bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a SARS-CoV-2 rapid antigen test: potential to help reduce community spread?
Authors: Toptan Tuna , Eckermann Lisa , Pfeiffer Annika E. , Hoehl Sebastian , Ciesek Sandra , Drosten Christian , Corman Victor M.
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from symptomatic patients with COVID-19, but also from asymptomatic individuals. Therefore, robust surveillance and timely interventions are essential for the control of virus spread within the community. In this regard the frequency of testing and speed of reporting, but not the test sensitivity alone, play a crucial role. In order to reduce the costs and meet the expanding demands in real-time RT-PCR (rRT-PCR) testing for SARS-CoV-2, complementary assays, such as rapid antigen tests, have been developed. Rigorous analysis under varying conditions is required to assess the clinical performance of these tests and to ensure reproducible results. We evaluated the sensitivity and specificity of a recently licensed rapid antigen test using 137 clinical samples in two institutions. Test sensitivity was between 88.2-89.6% when applied to samples with viral loads typically seen in infectious patients. Of 32 rRT-PCR positive samples, 19 demonstrated infectivity in cell culture, and 84% of these samples were reactive with the antigen test. Seven full-genome sequenced SARS-CoV-2 isolates and SARS-CoV-1 were detected with this antigen test, with no cross-reactivity against other common respiratory viruses. Numerous antigen tests are available for SARS-CoV-2 testing and their performance to detect infectious individuals may vary. Head-to-head comparison along with cell culture testing for infectivity may prove useful to identify better performing antigen tests. The antigen test analyzed in this study is easy-to-use, inexpensive, and scalable. It can be helpful in monitoring infection trends and thus has potential to reduce transmission.
Malaria awareness of adults in high, moderate and low transmission settings: A cross-sectional study in rural East Nusa Tenggara Province, Indonesia
Authors: Guntur Robertus Dole , Kingsley Jonathan , Islam Fakir M. Amirul
Published: December 2020

Introduction

The Indonesian roadmap to malaria elimination in 2009 indicated that the nation is progressing towards achieve malaria elimination by 2030. Currently, most of the districts in the Western part of Indonesia have eliminated malaria, however, none of the districts in East Nusa Tenggara Province (ENTP) have met set targets. This study aims to investigate the status of malaria awareness of rural adults in the ENTP.

Methods

A cross-sectional study was conducted between October and December 2019 in high, moderate, and low malaria endemic settings (MES) in ENTP. 1495 participants recruited by multi-stage sampling method were interviewed using a validated questionnaire, after obtaining informed consent. A malaria awareness index was developed based on ten questions. Logistic regression method was applied to investigate the significance of associations of malaria awareness with the three malaria endemic settings.

Results

Participants were between the age of 18 and 89 years old, 51.4% were female and 45.5% had completed primary education. Malaria awareness index was very low (48.8%, 95% confidence interval (CI): 45.2 – 52.4). Malaria awareness of rural adults residing in low endemic settings was three times higher compared to those were living in high endemic settings (Odds ratio (OR): 3.11, 95% CI: 2.40 – 4.03, p < 0.001) and the basic malaria knowledge for participants living in low malaria endemic setting was almost five times higher than that of in high endemic setting (OR: 4.66, 95% CI: 3.50 – 6.20, p < 0.001). Of total participants, 81.3% (95% CI: 79.1 – 83.5) were aware that malaria could be prevented and 75.1% (95% CI: 72.6 – 77.6) knew at least one prevention measure. Overall, the awareness of fever as the main symptom of malaria, mosquito bites as the transmission mode of malaria, and seeking treatment within 24 hours when suffering with malaria was poor, 37.9% (95% CI: 33.9 – 41.9), 59.1% (95% CI: 55.9 – 62.3), and 46.0% (95% CI: 42.3 – 49.7) respectively. The poor level of awareness was statistically significantly different amongst three MES, the level of awareness was the lowest in the high endemic setting.

Conclusion

Malaria awareness of rural adults needs to be improved to address Indonesia’s national roadmap to malaria elimination. Results indicate public health programs at a local government level should incorporate the malaria awareness index in their key strategic intervention packages to address local malaria awareness.
Synthetic Data Generation for Improved covid-19 Epidemic Forecasting
Authors: Bannur Nayana , Shah Vishwa , Raval Alpan , White Jerome
Published: December 2020

During an epidemic, accurate long term forecasts are crucial for decision-makers to adopt appropriate policies and to prevent medical resources from being overwhelmed. This came to the forefront during the covid-19 pandemic, during which there were numerous efforts to predict the number of new infections. Various classes of models were employed for forecasting including compartmental models and curve-fitting approaches. Curve fitting models often have accurate short term forecasts. Their parameters, however, can be difficult to associate with actual disease dynamics. Compartmental models take these dynamics into account, allowing for more flexible and interpretable models that facilitate qualitative comparison of scenarios. This paper proposes a method of strengthening the forecasts from compartmental models by using short term predictions from a curve fitting approach as synthetic data. We discuss the method of fitting this hybrid model in a generalized manner without reliance on region specific data, making this approach easy to adapt. The model is compared to a standard approach; differences in performance are analyzed for a diverse set of covid-19 case counts.
Association of COVID-19 spread with on-demand testing
Authors: Robertson Leon S.
Published: December 2020

