bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis
Authors: Gordon Spencer G. , Kursel Lisa E. , Xu Kewei , Rog Ofer
Published: March 2021

During sexual reproduction the parental homologous chromosomes find each other (pair) and align along their lengths by integrating local sequence homology with large-scale contiguity, thereby allowing for precise exchange of genetic information. The Synaptonemal Complex (SC) is a conserved zipper-like structure that assembles between the homologous chromosomes, bringing them together and regulating exchanges between them. However, the molecular mechanisms by which the SC carries out these functions remain poorly understood. Here we isolated and characterized two mutations in the dimerization interface in the middle of the SC zipper inC.elegans. The mutations perturb both chromosome alignment and the regulation of genetic exchanges. Underlying the chromosome-scale phenotypes are distinct alterations to the way SC subunits interact with one another. We propose a model whereby the SC brings homologous chromosomes together through two activities: obligate zipping that prevents assembly on unpaired chromosomes; and a tendency to extend pairing interactions along the entire length of the chromosomes.
A systematic review and an individual patient data meta-analysis of ivermectin use in children weighing less than fifteen kilograms: Is it time to reconsider the current contraindication?
Authors: Jittamala Podjanee , Monteiro Wuelton , Smit Menno R. , Pedrique Belen , Specht Sabine , Chaccour Carlos J. , Dard Céline , Del Giudice Pascal , Khieu Virak , Maruani Annabel , Failoc-Rojas Virgilio E. , Sáez-de-Ocariz Marimar , Soriano-Arandes Antoni , Piquero-Casals Jaime , Faisant Anne , Brenier-Pinchart Marie-Pierre , Wimmersberger David , Coulibaly Jean T. , Keiser Jennifer , Boralevi Franck , Sokana Oliver , Marks Michael , Engelman Daniel , Romani Lucia , Steer Andrew C. , von Seidlein Lorenz , White Nicholas J. , Harriss Eli , Stepniewska Kasia , Humphreys Georgina S. , Kennon Kalynn , Guerin Philippe J. , Kobylinski Kevin C.
Published: March 2021

Background

Oral ivermectin is a safe broad spectrum anthelminthic used for treating several neglected tropical diseases (NTDs). Currently, ivermectin use is contraindicated in children weighing less than 15 kg, restricting access to this drug for the treatment of NTDs. Here we provide an updated systematic review of the literature and we conducted an individual-level patient data (IPD) meta-analysis describing the safety of ivermectin in children weighing less than 15 kg.

Methodology/Principal findings

A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for IPD guidelines by searching MEDLINE via PubMed, Web of Science, Ovid Embase, LILACS, Cochrane Database of Systematic Reviews, TOXLINE for all clinical trials, case series, case reports, and database entries for reports on the use of ivermectin in children weighing less than 15 kg that were published between 1 January 1980 to 25 October 2019. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017056515. A total of 3,730 publications were identified, 97 were selected for potential inclusion, but only 17 sources describing 15 studies met the minimum criteria which consisted of known weights of children less than 15 kg linked to possible adverse events, and provided comprehensive IPD. A total of 1,088 children weighing less than 15 kg were administered oral ivermectin for one of the following indications: scabies, mass drug administration for scabies control, crusted scabies, cutaneous larva migrans, myiasis, pthiriasis, strongyloidiasis, trichuriasis, and parasitic disease of unknown origin. Overall a total of 1.4% (15/1,088) of children experienced 18 adverse events all of which were mild and self-limiting. No serious adverse events were reported.

Conclusions/Significance

Existing limited data suggest that oral ivermectin in children weighing less than 15 kilograms is safe. Data from well-designed clinical trials are needed to provide further assurance.
Efficacy of praziquantel has been maintained over four decades (from 1977 to 2018): A systematic review and meta-analysis of factors influence its efficacy
Authors: Fukushige Mizuho , Chase-Topping Margo , Woolhouse Mark E. J. , Mutapi Francisca
Published: March 2021

Background

The antihelminthic drug praziquantel has been used as the drug of choice for treating schistosome infection for more than 40 years. Although some epidemiological studies have reported low praziquantel efficacy in cure rate (CR) and/or egg reduction rate (ERR), there is no consistent robust evidence of the development of schistosome resistance to praziquantel (PZQ). There is need to determine factors that lead to variable treatment CR and/or ERR. Therefore, we conducted a systematic review and meta-analysis to review CR and ERR as well as identify their predictors.

Methodology/Principal findings

In this systematic review and meta-analysis, a literature review was conducted using Biosis Citation Index, Data Citation Index, MEDLINE, and Web of Science Core Collection all of which were provided through Web of Science. Alongside these, EMBASE, and CAB abstracts were searched to identify relevant articles. Random effect meta-regression models were used to identify the factors that influence CR and/or ERR by considering differences in host characteristics and drug dose. In total, 12,127 potential articles were screened and 146 eligible articles (published from 1979 to 2020) were identified and included for the meta-analysis. We found that there has been no significant reduction in CR or ERR over the study period. The results showed more variability in CR, compared with ERR which was more consistent and remained high. The results showed a positive effect of “PZQ treatment dose” with the current recommended dose of 40 mg/kg body weight achieving 57% to 88% CR depending on schistosome species, age of participants, and number of parasitological samples used for diagnosis, and ERR of 95%.

