bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing dynamics and determinants of SARS-CoV-2 transmissions among health care workers of adult and pediatric settings in central Paris
Authors: CONTEJEAN Adrien , LEPORRIER Jeremie , CANOUI Etienne , ALBY-LAURENT Fanny , LAFONT Emmanuel , BEAUDEAU Lauren , PARIZE Perrine , LECIEUX Fabienne , GREFFET Agnes , CHERON Gerard , GAUZIT Remy , FOURGEAUD Jacques , L'HONNEUR Anne-Sophie , TRELUYER Jean-Marc , CHARLIER Caroline , CASETTA Anne , FRANGE Pierre , LERUEZ-VILLE Marianne , ROZENBERG Flore , LORTHOLARY Olivier , KERNEIS Solen
Published: May 2020

Background: From the start of the pandemic, health-care workers (HCW) have paid a heavy toll to the coronavirus disease-19 (COVID-19) outbreak.
Objectives: To describe the dynamics and determinants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in HCW.
Design: Prospective observational study conducted from February 24th until April 10th, 2020.
Setting: Comparison of a 1,500-bed adult and a 600-bed pediatric setting of a tertiary-care university hospital located in central Paris.
Participants: All symptomatic HCW screened for SARS-CoV-2 on a nasopharyngeal swab.
Measurements: HCW screened positive were prospectively questioned on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2.
Results: Among 1344 symptomatic HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death were reported. Most HCW (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on March 23rd, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric setting, respectively (p=0.0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0.046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period.
Limitations: Lack of COVID-19 negative controls and recall bias.
Conclusion: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities.
Use and appropriateness of Reporting Guidelines in physical therapy research: a protocol for a meta-research study
Authors: Innocenti Tiziano , Salvioli Stefano , Giagio Silvia , Feller Daniel , Chiarotto Alessandro , Cartabellotta Nino
Published: May 2020

Introduction: Problems about reporting of a scientific study can affect dissemination of research in different manners. It is known that study methods are frequently not described in adequate detail and that results are presented ambiguously or selectively. To overcome these problems, reporting guidelines (e.g. CONSORT, PRISMA, STARD and STROBE statements) have been developed to increase the transparency of research. While recent evidence suggested that these guidelines are frequently used inappropriately in studies published in the major medical journals, the extent and appropriateness of use in physical therapy research has not been systematically evaluated. The aim of this meta-research study will be to evaluate the frequency of using reporting guidelines and their appropriate use in physical therapy published research.
Methods and Analysis: A cross-sectional analysis is planned on a random sample of 200 studies published in the last ten years (2010-2019) in the five generic rehabilitation journals with the highest 5-year impact factor. Randomization will be stratified for publication date to include an equal number of studies from 2010 to 2014 (n=100), and from 2015 to 2019 (n=100). Randomised controlled trials, systematic reviews, diagnostic accuracy studies and observational studies will be included. Crude prevalence estimates with 95% confidence intervals of using and appropriateness of using will be estimated. A bivariate analysis will assess the relationship between the use of reporting guidelines and the year of publication.
Ethics and Dissemination: Several studies have shown the positive influence of reporting guidelines on the completeness of research reporting but no one investigated the use and the appropriateness of reporting guidelines in physical therapy research. Therefore, this study will add relevant knowledge that may contribute to improve further the reporting of rehabilitation research. The results of this research will be published in a peer-reviewed journal and will be presented at relevant (inter)national scientific events.
Association of Renin-Angiotensin-Aldosterone System Inhibition with Risk of COVID-19, Inflammation Level, Severity and Death in Patients With COVID-19: A Rapid Systematic Review and Meta-Analysis
Authors: Liu Xiao , Long Chuyan , Xiong Qinmei , Chen Chen , Ma Jianyong , Su Yuhao , Hong Kui
Published: May 2020

Background

An association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear.

Methods

PubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity.

Results

Eleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12).

Conclusion

On the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings.
Gene regulatory networks controlling differentiation, survival, and diversification of hypothalamic Lhx6-expressing GABAergic neurons
Authors: Kim Dong Won , Liu Kai , Wang Zoe Qianyi , Zhang Yi Stephanie , Bathini Abhijith , Brown Matthew P , Lin Sonia Hao , Washington Parris Whitney , Sun Changyu , Lindtner Susan , Lee Bora , Wang Hong , Shimogori Tomomi , Rubenstein John L.R. , Blackshaw Seth
Published: May 2020

