bluuebunny/crossref_metadata_2025 huggingface dataset:
Alloplastic Auricular Reconstruction: Review of Implant Types, Adverse Events, and Aesthetic Outcomes
Authors: Oliver Jeremie D. , Rodriguez Daniel , Scott Derek , Santosa Katherine B. , Hu Michael S.
Published: May 2020

Importance:

Alloplastic implants have been applied successfully in reconstruction of the external ear, either for congenital microtia or traumatic injury.

Objective:

The objective of this study was to conduct a comprehensive systematic review of alloplastic implant materials utilized in the reconstruction of the external ear stratified by indication, specific implant type, postoperative complications, and aesthetic outcomes.

Evidence Review:

A comprehensive systematic review of published literature on alloplastic external ear reconstruction data was conducted utilizing Medline/PubMed database without timeframe limitations in June 2019. Articles were stratified by (1) indication (microtia versus trauma reconstruction) and (2) implant material type. All postoperative complications were recorded and comparatively analyzed between implant types. Aesthetic outcomes were also identified and compared between implant types.

Findings:

A total of 755 patients (14 case series; follow-up range = 3 months--10 years) met the criteria for this study. Overall complication rate was 12.05% across all indications and materials used. The most frequent complications reported were graft exposure (7.8%), graft explantation (1.72%), and wound dehiscence (0.8%). Of the patients requiring graft explantation (n = 13), 7 (53.85%) received Medpor implants, and the other 6 (46.15%) were identified in silicone implants. Infection was only reported in Medpor implants. The overall rate of an acceptable aesthetic outcome was 99.34%.

Conclusions and Relevance:

Alloplastic implants are a reliable means of achieving an acceptable complication profile in external ear reconstruction. While there was an overall high rate of acceptable aesthetic outcomes, the studies evaluated in this systematic review differed in their criteria for final evaluation of aesthetic outcomes.
Anesthetic and Analgesic Efficient of Regional Nerve Blockade in Otoplasty
Authors: Kepekçi Ali Bestemi , Kepekçi Ahmet Hamdi
Published: May 2020

Aim:

The prominent ear is the most common congenital deformity of the external ear. Otoplasty is performed to correct the appearance of the prominent ear. This study was planned to compare the analgesic and anesthetic effects of local nerve blockade and local infiltration anesthesia in the otoplasties.

Method:

Thirty-two patients who underwent otoplasty in both ears between February 2018 and March 2019 were included in the study. Three patients were excluded because they refused regional anesthesia. In the patients included in the study, only local infiltration anesthesia was applied to 1 ear and regional nerve blockade was applied to the other ear. Regional nerve blockade was applied to the study group; local infiltration anesthesia was applied to the control group. Surgical and anesthetic complications were recorded. The onset time, duration and severity of pain were followed. Numerical evaluation scale scores were used to evaluate pain levels.

Results:

It was observed that the first pain of the patients On the side where regional nerve block (RNB) anesthesia was applied after an average of 10.5 hours. On the other hand on the side where local infiltration anesthesia was applied; the pain was observed to start after an average of 3.5 hours. At the 6th and 12th hours postoperatively, the scores of the numerical evaluation scale were significantly lower in the study group than the control group (P < 0.05). At the 24th-hour pain score, the values were lower in the study group, but the difference was not significant between the groups (P > 0.05). In the regional anesthesia group, can develop such as difficulty in swallowing, weakness in the neck, weakness in the upper extremity, nausea, Horner syndrome; but all side effects resolve spontaneously within 6 to 12 hours.

Conclusion:

The application of regional anesthesia in prominent ear surgical procedures can be considered as an alternative method to provide better quality preoperative anesthesia and better quality postoperative analgesia in patients.
Anti-gamma-aminobutyric acid receptor type A encephalitis: a review
Authors: Guo Chu-Yueh , Gelfand Jeffrey M. , Geschwind Michael D.
Published: May 2020

Purpose of review

To systematically review the clinical features, diagnosis, and management of anti-gamma-aminobutyric acid receptor Type A (GABAA) autoimmune encephalitis with a focus on recent data.

Recent findings

In a review of published reports, we identified 50 cases of anti-GABAA receptor encephalitis with clinical features reported. The median age at presentation was 47 years old (range, 2.5 months–88 years old), 64% were adults, 36% were children and it occurred in both males and females. Eight-two percent (41/50) presented with seizures, 72% (36/50) with encephalopathy, and 58% (29/50) with both. Of those presenting with seizures, 42% developed status epilepticus during their disease course. Ninety-six percent (48/50) had MRI results reported, with 83% of these cases having abnormal findings, most commonly multifocal/diffuse cortical and subcortical T2/FLAIR hyperintense lesions without associated gadolinium enhancement. Almost one-third, 28% (14/50), had an associated malignancy detected by the time of diagnosis, 64% (9/14) of which was thymoma. Of 44 patients with outcomes reported, 80% had partial or complete recovery, whereas 20% had poor outcomes including 11% (5/44) who died. Of the 42 patients with type of treatment(s) and outcomes reported, 54% (23/42) received only first-line immunotherapy and 31% (13/42) received first-line and second-line immunotherapy. Receiving a combination of first-line and second-line immunotherapy may be associated with higher likelihood of complete recovery. When follow-up MRIs were reported, all showed improvement, and sometimes complete resolution, of T2/FLAIR hyperintensities.