Conclusions/Significance

Based on a review of over 40 years of research there is no evidence to support concerns about schistosomes developing resistance to PZQ. These results indicate that PZQ remains effective in treating schistosomiasis.
Hunting and consumption of rodents by children in the Lassa fever endemic area of Faranah, Guinea
Authors: Douno Moussa , Asampong Emmanuel , Magassouba N’Faly , Fichet-Calvet Elisabeth , Almudena Marí Sáez
Published: March 2021

As a consequence of the Ebola outbreak, human–animal contact has gained importance for zoonotic transmission surveillance. In Faranah (Upper Guinea), daily life is intertwined with rodents, such as the Natal multimammate mouse,Mastomys natalensis;a reservoir for Lassa virus (LASV). However, this contact is rarely perceived as a health risk by residents, although Lassa fever (LF) is known to be endemic to this region. Conversely, these observations remain a great concern for global health agendas. Drawing on ethnographic research involving interviews, focus group discussions, participant observations, and informal discussions over four months, we first identified factors that motivated children to hunt and consume rodents in Faranah villages, and thereafter, explored the knowledge of LF infection in children and their parents. Furthermore, we studied two dimensions of human-rodent encounters: 1) space-time of interaction and 2) factors that allowed the interaction to occur and their materiality. This approach allowed us to contextualize child-rodent contacts beyond domestic limits in the fallow fields, swamps, and at other times for this practice. A close look at these encounters provided information on rodent trapping, killing, and manipulation of cooking techniques and the risk these activities posed for the primary transmission of LASV. This research facilitated the understanding of children’s exposure toM.natalensisduring hunting sessions and the importance of rodent hunting, which is a part of their boyish identity in rural areas. Determination of when, where, why, and how children, rodents, and environments interacted allowed us to understand the exposures and risks important for human and animal surveillance programs in the Lassa-endemic region.
The influence of social support on COPD outcomes mediated by depression
Authors: Turnier Leonard , Eakin Michelle , Woo Han , Dransfield Mark , Parekh Trisha , Krishnan Jerry A. , Kanner Richard , Cooper Christopher B. , Woodruff Prescott G. , Wise Robert , Han MeiLan K. , Romero Karina , Paulin Laura M. , Peters Stephen , Drummond Brad , Bleecker Eugene R. , Bowler Russell , Comellas Alejandro P. , Couper David , Paine Robert , Martinez Fernando , Barr Graham , Putcha Nirupama , Hansel Nadia N.
Published: March 2021

Background

The purpose of this study was to explore the association between perceived social support and COPD outcomes and to determine whether the associations are mediated by depressive symptoms.

Methods

Subjects with COPD who were enrolled as part of SPIROMICS were included in this analysis. Questionnaires relating to quality of life, symptom burden, and functional status were administered at annual clinic visits for over a 3 year period. In both cross-sectional and longitudinal analyses, we examined the association of social support as measured by the FACIT-F with COPD outcomes. Cross sectional analyses used multivariable linear or logistic regression, adjusting for covariates. For longitudinal analyses, generalized linear mixed models with random intercepts were used. Models were adjusted with and without depressive symptoms and mediation analyses performed.

Results

Of the 1831 subjects with COPD, 1779 completed the FACIT- F questionnaire. In adjusted cross-sectional analysis without depressive symptoms, higher perceived social support was associated with better quality of life, well-being, 6 minute walk distance, and less dyspnea. When also adjusting for depressive symptoms, all associations between social support and COPD outcomes were attenuated and no longer statistically significant. Mediation analysis suggested that depressive symptoms explained the majority (> = 85%) of the association between social support and measured COPD outcomes. Results of the longitudinal analysis were consistent with the cross-sectional analyses. There was no association between social support and odds of exacerbations.

Conclusion

Higher social support was associated with better COPD outcomes across several measures of morbidity including quality of life, respiratory symptoms, and functional status. In addition, these associations were largely attenuated when accounting for depressive symptoms suggesting that the beneficial association of social support with COPD outcomes may be largely mediated by the association between social support and depression.

