bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Chinese medicine for oral squamous cell carcinoma
Authors: Wang Dong , Duan XiaoJie , Zhang Yuhui , Meng Zhen , Wang Jing
Published: October 2020

Background:

Traditional Chinese medicine is frequently used for malignant tumors in China, but in clinical practice, most practitioners choose appropriate Chinese medicines based on personal experience. In our study, Bayesian network meta-analysis will be used to identify differences in efficacy and safety between diverse traditional Chinese drugs for oral squamous cell carcinoma (OSCC).

Methods:

Relevant randomized controlled trials and prospective controlled clinical trials were searched from Medline, PubMed, Cochrane Library, Google Scholar, Excerpt Medica Database, Web of Science, China National Knowledge Infrastructure, China Scientific Journal Database, Chinese Biomedical Literature Database, and Wanfang Database from their establishment to September 2020. Study selection and data extraction will be performed independently by 2 researchers. Aggregate Data Drug Information System and R software were used for data synthesis. The evidentiary grade of the results will be also evaluated.

Results:

The results of this study will be published in a peer-reviewed journal, and provide reliable evidence for different traditional Chinese drugs on OSCC.

Conclusions:

The findings will provide reference for evaluating the efficacy and safety of different traditional Chinese medicine for OSCC, and provide a helpful evidence for clinicians to formulate the best adjuvant treatment strategy for OSCC patients.

Trial registration number:

INPLASY202090082.
Subjective oral health status in an adult Korean population with asthma or allergic rhinitis
Authors: Wee Jee Hye , Yoo Dae Myoung , Byun Soo Hwan , Lee Hyo-Jeong , Park Bumjung , Park Min Woo , Choi Hyo Geun
Published: October 2020

Oral health can affect or be a manifestation of general health. Although oral health assessment has been used as a proxy for general health, few studies have reported an association between oral health status and allergic diseases. This cross-sectional study aimed to investigate the relationship between subjective oral health status and asthma/allergic rhinitis in a nationwide representative sample of Korean adults.

A total of 227,977 participants from the Korean Community Health Survey 2015 were enrolled. Participants were asked about their subjective oral health status (very good, good, normal, poor, very poor), periodontal status (mobility, swelling, calculus, bleeding), teeth brushing frequency, and scaling history within the past 12 months. Histories of physician-diagnosed asthma and allergic rhinitis throughout life were surveyed. The associations between subjective oral health status and allergic diseases were analyzed using multiple logistic regression analysis. Age, sex, economic level, educational level, region of residence, smoking, alcohol, obesity, subjective general health status, stress level, physical activity, periodontal status, teeth brushing frequency, and scaling history within the past 12 months were adjusted as covariates.

A higher prevalence of asthma (3.6%) was reported in the poor oral health group than in the good (1.8%) and normal (2.1%) groups (P < .001). Poor oral health status was significantly related to asthma, with an adjusted odds ratio (aOR) of 1.19 (95% CI = 1.07–1.33, P = .002). Although the prevalence of allergic rhinitis was not higher in the poor oral health group (13.4%) than in the good (15.4%) and normal oral health groups (15.9%), the aOR for allergic rhinitis was 1.05 (95% CI = 1.00–1.11, P = .045) in the poor oral health group after adjusting for covariates.

Subjective poor oral health status was significantly associated with asthma and allergic rhinitis in Korean adults.
Screening and identification of key genes and pathways in metastatic uveal melanoma based on gene expression using bioinformatic analysis
Authors: Xie Jialu , Wu Zhenyu , Xu Xiaogang , Liang Guanlu , Xu Jiehui
Published: October 2020

The current study aimed to elucidate the molecular mechanisms and identify the potential key genes and pathways for metastatic uveal melanoma (UM) using bioinformatics analysis.

Gene expression microarray data from GSE39717 included 39 primary UM tissue samples and 2 metastatic UM tissue samples. Differentially expressed genes (DEGs) were generated using Gene Expression Omnibus 2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the online Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. The web-based STRING tool was adopted to construct a protein--protein interaction (PPI) network. The MCODE tool in Cytoscape was used to generate significant modules of the PPI network.

A total of 213 DEGs were identified. GO and KEGG analyses revealed that the upregulated genes were mainly enriched in extracellular matrix organization and blood coagulation cascades, while the downregulated DEGs were mainly related to protein binding, negative regulation of ERK cascade, nucleus and chromatin modification, and lung and renal cell carcinoma. The most significant module was extracted from the PPI network. GO and KEGG enrichment analyses of the module revealed that the genes were mainly enriched in the extracellular region and space organization, blood coagulation process, and PI3K-Akt signaling pathway. Hub genes, includingFN1, APOB, F2, SERPINC1, SERPINA1, APOA1, FGG, PROC, ITIH2, VCAN, TFPI, CXCL8, CDH2, andHP,were identified from DEGs. Survival analysis and hierarchical clustering results revealed that most of the hub genes were associated with prognosis and clinical progression.

