bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum NfL in spinocerebellar ataxia type 1 is increased already at the preataxic stage, correlating with proximity to clinical onset
Authors: Wilke Carlo , Mengel David , Schöls Ludger , Hengel Holger , Rakowicz Maria , Klockgether Thomas , Durr Alexandra , Filla Alessandro , Melegh Bela , Schüle Rebecca , Reetz Kathrin , Jacobi Heike , Synofzik Matthis 
Published: September 2021

AbstractBackground and ObjectivesNeurofilament light (NfL) appears a promising fluid biomarker in repeat-expansion spinocerebellar ataxias (SCAs), with piloting studies in mixed SCA cohorts suggesting that NfL might be increased at the ataxic stage of spinocerebellar ataxia type 1 (SCA1). We here hypothesised that NfL is increased not only at the ataxic stage of SCA1, but also at its – likely most treatment-relevant – preataxic stage.MethodsWe assessed serum (sNfL) and cerebrospinal fluid (cNfL) levels of NfL in both preataxic and ataxic SCA1, leveraging a multicentric cohort of 40 SCA1 carriers (23 preataxic, 17 ataxic) and >80 controls, and clinical follow-up data including actually observed (rather than only predicted) conversion to the ataxic stage (11 carriers).ResultssNfL levels were increased with high age-corrected effect sizes at the preataxic (r=0.62) and ataxic stage (r=0.63), paralleling increases of cNfL levels. In preataxic subjects, sNfL levels increased with proximity topredictedataxia onset, with significant sNfL elevations already 5 years before onset, and confirmed in preataxic subjects withactually observedataxia onset. sNfL increases were detected already in preataxic SCA1 subjects without volumetric atrophy of cerebellum or pons, suggesting that sNfL might be more sensitive to early preataxic neurodegeneration than the currently known most change-sensitive regions in volumetric MRI. Using longitudinal sNfL measurements, we estimated sample sizes for clinical trials using the reduction of sNfL as endpoint.ConclusionssNfL levels might thus provide easily accessible peripheral biomarkers in both preataxic and ataxic SCA1, allowing stratification of preataxic subjects regarding proximity-to-onset, early detection of neurodegeneration even before volumetric MRI alterations, and potentially capture of treatment response in clinical trials.
Accurately Estimating Unreported Infections using Information Theory
Authors: Cui Jiaming , Adhikari Bijaya , Haddadan Arash , Haque A S M Ahsan-Ul , Vreeken Jilles , Vullikanti Anil , Prakash B. Aditya 
Published: September 2021

AbstractOne of the most significant challenges in combating against the spread of infectious diseases was the difficulty in estimating the true magnitude of infections. Unreported infections could drive up disease spread, making it very hard to accurately estimate the infectivity of the pathogen, therewith hampering our ability to react effectively. Despite the use of surveillance-based methods such as serological studies, identifying the true magnitude is still challenging. This paper proposes an information theoretic approach for accurately estimating the number of total infections. Our approach is built on top of Ordinary Differential Equations (ODE) based models, which are commonly used in epidemiology and for estimating such infections. We show how we can help such models to better compute the number of total infections and identify the parametrization by which we need the fewest bits to describe the observed dynamics of reported infections. Our experiments on COVID-19 spread show that our approach leads to not only substantially better estimates of the number of total infections but also better forecasts of infections than standard model calibration based methods. We additionally show how our learned parametrization helps in modeling more accurate what-if scenarios with non-pharmaceutical interventions. Our approach provides a general method for improving epidemic modeling which is applicable broadly.
Monitoring the COVID-19 immunisation programme through a National Immunisation Management System – England’s experience
Authors: Tessier Elise , Stowe Julia , Tsang Camille , Rai Yuma , Clarke Eleanor , Lakhani Anissa , Makwana Ashley , Heard Heather , Rickeard Tim , Kirsebom Freja , Quinot Catherine , Lakhani Shreya , Power Linda , Edelstein Michael , Evans Andy , Ramsay Mary , Lopez-Bernal Jamie , White Joanne , Gower Charlotte , Andrews Nick , Campbell Colin 
Published: September 2021

