bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Three Widely Used Antibiotics and Their Mixture on the Haemocytes of the Clam Ruditapes philippinarum
Authors: Nicolussi Greta , Fabrello Jacopo , Asnicar Davide , Ciscato Maria , Matozzo Valerio , Marin Maria Gabriella 
Published: February 2022

Although the presence of pharmaceutical and personal care products in aquatic ecosystems is well documented, little information is available about their sublethal effects, on aquatic invertebrates. From an ecotoxicological point of view, the use of in vitro approaches has been recommended as a tool to assess adverse effects and to understand the mechanisms of action of chemicals at the cellular level. In the present in vitro study, the effects of Amoxicillin (AMX), Trimethoprim (TMP) and Ciprofloxacin (CIP) (1 µg/L, each) were tested alone and—for the first time—as a mixture (MIX) on haemocytes of the clam Ruditapes philippinarum. After the exposure, a battery of cellular parameters was evaluated, such as haemocyte viability, lysosomal membrane stability, superoxide anion production, acid phosphatase activity, the frequency of micronuclei and chromosomal aberrations. The results demonstrated that AMX, TMP, CIP and MIX affected lysosomal membrane stability, as well as superoxide anion and acid phosphatase production, and promoted chromosomal aberrations. This study highlighted that Manila clam haemocytes are a sensitive cell model to assess the effects of exposure to pharmaceutical products on non-target species. Our study demonstrated that the effects of pharmaceutical mixtures on marine species should be experimentally evaluated because they are not predictable from single exposures as the compounds can interact in different ways on the various biological endpoints considered.
Set of 15 SNP-SNP Markers for Detection of Unbalanced Degraded DNA Mixtures and Noninvasive Prenatal Paternity Testing
Authors: Zhang Ranran , Tan Yu , Wang Li , Jian Hui , Zhu Jing , Xiao Yuanyuan , Tan Mengyu , Xue Jiaming , Yang Fan , Liang Weibo 
Published: February 2022

Unbalanced and degraded mixtures (UDM) are very common in forensic DNA analysis. For example, DNA signals from criminal suspects are masked by a large amount of DNA from victims, or cell-free fetal DNA (cffDNA) in maternal plasma is masked by a high background of maternal DNA. Currently, detecting minor DNA in these mixtures is complex and challenging. We developed a new set of SNP-SNP microhaplotypes with short amplicons, and we successfully genotyped them using the new method of amplification-refractory mutation system PCR (ARMS-PCR) combined with SNaPshot technology based on a capillary electrophoresis (CE) platform. This panel reflects a high polymorphism in the Southwest Chinese Han population and thus has excellent potential for mixture studies. We evaluated the feasibility of this panel for UDM detection and noninvasive prenatal paternity testing (NIPPT). Fifteen SNP-SNPs detected minor DNA of homemade DNA mixtures, with a sensitivity of 0.025–0.05 ng and a specificity of 1:1,000. In addition, the panel successfully genotyped degraded DNA from single and mixed samples. Finally, 15 SNP-SNPs were applied to 26 trios. All samples displayed positive results with at least one marker to detect cffDNA. Besides, all fetal alleles in maternal plasma were confirmed by genotyping fetal genomic DNA from amniocentesis and paternal genomic DNA from peripheral blood. The results indicated that the SNP-SNP strategy based on the CE platform was useful for UDM detection and NIPPT.
Weighted Co-Expression Network Analysis Identifies RNF181 as a Causal Gene of Coronary Artery Disease
Authors: Dang Ruoyu , Qu Bojian , Guo Kaimin , Zhou Shuiping , Sun He , Wang Wenjia , Han Jihong , Feng Ke , Lin Jianping , Hu Yunhui 
Published: February 2022