Comparisons of COVID-19 testing policies in 99 countries indicate that testing on demand is associated with an increase in cases 14 days after the tests. Adjusted for number of new cases and the positivity rate, for each 10,000 negative tests on a given day there were 90-110 new cases in 14 days that would not have otherwise occurred. Approximately 3.1 million or 21 percent of new cases in periods of on-demand testing are likely due to that policy through early November 2020. During periods in a given country when only persons with symptoms were tested, or persons with symptoms and key vulnerable populations were tested, negative tests were associated with fewer new cases 14 days out. Apparently when tests are available on demand, those who test negative are engaging in activities that increase the risk of exposure.
N95 Filtering Facepiece Respirators Remain Effective After Extensive Reuse During the COVID-19 Pandemic
Authors: Fabre Valeria , Cosgrove Sara E. , Hsu Yea-Jen , Jones George , Helsel Taylor , Bukowski James , Sobota Mark , Sick-Samuels Anna C. , Milstone Aaron M. , Maragakis Lisa L. , Rock Clare ,   for the Centers for Disease Control and Prevention Epicenters Program
Published: December 2020

In a cross-sectional evaluation of healthcare worker reuse of their own 3M N95 respirators, 83% (76/92) passed the seal check and the fit-test after a median of 40 repeated donnings. The user seal-check had 31% sensitivity to detect N95 respirator failure but 100% specificity.
Self-harm and the COVID-19 pandemic: a study of factors contributing to self-harm during lockdown restrictions
Authors: Hawton Keith , Lascelles Karen , Brand Fiona , Casey Deborah , Bale Liz , Ness Jennifer , Kelly Samantha , Waters Keith
Published: December 2020

Introduction

The COVID-19 pandemic and resulting public health measures may have major impacts on mental health, including on self-harm. We have investigated what factors related to the pandemic influenced hospital presentations following self-harm during lockdown in England.

Method

Mental health clinicians assessing individuals aged 18 years and over presenting to hospitals in Oxford and Derby following self-harm during the period March 23rd to 17th May 2020 recorded whether the self-harm was related to the impact of COVID- 19 and, if so, what specific factors were relevant. These factors were organized into a classification scheme. Information was also collected on patients’ demographic characteristics, method of self-harm and suicide intent.

Results

Of 228 patients assessed, in 46.9% (N=107) COVID-19 and lockdown restrictions were identified as influencing self-harm. This applied more to females than males (53.5%, N=68/127 v 38.6%, N=39/101, χ2 = 5.03, p=0.025), but there were no differences in age, methods of self-harm or suicide intent between the two groups. The most frequent COVID-related factors were mental health issues, including new and worsening disorders, and cessation or reduction of services (including absence of face-to-face support), isolation and loneliness, reduced contact with key individuals, disruption to normal routine, and entrapment. Multiple, often inter- connected COVID-related factors were identified in many patients.

Conclusions

COVID-related factors were identified as influences in nearly half of individuals presenting to hospitals following self-harm in the period following introduction of lockdown restrictions. Females were particularly affected. The fact that mental health problems, including issues with delivery of care, predominated has implications for organisation of services during such periods. The contribution of isolation, loneliness and sense of entrapment highlight the need for relatives, friends and neighbours to be encouraged to reach out to others, especially those living alone. The classification of COVID-related factors can be used as an aide-memoire for clinicians.
Fatigue outcomes following coronavirus or influenza virus infection: A systematic review and meta-analysis
Authors: Poole-Wright Kim , Gaughran Fiona , Evans Rachael , Chalder Trudie
Published: December 2020

Objectives

Fatigue is a pervasive clinical symptom for many infected with respiratory viruses such as influenza or coronaviruses. Prior evidence from influenza and coronavirus epidemics suggest that fatigue symptomology may continue beyond the acute phase, lasting for several months to several years post-discharge. This systematic review aimed to examine long-term fatigue prevalence among survivors and among communities, as well as investigate the current evidence for associated factors.

Design

Systematic review and meta-analysis.

Setting

Hospitalised and community samples.

Participants

Patient populations with a confirmed diagnosis of a named influenza virus or coronavirus.

Main outcomes measured

Fatigue, fatigue syndromes

Results

Ten studies met the inclusion criteria for a pooled prevalence analysis and five studies were identified as eligible for a means differences analysis. A fatigue prevalence of 41% (95% CI 0.299-0.488) was found among a total population of 1,310. Using the ‘vitality’ subscale of the SF-36 as a proxy for fatigue, the estimate for means differences indicated a lower mean vitality score for survivors compared to population norms (M -1.523, CI -13.53 – 10.48), although this was not significant (p = 0.803). The most common associations with fatigue were PTSD, depression and anxiety, female gender and higher age.