Trial registration

SPIROMICS was approved by Institutional Review Boards at each center and all participants provided written informed consent (clinicaltrials.gov:NCT01969344).
Evaluation of the effectiveness of macaíba palm seed kernel (Acrocomia intumescens drude) on anxiolytic activity, memory preservation and oxidative stress in the brain of dyslipidemic rats
Authors: de França Silva Roberta Cristina , de Souza Mikaelle Albuquerque , da Silva Jaielison Yandro Pereira , Ponciano Carolina da Silva , Bordin Viera Vanessa , de Menezes Santos Bertozzo Camila Carolina , Guerra Gerlane Coelho , de Souza Araújo Daline Fernandes , da Conceição Marta Maria , Querino Dias Celina de Castro , Oliveira Maria Elieidy , Soares Juliana Kessia Barbosa
Published: March 2021

Macaíba palm seed kernel is a source of lipids and phenolic compounds. The objective of this study was to evaluate the effects of macaíba palm seed kernel on anxiety, memory, and oxidative stress in the brain of health and dyslipidemic rats. Forty rats were used, divided into 4 groups (n = 10 each): control (CONT), dyslipidemic (DG), kernel (KG), and Dyslipidemic kernel (DKG). Dyslipidemia was induced using a high fat emulsion for 14 days before treatment. KG and DKG received 1000 mg/kg of macaíba palm seed kernel per gavage for 28 days. After treatment, anxiety tests were carried out using the Open Field Test (OFT), Elevated Plus Maze (EPM), and the Object Recognition Test (ORT) to assess memory. In the animals’ brain tissue, levels of malondialdehyde (MDA) and total glutathione (GSH) were quantified to determine oxidative stress. The data were treated with Two Way ANOVA followed by Tukey (p <0.05). Results demonstrated that the animals treated with kernel realized more rearing. DG and KG groomed less compared with CONT and DKG compared with all groups in OFT. KG spent more time in aversive open arms compared with CONT and DKG compared with all groups in EPM. Only DKG spent more time in the central area in EMP. KG and DKG showed a reduction in the exploration rate and MDA values (p <0.05). Data showed that macaíba palm seed kernel consumption induced anxiolytic-like behaviour and decreased lipids peroxidation in rats’ brains. On the other hand, this consumption by healthy and dyslipidemic animals compromises memory.
Late glacial (17,060–13,400 cal yr BP) sedimentary and paleoenvironmental evolution of the Sekhokong Range (Drakensberg), southern Africa
Authors: Kylander Malin E. , Holm Mikaela , Fitchett Jennifer , Grab Stefan , Martinez Cortizas Antonio , Norström Elin , Bindler Richard
Published: March 2021

Southern Africa sits at the junction of tropical and temperate systems, leading to the formation of seasonal precipitation zones. Understanding late Quaternary paleoclimatic change in this vulnerable region is hampered by a lack of available, reliably-dated records. Here we present a sequence from a well-stratified sedimentary infill occupying a lower slope basin which covers 17,060 to 13,400 cal yr BP with the aim to reconstruct paleoclimatic variability in the high Drakensberg during the Late Glacial. We use a combination of pollen, total organic carbon and nitrogen, δ13C, Fourier transform infrared spectroscopy attenuated total reflectance (FTIR-ATR) spectral and elemental data on contiguous samples with high temporal resolution (10 to 80 years per sample). Our data support a relatively humid environment with considerable cold season precipitation during what might have been the final stage of niche-glaciation on the adjoining southern aspects around 17,000 cal yr BP. Then, after an initial warmer and drier period starting ~15,600 cal yr BP, we identify a return to colder and drier conditions with more winter precipitation starting ~14,380 cal yr BP, which represents the first local evidence for the Antarctic Cold Reversal (ACR) in this region. On decadal to centennial timescales, the Late Glacial period was one marked by considerable climatic fluctuation and bi-directional environmental change, which has not been identified in previous studies for this region. Our study shows complex changes in both moisture and thermal conditions providing a more nuanced picture of the Late Glacial for the high Drakensburg.
The short-term impact of 3 smoked cannabis preparations versus placebo on PTSD symptoms: A randomized cross-over clinical trial
Authors: Bonn-Miller Marcel O. , Sisley Sue , Riggs Paula , Yazar-Klosinski Berra , Wang Julie B. , Loflin Mallory J. E. , Shechet Benjamin , Hennigan Colin , Matthews Rebecca , Emerson Amy , Doblin Rick
Published: March 2021

Importance

There is a pressing need for development of novel pharmacology for the treatment of Posttraumatic Stress Disorder (PTSD). Given increasing use of medical cannabis among US military veterans to self-treat PTSD, there is strong public interest in whether cannabis may be a safe and effective treatment for PTSD.

Objective

The aim of the present study was to collect preliminary data on the safety and potential efficacy of three active concentrations of smoked cannabis (i.e., High THC = approximately 12% THC and < 0.05% CBD; High CBD = 11% CBD and 0.50% THC; THC+CBD = approximately 7.9% THC and 8.1% CBD, and placebo = < 0.03% THC and < 0.01% CBD) compared to placebo in the treatment of PTSD among military veterans.

