bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective examination of mental health in university students during the COVID-19 pandemic
Authors: Jia Ru , Knight Holly , Ayling Kieran , Coupland Carol , Corner Jessica , Denning Chris , Ball Jonathan , Bolton Kirsty , Morling Joanne R , Figueredo Grazziela , Morris David Ed , Tighe Patrick , Villalon Armando , Blake Holly , Vedhara Kavita 
Published: July 2021

AbstractBackgroundThe impact of changing social restrictions on the mental health of students during the COVID-19 pandemic warrants exploration.AimsTo prospectively examine changes to university students’ mental health during the pandemic.MethodsStudents completed repeated online surveys at three time points (October 2020 (baseline), February 2021, March 2021) to explore relationships between demographic and psychological factors (loneliness and positive mood) and mental health outcomes (depression, anxiety, and stress).ResultsA total of 893 students participated. Depression and anxiety levels were higher at all timepoints than pre-pandemic normative data (p<.001). Scores on all mental health measures were highest in February, with depression and anxiety remaining significantly higher in March than baseline. Female students and those with previous mental health disorders were at greatest risk of poor mental health outcomes. Lower positive mood and greater loneliness at baseline were associated with greater depression and anxiety at follow-ups. Baseline positive mood predicted improvement of depression and anxiety at follow-ups.ConclusionDepression and anxiety were significantly higher than pre-pandemic norms, with female students and those with previous mental health difficulties being at greatest risk. Given these elevated rates, universities should ensure adequate support is available to meet potentially increased demand for services.
Amplitude-integrated EEG amplitudes differ between wakefulness and sleep states in children
Authors: Löffelhardt Verena T. , Marina Adela Della , Greve Sandra , Müller Hanna , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora 
Published: July 2021

AbstractIntroductionInterpretation of pediatric amplitude-integrated EEG (aEEG) is hindered by the lack of knowledge on physiological background patterns in children. The aim of this study was to assess the amplitudes and bandwidths of background patterns during wakefulness and sleep in children from long-term EEGs.MethodsForty long-term EEGs from patients < 18 years of age without or only solitary interictal epileptiform discharges were converted into aEEGs. Upper and lower amplitudes (µV) of the C3 – C4, P3 – P4, C3 – P3, C4 – P4, and Fp1 – Fp2 channels were measured during wakefulness and sleep. Bandwidths (BW, µV) were calculated, and sleep states assessed during the episodes of interest. A sensitivity analysis excluded patients who received antiepileptic drugs.ResultsMedian age was 9.9 years (interquartile range 6.1 – 14.7). All patients displayed continuous background patterns. Amplitudes and BW differed between wakefulness (C3-C4 channel: upper 35 (27 – 49), lower 13 (10 – 19), BW 29 (21 – 34)) and sleep. During sleep, episodes with high amplitudes (upper 99 (71 – 125), lower 35 (25 – 44), BW 63 (44 – 81)) corresponded to sleep states N2 – N4. These episodes were interrupted by low amplitudes that were the dominating background pattern towards the morning (upper 39 (30 – 51), lower 16 (11 – 20), BW 23 (19 – 31), sleep states REM, N1, and N2). With increasing age, amplitudes and bandwidths declined. The sensitivity analysis yielded no differences in amplitude values or bandwidths.ConclusionaEEG amplitudes and bandwidths were low during wakefulness and light sleep and high during deep sleep in stable children undergoing 24 hour EEG recordings. aEEG values were not altered by antiepileptic drugs in this study.
Gender differences in housework and childcare among Japanese workers during the COVID-19 pandemic
Authors: Sakuragi Toshihide , Tanaka Rie , Tsuji Mayumi , Tateishi Seiichiro , Hino Ayako , Ogami Akira , Nagata Masako , Matsuda Shinya , Fujino Yoshihisa ,   CORoNaWork Project
Published: July 2021

