bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generic qPCR assays for quality control in environmental DNA research
Authors: Zhu Xiaocheng , Bell Karen L. , Rourke Meaghan L. , Wu Hanwen , Gopurenko David 
Published: April 2024

AbstractEnvironmental DNA (eDNA) has been widely used for species surveillance. However, the lack of adequate quality control in many eDNA research projects and applications can lead to false‐negative results, greatly affecting biosecurity surveillance and conservation efforts. Exogenous DNA is routinely added to eDNA samples and used as a positive control, typically after DNA extraction. However, this type of positive control is only able to identify false negatives due to errors at the amplification stage. Therefore, errors in upstream processes, such as sample collection will not be identified by an exogenous control. We designed two independent sets of generic quality control qPCR assays (QCqPCR) targeting abundant endogenous DNA that is obtained during sample collection. Our QCqPCR assays target the chloroplast 16S and 23S ribosomal RNA sequences. In silico analyses indicated these regions were highly conserved among plants, algae and bacteria commonly found in freshwater, marine, or terrestrial environments. These QCqPCR assays were purposely mismatched against the human genome to avoid false positives resulting from human DNA contamination. Both assays remained highly efficient and sensitive under annealing temperatures between 58 and 62°C, allowing them to be multiplexed with most qPCR analyses. We validated our assays by multiplexing with a species‐specific Murray cod (Maccullochella peelii) assay on field‐collected environmental water samples. Potential false‐negative reactions can be identified by the failed or suppressed QCqPCR assay and the negative species‐specific assay. We recommend incorporating either one of the QCqPCR assays in qPCR‐based eDNA analysis to identify potential false negatives and improve the reliability of eDNA surveys.
Identification of common mechanisms and biomarkers of atrial fibrillation and heart failure based on machine learning
Authors: Zhang Zhijun , Ding Jianying , Mi Xiaolong , Lin Yuanyuan , Li Xinjian , Lian Jun , Liu Jinwen , Qu Lijuan , Zhao Bingye , Li Xuewen 
Published: April 2024

AbstractAimsAtrial fibrillation (AF) is the most common arrhythmia. Heart failure (HF) is a disease caused by heart dysfunction. The prevalence of AF and HF were progressively increasing over time. The co‐existence of AF and HF presents a significant therapeutic challenge. In order to provide new ideas for the diagnosis of AF and HF, it is necessary to carry out biomarker related studies.Methods and resultsThe training set and validation set data of AF and HF patient samples were downloaded from the GEO database, ‘limma’ was used to compare the differences in gene expression levels between the disease group and the normal group to screen for differentially expressed genes (DEGs). Weighted correlation network analysis (WGCNA) identified the modules with the highest positive correlation with AF and HF. Functional enrichment and PPI network construction of key genes were carried out. Biomarkers were screened by machine learning. The infiltration of immune cells in AF and HF groups was evaluated by R‐packet ‘CIBERSORT’. The miRNA network was constructed and potential therapeutic agents for biomarker genes were predicted through the drugbank database. Through WGCNA analysis, it was found that the modules most positively correlated with AF and HF were MEturquoise (r = 0.21, P value = 0.09) and MEbrown (r = 0.62, P value = 8e‐12), respectively. We screened 25 genes that were highly correlated with both AF and HF. Lasso regression analysis results showed 7 and 20 core genes in AF and HF groups, respectively. The top 20 important genes in AF and HF groups were obtained as core genes by RF model analysis. Four biomarkers were obtained after the intersection of core genes in four groups, namely, GLUL, NCF2, S100A12, and SRGN. The diagnostic efficacy of four genes in AF validation sets was good (AUC: GLUL 0.76, NCF2 0.64, S100A12 0.68, and SRGN 0.76), as well as in the HF validation set (AUC: GLUL 0.76, NCF2 0.84, S100A12 0.92, and SRGN 0.68). The highest correlation with neutrophils was observed for GLUL, NCF2, and S100A12, while SRGN exhibited the strongest correlation with T cells CD4 memory resting in the AF group. GLUL, NCF2, S100A12, and SRGN were most associated with neutrophils in the HF group. A total of 101 miRNAs were predicted by four genes, and GLUL, NCF2, and S100A12 predicted a total of 10 potential therapeutic agents.ConclusionsWe identified four biological markers that are highly correlated with AF and HF, namely, GLUL, NCF2, S100A12, and SRGN. Our findings provide theoretical basis for the clinical diagnosis and treatment of AF and HF.
The impact of IL‐10 and IL‐17 on myeloid‐derived suppressor cells in vitro and in vivo in a murine model of asthma
Authors: Vetter Charlotte , Schieb Jakob , Vedder Nora , Lange Tim , Brunn Tobias , van Geffen Chiel , Gercke Philipp , Kolahian Saeed 
Published: April 2024