Anti-GABAA receptor encephalitis can present across the age spectrum and should be considered in patients who present with rapidly progressive encephalopathy and/or seizures. Brain MRI often shows a distinctive pattern of multifocal cortical and subcortical T2/FLAIR hyperintense lesions, generally not typical of other known central nervous system autoantibody associated encephalitis syndromes. High clinical suspicion and early diagnosis are important given the potential for clinical improvement with immunotherapy.
Prevention and management of adverse effects of disease modifying treatments in multiple sclerosis
Authors: Moiola Lucia , Rommer Paulus S. , Zettl Uwe K.
Published: May 2020

Purpose of review

To summarize the currently known side effects of the approved therapies of multiple sclerosis and to suggest monitoring procedures.

Recent findings

The progress in the treatment of multiple sclerosis with new very effective therapies is accompanied by a number of side effects. Some of these have already been described in the approval studies, but some only after approval in a real world situation. The reason for this is the short duration of the clinical studies, the very heterogeneous patient profile in the real world setting with a number of comorbidities, pretherapies, and wider age range. The side effects may occur during application of therapies or afterwards during the course of the treatment. The side effects may range from mild infections, mild laboratory abnormalities, secondary autoimmune diseases to life-threatening side effects such as progressive multifocal leukoencephalopathy.

It has to be pointed out that these side effects are not to be considered as final and neurologists should be vigilant against new unknown side effects. The doctor should be aware of these undesirable effects, should weigh the benefits of the therapies against the risks, but at the same time she/he should keep in mind that multiple sclerosis can be a very disabling disease if not treated properly.
Liquid dispensing in the adhesive hairy pads of dock beetles
Authors: Iazzolino Antonio , Cerkvenik Uroš , Tourtit Youness , Ladang Auxane , Compère Philippe , Gilet Tristan
Published: May 2020

Many insects can climb on smooth inverted substrates using adhesive hairy pads on their legs. The hair–surface contact is often mediated by minute volumes of liquid, which form capillary bridges in the contact zones and aid in adhesion. The liquid transport to the contact zones is poorly understood. We investigated the dynamics of liquid secretion in the dock beetleGastrophysa viridulaby quantifying the volume of the deposited liquid footprints during simulated walking experiments. The footprint volume increased with pad–surface contact time and was independent of the non-contact time. Furthermore, the footprint volume decreased to zero after reaching a threshold cumulative volume (approx. 30 fl) in successive steps. This suggests a limited reservoir with low liquid influx. We modelled our results as a fluidic resistive system and estimated the hydraulic resistance of a single attachment hair of the order of MPa · s/fl. The liquid secretion in beetle hairy pads is dominated by passive suction of the liquid during the contact phase. The high calculated resistance of the secretion pathway may originate from the nanosized channels in the hair cuticle. Such nanochannels presumably mediate the transport of cuticular lipids, which are chemically similar to the adhesive liquid.
A minimal mechanosensing model predicts keratocyte evolution on flexible substrates
Authors: Zhang Zhiwen , Rosakis Phoebus , Hou Thomas Y. , Ravichandran Guruswami
Published: May 2020

A mathematical model is proposed for shape evolution and locomotion of fish epidermal keratocytes on elastic substrates. The model is based on mechanosensing concepts: cells apply contractile forces onto the elastic substrate, while cell shape evolution depends locally on the substrate stress generated by themselves or external mechanical stimuli acting on the substrate. We use the level set method to study the behaviour of the model numerically, and predict a number of distinct phenomena observed in experiments, such as (i) symmetry breaking from the stationary centrosymmetric to the well-known steadily propagating crescent shape, (ii) asymmetric bipedal oscillations and travelling waves in the lamellipodium leading edge, (iii) response to remote mechanical stress externally applied to the substrate (tensotaxis) and (iv) changing direction of motion towards an interface with a rigid substrate (durotaxis).
‘What he hath gather'd together shall not be lost’: remembering James Petiver
Authors: Coulton Richard
Published: May 2020

James Petiver FRS (
ca
1663–1718) was a professional apothecary and prominent natural historian in London at the turn of the eighteenth century. This essay introduces a special issue of
Notes and Records
, ‘Remembering James Petiver’, marking the 300th anniversary of his death. Combining his known biography with new research, it accounts for Petiver's formation as urban apothecary and botanist, his emergence as public natural historian in the mid 1690s, and his subsequent career as natural history collector and author. Petiver's museum of plants and invertebrates was accumulated by co-ordinating an unprecedented network of relatively ordinary people, many of them medical practitioners, to collect for him wherever they travelled: North and South America, western and southern Africa, mainland Europe, South and East Asia, Indonesia and the Philippines. This network and its achievements were predicated upon Britain's expanding global commercial and colonial interests (including those that exploited the traffic in and labour of enslaved human beings). It also depended upon Petiver's strategic management of his collaborators, through the exchange of correspondence and material objects. New analysis of Petiver's network, specimens, publications and manuscripts revises the prevailing view that he was careless and disorganized, to reveal a socially industrious and intellectually discriminating natural scientist.
SUMOylation in the control of cholesterol homeostasis
Authors: Talamillo Ana , Ajuria Leiore , Grillo Marco , Barroso-Gomila Orhi , Mayor Ugo , Barrio Rosa
Published: May 2020