GABAergic neurons of the hypothalamus regulate many innate behaviors, but little is known about the mechanisms that control their development. We previously identified hypothalamic neurons that express the LIM homeodomain transcription factor Lhx6, a master regulator of cortical interneuron development, as sleep-promoting. In contrast to telencephalic interneurons, hypothalamic Lhx6 neurons do not undergo long-distance tangential migration and do not express cortical interneuronal markers such asPvalb. Here, we show thatLhx6is necessary for the survival of hypothalamic neurons.Dlx1/2,Nkx2-2, andNkx2-1are each required for specification of spatially distinct subsets of hypothalamic Lhx6 neurons, and that Nkx2-2+/Lhx6+ neurons of the zona incerta are responsive to sleep pressure. We further identify multiple neuropeptides that are enriched in spatially segregated subsets of hypothalamic Lhx6 neurons, and that are distinct from those seen in cortical neurons. These findings identify common and divergent molecular mechanisms by which Lhx6 controls the development of GABAergic neurons in the hypothalamus.
Supracategorical fear information revealed by aversively conditioning multiple categories
Authors: Levine Seth M. , Kumpf Miriam , Rupprecht Rainer , Schwarzbach Jens V.
Published: May 2020

Fear-generalization is a critical function for survival, in which an organism extracts information from a specific instantiation of a threat (e.g., the western diamondback rattlesnake in my front yard on Sunday) and learns to fear—and accordingly respond to—pertinent higher-order information (e.g., snakes live in my yard). Previous work investigating fear-conditioning in humans has used functional magnetic resonance imaging (fMRI) to demonstrate that activity-patterns of stimuli from an aversively-conditioned category (CS+) are more similar to each other than those of a neutral category (CS-). Here we designed a three-phase (i.e., baseline, conditioned, extinction) experiment using fMRI and multiple aversively-conditioned categories to ask whether we would find only similarity increases within the CS+ categories or also an increase in similarity between the CS+ categories. Using representational similarity analysis, we correlated a set of models to activity-patterns underlying several regions of interest and found that, following fear-conditioning, between-category and within-category similarity increased for the CS+ categories in the superior frontal gyrus (SFG) and the right temporal pole (rTP). Activity patterns in the object-selective lateral occipital cortex tended to prefer the semantic model, regardless of the experimental phase. These results advance prior pattern-based neuroimaging work by exploring the effect of aversively-conditioning multiple categories and indicate an extended role for the SFG and rTP in potentially linking discrete information or abstractly representing supracategorical information during fear-learning for the purpose of proper generalization.
Design and Validation of a Frugal, Automated, Solid-Phase Peptide Synthesizer
Authors: Kallmyer Nathaniel E. , Rider Nathan E. , Reuel Nigel F.
Published: May 2020

Solid phase peptide synthesis (SPPS) has enabled widespread use of synthetic peptides in applications ranging from pharmaceuticals to materials science. The demand for synthetic peptides has driven recent efforts to produce automated SPPS synthesizers which utilize fluid-handling components common to chemistry laboratories to drive costs down to several thousand dollars. Herein, we describe the design and validation of a more ‘frugal’ SPPS synthesizer that uses inexpensive, consumer-grade fluid-handling components to achieve a prototype price point between US$300 and $600. We demonstrated functionality by preparing and characterizing peptides with a variety of distinct properties including binding functionality, nanoscale self-assembly, and oxidation-induced fluorescence. This system yielded micromoles of peptide at a cost of approximately $1/residue, a cost which may be further reduced by optimization and bulk purchasing.
Inferring Telomerase Enzymatic Activity from Expression Data
Authors: Noureen Nighat , Wu Shaofang , Lyu Yingli , Yang Juechen , Yung WK Alfred , Gelfond Jonathan , Wang Xiaojing , Koul Dimpy , Ludlow Andrew , Zheng Siyuan
Published: May 2020

Active telomerase is essential for stem cells and most cancers to maintain telomeres. The enzymatic activity of telomerase is related but not equivalent to the expression of TERT, the catalytic subunit of the complex. Here we show that telomerase enzymatic activity can be robustly estimated from the expression of a 13-gene signature. We demonstrate the validity of the expression-based approach, named EXTEND, using cell lines, cancer samples, and non-neoplastic samples. When applied to over 9,000 tumors and single cells, we find a strong correlation between telomerase activity and cancer stemness. This correlation is largely driven by a small proliferating cancer cell population that exhibits both high telomerase activity and cancer stemness. This study establishes a novel computational framework for quantifying telomerase enzymatic activity and provides new insights into the relationships among telomerase, cancer proliferation, and stemness.
Application of Generalized Concentration Addition to Predict Mixture Effects of Glucocorticoid Receptor Ligands
Authors: de la Rosa Rosemarie , Schlezinger Jennifer J. , Smith Martyn T. , Webster Thomas F.
Published: May 2020

