bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a biomarker signature using grating-coupled fluorescence plasmonic microarray for diagnosis of MIS-C
Authors: Maltz-Matyschsyk Michele , Melchiorre Clare K. , Herbst Katherine W. , Hogan Alexander H. , Dibble Kristina , O’Sullivan Brandon , Graf Joerg , Jadhav Aishwarya , Lawrence David A. , Lee William T. , Carson Kyle J. , Radolf Justin D. , Salazar Juan C. , Lynes Michael A. ,   Connecticut Children’s COVID Collaborative
Published: March 2023

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can develop 4–6 weeks after a school age child becomes infected by SARS-CoV-2. To date, in the United States more than 8,862 cases of MIS-C have been identified and 72 deaths have occurred. This syndrome typically affects children between the ages of 5–13; 57% are Hispanic/Latino/Black/non-Hispanic, 61% of patients are males and 100% have either tested positive for SARS-CoV-2 or had direct contact with someone with COVID-19. Unfortunately, diagnosis of MIS-C is difficult, and delayed diagnosis can lead to cardiogenic shock, intensive care admission, and prolonged hospitalization. There is no validated biomarker for the rapid diagnosis of MIS-C. In this study, we used Grating-coupled Fluorescence Plasmonic (GCFP) microarray technology to develop biomarker signatures in pediatric salvia and serum samples from patients with MIS-C in the United States and Colombia. GCFP measures antibody-antigen interactions at individual regions of interest (ROIs) on a gold-coated diffraction grating sensor chip in a sandwich immunoassay to generate a fluorescent signal based on analyte presence within a sample. Using a microarray printer, we designed a first-generation biosensor chip with the capability of capturing 33 different analytes from 80 μL of sample (saliva or serum). Here, we show potential biomarker signatures in both saliva and serum samples in six patient cohorts. In saliva samples, we noted occasional analyte outliers on the chip within individual samples and were able to compare those samples to 16S RNA microbiome data. These comparisons indicate differences in relative abundance of oral pathogens within those patients. Microsphere Immunoassay (MIA) of immunoglobulin isotypes was also performed on serum samples and revealed MIS-C patients had several COVID antigen-specific immunoglobulins that were significantly higher than other cohorts, thus identifying potential new targets for the second-generation biosensor chip. MIA also identified additional biomarkers for our second-generation chip, verified biomarker signatures generated on the first-generation chip, and aided in second-generation chip optimization. Interestingly, MIS-C samples from the United States had a more diverse and robust signature than the Colombian samples, which was also illustrated in the MIA cytokine data. These observations identify new MIS-C biomarkers and biomarker signatures for each of the cohorts. Ultimately, these tools may represent a potential diagnostic tool for use in the rapid identification of MIS-C.
Helicobacter pylori infection increases the risk of thyroid nodules in adults of Northwest China
Authors: Di Jia , Ge Zhuang , Xie Qingwei , Kong Danfeng , Liu Sha , Wang Pengwei , Li Jie , Ning Ning , Qu Wei , Guo Rong , Chang Danyan , Zhang Jun , Zheng Xiang-hong 
Published: March 2023

BackgroundThyroid nodules (TNs) are very common in the adults of Northwest China. The role of Helicobacter pylori (H. pylori) infection in TNs is poorly investigated and even with controversial conclusions. Our study aimed at highlighting the relationship between H. pylori infection and the risk of TNs.Methods9,042 individuals were enrolled with thyroid ultrasonography and 14C-urea breath test (14C-UBT). Baseline characteristics and relevant covariates were obtained, including basic and laboratory indicators. After applying the exclusion criteria, 8,839 patients were included and divided into 2 groups: a cross-sectional study of single follow-up (n=8,711) and a retrospective cohort study of multiple follow-ups for 5 years (n=139).ResultsThe prevalence of H. pylori infection and TNs was 39.58% and 47.94% in the adults of Northwest China, respectively. The prevalence of TNs was significantly higher among H. pylori-positive individuals than those without infection (52.55% vs. 44.92%, p&lt;0.01). The result of binary logistic regression revealed that the crude odds ratio (OR) was 1.624 (95% CI 1.242~2.123) in Model 1 without adjustment compared to H. pylori-negative group, and was also positive in Model 2, 3, and 4 (Model 2: OR=1.731, 95% CI 1.294~2.316; Model 3: OR=2.287, 95% CI 1.633~3.205; Model 4: OR=2.016, 95% CI 1.390~2.922) after the adjustment. The data of 5-year follow-up showed that the annual incidence of TNs was significantly higher in individuals with persistent H. pylori infection than non-infected counterparts (all p&lt;0.05).ConclusionsH. pylori is an independent risk factor for TNs in the adults of Northwest China.
Statistical optimization of a podoviral anti-MRSA phage CCASU-L10 generated from an under sampled repository: Chicken rinse
Authors: Abd-Allah Israa M. , El-Housseiny Ghadir S. , Al-Agamy Mohamed H. , Radwan Hesham H. , Aboshanab Khaled M. , Hassouna Nadia A. 
Published: March 2023

