bluuebunny/crossref_metadata_2025 huggingface dataset:
CONE PHOTORECEPTOR INTEGRITY ASSESSED WITH ADAPTIVE OPTICS IMAGING AFTER LASER POINTER-INDUCED RETINAL INJURY
Authors: Vitellas Carol , Doble Nathan , Wells-Gray Elaine M. , Challa Nayanika , Davidorf Frederick , Choi Stacey S.
Published: June 2020

Purpose:

To examine the three-dimensional foveal cone photoreceptor structure in a patient who had suffered laser pointer-induced retinal injury.

Methods:

Patient underwent standard fundus photography and clinical spectral domain optical coherence tomography imaging. High-resolution imaging was performed using an adaptive optics-optical coherence tomography-scanning laser ophthalmoscope.

Results:

Adaptive optics imaging revealed loss of inner and outer segments of cone photoreceptors whereas the anterior retinal layers appeared healthy. Analysis of cone topology showed an increase in Voronoi domain area and a less regular hexagonal packing structure closer to the lesion site.

Conclusion:

Exposure to laser pointer radiation, however brief, can result in damage to the retina. Here, repeated imaging nine months later showed a decrease in the size of the lesions (ranging from 3.7 to 23.9%) compared with the first time point. However, the longer-term prognosis is likely permanent scarring.
Paved With Good Intentions: Hospital Visitation Restrictions in the Age of Coronavirus Disease 2019*
Authors: Andrist Erica , Clarke Rachel G. , Harding Meghan
Published: June 2020

Hospital visitation restrictions have been widely implemented during the coronavirus disease 2019 pandemic as a means of decreasing the transmission of coronavirus. While decreasing transmission is an important goal, it is not the only goal that quality healthcare must aim to achieve. Severely restricted visitation policies undermine our ability to provide humane, family-centered care, particularly during critical illness and at the end of life. The enforcement of these policies consequently increases the risk of moral distress and injury for providers. Using our experience in a PICU, we survey the shortcomings of current visitation restrictions. We argue that hospital visitation restrictions can be implemented in ways that are nonmaleficent, but this requires unwavering acknowledgment of the value of social and familial support during illness and death. We advocate that visitation restriction policies be implemented by independent, medically knowledgeable decision-making bodies, with the informed participation of patients and their families.
Hydroxychloroquine plus standard care compared with the standard care alone in COVID-19: a meta-analysis of randomized controlled trials
Authors: Amani Bahman , Khanijahani Ahmad , Amani Behnam
Published: June 2020

Background & Objective

The efficacy and safety of Hydroxychloroquine (HCQ) in treating coronavirus disease COVID-19 pandemic is disputed. This study aimed to examine the efficacy and safety of HCQ plus the standard of care in COVID-19 patients.

Methods

PubMed, The Cochrane Library, Embase, and web of sciences were searched up to June 1, 2020. The references list of the key studies was reviewed for additional relevant resources. Clinical studies registry databases were searched for identifying potential clinical trials. The quality of the included studies was evaluated using the Cochrane Collaboration’s tool. Meta-analysis was performed using RevMan software (version 5.3).

Results

Three randomized controlled trials with total number of 242 patients were identified eligible for meta-analysis. No significant differences were observed between HCQ and standard care in terms of viral clearance (Risk ratio [RR] = 1.03; 95% confidence interval [CI] = 0.91, 1.16; P = 0.68), disease progression (RR = 0.92; 95% CI = 0.10, 0.81; P = 0.94), Chest CT (RR = 1.40; 95% CI = 1.03, 1.91; P = 0.03). There is a significant difference between HCQ and standard care for adverse events (RR = 2.88; 95% CI = 1.50, 5.54; P = 0.002).

Conclusion

Although the current meta-analysis failed to confirm the efficacy and safety of HCQ in the treatment of COVID-19 patients, further rigorous randomized clinical trials are necessary to evaluate conclusively the efficacy and safety of HCQ against COVID-19.
The effectiveness of social bubbles as part of a Covid-19 lockdown exit strategy, a modelling study
Authors: Leng Trystan , White Connor , Hilton Joe , Kucharski Adam , Pellis Lorenzo , Stage Helena , Davies Nick ,   CMMID-Covid-19 WG, Keeling Matt J. , Flasche Stefan
Published: June 2020

Background

During the Covid-19 lockdown, contact clustering in social bubbles may allow extending contacts beyond the household at minimal additional risk and hence has been considered as part of modified lockdown policy or a gradual lockdown exit strategy. We estimated the impact of such strategies on epidemic and mortality risk using the UK as a case study.

Methods

We used an individual based model for a synthetic population similar to the UK, that is stratified into transmission risks from the community, within the household and from other households in the same social bubble. The base case considers a situation where non-essential shops and schools are closed, the secondary household attack rate is 20% and the initial reproduction number is 0.8. We simulate a number of strategies including variations of social bubbles, i.e. the forming of exclusive pairs of households, for particular subsets of households (households including children and single occupancy households), as well as for all households. We test the sensitivity of the results to a range of alternative model assumptions and parameters.

