bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct to operating room trauma resuscitation: Optimizing patient selection and time-critical outcomes when minutes count
Authors: Johnson Amelia , Rott Michael , Kuchler Andrea , Williams Emma , Cole Fredrick , Ramzy Ameen , Barbosa Ronald , Long William , Martin Matthew J.
Published: March 2020

BACKGROUND

Although several trauma centers have developed direct to operating room (DOR) trauma resuscitation programs, there is little published data on optimal patient selection, practices, and outcomes. We sought to analyze triage criteria and interventions associated with optimal DOR outcomes and resource utilization.

METHODS

Retrospective review of all adult DOR resuscitations for a 6-year period was performed. Triage criteria were analyzed individually and grouped into categories: mechanism, physiology, anatomy/injury, or other. The best univariate and multivariate predictors of requiring lifesaving interventions (LSIs) or emergent surgery (ES) were analyzed. Actual and predicted mortality were compared for all patients and for predefined time-sensitive subgroups.

RESULTS

There were 628 DOR patients (5% of all admissions) identified; the majority were male (79%), penetrating mechanism (70%), severely injured (40% ISS >15), and 17% died. Half of patients required LSI and 23% required ES, with significantly greater need for ES and lower need for LSI after penetrating versus blunt injury (p < 0.01). Although injury mechanism criteria triggered most DOR cases and best predicted need for ES, the physiology and anatomy/injury criteria were associated with greater need for LSI and mortality. Observed mortality was significantly lower than predicted mortality with DOR for several key subgroups. Triage schemes for both ES and LSI could be simplified to four to six independent predictors by regression analysis.

CONCLUSION

The DOR program identified severely injured trauma patients at increased risk for requiring LSI and/or ES. Different triage variable categories drive the need for ES versus LSI and could be simplified or optimized based on local needs or preferences. Direct to operating room was associated with better than expected survival among specific time-sensitive subgroups.

LEVEL OF EVIDENCE

Therapeutic/Care Management, Level IV.
Liver Transplantation for Colorectal and Neuroendocrine Liver Metastases and Hepatoblastoma. Working Group Report From the ILTS Transplant Oncology Consensus Conference
Authors: Hibi Taizo , Rela Mohamed , Eason James D. , Line Pål-Dag , Fung John , Sakamoto Seisuke , Selzner Nazia , Man Kwan , Ghobrial R. Mark , Sapisochin Gonzalo
Published: March 2020

Liver transplantation (LT) for unresectable colorectal liver metastases has long been abandoned because of dismal prognoses. After the dark ages, advances in chemotherapy and diagnostic imaging have enabled strict patient selection, and the pioneering study from the Oslo group has contributed to the substantial progress in this field. For unresectable neuroendocrine liver metastases, LT for patients who met the Milan criteria was able to achieve excellent long-term outcomes. The guidelines further adopted in the United States and Europe were based on these criteria. For hepatoblastoma, patients with unresectable and borderline-resectable disease are considered good candidates for LT; however, the indications are yet to be defined. In the budding era of transplant oncology, it is critically important to recognize the current status and unsolved questions for each disease entity. These guidelines were developed to serve as a beacon of light for optimal patient selection for LT and set the stage for future basic and clinical studies.
“My Parent’s Body Is Sacred”
Authors: Montoya Yadira , Balbim Guilherme M. , Glover Crystal M. , Marquez David X.
Published: March 2020

Introduction:

Brain donation is a critical part of advancing research addressing Alzheimer disease and related dementias (ADRD). Studies on ADRD with an option for brain donation are reliant on family members to fulfill the research participant’s plan for brain donation. Thus, family members play a pivotal role in increasing brain donation rates, particularly among under-represented groups.

Methods:

This study examines knowledge, attitudes, and beliefs about brain donation for research among Latinos. Latino men (N=4) and Latina women (N=11) 18 years of age or older with a parental figure age 65 years and over were invited to participate in a focus group.

Results:

Data analyses revealed 3 themes. Two themes focused on factors influencing a family’s willingness to support brain donation: (a) social and cultural contexts, and (b) lack of knowledge and information about the brain donation process. The last theme provided recommendations for engaging older Latino adults in ADRD research and brain donation.