Results of this bioinformatics analysis may provide predictive biomarkers and potential candidate therapeutic targets for individuals with metastatic UM.
Association between personal protective equipment and SARS-CoV-2 infection risk in emergency department healthcare workers
Authors: Schmitz Danique , Vos Marieke , Stolmeijer Renate , Lameijer Heleen , Schönberger Titus , Gaakeer Menno I. , de Groot Bas , Eikendal Ties , Wansink Luuk , ter Avest Ewoud.
Published: October 2020

Background and importance

Healthcare personnel working in the emergency department (ED) is at risk of acquiring severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2). So far, it is unknown if the reported variety in infection rates among healthcare personnel is related to the use of personal protective equipment (PPE) or other factors.

Objective

The aim of this study was to investigate the association between PPE use and SARS-CoV-2 infections among ED personnel in the Netherlands.

Design, setting and participants

A nationwide survey, consisting of 42 questions about PPE-usage, ED layout - and workflow and SARS-CoV-2 infection rates of permanent ED staff, was sent to members of the Dutch Society of Emergency Physicians. Members were asked to fill out one survey on behalf of the ED of their hospital. The association between PPE use and the infection rate was investigated using univariable and multivariable regression analyses, adjusting for potential confounders.

Outcome measures

Primary outcome was the incidence of confirmed SARS-CoV-2 infections among permanent ED staff between 1 March and 15 May 2020.

Results

Surveys were sent to 64 EDs of which 45 responded (70.3%). In total, 164 ED staff workers [5.1 (3.2–7.0)%] tested positive for COVID-19 during the study period compared to 0.087% of the general population. There was significant clustering of infected ED staff in some hospitals (range: 0–23 infection). In 13 hospitals, an FFP2 (filtering facepiece particles >94% aerosol filtration) mask or equivalent and eye protection was worn for all contacts with patients with suspected or confirmed SARS-CoV-2 during the whole study period. The unadjusted staff infection rate was higher in these hospitals [7.3 (3.4–11.1) vs. 4.0 (1.9–6.1)%, absolute difference + 3.3%]. Hospital staff testing policy was identified as a potential confounder of the relation between PPE use and confirmed SARS-CoV-2 infections (collinearity statistic 0.95). After adjusting for hospital testing policy, type of PPE was not associated with incidence of COVID 19 infections among ED staff (P = 0.40).

Conclusion

In this cross-sectional study, the use of high-level PPE (FFP2 or equivalent and eye protection) by ED personnel during all contacts with patients with suspected or confirmed SARS-CoV-2 does not seem to be associated with a lower infection rate of ED staff compared to lower level PPE use. Attention should be paid to ED layout and social distancing to prevent cross-contamination of ED personnel.
Management of submucous cleft palate
Authors: Dean Kelly M. , Leeper Lauren K.
Published: October 2020

Purpose of review

Submucous cleft palate (SMCP) represents an uncommon congenital palatal anomaly with a variable rate of velopharyngeal dysfunction or resulting speech abnormality. Classic teaching regarding management of this entity involves delayed repair until a perceptual speech assessment by a skilled speech-language pathologist can be performed, typically at age 3–5 years. An assessment of timing of intervention, surgical techniques, and patient comorbidities is critical for optimized outcomes.

Recent findings

Early diagnosis and surgical intervention for SMCP are associated with improved speech outcomes. Expanding indications for surgery are being actively investigated. Timing of intervention and surgical technique may be influenced by a syndromic diagnosis, specifically 22q11.2 deletion syndrome.

Diagnosis of classic SMCP and occult SMCP may be difficult based on provider experience. Variable surgical techniques may be used with good outcomes; patient comorbidities including syndromic diagnoses may determine best surgical technique. Expanding indications for surgery and timing of repair continue to evolve and warrant additional study.
Ethical and legal considerations related to disorders of consciousness
Authors: Rissman Lauren , Paquette Erin Talati
Published: October 2020

Purpose of review

The purpose of this review is to describe ethical and legal issues that arise in the management of patients with disorders of consciousness ranging from the minimally conscious state to the coma state, as well as brain death.

Recent findings

The recent literature highlights dilemmas created by diagnostic and prognostic uncertainties in patients with disorders of consciousness. The discussion also reveals the challenges experienced by the disability community, which includes individuals with severe brain injury who are classified as having a disorder of consciousness. We review current guidelines for management of patients with disorders of consciousness including discussions around diagnosis, prognosis, consideration of neuropalliation, and decisions around life sustaining medical treatment.

In the setting of uncertainty, this review describes the utility of applying a disability rights perspective and shared decision-making process to approach medical decision-making for patients with disorders of consciousness. We outline approaches to identifying surrogate decision makers, standards for decision-making and decision-making processes, specifically addressing the concept of futility as a less useful framework for making decisions. We also highlight special considerations for research, innovative and controversial care, brain death, organ donation, and child abuse and neglect.
Postneoadjuvant Pure and Predominantly Pure Intralymphatic Breast Carcinoma
Authors: MacColl Christine E. , Paré Guillaume , Salehi Amir , Hodgson Nicole , Williams Phillip
Published: October 2020