Results

Clustering contacts outside the household into exclusive social bubbles is an effective strategy of increasing contacts while limiting some of the associated increase in epidemic risk. In the base case scenario social bubbles reduced cases and fatalities by 17% compared to an unclustered increase of contacts. We find that if all households were to form social bubbles the reproduction number would likely increase to 1.1 and therefore beyond the epidemic threshold of one. However, strategies that allow households with young children or single occupancy households to form social bubbles only increased the reproduction number by less than 10%. The corresponding increase in morbidity and mortality is proportional to the increase in the epidemic risk but is largely focussed in older adults independently of whether these are included in the social bubbles.

Conclusions

Social bubbles can be an effective way of extending contacts beyond the household limiting the increase in epidemic risk, if managed appropriately.
Estimation of Individual Probabilities of COVID-19 Infection, Hospitalization, and Death From A County-level Contact of Unknown infection Status
Authors: Bhatia Rajiv , Klausner Jeffrey
Published: June 2020

Objective

Our objective is to demonstrate a method to estimate the probability of a laboratory confirmed COVID19 infection, hospitalization, and death arising from a contact with an individual of unknown infection status.

Methods

We calculate the probability of a confirmed infection, hospitalization, and death resulting from a county-level person-contact using available data on current case incidence, secondary attack rates, infectious periods, asymptomatic infections, and ratios of confirmed infections to hospitalizations and fatalities.

Results

Among US counties with populations greater than 500,000 people, during the week ending June 13,2020, the median estimate of the county level probability of a confirmed infection is 1 infection in 40,500 person contacts (Range: 10,100 to 586,000). For a 50 to 64 year-old individual, the median estimate of the county level probability of a hospitalization is 1 in 709,000 person contacts (Range: 177,000 to 10,200,000) and the median estimate of the county level probability of a fatality is 1 in 6,670,000 person contacts (Range 1,680,000 to 97,600.000).

Conclusions and Relevance

Estimates of the individual probabilities of COVID19 infection, hospitalization and death vary widely but may not align with public risk perceptions. Systematically collected and publicly reported data on infection incidence by, for example, the setting of exposure, type of residence and occupation would allow more precise estimates of probabilities than possible with currently available public data. Calculation of secondary attack rates by setting and better measures of the prevalence of seropositivity would further improve those estimates.
COVID-19: How Many Years of Life Lost?
Authors: Wetzler Harry P. , Wetzler Erica A. , Cobb Herbert W.
Published: June 2020

Background

COVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19’s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020.

Methods

Years of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020.

Results

COVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US.

Conclusion

Each COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states “Prediction is difficult, especially when dealing with the future.” We suggest that while dying is bad, losing life is even worse.
Disproportionate COVID-19 Related Mortality Amongst African Americans in Four Southern States in the United States
Authors: Betson Nicole , Maitra Anirban
Published: June 2020

Background

African Americans have been severely affected by COVID-19 noted with the rising mortality rates within the African American community. Health disparities, health inequities and issues with systemic health access are some of the pre-existing issues African Americans were subjected to within the southern states in the United States. Second, social distancing is a critical non-pharmacological intervention to reduce the spread of COVID-19. However, social distancing was not practical and presented a challenge within the African American community, specifically, in the southern states.

Objective

This article assesses the effect of COVID-19 on African Americans in the southern states.

Methodology

This short communication queried the publicly available Department of Health statistics on COVID-19 related mortality and underlying health conditions in four southern states (Alabama [AL], Georgia [GA], Louisiana [LA] and Mississippi [MS]) with a high proportion of African American residents. Second, the unacast COVID-19 toolkit was used to derive a social distancing (SD) grade for any given state, based on three different metrics: (i) percent change in average distance travelled (ii) percent change in non-essential visits and (iii) decrease in human encounters (compared to national baseline).

Results

Across the four states, on average, as many as 54% of COVID-19 related deaths are in the African American community, although this minority group comprises only 32% of the population cumulatively. This article finds that all four southern states received a social distancing grade of F. COVID-19 have demonstrated that adverse outcomes are higher in individuals with underlying health conditions such as diabetes, cardiovascular diseases, or pre-existing pulmonary compromise.

Conclusion

The COVID-19 pandemic has exposed racial disparities in our healthcare system that disproportionately impacts African Americans within the four states of the southern United States. In addition, the lack of diversity in the healthcare system likely impacts this disproportionate impact on African American communities because it is not able to address its primary obligations within minority communities. Recognizing that there is a great need for African American representation or diversity in the health workforce would be able to better address the health disparities.
Machine learning reduced gene/non-coding RNA features that classify Schizophrenia patients accurately and highlight insightful gene clusters
Authors: Liu Yichuan , Qu Hui-Qi , Chang Xiao , Tian Lifeng , Glessner Joseph , Sleiman Patrick A. M. , Hakonarson Hakon
Published: June 2020

