bluuebunny/crossref_metadata_2025_split huggingface dataset:
dCCA: detecting differential covariation patterns between two types of high-throughput omics data
Authors: Lee Hwiyoung , Ma Tianzhou , Ke Hongjie , Ye Zhenyao , Chen Shuo 
Published: June 2024

Abstract

Motivation
The advent of multimodal omics data has provided an unprecedented opportunity to systematically investigate underlying biological mechanisms from distinct yet complementary angles. However, the joint analysis of multi-omics data remains challenging because it requires modeling interactions between multiple sets of high-throughput variables. Furthermore, these interaction patterns may vary across different clinical groups, reflecting disease-related biological processes.

Results
We propose a novel approach called Differential Canonical Correlation Analysis (dCCA) to capture differential covariation patterns between two multivariate vectors across clinical groups. Unlike classical Canonical Correlation Analysis, which maximizes the correlation between two multivariate vectors, dCCA aims to maximally recover differentially expressed multivariate-to-multivariate covariation patterns between groups. We have developed computational algorithms and a toolkit to sparsely select paired subsets of variables from two sets of multivariate variables while maximizing the differential covariation. Extensive simulation analyses demonstrate the superior performance of dCCA in selecting variables of interest and recovering differential correlations. We applied dCCA to the Pan-Kidney cohort from the Cancer Genome Atlas Program database and identified differentially expressed covariations between noncoding RNAs and gene expressions.

Availability and Implementation
The R package that implements dCCA is available at https://github.com/hwiyoungstat/dCCA.
Evergene: an interactive webtool for large-scale gene-centric analysis of primary tumours
Authors: Kennedy Anna , Richardson Ella , Higham Jonathan , Kotsantis Panagiotis , Mort Richard , Shih Barbara Bo-Ju 
Published: June 2024

Abstract

Motivation
The data sharing of large comprehensive cancer research projects, such as The Cancer Genome Atlas (TCGA), has improved the availability of high-quality data to research labs around the world. However, due to the volume and inherent complexity of high-throughput omics data, analysis of this is limited by the capacity for performing data processing through programming languages such as R or Python. Existing webtools lack functionality that supports large-scale analysis; typically, users can only input one gene, or a gene list condensed into a gene set, instead of individual gene-level analysis. Furthermore, analysis results are usually displayed without other sample-level molecular or clinical annotations. To address these gaps in the existing webtools, we have developed Evergene using R and Shiny.

Results
Evergene is a user-friendly webtool that utilizes RNA-sequencing data, alongside other sample and clinical annotation, for large-scale gene-centric analysis, including principal component analysis (PCA), survival analysis (SA), and correlation analysis (CA). Moreover, Evergene achieves in-depth analysis of cancer transcriptomic data which can be explored through dimensional reduction methods, relating gene expression with clinical events or other sample information, such as ethnicity, histological classification, and molecular indices. Lastly, users can upload custom data to Evergene for analysis.

Availability and implementation
Evergene webtool is available at https://bshihlab.shinyapps.io/evergene/. The source code and example user input dataset are available at https://github.com/bshihlab/evergene.
RNA m6A detection using raw current signals and basecalling errors from Nanopore direct RNA sequencing reads
Authors: Ni Peng , Xu Jinrui , Zhong Zeyu , Luo Feng , Wang Jianxin 
Published: June 2024

Abstract

Motivation
Nanopore direct RNA sequencing (DRS) enables the detection of RNA N6-methyladenosine (m6A) without extra laboratory techniques. A number of supervised or comparative approaches have been developed to identify m6A from Nanopore DRS reads. However, existing methods typically utilize either statistical features of the current signals or basecalling-error features, ignoring the richer information of the raw signals of DRS reads.

Results
Here, we propose RedNano, a deep-learning method designed to detect m6A from Nanopore DRS reads by utilizing both raw signals and basecalling errors. RedNano processes the raw-signal feature and basecalling-error feature through residual networks. We validated the effectiveness of RedNano using synthesized, Arabidopsis, and human DRS data. The results demonstrate that RedNano surpasses existing methods by achieving higher area under the ROC curve (AUC) and area under the precision-recall curve (AUPRs) in all three datasets. Furthermore, RedNano performs better in cross-species validation, demonstrating its robustness. Additionally, when detecting m6A from an independent dataset of Populus trichocarpa, RedNano achieves the highest AUC and AUPR, which are 3.8%–9.9% and 5.5%–13.8% higher than other methods, respectively.