AbstractMyeloid‐derived suppressor cells (MDSCs) hold promise for clinical applications due to their immunosuppressive properties, particularly in the context of inflammation. In the present study, the number and immunosuppressive activity of MDSCs isolated from naïve Il10−/−, Il17−/−, and WT mice as control, as well as from house dust mite extract (HDM)‐induced asthmatic Il10−/− and Il17−/− mice, were investigated. IL‐10 deficiency increased the number of polymorphonuclear (PMN)‐MDSCs in the lung, spleen, and bone marrow, without concurrent impairment of their suppressive activity in vitro. In the asthma model, the IL‐17 knockout was concomitant with a lower number and activity of monocytic (M)‐MDSCs and an altered inflammatory reaction with impaired lung function. Additionally, we found a higher baseline inflammation of the Il17−/− mice in the lung, manifested in increased airway resistance. We conclude that the impact of IL‐10 and IL‐17 deficiency on MDSCs differs in the context of inflammation. Accordingly, the in vitro experiments demonstrated an increased number of PMN‐MDSCs across tissues in Il10−/− mice, which indicates that IL‐10 might serve a pivotal role in preserving immune homeostasis under physiological circumstances. In the context of HDM‐induced airway inflammation, IL‐17 was found to be an important player in the suppression of pulmonary inflammation and regulation of M‐MDSCs.
Diastereoselective Synthesis and Functionalization of tert‐Butylsulfinyl‐2‐(Chlorodiphenylmethyl)Pyrrolidine
Authors: Carboni Davide , Di Remigio Simone , Quintavalla Arianna , Lombardo Marco 
Published: April 2024

AbstractThe addition of the carbenoid species (chlorodiphenylmethyl)lithium to chiral N‐(4‐bromobutylidene)‐2‐methylpropane‐2‐sulfinamide affords in high yield (up to 81 %) and excellent diastereoselectivity (>99 : 1) the yet undisclosed tert‐butylsulfinyl‐2‐(chlorodiphenylmethyl)pyrrolidine. Preliminary investigations into SN1 solvolysis reactions of this chloride with different alcohols revealed its potential for further functionalizations leading to differently substituted chiral pyrrolidines, yet showing a relative lability of the tert‐butylsulfinyl chiral auxiliary under the employed reaction conditions. Most notably, reactions with sterically hindered alcohols yielded unprecedented derivatives, not easily obtainable using the currently reported procedures for the stereoselective synthesis of diphenylprolinol derivatives.
Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma
Authors: Wei Shuanzeng , Pei Jianming , Belser Paul , Lee Teresa , Farma Jeffrey M. , Patchefsky Arthur S. , Flieder Douglas B. , Montgomery Elizabeth A. 
Published: April 2024

AbstractMyxoid leiomyosarcoma (MLS) is a rare but well‐documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor PLAG1 fusions (TRPS1::PLAG1, RAD51B::PLAG1, and TRIM13::PLAG1). In this report, we present a case of rectal MLS with a novel MIR143HG::PLAG1 fusion detected by RNA next‐generation sequencing.
Meta‐analysis of breast cancer risk for individuals with PALB2 pathogenic variants
Authors: Ruberu Thanthirige L. M. , Braun Danielle , Parmigiani Giovanni , Biswas Swati 
Published: April 2024

