bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of SARS-CoV-2 Infection in 121 Patients With Inborn Errors of Immunity: A Cross-sectional Study
Authors: goudouris ekaterini , Pinto-Mariz Fernanda , Mendonça Leonardo Oliveira , Aranda Carolina Sanchez , Guimarães Rafaela Rolla , Kokron Cristina , Barros Myrthes Toledo , Anísio Flávia , Alonso Maria Luiza Oliva , Marcelino Fernanda , Valle Solange Oliveira Rodrigues , Junior Sergio Dortas , Barreto Irma Douglas Paes , Fernandes Janáira , Roxo Pérsio , Silva Almerinda , Campinho Fernanda Lugão , Bonfim Carmem , Loth Gisele , Fernandes Juliana Folloni , Garcia Julia Lopes , Capelo Albertina , Takano Olga Akiko , Nada Maria Isabel Valdomir , Toledo Eliana , Cunha Luciana Araújo Oliveira , Gesu Regina Sumiko Watanabe Di , Schidlowsk Laire , Fillipo Priscila , Bichuetti Danielli , Soldateli Gustavo , Ferraroni Natasha Rebouças , Dantas Ellen , Pestana Simone , Mansour Eli , Ulaf Raisa Gusso , Prando Carolina , Condino-Neto Antonio , Grumach Anete Sevciovic 
Published: March 2021

Abstract
Purpose: There is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and to identify factors influencing the outcome of infection.Methods: We did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection. Results: 121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n=53). The infection presented mostly as asymptomatic (n=21) and mild (n=66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex related susceptibility and observed a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency. Conclusion: The outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. Patients with complement deficiencies had milder COVID-19. However, the type of IEI was not a determining factor for severity. The severity of SARS-CoV-2 infection seems to be more related to older age, higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).
Down-regulated CLDN10&nbsp;Predicts Favorable Prognosis and Correlates With Immune Infiltration in Gastric Cancer
Authors: Rao XiongHui , Jiang JianLong , Liang ZhiHao , Zhang JianBao , Zhuang ZheHong , Huang Rui , Qiu HuaiYu , Weng Nuoqing , Wu XiaoBin 
Published: March 2021

Abstract
Background: CLDN10, an important component of the tight junctions of epithelial cells, plays a crucial role in a variety of tumors. The effect of CLDN10 expression in gastric cancer, however, has yet to be elucidated.Methods: Differential expression of CLDN10 was evaluated using Oncomine, ULCAN, and TIMER2.0 databases. Correlations between CLDN10 expression and clinical outcomes of gastric cancer were explored by Kaplan-Meier Plotter. The correlations between CLDN10 expression and immune cell infiltration and somatic copy number mutation (SCNA) in gastric cancer were explored by TIMER2.0 and GEPIA2.0.Results: CLDN10 expression was lower in gastric cancer compared to adjacent normal tissues, and associated with better prognosis. CLDN10 also showed significant differences at different T stages, Lauren classification, treatments and HER2 status. Low expression of CLDN10 was associated with increased infiltration levels of certain immune cells in the tumor microenvironment. In addition, it was found that different somatic copy number changes (SCNA) in CLDN10 might affect the level of immune cell infiltration. Furthermore, the expression of CLDN10 was significantly associated with the expression of several immune cell markers, especially B cell markers, follicular helper T cell (Tfh) markers and T cell exhaustion markers.Conclusion: CLDN10 may act as a potential prognostic biomarker and correlate to immune infiltration levels in gastric cancer.
Validity and Reliability of the Georgian-language Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)&nbsp;
Authors: Botchorishvili Nazibrola , Shiukashvili Nino , Mikeladze Nina , Dzagnidze Ann , Miqava Nino , Tighashvili Maia , Janelidze Marina 
Published: March 2021