Methods

The study used a double-blind, cross-over design, where participants were randomly assigned to receive three weeks of either active treatment or placebo in Stage 1 (N = 80), and then were re-randomized after a 2-week washout period to receive one of the other three active treatments in Stage 2 (N = 74). The primary outcome measure was change in PTSD symptom severity from baseline to end of treatment in Stage 1.

Results

The study did not find a significant difference in change in PTSD symptom severity between the active cannabis concentrations and placebo by the end of Stage 1. All three active concentrations of smoked cannabis were generally well tolerated.

Conclusions and relevance

The present study is the first randomized placebo-controlled trial of smoked cannabis for PTSD. All treatment groups, including placebo, showed good tolerability and significant improvements in PTSD symptoms during three weeks of treatment, but no active treatment statistically outperformed placebo in this brief, preliminary trial. Additional well-controlled and adequately powered studies with cannabis suitable for FDA drug development are needed to determine whether smoked cannabis improves symptoms of PTSD.

Trial registration

Identifier: NCT02759185; ClinicalTrials.gov.
Anisotropic shock responses of nanoporous Al by molecular dynamics simulations
Authors: Tian Xia , Ma Kaipeng , Ji Guangyu , Cui Junzhi , Liao Yi , Xiang Meizhen
Published: March 2021

Mechanical responses of nanoporous aluminum samples under shock in different crystallographic orientations (<100>, <111>, <110>, <112> and <130>) are investigated by molecular dynamics simulations. The shape evolution of void during collapse is found to have no relationship with the shock orientation. Void collapse rate and dislocation activities at the void surface are found to strongly dependent on the shock orientation. For a relatively weaker shock, void collapses fastest when shocked along the <100> orientation; while for a relatively stronger shock, void collapses fastest in the <110> orientation. The dislocation nucleation position is strongly depended on the impacting crystallographic orientation. A theory based on resolved shear stress is used to explain which slip planes the earliest-appearing dislocations prefer to nucleate on under different shock orientations.
Comparison of gamma and x-ray irradiation for myeloablation and establishment of normal and autoimmune syngeneic bone marrow chimeras
Authors: Wittenborn Thomas Rea , Fahlquist Hagert Cecilia , Ferapontov Alexey , Fonager Sofie , Jensen Lisbeth , Winther Gudrun , Degn Søren Egedal
Published: March 2021

Murine bone marrow (BM) chimeras are a versatile and valuable research tool in stem cell and immunology research. Engraftment of donor BM requires myeloablative conditioning of recipients. The most common method used for mice is ionizing radiation, and Cesium-137 gamma irradiators have been preferred. However, radioactive sources are being out-phased worldwide due to safety concerns, and are most commonly replaced by X-ray sources, creating a need to compare these sources regarding efficiency and potential side effects. Prior research has proven both methods capable of efficiently ablating BM cells and splenocytes in mice, but with moderate differences in resultant donor chimerism across tissues. Here, we compared Cesium-137 to 350 keV X-ray irradiation with respect to immune reconstitution, assaying complete, syngeneic BM chimeras and a mixed chimera model of autoimmune disease. Based on dose titration, we find that both gamma and X-ray irradiation can facilitate a near-complete donor chimerism. Mice subjected to 13 Gy Cesium-137 irradiation and reconstituted with syngeneic donor marrow were viable and displayed high donor chimerism, whereas X-ray irradiated mice all succumbed at 13 Gy. However, a similar degree of chimerism as that obtained following 13 Gy gamma irradiation could be achieved by 11 Gy X-ray irradiation, about 85% relative to the gamma dose. In the mixed chimera model of autoimmune disease, we found that a similar autoimmune phenotype could be achieved irrespective of irradiation source used. It is thus possible to compare data generated, regardless of the irradiation source, but every setup and application likely needs individual optimization.
Development, manufacturing, and preliminary validation of a reusable half-face respirator during the COVID-19 pandemic
Authors: Anwari Vahid , Ng William C. K. , Mbadjeu Hondjeu Arnaud Romeo , Xiao Zixuan , Afenu Edem , Trac Jessica , Kazlovich Kate , Hiansen Joshua , Mashari Azad
Published: March 2021

Introduction

The COVID-19 pandemic has led to widespread shortages of N95 respirators and other personal protective equipment (PPE). An effective, reusable, locally-manufactured respirator can mitigate this problem. We describe the development, manufacture, and preliminary testing of an open-hardware-licensed device, the “simple silicone mask” (SSM).

Methods

A multidisciplinary team developed a reusable silicone half facepiece respirator over 9 prototype iterations. The manufacturing process consisted of 3D printing and silicone casting. Prototypes were assessed for comfort and breathability. Filtration was assessed by user seal checks and quantitative fit-testing according to CSA Z94.4–18.

Results

The respirator originally included a cartridge for holding filter material; this was modified to connect to standard heat-moisture exchange (HME) filters (N95 or greater) after the cartridge showed poor filtration performance due to flow acceleration around the filter edges, which was exacerbated by high filter resistance. All 8 HME-based iterations provided an adequate seal by user seal checks and achieved a pass rate of 87.5% (N = 8) on quantitative testing, with all failures occurring in the first iteration. The overall median fit-factor was 1662 (100 = pass). Estimated unit cost for a production run of 1000 using distributed manufacturing techniques is CAD $15 in materials and 20 minutes of labor.

