bluuebunny/crossref_metadata_2025 huggingface dataset:
Histological correlates of hippocampal magnetization transfer images in drug-resistant temporal lobe epilepsy patients
Authors: Peixoto-Santos Jose Eduardo , Velasco Tonicarlo R , Carlotti Carlos Gilberto , Assirati Joao Alberto , de Souza e Rezende Gustavo Henrique , Kobow Katja , Coras Roland , Blümcke Ingmar , Salmon Carlos Ernesto Garrido , dos Santos Antonio Carlos , Leite Joao Pereira
Published: July 2020

Objective

Temporal lobe epilepsy patients (TLE) often present with hippocampal atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR) in magnetic resonance images (MRI). The histological correlates of the reduced MTR are so far unknown. Since MTR is dependent on the tissue’s macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients.

Methods

Patients with TLE (n=27) and voluntaries (=20) were scanned in a 3 Tesla MRI scanner, and MTR images were calculated from 3DT1 sequences with magnetization pulse on resonance. Immunohistochemistry for neurons, reactive astrocytes, activated microglia, and extracellular matrix chondroitin sulfate were performed in formalin fixed, paraffin embedded tissues of TLE and autopsy controls (n=10). Results were considered significant at p<0.05.

Results

Compared to the respective controls, TLE patients had reduced hippocampal MTR, increased reactive astrocytes and activated microglia, increased extracellular chondroitin sulfate, and reduced neuron density, compares to controls. MTR correlated positively with neuron density in CA3 and with chondroitin sulfate in CA3 and CA1. Multiple linear regressions reinforced the correlations between chondroitin sulfate and MTR.

Significance

Our data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.
The 4C Initiative (Clinical Care for Cardiovascular disease in the COVID-19 pandemic) – monitoring the indirect impact of the coronavirus pandemic on services for cardiovascular diseases in the UK
Authors:   4C Initiative of the CVD-COVID-UK consortium, Ball S , Banerjee A , Berry C , Boyle J , Bray B , Bradlow W , Chaudhry A , Crawley R , Danesh J , Denniston A , Falter F , Figueroa JD , Hall C , Hemingway H , Jefferson E , Johnson T , King G , Lee K , McKean P , Mason SM , Mills N , Pearson E , Pirmohamed M , Poon MTC , Priedon R , Shah A , Sofat R , Sterne J , Strachan F , Sudlow CLM , Szarka Z , Whiteley W , Wyatt M
Published: July 2020

Background

The coronavirus (COVID-19) pandemic affects cardiovascular diseases (CVDs) directly through infection and indirectly through health service reorganisation and public health policy. Real-time data are needed to quantify direct and indirect effects. We aimed to monitor hospital activity for presentation, diagnosis and treatment of CVDs during the pandemic to inform on indirect effects.

Methods

We analysed aggregate data on presentations, diagnoses and treatments or procedures for selected CVDs (acute coronary syndromes, heart failure, stroke and transient ischaemic attack, venous thromboembolism, peripheral arterial disease and aortic aneurysm) in UK hospitals before and during the COVID-19 epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.

Findings

Nine hospitals across England and Scotland contributed hospital activity data from 28 Oct 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown), and for the same weeks during 2018-2019. Across all hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1-58.6%) and 52.9% (52.2-53.5%) respectively compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown, and fell by 31-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances RR 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020.

Interpretation

Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

Funding

British Heart Foundation, Health Data Research UK
Microbial ecology ofIxodes scapularisfrom Central Pennsylvania, USA
Authors: Sakamoto Joyce M. , Diaz Gabriel Enrique Silva , Wagner Elizabeth Anne
Published: July 2020

(1) Background: Native microbiota represent a potential resource for biocontrol of arthropod vectors.Ixodes scapularisare mostly inhabited by the endosymbioticRickettsia buchneri,but the bacterial communty composition varies with life stage, fed status, and/or geographic location. We investigated sex-specific bacterial community diversity fromI. scapulariscollected from central Pennsylvania between populations within a small geographic range. (2) Methods: We sequenced the bacterial 16S rRNA genes from individuals and pooled samples and investigated the abundance or infection frequency of key taxa using taxon-specific PCR and/or qPCR. (3) Results: Bacterial communities were more diverse in pools of males than females. WhenR. buchneriwas not the dominant taxon, Coxiellaceae was dominant. We determined that the infection frequency ofBorrelia burgdorferiranged between 20 to 75%. Titers ofAnaplasma phagocytophilumwere significantly different between sexes. HighRickettsiellatiter in pools were likely due to a few heavily infected males. (4) Conclusion: Bacterial 16S sequencing is useful for establishing the baseline community diversity and focusing hypotheses for targeted experiments. However, care should be taken not to overinterpret data concerning microbial dominance between geographic locations based on a few individuals as this may not accurately represent the bacterial community within tick populations.
A Highly Immunogenic Measles Virus-based Th1-biased COVID-19 Vaccine
Authors: Hörner Cindy , Schürmann Christoph , Auste Arne , Ebenig Aileen , Muraleedharan Samada , Herrmann Maike , Schnierle Barbara , Mühlebach Michael D.
Published: July 2020

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread world-wide with millions of cases and hundreds of thousands of deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+and CD4+T cell responses with S protein-specific killing activity were detected. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.