Abstract
Background: Cognitive impairment is one of the common features of multiple sclerosis (MS). Despite high prevalence, cognitive decline is often overlooked by neurologists. The Brief International Cognitive Assessment for MS (BICAMS) was therefore introduced by the international expert committee as a brief and effective tool for the assessment and monitoring of cognitive functions in patients with MS. The validity and reliability of BICAMS have been demonstrated in many countries. Our aim was to validate the BICAMS in Georgian patients with MS.Methods: A total of 68 patients with MS and 68 matched controls were assessed by the Georgian-language BICAMS. All healthy controls and seven patients were re-evaluated with identical tests to assess retest reliability. Results: In comparison to healthy controls, patients with MS performed significantly worse on all tests in the assessment battery. Test-retest reliability measures were good for all tests. The prevalence of cognitive impairment in patients with MS was 43%. Conclusion: The Georgian-language BICAMS is a reliable and valid battery for the assessment of cognitive function in patients with MS.
WITHDRAWN: Knowledge and Attitudes of Young Adults Towards Donation of COVID-19&nbsp;Convalescent Plasma and Its Therapeutic Properties
Authors: Perenc Lidia , Pęczkowski Ryszard 
Published: March 2021

Abstract
Objectives: To investigate the level of knowledge of the young adults towards possible use of the convalescent plasma (CP) in treatment of COVID-19 infection and their attitudes towards its donation.Methods: Cross-sectional questionnaire was administered online to 1058 university students, representing 4 different colleges, in the middle of the academic year. The questionnaire included demographic data and 20 questions related to the knowledge and attitudes of respondents about possible use of the convalescent plasma in treatment of COVID-19 infection and its donation. Comparative analyses were made to determine the significance of relationships between the obtained scores and selected variables, using the Mann-Whitney and Kruskal-Wallis tests and the Spearman correlation coefficient. Results: Significant relationships were found between dependent variables (level of knowledge and intensity of attitude) and gender, age, and student’s college affiliation. There was no statistically significant correlation between dependent variables and respondents’ social background and religious commitment.Conclusions: Young adults, represented by university students, show an above-average level of knowledge relating to the therapeutic and preventive properties of the COVID-19 convalescent plasma. They also express a sufficient intensity of positive attitude towards CP donation. This study confirms the need for appropriate health promotional campaigns and educational programs aimed at popularization of CP donation in general public which would increase the chances of involving more patients recovered from COVID-19 disease.
SETD2 and miR-21 as therapeutic targets for NUT midline carcinoma
Authors: Yoshida Nana , Okumura Shunsuke , Sasaki Takaaki , Chiba Shin-ichi , Sado Masatoshi , Oyama Kyohei , Yoshida Ryohei , Hirai Noriko , Minami Yoshinori , Kitada Masahiro , Ohsaki Yoshinobu 
Published: March 2021

Abstract
Background:Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and highly aggressive tumor with the bromodomain containing 4 (BRD4)-NUT (NUTM1) gene fusion. BRD4 is a member of the bromodomain and extra-terminal domain (BET) family of proteins, and BET inhibitors have been investigated in NMC clinical trials. However, few targeted therapies are available for NMC, and novel therapeutic targets remain to be determined. We determined the role of two epigenetic regulators as possible therapeutic targets for NMC. Methods:We performed next-generation sequencing (NGS) in NMC cell lines (HCC2429 and Ty82). H3K36me3 expression was studied using western blotting. The efficacy of AZD1775, a WEE1 inhibitor, was evaluated using the MTS and γH2AX assays. We established an NMC cell line that was resistant to BET inhibitors. The sensitivity of the cells resistant to AZD1775 was analyzed using the MTS assay. RNA sequencing was performed to determine miRNA expression levels. TaqMan miRNA assays were used to analyze miR-21 expression. The efficacy of the miR-21 inhibitor was evaluated using the MTS assay. We established a digital PCR (dPCR) assay to detect NUT gene rearrangements to identify patients with NMC. Using NGS, a patient with NMC was identified with the SETD2 mutation.Results:SETD2 mutation (p.Ser2382fs) was determined in NMC cells, in which H3K36me3 expression was depleted, indicating SETD2 loss. NMC cells were sensitive to the WEE1 inhibitor, AZD1775 in cancer cells with SETD2 deficiency. γH2AX expression was increased in NMC cells treated with AZD1775. The efficacy of the combination of AZD1775 and JQ-1 was additive. We established NMC cells that were resistant to BET inhibitors. The resistant cells were also sensitive to AZD1775. miRNA analysis revealed increased miR-21 expression in BET-inhibitor-resistant NMC cells. MiR-21 regulated the growth of NMCs. The miR-21 inhibitor suppressed the growth of BET-inhibitor-resistant cells. Thirty-two clinical samples were analyzed and NMC was identified using digital PCR assays. Tumors with the SETD2 mutation were analyzed using NGS.Conclusions:We report for the first time SET domain-containing protein 2 (SETD2) deficiency and miR-21 as novel therapeutic targets for NMC. SETD2 loss and miR-21 may be therapeutic targets for NMC.Trial registrationIn this study, we analyzed the gene alterations in human tumor samples. This study was registered in the UMIN clinical trial registered system (UMIN000043147, January 27, 2021).
Selective Activation of Cannabinoid Receptor-2 Reduces White Matter Injury via Perk Signaling in a Rat Model of Traumatic Brain Injury
Authors: jiang li , Li Lin , Luo Qing , Shang Bin , Yang Xiaomin , Zhou Jiru , Pan Qiuling , Wu Na , Tang Wei , Sun Xiaochuan , Du Donglin 
Published: March 2021

