bluuebunny/crossref_metadata_2025 huggingface dataset:
Helping decisions and kin recognition in long-tailed tits: is call similarity used to direct help towards kin?
Authors: Leedale Amy E. , Lachlan Robert F. , Robinson Elva J. H. , Hatchwell Ben J.
Published: May 2020

Most cooperative breeders live in discrete family groups, but in a minority, breeding populations comprise extended social networks of conspecifics that vary in relatedness. Selection for effective kin recognition may be expected for more related individuals in such kin neighbourhoods to maximize indirect fitness. Using a long-term social pedigree, molecular genetics, field observations and acoustic analyses, we examine how vocal similarity affects helping decisions in the long-tailed titAegithalos caudatus. Long-tailed tits are cooperative breeders in which help is typically redirected by males that have failed in their own breeding attempts towards the offspring of male relatives living within kin neighbourhoods. We identify a positive correlation between call similarity and kinship, suggesting that vocal cues offer a plausible mechanism for kin discrimination. Furthermore, we show that failed breeders choose to help males with calls more similar to their own. However, although helpers fine-tune their provisioning rates according to how closely related they are to recipients, their effort was not correlated with their vocal similarity to helped breeders. We conclude that although vocalizations are an important part of the recognition system of long-tailed tits, discrimination is likely to be based on prior association and may involve a combination of vocal and non-vocal cues.

This article is part of the theme issue ‘Signal detection theory in recognition systems: from evolving models to experimental tests’.
Halocatena pleomorpha gen. nov. sp. nov., an extremely halophilic archaeon of family Halobacteriaceae isolated from saltpan soil
Authors: Verma Ashish , Pal Yash , Kumar Pravin , Krishnamurthi Srinivasan
Published: May 2020

A novel archaeal strain designated as SPP-AMP-1T was isolated from saltpan soil, using the serial dilution method on a halophilic archaeal medium supplemented with ampicillin. Cells were both rod-shaped and pleomorphic in nature, non-motile, unable to produce acid from a variety of sugars or grow anaerobically with different substrates (l-arginine) and electron acceptors (DMSO, nitrate). Optimal growth was observed at 42 °C, 3.4–4.2 M NaCl and pH 7.2. Cells did not lyse in distilled water and grew in the absence of Mg2+ ions. Phylogenetic analysis based on the sequences of 16S rRNA gene, amino acid sequence of β′-subunit of RNA polymerase and 400 conserved proteins retrieved from the whole genome assemblies showed that strain SPP-AMP-1T was distantly related to any existing genera within the family

Halobacteriaceae

. MK-8 was the only quinone detected. Polar lipid analysis showed a unique combination of diethyl derivatives of phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, glycosyl-mannosyl-glucosyl diether and sulphated glycosyl-mannosyl-glucosyl diether as the major lipids. The G+C content of genomic DNA is 57.7 mol%. The phenotypic, phylogenetic and genomic data supported the concept of the novel genus status of strain SPP-AMP-1T in the family

Halobacteriaceae

for which the name Halocatena pleomorpha gen. nov., sp. nov., is proposed; the type strain is SPP-AMP-1T (=JCM 31368T=KCTC 4276T=MTCC 12579T).
Characterization of a novel picornavirus isolated from moribund aquacultured clownfish
Authors: Scherbatskoy Elizabeth C. , Subramaniam Kuttichantran , Al-Hussinee Lowia , Imnoi Kamonchai , Thompson Patrick M. , Popov Vsevolod L. , Ng Terry Fei Fan , Kelley Karen L. , Alvarado Rodolfo , Wolf Jeffrey C. , Pouder Deborah B. , Yanong Roy P.E. , Waltzek Thomas B.
Published: May 2020