Conclusions

This study reveals that a significant proportion of survivors (41%) experienced fatigue following their recovery from novel respiratory viruses such as SARS, MERS, SARS-CoV2 or influenza and that this fatigue can be long-lasting. Also, some factors such as female gender and psychological factors may contribute to continuing fatigue outcomes for this population.

Strengths and limitations

(a) this study provides support for long-term fatigue outcomes in people with a confirmed influenza, SARS, MERS, SARS-CoV2 virus infection (b) the study suggests individual, psychological and social factors are associated with fatigue, (c) findings are limited by the availability of fatigue data and lack of pre-morbid fatigue information; (d) a meta-analysis on the associations was prohibited by the small number of studies investigating long-term fatigue correlates and (e) the heterogeneity of the studies (>75%) suggests the pooled estimates should be interpreted with caution.
Retrospective analysis ofThe Two Sister Studyusing haplotype-based association testing to identify loci associated with early-onset breast cancer
Authors: Gilbert James R. , Cray James J. , Losee Joseph E. , Cooper Gregory M.
Published: December 2020

Breast cancer is a polygenic disorder and is the leading cause of cancer related mortality among women. Early-onset breast cancer (EOBC) is diagnosed in women prior to 45 years-of-age and is associated with worse clinical outcomes, a more aggressive disease phenotype, and poor prognosis for disease-free survival. While substantial progress has been made in defining the genetics of breast cancer, EOBC remains less well understood. In the current study we perform a retrospective analysis of data derived fromThe Two Sister Study. The use of alternate strategies for handling age-at-diagnosis in conjunction with haplotype-based methods yielded novel findings that help to explain the heritability of EOBC. These findings are validated through comparison against discordant sibs fromThe Two Sister Studyas well as using data derived The Cancer Genome Atlas (TCGA).
PD-L1 expression is associated with higher residual cancer burden in triple-negative breast cancers with residual disease after neoadjuvant chemotherapy
Authors: Grandal Beatriz , Mangiardi-Veltin Manon , Laas Enora , Laé Marick , Meseure Didier , Bataillon Guillaume , El-Alam Elsy , Darrigues Lauren , Dumas Elise , Daoud Eric , Vincent-Salomon Anne , Talagrand Laure-Sophie , Pierga Jean-Yves , Reyal Fabien , Hamy Anne-Sophie
Published: December 2020

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well understood. This is an important issue as immune checkpoint inhibitors (ICI) are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression (E1L3N clone, cutoff for positivity: ≥ 1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of surgical specimens of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p=0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with DFS (p=0.38) or OS (p=0.48), but high Ki67 levels after NAC were strongly associated with a poor prognosis (DFS p=0.0014 and OS p=0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.
Strong association between Apgar score at 5 minutes and neonatal survival among at-risk neonates
Authors: Dueñas-Espín Iván , Aguilar-Molina Andrea , Aguinaga Fernando , Armijos-Acurio Luciana , Jimbo Ruth , León-Cáceres Ángela , Rivadeneira María F. , Rivera-Guerra Silvana , Sánchez Xavier
Published: December 2020

Objective

To assess the association between 5-minutes Apgar score and neonatal survival among at-risk neonates.

Design

Retrospective survival analysis.

Setting

Ecuadorian neonates who died at ≤28 days of life.

Patients

We analyzed the nationwide neonatal deaths registered by the Ministry of Public Health of Ecuador between January 2014 to September 2017.

Main outcome measures

We performed a survival analysis and estimated adjusted hazard ratios (HR)pereach 5-minutes Apgar scorestratum, by Cox proportional hazards models.

Results

We included in the study 2893 neonates, 1380 (48%) were female and had a median (P25 to P75) gestational age at birth of 31 (27 to 36) weeks. On univariate analyses, the median survival time in days of life was significantly longer per each increase in the 5-minutes Apgar score, as follows: 0.2 days for ≤4 points, 2 days for 5 points, 2.9 days for 6 points, 3.1 days for 7 points, 3.8 days for 8 points, 4.4 days for 9 points, and 5.5 days for 10 points. On multivariate analyses, and after adjusting for individual and contextual variables, and considering an Apgar score of 9 to 10 points as the reference, the HR was 32% (95% CI: 27% to 37%) higher per each decrease in the Apgar score category of two-to-three points (p-valuefor trend <0.01).

Conclusions

There is a strong direct association between Apgar score at 5 minutes and neonatal survival in neonates considered at-risk. This association is independent of gestational age and other neonatal determinants of neonatal mortality.
GeneTerpret: a customizable multilayer approach to genomic variant prioritization and interpretation
Authors: Manshaei Roozbeh , DeLong Sean , Andric Veronica , Joshi Esha , Okello John B. A. , Dhir Priya , Farncombe Kirsten M. , Kalbfleisch Kelsey , Somerville Cherith , Jobling Rebekah K. , Scherer Stephen W. , Kim Raymond H. , Hosseini S. Mohsen
Published: December 2020

Variant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually scouring through a multitude of independent databases, often with the aid of several and mostly independent computational tools.