Locally advanced breast cancer is typically treated with neoadjuvant chemotherapy to decrease tumor size and optimize surgical results. Cases of pathologic complete response, are associated with favorable long-term outcomes. The American Joint Committee on Cancer (AJCC) defines pathologic complete response as a lack of residual invasive disease in the breast or lymph nodes or only residual ductal carcinoma in situ. Three studies have examined the unique pattern of postneoadjuvant pure or predominantly pure intralymphatic carcinoma. These studies are small and the prognosis associated with this disease pattern is still unclear. The current study aims to describe clinicopathologic findings associated with pure and predominantly pure intralymphatic carcinoma postneoadjuvant chemotherapy. Electronic medical records were searched to identify patients treated with postneoadjuvant mastectomy between 2010 and 2017. Cases were included if they met the previously defined definitions for pure or predominantly pure intralymphatic carcinoma. Of 479 postneoadjuvant mastectomies, 5 patients had pure intralymphatic carcinoma and 6 patients had predominantly pure. Overall, 50% (3/6) of patients with predominantly pure pattern died of metastatic disease within 14 months of mastectomy, whereas 1 patient with pure intralymphatic carcinoma (ypN0) died of metastatic disease 25 months postmastectomy, revealing a better prognosis associated with pure intralymphatic carcinoma when compared with predominantly pure. The diligent gross examination is required to identify patients with both patterns of residual disease. A standardized approach to incorporating lymphovascular invasion into postneoadjuvant staging may be useful from both a clinical and research perspective. The published case numbers remain small and understanding the true clinical significance still depends on additional studies.
Effectiveness of Pediatric Asthma Pathways in Community Hospitals: A Multisite Quality Improvement Study
Authors: Desai Mansi , Caldwell Katherine , Gupta Nisha , Bekmezian Arpi , Cabana Michael D. , Auerbach Andrew D. , Kaiser Sunitha V.
Published: October 2020

Introduction:

Pathways guide clinicians through evidence-based care of specific conditions. Pathways have been demonstrated to improve pediatric asthma care, but mainly in studies at tertiary children’s hospitals. Our global aim was to enhance the quality of asthma care across multiple measures by implementing pathways in community hospitals.

Methods:

This quality improvement study included children ages 2–17 years with a primary diagnosis of asthma. Data were collected before and after pathway implementation (total 28 mo). Pathway implementation involved local champions, educational meetings, audit/feedback, and electronic health record integration. Emergency department (ED) measures included severity assessment at triage, timely systemic corticosteroid administration (within 60 mins), chest radiograph (CXR) utilization, hospital admission, and length of stay (LOS). Inpatient measures included screening for secondhand tobacco and referral to cessation resources, early administration of bronchodilator via metered-dose inhaler, antibiotic prescription, LOS, and 7-day readmission/ED revisit. Analyses were done using statistical process control.

Results:

We analyzed 881 ED visits and 138 hospitalizations from 2 community hospitals. Pathways were associated with increases in the proportion of children with timely systemic corticosteroid administration (Site 1: 32%–57%, Site 2: 62%–75%) and screening for secondhand tobacco (Site 1: 82%–100%, Site 2: 54%–89%); and decreases in CXR utilization (Site 1: 44%–29%), ED LOS (Site 1: 230–197 mins), and antibiotic prescription (Site 2: 23%–3%). There were no significant changes in other outcomes.

Conclusions:

Pathways improved pediatric asthma care quality in the ED and inpatient settings of community hospitals.
Conventional and Biologic Disease-Modifying Antirheumatic Drugs Are Not Associated With Increase in or Progression of Cervical Neoplasia Among Patients With Spondyloarthritis
Authors: Li Philip Hei , Chan Shirley Chiu Wai , Lau Chak Sing , Seto Mimi Tin Yan , Chung Ho Yin
Published: October 2020

Objectives

Using a centralized electronic database, we investigated the risk of cervical neoplasia (CN) and progression of cervical intraepithelial neoplasia (CIN) among patients with spondyloarthritis (SpA) receiving disease-modifying antirheumatic drugs (DMARDs).

Method

A total of 951 patients with SpA were reviewed. Incidence and progression of CN and clinical data including age, ethnicity, smoking and drinking status, dates of first and last follow-up, history of psoriasis, inflammatory bowel disease, medications used, mean dose and duration of medications, and comorbidities were reviewed. Cox regression models were used to evaluate the individual risk of DMARDs with CN and the risk of CIN progression.

Results

During a mean follow-up duration of 9.2 ± 5.9 years, 34 patients had developed CN, which translates to an incidence for development of CN in patients with SpA of 3.9 per 1000 patient-years. Univariate Cox regression analyses showed no differences in clinical characteristics (psoriasis hazards ratio [HR] = 0.92, p = 0.82; inflammatory bowel disease HR = 0.05, p = 0.61; diabetes mellitus HR = 2.82, p = 0.21; chronic kidney disease HR = 0.39, p = 0.35) and medications exposure (sulfasalazine HR = 0.49, p = 0.30; methotrexate HR = 0.52, p = 0.11; leflunomide HR = 0.52, p = 0.37; adalimumab HR = 0.83, p = 0.80; certolizumab HR = 0.05, p = 0.74; etanercept HR = 0.40, p = 0.36; golimumab HR = 0.05, p = 0.32; infliximab HR = 0.05, p = 0.39; secukinumab HR = 1.00, p = 1.00; ustekinumab HR = 0.05, p = 0.78) between patients who had and had not develop CN during the study period. Progression of CIN was independently associated with higher grades of CIN lesion (HR = 6.20; p = 0.05).