Over the last decade, a number of USA aquaculture facilities have experienced periodic mortality events of unknown aetiology in their clownfish (Amphiprion ocellaris). Clinical signs of affected individuals included lethargy, altered body coloration, reduced body condition, tachypnea, and abnormal positioning in the water column. Samples from outbreaks were processed for routine parasitological, bacteriological, and virological diagnostic testing, but no consistent parasitic or bacterial infections were observed. Histopathological evaluation revealed individual cell necrosis and mononuclear cell inflammation in the branchial cavity, pharynx, oesophagus and/or stomach of four examined clownfish, and large basophilic inclusions within the pharyngeal mucosal epithelium of one fish. Homogenates from pooled external and internal tissues from these outbreaks were inoculated onto striped snakehead (SSN-1) cells for virus isolation and cytopathic effects were observed, resulting in monolayer lysis in the initial inoculation and upon repassage. Transmission electron microscopy of infected SSN-1 cells revealed small round particles (mean diameter=20.0–21.7 nm) within the cytoplasm, consistent with the ultrastructure of a picornavirus. Full-genome sequencing of the purified virus revealed a novel picornavirus most closely related to the bluegill picornavirus and other members of the genus Limnipivirus. Additionally, pairwise protein alignments between the clownfish picornavirus (CFPV) and other known members of the genus Limnipivirus yielded results in accordance with the current International Committee on Taxonomy of Viruses criteria for members of the same genus. Thus, CFPV represents a proposed new limnipivirus species. Future experimental challenge studies are needed to determine the role of CFPV in disease.
Subnational analysis of the COVID-19 epidemic in Brazil
Authors: Mellan Thomas A , Hoeltgebaum Henrique H , Mishra Swapnil , Whittaker Charlie , Schnekenberg Ricardo P , Gandy Axel , Unwin H Juliette T , Vollmer Michaela A C , Coupland Helen , Hawryluk Iwona , Faria Nuno Rodrigues , Vesga Juan , Zhu Harrison , Hutchinson Michael , Ratmann Oliver , Monod Mélodie , Ainslie Kylie E C , Baguelin Marc , Bhatia Sangeeta , Boonyasiri Adhiratha , Brazeau Nicholas , Charles Giovanni , Cucunuba Zulma , Cuomo-Dannenburg Gina , Dighe Amy , Eaton Jeff , Elsland Sabine L van , Gaythorpe Katy A M , Green Will , Knock Edward , Laydon Daniel , Lees John A , Mousa Andria , Nedjati-Gilani Gemma , Nouvellet Pierre , Parag Kris V , Thompson Hayley A , Verity Robert , Walters Caroline E , Wang Haowei , Wang Yuanrong , Watson Oliver J , Whittles Lilith , Xi Xiaoyue , Dorigatti Ilaria , Walker Patrick , Ghani Azra C , Riley Steven , Ferguson Neil M , Donnelly Christl A , Flaxman Seth , Bhatt Samir
Published: May 2020

1

Brazil is currently reporting the second highest number of COVID-19 deaths in the world. Here we characterise the initial dynamics of COVID-19 across the country and assess the impact of non-pharmaceutical interventions (NPIs) that were implemented using a semi-mechanistic Bayesian hierarchical modelling approach. Our results highlight the significant impact these NPIs had across states, reducing an average Rt > 3 to an average of 1.5 by 9-May-2020, but that these interventions failed to reduce Rt < 1, congruent with the worsening epidemic Brazil has experienced since. We identify extensive heterogeneity in the epidemic trajectory across Brazil, with the estimated number of days to reach 0.1% of the state population infected since the first nationally recorded case ranging from 20 days in São Paulo compared to 60 days in Goiás, underscoring the importance of sub-national analyses in understanding asynchronous state-level epidemics underlying the national spread and burden of COVID-19.
Household transmission of COVID-19, Shenzhen, January-February 2020
Authors: Wei Lan , Lv Qiuying , Wen Ying , Feng Shuo , Gao Wei , Chen Zhigao , Cao Bin , Wu Xiaoliang , Lu Yan , Zhao Jin , Zou Xuan , Feng Tiejian , Cowling Benjamin J , Mei Shujiang
Published: May 2020

Coronavirus disease 2019 has led to more than three million cases globally. Since the first family cluster of COVID-19 cases identified in Shenzhen in early January, most of the local transmission occurred within household contacts. Identifying the factors associated with household transmission is of great importance to guide preventive measures.
Symptom-based ordinal scale fuzzy clustering of functional gastrointestinal disorders
Authors: Mansourian Marjan , Marateb Hamid Reza , Hassanzadeh Keshteli Ammar , Daghagh Zadeh Hamed , Mananas Miquel Angel , Adibi Peyman
Published: May 2020

Background
The validity of Rome III criteria for diagnosing functional gastrointestinal disorders (FGIDs) have been frequently questioned in the literature. In epidemiology, when a disease is diagnosed, the existence of a true cluster must be proven. Thus, clustering the common GI symptoms of individuals and comparing the clusters with FGIDs defined by the Rome III criteria could provide insights about the validity of FGIDs defined by those criteria.
Well-separated compact clusters were detected in responses to questionnaires of the epidemiological features of different FGIDs in Iranian adults using fuzzy ordinal clustering. The representative sample from each cluster i.e. Cluster Representative (CR) was formed whose corresponding FGID was diagnosed with Rome III criteria. Then, FGID diagnosis was performed for all participants in each cluster and the percentage of cases whose FGID was the same as the cluster's identified FGID (agreement) was reported.
Results
Fourteen valid clusters were detected in 4763 people. The average membership of the objects in each cluster was 77.3%, indicating similarity of the objects in clusters to their corresponding CRs. Eight clusters were assigned to single FGIDs (irritable bowel syndromes: constipation IBS-C, diarrhea IBS-D and un-subtyped IBS-U; functional bloating FB; functional constipation FC; belching disorder BD. The agreement was higher than 50% in single FGID clusters except those whose diagnosis was IBS-U.
Conclusions
IBS-C, IBS-D, FC, BD, and FB defined with Rome III criteria exist in the population, which is not the case for IBS-U.
Induction of Cross-reactive Hemagglutination Inhibiting Antibody and Polyfunctional CD4+ T-cell Responses by a Recombinant Matrix-M-Adjuvanted Hemagglutinin Nanoparticle Influenza Vaccine
Authors: Shinde Vivek , Cai Rongman , Plested Joyce , Cho Iksung , Fiske Jamie , Pham Xuan , Zhu Mingzhu , Cloney-Clark Shane , Wang Nan , Zhou Haixia , Zhou Bin , Patel Nita , Massare Michael J , Fix Amy , Spindler Michelle , Thomas David Nigel , Smith Gale , Fries Louis , Glenn Gregory M
Published: May 2020

Background

Recurrent reports of suboptimal influenza vaccine effectiveness have renewed calls to develop improved, broadly cross-protective influenza vaccines. Here, we evaluated the safety and immunogenicity of a novel, saponin (Matrix-M)-adjuvanted, recombinant hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV).