Discussion:

Results suggest being inclusive of family members during all stages of the research process, from recruitment to dissemination. In addition, addressing information gaps among Latinos about the process and benefits of brain donation may help mitigate mistrust and misperceptions and increase participation rates in brain donation.
Antarcticibacterium arcticum sp. nov., a bacterium isolated from marine sediment of the Canadian Beaufort Sea
Authors: Lee Yung Mi , Baek Kiwoon , Lee Dong-Hun , Park Yerin , Shin Seung Chul , Jin Young Keun
Published: March 2020

A Gram-stain-negative, aerobic, yellow-pigmented, flexirubin-negative, rod-shaped and non-motile bacterial strain, PAMC 28998T, was isolated from a surface sediment sample collected from the Canadian Beaufort Sea. Strain PAMC 28998T grew at 4–37 °C (optimum, 25 °C), at pH 7.0–9.0 (optimum, pH 7.5) and in the presence of 1.0–10.0 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain PAMC 28998T belongs to the genus

Antarcticibacterium

showing the highest sequence similarity (96.8 %) with

Antarcticibacterium flavum

JB01H24T. The average nucleotide identity and genome-to-genome distance values between PAMC 28998T and the most closely related species (

A. flavum

JB01H24T) were 74.1 and 18.5 %, respectively, indicating that strain PAMC 28998T is clearly distinguished from

A. flavum

. The genomic DNA G+C content calculated from genome sequences was 39.8 %. The major fatty acids (>10 %) were iso-C15 : 0 (19.5 %), anteiso-C15 : 0 (18.0 %), iso-C16 : 0 (11.6 %) and summed feature 3 (C16:1 ω6c and/or C16:1 ω7c; 11.4 %). The major polar lipids were phosphatidylethanolamine, aminoglycolipid, two unidentified aminolipids, three unidentified phospholipids and four unidentified lipids. The major respiratory quinone was MK-6. Based on the phylogenetic, genomic and phenotypic data presented here, strain PAMC 28998T is considered to represent a novel species of the genus

Antarcticibacterium

, for which the name Antarcticibacterium arcticum sp. nov. is proposed with the strain PAMC 28998T (=KCCM 43316 T=JCM 33514T).
Deciphering the role of insertion sequences in the evolution of bacterial epidemic pathogens with panISa software
Authors: Couchoud Charlotte , Bertrand Xavier , Valot Benoit , Hocquet Didier
Published: March 2020

Next-generation sequencing (NGS) is now widely used in microbiology to explore genome evolution and the structure of pathogen outbreaks. Bioinformatics pipelines readily detect single-nucleotide polymorphisms or short indels. However, bacterial genomes also evolve through the action of small transposable elements called insertion sequences (ISs), which are difficult to detect due to their short length and multiple repetitions throughout the genome. We designed panISa software for the ab initio detection of IS insertions in the genomes of prokaryotes. PanISa has been released as open source software (GPL3) available from https://github.com/bvalot/panISa. In this study, we assessed the utility of this software for evolutionary studies, by reanalysing five published datasets for outbreaks of human major pathogens in which ISs had not been specifically investigated. We reanalysed the raw data from each study, by aligning the reads against reference genomes and running panISa on the alignments. Each hit was automatically curated and IS-related events were validated on the basis of nucleotide sequence similarity, by comparison with the ISFinder database. In

Acinetobacter baumannii

, the panISa pipeline identified ISAba1 or ISAba125 upstream from the ampC gene, which encodes a cephalosporinase in all third-generation cephalosporin-resistant isolates. In the genomes of

Vibrio cholerae

isolates, we found that early Haitian isolates had the same ISs as Nepalese isolates, confirming the inferred history of the contamination of this island. In

Enterococcus faecalis

, panISa identified regions of high plasticity, including a pathogenicity island enriched in IS-related events. The overall distribution of ISs deduced with panISa was consistent with SNP-based phylogenic trees, for all species considered. The role of ISs in pathogen evolution has probably been underestimated due to difficulties detecting these transposable elements. We show here that panISa is a useful addition to the bioinformatics toolbox for analyses of the evolution of bacterial genomes. PanISa will facilitate explorations of the functional impact of ISs and improve our understanding of prokaryote evolution.
Preventing respiratory illness in older adults aged 60 years and above living in long-term care
Authors: Rios Patricia , Radhakrishnan Amruta , Thomas Sonia M. , Darvesh Nazia , Straus Sharon E. , Tricco Andrea C.
Published: March 2020

Background

The overall objective of this rapid overview of reviews (overview hereafter) was to identify evidence from systematic reviews (SRs) for infection control and prevention practices for adults aged 60 years and older in long-term care settings.

Methods

Comprehensive searches in MEDLINE, EMBASE, the Cochrane Library, biorxiv.org/medrxiv.org, clinicaltrials.gov and the Global Infectious Disease Epidemiology Network (GIDEON) were carried out in early March 2020. Title/abstract and full-text screening, data abstraction, and quality appraisal (AMSTAR 2) were carried out by single reviewers.

