bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of Community Health Worker based cardiovascular risk reduction strategies in urban slums of Bhopal: Rationale, design and baseline results of community based study
Authors: Pakhare Abhijit , Joshi Ankur , Khadanga Sagar , Kumar Sanjeev , Atal Shubham , Ingle Vaibhav , Sabde Yogesh , Shrivastava Neelesh , Lahiri Anuja , Ranjan Akash , Joshi Rajnish 
Published: September 2020

AbstractIn urban India, about 35-40% of all adults have hypertension and about 10-15% have diabetes mellitus. National Program for Prevention and Control of Diabetes, Cancer and Stroke (NPCDCS) launched by Government of India has envisaged to screen all adults aged 30 years and above for presence of hypertension and diabetes mellitus in the community through population-based screening, initiate positively screened and diagnosed on drug therapy, and follow them up for treatment adherence. In this context, the current study aims to estimate burden of high cardiovascular disease (CVD) risk and to evaluate feasibility of community health workers-based strategies in reducing CVD among adults living in urban slums. We have identified and trained CHWs from within the urban slum communities in Bhopal, in chronic disease identification, skills in self-care and adherence promotion skills. At-risk individuals were linked to public health facilities as outlined under NPCDCS. Primary outcome is assessment of burden of high cardiovascular risk and its determinants. Secondary outcome is feasibility of community health worker-based adherence promotion. Between November 2017 and June 2018, CHWs in 14 urban slum clusters, screened a total of 6178 individuals out of which 4781 (77.43%) attended confirmation camp. Around 2393 (38.8%) were current tobacco users (smoking and/or smokeless), and 4697 (76.1%) has a sedentary lifestyle. Out of 758 (12.3%) known hypertensives, 354 (46.7%) had controlled hypertension whereas out of 333 (5.4%) known diabetes patients, 169 (57.5%) has controlled level of diabetes. In 813 (15%) out of 5416 and 151 (3.4%) out of 4486 adults, hypertension and diabetes was newly detected respectively. Results of this study have a potential to strengthen NPCDCS across all urban areas of the country. This manuscript describes detailed protocol of the study and presents baseline summary of CVD risk factor burden in urban slums of Bhopal.
Exome sequencing identifies rare coding variants in 10 genes which confer substantial risk for schizophrenia
Authors: Singh Tarjinder , Neale Benjamin M. , Daly Mark J. 
Published: September 2020

AbstractBy meta-analyzing the whole-exomes of 24,248 cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in ten genes as conferring substantial risk for schizophrenia (odds ratios 3 - 50, P < 2.14 × 10-6), and 32 genes at a FDR < 5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure, and function of the synapse. The associations of NMDA receptor subunit GRIN2A and AMPA receptor subunit GRIA3 provide support for the dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We find significant evidence for an overlap of rare variant risk between schizophrenia, autism spectrum disorders (ASD), and severe neurodevelopmental disorders (DD/ID), supporting a neurodevelopmental etiology for schizophrenia. We show that protein-truncating variants in GRIN2A, TRIO, and CACNA1G confer risk for schizophrenia whereas specific missense mutations in these genes confer risk for DD/ID. Nevertheless, few of the strongly associated schizophrenia genes appear to confer risk for DD/ID. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk, suggesting that common and rare genetic risk factors at least partially converge on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, implying that more schizophrenia risk genes await discovery using this approach.
SARS-CoV-2 antibody seroprevalence in Tbilisi, the capital city of country of Georgia
Authors: Tsertsvadze Tengiz , Gatserelia Lana , Mirziashvili Marine , Dvali Natia , Abutidze Akaki , Metchurtchlishvili Revaz , el Rio Carlos , Chkhartishvili Nikoloz 
Published: September 2020