SUMOylation—protein modification by the small ubiquitin-related modifier (SUMO)—affects several cellular processes by modulating the activity, stability, interactions or subcellular localization of a variety of substrates. SUMO modification is involved in most cellular processes required for the maintenance of metabolic homeostasis. Cholesterol is one of the main lipids required to preserve the correct cellular function, contributing to the composition of the plasma membrane and participating in transmembrane receptor signalling. Besides these functions, cholesterol is required for the synthesis of steroid hormones, bile acids, oxysterols and vitamin D. Cholesterol levels need to be tightly regulated: in excess, it is toxic to the cell, and the disruption of its homeostasis is associated with various disorders like atherosclerosis and cardiovascular diseases. This review focuses on the role of SUMO in the regulation of proteins involved in the metabolism of cholesterol.
Spatiophylogenetic modelling of extinction risk reveals evolutionary distinctiveness and brief flowering period as threats in a hotspot plant genus
Authors: Dinnage Russell , Skeels Alexander , Cardillo Marcel
Published: May 2020

Comparative models used to predict species threat status can help identify the diagnostic features of species at risk. Such models often combine variables measured at the species level with spatial variables, causing multiple statistical challenges, including phylogenetic and spatial non-independence. We present a novel Bayesian approach for modelling threat status that simultaneously deals with both forms of non-independence and estimates their relative contribution, and we apply the approach to modelling threat status in the Australian plant genusHakea.We find that after phylogenetic and spatial effects are accounted for, species with greater evolutionary distinctiveness and a shorter annual flowering period are more likely to be threatened. The model allows us to combine information on evolutionary history, species biology and spatial data, calculate latent extinction risk (potential for non-threatened species to become threatened), estimate the most important drivers of risk for individual species and map spatial patterns in the effects of different predictors on extinction risk. This could be of value for proactive conservation decision-making based on the early identification of species and regions of potential conservation concern.
Towards a unified study of multiple stressors: divisions and common goals across research disciplines
Authors: Orr James A. , Vinebrooke Rolf D. , Jackson Michelle C. , Kroeker Kristy J. , Kordas Rebecca L. , Mantyka-Pringle Chrystal , Van den Brink Paul J. , De Laender Frederik , Stoks Robby , Holmstrup Martin , Matthaei Christoph D. , Monk Wendy A. , Penk Marcin R. , Leuzinger Sebastian , Schäfer Ralf B. , Piggott Jeremy J.
Published: May 2020

Anthropogenic environmental changes, or ‘stressors’, increasingly threaten biodiversity and ecosystem functioning worldwide. Multiple-stressor research is a rapidly expanding field of science that seeks to understand and ultimately predict the interactions between stressors. Reviews and meta-analyses of the primary scientific literature have largely been specific to either freshwater, marine or terrestrial ecology, or ecotoxicology. In this cross-disciplinary study, we review the state of knowledge within and among these disciplines to highlight commonality and division in multiple-stressor research. Our review goes beyond a description of previous research by using quantitative bibliometric analysis to identify the division between disciplines and link previously disconnected research communities. Towards a unified research framework, we discuss the shared goal of increased realism through both ecological and temporal complexity, with the overarching aim of improving predictive power. In a rapidly changing world, advancing our understanding of the cumulative ecological impacts of multiple stressors is critical for biodiversity conservation and ecosystem management. Identifying and overcoming the barriers to interdisciplinary knowledge exchange is necessary in rising to this challenge. Division between ecosystem types and disciplines is largely a human creation. Species and stressors cross these borders and so should the scientists who study them.
Yamadazyma cocois f.a., sp. nov., an ascomycetous yeast isolated from coconuts
Authors: Maksimova Irina A. , Glushakova Anna M. , Thanh Vu Nguyen , Kachalkin Aleksey V.
Published: May 2020

During studies on the endophytic yeast communities associated with fruits from Vietnam, three fermenting yeast strains were isolated from fruits of the coconut palm (Cocos nucifera). Phylogenetic analysis based on the sequences of the ITS regions and D1/D2 domains of the large subunit rRNA gene showed that these strains represented a single species of the Yamadazyma clade that was distinct from the other related species. The new species represented a basal branch of the clade formed by the Yamadazyma species i.e. Y. insecticola and Y. takamatsuzukensis. Based on the phylogenetic analysis and phenotypic characteristics, the studied strains were assigned to a novel species of the genus Yamadazyma, for which the name Yamadazyma cocois f.a., sp. nov. is proposed. The holotype is VCIM 4241, with the ex-type cultures VTCC 920004=VKM Y-3049=KBP Y-6091 code 17–68. The MycoBank number is MB 834435.
Is Hydroxychloroquine Safe During Pregnancy? Observations from Penn Medicine
Authors: Davidson Lena , Canelón Silvia P. , Boland Mary Regina
Published: May 2020