AbstractObjectivesAlthough gender stereotypes regarding paid work and unpaid work are changing, most wives are responsible for taking care of the family and home in Japan. It is unclear how time spent on housework and childcare has changed between working men and women during the COVID-19 pandemic in Japan. The purpose of this study is to investigate how working men and women’s responsibilities for housework and childcare changed during the COVID-19 pandemic in Japan depending on occupation, job type, and the number of employees in the workplace.MethodsA cross-sectional analysis (N=14,454) was conducted using data from an internet monitoring study (CORoNa Work Project), which was conducted in December 2020. A multilevel logistic model with nested prefectures of residence was conducted to estimate the odds ratio (OR) for change in time devoted to housework and childcare among men and women adjusting for age, household income, frequency of telecommuting, presence of spouse who work, occupation, job type, the number of employees in the workplace, and the incidence rate of COVID-19 by prefecture.ResultsRegardless of occupation related factors, more women than men reported increased time spent on housework and childcare. Furthermore, women were significantly more likely to experience an increase in time spent on those activities than men (housework: OR 1.97, 95% CI [1.75, 2.21], p < 0.001; childcare: OR 1.66, 95% CI [1.37, 2.02], p < 0.001).ConclusionsThe time spent by women on housework and childcare increased significantly compared to men during the COVID-19 pandemic in Japan.
Perceptions of gender equity and markers of achievement in a National Institute for Health Research (NIHR) Biomedical Research Centre (BRC): A qualitative study
Authors: Henderson Lorna R , Dam Rinita , Sarwar Shah Syed Ghulam , Ovseiko Pavel V , Kiparoglou Vasiliki 
Published: July 2021

ABSTRACTBackgroundThe need to improve gender equity (GE) in academic medicine is well documented. Biomedical Research Centres (BRCs), partnerships between leading National Health Service (NHS) organisations and universities in England, conduct world-class translational research funded by the National Institute for Health Research (NIHR). In 2011, eligibility for BRC funding was restricted to universities demonstrating sustained GE success recognised by the Athena SWAN Charter for Women in Science Silver awards. Despite this structural change, GE research in BRC settings is underdeveloped, yet critical to the acceleration of women’s advancement and leadership.ObjectivesTo explore both women’s and men’s perceptions of GE and current markers of achievement in a BRC setting.MethodsThematic analysis of data from two discrete research projects: 53 GE survey respondents’ free text comments (34 women, 16 men), and 16 semi structured interviews with women affiliated to the NIHR Oxford BRC.ResultsFour major themes emerged from the analysis: perceptions of the Athena Swan Charter for Women in Science (GE policy); views on monitoring GE in BRCs; views on current markers of achievement in academia and GE; and recommendations for actions to improve GE in BRC settings. Monitoring of GE in BRCs was deemed to be important, but complex. Participants felt current markers of achievement were not equitable to women as they did not take contextual factors into account such as maternity leave and caring responsibilities. BRC specific organisational policies and metrics are required to monitor and catalyse GE.ConclusionsMarkers of achievement for monitoring GE in BRCs should take into account contextual factors specific to BRCs and women’s career progression and professional advancement. GE markers of achievement should be complimented with broader aspects of equality, diversity and inclusion.
COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters
Authors: Xu Zhaowei , Li Yang , Lei Qing , Huang Likun , Lai Dan-yun , Guo Shu-juan , Jiang He-wei , Hou Hongyan , Zheng Yun-xiao , Wang Xue-ning , Wu Jiaoxiang , Ma Ming-liang , Zhang Bo , Chen Hong , Yu Caizheng , Xue Jun-biao , Zhang Hai-nan , Qi Huan , Yu Siqi , Lin Mingxi , Zhang Yandi , Lin Xiaosong , Yao Zongjie , Sheng Huiming , Sun Ziyong , Wang Feng , Fan Xionglin , Tao Sheng-ce 
Published: July 2021

AbstractCoronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.
Structural basis for the therapeutic advantage of dual and triple agonists at the human GIP, GLP-1 or GCG receptors
Authors: Zhao Fenghui , Zhou Qingtong , Cong Zhaotong , Hang Kaini , Zou Xinyu , Zhang Chao , Chen Yan , Dai Antao , Liang Anyi , Ming Qianqian , Wang Mu , Chen Linan , Xu Peiyu , Chang Rulue , Feng Wenbo , Xia Tian , Zhang Yan , Wu Beili , Yang Dehua , Zhao Lihua , Xu H. Eric , Wang Ming-Wei 
Published: July 2021

SummaryGlucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed to maximize metabolic benefits with reduced side-effects, are in clinical trials to treat type 2 diabetes and obesity. To elucidate the molecular mechanisms by which tirzepatide, a GIPR/GLP-1R dualagonist, and peptide 20, a GIPR/GLP-1R/GCGR triagonist, manifest their superior efficacies over monoagonist such as semaglutide, we determined cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR The structures reveal both common and unique features for the dual and triple agonism by illustrating key interactions of clinical relevance at the atomic level. Retention of glucagon function is required to achieve such an advantage over GLP-1 monotherapy. Our findings provide valuable insights into the structural basis of functional versatility and therapeutic supremacy of tirzepatide and peptide 20.
Identification of an isoflavonoid transporter required for the nodule establishment of the Rhizobium-Fabaceae symbiotic interaction
Authors: Biała-Leonhard Wanda , Zanin Laura , Gottardi Stefano , de Brito Francisco Rita , Venuti Silvia , Valentinuzzi Fabio , Mimmo Tanja , Cesco Stefano , Bassin Barbara , Martinoia Enrico , Pinton Roberto , Jasiński Michał , Tomasi Nicola 
Published: July 2021

SUMMARYNitrogen (N) as well as Phosphorus (P) are key nutrients determining crop productivity. Legumes have developed strategies to overcome nutrient limitation by e.g., forming a symbiotic relationship with N-fixing rhizobia and the release of P-mobilizing exudates and are thus able to grow without supply of N or P fertilizers. The legume-rhizobial symbiosis starts with root release of isoflavonoids, that act as signaling molecules perceived by compatible bacteria. Subsequently, bacteria release nod factors, which induce signaling cascades allowing the formation of functional N-fixing nodules.We report here the identification and functional characterization of a plasma membrane-localized MATE-type transporter (LaMATE2) involved in the release of genistein from white lupin roots.The LaMATE2 expression in the root is upregulated under N deficiency as well as low phosphate availability, two nutritional deficiencies that induce the release of this isoflavonoid. LaMATE2 silencing reduced genistein efflux and even more the formation of symbiotic nodules, supporting the crucial role of LaMATE2 in isoflavonoid release and nodulation. Furthermore, silencing of LaMATE2 limited the P-solubilization activity of lupin root exudates. Transport assays in yeast vesicles demonstrated that LaMATE2 acts as a proton-driven isoflavonoid transporter.
A method for the generation of pseudotyped virus particles bearing SARS coronavirus spike protein in high yields
Authors: Fujioka Yoichiro , Kashiwagi Sayaka , Yoshida Aiko , Satoh Aya O. , Fujioka Mari , Amano Maho , Yamauchi Yohei , Ohba Yusuke 
Published: July 2021

SUMMARYThe ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has threatened human health and the global economy. Development of additional vaccines and therapeutics is urgently required, but such development with live virus must be conducted with biosafety level 3 confinement. Pseudotyped viruses have been widely adopted for studies of virus entry and pharmaceutical development to overcome this restriction. Here we describe a modified protocol to generate vesicular stomatitis virus (VSV) pseudotyped with SARS-CoV or SARS-CoV-2 Spike protein in high yield. We found that pseudovirions produced with the conventional transient expression system lacked coronavirus Spike protein at their surface as a result of inhibition of parental VSV infection by overexpression of this protein. Establishment of stable cell lines with an optimal expression level of coronavirus Spike protein allowed the efficient production of progeny pseudoviruses decorated with Spike protein. This improved VSV pseudovirus production method should facilitate studies of coronavirus entry and development of antiviral agents.
Mechanism of Antiviral Activity of Nitazoxanide against the Influenza Virus: Effect of Tizoxanide on AdenosineTriphosphate in Influenza-virus Infected Madin Darby Canine Kidney Cells
Authors: Rossignol J.F. , Tijsma A.S.L. , van Baalen C.A. 
Published: July 2021

