bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expanded T cell clones with lymphoma driver somatic mutations in refractory celiac disease
Authors: Singh Mandeep , Louie Raymond H. Y. , Samir Jerome , Field Matthew A. , Milthorpe Claire , Aldiriki Thiruni , Mackie Joseph , Roper Ellise , Faulks Megan , Jackson Katherine J. L. , Calcino Andrew , Hardy Melinda Y. , Blombery Piers , Amos Timothy G. , Deveson Ira W. , Read Scott A. , Shek Dmitri , Guerin Antoine , Ma Cindy S , Tangye Stuart G. , Sabatino Antonio Di , Lenti Marco V. , Pasini Alessandra , Ciccocioppo Rachele , Ahlenstiel Golo , Suan Dan , Tye-Din Jason A. , Goodnow Christopher C. , Luciani Fabio 
Published: March 2024

AbstractIntestinal inflammation continues in a subset of celiac disease (CD) patients despite a gluten-free diet. Here, by applying multiomic single cell analysis to duodenal biopsies, we find low-grade malignancies with lymphoma driver mutations in refractory CD type 2 (RCD2) patients comprise surface CD3 negative (sCD3-) lymphocytes stalled at an innate lymphoid cell (ILC) - progenitor T cell stage undergoing extensiveTCRrecombination. In people with refractory CD type 1 (RCD1), who currently lack explanation, we discover sCD3+ T cells with lymphoma driver mutations forming large clones displaying inflammatory and cytotoxic molecular profiles in 6 of 10 individuals, and a single small clone in 1 of 4 active recently diagnosed CD cases. Accumulation of driver-mutated T cells and their sCD3-progenitors may explain chronic, non-responsive autoimmunity.One-Sentence SummaryTreatment refractory autoimmunity in celiac disease may be explained by dysregulated T cells and progenitors that have acquired lymphoma-driver mutations.
Patient-specific compliant simulation framework informed by 4DMRI-extracted Pulse Wave Velocity: Application post-TEVAR
Authors: Girardin Louis , Lind Niklas , von Tengg-Kobligk Hendrik , Balabani Stavroula , Díaz-Zuccarini Vanessa 
Published: March 2024

AbstractWe introduce a new computational framework that makes use of the Pulse Wave Velocity (PWV) extracted exclusively from 4D flow MRI (4DMRI) to inform patient-specific compliant computational fluid dynamics (CFD) simulations of a Type-B aortic dissection (TBAD), post-thoracic endovascular aortic repair (TEVAR). From 4DMRI and brachial pressure, a 3D inlet velocity profile (IVP), dynamic outlet boundary, and reconstructed thoracic aortic geometry are obtained. A moving boundary method (MBM) is applied to simulate aortic wall displacement. The aortic wall stiffness was estimated through two methods: one relying on area-based distensibility and the other utilising regional pulse wave velocity (RPWV) distensibility, further fine-tuned to align within vivovalues. Predicted pressures and outlet flow rates were within 2.3% of target values. RPWV-based simulations were more accurate in replicatingin vivohemodynamic compared to the area-based ones. RPWVs were closely predicted in most regions, with the exception being the endograft, and systolic flow reversal ratios (SFRR) were accurately captured, while a difference of above 60% on in-plane rotational flow (IRF) between the simulations. Significant disparities between the wall shear stress (WSS)-based indices were observed between the two approaches, especially the endothelial cell activation potential (ECAP). At the isthmus, the RPWV-driven simulation indicated a mean ECAP>1.4Pa−1(critical threshold), indicating areas potentially prone to thrombosis. In contrast, the area-based simulation did not depict this. RPWV-driven simulation results agree well with 4DMRI measurements, emphasising that RPWV simulations are accurate in simulating haemodynamics, consequently facilitating a comprehensive assessment of surgery decision-making and potential complications, such as thrombosis and aortic growth.
Associations of cholecystectomy with the risk of gastroesophageal reflux disease: a Mendelian randomization study
Authors: Qian Jin , Xu Huawei , Liu Jun , Zheng Yihu 
Published: March 2024

