bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Translational Study Investigating Molecular PrEdictors of Resistance to First-Line PazopanIb in Metastatic reNal CEll Carcinoma (PIPELINE Study)
Authors: Sepe Pierangela , Martinetti Antonia , Mennitto Alessia , Verzoni Elena , Claps Melanie , Raimondi Alessandra , Sottotetti Elisa , Grassi Paolo , Guadalupi Valentina , Stellato Marco , Zattarin Emma , Di Maio Massimo , Procopio Giuseppe
Published: May 2020

Objectives:

Despite the initial clinical benefit, resistance to antiangiogenic therapies develops through the activation of alternative pathways. We measured plasma levels of circulating angiogenic factors to explore their predictive role in metastatic renal cell carcinoma (mRCC) patients treated with pazopanib.

Materials and Methods:

mRCC patients receiving first-line pazopanib were prospectively enrolled. The levels of circulating interleuchine (IL)-6, IL-8, stromal derived factor-1, vascular endothelial growth factor-A, hepatocyte growth factor (HGF), osteopontin, and E-selectin were quantified at baseline and every 4 weeks until disease progression (PD). Patients were dichotomized into “low” and “high” subgroups by a cutoff point defined by the respective median circulating angiogenic factor (CAF) value at baseline. Then, association with the objective response was determined. Changes in CAF levels between baseline and PD were also compared.

Results:

Among 25 patients included in the final data set, 6 patients were still on treatment. As best response, 12 patients presented a partial response (48%), 9 showed stable disease, and 4 showed PD. The median follow-up was 31.9 months. The median progression-free survival was 14.8 months. Low baseline levels of IL-6, IL-8, HGF, and osteopontin were found to be significantly associated with objective response. In addition, patients with low baseline levels of HGF showed longer progression-free survival and overall survival, whereas patients with low baseline levels of IL-8 showed longer overall survival. Among patients experiencing PD, the median plasma levels of stromal derived factor-1 and vascular endothelial growth factor-A were significantly higher compared with the baseline (P=0.01; P=0.011). Conversely, the median levels of E-selectin were significantly lower compared with the baseline (P=0.017).

Conclusion:

Changes in levels of selected CAFs were associated with response/resistance to pazopanib in mRCC patients.
Assessing Workplace Clinic Utilization and Performance
Authors: Kalia Nimisha , Alfriend Amy S. , Minor Sebastian A. , Bernacki Edward J. , Lavin Robert A. , Leung Nina , Yuspeh Larry , Tsourmas Nicholas F. , Tao Xuguang (Grant)
Published: May 2020

Many large employers utilize on-site medical clinics as a major component of their long-term healthcare cost management strategy. This study aims to quantify on-site clinic return on investment (ROI) associated with the avoidance of direct healthcare expenditures for preventive, urgent care and occupational medical services at an international beverage company. A multivariable linear regression model indicated there was a significant association between the ROI and increasing penetration rates, number of employees, and clinic age (P < 0.0001). Over a 10-year period, while the types of services delivered changed, onsite clinics continued to demonstrate significant and increasing cost savings for this employer.
The Association Between PHQ-9 and Fitness for Work Among Depressive Patients
Authors: Zack Oren , Strul Iris , Segal Noa , Eden Izhak , Rinsky-Halivni Lilah , Moshe Shlomo
Published: May 2020

Objective:

One of the tools to assess depression severity is the Patient Health Questionnaire (PHQ-9). Our aim was to investigate the correlation between PHQ-9 scores and fitness for work (FFW) in major depressive disorder (MDD).

Methods:

A cross-sectional study in patients who were evaluated for their FFW and later compared with PHQ-9.

Results:

Questionnaires were collected for 125 patients. A negative correlation between depression severity and absolute working ability (WA) was found for both women (β = –0.4, P < 0.001) and men (β = –0.4, P = 0.05). Multivariate linear regression revealed a negative correlation between WA and depression severity based on PHQ-9 scores (β = –0.4, P < 0.05).

Conclusions:

A negative correlation exists between absolute and relative WA and depression severity, meaning, with the higher severity of depression the lower the WA.
Preworkout Supplement Induced Hemorrhagic Stroke: A Case Report
Authors: Amatto Alycia N. , Amatto Michael D. , Yu Jaime C.
Published: May 2020

Hemorrhagic stroke is a catastrophic cause of both long-term morbidity and mortality. Many risk factors for development of these strokes are in fact preventable or modifiable in nature. This case report outlines an incident involving a previously healthy 24-year-old man with no apparent risk factors apart from consumption of preworkout supplementation who developed a hemorrhagic stroke. The supplements that this particular patient was consuming included various potential causative agents—with the most significant being Dendrobium extract, which contains compound B-phenylethylamine, a precursor in the amphetamine formation pathway. This case study highlights the potential correlation between the consumption of preworkout supplementation and occurrence of hemorrhagic stroke, as well as the implications of understanding potential effects of the constituent ingredients in commercially available preworkout supplements.
Keys to Success in Forging Global Leadership in Sustainable Nutrition
Authors: Finn Susan , Kennedy Eileen , Brown Katie
Published: May 2020

