bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Degradome Sequencing Protocol via Reagent Recycling from sRNAseq Library Preparations
Authors: Puchta-Jasińska Marta , Groszyk Jolanta , Boczkowska Maja 
Published: August 2024

ABSTRACTBackgroundOne of the key elements in the analysis of gene expression and its post-translational regulation is miRNAs. Degradome-seq analyses are performed to analyze the cleavage of target RNAs in the transcriptome. In this work, an improved library preparation protocol for degradome sequencing is presented. The developed protocol improves the efficiency of library preparation in degradome-seq analysis used to identify microRNA targets, reduces the time of library preparation and lowers the cost of purchasing reagents..ResultsThe aim of this study was the development of an efficient protocol for the construction of degradome sequencing libraries using residual reagents from the sRNA-seq library preparation kit. To this end, modified primers and adaptors were designed. The library purification step based on automated electrophoresis and high-resolution agarose was modified and optimized in the presented protocol. Size standards of 60 and 65 bp were developed. They were prepared for precise band excision from the gel. Cloning to plasmid and sequencing of the inserted fragment, i.e., a fragment from the degradome library, verified the correctness of the library preparation using the developed protocol.ConclusionThe developed protocol allowed the construction and sequencing of degradome libraries even from RNA samples with low RIN. It significantly reduces the cost of library construction. This is due to the use of residues from the sRNA-seq library kit. The precision of the excised fragment after electrophoresis performed during the procedure to isolate fragments of the correct length is significantly improved by the use of additional size markers. Compared to previously used methods, optimizing the purification method of degradom-seq libraries allowed to increase the yield of fragments obtained. Notably, the time required for the entire library preparation protocol does not exceed three days, also a significant time savings.
Optimized semi-specific PCR amplification using arbitrarily degenerate primer for genome-wide genotyping and its application in peanut genetic diversity study
Authors: Zhao Sheng , Wang Yue , Zhang Xuejiao , Xie Shuxian , Chen Haotian , Yan Yiming , Gu Jiaqi , Chen Peng , Chang Yuxiao , Xu Zhijun 
Published: August 2024

AbstractCultivated peanut (Arachis hypogaeaL.) is an important legume crop with a large genome size but a limited genetic diversity. Evaluating the genetic variation among diverse peanut germplasms using genome-wide molecular markers is an effective strategy to explore its genetic diversity and thereby facilitate peanut improvement. In this study, we introduced a novel whole-genome genotyping (WGG) technique named dRAPD-seq (degenerate Random Amplification Polymorphic DNA and sequencing), which relies on semi-specific PCR amplification by arbitrarily degenerate (AD) primer and next-generation sequencing (NGS), and demonstrated its robust reproducibility and high accuracy. Subsequently, we applied dRAPD-seq to investigate the genetic relatedness within a population of 101 diverse peanut accessions and identified a low genetic diversity among these accessions. Our phylogenetic tree, population structure analyses, and principal component analysis (PCA) indicated that this population could be clustered into three subpopulations, largely corresponding to three botanical types. In conclusion, this research not only introduced a cost-effective and easy-to-conduct WGG method but also provided valuable insights for utilizing these peanut accessions in future breeding programs.
Decoding the Dewlap: Multiple signals in females and males of a gliding lizard
Authors: Sharma Avantika Deep , Sridharan Aravind , Isvaran Kavita 
Published: August 2024