Background: Coronary artery disease (CAD) exerts a global challenge to public health. Genetic heritability is one of the most vital contributing factors in the pathophysiology of CAD. Co-expression network analysis is an applicable and robust method for the interpretation of biological interaction from microarray data. Previous CAD studies have focused on peripheral blood samples since the processes of CAD may vary from tissue to blood. It is therefore necessary to find biomarkers for CAD in heart tissues; their association also requires further illustration.Materials and Methods: To filter for causal genes, an analysis of microarray expression profiles, GSE12504 and GSE22253, was performed with weighted gene co-expression network analysis (WGCNA). Co-expression modules were constructed after batch effect removal and data normalization. The results showed that 7 co-expression modules with 8,525 genes and 1,210 differentially expressed genes (DEGs) were identified. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Four major pathways in CAD tissue and hub genes were addressed in the Hybrid Mouse Diversity Panel (HMDP) and Human Protein Atlas (HPA), and isoproterenol (ISO)/doxycycline (DOX)-induced heart toxicity models were used to validate the hub genes. Lastly, the hub genes and risk variants were verified in the CAD cohort and in genome-wide association studies (GWAS).Results: The results showed that RNF181 and eight other hub genes are perturbed during CAD in heart tissues. Additionally, the expression of RNF181 was validated using RT-PCR and immunohistochemistry (IHC) staining in two cardiotoxicity mouse models. The association was further verified in the CAD patient cohort and in GWAS.Conclusion: Our findings illustrated for the first time that the E3 ubiquitination ligase protein RNF181 may serve as a potential biomarker in CAD, but further in vivo validation is warranted.
Effective Identification of Maternal Malignancies in Pregnancies Undergoing Noninvasive Prenatal Testing
Authors: Li Jia , Ju Jia , Zhao Qiang , Liu Weiqiang , Yuan Yuying , Liu Qiang , Zhou Lijun , Han Yuan , Yuan Wen , Huang Yonghua , Xie Yingjun , Li Zhihua , Chen Jingsi , Huang Shuyu , Chen Rufang , Li Wei , Tan Meihua , Wang Danchen , Zhou Si , Zhang Jian , Zeng Fanwei , Yu Nan , Su Fengxia , Chen Min , Ge Yunsheng , Huang Yanming , Jin Xin 
Published: February 2022

Background: The existence of maternal malignancy may cause false-positive results or failed tests of NIPT. Though recent studies have shown multiple chromosomal aneuploidies (MCA) are associated with malignancy, there is still no effective solution to identify maternal cancer patients from pregnant women with MCA results using NIPT. We aimed to develop a new method to effectively detect maternal cancer in pregnant women with MCA results using NIPT and a random forest classifier to identify the tissue origin of common maternal cancer types.Methods: For examination, 496 participants with MCA results via NIPT were enrolled from January 2016 to June 2019 at BGI. Cancer and non-cancer participants were confirmed through the clinical follow-up. The cohort comprising 42 maternal cancer cases and 294 non-cancer cases enrolled from January 2016 to December 2017 was utilized to develop a method named mean of the top five chromosome z scores (MTOP5Zscores). The remaining 160 participants enrolled from January 2018 to June 2019 were used to validate the performance of MTOP5Zscores. We established a random forest model to classify three common cancer types using normalized Pearson correlation coefficient (NPCC) values, z scores of 22 chromosomes, and seven plasma tumor markers (PTMs) as predictor variables.Results: 62 maternal cancer cases were confirmed with breast cancer, liver cancer, and lymphoma, the most common cancer types. MTOP5Zscores showed a sensitivity of 85% (95% confidence interval (CI), 62.11–96.79%) and specificity of 80% (95% CI, 72.41–88.28%) in the detection of maternal cancer among pregnant women with MCA results. The sensitivity of the classifier was 93.33, 66.67, and 50%, while specificity was 66.67, 90, and 97.06%, and positive predictive value (PPV) was 60.87, 72.73, and 80% for the prediction of breast cancer, liver cancer, and lymphoma, respectively.Conclusion: This study presents a solution to identify maternal cancer patients from pregnant women with MCA results using NIPT, indicating it as a value-added application of NIPT in the detection of maternal malignancies in addition to screening for fetal aneuploidies with no extra cost.
Guanylate-Binding Protein 1 as a Potential Predictor of Immunotherapy: A Pan-Cancer Analysis
Authors: Zhao Yaqi , Wu Jie , Li Lan , Zhang Huibo , Zhang Haohan , Li Jing , Zhong Hao , Lei Tianyu , Jin Yan , Xu Bin , Song Qibin 
Published: February 2022