Methods

We conducted a randomized, observer-blind, comparator-controlled (trivalent high-dose inactivated influenza vaccine [IIV3-HD], or quadrivalent recombinant influenza vaccine [RIV4]), safety and immunogenicity trial of qNIV (in 5 different doses/formulations) in healthy adults aged ≥65 years. Vaccine immunogenicity was measured by hemagglutination-inhibition assays using reagents expressing wild-type HA sequences (wt-HAI) and cell-mediated immune (CMI) responses.

Results

A total of 1375 participants were randomized, immunized, and followed for safety and immunogenicity. Matrix-M-adjuvanted qNIV induced superior wt-HAI antibody responses against 5 of 6 homologous or drifted strains evaluated compared to unadjuvanted qNIV. Adjuvanted qNIV induced post-vaccination wt-HAI antibody responses at Day 28 that were: statistically higher than IIV3-HD against a panel of homologous or drifted A/H3N2 strains; similar to IIV3-HD against homologous A/H1N1 and B (Victoria) strains; and similar to RIV4 against all homologous and drifted strains evaluated. The qNIV formulation with 75 μg Matrix-M adjuvant induced substantially higher post-vaccination geometric mean fold-increases of influenza HA-specific polyfunctional CD4+ T-cells compared to IIV3-HD or RIV4. Overall, similar frequencies of solicited and unsolicited adverse events (AEs) were reported in all treatment groups.

Conclusions

qNIV with 75 μg Matrix-M adjuvant was well tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses. Further investigation in a pivotal phase 3 trial is underway.

SHORT SUMMARY

We compared multiple formulations of a recombinant Matrix-M-adjuvanted nanoparticle influenza vaccine to 2 licensed influenza vaccines in older adults. The nanoparticle vaccine was well tolerated, and induced hemagglutination-inhibition antibody and CD4+ T-cell responses to vaccine-homologous and drifted A/H3N2 influenza viruses.
Fuzzy logic use in classification of the severity of diabetic retinopathy
Authors: de Oliveira Andrade Luís Jesuino , França Caroline Santos , Andrade Rafael , Bittencourt Alcina Maria Vinhaes , de Oliveira Gabriela Correia Matos
Published: May 2020

Purpose

Employ fuzzy logic to auxiliary in identification and diagnosis the gravity of diabetic retinopathy (DR).

Methods

A cross-sectional study was performed, being assessed 100 diabetes mellitus patients with DR. The following ultrasound findings were measured employing a semi-quantitative punctuation method: vitreous hemorrhage, posterior vitreous detachment, epiretinal fibrosis, retinal detachment. The fundus photography (FP) aspects evaluated for diagnosis of DR were at least four or more microaneurysms with or without hard or soft exudates, and neovascularization, graded using the Early Treatment of Diabetic Retinopathy Scale. With the combination between ultrasound punctuation and FP aspects through fuzzy logic, a classification for DR has been built.

Results

Microaneurysms were the findings which presented the better interaction with the DR severity on ultrasound, while the hard exudates showed the minors estimation errors when compared to soft exudates. A classification for DR was suggested based on the 95% confidence interval of number of microaneurysms: mild group (< 24.6); moderately mild (24.6 - 48.0); moderate (48.1 - 64.5); moderately severe (64.6 - 77.0); severe (77.1 - 92.7); and very severe (> 92.7).

Conclusion

By the fuzzy logic, a DR classification was constructed supported on number of microaneurysms measurement with a simple practical application.
Higher Body Mass Index is an Important Risk factor in COVID-19 patients: A Systematic Review
Authors: Malik Vivek Singh , Khaiwal Ravindra , Attri Savita Verma , Bhadada Sanjay Kumar , Singh Meenu
Published: May 2020

