bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody Response after Second-dose of ChAdOx1-nCOV (Covishield™®) and BBV-152 (Covaxin™®) among Health Care Workers in India: Final Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study
Authors: Kumar Singh Awadhesh , Phatak Sanjeev Ratnakar , Singh Ritu , Bhattacharjee Kingshuk , Singh Nagendra Kumar , Gupta Arvind , Sharma Arvind 
Published: June 2021

AbstractBackgroundWe assessed the humoral immune response after the completion of two doses of both ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccines in Indian health care workers (HCW).MethodA Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study was conducted that measured SARS-CoV-2 anti-spike binding antibody quantitatively, 21 days or more after the first and second dose of two vaccines in both severe acute respiratory syndrome (SARS-CoV-2) naïve and recovered HCW. Primary aim was to analyze antibody response (seropositivity rate and median [inter-quartile range, IQR] antibody titre) following each dose of both vaccines and its correlation to age, sex, blood group, body mass index (BMI) and comorbidities. Here we report the final results of anti-spike antibody response after the two completed doses.ResultsAmong the 515 HCW (305 Male, 210 Female), 95.0% showed seropositivity after two doses of both vaccines. Of the 425 Covishield and 90 Covaxin recipients, 98.1% and 80.0% respectively, showed seropositivity. However, both seropositivity rate and median (IQR) rise in anti-spike antibody was significantly higher in Covishield vs. Covaxin recipient (98.1 vs. 80.0%; 127.0 vs. 53 AU/mL; both p<0.001). This difference persisted in 457 SARS-CoV-2 naïve cohorts and propensity-matched (age, sex and BMI) analysis of 116 cohorts. While no difference was observed in relation to sex, BMI, blood group and any comorbidities; people with age >60 years or those with type 2 diabetes had a significantly lower seropositivity rates. Both vaccine recipients had similar solicited mild to moderate adverse events and none had severe or unsolicited side effects. In SARS-CoV-2 naïve cohorts, sex, presence of comorbidities, and vaccine type were independent predictors of antibody positivity rate in multiple logistic regression analysis.ConclusionsBoth vaccines elicited good immune response after two doses, although seropositivity rates and median anti-spike antibody titre was significantly higher in Covishield compared to Covaxin arm.HighlightsThis study evaluated the humoral antibody response after 2 doses of SARS-CoV-2 vaccine Covishield™ and Covaxin™ in Indian health-care workers.Combined results of both vaccines showed 95% seropositivity to anti-spike antibody, 21-36 days after the second completed dose.Seropositivity rates were higher in Covishield recipients compared to Covaxin in the propensity-matched analysis of SARS-CoV-2 naïve cohorts.Gender, presence of comorbidities and the type of vaccine received were independent predictors of antibody response after the second dose.
SSMD: Semi-Supervised Medical Image Detection with Adaptive Consistency and Heterogeneous Perturbation
Authors: Zhou Hong-Yu , Wang Chengdi , Li Haofeng , Wang Gang , Zhang Shu , Li Weimin , Yu Yizhou 
Published: June 2021

AbstractSemi-Supervised classification and segmentation methods have been widely investigated in medical image analysis. Both approaches can improve the performance of fully-supervised methods with additional unlabeled data. However, as a fundamental task, semi-supervised object detection has not gained enough attention in the field of medical image analysis. In this paper, we propose a novel Semi-Supervised Medical image Detector (SSMD). The motivation behind SSMD is to provide free yet effective supervision for unlabeled data, by regularizing the predictions at each position to be consistent. To achieve the above idea, we develop a novel adaptive consistency cost function to regularize different components in the predictions. Moreover, we introduce heterogeneous perturbation strategies that work in both feature space and image space, so that the proposed detector is promising to produce powerful image representations and robust predictions. Extensive experimental results show that the proposed SSMD achieves the state-of-the-art performance at a wide range of settings. We also demonstrate the strength of each proposed module with comprehensive ablation studies.
Efficacy of clarithromycin on COVID-19 pneumonia without oxygen administration; protocol for multicenter, open-label, randomized-controlled, 3-armed parallel group comparison, exploratory trial (CAME COVID study)
Authors: Yamamoto Kazuko , Hosogaya Naoki , Sakamoto Noriho , Yoshida Haruo , Ishii Hiroshi , Yatera Kazuhiro , Izumikawa Koichi , Yanagihara Katsunori , Mukae Hiroshi 
Published: June 2021