A novel strain of coronavirus appeared in December 2019. Over the next few months, this novel coronavirus spread throughout the world, being declared a pandemic by the World Health Organization on March 11, 2020. As of this writing (March 28, 2020) over one hundred thousand individuals in the United States of America were confirmed cases. One way of treating the associated disease, COVID-19, is to reuse existing FDA-approved medications. One medication that has shown promise is hydroxychloroquine (HCQ). However, the utility and safety of HCQ among pregnant COVID-19 patients remains a concern.
Lung disease severity, Coronary Artery Calcium, Coronary inflammation and Mortality in Coronavirus Disease 2019
Authors: Gaibazzi Nicola , Martini Chiara , Mattioli Maria , Tuttolomondo Domenico , Guidorossi Angela , Suma Sergio , Dey Damini , Palumbo Anselmo , Filippo Massimo De
Published: May 2020

The authors have withdrawn this manuscript at the request of their local IRB, because the objectives outlined in this study were not specifically approved by the IRB. 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.
National and state wise estimate of time varying reproduction number for COVID-19 in India during the nationwide lockdown
Authors: Venkatesan Padmanaban
Published: May 2020

To understand the effect of nationwide lockdown on transmissibilty of SARS-CoV-2 in India, time varying reproduction number during the first weeks of April, 2020 was estimated. The time varying reproduction number was estimated using EpiEstim package in R programming language. The reproduction number has come down significantly during the lockdown period both at national level and in most states but it wasn’t reduced to less than 1. This calls for urgent need for more effective control measures in addition to lockdown to stop the epidemic spread of the virus.
Does BCG protect against SARS-CoV-2 infection ?: elements of proof
Authors: Ouanes Yassine , Bibi Mokhtar , Baradai Nesrine , Boukhris Marouane , Chaker Kays , Kacem Aziz , Hedhli Houcem , Deli Kheireddine Mrad , Sellami Ahmed , Rhouma Sami Ben , Nouira Yassine
Published: May 2020

Background

There are several factors explaining the difference in the spread of SARS-CoV-2 infection including the BCG vaccination. This fact is supported by the concept of beneficial non specific effect of this live vaccine associated to its interaction with the immune system.

Our study aims to identify the correlation between the universal BCG vaccination policy and the mortality attributed to COVID-19.

Methods

We conducted an epidemiological study in which we collected COVID-19 pandemic data of April 11th, 2020 from the web site worldometers.info. The exclusion criteria for our study were a number of inhabitants less than one million, low-income countries according to the World Bank classification, a total number of infection cases less than 500 and countries that have performed less than one hundred tests per million inhabitants.

Results

Countries that never had universal BCG vaccination policy have a higher mortality (correlated to performed diagnostic tests) attributed to SARS-CoV-2 infection (p<0.001).

We found that the year of introduction of vaccination influenced significantly the mortality. Countries that started immunization policy before 1960 had more favorable results (p=0.049).

For countries that started the BCG vaccination after 1960, countries with current policies have lower mortality attributed to SARS-CoV-2 infection than countries that have stopped immunization (p=0.047).

Conclusions

Countries that have a BCG vaccination policy have a lower mortality attributed to SARS-CoV-2 infection. The populations of countries that applied this immunization before 1960 are more protected even if this universal policy has been interrupted.
COVID-19 AND PATIENTS UNDERGOING PHARMACOLOGICAL TREATMENTS FOR IMMUNE-MEDIATED INFLAMMATORY DISEASES: PROTOCOL FOR A RAPID LIVING SYSTEMATIC REVIEW
Authors: da Rocha Aline Pereira , Atallah Alvaro Nagib , Pinto Ana Carolina Pereira Nunes , Rocha-Filho César Ramos , de Assis Reis Felipe Sebastião , Milby Keilla Martins , Civile Vinicius Tassoni , Carvas Junior Nelson , Santos Rodolfo Rodrigo Pereira , Ferla Laura Jantsch , Trevisani Giulia Fernandes Moça , Ramalho Gabriel Sodré , Puga Maria Eduarda Santos , Trevisani Virgínia Fernandes Moça
Published: May 2020

CONTEXT AND OBJECTIVE

We propose to systematically review the available evidence to evaluate if patients with immune mediated inflammatory diseases under pharmacological treatment with immunosuppressants, immunobiologics, Disease-Modifying Anti-Rheumatic Drugs (DMARD) or targeted synthetic DMARDs have better or worse outcomes when infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study is a protocol for our rapid living systematic review. METHODS: Protocol for a rapid living systematic review methodology following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidance. To conduct the rapid systematic review, we will employ abbreviated systematic review methods, including: not performing independent screens of abstracts and not searching grey literature. As this will be a living review, it will be continuously updated.
Personalized Early Stage Alzheimer’s Disease Detection: A Case Study of President Reagan’s Speeches
Authors: Wang Ning , Peddagangireddy Vishal , Luo Fan , Subbalakshmi K.P. , Chandramouli R.
Published: May 2020

Alzheimer’s disease (AD)-related global healthcare cost is estimated to be $1 trillion by 2050. Currently, there is no cure for this disease; however, clinical studies show that early diagnosis and intervention helps to extend the quality of life and inform technologies for personalized mental healthcare. Clinical research indicates that the onset and progression of Alzheimer’s disease lead to dementia and other mental health issues. As a result, the language capabilities of patient start to decline.