Author Contributions

CH performed research, analyzed data, and wrote the paper; CS performed research and analyzed data; AA performed research and analyzed data; AE performed research and analyzed data; SM performed research, analyzed data, and wrote the paper; MH developed the bioinformatics pipeline and analyzed data; BS contributed new reagents and concepts; MDM designed and supervised research, analyzed data and wrote the paper; all authors read, corrected and approved the final manuscript.

Significance Statement

The COVID-19 pandemic has caused hundreds of thousands of deaths, yet. Therefore, effective vaccine concepts are urgently needed. In search for such a concept, we have analysed a measles virus-based vaccine candidate targeting SARS-CoV-2. Using this well known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity with the desired immune bias. Therefore, occurrence of immunopathologies such as antibody-dependent enhancement or enhanced respiratory disease is rather unlikely. Moreover, the candidate still induces immunity against the measles, recognized as a looming second menace, when countries are entrapped to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles-based COVID-19 vaccine could be the solution for two significant public health threats.
Sensory neurons expressing the atypical olfactory receptor guanylyl cyclase D are required for the acquisition of odor preferences by mice in diverse social contexts
Authors: Zimmerman Arthur D. , Nagy Christina R. , Munger Steven D.
Published: July 2020

Animals use social communication to learn important information from conspecifics that can guide appropriate behavioral choices. For example, during the social transmission of food preference (STFP), conspecific semiochemicals detected by mouse olfactory sensory neurons (OSNs) expressing the atypical olfactory receptor guanylyl cyclase D (GC-D+ OSNs) promote the acquisition of food preferences in the recipient animal, mitigating the risk of ingesting food contaminated with toxins or pathogens. However, it is unclear if GC-D+ OSNs mediate preference learning outside this specific context. Here, we report that GC-D+ OSNs are required for the acquisition of odor preferences by both adult and juvenile mice, and that GC-D-dependent preference could be formed for conditionally aversive odors. We used a two-choice olfactory behavioral test to assess odor preferences in adult Gucy2d +/+, +/- and -/- mice that encountered novel odors together with GC-D+ OSN stimuli (guanylin family peptides), during social investigation of a live conspecific, or during suckling as pups. Gucy2d +/+ and +/-mice (which express functional GC-D), but not Gucy2d -/- littermates, successfully acquire a preference for the demonstrated odor in any of these behavioral paradigms. Mice could even acquire a GC-D-dependent preference for odors to which they had recently formed a conditioned aversion. Together, these results demonstrate that GC-D+ OSNs mediate the acquisition of socially-transmitted odor preferences in different social and experiential contexts and at different life stages.
Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features
Authors: Dejima Hitoshi , Hu Xin , Chen Runzhe , Zhang Jiexin , Fujimoto Junya , Parra Edwin R. , Haymaker Cara , Hubert Shawna , Duose Dzifa , Solis Luisa M. , Su Dan , Fukuoka Junya , Tabata Kazuhiro , Pharm Hoa , Mcgranahan Nicholas , Zhang Baili , Ye Jie , Ying Lisha , Little Latasha , Gumbs Curtis , Chow Chi-Wan , Estecio Marcos Roberto , Godoy Myrna C.B. , Antonoff Mara B. , Sepesi Boris , Pass Harvey , Behrens Carmen , Zhang Jianhua , Vaporciyan Ara A. , Heymach John V. , Scheet Paul , Lee J. Jack , Futreal P. Andrew , Reuben Alexandre , Kadara Humam , Wistuba Ignacio , Zhang Jianjun
Published: July 2020

How anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. We characterized immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence. Our results demonstrated that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensely regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, higher infiltration of CD4+ T cells, lower infiltration of CD8+ T cells, decreased T cell clonality, and lower frequencies of top T cell clones in later stages. Driver mutations, HLA loss, chromosomal copy number aberrations and DNA methylation changes may collectively impinge host immune responses and facilitate immune evasion as a potential mechanism underlying outgrowth of the most fit subclones in preneoplasia into dominant clones in invasive ADC.