To streamline the variant interpretation process, we developedGeneTerpretplatform that collates data from current interpretation tools and databases, and applies a phenotype-driven query to categorize the variants identified in a given genome. The platform assigns quantitative validity scores to genes by query and assembly of the current genotype-phenotype data, sequence homology, molecular interactions, expression data, and animal models. The platform uses the American College of Medical Genetics (ACMG) criteria to categorize variants into five tiers (from benign to pathogenic). The platform then outputs a prioritized list of potentially causal variants/genes in a given genome for a specific case.

GeneTerpretis a flexible and free platform designed to streamline the variant interpretation process through a unique interface, with improved ease, speed and accuracy. This unique integrated system provides effective validity and pathogenicity modules to assess genetic variant data and allows the user to decide which output and impact level should be considered in this process. The platform can be accessed and used online athttps://geneterpret.com.
Ppard Is Essential in Acceleration of Pancreatic Ductal Adenocarcinoma Development by High-Fat Diet in MutantKrasMice
Authors: Liu Yi , Deguchi Yasunori , Wei Daoyan , Moussalli Micheline J. , Li Donghui , Wang Huamin , Valentin Lovie Ann , Colby Jennifer K. , Liu Fuyao , Wang Jing , Zheng Xiaofeng , Ji Baoan , Yao James C. , Zuo Xiangsheng , Shureiqi Imad
Published: December 2020

Pro-obesity high-fat diet is linked with an increased incidence of pancreatic cancers, but the molecular underpinnings of this association remain poorly understood. Here, we report that PPARD is upregulated in pancreatic intraepithelial neoplasia lesions (PanINs) at early stages of pancreatic tumorigenesis in humans and mutantKrasmice. Transgenic overexpression of Ppard in pancreatic epithelial cells drastically accelerates the development and progression of pancreatic ductal adenocarcinoma in mutantKrasmice when activated by feeding the mice with a high-fat diet or a diet containing GW501516 (50 mg/kg), a selective PPARD agonist. In contrast, pancreatic Ppard genetic deletion significantly suppressed the promotion of pancreatic tumorigenesis by these diets. Mechanistically, we found that this Ppard hyperactivation in pancreatic epithelial cells of mutantKrasmice increased production of chemokines and cytokines (e.g., CcI2, CcI4-5, CxcI5 and II6), leading to the robustly increased recruitment of myeloid-derived suppressor cells and macrophages into pancreata, which fostered an immune suppressive microenvironment and subsequently accelerated pancreatic ductal adenocarcinoma development and progression. Our findings demonstrate that PPARD plays an essential role in the promotion of pancreatic tumorigenesis by a high-fat diet. Targeted inhibition of PPARD activation is a potential interventive strategy for pancreatic cancer prevention and therapy.
Decontamination of Common Healthcare Facility Surfaces Contaminated with SARS-CoV-2 using Peracetic Acid Dry Fogging
Authors: Cutts Todd , Kasloff Samantha , Safronetz David , Krishnan Jay
Published: December 2020

Background

The SARS-Cov-2 pandemic has highlighted the urgent need for safe and effective surface decontamination methods, particularly in healthcare settings.

Methods

The effectiveness of peracetic acid (PAA) dry fogging in decontaminating common healthcare setting surfaces was evaluated after experimentally contaminating nine surfaces (stainless steel, latex painted wood, unsealed hardwood, melamine countertop, vinyl flooring, clear plastic, faux leather, computer keyboard button and smartphone touch screen) with more than 106 TCID50 of SARS-CoV-2.

Results

When fumigated with PAA dry fog for an hour, no infectious SARS-CoV-2 virus was recovered from experimentally inoculated coupons of representing nine different surface types. In contrast, high titer recovery of infectious virus was demonstrated for corresponding untreated drying controls of the same materials.

Conclusion

Standard surface decontaminating processes, including sprays and wipes, are laborious and often cannot completely decontaminate sensitive electronic equipment. The ease of use, low cost and overall effectiveness of a PAA dry fogging suggest it should be considered for decontaminating settings, particularly intensive care units where severely ill SARS-CoV-2 patients are cared for.
Double Mammary In Situ: Predicting Feasibility of Right Mammary Artery In Situ for Circumflex Coronary Artery System
Authors: Margaryan Rafik , Latta Daniele Della , Bianchi Giacomo , Martini Nicola , Gori Andrea , Solinas Marco
Published: December 2020

Objectives

Double (bilateral) mammary artery in situ revascularization seems less attractive to surgeons because of limited mammary length of right mammary artery, scare, or no means of its length estimation.

Methods

We’ve selected patients who have used bilateral mammary artery for revascularization and divvied them into two groups: in situ and y-graft groups. We have used preoperative chest x-rays to build a predictive model with neural networks that could predict feasibility of in situ bilateral mammary revascularization.

