bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiotherapy Under Pressure: A Cross-Sectional Study on The Interplay Between Perfectionism, Moral Injury, and Burnout
Authors: Biggs Daniel , Blackburn Laura , Black Cameron , Shanmugam Sivaramkumar 
Published: February 2024

AbstractBackgroundGiven the escalating challenges for UK-based physiotherapists in workload pressures, budget constraints, staff shortages and patient wait times, the profession (of 65,000 registered physiotherapists) requires immediate care and review of therapist health. This pioneering study aims to examine perfectionism, moral injury, and burnout among UK-based physiotherapists across the NHS, private practice, sports, and academia.MethodThis cross-sectional study utilised an online survey and implementation of Structure Equation Modelling (SEM) to assess the interplay of Perfectionism (Multidimension Perfectionism Scale-Short Form), Moral Injury (Moral Injury Symptoms Scale-Healthcare Professionals) and Burnout (Shirom-Melamed Burnout Questionnaire). Our sample size calculation shows representation of the UK physiotherapy profession via utilisation of 95% confidence interval with a 5% margin of error.FindingsOur analysis conducted on (n=402) UK-based physiotherapists reveals significant burnout levels – 96% are categorised as moderate to high. Furthermore, associations and SEM of Perfectionism and Moral Injury collectively account for a substantial proportion of burnout variability (r2.62), highlighting their sequential impact on burnout manifestation.InterpretationWith such high levels of burnout, urgent intervention is paramount. Elevated burnout presents challenges for the physiotherapy profession as staff retention, accurate and effective patient care, and overall health are severely impacted due to burnout. Recognising and addressing perfectionism and moral injury becomes pivotal to mitigate its impact on individual and collective health.FundingNo funding was acquired for this research project.
Conformal Triage for Medical Imaging AI Deployment
Authors: Angelopoulos Anastasios N. , Pomerantz Stuart , Do Synho , Bates Stephen , Bridge Christopher P. , Elton Daniel C. , Lev Michael H. , González R. Gilberto , Jordan Michael I. , Malik Jitendra 
Published: February 2024

AbstractBackgroundThe deployment of black-box AI models in medical imaging presents significant challenges, especially in maintaining reliability across different clinical settings. These challenges are compounded by distribution shifts that can lead to failures in reproducing the accuracy attained during the AI model’s original validations.MethodWe introduce the conformal triage algorithm, designed to categorize patients into low-risk, high-risk, and uncertain groups within a clinical deployment setting. This method leverages a combination of a black-box AI model and conformal prediction techniques to offer statistical guarantees of predictive power for each group. The high-risk group is guaranteed to have a high positive predictive value, while the low-risk group is assured a high negative predictive value. Prediction sets are never constructed; instead, conformal techniques directly assure high accuracy in both groups, even in clinical environments different from those in which the AI model was originally trained, thereby ameliorating the challenges posed by distribution shifts. Importantly, a representative data set of exams from the testing environment is required to ensure statistical validity.ResultsThe algorithm was tested using a head CT model previously developed by Do and col-leagues [9] and a data set from Massachusetts General Hospital. The results demonstrate that the conformal triage algorithm provides reliable predictive value guarantees to a clinically significant extent, reducing the number of false positives from 233 (45%) to 8 (5%) while only abstaining from prediction on 14% of data points, even in a setting different from the training environment of the original AI model.ConclusionsThe conformal triage algorithm offers a promising solution to the challenge of deploying black-box AI models in medical imaging across varying clinical settings. By providing statistical guarantees of predictive value for categorized patient groups, this approach significantly enhances the reliability and utility of AI in optimizing medical imaging workflows, particularly in neuroradiology.
Will ChatGPT-4 improve the quality of medical abstracts?
Authors: Gravel Jocelyn , Dion Chloé , Fadaei Kermani Mandana , Mousseau Sarah , Osmanlliu Esli 
Published: February 2024