Conclusions

There was low risk of development and progression of CN in patients with SpA on conventional or biologic DMARD therapy.
The effect of COVID-19 on critical care research during the first year of the pandemic: A prospective longitudinal multinational survey
Authors: Duffett Mark , Cook Deborah J , Strong Geoff , Lee Jan Hau , Kho Michelle E
Published: October 2020

Importance

The COVID-19 pandemic has increased the need for high-quality evidence in critical care, while also increasing the barriers to conducting the research needed to produce such evidence.

Objective

To determine the effect of the first wave of the COVID-19 pandemic on critical care clinical research.

Design

Monthly electronic survey (March 2020 - February 2021).

Setting

Adult or pediatric intensive care units (ICUs) from any country participating in at least one research study before the COVID-19 pandemic.

Participants

We recruited one researcher or research coordinator per center, identified via established research networks.

Intervention(s)

None

Main Outcome(s) and Measure(s)

Primary: Suspending recruitment in clinical research; Secondary: impact of specific factors on research conduct (5-point scales from no effect to very large effect). We assessed the association between research continuity and month, presence of hospitalized patients with COVID-19, and population (pediatric vs. adult ICU) using mixed-effects logistic regression.

Results

127 centers (57% pediatric) from 23 countries participated. 95 (75%) of centers suspended recruitment in at least some studies and 37 (29%) suspended recruitment in all studies on at least one month. The proportion of centers reporting recruitment in all studies increased over time (OR per month 1.3, 95% CI 1.2 to 1.4, p < 0.001), controlling for hospitalized patients with COVID-19 and type of ICU (pediatric vs. other). The five factors most frequently identified as having a large or very large effect on clinical research were: local prioritization of COVID-19 specific research (68, 54%), infection control policies limiting access to patients with COVID-19 (61, 49%), infection control policies limiting access to the ICU (52, 41.6%), increased workload of clinical staff (38, 30%), and safety concerns of research staff (36, 29%).

Conclusions and Relevance

Decisions to pause or pursue clinical research varied across centers. Research activity increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles with local adaptation to safely sustain research during this and future pandemics are urgently needed.

Key Points

Question

What was the effect of the COVID-19 pandemic on research in 127 adult and pediatric intensive care units (ICUs) between March 2020 and February 2021?

Findings

95 (75%) centers suspended recruitment into at least some studies. Active recruitment into studies increased over time (OR per month 1.3, 95% CI 1.2 to 1.4, p < 0.001), controlling for ICU type and the presence of patients with COVID-19.

Meaning

Research activity varied across centers and increased over time, despite the presence of hospitalized patients with COVID-19. Guiding principles to safely sustain research during this and future pandemics are urgently needed.
Does Obstructive sleep apnea increase the risk of Parkinson Disease? A systematic review and meta-analysis
Authors: Zhao Tianming , Xuan Kun , Sun Chenyu , Liu Haixia , Chen Xin , Sun Yehuan
Published: October 2020

Objectives

The evidence of whether the obstructive sleep apnea (OSA) could increase the risk of Parkinson disease (PD) remains controversial. This meta-analysis was conducted in hopes of providing evidence of associations between the OSA and the risk of PD incidence.

Methods

Relevant studies published until 7 September, 2020 were retrieved from 6 databases. 6 studies were finally included based on our selection criteria. Hazard Ratios (HRs) and their 95%CI of each study were collected to evaluate the relationship between obstructive sleep apnea and Parkinson disease risk. Subgroup analysis was performed based on gender and sample size.

Results

We find a positive association between obstructive sleep apnea and Parkinson disease risk (HR=1.64, 95%CI:1.56-1.73, I2=23.8%). OSA patients have a higher risk of Parkinson disease than subjects without OSA, especially in male patients (HR=1.56, 95%CI: 1.30-1.87, I2=0.0%). Based on results of sensitivity analysis, our study results were quite stable.

Conclusions

Our results provided evidence of a modest positive association between obstructive sleep apnea and Parkinson disease. It is a certain degree of significance to improve our understanding of obstructive sleep apnea and take measures to prevent and treat it. Moreover, additional studies are recommended to explore this topic in more detail. This study was registered in PROSPERO (CRD42020207528).
Personalized Single-Cell Proteogenomics to Distinguish Acute Myeloid Leukemia from Non-Malignant Clonal Hematopoiesis
Authors: Dillon Laura W. , Ghannam Jack , Nosiri Chidera , Gui Gege , Goswami Meghali , Calvo Katherine R. , Lindblad Katherine E. , Oetjen Karolyn A. , Wilkerson Matthew , Soltis Anthony R. , Sukumar Gauthaman , Dalgard Clifton L. , Thompson Julie , Valdez Janet , DeStefano Christin B. , Lai Catherine , Sciambi Adam , Durruthy-Durruthy Robert , Llanso Aaron , Gulati Saurabh , Wang Shu , Ooi Aik , Dagur Pradeep K. , McCoy J. Philip , Burr Patrick , Li Yuesheng , Hourigan Christopher S.
Published: October 2020