Background: Mainstream application of cancer immunotherapy is hampered by the low response rate of most cancer patients. A novel immunotherapeutic target or a biomarker predicting response to immunotherapy needs to be developed. Guanylate-binding protein 1 (GBP1) is an interferon (IFN)-inducible guanosine triphosphatases (GTPases) involving inflammation and infection. However, the immunological effects of GBP1 in pan-cancer patients are still obscure.Methods: Using large-scale public data, we delineated the landscape of GBP1 across 33 cancer types. The correlation between GBP1 expression or mutation and immune cell infiltration was estimated by ESTIMATE, TIMER, xCell, and quanTIseq algorithms. GBP1-related genes and proteins were subjected to function enrichment analysis. Clustering analysis explored the relationship between GBP1 expression and anti-tumor immune phenotypes. We assessed the patient’s response to immunotherapy using the tumor immune dysfunction and exclusion (TIDE) score and immunophenoscore (IPS). Furthermore, we validated the predictive power of GBP1 expression in four independent immunotherapy cohorts.Results: GBP1 was differentially expressed in tumors and normal tissues in multiple cancer types. Distinct correlations existed between GBP1 expression and prognosis in cancer patients. GBP1 expression and mutation were positively associated with immune cell infiltration. Function enrichment analysis showed that GBP1-related genes were enriched in immune-related pathways. Positive correlations were also observed between GBP1 expression and the expression of immune checkpoints, as well as tumor mutation burden (TMB). Pan-cancer patients with higher GBP1 expression were more inclined to display “hot” anti-tumor immune phenotypes and had lower TIDE scores and higher immunophenoscore, suggesting that these patients had better responses to immunotherapy. Patients with higher GBP1 expression exhibited improved overall survival and clinical benefits in immunotherapy cohorts, including the Gide et al. cohort [area under the curve (AUC): 0.813], the IMvigor210 cohort (AUC: 0.607), the Lauss et al. cohort (AUC: 0.740), and the Kim et al. cohort (AUC: 0.793).Conclusion: This study provides comprehensive insights into the role of GBP1 in a pan-cancer manner. We identify GBP1 expression as a predictive biomarker for immunotherapy, potentially enabling more precise and personalized immunotherapeutic strategies in the future.
CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer
Authors: Wu Zhiheng , Zheng Yu , Sheng Jin , Han Yicheng , Yang Yanyan , Pan Hongming , Yao Junlin 
Published: February 2022

The crucial role of CD4+ and CD8+ T cells in shaping and controlling immune responses during immune disease and cancer development has been well established and used to achieve marked clinical benefits. CD3+CD4-CD8- double-negative (DN) T cells, although constituting a rare subset of peripheral T cells, are gaining interest for their roles in inflammation, immune disease and cancer. Herein, we comprehensively review the origin, distribution and functions of this unique T cell subgroup. First, we focused on characterizing multifunctional DN T cells in various immune responses. DN regulatory T cells have the capacity to prevent graft-versus-host disease and have therapeutic value for autoimmune disease. T helper-like DN T cells protect against or promote inflammation and virus infection depending on the specific settings and promote certain autoimmune disease. Notably, we clarified the role of DN tumor-infiltrating lymphocytes and outlined the potential for malignant proliferation of DN T cells. Finally, we reviewed the recent advances in the applications of DN T cell-based therapy for cancer. In conclusion, a better understanding of the heterogeneity and functions of DN T cells may help to develop DN T cells as a potential therapeutic tool for inflammation, immune disorders and cancer.
High TRGV 9 Subfamily Expression Marks an Improved Overall Survival in Patients With Acute Myeloid Leukemia
Authors: Kong Xueting , Zheng Jiamian , Liu Xiaxin , Wang Wandi , Jiang Xuan , Chen Jie , Lai Jing , Jin Zhenyi , Wu Xiuli 
Published: February 2022