AbstractBackgroundCholecystectomy is the standard surgery for patients with gallbladder disease, but the impact of cholecystectomy on gastroesophageal reflux (GERD) is not clear.MethodsWe obtained genetic variants associated with cholecystectomy at a genome-wide significant level (Pvalue < 5 × 10−8) as instrumental variables (IVs) and performed Mendelian randomization (MR) to explore the relationship with GERD.ResultsThe Inverse Variance Weighted analysis (IVW) showed that the risk of GERD in patients after cholecystectomy increased (OR = 2.19; 95% CI: 1.18 – 4.09). At the same time, the analysis results of weighted median (OR = 2.30; 95% CI: 1.51 – 3.48) and weighted mode (OR = 2.21; 95% CI: 1.42 – 3.45) were also consistent with the direction of the IVW analysis and were statistically significant (P< 0.05).ConclusionsThis study shows that patients who have undergone cholecystectomy are a susceptible population of GERD.
Feasibility of individualized home exercise programs for patients with head and neck cancer – study protocol and first results of a multicentre single-arm intervention trial (OSHO #94)
Authors: Felser Sabine , Rogahn Julia , Glass Änne , Bonke Lars Arne , Strüder Daniel F. , Stolle Jana , Schulze Susann , Blaurock Markus , Kriesen Ursula , Junghanss Christian , Grosse-Thie Christina 
Published: March 2024

AbstractIntroductionPatients with head and neck cancer (PwHNC) benefit from targeted exercise interventions: symptom relief, compensation for dysfunction, improvement in quality of life (QoL). Data on acceptance physical interventions in PwHNC are rare. The ‘OSHO #94’ trial investigates the short- and medium-term effects of individualized home exercise in PwHNC on QoL, physical activity and functionality. The study includes a feasibility phase in order to evaluate the acceptance (Phase A), followed by a consecutive QoL endpoint Phase B. Here we present the study protocol as well as the feasibility results.Methods and analysisThis prospective, multicentre, single-arm intervention study includes PwHNC ≥18 years of age in aftercare or palliative care with stable remission under immunotherapy. The study opened in January 01, 2021, with estimated completion by December 31, 2024. The PwHNC receive an individualized home exercise program consisting of mobilization, coordination, strengthening and stretching exercises. This should be carried out at least three times a week over 12 weeks for 15 to 30 minutes, supplemented by aerobic training two to three times a week for 30 minutes (intervention). Once weekly telephone calls with a physiotherapist are performed. Subsequently, there is a 12-week follow-up (FU) without exercise specifications/contact. Outcomes are measured before and after the intervention and following the FU. Primary outcome of the feasibility phase (Phase A, n = 25) was the determination of the dropout rate during the intervention with a termination cut off if more than 30% PwHNC withdrew premature. The primary outcome of phases A + B (N = 53) are the change in global QoL score from pre- to post-intervention (EORTC QLQ-C30). Secondary outcomes include clinical and patient-reported measures, training details as well as functional diagnostic data (e.g. level of physical activity, training frequency, flexibility, fall risk and aerobic performance).Results25 PwHNC were enrolled onto the feasibility cohort. Only16% (4/25 patients) did not complete the study. Therefore, individualized home exercise programs in PwHNC seem feasible recruitment of PwHNC for phase B continued. The dropout rate was adjusted from 30% (N = 60) to 20% (N = 53, calculated sample size n = 42 PwHNC and 20% (n = 11) to dropout).Ethics and disseminationThe study protocol was approved by the Ethics Committee of the University of Rostock, University of Halle-Wittenberg and University of Greifswald. The findings will be disseminated in peer-reviewed journals and academic conferences.Trial registrationGerman Registry of Clinical Trials DRKS00023883.
A preliminary study to evaluate the exposure of human fetus to heavy metals in the umbilical cord blood in Syria
Authors: Kabbaa Maryana , Fadel Ekbal , Mayhoub Flora 
Published: March 2024

