bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ancient Mitogenomes Provide New Insights into the Origin and Early Introduction of Chinese Domestic Donkeys
Authors: Wang Linying , Sheng Guilian , Preick Michaela , Hu Songmei , Deng Tao , Taron Ulrike H. , Barlow Axel , Hu Jiaming , Xiao Bo , Sun Guojiang , Song Shiwen , Hou Xindong , Lai Xulong , Hofreiter Michael , Yuan Junxia 
Published: October 2021

Both molecular data and archaeological evidence strongly support an African origin for the domestic donkey. Recent genetic studies further suggest that there were two distinct maternal lineages involved in its initial domestication. However, the exact introduction time and the dispersal process of domestic donkeys into ancient China are still unresolved. To address these questions, we retrieved three near-complete mitochondrial genomes from donkey specimens excavated from Gaoling County, Shaanxi Province, and Linxia Basin, Gansu Province, China, dated at 2,349-2,301, 469-311, and 2,160-2,004 cal. BP, respectively. Maximum-likelihood and Bayesian phylogenetic analyses reveal that the two older samples fall into the two different main lineages (i.e., clade Ⅰ and clade Ⅱ) of the domestic donkey, suggesting that the two donkey maternal lineages had been introduced into Midwestern China at least at the opening of Silk Road (approximately the first century BC). Bayesian analysis shows that the split of the two donkey maternal lineages is dated at 0.323 Ma (95% CI: 0.583–0.191 Ma) using root-tip dating calibrations based on near-complete mitogenomes, supporting the hypothesis that modern domestic donkeys go back to at least two independent domestication events. Moreover, Bayesian skyline plot analyses indicate an apparent female population increase between 5,000 and 2,500 years ago for clade I followed by a stable population size to the present day. In contrast, clade II keeps a relatively stable population size over the past 5,000 years. Overall, our study provides new insights into the early domestication history of Chinese domestic donkeys.
The Predictive Role of Immune Related Subgroup Classification in Immune Checkpoint Blockade Therapy for Lung Adenocarcinoma
Authors: Yu Xiaozhou , Wang Ziyang , Chen Yiwen , Yin Guotao , Liu Jianjing , Chen Wei , Zhu Lei , Xu Wengui , Li Xiaofeng 
Published: October 2021

Background: In lung adenocarcinoma (LUAD), the predictive role of immune-related subgroup classification in immune checkpoint blockade (ICB) therapy remains largely incomplete.Methods: Transcriptomics analysis was performed to evaluate the association between immune landscape and ICB therapy in lung adenocarcinoma and the associated underlying mechanism. First, the least absolute shrinkage and selection operator (LASSO) algorithm and K-means algorithm were used to identify immune related subgroups for LUAD cohort from the Cancer Genome Atlas (TCGA) database (n = 572). Second, the immune associated signatures of the identified subgroups were characterized by evaluating the status of immune checkpoint associated genes and the immune cell infiltration. Then, potential responses to ICB therapy based on the aforementioned immune related subgroup classification were evaluated via tumor immune dysfunction and exclusion (TIDE) algorithm analysis, and survival analysis and further Cox proportional hazards regression analysis were also performed for LUAD. In the end, gene set enrichment analysis (GSEA) was performed to explore the metabolic mechanism potentially responsible for immune related subgroup clustering. Additionally, two LUAD cohorts from the Gene Expression Omnibus (GEO) database were used as validation cohort.Results: A total of three immune related subgroups with different immune-associated signatures were identified for LUAD. Among them, subgroup 1 with higher infiltration scores for effector immune cells and immune checkpoint associated genes exhibited a potential response to IBC therapy and a better survival, whereas subgroup 3 with lower scores for immune checkpoint associated genes but higher infiltration scores for suppressive immune cells tended to be insensitive to ICB therapy and have an unfavorable prognosis. GSEA revealed that the status of glucometabolic reprogramming in LUAD was potentially responsible for the immune-related subgroup classification.Conclusion: In summary, immune related subgroup clustering based on distinct immune associated signatures will enable us to screen potentially responsive LUAD patients for ICB therapy before treatment, and the discovery of metabolism associated mechanism is beneficial to comprehensive therapeutic strategies making involving ICB therapy in combination with metabolism intervention for LUAD.
Abnormalities in Gut Microbiota and Metabolism in Patients With Chronic Spontaneous Urticaria
Authors: Wang Xin , Yi Wanyu , He Liting , Luo Shuaihantian , Wang Jiaqi , Jiang Li , Long Hai , Zhao Ming , Lu Qianjin 
Published: October 2021