AbstractIn England, the National Immunisation Management System (NIMS) has been used to deliver COVID-19 vaccinations across England, monitor vaccine coverage, and assess vaccine effectiveness and safety.The NIMS was developed by a joint collaboration between a range of health and digital government agencies. Vaccinations delivered at large vaccination sites, pharmacies, hospitals and in primary care are entered on a point of care application which is verified using the unique NHS number in a centralised system containing information for everyone resident and registered with a GP in England. Vaccination details and additional data from hospital and GP records (such as priority groups) are sent to NHS Digital for data linkage. The NIMS constantly receives updated details from NHS Digital for all individuals and these data are provided to Public Health England (PHE) in a secure environment.PHE primarily use the NIMS for vaccine coverage, vaccine effectiveness and safety. Daily access to individual-level vaccine data has allowed PHE to rapidly and accurately estimate vaccine coverage and provide some of the world’s first vaccine effectiveness estimates.Other countries evaluating the roll-out and effect of COVID-19 vaccine programmes should consider a vaccine register or immunisation information system similar to the NIMS.
COVID-19 Vaccine Hesitancy in India: An Exploratory Analysis
Authors: Agarwal Sandip K. , Naha Maharnab 
Published: September 2021

AbstractVaccine hesitancy is context specific and varies over time and space. Therefore, strategies to tackle vaccine hesitancy based on evidence from high income countries are unlikely to serve the purpose adequately in LMICs. We use district level evidence on COVID-19 vaccine uptake rates from an LMIC - India to provide evidence of COVID-19 vaccine hesitancy. We argue that vaccination rates during the different phases of COVID-19 vaccination across the districts is likely to be related to vaccine hesitancy. Districts with larger rural population and lower literacy rates had lower vaccination rates. High past child immunization rates were positively correlated with COVID-19 vaccination uptake. Across the four phases of vaccination drive, vaccine hesitancy was the highest during the third phase of the vaccination drive, and therefore the above correlations were strongest during the third and the fourth phase. Measures of family planning indicators too seem to be correlated with vaccine uptakes during the third phase which indicate the regions most susceptible to vaccine hesitancy.
Startle responses in Duchenne muscular dystrophy: a novel biomarker of brain dystrophin deficiency
Authors: Maresh Kate , Papageorgiou Andriani , Ridout Deborah , Harrison Neil A. , Mandy William , Skuse David , Muntoni Francesco 
Published: September 2021

