bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda
Authors: Gonzales S. Jake , Clarke Kathleen N. , Batugedara Gayani , Braddom Ashley E. , Garza Rolando , Reyes Raphael A. , Ssewanyana Isaac , Garrison Kendra C. , Ippolito Gregory C. , Greenhouse Bryan , Bol Sebastiaan , Bunnik Evelien M. 
Published: November 2021

AbstractMemory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1- specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.
Humoral immune response to Covid-19 vaccination in diabetes: age-dependent but independent of type of diabetes and glycaemic control – the prospective COVAC-DM cohort study
Authors: Sourij Caren , Tripolt Norbert J , Aziz Faisal , Aberer Felix , Forstner Patrick , Obermayer Anna M , Kojzar Harald , Kleinhappl Barbara , Pferschy Peter N , Mader Julia K , Cvirn Gerhard , Goswami Nandu , Wachsmuth Nadine , Eckstein Max L. , Müller Alexander , Abbas Farah , Lenz Jacqueline , Steinberger Michaela , Knoll Lisa , Krause Robert , Stradner Martin , Schlenke Peter , Sareban Nazanin , Prietl Barbara , Kaser Susanne , Moser Othmar , Steinmetz Ivo , Sourij Harald 
Published: November 2021

AimsImmune response to COVID-19 vaccination and a potential impact of glycaemia on antibody levels in people with diabetes remains unclear. We investigated the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and analysed the response in comparison to individuals without diabetes.Materials and MethodsThis prospective, multicenter cohort study analysed people with type 1 and type 2 diabetes, well (HbA1c<7.5% or <58 mmol/mol) or insufficiently (HbA1c≥7.5% or ≥58 mmol/mol) controlled and healthy controls. Roche’s Elecsys anti-SARS-CoV-2 S was used to quantify anti-spike protein antibodies 7-14 days after the first and 14-21 days after the second vaccination.Results86 healthy controls and 161 participants with diabetes were enrolled, 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% in the type 1 diabetes group and 48.0% in the type 2 diabetes group showed antibody levels above the cut-off for positivity. Antibody levels after the second vaccination were similar in people with type1, type 2 diabetes and healthy controls if adjusted for age, sex and multiple testing (p>0.05). Age (r=−0.45, p<0.001) and glomerular filtration rate (r=0.28, p=0.001) were significantly associated with antibody response.ConclusionsAnti-SARS-CoV-2 S antibody levels after the second vaccination were comparable in healthy controls, people with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels.
Length of hospital stay and risk of intensive care admission and in-hospital death among COVID-19 patients in Norway: a register-based cohort study comparing patients fully vaccinated with an mRNA vaccine to unvaccinated patients
Authors: Whittaker Robert , Bråthen Kristofferson Anja , Valcarcel Salamanca Beatriz , Seppälä Elina , Golestani Karan , Kvåle Reidar , Watle Sara Viksmoen , Buanes Eirik Alnes 
Published: November 2021

AbstractObjectivesWith most of the Norwegian population vaccinated against COVID-19, an increasing number and proportion of COVID-19 related hospitalisations are occurring among vaccinated patients. We estimated the length of stay (LoS) in hospital and an intensive care unit (ICU), and risk of admission to ICU and in-hospital death among COVID-19 patients ≥18 years who had been fully vaccinated with an mRNA vaccine, compared to unvaccinated patients.MethodsUsing national registry data, we conducted a cohort study on SARS-CoV-2 positive patients hospitalised in Norway between 1 February and 30 November 2021, with COVID-19 as the main cause of hospitalisation. We ran Cox proportional hazards models to analyse differences in our outcomes. Explanatory variables included vaccination status, age, sex, county of residence, regional health authority, date of admission, country of birth, virus variant and underlying risk factors.ResultsWe included 3,203 patients, of whom 716 (22%) were fully vaccinated (at least two doses or one dose and previous SARS-CoV-2 infection). Fully vaccinated patients had a shorter overall LoS in hospital (aHR for discharge: 1.61, 95%CI: 1.24–2.08), shorter LoS without ICU (aHR: 1.27, 95%CI: 1.07–1.52), and lower risk of ICU admission (aHR: 0.50, 95%CI: 0.37–0.69) compared to unvaccinated patients. We observed no difference in the LoS in ICU, nor risk of in-hospital death between fully vaccinated and unvaccinated patients.ConclusionsFully vaccinated patients hospitalised with COVID-19 in Norway have a shorter LoS and lower risk of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.
Association of alcohol consumption and frequency with loneliness: A cross-sectional study among Japanese workers during the COVID-19 pandemic
Authors: Konno Yusuke , Okawara Makoto , Hino Ayako , Nagata Tomohisa , Muramatsu Keiji , Tateishi Seiichiro , Tsuji Mayumi , Ogami Akira , Yoshimura Reiji , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: November 2021

