bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aortic stenosis post-COVID-19: A mathematical model on waiting lists and mortality
Authors: Stickels Christian P , Nadarajah Ramesh , Gale Chris P , Jiang Houyuan , Sharkey Kieran J , Gibbison Ben , Holliman Nick , Lombardo Sara , Schewe Lars , Sommacal Matteo , Sun Louise , Weir-McCall Jonathan , Cheema Katherine , Rudd James H F , Mamas Mamas A. , Erhun Feryal 
Published: November 2021

AbstractObjectivesTo provide estimates for how different treatment pathways for the management of severe aortic stenosis (AS) may affect NHS England waiting list duration and associated mortality.DesignWe constructed a mathematical model of the excess waiting list and found the closed-form analytic solution to that model. From published data, we calculated estimates for how the following strategies may affect the time to clear the backlog of patients waiting for treatment and the associated waiting list mortality.Interventions1) increasing the capacity for the treatment of severe AS, 2) converting proportions of cases from surgery to transcatheter aortic valve implantation, and 3) a combination of these two.ResultsIn a capacitated system, clearing the backlog by returning to pre-COVID-19 capacity is not possible. A conversion rate of 50% would clear the backlog within 666 (95% CI, 533–848) days with 1419 (95% CI, 597–2189) deaths whilst waiting during this time. A 20% capacity increase would require 535 (95% CI, 434–666) days, with an associated mortality of 1172 (95% CI, 466–1859). A combination of converting 40% cases and increasing capacity by 20% would clear the backlog within a year (343 (95% CI, 281–410) days) with 784 (95% CI, 292–1324) deaths whilst awaiting treatment.ConclusionA strategy change to the management of severe AS is required to reduce the NHS backlog and waiting list deaths during the post-COVID-19 ‘recovery’ period. However, plausible adaptations will still incur a substantial wait and many hundreds dying without treatment.
Post-stroke executive function in relation to white matter damage on clinically acquired CT brain imaging
Authors: Hobden Georgina , Moore Margaret , Mair Grant , Pendlebury Sarah , Demeyere Nele 
Published: November 2021

ABSTRACTImportanceExecutive function impairments are highly prevalent post-stroke and are a feature of vascular dementia. Computed tomography (CT) neuroimaging is routinely acquired in clinical settings. Therefore, determining the prognostic utility of CT-derived markers for post-stroke cognitive outcomes is of key clinical and academic interest.ObjectiveTo determine whether post-stroke executive function is associated with stroke-related white matter damage and/or white matter hypoattenuations of presumed vascular origin (WMHs) on routine CT brain scans.DesignRetrospective cross-sectional analysis of data collected within the Oxford Cognitive Screening (OCS) programme (2016-2020).SettingPatients were recruited at Oxford University Hospital’s acute stroke unit. Follow-up cognitive assessment was conducted six-months post-stroke at patients’ homes.ParticipantsOCS programme recruited a consecutive patient sample with a confirmed diagnosis of stroke, who were minimum 18 years old, able to remain alert for 20 minutes, and able to provide informed consent. This study included all patients who completed six-month follow-up assessment with the Oxford Cognitive Screen-Plus (OCS-Plus) and had a usable acute CT scan with a visible stroke lesion.Main Outcome and MeasuresAssociation between post-stroke executive function and both stroke-specific white matter damage and WMHs on routine CT. Executive function was evaluated using the OCS-Plus Rule Finding task. Stroke lesions were manually delineated on CT, and stroke-related white matter damage was quantified then dichotomised using the HCP-842 atlas. WMHs were visually rated using the Age-Related White Matter Changes scale and dichotomised as present or absent.ResultsAmong 87 stroke patients (mean/SD age = 73.60/11.75; 41 female; 61 ischaemic stroke), multivariable linear regression analyses demonstrated that poorer executive function six-months post-stroke was associated with both stroke damage to the medial lemniscus (B= - 8.86, p< .001, 95% CI [-13.29 -4.43]) and the presence of WMHs (B= -5.42, p= .005, 95% CI [-9.12 -1.72]), after adjusting for covariates including age and education.Conclusions and RelevancePoorer post-stroke executive functioning was associated with both localised patterns of stroke-specific white matter damage and white matter degeneration. Our results confirm the necessary role of white matter integrity for executive functioning post-stroke and highlight the prognostic utility of CT-derived neuroimaging markers for long-term post-stroke cognitive outcomes.
Neurodevelopmental outcomes of infants secondary to in utero exposure to maternal SARS-CoV-2 infection: A national prospective study in Kuwait
Authors: Ayed Mariam , Embaireeg Alia , Kartam Mais , More Kiran , Alqallaf Mafaza , AlNafisi Abdullah , Alsaffar Zainab , Bahzad Zainab , Buhamad Yasmeen , Alsayegh Haneen , Al-Fouzan Wadha , Alkandari Hessa 
Published: November 2021