Results

A total of 6 SRs published between 1999 and 2018 were identified and included in the overview. The SRs included between 1 and 37 primary studies representing between 140 to 908 patients. All of the primary studies included in the SRs were carried out in long-term care facilities (LTCF) and examined pharmacological, non-pharmacological, or combined interventions. One high quality SR found mixed results for the effectiveness of hand hygiene to prevent infection (2 studies statistically significant positive results, 1 study non-statistically significant results). One moderate quality SR with meta-analysis found a moderate non-statistically significant effect for personal protective equipment (PPE) in preventing infection and found no statistically significant results for the effectiveness of social isolation. One moderate quality SR reported statically significant evidence for the effectiveness of amantadine and amantadine + PPE to prevent infection with respiratory illness in LTCF.

Conclusion

The current evidence suggests that with antiviral chemoprophylaxis with adamantine is effective in managing respiratory illness in residents of long-term care facilities. The rest of the strategies can be used in long-term care facilities, yet have limited evidence supporting their use from systematic reviews.
Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs
Authors: Li Zhe , Li Xin , Huang Yi-You , Wu Yaoxing , Liu Runduo , Zhou Lingli , Lin Yuxi , Wu Deyan , Zhang Lei , Liu Hao , Xu Ximing , Yu Kunqian , Zhang Yuxia , Cui Jun , Zhan Chang-Guo , Wang Xin , Luo Hai-Bin
Published: March 2020

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and, thus, repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a new virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a new restraint energy distribution (RED) function designed to accelerate the FEP-ABFE calculations and make the practical FEP-ABFE-based virtual screening of the existing drug library possible for the first time. As a result, out of twenty-five drugs predicted, fifteen were confirmed as potent inhibitors of SARS-CoV-2 Mpro. The most potent one is dipyridamole (Ki=0.04 μM) which has showed promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki=0.36 μM) and chloroquine (Ki=0.56 μM) were also found to potently inhibit SARS-CoV-2 Mprofor the first time. We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.

Significance Statement

Drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. It has been demonstrated that a new virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions can reach an unprecedently high hit rate, leading to successful identification of 16 potent inhibitors of SARS-CoV-2 main protease (Mpro) from computationally selected 25 drugs under a threshold of Ki= 4 μM. The outcomes of this study are valuable for not only drug repurposing to treat COVID-19, but also demonstrating the promising potential of the FEP-ABFE prediction-based virtual screening approach.
Are there Physical Linkages between Genes that have Synergistic Fitness Effects?
Authors: Byrnes Juliet , Murray John , Tanaka Mark M. , Goldys Ben , Bellanto Antony , Cayetano Luis , Sherwin William
Published: March 2020

Many of the effects on fitness in population genetics are due not to single locations in the genome, but to the interaction of genetic variants at multiple locations in the genome. Of particular interest are ‘completely epistatic’ interactions, where a combination of genetic variants is required to produce an effect, and the effect cannot occur with any other combination. In diploids, epistasis is strongly connected to meiotic recombination, a process which can both assemble and destroy beneficial combinations of genetic variants. Additionally, epistatic interactions can be hard to detect in empirical studies, and mathematical models of epistasis and recombination are challenging to analyse, so despite their ubiquity epistatic interactions are regularly not considered. As a result, there is little consensus on when high levels of recombination might be expected, or how strongly recombination affects beneficial or deleterious fitness effects controlled by epistatic interactions. We address this question by conducting a meta-analysis and simulations. The meta-analysis used data drawn and curated fromDrosophila melanogasterstudies in Flybase. We extracted studies relating genetic combinations and phenotypically detectable effects on fitness, then analysed the relationship between the rate of recombination and effect on fitness with a statistical model. We also ran simulations under a two-locus Wright-Fisher model with recombination and epistatic selection. The results of both approaches indicated a tendency for genetic combinations with an epistatic effect on fitness to occur in an environment of reduced meiotic recombination. Two possible explanations for this are that the variants controlling such interactions are selected for in regions where there is little recombination, or that such interactions lead to selection for lower rates of recombination in the regions where those variants appear.
CHARACTERIZATION OF THE PROPORTION OF CLUSTERED TUBERCULOSIS CASES IN GUATEMALA, CA: INSIGHTS FROM A MOLECULAR EPIDEMIOLOGY STUDY, 2010-2014
Authors: Castellanos María Eugenia , Lau-Bonilla Dalia , Moller Anneliese , Arathoon Eduardo , Quinn Frederick D. , Ebell Mark H. , Dobbin Kevin K. , Samayoa Blanca , Whalen Christopher C.
Published: March 2020

Background

There is little information about the proportion of clustering of tuberculosis cases from low-income settings, which can represent ongoing transmission events. We investigated for the first time the proportion of clustered tuberculosis cases based on genotypic matching in Guatemala City, Guatemala between 2010 and 2014 and potential risk factors associated with these clustered cases in HIV-infected subjects. Moreover, the genetic diversity of M. tuberculosis isolates in this country is presented.