AbstractBackgroundChatGPT received recognition for medical writing. Our objective was to evaluate whether ChatGPT 4.0 could improve the quality of abstracts submitted to a medical conference by clinical researchers.MethodsThis was an experimental study involving 24 international researchers who provided one original abstract intended for submission at the 2024 Pediatric Academic Society (PAS) conference. We created a prompt asking ChatGPT-4 to improve the quality of the abstract while adhering PAS submission guidelines. Researchers received the revised version and were tasked with creating a final abstract. The quality of each version (original, ChatGPT and final) was evaluated by the researchers themselves using a numeric scale (0-100). Additionally, three co-investigators assessed abstracts blinded to the version. The primary analysis focused on the mean difference in scores between the final and original abstracts.ResultsAbstract quality varied between the three versions with mean scores of 82, 65 and 90 for the original, ChatGPT and final versions, respectively. Overall, the final version displayed significantly improved quality compared to the original (mean difference 8.0 points; 95% CI: 5.6-10.3). Independent ratings by the co-investigator confirmed statistical improvements (mean difference 1.10 points; 95% CI: 0.54-1.66). Researchers identified minor (n=10) and major (n=3) factual errors in ChatGPT’s abstracts.ConclusionWhile ChatGPT 4.0 does not produce abstracts of better quality then the one crafted by researchers, it serves as a valuable tool for researchers to enhance the quality of their own abstracts. The utilization of such tools is a potential strategy for researchers seeking to improve their abstracts.FundingNone
A data management system for precision medicine
Authors: Jacobs John J. L. , Beekers Inés , Verkouter Inge , Richards Levi B. , Vegelien Alexandra , Bloemsma Lizan D. , Bongaerts Vera A. M. C. , Cloos Jacqueline , Erkens Frederik , Gradowska Patrycja , Hort Simon , Hudecek Michael , Juan Manel , Maitland-van der Zee Anke H. , Velázquez Sergio Navarro , Ngai Lok Lam , Rafiq Qasim A , Sanges Carmen , Tettero Jesse , van Os Hendrikus J. A. , Vos Rimke C. , de Wit Yolanda , van Dijk Steven 
Published: February 2024

AbstractIntroductionPrecision, or personalised medicine has advanced requirements for medical data management systems (MedDMSs). MedDMS for precision medicine should be able to process hundreds of parameters from multiple sites, be adaptable while remaining in sync at multiple locations, real-time syncing to analytics and be compliant with international privacy legislation. This paper describes the LogiqSuite software solution, aimed to support a precision medicine solution at the patient care (LogiqCare), research (LogiqScience) and data science (LogiqAnalytics) level. LogiqSuite is certified and compliant with international medical data and privacy legislations.MethodThis paper evaluates a MedDMS in five types of use cases for precision medicine, ranging from data collection to algorithm development and from implementation to integration with real-world data. The MedDMS is evaluated in seven precision medicine data science projects in prehospital triage, cardiovascular disease, pulmonology, and oncology.ResultsThe P4O2 consortium uses the MedDMS as an electronic case report form (eCRF) that allows real-time data management and analytics in long covid and pulmonary diseases. In an acute myeloid leukaemia study data from different sources were integrated to facilitate easy descriptive analytics for various research questions. In the AIDPATH project, LogiqCare is used to process patient data, while LogiqScience is used for pseudonymous CAR-T cell production for cancer treatment. In both these oncological projects the data in LogiqAnalytics is also used to facilitate machine learning to develop new prediction models for clinical-decision support (CDS). The MedDMS is also evaluated for real-time recording of CDS data from U-Prevent for cardiovascular risk management and from the Stroke Triage App for prehospital triage.DiscussionThe MedDMS is discussed in relation to other solutions for privacy-by-design, integrated data stewardship and real-time data analytics in precision medicine.ConclusionLogiqSuite is used for multi-centre research study data registrations and monitoring, data analytics in interdisciplinary consortia, design of new machine learning / artificial intelligence (AI) algorithms, development of new or updated prediction models, integration of care with advanced therapy production, and real-world data monitoring in using CDS tools. The integrated MedDMS application supports data management for care and research in precision medicine.
X-chromosome loss rescues Sertoli cell maturation and spermatogenesis in Klinefelter syndrome
Authors: Winge Sofia B. , Skakkebaek Niels E. , Aksglaede Lise , Saritaş Gülizar , Rajpert-De Meyts Ewa , Goossens Ellen , Juul Anders , Almstrup Kristian 
Published: February 2024