The role of nutrition and dietetics professionals across all areas of practice is more vital than ever, given the current global landscape in the context of climate change and resource scarcity. Shared values and goals connect nutrition and dietetics professionals across the world in learning, research, and nutrition practice. It is now possible for the nutrition and dietetics profession to move boldly into the sphere of food systems and sustainability, offering unique expertise and leadership for the future.
Transcranial Magnetic Stimulation as Treatment for Mal de Debarquement Syndrome: Case Report and Literature Review
Authors: Buard Isabelle , Lopez-Esquibel Natalie , Schoeneberger Stefanie , Berliner Jean M. , Kluger Benzi M.
Published: May 2020

This manuscript presents the case of an adult, male patient with mal de debarquement syndrome (MdDS); results from his experimental treatment with repetitive transcranial magnetic stimulation (rTMS) are also provided. Additionally, we included a review of literature related to the neurophysiology of MdDS and its treatment with rTMS. A 41-year-old man had been experiencing symptoms of MdDS, which initially emerged following a car ride, for 11 to 12 years. Pharmacologic approaches had failed to provide symptom relief; thus, we investigated an intervention using low-frequency (1 Hz) rTMS unilaterally for 2 consecutive weeks. The outcome measures included a standardized, computerized dynamic posturography test to quantify the patient’s balance and identify abnormalities in his use of the sensory systems contributing to postural control, as well as the Hospital Anxiety and Depression Scale (HADS) to measure his anxiety and depression. An rTMS treatment log was created to document any adverse events. Following rTMS, the patient’s balance scores improved significantly; these improvements were mostly related to the patient’s increased reliance on the visual and vestibular systems. Our patient’s HADS Anxiety and Depression subscores also showed improvement post-rTMS. The presented case study provides preliminary evidence that rTMS may be a noninvasive treatment option for improving balance, specifically in individuals with MdDS. This evidence can be used to further therapeutic research on, and provide strategies for treating, MdDS.
Sneathiella aquimaris sp. nov., isolated from aquaculture seawater
Authors: Li Guizhen , Lai Qiliang , Yan Peisheng , Gu Li , Shao Zongze
Published: May 2020

A novel marine bacterium, designated strain 216LB-ZA1-12T, was isolated from a Penaeus vannamei aquaculture seawater sample. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 216LB-ZA1-12T belonged to the genus

Sneathiella

, with the highest sequence similarity to

Sneathiella glossodoripedis

MKT133T (97.7 %), followed by

Sneathiella limimaris

GH1-24T (97.0 %),

Sneathiella chungangensis

CAU 1294T (96.6 %) and

Sneathiella chinensis

LMG 23452T (96.1 %). The average nucleotide identity and the DNA–DNA hybridization estimate values between strain 216LB-ZA1-12T and four close type strains were between 69.2–71.3% and 16.7–17.8 %, respectively. The bacterium was Gram-stain-negative, facultatively anaerobic, oxidase and catalase positive, oval- to rod-shaped, and motile. Growth was observed at pH 7–9, salinities of 1–15% and temperatures of 4–42 °C. The G+C content of the chromosomal DNA was 48.50 mol%. The major respiratory quinone was determined to be Q-10. The principal fatty acids were summed feature 8 (C18 : 1
 ω7c/ω6c) and C16 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and aminophospholipid. The combined genotypic and phenotypic data show that strain 216LB-ZA1-12T represents a novel species within the genus

Sneathiella

, for which the name Sneathiella aquimaris sp. nov. is proposed, with the type strain 216LB-ZA1-12T (=MCCC 1A14570T=KCTC 72144T).
The antidepressant sertraline provides a novel host directed therapy module for augmenting TB therapy
Authors: Shankaran Deepthi , Singh Anjali , Dawa Stanzin , Prabhakar A , Gandotra Sheetal , Rao Vivek
Published: May 2020

A prolonged therapy, primarily responsible for development of drug resistance byMycobacterium tuberculosis(Mtb), obligates any new TB regimen to not only reduce treatment duration but also escape pathogen resistance mechanisms. With the aim of harnessing the host response in providing support to existing regimens, we used sertraline (SRT) to stunt the pro-pathogenic type I IFN response of macrophages to infection. While SRT alone could only arrest bacterial growth, it effectively escalated the bactericidal activities of Isoniazid (H) and Rifampicin (R) in macrophages. This strengthening of antibiotic potencies by SRT was more evident in conditions of ineffective control by these frontline TB drug, against tolerant strains or dormant Mtb. SRT, could significantly combine with standard TB drugs to enhance early pathogen clearance from tissues of mice infected with either drug sensitive/ tolerant strains of Mtb. Further, we demonstrate an enhanced protection in acute TB infection of the highly susceptible C3HeB/FeJ mice with the combination therapy signifying the use of SRT as a potent adjunct to standard TB therapeutic regimens against bacterial populations of diverse physiology. This study advocates a novel host directed adjunct therapy regimen for TB with a clinically approved anti-depressant to achieve quicker and greater control of infection.
Sponges as bioindicators for microparticulate pollutants
Authors: Girard Elsa B. , Fuchs Adrian , Kaliwoda Melanie , Lasut Markus , Ploetz Evelyn , Schmahl Wolfgang W. , Wörheide Gert
Published: May 2020