Availability and implementation
The source code of RedNano is freely available at https://github.com/Derryxu/RedNano.
A protocol to isolate, identify, and verify glucose- or carbohydrate-binding receptors
Authors: Rashid Nadia , Chhabra Kavaljit H 
Published: June 2024

Abstract
Sensing, transport, and utilization of glucose is pivotal to the maintenance of energy homeostasis in animals. Although transporters involved in mobilizing glucose across different cellular compartments are fairly well known, the receptors that bind glucose to mediate its effects independently of glucose metabolism remain largely unrecognized. Establishing precise and reproducible methods to identify glucose receptors in the brain or other peripheral organs will pave the way for comprehending the role of glucose signaling pathways in maintaining, regulating, and reprogramming cellular metabolic needs. Identification of such potential glucose receptors will also likely lead to development of effective therapeutics for treatment of diabetes and related metabolic disorders. Commercially available biotin or radiolabeled glucose conjugates have low molecular weight; therefore, they do not provide enough sensitivity and density to isolate glucose receptors. Here, we describe a protocol to isolate, identify, and verify glucose-binding receptor/s using high molecular weight glucose (or other carbohydrate) conjugates. We have produced 30 kDa glucose– (or other carbohydrate–) biotin–polyacrylamide (PAA) conjugates with mole fractions of 80:5:15% respectively. These conjugates are used with biotin-streptavidin biochemistry, In-cell ELISA, and surface plasmon resonance (SPR) methods to isolate, identify, and verify glucose- or carbohydrate-binding receptors. We first demonstrate how streptavidin-coated magnetic beads are employed to immobilize glucose–biotin–PAA conjugates. Then, these beads are used to enrich and isolate glucose-binding proteins from tissue homogenates or from single-cell suspensions. The enriched or isolated proteins are subjected to mass spectrometry/proteomics to reveal the identity of top candidate proteins as potential glucose receptors. We then describe how the In-cell ELISA method is used to verify the interaction of glucose with its potential receptor through stable expression of the receptor in-vitro. We further demonstrate how a highly sensitive SPR method can be used to measure the binding kinetics of glucose with its receptor. In summary, we describe a protocol to isolate, identify, and verify glucose- or carbohydrate-binding receptors using magnetic beads, In-cell ELISA, and SPR. This protocol will form the future basis of studying glucose or carbohydrate receptor signaling pathways in health and in disease.
The early after discharge cardiac CT for low-risk chest pain study: the ED-CT study
Authors: Cronin Michael , Gill Aisling , Blake Eve , Dunne Niamh , Sheehy Niall , McMahon Geraldine , Murphy Ross , Daly Caroline 
Published: June 2024

Abstract

Objectives
An accelerated diagnostic pathway is created to aid the management of low-risk patients presenting to the emergency room with chest pain. Records are taken of patient outcomes and factors influencing physician decision-making between inpatient invasive angiography versus early outpatient cardiac CT angiography.

Methods
A cohort study at 30 days post discharge is undertaken over 1 year. Differences are observed between a population of patients who underwent early outpatient CT and a population of ambulatory haemodynamically stable patients who underwent inpatient fluoroscopic angiography.

Results
Totally, 369 patients underwent CT (F = 46%) and 37 underwent angiography (F = 30%). Median outpatient CT was at 14 days. At 30 days, 0 patients suffered mortality or myocardial infarction. Eleven percent were recommended for invasive angiography. Two percent of CT patients underwent coronary revascularization. Median calcium score was 0. Twenty percent of the CT population were commenced on high-potency statin or had their pre-existing statin dose intensified. Calcium score affected a composition of statin commencement, angiography, and revascularization (OR 59, P &lt; .001). Age, troponin, vascular disease, and previous coronary revascularization appeared to influence choice between coronary computed tomography angiography (CCTA) and invasive angiography.

Conclusion
An accelerated diagnostic pathway for outpatient cardiac CT for chest pain resulted in no mortality or myocardial infarction, with a low level of downstream testing and coronary revascularization.

Advances in knowledge
At a median time to CCTA of 14 days post discharge from the emergency department, there is no effect on patient major adverse cardiac events.
Four dimensions of naturalistic language production in aphasia after stroke
Authors: Casilio Marianne , Kasdan Anna V , Bryan Katherine , Shibata Kiiya , Schneck Sarah M , Levy Deborah F , Entrup Jillian L , Onuscheck Caitlin , de Riesthal Michael , Wilson Stephen M 
Published: June 2024

