bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Blood Group Variants in an Omani Population by Comparison of Whole Genome Sequencing and Serology
Authors: Haffener Paige E. , Al-Riyami Arwa Z. , Al-Zadjali Shoaib , Al-Rawahi Mohammed , Al Hosni Saif , Al Marhoobi Ali , Al Sheriyani Ammar , Leffler Ellen M. 
Published: June 2024

AbstractAlthough blood group variation was first described over a century ago, our understanding of the genetic variation affecting antigenic expression on the red blood cell surface in many populations is lacking. This deficit limits the ability to accurately type patients, especially as serological testing is not available for all described blood groups, and targeted genotyping panels may lack rare or population-specific variants. Here, we perform serological assays across 24 antigens and whole genome sequencing on 100 Omanis, a population underrepresented in genomic databases. We inferred blood group phenotypes using the most commonly typed genetic variants. The comparison of serological to inferred phenotypes resulted in an average concordance of 96.9%. Among the 22 discordances, we identify seven known variants in four blood groups that, to our knowledge, have not been previously reported in Omanis. Incorporating these variants for phenotype inference, concordance increases to 98.8%. Additionally, we describe five candidate variants in the Lewis, Lutheran, MNS, and P1 blood groups that may affect antigenic expression, although further functional confirmation is required. Notably, we identify several blood group alleles most common in African populations, likely introduced to Oman by gene flow over the last thousand years. These findings highlight the need to evaluate individual populations and their population history when considering variants to include in genotype panels for blood group typing. This research will inform future work in blood banks and transfusion services.Key PointsUtilizing whole genome sequencing to infer blood types in Omanis demonstrates high sensitivity for most blood groupsPopulation history influences blood group variation, necessitating population-specific genotype panels
Discovery of tumour indicating morphological changes in benign prostate biopsies through AI
Authors: Chelebian Eduard , Avenel Christophe , Järemo Helena , Andersson Pernilla , Bergh Anders , Wählby Carolina 
Published: June 2024

AbstractBackground and ObjectiveDiagnostic needle biopsies that miss clinically significant prostate cancers (PCa) likely sample benign tissue adjacent to cancer. Such samples may contain changes indicating the presence of cancer elsewhere in the organ. Our goal is to evaluate if artificial intelligence (AI) can identify morphological characteristics in benign biopsies of men with raised PSA that predict the future detection of clinically significant PCa during a 30-month follow-up.MethodsA retrospective cohort of 232 patients with raised PSA and benign needle biopsies, paired by age, year of diagnosis and PSA levels was collected. Half were diagnosed with PCa within 30 months, while the other half remained cancer-free for at least eight years. AI model performance was assessed using the area under the receiver operating characteristic curve (AUC) and attention maps were used to visualise the morphological patterns relevant for cancer diagnosis as captured by the model.Key findings and LimitationsThe AI model could identify patients that were later diagnosed with PCa from their initial benign biopsies with an AUC of 0.82. Distinctive morphological patterns, such as altered stromal collagen and changes in glandular epithelial cell composition, were revealed.Conclusions and Clinical ImplicationsAI applied to standard haematoxylin-eosin sections identifies patients initially diagnosed as negative but later found to have clinically significant PCa. Morphological patterns offer insights into the long-ranging effects of PCa in the benign parts of the tumour-bearing organ.Patient SummaryUsing AI, we identified subtle changes in normal prostate tissue suggesting the presence of tumours elsewhere in the prostate. This could aid in the early identification of potentially high-risk tumours, limiting overuse of prostate biopsies.
A causal link between autoantibodies and neurological symptoms in long COVID
Authors: Santos Guedes de Sa Keyla , Silva Julio , Bayarri-Olmos Rafael , Brinda Ryan , Alec Rath Constable Robert , Colom Diaz Patricia A. , Kwon Dong-il , Rodrigues Gisele , Wenxue Li , Baker Christopher , Bhattacharjee Bornali , Wood Jamie , Tabacof Laura , Liu Yansheng , Putrino David , Horvath Tamas L. , Iwasaki Akiko 
Published: June 2024