Genetic mutations associated with acute myeloid leukemia can also be detected in age-related clonal hematopoiesis, making confident assignment of detected variants to malignancy challenging particularly in the post-treatment setting. This has implications for measurable residual disease monitoring, where the relationship between sequencing and flow cytometry is also imperfect. We show, using whole-genome-sequencing informed patient-personalized single-cell DNA and antibody-oligonucleotide sequencing, that it is possible to resolve immunophenotypic identity of clonal architecture.
Digital contact-tracing during the Covid-19 pandemic: an analysis of newspaper coverage in Germany, Austria, and Switzerland
Authors: Amann Julia , Sleigh Joanna , Vayena Effy
Published: October 2020

Governments around the globe have started to develop and deploy digital contact tracing apps to gain control over the spread of the novel coronavirus (Covid-19). The appropriateness and usefulness of these technologies as a containment measure have since sparked political and academic discussions globally. The present paper contributes to this debate through an exploration of how the national daily newspapers in Germany, Austria, and Switzerland reported on the development and adoption of digital contact-tracing apps during early and after stages of the lockdown. These countries were among the first in Europe to develop apps and were critical voices in the debate of decentralized vs. centralized data processing. We conducted thematic analysis on news coverage published between January and May 2020 in high-circulation national daily newspapers (print) from Germany, Austria, and Switzerland. A total of 148 newspaper articles were included in the final analysis. From our analysis emerged six core themes of the development and adoption of digital contact tracing apps: 1) data governance; 2) role of IT giants; 3) scientific rigor; 4) voluntariness; 5) functional efficacy; 6) role of the app. These results shed light on the different facets of discussion regarding digital contact tracing as portrayed in German-speaking media. As news coverage can serve as a proxy for public perception, this study complements emerging survey data on public perceptions of digital contact tracing apps by identifying potential issues of public concern.
Food Insecurity Increases in Brazil from 2004 to 2018: Analysis of national surveys
Authors: Salles-Costa Rosana , Ferreira Aline Alves , de Mattos Ruben Araujo , Reichenheim Michael E. , Pérez-Escamilla Rafael , Segall-Corrêa Ana Maria
Published: October 2020

Objective

Describe secular changes in food security (FS) and severe food insecurity (FI) in Brazil.

Design

We analyzed four national surveys that assessed FI with the Brazilian Household Food Insecurity Measurement Scale (EBIA), and estimated the percentage changes of FS/FI levels between 2004 and 2013 (1st period) and between 2013 and 2018 (2nd period) by sociodemographic variables.

Setting

Data from the cross-sectional Brazilian National Households Sample Surveys (2004, 2009 and 2013) and Household Budget Survey (2018).

Participants

Nationally representative samples of household surveys (2004=112,530; 2009=120,910;2013=116,196; and 2018=57,920).

Results

The 1stperiod was marked by a significant increase in FS (+18.9%) and by a reduction in severe FI (−53.6%). The 2ndperiod showed a decrease in FS (−18.2%) and an increase of severe FI (+43.8%). The greater increase FS in the 1stperiod was in the Northeast (+33.4%), among households with more than 7 residents (+40.8%), and in households where the reference person self-identified as black or mulatto (+27.6%). In the 2ndperiod, the lower increase in severe FI was observed among households with children under 4 years old (+ 6.3%) and with members over 65 years old (+12.5%).

Conclusions

After a significant reduction in FS from 2004 to 2013, FS was strongly compromised from 2014 to 2018 likely as result of disruptions in access to foods in all regions, intensified by the sociodemographic inequality in Brazil. Hunger in Brazil has re-emerged as a national concern.
Forecasting the spread of COVID-19 pandemic in Bangladesh using ARIMA model
Authors: Kundu Lakshmi Rani , Ferdous Most. Zannatul , Islam Ummay Soumayia , Sultana Marjia
Published: October 2020

Background

COVID-19 is one of the most serious global public health threats creating an alarming situation. Therefore, there is an urgent need for investigating and predicting COVID-19 incidence to control its spread more effectively. This study aim to forecast the expected number of daily total confirmed cases, total confirmed new cases, total deaths and total new deaths of COVID-19 in Bangladesh for next 30 days.

Methods

The number of daily total confirmed cases, total confirmed new cases, total deaths and total new deaths of COVID-19 from 8 March 2020 to 16 October, 2020 was collected to fit an Autoregressive Integrated Moving Average (ARIMA) model to forecast the spread of COVID-19 in Bangladesh from 17th October 2020 to 15th November 2020. All statistical analyses were conducted using R-3.6.3 software with a significant level of p< 0.05.

Results

The ARIMA (0,2,1) and ARIMA (0,1,1) model was adopted for forecasting the number of daily total confirmed cases, total deaths and total confirmed new cases, new deaths of COVID-19, respectively. The results showed that an upward trend for the total confirmed cases and total deaths, while total confirmed new cases and total new death, will become stable in the next 30 days if prevention measures are strictly followed to limit the spread of COVID-19.