Abstract
There is a rich tradition of research on the neuroanatomical correlates of spoken language production in aphasia using constrained tasks (e.g. picture naming), which offer controlled insights into the distinct processes that govern speech and language (i.e. lexical-semantic access, morphosyntactic construction, phonological encoding, speech motor programming/execution). Yet these tasks do not necessarily reflect everyday language use. In contrast, naturalistic language production (also referred to as ‘connected speech’ or ‘discourse’) more closely approximates typical processing demands, requiring the dynamic integration of all aspects of speech and language. The brain bases of naturalistic language production remain relatively unknown, however, in part because of the difficulty in deriving features that are salient, quantifiable and interpretable relative to both speech-language processes and the extant literature. The present cross-sectional observational study seeks to address these challenges by leveraging a validated and comprehensive auditory-perceptual measurement system that yields four explanatory dimensions of performance—Paraphasia (misselection of words and sounds), Logopenia (paucity of words), Agrammatism (grammatical omissions) and Motor speech (impaired speech motor programming/execution).
We used this system to characterize naturalistic language production in a large and representative sample of individuals with acute post-stroke aphasia (n = 118). Scores on each of the four dimensions were correlated with lesion metrics, and multivariate associations among the dimensions and brain regions were then explored.
Our findings revealed distinct yet overlapping neuroanatomical correlates throughout the left-hemisphere language network. Paraphasia and logopenia were associated primarily with posterior regions, spanning both dorsal and ventral streams, which are critical for lexical-semantic access and phonological encoding. In contrast, agrammatism and motor speech were associated primarily with anterior regions of the dorsal stream that are involved in morphosyntactic construction and speech motor planning/execution, respectively.
Collectively, we view these results as constituting a brain–behaviour model of naturalistic language production in aphasia, aligning with both historical and contemporary accounts of the neurobiology of spoken language production.
Risk-stratified analysis of long-term clinical outcomes and cumulative costs in Finnish patients with recent acute coronary syndrome or coronary revascularization: a 5-year real-world study using electronic health records
Authors: Oksanen Minna , Parviainen Jenna , Asseburg Christian , Hageman Steven , Rissanen Tuomas T , Kivelä Annukka , Taipale Kristian , Visseren Frank , Martikainen Janne 
Published: June 2024

Abstract

Aims
Risk assessment is essential in the prevention of cardiovascular disease. In patients with recent acute coronary syndrome (ACS) or coronary revascularization, risk prediction tools, like the European Society of Cardiology guideline recommended SMART-REACH risk score, are increasingly used to predict the risk of recurrent cardiovascular events enabling risk-based personalized prevention. However, little is known about the association between risk stratification and the social and healthcare costs at a population level. This study evaluated the associations between baseline SMART-REACH risk scores, long-term recurrent clinical events, cumulative costs, and post-index event LDL-C goal attainment in patients with recent ACS and/or revascularization.

Methods and results
This retrospective study used electronic health records and was conducted in the North Karelia region of Finland. The study cohort included all patients aged 45–85 admitted to a hospital for ACS or who underwent percutaneous coronary intervention or coronary artery bypass surgery between 1 January 2017 and 31 December 2021. Patients were divided into quintiles based on their baseline SMART-REACH risk scores to examine the associations between predicted 5-year scores and selected clinical and economic outcomes. In addition, simple age-based stratification was conducted as a sensitivity analysis. The observed 5-year cumulative incidence of recurrent events ranged from 20% in the lowest to 41% in the highest risk quintile, whereas the corresponding predicted risks ranged from 13% to 51%, and cumulative 5-year mean total costs per patient ranged from 15 827 to 46 182€, respectively. Both monitoring and attainment of low LDL-C values were suboptimal.

Conclusion
The use of the SMART-REACH quintiles as a population-level risk stratification tool successfully stratified patients into subgroups with different cumulative numbers of recurrent events and cumulative total costs. However, more research is needed to define clinically and economically optimal threshold values for a population-level stratification.
Remembering Episcopalian Conformity in Restoration England
Authors: White William 
Published: June 2024

Abstract
This article examines how the phenomenon of episcopalian conformity in the late 1640s and 1650s was remembered, debated and explained after the Restoration. Drawing on petitions, pamphlets, funeral sermons and clerical biographies, it shows that both personal ambition and polemical advantage encouraged episcopalians to suppress evidence of Interregnum conformity from the moment the king returned in May 1660. Crucially, however, this kind of whitewashing was by no means the only—or even the principal—way in which episcopalian conformists retrospectively presented their own careers. Many clergymen after 1660 were eager to defend their decision to continue ministering publicly under the English Republic, claiming that their proselytising activities in these years had ultimately helped to advance the interests of Church and king. It is argued that these contrasting approaches to remembering conformity reflect the unstable, contested meaning of loyalty, especially after 1649. As well as adding a new dimension to recent literature on the significance of memories of the English Revolution in the late seventeenth century, the article therefore enhances our understanding of episcopalian identities during the 1640s and 1650s, helping to explain why clergymen who considered themselves loyal to the pre-war order could embark on such divergent trajectories when confronted with defeat, disestablishment and regicide.
Regulation of memory CD4+ T-cell generation by intrinsic and extrinsic IL-27 signaling during malaria infection
Authors: Tsogtsaikhan Sanjaadorj , Inoue Shin-Ichi , Bayarsaikhan Ganchimeg , Macalinao Maria Lourdes , Kimura Daisuke , Miyakoda Mana , Yamamoto Masahiro , Hara Hiromitsu , Yoshida Hiroki , Yui Katsuyuki 
Published: June 2024