AbstractThe environmental situation in Syria needs a comprehensive assessment, especially in light of the conditions it has been experiencing for thirteen years, which have exacerbated pollution with heavy metals (HM) in various regions, including the coastal one.This preliminary and first survey in Syria aims to evaluate the exposure of human fetus in the population to HM by measuring the toxic metals spread in the coastal environment in the umbilical cord blood (UCB), which are lead (Pb), mercury (Hg), cadmium (Cd), arsenic (As), chromium (Cr) and nickel (Ni).The study was conducted between May 2022 and April 2023 among healthy newborns of the National Maternity Hospital in the Mediterranean coastal city of Tartous. This study adopted the official method of the American Association for Analytical Chemistry (AOAC, 2002) in collecting, preserving and processing UCB samples, and the heavy metals were measured using an Atomic Absorption Spectrometer. The statistical study was carried out using SPSS Statistics 23.0 (Statistical Package for Social Sciences).The lower and upper limits for the concentrations of the studied elements in UCB range between: Pb (6.18-17.60µg/L), Hg (1.05-7.62µg/L), Cd (0.01-0.67µg/L), As (0.30-5.70µg/L), Cr (0.02-0.43µg/L), Ni (0.01-0.94µg/L).The concentrations of all HM measured in UCB are below the recommended international reference limits. This paper represents the first step in studying the assessment of fetal exposure to HM in our region. The current and future studies aim to expand the study area to include all of Syria, in addition to linking laboratory levels of HM with various sources of exposure and pregnancy outcomes observed at birth.
Analyzing the efficacy of a decade-long endeavor: extracurricular medical research training amidst the turmoil of Syria
Authors: Hanafi Ibrahem , Alsalkini Marah , Kheder Kheder , Al Nafouri Maarouf Gorra , Rahmeh Ahmad Rami , Sabouni Rami 
Published: March 2024

ABSTRACTObjectivesMedical research in Syria faced significant limitations due to inadequate human and financial resources, exacerbated by the ongoing war. Until recently, the curriculum did not incorporate sufficient training on research skills. Consequently, extracurricular workshops were initiated or utilized nationwide to acquire research-related expertise, aiming to bolster research output. This study aims to characterize and evaluate these training endeavors concerning research-related knowledge, attitudes, barriers, as well as research productivity.MethodsThis case-control study encompassed all training initiatives in Syria from 2011 to 2020, both on-site and online. Participants consisted of early career healthcare professionals affiliated with all Syrian universities and were recruited into four equal groups based on the quantity of research projects they undertook and published. Our participants reported and assessed individual extracurricular workshops regarding their gained knowledge, attitudes, and practical skills. These initiatives were compared to curricular training and practical peer-led support regarding these outcomes.ResultsThe study included 53 on-site and 30 online workshops, displaying diverse distributions and features. Attendance of extracurricular workshops correlated with participants’ knowledge, attitudes, and research productivity (p<0.001). The most effective interventions were massive open online courses and workshops lasting over 12 hours. Extracurricular workshops and peer-led support has comparable effectiveness and associated with higher knowledge, attitudes, and practical skills of their beneficiaries in comparison to curricular training (adjusted p<0.05). Lastly, peer trainers in these workshops exhibited more publications and higher levels of knowledge and attitude than the rest of the sample (adjusted p<0.05).ConclusionsOverall, extracurricular interventions and peer support demonstrated their superiority over curricular training. Despite the varied nature of these workshops and the absence of institutional organization, these approaches exhibited significant potential in enhancing research-related knowledge, promoting positive attitudes, and augmenting research productivity in resource-constrained settings such as Syria.
The relationship between payer type and quality of care for women undergoing emergency cesarean section at three hospitals in rural Uganda
Authors: Mwiindi Jonathan , Delgado Rigoberto , Revere Lee , Wangigi Beth , Muguthu Edward , Busingye Priscilla 
Published: March 2024