In this paper, we show that machine learning-based unsupervised clustering of and anomaly detection with linguistic biomarkers are promising approaches for intuitive visualization and personalized early stage detection of Alzheimer’s disease. We demonstrate this approach on 10 year’s (1980 to 1989) of President Ronald Reagan’s speech data set. Key linguistic biomarkers that indicate early-stage AD are identified. Experimental results show that Reagan had early onset of Alzheimer’s sometime between 1983 and 1987. This finding is corroborated by prior work that analyzed his interviews using a statistical technique. The proposed technique also identifies the exact speeches that reflect linguistic biomarkers for early stage AD.
Spatial Inequities in COVID-19 Testing, Positivity, Confirmed Cases and Mortality in 3 US Cities: an Ecological Study
Authors: Bilal Usama , Tabb Loni P. , Barber Sharrelle , Roux Ana V. Diez
Published: May 2020

Background

Preliminary evidence has shown inequities in COVID-19 related cases and deaths in the US.

Objective

We explored the emergence of spatial inequities in COVID-19 testing, positivity, confirmed cases, and mortality in New York City, Philadelphia, and Chicago during the first six months of the pandemic.

Design

Ecological, observational study at the zip code tabulation area (ZCTA) level from March to September 2020.

Setting

Chicago, New York City and Philadelphia.

Participants

All populated ZCTAs in the three cities.

Measures

Outcomes were ZCTA-level COVID-19 testing, positivity, confirmed cases, and mortality cumulatively through the end of September. Predictors were the CDC social vulnerability index and its four domains, obtained from the 2014-2018 American Community Survey. We examined the spatial autocorrelation of COVID-19 outcomes using global and local Moran’s I and estimated associations using spatial conditional autoregressive negative binomial models.

Results

We found spatial clusters of high and low positivity, confirmed cases and mortality, co-located with clusters of low and high social vulnerability. We also found evidence for the existence of spatial inequities in testing, positivity, confirmed cases and mortality for the three cities. Specifically, neighborhoods with higher social vulnerability had lower testing rates, higher positivity ratios, confirmed case rates and mortality rates.

Limitations

ZCTAs are imperfect and heterogeneous geographical units of analysis. We rely on surveillance data, which may be incomplete.

Conclusion

We found spatial inequities in COVID-19 testing, positivity, confirmed cases, and mortality in three large cities of the US.

Registration

N/A

Funding source

NIH (DP5OD26429) and RWJF (77644)
Safe clinical practice for patients hospitalised in mental health wards during a suicidal crisis: a qualitative study of patient experiences
Authors: Berg Siv Hilde , Rørtveit Kristine , Walby Fredrik A. , Aase Karina
Published: May 2020

Aim

The aim of this study was to explore suicidal patients’ experiences of safe clinical practice during hospitalisation in mental healthcare. The study was guided by the following research question: How do suicidal patients experience safe clinical practice during hospitalisation in mental health wards?

Design, setting and participants

A qualitative design with semi-structured individual interviews was applied. Eighteen patients hospitalised with suicidal behaviour in specialised mental healthcare for adults at a Norwegian hospital participated in the study. Data were analysed thematically and inductively using qualitative content analysis.

Results

Patients in a suicidal crisis experienced safe clinical care in mental health wards characterised by the following three themes: (1) being detected by mindful healthcare professionals, (2) receiving tailor-made treatment and (3) being protected by adaptive practice.

Conclusion

This study illuminates the experiences of safe clinical practice for patients in a suicidal crisis. The patient group was multifaceted with fluctuating suicidal behaviour, which highlights the importance of embracing personalised activities. Safe clinical practice needs to recognise rather than efface patients’ variability.

Strengths and limitations of this study

•

This study used qualitative interviews to provide rich and variable in-depth data of inpatients with suicidal behaviour, which is an under-researched group.

•

Patient experience consultants were involved in the design of the study.

•

The study results are suitable for conceptual development of safe clinical practice for suicidal patients.

•

The patient sample provided rich variability regarding diagnoses, symptom/function level, sex, number of previous hospital admissions and compulsory/voluntary admissions.

•

The qualitative methodological approach is not suited for assessing the effects of interventions.
COVID-19 in Children with Brain-Based Developmental Disabilities: A Rapid Review
Authors: Dugas Michèle , Carnovale Valérie , Poirier Andrée-Anne , Mailhot Benoit , Skidmore Becky , Faust Lena , Costello Carrie , Thomson Donna , Majnemer Annette , Goldowitz Dan , Miller Steven P. , LeBlanc Annie
Published: May 2020

Background

The prevalence of symptomatic COVID-19 in children remains low to date. In just a few months, COVID-19 has affected millions of people worldwide, and as of the date of this publication, the pandemic continues. Based on the current available evidence, children do not appear to be at higher risk of contracting COVID-19 than adults. However, children with neurological and neuromuscular conditions are vulnerable to the respiratory complications of other viral infections.