Environmental exposures often occur in complex mixtures and at low concentrations. Generalized concentration addition (GCA) is a method used to estimate the joint effect of receptor ligands that vary in efficacy. GCA models have been successfully applied to mixtures of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) ligands, each of which can be modeled as a receptor with a single binding site. Here, we evaluated whether GCA could be applied to homodimer nuclear receptors, which have two binding sites, to predict the combined effect of full glucocorticoid receptor (GR) agonists with partial agonists. We measured transcriptional activation of GR using a cell-based bioassay. Individual dose response curves for dexamethasone (full agonist), prednisolone (full agonist), and medroxyprogesterone 17-acetate (partial agonist) were generated and applied in three additivity models, GCA, effect summation (ES), and relative potency factor (RPF), to generate response surfaces. GCA and RPF yielded adequate predictions of the experimental data for two full agonists. However, GCA fit experimental data significantly better than ES and RPF for all other binary mixtures. This work extends the application of GCA to homodimer nuclear receptors and improves prediction accuracy of mixture effects of GR agonists.
Microstructural integrity of the major nuclei of the thalamus in Parkinson’s disease
Authors: Borlase Nadia , Myall Daniel , Melzer Tracy R. , Livingston Leslie , Watts Richard , Keenan Ross J , MacAskill Michael , Anderson Tim , Dalrymple-Alford John C.
Published: May 2020

Background

Previous research has shown an association between thalamus and cognition in Parkinson’s disease (PD).

Objectives

To investigate the microstructural integrity of the nuclei of the thalamus and relationship with cognition.

Methods

Level II Movement Disorder Society Task Force Criteria characterised patients with Parkinson’s disease as cognitively normal (PDN, n=51); with mild cognitive impairment (PD-MCI, n=16) or with dementia (PDD, n=15). Twenty-three healthy control subjects were included for comparison. Ak-means clustering approach segmented the thalamus into regions representing nine major nuclei. Volume, fractional anisotropy and mean diffusivity of nuclei were compared between cognitive groups and the relationship with cognitive domain z-scores investigated using hierarchical Bayesian regression models.

Results

There was an overall progressive increase in mean diffusivity as cognition deteriorated (PDN: 1.4 µm2/s (95% uncertainty interval [0.2, 2.7]), PDMCI: 2.4 µm2/s [0.8,4.0], PDD: 4.5 µm2/s [2.8, 6.3]). The largest increase was in the lateral dorsal nucleus (PDN: 0.3 µm2/s [-6.7, 7.2], PDMCI: 5.4 µm2/s [-4.7, 16.1], PDD: 14.8 µm2/s [5.0, 25.0]). Fractional anisotropy showed minimal change between cognitive groups (PDN: 0.001 [-0.005, 0,007], PDMCI: −0.005 [-0.013, 0.003], PDD: −0.005 [-0.014, 0.003]). Increase in mean diffusivity of the thalamus is associated with a global decline in cognition, the magnitude of the effect was greatest in lateral dorsal nucleus. Fractional anisotropy only showed evidence of a relationship with cognitive domain scores in the lateral dorsal nucleus.

Conclusions

The relationship between lateral dorsal nucleus integrity and cognitive changes is likely due to its primary connectivity with frontal and temporal regions.
The estimated impact of the COVID-19 epidemic in the general population of France
Authors: Toubiana Laurent , Bouaud Jacques
Published: May 2020

The authors have withdrawn their manuscript whilst they perform additional experiments to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Subcellular resolution 3D light field imaging with genetically encoded voltage indicators
Authors: Quicke Peter , Howe Carmel L. , Song Pingfan , Jadan Herman Verinaz , Song Chenchen , Knöpfel Thomas , Neil Mark , Dragotti Pier Luigi , Schultz Simon R. , Foust Amanda J.
Published: May 2020

Light field microscopy (LFM) enables high signal-to-noise ratio (SNR), light efficient volume imaging at fast frame rates, and has been successfully applied to single-cell resolution functional neuronal calcium imaging. Voltage imaging with genetically encoded voltage indicators (GEVIs) stands to particularly benefit from light field microscopy’s volumetric imaging capability due to high required sampling rates, and limited probe brightness and functional sensitivity. Previous LFM studies have imaged GEVIs to track population-level interactions only in invertebrate preparations and without single cell resolution. Here we demonstrate sub-cellular resolution GEVI light field imaging in acute mouse brain slices resolving dendritic voltage signals localized in three dimensions. We characterize the effects of different light field reconstruction techniques on the SNR and signal localization and compare the SNR to fluorescence transients imaged in wide field. Our results demonstrate the potential of light field voltage imaging for studying dendritic integration and action potential propagation and backpropagation in 3 spatial dimensions.
A ‘Naturalistic Neuroimaging Database’ for understanding the brain using ecological stimuli
Authors: Aliko Sarah , Huang Jiawen , Gheorghiu Florin , Meliss Stefanie , Skipper Jeremy I
Published: May 2020