SIGNIFICANCE

There has been a drastic increase in the detection of lung nodules, many of which are lung ADC precursors. The management of these lung nodules is controversial. We discovered that immune activation and evasion have started at preneoplastic stage and lung ADC precursors may exhibit an overall better-preserved anti-tumor immune contexture suggesting therapeutic strategies reprograming the immune microenvironment in patients with lung ADC precursors prior to further immunosuppression in invasive lung cancers may be beneficial. These findings have served as the critical scientific rationale for our immunoprevention clinical trial IMPRINT-Lung (NCT03634241) recruiting individuals diagnosed with lung nodules at high risk developing invasive lung cancers.
The effectiveness of acupuncture point stimulation for the prevention of post-operative sore throat: a meta-analysis
Authors: Jau Pin-Yu , Chang Shang-Chih
Published: July 2020

Background

Enhanced recovery pathways can be further improved for postoperative sore throat (POST) which usually occurs after surgery with general anesthesia. Medications have shown some effectiveness in treating and preventing POST, but acupuncture or related techniques with better safety and less cost likely can be used as an alternative or adjuvant therapy to treat perioperative symptoms by stimulating acupuncture point (acupoint). Therefore, we aim to conduct a meta-analysis to assess whether acupoint stimulation help patients prevent or treat POST in adults undergoing tracheal intubation for general anesthesia.

Methods

Publication in PubMed, the Cochrane Central Register, ScienceDirect, and ClinicalTrial.gov were surveyed from Jan. 2000 through Jan. 2020. Studies that compared intervention between point stimulation and none or sham point stimulation, were included. Primary outcomes were the incidence and severity of POST at 24h. Secondary outcomes were the incidence of postoperative nausea and vomiting, choking cough, and sputum.

Results

Three randomized control trials and one comparative study involving 1358 participants were included. Compared with control, acupoint stimulation was associated with a reduced incidence (risk ratio, 0.3; 95% confidence interval (CI), 0.2–0.45; p < 0.001) and severity (standardized mean difference, −2.21; 95% CI, −2.67 to −1.76; p < 0.001) of POST. Secondary outcomes are also in favor of acupoint stimulation. There were no significant adverse events related to acupoint stimulation. Subgroup, the sensitivity, and the trial sequence analyses confirmed that the finding for POST was adequate.

Conclusions

Acupoint stimulation with various methods may reduce the occurrence of POST. It could be considered as one of nonpharmacological ways to prevent POST in enhanced recovery pathways. Further rigorous studies are needed to determine the effectiveness of acupoint stimulation.

Question

Can acupoint stimulation prevent postoperative sore throat after tracheal intubation?

Findings

Acupoint stimulation by acupuncture or related techniques more significantly reduces the incidence and the severity of postoperative sore throat than non- /sham-treatment at 24 hours.

Meaning

Acupoint stimulation by acupuncture or related techniques could be an effective, nonpharmacological approach to prevent postoperative sore throat in enhanced recovery after tracheal intubation.
The Association of Serum Lipid and Lipoprotein Levels with Total and Differential Leukocyte Counts: Results of a Cross-sectional and Longitudinal Analysis of the UK Biobank
Authors: Tucker Bradley , Sawant Sonia , McDonald Hannah , Rye Kerry-Anne , Patel Sanjay , Ong Kwok Leung , Cochran Blake J
Published: July 2020

Background and aims

There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort.

Methods

The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9,058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression.

Results

Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors a higher eosinophil count was associated with lower HDL cholesterol and apolipoproteinA-I concentration (p<0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p<0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p<0.001). In the longitudinal analysis lipoprotein(a) was inversely associated with basophil count in men but not women (p<0.001).

Conclusion

Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leuokogenesis. However, unlike in murine models, the remainder of these relationships are modest which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans.
Knowledge and Behaviors towards COVID-19 among University of Aleppo Students: An Online Cross-sectional Survey
Authors: Alhamid Aos , Aljarad Ziad , Alhamid Ahmad
Published: July 2020

Background

Coronavirus Disease 2019 (COVID-19) is an infection caused by a novel coronavirus that affects respiratory tract. People’s awareness and knowledge of, and behavior and attitude toward COVID-19 are scarcely investigated, making medical literature related to this point poor. we aim to measure the knowledge of, and the reaction to COVID-19 among University of Aleppo students in Syria, and the determinants of their awareness and behavior regarding this disease.

Materials and Methods

This was an online, questionnaire-based cross-sectional study, that was conducted from 21st March to 30 March 2020. We included undergraduate students of the University of Aleppo (Syria). The questionnaire consisted of three sections: Demographics,knowledge and behaviours. Every participant’s knowledge was scored from 0-13 depending on the number of correct answers in the knowledge section. The correctness was judged depending on WHO recommendations at the time of questionnaire administration. P-value of 0.05 was considered significant.

Results

Among this well-educated and predominantly medical and health-related students, 682 (45.4%) students had a good knowledge level, which is somehow disappointing. The current study shows that 1st year students and non-medical specialties students and smokers had significantly lower knowledge levels than others. On contrary, residing with less people-which may indicate a higher socioeconomic status-, was associated with a higher knowledge level. We also found that commitment to preventive measures was in general satisfying and correlated significantly with knowledge level and gender in most cases.