AbstractBackgroundAn increasing proportion of women are being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study is to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy.MethodsIn this prospective cohort study, the neurodevelopment status of infants (N=298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff score: ≤2 standard deviations (SDs) below the population mean) and no delay (score >2 SDs above the population mean).ResultsApproximately 10% of infants born to mothers with SARS-CoV-2 infections during pregnancy showed developmental delays. Two of 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infection during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P=0.039) and second trimesters (P=0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. Infants born at <31 weeks gestation were more prone to developmental delays than those born at >31 weeks gestation (10% versus 0.8%; P=0.002).ConclusionThe findings of the study highlight the need for long term neurodevelopmental assessment of infants born to mothers with SARS-CoV-2 infection.
Covid-19 Pandemic and its Effect on Residents’ Mental Well-Being
Authors: Yazdani Anwar , Esmaeili Hend , AlSaleh Abdulla K , Sultan Ahmed , Alamad Esam , Bandar Ali , Rawdhan Hanouf , Ayed Mariam 
Published: November 2021

AbstractConcerns about COVID-19’s long-term consequences on the mental health of frontline health professionals are mounting as the entire world strives anew to contain it. The primary objective of this research is to describe the impact of working during the COVID-19 pandemic on junior doctors’ mental health and to investigate the effect of the COVID-19 pandemic on junior doctors’ training and professional performance. A cross-sectional online survey using the Google Forms platform was conducted from May 1stto May 30th, 2021, in 311 healthcare workers who were currently enrolled in a residency program at the Kuwait Institutional of Medical Specialization (KIMS). Socio-demographic details of each health worker were collected and the scores related to depression, anxiety, and stress were measured using the previously validated depression anxiety stress scale-21 (DASS-21). Higher stress scores were seen in those who were devoid of the option to work with COVID-19 patients (adjusted β 5.1 (95%CI:1.2-9);p=0.01), who reported that working during the pandemic affected their study schedule (adjusted β 4.8 (95%CI:1.6-8.1);p=0.004), and who lost off service training time (adjusted β 2.7 (95%CI:0.13-5.2);p=0.034). Further, the anxiety scores were significantly higher in females. The impact of the ongoing pandemic on residents’ mental health is grave, necessitating psychological treatment and support. The study discovered various factors linked to depression, anxiety, and stress. As a result, these aspects must be regarded to protect the residents’ mental health.
The Transcriptome Architecture of Polyomaviruses
Authors: Nomburg Jason , Zou Wei , Frost Thomas C. , Datta Chandreyee , Vasudevan Shobha , Starrett Gabriel J. , Imperiale Michael J. , Meyerson Matthew , DeCaprio James A. 
Published: November 2021

AbstractPolyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized. Here, we compare short- and long-read RNA sequencing data from eight human and non-human PyV. We provide a detailed transcriptome atlas for BK polyomavirus (BKPyV), an important human pathogen, and the prototype PyV, simian virus 40 (SV40). We identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times. Comparative analyses identify novel, conserved transcripts that increase PyV coding capacity. One of these conserved transcripts encodes superT, a T antigen containing two RB-binding LxCxE motifs. We find that superT-encoding transcripts are abundant in PyV-associated human cancers. Together, we show that comparative transcriptomic approaches can greatly expand known transcript and coding capacity in one of the simplest and most well-studied viral families.
Recombinant Group A Carbohydrate backbone embedded into Outer Membrane Vesicles is a potent vaccine candidate targeting Group A Streptococcus from Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis
Authors: Castro Sowmya Ajay , Thomson Sarah , Zorzoli Azul , Meyer Benjamin H , Reglinski Mark , Dorfmueller Helge C. 
Published: November 2021