Neuroimaging has advanced our understanding of human psychology using reductionist stimuli that often do not resemble information the brain naturally encounters. It has improved our understanding of the network organization of the brain mostly through analyses of ‘resting-state’ data for which the functions of networks cannot be verifiably labelled. We make a ‘Naturalistic Neuroimaging Database’ (NNDb v1.0) publically available to allow for a more complete understanding of the brain under more ecological conditions during which networks can be labelled. Eighty-six participants underwent behavioural testing and watched one of 10 full-length movies while functional magnetic resonance imaging was acquired. Resulting timeseries data are shown to be of high quality, with good signal-to-noise ratio, few outliers and low movement. Data-driven functional analyses provide further evidence of data quality. They also demonstrate accurate timeseries/movie alignment and how movie annotations might be used to label networks. The NNDb can be used to answer questions previously unaddressed with standard neuroimaging approaches, progressing our knowledge of how the brain works in the real world.
In vivoimaging of individual islets across the mouse pancreas reveals a heterogeneous insulin secretion response to glucose
Authors: Frikke-Schmidt Henriette , Arvan Peter , Seeley Randy J , Cras-Méneur Corentin
Published: May 2020

While numerous techniques can be used to measure and analyze insulin secretion in isolated islets in culture, assessments of insulin secretionin vivoare typically indirect and only semiquantitative. The CpepSfGFP reporter mouse line allows thein vivoimaging of insulin secretion from individual islets after a glucose challenge, in live, anesthetized mice, addressing secretion from the pancreas as a whole. Imaging the whole pancreas at high resolution in live mice includes numerous technical challenges. Using rapid-fire imaging in high dynamic range and tiling combined with computer-assisted masked morphometry, we have developed a method to overcome motion blur, and the effects of anesthesia, to be able to monitor and quantify insulin (CpepSfGFP) content simultaneously and longitudinally for the first time in hundreds of individual islets, throughout a glucose challenge.

Through this approach we demonstrate that while isolated islets respond homogeneously to glucose in culture, their response profile differs significantlyin vivo. Independent of size or location, some islets respond sharply to a glucose stimulation while others barely secrete at all. This platform therefore provides a powerful approach to study the impact of disease, diet, surgery or pharmacological treatments on insulin secretion in the intact pancreasin vivo.
Targeted Genome Mining Discovery of the Ramoplanin Congener Chersinamycin from the Dynemicin-ProducerMicromonospora chersinaDSM 44154
Authors: Morgan Kelsey T. , Zheng Jeffrey , McCafferty Dewey G.
Published: May 2020

The availability of genome sequence data combined with bioinformatic genome mining has accelerated the identification of biosynthetic gene clusters (BGCs). Ramoplanins and enduracidins are lipodepsipeptides produced byActinoplanes ramoplaniniferATCC 33076 andStreptomyces fungicidicusB-5477, respectively, that exhibit excellent in vitro activity against a broad spectrum of Gram-positive pathogens. To explore if ramoplanin/enduracidin-like BGCs exist within genomes of organisms sequenced to date, we devised a targeted genome mining strategy that employed structure-activity relationships to identify conserved, essential biosynthesis genes from the ramoplanin and enduracidin BGCs. Five microorganisms were found to contain ramoplanin-like BGCs: the enediyne antibiotic producerMicromonospora chersinastrain DSM 44151(dynemycin); the glycopeptide antibiotic producersAmycolatopsis orientalisstrain B-37 (norvancomycin),Amycolatopsis orientalisstrain DSM 40040 (vancomycin), andAmycolatopsis balhimycinaFH1894 strain DSM 44591 (balhimycin); andStreptomycessp. TLI_053. A single compound from fermentation ofM. chersinawas purified to homogeneity and found to possess good antibiotic activity against several Gram-positive bacterial test strains (1-2 μg/mL), comparing favorably to ramoplanin family members. We named this compoundchersinamycinand elucidated its covalent structure, which differs distinctly from ramoplanins and enduracidins. Further, the chersinamycin BGC was validated through insertional gene inactivation using CRISPR-Cas9 gene editing. In addition to the information gained by comparing and contrasting the sequence and organization of these five new BGCs, the amenability ofM. chersinato genetic manipulation provides a much-needed tool to investigate the fundamental aspects of lipodepsipeptide biosynthesis and to facilitate metabolic engineering efforts for the production of novel antibiotics capable of combating antibiotic-resistant infections.
Computational methods for continuous eye-tracking perimetry based on spatio-temporal integration and a deep recurrent neural network
Authors: Grillini Alessandro , Hernández-García Alejandro , Renken Remco J. , Demaria Giorgia , Cornelissen Frans W.
Published: May 2020