AbstractIntroductionThe coronavirus disease 2019 (COVID-19) epidemic has been emerged worldwide. Although several medications have been approved for treating moderate-to-severe COVID-19, no treatment strategy has been established for mild COVID-19 patients who do not require oxygen administration. The spread of SARS -CoV-2 has been mostly through patients with mild COVID-19; therefore, treating patients with mild COVID-19 is critical in society. Clarithromycin is a macrolide antimicrobial agent that has been widely used for bacterial respiratory infectious diseases. Clarithromycin also acts an immunomodulating drug and suppresses cytokine storms in viral respiratory diseases, including influenza infection. In this study, we aimed to evaluate the efficacy of clarithromycin in patients with mild COVID-19.Methods and analysisThis is a multicenter, open-label, randomized controlled, 3-armed parallel group comparison, exploratory trial. Subjects with mild COVID-19 pneumonia who did not require oxygen administration were enrolled and randomly assigned in a 1:1:1 ratio to Group A (administration of clarithromycin 800 mg/day), Group B (administration of clarithromycin 400 mg/day), or Group C (standard treatment without clarithromycin). The primary endpoint was the number of days required to improve clinical symptoms as measured by the severity score. Secondary endpoints included days to recover the body temperature, proportion of subjects with oxygen administration, inflammatory cytokines, viral load, serum immunoglobulins, peripheral blood lymphocytes, blood biomarkers, and pneumonia infiltrations.Ethics and disseminationThe study protocol was approved by the Clinical Research Review Board of Nagasaki University in accordance with the Clinical Trials Act in Japan. The study will be conducted in accordance with the Declaration of Helsinki, the Clinical Trials Act, and other current legal regulations in Japan. Written informed consent will be obtained from all participants. The results of this study will be reported as journal publications.RegistrationThis study was registered at the Japan Registry of Clinical Trials (registration number: jRCTs071210011).Strengths and limitations of this studyThis is the first randomized controlled trial to evaluate the efficacy of clarithromycin against COVID-19 pneumonia, especially in patients with mild COVID-19 pneumonia who do not require oxygen administration.To date, no treatment strategy has been established for mild COVID-19 pneumonia.The major limitations of this study are its exploratory nature and relatively small sample size.Another limitation is the open-label study design and generalizability because this study was conducted only in Japan with Japanese patients.
A rare variant in D-amino acid oxidase implicates NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder
Authors: Hasin Naushaba , Riggs Lace M. , Shekhtman Tatyana , Ashworth Justin , Lease Robert , Oshone Rediet T. , Humphries Elizabeth M. , Badner Judith A. , Thompson Pippa A. , Glahn David C. , Craig David W. , Edenberg Howard J. , Gershon Elliot S. , McMahon Francis J. , Nurnberger John I. , Zandi Peter P. , Kelsoe John R. , Roach Jared C. , Gould Todd D. , Ament Seth A. 
Published: June 2021