BackgroundGroup A Streptococcus (GAS) are responsible for a wide range of human-exclusive infections, annually killing more than 500,000 people. Antibiotic resistance incidence of invasive GAS tripled in the past decade and emphasises the need to develop a universal GAS vaccine. We have produced, for the first time, a recombinant polyrhamnose backbone (pRha), a validated universal GAS vaccine candidate. E. coli outer membrane vesicles (OMVs) carrying pRha were investigated for their immunogenicity and efficacy in an animal model.MethodsOMVs decorated with pRha were administered to C57BL/6J mouse and rabbit models. Flow cytometry, ELISA, Luminex, immunofluorescence microscopy and serum bactericidal assay assays were conducted to investigate the ability of pRha-specific antibodies to recognise and kill clinical (hypervirulent) GAS strains.ResultsOur results suggest that pRha-OMVs induce specific antibodies which recognise Group A Carbohydrate (GAC) from S pyogenes and S. dysgalactiae subsp. equisimilis. Increased IgG levels correlate with increased bactericidal killing of the hypervirulent GAS M89 strain. Elevated IL-17a from pRha-OMV-immunised splenocytes indicates possible stimulation of long-term memory immune cells.ConclusionWe are the first to report efficacy and potency of this unique, exogenously produced polysaccharide, pRha, in the induction of humoral-mediated immune responses to GAS.TopicStreptococcus pyogenes, immunoglobulins, polysaccharides, opsonophagocytosis, acute rheumatic fever, M protein, invasive Group A Streptococcus, hyaluronic acid
New neurons in old brains: A cautionary tale for the analysis of neurogenesis in post-mortem tissue
Authors: Terstege Dylan J. , Addo-Osafo Kwaku , Teskey G. Campbell , Epp Jonathan R. 
Published: November 2021

AbstractAdult neurogenesis has primarily been examined in two key regions in the mammalian brain, the subgranular zone of the hippocampus and the subventricular zone. The proliferation and integration of newly generated neurons has been observed widely in adult mammalian species including the human hippocampus. Recent high-profile studies have suggested however, that this process is considerably reduced in humans, occurring in children but declining rapidly and nearly completely in the adult brain. In comparison, rodent studies also show age-related decline but a greater degree of proliferation of new neurons in adult animals. Here, we examine whether differences in tissue fixation, rather than biological difference in human versus rodent studies might account for the diminished levels of neurogenesis sometimes observed in the human brain. To do so we analyzed neurogenesis in the hippocampus of rats that were either perfusion-fixed or the brains extracted and immersion-fixed at various post-mortem intervals. We observed an interaction between animal age and the time delay between death and tissue fixation. While similar levels of neurogenesis were observed in young rats regardless of fixation, older rats had significantly fewer labeled neurons when fixation was not immediate. Furthermore, the morphological detail of the labeled neurons was significantly reduced in the delayed fixation conditions at all ages. This study highlights critical concerns that must be considered when using post-mortem tissue to quantify adult neurogenesis.
USE OF FLUNARIZINE AS A PREVENTIVE FOR VESTIBULAR MIGRAINE CRISES IN COMPARISON WITH OTHER DRUGS: SYSTEMATIC LITERATURE REVIEW
Authors: Braghieri Lara Estupina , Person Osmar Clayton , Bogar Priscila , Junior Fernando Veiga Angélico , Lopes Paula Ribeiro 
Published: November 2021