Design and methods

This study was a retrospective observational study conducted on Mycobacterium tuberculosis isolates from HIV-infected and non-HIV infected tuberculosis cases that submitted samples to a referral tuberculosis laboratory in Guatemala City, Guatemala from 2010-2014. Genotyping results were compared with the international spoligotyping database, SITVIT2 and classified accordingly. We generated a spoligoforest using the MERCAT program. We categorized spoligotype patterns as clustered or non-clustered depending of their genotype and estimated the proportion of clustering and the recent transmission index (RTIn-1). We analyzed the crude association between demographic, clinical and behavioral variables and clustering in the HIV-population.

Results

From 2010 to 2014, a total of 479 patients were confirmed as tuberculosis cases by culture at the study site. Spoligotype patterns were available from 391 patients (82%), nine of them with two isolates included in the study. We detected 71 spoligotype patterns and overall, the most frequent spoligotyping families were LAM (39%), followed by T (22%), Haarlem (14%), X (13%), Unknown (6%) and Beijing (3%), representing 97% of the isolates. Out of the 400 isolates, 365 (91%) were grouped in 36 clusters (range: 2-92). The recent transmission index (RTIn-1) was 82%. Pulmonary tuberculosis was strongly associated with clustering in the 113 HIV-infected group with available data (OR=4.3, 95% CI 1.0-17.7).

Conclusion

There might be high levels of ongoing transmission of M. tuberculosis in Guatemala City, Guatemala as indicated by clustering in a convenience sample. Among HIV-infected patients, clustering was more likely in pulmonary disease.
Transmission Potential of SARS-CoV-2 in Viral Shedding Observed at the University of Nebraska Medical Center
Authors: Santarpia Joshua L. , Rivera Danielle N. , Herrera Vicki , Morwitzer M. Jane , Creager Hannah , Santarpia George W. , Crown Kevin K. , Brett-Major David M. , Schnaubelt Elizabeth , Broadhurst M. Jana , Lawler James V. , Reid St. Patrick , Lowe John J.
Published: March 2020

Lack of evidence on SARS-CoV-2 transmission dynamics has led to shifting isolation guidelines between airborne and droplet isolation precautions. During the initial isolation of 13 individuals confirmed positive with COVID-19 infection, air and surface samples were collected in eleven isolation rooms to examine viral shedding from isolated individuals. While all individuals were confirmed positive for SARS-CoV-2, symptoms and viral shedding to the environment varied considerably. Many commonly used items, toilet facilities, and air samples had evidence of viral contamination, indicating that SARS-CoV-2 is shed to the environment as expired particles, during toileting, and through contact with fomites. Disease spread through both direct (droplet and person-to-person) as well as indirect contact (contaminated objects and airborne transmission) are indicated, supporting the use of airborne isolation precautions.

One Sentence Summary

SARS-CoV-2 is shed during respiration, toileting, and fomite contact, indicating that infection may occur in both direct and indirect contact.
m6A RNA methylation regulates the fate of endogenous retroviruses
Authors: Chelmicki Tomasz , Roger Emeline , Teissandier Aurélie , Rucli Sofia , Dossin François , Dura Mathilde , Fouassier Camille , Lameiras Sonia , Bourc’his Deborah
Published: March 2020

Endogenous retroviruses (ERVs) are abundant and heterogenous groups of integrated retroviral sequences that impact genome regulation and cell physiology throughout their RNA-centered life cycle1. Failure to repress ERVs is associated with cancer, infertility, senescence and neurodegenerative diseases2–4. Here, using an unbiased genome-scale CRISPR knockout screen in mouse embryonic stem cells, we identify m6A RNA methylation as a novel means of ERV restriction. Methylation of ERV mRNAs is catalyzed by the complex of methyltransferase-like METTL3/METTL145proteins whose depletion, along with their accessory subunits, WTAP and ZC3H13, led to increased mRNA abundance of Intracisternal A-particles (IAPs) and related ERVK elements specifically, by targeting their 5’UTR region. Using controlled auxin-dependent degradation of the METTL3/METTL14 enzymatic complex, we showed that IAP mRNA and protein abundance is dynamically and inversely correlated with m6A catalysis. By monitoring mRNA degradation rates upon METTL3/14 double degron, we further proved that m6A methylation destabilizes IAP transcripts. Finally, similarly to m6A writers, triple knockout of the m6A readers YTHDF1, DF2 and DF36increased IAP mRNA abundance. This study sheds light onto a novel function of RNA methylation in protecting cellular integrity by clearing reactive ERV-derived RNA species, which may be especially important when transcriptional silencing is less stringent.
Ghosts of a structured past: Impacts of ancestral patterns of isolation-by-distance on divergence-time estimation
Authors: Hancock Zachary B. , Blackmon Heath
Published: March 2020