AbstractBipolar disorder is an often-severe mental health disorder characterized by alternation between extreme mood states of mania and depression. Despite strong heritability and the recent identification of 64 loci of small effect, pathophysiological mechanisms and much of the genetic risk remain unknown. Here, through genome sequencing and linkage and association analyses, we found that rare variants co-segregating with bipolar disorder in large multiply affected families cluster within gene networks enriched for synaptic and nuclear functions. The top variant in this analysis prioritized by statistical association, predicted deleteriousness, and network centrality was a missense variant in the gene encodingD-amino acid oxidase (DAOG131V). Heterologous expression of DAOG131Vin human cells resulted in decreased DAO protein abundance and enzymatic activity. In a knock-in mouse harboring this humanDAOG131Vvariant,DaoG130V/+, we similarly found decreased DAO protein abundance, as well as enhanced stress susceptibility and blunted behavioral responses to pharmacological inhibition ofN-methyl-D-aspartate receptors (NMDARs). RNA sequencing of cerebellar tissue revealed thatDaoG130Vresulted in decreased expression of two gene networks that are enriched for synaptic functions and for genes expressed specifically in Purkinje cells and granule neurons. Similar expression changes in both of these gene networks were also identified in the cerebellum of bipolar disorder cases vs. controls. These findings implicate dysregulation of NMDAR signaling and of gene expression in cerebellar neurons in bipolar disorder pathophysiology and provide insight into its genetic architecture.One Sentence SummaryFunctional studies of a rare hypofunctional variant in the D-amino acid oxidase gene implicate stress susceptibility, NMDA receptor signaling, and cerebellar circuits in risk for bipolar disorder.
African swine fever virus structural protein p17 inhibits cGAS-STING signaling pathway through interacting with STING
Authors: Zheng Wanglong , Xia Nengwen , Luo Jia , Jiang Sen , Zhang Jiajia , Wang Hui , Ao Da , Xu Yulin , Liu Xueliang , Shao Qi , Cao Qi , Zhang Youwen , Chen Nanhua , Zhang Quan , Da Jiansen , Chen Hongjun , Guo Xiaoyu , Zhu Hongfei , Meurens François , Zhu Jianzhong 
Published: June 2021

AbstractAfrican swine fever (ASF) is highly contagious, causes high mortality in domestic and feral swine, and has a significant economic impact on the global swine industry due to the lack of a vaccine or an effective treatment. African swine fever virus (ASFV) encodes more than 150 polypeptides, which may have intricate and delicate interactions with the host for the benefit of the virus to evade the host’s defenses. However, currently, there is still a lack of information regarding the roles of the viral proteins in host cells. Here, our data demonstrated that the p17, encoded by D117L gene could suppress porcine cGAS-STING signaling pathway, exhibiting the inhibitions of TBK1 and IRF3 phosphorylations, downstream promoter activities, cellular mRNA transcriptions and ISG56 induction, and antiviral responses. Further, we found that p17 was located in endoplasmic reticulum (ER) and Golgi apparatus, and interacted with STING, perturbing it in the recruitment of TBK1 and IKKε. Additionally, it appeared that the transmembrane domain (amino acids 39–59) of p17 could be required for interacting with STING and inhibiting cGAS-STING pathway. Taken together, p17 could inhibit the cGAS-STING pathway through its interaction with STING and interference with STING in the recruitment of TBK1 and IKKε.ImportanceAfrican swine fever (ASF) is a highly contagious disease in domestic and feral swine, posing significant economic impacts on the global swine industry, and the pathogen ASFV is a large icosahedral DNA virus. The innate immune cGAS-STING DNA sensing pathway plays a critical role in sensing invading ASFV and triggering antiviral responses. However, there is still a lack of information regarding the molecular mechanisms of ASFV evasion of the cGAS-STING pathway. We have analyzed the effects of whole genomic open reading frames (ORFs) of ASFV China 2018/1 on the activation of cGAS-STING pathway, and found that p17 was able to inhibit cGAS-STING mediated type I IFN production by targeting STING, altering its capacity to recruit both TBK1 and IKKε. Findings presented here will expand our knowledge on the molecular mechanisms by which ASFV counteracts the antiviral innate immunity and provide deep insights into ASF pathogenesis.
The Movember Global Action Plan 1 (GAP1) - Unique Prostate Cancer Tissue Microarray Resource
Authors: Ouellet Véronique , Erickson Andrew , Wiley Kathy , Morrissey Colm , Berge Viktor , Moreno Carlos S. , Tasken Kristin Austlid , Trudel Dominique , True Lawrence D. , Lewis Michael S. , Svindland Aud , Ertunc Onur , Vidal Igor Damasceno , Osunkoya Adeboye O. , Jones Tracy , Bova G. Steven , Lamminen Tarja , Achtman Ariel H. , Buzza Mark , Kouspou Michelle M ,   GAP1 UTMAs Contributing Investigators, Bigler Steven A , Zhou Xinchun , Freedland Stephen J. , Mes-Masson Anne-Marie , Garraway Isla P. , Trock Bruce J. , Taimen Pekka , Saad Fred , Mirtti Tuomas , Knudsen Beatrice S. , De Marzo Angelo M. 
Published: June 2021