AbstractBackgroundGeorgia timely implemented effective response measures, with testing, contact tracing and isolation being the main pillar of the national response, achieving the lowest cumulative incidence of SARS-CoV-2 in the European region.MethodsWe conducted a survey to estimate SARS-CoV-2 IgG antibody seroprevalence among adult residents of capital city of Tbilisi (adult population: 859,328). Participants were recruited through respondent driven sampling during May 18-27, 2020. Blood specimens were tested for SARS-CoV-2 IgG antibodies using commercially available lateral flow immunoassay (COVID-19 IgG/IgM Rapid Test Cassette, Zhejiang Orient Gene Biotech). Crude seroprevalence was weighted by population characteristics (age, sex, district of Tbilisi) and further adjusted for test accuracy.ResultsAmong 1,068 adults recruited 963 (90.2%) were between 18 and 64 years-old, 682 (63.9%) women. 176 (16.5%) reported symptoms indicative of SARS-CoV-2 infection occurring in previous three months. Nine persons tested positive for IgG: crude seroprevalence: 0.84%, (95% CI: 0.33%-1.59%), weighted seroprevalence: 0.94% (95% CI: 0.37%-1.95%), weighted and adjusted for test accuracy: 1.02% (95% CI: 0.38%-2.18%). The seroprevalence estimates translate into 7,200 to 8,800 infections among adult residents of Tbilisi, which is at least 20 times higher than the number of confirmed cases.ConclusionsLow seroprevalence confirms that Georgia successfully contained spread of SARS-CoV-2 during the first wave of pandemic. Findings also suggest that undocumented cases due to asymptomatic or very mild disease account for majority of infections. Given that asymptomatic persons can potentially spread the virus, test and isolate approach should be further expanded to control the epidemic.
Communicating polygenic and non-genetic risk for atherosclerotic cardiovascular disease - An observational follow-up study
Authors: Widén Elisabeth , Junna Nella , Ruotsalainen Sanni , Surakka Ida , Mars Nina , Ripatti Pietari , Partanen Juulia J , Aro Johanna , Mustonen Pekka , Tuomi Tiinamaija , Palotie Aarno , Salomaa Veikko , Kaprio Jaakko , Partanen Jukka , Hotakainen Kristina , Pöllänen Pasi , Ripatti Samuli 
Published: September 2020

AbstractBackgroundAlgorithms including both traditional risk factors and polygenic risk scores (PRS) can significantly improve prediction of atherosclerotic cardiovascular disease (ASCVD). However, the clinical benefit of adding PRS to clinical risk evaluation remains unclear.ObjectivesThe study evaluated the attitudes of 7,342 individuals (64% women, mean age 56 yrs) upon receiving personal genome-enhanced ASCVD risk information, and prospectively assessed the impact on the participants’ health behavior.MethodsThe participant’s 10-year risk for ASCVD was estimated using both a traditional clinical risk score and a PRS-enhanced score, and both scores were communicated directly to study participants with an interactive web-tool.ResultsWhen reassessed after 1.5 years by a clinical visit and questionnaires, 20.8% of individuals at high (>10%) ASCVD risk had seen a doctor, 12.4% reported weight loss, 14.2% of smokers had quit smoking, and 15.4% had signed up for health coaching online. Altogether, 42.6% of individuals at high risk had made some health behavioral change compared to 33.5% of persons at low/average risk such that a higher baseline risk predicted a favorable change (p<0.001), with both clinical (p<0.001) and genomic factors (p=0.003) contributing independently. Seeing a doctor and weight loss both resulted in clinically significant improvement of lipid profiles (lower LDL-cholesterol and triglycerides) and lower systolic blood pressure (p<0.01).ConclusionsWeb-based communication of personal ASCVD risk-data including polygenic risk to middle-aged persons can motivate positive changes in health behavior. It supports integration of genomic information into clinical risk calculators as a feasible approach to enhance disease prevention.Condensed AbstractPrediction tools that combine polygenic risk scores (PRS) with clinical factors provide a new opportunity for improved risk assessment and prevention of atherosclerotic cardiovascular disease (ASCVD), but the clinical impact of PRS has hitherto remained unclear. We evaluated the longitudinal effects of using a web-based tool to communicate genome-based ASCVD risk-information to 7,342 middle-aged individuals. 42% of persons at high risk improved their health behavior during follow-up which resulted in clinically significant improvement of lipid profiles and lower systolic blood pressure. This supports integration of PRS into clinical risk calculators as a feasible approach to enhance disease prevention.
Apparent reductions in COVID-19 Case Fatality Rates reflect changes in average age of those testing positive
Authors: Grant Alastair 
Published: September 2020

AbstractNumbers of COVID-19 infections are rising in many countries, while death and hospitalisation rates remain low. Infection Fatality Rates (IFR) for individual year classes calculated from seroprevalence data and the ages of those dying in England show a very strong log-linear relationship with age, and allow us to predict fatality rates for those testing positive on each day based on their ages. Since the peak of the epidemic, reductions in the ages of cases account for an eight fold fall in fatality rates. Over the same period, increased testing intensity appears to have increased infections detected amongst the most vulnerable by a factor of at least five, and between 15 and 24 fold in the population as a whole. Together these two factors are sufficient to explain the large observed change in the ratio of deaths to reported cases. We can also use these methods to give a more precise early warning system of future increases in mortality rates than raw case numbers. Although case numbers are currently increasing markedly, a continuing reduction in numbers of older individuals being infected means that the predicted increase in mortality rates is much slower.
COPD in the time of COVID-19: An analysis of acute exacerbations and reported behavioural changes in patients with COPD
Authors: McAuley Hamish , Hadley Kate , Elneima Omer , Brightling Christopher E , Evans Rachael A , Steiner Michael C , Greening Neil J 
Published: September 2020