AbstractBackgroundThere are increasing concerns that prevention measures against coronavirus disease 2019 (COVID-19) such as social distancing and telework are leading to loneliness and poor lifestyle habits like increased alcohol consumption. The purpose of this study was to assess whether loneliness reported among workers during the COVID-19 pandemic is associated with changes in alcohol consumption.MethodsThe study comprised a cross-sectional, online survey of 27,036 workers between December 22 and 26, 2020. A questionnaire was used to assess loneliness, usual alcohol consumption and whether that consumption had changed. The odds ratios (ORs) were estimated by logistic regression analysis.ResultsA total of 2831 (10.5%) workers indicated they had increased alcohol consumption during the pandemic. Increased alcohol consumption was significantly associated with loneliness (OR=1.94, 95%CI 1.70–2.21). This association held true for those who indicated they were drinking two or more days per week (OR=1.98 95%CI 1.71–2.30) and those who drank less than one day per week (OR=1.51 95%CI 0.71–3.25). In contrast, there was no association between increased drinking and loneliness among those who indicated they hardly ever drank (OR=1.22 95%CI 0.55–2.72).ConclusionsAmong those with a drinking habit, increased alcohol consumption is associated with loneliness.
The preparedness and response to COVID-19 in a quaternary Intensive Care Unit in Australia: perspectives and insights from frontline critical care clinicians
Authors: Sundararajan Krishnaswamy , Bi Peng , Milazzo Adriana , Poole Alexis , Reddi Benjamin , Mahmood Mohammad Afzal 
Published: November 2021

ABSTRACTObjectivesThis study was conducted to explore the perspectives and opinions of Intensive Care Unit (ICU) nurses and doctors at a COVID-19 designated pandemic hospital concerning the preparedness and response to COVID-19 and to consolidate the lessons learnt for crisis/disaster management in the future.DesignA qualitative study using in-depth interviews (IDIs) and focus group discussions (FGDs). Purposeful sampling was conducted to identify participants. A semi-structured guide was utilised to facilitate in-depth interviews with individual participants. Two focus group discussions were conducted, one with the ICU doctors and another with the ICU nurses. Thematic analysis identified themes and subthemes informing about the level of preparedness, response measures, processes, and factors that were either facilitators or those that triggered challenges.SettingICU in a quaternary referral centre affiliated to a university teaching COVID-19 designated pandemic hospital, in Adelaide, South Australia.ParticipantsThe participants included eight ICU doctors and eight ICU nurses for the in-depth interviews. Another sixteen clinicians participated in focus group discussions.ResultsThe study identified six themes relevant to preparedness for, and responses to, COVID-19. The themes included: (1) Staff competence and planning, (2) Information transfer and communication, (3) Education and skills for the safe use of PPE, (4) Team dynamics and clinical practice, (5) leadership, and (6) Managing End-of life situations and expectations of caregivers.ConclusionFindings highlight that preparedness and response to the COVID-19 crisis were proportionate to the situation’s gravity. More enablers than barriers were identified. However, opportunities for improvement were recognised in the domains of planning, logistics, self-sufficiency with equipment, operational and strategic oversight, communication, and managing end-of-life care.ARTICLE SUMMARYStrengths and limitations of this studyThis is the first study that provided insights about clinicians’ perspectives and viewpoints to preparing and responding to COVID-19 in Australia.The study used qualitative methodological framework allowing participants to provide in-depth accounts of processes and enabling factors and barriers.Our study provides information on issues that needs to be addressed from a critical care viewpoint and interventions that were effective and efficientThis is a single-center study in a developed country where experience is vastly different from other centers with higher demand and fewer resourcesWe acknowledge the potential for selection bias because of the qualitative design
ACPA-IgG variable domain glycosylation increases before the onset of rheumatoid arthritis and stabilizes thereafter; a cross-sectional study encompassing over 1500 samples
Authors: Kissel T. , Hafkenscheid L. , Wesemael T.J. , Tamai M. , Kawashiri S.Y. , Kawakami A. , El-Gabalawy H.S. , van Schaardenburg D. , Rantapää-Dahlqvist S. , Wuhrer M. , van der Helm-van Mil A.H.M. , Allaart C.F. , van der Woude D. , Scherer H.U. , Toes R.E.M. , Huizinga T.W.J. 
Published: November 2021