Background: Globally, both obesity and underweight are severe health risks for various diseases. The current study systematically examines the emerging evidence to identify an association between Body Mass Index (BMI) and COVID-19 disease outcome.
Methods: Online literature databases (e.g., Google Scholar, PubMed, MEDLINE, EMBASE, Scopus, Medrixv and BioRixv) were screened following standard search strategy having the appropriate keyword such as Obesity, Underweight, BMI, Body Mass Index, 2019-nCov, COVID-19, novel coronavirus, coronavirus disease. Studies published till 20th April 2020 were included without language restriction. These studies include case reports, case series, cohort, and any other which reported BMI, overweight/obesity or underweight, and its complication with COVID-19 disease.
Findings: Obesity plays a significant part in the pathogenesis of COVID-19 patients, though the role of BMI in the COVID-19 pandemic must not be ignored.
Interpretation: Consequences of inflammation of adipose tissue has been reported as a leading cause of insulin resistance and hypertension due to metabolic dysfunction. The results of the current study show that BMI plays a significant role in COVID-19 severity in all ages, especially the elderly population. A panel should review COVID-19 patients with higher BMI and other co-morbidities, and they should be given increased vigilance, testing priority, and therapy. Further, the COVID-19 patients whose illness entered 7-10 days, age >50 yrs, and elevated CRP levels should have additional medical considerations.
Recommendation: Population and patients with high BMI have moderate to high risk of medical complications with COVID-19, and hence their health status should be monitored more frequently.
Keywords: Age, BMI, COVID-19, Obesity.
FREQUENCY OF ELEVATED BLOOD PRESSURE ASSOCIATED WITH LIFESTYLE CHOICES AMONG SCHOOL GOING ADOLESCENTS IN KARACHI: A CROSS SECTIONAL SURVEY
Authors: Pereira Felicianus Anthony , Qadir Jumana Abdul , Kamran Sajida
Published: May 2020

Background: Studies have suggested that atherosclerotic changes take place in the body since childhood due to altered dietary patterns and sedentary lifestyle. It is critical to identify gap areas and update current literature to produce effective changes in our lifestyle.
Study design: A cross-sectional survey conducted among school going adolescents in Karachi.
Methods: A cross sectional study was performed in three different schools of Karachi. A sample size of 288 was drawn through non-probability, purposive sampling technique. Students were given a questionnaire comprising of questions regarding their physical activity levels, dietary patterns and knowledge regarding blood pressure. Blood pressure and Body Mass Index data was also recorded.
Results: Mean age of participants was around 14. Of the 288 students that participated in this study (122 boys and 166 girls), 227 were normal for hypertension status (93 boys and 134 girls), 27 were pre-hypertensive (7 boys and 20 girls), and 34 were hypertensive (22 boys and 12 girls). Mean systolic blood pressure was approximately 112.73, and mean diastolic blood pressure was approximately 71.25. Awareness among participants was high regarding hypertension being linked to the foods they consumed (62.8%).
Conclusion: Our study did not show strong correlation between physical activity and dietary patterns, with status of hypertension. Screening programs should be conducted in schools to monitor blood pressure and body mass index. High risk groups should be approached and advised for lifestyle modification.
The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States
Authors: Laise Pasquale , Bosker Gideon , Sun Xiaoyun , Shen Yao , Douglass Eugene F. , Karan Charles , Realubit Ronald B. , Pampou Sergey , Califano Andrea , Alvarez Mariano J.
Published: May 2020

Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of infected-coronavirus cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to established treatments. Specifically, we propose that a small module of host cell Master Regulator proteins (ViroCheckpoint) is hijacked by the virus to support its efficient replication and release. Conventional methodologies are not well suited to elucidate these potentially targetable proteins. By using the VIPER network-based algorithm, we successfully interrogated 12h, 24h, and 48h signatures from Calu-3 lung adenocarcinoma cells infected with SARS-CoV, to elucidate the time-dependent reprogramming of host cells and associated Master Regulator proteins. We used the NYS CLIA-certified Darwin OncoTreat algorithm, with an existing database of RNASeq profiles following cell perturbation with 133 FDA-approved and 195 late-stage experimental compounds, to identify drugs capable of virtually abrogating the virus-induced Master Regulator signature. This approach to drug prioritization and repurposing can be trivially extended to other viral pathogens, including SARS-CoV-2, as soon as the relevant infection signature becomes available.
Upper arm length along with mid-upper arm circumference to enhance wasting prevalence estimation and diagnosis : sensitivity and specificity in 6 to 59 month-old children.
Authors: Barro Mouhamed , Baro Mohamed Daouda , Cisse Djibril , Zagre Noel , Ba Thierno , Neff Baro Shanti , Diagana Yacouba
Published: May 2020