Schizophrenia (SCZ) is a chronic and severely disabling neurodevelopmental disorder that affects people worldwide. RNA-seq has been a powerful method to detect the differentially expressed genes/non-coding RNAs in patients; however, due to overfitting problems differentially expressed targets (DETs) cannot be used properly as biomarkers. In this study, dorsolateral prefrontal cortex (dlpfc) RNA-seq data from 254 individuals’ was obtained from the CommonMind consortium and analyzed with machine learning methods, including random forest, forward feature selection (ffs), and factor analysis, to reduce the numbers of gene/non-coding RNA feature vectors to overcome overfitting problem and explore involved functional clusters. In 2-fold shuffle testing, the average predictive accuracy for SCZ patients was 67% based on coding genes, and the 96% based on long non-coding RNAs (lncRNAs). Coding genes were further clustered into 14 factors and lncRNAs were clustered into 45 factors to represent the underlying features. The largest contribution factor for coding genes contains number of genes critical in neurodevelopment and previously reported in relation with various brain disorders. Genomic loci of lncRNAs were more insightful, enriched for genes critical in synapse function (p=7.3E-3), cell junction (p=0.017), neuron differentiation (p=8.3E-3), phosphorylation (8.2E-4), and involving the Wnt signaling pathway (p=0.029). Taken together, machine learning is a powerful algorithm to reduce functional biomarkers in SCZ patients. The lncRNAs capture the characteristics of SCZ tissue more accurately than mRNA as the formers regulate every level of gene expression, not limited to mRNA levels.
FastTrack, A Strategy to Shorten Time to Degree
Authors: Schaller Michael D. , Barbier Mariette
Published: June 2020

Recent reports express concern about the sustainability of the biomedical research enterprise in its current form. Recurring concerns include the predictability and sustainability of funding for research, regulatory burden and training the next generation in the biomedical workforce. One specific concern is the duration of training periods during pre-doctoral and post-doctoral studies. This article addresses the issue of time-to-degree (TTD) for doctorates. Many reports stress the importance of shortening the TTD, but provide no recommendations to achieve this goal. Herein, factors potentially affecting TTD are discussed and one mechanism that harmonizes undergraduate and graduate programs is proposed as a strategy to reduce the TTD.
14-3-3 protein Bmh1 triggers short-range compaction of mitotic chromosomes by recruiting sirtuin deacetylase Hst2
Authors: Jain Neha , Janning Petra , Neumann Heinz
Published: June 2020

Mitotic chromosome compaction is licensed by kinetochores in yeast. Recruitment of Aurora kinase B elicits a cascade of events starting with phosphorylation of H3 S10, which signals the recruitment of lysine deacetylase Hst2 and the removal of H4 K16ac. The unmasked H4 tails interact with the acidic patch of neighbouring nucleosomes to drive short-range compaction of chromatin. Here, we demonstrate that the interaction of Hst2 with H3 S10ph is mediated by 14-3-3 protein Bmh1. As a homodimer, Bmh1 binds simultaneously to H3 S10ph and the phosphorylated C-terminus of Hst2. The Hst2-Bmh1 interaction is cell cycle dependent, reaching its maximum in M phase. Furthermore, we show that phosphorylation of C-terminal residues of Hst2 stimulates its deacetylase activity. Hence, the data presented here identify Bmh1 as a key player in the mechanism of licensing of chromosome compaction in mitosis.

Key Points

14-3-3 protein Bmh1 bridges the interaction of Hst2 with phosphorylated H3 tails

Hst2 is multiply phosphorylated on its unstructured C-terminal tail

The interaction of Bmh1 with Hst2 is cell cycle dependent

Hst2 phosphorylation enhances its enzymatic activity
Living in the concrete jungle: carnivore spatial ecology in urban parks
Authors: Gámez Siria , Harris Nyeema C.
Published: June 2020

People and wildlife are living in an increasingly urban world, replete with unprecedented human densities, sprawling built environments, and altered landscapes. Such anthropogenic pressures can affect multiple processes within an ecological community, from spatial patterns to interspecific interactions. We tested two competing hypotheses, human shields versus human competitors, to characterize how humans affect the carnivore community using multi-species occupancy models. From 2017-2020, we conducted the first camera survey of city parks in Detroit, Michigan, and collected spatial occurrence data of the local native carnivore community. Our 12,106-trap night survey captured detected data for coyotes (Canis latrans), red foxes (Vulpes vulpes), gray foxes (Urocyon cinereoargenteus), raccoons (Procyon lotor), and striped skunks (Mephitis mephitis). Overall occupancy varied across species (Ψcoyote=0.40, Ψraccoon=0.54, Ψred fox=0.19, Ψstriped skunk=0.09). Contrary to expectations, humans did not significantly affect individual occupancy for these urban carnivores. However, co-occurrence between coyote and skunk only increased with human activity. The observed positive spatial association between an apex and subordinate pair supports the human shield hypothesis. Our findings demonstrate how urban carnivores can exploit spatial refugia and coexist with humans in the cityscape.
Compensation of physiological motion enables high-yield whole-cell recordingin vivo
Authors: Stoy William M. , Yang Bo , Kight Ali , Wright Nathaniel C. , Borden Peter Y. , Stanley Garrett B. , Forest Craig R.
Published: June 2020