Isolation by distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to the potential for allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the product of the population size and the deme number. Next, we simulate whole genomes to obtain SNPs, and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. We conclude that studies estimating divergence times be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.
Piezo2, a pressure sensitive channel is expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses
Authors: Wang Jigong , Hamill Owen P.
Published: March 2020

Piezo2 expression in the normal, young adult mouse brain was examined using an anti-PIEZO2 Ab generated against a C-terminal fragment of the human PIEZO2 protein. As a positive control for Ab staining of mouse neurons, the Ab was shown to stain the majority (~90%) of mouse dorsal root ganglia (DRG) neurons, consistent with recent in situ hybridization and transcriptomic studies that also indicatePiezo2gene expression in ~90% mouse DRG neurons. As a negative control and stringent test for specificity, the Ab failed to stain DRG satellite glial cells, which do not expressPiezo2but rather its paralog,Piezo1. In slices of brains isolated from the same mice as the DRG, the Ab displayed high selectivity in staining only specific neuron types, including some pyramidal neurons in the neocortex and hippocampus, Purkinje cells in the cerebellar cortex, and most notably mitral cells within the olfactory bulb. Given the demonstrated role ofPiezo2channels in peripheral neurons as a low-threshold pressure sensor (i.e., ≤ 5 mm Hg) critical for gentle touch, proprioception, and the regulation of breathing and blood pressure, its expression in select brain neurons has interesting implications. In particular, we propose that the pressure sensitive channel may provide specific brain neurons with an intrinsic resonance that acts to synchronize their firing with the normal pulsatile changes in intracranial pressure (ICP) associated with breathing and cardiac cycles. This novel mechanism could serve to increase the robustness of the respiration entrained oscillations that have been recorded in both rodent and human brains across widely distributed neuronal networks. The idea of a “global rhythm” within the brain has been mainly related to the effect of nasal airflow activating mechanosensitive neurons within the olfactory epithelium, which in turn synchronize, through direct synaptic connections, mitral neurons within the olfactory bulb and then through their projections, the activity of neural networks in other brain regions, including the hippocampus and neocortex. Our proposed, non-synaptic, intrinsic resonance mechanism for tracking pulsatile ICP changes would have the advantage that spatially separated brain networks could be globally synchronized effectively at the speed of sound.
Photoperiod-dependent developmental reprogramming of the transcriptional response to seawater entry in Atlantic salmon (Salmo salar)
Authors: Iversen Marianne , Mulugeta Teshome , West Alexander , Jørgensen Even , Martin Samuel A. M. , Sandve Simen Rød , Hazlerigg David
Published: March 2020

The developmental transition of juvenile salmon from a freshwater resident morph (parr) to a seawater (SW) migratory morph (smolt) requires a range of physiological adaptations, including the capacity to hypo-osmoregulate. This process, known as smolting, involves both photoperiod-dependent preparative changes before SW is encountered, and activational changes stimulated by exposure to SW. To explore the relationship between these two aspects we undertook experiments in which physiological and transcriptomic responses to SW-challenge were assessed in fish that had experienced different histories of photoperiodic exposure. Compared to fish held on constant light (LL), exposure to short photoperiod (SP) dramatically impaired hypo-osmoregulation in SW, and was associated with extensive glucocorticoid-related changes in gill gene expression. Additionally, a major effect of photoperiodic history was observed in the transcriptional response of LL-acclimated fish to SW, with the response profiles of fish held on LL throughout life being quite distinctive from those of fish which had experienced an 8 week period of exposure to SP prior to return to LL (SPLL). These differences in profile likely reflect a diminishing role for NFAT-mediated responses in SPLL fish, as pathways linked to acute changes in cellular tonicity or intracellular calcium levels decline in importance with preparation for SW.
Symptomatology during seasonal coronavirus infections in children is associated with viral and bacterial co-detection
Authors: de Koff Emma M. , Van Houten Marlies A. , Sanders Elisabeth A.M. , Bogaert Debby
Published: March 2020

Lower respiratory tract symptoms during seasonal coronavirus infections in children are associated with RSV co-detection and increased levels of Haemophilus and Fusobacterium species.
Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study
Authors: Zhang Yan , Cui Yanhui , Shen Minxue , Zhang Jianchu , Liu Ben , Dai Minhui , Chen Linli , Han Duoduo , Fan Yifei , Zeng Yanjun , Li Wen , Lin Fengyu , Li Sha , Chen Xiang , Pan Pinhua
Published: March 2020

Background

The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet.