Conclusions

The forecasting results of COVID-19 will not be dreadful for upcoming month in Bangladesh. However, the government and health authorities should take new approaches and keep strong monitoring of the existing strategies to control the further spread of this pandemic.
De novodesign of transmembrane β-barrels
Authors: Vorobieva Anastassia A. , White Paul , Liang Binyong , Horne Jim E , Bera Asim K. , Chow Cameron M. , Gerben Stacey , Marx Sinduja , Kang Alex , Stiving Alyssa Q. , Harvey Sophie R. , Marx Dagan C. , Khan G. Nasir , Fleming Karen G. , Wysocki Vicki H. , Brockwell David J. , Tamm Lukas K. , Radford Sheena E. , Baker David
Published: October 2020

The ability of naturally occurring transmembrane β-barrel proteins (TMBs) to spontaneously insert into lipid bilayers and form stable transmembrane pores is a remarkable feat of protein evolution and has been exploited in biotechnology for applications ranging from single molecule DNA and protein sequencing to biomimetic filtration membranes. Because it has not been possible to design TMBs from first principles, these efforts have relied on re-engineering of naturally occurring TMBs that generally have a biological function very different from that desired. Here we leverage the power ofde novocomputational design coupled with a “hypothesis, design and test” approach to determine principles underlying TMB structure and folding, and find that, unlike almost all other classes of protein, locally destabilizing sequences in both the β-turns and β-strands facilitate TMB expression and global folding by modulating the kinetics of folding and the competition between soluble misfolding and proper folding into the lipid bilayer. We use these principles to design new eight stranded TMBs with sequences unrelated to any known TMB and show that they insert and fold into detergent micelles and synthetic lipid membranes. The designed proteins fold more rapidly and reversibly in lipid membranes than the TMB domain of the model native protein OmpA, and high resolution NMR and X-ray crystal structures of one of the designs are very close to the computational model. The ability to design TMBs from first principles opens the door to custom design of TMBs for biotechnology and demonstrates the value ofde novodesign to investigate basic protein folding problems that are otherwise hidden by evolutionary history.

One sentence summary

Success inde novodesign of transmembrane β-barrels reveals geometric and sequence constraints on the fold and paves the way to design of custom pores for sequencing and other single-molecule analytical applications.
MITF Isoforms- Insights from an RNA-Seq study
Authors: Kirty Kritika , Sigurðsson Snævar , Guðjόnsson Þorkell , Einarsdóttir Berglind Ósk , Sigurðsson Stefán
Published: October 2020

The manuscript has been withdrawn because of lack of full consent from all co-authors. Therefore, the corresponding author does not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
How subtle changes in 3D structure can create large changes in transcription
Authors: Xiao Jordan , Hafner Antonina , Boettiger Alistair N.
Published: October 2020

Animal genomes are organized into topologically associated domains (TADs), which exhibit more intra-domain than inter-domain contact. However, the absolute difference in contact is usually no more than twofold, even though disruptions to TAD boundaries can change gene expression by 8-10 fold. Existing models fail to explain this superlinear transcriptional response to changes in genomic contact. Here, we propose a futile cycle model where an enzyme stimulated by association with its products can exhibit bistability and hysteresis, allowing a small increase in enhancer-promoter contact to produce a large change in expressionwithoutobvious correlation between E-P contact and promoter activity. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of enhancer-promoter specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile recent global cohesin loop disruption and TAD boundary deletion experiments. We discuss the model in the context of these recent controversial experiments. Together, these analyses advance our interpretation and understanding of cis-regulatory contacts in controlling gene expression, and suggest new experimental directions.
Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects
Authors: Nguyen Hanh T. , Zhang Shijian , Wang Qian , Anang Saumya , Wang Jia , Ding Haitao , Kappes John C. , Sodroski Joseph
Published: October 2020

SARS-CoV-2, a betacoronavirus, is the cause of the COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein trimer mediates virus entry into host cells and cytopathic effects. We studied the contribution of several S glycoprotein features to these functions, focusing on those that differ among related coronaviruses. Acquisition of the furin cleavage site by the SARS-CoV-2 S glycoprotein decreased virus stability and infectivity, but greatly enhanced the ability to form lethal syncytia. Notably, the D614G change found in globally predominant SARS-CoV-2 strains restored infectivity, modestly enhanced responsiveness to the ACE2 receptor and susceptibility to neutralizing sera, and tightened association of the S1 subunit with the trimer. Apparently, two unique features of the SARS-CoV-2 S glycoprotein, the furin cleavage site and D614G, have evolved to balance virus infectivity, stability, cytopathicity and antibody vulnerability. Although the endodomain (cytoplasmic tail) of the S2 subunit was not absolutely required for virus entry or syncytium formation, alteration of palmitoylated cysteine residues in the cytoplasmic tail decreased the efficiency of these processes. As proteolytic cleavage contributes to the activation of the SARS-CoV-2 S glycoprotein, we evaluated the ability of protease inhibitors to suppress S glycoprotein function. Matrix metalloprotease inhibitors suppressed S-mediated cell-cell fusion, but not virus entry. Synergy between inhibitors of matrix metalloproteases and TMPRSS2 suggests that both proteases can activate the S glycoprotein during the process of syncytium formation. These results provide insights into SARS-CoV-2 S glycoprotein-host cell interactions that likely contribute to the transmission and pathogenicity of this pandemic agent.