AbstractMultigene panel testing now allows efficient testing of many cancer susceptibility genes leading to a larger number of mutation carriers being identified. They need to be counseled about their cancer risk conferred by the specific gene mutation. An important cancer susceptibility gene is PALB2. Multiple studies reported risk estimates for breast cancer (BC) conferred by pathogenic variants in PALB2. Due to the diverse modalities of reported risk estimates (age‐specific risk, odds ratio, relative risk, and standardized incidence ratio) and effect sizes, a meta‐analysis combining these estimates is necessary to accurately counsel patients with this mutation. However, this is not trivial due to heterogeneity of studies in terms of study design and risk measure. We utilized a recently proposed Bayesian random‐effects meta‐analysis method that can synthesize estimates from such heterogeneous studies. We applied this method to combine estimates from 12 studies on BC risk for carriers of pathogenic PALB2 mutations. The estimated overall (meta‐analysis‐based) risk of BC is 12.80% (6.11%−22.59%) by age 50 and 48.47% (36.05%−61.74%) by age 80. Pathogenic mutations in PALB2 makes women more susceptible to BC. Our risk estimates can help clinically manage patients carrying pathogenic variants in PALB2.
Intracortical brain‐heart interplay: An EEG model source study of sympathovagal changes
Authors: Catrambone Vincenzo , Candia‐Rivera Diego , Valenza Gaetano 
Published: April 2024

AbstractThe interplay between cerebral and cardiovascular activity, known as the functional brain‐heart interplay (BHI), and its temporal dynamics, have been linked to a plethora of physiological and pathological processes. Various computational models of the brain‐heart axis have been proposed to estimate BHI non‐invasively by taking advantage of the time resolution offered by electroencephalograph (EEG) signals. However, investigations into the specific intracortical sources responsible for this interplay have been limited, which significantly hampers existing BHI studies. This study proposes an analytical modeling framework for estimating the BHI at the source‐brain level. This analysis relies on the low‐resolution electromagnetic tomography sources localization from scalp electrophysiological recordings. BHI is then quantified as the functional correlation between the intracortical sources and cardiovascular dynamics. Using this approach, we aimed to evaluate the reliability of BHI estimates derived from source‐localized EEG signals as compared with prior findings from neuroimaging methods. The proposed approach is validated using an experimental dataset gathered from 32 healthy individuals who underwent standard sympathovagal elicitation using a cold pressor test. Additional resting state data from 34 healthy individuals has been analysed to assess robustness and reproducibility of the methodology. Experimental results not only confirmed previous findings on activation of brain structures affecting cardiac dynamics (e.g., insula, amygdala, hippocampus, and anterior and mid‐cingulate cortices) but also provided insights into the anatomical bases of brain‐heart axis. In particular, we show that the bidirectional activity of electrophysiological pathways of functional brain‐heart communication increases during cold pressure with respect to resting state, mainly targeting neural oscillations in the , , and bands. The proposed approach offers new perspectives for the investigation of functional BHI that could also shed light on various pathophysiological conditions.
Atomic Tailoring of Ubiquitin Side Chains Influences E2‐Mediated Ubiquitin Chain Formation
Authors: Song Haewon , Mikami Toshiki , Majima Sohei , Bode Jeffrey W. 
Published: April 2024

AbstractUbiquitin (Ub) is a small, highly conserved protein essential for eukaryotic biology, and is unique in its formation of polyubiquitin chains by conjugation to one of its seven lysine side chains. Here we report that atomic tailoring of Ub side chains – i. e. the insertion, deletion, or replacement of specific atoms – has significant and unexpected consequences on the enzymatic conjugation of Ub oligomers by isopeptide bond formation mediated by E2 conjugating enzymes. These studies employed chemical synthesis and ligation methods to prepare numerous specifically tailored Ub monomers on multi‐milligram scales. While some modifications including N‐terminal acylation and methionine replacement did not affect protein folding or Ub chain formation with Ube2 K, other modifications had a pronounced effect of oligomerization with Ubc13/Mms2. We observed that Ala46Hse mutation obliterates the ability of this Ub monomer to accept another Ub at Lys63 in Ubc13‐mediated conjugations. Exhaustive replacement of all seven lysines with shorter surrogates Orn, Dab, or Dap essentially blocks Ub chain formation, and in the case of Dap, precludes proper folding of the Ub protein.
Upper gastrointestinal bleeding: Diagnosis of Helicobacter pylori infection—Descriptive study
Authors: Azadbakht Saleh , Azadbakht Salehe , Azadbakht Morteza 
Published: April 2024