Methods

In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020.

Results

Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders.

Conclusions

Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.
Early chest computed tomography to diagnose COVID-19 from suspected patients: A multicenter retrospective study
Authors: Miao Congliang , Jin Mengdi , Miao Li , Yang Xinying , Huang Peng , Xiong Huanwen , Huang Peijie , Zhao Qi , Du Jiang , Hong Jiang
Published: March 2020

Objective

The purpose of this study is to distinguish the imaging features of COVID-19 with other chest infectious diseases and evaluate diagnostic value of chest CT for suspected patients.

Methods

Adult suspected patients aged>18 years within 14 days who underwent chest CT scan and reverse-transcription polymerase-chain-reaction (RT-PCR) tests were enrolled. The enrolled patients were confirmed and grouped according to results of RT-PCR tests. The data of basic demographics, single chest CT features, and combined chest CT features were analyzed for confirmed and non-confirmed groups.

Results

A total of 130 patients were enrolled with 54 cases positive and 76 cases negative. The typical CT imaging features of positive group were ground glass opacity (GGO), crazy-paving pattern and air bronchogram. The lesions were mostly distributed bilaterally, close to the lower lungs or the pleura. When features combined, GGO with bilateral pulmonary distribution and GGO with pleural distribution were more common, of which were 31 cases (57.4%) and 30 cases (55.6%) respectively. The combinations were almost presented statistically significant (P<0.05) except for the combination of GGO with consolidation. Most combinations presented relatively low sensitivity but extremely high specificity. The average specificity of these combinations is around 90%.

Conclusions

The combinations of GGO could be useful in the identification and differential diagnosis of COVID-19, which alerts clinicians to isolate patients for treatment promptly and repeat RT-PCR tests until incubation ends.
Modes of contact and risk of transmission in COVID-19 among close contacts
Authors: Luo Lei , Liu Dan , Liao Xin-long , Wu Xian-bo , Jing Qin-long , Zheng Jia-zhen , Liu Fang-hua , Yang Shi-gui , Bi Bi , Li Zhi-hao , Liu Jian-ping , Song Wei-qi , Zhu Wei , Wang Zheng-he , Zhang Xi-ru , Chen Pei-liang , Liu Hua-min , Cheng Xin , Cai Miao-chun , Huang Qing-mei , Yang Pei , Yang Xing-fen , Han Zhi-gang , Tang Jin-ling , Ma Yu , Mao Chen
Published: March 2020

Background

Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated.

Methods

We included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts.

Results

Among 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases.

Conclusions

In conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.
COVID-19 clinical characteristics, and sex-specific risk of mortality: Systematic Review and Meta-analysis
Authors: Nasiri Mohammad Javad , Haddadi Sara , Tahvildari Azin , Farsi Yeganeh , Arbabi Mahta , Hasanzadeh Saba , Jamshidi Parnian , Murthi Mukunthan , Mirsaeidi Mehdi
Published: March 2020

Objectives: The rapidly evolving coronavirus disease 2019 (COVID-19), was declared a pandemic by the World Health Organization on March 11, 2020. It was first detected in the city of Wuhan in China and has spread globally resulting in substantial health and economic crisis in many countries. Observational studies have partially identified the different aspects of this disease. Up to this date, no comprehensive systematic review for the clinical, laboratory, epidemiologic and mortality findings has been published. We conducted this systematic review and meta-analysis for a better understanding of COVID-19.
Methods: We reviewed the scientific literature published from January 1, 2019 to March 3, 2020. Statistical analyses were performed with STATA (version 14, IC; Stata Corporation, College Station, TX, USA). The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. Publication bias was assessed and p <0.05 was considered a statistically significant publication bias.
Results: Out of 1102 studies, 32 satisfied the inclusion criteria. A total of 4789 patients with a mean age of 49 years were evaluated. Fever (83.0%, CI 77.5 to 87.6), cough (65.2%, CI 58.6 to 71.2) and myalgia/fatigue (34.7, CI 26.0 to 44.4) were the most common symptoms. The most prevalent comorbidities were hypertension (18.5 %, CI 12.7 to 24.4) and Cardiovascular disease (14.9 %, CI 6.0 to 23.8). Among the laboratory abnormalities, elevated C-Reactive Protein (CRP) (72.0% (CI 54.3 to 84.6) and lymphopenia (50.1%, CI 38.0 to 62.4) were the most common findings. Bilateral ground-glass opacities (66.0%, CI 51.1 to 78.0) was the most common CT-Scan presentation. Pooled mortality rate was 6.6%, with males having significantly higher mortality compared to females (OR 3.4; 95% CI 1.2 to 9.1, P = 0.01).
Conclusion: COVID-19 commonly presented with a progressive course of cough and fever with more than half of hospitalized patients showing leukopenia or a high CRP on their laboratory findings. Mortality associated with COVID19 was higher than that reported in studies in China with Males having a 3-fold higher risk of mortality in COVID19 compared to females.
Effect of Diverse Recoding of Granule Cells on Optokinetic Response in A Cerebellar Ring Network with Synaptic Plasticity
Authors: Kim Sang-Yoon , Lim Woochang
Published: March 2020