1.1.1

Whole-cell patch-clamp recordingin vivois the gold-standard method for measuring subthreshold electrophysiology from single cells during behavioural tasks, sensory stimulations, and optogenetic manipulation. However, these recordings require a tight, gigaohm resistance, seal between a glass pipette electrode’s aperture and a cell’s membrane. These seals are difficult to form, especially in vivo, in part because of a strong dependence on the distance between the pipette aperture and cell membrane. We elucidate and utilize this dependency to develop an autonomous method for placement and synchronization of pipette’s tip aperture to the membrane of a nearby, moving neuron, which enables high-yield seal formation and subsequent recordings in the deep in the brain of the living mouse, in the thalamus. This synchronization procedure nearly doubles the reported gigaseal yield in the thalamus (>3 mm below the pial surface) from 26% (n=17/64) to 48% (n=32/66). Whole-cell recording yield improved from 10% (n = 9/88) to 24% (n=18/76) when motion compensation was used during the gigaseal formation. As an example of its application, we utilized this system to investigate the role of the sensory environment and ventral posterior medial region (VPM) projection synchrony on intracellular dynamics in the barrel cortex. This method results in substantially greater subcortical whole-cell recording yield than previously reported and thus makes pan-brain whole-cell electrophysiology practical in the living mouse brain.
Harnessing endogenous repair mechanisms for targeted gene knock-in of bovine embryos
Authors: Owen Joseph R. , Hennig Sadie L. , McNabb Bret R. , Lin Jason C. , Young Amy E. , Murray James D. , Ross Pablo J. , Van Eenennaam Alison L.
Published: June 2020

Introducing useful traits into livestock breeding programs through gene knock-ins has proven challenging. Typically, targeted insertions have been performed in cell lines, followed by somatic cell nuclear transfer cloning, which can be inefficient. An alternative is to introduce genome editing reagents and a homologous recombination (HR) donor template into embryos to trigger homology-directed repair (HDR). However, the HR pathway is primarily restricted to actively dividing cells (S/G2-phase) and its efficiency is low in zygotes, especially for the introduction of large DNA sequences. The homology-mediated end joining (HMEJ)-based strategy harnesses HDR by direct injection of embryos, and has been shown to have an improved knock-in efficiency in non-dividing cells. The knock-in efficiency for a 1.8kb gene was contrasted when combining a gRNA/Cas9 ribonucleoprotein complex with either a traditional HR donor template, or a HMEJ template in bovine zygotes. The HMEJ template resulted in a significantly higher rate of gene knock-in as compared to the HR template (37.0% and 13.8%; P < 0.05). Additionally, more than a third of the knock-in embryos (36.9%) were non-mosaic. This approach will facilitate the one-step introduction of gene constructs at a specific location of the bovine genome and contribute to the next generation of elite cattle.
Pre exposure Hydroxychloroquine Prophylaxis for COVID-19 in healthcare workers: a retrospective cohort
Authors: Bhattacharya Raja , Chowdhury Sampurna , Mukherjee Rishav , Kulshrestha Manish , Ghosh Rohini , Saha Souvik , Nandi Anita
Published: June 2020

Background

While several trials are ongoing for treatment of COVID-19, scientific research on chemoprophylaxis is still lacking even though it has potential to delay the pandemic allowing us time to complete research on vaccines.

Methods

We have conducted a cohort study amongst Health Care Workers (HCW) exposed to COVID-19 patients, at a tertiary care center in India where there was an abrupt cluster outbreak within on duty personnel. HCWs who had voluntarily taken hydroxychloroquine (HCQ) prior to exposure were considered one cohort while those who had not were considered to be another. All participants with a verifiable contact history were tested for COVID-19 by rtPCR. The two cohorts were comparable in terms of age, gender, comorbidities and exposure. The primary outcome was incidence rates of rtPCR positive COVID-19 infection amongst HCQ users and non users.

Results

106 healthcare workers were examined in this cohort study of whom 54 were HCQ users and rest were not. The comparative analysis of incidence of infection between the two groups demonstrated that voluntary HCQ usage was associated with lesser likelihood of developing SARS-CoV-2 infection, compared to those who were not on it, X2=14.59, p<0.001. None of the HCQ users noted any serious adverse effects.

Conclusions

This study demonstrated that voluntary HCQ consumption as pre-exposure prophylaxis by HCWs is associated with a statistically significant reduction in risk of SARS-CoV-2. These promising findings therefore highlight the need to examine this association in greater detail among a larger sample using Randomised Controlled Trials (RCT).
Quantification of the relative arm-use in patients with hemiparesis using inertial measurement units
Authors: David Ann , ReethaJanetSureka StephenSukumaran , Gayathri Sankaralingam , Annamalai Salai Jeyseelan , Samuelkamleshkumar Selvaraj , Kuruvilla Anju , Magimairaj Henry Prakash , Varadhan SKM , Balasubramanian Sivakumar
Published: June 2020

Background

The most popular method for measuring upper limb activity is based on accelerometery. However, this method is prone to overestimation and is agnostic to the functional utility of a movement. In this study, we used an inertial measurement unit(IMU)-based gross movement score to quantify arm-use in hemiparetic patients at home.

Objectives

(i) Validate the gross movement score detected by wrist-worn IMUs against functional movements identified by human assessors. (ii) Test the feasibility of using wrist-worn IMUs to measure arm-use in patients’ natural settings.