AbstractBackground and AimThe presence of blood in the stomach has been thought to affect the performance of diagnostic tests used in detecting Helicobacter pylori (H. pylori) in the stomach. This study evaluates the effect of upper gastrointestinal bleeding on the efficacy of a rapid urease test (RUT) and compares the results with the pathologic method.MethodsIn this descriptive study, 100 patients presented with upper gastrointestinal bleeding, confirmed from endoscopy, referred to Shahid Rahimi Hospital in Khorramabad were enrolled. Antral biopsy was performed in all the patients and the samples were extracted for histopathology and RUT. A questionnaire was used to collect rapid urease test outcomes and associated parameters (antibiotic, bismuth, and proton pump inhibitors), histology and demographic data. Histopathology was used as the gold standard for diagnosis of H. pylori.ResultsOf the 52 patients who were reported positive for H. pylori in pathology, 36 had RUT‐positive H. pylori, sensitivity 69.2%, and of 48 patients whose pathology was negative, 25 had negative RUT, specificity 52.1%. Of 59 RUT, 36 had positive pathology, positive predictive value was 61% and from 41 with negative RUT, 25 had negative pathology, negative predictive value was 61%. The prevalence of H. pylori infection was significantly associated with the age of 50 years and above, p = 0.042, and previous history of bleeding, p = 0.019.ConclusionGastrointestinal bleeding can reduce the sensitivity of RUT. The negative results of these tests in acute upper gastrointestinal bleeding should therefore be interpreted carefully.
Trade and flow of value in global value chains
Authors: Wang Peijie , Liu Zhiyuan 
Published: April 2024

AbstractThis paper examines flow of value that goes with trade flows in global value chains (GVCs) by a residence‐based domestic value‐added trade measure. Accordingly, the paper puts forward a concept of residence‐based domestic value‐added exports from activity domains and develops a corresponding trade measure. Export activities of G20 economies are scrutinized empirically, with which sizeable differences are observed between figures in the proposed residence‐based domestic value‐added trade measure and the conventional domestic value‐added trade measure. This calls for new measures, to which the present study responds. It has been demonstrated that the developed G20 gains persistently in residence‐based domestic value‐added exports, increasing from the conventional domestic value‐added exports measure. Whereas trade performance of the developing G20 deteriorates with considerably reduced surpluses in the new measure. Considerable additional value flows out from developing to developed economies in GVCs. Developed economies continue to gain from international trade as a matter of fact.
Cytotoxicity and toxicoproteomics analysis of thiazolidinedione exposure in human‐derived cardiomyocytes
Authors: Al Sultan Abdullah , Rattray Zahra , Rattray Nicholas J. W. 
Published: April 2024

AbstractThiazolidinediones (TZDs) (e.g. pioglitazone and rosiglitazone), known insulin sensitiser agents for type II diabetes mellitus, exhibit controversial effects on cardiac tissue. Despite consensus on their association with increased heart failure risk, limiting TZD use in diabetes management, the underlying mechanisms remain uncharacterised. Herein, we report a comprehensive in vitro investigation utilising a novel toxicoproteomics pipeline coupled with cytotoxicity assays in human adult cardiomyocytes to elucidate mechanistic insights into TZD cardiotoxicity. The cytotoxicity assay findings showed a significant loss of mitochondrial adenosine triphosphate production upon exposure to either TZD agents, which may underpin TZD cardiotoxicity. Our toxicoproteomics analysis revealed that mitochondrial dysfunction primarily stems from oxidative phosphorylation impairment, with distinct signalling mechanisms observed for both agents. The type of cell death differed strikingly between the two agents, with rosiglitazone exhibiting features of caspase‐dependent apoptosis and pioglitazone implicating mitochondrial‐mediated necroptosis, as evidenced by the protein upregulation in the phosphoglycerate mutase family 5–dynamin‐related protein 1 axis. Furthermore, our analysis revealed additional mechanistic aspects of cardiotoxicity, showcasing drug specificity. The downregulation of various proteins involved in protein machinery and protein processing in the endoplasmic reticulum was observed in rosiglitazone‐treated cells, implicating proteostasis in the rosiglitazone cardiotoxicity. Regarding pioglitazone, the findings suggested the potential activation of the interplay between the complement and coagulation systems and the disruption of the cytoskeletal architecture, which was primarily mediated through the integrin‐signalling pathways responsible for pioglitazone‐induced myocardial contractile failure. Collectively, this study unlocks substantial mechanistic insight into TZD cardiotoxicity, providing the rationale for future optimisation of antidiabetic therapies.
Nanopore adaptive sampling of a metagenomic sample derived from a human monkeypox case
Authors: Hewel Charlotte , Schmidt Hanno , Runkel Stefan , Kohnen Wolfgang , Schweiger‐Seemann Susann , Michel André , Bikar Sven‐Ernö , Lieb Bettina , Plachter Bodo , Hankeln Thomas , Linke Matthias , Gerber Susanne 
Published: April 2024