Abstract
Background and Purpose: Traumatic brain injury (TBI) destroys white matter, and this destruction is aggravated by secondary neuroinflammatory reactions. Although white matter injury (WMI) is strongly correlated with poor neurological function, understanding of white matter integrity maintenance is limited, and no available therapies can effectively protect white matter. One candidate approach that may fulfill this goal is cannabinoid receptor 2 (CB2) agonist treatment. Here, we confirmed that a selective CB2 agonist, JWH133, protected white matter after TBI.﻿Methods: TBI was induced by Controlled cortical impact (CCI). The motor evoked potentials (MEPs), open field test, and Morris water maze test were used to assess neurobehavioral outcomes. Brain tissue loss, WM damage, Endoplasmic reticulum stress (ER stress), and microglia responses were evaluated after TBI. The functional integrity of WM was measured by diffusion tensor imaging (DTI) and transmission electron microscopy (TEM). Primary microglia and oligodendrocyte cocultures were used for additional mechanistic studies.Results: JWH133 increased myelin basic protein (MBP) and neurofilament heavy chain (NF200) levels and anatomic preservation of myelinated axons revealed by DTI and TEM. JWH133 also increased the numbers of oligodendrocyte precursor cells and mature oligodendrocytes. Furthermore, JWH133 drove microglial polarization toward the protective M2 phenotype and modulated the redistribution of microglia in the striatum. Further investigation of the underlying mechanism revealed that JWH133 downregulated phosphorylation of the ﻿protein kinase R (PKR)-like endoplasmic reticulum (ER) kinase (PERK) signaling pathway and its downstream signals eukaryotic translation initiation factor 2 α (eIF2α), activating transcription factor 4 (ATF4) and Growth arrest and DNA damage-inducible protein (GADD34); this downregulation was followed by p-Protein kinase B(p-Akt) upregulation. In primary cocultures of microglia and oligodendrocytes, JWH133 decreased phosphorylated PERK expression in microglia stimulated with tunicamycin and ﻿facilitated oligodendrocyte survival. ﻿These data reveal that JWH133 ultimately alleviates WMI and improves neurological behavior following TBI.Conclusions: This work illustrates the PERK-mediated interaction between microglia and oligodendrocytes. In addition, the results are consistent with recent findings that microglial polarization switching accelerates WMI, highlighting a previously unexplored role for CB2 agonists. Thus, CB2 agonists are potential therapeutic agents for TBI and other neurological conditions involving white matter destruction.
Anti-tumour Effect of Cyanidin-3-o-glucoside Combined With Cisplatin in the Mice Xenograft Models of Cervical Cancer
Authors: Li Xu , Mu Jingjing , Meng Xianjun 
Published: March 2021

Abstract
Cervical cancer is the fourth most common carcinoma in women. Cisplatin (DDP) is the first-line drug for the treatment of cervical cancer. Although efficacious, its application is constrained by the intolerance and serious adverse effects associated with cisplatin. Here, we aimed to investigate the in vivo anti-cervical cancer effects of cyanidin-3-o-glucoside (C3G), a type of anthocyanin, and DDP, when used alone or in combination; a BALB/c nude mouse xenograft tumour model was used. The tumour was inhibited in the three treatment groups when compared with untreated controls. The inhibition of tumour was 40.49%, 50.15%, and 58.49% when treated with C3G alone [40 mg/kg body weight (bw)], DDP alone (3 mg/kg bw), or a combination of C3G and DDP, respectively. Immunohistochemistry analysis indicated that treatment with C3G, DDP, or the combination induced apoptosis in xenograft tumours. Furthermore, after treatment, Bcl-2 level was decreased, Bax and cleaved caspase-3 expression was activated, and the PI3K/AKT/mTOR signalling pathway was modulated. These results suggest that the combination of C3G and DDP may have significant synergistic anti-tumour efficacy in patients; therefore, this combination therapy has great potential for the treatment of cervical cancer.
MyotonPRO is a reliable and repeatable tool for measuring mechanical properties of the upper limp muscles in patients with chronic stroke
Authors: Taş Serkan , Aktaş Arda , Tüfek Muhammed Taha , Dağ Figen 
Published: March 2021

