analysis (Qg-comp) were conducted to assess the impact of five trace elements (lead, cadmium, mercury, manganese, and selenium) in blood on cognitive function under the anti-inflammatory and pro-inflammatory diet.

Results
The GLM analysis showed a positive correlation between selenium (Se) and both the instant recall test (IRT) and digit symbol substitution test (DSST) (β = 2.06, 95% CI: 0.70 ~ 3.41; and β = 6.41, 95% CI: 2.35 ~ 10.46, respectively). In contrast, cadmium (Cd) was negatively associated with DSST (β = -1.17, 95% CI: -2.13~ -0.22), and lead (Pb) was negatively associated with IRT (β = -0.47, 95% CI: -0.82~ -0.11). For the animal fluency test (AFT), the highest quartile of manganese (Mn) was negatively associated with the lowest quartile (β = -0.72, 95% CI: -1.34~-0.10), while mercury (Hg) showed no significant associations with cognitive function tests. Subgroup analysis revealed the effects of Cd on IRT and DSST and Se on DSST under the pro-inflammatory diet. Furthermore, The BKMR analysis showed an inverted U-shaped curve with the negative impact of trace element mixtures and DSST and a linearly negative trend with IRT in the pro-inflammatory diet. Among them, Cd was emphasized as the most potent risk factor, and Se was the most vital protective factor for IRT and DSST in WQS and Qg-comp analysis.

Conclusions
The study suggests that a high-quality diet might alleviate the adverse effects of Cd on IRT and DSST. High Se levels were also associated with better IRT and DSST scores in the pro-inflammatory diet. These findings provide valuable insights into the connection between diet, trace element exposure, and cognitive function in elderly adults.
Experiences as a clinical teaching fellow: interviews with clinical teaching fellows in the West Midlands
Authors: Harris Isobel Marion , Dennis Nicola , Ward Derek J , Sitch Alice J , Parry Jayne , Greenfield Sheila 
Published: September 2024

Abstract
Background
The majority of junior doctors in the UK do not proceed directly into specialty training after completing mandatory foundation training but instead take a year out of training. A common post undertaken during a year out of training is a clinical teaching fellow (CTF) role which is used to provide undergraduate medical student teaching. There is only a small amount of literature available regarding CTF posts, and very little of this explores experiences or reasons for taking up such as post. An understanding of the reasons why doctors are choosing to work as CTFs and what their experiences are in post will contribute to how the role is further developed and utilised within the NHS. This study aimed to explore the experiences of CTFs employed in the West Midlands at NHS hospital Trusts.

Methods
CTFs working in Trusts in the West Midlands region registered as students on the Education for Healthcare Professionals Post Graduate Certificate course at the University of Birmingham in August 2019 and 2020 who were enrolled in a longitudinal study were invited to take part in an individual interview asking about their experiences as CTFs.

Results
Nine CTFs participated in an interview. Five main themes were identified which related to their experiences in post and plans for future careers. Participants reported choosing to undertake a CTF role due to wanting a break from clinical work and having previously enjoyed delivering teaching. Positive experiences in post included lifestyle related benefits and self-development opportunities. Challenges identified with the role included the impact of COVID-19 and volume of students.

Conclusion
This is the first study to use interview methodology to explore experiences of CTFs, and has provided a valuable insight into the experiences of those in post in the West Midlands region. Understanding why doctors chose this job and what their experiences are could help to further develop and refine the role. To guarantee demands for teaching staff are met those employing CTFs should be aware of reasons why doctors apply for the post and ensure the post remains a desirable option.
Enhancing clinical data retrieval with Smart Watchers: a NiFi-based ETL pipeline for Elasticsearch queries
Authors: Al-Agil Mohammad , Obee Stephen J. , Dinu Vlad , Teo James , Brawand David , Patten Piers E. M. , Alhaq Anwar 
Published: September 2024

Abstract
Background
The aim is to develop and deploy an automated clinical alert system to enhance patient care and streamline healthcare operations. Structured and unstructured data from multiple sources are used to generate near real-time alerts for specific clinical scenarios, with an additional goal to improve clinical decision-making through accuracy and reliability.