AbstractIn 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Setup of proper genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore (PromethION P24) and Illumina (NextSeq. 2000) Whole Genome Sequencing (WGS) of a monkeypox sample. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. In addition to that, only Nanopore data allowed us to resolve the entire monkeypox virus genome, with respect to two structural variants belonging to the genes OPG015 and OPG208. These SVs in important host range genes seem stable throughout the outbreak and are frequently misassembled and/or misannotated due to the prevalence of short read sequencing or short read first assembly. Ideally, standalone standard Illumina sequencing should not be used for Monkeypox WGS and de novo assembly, since it will obfuscate the structure of the genome, which has an impact on the quality and completeness of the genomes deposited in public databases and thus possibly on the ability to evaluate the complete genetic reason for the host range change of monkeypox in the current pandemic.
4R‐cembranoid suppresses glial cells inflammatory phenotypes and prevents hippocampal neuronal loss in LPS‐treated mice
Authors: Rojas‐Colón Luis A. , Redell John B. , Dash Pramod K. , Vegas Pedro E. , Vélez‐Torres Wanda 
Published: April 2024

AbstractChronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R‐cembranoid (4R) is a natural compound that inhibits hippocampal pro‐inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild‐type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for microglial, astrocyte, and neuronal markers were used to quantify cellular hippocampal phenotypes and neurons. Hippocampal lysates were used to measure the expression levels of neuronal nuclear protein (NeuN), inducible nitrous oxide synthase (iNOS), arginase‐1, thrombospondin‐1 (THBS1), glial cell‐derived neurotrophic factor (GDNF), and orosomucoid‐2 (ORM2) by western blot. iNOS and arginase‐1 are widely used protein markers of pro‐ and anti‐inflammatory microglia, respectively. GDNF promotes neuronal survival, and ORM2 and THBS1 are astrocytic proteins that regulate synaptic plasticity and inhibit microglial activation. 4R administration significantly reduced neuronal loss and the number of pro‐inflammatory microglia 72 h after LPS injection. It also decreased the expression of the pro‐inflammatory protein iNOS while increasing arginase‐1 expression, supporting its anti‐inflammatory role. The protein expression of THBS1, GDNF, and ORM2 was increased by 4R. Our data show that 4R preserves the integrity of hippocampal neurons against LPS‐induced neuroinflammation in mice.
A coupled finite difference‐spectral boundary integral method with applications to fluid diffusion in fault structures
Authors: Wang Yuhan , Heimisson Elías Rafn 
Published: April 2024

AbstractFluid migration in geological materials, a subject of great interest in various geophysical applications, has been interpreted through multiple numerical methods. Taking advantage of both a volume‐based method and a boundary integral method, we innovate a hybrid spectral‐boundary‐integral and finite‐difference method (SBI‐FDM) to describe the fluid injection and propagation in the fault structure. The coupling of the two methods is established from the consistent exchange of the pressure gradient from the volume‐based method and the boundary flux applied in the SBI boundary. The hybrid method benefits from its capability to truncate the domain and capture the fluid‐induced pore pressure in geological systems without modeling the whole bulk. After establishing the numerical framework, we verify the SBI‐FDM under both homogeneous and heterogeneous mediums using an analytical solution and the FDM results, respectively. After model verification, a sensitivity test showcases the stability of the numerical scheme. A speedup comparison of the SBI‐FDM against the FDM is presented. We observe that the proposed method can achieve better computational efficiency with up to one thousand times speedup in our test. Utilizing the proposed hybrid method, we also perform parametric studies to reveal the significance of mobility contrast between the damage zone and host rock, as well as the role of fault width during fault injection.