AbstractKlinefelter syndrome (47,XXY) causes infertility with a testicular histology comprising two types of Sertoli cell-only tubules, representing mature and immature-like Sertoli cells, and occasionally focal spermatogenesis. Here, we show that the immature Sertoli cells highly expressedXISTand have two X-chromosomes, while the mature Sertoli cells lackXISTexpression and have only one X-chromosome. Sertoli cells supporting focal spermatogenesis also lackXISTexpression and the additional X-chromosome, while the spermatogonia expressedXISTdespite having only one X-chromosome.XISTwas expressed in Sertoli cells until puberty, where a gradual loss was observed. Our results suggest that a micro-mosaic loss of the additional X-chromosome is needed for Sertoli cells to mature and to allow focal spermatogenesis.
Thermostability and binding properties of single-chained Fv fragments derived from therapeutic antibodies
Authors: Tadokoro Takashi , Tsuboi Harumi , Nakamura Kota , Hayakawa Tetsushi , Ohmura Reo , Kato Izumi , Inoue Masaki , Tsunoda Shin-ichi , Niizuma Sayaka , Okada Yukari , Otsuguro Satoko , Maenaka Katsumi 
Published: February 2024

AbstractSmall antibody fragments have recently been used as alternatives to full-length monoclonal antibodies in therapeutic applications. One of the most popular fragment antibodies is single-chain fragment variables (scFvs), consisting of variable heavy (VH) and variable light (VL) domains linked by a flexible peptide linker. scFvs have small molecular sizes, which enables good tissue penetration and low immunogenicity. Despite these advantages, the use of scFvs, especially for therapeutic purpose, is still limited because of the difficulty to regulate the binding activity and conformational stability. In this study, we constructed and analyzed 10 scFv fragments derived from 10 representatives of FDA-approved mAbs to evaluate their physicochemical properties. Differential scanning calorimetry analysis showed that scFvs exhibited relatively high but varied thermostability, from 50 to 70 °C of melting temperatures, and different unfolding cooperativity. Surface plasmon resonance analysis revealed that scFvs fragments that exhibit high stability and cooperative unfolding likely tend to maintain antigen binding. This study demonstrated the comprehensive physicochemical properties of scFvs derived from FDA-approved antibodies, providing insights into antibody design and development.
Unselfish meiotic drive maintains heterozygosity in a parthenogenetic ant
Authors: Lacy Kip D. , Hart Taylor , Kronauer Daniel J.C. 
Published: February 2024

AbstractAccording to Mendel’s second law, chromosomes segregate randomly in meiosis. Non-random segregation is primarily known for cases of selfish meiotic drive in females, in which particular alleles bias their own transmission into the oocyte1,2. Here, we report a rare example of unselfish meiotic drive for crossover inheritance in the clonal raider ant,Ooceraea biroi. This species produces diploid offspring parthenogenetically via fusion of two haploid nuclei from the same meiosis3. This process should cause rapid genotypic degeneration due to loss of heterozygosity, which results if crossover recombination is followed by random (Mendelian) segregation of chromosomes4,5. However, by comparing whole genomes of mothers and daughters, we show that loss of heterozygosity is exceedingly rare, raising the possibility that crossovers are infrequent or absent inO. biroimeiosis. Using a combination of cytology and whole genome sequencing, we show that crossover recombination is, in fact, common, but that loss of heterozygosity is avoided because crossover products are faithfully co-inherited. This results from a programmed violation of Mendel’s law of segregation, such that crossover products segregate together rather than randomly. This discovery highlights an extreme example of cellular “memory” of crossovers, which could be a common yet cryptic feature of chromosomal segregation.
Microtubule-dependent orchestration of centriole amplification in brain multiciliated cells
Authors: Boudjema Amélie-Rose , Balagué Rémi , Jewett Cayla E , LoMastro Gina M , Mercey Olivier , Jord Adel Al , Faucourt Marion , Schaeffer Alexandre , Noûs Camille , Delgehyr Nathalie , Holland Andrew J , Spassky Nathalie , Meunier Alice 
Published: February 2024