IntroductionThe insurgence of antimicrobial resistance is an imminent health danger globally. A wide range of challenging diseases are attributed to methicillin-resistant Staphylococcus aureus (MRSA) as it is weaponized with a unique array of virulence factors, and most importantly, the resistance it develops to most of the antibiotics used clinically. On that account, the present study targeted the optimization of the production of a bacteriophage active against MRSA, and evaluating some of its characters.Methods and resultsThe bacteriophage originated from a quite peculiar environmental source, raw chicken rinse and was suggested to belong to Podoviridae, order Caudovirales. It withstood a variety of extreme conditions and yield optimization was accomplished via the D-optimal design by response surface methodology (RSM). A reduced quadratic model was generated, and the ideal production conditions recommended were pH 8, glycerol 0.9% v/v, peptone 0.08% w/v, and 107 CFU/ml as the host inoculum size. These conditions led to a two-log fold increase in the phage titer (1.17x10¹² PFU/ml), as compared to the regular conditions.DiscussionTo conclude, statistical optimization successfully enhanced the output of the podoviral phage titer by two-log fold and therefore, can be regarded as a potential scale-up strategy. The produced phage was able to tolerate extreme environmental condition making it suitable for topical pharmaceutical preparations. Further preclinical and clinical studies are required to ensure its suitability for use in human.
Long-term variations in trophic groups of coral reef fishes in the lagoon of Meiji Reef in the South China Sea
Authors: Zhang Jun , Gong Yuyan , Cai Yancong , Yang Yutao , Chen Zuozhi 
Published: March 2023

Fishes play significant ecological functions though many ways in coral reef, and feeding process is one of the most important. To understand responses of reef fish communities to external disturbances, we studied variations in trophic groups of fishes in the lagoon of Meiji Reef in the South China Sea based on fish specimens collected by hand-line and gillnet in 1998—2018, databases and literatures. Differences in species richness, abundance, weight and size of fish in different trophic groups among years were analysed, especially herbivorous and high-economy fish. The results indicated that the percentages of species number and weight of herbivores, piscivores and detritivores decreased significantly from 1998—1999/2016—2018. Herbivorous fishes saw the biggest decline. In the gillnet surveys, the percentages of species number and weight of herbivorous fishes in 1999 were 33.33% and 56.14%, respectively, while the percentages in 2016—2018 were all zero. The species number percentage of large-sized fishes (maximum total length ≥ 65 cm) in 1998—1999 was significantly larger than that in 2016—2018. Thirty-two fish species being found in the lagoon of Meiji Reef during 1998—1999 were not discovered during 2012—2018. Contingency table analysis showed that the disappearance of fish was not significantly related to the vulnerability or resilience of fish rather than economic value. The mean body weight of very high &amp; high-value fish in 1998—1999 was significantly larger than that in 2016—2018. Simple linear regression showed that coral cover had the greater effect on the species number and weight of herbivorous fishes as compare to fishing power. Both fishing power and coral cover had significant effects on the mean body weight. To protect fish on Meiji Reef, we propose to strengthen the conservation initiatives (e.g., creating protected areas, prohibiting fishing, and reconstructing habitat).
Adverse cardiovascular effect following gonadotropin-releasing hormone antagonist versus GnRH agonist for prostate cancer treatment: A systematic review and meta-analysis
Authors: Gu Li , Li Xurui , Liu Wentao 
Published: March 2023