BackgroundIncreasing evidence suggests that the gut microbiome plays a role in the pathogenesis of allergy and autoimmunity. The association between abnormalities in the gut microbiota and chronic spontaneous urticaria (CSU) remains largely undefined.MethodsFecal samples were obtained from 39 patients with CSU and 40 healthy controls (HCs). 16S ribosomal RNA (rRNA) gene sequencing (39 patients with CSU and 40 HCs) and untargeted metabolomics (12 patients with CSU and 12 HCs) were performed to analyze the compositional and metabolic alterations of the gut microbiome in CSU patients and HCs.ResultsThe 16S rRNA gene sequencing results showed a significant difference in the β-diversity of the gut microbiota, presented as the Jaccard distance, between CSU patients and HCs. No significant differences were found in the α-diversity of the gut microbiota between patients and HCs. At the phylum level, the major bacteria in the gut microbiome of patients with CSU were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. At the genus level, Lactobacillus, Turicibacter, and Lachnobacterium were significantly increased and Phascolarctobacterium was decreased in patients with CSU. PICRUSt and correlation analysis indicated that Lactobacillus, Turicibacter, and Phascolarctobacterium were positively related to G protein-coupled receptors. Metabolomic analysis showed that α-mangostin and glycyrrhizic acid were upregulated and that 3-indolepropionic acid, xanthine, and isobutyric acid were downregulated in patients with CSU. Correlation analysis between the intestinal microbiota and metabolites suggested that there was a positive correlation between Lachnobacterium and α-mangostin.ConclusionsThis study suggests that disturbances in the gut microbiome composition and metabolites and their crosstalk or interaction may participate in the pathogenesis of CSU.
Dexamethasone-Induced FKBP51 Expression in CD4+ T-Lymphocytes Is Uniquely Associated With Worse Asthma Control in Obese Children With Asthma
Authors: Tejwani Vickram , McCormack Amanda , Suresh Karthik , Woo Han , Xu Ningchun , Davis Meghan F. , Brigham Emily , Hansel Nadia N. , McCormack Meredith C. , D’Alessio Franco R. 
Published: October 2021

IntroductionThere is evidence that obesity, a risk factor for asthma severity and morbidity, has a unique asthma phenotype which is less atopic and less responsive to inhaled corticosteroids (ICS). Peripheral blood mononuclear cells (PBMC) are important to the immunologic pathways of obese asthma and steroid resistance. However, the cellular source associated with steroid resistance has remained elusive. We compared the lymphocyte landscape among obese children with asthma to matched normal weight children with asthma and assessed relationship to asthma control.MethodsHigh-dimensional flow cytometry of PBMC at baseline and after dexamethasone stimulation was performed to characterize lymphocyte subpopulations, T-lymphocyte polarization, proliferation (Ki-67+), and expression of the steroid-responsive protein FK506-binding protein 51 (FKBP51). T-lymphocyte populations were compared between obese and normal-weight participants, and an unbiased, unsupervised clustering analysis was performed. Differentially expressed clusters were compared with asthma control, adjusted for ICS and exhaled nitric oxide.ResultsIn the obese population, there was an increased cluster of CD4+T-lymphocytes expressing Ki-67 and FKBP51 at baseline and CD4+T-lymphocytes expressing FKBP51 after dexamethasone stimulation. CD4+Ki-67 and FKBP51 expression at baseline showed no association with asthma control. Dexamethasone-induced CD4+FKBP51 expression was associated with worse asthma control in obese participants with asthma. FKBP51 expression in CD8+T cells and CD19+B cells did not differ among groups, nor did polarization profiles for Th1, Th2, Th9, or Th17 percentage.DiscussionDexamethasone-induced CD4+FKBP51 expression is uniquely associated with worse asthma control in obese children with asthma and may underlie the corticosteroid resistance observed in this population.
Diphtheria And Tetanus Vaccination History Is Associated With Lower Odds of COVID-19 Hospitalization
Authors: Monereo-Sánchez Jennifer , Luykx Jurjen J. , Pinzón-Espinosa Justo , Richard Geneviève , Motazedi Ehsan , Westlye Lars T. , Andreassen Ole A. , van der Meer Dennis 
Published: October 2021

BackgroundCOVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity: while some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. Previous vaccinations for other pathogens, in particular tetanus, may partly explain this variation, possibly by readying the immune system.MethodsWe made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.5 years, 54.2% female), coupled to immunization records of the last ten years. Using logistic regression, covarying for age, sex, respiratory disease diagnosis, and socioeconomic status, we tested whether individuals vaccinated for tetanus, diphtheria or pertussis, differed from individuals that had only received other vaccinations on 1) undergoing a COVID-19 test, 2) being diagnosed with COVID-19, and 3) whether they developed severe COVID-19 symptoms.ResultsWe found that individuals with registered diphtheria or tetanus vaccinations are less likely to develop severe COVID-19 than people who had only received other vaccinations (diphtheria odds ratio (OR)=0.47, p-value=5.3*10-5; tetanus OR=0.52, p-value=1.2*10-4).DiscussionThese results indicate that a history of diphtheria or tetanus vaccinations is associated with less severe manifestations of COVID-19. These vaccinations may protect against severe COVID-19 symptoms by stimulating the immune system. We note the correlational nature of these results, yet the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations.
Interstitial Lung Disease Associated With Autoimmune Rheumatic Diseases: Checklists for Clinical Practice
Authors: Bosello Silvia Laura , Beretta Lorenzo , Del Papa Nicoletta , Harari Sergio , Palmucci Stefano , Pesci Alberto , Rechichi Gilda , Varone Francesco , Sebastiani Marco 
Published: October 2021

Background: Interstitial lung diseases (ILDs) are often associated with rheumatic diseases. Their early diagnosis and management are not only difficult, but also crucial, because they are associated with major morbidity and mortality and can be the first cause of death in autoimmune rheumatic diseases (ARDs).Objectives: By using methodologies, such as Nominal Group Technique (NGT) and Delphi Survey, the aims of this study were (1) to measure consensus between pulmonologists, radiologists, and rheumatologists experienced in the management of ARD-ILD; (2) to highlight the importance of a multidisciplinary approach; and (3) to provide clinicians with a practical tool aimed at improving the prompt recognition and follow-up of ILD associated with ARDs and of any possible rheumatic conditions underlying ILD.Results: During the NGT round, the Steering Committee defined 57 statements to be used in the Delphi survey. A total of 78 experts participated in the Delphi survey, namely 28 pulmonologists, 33 rheumatologists, and 17 radiologists. During this round, consensus on agreement was reached in 47 statements, while disagreement was not reached in any statements. A secondary questionnaire was drafted by the Steering Committee to obtain clearer indications on ILD-ARD “red-flags” and follow-up. Delphi Panelists took part also in the second-questionnaire survey. Answers from both surveys were used to draft two checklists of “red flags” sign or symptom suggestive of ILD and ARD, respectively, and two checklists on identification and monitoring of rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD.Limitations: This study is a consensus work, which cannot produce empiric data, and is limited to the Italian scenario.Conclusions: This work showed a high level of agreement, but also shows some divergent opinions between different experts. This underlines the importance of a multidisciplinary approach. Eventually, we believe the drafted checklists can help clinicians in the diagnosis and follow-up of ILD-ARD.
Acute-On-Chronic Liver Failure Defined by Asian Pacific Association for the Study of the Liver Should Include Decompensated Cirrhosis
Authors: Xu Manman , Kong Ming , Yu Pengfei , Cao Yingying , Liu Fang , Zhu Bing , Zhang Yizhi , Lu Wang , Zou Huaibin , You Shaoli , Xin Shaojie , Duan Zhongping , Han Tao , Chen Yu 
Published: October 2021