AbstractBackgroundNitazoxanide (NTZ) is a broad-spectrum antiviral undergoing clinical development for treating influenza and other viral respiratory infections such as those caused by rhinovirus/enterovirus and coronavirus including the emerging SARS-CoV-2.MethodsNitazoxanide is a mild uncoupler of oxidative phosphorylation, which is modulating the ATP production in cells. ATP is an essential component of viral replication, and we have evaluated the effect of tizoxanide (TIZ), the active circulating metabolite of NTZ, on ATP in Madin-Darby canine kidney (MDCK) cells and in MDCK cells infected with influenza A and B viruses.ResultsTIZ decreased cellular ATP in a dose-dependent manner in MDCK cells and in MDCK cells infected with influenza A and B viruses. Maximum inhibition of ATP in influenza infected or uninfected MDCK cells reached up to 45% after 6 and 24 hours of exposure to 100µM TIZ. The decrease in cellular ATP did not affect cell viability and was reversible after eliminating TIZ from the culture.ConclusionThe concentrations of TIZ required to decrease cellular ATP levels were similar to those reported to inhibit replication of influenza A and B viruses in our laboratory. A decrease in ATP triggers activation of AMP-activated protein kinase, which is known to suppress the secretion of pro-inflammatory cytokines. Additional studies are warranted to evaluate the effect of TIZ on mitochondrial function.
CD49a Identifies Polyfunctional Memory CD8 T cell Subsets that Persist in the Lungs after Influenza Infection
Authors: Reilly Emma C. , Sportiello Mike , Emo Kris Lambert , Amitrano Andrea M. , Jha Rakshanda , Kumar Ashwin B.R. , Laniewski Nathan G. , Yang Hongmei , Kim Minsoo , Topham David J. 
Published: July 2021

AbstractCD8 T cell memory offers critical antiviral protection, even in the absence of neutralizing antibodies. The paradigm is that CD8 T cell memory within the lung tissue consists of a mix of circulating TEMcells and non-circulating TRMcells. However, based on our analysis, the heterogeneity within the tissue is much higher, identifying TCM, TEM, TRM, and a multitude of populations which do not perfectly fit these classifications. Further interrogation of the populations shows that TRMcells that express CD49a, both with and without CD103, have increased and diverse effector potential compared with CD49a negative populations. These populations function as a one-man band, displaying antiviral activity, chemokine production, release of GM-CSF, and the ability to kill specific targetsinvitro with delayed kinetics compared with effector CD8 T cells. Together, this study establishes that CD49a defines multiple polyfunctional CD8 memory subsets after clearance of influenza infection, which act to eliminate virus in the absence of direct killing, recruit and mature innate immune cells, and destroy infected cells if the virus persists.Contribution to the fieldProtection from previously seen infections requires specialized immune memory cells properly positioned throughout the body to combat the newly invading pathogen. In the case of re-exposure to influenza virus, CD8 T cells resident within the respiratory tract (TRM) are critical for eliminating the virus. Previously, TRMwere viewed as mostly homogenous, with a limited range of immune functions. In this study, lung TRMwere compared with circulating memory CD8 T cells transiently present within the lung, to define the breadth of their effector capabilities. Using TRMdefining surface proteins CD49a and CD103 to identify different memory CD8 T cell subsets, gene and protein expression were evaluated. In addition to demonstrating higher levels of diversity than previously reported, multiple polyfunctional subsets were identified. This polyfunctionality was primarily associated with cell populations expressing CD49a, and these cells produced multiple antiviral factors, chemokines to recruit other immune cells, a growth factor associated with improved antigen presenting cell function, and cytolytic granules. Functional assays further demonstrated killing of target cells by TRM. This study paints a more holistic, complete picture of the phenotype and functions of lung CD8 T cells after viral infection, revealing CD49a as a marker of cells with high effector capacity.
Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats
Authors: Blanco Jorge C.G. , McGinnes-Cullen Lori , Kamali Arash , Sylla Fatoumata Y. D. , Boukhavalova Marina S. , Morrison Trudy G. 
Published: July 2021

AbstractMaternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge (Blanco, et al Journal of Virology 93: e00914-19, https://doi.org/10.1128/JVI.00914-19). Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.Author SummaryRespiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection of infants. Because there is no licensed vaccine for RSV as well as potential safety issues with any new vaccine, protection of infants from RSV is problematic. A possible safe approach for infant protection is the transfer of maternal anti-RSV antibodies, induced by immunization, across the placenta to the fetus serving to protect the newborn for months after birth. In a cotton rat model, we have previously shown that maternal immunization with virus-like particles assembled with the RSV F and G proteins protects offspring from RSV infection. Here we describe protection of offspring, following a single immunization, through two pregnancies showing that offspring of the first were well protected from RSV challenge. However, offspring of the second pregnancy were very weakly protected although the levels of total anti-pre-F antibodies and neutralizing antibody titers in the dams remained at constant and high levels before and after the second pregnancy. This result is consistent with an evolution of antibody properties in the dams to those less efficiently transferred to offspring and highlights the importance of appropriate strategies for maternal immunization, such as immunization during each pregnancy.