AbstractSocial interactions across taxa are often mediated through multiple signals. Studies examining the maintenance of multiple signals are mostly focused on males and often fail to capture female signalling diversity and strategies. In the recent decade, there has been a surge in the documentation of female signalling, however, our understanding of the functional relevance of multiple signals in females still lags behind. In this study, we examined multiple signals in females of an arboreal gliding lizard,Draco dussumieri, and compared them to those in males. We specifically tested the relative role of the backup signal and the multiple receiver hypotheses in the maintenance of multiple signals in both sexes. FemaleD.dussumieriused a variety of signals to socially interact with conspecifics, especially using their dewlap. The signalling repertoire of females was as diverse as that of males, although the relative use of the signals varied. In females, a few signals seem to be maintained by the backup signal hypothesis, with limited support for the multiple receiver hypothesis as well. For males too, both mechanisms appeared to maintain multiple signals. Interestingly, for some signals, the sexes differed in the context in which they used a given signal. Overall, these findings highlight the functional role of multiple signals in females, which can differ from that observed in males. Therefore, traits conventionally considered male-exclusive when also examined in females can provide finer insights into trait function and evolution.
Diagnosis of celiac disease on a gluten-free diet: a multicenter prospective quasi-experimental clinical study
Authors: Gómez-Aguililla Sara , Farrais Sergio , López-Palacios Natalia , Arau Beatriz , Senosiain Carla , Corzo María , Fernandez-Jimenez Nora , Ruiz-Carnicer Ángela , Fernández-Bañares Fernando , González-García Bárbara P. , Tristán Eva , Montero-Calle Ana , Garranzo-Asensio María , Casado Isabel , Pujals Mar , Hernández Juana María , Infante-Menéndez Jorge , Roy Garbiñe , Sousa Carolina , Núñez Concepción 
Published: August 2024

BackgroundDiagnosing celiac disease (CD) in individuals adhering to a gluten-free diet (GFD) presents significant challenges. Current guidelines recommend a gluten challenge (GC) lasting at least 6-8 weeks, which has several limitations.ObjectivesThis study compares four approaches previously proposed for diagnosing CD on a GFD: IL-2 serum levels, gut-homing CD8+T cells, %TCRγδ+intraepithelial lymphocytes (IELs), andUBE2L3gene expression. Additionally, we evaluated the CD8+T-cell based method with a 3-day GC against the standard GC protocol.MethodsWe conducted a multicenter prospective quasi-experimental clinical study. Two subsets of individuals were considered: 1) 20 patients with CD and 15 non-CD controls previously diagnosed, to evaluate the first aim; 2) 45 individuals with uncertain diagnosis who were on a GFD and required GC following current clinical guidelines, to assess the second aim. All participants underwent a 3-day GC (10 g gluten/day).ResultsAmong CD patients and non-CD controls, the sensitivity and specificity of IL-2, gut-homing CD8+T cells, andUBE2L3were 82.4% and 83.3%, 88.2% and 100%, and 52.9% and 100%, respectively. The percentage of TCRγδ+IELs showed 88.2% sensitivity. In the uncertain diagnosis group, a CD8+T-cell positive response was observed in 8 of the 45 subjects.ConclusionThe percentage of TCRγδ+IELs and the gut-homing CD8+T-cell assay are promising diagnostic methods for CD on a GFD. Notably, the CD8+T-cell assay provides a consistent and reliable alternative to the extended GC, eliminating the need for the invasive procedures to obtain duodenal samples and the prolonged gluten ingestion.
Functions of PMS2 and MLH1 important for regulation of divergent repeat-mediated deletions
Authors: Trost Hannah , Lopezcolorado Felicia Wednesday , Merkell Arianna , Stark Jeremy M. 
Published: August 2024

ABSTRACTRepeat-mediated deletions (RMDs) are a type of deletion rearrangement that utilizes two repetitive elements to bridge a DNA double-strand break (DSB) that leads to loss of the intervening sequence and one of the repeats. Sequence divergence between repeats causes RMD suppression and indeed this divergence must be resolved in the RMD products. The mismatch repair factor, MLH1, was shown to be critical for both RMD suppression and a polarity of sequence divergence resolution in RMDs. Here, we sought to study the interrelationship between these two aspects of RMD regulation (i.e., RMD suppression and polar divergence resolution), by examining several mutants of MLH1 and its binding partner PMS2. To begin with, we show that PMS2 is also critical for both RMD suppression and polar resolution of sequence divergence in RMD products. Then, with six mutants of the MLH1-PMS2 heterodimer, we found several different patterns: three mutants showed defects in both functions, one mutant showed loss of RMD suppression but not polar divergence resolution, whereas another mutant showed the opposite, and finally one mutant showed loss of RMD suppression but had a complex effect on polar divergence resolution. These findings indicate that RMD suppression vs. polar resolution of sequence divergence are distinct functions of MLH1-PMS2.HIGHLIGHTSMLH1-PMS2 suppresses divergent repeat-mediated deletions (RMDs).MLH1-PMS2 promotes polar resolution of sequence divergence.Several mutants of MLH1-PMS2 affect both aspects of RMDs.Some MLH1-PMS2 mutants affect only one aspect of RMDs.Suppression of RMDs vs. polar resolution of divergence appear distinct.
The PVT1, HULC, and HOTTIP expression changes due to treatment in Diffuse Large B-cell lymphoma
Authors: Shahsavari Milad , Arbabian Sedigheh , Hosseini Farzaneh , Razavi Mohamad Reza 
Published: August 2024