Conclusion

Small-scale manufacturing of an effective, reusable N95 respirator during a pandemic is feasible and cost-effective. Required quantities of reusables are more predictable and less vulnerable to supply chain disruption than disposables. With further evaluation, such devices may be an alternative to disposable respirators during public health emergencies. The respirator described above is an investigational device and requires further evaluation and regulatory requirements before clinical deployment. The authors and affiliates do not endorse the use of this device at present.
Deceased by default: Consent systems and organ-patient mortality
Authors: Golsteyn Bart H. H. , Verhagen Annelore M. C.
Published: March 2021

Previous research shows that countries with opt-out consent systems for organ donation conduct significantly more deceased-donor organ transplantations than those with opt-in systems. This paper investigates whether the higher transplantation rates in opt-out systems translate into equally lower death rates among organ patients registered on a waiting list (i.e., organ-patient mortality rates). We show that the difference between consent systems regarding kidney- and liver-patient mortality rates is significantly smaller than the difference in deceased-donor transplantation rates. This is likely due to different incentives between the consent systems. We find empirical evidence that opt-out systems reduce incentives for living donations, which explains our findings for kidneys. The results imply that focusing on deceased-donor transplantation rates alone paints an incomplete picture of opt-out systems’ benefits, and that there are important differences between organs in this respect.
Reduced soil fauna decomposition in a high background radiation area
Authors: Haanes Hallvard , Gjelsvik Runhild
Published: March 2021

Decomposition of litter and organic matter is a very important soil ecosystem function where soil fauna play an important role. Knowledge of the responses in decomposition and soil fauna to different stressors is therefore crucial. However, the extent to which radioactivity may affect soil fauna is not so well known. There are some results showing effects on soil fauna at uranium mines and near Chernobyl from relatively high levels of anthropogenic radionuclides. We hypothesize that naturally occurring radionuclides affect soil fauna and thus litter decomposition, which will covary with radionuclide levels when accounting for important soil parameters. We have therefore used standardised litterbags with two different mesh sizes filled with birch leaves (Betula pubescens) to assess litter decomposition in an area with enhanced levels of naturally occurring radionuclides in the thorium (232Th) and uranium (238U) decay chains while controlling for variation in important soil parameters like pH, organic matter content, moisture and large grain size. We show that decomposition rate is higher in litterbags with large mesh size compared to litterbags with a fine mesh size that excludes soil fauna. We also find that litter dried at room temperature is decomposed at a faster rate than litter dried in oven (60⁰C). This was surprising given the associated denaturation of proteins and anticipated increased nutritional level but may be explained by the increased stiffness of oven-dried litter. This result is important since different studies often use either oven-dried or room temperature-dried litter. Taking the above into account, we explore statistical models to show large and expected effects of soil parameters but also significant effects on litter decomposition of the naturally occurring radionuclide levels. We use the ERICA tool to estimate total dose rate per coarse litterbag for four different model organisms, and in subsequent different statistical models we identify that the model including the dose rates of a small tube-shape is the best statistical model. In another statistical model including soil parameters and radionuclide distributions,226Ra (or uranium precursory radionuclides) explain variation in litter decomposition while228Ra (and precursors) do not. This may hint to chemical toxicity effects of uranium. However, when combining this model with the best model, the resulting simplified model is equal to the tube-shape dose-rate model. There is thus a need for more research on how naturally occurring radionuclides affect soil fauna, but the study at hand show the importance of an ecosystem approach and the ecosystem parameter soil decomposition.
HPLC method development/validation and skin diffusion study of caffeine, methyl paraben and butyl paraben as skin–diffusing model drugs
Authors: Mansour Randa S. H. , Hamdan Imad I. , Salem Mutaz S. H. , Khalil Enam A. , Sallam ALSayed A.
Published: March 2021

The focus of this research was to develop and validate a suitable HPLC method, which allows simultaneous determination of three proposed skin model penetrants to investigate the percutaneous diffusion behavior of their combination: caffeine, methyl paraben and butyl paraben. These penetrants were selected because they represent a wide range of lipophilicities. This model highlights the effect of combining penetrants of different molecular properties on their diffusion behavior through skin. The proposed method employed a gradient system that was systematically optimized for separation and quantification of the penetrants. The effect of the stationary phase (C18, C4 and cyano (CN)) was assessed with CN proven to be superior in terms of peak shape, retentivity and dynamic linear range. Significant differences in retention time, peak broadening, and quantifiability between different stationary phases could be demonstrated. The method was validated as per ICH guidelines Q2 (R1) with a satisfactory outcome. The method was successfully applied for real diffusion experiments, and revealed notable differences between the individual penetrants and their ternary mixture on transdermal permeation. The method could potentially be extended to determine these analytes in other related skin permeation investigations.
Radiologist observations of computed tomography (CT) images predict treatment outcome in TB Portals, a real-world database of tuberculosis (TB) cases
Authors: Rosenfeld Gabriel , Gabrielian Andrei , Wang Qinlu , Gu Jingwen , Hurt Darrell E. , Long Alyssa , Rosenthal Alex
Published: March 2021