BackgroundAndrogen deprivation therapy is the mainstay of medical treatment for prostate cancer (Pca); however, it is associated with an increased risk of adverse cardiovascular (CV) events and death. To date, CV death has been the leading noncancer cause of death in Pca patients. Both GnRH antagonists (an emerging class of drugs) and GnRH agonists (most frequently prescribed) are efficacious against Pca. However, the adverse effects, especially the adverse CV effect between them remain unclear.MethodsThrough a literature search using MEDLINE, EMBASE and the Cochrane Library, all available studies comparing the safety of CV risk between GnRH antagonists and GnRH agonists in Pca patients were extracted. Comparisons of outcomes of interest between these two classes of drugs were calculated using the risk ratio (RR). Subgroup analyses were performed depending on the study design and preexisting CV disease at baseline.ResultsNine randomized controlled clinical trials (RCTs) and five real-world observational studies comprising 62160 Pca patients were included in our meta-analysis. Patients receiving GnRH antagonists experienced fewer CV events (RR: 0.66, 95% CI:0.53-0.82, P&lt;0.001), CV death (RR:0.4, 95% CI: 0.24-0.67, P&lt;0.001) and myocardial infarctions (RR: 0.71, 95% CI: 0.52-0.96, P=0.03). No difference was found in the incidence of stroke and heart failure. Moreover, GnRH antagonists were associated with fewer CV events in patients with preexisting CV disease but not in those without preexisting CV disease in the RCT series.ConclusionGnRH antagonists appear to offer favorable safety in terms of adverse CV events and CV death compared with GnRH agonists among men diagnosed with Pca, especially those who had established CV disease at baseline.Systematic review registrationhttps://inplasy.com/inplasy-2023-2-0009/, identifier INPLASY202320009.
Uncovering a novel role of focal adhesion and interferon-gamma in cellular rejection of kidney allografts at single cell resolution
Authors: Halawi Ahmad , El Kurdi Abdullah B. , Vernon Katherine A. , Solhjou Zhabiz , Choi John Y. , Saad Anis J. , Younis Nour K. , Elfekih Rania , Mohammed Mostafa Tawfeek , Deban Christa A. , Weins Astrid , Abdi Reza , Riella Leonardo V. , De Serres Sasha A. , Cravedi Paolo , Greka Anna , Khoueiry Pierre , Azzi Jamil R. 
Published: March 2023

BackgroundKidney transplant recipients are currently treated with nonspecific immunosuppressants that cause severe systemic side effects. Current immunosuppressants were developed based on their effect on T-cell activation rather than the underlying mechanisms driving alloimmune responses. Thus, understanding the role of the intragraft microenvironment will help us identify more directed therapies with lower side effects.MethodsTo understand the role of the alloimmune response and the intragraft microenvironment in cellular rejection progression, we conducted a Single nucleus RNA sequencing (snRNA-seq) on one human non-rejecting kidney allograft sample, one borderline sample, and T-cell mediated rejection (TCMR) sample (Banff IIa). We studied the differential gene expression and enriched pathways in different conditions, in addition to ligand-receptor (L-R) interactions.ResultsPathway analysis of T-cells in borderline sample showed enrichment for allograft rejection pathway, suggesting that the borderline sample reflects an early rejection. Hence, this allows for studying the early stages of cellular rejection. Moreover, we showed that focal adhesion (FA), IFNg pathways, and endomucin (EMCN) were significantly upregulated in endothelial cell clusters (ECs) of borderline compared to ECs TCMR. Furthermore, we found that pericytes in TCMR seem to favor endothelial permeability compared to borderline. Similarly, T-cells interaction with ECs in borderline differs from TCMR by involving DAMPS-TLRs interactions.ConclusionOur data revealed novel roles of T-cells, ECs, and pericytes in cellular rejection progression, providing new clues on the pathophysiology of allograft rejection.
Three-dimensional and single-cell sequencing of liver cancer reveals comprehensive host-virus interactions in HBV infection
Authors: Guo Mengbiao , Yao Zhicheng , Jiang Chen , Songyang Zhou , Gan Lian , Xiong Yuanyan 
Published: March 2023

BackgroundsHepatitis B virus (HBV) infection is a major risk factor for chronic liver diseases and liver cancer (mainly hepatocellular carcinoma, HCC), while the underlying mechanisms and host-virus interactions are still largely elusive.MethodsWe applied HiC sequencing to HepG2 (HBV-) and HepG2-2.2.15 (HBV+) cell lines and combined them with public HCC single-cell RNA-seq data, HCC bulk RNA-seq data, and both genomic and epigenomic ChIP-seq data to reveal potential disease mechanisms of HBV infection and host-virus interactions reflected by 3D genome organization.ResultsWe found that HBV enhanced overall proximal chromatin interactions (CIs) of liver cells and primarily affected regional CIs on chromosomes 13, 14, 17, and 22. Interestingly, HBV altered the boundaries of many topologically associating domains (TADs), and genes nearby these boundaries showed functional enrichment in cell adhesion which may promote cancer metastasis. Moreover, A/B compartment analysis revealed dramatic changes on chromosomes 9, 13 and 21, with more B compartments (inactive or closed) shifting to A compartments (active or open). The A-to-B regions (closing) harbored enhancers enriched in the regulation of inflammatory responses, whereas B-to-A regions (opening) were enriched for transposable elements (TE). Furthermore, we identified large HBV-induced structural variations (SVs) that disrupted tumor suppressors, NLGN4Y and PROS1. Finally, we examined differentially expressed genes and TEs in single hepatocytes with or without HBV infection, by using single-cell RNA-seq data. Consistent with our HiC sequencing findings, two upregulated genes that promote HBV replication, HNF4A and NR5A2, were located in regions with HBV-enhanced CIs, and five TEs were located in HBV-activated regions. Therefore, HBV may promote liver diseases by affecting the human 3D genome structure.ConclusionOur work promotes mechanistic understanding of HBV infection and host-virus interactions related to liver diseases that affect billions of people worldwide. Our findings may also have implications for novel immunotherapeutic strategies targeting HBV infection.
Online breath analysis with SESI/HRMS for metabolic signatures in children with allergic asthma
Authors: Weber Ronja , Streckenbach Bettina , Welti Lara , Inci Demet , Kohler Malcolm , Perkins Nathan , Zenobi Renato , Micic Srdjan , Moeller Alexander 
Published: March 2023