ABSTRACTIntroductionThe impact of the SARS-CoV-2 pandemic, and lockdown measures, on acute exacerbations of COPD (AECOPD) is unknown. We aimed to evaluate the change in AECOPD treatment frequency during the first six weeks of lockdown in the UK compared with 2019 and assess changes in self-reported behaviour and well-being.MethodsIn this observational study patients with established COPD were recruited. Exacerbation frequency was measured in the first six weeks of COVID lockdown and compared with the same period in 2019 using electronic health records. A telephone survey was used to assess changes in anxiety, inhaler adherence, physical activity, shopping and visitor behaviour during the pre-lockdown and lockdown periods compared to normal.Results160 participants were recruited (mean [SD] age 67.3 [8.1] years, 88 [55%] male, FEV1 34.3 [13] % predicted) and 140 [88%] reported at least one AECOPD in the previous year. Significantly more community treated exacerbations were observed in 2020 compared with 2019 (126 vs 99, p=0.026). The increase was as a result of multiple courses of treatment, with a similar proportion of patients receiving at least one course (34.4% vs 33.8%).During “lockdown” participants reported significantly increased anxiety, adherence to their preventative inhalers, and good adherence to shielding advice (all p<0.001). A significant reduction in self-reported physical activity and visitors was reported (both p<0.001).DiscussionTreatment for AECOPD events increased during the first six weeks of the SARS-CoV-2 pandemic in the UK compared to 2019. This was associated with increased symptoms of anxiety and significant behavioural change.What is the key question?How has the COVID-19 pandemic lockdown affected exacerbation patterns and behaviour in patients with COPD?What is the bottom line?A 38% increase in the number of community treated exacerbations was seen in 2020 compared with 2019. Increased symptoms of anxiety were seen in patients, alongside increased inhaler adherence and reduced physical activity.Why read on?The impact of the COVID-19 pandemic has led to significant changes in treatment for exacerbations of COPD in the community, as well as increased anxiety amongst patients.
On the relationship between serial interval, infectiousness profile and generation time
Authors: Lehtinen Sonja , Ashcroft Peter , Bonhoeffer Sebastian 
Published: September 2020

AbstractThe timing of transmission plays a key role in the dynamics and controllability of an epidemic. However, observing the distribution of generation times (time interval between the points of infection of an infector and infectee in a transmission pair) requires data on infection times, which are generally unknown. The timing of symptom onset is more easily observed; the generation time distribution is therefore often estimated based on the serial interval distribution (distribution of time intervals between symptom onset of an infector and an infectee). This estimation follows one of two approaches: i) approximating the generation time distribution by the serial interval distribution; or ii) deriving the generation time distribution from the serial interval and incubation period (time interval between infection and symptom onset in a single individual) distributions. These two approaches make different – and not always explicitly stated – assumptions about the relationship between infectiousness and symptoms, resulting in different generation time distributions with the same mean but unequal variances. Here, we clarify the assumptions that each approach makes and show that neither set of assumptions is plausible for most pathogens. However, the variances of the generation time distribution derived under each assumption can reasonably be considered as upper (approximation with serial interval) and lower (derivation from serial interval) bounds. Thus, we suggest a pragmatic solution is to use both approaches and treat these as edge cases in downstream analysis. We discuss the impact of the variance of the generation time distribution on the controllability of an epidemic through strategies based on contact tracing, and we show that underestimating this variance is likely to overestimate controllability.
“Average of neck circumference in Latin American adults: protocol for a systematic review and meta-analysis”
Authors: Lopez Patricia Espinoza , Landeo Kelly Fernández , Silva Mercado Rodrigo Pérez , Ardela Jesús Quiñones , Larco Rodrigo Carillo 
Published: September 2020