The TB Portals program provides a publicly accessible repository of TB case data containing multi-modal information such as case clinical characteristics, pathogen genomics, and radiomics. The real-world resource contains over 3400 TB cases, primarily drug resistant cases, and CT images with radiologist annotations are available for many of these cases. The breadth of data collected offers a patient-centric view into the etiology of the disease including the temporal context of the available imaging information. Here, we analyze a cohort of new TB cases with available radiologist observations of CTs taken around the time of initial registration of the case into the database and with available follow up to treatment outcome of cured or died. Follow up ranged from 5 weeks to a little over 2 years consistent with the longest treatment regimens for drug resistant TB and cases were registered within the years 2008 to 2019. The radiologist observations were incorporated into machine learning pipelines to test various class balancing strategies on the performance of predictive models. The modeling results support that the radiologist observations are predictive of treatment outcome. Moreover, inferential statistical analysis identifies markers of TB disease spread as having an association with poor treatment outcome including presence of radiologist observations in both lungs, swollen lymph nodes, multiple cavities, and large cavities. While the initial results are promising, further data collection is needed to incorporate methods to mitigate potential confounding such as including additional model covariates or matching cohorts on covariates of interest (e.g. demographics, BMI, comorbidity, TB subtype, etc.). Nonetheless, the preliminary results highlight the utility of the resource for hypothesis generation and exploration of potential biomarkers of TB disease severity and support these additional data collection efforts.
Advancing health equity by addressing social determinants of health: Using health data to improve educational outcomes
Authors: Rattermann Mary Jo , Angelov Azure , Reddicks Tommy , Monk Jess
Published: March 2021

Data from two social determinants of health—access to health care and access to a quality education—are combined to examine the impact of health on student achievement. Data from a high poverty, high performing K-8 school revealed a significant negative correlation between the number of visits to a school-based nurse and standardized academic assessments. Fixed effect regression confirmed the effect of total number of visits to the school-based nurse on performance on standardized assessments, and also revealed that two types of visits, neurological and gastrointestinal, were predictive of student performance. Taken together, these results suggest that when students are suffering from ill health their academic performance is negatively impacted. Implications for improving health equity through data-driven educational interventions are discussed.
Immuno-informatics design of a multimeric epitope peptide based vaccine targeting SARS-CoV-2 spike glycoprotein
Authors: Chukwudozie Onyeka S. , Gray Clive M. , Fagbayi Tawakalt A. , Chukwuanukwu Rebecca C. , Oyebanji Victor O. , Bankole Taiwo T. , Adewole Richard A. , Daniel Eze M.
Published: March 2021

Developing an efficacious vaccine for SARS-CoV-2 infection is critical to stemming COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in designing an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers and 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC I and II alleles, respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. With our In silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We, therefore, propose that potential vaccine designs consider this approach.
COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients
Authors: Stewart Mark , Rodriguez-Watson Carla , Albayrak Adem , Asubonteng Julius , Belli Andrew , Brown Thomas , Cho Kelly , Das Ritankar , Eldridge Elizabeth , Gatto Nicolle , Gelman Alice , Gerlovin Hanna , Goldberg Stuart L. , Hansen Eric , Hirsch Jonathan , Ho Yuk-Lam , Ip Andrew , Izano Monika , Jones Jason , Justice Amy C. , Klesh Reyna , Kuranz Seth , Lam Carson , Mao Qingqing , Mataraso Samson , Mera Robertino , Posner Daniel C. , Rassen Jeremy A. , Siefkas Anna , Schrag Andrew , Tourassi Georgia , Weckstein Andrew , Wolf Frank , Bhat Amar , Winckler Susan , Sigal Ellen V. , Allen Jeff
Published: March 2021

Background

The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments.

Methods

Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined.

Results

Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events.