Objective: To evaluate the added value of the use of upper arm length (UAL) along with MUAC (mid-upper arm circumference) to diagnose and estimate the prevalence of wasting in comparison to current WHO standard and others MUAC based methods.
Design: We included UAL to usual anthropometric measurements during a Mauritanian national 6-59-month-old cross-sectional nutritional survey. Children were classified into 3 groups UALG1, UALG2 and UALG3 according to the following UAL limits: ≤ 150 mm, 151-180, and > 180mm respectively. We used a Receiver Operating Characteristic curve to determine the best MUAC cut-off for each group with weight-for-height Z score as a reference standard. We compared the wasting prevalence, sensitivity, and specificity, of all diagnostic methods.
Findings: In total, 12 619 children were included in the study. Wasting prevalence was 16.1%, 5.0% and 12.5% when diagnosed by WHZ < -2, MUAC < 125 mm and MUAC-UALG methods respectively. Using the MUAC-UALG method increased the sensitivity for wasting diagnosis from 17.98 % with MUAC < 125 mm to 39.43% with MUAC-UALG. The specificity decreased from 97.49% with MUAC < 125 to 92.71% with MUAC-UALG. With MUAC-height Z score and MUAC < 138 mm, sensitivity was 26.04% and 69.76%and specificity were 97.40%and 75.64% respectively.
Conclusion: This alternative method using MUAC measuring tape to measure UAL increases the wasting diagnosis accuracy and allows for a better estimation of wasting prevalence. This method could be used as a potential alternative method for quick surveys in emergency settings such as Corona virus disease 2019 context.
COVID-19 OUTCOMES IN MS: EARLY EXPERIENCE FROM NYU MULTIPLE SCLEROSIS COMPREHENSIVE CARE CENTER
Authors: Parrotta Erica , Kister Ilya , Charvet Leigh , Sammarco Carrie , Saha Valerie , Charlson R.E. , Howard Jonathan , Gutman Josef Maxwell , Gottesman Malcolm , Abou-Fayssal Nada , Wolintz Robyn , Keilson Marshall , Fernandez-Carbonell Cristina , Krupp Lauren B , Zhovtis Ryerson Lana
Published: May 2020

Objective: Report outcomes on patients with Multiple Sclerosis (MS) and related disorders with COVID-19 illness.
Methods: From March 16 to April 30th, 2020, patients with MS or related disorders at NYU Langone MS Comprehensive Care Center (MSCC) were identified with laboratory-confirmed or suspected COVID-19. The diagnosis was established using a standardized questionnaire or by a review of in-patient hospital records.
Results: We identified 76 patients (55 with relapsing MS of which 9 had pediatric-onset;17 with progressive MS; and 4 with related disorders). 37 underwent PCR testing and were confirmed positive. Of the entire group, 64 (84%) patients were on disease-modifying therapy (DMT) including anti-CD20 therapies (n=34, 44.7%) and sphingosine 1-phosphate receptor modulators (n=10, 13.5%). The most common COVID-19 symptoms were fever and cough, but 21.1% of patients had neurologic symptom recrudescence preceding or coinciding with the infection. A total of 18 (23.7%) were hospitalized; 8 (10.5%) had COVID-19 critical illness or related death. Features more common among those hospitalized or with critical illness or death were older age, presence of comorbidities, progressive disease, and a non-ambulatory status. No DMT class was associated with an increased risk of hospitalization or fatal outcome.
Conclusions: Most MS patients with COVID-19 do not require hospitalization despite being on DMTs. Factors associated with critical illness were similar to the general at risk patient population. DMT use did not emerge as a predictor of poor COVID-19 outcome in this preliminary sample.
Cardiac Structural and Functional Characteristics in Patients with Coronavirus Disease 2019: A Serial Echocardiographic Study
Authors: Heng Ge , Mingli Zhu , Jing Du , Yong Zhou , Wei Wang , Wei Zhang , Handong Jiang , Zhiqing Qiao , Zhichun Gu , Fenghua Li , Jun Pu
Published: May 2020

BACKGROUND

Increasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients.

METHODS

We conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020.

RESULTS

Of 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0–69.0%), with most (44/86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test).

CONCLUSIONS

Typical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19.

CLINICAL TRIAL REGISTRATION

Unique identifier: NCT04352842.
Trimodality Treatment in Malignant Pleural Mesothelioma: An Ordeal or The Real Deal?
Authors: Mummudi Naveen , Khan Asfiya , Tibdewal Anil , Kumar Rajiv , Jiwnani Sabita , Karimundackal George , C Pramesh S , Agarwal Jai Prakash
Published: May 2020

BACKGROUND: Malignant Pleural Mesothelioma is an uncommon and aggressive disease associated with asbestos exposure. Management of MPM is complex and controversial as there is paucity of good quality evidence. Multimodality treatment with surgery, systemic therapy and radiation therapy is an option in non-metastatic MPM. We intend to analyze toxicity and outcomes in patients who received trimodality treatment for non-metastatic MPM at our institution.
METHODS and MATERIALS: We reviewed the electronic medical records of surgically managed MPM patients at our institution in the last decade. Patient details, disease characteristics and treatment information were retrieved from the institutional electronic medical record and radiation oncology information system. Dosimetric parameters of target volume and organs at risk were documented from Eclipse workstation (v13.6, Varian medical systems). SPSS was used for statistical analysis.
RESULTS: Between January 2008 and October 2018, 21 patients (17 male and 4 female) underwent surgery for MPM, all but 2 patients underwent extra-pleural pneumonectomy (EPP). Primary was located in the right and left in 11 and 10 patients respectively. Epithelioid MPM was the commonest histology (17 patients: 81%). Resection was R0 in 18 patients and R2 in 2 patients. Four patients had minor complications like wound erythema, wound seroma with cellulitis and hypotension and 8 Patients had major complications like pneumonia, rib fracture, pulmonary hypertension and pulmonary stump thrombus. All patients received neoadjuvant Pemetrexed/platinum doublet chemotherapy, except for 2. Fourteen patients received adjuvant hemithoracic RT; of these, 2 underwent treatment elsewhere and 2 were treated with conventional technique. Ten patients treated with conformal technique at our institute and dosimetric data was available for analysis. Average time to start RT after surgery was 51 days (range 32 to 82 days). All patients were treated with conformal technique using IMRT/VMAT to a dose of 45Gy in 25 fractions; one patient received a further boost of 5.4Gy. Mean overall RT duration was 35 days (range 30 to 42 days). Acute toxicity was uncommon; Grade I/II Pneumonitis was seen in 4 patients. One patient developed grade III acute lung toxicity unrelated to RT. At a median follow up of 25 months, 8 patients developed progressive disease. Eight patients had died, of whom six died due to disease and two died in immediate post op period. Two-year DFS and OS were 58% and 73% respectively.
CONCLUSION: In spite of the extensive surgery and complex hemithoracic RT, we demonstrated excellent dosimetric, toxicity profile and favorable outcomes in non-metastatic MPM.
No SARS-CoV-2 carriage observed in children attending daycare centers during the first weeks of the epidemic in Belgium
Authors: Desmet Stefanie , Ekinci Esra , Wouters Ine , Decru Bram , Beuselinck Kurt , Malhotra-Kumar Surbhi , Theeten Heidi
Published: May 2020