AbstractBackgroundThe study examined the relationship between payer type, and quality of care among mothers who deliver through emergency cesarean section in rural Ugandan hospitals.MethodsWe analyzed retrospective, de-identified patient data from three rural private-not-for-profit hospitals in Uganda. Two groups were included in the study, a self-payer patient group and a group fully sponsored by an international funding organization. The data was analyzed using hierarchical linear regression models comparing length of stay against payer type, and controlling for patient age, education level, parity, and indication for C-section. Length of stay (LOS) was assumed to represent a realistic proxy variable for patient quality of care.ResultsThe self-pay group had statistically significant longer postoperative LOS (surgery to clinical discharge), and longer aggregate LOS, or admission to clinical discharge, compared to the sponsored group. Payer type was not significant in the admission-to-decision LOS, but payer type was highly significant for aggregate LOS (p <.001).ConclusionCase management in rural Ugandan hospitals influences quality of post-operative care for patients undergoing emergency C-sections. Expanding surgical funding, combined with effective case management approaches, is likely to increase quality of surgical care as measured by length of stay.Synopsis: Post-operative quality of care for emergency C-section cases, measured by length of stay in Ugandan rural hospitals, is impacted by case management.
Comprehensive evaluation of pipelines for diagnostic biomarkers of major depressive disorder using multi-site resting-state fMRI datasets
Authors: Takahara Yuji , Kashiwagi Yuto , Tokuda Tomoki , Yoshimoto Junichiro , Sakai Yuki , Yamashita Ayumu , Yoshioka Toshinori , Takahashi Hidehiko , Mizuta Hiroto , Kasai Kiyoto , Kunimitsu Akira , Okada Naohiro , Itai Eri , Shinzato Hotaka , Yokoyama Satoshi , Masuda Yoshikazu , Mitsuyama Yuki , Okada Go , Okamoto Yasumasa , Itahashi Takashi , Ohta Haruhisa , Hashimoto Ryu-ichiro , Harada Kenichiro , Yamagata Hirotaka , Matsubara Toshio , Matsuo Koji , Tanaka Saori C. , Imamizu Hiroshi , Ogawa Koichi , Momosaki Sotaro , Kawato Mitsuo , Yamashita Okito 
Published: March 2024

AbstractThe objective diagnostic and stratification biomarkers developed with resting-state functional magnetic resonance imaging (rs-fMRI) data are expected to contribute to more effective treatment for mental disorders. Unfortunately, there are currently no widely accepted biomarkers, partially due to the large variety of analysis pipelines for developing them. In this study we comprehensively evaluated analysis pipelines using a large-scale, multi-site fMRI dataset for major depressive disorder (MDD) (1162 participants from eight imaging sites). We explored the combinations of options in four subprocesses of analysis pipelines: six types of brain parcellation, four types of estimations of functional connectivity (FC), three types of site difference harmonization, and five types of machine learning methods. 360 different MDD diagnostic biomarkers were constructed using the SRPBS dataset acquired with unified protocols (713 participants from four imaging sites) as a discovery dataset and evaluated with datasets from other projects acquired with heterogeneous protocols (449 participants from four imaging sites) for independent validation. To identify the optimal options regardless of the discovery dataset, we repeated the same procedure after swapping the roles of the two datasets. We found pipelines that included Glasser’s parcellation, tangent-covariance, no harmonization, and non-sparse machine learning methods tended to result in high classification performance. The diagnosis results of the top 10 biomarkers showed high similarity, and weight similarity was also observed between eight of the biomarkers, except two that used both data-driven parcellation and FC computation. We applied the top 10 pipelines to the datasets of other mental disorders (autism spectral disorder: ASD and schizophrenia: SCZ) and eight of the ten biomarkers showed sufficient classification performances for both disorders, except two pipelines that included Pearson correlation, ComBat harmonization and random forest classifier combination.HighlightsWe evaluated the analysis pipelines of rsFC biomarker development.Four subprocesses in them were investigated with two multi-site datasets.Glasser’s parcellation, tangent covariance, and non-sparse methods were preferred.The weight patterns of eight of the top 10 biomarkers showed high commonality.Eight of the top 10 pipelines were successful for developing SCZ/ASD biomarkers.
Nanoparticle-mediated delivery of peptide-based degraders enables targeted protein degradation
Authors: Ghosal Souvik , Robertus Cara , Wang Jeanette , Chan Harrison W. , Alamgir Azmain , Almonte Joshua , Alabi Christopher A. 
Published: March 2024