Abstract
The purpose of the present study was to investigate the inter-rater and intra-rater reliability of the MyotonPRO for measuring the mechanical properties of the upper limp muscles in patients with chronic stroke. The study was conducted with 20 stroke patients (14 males, 6 females) with age range of 36–84 years (65.1 ± 11.2 years). The oscillation frequency, stiffness, and logarithmic decrement of the biceps brachii, triceps brachii, deltoid, and upper trapezius muscles were measured using a MyotonPRO (Muomeetria Ltd., Tallinn, Estonia). The measurements were conducted by two physiotherapists to determine the inter-rater reliability of the device. A physiotherapist repeated the measurements 3 days after the first measurements for determining the intra-rater reliability of the device. The ICCs of the all assessed muscles ranged between 0.72 and 0.97. The coefficient of variation of all muscles ranged within 3.2%-11.0%, from 3.4–9.7% for oscillation frequency, from 3.9–7.4% for stiffness, and from 3.2–11.0% for decrement. The standard error of measurement in the assessed muscles ranged from 0.5 to 1.2 Hz for frequency, from 9.2 to 21.2 N/m for stiffness, and from 0.1 to 0.4 for decrement. The results obtained show that MyotonPRO has a good to excellent intra-rater and inter-rater reliability for measuring the tone, stiffness, and elasticity of the deltoid, biceps brachii, triceps brachii, and upper trapezius muscles in patients with chronic stroke. MyotonPRO can be used for the diagnostic and therapeutic intention in patients with chronic stroke.
Exploring Flexibility, Intermolecular Interactions and Admet Profiles of Anti-influenza Agent Isorhapontigenin: A Quantum Chemical and Molecular Docking Study
Authors: Bangaru Sathya , Manivannan Prasath , Murugesan Sivakumar , Madhu Govindammal 
Published: March 2021

Abstract

Isorhapontigenin (IRPG) drug emerges as promising efficient inhibitor for H1N1 and H3N2 subtypes which belong to influenza A virus; reported with IC50 value of 35.62 and 63.50 μM respectively. The computed geometrical parameters and vibrational assignments (FT-IR and FT-Raman) are compared with experimental results, these results exhibits good correlation with each other. UV-Vis electronic property reveals that the absorption bands of π→π* transitions, this authorizes that the bands are very strong in the IRPG molecule. The kinetic stability and chemical reactivity of the IRPG molecule was probed through NBO and HOMO-LUMO analysis. Electrophilic and nucleophilic site selectivity of IRPG was explored through MEP map and Fukui function. In molecular docking analysis, the IRPG molecule exhibits the better inhibition constant and binding affinity for H1N1 and H3N2 influenza virus. As a result, the IRPG molecule exposes virtuous biological deeds in nature and it can be performed as a prospective drug candidate for H1N1 and H3N2 viral A influenza.
Silencing lncRNA HOTAIR improves the recovery of neurological function in ischemic stroke via the miR-148a-3p/KLF6 axis
Authors: Huang Yiwen , Wang Yuanyuan , Liu Xiaobin , Ouyang Yingjun 
Published: March 2021