We consider a cerebellar ring network for the optokinetic response (OKR), and investigate the effect of diverse recoding of granule (GR) cells on OKR by varybing the connection probabilitypcfrom Golgi to GR cells. For an optimal value of, individual GR cells exhibit diverse spiking patterns which are in-phase, anti-phase, or complex out-of-phase with respect to their population-averaged firing activity. Then, these diversely-recoded signals via parallel fibers (PFs) from GR cells are effectively depressed by the error-teaching signals via climbing fibers from the inferior olive which are also in-phase ones. Synaptic weights at in-phase PF-Purkinje cell (PC) synapses of active GR cells are strongly depressed via strong long-term depression (LTD), while those at anti-phase and complex out-of-phase PF-PC synapses are weakly depressed through weak LTD. This kind of “effective” depression (i.e., strong/weak LTD) at the PF-PC synapses causes a big modulation in firings of PCs, which then exert effective inhibitory coordination on the vestibular nucleus (VN) neuron (which evokes OKR). For the firing of the VN neuron, the learning gain degree ℒg, corresponding to the modulation gain ratio, increases with increasing the learning cycle, and it saturates at about the 300th cycle. By varyingpcfrom, we find that a plot of saturated learning gain degreeversuspcforms a bell-shaped curve with a peak at(where the diversity degree in spiking patterns of GR cells is also maximum). Consequently, the more diverse in recoding of GR cells, the more effective in motor learning for the OKR adaptation.
Global computational alignment of tumor and cell line transcriptional profiles
Authors: Warren Allison , Jones Andrew , Shibue Tsukasa , Hahn William C. , Boehm Jesse S. , Vazquez Francisca , Tsherniak Aviad , McFarland James M.
Published: March 2020

Cell lines are key tools for preclinical cancer research, but it remains unclear how well they represent patient tumor samples. Identifying cell line models that best represent the features of particular tumor samples, as well as tumor types that lackin vitromodel representation, remain important challenges. Gene expression has been shown to provide rich information that can be used to identify tumor subtypes, as well as predict the genetic dependencies and chemical vulnerabilities of cell lines. However, direct comparisons of tumor and cell line transcriptional profiles are complicated by systematic differences, such as the presence of immune and stromal cells in tumor samples and differences in the cancer-type composition of cell line and tumor expression datasets. To address these challenges, we developed an unsupervised alignment method (Celligner) and applied it to integrate several large-scale cell line and tumor RNA-Seq datasets. While our method aligns the majority of cell lines with tumor samples of the same cancer type, it also reveals large differences in tumor/cell line similarity across disease types. Furthermore, Celligner identifies a distinct group of several hundred cell lines from diverse lineages that present a more mesenchymal and undifferentiated transcriptional state and which exhibit distinct chemical and genetic dependencies. This method could thus be used to guide the selection of cell lines that more closely resemble patient tumors and improve the clinical translation of insights gained from cell line models.
An artificial intelligence-based first-line defence against COVID-19: digitally screening citizens for risks via a chatbot
Authors: Martin Alistair , Nateqi Jama , Gruarin Stefanie , Munsch Nicolas , Abdarahmane Isselmou , Knapp Bernhard
Published: March 2020