AbstractBackgroundBecause these are inexpensive and (fairly) easy to conduct, anthropometric measurements have been widely used as risk factors for many diseases (e.g., cardiovascular or cancer). Recently, there have been several reports pinpointing the association between neck circumference and obstructive sleep apnea, cardiovascular and metabolic diseases. These conditions are highly prevalent Latin American and the Caribbean (LAC), where they carry a large disease and disability burden. Neck circumference arises as a potential complement of established anthropometric measurements, namely weight, height and waist/hip circumference. However, unlike these well-known measurements, evidence about neck circumference is scarce and has not been systematically collected in LAC.ObjectiveTo summarize the average neck circumference in LAC adults; and, exploratorily, to summarize the prevalence of large neck circumference (i.e., neck/cervical obesity).MethodsSystematic review and meta-analysis. We will conduct a search in OVID (MEDLINE, Embase, Global Health) and LILACS. Search terms include those related to neck circumference, along with countries in LAC. We seek observational studies with a random sample of the general population, closed populations (e.g., workers), and patients; results will be presented for each of these groups. We will screen titles and abstracts; we will study in detail the selected papers. Both phases will be conducted by two reviewers independently. We will develop an extraction form to collate: country/year of data collection, methods of data collection, average neck circumference and, if available, prevalence of large neck circumference. Data extraction will be conducted by two reviewers independently. We will use the tool proposed by Hoy et al. and the Newcastle-Ottawa scale to assess the risk of bias.ConclusionsThis systematic review and meta-analysis will provide the average neck circumference in LAC adults. Currently, evidence about neck circumference in LAC has not been systematically studied, appraised or summarized. This work will provide information about this novel anthropometric measurement, and spark attention about its role as a potential anthropometric indicator and health risk factor.Conflicts of interestAll authors declare to have no conflicts of interest.FundingRodrigo M Carrillo-Larco is supported by a Wellcome Trust International Training Fellowship (214185/Z/18/Z).
Cortical actin properties controlled byDrosophilaFos aid macrophage infiltration against surrounding tissue resistance
Authors: Belyaeva Vera , Wachner Stephanie , Gyoergy Attila , Emtenani Shamsi , Gridchyn Igor , Akhmanova Maria , Linder Markus , Roblek Marko , Sibilia Maria , Siekhaus Daria 
Published: September 2020

ABSTRACTThe infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion ofDrosophilamacrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by theDrosophilamember of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue theDfosmacrophage invasion defect.In vivoimaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues.
Distributed sensory coding by cerebellar complex spikes in units of cortical segments
Authors: Michikawa Takayuki , Yoshida Takamasa , Kuroki Satoshi , Ishikawa Takahiro , Kakei Shinji , Itohara Shigeyoshi , Miyawaki Atsushi 
Published: September 2020

SummarySensory processing is essential for motor control. Climbing fibers from the inferior olive transmit sensory signals to Purkinje cells, but how the signals are represented in the cerebellar cortex remains elusive. We examined the olivocerebellar organization of the mouse brain by optically measuring complex spikes (CSs) evoked by climbing fiber inputs over the entire dorsal surface of the cerebellum. We discovered that the surface was divided into approximately 200 segments each composed of ∼100 Purkinje cells that fired CSs synchronously. Ourin vivoimaging of evoked responses revealed that whereas stimulation of four limb muscles individually similar global CS responses across nearly all segments, the timing and location of a stimulus were derived by Bayesian inference from coordinated activation and inactivation of multiple segments on a single trial basis. Our findings suggest that the cerebellum performs segment-based distributed population coding by assembling probabilistic sensory representation in individual segments.
Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis
Authors: Bakochi Anahita , Mohanty Tirthankar , Pyl Paul Theodor , Malmström Lars , Linder Adam , Malmström Johan 
Published: September 2020

AbstractMeningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.
CIB2 regulates autophagy via Rheb-mTORC1 signaling axis
Authors: Sethna Saumil , Bernstein Steven L. , Jian Xiaoying , Riazuddin Sheikh , Randazzo Paul A. , Riazuddin Saima , Ahmed Zubair M. 
Published: September 2020

SUMMARYAge-related macular degeneration (AMD), a multifactorial neurodegenerative disorder, is the most common cause of vision loss in the elderly. Deficits in autophagy have been associated with age-related retinal pigment epithelium (RPE) pathology in mice, and dry-AMD in humans. In this study, we establish that the calcium and integrin binding protein 2 (CIB2) regulates autophagy in the RPE via Rheb-mTORC1 signaling axis.Cib2mutant mice have reduced autophagic clearance in RPE and increased mTORC1 signaling – a negative regulator of autophagy. Concordant molecular deficits were also observed in RPE/choroid tissues from humans affected with dry AMD. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to ‘nucleotide empty’ or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in aging, Tuberous sclerosis complex (TSC), and lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 in LAM patient-derived fibroblasts andTsc2null cell line down-regulates hyperactive mTORC1 signaling. Thus, our findings have significant ramifications for the etiology of AMD and mTORC1 hyperactivity disorders and treatments.