AbstractDiffuse large B-cell lymphoma is the most common histological subtype of non-Hodgkin’s lymphomas. It is an aggressive malignancy that displays great heterogeneity in morphology, genetics, biological behavior and treatment response owing to chromatin remodeling and epigenetics.Bioinformatic-based approaches were used to understand the possible signaling pathways of the three lncRNAsPVT1,HULC, andHOTTIP. Furthermore, their expression levels were quantitatively evaluated in 100 patients before and after the treatment.The results revealed that gene expression was significantly upregulated inPVT1,HULC, andHOTTIPby 7.39±8.48-, 5.924±7.536-, and 4.137±5.863 fold, respectively, relative to normal cases. Post-treatment measurement of lncRNA expression indicated thatPVT1andHOTTIPwere significantly downregulated.Interestingly, the expression levels ofPVT1,HULC, andHOTTIPwere significantly higher in DLBCL patients aged > 60 years than in those aged < 60 years. In addition, there was a significant positive correlation betweenHULCandHOTTIPexpression.The analysis of overexpressed lncRNA-miRNA interaction indicated different deregulated miRNA targets and the protein targets of upregulated lncRNAs are mainly with histone modification, DNA methylation/demethylation, and protein methyltransferase activity.Summary blurbThe lncRNAsPVT1,HULC, andHOTTIPexpression is significantly upregulated before treatment and reduce to normal level after treatment. It can be used as diagnostic marker or prognostic means especially in Relapsed/refractory DLBCL.
Exploit Spatially Resolved Transcriptomic Data to Infer Cellular Features from Pathology Imaging Data
Authors: Sui Zhining , Li Ziyi , Sun Wei 
Published: August 2024

AbstractDigital pathology is a rapidly advancing field where deep learning methods can be employed to extract meaningful imaging features. However, the efficacy of training deep learning models is often hindered by the scarcity of annotated pathology images, particularly images with detailed annotations for small image patches or tiles. To overcome this challenge, we propose an innovative approach that leverages paired spatially resolved transcriptomic data to annotate pathology images. We demonstrate the feasibility of this approach and introduce a novel transfer-learning neural network model, STpath (Spatial Transcriptomics and pathology images), designed to predict cell type proportions or classify tumor microenvironments. Our findings reveal that the features from pre-trained deep learning models are associated with cell type identities in pathology image patches. Evaluating STpath using three distinct breast cancer datasets, we observe its promising performance despite the limited training data. STpath excels in samples with variable cell type proportions and high-resolution pathology images. As the influx of spatially resolved transcriptomic data continues, we anticipate ongoing updates to STpath, evolving it into an invaluable AI tool for assisting pathologists in various diagnostic tasks.
Influential drivers of the cost-effectiveness of respiratory syncytial virus vaccination in European older adults: A multi-country analysis
Authors: Li Xiao , Willem Lander , Johannesen Caroline Klint , Urchueguía-Fornes Arantxa , Lehtonen Toni , Osei-Yeboah Richard , Salo Heini , Orrico-Sánchez Alejandro , Díez-Domingo Javier , Jit Mark ,   PROMISE investigators, Bilcke Joke , Nair Harish , Beutels Philippe 
Published: August 2024