AbstractObjectiveThe autoimmune response in rheumatoid arthritis (RA) is marked by anti-citrullinated protein antibodies (ACPA). A remarkable feature of ACPA-IgG is the abundant expression of N-linked glycans in the variable domain. Nonetheless, the presence of ACPA variable domain glycans (VDG) across disease stages and its’ response to therapy is poorly described. To understand its dynamics, we investigated the abundance of ACPA-IgG VDG in 1574 samples from individuals in different clinical disease stages.MethodsUsing liquid chromatography, we analyzed ACPA-IgG VDG profiles of 7 different cohorts from Japan, Canada, the Netherlands and Sweden. We assessed 184 healthy, 228 pre-symptomatic, 277 arthralgia, 305 patients at RA-onset and 117 RA-patients 4, 8 and 12 months after disease onset. Additionally, we measured VDG of 234 samples from RA-patients that did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up.ResultsOur data show that ACPA-IgG VDG significantly increases (p<0.0001) towards disease-onset and associates with ACPA-levels and epitope spreading pre-diagnosis. A slight increase in VDG was observed in established RA and a moderate influence of treatment. Individuals who later achieved DFR displayed reduced ACPA-IgG VDG already at RA-onset.ConclusionThe abundance of ACPA-IgG VDG rises towards RA-onset and correlates with maturation of the ACPA-response. Although, ACPA-IgG VDG levels are rather stable in established disease, a lower degree at RA-onset correlates with DFR. Even though the underlying biological mechanisms are still elusive, our data support the concept that VDG relates to an expansion of the ACPA-response pre-disease and contributes to disease-development.
Recurrent urinary tract infection and estrogen shape the taxonomic ecology and functional potential of the postmenopausal urobiome
Authors: Neugent Michael L. , Kumar Ashwani , Hulyalkar Neha V. , Lutz Kevin C. , Nguyen Vivian H. , Fuentes Jorge L. , Zhang Cong , Nguyen Amber , Sharon Belle M. , Kuprasertkul Amy , Arute Amanda P. , Ebrahimzadeh Tahmineh , Natesan Nitya , Li Qiwei , Xing Chao , Shulaev Vladimir , Zimmern Philippe E. , Palmer Kelli L. , De Nisco Nicole J. 
Published: November 2021

AbstractCommunity-acquired urinary tract infection (UTI) is among the most common bacterial infections observed in humans. Postmenopausal women are a rapidly growing and underserved demographic group who are severely affected by recurrent UTI (rUTI) with a >50% recurrence rate. In this population, rUTI can persist for years, reducing quality of life and imposing a significant healthcare burden. rUTI is most often treated by antibiotics, but development of antibiotic resistance and allergy limit therapeutic options. The female urinary microbiome (urobiome) has been identified as a key component of the urogenital environment. However, compositional and functional changes in the urobiome underlying rUTI susceptibility in postmenopausal women are not well understood. Here, we used a controlled, cross-sectional cohort of postmenopausal women, to interrogate changes in urobiome structure and function linked to rUTI susceptibility by whole genome metagenomic sequencing (WGMS), advanced urine culture, estrogen metabolite profiling, and antibiotic sensitivity testing. Overall, we detected 276 bacterial, archaeal, and fungal species representing 106 genera. We find a putative commensal population consisting of species known to protect against bacterial vaginosis, such as Lactobacillus crispatus, within the urobiome of postmenopausal women who do not experience UTI. Integration of clinical metadata detected an almost exclusive enrichment of lactobacilli, including L. crispatus and L. vaginalis, in women taking estrogen hormone therapy (EHT). Integrating quantitative metabolite profiling of urinary estrogens with WGMS, we observed robust correlations between urobiome taxa, such as Bifidobacterium breve and L. crispatus, and urinary estrogen conjugate concentrations in women with no history of UTI that were absent in women with rUTI history. We further used functional metagenomic profiling and patient-derived isolate phenotyping to identify microbial metabolic pathways, antimicrobial resistance genes (ARGs), and clinically relevant antimicrobial resistance phenotypes enriched between disease-states. Our data indicate that distinct urobiome metabolic and ARG signatures are associated with current rUTI status and history. Importantly, we observed that rUTI history leaves an imprint of enriched ARGs even in women not currently experiencing UTI. Taken together, our data suggests that rUTI history and estrogen strongly shape the functional and taxonomic composition of the urobiome in postmenopausal women.
Coffee, smoking and aspirin are associated with age at onset and clinical severity in idiopathic Parkinson’s disease
Authors: Gabbert Carolin , König Inke R. , Lüth Theresa , Kolms Beke , Kasten Meike , Vollstedt Eva-Juliane , Balck Alexander ,   Fox Insight Study, Grünewald Anne , Klein Christine , Trinh Joanne 
Published: November 2021