Conclusion

Junior students, non-medical specialties, smokers and those who live with high number of people are vulnerable to less knowledge level and awareness campaigns should concentrate on them. Increasing awareness is useful to increase commitment to preventive measures, and groups that have less adherence to preventive measures, as described in detail, should be taken into consideration while designing public health responses. Finally, we should be aware of the negative impact of quarantine on public health to take it into consideration for current campaigns and future policies.
‘Trained immunity’ from Mycobacterium spp. exposure or BCG vaccination and COVID-19 outcomes
Authors: Singh Samer , Maurya Rajendra P. , Singh Rakesh K.
Published: July 2020

Protective variables for COVID-19 are unknown. ‘Trained immunity’ of the populace as a result of BCG immunization policy implementation and coverage had been suggested to be one of the factors responsible for the differential impact of COVID-19 on different countries. Several trials are underway to evaluate the potential protective role of BCG vaccination in COVID-19. However, the lack of clarity on the use of appropriate controls concerning the measures of ‘trained immunity’ or the heterologous cell-mediated immunity conferred by BCG vaccination has been a cause of concern leading to more confusion as exemplified by a recently concluded trial in Israel that failed to find any protective correlation with regard to BCG vaccination. Whereas, when we analyze the COVID-19 data of European countries without any regard for BCG vaccination policy but with similar age distribution, comparable confounding variables, and the stage of the pandemic, the prevalence of tuberculin immunoreactivity - a measure of cell-mediated immunity persistence as a result of Mycobacterium spp. (including BCG vaccine) exposure of the populations, is found consistently negatively correlated with COVID-19 infections and mortality per million population, at all the time points evaluated. We propose that on-going and future studies evaluating the effect of BCG vaccination on COVID-19 outcomes may actively consider, if not already, the inclusion of controls for underlying ‘trained immunity’ and heterologous cell-mediated immunity prevalence that may be pre-existing or resulting from the intervention (e.g., BCG vaccine) in such trials to arrive at more dependable conclusions concerning their potential benefit.
Diagnosis of COVID-19 using CT scan images and deep learning techniques
Authors: Shah Vruddhi , Keniya Rinkal , Shridharani Akanksha , Punjabi Manav , Shah Jainam , Mehendale Ninad
Published: July 2020

Early diagnosis of the coronavirus disease in 2019 (COVID-19) is essential for controlling this pandemic. COVID-19 has been spreading rapidly all over the world. There is no vaccine available for this virus yet. Fast and accurate COVID-19 screening is possible using computed tomography (CT) scan images. The deep learning techniques used in the proposed method was based on a convolutional neural network (CNN). Our manuscript focuses on differentiating the CT scan images of COVID-19 and non-COVID 19 CT using different deep learning techniques. A self developed model named CTnet-10 was designed for the COVID-19 diagnosis, having an accuracy of 82.1 %. Also, other models that we tested are DenseNet-169, VGG-16, ResNet-50, InceptionV3, and VGG-19. The VGG-19 proved to be superior with an accuracy of 94.52 % as compared to all other deep learning models. Automated diagnosis of COVID-19 from the CT scan pictures can be used by the doctors as a quick and efficient method for COVID-19 screening.
Correlations between individual factors, meteorological factors, and hemorrhagic fever with renal syndrome in the Tai’an area of China, 2005–2019
Authors: Bi XiuJuan , Yi Shuying , Zhang Aihua , Zhao Zhenghua , Liu Yunqiang , Wang Tao , Zhang Chao , Ye Zhen
Published: July 2020

Hemorrhagic fever with renal syndrome (HFRS), is a serious threat to human health. The relative risks factors for different occupations, ages, and sexes are unknown.

The results showed that compared with the whole population, the risk ratio was 5.05 (p <0.05) among the rural medical staff. GAM showed that air temperature was positively correlated with disease risk from January to June and that relative humidity was negatively correlated with risk from July to December. From January to June, the cumulative risk of disease increased at low temperatures.

Rural medical staff showed a high risk of developing the disease. The possibility of human-to-human transmission of HFRS among rural medical staff is worthy of interest and deserves to be explored by further studies. Moreover, air temperature and relative humidity are important factors that affect the occurrence of the disease. These associations show lagged effects and differing effects according to the season.
The competing risk between in-hospital mortality and recovery: A pitfall in COVID-19 survival analysis research
Authors: Oulhaj Abderrahim , Ahmed Luai A. , Prattes Juergen , Suliman Abubaker , Alsuwaidi Ahmed R. , Al-Rifai Rami H. , Sourij Harald , Van Keilegom Ingrid
Published: July 2020

Background

A plethora of studies on COVID-19 investigating mortality and recovery have used the Cox Proportional Hazards (Cox PH) model without taking into account the presence of competing risks. We investigate, through extensive simulations, the bias in estimating the hazard ratio (HR) and the absolute risk reduction (ARR) of death when competing risks are ignored, and suggest an alternative method.