Results

The predictive model was able to predict a positive outcome with 96% percent accuracy (p < 0.01). Models sensitivity and specificity were 96% and 95% respectively. Neural networks can be used to predict double mammary feasibility using chest x-rays. Model is capable of predicting positive outcomes with 95% accuracy.

Conclusions

Chest x-ray base model can accurately predict the feasibility of in situ bilateral mammary artery revascularization.
Seroconversion stages COVID19 into distinct pathophysiological states
Authors: Galbraith Matthew D. , Kinning Kohl T. , Sullivan Kelly D. , Baxter Ryan , Araya Paula , Jordan Kimberly R. , Russell Seth , Smith Keith P. , Granrath Ross E. , Shaw Jessica , Dzieciatkowska Monika , Ghosh Tusharkanti , Monte Andrew A. , D’Alessandro Angelo , Hansen Kirk C. , Bennett Tellen D. , Hsieh Elena W.Y. , Espinosa Joaquin M.
Published: December 2020

COVID19 is a heterogeneous medical condition involving a suite of underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Seronegative COVID19 patients harbor hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, neutropenia, lymphopenia and thrombocytopenia. In seropositive patients, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased markers of platelet activation, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.
Genome-Wide Polygenic Scores for Common Traits and Psychiatric Disorders Identify Young Children with Risk for Suicides
Authors: Joo Yoonjung Yoonie , Moon Seo-Yoon , Wang Hee-Hwan , Kim Hyeonjin , Lee Eun-Ji , Jung Seung-Min , Ahn Woo-Young , Choi Incheol , Kim Jae-Won , Cha Jiook
Published: December 2020

Background

Suicide is the leading cause of death in youth worldwide.1 Identifying children with high risk for suicide remains challenging.2 Here we test the extents to which genome-wide polygenic scores (GPS) for common traits and psychiatric disorders are linked to the risk for suicide in young children.

Methods

We constructed GPSs of 24 traits and psychiatric disorders broadly related to suicidality from 8,212 US children with ages of 9 to 10 from the Adolescent Brain Cognitive Development study. We performed multiple logistic regression to test the association between childhood suicidality, defined as suicidal ideation or suicidal attempt, and the GPSs. Machine learning techniques were used to test the predictive utility of the GPSs and other phenotypic outcomes on suicide and suicidal behaviors in the youth.

Outcomes

We identified three GPSs significantly associated with childhood suicidality: Attention deficit hyperactivity disorder (ADHD) (P = 2.83×10−4; odds ratio (OR) = 1.12, FDR correction), general happiness with belief that own life is meaningful (P = 1.30×10−3; OR = 0.89) and autism spectrum disorder (ASD) (P = 1.81×10−3; OR = 1.14). Furthermore, the ASD GPS showed significant interaction with ELS such that a greater polygenic score in the presence of a greater ELS has even greater likelihood of suicidality (with active suicidal ideation, P = 1.39×10−2, OR = 1.11). In machine learning predictions, the cross validated and optimized model showed an ROC-AUC of 0.72 and accuracy of 0.756 for the hold-out set of overall suicidal ideation prediction, and showed an ROC-AUC of 0.765 and accuracy of 0.750 for the hold-out set of suicidal attempts.

Interpretation

Our results show that childhood suicidality is linked to the GPSs for psychiatric disorders, ADHD and ASD, and for a common trait, general happiness, respectively; and that GPSs for ASD and insomnia, respectively, have synergistic effects on suicidality via an interaction with early life stress. By providing the quantitative account of the polygenic and environmental factors of childhood suicidality in a large, representative population, this study shows the potential utility of the GPS in investigation of childhood suicidality for early screening, intervention, and prevention.
Features and outcomes of secondary sepsis and urinary tract infections in COVID-19 patients treated with stem cell nebulization
Authors: Torres Zambrano Gina M. , Rivero Rene Antonio , Villegas Valverde Carlos A. , Carmenate Yendry Ventura
Published: December 2020

Background

COVID-19 is the defining global crisis of our time. Secondary complication such as urinary tract infections and sepsis, worsen the already established problem, creating a new challenge.

Objective

To characterize the features and outcomes in COVID-19 patients with sepsis and urinary tract infection.

Methods

An observational and analytical study was conducted within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center, were the patients received a nebulization therapy with the use of autologous stem cells (group A). Those patients were compared with a not stem cells treated control arm (group B), and both received the UAE COVID 19 standard management. An analysis of the culture samples, antimicrobial agents and the efficacy of the therapy on patient’s outcomes was done.

Results

A significant difference between the groups was found in the UTI incidence (p=*0.0206). Patients in group A showed a lower tendency to sepsis in comparison with group B (7% vs 21%), HR=0.35, (95% Confidence Interval: 0.13 – 0.91), p=0.0175. It was calculated a NNT=7.3. Candida albicans was the most frequently agent causing sepsis and UTI. The massive use of broad-spectrum antimicrobials was striking.