Abstract
The generation and maintenance of memory T cells are regulated by various factors, including cytokines. Previous studies have shown that IL-27 is produced during the early acute phase of Plasmodium chabaudi chabaudi AS (Pcc) infection and inhibits the development of Th1-type memory CD4+ T cells. However, whether IL-27 acts directly on its receptor on Plasmodium-specific CD4+ T cells or indirectly via its receptor on other immune cells remains unclear. We aimed to determine the role of IL-27 receptor signaling in different immune cell types in regulating the generation and phenotype of memory CD4+ T cells during Plasmodium infection. We utilized Plasmodium-specific T-cell antigen receptor (TCR) transgenic mice, PbT-II, and Il27rα−/− mice to assess the direct and indirect effects of IL-27 signaling on memory CD4+ T-cell generation. Mice were transferred with PbT-II or Il27rα−/− PbT-II cells and infected with Pcc. Conditional knockout mice lacking the IL-27 receptor in T cells or dendritic cells were employed to discern the specific immune cell types involved in IL-27 receptor signaling. High levels of memory in PbT-II cells with Th1-shift occurred only when both PbT-II and host cells lacked the IL-27 receptor, suggesting the predominant inhibitory role of IL-27 signaling in both cell types. Furthermore, IL-27 receptor signaling in T cells limited the number of memory CD4+ T cells, while signaling in both T and dendritic cells contributed to the Th1 dominance of memory CD4+ T cells. These findings underscore the complex cytokine signaling network regulating memory CD4+ T cells during Plasmodium infection.
SeqCode in the golden age of prokaryotic systematics
Authors: Jiménez Diego Javier , Rosado Alexandre Soares 
Published: June 2024

Abstract
The SeqCode is a new code of prokaryotic nomenclature that was developed to validate taxon names using genome sequences as the type material. The present article provides an independent view about the SeqCode, highlighting its history, current status, basic features, pros and cons, and use to date. We also discuss important topics to consider for validation of novel prokaryotic taxon names using genomes as the type material. Owing to significant advances in metagenomics and cultivation methods, hundreds of novel prokaryotic species are expected to be discovered in the coming years. This manuscript aims to stimulate and enrich the debate around the use of the SeqCode in the upcoming golden age of prokaryotic taxon discovery and systematics.
Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial
Authors: Delahaye Audrey , Eldin Carole , Bleibtreu Alexandre , Djossou Félix , Marrie Thomas J , Ghanem-Zoubi Nesrin , Roeden Sonja , Epelboin Loïc 
Published: June 2024

Abstract
Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment’s duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s–2000s. Retrospective studies from the large Dutch outbreak of Q fever (&gt;4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of ‘chronic’ Q fever. Reinforcing the guidelines’ level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.
Genetic profile and characterization of antimicrobial resistance in Acinetobacter baumannii post-COVID-19 pandemic: a study in a tertiary hospital in Recife, Brazil
Authors: Rocha Igor Vasconcelos , Martins Lamartine Rodrigues , Pimentel Maria Izabely Silva , Mendes Renata Pessôa Germano , Lopes Ana Catarina de Souza 
Published: June 2024

Abstract

Aims
To investigate the genetic profile and characterize antimicrobial resistance, including the main β-lactam antibiotic resistance genes, in Acinetobacterbaumannii isolates from a tertiary hospital in Recife-PE, Brazil, in the post-COVID-19 pandemic period.

Methods and Results
Acinetobacter baumannii isolates were collected between 2023 and 2024 from diverse clinical samples. Antimicrobial resistance testing followed standardized protocols, with β-lactamase-encoding genes detected via PCR and sequencing. Investigation into ISAba1 upstream of blaOXA-carbapenemase and blaADC genes was also conducted. Genetic diversity was assessed through ERIC-PCR. Among the 78 A. baumannii, widespread resistance to multiple antimicrobials was evident. Various acquired β-lactamase-encoding genes (blaOXA-23,-24,-58,-143, blaVIM, and blaNDM) were detected. Furthermore, this is the first report of blaVIM-2 in A. baumannii isolates harboring either the blaOXA-23-like or the blaOXA-143 gene in Brazil. Molecular typing revealed a high genetic heterogeneity among the isolates, and multi-clonal dissemination.

Conclusion
The accumulation of genetic resistance determinants underscores the necessity for stringent infection control measures and robust antimicrobial stewardship programs to curb multidrug-resistant strains.