Methods

We simulated a fictive clinical trial on COVID-19 mimicking studies investigating interventions such as Hydroxychloroquine, Remdesivir, or convalescent plasma. The outcome is time from randomization until death. Six scenarios for the effect of treatment on death and recovery were considered. The HR and the 28-day ARR of death were estimated using the Cox PH and the Fine and Gray (FG) models. Estimates were then compared with the true values, and the magnitude of misestimation was quantified.

Results

The Cox PH model misestimated the true HR and the 28-day ARR of death in the majority of scenarios. The magnitude of misestimation increased when recovery was faster and/or chance of recovery was higher. In some scenarios, this model has shown harmful treatment effect when it was beneficial. Estimates obtained from FG model were all consistent and showed no misestimation or changes in direction.

Conclusion

There is a substantial risk of misleading results in COVID-19 research if recovery and death due to COVID-19 are not considered as competing risk events. We strongly recommend the use of a competing risk approach to re-analyze relevant published data that have used the Cox PH model.
Municipality- level predictors of COVID-19 mortality in Mexico: a cautionary tale
Authors: Contreras-Manzano Alejandra , Guerrero-López Carlos M. , Aguerrebere Mercedes , Sedas Ana Cristina , Lamadrid-Figueroa Héctor
Published: July 2020

Background

Inequalities and burden of comorbidities of the Coronavirus disease 2019 (COVID-19) vary importantly inside the countries. We aimed to analyze the Municipality-level factors associated with a high COVID-19 mortality rate of in Mexico.

Methods

We retrieved information from 142,643 cumulative confirmed symptomatic cases and 18,886 deaths of COVID-19 as of June 20th, 2020 from the publicly available database of the Ministry of Health of Mexico. Public official data of the most recent census and surveys of the country were used to adjust a negative binomial regression model with the quintiles (Q) of the distribution of sociodemographic and health outcomes among 2,457 Municipality-level. Expected Mortality Rates (EMR), Incidence Rate Ratios (IRR) and 95% Confidence Intervals are reported.

Results

Factors associated with high MR of COVID-19, relative to Quintile 1 (Q1), were; diabetes prevalence (Q4, IRR=2.60), obesity prevalence (Q5, IRR=1.93), diabetes mortality rate (Q5, IRR=1.58), proportion of indigenous population (Q2, IRR=1.68), proportion of economically active population (Q5, IRR=1.50), density of economic units that operate essential activities (Q4, IRR=1.54) and population density (Q5, IRR=2.12). We identified 1,351 Municipality-level without confirmed COVID-19 deaths, of which, 202 had nevertheless high (Q4, Mean EMR= 8.0 deaths per 100,000) and 82 very high expected COVID-19 mortality (Q5, Mean EMR= 13.8 deaths per 100,000).

Conclusion

This study identified 1,351 Municipality-level of Mexico that, in spite of not having confirmed COVID-19 deaths yet, share characteristics that could eventually lead to a high mortality scenario later in the epidemic and warn against premature easing of mobility restrictions. Local information should be used to reinforce strategies of prevention and control of outbreaks in communities vulnerable to COVID-19.

Key messages

Predictors of COVID-19 mortality varied importantly between Municipality-level.

Municipality-level factors associated with high mortality of COVID-19 were the prevalence of obesity and diabetes, mortality rate of diabetes, the proportion of indigenous and economically active population and population density.

Municipality-level with high case-fatality rates of COVID-19 are likely undergoing insufficient testing and should improve its availability.

Identified predictors ought to be considered by local governments to reinforce tailored strategies to prevent casualties in populations vulnerable to COVID-19, as mortality is expected to be eventually high in some Municipality-level that may not have reached the apex of the epidemic yet.
COVID-19 among people living with HIV: A systematic review
Authors: Mirzaei Hossein , McFarland Willi , Karamouzian Mohammad , Sharifi Hamid
Published: July 2020

This systematic review summarizes the evidence on the earliest patients with COVID-19-HIV co-infection. We searched PubMed, Scopus, Web of Science, Embase, preprint databases, and Google Scholar from December 01, 2019 to June 1, 2020. From an initial 547 publications and 75 reports, 25 studies provided specific information on COVID-19 patients living with HIV. Studies described 252 patients, 80.9% were male, mean age was 52.7 years, and 98% were on ART. Co-morbidities in addition to HIV and COVID-19 (multimorbidity) included hypertension (39.3%), obesity or hyperlipidemia (19.3%), chronic obstructive pulmonary disease (18.0%), and diabetes (17.2%). Two-thirds (66.5%) had mild to moderate symptoms, the most common being fever (74.0%) and cough (58.3%). Among patients who died, the majority (90.5%) were over 50 years old, male (85.7%), and had multimorbidity (64.3%). Our findings highlight the importance of identifying co-infections, addressing co-morbidities, and ensuring a secure supply of ART for PLHIV during the COVID-19 pandemic.
Comparisons of the genome of SARS-CoV-2 and those of other betacoronaviruses
Authors: Rodríguez-Román Eduardo , Gibbs Adrian J.
Published: July 2020