Amongst other threats, the world’s oceans are faced with man-made pollution, including an increasing number of microparticulate pollutants. Sponges, aquatic filter-feeding animals, are able to incorporate fine foreign particles, and thus may be a potential bioindicator for microparticulate pollutants. To address this question, 15 coral reef demosponges sampled around Bangka Island (North Sulawesi, Indonesia) were analyzed for the nature of their foreign particle content using traditional histological methods, advanced light microscopy, and Raman spectroscopy. Sampled sponges accumulated and embedded the very fine sediment fraction (< 200 µm), absent in the surrounding sand, in the ectosome (outer epithelia) and spongin fibers (skeletal elements), which was confirmed by two-photon microscopy. A total of 34 different particle types were identified, of which degraded man-made products, i.e., polystyrene, cotton, titanium dioxide and blue-pigmented particles, were incorporated by eight specimens at concentrations between 91 to 612 particle/g dry sponge tissue. As sponges can weigh several hundreds of grams, we conservatively extrapolate that sponges can incorporate on average 10,000 microparticulate pollutants in their tissue. The uptake of particles, however, appears independent of the material, which suggests that the fluctuation in material ratios is due to the spatial variation of surrounding microparticles. Therefore, sponges have a strong potential to biomonitor microparticulate pollutants, such as microplastics and other degraded industrial products.
“Select and retrieve via direct upsampling” network (SARDU-Net): a data-driven, model-free, deep learning approach for quantitative MRI protocol design
Authors: Grussu Francesco , Blumberg Stefano B. , Battiston Marco , Kakkar Lebina S. , Lin Hongxiang , Ianuş Andrada , Schneider Torben , Singh Saurabh , Bourne Roger , Punwani Shonit , Atkinson David , Gandini Wheeler-Kingshott Claudia A. M. , Panagiotaki Eleftheria , Mertzanidou Thomy , Alexander Daniel C.
Published: May 2020

Purpose

We introduce“Select and retrieve via direct upsampling”network (SARDU-Net), a data-driven framework for model-free quantitative MRI (qMRI) protocol design, and demonstrate it onin vivobrain and prostate diffusion-relaxation imaging (DRI).

Methods

SARDU-Net selects subsets of informative measurements within lengthy pilot scans, without the requirement to identify tissue parameters for which to optimise for. The algorithm consists of aselector, identifying measurement subsets, and apredictor, estimating fully-sampled signals from the subsets. We implement both using deep neural networks, which are trained jointly end-to-end. We demonstrate the algorithm on brain (32 diffusion-/T1-weightings) and prostate (16 diffusion-/T2-weightings) DRI scans acquired on 3 healthy volunteers on two separate 3T Philips systems each. We used SARDU-Net to identify sub-protocols of fixed size, assessing the reproducibility of the procedure and testing sub-protocols for their potential to inform multi-contrast analyses viaT1-weighted spherical mean diffusion tensor(T1-SMDT, brain) andhybrid multi-dimensionalMRI (HM-MRI, prostate) modelling.

Results

In both brain and prostate, SARDU-Net identifies sub-protocols that maximise information content in a reproducible manner across training instantiations. The sub-protocols enable multi-contrast modelling for which they were not optimised explicitly, providing robust T1-SMDT and HM-MRI maps and goodness-of-fit in the top 5% against extensive sub-protocol comparisons.

Conclusions

SARDU-Net gives new opportunities to identify economical but informative qMRI protocols from a subset of the pilot scans that can be used for acquisition-time-sensitive applications. The simple architecture makes the algorithm easy to train when exhaustive searches are intractable, and applicable to a variety of anatomical contexts.
NF45/NF90-mediated rDNA transcription provides a novel target for immunosuppressant development
Authors: Tsai Hsiang-i , Zeng Xiaobin , Liu Longshan , Xin Shengchang , Wu Yingyi , Xu Zhanxue , Zhang Huanxi , Liu Gan , Bi Zirong , Su Dandan , Yang Min , Tao Yijing , Wang Changxi , Zhao Jing , Eriksson John E. , Deng Wenbin , Cheng Fang , Chen Hongbo
Published: May 2020