Objectives

To assess whether children with brain-based developmental disabilities were more likely to develop COVID-19 and have complications or poorer outcomes following infection.

Methods

We conducted a two-week rapid review on studies with primary data regarding children aged between zero and 18 years old with brain-based developmental disabilities, or who were at risk of developing such disabilities, with confirmed or suspected COVID-19. We performed our literature searches on April 18, 2020.

Results

Our search strategy identified 538 individual records, of which four were included in our review. Of the 50 COVID-19 pediatric patients reported in the included studies, a total of seven children were at risk of developing brain-based disabilities. Symptoms ranged in severity. However, generally, patients were discharged or saw improvements in their symptoms by the end of the study period. No deaths were reported.

Discussion

Our study highlights a knowledge gap regarding the impact of COVID-19 in children with brain-based developmental disabilities.
Associations of stay-at-home order and face-masking recommendation with trends in daily new cases and deaths of laboratory-confirmed COVID-19 in the United States
Authors: Xu Jie , Hussain Sabiha , Lu Guanzhu , Zheng Kai , Wei Shi , Bao Wei , Zhang Lanjing
Published: May 2020

Background and objectives

Public health interventions were associated with reduction in coronavirus disease 2019 (COVID-19) transmission in China, but their impacts on COVID-19 epidemiology in other countries are unclear. We examined the associations of stay-at-home order (SAHO) and face-masking recommendation with epidemiology of laboratory-confirmed COVID-19 in the United States.

Methods

In this quasi-experimental study, we modeled the temporal trends in daily new cases and deaths of COVID-19, and COVID-19 time-varying reproduction numbers (Rt) in the United States between March 1 and April 20, 2020, and conducted simulation studies.

Results

The number and proportion of U.S. residents under SAHO increased between March 19 and April 7, and plateaued at 29,0829,980 and 88.6%, respectively. Trends in COVID-19 daily cases and Rt reduced after March 23 (P<0.001) and further reduced on April 3 (P<0.001), which was associated with implementation of SAHO by 10 states on March 23, and face-masking recommendation on April 3, respectively. The estimates of Rt eventually fell below/around 1.0 on April 13. Similar turning points were identified in the trends of daily deaths with a lag time. Early implementation and early-removal of SAHO would be associated with significantly reduced and increased daily new cases and deaths, respectively.

Conclusions

There were 2 turning points of COVID-19 daily new cases or deaths in the U.S., which appeared to associate with implementation of SAHO and the CDC’s face-masking recommendation. These findings may inform decision-making of lifting SAHO and face-masking recommendation.
The Histopathological Diagnosis of Adenocarcinoma & Squamous Cells Carcinoma of Lungs by Artificial intelligence: A comparative study of convolutional neural networks
Authors: Abbas Mohammad Ali , Bukhari Syed Usama Khalid , Syed Asmara , Shah Syed Sajid Hussain
Published: May 2020

Introduction

Malignant tumors of the lung are the most important cause of morbidity and mortality due to cancer all over the world. A rising trend in the incidence of lung cancer has been observed. Histopathological diagnosis of lung cancer is a vital component of patient care. The use of artificial intelligence in the histopathological diagnosis of lung cancer may be a very useful technology in the near future.

Aim

The aim of the present research project is to determine the effectiveness of convolutional neural networks for the diagnosis of squamous cell carcinoma and adenocarcinoma of the lung by evaluating the digital pathology images of these cancers.

Materials & Methods

A total of 15000 digital images of histopathological slides were acquired from the LC2500 dataset. The digital pathology images from lungs are comprised of three classes; class I contains 5000 images of benign lung tissue, class II contains 5,000 images of squamous cell carcinoma of lungs while Class III contains 5,000 images of adenocarcinoma of lungs. Six state of the art off the shelf convolutional neural network architectures, VGG-19, Alex Net, ResNet: ResNet-18, ResNet-34, ResNet-50, and ResNet-101, are used to assess the data, in this comparison study. The dataset was divided into a train set, 55% of the entire data, validation set 20%, and 25% into the test data set.

Results

A number of off the shelf pre-trained (on ImageNet data set) convolutional neural networks are used to classify the histopathological slides into three classes, benign lung tissue, squamous cell carcinoma-lung and adenocarcinoma - lung. The F-1 scores of AlexNet, VGG-19, ResNet-18, ResNet-34, ResNet-50 and ResNet-101, on the test dataset show the result of 0.973, 0.997, 0.986, 0.992, 0.999 and 0.999 respectively.

Discussion

The diagnostic accuracy of more 97% has been achieved for the diagnosis of squamous cell carcinoma and adenocarcinoma of the lungs in the present study. A similar finding has been reported in other studies for the diagnosis of metastasis of breast carcinoma in lymph nodes, basal cell carcinoma, and prostatic cancer.