The genome of SARS-CoV-2 virus causing the worldwide pandemic of COVID-19 is most closely related to viral metagenomes isolated from bats and, more distantly, pangolins. All are of sarbecoviruses of the genusBetacoronavirus. We have unravelled their recombinational and mutational histories. All showed clear evidence of recombination, most events involving the 3’ half of the genomes. The 5’ region of their genomes was mostly recombinant free, and a phylogeny calculated from this region confirmed that SARS-CoV-2 is closer to RmYN02 than RaTG13, and showed that SARS-CoV-2 diverged from RmYN02 at least 26 years ago, and both diverged from RaTG13 at least 37 years ago; recombinant regions specific to these three viruses provided no additional information as they matched no other Genbank sequences closely. Simple pairwise comparisons of genomes show that there are three regions where most non-synonymous changes probably occurred; the DUF3655 region of the nsp3, the S gene and ORF 8 gene. Differences in the last two of those regions have probably resulted from recombinational changes, however differences in the DUF3655 region may have resulted from selection. A hexamer of the proteins encoded by the nsp3 region may form the molecular pore spanning the double membrane of the coronavirus replication organelle (Wolff et al., 2020), and perhaps the acidic polypeptide encoded by DUF3655 lines it, and presents a novel target for pharmaceutical intervention.
Outbreak of COVID-19 and Interventions in One of the Largest Jails in the United States — Cook County, IL, 2020
Authors: Zawitz Chad , Welbel Sharon , Ghinai Isaac , Mennella Connie , Levin Rebecca , Samala Usha , Smith Michelle Bryant , Gubser Jane , Jones Bridgette , Varela Kate , Kirbiyik Uzay , Rafinski Josh , Fitzgerald Anne , Orris Peter , Bahls Alex , Black Stephanie R. , Binder Alison M. , Armstrong Paige A.
Published: July 2020

Background

Correctional and detention facilities are disproportionately affected by COVID-19 due to shared space, contact between staff and detained persons, and movement within facilities of detained persons, many with pre-existing medical conditions. On March 18, 2020, Cook County Jail, one of the United States’ largest, identified its first suspected case of COVID-19 in a detained person.

Methods

This analysis includes SARS-CoV-2 cases confirmed by molecular detection among detained persons and Cook County Sheriff’s Office staff. We examined occurrence of symptomatic cases in each building and proportions of asymptomatic detained persons testing positive. We describe timing of interventions including social distancing, mask use, and expanded testing and show outbreak trajectory in the jail versus contemporaneous case counts in Chicago.

Results

During March 1–April 30, 907 symptomatic and asymptomatic cases of SARS-CoV-2 infection were detected among detained persons (n = 628) and staff (n = 279), with nine deaths. Symptomatic cases occurred in all housing divisions; in 9/13 buildings, staff cases occurred first. Among asymptomatic detained persons in quarantine, 23.6% tested positive. Visitation stopped March 15, programmatic activities were suspended March 23, cells were converted into single occupancy beginning March 26, and universal masking was implemented for staff (April 2) and detained persons (April 13). Cases at the jail declined while cases in Chicago increased.

Conclusion

Aggressive intervention strategies coupled with widespread diagnostic testing of detained and staff populations can limit introduction and mitigate transmission of SARS-CoV-2 infection in correctional and detention facilities.
Identification of novel mechanistically distinct endotypes of pandemic influenza-associated acute respiratory failure
Authors: Samanta Romit , Dunning Jake , Taylor Adam , Bayliffe Andrew I. , Chambers Rachel C. , Chilvers Edwin R. , Openshaw Peter JM. , Summers Charlotte
Published: July 2020

Respiratory viral pandemics result in large numbers of cases of acute respiratory failure arising from a single etiology, thus reducing the heterogeneity of precepting insult and allowing improved insight into the variation of host responses. In 2009-2011, an influenza pandemic occurred, with pH1N1 infecting millions of people worldwide. Here, we have used novel bioinformatic methods to combine clinical, protein biomarker, and genomic data from patients with influenza-associated acute respiratory failure to identify three mechanistically discrete sub-types with significantly different clinical outcomes. The three endotypes identified can be described as “neutrophil-driven” (16.3%), “adaptive” (51.9%), and “endothelial leak” (31.7%). The neutrophil driven patients display evidence of innate immune activation with associated multi-organ dysfunction and reduced 30-day survival. These patients could be differentiated from the adaptive endotype by an alteration in the GAIT-mechanism, a late transcriptional regulatory response to IFN-γ that acts to suppress innate immunity by reducing caeruloplasmin mRNA translation. Patients with the neutrophil-driven endotype had significantly increased IFN-γ levels but appeared unable to suppress their innate immune response. The endothelial leak endotype could be distinguished from both the neutrophil driven and adaptive endotypes by alterations in Slit-Robo signalling, a pathway important in the maintenance of endothelial barrier integrity; Although patients with this endotype required mechanical ventilation, they did not develop multi-organ failure in the manner of the neutrophil-driven endotype patients, and had significantly better clinical outcomes. Importantly, the endotypes identified were stable over 48 hours opening up the possibility of stratified interventional clinical trials in the future.