Methods

To validate the gross movement score two independent assessors analyzed and annotated the video recordings of 5 hemiparetic patients and 10 healthy controls performing a set of activities while wearing IMUs. The second study tracked arm-use of 5 hemiparetic patients and 5 healthy controls using two wrist-worn IMUs for 7 days and 3 days, respectively. The IMU data obtained from this study was used to develop quantitative measures (total and relative arm-use (RAU)) and a visualization method for arm-use.

Results

The gross movement score detects functional movement with 50–60% accuracy in hemiparetic patients, and is robust to non-functional movements. Healthy controls showed a slight bias towards the dominant arm (RAU: 40.52º). Patients’ RAU varied between 15–47º depending upon their impairment level and pre-stroke hand dominance.

Conclusions

The gross movement score performs moderately well in detecting functional movements while rejecting non-functional movements. The patients’ total arm-use is less than healthy controls, and their relative arm-use is skewed towards the less-impaired arm.

Clinical trial registry number

CTRI/2018/09/015648
Point of care lung ultrasound is useful when screening for CoVid-19 in Emergency Department patients
Authors: Walsh Paul , Hankins Andrea , Bang Heejung
Published: June 2020

Background

CoVid-19 can be a life-threatening lung disease or a trivial upper respiratory infection depending on whether the alveoli are involved. Emergency department (ED) screening in symptomatic patients with normal vital signs is frequently limited to oro-nasopharyngeal swabs. We tested the null hypothesis that patients being screened for CoVid-19 in the ED with normal vital signs and without hypoxia would have a point-of-care lung ultrasound (LUS) consistent with CoVid-19 less than 2% of the time.

Methods

Subjects

Subjects were identified from ED ultrasound logs.

Inclusion criteria

Age 14 years or older with symptoms prompting ED screening for CoVid-19.

Exclusion criteria

Known congestive heart failure or other chronic lung condition likely to cause excessive B lines on LUS.

Intervention

Structured blinded ultrasound review and chart review

Analysis

We used a two-sided exact hypothesis test for binomial random variables. We also measured LUS diagnostic performance using computed tomography as the gold standard.

Results

We reviewed 77 charts; 49 met inclusion criteria. Vital signs were normal in 30/49 patients; 10 (33%) of these patients had LUS consistent with CoVid-19. We rejected the null hypothesis (p-value < 0.001). The treating physicians’ interpretation of their own point of care lung ultrasounds had a sensitivity of 100% (95% CI 75%, 100%) and specificity of 80% (95% CI 68%, 89%).

Conclusion

LUS has a meaningful detection rate for CoVid-19 in symptomatic ED patients with normal vital signs. We recommend at least LUS be used in addition to PCR testing when screening symptomatic ED patients for CoVid-19.

Capsule

What is known

Auscultation and chest x-ray are insufficient to screen for lung involvement when SARS-CoV-2 infection is suspected. Point of care lung ultrasound is widely available, safer, and less resource intensive than CT imaging.

What we found

In symptomatic patients presenting to the ED even those with normal vital signs had point of care lung ultrasound evidence of alveolar level involvement 33%of patients. Point of care lung ultrasound was 100% sensitive and 80% specific compared to CT (reference standard) when evaluating patients for Covid-19.

What this adds

Point of care lung ultrasound or similar imaging should performed when screening symptomatic patients in whom SARS-CoV-2 infection is suspected.
Clinical characteristics and factors associated with admission to intensive care units in hospitalized COVID-19 patients in Lyon University Hospitals, France
Authors: Vanhems Philippe , Gustin Marie-Paule , Elias Christelle , Henaff Laetitia , Dananché Cédric , Grisi Beatrice , Marion Elodie , Khanafer Nagham , Hilliquin Delphine , Gardes Sophie , Gerbier-Colomban Solweig , Amour Selilah , Kuczewski Elisabetta , Escuret Vanessa , Lina Bruno , Saadatian-Elahi Mitra
Published: June 2020

Introduction

A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analyzing clinical presentation on admission and the determinants associated with direct admission or transfer to intensive care units (ICUs) in hospitalized COVID-19 patients.

Patients and Methods

In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients were prospectively collected and analyzed. The outcome was admission/transfer to intensive care units compared with total hospital stay in medical wards according to patient characteristics.

Results

Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of admission/transfer to ICUs with male gender (OR, 1.99 [95%CI, 1.07-3.73]), temperature (OR, 1.37 [95% CI, 1.01-1.88] per degree Celsius increase), abnormal lung auscultation on admission (OR, 2.62 [95% CI, 1.40-4.90]), elevated level of CRP (OR, 6.96 [95% CI, 1.45-33.35 for CRP>100mg/L vs CRP<10mg/L). Increased time was observed between symptom onset and hospital admission (OR, 4.82 [95% CI, 1.61-14.43] for time >10 days vs time <3 days) and monocytopenia (OR, 2.49 [95% CI, 1.29-4.82]). Monocytosis was associated with lower risk of admission/transfer to ICUs (OR, 0.25 [95% CI, 0.05-1.13]).