AbstractBackgroundWe aimed to identify influential drivers of the cost-effectiveness of older adult respiratory syncytial virus (RSV) vaccination in Denmark, Finland, the Netherlands and Valencia-Spain.MethodsA static multi-cohort model was parameterised using country-and age-specific hospitalisations using three approaches: (1) the International Classification of Diseases (ICD)-coded hospitalisations, (2) laboratory RSV-confirmed hospitalisations and (3) time-series modelling (TSM). Plausible hypothetical RSV vaccine characteristics were derived from two protein subunit vaccines for adults aged ³60 years (“60y+”). Costs and quality-adjusted life-years (QALYs) were compared between four strategies: (a) “no intervention” and RSV vaccination in adults (b) 60y+; (c) 65y+; (d) 75y+, from both the healthcare payers’ and societal perspectives. Value of information, probabilistic sensitivity and scenario analyses identified influential drivers.ResultsBesides vaccine price, the hospitalisation estimates were most influential: Using adjusted RSV-ICD-coded hospitalisations at a vaccine price of €150 per dose, no intervention was cost-effective up to willingness-to-pay (WTP) values of €150 000 per QALY gained in Denmark and the Netherlands, and up to €125 000 per QALY gained in Finland. Using the adjusted RSV-confirmed dataset, the findings were consistent in Denmark and comparable in Finland. In Spain-Valencia, the 75y+ strategy became cost-effective at WTP >€55 000. Using TSM-based estimates, the 75y+ strategy was cost-effective at WTP >€45 000, >€101 000, >€41 000 and >€114 000 in Denmark, Finland, the Netherlands and Spain-Valencia, respectively. The (in-hospital) case fatality ratio and the specification of its age dependency were both influential. Duration of protection was found more influential than a variety of plausible waning patterns over the duration of protection.ConclusionData gaps and uncertainties on the RSV-related burden in older adults persist and influence the cost-effectiveness of RSV vaccination. More refined age-and country-specific data on the RSV attributable burden are crucial to aid decision making.
Preliminary reference values for Alzheimer’s disease plasma biomarkers in Congolese individuals with and without Alzheimer’s disease
Authors: Ikanga Jean , Jean Kharine , Medina Priscilla , Patel Saranya Sundaram , Schwinne Megan , Epenge Emmanuel , Gikelekele Guy , Tshengele Nathan , Kavugho Immaculee , Mampunza Samuel , Mananga Lelo , Teunissen Charlotte E. , Stringer Anthony , Rojas Julio C. , Chan Brandon , Lago Argentina Lario , Kramer Joel H. , Boxer Adam L. , Jeromin Andreas , Gross Alden L. , Alonso Alvaro 
Published: August 2024

ABSTRACTBackgroundWestern countries have provided reference values (RV) for Alzheimer’s disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations.ObjectiveWe provide preliminary RV for AD and other plasma biomarkers including amyloid- β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor α (TNFα) in Congolese adults with and without dementia.Methods85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers Aβ42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFα analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youden’s index.ResultsIn this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for Aβ42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers.ConclusionsThis study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.
Global Stroke Burden from Metabolic Risks Across Demographics: Findings from the 2021 Global Burden of Disease Study
Authors: Xue Song , Wu Guoqing 
Published: August 2024

AbstractBackgroundStroke is the second leading cause of death and the primary cause of disability worldwide. Metabolic risks are major contributors to stroke. The global trends in metabolic risk-related stroke from 1990 to 2019, and the differences in mortality and DALYs across various demographic factors, remain unclear.MethodsAll analyses were based on rates derived from the GBD2021 results (https://vizhub.healthdata.org/gbd-results/). Data were stratified by gender, region, and age. Joinpoint software was used to perform regression analysis of the average annual percent change (AAPC) and its 95% confidence interval to analyze trends from 1990 to 2019. Excel, PowerPoint, and R software were used for plotting and analysis, with p<0.05 considered statistically significant.ResultsFrom 1990 to 2019, the average annual percent change (AAPC) for age-standardized rates (ASR) of DALYs was -1.70% (−1.81%, -1.58%), and for mortality, the AAPC was -1.57% (−1.68%, -1.46%). As the SDI increased, both the ASR of DALYs and mortality in 2019 showed a significant decline. The AAPC from 1990 to 2019 also exhibited a downward trend with increasing SDI levels. The DALYs and mortality rates of metabolic risk-related stroke predominantly affected individuals aged 75 and above, with a lesser impact on those under 55. For both genders, the 10-55 and 50-74 age groups had the highest DALYs and mortality rates due to metabolic-related intracerebral hemorrhage. For those aged 75-84 and over 85, ischemic stroke was the leading subtype of metabolic-related stroke contributing to DALYs and mortality rates.ConclusionThis is the first retrospective study on metabolic risk-related stroke on a global scale, summarizing its temporal trends and demographic distribution characteristics. Effective public health strategies are needed to address these disparities and continue reducing the global burden of metabolic risk-related strokes.
All of Us diversity and scale improve polygenic prediction contextually with greatest improvements for under-represented populations
Authors: Tsuo Kristin , Shi Zhuozheng , Ge Tian , Mandla Ravi , Hou Kangcheng , Ding Yi , Pasaniuc Bogdan , Wang Ying , Martin Alicia R. 
Published: August 2024