Conclusions

We found a protective factor of stem cells against secondary infection in COVID 19 cases, in terms of sepsis and UTI. The suggested immunomodulatory effect of stem cells offers a therapeutic strategy to manage the disease and avoid several complications. Antimicrobial agents can lead to increased opportunistic infections, so a rational approach to these treatments must be considered.
Visualizing subcellular structures in neuronal tissue with expansion microscopy
Authors: Campbell Logan A. , Pannoni Katy E. , Savory Niesha A. , Lal Dinesh , Farris Shannon
Published: December 2020

Protein expansion microscopy (proExM) is a powerful technique that crosslinks proteins to a swellable hydrogel to physically expand and optically clear biological samples. The resulting increased resolution (~70 nm) and physical separation of labeled proteins make it an attractive tool for studying the localization of subcellular organelles in densely packed tissues, such as the brain. However, the digestion and expansion process greatly reduces fluorescence signals making it necessary to optimize ExM conditions per sample for specific end goals. Here we describe a proExM workflow optimized for resolving subcellular organelles (mitochondria and the Golgi apparatus) and reporter-labeled spines in fixed mouse brain tissue. By directly comparing proExM staining and digestion protocols, we found that immunostaining before proExM and using a proteinase K based digestion for 8 hours consistently resulted in the best fluorescence signal to resolve subcellular organelles while maintaining sufficient reporter labeling to visualize spines and trace individual neurons. With these methods, we more accurately quantified mitochondria size and number and better visualized Golgi ultrastructure in reconstructed CA2 neurons of the hippocampus.
Swallowing-related neural oscillation: An intracranial EEG study
Authors: Hashimoto Hiroaki , Takahashi Kazutaka , Kameda Seiji , Yoshida Fumiaki , Maezawa Hitoshi , Oshino Satoru , Tani Naoki , Khoo Hui Ming , Yanagisawa Takufumi , Yoshimine Toshiki , Kishima Haruhiko , Hirata Masayuki
Published: December 2020

Swallowing is a unique movement due to the indispensable orchestration of voluntary and involuntary movement. The transition from voluntary to involuntary swallowing is executed on the order of milliseconds. We hypothesized that its neural mechanism is revealed by high frequency cortical activities. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus, and cortical oscillatory changes, including high γ band (75–150 Hz) and β band (13–30 Hz) were investigated at the time of mouth-opening, water-injection, and swallowing. High γ power increases associated with mouth-opening were observed in the ventrolateral prefrontal cortex with water-injection in the lateral central sulcus and with swallowing in the region along the Sylvian fissure. Mouth-opening induced a β power decrease, which continued until the completion of swallowing. The high γ burst activity was focal and specific to swallowing, however, the β activities were extensive and not specific to swallowing. At the boundary time between voluntary and involuntary swallowing, swallowing-related high γ power achieved the peak, and subsequently, the power decreased. We demonstrated three distinct activities related to mouth-opening, water-injection, and swallowing induced at different timings, using high γ activities. The peak of high γ power related to swallowing suggests that during voluntary swallowing phases, the cortex is the main driving force for swallowing rather than the brain stem.
Dynamic larval dispersal can mediate the response of marine metapopulations to multiple climate change impacts
Authors: Bani Ridouan , Marleau Justin , Fortin Marie-Josée , Daigle Rémi M. , Guichard Frédéric
Published: December 2020

Climate change is having multiple impacts on marine species characterized by sedentary adult and pelagic larval phases, from increasing adult mortality to changes in larval duration and ocean currents. Recent studies have shown impacts of climate change on species persistence through direct effects on individual survival and development, but few have considered the indirect effects mediated by ocean currents and species traits such as pelagic larval duration. We used a density-dependent and stochastic metapopulation model to predict how changes in adult mortality and dynamic connectivity can affect marine metapopulation stability. We analyzed our model with connectivity data simulated from a biophysical ocean model of the northeast Pacific coast forced under current (1998-2007) and future (2068-2077) climate scenarios in combination with scenarios of increasing adult mortality and decreasing larval duration. Our results predict that changes of ocean currents and larval duration mediated by climate change interact in complex and opposing directions to shape local mortality and metapopulation connectivity with synergistic effects on regional metapopulation stability: while species with short larval duration are most sensitive to temperature-driven reduction in larval duration, the response of species with longer larval duration are mostly mediated by changes in both the mean and variance of larval connectivity driven by ocean currents. Our results emphasize the importance of considering the spatiotemporal structure of connectivity in order to predict how the multiple effects of climate change will impact marine populations.
Shaping sustainable harvest boundaries for marine populations despite estimation bias
Authors: Goto Daisuke , Devine Jennifer A. , Umar Ibrahim , Fischer Simon H. , De Oliveira José A. A. , Howell Daniel , Jardim Ernesto , Mosqueira Iago , Ono Kotaro
Published: December 2020