ABSTRACTThe development of small molecule-based degraders against intracellular protein targets is a rapidly growing field that is hindered by the limited availability of high-quality small molecule ligands that bind to the target of interest. Despite the feasibility of designing peptide ligands against any protein target, peptide-based degraders still face significant obstacles such as, limited serum stability and poor cellular internalization. To overcome these obstacles, we repurposed lipid nanoparticle (LNP) formulations to facilitate the delivery of Peptide-based proteolysis TArgeting Chimeras (PepTACs). Our investigations reveal robust intracellular transport of PepTAC-LNPs across various clinically relevant human cell lines. Our studies also underscore the critical nature of the linker and hydrophobic E3 binding ligand for efficient LNP packaging and transport. We demonstrate the clinical utility of this strategy by engineering PepTACs targeting two critical transcription factors, β-catenin and CREPT (cell-cycle-related and expression-elevated protein in tumor), involved in the Wnt-signalling pathway. The PepTACs induced target-specific protein degradation and led to a significant reduction in Wnt-driven gene expression and cancer cell proliferation. Mouse biodistribution studies revealed robust accumulation of PepTAC-LNPs in the spleen and liver, among other organs, and PepTACs designed against β-catenin and formulated in LNPs showed a reduction in β-catenin levels in the liver. Our findings demonstrate that LNPs can be formulated to encapsulate PepTACs, thus enabling robust delivery and potent intracellular protein degradation.
Ornamental radiance as a defence against mimicry at the monogamy-polygyny interface
Authors: Crompton Andrew 
Published: March 2024

AbstractOrnament evolves though sexual selection when both monogamy or polygyny are equally viable. In this special situation monogamous females will be be able to reject unwanted polygynous suitors only if monogamous males are able distinguish themselves with a sign of fidelity. Since the most sexually advantageous trait value for any male to possess is the one that matches the mean female preference, any signs so created will persist when either monogamy or polygyny subsequently becomes a dominant strategy. Species will therefore accumulate traces of each passage through the monogamous-polygynous boundary which, in birds, can lead, among other outcomes, to a collage of patches of coloured plumage. If a species lives at the interface long enough a polygynous bird might be able to copy the sign of fidelity. One defence against this aggressive mimicry will be to evolve to a sign that is costly or difficult to copy. This process is modelled mathematically showing that if variation of female preference is increased the male phenotype will alter in unpredictable ways that defy a mimic, at a cost of possibly being maladapted. This causes an ornamental radiance that matches ideas of beauty in the human world.
Rapid High-Throughput Isolation and purification of Chicken Myoblasts Based on Deterministic Lateral Displacement Microfluidic Chips
Authors: Gu Lihong , Liu Hongju , Wang Long , Fan Haokai , Zheng Xinli , Xu Tieshan , Jiang Qicheng , Zhou Teng , Shi Liuyong 
Published: March 2024

AbstractMyoblasts are defined as stem cells containing skeletal muscle cell precursors. However, there are some challenges associated with the purification of myoblast samples, including long culture times and ease of bacterial contamination. In this study, we propose a microfluidic myoblast cell enrichment and purification platform based on the principle of deterministic lateral displacement (DLD). To achieve this, we designed a DLD chip with three outlets and tested it on 11-day-old Wenchang chicken pectoral muscle tissue. A cell suspension was prepared using the collagenase method, pretreated, and then passed into the designed DLD chip for myoblast enrichment and purification. In this study, the number of myoblasts and the diameter of myoblasts increased slowly before E9, and the diameter of myofibers decreased and the number of myofibers increased rapidly after E9. The period when the number of muscle fibers is highest is E12, and the period when the diameter of muscle fibers increases again after the lowest point is also E12. After E12, the diameter of the muscle fibers increased and the number of muscle fibers decreased. At E12, myoblasts clustered and fused, and the proliferation of myoblasts was greatly reduced. E12 is both intact myoblasts and the most vigorous proliferation period, so the best time to determine isolation is E12. We attained a myoblast cell recovery rate of 80%, a target outlet collection purity of 99%, and a chip throughput of 50 μ m/min. This study provides a novel and effective method for the isolation and purification of skeletal muscle myoblasts.