BackgroundHeterogeneous T cells in acute myeloid leukemia (AML) have the combinatorial variety generated by different T cell receptors (TCRs). γδ T cells are a distinct subgroup of T cells containing TCRγ (TRGV) and TCRδ (TRDV) subfamilies with diverse structural and functional heterogeneity. Our previous study showed that clonally expanded TRDV T cells might benefit the immune response directed against AML. However, the features of the TRGV repertoire in AML remain unknown. To fully characterize the features of γδ T cells, we analyzed the distribution and clonality of TRGV I-III subfamilies (TRGV II is also termed TRVG 9), the proportions of γδ T cell subsets, and their effects on the overall survival (OS) of patients with AML.MethodsIn this study, the complementarity-determining region 3 (CDR3) size of TRGV subfamilies in γδ T cells of peripheral blood (PB) from de novo AML patients were analyzed by Genescan analysis. Expression levels of TRGV subfamilies were performed by real-time quantitative PCR. The proportions of total γδ T cells and their Vγ9+ Vδ2+ T cells subsets were detected by multicolor flow cytometry assay. We further compared the correlation among the TRGV gene expression levels, the proportion of Vγ9+ Vδ2+ T cells, and OS in AML.ResultsWe first found that the distribution pattern and clonality of TRGV subfamilies were changed. The expression frequencies and gene expression levels of three TRGV subfamilies in AML samples were significantly lower than those in healthy individuals (HIs). Compared with HIs, the proportions of total γδ T cells and Vγ9+ Vδ2+ T cells were also significantly decreased in patients with AML. In addition, patients with AML who had higher expression levels of the TRGV gene and higher proportion of Vγ9+ Vδ2+ T cells showed better OS than their counterparts. Furthermore, high expression levels of TRGV 9 and proportion of Vγ9+ Vδ2+ T cells were identified as independent protective factors for complete remission in patients with AML.ConclusionsThe restriction of TRGV usage might be related to the preference of usage of γδ T cells. Higher expression of TRGV subfamilies might be associated with better OS in AML. Higher TRGV 9 expression and increased Vγ9+ Vδ2+ T cells subfamilies might indicate a better prognosis in patients with AML.
Predicting Severe Disease and Critical Illness on Initial Diagnosis of COVID-19: Simple Triage Tools
Authors: Kurban Lutfi Ali S. , AlDhaheri Sharina , Elkkari Abdulbaset , Khashkhusha Ramzi , AlEissaee Shaikha , AlZaabi Amna , Ismail Mohamed , Bakoush Omran 
Published: February 2022

RationaleThis study was conducted to develop, validate, and compare prediction models for severe disease and critical illness among symptomatic patients with confirmed COVID-19.MethodsFor development cohort, 433 symptomatic patients diagnosed with COVID-19 between April 15th 2020 and June 30th, 2020 presented to Tawam Public Hospital, Abu Dhabi, United Arab Emirates were included in this study. Our cohort included both severe and non-severe patients as all cases were admitted for purpose of isolation as per hospital policy. We examined 19 potential predictors of severe disease and critical illness that were recorded at the time of initial assessment. Univariate and multivariate logistic regression analyses were used to construct predictive models. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Calibration and goodness of fit of the models were assessed. A cohort of 213 patients assessed at another public hospital in the country during the same period was used to validate the models.ResultsOne hundred and eighty-six patients were classified as severe while the remaining 247 were categorized as non-severe. For prediction of progression to severe disease, the three independent predictive factors were age, serum lactate dehydrogenase (LDH) and serum albumin (ALA model). For progression to critical illness, the four independent predictive factors were age, serum LDH, kidney function (eGFR), and serum albumin (ALKA model). The AUC for the ALA and ALKA models were 0.88 (95% CI, 0.86–0.89) and 0.85 (95% CI, 0.83–0.86), respectively. Calibration of the two models showed good fit and the validation cohort showed excellent discrimination, with an AUC of 0.91 (95% CI, 0.83–0.99) for the ALA model and 0.89 (95% CI, 0.80–0.99) for the ALKA model. A free web-based risk calculator was developed.ConclusionsThe ALA and ALKA predictive models were developed and validated based on simple, readily available clinical and laboratory tests assessed at presentation. These models may help frontline clinicians to triage patients for admission or discharge, as well as for early identification of patients at risk of developing critical illness.
Diversity in the Characteristics of Klebsiella pneumoniae ST101 of Human, Environmental, and Animal Origin
Authors: De Koster Sien , Rodriguez Ruiz Juan Pablo , Rajakani Sahaya Glingston , Lammens Christine , Glupczynski Youri , Goossens Herman , Xavier Basil Britto 
Published: February 2022