ABSTRACTBackgroundThe need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated TMAs from prostate cancer samples obtained from multiple institutions across several global locations.MethodsThree separate TMA sets were built that differ by purpose and disease state.ResultsThe intended use of TMA1 is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration resistant metastatic disease, and to compare molecular properties of high risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 was designed to address questions regarding risk of castration resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3’s intended use is to assess and better understand the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases.ConclusionThe GAP1-UTMA project has succeeded in combining a large set of rare tissue specimens from 501 prostate cancer patients with rich clinical annotation.ImpactThis resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.
Down-regulation of A Human Herpesvirus 1 (HHV-1) MicroRNA in Infected Cells by Goniothalamin Treatment
Authors: Yip Chee Wai , Md Nor Norefrina Shafinaz , Ibrahim Nazlina 
Published: June 2021

AbstractGoniothalamin (GTN) has been proven to cause cell cycle arrest and apoptosis in human herpesvirus 1 (HHV-1) infected cells, but interestingly our preliminary transcriptomic analysis revealed other possible modes of action. The data showed that GTN treatment of HHV-1 clinical strain infected cells induced expression of theKLHL24gene that encodes the Kelch-like 24 protein (KLHL24), a transcriptional inhibitor of HHV-1 immediate-early and early genes. An miRNA, hsv1-miR-H27, produced by HHV-1 has also been discovered to control the expression of KLHL24. In order to understand the cause ofKLHL24up-regulation, a time point study was conducted to investigate the effect of GTN onKLHL24and hsv1-miR-H27 expression. Through RT-qPCR analysis, we found that HHV-1 down-regulatedKLHL24significantly (p < 0.05) starting from 12 hpi, while a significant up-regulation (p < 0.05) was observed upon GTN treatment of the infected cells at 4 and 8 hpi. For protein level analysis, significant down-regulation of KLHL24 (p < 0.05) was observed at all time points in HHV-1 infected cells. Intriguingly, treatment with GTN on HHV-1 infected cells showed no significant changes in protein expression compared to cells without any treatment. In addition, the miRNA hsv1-miR-H27 was detected from 16 hpi and treatment with GTN on infected cells showed down-regulation of the miRNA. This was in congruity with the recovery ofKLHL24down-regulation in GTN treated HHV-1 infected cells, confirming that GTN caused down-regulation of hsv1-miR-H27 that governs the expression ofKLHL24. This study provides insights that GTN could be a potential multifaceted antiviral.ImportanceThis study provides evidence that GTN possesses a distinct mode of antivirus against HHV-1 compared to currently available antivirals. Our findings showed that GTN caused the down-regulation of a viral miRNA, which inhibits the expression of a cellular protein known as KLHL24. This protein serves as a transcriptional inhibitor of HHV-1 immediate-early and early genes. The down-regulation of this miRNA lead to the up-regulation of KLHL24 and eventually halted HHV-1 replication. With the previously reported antiviral mechanism and the outcome of this study, GTN is a potential multifaceted anti-HHV-1 agent.
Fungal extracellular vesicles are involved in intraspecies intracellular communication
Authors: Bitencourt Tamires A. , Hatanaka Otavio , Pessoni Andre M. , Freitas Mateus S. , Trentin Gabriel , Santos Patrick , Rossi Antonio , Martinez-Rossi Nilce M. , Alves Lysangela L. , Casadevall Arturo , Rodrigues Marcio L. , Almeida Fausto 
Published: June 2021