Perimetry, the mapping of the sensitivity of different visual field locations, is an essential procedure in ophthalmology. Unfortunately, standard automated perimetry (SAP), suffers from some practical issues: it can be tedious, requires manual feedback and a high level of patient compliance. These factors limit the effectiveness of perimetry in some clinical populations. In an attempt to remove some of these limitations, alternatives to SAP have been tried based on tracking eye movements. These new approaches have attempted to mimic SAP, thus presenting stimuli on a fixed grid, and replacing manual by ocular responses. While this solves some issues of SAP, these approaches hardly exploit the high spatial and temporal resolution facilitated by eye-tracking. In this study, we present two novel computational methods that do tap into this potential: (1) an analytic method based on the spatio-temporal integration of positional deviations by means of Threshold Free Cluster Enhancement (TFCE) and (2) a method based on training a recursive deep artificial neural network (RNN). We demonstrate that it is possible to reconstruct visual field maps based on continuous gaze-tracking data acquired in a relatively short amount of time.
Use of High Flow Nasal Therapy to Treat Moderate to Severe Hypoxemic Respiratory Failure in COVID-19
Authors: Patel Maulin , Gangemi Andrew , Marron Robert , Chowdhury Junad , Yousef Ibraheem , Zheng Matthew , Mills Nicole , Tragesser Lauren , Giurintano Julie , Gupta Rohit , Gordon Matthew , Rali Parth , D’Alonzo Gilbert , Fleece David , Zhao Huaqing , Patlakh Nicole , Criner Gerard J. ,   for the Temple University COVID-19 Research Group
Published: May 2020

Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of High flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.

Methods

This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to April 24, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). Primary outcome was prevention of intubation.

Results

Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (±13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. SF and chest Xray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital/ventilator associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of VAP/HAP was statistically higher in the progressed to intubation group.

Conclusion

HFNT use is associated with a reduction in the rate of Invasive mechanical ventilation and overall mortality in patients with COVID-19 infection.

Key Points

Key Question

What is the utility of High Flow Nasal Therapy (HFNT) in COVID-19 related Hypoxemic Respiratory Failure?

Bottom Line

In this retrospective analysis of moderate to severe hypoxic respiratory failure for COVID 19 patients, 67 patients (65.4%) were able to avoid intubation despite severely low SF ratio (Mean 121.9).

Why Read on

HFNT has a significant role in COVID-19 for reducing rate of intubations and associated mortality
IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY
Authors: Fernández Cruz Ana , Ruiz-Antorán Belén , Gómez Ana Muñoz , Sancho López Aránzazu , Sánchez Patricia Mills , Soto Gustavo Adolfo Centeno , Alonso Silvia Blanco , Garachana Laura Javaloyes , Gómez Amy Galán , Alijo Ángela Valencia , Irusta Javier Gómez , Payares-Herrera Concepción , Torre Ignacio Morrás , Chica Enrique Sánchez , de Cepeda Laura Delgado Téllez , Díaz Alejandro Callejas , Ramos Martínez Antonio , Rubio Elena Múñez , Avendaño-Solá Cristina
Published: May 2020

Objective

We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality.

Design

We performed a single-centre retrospective cohort study.

Setting

A University hospital in Madrid, Spain, during March 2020.

Participants

Patients admitted with SARS-CoV-2 pneumonia.

Exposures

Patients treated with steroids were compared to patients not treated with steroids. A propensity-score for steroid treatment was developed. Different steroid regimens were also compared, and adjusted with a second propensity score.

Main Outcomes and Measures

To determine the role of steroids in in-hospital mortality, univariable and multivariable analyses were performed, and adjusted including the propensity score as a covariate. Survival times were compared using a log-rank test.

Results

During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) consecutive patients were treated with steroids and 67 patients were assigned to the control cohort. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8 to13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], OR 0.51 [0.27 to 0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048 to 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone (or equivalent) versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710).

Conclusions

Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone or equivalent and glucocorticoid pulses. These results support the use of glucocorticoids in SARS-CoV2 infection.

We investigated in-hospital mortality of patients with SARS-CoV-2 pneumonia in a large series of patients treated with steroids compared to controls, and adjusted using a propensity score. Our results show a beneficial impact of steroid treatment in SARS-CoV-2 pneumonia.
Dragon III- Phase 1: Feasibility and safety of neoadjuvant chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) for locally-advanced gastric cancer patients in China
Authors: Sah Birendra Kumar , Xu Wei , Zhang Benyan , Zhang Huan , Yuan Fei , Li Jian , Liu Wentao , Yan Chao , Li Chen , Yan Min , Zhu Zhenggang
Published: May 2020

Background

Neoadjuvant fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) has shown significant benefits for gastric cancer patients. However, it has not been well accepted in Asian countries. We conducted a prospective study on the safety and feasibility of FLOT regimen in Chinese patients.