Methods
The automated clinical alert system, named Smart Watchers, was developed using Apache NiFi and Python scripts to create flexible data processing pipelines and customisable clinical alerts. A comparative analysis between Smart Watchers and the legacy Elastic Watchers was conducted to evaluate performance metrics such as accuracy, reliability, and scalability. The evaluation involved measuring the time taken for manual data extraction through the electronic patient record (EPR) front-end and comparing it with the automated data extraction process using Smart Watchers.

Results
Deployment of Smart Watchers showcased a consistent time savings between 90% to 98.67% compared to manual data extraction through the EPR front-end. The results demonstrate the efficiency of Smart Watchers in automating data extraction and alert generation, significantly reducing the time required for these tasks when compared to manual methods in a scalable manner.

Conclusions
The research underscores the utility of employing an automated clinical alert system, and its portability facilitated its use across multiple clinical settings. The successful implementation and positive impact of the system lay a foundation for future technological innovations in this rapidly evolving field.
Differences in changes of data completeness after the implementation of an electronic medical record in three surgical departments of a German hospital–a longitudinal comparative document analysis
Authors: Wurster Florian , Herrmann Christin , Beckmann Marina , Cecon-Stabel Natalia , Dittmer Kerstin , Hansen Till , Jaschke Julia , Köberlein-Neu Juliane , Okumu Mi-Ran , Pfaff Holger , Rusniok Carsten , Karbach Ute 
Published: September 2024

Abstract
Purpose
The European health data space promises an efficient environment for research and policy-making. However, this data space is dependent on high data quality. The implementation of electronic medical record systems has a positive impact on data quality, but improvements are not consistent across empirical studies. This study aims to analyze differences in the changes of data quality and to discuss these against distinct stages of the electronic medical record’s adoption process.

Methods
Paper-based and electronic medical records from three surgical departments were compared, assessing changes in data quality after the implementation of an electronic medical record system. Data quality was operationalized as completeness of documentation. Ten information that must be documented in both record types (e.g. vital signs) were coded as 1 if they were documented, otherwise as 0. Chi-Square-Tests were used to compare percentage completeness of these ten information and t-tests to compare mean completeness per record type.

Results
A total of N = 659 records were analyzed. Overall, the average completeness improved in the electronic medical record, with a change from 6.02 (SD = 1.88) to 7.2 (SD = 1.77). At the information level, eight information improved, one deteriorated and one remained unchanged. At the level of departments, changes in data quality show expected differences.

Conclusion
The study provides evidence that improvements in data quality could depend on the process how the electronic medical record is adopted in the affected department. Research is needed to further improve data quality through implementing new electronical medical record systems or updating existing ones.
Light sampling behaviour regulates circadian entrainment in mice
Authors: Steel Laura C. E. , Tam Shu K. E. , Brown Laurence A. , Foster Russell G. , Peirson Stuart N. 
Published: September 2024

Abstract
Background
The natural light environment is far more complex than that experienced by animals under laboratory conditions. As a burrowing species, wild mice are able to self-modulate their light exposure, a concept known as light environment sampling behaviour. By contrast, under laboratory conditions mice have little opportunity to exhibit this behaviour. To address this issue, here we introduce a simple nestbox paradigm to allow mice to self-modulate their light environment. Dark nestboxes fitted with passive infrared sensors were used to monitor locomotor activity, circadian entrainment, decision making and light environment sampling behaviour.

Results
Under these conditions, mice significantly reduce their light exposure to an average of just 0.8 h across a 24 h period. In addition, mice show a distinct pattern of light environment sampling behaviour, with peaks at dawn and dusk under a ramped light dark cycle. Furthermore, we show that the timing of light environment sampling behaviour depends upon endogenous circadian rhythms and is abolished in mice lacking a circadian clock, indicating a feedback loop between light, the circadian clock and behaviour.