AbstractDuchenne muscular dystrophy (DMD) is characterised by loss of dystrophin in muscle. Patients affected by DMD also have variable degree of intellectual disability and neurobehavioural co-morbidities. In contrast to muscle, in which a single full-length isoform (Dp427) is produced, multiple dystrophin isoforms are produced in the brain, and their deficiency accounts for the variability of CNS manifestations, with increased risk of comorbidities in patients carrying mutations affecting the 3’ end of gene, disrupting the shorter Dp140 and Dp71 isoforms. The mdx mouse model of DMD lacks Dp427 in muscle and CNS and exhibits exaggerated startle responses to threat, linked to the deficiency of dystrophin in limbic structures such as the amygdala, which normalise with postnatal brain dystrophin-restoration therapies. A pathological startle response is not a recognised feature of DMD, and its characterisation has implications for improved clinical management and translational research.To investigate startle responses in DMD, we used a novel fear-conditioning task in an observational study of 56 males aged 7-12 years (31 DMD, mean age 9.7±1.8 years; 25 Controls, mean age 9.6±1.4 years). Trials of two neutral visual stimuli were presented to participants: one ‘safe’ cue presented alone; one ‘threat’ cue paired with an aversive noise to enable conditioning of physiological startle responses (skin conductance response, SCR; heart rate, HR). Retention of conditioned physiological responses was subsequently tested with presentation of both cues without the aversive noise in an ‘extinction’ phase. Primary outcomes were the magnitude of the initial unconditioned SCR and HR change responses to the aversive ‘threat’ and acquisition and retention of conditioned responses after conditioning. Secondary outcomes were neuropsychological measures and genotype associations.The initial (unconditioned) mean SCR to threat was greater in DMD than Controls (Mean difference 3.0 µS (95% CI 1.0, 5.1), P=.004), associated with a significant threat-induced bradycardia only in the DMD group (mean difference -5.6 bpm (95% CI 0.51, 16.9); P=.04). DMD participants found the task more aversive than Controls, consequently early termination during the extinction phase occurred in 26% of the DMD group (vs. 0% Controls; P=.007).This study provides the first evidence that boys with DMD show increased unconditioned startle responses to threat, similar to the mdx mouse phenotype that also responds to brain dystrophin restoration. Our study provides new insights into the neurobiology underlying the complex neuropsychiatric co-morbidities in DMD and defines an objective measure of this CNS phenotype, which will be valuable for future CNS-targeted dystrophin-restoration studies.
The removal of airborne SARS-CoV-2 and other microbial bioaerosols by air filtration on COVID-19 surge units
Authors: Conway-Morris Andrew , Sharrocks Katherine , Bousfield Rachel , Kermack Leanne , Maes Mailis , Higginson Ellen , Forrest Sally , Pereira-Dias Joana , Cormie Claire , Old Tim , Brooks Sophie , Hamed Islam , Koenig Alicia , Turner Andrew , White Paul , Floto R. Andres , Dougan Gordon , Gkrania-Klotsas Effrossyni , Gouliouris Theodore , Baker Stephen , Navapurkar Vilas 
Published: September 2021

SummaryBackgroundThe COVID-19 pandemic has overwhelmed the respiratory isolation capacity in hospitals; many wards lacking high-frequency air changes have been repurposed for managing patients infected with SARS-CoV-2 requiring either standard or intensive care. Hospital-acquired COVID-19 is a recognised problem amongst both patients and staff, with growing evidence for the relevance of airborne transmission. This study examined the effect of air filtration and ultra-violet (UV) light sterilisation on detectable airborne SARS-CoV-2 and other microbial bioaerosols.MethodsWe conducted a crossover study of portable air filtration and sterilisation devices in a repurposed ‘surge’ COVID ward and ‘surge’ ICU. National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR assays were used to detect the presence of airborne SARS-CoV-2 and other microbial bioaerosol with and without air/UV filtration.ResultsAirborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off. Airborne SARS-CoV-2 was infrequently detected in the ICU. Filtration significantly reduced the burden of other microbial bioaerosols in both the ward (48 pathogens detected before filtration, two after, p=0.05) and the ICU (45 pathogens detected before filtration, five after p=0.05).ConclusionsThese data demonstrate the feasibility of removing SARS-CoV-2 from the air of repurposed ‘surge’ wards and suggest that air filtration devices may help reduce the risk of hospital-acquired SARS-CoV-2.FundingWellcome Trust, MRC, NIHR
Mortality in Rural Coastal Kenya measured using the Kilifi Health and Demographic Surveillance System: A 16-year descriptive analysis
Authors: Otiende Mark , Bauni Evasius , Nyaguara Amek , Amadi David , Nyundo Christopher , Tsory Emmanuel , Walumbe David , Kinuthia Michael , Kihuha Norbert , Kahindi Michael , Nyutu Gideon , Moisi Jennifer , Deribew Amare , Agweyu Ambrose , Marsh Kevin , Tsofa Benjamin , Bejon Philip , Bottomley Christian , Williams Thomas N. , Scott J. Anthony G. 
Published: September 2021