Abstract
Ischemic stroke (IS), caused by a permanent or transient local reduction in blood supply to the brain, is one of the most widespread causes of public health problems in modern society. Long non-coding RNA (LncRNA) has been reported to be related to angiogenesis following IS. In this study, we explored the effect and potential molecular mechanism of lncRNA HOTAIR in IS. Permanent middle cerebral artery occlusion (pMCAO) model and oxygen and glucose deprivation (OGD) model were established. HOTAIR was increased in vivo and in vitro models post-ischemic. HOTAIR knockdown promoted neurological function recovery, manifesting in decreased modified neurological severity score, cerebral infarcted area, apoptosis and inflammation, and improved balance ability, spatial learning and memory ability. Silencing HOTAIR also improved the viability of OGD-induced N2a cells, and attenuated apoptosis and inflammation. HOTAIR can compete with KLF6 to bind to miR-148a-3p. miR-148a-3p knockdown or KLF6 overexpression partially reversed the effect of sh-HOTAIR on OGD-induced N2a cells. HOTAIR suppressed the activation of STAT3 pathway via the miR-148a-3p/KLF6 axis. To summarize, this study demonstrated that lncRNA HOTAIR absorbed miR-148a-3p and up-regulate KLF6 expression through ceRNA mechanism, and inhibited STAT3 pathway, promoted apoptosis and inflammation, and aggravated neurological injury post-IS.
A Novel Circular RNA circPLCE1&nbsp;Facilitates&nbsp;the Malignant Progression of Colorectal Cancer&nbsp;by Repressing the SRSF2-dependent PLCE1 pre-RNA&nbsp;Splicing
Authors: Chen Zhi-Lei , Chen Hong-Yu , Yang Lei , Li Xiang-Nan , Wang Zhenjun 
Published: March 2021

Abstract
Background: Studies have demonstrated that circular RNAs (circRNAs) play important roles in various types of cancer; however, the mechanisms of circRNAs located in the nucleus have rarely been explored. Here, we reported a novel circular RNA circPLCE1 facilitates the malignant progression of colorectal cancer (CRC) via repression of SRSF2-dependent PLCE1 pre-RNA splicing. Methods: qRT-PCR was used to determine the expression of circPLCE1 in CRC tissues and cells. CCK-8, transwell and flow cytometric assays were used to assess the role of circPLCE1 in CRC cell proliferation, migration and apoptosis, respectively. Animal study was carried to test the role of circPLCE1 in vivo. Further, catRAPID and RPISeq were applied to predict the possible binding protein of circPLCE1. RNA fractionation and RIP assays were used to confirm the RNA-protein interaction. Results: In this study, we found that circPLCE1 was significantly downregulated in CRC tissues compared with adjacent normal tissues. However, circPLCE1 knockdown suppresses CRC cell proliferation, migration, invasion and increased apoptosis. Nude mice experiments showed that ectopic expression of circPLCE1 dramatically increased tumor growth in vivo. Mechanically, circPLCE1 directly binding to SRSF2 protein, repressing SRSF2-dependent PLCE1 pre-RNA splicing, resulting in the progression of CRC. Individually mutating the binding sites of circPLCE1 derepressed the production of PLCE1 mRNA. Conclusions: Our studies revealed a novel molecular mechanism in the regulation of PLCE1 and implicated a new function of circular RNA, supporting the pursuit of circPLCE1 as a potential tool for future CRC treatment.
Functional and structural analysis of a catabolite control protein C that responds to citrate
Authors: Liu Wei , Chen Jinli , Jin Liming , Liu Zi-Yong , Lu Ming , Jiang Ge , Yang Qing , Quan Chunshan , Nam Ki Hyun , Xu Yongbin 
Published: March 2021

Abstract
Catabolite control protein C (CcpC) belongs to the LysR-type transcriptional regulator (LTTR) family that regulates the transcription of genes encoding the tricarboxylic acid branch enzymes of the TCA cycle by responding to a pathway-specific metabolite, citrate. The biological function of CcpC has been characterized several times, but the structural basis for the molecular function of CcpC remains elusive. Here, we report characterization of a full-length CcpC from Bacillus amyloliquefaciens (BaCcpC-FL) and a crystal structure of the C-terminal inducer-binding domain (IBD) complexed with citrate. BaCcpC required both dyad symmetric regions I and II to recognize the citB promoter, and the presence of citrate reduced citB promoter binding. The crystal structure of CcpC-IBD shows two subdomains, IBD-I and IBD-II, and a citrate molecule buried between them. Ile100, two arginines (Arg147 and Arg260), and three serines (Ser129, Ser189, and Ser191) have strong hydrogen-bond interactions with citrate molecules. A structural comparison of BaCcpC-IBD with its homologues shows that they share the same tail-to-tail dimer alignment, but the dimeric interface and the rotation between these molecules exhibit significant differences. In addition, citrate can convert large BaCcpC-FL oligomers to monomers in solution. Taken together, our results provide a framework for understanding the mechanism underlying the functional divergence of the CcpC protein.