Methods

Patients with adenocarcinoma of the stomach or esophagogastric junction received 4 cycles of neoadjuvant chemotherapy (NAC) and 4 cycles of adjuvant chemotherapy (AC) with the FLOT regimen. The completion status of chemotherapy, adverse events, postoperative morbidities and pathological tumor regression were analyzed. The two-year overall survival (OS) and relapse-free survival are presented.

Results

Altogether, 10 patients were enrolled, and all patients completed 4 cycles of neoadjuvant chemotherapy. There were no severe hematological adverse events (grade 3 or above), except for a case of grade 3 anemia. All 10 patients underwent radical gastrectomy. Nine patients had R0 resection, and 3 patients had complete or subtotal pathological tumor regression. Nine patients completed 4 cycles of adjuvant chemotherapy, but only one patient completed the full dose of adjuvant chemotherapy. The dose of adjuvant chemotherapy was reduced by 25% or less in the other patients. The median follow-up time was 23.13 months, 8 patients achieved the overall survival endpoint, and 7 patients had relapse-free survival for this period. Two patients died of disease progression.

Conclusions

Our study demonstrates that the neoadjuvant FLOT regimen is safe and effective for Chinese patients. Dose adjustment is necessary for adjuvant chemotherapy. The pathological regression and survival rates need reevaluation in a larger cohort.

The trial is registered with ClinicalTrials.gov (number NCT03646591).
Multiplexing of EEG signatures for temporal and spatial distance estimates
Authors: Robinson Eva Marie , Wiener Martin
Published: May 2020

The perception and measurement of spatial and temporal dimensions have been widely studied. However, whether these two dimensions are processed independently is still being debated. Additionally, whether EEG components are uniquely associated with time or space, or whether they reflects a more general measure of magnitude remains unknown. While undergoing EEG, subjects traveled a randomly predetermined spatial or temporal interval and were then instructed to reproduce the interval traveled. In the task, the subject’s travel speed varied for the estimation and reproduction phases of each trial, so that one dimension could not inform the other. Behaviorally, subject performance was more variable when reproducing time than space, but overall, just as accurate; notably, behavior was not correlated between tasks. EEG data revealed during estimation the contingent negative variation (CNV) tracked the probability of the upcoming interval, regardless of dimension. However, during reproduction, the CNV exclusively oriented to the upcoming temporal interval at the start of reproduction. Further, a dissociation between relatively early frontal beta and late posterior alpha oscillations was observed for time and space reproduction, respectively. Our findings indicate that time and space are neurally separable dimensions, yet are hierarchically organized across task contexts within the CNV signal.
Single-Cell Analysis Reveals Macrophage-Driven T Cell Dysfunction in Severe COVID-19 Patients
Authors: Liu Xiaoqing , Zhu Airu , He Jiangping , Chen Zhao , Liu Longqi , Xu Yuanda , Ye Feng , Feng Huijian , Luo Lin , Cai Baomei , Mai Yuanbang , Lin Lihui , Zhang Zhekun , Chen Sibei , Shi Junjie , Wen Lilan , Wei Yuanjie , Zhuo Jianfen , Zhao Yingying , Li Fang , Wei Xiaoyu , Chen Dingbin , Zhang Xinmei , Zhong Na , Huang Yaling , Liu He , Wang Jinyong , Xu Xun , Wang Jie , Chen Ruchong , Chen Xinwen , Zhong Nanshan , Zhao Jinxian , Li Yimin , Zhao Jincun , Chen Jiekai
Published: May 2020

The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, SARS-CoV-2-specific T cells were observed in pleural effusion earlier than in peripheral blood. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.
Explainable machine learning models to understand determinants of COVID-19 mortality in the United States
Authors: Mathur Piyush , Sethi Tavpritesh , Mathur Anya , Maheshwari Kamal , Cywinski Jacek B , Khanna Ashish K , Dua Simran , Papay Frank
Published: May 2020

Background

COVID-19 is now one of the leading causes of mortality amongst adults in the United States for the year 2020. Multiple epidemiological models have been built, often based on limited data, to understand the spread and impact of the pandemic. However, many geographic and local factors may have played an important role in higher morbidity and mortality in certain populations.

Objective

The goal of this study was to develop machine learning models to understand the relative association of socioeconomic, demographic, travel, and health care characteristics of different states across the United States and COVID-19 mortality.

Methods

Using multiple public data sets, 24 variables linked to COVID-19 disease were chosen to build the models. Two independent machine learning models using CatBoost regression and random forest were developed. SHAP feature importance and a Boruta algorithm were used to elucidate the relative importance of features on COVID-19 mortality in the United States.