One Sentence Summary

We have identified three new mechanistically distinct subtypes of influenza associated acute respiratory failure, with differential clinical outcomes.
Public Opinions towards COVID-19 in California and New York on Twitter
Authors: Wang Xueting , Zou Canruo , Xie Zidian , Li Dongmei
Published: July 2020

Background

With the pandemic of COVID-19 and the release of related policies, discussions about the COVID-19 are widespread online. Social media becomes a reliable source for understanding public opinions toward this virus outbreak.

Objective

This study aims to explore public opinions toward COVID-19 on social media by comparing the differences in sentiment changes and discussed topics between California and New York in the United States.

Methods

A dataset with COVID-19-related Twitter posts was collected from March 5, 2020 to April 2, 2020 using Twitter streaming API. After removing any posts unrelated to COVID-19, as well as posts that contain promotion and commercial information, two individual datasets were created based on the geolocation tags with tweets, one containing tweets from California state and the other from New York state. Sentiment analysis was conducted to obtain the sentiment score for each COVID-19 tweet. Topic modeling was applied to identify top topics related to COVID-19.

Results

While the number of COVID-19 cases increased more rapidly in New York than in California in March 2020, the number of tweets posted has a similar trend over time in both states. COVID-19 tweets from California had more negative sentiment scores than New York. There were some fluctuations in sentiment scores in both states over time, which might correlate with the policy changes and the severity of COVID-19 pandemic. The topic modeling results showed that the popular topics in both California and New York states are similar, with “protective measures” as the most prevalent topic associated with COVID-19 in both states.

Conclusions

Twitter users from California had more negative sentiment scores towards COVID-19 than Twitter users from New York. The prevalent topics about COVID-19 discussed in both states were similar with some slight differences.
Clinical Ordering Practices of the SARS-CoV-2 Antibody Test at a Large Academic Medical Center
Authors: Wiencek Joesph R , Head Carter L , Sifri Costi D , Parsons Andrew S
Published: July 2020

Background: The novel severe acute respiratory coronavirus 2 (SARS-CoV-2) that causes COVID-19 originated in December 2019 and has now infected over 3 million people in the United States. In Spring of 2020, private laboratories and some hospitals began antibody testing despite lacking evidence-based guidance.
Objective: To describe clinician-described indications for SARS-CoV-2 antibody testing, including cost implications, immediately following testing availability.
Design: Retrospective chart review of patients who received antibody testing from May 14, 2020 to June 15, 2020.
Setting: A large academic medical center, one of the first in the US to provide antibody testing capability to individual clinicians.
Patients: 447 consecutive patients who received SARS-CoV-2 antibody testing.
Measurements: Clinician-described indications for SARS-CoV-2 antibody testing, cost implications, and comparison with current expert-based guidance from the IDSA and CDC.
Results: Of 444 individual antibody test results meeting inclusion criteria, the two most commonly described indications for ordering the antibody test, apart from public health epidemiology studies (n=223), were for patients with a now resolved COVID-19 compatible illness (n=105) with no previous molecular testing and in asymptomatic patients believed to have had a past exposure or contact with a person with COVID-19 compatible illness (n=60). The rate of positive SARS-CoV-2 antibody testing among those indications consistent with current IDSA and CDC guidance was 17% compared with 5% (p<0.0001) among those indications inconsistent with current IDSA and CDC guidance. Total cost estimates ranged from $57,720 to $97,680, of which 42% was for testing inconsistent with current expert-based guidance.
Limitations: The duration of antibody response following infection is unclear and asymptomatic individuals may not develop a positive antibody response.
Conclusions: Our findings demonstrate a dissociation between clinician described indications for testing and expert-based guidance and a significantly different rate of positive testing between these two groups. Clinical curiosity and patient preference appear to have played a significant role in testing decisions and substantially contributed to testing costs.
SNT: A Unifying Toolbox for Quantification of Neuronal Anatomy
Authors: Arshadi Cameron , Günther Ulrik , Eddison Mark , Harrington Kyle I. S. , Ferreira Tiago A.
Published: July 2020

Quantification of neuronal morphology is essential for understanding neuronal connectivity and many software tools have been developed for neuronal reconstruction and morphometry. However, such tools remain domain-specific, tethered to specific imaging modalities, and were not designed to accommodate the rich metadata generated by recent whole-brain cellular connectomics. To address these limitations, we created SNT: a unifying framework for neuronal morphometry and analysis of single-cell connectomics for the widely used Fiji and ImageJ platforms.

We demonstrate that SNT can be used to tackle important problems in contemporary neuroscience, validate its utility, and illustrate how it establishes an end-to-end platform for tracing, proof-editing, visualization, quantification, and modeling of neuroanatomy.