Herein, we demonstrate that NFAT, a key regulator of the immune response, translocates from cytoplasm to nucleolus and interacts with NF45/NF90 complex to collaboratively promote rDNA transcription via triggering the directly binding of NF45/NF90 to the ARRE2-like sequences in rDNA promoter upon T cell activationin vitro. The elevated pre-rRNA level of T cells is also observed in both mouse heart or skin transplantation models, and in kidney transplanted patients. Importantly, T cell activation can be significantly suppressed by inhibiting NF45/NF90-dependent rDNA transcription. Amazingly, CX5461, a rDNA transcription specific inhibitor, outperformed FK506, the most commonly used immunosuppressant, both in terms of potency and off-target activity (i.e. toxicity), as demonstrated by a series of skin and heart allograft models. Collectively, this reveals NF45/NF90-mediated rDNA transcription as a novel signaling pathway essential for T cell activation and as a new target for the development of safe and effective immunosuppressants.
Immune Response Drives Outcomes in Prostate Cancer: Implications for Immunotherapy
Authors: Meng Jialin , Zhou Yujie , Lu Xiaofan , Bian Zichen , Chen Yiding , Fan Song , Zhou Jun , Zhang Li , Hao Zongyao , Zhang Meng , Liang Chaozhao
Published: May 2020

Background

The heterogeneity of the immune microenvironment leads to the different response results of immune checkpoint blockade therapy. We aimed to propose a robust molecular classification of prostate cancer microenvironment to identify ideal patients for delivering effective immunotherapy.

Methods

A total of 1,557 prostate cancer patients were enrolled in the current study, including 69 real-world samples from the AHMU-PC cohort. Non-negative matrix factorization algorithm was employed to virtually microdissect the patients to immune and non-immune subclasses. The patients in the immune class were dichotomized to immune activated and suppressed subtypes by the nearest template prediction of activated stroma signature. The curative effects of different immune subclasses in response to immunotherapy were also predicted.

Results

We termed the newly identified molecular class of tumors as “immune class”, which was characterized by a high enrichment of T cell, B cell, NK cell, macrophage associated signatures,etc., compared with the non-immune class (all,P< 0.05). Subsequently, the immune class was subclassified into immune activated and suppressed subtypes determined by the activation status of WNT/TGF-β, TGF-β1, and C-ECM signatures. As a result, around 14.9% to 24.3% of overall patients belonged to the immune activated subgroup, and they were proved with the favorable recurrence-free survival outcomes than others and showed potential curative effects in response to the anti-PD-1/PD-L1 immunotherapy.

Conclusion

Our study identifies a novel immune class in prostate cancer, which is further described by active or exhausted immune responses. These findings provide novel insights into tailoring immunotherapeutic strategies for different prostate cancer subgroups.

Highlights

▪

Immunotherapy could trigger a durable response in advanced prostate cancer, but it only benefits a minority of patients;

▪

Immune response drives recurrence-free survival outcomes in prostate cancer;

▪

The robust molecular classification system helps identify more ideal patients for delivering anti-PD-1/PD-L1 immunotherapy.
A Reference Genome from the symbiotic hydrozoan,Hydra viridissima
Authors: Hamada Mayuko , Satoh Noriyuki , Khalturin Konstantin
Published: May 2020

Cnidarians are one of the oldest eumetazoan taxa, and are thought to be a sister group to all bilaterians. In spite of comparatively simple morphology, cnidarians exhibit diverse body forms and life histories. In addition, many cnidarian species establish symbiotic relationships with microalgae. VariousHydraspecies have been employed as model organisms since the 18th century. Introduction of transgenic and knock-down technologies made them ideal experimental systems for studying cellular and molecular mechanisms involved in regeneration, body-axis formation, senescence, symbiosis, and holobiosis. In order to provide an important reference for genetic studies, theHydra magnipapillatagenome was sequenced. However, the initial published version of theH. magnipapillatagenome did not achieve assembly continuity comparable to those of other model systems, due mainly to a large number of transposable elements. For almost a decade, the highly fragmented genome assembly ofH. magnipapillata(scaffold N50=128Kb) has remained the only genomic resource for this genus with several dozen species. Here we report a draft 280-Mbp genome assembly forHydra viridissimastrain A99, a symbiotic, early diverging member of theHydraclade, with a scaffold N50 of 1.1 Mbp. TheH. viridissimagenome contains an estimated 21,476 protein-coding genes. Comparative analysis of Pfam domains and orthologous proteins highlights characteristic features ofH. viridissima, such as diversification of innate immunity genes that are important for host-symbiont interactions. Thus, theHydra viridissimaassembly provides an important hydrozoan genome reference that will facilitate symbiosis research and better comparisons of metazoan genome architectures.
Belief in Conspiracy Theory about COVID-19 Predicts Mental Health and Well-being: A Study of Healthcare Staff in Ecuador
Authors: Chen Xi , Zhang Stephen X. , Jahanshahi Asghar Afshar , Alvarez-Risco Aldo , Dai Huiyang , Li Jizhen , Ibarra Verónica García
Published: May 2020

Background

Social media are becoming hotbeds of conspiracy theories, which aim to give resolute explanations on the cause of COVID-19 pandemic. Yet, no research has investigated whether individuals’ belief in conspiracy theory about COVID-19 is associated with mental health and well-being issues. This association enables an assessable channel to identify and reach people with mental health and well-being issues during the pandemic.