AbstractFungal infections are associated with high mortality rates in humans. The risk of fungal diseases creates the urgent need to broaden the knowledge base regarding their pathophysiology. In this sense, the role of extracellular vesicles (EVs) has been described to convey biological information and participate in the fungal-host interaction process. EVs play many roles, including cellular physiology, responding to environmental cues, mediating a complex circuit of cellular communication in bidirectional crosstalk with other organisms, and the communication between fungal cells has been speculated. This study demonstrated the intra species uptake of EVs in fungi, including Candida albicans, Aspergillus fumigatus, and Paracoccidioides brasiliensis, and the effects triggered by EVs in fungal cells. In C. albicans, we evaluated the involvement of EVs in yeast to hyphae transition, whilst in P. brasiliensis and A. fumigatus the function of EVs as stress transducers was investigated. Both P. brasiliensis and A. fumigatus were exposed to an inhibitor of glycosylation or UV light, respectively. The results demonstrated the role of EVs in regulating the expression of target genes and phenotype features. The EVs treatment induced cellular proliferation and boosted the transition yeast to hyphal transition in C. albicans, while they enhanced stress signals in A. fumigatus and P. brasiliensis, establishing a role for EVs in fungal intra species communication. Thus, fungal EVs regulate the virulence and adaptive traits in fungal interaction systems as potent message effectors, and understanding their effects and mechanism(s) of action could be exploited in antifungal therapies.Author SummaryExtracellular vesicles (EVs) play an important role in export systems. They act as vehicles for the transference of complex cargoes with broad biological functions, such as proteins, carbohydrates, pigments, nucleic acids, and lipids. EVs can contribute to fungal infection outcomes. The EV content exerts immunomodulatory functions during fungus-host interactions. Furthermore, the participation of EVs in communication between fungal cells has been speculated. This study investigated the capacity of EVs to mediate intra-species in three genera of human pathogenic fungi and established a regulatory function of EVs. We also assessed the features of this regulation by analyzing the cellular morphological aspects of fungi after stimulation with EVs. Our data suggest fungal EVs can function as potent signal mediators that mediate virulence and adaptive responses.
A Prospective Observational Study to Investigate Performance of a Chest X-ray Artificial Intelligence Diagnostic Support Tool Across 12 U.S. Hospitals
Authors: Sun Ju , Peng Le , Li Taihui , Adila Dyah , Zaiman Zach , Melton Genevieve B. , Ingraham Nicholas , Murray Eric , Boley Daniel , Switzer Sean , Burns John L. , Huang Kun , Allen Tadashi , Steenburg Scott D. , Gichoya Judy Wawira , Kummerfeld Erich , Tignanelli Christopher 
Published: June 2021

AbstractImportanceAn artificial intelligence (AI)-based model to predict COVID-19 likelihood from chest x-ray (CXR) findings can serve as an important adjunct to accelerate immediate clinical decision making and improve clinical decision making. Despite significant efforts, many limitations and biases exist in previously developed AI diagnostic models for COVID-19. Utilizing a large set of local and international CXR images, we developed an AI model with high performance on temporal and external validation.ObjectiveInvestigate real-time performance of an AI-enabled COVID-19 diagnostic support system across a 12-hospital system.DesignProspective observational study.SettingLabeled frontal CXR images (samples of COVID-19 and non-COVID-19) from the M Health Fairview (Minnesota, USA), Valencian Region Medical ImageBank (Spain), MIMIC-CXR, Open-I 2013 Chest X-ray Collection, GitHub COVID-19 Image Data Collection (International), Indiana University (Indiana, USA), and Emory University (Georgia, USA)ParticipantsInternal (training, temporal, and real-time validation): 51,592 CXRs; Public: 27,424 CXRs; External (Indiana University): 10,002 CXRs; External (Emory University): 2002 CXRsMain Outcome and MeasureModel performance assessed via receiver operating characteristic (ROC), Precision-Recall curves, and F1 score.ResultsPatients that were COVID-19 positive had significantly higher COVID-19 Diagnostic Scores (median .1 [IQR: 0.0-0.8] vs median 0.0 [IQR: 0.0-0.1], p < 0.001) than patients that were COVID-19 negative. Pre-implementation the AI-model performed well on temporal validation (AUROC 0.8) and external validation (AUROC 0.76 at Indiana U, AUROC 0.72 at Emory U). The model was noted to have unrealistic performance (AUROC > 0.95) using publicly available databases. Real-time model performance was unchanged over 19 weeks of implementation (AUROC 0.70). On subgroup analysis, the model had improved discrimination for patients with “severe” as compared to “mild or moderate” disease, p < 0.001. Model performance was highest in Asians and lowest in whites and similar between males and females.Conclusions and RelevanceAI-based diagnostic tools may serve as an adjunct, but not replacement, for clinical decision support of COVID-19 diagnosis, which largely hinges on exposure history, signs, and symptoms. While AI-based tools have not yet reached full diagnostic potential in COVID-19, they may still offer valuable information to clinicians taken into consideration along with clinical signs and symptoms.