With an open and scriptable architecture, a large user base, and thorough community-based documentation, SNT is an accessible and scalable resource for the broad neuroscience community that synergizes well with existing software.
Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice
Authors: Lee Katie J. , Rambault Lisa , Bou-Gharios George , Clegg Peter D. , Akhtar Riaz , Czanner Gabriela , van ‘t Hof Rob , Canty-Laird Elizabeth G.
Published: July 2020

Type I collagen is the major structural component of bone where it exists as an (α1)2(α2)1heterotrimer in all vertebrates. The osteogenesis imperfecta (oim) mouse model comprising solely homotrimeric (α1)3type I collagen, due to a dysfunctional α2 chain, has a brittle bone phenotype implying that the heterotrimeric form is required for physiological bone function. However, humans with rare null alleles preventing synthesis of the α2 chain have connective tissue and cardiovascular abnormalities (cardiac valvular Ehlers Danlos Syndrome), without evident bone fragility. Conversely a prevalent human single nucleotide polymorphism leading to increased homotrimer synthesis is associated with osteoporosis. Whilst the oim line is well-studied, whether homotrimeric type I collagen is functionally equivalent to the heterotrimeric form in bone has not been demonstrated. Col1a2 null and oim mouse lines were used in this study and bones analysed by microCT and 3-point bending. RNA was also extracted from heterozygote tissues and allelic discrimination analyses performed using qRT-PCR. Here we comprehensively show for the first time that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice. However Mendelian inheritance was affected in male mice of both lines and male mice null for the α2 chain exhibited age-related loss of condition. The brittle bone phenotype of oim homozygotes could result from detrimental effects of the oim mutant allele, however, the phenotype of oim heterozygotes is known to be less severe. We used allelic discrimination to show that the oim mutant allele is not downregulated in heterozygotes. We then tested whether gene dosage was responsible for the less severe phenotype of oim heterozygotes by generating compound heterozygotes. Data showed that compound heterozygotes had impaired bone structural properties as compared to oim heterozygotes, albeit to a lesser extent than oim homozygotes. Hence, we concluded that the presence of heterotrimeric collagen-1 in oim heterozygotes alleviates the effect of the oim mutant allele but a genetic interaction between homotrimeric collagen-1 and the oim mutant allele leads to bone fragility.
Super-elasticity of plasma- and synthetic membranes by coupling of membrane asymmetry and liquid-liquid phase separation
Authors: Steinkühler Jan , Bhatia Tripta , Zhao Ziliang , Lipowsky Reinhard , Dimova Rumiana
Published: July 2020

Biological cells are contained by a fluid lipid bilayer (plasma membrane, PM) that allows for large deformations, often exceeding 50% of the initial (or projected) PM area. Biochemically isolated lipids self-organize into membranes, but the extraordinary deformability of the plasma membrane is lost. Pure lipid bilayers are prone to rupture at small (<2-4%) area strains and this limits progress for synthetic reconstitution of cellular features such as migration, phagocytosis and division. Here, we show that by preserving PM structure and composition during isolation from cells, vesicles with cell-like elasticity are obtained. We found that these plasma membrane vesicles store significant area in the form of nanotubes in their lumen. These are recruited by mechanical tension applied to the outer vesicle membrane showing an apparent elastic response. This “super-elastic” response emerges from the interplay of lipid liquid-liquid phase separation and membrane asymmetry. This finding allows for bottom-up engineering of synthetic vesicles that appear over one magnitude softer and with three fold larger deformability than conventional lipid vesicles.
Prophage-encoded phage defense proteins with cognate self-immunity
Authors: Owen Siân V. , Wenner Nicolas , Dulberger Charles L. , Rodwell Ella V. , Bowers-Barnard Arthur , Quinones-Olvera Natalia , Rigden Daniel J. , Rubin Eric J. , Garner Ethan C. , Baym Michael , Hinton Jay C. D.
Published: July 2020

Temperate phages are pervasive in bacterial genomes, existing as vertically-inherited islands called prophages. Prophages are vulnerable to the predation of their host bacterium by exogenous phages. Here we identify BstA, a novel family of prophage-encoded phage defense proteins found in diverse Gram-negative bacteria. BstA drives potent suppression of phage epidemics through abortive infection. During lytic replication, thebstA-encoding prophage is not itself inhibited by BstA due to a self-immunity mechanism conferred by the anti-BstA (aba) element, a short stretch of DNA within thebstAlocus. Inhibition of phage replication by distinct BstA proteins fromSalmonella, KlebsiellaandEscherichiaprophages is functionally interchangeable, but each possesses a cognateabaelement. The specificity of theabaelement ensures that immunity is exclusive to the replicating prophage, and cannot be exploited by heterologous BstA-encoding phages. BstA allows prophages to defend host cells against exogenous phage attack, without sacrificing their own lytic autonomy.