Objective

We aim to provide the first evidence of belief in conspiracy theory regarding the COVID-19 virus as a predictor of the mental health and well-being of healthcare workers.

Methods

We conducted a survey of 252 healthcare workers in Ecuador from April 10 to May 2, 2020. We analyzed the data of distress and anxiety caseness with logistic regression and life and job satisfaction with linear regression.

Results

Among the sampled healthcare workers in Ecuador, 24.2% believed that the virus was developed intentionally in a lab; 32.54% experienced distress disorder, and 28.17% had anxiety disorder. Compared to healthcare workers who were not sure where the virus originated, those who believed the virus was developed intentionally in a lab were more likely to have distress disorder and anxiety disorder and had lower levels of job satisfaction and life satisfaction.

Conclusions

This paper identifies belief in a COVID-19 conspiracy theory as an important predictor of distress, anxiety, and job and life satisfaction of healthcare workers. It enables mental health services to better target and help mentally vulnerable healthcare workers during the ongoing COVID-19 pandemic.
Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities
Authors: Guillier Laurent , Martin-Latil Sandra , Chaix Estelle , Thébault Anne , Pavio Nicole , Poder Sophie Le , Batéjat Christophe , Biot Fabrice , Koch Lionel , Schaffner Don , Sanaa Moez
Published: May 2020

Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.

Importance

The prediction of the persistence of SARS-CoV-2 on fomites is essential to investigate the importance of contact transmission. This study collects available information on inactivation kinetics of coronaviruses in both solid and liquid fomites and creates a mathematical model for the impact of temperature and relative humidity on virus persistence. The predictions of the model can support more robust decision-making and could be useful in various public health contexts. Having a calculator for the natural clearance of SARS-CoV-2 depending on temperature and relative humidity could be a valuable operational tool for public authorities.
Analysis of Rapidly Emerging Variants in Structured Regions of the SARS-CoV-2 Genome
Authors: Ryder Sean P. , Morgan Brittany R. , Massi Francesca
Published: May 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around the globe. They also provide a unique opportunity to observe virus evolution in real time. Here, we evaluate two cohorts of SARS-CoV-2 genomic sequences to identify rapidly emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, twenty variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5’UTR, including a set of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-stable molecular switch in the 3’UTR. Finally, five variants destabilize structured elements within the 3’UTR hypervariable region, including the S2M stem loop, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. This analysis has implications for the development of therapeutics that target viral cis-regulatory RNA structures or sequences, as rapidly emerging variations in these regions could lead to drug resistance.
Evidence for anti-viral effects of complete Freund’s adjuvant in the mouse model of enterovirus infection
Authors: Gangaplara Arunakumar , Massilamany Chandirasegaran , Lasrado Ninaad , Steffen David , Reddy Jay
Published: May 2020

Group B Coxsackieviruses belonging to the genus, Enterovirus, contain six serotypes that induce various diseases, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within CVB3 viral protein 1 that induce anti-viral T cell responses in mouse models of CVB infections. In our investigations to determine the protective responses of the viral epitopes, we unexpectedly noted that animals immunized with complete Freund’s adjuvant (CFA) alone and later challenged with CVB3 were completely protected against myocarditis. Similarly, the pancreatitis-inducing ability of CVB3 was remarkably reduced to only 10% in the CFA group as opposed to 73.3% in the control group that received no CFA. Additionally, no mortalities were noted in the CFA group, whereas 40% of control animals died during the course of 21 days post-infection with CVB3. Taken together, our data suggest that the adjuvant effects of CFA may be sufficient for protection against CVB infections. These observations may provide new insights into our understanding of the occurrence of viral infections. One example is Coronavirus disease-19 (COVID-19) as individuals suffering from COVID-19 who have been vaccinated with Bacillus Calmette–Guérin appear to have fewer morbidities and mortalities than unvaccinated individuals.
Etiology and Outcomes of Acute Flaccid Paralysis in Adults: A Study in Tertiary Care Center.
Authors: Gupta Mohit , Daid Sarav Gunjit Singh
Published: May 2020

INTRODUCTION:
The World Health Organization defines acute flaccid paralysis syndrome as rapid onset of weakness of an individual's extremities, often including weakness of the muscles of respiration and swallowing, progressing to maximum severity within 1 to 10 days. We carried out this observational study in a tertiary care center in North India with the aim of determining the etiology and outcome of Acute Flaccid Paralysis in adults.

METHODS:
In this observational study, all cases diagnosed with Acute flaccid paralysis admitted to the tertiary care center from 1st January 2015 till 30th June 2016 were enrolled. Ninety-seven consecutive patients of age above 18 years presenting with weakness of duration less than two weeks were enrolled after obtaining informed consent and various investigations were studied.