To gain knowledge about the role of young children attending daycare in the SARS-CoV-2 epidemic, a random sample of children (n=84) aged between 6 and 30 months attending daycare in Belgium was studied shortly after the start of the epidemic (February 29th) and before the lockdown (March 18th). No asymptomatic carriage of SARS-CoV-2 was detected, whereas common cold symptoms were common (51.2%).
A Novel Cohorting and Isolation Strategy for Suspected COVID-19 Cases during a Pandemic
Authors: Patterson Benjamin , Marks Michael , Martinez-Garcia Gemma , Bidwell Gabriella , Luintel Akish , Ludwig Dalia , Parks Tom , Gothard Philip , Thomas Rik , Logan Sarah , Shaw Karen , Stone Neil , Brown Mike
Published: May 2020

Introduction
The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem.

Methods
We implemented a triage tool aimed at minimising hospital acquired COVID-19 particularly to patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission.

Results
93 patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. 28 (30%) suspected COVID-19 patients were evaluated to be low risk (groups C & D) and eligible for cohorting. No symptomatic hospital acquired infections were detected in the cohorted patients.
Discussion
Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.
Retrospective Pooled Screening for SARS-CoV-2 RNA in late 2019
Authors: Hogan Catherine A. , Garamani Natasha , Sahoo Malaya K. , Huang ChunHong , Zehnder James , Pinsky Benjamin A.
Published: May 2020

Reports have emerged documenting earlier SARS-CoV-2 cases than previously recognized. To investigate this possibility in the Bay Area, we retrospectively tested 1,700 samples from symptomatic individuals for the last 2 months of 2019. No SARS-CoV-2 positive pools were identified, consistent with limited transmission in this population at this time.
ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS
Authors: Akgun Emel , Tuzuner Mete B , Sahin Betul , Kilercik Meltem , Kulah Canan , Cakiroglu Hacer N , Serteser Mustafa , Unsal Ibrahim , Baykal Ahmet T
Published: May 2020

COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 3.6 million people and caused the death of around 252,000 people. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Currently around 50,000 patients are in a seriously critical situation. Although 1.2 million patients recovered from the disease there are still more than 2.1 Million active cases. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative naso-oropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.
The effects of cannabis use on cognitive function in healthy aging: A systematic scoping review
Authors: Pocuca Nina , Walter T. Jordan , Minassian Arpi , Young Jared W. , Geyer Mark A. , Perry William
Published: May 2020