Introduction: There is a need to improve the diagnosis and management of pediatric asthma. Breath analysis aims to address this by non-invasively assessing altered metabolism and disease-associated processes. Our goal was to identify exhaled metabolic signatures that distinguish children with allergic asthma from healthy controls using secondary electrospray ionization high-resolution mass spectrometry (SESI/HRMS) in a cross-sectional observational study.Methods: Breath analysis was performed with SESI/HRMS. Significant differentially expressed mass-to-charge features in breath were extracted using the empirical Bayes moderated t-statistics test. Corresponding molecules were putatively annotated by tandem mass spectrometry database matching and pathway analysis.Results: 48 allergic asthmatics and 56 healthy controls were included in the study. Among 375 significant mass-to-charge features, 134 were putatively identified. Many of these could be grouped to metabolites of common pathways or chemical families. We found several pathways that are well-represented by the significant metabolites, for example, lysine degradation elevated and two arginine pathways downregulated in the asthmatic group. Assessing the ability of breath profiles to classify samples as asthmatic or healthy with supervised machine learning in a 10 times repeated 10-fold cross-validation revealed an area under the receiver operating characteristic curve of 0.83.Discussion: For the first time, a large number of breath-derived metabolites that discriminate children with allergic asthma from healthy controls were identified by online breath analysis. Many are linked to well-described metabolic pathways and chemical families involved in pathophysiological processes of asthma. Furthermore, a subset of these volatile organic compounds showed high potential for clinical diagnostic applications.
Association of APOE ε4/ε4 with fluid biomarkers in patients from the PUMCH dementia cohort
Authors: Shang Li , Dong Liling , Huang Xinying , Wang Tianyi , Mao Chenhui , Li Jie , Wang Jie , Liu Caiyan , Gao Jing 
Published: March 2023

BackgroundApolipoprotein-E (APOE) ε4 is a major genetic risk factor for Alzheimer’s disease (AD). Current studies, which were mainly based on the clinical diagnosis rather than biomarkers, come to inconsistent conclusions regarding the associations of APOE ε4 homozygotes (APOE ε4/ε4) and cerebrospinal fluid (CSF) biomarkers of AD. In addition, few studies have explored the associations of APOE ε4/ε4 with plasma biomarkers. Therefore, we aimed to investigate the associations of APOE ε4/ε4 with fluid biomarkers in dementia and biomarker-diagnosed AD.MethodsA total of 297 patients were enrolled. They were classified into Alzheimer’s continuum, AD, and non-AD, according to CSF biomarkers and/or β amyloid PET results. AD was a subgroup of the AD continuum. Plasma Amyloid β (Aβ) 40, Aβ42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and phosphorylated tau (P-tau)181 were quantified in 144 of the total population using an ultra-sensitive Simoa technology. We analyzed the associations of APOE ε4/ε4 on CSF and plasma biomarkers in dementia and biomarker diagnosed AD.ResultsBased on the biomarker diagnostic criteria, 169 participants were diagnosed with Alzheimer’s continuum and 128 individuals with non-AD, and among the former, 120 patients with AD. The APOE ε4/ε4 frequencies were 11.8% (20/169), 14.2% (17/120), and 0.8% (1/128) in Alzheimer’s continuum, AD and non-AD, respectively. Only CSF Aβ42 was shown to be decreased in APOE ε4/ε4 carriers than in non-carriers for patients with AD (p = 0.024). Furthermore, we did not find any associations of APOE ε4 with plasma biomarkers of AD and non-AD. Interestingly, we found that in non-AD patients, APOE ε4 carriers had lower CSF Aβ42 (p = 0.018) and higher T-tau/Aβ42 ratios (p &lt; 0.001) and P-tau181/Aβ42 ratios (p = 0.002) than non-carriers.ConclusionOur data confirmed that of the three groups (AD continuum, AD, and non-AD), those with AD had the highest frequency of APOE ɛ4/ɛ4 genotypes. The APOE ɛ4/ɛ4 was associated with CSF levels of Aβ42 but not tau for AD and non-AD, suggesting that APOE ɛ4/ɛ4 affected the Aβ metabolism of both. No associations between APOE ε4/ɛ4 and plasma biomarkers of AD and non-AD were found.
Lateral septal nucleus, dorsal part, and dentate gyrus are necessary for spatial and object recognition memory, respectively, in mice
Authors: Jiang Ying-Ke , Dong Fei-Yuan , Dong Yi-Bei , Zhu Xin-Yi , Pan Lu-Hui , Hu Lin-Bo , Xu Le , Xu Xiao-Fan , Xu Li-Min , Zhang Xiao-Qin 
Published: March 2023