Conclusions
Our results highlight the important role of behaviour in modifying the light signals available for circadian entrainment under natural conditions.
The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes
Authors: Borlak Jürgen , Ciribilli Yari , Bisio Alessandra , Selvaraj Saravanakumar , Inga Alberto , Oh Jung-Hwa , Spanel Reinhard 
Published: September 2024

Abstract
Background
Doxorubicin is an important anticancer drug, however, elicits dose-dependently cardiomyopathy. Given its mode of action, i.e. topoisomerase inhibition and DNA damage, we investigated genetic events associated with cardiomyopathy and searched for mechanism-based possibilities to alleviate cardiotoxicity. We treated rats at clinically relevant doses of doxorubicin. Histopathology and transmission electron microscopy (TEM) defined cardiac lesions, and transcriptomics unveiled cardiomyopathy-associated gene regulations. Genomic-footprints revealed critical components of Abl1-p53-signaling, and EMSA-assays evidenced Abl1 DNA-binding activity. Gene reporter assays confirmed Abl1 activity on p53-targets while immunohistochemistry/immunofluorescence microscopy demonstrated Abl1, p53&p73 signaling.

Results
Doxorubicin treatment caused dose-dependently toxic cardiomyopathy, and TEM evidenced damaged mitochondria and myofibrillar disarray. Surviving cardiomyocytes repressed Parkin-1 and Bnip3-mediated mitophagy, stimulated dynamin-1-like dependent mitochondrial fission and induced anti-apoptotic Bag1 signaling. Thus, we observed induced mitochondrial biogenesis. Transcriptomics discovered heterogeneity in cellular responses with minimal overlap between treatments, and the data are highly suggestive for distinct cardiomyocyte (sub)populations which differed in their resilience and reparative capacity. Genome-wide footprints revealed Abl1 and p53 enriched binding sites in doxorubicin-regulated genes, and we confirmed Abl1 DNA-binding activity in EMSA-assays. Extraordinarily, Abl1 signaling differed in the heart with highly significant regulations of Abl1, p53 and p73 in atrial cardiomyocytes. Conversely, in ventricular cardiomyocytes, Abl1 solely-modulated p53-signaling that was BAX transcription-independent. Gene reporter assays established Abl1 cofactor activity for the p53-reporter PG13-luc, and ectopic Abl1 expression stimulated p53-mediated apoptosis.

Conclusions
The tyrosine kinase Abl1 is of critical importance in doxorubicin induced cardiomyopathy, and we propose its inhibition as means to diminish risk of cardiotoxicity.
Fatal infection caused by a genetically distinct elephant endotheliotropic herpesvirus type 5 in a captive Asian elephant in Germany
Authors: Abdelgawad Azza , Nascimento Mariana , Prahl Adriane , Flügger Michael , Szentiks Claudia A. , Holtze Susanne , Hildebrandt Thomas B. , Trimpert Jakob 
Published: September 2024

Abstract
Background
Elephant endotheliotropic herpesvirus (EEHV) infection is the most common cause for lethal hemorrhagic disease in captive juvenile Asian elephants (Elephas maximus). Although EEHV1 is known as the most likely cause of fatal haemorrhagic disease in Asian elephants, EEHV5 was lately involved in lethal cases of haemorrhagic disease in captive elephants.

Case presentation
Here we report the first death of a four-year old Asian elephant diagnosed with EEHV5 in Germany. Molecular diagnosis yielded detection of EEHV5 DNA in all tested tissues. Histopathological examination revealed typical features of hemorrhagic disease in all examined organs. EEHV5 was sequenced from total DNA isolated from heart tissue by Illumina and Nanopore sequencing. Sequencing data showed 3,881 variants, distributed across the entire genome, compared to the published EEHV5 sequence.

Conclusions
We have detected EEHV5 in a fatal disease case of a male Asian elephant. Whole genome sequencing revealed substantial differences of our DNA isolate compared to available EEHV5 sequences. This report of fatal haemorrhagic disease associated with EEHV5 infection should raise awareness for EEHV5 as an important elephant pathogen. Genome sequencing and downstream SNPs analysis will further encourage future research to understand genetic diversity, pathogenesis and virulence of EEHVs with respect to developing new diagnostic methods, prophylactic strategies, and implementation of surveillance and control measures.