SummaryAcute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.
Novel Loci (EIF4A2, ADIPOQ, TPRG1) for Triglyceride / High-density Lipoprotein Cholesterol Ratio Longitudinal Change (ΔTHR) among Subjects without Type 2 Diabetes: Evidence from the Long Life Family Study (LLFS) and the Framingham Heart Study (FHS) Offspring Cohort (OS)
Authors: Wang Lihua , Wang Siyu , Anema Jason A. , Moghaddam Vaha A. , Lu Yanli , Lin Shiow , Daw E. Warwick , Kuipers Allison L. , Miljkovic Iva , Brent Michael , Patti Gary , Thygarajan Bharat , Zmuda Joseph M. , Province Michael A. , An Ping 
Published: June 2024

AbstractAims/hypothesisTriglyceride (TG)/High density lipoprotein cholesterol (HDL-C) ratio (THR) represents a single surrogate predictor of hyperinsulinemia or insulin resistance that is associated with premature aging processes, risk of diabetes and increased mortality. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among subjects of European ancestry who had complete data from two exams collected about seven years apart from the Long Life Family Study (LLFS, n=1384), a study with familial clustering of exceptional longevity in the US and Denmark.MethodsSubjects with diabetes or using medications for dyslipidemia were excluded from this analysis. ΔTHR was derived using growth curve modeling, and adjusted for age, sex, field centers, and principal components (PCs). GWAS was conducted using a linear mixed model accounted for familial relatedness. Our linkage scan was built on haplotype-based IBD estimation with 0.5 cM average spacing.ResultsHeritability of ΔTHR was moderate (46%). Our GWAS identified a significant locus at theLPL(p=1.58e-9) for ΔTHR; this gene locus has been reported before influencing baseline THR levels. Our GWLS found evidence for a significant linkage with a logarithm of the odds (LODs) exceeding 3 on3q28(LODs=4.1). Using a subset of 25 linkage enriched families (pedigree-specific LODs>0.1), we assessed sequence elements under3q28and identified two novel variants (EIF4A2/ADIPOQ-rs114108468,p=5e-6, MAF=1.8%;TPRG1-rs16864075,p=3e-6, MAF=8%; accounted for ∼28% and ∼29% of the linkage, respectively, and 57% jointly). While the former variant was associated withEIF4A2(p=7e-5) /ADIPOQ(p=3.49e-2) RNA transcriptional levels, the latter variant was not associated withTPRG1(p=0.23) RNA transcriptional levels. Replication in FHS OS observed modest effect of these loci on ΔTHR. Of 188 metabolites from 13 compound classes assayed in LLFS, we observed multiple metabolites (e.g., DG.38.5, PE.36.4, TG.58.3) that were significantly associated with the variants (p<3e-4).ConclusionsOur linkage-guided sequence analysis approach permitted our discovery of two novel gene variantsEIF4A2/ADIPOQ-rs114108468 andTPRG1-rs16864075 on3q28for ΔTHR among subjects without diabetes selected for exceptional survival and healthy aging.
Dorsal root ganglia atrophy and serum biomarkers supporting the diagnosis of chronic postsurgical inguinal pain
Authors: Herrmann Eva , Schindehütte Magnus , Kindl Gudrun , Reinhold Ann-Kristin , Aulbach Felix , Rose Norman , Dreiling Johannes , Schwarzkopf Daniel , Meir Michael , Jin Yuying , Teichmüller Karolin , Widder Anna , Blum Robert , Sawalma Abdelrahman , Cebulla Nadine , Sendtner Michael , Meissner Winfried , Brack Alexander , Pham Mirko , Sommer Claudia , Schlegel Nicolas , Rittner Heike L. 
Published: June 2024