AbstractRecent studies have demonstrated that polygenic risk scores (PRS) trained on multi-ancestry data can improve prediction accuracy in groups historically underrepresented in genomic studies, but the availability of linked health and genetic data from large-scale diverse cohorts representative of a wide spectrum of human diversity remains limited. To address this need, the All of Us research program (AoU) generated whole-genome sequences of 245,388 individuals who collectively reflect the diversity of the USA. Leveraging this resource and another widely-used population-scale biobank, the UK Biobank (UKB) with a half million participants, we developed PRS trained on multi-ancestry and multi-biobank data with up to ∼750,000 participants for 32 common, complex traits and diseases across a range of genetic architectures. We then compared effects of ancestry, PRS methodology, and genetic architecture on PRS accuracy across a held out subset of ancestrally diverse AoU participants. Due to the more heterogeneous study design of AoU, we found lower heritability on average compared to UKB (0.075 vs 0.165), which limited the maximal achievable PRS accuracy in AoU. Overall, we found that the increased diversity of AoU significantly improved PRS performance in some participants in AoU, especially underrepresented individuals, across multiple phenotypes. Notably, maximizing sample size by combining discovery data across AoU and UKB is not the optimal approach for predicting some phenotypes in African ancestry populations; rather, using data from only AoU for these traits resulted in the greatest accuracy. This was especially true for less polygenic traits with large ancestry-enriched effects, such as neutrophil count (R2: 0.055 vs. 0.035 using AoU vs. cross-biobank meta-analysis, respectively, because of e.g.DARC). Lastly, we calculated individual-level PRS accuracies rather than grouping by continental ancestry, a critical step towards interpretability in precision medicine. Individualized PRS accuracy decays linearly as a function of ancestry divergence, but the slope was smaller using multi-ancestry GWAS compared to using European GWAS. Our results highlight the potential of biobanks with more balanced representations of human diversity to facilitate more accurate PRS for the individuals least represented in genomic studies.
Viral piracy of host RNA phosphatase DUSP11 by avipoxviruses
Authors: Szymanik Kayla H. , Hancks Dustin C. , Sullivan Christopher S. 
Published: August 2024

AbstractProper recognition of viral pathogens is an essential part of the innate immune response. A common viral replicative intermediate and chemical signal that cells use to identify pathogens is the presence of a triphosphorylated 5’ end (5’ppp) RNA, which activates the cytosolic RNA sensor RIG-I and initiates downstream antiviral signaling. While 5’pppRNA generated by viral RNA-dependent RNA polymerases (RdRps) can be a potent activator of the immune response, endogenous RNA polymerase III (RNAPIII) transcripts can retain the 5’pppRNA generated during transcription and induce a RIG-I-mediated immune response. We have previously shown that host RNA triphosphatase dual-specificity phosphatase 11 (DUSP11) can act on both host and viral RNAs, altering their levels and reducing their ability to induce RIG-I activation. Our previous work explored how artificially altered DUSP11 can impact immune activation, prompting further exploration into natural contexts of altered DUSP11. Here, we have identified viral DUSP11 homologs (vDUSP11s) present in some avipoxviruses. Consistent with the known functions of endogenous DUSP11, we have shown that expression of vDUSP11s: 1) reduces levels of endogenous RNAPIII transcripts, 2) reduces a cell’s sensitivity to 5’pppRNA-mediated immune activation, and 3) restores virus infection defects seen in the absence of DUSP11. Our results identify a virus-relevant context where DUSP11 activity has been co-opted to alter RNA metabolism and influence the outcome of infection.