Conclusions

Clinical and biological features on admission and time until admission were associated with admission to ICUs. Signs to predict worsening on admission could be partially associated with the time until admission. This finding reinforces the need for appropriate guidelines to manage COVID-19 patients in this time window.
Age at Diagnosis Shapes the Prognosis of Childhood Immune Thrombocytopenia
Authors: Schmidt David E. , Edslev Pernille Wendtland , Heitink-Pollé Katja M.J. , Kapur Rick , Porcelijn Leendert , van der Schoot C. Ellen , Vidarsson Gestur , Bruin Marrie C.A. , Rosthøj Steen , de Haas Masja
Published: June 2020

Objective

Childhood immune thrombocytopenia (ITP), an acquired bleeding disorder, occurs at any age. Studies have indicated a less favourable prognosis in children aged above ten years. Low lymphocyte counts have been proposed as predictors of chronic disease. Detailed knowledge of ITP disease characteristics and prognosis at various ages may be useful to support clinical decision-making. We aimed to define how age shapes the clinical characteristics, biological parameters and disease outcomes in childhood ITP.

Design

Post-hoc analysis of two prospective European studies (NOPHO ITP study and TIKI trial). Children were followed for 6-12 months.

Setting

Patient inclusion in paediatrics departments in the Netherlands and the five Nordic countries.

Patients

Children aged <16 years with newly diagnosed ITP (N=577) and severe thrombocytopenia (diagnosis platelet count ≤20 × 109/L).

Results

By analysing age effects on a continuous scale, we observed that recovery rates at 3-12 months follow-up were gradually reduced in children aged above five years. An absence of a response to IVIg was observed at all ages, but was more common in older children, in particular above 6 years of age. Leukocyte and lymphocyte subset counts were reduced with age, but not elevated or decreased compared to age-appropriate reference intervals. Children aged below seven years showed elevated thrombopoietin levels.

Conclusions

Already from five years of age onwards, there is an increasing risk for a long-lasting course of ITP. Given the varying treatment responses and biological variation, age differences should be considered for the design of clinical trials, prediction models and biological studies.
Assessing the reliability of species distribution projections in climate change research
Authors: Santini Luca , Benítez-López Ana , Maiorano Luigi , Čengić Mirza , Huijbregts Mark A.J.
Published: June 2020

Aim

Forecasting changes in species distribution under future scenarios is one of the most prolific areas of application for species distribution models (SDMs). However, no consensus yet exists on the reliability of such models for drawing conclusions on species distribution response to changing climate. In this study we provide an overview of common modelling practices in the field and assess model predictions reliability using a virtual species approach.

Location

Global

Methods

We first provide an overview of common modelling practices in the field by reviewing the papers published in the last 5 years. Then, we use a virtual species approach and three commonly applied SDM algorithms (GLM, MaxEnt and Random Forest) to assess the estimated (cross-validated) and actual predictive performance of models parameterized with different modelling settings and violations of modelling assumptions.

Results

Our literature review shows that most papers that model species distribution under climate change rely on single models (65%) and small samples (< 50 presence points, 62%), use presence-only data (85%), and binarize models’ output to estimate range shift, contraction or expansion (74%). Our virtual species approach reveals that the estimated predictive performance tends to be over-optimistic compared to the real predictive performance. Further, the binarization of predicted probabilities of presence reduces models’ predictive ability considerably. Sample size is one of the main predictors of real accuracy, but has little influence on estimated accuracy. Finally, the inclusion of irrelevant predictors and the violation of modelling assumptions increases estimated accuracy but decreases real accuracy of model projections, leading to biased estimates of range contraction and expansion.

Main conclusions

Our study calls for extreme caution in the application and interpretation of SDMs in the context of biodiversity conservation and climate change research, especially when modelling a large number of species where species-specific model settings become impracticable.
Critical role for astrocyte NAD+glycohydrolase in myelin injury and regeneration
Authors: Langley Monica R. , Choi Chan-Il , Peclat Thais R. , Guo Yong , Simon Whitney , Yoon Hyesook , Kleppe Laurel , Lucchinetti Claudia F. , Chini Claudia C.S. , Chini Eduardo N. , Scarisbrick Isobel A.
Published: June 2020

Western-style diets cause disruptions in myelinating cells and astrocytes within the mouse CNS. CD38 has increased expression in the cuprizone and EAE demyelination models and is the main NAD+depleting enzyme in CNS tissue. Altered NAD+metabolism has been linked to both high fat consumption and Multiple Sclerosis (MS). We identified increased CD38 expression in the male mouse spinal cord following chronic high fat consumption or focal lysolecithin-induced demyelinating injury as well as in reactive astrocytes within an active MS lesion. CD38-catalytically inactive mice are significantly protected from high fat-induced NAD+depletion, oligodendrocyte loss, oxidative damage, and astrogliosis. 78c, a CD38 inhibitor, increased NAD+and attenuated neuroinflammatory changes in astrocytes induced by saturated fat. Conditioned media from saturated fat-treated astrocytes impaired oligodendrocyte differentiation pointing to indirect mechanisms of oligodendrogliopathy. Combined saturated fat and lysolecithin demyelination in cerebellar slices resulted in additional deficits in myelin proteins that were mitigated by concomitant 78c treatment. Importantly, oral 78c increased counts of oligodendrocytes and remyelinated axons after focal demyelination. Our findings suggest high fat diet impairs oligodendrocyte survival and differentiation through astrocyte-linked mechanisms mediated by the NAD+ase CD38, and highlight the use of CD38 inhibitors as potential therapeutic candidates to improve myelin regeneration.
Does rainforest biodiversity stand on the shoulders of giants? Effect of disturbances by forest elephants on trees and insects on Mount Cameroon
Authors: Maicher Vincent , Delabye Sylvain , Murkwe Mercy , Doležal Jiří , Altman Jan , Kobe Ishmeal N. , Desmist Julie , Fokam Eric B. , Pyrcz Tomasz , Tropek Robert
Published: June 2020