Conclusion

Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.
First estimates of inequality benchmark incomes for a range of countries
Authors: Roope Laurence S. J.
Published: March 2021

It is known that virtually all inequality measures imply the existence of a ‘benchmark income’, above which adding incremental income increases inequality, and below which it decreases inequality. Benchmark incomes can be interpreted as social reference levels that identify the richest individual for whom it would be just to subsidize their income. Despite the intuitive appeal of benchmark incomes, there have been hardly any empirical applications to date. This paper provides the first estimates of benchmark incomes for a range of contrasting countries and different inequality measures. All benchmark incomes lie far above official national poverty lines. The results suggest that economic growth together with falling inequality need not necessarily be poverty reducing.
High mutation burden in the checkpoint and micro-RNA processing genes in myelodysplastic syndrome
Authors: Moiseev Ivan Sergeevich , Tcvetkov Nikolay Yurevich , Barkhatov Ildar Munerovich , Barabanshikova Maria Vladimirovna , Bug Dmitrii Sergeevich , Petuhova Natalya Vitalievna , Tishkov Artem Valerievich , Bakin Evgenyi Alexandrovich , Izmailova Ekaterina Andreevna , Shakirova Alena Igorevna , Kulagin Alexandr Dmitrievich , Morozova Elena Vladislavovna
Published: March 2021

A number of sequencing studies identified the prognostic impact of somatic mutations in myelodysplastic syndrome (MDS). However the majority of them focused on methylation regulation, apoptosis and proliferation genes. Despite the number of experimental studies published on the role of micro-RNA processing and checkpoint genes in the development of MDS, the clinical data about mutational landscape in these genes is limited. We performed a pilot study which evaluated mutational burden in these genes and their association with common MDS mutations. High prevalence of mutations was observed in the genes studied: 54% had mutations in DICER1, 46% had mutations in LAG3, 20% in CTLA4, 23% in B7-H3, 17% in DROSHA, 14% in PD-1 and 3% in PD-1L. Cluster analysis that included these mutations along with mutations in ASXL1, DNMT3A, EZH2, IDH1, RUNX1, SF3B1, SRSF2, TET2 and TP53 effectively predicted overall survival in the study group (HR 4.2, 95%CI 1.3–13.6, p = 0.016). The study results create the rational for incorporating micro-RNA processing and checkpoint genes in the sequencing panels for MDS and evaluate their role in the multicenter studies.
Male partner involvement in HIV testing and counseling among partners of pregnant women in the Delanta District, Ethiopia
Authors: Chanyalew Haile , Girma Eshetu , Birhane Tesfaye , Chanie Muluken Genetu
Published: March 2021

Background

Only screening a pregnant mother is not satisfactory to prevent mother-to-child transmission of HIV (PMTCT). A male partner’s involvement in HIV testing and counseling is also critical for PMTCT, however, it is one of the biggest challenges in Ethiopia. This study aimed to assess a male partner’s involvement in HIV testing and counseling and associated factors among partners of pregnant women in the Delanta District, Northern Ethiopia.

Methods

A community-based cross-sectional study design was conducted in the Delanta District from March 15 to May 10, 2018. During the study period, 609 male partners were involved. A binary and multiple logistic regression model was used to examine the association between variables.

Results

Out of all, 325 (53.7% at 95% CI: 49.6 to 57.5) of male partners were involved in HIV testing and counseling in the District. Male partners who were living together, ever heard about HIV from health professionals, pregnant women’s antenatal care (ANC) visit, partner visited the PMTCT clinic with wife, and partner and wife discussion before HIV testing and counseling were factors associated with male partner involvement.

Conclusion

The proportion of male partner involvement was found to be low as compared to the national standards. Local health authorities and health care workers need to develop and conduct interventions that help partners with their wife to live together, improve their awareness about HIV and testing, ANC visit by pregnant women, and encourage having home discussion before HIV testing through counseling, by so doing finally raise the level of male partner involvement in HIV testing and counseling.
Prognostic role of perioperative acid-base disturbances on the risk of Clostridioides difficile infection in patients undergoing cardiac surgery
Authors: Rzucidło-Hymczak Anna , Hymczak Hubert , Kędziora Anna , Kapelak Bogusław , Drwiła Rafał , Plicner Dariusz
Published: March 2021

Background

It is unclear whether acid-base balance disturbances during the perioperative period may impactClostridium difficileinfection (CDI), which is the third most common major infection following cardiac surgery. We hypothesized that perioperative acid-base abnormalities including lactate disturbances may predict the probability of incidence of CDI in patients after cardiac procedures.

Methods

Of the 12,235 analyzed patients following cardiac surgery, 143 (1.2%) developed CDI. The control group included 200 consecutive patients without diarrhea, who underwent cardiac procedure within the same period of observation. Pre-, intra and post-operative levels of blood gases, as well as lactate and glucose concentrations were determined. Postoperatively, arterial blood was drawn four times: immediately after surgery and successively; 4, 8 and 12 h following the procedure.