Biased estimates of population status are a pervasive conservation problem. This problem has plagued assessments of commercial exploitation of marine species and can threaten the sustainability of both populations and fisheries. We develop a computer-intensive approach to minimize adverse effects of persistent estimation bias in assessments by optimizing operational harvest measures (harvest control rules) with closed-loop simulation of resource–management feedback systems: management strategy evaluation. Using saithe (Pollachius virens), a bottom-water, apex predator in the North Sea, as a real-world case study, we illustrate the approach by first diagnosing robustness of the existing harvest control rule and then optimizing it through propagation of biases (overestimated stock abundance and underestimated fishing pressure) along with select process and observation uncertainties. Analyses showed that severe biases lead to overly optimistic catch limits and then progressively magnify the amplitude of catch fluctuation, thereby posing unacceptably high overharvest risks. Consistent performance of management strategies to conserve the resource can be achieved by developing more robust control rules. These rules explicitly account for estimation bias through a computational grid search for a set of control parameters (threshold abundance that triggers management action,Btrigger, and target exploitation rate,Ftarget) that maximize yield while keeping stock abundance above a precautionary level. When the biases become too severe, optimized control parameters– for saithe, raisingBtriggerand loweringFtarget–would safeguard against overharvest risk (<3.5% probability of stock depletion) and provide short-term stability in catch limit (<20% year-to-year variation), thereby minimizing disruption to fishing communities. The precautionary approach to fine-tuning adaptive risk management through management strategy evaluation offers a powerful tool to better shape sustainable harvest boundaries for exploited resource populations when estimation bias persists. By explicitly accounting for emergent sources of uncertainty our proposed approach ensures effective conservation and sustainable exploitation of living marine resources even under profound uncertainty.

Open Research Statement

Data sets and code utilized for this research are available on Figshare. DOI:https://doi.org/10.6084/m9.figshare.13281266
Pollinators mediate floral microbial diversity and network under agrochemical disturbance
Authors: Wei Na , Russell Avery L. , Jarrett Abigail R. , Ashman Tia-Lynn
Published: December 2020

How pollinators mediate microbiome assembly in the anthosphere is a major unresolved question of theoretical and applied importance in the face of anthropogenic disturbance. We addressed this question by linking visitation of diverse pollinator functional groups (bees, wasps, flies, butterflies, beetles, true bugs and other taxa) to the key properties of floral microbiome (microbial α- and β-diversity and microbial network) under agrochemical disturbance, using a field experiment of bactericide and fungicide treatments on cultivated strawberries that differ in flower abundance. Structural equation modeling was used to link agrochemical disturbance and flower abundance to pollinator visitation to floral microbiome properties. Our results revealed that (1) pollinator visitation influenced the α- and β-diversity and network centrality of floral microbiome, with different pollinator functional groups affecting different microbiome properties; (2) flower abundance influenced floral microbiome both directly by governing the source pool of microbes and indirectly by enhancing pollinator visitation; and (3) agrochemical disturbance affected floral microbiome primarily directly by fungicide, and less so indirectly via pollinator visitation. These findings improve the mechanistic understanding of floral microbiome assembly, and may be generalizable to many other plants that are visited by diverse insect pollinators in natural and managed ecosystems.
More from less: Genome skimming for nuclear markers for animal phylogenomics, a case study using decapod crustaceans
Authors: Tan Mun Hua , Gan Han Ming , Bracken-Grissom Heather , Chan Tin-Yam , Grandjean Frederic , Austin Christopher M.
Published: December 2020

Low coverage genome sequencing is rapid and cost-effective for recovering complete mitochondrial genomes for animal phylogenomics. The recovery of high copy number nuclear genes, including histone H3, 18S and 28S ribosomal RNAs, is also possible using this approach. In this study, we explore the potential of the genome skimming (GS) to recover additional nuclear genes from shallow sequencing projects. Using anin silicobaited approach, we recover three additional core histone genes (H2A, H2B and H4) from our existing collection of low coverage decapod crustacean dataset (99 species, 69 genera, 38 families, 10 infraorders). Phylogenetic analyses based on various combinations of mitochondrial and nuclear genes for the entire decapod dataset and 40 species of crayfish (Infraorder Astacidea) found that the evolutionary rates for different classes of genes varied widely. The highlight being a very high level of congruence found between trees from the six nuclear genes and those derived from the mitogenome sequences for freshwater crayfish. These findings indicate that nuclear genes recovered from the same genome skimming datasets designed to obtain mitogenomes can be used to support more robust and comprehensive phylogenetic analyses. Further, a search for additional intron-less nuclear genes identified several high copy number genes across the decapod dataset and recovery of NaK, PEPCK and GAPDH gene fragments is possible at slightly elevated coverage, suggesting the potential and utility of GS in recovering even more nuclear genetic information for phylogenetic studies from these inexpensive and increasingly abundant datasets.
Seasonality and Progression of COVID-19 among Countries With or Without Lock-downs.
Authors: Sagripanti Dr. Jose-Luis
Published: December 2020