AbstractBackgroundChronic postsurgical inguinal pain (CPIP) is the most common complication of groin hernia surgery. The characteristics of patients, their medical care, and choice of the best diagnostic tools remain to be defined to optimize preventive and therapeutic interventions.MethodsClaims data from 2018 and a 1-year follow-up were analysed and deep phenotyping including sensory testing, blood and skin biopsies, MRI imaging of the dorsal root ganglion (DRG), and patient-reported outcomes were used to define normative values, as well as incidence, medical care, and pathophysiological factors.Results11,221 patients with hernia surgery in 2018 were identified; 8.5% had pain before which was relieved by surgery, but a similar percentage had novel groin pain. Deep phenotyping of 141 healthy controls provided a map of the inguinal sensory system. CPIP patients suffered from moderate pain with neuropathic features, individual sensory abnormalities, and unilateral L1 DRG atrophy. In the blood, C-C-motif chemokine ligand (CCL2) and brain-derived neurotrophic factor (BDNF) were upregulated while apolipoprotein A1 (ApoA1) was reduced. A cluster of DRG atrophy, BDNF, ApoA1 and anxiety correlated best with the diagnosis. CPIP patients with novel pain had significantly more DRG atrophy (−22% ipsi vs. contra).ConclusionCPIP is relevant and often newly acquired after surgery. A combination of DRG imaging, serum markers, and anxiety screening can support the diagnosis. Using this core set of markers could guide surgeons towards more personalized therapies and possible preventive intraoperative techniques.Trial registrationGerman Trial Registry DRKS00024588 and DRKS00016790
Y RNA-derived fragments in a complex with YBX1 modulate PARP1 residency at DNA double strand breaks
Authors: Shaw Annabelle , Ajit Kamal , Gullerova Monika 
Published: June 2024

SummaryTo protect genome integrity from pervasive threats of damage and prevent diseases like cancer, cells employ an integrated network of signalling pathways called the DNA damage response. These pathways involve both protein and RNA components which can act within the damaged cell or be transferred intercellularly to influence population-wide responses to damage. Here, we show that radioprotection can be conferred by damage-derived exosomes and is dependent on YBX1-packaged Y3-derived ysRNA. In recipient cells, ysRNA are methylated on cytosine by an RNA methyltransferase NSUN2, and bound by m5C reader, YBX1. YBX1/ysRNA localises at double strand break (DSB) sites to promote efficient DNA repair and cell survival through complex formation with PARP1. YBX1 modulates PARP1 auto-modification by facilitating ysRNA ADP-ribosylation, promoting increased PARP1 residency at DSBs. Our data highlight an unprecedented role for these under-studied species of small non-coding RNA, identifying them as a novel substrate for PARP1 mediated ADP-ribosylation and their function in DNA repair.
A Coronaviral Pore-Replicase Complex Drives RNA Synthesis in Double Membrane Vesicles
Authors: Chen Anan , Lupan Ana-Mihaela , Quek Rui Tong , Stanciu Stefan G. , Asaftei Mihaela , Stanciu George A. , Hardy Kierra S. , de Almeida Magalhães Taciani , Silver Pamela A. , Mitchison Timothy J. , Salic Adrian 
Published: June 2024

AbstractCoronavirus-infected cells contain double-membrane vesicles (DMVs) that are key for viral RNA replication and transcription, perforated by hexameric pores connecting the vesicular lumen to the cytoplasm. How pores form and traverse two membranes, and how DMVs organize RNA synthesis, is unknown. Using structure prediction and functional assays, we show that the non-structural viral membrane protein nsp4 is the key DMV pore organizer, spanning the double membrane and forming most of the pore lining. Nsp4 interacts with nsp3 on the cytoplasmic side and with the viral replicase inside the DMV. Newly synthesized mRNAs exit the DMV into the cytoplasm, passing through a narrow ring of conserved nsp4 residues. Steric constraints imposed by the ring predict that modified nucleobases block mRNA transit, with broad spectrum anti-coronaviral activity.
DNA replication initiation timing is important for maintaining genome integrity
Authors: Reed Tristan T. , Kendal Abigail H. , Wozniak Katherine J. , Simmons Lyle A. 
Published: June 2024