Background and Aims: Acute-on-chronic liver failure (ACLF) is an acute deterioration of chronic liver disease with high short-term mortality. The inclusion or exclusion of previously decompensated cirrhosis (DC) in the diagnostic criteria of ACLF defined by the Asian Pacific Association for the Study of the Liver (APASL-ACLF) has not been conclusive. We aimed to evaluate the prognostic impact of decompensated cirrhosis in ACLF.Methods: We retrospectively collected a cohort of patients with a diagnosis of APASL-ACLF (with or without DC) hospitalized from 2012 to 2020 at three liver units in tertiary hospitals. Baseline characteristics and survival data at 28, 90, 180, 360, 540, and 720 days were collected.Results: Of the patients assessed using APASL-ACLF criteria without the diagnostic indicator of chronic liver disease, 689 patients were diagnosed with ACLF, of whom 435 had no decompensated cirrhosis (non-DC-ACLF) and 254 had previously decompensated cirrhosis (DC-ACLF). The 28-, 90-, 180-, 360-, 540-, and 720-day mortality were 24.8, 42.9, 48.7, 57.3, 63.4, and 68.1%, respectively, in DC-ACLF patients, which were significantly higher than in non-DC-ACLF patients (p &lt; 0.05). DC was independently associated with long-term (180/360/540/720 days) but not short-term (28/90 days) mortality in patients with ACLF. Age, total bilirubin, international normalized ratio, and hepatic encephalopathy were independent risk factors for short- and long-term mortality risk in ACLF patients (p &lt; 0.05).Conclusions: Patients with DC-ACLF have a higher mortality rate, especially long-term mortality, compared to non-DC-ACLF patients. Therefore, DC should be included in the diagnostic criteria of APASL-ACLF and treated according to the ACLF management process.
Psoriasis Is Associated With Myosteatosis but Not Sarcopenia: A Case-Control Study
Authors: Chen Xiaomei , Xiang Hongmei , Tan Lingling , Zhou Jie , Tang Jing , Hu Xiaoyi , Yang Ming 
Published: October 2021

Background: The link between psoriasis and body fat (or obesity) has been well established. However, there are no reports detailing the possible relationship between psoriasis and fat infiltration in skeletal muscle, also known as myosteatosis. A recent study reported the possible association between psoriasis, arthritis, and sarcopenia (the loss of skeletal muscle mass or function). The present study aimed to explore the possible associations of chronic plaque psoriasis with myosteatosis and sarcopenia.Methods: We conducted a case-control study. In-patients with chronic plaque psoriasis were retrospectively recruited. Healthy controls were prospectively and continuously recruited. Unenhanced cross-sectional chest computed tomography images at the 12th thoracic vertebral level were analyzed using Mimics software. Skeletal muscle area (SMA), skeletal muscle radiodensity (SMD), and intermuscular adiposity tissue (IMAT) were measured. The skeletal muscle index (SMI) was calculated as SMA/height2. The percentage of IMAT (IMAT%) was calculated as IMAT/SMA × 100%. Myosteatosis was defined by SMD or IMAT%, whereas sarcopenia was defined by SMI. Propensity score matching was performed to adjust for the main confounders. Logistic regression models were used to evaluate the associations of psoriasis with myosteatosis and sarcopenia.Results: We included 155 psoriasis patients and 512 healthy controls. After propensity score matching, we retained 310 controls. The prevalence of sarcopenia was not significantly different between the psoriasis and control groups (men: 9.8% vs. 14.4%, p = 0.244; women: 7.0% vs. 11.7%, p = 0.548). Psoriasis patients were more prone to SMD-defined myosteatosis (men: 39.3% vs. 20.8%; women: 46.5% vs. 16.0%; both p &lt; 0.001) and IMAT%-defined myosteatosis (men: 21.4% vs. 12.5%, p = 0.034; women: 46.5 vs. 28.7%, p = 0.042) than the control group. After adjustment for potential confounders, psoriasis was not significantly associated with sarcopenia (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.25–1.19, p = 0.136). However, psoriasis was associated with SMD-defined myosteatosis (OR 3.16, 95% CI 1.86–5.37, p &lt; 0.001) and IMAT%-defined myosteatosis (OR 1.76, 95% CI 1.04–3.00; p = 0.037).Conclusions: Chronic plaque psoriasis is independently associated with myosteatosis but not sarcopenia. Since fat and muscle are considered endocrine organs and can drive the inflammatory process, further studies detailing the interaction between psoriasis, fat, and skeletal muscle are warranted.
Infection Kinetics and Transmissibility of a Reanimated Dengue Virus Serotype 4 Identified Originally in Wild Aedes aegypti From Florida
Authors: Ayers Jasmine B. , Xie Xuping , Coatsworth Heather , Stephenson Caroline J. , Waits Christy M. , Shi Pei-Yong , Dinglasan Rhoel R. 
Published: October 2021