Middle-to-older-aged adults (>50 years) represent the fastest-growing cannabis-using population. Given aging and cannabis use are associated with cognitive decline, it is important to establish the effects of cannabis on cognitive function in this population. This systematic scoping review used PRISMA guidelines to critically examine the extent of literature on this topic and highlight areas for future research. A search of six databases (PubMed, EMBASE, PsycINFO, Web of Science, Family and Society Studies Worldwide, and CINAHL) for articles published by September 2019, yielded 1,014 unique results. Only six articles reported findings for middle-to-older-aged populations (three human and three rodent studies), highlighting the paucity of research. Available human studies revealed largely null results, likely due to several methodological limitations. Nevertheless, the better-controlled rodent studies indicated an age and dose-dependent relationship between ∆9-tetrahydrocannabinol (THC) and cognitive function in aging. Extremely low doses of THC improved cognitive function in very old rodents. Somewhat higher chronic doses were required to improve cognitive function in moderately aged rodents. No studies examined the effects of cannabidiol (CBD) or high-CBD cannabis on cognition. Future research should examine the relevance of age and dose-dependent effects of THC in humans and the effects of CBD on cognitive function in aging.
Proinflammatory IgG Fc structures in patients with severe COVID-19
Authors: Chakraborty Saborni , Gonzalez Joseph , Edwards Karlie , Mallajosyula Vamsee , Buzzanco Anthony S. , Sherwood Robert , Buffone Cindy , Kathale Nimish , Providenza Susan , Xie Markus M. , Andrews Jason R. , Blish Catherine A. , Singh Upinder , Dugan Haley , Wilson Patrick C. , Pham Tho D. , Boyd Scott D. , Nadeau Kari C. , Pinsky Benjamin A. , Zhang Sheng , Memoli Matthew J. , Taubenberger Jeffery K. , Morales Tasha , Schapiro Jeffrey M. , Tan Gene S. , Jagannathan Prasanna , Wang Taia T.
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause Coronavirus Disease 2019 (COVID-19), which manifests with a range of severities from mild illness to life threatening pneumonia and multi-organ failure. Severe COVID-19 is characterized by an inflammatory signature including high levels of inflammatory cytokines, alveolar inflammatory infiltrates and vascular microthrombi. Here we show that severe COVID-19 patients produced a unique serologic signature, including increased IgG1 with afucosylated Fc glycans. This Fc modification on SARS-CoV-2 IgGs enhanced interactions with the activating FcγR, FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including IL-6 and TNF. These results show that disease severity in COVID-19 correlates with the presence of afucosylated IgG1, a pro-inflammatory IgG Fc modification.
SARS-CoV-2 Antibody responses do not predict COVID-19 disease severity
Authors: Phipps William S. , SoRelle Jeffrey A. , Li Quan-Zhen , Mahimainathan Lenin , Araj Ellen , Markantonis John , Lacelle Chantale , Balani Jyoti , Parikh Hiren , Solow E. Blair , Karp David R. , Sarode Ravi , Muthukumar Alagarraju
Published: May 2020

Background

Initial reports indicate adequate performance of some serological-based SARS-CoV-2 assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course.

Methods

In this study, a total of 968 subjects were tested for IgG antibodies reactive to SARS-CoV-2. We confirmed analytic specificity using 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for PCR-based respiratory viral panel. One-hundred seventy-three cases of confirmed or suspected SARS-CoV-2 were tested for IgG. A subgroup of 37 SARS-CoV-2 PCR-positive cases was tested for nucleocapsid-specific IgM antibody using an in-house developed microarray method. Antibody levels were compared between disease severity groups.

Results

All specificity specimens were negative for SARS-CoV-2 IgG antibodies (0/656, 0%). Cross reactivity was not detected in specimens with antinuclear antibodies and rheumatoid factor, or cases with previous diagnosis of viral infection including human coronavirus. Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels.

Conclusions

The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Index values of IgG and IgM antibodies did not predict disease severity in our patient population.
Establishment of an African green monkey model for COVID-19
Authors: Woolsey Courtney , Borisevich Viktoriya , Prasad Abhishek N. , Agans Krystle N. , Deer Daniel J. , Dobias Natalie S. , Heymann John C. , Foster Stephanie L. , Levine Corri B. , Medina Liana , Melody Kevin , Geisbert Joan B. , Fenton Karla A. , Geisbert Thomas W. , Cross Robert W.
Published: May 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an unprecedented global pandemic of COVID-19. Animal models are urgently needed to study the pathogenesis of COVID-19 and to screen candidate vaccines and treatments. Nonhuman primates (NHP) are considered the gold standard model for many infectious pathogens as they usually best reflect the human condition. Here, we show that African green monkeys support a high level of SARS-CoV-2 replication and develop pronounced respiratory disease that may be more substantial than reported for other NHP species including cynomolgus and rhesus macaques. In addition, SARS-CoV-2 was detected in mucosal samples of all animals including feces of several animals as late as 15 days after virus exposure. Importantly, we show that virus replication and respiratory disease can be produced in African green monkeys using a much lower and more natural dose of SARS-CoV-2 than has been employed in other NHP studies.
Nuclear phosphatidylinositol 3,4,5-trisphosphate interactome uncovers an enrichment in nucleolar proteins
Authors: Gavgani Fatemeh Mazloumi , Morovicz Andrea Papdiné , D’Santos Clive S. , Lewis Aurélia E.
Published: May 2020

Polyphosphoinositides (PPIn) play essential functions as lipid signalling molecules and many of their functions have been elucidated in the cytoplasm. However, PPIn are also intranuclear where they contribute to chromatin remodelling, transcription and mRNA splicing. The PPIn, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) has been mapped to the nucleus and nucleoli but its role remains unclear in this subcellular compartment. To gain further insights into the nuclear functions of PtdIns(3,4,5)P3, we applied a previously developed quantitative mass spectrometry-based approach to identify the targets of PtdIns(3,4,5)P3from isolated nuclei. We identified 179 potential PtdIns(3,4,5)P3-interacting proteins and gene ontology analysis for the biological functions of this dataset revealed an enrichment in RNA processing/splicing, cytokinesis, protein folding and DNA repair. Interestingly, about half of these interactors were common to nucleolar protein datasets, some of which had dual functions in rRNA transcription and DNA repair, including Poly(ADP-Ribose) Polymerase 1 (PARP1/ARTD1). PARP1 was found to interact directly with PtdIns(3,4,5)P3as well as PtdIns(3,4)P2and to co-localise with PtdIns(3,4,5)P3in the nucleolus and with PtdIns(3,4)P2in nucleoplasmic foci. In conclusion, the PtdIns(3,4,5)P3interactome reported here identified several nucleolar proteins and further pointed to roles for this lipid in these processes.
Binding of the SARS-CoV-2 Spike Protein to Glycans
Authors: Hao Wei , Ma Bo , Li Ziheng , Wang Xiaoyu , Gao Xiaopan , Li Yaohao , Qin Bo , Shang Shiying , Cui Sheng , Tan Zhongping
Published: May 2020