ABSTRACTDNA replication is regulated by factors that promote or inhibit initiation. InBacillus subtilis,YabA is a negative regulator of DNA replication initiation while the newly identified kinase CcrZ is a positive regulator. The consequences of under-initiation or over-initiation of DNA replication to genome stability remain unclear. In this work, we measure origin to terminus ratios as a proxy for replication initiation activity. We show that ΔccrZand severalccrZalleles under-initiate DNA replication while ablation ofyabAor overproduction of CcrZ leads to over-initiation. We find that cells under-initiating DNA replication have few incidents of replication fork stress as determined by low formation of RecA-GFP foci compared with wild type. In contrast, cells over-initiating DNA replication show levels of RecA-GFP foci formation analogous to cells directly challenged with DNA damaging agents. We show that cells under-initiating and over-initiating DNA replication were both sensitive to mitomycin C and that changes in replication initiation frequency cause increased sensitivity to genotoxic stress. With these results, we propose that cells under-initiating DNA replication are sensitive to DNA damage due to a shortage of DNA for repair through homologous recombination. For cells over-initiating DNA replication, we propose that an increase in the number of replication forks leads to replication fork stress which is further exacerbated by chromosomal DNA damage. Together, our study shows that DNA replication initiation frequency must be tightly controlled as changes in initiation influence replication fork fate and the capacity of cells to efficiently repair damage to their genetic material.IMPORTANCEThe regulation of DNA replication is fundamental to cell growth and cell cycle control. In eukaryotes under-initiation or over-initiation leads to genome instability. For bacteria, it is unclear how changes in replication initiation frequency impact DNA replication status and genome integrity. We show that tight regulation of DNA replication initiation is critical for maintaining genome integrity. Cells over-initiating or under-initiating DNA replication are sensitive to DNA damage. Further, cells over-initiating DNA replication experience replication fork stress at levels that phenocopy cells encountering DNA damage from the crosslinking agent mitomycin C. Our results establish the critical importance of properly regulating DNA replication initiation frequency because an imbalance in initiation results in replication fork perturbations, deficiencies in DNA repair, and genome instability.
An independent, multi-country head-to-head accuracy comparison of automated chest x-ray algorithms for the triage of pulmonary tuberculosis
Authors: Worodria William , Castro Robert , Kik Sandra V. , Dalay Victoria , Derendinger Brigitta , Festo Charles , Nguyen Thanh Quoc , Raberahona Mihaja , Sudarsan Swati , Andama Alfred , Thangakunam Balamugesh , Lyimo Issa , Nguyen Viet Nhung , Rakotoarivelo Rivo , Theron Grant , Yu Charles , Denkinger Claudia M. , Lapierre Simon Grandjean , Cattamanchi Adithya , Christopher Devasahayam J. , Jaganath Devan ,   R2D2 TB Network
Published: June 2024

ABSTRACTBackgroundComputer-aided detection (CAD) algorithms for automated chest X-ray (CXR) reading have been endorsed by the World Health Organization for tuberculosis (TB) triage, but independent, multi-country assessment and comparison of current products are needed to guide implementation.MethodsWe conducted a head-to-head evaluation of five CAD algorithms for TB triage across seven countries. We included CXRs from adults who presented to outpatient facilities with at least two weeks of cough in India, Madagascar, the Philippines, South Africa, Tanzania, Uganda, and Vietnam. The participants completed a standard evaluation for pulmonary TB, including sputum collection for Xpert MTB/RIF Ultra and culture. Against a microbiological reference standard, we calculated and compared the accuracy overall, by country and key groups for five CAD algorithms: CAD4TB (Delft Imaging), INSIGHT CXR (Lunit), DrAid (Vinbrain), Genki (Deeptek), and qXR (qure.AI). We determined the area under the ROC curve (AUC) and if any CAD product could achieve the minimum target accuracy for a TB triage test (≥90% sensitivity and ≥70% specificity). We then applied country- and population-specific thresholds and recalculated accuracy to assess any improvement in performance.ResultsOf 3,927 individuals included, the median age was 41 years (IQR 29-54), 12.9% were people living with HIV (PLWH), 8.2% living with diabetes, and 21.2% had a prior history of TB. The overall AUC ranged from 0.774-0.819, and specificity ranged from 64.8-73.8% at 90% sensitivity. CAD4TB had the highest overall accuracy (73.8% specific, 95% CI 72.2-75.4, at 90% sensitivity), although qXR and INSIGHT CXR also achieved the target 70% specificity. There was heterogeneity in accuracy by country, and females and PLWH had lower sensitivity while males and people with a history of TB had lower specificity. The performance remained stable regardless of diabetes status. When country- and population-specific thresholds were applied, at least one CAD product could achieve or approach the target accuracy for each country and sub-group, except for PLWH and those with a history of TB.ConclusionsMultiple CAD algorithms can achieve or exceed the minimum target accuracy for a TB triage test, with improvement when using setting- or population-specific thresholds. Further efforts are needed to integrate CAD into routine TB case detection programs in high-burden communities.
Optimization of steady spin prediction by nonlinear iterative inversion algorithm
Authors: Yan Chao , Tu Lianghui 
Published: June 2024