BackgroundKlebsiella pneumoniae ST101 is an emerging high-risk clone which exhibits extensive drug resistance. Bacterial strains residing in multiple hosts show unique signatures related to host adaptation. In this study, we assess the genetic relationship of K. pneumoniae ST101 isolated from hospital samples, the environment, community, and livestock using whole genome sequencing (WGS).Materials and MethodsWe selected ten K. pneumoniae ST101 strains from hospitalized patients in Italy (n = 3) (2014) and Spain (n = 5) (2015–2016) as well as Belgian livestock animals (n = 2) (2017–2018). WGS was performed with 2 × 250 bp paired-end sequencing (Nextera XT) sample preparation kit and MiSeq (Illumina Inc.). Long-read sequencing (Pacbio Sequel I) was used to sequence the two livestock strains and three Italian hospital-associated strains. Furthermore, a public ST101 sequence collection of 586 strains (566 hospital-associated strains, 12 environmental strains, six strains from healthy individuals, one food-associated strain and one pig strain) was obtained. BacPipe and Kleborate were used to conduct genome analysis. ISFinder was used to find IS elements, and PHASTER was utilized to identify prophages. A phylogenetic tree was constructed to illustrate genetic relatedness.ResultsHospital-associated K. pneumoniae ST101 showed higher resistance scores than non-clinical isolates from healthy individuals, the environment, food and livestock (1.85 ± 0.72 in hospital-associated isolates vs. 1.14 ± 1.13 in non-clinical isolates, p &lt; 0.01). Importantly, the lack of integrative conjugative elements ICEKp bearing iron-scavenging yersiniabactin siderophores (ybt) in livestock-associated strains suggests a lower pathogenicity potential than hospital-associated strains. Mobile genetic elements (MGE) appear to be an important source of diversity in K. pneumoniae ST101 strains from different origins, with a highly stable genome and few recombination events outside the prophage-containing regions. Core genome MLST based analysis revealed a distinct genetic clustering between human and livestock-associated isolates.ConclusionThe study of K. pneumoniae ST101 hospital-associated and strains from healthy individuals and animals revealed a genetic diversity between these two groups, allowing us to identify the presence of yersiniabactin siderophores in hospital-associated isolates. Resistance and virulence levels in livestock-associated strains were considerably lower than hospital-associated strains, implying that the public health risk remains low. The introduction of an ICEKp into animal strains, on the other hand, might pose a public threat over time.
The Neuropsychiatric Changes After COVID-19 Quarantine in Patients With Cognitive Impairment and Their Caregivers in Chongqing, China: A Cohort Study
Authors: Yuan Shiyun , Zhang Wenbo , Yao Qiang , Lü Wenqi , Yu Wuhan , Zhong Fuxin , Wang Yan , Xing Dianxia , Wang Xiaoqin , Song Jiaqi , Huang Hong , Chen Chenxi , Liu Junjin , Yu Weihua , Lü Yang 
Published: February 2022

BackgroundThe follow-up study on neuropsychiatric changes after the lifting of coronavirus disease 2019 (COVID-19) quarantine in patients with cognitive impairment and their caregivers is still lacking, and relative information is needed to formulate more comprehensive healthcare prevention measures worldwide.AimsTo provide data on the changes in neuropsychiatric performance after the lifting of COVID-19 quarantine in patients with cognitive disorders and their caregivers.MethodsTwo surveys in Chongqing, China were conducted via telephonic interview with 531 patients and their caregivers. The baseline survey was performed from February 11 to 23, 2020, and the follow-up was from October 24 to November 9, 2020. The data of neuropsychiatric symptoms (NPSs), sleep, nutrition, and chronic diseases of patients, as well as the burden of care, anxiety, and depression of caregivers were evaluated.ResultsSignificant alleviation of NPSs after the lifting of COVID-19 quarantine was observed in patients with mild cognitive impairment (MCI) and dementia (both P &lt; 0.05). Compared with baseline, the prevalence for NPSs of all participants dropped from 57.94 to 38.82%. Among NPS subdomains, apathy displayed the biggest decline at follow-up by 10.72%, followed by nighttime behavior by 8.65%. Mixed effect generalized estimation equation analysis showed significant amelioration in hallucination, depression, apathy, irritability, aberrant motor behavior, and nighttime behavior (all P &lt; 0.05), with the most prominent changes in nighttime behavior and apathy. Among the patients with unsatisfactory control of chronic disease, the medication adherence rate dropped by approximately 30% after the lifting of quarantine. More importantly, around 13% increase of care burden was observed among the caregivers at follow-up, with both depression and anxiety rising by nearly 4%.ConclusionThe prolonged quarantine may exacerbate NPS in patients with memory disorders, while the care burden and mental stability of the caregivers after the pandemic should also be concerned.