Conclusion

The development of algorithms for the recognition of a specific pattern of the particular malignant tumor by analyzing the digital images will reduce the chance of human errors and improve the efficiency of the laboratory for the rapid and accurate diagnosis of cancer.
Predicting re-emergence times of dengue epidemics at low reproductive numbers: DENV1 in Rio de Janeiro, 1986-1990
Authors: Subramanian Rahul , Romeo-Aznar Victoria , Ionides Edward , Codeço Claudia T. , Pascual Mercedes
Published: May 2020

Predicting arbovirus re-emergence remains challenging in regions with limited off-season transmission and intermittent epidemics. Current mathematical models treat the depletion and replenishment of susceptible (non-immune) hosts as the principal drivers of re-emergence, based on established understanding of highly transmissible childhood diseases with frequent epidemics. We extend an analytical approach to determine the number of ‘skip’ years preceding re-emergence for diseases with continuous seasonal transmission, population growth and under-reporting. Re-emergence times are shown to be highly sensitive to small changes in lowR0(secondary cases produced from a primary infection in a fully susceptible population). We then fit a stochastic SIR (Susceptible-Infected-Recovered) model to observed case data for the emergence of dengue serotype DENV1 in Rio de Janeiro. This aggregated city-level model substantially over-estimates observed re-emergence times either in terms of skips or outbreak probability under forward simulation. The inability of susceptible depletion and replenishment to explain re-emergence under ‘well-mixed’ conditions at a city-wide scale demonstrates a key limitation of SIR aggregated models including those applied to other arboviruses. The predictive uncertainty and high skip sensitivity to epidemiological parameters suggest a need to investigate the relevant spatial scales of susceptible depletion and the scaling of microscale transmission dynamics to formulate simpler models that apply at coarse resolutions.
Validation of a commercially available SARS-CoV-2 serological Immunoassay
Authors: Meyer Benjamin , Torriani Giulia , Yerly Sabine , Mazza Lena , Calame Adrien , Arm-Vernez Isabelle , Zimmer Gert , Agoritsas Thomas , Stirnemann Jérôme , Spechbach Hervé , Guessous Idris , Stringhini Silvia , Pugin Jérôme , Roux-Lombard Pascale , Fontao Lionel , Siegrist Claire-Anne , Eckerle Isabella , Vuilleumier Nicolas , Kaiser Laurent ,   for the Geneva Center for Emerging Viral Diseases
Published: May 2020

Objectives

To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19.

Methods

In this unmatched (1:1) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 176 controls collected before SARS-CoV-2 emergence. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay.

Results

COVID-19 patients were more likely to be male and older than controls, and 50.3% were hospitalized. ROC curve analyses indicated that IgG and IgA had high diagnostic accuracies with AUCs of 0.992 (95% Confidence Interval [95%CI]: 0.986-0.996) and 0.977 (95%CI: 0.963-0.990), respectively. IgG assays outperformed IgA assays (p=0.008). Taking an assessed 15% inter-assay imprecision into account, an optimized IgG ratio cut-off > 1.5 displayed a 100% specificity (95%CI: 98–100) and a 100% positive predictive value (95%CI: 97-100). A 0.5 cut-off displayed a 97% sensitivity (95%CI: 93–99) and a 97% negative predictive value (95%CI: 93–99). Substituting these thresholds for the manufacturer’s, improved assay performance, leaving 12% of IgG ratios indeterminate between 0.5-1.5.

Conclusions

The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in patient samples, with no obvious gains from IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals in our study population have been exposed to SARS-CoV-2 or not. IgG serology should however not be considered as a surrogate of protection at this stage.
Voluntary Cyclical Distancing: A potential alternative to constant level mandatory social distancing, relying on an ‘infection weather report’
Authors: Goldman Daniel
Published: May 2020

1

COVID-19 has significantly changed our daily lives. Stay-at-home orders and forced closings of all non-essential businesses has had a significant impact on our economy. While it is important to ensure that the healthcare system is not overwhelmed, there are many questions that remain about the efficacy of extreme social distancing, and whether there are alternatives to mandatory lockdowns. This paper analyzes the utility of various levels of social distancing, and suggests an alternative approach using voluntary distancing informed by an infectious load index or ‘infection weather report.’
“Changes in soluble CD163 indicate monocyte involvement in cognitive deficits in Parkinson’s disease”
Authors: Nissen Sara K. , Ferreira Sara A. , Schulte Claudia , Shrivastava Kalpana , Hennig Dorle , Graversen Jonas , Maetzler Walter , Berg Daniela , Panhelainen Anne , Møller Holger J. , Brockmann Kathrin , Romero-Ramos Marina
Published: May 2020