Results

Feature importances from both the categorical models, i.e., CatBoost and random forest consistently showed that a high population density, number of nursing homes, number of nursing home beds and foreign travel were strongest predictors of COVID-19 mortality. Percentage of African American amongst the population was also found to be of high importance in prediction of COVID-19 mortality whereas racial majority (primarily, Caucasian) was not. Both models fitted the data well with a training R2 of 0.99 and 0.88 respectively. The effect of median age,median income, climate and disease mitigation measures on COVID-19 related mortality remained unclear.

Conclusions

COVID-19 policy making will need to take population density, pre-existing medical care and state travel policies into account. Our models identified and quantified the relative importance of each of these for mortality predictions using machine learning.
Comprehensive genome analysis of 6,000 USA SARS-CoV-2 isolates reveals haplotype signatures and localized transmission patterns by state and by country
Authors: Shen Lishuang , Bard Jennifer Dien , Biegel Jaclyn A. , Judkins Alexander R. , Gai Xiaowu
Published: May 2020

Genomic analysis of SARS-CoV-2 sequences is crucial in determining the effectiveness of prudent safer at home measures in the United States (US). By haplotype analysis of 6,356 US isolates, we identified a pattern of strongly localized outbreaks at the city-, state-, and country-levels, and temporal transmissions. This points to the effectiveness of existing travel restriction policies and public health measures in controlling the transmission of SARS-CoV-2.
Association of age, sex, comorbidities, and clinical symptoms with the severity and mortality of COVID-19 cases: a meta-analysis with 85 studies and 67299 cases
Authors: Islam Mohammad Safiqul , Barek Md. Abdul , Aziz Md. Abdul , Aka Tutun Das , Jakaria Md.
Published: May 2020

Background

A new pathogenic disease named COVID-19 became a global threat, first reported in Wuhan, China, in December 2019. The number of affected cases growing exponentially and now, more than 210 countries confirmed the cases.

Objective

This meta-analysis aims to evaluate risk factors, the prevalence of comorbidity, and clinical characteristics in COVID-19 death patients compared to survival patients that can be used as a reference for further research and clinical decisions.

Methods

PubMed, Science Direct, SAGE were searched to collect data about demographic, clinical characteristics, and comorbidities of confirmed COVID-19 patients from January 1, 2020, to May 17, 2020. Meta-analysis was performed with the use of Review Manager 5.3

Results

Eighty-five studies were included in Meta-analysis, including a total number of 67,299 patients with SARS-CoV-2 infection. Males are severely affected or died than females (OR = 2.26, p < 0.00001; OR = 3.59, p < 0.00001) are severely affected, or died by COVID-19 and cases with age ≥50 are at higher risk of death than age <50 years (OR=334.23). Presence of any comorbidity or comorbidities like hypertension, cardiovascular disease, diabetes, cerebrovascular disease, respiratory disease, kidney disease, liver disease, malignancy significantly increased the risk of death compared to survival (OR = 3.46, 3.16, 4.67, 2.45, 5.84, 2.68, 5.62, 2.81,2.16). Among the clinical characteristics such as fever, cough, myalgia, diarrhea, abdominal pain, dyspnea, fatigue, sputum production, chest tightness headache and nausea or vomiting, only fatigue (OR = 1.31, 95%) and dyspnea increased the death significantly (OR= 1.31, 4.57). The rate of death of COVID-19 cases is 0.03-times lower than the rate of survival (OR = 0.03).

Conclusion

Our result indicates that male patients are affected severely or died, the rate of death is more in the age ≥50 group, and the rate of death is affected by comorbidities and clinical symptoms.
The impact of thermal pasteurization on viral load in human milk and other matrices: A rapid review
Authors: Pitino Michael A. , O’Connor Deborah L. , McGeer Allison J. , Unger Sharon
Published: May 2020

Holder pasteurization (62.5°C, 30 min) of human milk (HM) is thought to reduce the risk of transmitting viruses to an infant. Some viruses may be secreted into milk – others may be contaminants. The effect of thermal pasteurization on viruses in HM has yet to be rigorously reviewed. The objective of this study is to characterize the effect of commonly used pasteurization techniques on viruses in HM and non-HM matrices. Databases (MEDLINE, Embase, Web of Science) were searched from inception to April 20th, 2020 for primary research articles assessing the impact of pasteurization on viral load or detection of live virus. Reviews were excluded, as were studies lacking quantitative measurements or those assessing pasteurization as a component of a larger process. Overall, 65,131 reports were identified, and 108 studies included. Pasteurization of HM at a minimum temperature of 56°C-60°C is effective at reducing detectable live virus. In cell culture media or plasma, coronaviruses (e.g., SARS-CoV, SARS-CoV-2, MERS) are highly susceptible to heating at ≥56°C. Although pasteurization parameters and matrices reported vary, all viruses studied, with the exception of parvoviruses, were susceptible to thermal killing. Future research important for the study of novel viruses should standardize pasteurization protocols and should test viral inactivation using a human milk matrix.