IntroductionCognitive impairment includes the abnormality of learning, memory and judgment, resulting in severe learning and memory impairment and social activity impairment, which greatly affects the life quality of individuals. However, the specific mechanisms underlying cognitive impairment in different behavioral paradigms remain to be elucidated.MethodsThe study utilized two behavioral paradigms, novel location recognition (NLR) and novel object recognition (NOR), to investigate the brain regions involved in cognitive function. These tests comprised two phases: mice were presented with two identical objects for familiarization during the training phase, and a novel (experiment) or familiar (control) object/location was presented during testing. Immunostaining quantification of c-Fos, an immediate early gene used as a neuronal activity marker, was performed in eight different brain regions after the NLR or NOR test.ResultsThe number of c-Fos-positive cells was significantly higher in the dorsal part of the lateral septal nucleus (LSD) in the NLR and dentate gyrus (DG) in the NOR experiment group than in the control group. We further bilaterally lesioned these regions using excitotoxic ibotenic acid and replenished the damaged areas using an antisense oligonucleotide (ASO) strategy.DiscussionThese data reinforced the importance of LSD and DG in regulating spatial and object recognition memory, respectively. Thus, the study provides insight into the roles of these brain regions and suggests potential intervention targets for impaired spatial and object recognition memory.
Investigating the causal association between branched-chain amino acids and Alzheimer's disease: A bidirectional Mendelian randomized study
Authors: Qian Xiao-hang , Liu Xiao-li , Zhang Bin , Lin Yuan , Xu Jian-hua , Ding Gang-yu , Tang Hui-dong 
Published: March 2023

BackgroundThere are many metabolic pathway abnormalities in Alzheimer's disease (AD). Several studies have linked branched-chain amino acid (BCAA) metabolism disorders with AD but have not obtained consistent results. The purpose of this study is to explore the causal association between BCAA concentration and the risk of AD.MethodsA bidirectional Mendelian randomized (MR) study was applied to explore the causal effect between BCAA level and the risk of AD. Genetic instrumental variables from the genome-wide association study (GWAS) of serum BCAA levels [total BCAAs (115,047 participants), valine (115,048 participants), leucine (115,074 participants), and isoleucine (115,075 participants)] from the UK Biobank and AD (21,982 AD cases and 41,944 controls) from the International Genomics of Alzheimer's Project were applied to explore the causal effect through the inverse variance-weighted (IVW) method, MR-Egger, and weighted median, accompanied by multiple pluripotency and heterogeneity tests.ResultsThe forward MR analysis showed that there was no causal effect of total BCAAs (OR: 1.067, 95% CI: 0.838–1.358; p = 0.838), valine (OR: 1.106, 95% CI: 0.917–1.333; p = 0.292), leucine (OR: 1.096, 95% CI: 0.861–1.396; p = 0.659), and isoleucine (OR: 1.457, 95% CI: 1.024–2.742; p = 0.037) levels on the risk of AD. The reverse analysis showed that AD was related to reduced levels of total BCAAs (OR: 0.979, 95% CI: 0.989–0.990; p &lt; 0.001), valine (OR: 0.977, 95% CI: 0.963–0.991; p = 0.001), leucine (OR: 0.983, 95% CI: 0.973–0.994; p = 0.002), and isoleucine (OR: 0.982, 95% CI: 0.971–0.992; p = 0.001).ConclusionWe provide robust evidence that AD was associated with a decreased level of BCAAs, which can serve as a marker for early diagnosis of AD.