Natural disturbances are essential for dynamics of tropical rainforests, contributing to their tremendous biodiversity. In the Afrotropical rainforests, megaherbivores have played a key role before their recent decline. Although the influence of savanna elephants on ecosystems has been documented, their close relatives, forest elephants, remain poorly studied. Few decades ago, in the unique ‘natural enclosure experiment’ on Mount Cameroon, West/Central Africa, the rainforests were divided by lava flows which are not crossed by the local population of forest elephants. We assessed communities of trees, butterflies and two ecological guilds of moths in disturbed and undisturbed forests split by the longest lava flow at upland and montane elevations. Altogether, we surveyed 32 forest plots resulting in records of 2,025 trees of 97 species, and 7,853 butterflies and moths of 437 species. The disturbed forests differed in reduced tree density, height, and high canopy cover, and in increased DBH. Forest elephants also decreased tree species richness and altered their composition, probably by selective browsing and foraging. The elephant disturbance also increased species richness of butterflies and had various effects on species richness and composition of all studied insect groups. These changes were most probably caused by disturbance-driven alterations of (micro)habitats and species composition of trees. Moreover, the abandonment of forests by elephants led to local declines of range-restricted butterflies. Therefore, the current appalling decline of forest elephant populations across the Afrotropics most probably causes important changes in rainforest biodiversity and should be reflected by regional conservation authorities.
Viral miRNAs Confer Survival in Host Cells by Targeting Apoptosis Related Host Genes
Authors: Islam Md. Sajedul , Islam Abul BMMK
Published: June 2020

Background

miRNAs are small non-coding RNAs that regulate the expression of genes by RNA silencing method. Like eukaryotic organisms, some viruses also produce miRNAs. While contribution of host miRNA in the prevention of viral pathogenesis has been studied, it is not known very well how viral miRNA can confer its survival in the host. Here we hypothesized that viral miRNAs can bind to the host target genes to confer their pathogenicity by down-regulating specific pathways and related genes that otherwise pose threat to cell survival.

Methods and Results

Using targets of 168 viral miRNAs from 13 different viruses overrepresentation analysis was done. Functional enrichment analysis of the genes targeted by the miRNAs indicates that viruses target specific immune system and host defense related pathways via miRNA mediated gene silencing. Integration and analysis of the publicly available experimental host gene expression data by RNA-seq provided insight that viruses target host apoptosis process by switching off related genes through miRNA induced mechanisms and thus probably ensure their survival.

Conclusions

As switching off the apoptosis of host cells would provide the viruses with selective advantages in surviving inside host, our findings therefore envisage an important function of viral miRNA which demands furtherin vivoexperiments for better understanding in this regard.
CCM signaling complex (CSC) is a master regulator governing homeostasis of progestins and their mediated signaling cascades
Authors: Abou-Fadel Johnathan , Jiang Xiaoting , Padarti Akhil , Goswami Dinesh , Smith Mark , Grajeda Brian , Walker Wendy , Zhang Jun
Published: June 2020

We demonstrate that a novel signaling network among the CSC and mPRS is dynamically modulated and fine-tuned with intricate feedback regulations in PR negative cells, especially endothelial cells (ECs). Depletion of any of three CCMs (1, 2, 3) genes results in the disruption of non-classic mPRs-mediated signalingin-vitroas well as defective homeostasis of PRGin-vivo. Therefore, we propose the CSC is a master regulator of homeostasis of PRG and its associated classic and non-classic signaling cascades. Assisted with omic approaches, we identified signaling pathways involved and specific biomarkers associated with hemorrhagic events during CCM pathogenesisin-vitroandin-vivo. To our knowledge, this is the first report detailing etiology to predict the occurrence of early hemorrhagic events with a set of serum biomarkers.
Transcriptional heterogeneity of stemness phenotypes in the ovarian epithelium
Authors: Carter LE. , Cook DP. , McCloskey CW. , Dang T. , Collins O. , Gamwell LF. , Dempster HA. , Vanderhyden BC.
Published: June 2020