IMPORTANCE

The development of an effective and durable SARS-CoV-2 vaccine is essential for combating the growing COVID-19 pandemic. The SARS-CoV-2 spike (S) glycoprotein is the main target of neutralizing antibodies elicited during virus infection or following vaccination. Knowledge of the spike glycoprotein evolution, function and interactions with host factors will help researchers to develop effective vaccine immunogens and treatments. Here we identify key features of the spike glycoprotein, including the furin cleavage site and the D614G natural mutation, that modulate viral cytopathic effects, infectivity and sensitivity to inhibition. We also identify two inhibitors of host metalloproteases that block S-mediated cell-cell fusion, which contributes to the destruction of the virus-infected cell.
A novel method for measuring phenotypic colistin resistance inEscherichia colipopulations from chicken flocks
Authors: Nguyen Nhung Thi , Yen Nguyen Thi Phuong , Van Ky Thien Nguyen , Van Cuong Nguyen , Kiet Bach Tuan , Campbell James , Thwaites Guy , Baker Stephen , Geskus Ronald B. , Carrique-Mas Juan
Published: October 2020

Colistin is extensively used in animal production in many low- and middle-income countries. There is a need to develop methodologies to benchmark and monitor changes in resistance in commensal bacterial populations in farms. We aimed to evaluate the performance of a broth microdilution method based on culturing a pooledEscherichia colisuspension (30-50 organisms) from each sample. In order to confirm the biological basis and sensitivity of the method, we prepared 16 standard suspensions containing variable ratios of colistin-susceptible andmcr-1 encoded colistin-resistantE. coliwhich were grown in 2mg/L colistin. The optical density (OD600nm) readings over time were used to generate a growth curve, and were adjusted to the values obtained in the absence of colistin. The median limit of detection of the method was 1 colistin-resistant in 104susceptible colonies [1st- 3rdquartile, 1:102– 1:105]. We applied this method to 108 pooled faecal samples from 36 chicken flocks in the Mekong Delta (Vietnam) over the production cycle. The correlation between this method and the prevalence of colistin resistance in individual colonies harvested from field samples, determined by the Minimum Inhibitory Concentration (MIC), was established. The overall prevalence of colistin resistance at sample and isolate level was 38.9% and 19.4%, respectively. Increased colistin resistance was associated with recent (2 weeks) use of colistin and other, non-colistin antimicrobials (OR=3.67 and OR=1.84, respectively). Our method is a sensitive and affordable approach to monitor changes in colistin resistance in pooledE. colipopulations from faecal samples over time.

IMPORTANCE

Colistin (polymyxin E) is an antimicrobial with poor solubility properties, and therefore broth microdilution is the only appropriate method for testing colistin resistance. However, estimating colistin resistance in commensal mixedEscherichia colipopulations is laborious since it requires individual colony isolation, identification and susceptibility testing. We developed a growth-based microdilution method suitable for pooled faecal samples. We validated the method by comparing it with results from individual MIC testing of 909E. coliisolates. We used the method to investigate phenotypic colistin resistance in 108 pooled faecal samples from 36 healthy chicken flocks, each sampled three times over the production cycle. A higher level of resistance was seen in flocks recently supplemented with colistin in drinking water, although the observed generated resistance was short-lived. Our method is affordable, and may potentially be integrated into surveillance systems aiming at estimating the prevalence of resistance at colony level in flocks/herds. Furthermore, it may also be adapted to other complex biological systems, such as farms and abattoirs.
Dynamics of sex chromosome evolution in a rapid radiation of cichlid fishes
Authors: Taher Athimed El , Ronco Fabrizia , Matschiner Michael , Salzburger Walter , Böhne Astrid
Published: October 2020

Sex is a fundamental trait that is determined, depending on the species, by different environmental and/or genetic factors, including various types of sex chromosomes. While the functioning and emergence of sex chromosomes have been explored in species scattered across the eukaryotic tree of life, little is known about tempo and mode of sex chromosome evolution in closely related species. Here, we examine the dynamics of sex chromosome evolution in an archetypical example of adaptive radiation, the cichlid fishes of African Lake Tanganyika. Through inspection of male and female genomes from 244 cichlid taxa and the analysis of transcriptomes from 66 taxa, we identify signatures of sex chromosomes in 79 taxa, involving 12 different linkage groups. We estimate that Tanganyikan cichlids have the highest rates of sex chromosome turnover and heterogamety transitions known to date. We further show that the recruitment of chromosomes as sex chromosomes is not at random and that some chromosomes have convergently emerged as sex chromosomes in cichlids, which provides empirical support to the “limited options” hypothesis of sex chromosome evolution.
Morphological and phylogeographic evidence for budding speciation: an example in hominins
Authors: Parins-Fukuchi Caroline
Published: October 2020