AbstractCentriole number must be restricted to two in cycling cells to avoid pathological cell divisions. Multiciliated cells (MCC), however, need to produce a hundred or more centrioles to nucleate the same number of motile cilia required for fluid flow circulation. These centrioles are produced by highjacking cell cycle and centriole duplication programs. However, how the MCC progenitor handles such a massive number of centrioles to finally organize them in an apical basal body patch is unclear. Here, using new cellular models and high-resolution imaging techniques, we identify the microtubule network as the bandleader, and show how it orchestrates the process in space and in time. Organized by the pre-existing centrosome at the start of amplification, microtubules build a nest of centriolar components from which procentrioles emerge. When amplification is over, the centrosome’s dominance is lost as new centrioles mature and become microtubule nucleators. Microtubules then drag all the centrioles to the nuclear membrane, assist their isotropic perinuclear disengagement and their subsequent collective apical migration. These results reveal that in brain MCC as in cycling cells, the same dynamics - from the centrosome to the cell pole via the nucleus-exists, is the result of a reflexive link between microtubules and the progressive maturation of new centrioles, and participates in the organized reshaping of the entire cytoplasm. On the other hand, new elements described in this work such as microtubule-driven organization of a nest, identification of a spatio-temporal progression of centriole growth and microtubule-assisted disengagement, may shed new light on the centriole duplication program.Graphical Abstract
Genetic regulation of injury induced heterotopic ossification in adult zebrafish
Authors: Kaliya-Perumal Arun-Kumar , Celik Cenk , Carney Tom J. , Harris Matthew P. , Ingham Philip W. 
Published: February 2024

AbstractHeterotopic ossification is the inappropriate formation of bone in soft tissues of the body. It can manifest spontaneously in rare genetic conditions or as a response to injury, known as acquired heterotopic ossification. There are several experimental models for studying heterotopic ossification from different sources of damage. However, their tenuous mechanistic relevance to the human condition, invasive and laborious nature and/or lack of amenability to chemical and genetic screens, limit their utility. To address these limitations, we developed a simple zebrafish injury model that manifests heterotopic ossification in response to micro-fractures in combination with muscle injury. These findings indicate that clinically-emulated injuries in zebrafish can lead to osteo-induction and proliferation as observed in heterotopic ossification inmyositis ossificans traumatica. Exploiting this model, we analysed the penetrance and expressivity of heterotopic ossification and defined the transcriptional response to trauma, identifying differentially regulated genes. Taking advantage of defined mutants in several of these candidates, we explored their impact on heterotopic bone formation. Our findings revealed that an increase in potassium channel Kcnk5b activity potentiates injury response. In contrast, we demonstrate that inflammatory responses are essential for the ectopic bone growth, as mutations in Interleukin 11 receptor paralogue (Il11ra) exhibit a drastically reduced ossification response. Based on these findings, we postulate that enhanced ionic signaling, specifically through Kcnk5b, regulates the intensity of the skeletogenic injury response, which, in part, requires immune response regulated by Il11ra.
Computational hemodynamic indices to identify Transcatheter Aortic Valve Implantation degeneration
Authors: Crugnola Luca , Vergara Christian , Fusini Laura , Fumagalli Ivan , Luraghi Giulia , Redaelli Alberto , Pontone Gianluca 
Published: February 2024