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder. Genetic modifiers, environmental factors and gene-environment interactions have been found to modify PD risk and disease progression. The objective of this study was to evaluate the association of smoking, caffeine and anti-inflammatory drugs with age at onset (AAO) and clinical severity in a large PD cohort. A total of 35,963 American patients with idiopathic PD (iPD) from the Fox Insight Study responded to health and lifestyle questionnaires. We compared the median AAO between different groups using the non-parametric Mann-Whitney U test. Non-parametric Spearman correlation was used for correlation assessments and regression analysis was used to assess interaction between variables. Reported p-values remain descriptive because they are not corrected for multiple testing and results are exploratory. We found that smoking (r=0.08, p<0.0001), coffee drinking (r=0.69, p<0.0001) and aspirin intake (r=0.23, p<0.0001) show an exploratory association with AAO in iPD. However, the effect of aspirin diminished as an independent predictor after including comorbidities (heart diseases and arthritis). Smoking was associated with higher (more severe) motor scores, while coffee drinking was linked to lower (less severe) motor scores (p<0.05). In addition, smokers reported anxiety, depression and other non-motor symptoms such as unexplained pains and problems remembering (p<0.05). The association of aspirin with PD AAO was replicated in another cohort (EPIPARK) (n=237 patients with PD), although again the effect diminished after including age in the regression model. Future longitudinal studies are warranted to investigate the clinical severity over time.
Listening to mental health crisis needs at scale: using Natural Language Processing to understand and evaluate a mental health crisis text messaging service
Authors: Liu Zhaolu , Peach Robert L. , Lawrance Emma L. , Noble Ariele , Ungless Mark A. , Barahona Mauricio 
Published: November 2021

AbstractThe current mental health crisis is a growing public health issue requiring a large-scale response that cannot be met with traditional services alone. Digital support tools are proliferating, yet most are not systematically evaluated, and we know little about their users and their needs. Shout is a free mental health text messaging service run by the charity Mental Health Innovations, which provides support for individuals in the UK experiencing mental or emotional distress and seeking help. Here we study a large data set of anonymised text message conversations and post-conversation surveys compiled through Shout. This data provides an opportunity to hear at scale from those experiencing distress; to better understand mental health needs for people not using traditional mental health services; and to evaluate the impact of a novel form of crisis support. We use natural language processing (NLP) to assess the adherence of volunteers to conversation techniques and formats, and to gain insight into demographic user groups and their behavioural expressions of distress. Our textual analyses achieve accurate classification of conversation stages (weighted accuracy = 88%), behaviours (1-hamming loss = 95%) and texter demographics (weighted accuracy = 96%), exemplifying how the application of NLP to frontline mental health data sets can aid with post hoc analysis and evaluation of quality of service provision in digital mental health services.
The effect of notification window length on the epidemiological impact of COVID-19 contact tracing mobile applications
Authors: Leng Trystan , Hill Edward M. , Keeling Matt J. , Tildesley Michael J. , Thompson Robin N. 
Published: November 2021

1AbstractThe reduction in SARS-CoV-2 transmission from contact tracing applications (apps) depends both on the number of contacts notified and on the probability that those contacts quarantine after notification. Referring to the number of days preceding a positive test that contacts are notified as an app’s notification window, we use an epidemiological model of SARS-CoV-2 transmission that captures the profile of infection to consider the trade-off between notification window length and active app-usage. We focus on 5-day and 2-day windows, the lengths used by the NHS COVID-19 app in England and Wales before and after 2nd August 2021, respectively. Short windows can be more effective at reducing transmission if they are associated with higher levels of active app usage and adherence to isolation upon notification, demonstrating the importance of understanding adherence to control measures when setting notification windows for COVID-19 apps.
A multiscale computational study of the conformation of the full-length intrinsically disordered protein MeCP2
Authors: Chávez-García Cecilia , Hénin Jérôme , Karttunen Mikko 
Published: November 2021

ABSTRACTThe malfunction of the Methyl CpG binding protein 2 (MeCP2) is associated to the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modelling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and TRD domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent accessible, and having 4.1% of α-helix content, compared to the 4% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.