Parametric phylogenetic approaches that attempt to delineate between distinct ‘modes’ of speciation (splitting cladogenesis, budding cladogenesis, and anagenesis) between fossil taxa have become increasingly popular among comparative biologists. But it is not yet well-understood how clearly morphological data from fossil taxa speak to detailed questions of speciation mode as compared to the lineage diversification models that serve as their basis. In addition, the congruence of inferences made using these approaches with geographic patterns has not been explored. Here, I extend a previously introduced maximum-likelihood approach for the examination of ancestor-descendant relationships to accommodate budding speciation and apply it to a dataset of fossil hominins. I place these results in a phylogeographic context to better understand spatial dynamics underlying the hypothesized speciation patterns. The spatial patterns implied by the phylogeny hint at the complex demographic processes underlying the spread and diversification of hominins throughout the Pleistocene. I also find that inferences of budding are driven primarily by stratigraphic, versus morphological, data and discuss the ramifications for interpretations of speciation process in hominins specifically and from phylogenetic data in general.
Single cell analyses reveal phosphate availability as critical factor for nutrition ofSalmonella entericawithin mammalian host cells
Authors: Röder Jennifer , Hensel Michael
Published: October 2020

Salmonella entericaserovar Typhimurium (STM) is an invasive, facultative intracellular pathogen that resides in a specialized membrane-bound compartment termedSalmonella-containing vacuole (SCV). Essential for survival and proliferation in the SCV isSalmonellapathogenicity island II (SPI2) that encodes a type III secretion system (T3SS). The SPI2-T3SS and the effector translocation maintain SCV integrity and formation of specific tubular membrane compartments, calledSalmonella-induced filaments (SIFs). The SCV/SIF continuum allows STM to bypass nutritional restriction in the intracellular environment by acquiring nutrients from the host cell. Phosphate is one of the most abundant elements in living organisms and in STM, inorganic phosphate (Pi) homeostasis is mediated by the two-component regulatory system PhoBR, resulting in expression of the high affinity phosphate transporterpstSCAB-phoU.Using fluorescent protein reporters, we investigate Piavailability for STM at single cell level over time within the intracellular habitats of different host cells. We observed that thepstSCAB-phoUencoded phosphate uptake system is essential for intracellular replication of STM because there is a Piion concentration less 10 μM within the SCV. Additionally, the demand and consumption of Picorrelates with intracellular proliferation of STM and we identify a dependency of SPI2 activity and Pistarvation.
An evaluation of the interpretability and predictive performance of the BayesR model for genomic prediction
Authors: Mollandin Fanny , Rau Andrea , Croiseau Pascal
Published: October 2020

Technological advances and decreasing costs have led to the rise of increasingly dense genotyping data, making feasible the identification of potential causal markers. Custom genotyping chips, which combine medium-density genotypes with a custom genotype panel, can capitalize on these candidates to potentially yield improved accuracy and interpretability in genomic prediction. A particularly promising model to this end is BayesR, which divides markers into four effect size classes. BayesR has been shown to yield accurate predictions and promise for quantitative trait loci (QTL) mapping in real data applications, but an extensive benchmarking in simulated data is currently lacking. Based on a set of real genotypes, we generated simulated data under a variety of genetic architectures, phenotype heritabilities, and we evaluated the impact of excluding or including causal markers among the genotypes. We define several statistical criteria for QTL mapping, including several based on sliding windows to account for linkage disequilibrium. We compare and contrast these statistics and their ability to accurately prioritize known causal markers. Overall, we confirm the strong predictive performance for BayesR in moderately to highly heritable traits, particularly for 50k custom data. In cases of low heritability or weak linkage disequilibrium with the causal marker in 50k genotypes, QTL mapping is a challenge, regardless of the criterion used. BayesR is a promising approach to simultaneously obtain accurate predictions and interpretable classifications of SNPs into effect size classes. We illustrated the performance of BayesR in a variety of simulation scenarios, and compared the advantages and limitations of each.
Morphometric and Molecular Discrimination of the sugarcane aphid,Melanaphis sacchari, (Zehntner, 1897) and the sorghum aphidMelanaphis sorghi(Theobald, 1904)
Authors: Nibouche Samuel , Costet Laurent , Medina Raul F. , Holt Jocelyn R. , Sadeyen Joëlle , Zoogones Anne-Sophie , Brown Paul , Blackman Roger L.
Published: October 2020

Melanaphis sacchari(Zehntner, 1897) andMelanaphis sorghi(Theobald, 1904) are major worldwide crop pests causing direct feeding damage on sorghum and transmitting viruses to sugarcane. It is common in the scientific literature to consider these two species as synonyms, referred to as the ‘sugarcane aphid’, although no formal study has validated this synonymy. In this study, based on the comparison of samples collected from their whole distribution area, we use both morphometric and molecular data to better characterize the discrimination betweenM. sacchariandM. sorghi. An unsupervised multivariate analysis of morphometric data clearly confirmed the separation of the two species. The best discriminating characters separating these species were length of the antenna processus terminalis relative to length of hind tibia, siphunculus or cauda. However, those criteria sometimes do not allow an unambiguous identification. Bayesian clustering based on microsatellite data delimited two clusters, which corresponded to the morphological species separation. The DNA sequencing of three nuclear and three mitochondrial regions revealed slight divergence between species. In particular, the COI barcode region proved to be uninformative for species separation because one haplotype is shared by both species. In contrast, one SNP located on the nuclear EF1-α gene was diagnostic for species separation. Based on morphological and molecular evidence, the invasive genotype damaging to sorghum in the US, Mexico and the Caribbean since 2013 is found to beM. sorghi.