RESULTS:
The study analyzed data of 97 patients presenting with flaccid paralysis. They were analyzed for the demographic data, clinical features, investigations, electrophysiological data, and results of the treatment. The most common etiology of acute flaccid paralysis in this entire population was GBS, which was responsible for 50.5% of the cases, followed by the Hypokalemic paralysis (25.8%) followed by neuroparalytic snake bite (15.5%).In this study, 48% of patients with hypokalemic paralysis had a secondary cause for their condition. Primary hypokalemic periodic paralysis occurred in 52% of patients.

CONCLUSIONS:
In this observational study, GBS was found to be the most common cause for Acute Flaccid Paralysis followed by Neuroparalytic snake bite. Respiratory paralysis was an important risk factor associated with mortality.
“The expediency of local modelling to aid national responses to SARS-CoV-2.”
Authors: Groen Bernard M. , Turner Paul , Lacey Peter
Published: May 2020

Background

With the SARS-CoV-2 pandemic gripping most of the globe, healthcare and economic recovery strategies are being explored currently as a matter of urgency. The underpinning rationale of this paper is that we believe that health and care services are provided locally, therefore, local implications of national policy need to be reflected when informing national responses to the SARS-CoV-2 pandemic.

Methods

We adopted the assumptions underlying the United Kingdom government’s national epidemiological model which influences the national policy response to the SARS-CoV-2 pandemic. We used these in a local context and show projections in terms of presentations of symptomatic patients differ in a variety of settings. Setting:North of England, United Kingdom, population modelled at four local constituent levels which aggregated gives a total population of 3.2m.

Results

We clearly demonstrate that there is significant difference in the way the national modelling outputs are replicated at local levels. Specifically, in terms of projected increased levels of demand for services on the local health and care systems.

Conclusions

We present significant evidence of differing timelines specifically in terms of subsequent projected peak demands. Additionally, it clearly indicates varying levels of such demand throughout the four modelled localities. These idiosyncrasies are ‘masked’ by both regional and national approaches to modelling. We urge readers to ensure that any national policy is appropriately adopted through the use of complementary bottom up approach, to suit local health and care systems. Finally, we share our methodology to ensure other professionals could replicate this study elsewhere.
A Gynecology-Led Transgender Clinic: Retrospective Review of Referral Patterns and Quality Indicators
Authors: McCall Jennifer , She Jennifer , Pudwell Jessica , Kielly Maria , Waddington Ashley
Published: May 2020

Background

The Transgender Clinic at the Kingston Health Sciences Centre (KTC) was created in 2017 to meet the needs of transgender patients.

Methods

A retrospective review of all KTC patient charts was completed. The primary outcomes were the referral pattern to, and services provided by KTC. The secondary outcomes were the quality indicators i) rates of cervical screening and ii) offers of fertility preservation.

Results

108 patients were referred and 92 were seen; the median age was 20 years old. 77.2% of all patients sought, and 72.8% ultimately received, hormone therapy. Cervical cancer screening was documented as up to date for 69.8% of eligible people. 81.7% of eligible patients had documented fertility preservation offers.

Conclusion

Accessible local transgender care is a standard that can and should be met in Canada and internationally.

77.2% of patients sought hormone therapy, which is in the scope of providers from many specialties

Accessible local transgender care is a standard than can and should be met in Canada and internationally

Gynecologists, pediatricians, and primary care providers are well-suited to provide transgender care
Knowledge, attitude, and perceptions towards the 2019 Coronavirus Pandemic: A bi-national survey in Africa
Authors: Hager Elnadi , Odetokun Ismail A. , Bolarinwa Obasanjo , Zainab Ahmed , Okechukwu Ochulor , Ibrahim Al-Mustapha A.
Published: May 2020

The current Coronavirus (COVID-19) pandemic has changed and impacted lives on a global scale since its emergence and spread from China in late 2019. It has caused millions of infections, and thousands of deaths worldwide. However, the control of this pandemic still remains unachievable in many African countries including Egypt and Nigeria, despite the application of some strict preventive and control measures. Therefore, this study assessed the knowledge, attitude and perceptions of Egyptians and Nigerians towards COVID-19 pandemic.

A total of 1437 respondents were included in this preliminary cross-sectional survey. The mean knowledge score was 14.7±2.3. The majority of the respondents (61.6%) had a satisfactory knowledge of the disease. Age (18-39 years), education (College/bachelors) and background of respondents were factors influencing knowledge levels. The attitude of most respondents (68.9%) towards the preventive measures was satisfactory with an average attitude score of 6.9 ± 1.2. The majority of the respondents (96%) practiced self-isolation and social-distancing but only 36% follow all health recommendations. The perception of most respondents (62.1%) on the global efforts at controlling the virus and preventing further spread was satisfactory with an average score of 10.9 ± 2.7. A satisfactory knowledge of COVID-19 was significantly associated with good attitude and perceptions (p < 0.001) of respondents. Only 22% of the respondents were satisfied with their country’s handling of the pandemic.