Parkinson’s disease is a neurodegenerative disorder with a significant immune component. Numerous studies have reported alterations on immune biomarkers in CSF and serum that associate with symptoms in PD patients. However, it is unclear, which specific immune cells are responsible for the changes in those biomarkers; since most of these cytokines or chemokines, can be produced by a variety of immune cells, or even neurons or glia cells in the brain. Here, we investigate a monocyte/macrophage-specific biomarker: sCD163, the soluble form of the receptor CD163. Our data from tow cohorts show that the CSF-sCD163 increases as the disease progresses, together with a correlated increase in PD-specific as well as neurodegeneration-associated disease biomarkers: alpha-synuclein, tau, and phosphorylated-Tau. Moreover, CSF-sCD163 levels were inversely correlated to the cognitive scores MMSE and MOCA, with higher sCD163 indicating lower cognitive capacity. sCD163 was also increased in serum, although only in female PD patients, suggesting a gender distinctive monocyte-related immune response. CSF-sCD163 also correlated with molecules associated with endothelial cells, tissue infiltration, and activation of B cells and T cells in the PD patients. This suggests activation of both the adaptive and the innate immune system along with recruitment of lymphocytes and monocytes to sites of inflammation in the brain. In serum, sCD163 was associated with pro-inflammatory cytokines and acute phase proteins, suggesting a relation to chronic systemic inflammation. Interestingly, our in vitro study suggests that sCD 163 might enhance alpha-synuclein uptake by myeloid cells without direct binding, thus participating in the clearance of alpha-synuclein. Accordingly, our data supports sCD163 as a potential cognition-related biomarker in PD and corroborates a role for monocytes both in peripheral and brain immune responses that could have direct consequences in the handling of alpha-synuclein.
Differential Levels of Telomeric Oxidized Bases and TERRA Transcripts in Childhood Autism
Authors: Eftekhar Mohammad , Panahi Yasin , Moghaddam Fahimeh Salasar , Eskandari Mohammad Reza , Pezeshk Hamid , Pedram Mehrdad
Published: May 2020

Abstract

The underlying molecular mechanisms responsible for the etiology of autism and its sex-biased prevalence remain largely elusive. Abnormally shortened telomeres have recently been associated with autism. We have previously shown that children with non-syndromic autism exhibit a sexually dimorphic pattern of relative telomere length (RTL). Only male children with autism have significantly shorter RTLs than the healthy controls and paired siblings. Autistic females have substantially longer RTLs than autistic males. Aberrantly high levels of oxidative stress plays a fundamental role in the pathophysiology of autism, and telomeres are thought to be susceptible to oxidative damage due to their high guanine-repeat content. Employing a quantitative PCR (qPCR)-based method, telomeric oxidized base lesions were measured using genomic DNA extracted from saliva samples, and levels of telomeric RNA transcripts know as TERRA were evaluated using reverse transcriptase qPCR technique. Our data show that the autistic children exhibit substantially higher levels of oxidative base lesions at their telomeres than the healthy controls and paired siblings. Intriguingly, despite having significantly longer RTLs, female children with autism have even higher levels of telomeric oxidized bases than their male counterparts. Furthermore, despite having significantly shorter RTLs, the male children with autism exhibit lower levels of TERRA expression from the short arms of chromosomes 17 and X/P compared to their individually-matched healthy controls. These findings open a fresh angle into autism. Abnormal TL and high levels of telomeric oxidized bases may serve as biomarkers for childhood autism.
Alpha 1 Antitrypsin is an Inhibitor of the SARS-CoV-2–Priming Protease TMPRSS2
Authors: Azouz Nurit P. , Klingler Andrea M. , Callahan Victoria , Akhrymuk Ivan V. , Elez Katarina , Raich Lluís , Henry Brandon M. , Benoit Justin L. , Benoit Stefanie W. , Noé Frank , Kehn-Hall Kylene , Rothenberg Marc E.
Published: May 2020

Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry. The main cellular location where the SARS-CoV-2 S protein priming occurs remains debatable, therefore hampering the development of targeted treatments. Herein, we identified the human extracellular serine protease inhibitor (serpin) alpha 1 antitrypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease–inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity. Our data support the key role of extracellular serine proteases in SARS-CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.

Delivery of extracellular serine protease inhibitors (serpins) such as A1AT has the capacity to reduce SARS-CoV-2 dissemination by binding and inhibiting extracellular proteases on the host cells, thus, inhibiting the first step in SARS-CoV-2 cell cycle (i.e. cell entry).
SARS-CoV-2 Spike Glycoprotein Receptor Binding Domain is Subject to Negative Selection with Predicted Positive Selection Mutations
Authors: Li You , Wang Ye , Qiu Yaping , Gong Zhen , Deng Lei , Pan Min , Yang Huiping , Xu Jianan , Yang Li , Li Jin
Published: May 2020

COVID-19 is a highly contagious disease caused by a novel coronavirus SARS-CoV-2. The interaction between SARS-CoV-2 spike protein and the host cell surface receptor ACE2 is responsible for mediating SARS-CoV-2 infection. By analyzing the spike-hACE2 interacting surface, we predicted many hot spot residues that make major contributions to the binding affinity. Mutations on most of these residues are likely to be deleterious, leading to less infectious virus strains that may suffer from negative selection. Meanwhile, several residues with mostly advantageous mutations have been predicted. It is more probable that mutations on these residues increase the transmission ability of the virus by enhancing spike-hACE2 interaction. So far, only a limited number of mutations has been reported in this region. However, the list of hot spot residues with predicted downstream effects from this study can still serve as a tracking list for SARS-CoV-2 evolution studies. Coincidentally, one advantageous mutation, p.476G>S, started to surge in the last couple of weeks based on the data submitted to the public domain, indicating that virus strains with increased transmission ability may have already spread.