Results

Baseline pH was lower and PaO2was higher in CDI patients (p< 0.001 andp= 0.001, respectively). Additionally, these patients had greater base deficiency at each of the analyzed time points (p< 0.001,p= 0.004,p= 0.012,p= 0.001,p= 0.016 andp= 0.001, respectively). Severe hyperlactatemia was also more common in CDI patients; during the cardiac procedure, 4 h and 12 h after surgery (p= 0.027,p= 0.004 andp= 0.001, respectively). Multivariate logistic regression analysis revealed that independent risk factors for CDI following cardiac surgery were as follows: intraoperative severe hyperlactatemia (OR 2.387, 95% CI 1.155–4.933,p= 0.019), decreased lactate clearance between values immediately and 12 h after procedure (OR 0.996, 95% CI 0.994–0.999,p= 0.013), increased age (OR 1.045, 95% CI 1.020–1.070,p< 0.001), emergent surgery (OR 2.755, 95% CI 1.565–4.848,p< 0.001) and use of antibiotics other than periprocedural prophylaxis (OR 2.778, 95% CI 1.690–4.565,p< 0.001).

Conclusion

This study is the first to show that perioperative hyperlactatemia and decreased lactate clearance may be predictors for occurrence of CDI after cardiac surgery.
Assessing the educational performance of different Brazilian school cycles using data science methods
Authors: Maia Joyce de Souza Zanirato , Bueno Ana Paula Arantes , Sato João Ricardo
Published: March 2021

Educational indicators are metrics that assist in assessing the quality of the educational system. They are often associated with economic and social factors suggested to contribute to good school performance, however there is no consensus on the impact of these factors. The main objective of this work was to evaluate the factors related to school performance. Using a data set composed by Brazilian schools’ performance (IDEB), socioeconomic and school structure variables, we generated different models. The non-linear model predicted the best performance, measured by the error and determination coefficient metrics. The heterogeneity of the importance of the variable between school cycles and regions of the country was detected, this effect may contribute to the development of public educational policies.
Medical students’ perceptions and motivations during the COVID-19 pandemic
Authors: Tempski Patricia , Arantes-Costa Fernanda M. , Kobayasi Renata , Siqueira Marina A. M. , Torsani Matheus B. , Amaro Bianca Q. R. C. , Nascimento Maria Eduarda F. M. , Siqueira Saulo L. , Santos Itamar S. , Martins Milton A.
Published: March 2021

Background

There has been a rapid increase in the number of cases of COVID-19 in Latin America, Africa, Asia and many countries that have an insufficient number of physicians and other health care personnel, and the need for the inclusion of medical students on health teams is a very important issue. It has been recommended that medical students work as volunteers, undergo appropriate training, not undertake any activity beyond their level of competence, and receive continuous supervision and adequate personal protective equipment. However, the motivation of medical students must be evaluated to make volunteering a more evidence-based initiative. The aim of our study was to evaluate the motivation of medical students to be part of health teams to aid in the COVID-19 pandemic.

Methods and findings

We developed a questionnaire specifically to evaluate medical students’ perceptions about participating in the care of patients with suspected infection with coronavirus during the COVID-19 pandemic. The questionnaire had two parts: a) one part with questions on individual characteristics, year in medical school and geographic location of the medical school and b) a second part with twenty-eight statements assessed on a 5-point Likert scale (totally agree, agree, neither agree nor disagree, disagree and totally disagree). To develop the questionnaire, we performed consensus meetings with a group of faculty and medical students. The questionnaire was sent to student organizations of 257 medical schools in Brazil and answered by 10,433 students. We used multinomial logistic regression models to analyze the data. Statements associated with greater odds ratios for participation of medical students in the COVID-19 pandemic were related to a sense of purpose or duty (“It is the duty of the medical student to put himself or herself at the service of the population in the pandemic”), altruism (“I am willing to take risks by participating in practice in the context of the pandemic”), and perception of good performance and professional identity (“I will be a better health professional for having experienced the pandemic”). Males were more prone than females to believe that only interns should participate in the care of patients with COVID-19 (odds ratio 1.36 [coefficient interval 95%:1.24–1.49]) and that all students should participate (OR 1.68 [CI:1.4–1.91]).

Conclusions

Medical students are more motivated by a sense of purpose or duty, altruism, perception of good performance and values of professionalism than by their interest in learning. These results have implications for the development of volunteering programs and the design of health force policies in the present pandemic and in future health emergencies.
Estimating the basic reproduction number for COVID-19 in Western Europe
Authors: Locatelli Isabella , Trächsel Bastien , Rousson Valentin
Published: March 2021

Objective

To estimate the basic reproduction number (R0) for COVID-19 in Western Europe.

Methods

Data (official statistics) on the cumulative incidence of COVID-19 at the start of the outbreak (before any confinement rules were declared) were retrieved in the 15 largest countries in Western Europe, allowing us to estimate the exponential growth rate of the disease. The rate was then combined with estimates of the distribution of the generation interval as reconstructed from the literature.

Results

Despite the possible unreliability of some official statistics about COVID-19, the spread of the disease appears to be remarkably similar in most European countries, allowing us to estimate an averageR0in Western Europe of 2.2 (95% CI: 1.9–2.6).

Conclusions

The value ofR0for COVID-19 in Western Europe appears to be significantly lower than that in China. The proportion of immune persons in the European population required to stop the outbreak could thus be closer to 50% than to 70%.