ABSTRACTINTRODUCTIONVestibular migraine is the main cause of episodic vertigo and the second most common cause of dizziness in adults. Treatment for vestibular migraine encompasses the prevention of crises and the control of acute symptoms.Flunarizine works by preventing the contraction of labyrinthine vessels and altering blood flow, thus preventing symptoms. Due to the high prevalence of the disease, its negative impacts on individual health and increased expenditure on public health, preventive pharmacological and non-pharmacological treatment must be implemented early.PURPOSETo evaluate the efficacy of Flunarizine as a preventive for migraine and vestibular crises compared to other preventive drugs.MATERIAL AND METHODSScientific articles were searched in the databases using the terms (vestibular migraine OR migrainous vertigo) AND (flunarizine) AND (prophylaxis). Subsequently, a systematic literature review and meta-analysis was performed, including 3 randomized clinical trials comparing flunarizine and other preventive drugs in terms of efficacy and safety for preventing migraine vertigo attacks. The studies were analyzed using a ROB table, analysis using the GRADE method and meta-analysis.RESULTSQualitatively, the analysis showed that flunariniza was positive for decreasing the frequency of vertigo in cases of vestibular migraine, with a moderate degree of evidence, a relative risk of 0.34 and a confidence interval of 0.15 to 0.76.CONCLUSIONSThere are few studies available in the scientific literature on the use of flunarizine in vestibular migraine, many of which are heterogeneous among themselves, mainly in the way of evaluating and monitoring patients, carried out mainly through subjective methods.The meta-analysis showed a positive result for flunarizine as a preventive drug for the studied population. Furthermore, in all the studies analyzed, no serious side effects resulting from the use of the medication were reported, which makes it safe for patients to use.Flunarizine is a good drug for the prevention of vestibular migraine, especially in reducing the number of attacks, with a good level of evidence.
Mast cells differentiated in synovial fluid and resident in osteophytes exalt the inflammatory pathology of osteoarthritis
Authors: Kulkarni Priya , Harsulkar Abhay , Märtson Anne-Grete , Suutre Siim , Märtson Aare , Koks Sulev 
Published: November 2021

AbstractOsteophytes are a prominent feature of osteoarthritis (OA) pathology. RNA-seq of osteophytes revealed patterns corresponding to active ECM re-modulation and participation of mast cells. The cells recruitment and their activity status were confirmed by anti-TPSAB1 and anti-FC epsilon RI antibodies in immunohistochemistry. Besides subchondral bone, which is a logical yet unproven route for the cells deployment into osteophytes, the authors propose that OA synovial fluid (SF) is necessary and sufficient for maturation of mast cell precursors (MCPs) in this channel. The authors present evidences to support their claim in the form of IHC, proteomics analysis of SF samples and in vitro cell differentiation assay, wherein human monocytes (ThP1) and hematopoietic stem cells (HSCs) showed differentiation in HLA-DR+/CD206+ and FCERI+ phenotype respectively after 9 days of SF treatment. These observations expound osteophytes and resident mast cells as yet unexplained functional epicentre in OA pathology.
Controlling SARS-CoV-2 in schools using repetitive testing strategies
Authors: Torneri Andrea , Willem Lander , Colizza Vittoria , Kremer Cécile , Meuris Christelle , Darcis Gilles , Hens Niel , Libin Pieter 
Published: November 2021

AbstractSARS-CoV-2 remains a worldwide emergency. While vaccines have been approved and are widely administered, these are only available to adults and adolescents in Europe. Therefore, in order to mitigate the spread of more transmissible SARS-CoV-2 variants among children, the use of non-pharmaceutical interventions is still warranted. We investigate the impact of different testing strategies on the SARS-CoV-2 infection dynamics in a primary school environment, using an individual-based modelling approach. Specifically, we consider three testing strategies: 1) symptomatic isolation, where we test symptomatic individuals and isolate them when they test positive, 2) reactive screening, where a class is screened once one symptomatic individual was identified, and 3) repetitive screening, where the school in its entirety is screened on regular time intervals. Through this analysis, we demonstrate that repetitive testing strategies can significantly reduce the attack rate in schools, contrary to a reactive screening approach. Furthermore, we investigate the impact of these testing strategies on the average number of school days lost per child.
Assessment of breakthrough infections among post-vaccinated healthcare workers in a Tertiary Dental Hospital in New Delhi, India
Authors: Maurya Deepamala , Kaur Arundeep , Faraz Farrukh , Tandon Shruti , Rana Anju , Grover Shekhar 
Published: November 2021