It is imperative that to avoid Africa being the next epicenter of the pandemic. Governments need to strengthen health systems, improve their surveillance activities in detecting cases, and effectively apply standard infection prevention and control measures.
Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan
Authors: Wei Chen , Lee Chien-Chang , Hsu Tzu-Chun , Hsu Wan-Ting , Chan Chang-Chuan , Chen Shyr-Chyr , Chen Chien-Jen
Published: May 2020

Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics-population testing number and testing coverage-to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= −0.79, P=5.975e-09 vs rs = − 0.3, P=0.05) and case fatality rate (rs= −0.67, P=9.067e-06 vs rs= −0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.
Determinants of COVID-19 vaccine acceptance in Saudi Arabia: a web-based national survey
Authors: Padhi Bijaya Kumar , Al-Mohaithef Mohammed
Published: May 2020

Background

Vaccine hesitancy is a potential threat to global public health. Since, there is an unprecedented global effort to develop a vaccine against the COVID-19 pandemic, much less is known about its acceptance in the community. Understanding key determinants that influence the preferences and demands of a future vaccine by the community may help to develop strategies for improving the global vaccination program. This study aimed to assess the prevalence of the acceptance of COVID-19 vaccine, and their determinants among people in Saudi Arabia.

Methods

A web-based, cross-sectional study was conducted using snowball sampling strategy under a highly restricted environment. A bilingual, self-administered anonymous questionnaire was designed and sent to 1000 study participants through social media platforms and email. Study participants were recruited across the country, including the four major cities (Riyadh, Dammam, Jeddah, and Abha) in Saudi Arabia. Associations between COVID-19 vaccine acceptance and sociodemographic profile of the respondents were explored using the chi-squared test. Key determinants that predict vaccine acceptance among respondents were modelled using logistic regression analysis.

Results

Of the 1000 survey invitees, 992 responded to the survey (response rate, 99.2%). The majority (65.8%) of the study participants were female, 29.53% were in the age group (36–45 years), and 17.9% were non-Saudi. Of the 992 respondents, 642 (64.72%) showed interest to accept the COVID-19 vaccine if it is available. Willingness to accept the future COVID-19 vaccine is relatively high among older age groups (79.2% among 45+ year old), being married (69.3%), participants with education level postgraduate degree or higher (68.8%), non-Saudi (69.1%), employed in government sector (68.9%). In multivariate model, respondents who were above 45 years (aOR: 2.15; 95% CI: 1.08-3.21), and married (aOR: 1.79; 95% CI: 1.28-2.50) were significantly associated with vaccine acceptance (p <.05). Besides, people having trust in the health system were most likely to accept the vaccine (aOR: 3.05; 95% CI: 1.13-4.92), and those having a higher perceived risk of acquiring infection were 2.13 times (95% CI: 1.35-3.85) higher odds of accepting the vaccine.

Conclusion

Addressing sociodemographic determinants relating to the COVID-19 vaccination may help to increase uptake of the global vaccination program to tackle future pandemics. Targeted health education interventions are needed to increase the uptake of the future COVID-19 vaccine.
A SARS-CoV-2 serological assay to determine the presence of blocking antibodies that compete for human ACE2 binding
Authors: Byrnes James R. , Zhou Xin X. , Lui Irene , Elledge Susanna K. , Glasgow Jeff E. , Lim Shion A. , Loudermilk Rita , Chiu Charles Y. , Wilson Michael R. , Leung Kevin K. , Wells James A.
Published: May 2020

As SARS-CoV-2 continues to spread around the world, there is an urgent need for new assay formats to characterize the humoral response to infection. Convalescent serum is being used for treatment and for isolation of patient-derived antibodies. However, currently there is not a simple means to estimate serum bulk neutralizing capability. Here we present an efficient competitive serological assay that can simultaneously determine an individual’s seropositivity against the SARS-CoV-2 Spike protein and estimate the neutralizing capacity of anti-Spike antibodies to block interaction with the human angiotensin converting enzyme 2 (ACE2) required for viral entry. In this ELISA-based assay, we present natively-folded viral Spike protein receptor binding domain (RBD)-containing antigens via avidin-biotin interactions. Sera are then supplemented with soluble ACE2-Fc to compete for RBD-binding serum antibodies, and antibody binding quantified. Comparison of signal from untreated serum and ACE2-Fc-treated serum reveals the presence of antibodies that compete with ACE2 for RBD binding, as evidenced by loss of signal with ACE2-Fc treatment. In our test cohort of nine convalescent SARS-CoV-2 patients, we found all patients had developed anti-RBD antibodies targeting the epitope responsible for ACE2 engagement. This assay provides a simple and high-throughput method to screen patient sera for potentially neutralizing anti-Spike antibodies to enable identification of candidate sera for therapeutic use.
A reductive analysis of a compartmental model for COVID-19: data assimilation and forecasting for the United Kingdom
Authors: Ananthakrishna G. , Kumar Jagadish
Published: May 2020