ABSTRACTBackgroundThe Kilifi Health and Demographic Surveillance System (KHDSS) was established in 2000 to define the incidence and prevalence of local diseases and evaluate the impact of community-based interventions. KHDSS morbidity data have been reported comprehensively but mortality has not been described. This analysis describes mortality in the KHDSS over 16 years.MethodsWe calculated mortality rates from 2003-2018 in four intervals of equal duration and assessed differences in mortality across these intervals by age and sex. We calculated the period survival function and median survival using the Kaplan-Meier method and mean life expectancies using abridged life tables. We estimated trend and seasonality by decomposing a time series of monthly mortality rates. We used choropleth maps and random effects Poisson regression to investigate geographical heterogeneity.ResultsMortality declined by 36% overall between 2003-2018 and by 59% in children aged <5 years. Most of the decline occurred between 2003 and 2006. Among adults, the greatest decline (49%) was observed in those aged 15-54 years. Life expectancy at birth increased by 12 years. Females outlived males by 6 years. Seasonality was only evident in the 1-4 year age group in the first four years. Geographical variation in mortality was +/-10% of the median value and did not change over time.ConclusionsBetween 2003-2018 mortality among children and young adults has improved substantially. The steep decline in 2003-2006 followed by a much slower reduction thereafter suggests improvements in health and wellbeing have plateaued in the last 12 years. However, there is substantial inequality in mortality experience by geographical location.
Real-world serologic responses to Extended-interval and Heterologous COVID-19 mRNA vaccination in Frail Elderly - Interim report from a prospective observational cohort study
Authors: Vinh Donald C. , Gouin Jean-Philippe , Cruz-Santiago Diana , Canac-Marquis Michelle , Bernier Stéphane , Bobeuf Florian , Sengupta Avik , Brassard Jean-Philippe , Guerra Alyssa , Dziarmaga Robert , Perez Anna , Sun Yichun , Li Yongbiao , Roussel Lucie , Langelier Mélanie J. , Ke Danbing , Arnold Corey , Pelchat Martin , Langlois Marc-André , Evans Timothy G. , Zhang Xun , Mazer Bruce D. 
Published: September 2021

BackgroundThe Coronavirus disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted accelerated vaccines development. Their use was prioritized to protect the most vulnerable, notably, the elderly. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been employed. The effectiveness of these strategies in the frail elderly are unknown.MethodsIn this real-world vaccination study, under a government-decreed rationing strategy, elderly adults residing in long-term care facilities, with or without previously-documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. Clinical data and blood were serially collected during and after this interval period. Sera were tested for SARS-CoV-2-specific IgG antibodies (to trimeric S; RBD; nucleocapsid) by automated chemiluminescent ELISA.FindingsAfter a significant increase 4 weeks post-prime dose, there was a significant decline in anti-RBD and anti-S IgG levels until the boost dose, followed by an increase 4 weeks later. Previously uninfected individuals exhibited lower antibody responses up to 16 weeks post-prime dose, but achieved comparable levels to previously infected counterparts by 4 weeks post-second dose. Individuals primed with BNT162b2 exhibited larger decrease in anti-RBD and anti-S IgG levels with 16-week interval between doses, compared to those who received mRNA-1273. No differences in antibody levels 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations.InterpretationsThese interim results of this ongoing longitudinal study show that, among frail elderly, neither age, sex, nor comorbidity affect antigenicity of mRNA-based COVID vaccines, but previous SARS-CoV-2 infection and type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. Homologous/heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following second dose, supporting their interchangeability.FundingThis project was supported by funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference group and the COVID-19 Immunity Task Force (CITF).
Central oxidative stress and early vocational outcomes in first episode psychosis: A 7-Tesla Magnetic Resonance Spectroscopy study of glutathione
Authors: MacKinley Michael , Ford Sabrina D. , Jeon Peter , Théberge Jean , Palaniyappan Lena 
Published: September 2021