The pandemic of SARS-CoV-2 has caused a high number of deaths in the world. To combat it, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. In this study, we examined and compared the binding of the subunits and spike (S) proteins of SARS-CoV-2 and SARS-CoV, MERS-CoV to these glycans. Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner, the length of HS is not a critical factor for the binding, and no binding with sialic acid residues was detected. Overall, this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells, and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.
Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains
Authors: Khrameeva Ekaterina , Kurochkin Ilia , Han Dingding , Guijarro Patricia , Kanton Sabina , Santel Malgorzata , Qian Zhengzong , Rong Shen , Mazin Pavel , Sabirov Marat , Bulat Matvei , Efimova Olga , Tkachev Anna , Guo Song , Sherwood Chet C. , Camp J. Gray , Pääbo Svante , Treutlein Barbara , Khaitovich Philipp
Published: May 2020

Identification of gene expression traits unique to the human brain sheds light on the molecular mechanisms underlying human evolution. Here, we searched for uniquely human gene expression traits by analyzing 422 brain samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well as 88,047 cell nuclei composing three of these regions. Among 33 regions, cerebral cortex areas, hypothalamus, and cerebellar gray and white matter evolved rapidly in humans. At the cellular level, astrocytes and oligodendrocyte progenitors displayed more differences in the human evolutionary lineage than the neurons. Comparison of the bulk tissue and single-nuclei sequencing revealed that conventional RNA sequencing did not detect up to two-thirds of cell-type-specific evolutionary differences.
Black Holes in 4D
N=4
Super-Yang-Mills Field Theory
Authors: Benini Francesco , Milan Elisa
Published: May 2020

Black-hole solutions to general relativity carry a thermodynamic entropy, discovered by Bekenstein and Hawking to be proportional to the area of the event horizon, at leading order in the semiclassical expansion. In a theory of quantum gravity, black holes must constitute ensembles of quantum microstates whose large number accounts for the entropy. We study this issue in the context of gravity with a negative cosmological constant. We exploit the most basic example of the holographic description of gravity (AdS/CFT): type IIB string theory on AdS5×S5, equivalent to maximally supersymmetric Yang-Mills theory in four dimensions. We thus resolve a long-standing question: Does the four-dimensional N=4 SU(N) Super-Yang-Mills theory on S3 at large N contain enough states to account for the entropy of rotating electrically charged supersymmetric black holes in 5D anti–de Sitter space? Our answer is positive. By reconsidering the large

N

limit of the superconformal index, using the so-called Bethe-ansatz formulation, we find an exponentially large contribution which exactly reproduces the Bekenstein-Hawking entropy of the black holes. Besides, the large N limit exhibits a complicated structure, with many competing exponential contributions and Stokes lines, hinting at new physics. Our method opens the way toward a quantitative study of quantum properties of black holes in anti–de Sitter space.

Published by the American Physical Society
2020
Synthesis, structural elucidation, characterization and theoretical DFT study of 1-(o-tolyl)biguanidium chloride
Authors: Kaabi Kamel , Klai Kacem , Wenger Emmanuel , Jelsch Christian , Lefebvre Frédéric , Nasr Cherif Ben
Published: May 2020

The structure of the new salt 1-(o-tolyl)biguanidium chloride, C9H14N5
+·Cl−, has been determined by single-crystal X-ray diffraction. The salt crystallizes in the monoclinic space group C2/c. In this structure, the chloride and biguanidium hydrophilic ions are mostly connected to each other via N—H...N and N—H...Cl hydrogen bonds to form layers parallel to the ab plane around y = 1 \over 3 and y = 2 \over 3. The 2-methylbenzyl groups form layers between these layers around y = 0 and y = 1 \over 2, with the methyl group forming C—H...π interactions with the aromatic ring. Intermolecular interactions on the Hirshfeld surface were investigated in terms of contact enrichment and electrostatic energy, and confirm the role of strong hydrogen bonds along with hydrophobic interactions. A correlation between electrostatic energy and contact enrichment is found only for the strongly attractive (N—H...Cl−) and repulsive contacts. Electrostatic energies between ions reveal that the interacting biguanidium cation pairs are repulsive and that the crystal is maintained by attractive cation...Cl− dimers. The vibrational absorption bands were identified by IR spectroscopy.