We introduce a deterministic model that partitions the total population into the susceptible, infected, quarantined, and those traced after exposure, the recovered and the deceased. We hypothesize ‘accessible population for transmission of the disease’ to be a small fraction of the total population, for instance when interventions are in force. This hypothesis, together with the structure of the set of coupled nonlinear ordinary differential equations for the populations, allows us to decouple the equations into just two equations. This further reduces to a logistic type of equation for the total infected population. The equation can be solved analytically and therefore allows for a clear interpretation of the growth and inhibiting factors in terms of the parameters in the full model. The validity of the ‘accessible population’ hypothesis and the efficacy of the reduced logistic model is demonstrated by the ease of fitting the United Kingdom data for the cumulative infected and daily new infected cases. The model can also be used to forecast further progression of the disease. In an effort to find optimized parameter values compatible with the United Kingdom coronavirus data, we first determine the relative importance of the various transition rates participating in the original model. Using this we show that the original model equations provide a very good fit with the United Kingdom data for the cumulative number of infections and the daily new cases. The fact that the model calculated daily new cases exhibits a turning point, suggests the beginning of a slow-down in the spread of infections. However, since the rate of slowing down beyond the turning point is small, the cumulative number of infections is likely to saturate to about 3.52 × 105 around late July, provided the lock-down conditions continue to prevail. Noting that the fit obtained from the reduced logistic equation is comparable to that with the full model equations, the underlying causes for the limited forecasting ability of the reduced logistic equation are elucidated. The model and the procedure adopted here are expected to be useful in fitting the data for other countries and in forecasting the progression of the disease.
Clinical population genetic analysis of variants in the SARS-CoV-2 receptor ACE2
Authors: Ardeshirdavani Amin , Zakeri Pooya , Mehrtash Amirhosein , Hosseini Sayed Mostafa , Li Guangdi , Mirtavoos-Mahyari Hanifeh , Soltanpour Mohamad javad , Tavallaie Mahmoud , Moreau Yves
Published: May 2020

Purpose

SARS-CoV-2 infects cells via the human Angiotensin-converting enzyme 2 (ACE2) protein. The genetic variation of ACE2 function and expression across populations is still poorly understood. This study aims at better understanding the genetic basis of COVID-19 outcomes by studying association between genetic variation in ACE2 and disease severity in the Iranian population.

Methods

We analyzed two large Iranian cohorts and several publicly available human population variant databases to identify novel and previously known ACE2 exonic variants present in the Iranian population and considered those as candidate variants for association between genetic variation and disease severity. We genotyped these variants across three groups of COVID-19 patients with different clinical outcomes (mild disease, severe disease, and death) and evaluated this genetic variation with regard to clinical outcomes.

Results

We identified 32 exonic variants present in Iranian cohorts or other public variant databases. Among those, 11 variants are novel and have thus not been described in other populations previously. Following genotyping of these 32 candidate variants, only the synonymous polymorphism (c.2247G>A) was detected across the three groups of COVID-19 patients.

Conclusion

Genetic variability of known and novel exonic variants was low among our COVID-19 patients. Our results do not provide support for the hypothesis that exonic variation in ACE2 has a sizeable impact on COVID-19 severity across the Iranian population.
Assessment of Individual- and Community-level Risks for COVID-19 Mortality in the US and Implications for Vaccine Distribution
Authors: Jin Jin , Agarwala Neha , Kundu Prosenjit , Harvey Benjamin , Zhang Yuqi , Wallace Eliza , Chatterjee Nilanjan
Published: May 2020

Reducing COVID-19 illness and mortality for populations in the future will require equitable and effective risk-based allocations of scarce preventive resources, including early available vaccines. To aid in this effort, we develop a risk calculator for COVID-19 mortality based on various socio-demographic factors and pre-existing conditions for the US adult population by combining information from the UK-based OpenSAFELY study, with mortality rates by age and ethnicity available across US states. We tailor the tool to produce absolute risks for individuals in future time frames by incorporating information on pandemic dynamics at the community level as available from forecasting models. We apply this risk calculation model to available data on prevalence and co-occurrences of the risk-factors from a variety of data sources to project risk for the general adult population across 477 US cities (defined as Census Places) and for the 65 years and older Medicare population across 3,113 US counties, respectively. Validation analyses based on these projected risks and data on tens of thousands of recent deaths show that the model is well calibrated for the US population. Projections show that the model can identify relatively small fractions of the population (e.g. 4.3%) which will lead to a disproportionately large number of deaths (e.g. 49.8%), and thus will be useful for effectively targeting individuals for early vaccinations, but there will be wide variation in risk distribution across US communities. We provide a web-based tool for individualized risk calculations and interactive maps for viewing the city-, county- and state-level risk projections.