The ovarian surface epithelium (OSE) is a monolayer of epithelial cells covering the surface of the ovary. During ovulation, the OSE is ruptured to allow release of the oocyte. This wound is quickly repaired, but mechanisms of this repair are poorly understood. The contribution of tissue-resident stem cells in the homeostasis of several epithelial tissues is widely accepted, such as the intestinal epithelium, airway epithelium, and skin, but their involvement in OSE maintenance is unclear. While putative stem cell populations in the OSE have been described, how they are regulated is poorly defined. We show that traits associated with stem cells (stemness) can be increased in OSE following exposure to the cytokine TGFB1, overexpression of the transcription factorSnai1, or deletion ofBrca1. By assessing the gene expression profiles of these populations, we show that stemness is often linked to mesenchymal-associated gene expression and higher activation of ERK signalling, but it is not consistently dependent on their activation. Expression profiles of these populations are extremely context specific, suggesting that stemness may not correspond to a single, distinct population, but rather is a heterogenous state that can possibly emerge from diverse environmental cues. Together, these findings support that the OSE may not require distinct stem cell populations for long-term maintenance, and may achieve this through transient dedifferentiation into a stem-like state.
Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2
Authors: Rosenke Kyle , Jarvis Michael A. , Feldmann Friederike , Schwarz Benjamin , Okumura Atsushi , Lovaglio Jamie , Saturday Greg , Hanley Patrick W. , Meade-White Kimberly , Williamson Brandi N. , Hansen Frederick , Perez-Perez Lizette , Leventhal Shanna , Tang-Huau Tsing-Lee , Nason Martha , Callison Julie , Haddock Elaine , Scott Dana , Sewell Graham , Bosio Catharine M. , Hawman David , de Wit Emmie , Feldmann Heinz
Published: June 2020

We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.

One Sentence Summary

Hydroxychloroquine prophylaxis/treatment showed no beneficial effect in SARS-CoV-2 hamster and macaque disease models.
Ultrasonic Texture Analysis Identifies Cardiac Microstructural Alterations in Immune-Inflammatory Disease
Authors: Kwan Alan C. , Nguyen Trevor , Kim Elizabeth H. , Demosthenes Emmanuella , Salto Gerran , Luong Eric , Hiremath Pranoti , Li Debiao , Berman Daniel S. , Patel Jignesh , Cheng Susan
Published: June 2020

Background

Echocardiographic texture analysis using the signal intensity coefficient (SIC) can identify fibrosis-associated microstructural changes. This approach has not been tested in immune-inflammatory disease states such as myocarditis or transplant rejection.

Methods

Retrospective pilot analysis using the SIC was performed in populations including myocarditis (n=5), acute left anterior descending coronary artery STEMI (n=6), severe aortic stenosis with normal ejection fraction (n=7), ATTR amyloidosis (n=6), and cardiac transplant patients undergoing biopsy including patients with active rejection on histopathology (n=22), patients with history of rejection but no current rejection (n=15), and patients without history of or current rejection (n=5), and a healthy control group (n=28).

Results

Decreased SIC was noted in the myocarditis and transplant rejection populations, with decreasing SIC by presence and history of rejection. Consistent with prior literature, the SIC was elevated in cardiac conditions associated with fibrosis.

Conclusions

The SIC may be able to capture microstructural changes associated with immune-inflammatory processes such as cardiac transplant rejection and myocarditis.
Resource requirements for reintroducing elective surgery in England during the COVID-19 pandemic: a modelling study
Authors: Fowler A. J. , Dobbs T. D. , Wan Y. I. , Laloo R. , Hui S. , Nepogodiev D. , Bhangu A. , Whitaker I. S. , Pearse R. M. , Abbott T. E. F.
Published: June 2020

Background

The response to COVID-19 has required cancellation of all but the most urgent surgeries, including many cancer operations. We estimated the number of cancelled surgical procedures in the National Health Service (NHS) in England due to COVID-19 and how this deficit would change over time once elective surgery was reintroduced.

Methods

Modelling study using Hospital Episode Statistics (HES) data from 2014 to 2019. Using NHS England definitions, surgical procedures were grouped into four classes of urgency. We calculated time-weighted average numbers of surgical procedures from 1stMarch 2020 and extrapolated to 28thFebruary 2021 informed by activity in previous years. We estimated the procedure deficit using multiple conservative assumptions and then modelled the reintroduction of elective surgery between 1stJune 2020 and 28thFebruary 2021, estimating the resources required to achieve this. Costs of surgery were calculated using NHS reference costs. Estimates are reported with 95% confidence intervals.

Findings

4,547,534 (3,318,195 - 6,250,771) patients with pooled mean age of 53.5 years were expected to undergo surgery in the NHS in England between 1stMarch 2020 and 28thFebruary 2021. Due to COVID-19, 749,248 (513,565 - 1,077,448) surgical procedures were cancelled by 31stMay 2020. As current guidelines require a gradual reintroduction of elective surgery, this deficit will increase further and 2,270,178 (1,453,057 - 3,363,472) patients will be awaiting surgery by 28th February 2021. The cost of these delayed procedures is £4,688,318,443 (£2,726,364,240 - £7,070,166,056). However, the safe delivery of surgery during the pandemic will require substantial extra resources including personal protective equipment and universal preoperative screening, leading to additional costs of £606,252,901 (£521,159,931 - £730,720,808).

Interpretation

Reintroduction of elective surgery during the pandemic response in NHS England will be associated with substantial treatment delays for many patients, and a large increase in treatment costs.

Funding

NIHR (DRF-2018-11-ST2-062) to AJF.