Purpose
Since the inception of aircraft, the phenomenon of spin has persistently accompanied aircraft, and research into spin has been ongoing. This paper aims to introduce an optimization technique to enhance the traditional geometric method for predicting steady spin, aiming to achieve more precise predictive outcomes.

Design/methodology/approach
To begin with, the force and moment equations used for motion analysis are initially presented, followed by the establishment of the motion model. Subsequently, the forward problem is set up, and the equilibrium solutions for the left and right spins of the aircraft are determined using the geometric method under the basic and wingtip configurations, thus solving the forward problem. In the final stage, nonlinear inversion is applied, and the inversion objective function is formulated based on the least squares approach. Through iterative processes, the measured data are interpolated, leading to the acquisition of the accurate equilibrium solution.

Findings
The findings indicate that the utilization of the nonlinear iterative inversion algorithm has effectively optimized the geometric method, yielding favorable outcomes. Postoptimization, the prediction accuracy has been enhanced, and the error has significantly diminished when compared to the preoptimization results.

Originality/value
The nonlinear inversion algorithm is used to refine the steady spin prediction for general aviation aircraft. This approach significantly mitigates the precision issues inherent in the forward problem. As demonstrated through the simulations provided, the application of the nonlinear iterative algorithm to resolve the inversion function yields promising optimization outcomes.
Revolutionizing finance with bitcoin and blockchain: a literature review and research agenda
Authors: Han Sirui , Lu Haitian , Wu Hao 
Published: June 2024

PurposeOur analysis is targeted at researchers in the fields of economics and finance, and we place emphasis on the incremental contributions of each paper, key research questions, study methodology, main conclusions and data and identification tactics. By focusing on these critical areas, our review seeks to provide valuable insights and guidance for future research in this rapidly evolving and complex field.Design/methodology/approachThis paper conducts a structured literature review (SLR) of Bitcoin-related articles published in the leading finance, economics and accounting journals between 2018 and 2023. Following Massaro et al. (2016), SLR is a method for examining a corpus of scholarly work to generate new ideas, critical reflections and future research agendas. The goals of SLR are congruent with the three outcomes of critical management research identified by Alvesson and Deetz (2000): insight, critique and transformative redefinition.FindingsThe present state of research on Bitcoin lacks coherence and interconnectedness, leading to a limited understanding of the underlying mechanisms. However, certain areas of research have emerged as significant topics for further exploration. These include the decentralized payment system, equilibrium price, market microstructure, trading patterns and regulation of Bitcoin. In this context, this review serves as a valuable starting point for researchers who are unacquainted with the interdisciplinary field of bitcoin and blockchain research. It is essential to recognize the potential value of research in Bitcoin-related fields in advancing knowledge of the interaction between finance, economics, law and technology. Therefore, future research in this area should focus on adopting innovative and interdisciplinary methods to enhance our comprehension of these intricate and evolving technologies.Originality/valueOur review encompasses the latest research on Bitcoin, including its market microstructure, trading behavior, price patterns and portfolio analysis. It explores Bitcoin's market microstructure, liquidity, derivative markets, price discovery and market efficiency. Studies have also focused on trading behavior, investors' characteristics, market sentiment and price volatility. Furthermore, empirical studies demonstrate the advantages of including Bitcoin in a portfolio. These findings enhance our understanding of Bitcoin's potential impact on the financial industry.