Early predictions by computer simulation of 7 billion infections and 40 million deaths by COVID-19 during 2020 alone if lock-downs and other confining measures were not enforced may have justified restrictive policies mandated by governments of 165 countries. The objective of the present study was to determine differences between the infection and death rate in countries that established early, nation-wide curfews, state-at-home orders, or lock-downs versus countries that did not mandated any lock-downs to deal with the COVID-19 crisis. The analyzed epidemiological data indicates that lock-downs, and other confining measures had no effect on the chances of healthy individuals becoming infected with- ir dying off SARS-CoV-2. The highest incidence of COVID-19 infection progressed from countries in northern latitudes, where it was winter at the beginning of the pandemic, to countries in the southern hemisphere in July 21, 2020 were winter was starting.This trend reversed again during the last quarter of 2020. A considerable (4-fold) increase in COVID-19 infection rate is observed between fall and beginning of winter in countries in the southern hemisphere. This seasonal progression correlates with the variation in the germicidal solar flux received by these countries, suggesting that infectious virus in the environment plays a role in the evolution of COVID-19. In addition, hypotheses are presented that could explain the recurrent new spikes of COVID-19 as well as the mortality of SARS-Co V-2 observed in some developed countries higher than the mortality rate reported in several developing countries.
Personalise Dose Regimen of Vitamin D3 Using Physiologically-Based Pharmacokinetic Modelling
Authors: Huang Zhonghui , You Tao
Published: December 2020

Background and Aim

Vitamin D3 (i.e. cholecalciferol) produces an active metabolite 25-hydroxyvitamin D3 (i.e. 25(OH)D3) to promote intestinal calcium absorption. Given high population heterogeneity in 25(OH)D3 plasma concentration profiles, vitamin D3 dose regimen needs to be personalised. The objective of this study is to establish a model that accurately predicts 25(OH)D3 pharmacokinetics (PK) on an individual level to enable selection of an appropriate dose regimen for anyone.

Methods

Plasma or serum concentrations of Vitamin D3 and 25(OH)D3 from different trials were compiled together. We then developed a series of Physiologically-Based Pharmacokinetic (PBPK) models for vitamin D3 and 25(OH)D3 in a stepwise manner to select the best model to optimally recapitulate the 10μg and 100μg daily dose data. Each arm of the clinical trials was simulated individually. Model predictions were qualified with PK data at other doses.

Results

From data exploration, we observed an interesting phenomenon: the increase in plasma 25(OH)D3 after repeat dosing was negatively correlated with 25(OH)D3 baseline levels. Our final model assumes a first-order vitamin D3 absorption, linear vitamin D3 elimination and a non-linear 25(OH)D3 elimination which is described with an Emax function. This model offers a simple explanation to the apparent paradox: the negative correlation might arise from the non-linear 25(OH)D3 elimination process. The model was also able to accurately predict plasma 25(OH)D3 after repeat dosing at daily doses other than 10μg and 100μg, which was reassuring.

Conclusions

We developed a PBPK model to recapitulate PK of plasma vitamin D3 and 25(OH)D3. A personalised vitamin D3 supplementation protocol requires measurement of 25(OH)D3 baseline levels. This should be tested in the clinics for each individual.
Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma
Authors: Phillips Darci , Matusiak Magdalena , Gutierrez Belén Rivero , Bhate Salil S. , Barlow Graham L. , Jiang Sizun , Demeter Janos , Smythe Kimberly S. , Pierce Robert H. , Fling Steven P. , Ramchurren Nirasha , Cheever Martin A. , Goltsev Yury , West Robert B. , Khodadoust Michael S. , Kim Youn H. , Schürch Christian M. , Nolan Garry P.
Published: December 2020

Anti-PD-1 immunotherapies have transformed cancer treatment, yet the determinants of clinical response are largely unknown. We performed CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions from 14 advanced cutaneous T cell lymphoma (CTCL) patients enrolled in a clinical trial of pembrolizumab therapy. Clinical response was not associated with the frequency of tumor-infiltrating T cell subsets, but rather with striking differences in the spatial organization and functional immune state of the tumor microenvironment (TME). After treatment, pembrolizumab responders had a localized enrichment of tumor and CD4+ T cells, which coincided with immune activation and cytotoxic PD-1+ CD4+ T cells. In contrast, non-responders had a localized enrichment of Tregs pre- and post-treatment, consistent with a persistently immunosuppressed TME and exhausted PD-1+ CD4+ T cells. Integrating these findings by computing the physical distances between PD-1+ CD4+ T cells, tumor cells, and Tregs revealed a spatial biomarker predictive of pembrolizumab response. Finally, the chemokine CXCL13 was upregulated in tumor cells in responders post-treatment, suggesting that chemoattraction of PD-1+ CD4+ T cells towards tumor cells facilitates a positive outcome. Together, these data show that T cell topography reflects the balance of effector and suppressive activity within the TME and predicts clinical response to PD-1 blockade in CTCL.