To combat the pandemic of the coronavirus disease (COVID-19), numerous governments have established phone hotlines to prescreen potential cases. These hotlines have struggled with the volume of callers, leading to wait times of hours or, even, an inability to contact health authorities. Symptoma is a symptom-to-disease digital health assistant that can differentiate more than 20,000 diseases with an accuracy of more than 90%. We tested the accuracy of Symptoma to identify COVID-19 using a set of diverse clinical cases combined with case reports of COVID-19. We showed that Symptoma can accurately distinguish COVID-19 in 96.32% of clinical cases. When considering only COVID-19 symptoms and risk factors, Symptoma identified 100% of those infected when presented with only three signs. Lastly, we showed that Symptoma’s accuracy far exceeds that of simple “yes-no” questionnaires widely available online. In summary, Symptoma provides unparalleled accuracy in systematically identifying cases of COVID-19 while also considering over 20,000 other diseases. Furthermore, Symptoma allows free text input, furthered with disease-specific follow up questions, in 36 languages. Combined, these results and accessibility give Symptoma the potential to be a key tool in the global fight against COVID-19. The Symptoma predictor is freely available online athttps://www.symptoma.com.
Effects of Controlled Dual Growth Factor Delivery on Bone Regeneration Following Composite Bone-Muscle Injury
Authors: Subbiah Ramesh , Cheng Albert , Ruehle Marissa A. , Hettiaratchi Marian H. , Bertassoni Luiz E. , Guldberg Robert E.
Published: March 2020

The objective of this study was to investigate the controlled release of two growth factors (BMP-2 and VEGF) as a treatment strategy for clinically challenging composite injuries, consisting of a segmental bone defect and volumetric muscle loss. This is the first investigation of dual growth factor delivery in a composite injury model using an injectable smart delivery system consisting of heparin microparticles and alginate gel. The loading efficiency of growth factors into these biomaterials was found to be >90%, revealing a strong affinity of VEGF and BMP-2 to heparin and alginate. The system could achieve simultaneous or sequential release of VEGF and BMP-2 by varying the loading strategy. Single growth factor delivery (VEGF or BMP-2 alone) significantly enhanced vascular growthin vitro. However, no synergistic effect was observed for dual growth factor (BMP-2 + VEGF) delivery. Effective bone healing was achieved in all treatment groups (BMP-2, simultaneous or sequential delivery of BMP-2 and VEGF) in the composite injury model. The mechanics of the regenerated bone reached a maximum strength of ∼52% of intact bone with sequential delivery of VEGF and BMP-2. Overall, simultaneous or sequential co-delivery of low-dose BMP-2 and VEGF failed to fully restore the mechanics of bone in this injury model. Given the severity of the composite injury, VEGF alone may not be sufficient to establish mature and stable blood vessels when compared with previous studies co-delivering BMP-2+VEGF enhanced bone tissue regeneration. Hence, future studies are warranted to develop an alternative treatment strategy focusing on better control over growth factor dose, spatiotemporal delivery, and additional growth factors to regenerate fully functional bone tissue.

Highlights

We developed a smart growth factor delivery system using heparin microparticles and alginate that facilitates tunable delivery of VEGF and BMP-2 in a simultaneous or sequential manner by merely varying the loading strategy.

In vitro, both VEGF and BMP-2 alone promoted vascular growth; however, VEGF was significantly more potent, and there was no detectable benefit of co-delivery.

In vivo, both BMP-2 alone and co-delivery of VEGF and BMP-2 promoted bone formation in the challenging bone/muscle polytrauma model; however, none of the treatment groups restored biomechanical properties to that of uninjured bone.
Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Patients in Wuhan, China
Authors: Hu Ling , Chen Shaoqiu , Fu Yuanyuan , Gao Zitong , Long Hui , Ren Hong-wei , Zuo Yi , Li Huan , Wang Jie , Xu Qing-bang , Yu Wen-xiong , Liu Jia , Shao Chen , Hao Jun-jie , Wang Chuan-zhen , Ma Yao , Wang Zhanwei , Yanagihara Richard , Wang Jian-ming , Deng Youping
Published: March 2020

Background

With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. As such, data are urgently needed about risk factors associated with clinical outcomes.

Methods

A retrospective chart review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into three disease severity groups (non-severe, severe, and critical), based on their initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression.

Results

Current standard treatments did not show significant improvement on patient outcomes in the study. By univariate logistic regression model, 27 risk factors were significantly associated with clinical outcomes. Further, multivariate regression indicated that age over 65 years, smoking, critical disease status, diabetes, high hypersensitive troponin I (>0.04 pg/mL), leukocytosis (>10 × 109/L) and neutrophilia (>75 × 109/L) predicted unfavorable clinical outcomes. By contrast, the use of hypnotics was significantly associated with favorable outcomes. Survival analysis also confirmed that patients receiving hypnotics had significantly better survival.

Conclusions

To our knowledge, this is the first indication that hypnotics could be an effective ancillary treatment for COVID-19. We also found that novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.

(Funded by the Natural Science Foundation of Hubei Province ZRMS2019000029 and the Top Youth Talent Program in Hubei Province.)