Dengue virus is the most prevalent mosquito-borne virus, causing approximately 390 million infections and 25,000 deaths per year. Aedes aegypti, the primary mosquito vector of dengue virus, is well-established throughout the state of Florida, United States. Autochthonous transmission of dengue virus to humans in Florida has been increasing since 2009, alongside consistent importation of dengue cases. However, most cases of first infection with dengue are asymptomatic and the virus can be maintained in mosquito populations, complicating surveillance and leading to an underestimation of disease risk. Metagenomic sequencing of A. aegypti mosquitoes in Manatee County, Florida revealed the presence of dengue virus serotype 4 (DENV-4) genomes in mosquitoes from multiple trapping sites over 2years, in the absence of a human DENV-4 index case, and even though a locally acquired case of DENV-4 has never been reported in Florida. This finding suggested that: (i) DENV-4 may circulate among humans undetected; (ii) the virus was being maintained in the mosquito population, or (iii) the detected complete genome sequence may not represent a viable virus. This study demonstrates that an infectious clone generated from the Manatee County DENV-4 (DENV-4M) sequence is capable of infecting mammalian and insect tissue culture systems, as well as adult female A. aegypti mosquitoes when fed in a blood meal. However, the virus is subject to a dose dependent infection barrier in mosquitoes, and has a kinetic delay compared to a phylogenetically related wild-type (WT) control virus from a symptomatic child, DENV-4H (strain Homo sapiens/Haiti-0075/2015, GenBank accession MK514144.1). DENV-4M disseminates from the midgut to the ovary and saliva at 14days post-infection. Viral RNA was also detectable in the adult female offspring of DENV-4M infected mosquitoes. These results demonstrate that the virus is capable of infecting vector mosquitoes, is transmissible by bite, and is vertically transmitted, indicating a mechanism for maintenance in the environment without human-mosquito transmission. These findings suggest undetected human-mosquito transmission and/or long-term maintenance of the virus in the mosquito population is occurring in Florida, and underscore the importance of proactive surveillance for viruses in mosquitoes.GRAPHICAL ABSTRACTIn order to better assess the public health risk posed by a detection of DENV-4 RNA in Manatee County, FL Aedes aegypti, we produced an infectious clone using the sequence from the wild-caught mosquitoes and characterized it via laboratory infections of mosquitoes and mosquito tissues.
Single and Repeated Episodes of Candida Species Isolated From Cerebrospinal Fluid for Diagnosing Probable Candida meningitis
Authors: Xu Lijun , Zhao Handan , Zhou Minghan , Lang Guanjing , Lou Haiyan 
Published: October 2021

Background: The clinical relevance of single or repeated episodes of Candida spp. in cerebrospinal fluid (CSF) in adult patients is debatable.Methods: Forty-two patients with positive Candida episodes in CSF were enrolled in this retrospective study.Results: A total of 42.9% (18/42) were determined to have probable Candida meningitis (PCM). Neurosurgery [odds ratio (OR) (95% confidence interval), OR: 14.4 (1.6–126.1), P = 0.004], lumbar drainage [OR: 5.8 (1.5–23.3), P = 0.009], VP shunt [(OR: 5.6 (1.2–25.8), P = 0.020)], external ventricular drainage [OR: 4.7 (1.3–17.7), P = 0.018], CRP ≥ 10.0 mg/L [OR: 4.9 (1.3–18.1), P = 0.034], and postsurgical broad-spectrum antibiotics [OR: 9.5 (1.8–50.5), P = 0.004] were risk factors associated with PCM. A single CSF Candida episode for the diagnosis of PCM had 7.7% (0.4–37.9%) sensitivity and 20.7% (8.7–40.3%) specificity, whereas repeated episodes of Candida had 66.7% (41.2–85.6%) sensitivity and 95.8% (76.9–99.8%) specificity. No significant difference was found in radiological imaging or CSF profiles between PCM and non-PCM patients. A total of 37.5% (9/24) of patients without PCM received empirical antifungal treatment, and 88.9% (16/18) of patients with PCM received preemptive antifungal treatment. PCM patients had hospitalized mortality rates of 50.0% (9/18). The odds ratio of mortality was 23.0 (2.5–208.6) for PCM patients compared with non-PCM patients (P = 0.001).Conclusion: Both single and repeated positive CSF samples have low validity for the diagnosis of PCM, suggesting that novel strategies for diagnosis algorithms of PCM are urgently needed. Empirical antifungal treatment should be started immediately for suspicious patients with risk factors.