AbstractPurposeStructural Valve Deterioration (SVD) is the main limiting factor to the long-term durability of bioprosthetic valves, which are used for Transcatheter Aortic Valve Implantation (TAVI). The aim of this study is to perform a patient-specific computational analysis of post-TAVI blood dynamics to identify hemodynamic indices that correlate with a premature onset of SVD.MethodsThe study population comprises two subgroups: patients with and without SVD at long-term follow-up exams. Starting from pre-operative CT images, we created reliable post-TAVI scenarios by virtually inserting the bioprosthetic valve (stent and leaflets), and we performed numerical simulations imposing realistic inlet conditions based on patient-specific data. The numerical results were post-processed to build suitable synthetic scores based on normalized hemodynamic indices.ResultsWe defined three synthetic scores, based on hemodynamic indices evaluated in different contexts: on the leaflets, in the ascending aorta, and in the whole domain. Our proposed synthetic scores are able to clearly isolate the SVD group. Notably, we found that leaflets’ OSI individually shows statistically significant differences between the two subgroups of patients.ConclusionThe results of this computational study suggest that blood dynamics may play an important role in creating the conditions that lead to SVD. More-over, the proposed synthetic scores could provide further indications for clinicians in assessing and predicting TAVI valves’ long-term performance.
Time-series metagenomics reveals changing protistan ecology of a temperate dimictic lake
Authors: Krinos Arianna I. , Bowers Robert M. , Rohwer Robin R. , McMahon Katherine D. , Woyke Tanja , Schulz Frederik 
Published: February 2024

AbstractBackgroundProtists, single-celled eukaryotic organisms, are critical to food web ecology, contributing to primary productivity and connecting small bacteria and archaea to higher trophic levels. Lake Mendota is a large, eutrophic natural lake that is a Long-Term Ecological Research site and among the world’s best-studied freshwater systems. Metagenomic samples have been collected and shotgun sequenced from Lake Mendota for the last twenty years. Here, we analyze this comprehensive time series to infer changes to the structure and function of the protistan community, and to hypothesize about their interactions with bacteria.ResultsBased on small subunit rRNA genes extracted from the metagenomes and metagenome-assembled genomes of microeukaryotes, we identify shifts in the eukaryotic phytoplankton community over time, which we predict to be a consequence of reduced zooplankton grazing pressures after the invasion of a invasive predator (the spiny water flea) to the lake. The metagenomic data also reveal the presence of the spiny water flea and the zebra mussel, a second invasive species to Lake Mendota, prior to their visual identification during routine monitoring. Further, we use species co-occurrence and co-abundance analysis to connect the protistan community with bacterial taxa. Correlation analysis suggests that protists and bacteria may interact or respond similarly to environmental conditions. Cryptophytes declined in the second decade of the timeseries, while many alveolate groups (e.g. ciliates and dinoflagellates) and diatoms increased in abundance, changes that have implications for food web efficiency in Lake Mendota.ConclusionsWe demonstrate that metagenomic sequence-based community analysis can complement existing e↵orts to monitor protists in Lake Mendota based on microscopy-based count surveys. We observed patterns of seasonal abundance in microeukaryotes in Lake Mendota that corroborated expectations from other systems, including high abundance of cryptophytes in winter and diatoms in fall and spring, but with much higher resolution than previous surveys. Our study identified long-term changes in the abundance of eukaryotic microbes, and provided context for the known establishment of an invasive species that catalyzes a trophic cascade involving protists. Our findings are important for decoding potential long-term consequences of human interventions, including invasive species introduction.
Automated multimodal imaging ofCaenorhabditis elegansbehavior in multi-well plates
Authors: Ji Hongfei , Chen Dian , Fang-Yen Christopher 
Published: February 2024

ABSTRACTAssays of behavior in model organisms play an important role in genetic screens, drug testing, and the elucidation of gene-behavior relationships. We have developed an automated, high-throughput imaging and analysis method for assaying behaviors of the nematodeC. elegans. We use high-resolution optical imaging to longitudinally record the behaviors of 96 animals at a time in multi-well plates, and computer vision software to quantify the animals’ locomotor activity, behavioral states, and egg laying events. To demonstrate the capabilities of our system we used it to examine the role of serotonin inC. elegansbehavior. We found that egg-laying events are preceded by a period of reduced locomotion, and that this decline in movement requires serotonin signaling. In addition, we identified novel roles of serotonin receptors SER-1 and SER-7 in regulating the effects of serotonin on egg laying across roaming, dwelling, and quiescent locomotor states. Our system will be useful for performing genetic or chemical screens for modulators of behavior.