ABSTRACTFollowing the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Several lines of evidence from preclinical, genetic and biochemical studies suggest a role for high oxidative stress in poor functional outcomes. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) provides an opportunity to investigate the relationship between central antioxidant tone and functional outcomes at the time of first episode psychosis (FEP). A body of epidemiological studies indicates better functional outcomes in patients at early stages of schizophrenia compared to patients at a chronic, established phase of illness. We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimised the confounding effects of illness chronicity, long-term treatment exposure and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes. Patients with FEP who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in employment, education or training (NEET) did not differ from healthy subjects in their GSH levels. Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.
Effectiveness of vaccination in preventing severe SARS CoV-2 infection in South India-a hospital-based cross-sectional study
Authors: Charles Pon Ruban A , Aazmi M , Shantaraman K. 
Published: September 2021

AbstractBackground & objectivesEstablishing concrete evidence on the effect of vaccination on the severity of SARS CoV-2 infections in real-world situations is the need of the hour. This study aims to estimate the effectiveness of Covid 19 vaccines in preventing the new and severe SARS CoV-2 infections.DesignCross-sectional studySetting& ParticipantsWe did this cross-sectional study among the 4565 patients consecutive adult inpatients admitted in the Covid 19 wards of a tertiary care hospital from May 7, 2021, to October 7, 2021, during the second wave of the Covid 19 pandemic. Information on basic demographic variables, RT PCR status, vaccination status, outcome and clinical severity of illness were obtained from the electronic hospital patient records.ResultsOnly 4% of the study participants had prior vaccination. The type of vaccine and number of doses didn’t have any protective effect against the new SARS CoV-2 infection and breakthrough infection. Fully vaccinated RTPCR positive patients had an 82% reduction in the need for ICU admission (OR 0.09; AOR 0.18, CI (0.04 to 0.8), P <0.05) and a non-significant 79% in mortality (OR 0.19; AOR 0.21, CI (0.04 to 1.1) P>0.05).ConclusionVaccination doesn’t protect against new SARS Cov-2 infection and breakthrough infection however significant protection was documented against severe SARS Cov-2 infection. The protective effect shown by the vaccines in preventing the severe form of SARS Cov-2 infection among fully vaccinated patients was 82%. Vaccination coverage should be increased urgently to halt the impending wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Topological relationships between perivascular spaces and progression of white matter hyperintensities: a pilot study in a sample of the Lothian Birth Cohort 1936
Authors: Barnes Abbie , Ballerini Lucia , Valdés Hernández Maria del C. , Chappell Francesca M. , Muñoz Maniega Susana , Meijboom Rozanna , Backhouse Ellen V. , Stringer Michael S. , Coello Roberto Duarte , Brown Rosalind , Bastin Mark E. , Cox Simon R. , Deary Ian J. , Wardlaw Joanna M. 
Published: September 2021

AbstractEnlarged perivascular spaces (PVS) and white matter hyperintensities (WMH) are features of cerebral small vessel disease which can be seen in brain magnetic resonance imaging (MRI). Given the associations and proposed mechanistic link between PVS and WMH, they are hypothesised to also have topological proximity. However, this, and the influence of their spatial proximity on WMH progression are unknown. We analysed longitudinal MRI data from 29/32 participants (mean age at baseline = 71.9 years) in a longitudinal study of cognitive ageing, from three waves of data collection at 3-year intervals, alongside semi-automatic segmentation masks for PVS and WMH, to assess relationships. The majority of deep WMH clusters were found adjacent to or enclosing PVS (Wave – 1: 77%; 2: 76%; 3: 69%), especially in frontal, parietal and temporal regions. Of the WMH clusters in the deep white matter that increased between waves, most increased around PVS (Waves – 1-2: 73%; 2-3: 72%). Formal statistical comparisons of severity of each if these two SVD markers yielded no associations between deep WMH progression and PVS proximity. These findings may suggest deep WMH clusters preferentially form and grow around PVS, possibly reflecting the consequences of impaired interstitial fluid drainage via PVS. The utility of these relationships as predictors of WMH progression remains unclear.