AbstractBackgroundCOVID-19 vaccination in India has been rolled out on a national level, with healthcare workers (HCWs) becoming the first recipient of both Covishield and Covaxin. However, concerns over efficacy of vaccines have been much debated. This study highlights COVID-19 infections among vaccinated HCWs in a teaching dental hospital in Delhi, India.MethodologyThis cross-sectional survey was conducted using a pretested, validated, self-instituted questionnaire assessing COVID-19 like symptoms and/or confirmed infections among partially or fully vaccinated HCWs (all faculty, staff and students) of the institute from 16th January to 31st July 2021. The number of infections was also matched with hospital records.ResultsOut of 397 HCWs, 386 (97.2%) were vaccinated and 355 (89.4%) had received both doses. COVID-19 like symptoms appeared in 21 HCWs (5.4%) post any dose of vaccine. Symptomatic breakthrough infections >14 days after second dose occurred was seen in 16 HCWs (4.5%). Except one (required hospitalization), all other cases had mild infection. No significant difference was observed between Covishield and Covaxin. Most common symptom was fever and body ache.ConclusionThe study identifies the possibility of breakthrough infections among vaccinated HCWs, and ensures the impact of vaccination in limiting disease severity. The findings suggest that COVID-19 preventive measures should be continued even among vaccinated individuals.
Min waves without MinC can pattern FtsA-FtsZ filaments on model membranes
Authors: Godino Elisa , Doerr Anne , Danelon Christophe 
Published: November 2021

AbstractAlthough the essential proteins that drive bacterial cytokinesis have been identified and reconstituted in vitro, the precise mechanisms by which they dynamically interact to enable symmetrical division are largely unknown. In Escherichia coli, cell division begins with the formation of a proto-ring composed of FtsZ and its membrane-tethering proteins FtsA and ZipA. In the broadly proposed molecular scenario for ring positioning, Min waves composed of MinD and MinE distribute the FtsZ-polymerization inhibitor MinC away from mid-cell, where the Z-ring can form. Therefore, MinC is believed to be an essential element connecting the Min and FtsZ systems. Here, by using cell-free gene expression on planar lipid membranes, we demonstrate that MinDE drive the formation of dynamic, antiphase patterns of FtsZ-FtsA co-filaments even in the absence of MinC. This behavior is also observed when the proteins are compartmentalized inside microdroplets. These results suggest that Z-ring positioning may be achieved with a more minimal set of proteins than previously envisaged, providing a fresh perspective about the role of MinC. Moreover, we propose that MinDE oscillations may constitute the minimal localization mechanism of an FtsA-FtsZ constricting ring in a prospective synthetic cell.
Essential functions of MLL1 and MLL2 in retinal development and cone cell maintenance
Authors: Sun Chi , Zhang Xiaodong , Ruzycki Philip A. , Chen Shiming 
Published: November 2021

ABSTRACTMLL1 (KMT2A) and MLL2 (KMT2B) are homologous members of the mixed-lineage leukemia (MLL) family of histone methyltransferases involved in epigenomic transcriptional regulation. Their sequence variants have been associated with neurological and psychological disorders, but little is known about their roles and mechanism of action in CNS development. Using mouse retina as a model, we previously reported MLL1’s role in retinal neurogenesis and horizontal cell maintenance. Here we determine roles of MLL2 and MLL1/MLL2 together in retinal development using conditional knockout (CKO) mice. Deleting Mll2 from Chx10+ retinal progenitors resulted in a similar phenotype as Mll1 CKO, but removal of both alleles produced much more severe deficits than each single CKO: 1-month double CKO mutants displayed null light responses in electroretinogram; thin retinal layers, including shorter photoreceptor outer segments with impaired phototransduction gene expression; and reduced numbers of M-cones, horizontal and amacrine neurons, followed by fast retinal degeneration. Despite moderately reduced progenitor cell proliferation at P0, the neurogenic capacity was largely maintained in double CKO mutants. However, upregulated apoptosis and reactive gliosis were detected during postnatal retinal development. Finally, the removal of both MLLs in fated rods produced a normal phenotype, but the CKO in M-cones impaired M-cone function and survival, indicating both cell non-autonomous and autonomous mechanisms. Altogether, our results suggest that MLL1/MLL2 play redundant roles in maintaining specific retinal neurons after cell fate specification and are essential for establishing functional neural networks.