Novelty bullets

In all matrices, including human milk, pasteurization at temperatures of 62.5°C was generally sufficient to reduce surviving viral load by several logs or to below the limit of detection.

Holder pasteurization (62.5°C, 30 min) of human donor milk should be sufficient to inactivate non-heat resistant viruses, including coronaviruses, if present.
Association of Renin Angiotensin System Blockers with Outcomes in Patients with Covid-19: A Systematic Review and Meta-analysis
Authors: Garg Aakash , Rout Amit , Sharma Abhishek , Fiorello Brittany , Kostis John B.
Published: May 2020

Background

Patients with cardiovascular disease are at increased risk of critical illness and mortality from Covid-19 disease. Conflicting findings have raised concerns regarding the association of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) use with likelihood or severity of infection during this pandemic.

Objective

To study the cumulative evidence for association of ACEI/ARB use with outcomes among patients with confirmed Covid-19.

Methods

The MEDLINE and EMBASE databases were thoroughly searched from November 01, 2019 to May 15, 2020 for studies reporting on outcomes based on ACEI/ARB use in patients with confirmed Covid-19. Preferred reporting items for systematic review and meta-analysis guidelines were used for the present study. Relevant data was collected and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects model.

Main Outcome measures

In-hospital mortality was the primary end of interest. Second end-point was severe or critical illness defined as either need for intensive care unit, invasive mechanical ventilation, or mortality.

Results

Fifteen studies with total of 23,822 patients (N ACEI/ARB=6,650) were included in the present analysis. Overall, prevalence of ACEI/ARB use ranged from 7.7% to 46.2% across studies. Among 10 studies, patients using ACEI/ARB had similar odds of mortality [OR 1.03 (0.69-1.55)] and severe or critical illness [1.18 (0.91-1.54)] compared to those not on ACEI/ARB. In an analysis restricted to patients with hypertension, ACEI/ARB use was associated with significantly lower mortality [0.64 (0.45-0.89)], while the odds of severe/critical illness [0.76(0.52-1.12); p=0.16] remained non-significant compared with non-ACEI/ARB users.

Conclusion

There is no evidence for increased risk of severe illness or mortality in patients using ACEI/ARB compared with non-users. In patients with hypertension, ACE/ARB use might be associated with reduced mortality, however these findings need to be confirmed in prospective randomized controlled trials.
Enveloped Virus Inactivation on Personal Protective Equipment by Exposure to Ozone
Authors: Blanchard Emmeline L. , Lawrence Justin D. , Noble Jeffery A. , Xu Minghao , Joo Taekyu , Ng Nga Lee , Schmidt Britney E. , Santangelo Philip J. , Finn M.G.
Published: May 2020

Ozone is a highly oxidizing gas easily generated from atmospheric oxygen with inexpensive equipment and is commonly used for the disinfection of municipal water, foods, and surfaces. We report tests of the ability of ozone to inactivate enveloped respiratory viruses (influenza A virus and respiratory syncytial virus), chosen as more easily handled surrogates for SARS-CoV-2, on N95 respirators and other personal protective equipment (PPE) commonly used in hospitals. At 20 ppm, an ozone concentration easily achieved by standard commercial equipment, the viruses were inactivated with high efficiency as long as the relative humidity was above a threshold value of approximately 50%. In the absence of humidity control, disinfection is more variable and requires considerably longer exposure under relatively dry conditions. This report extends the observations of a previous publication (http://doi.org/10.1080/01919510902747969) to hospital-relevant materials and provides additional details about the relationship of humidity to the antiviral activity of ozone. Home CPAP disinfection devices using ozone can provide effective results for individuals. Ozone did not appear to degrade any of the materials tested except for elastic bands if strained during treatment (such as by the pressure exerted by stapled attachment to N95 respirators). The filtration efficiency of N95 respirator material was not compromised. Overall, we recommend exposures of at least 40 minutes to 20 ppm ozone and >70% relative humidity at ambient temperatures (21-24°C) for 4-log (99.99%) reduction of viral infectivity on a variety of PPE, including gowns, face shields, and respirators. Shorter exposure times are likely to be effective under these conditions, but at the risk of some variability for different materials. Higher ozone concentrations and higher humidity levels promoted faster inactivation of viruses. Our work suggests that ozone exposure can be a widely accessible method for disinfecting PPE, permitting safer re-use for healthcare workers and patients alike in times of shortage.