bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Hepatitis C Testing Strategy for Human Immunodeficiency Virus–Positive Men Who Have Sex With Men at the Sexually Transmitted Infections Outpatient Clinic of Amsterdam, the Netherlands
Authors: Jongen Vita W. , van Rooijen Martijn S. , Schim van der Loeff Maarten F. , Newsum Astrid M. , de Vos Klootwijk Louise , Hoornenborg Elske , Hogewoning Arjan , van der Valk Marc , van den Berk Guido E.L. , Prins Maria , Heijman Titia
Published: June 2020

Introduction

As the incidence of hepatitis C virus (HCV) infections remains high among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) an HCV testing strategy was introduced at the sexually transmitted infections (STI) clinic in Amsterdam in 2017. We aimed to evaluate this HCV testing strategy.

Methods

The HIV-positive MSM and transgender women (TGW) were eligible for HCV testing (anti-HCV and HCV ribonucleic acid) at the STI clinic if they did not visit their HIV clinician in the 3 months before the consultation and had not been tested for HCV at the STI clinic in the previous 6 months. All eligible individuals were administered the 6 questions on risk behavior of the HCV-MSM observational study of acute infection with hepatitis C (MOSAIC) risk score; a risk score of 2 or greater made a person eligible for testing.

Results

From February 2017 through June 2018, 1015 HIV-positive MSM and TGW were eligible for HCV testing in 1295 consultations. Eleven active HCV infections (HCV ribonucleic acid positive) were newly diagnosed (positivity rate, 0.9%; 95% confidence interval [CI], 0.4–1.5%). Sensitivity and specificity of the HCV-MOSAIC score for newly diagnosed active HCV infections were 80.0% (95% CI, 49.0–94.3%) and 53.7% (95% CI, 50.8–56.5%), respectively. If an HCV-MOSAIC score of 2 or greater were used to determine whom to test, 46.6% of individuals currently tested for HCV would be eligible for testing.

Conclusions

Using the new HCV testing strategy, HCV testing was done in 1295 consultations with HIV-positive MSM and TGW in 17 months. We newly diagnosed 11 active HCV infections. The HCV-MOSAIC risk score could reduce the number of tests needed, but some active HCV infections will be missed.
An Integrative Morphomolecular Classification System of Gastric Carcinoma With Distinct Clinical Outcomes
Authors: Tsai Jia-Huei , Jeng Yung-Ming , Chen Kuo-Hsing , Lee Chia-Hsiang , Yuan Chang-Tsu , Liau Jau-Yu
Published: June 2020

A robust morphomolecular classification system for gastric carcinoma is required. A 4-tier morphologic classification is proposed, including diffuse, intestinal, tubular, and lymphoid types. A tissue microarray for mismatch repair immunohistochemistry and Epstein-Barr virus (EBV) in situ hybridization were performed in 329 gastric carcinomas. DNA flow cytometry was used to detect aneuploidy in formalin-fixed paraffin-embedded samples. Lymphoid histology was the third most common histologic pattern at our institute and strongly associated with EBV infection and PMS2/MLH1-deficiency (both P<0.001). HER2 overexpression and SATB2 expression more frequently occurred in intestinal histology (both P<0.001). Loss of ARID1A expression was strikingly associated with lymphoid histology (P<0.001) and negative E-cadherin expression was correlated with diffuse histology (P=0.001). Programmed death-ligand 1 expression was most frequently present in lymphoid-type gastric carcinoma than other histologic subtypes and correlated with the molecular features of PMS2/MLH1-deficiency and EBV infection (all P<0.001). Aneuploidy was detected in 53% of gastric carcinomas and was highly correlated with intestinal type and the least with the lymphoid type (P<0.001). Notably, lymphoid-type gastric carcinoma showed the best outcome, whereas tubular type showed the worst survival rate (P<0.001). We integrated aneuploidy with morphologic patterns to propose a morphomolecular classification scheme, which served as a successful and independent prognostic factor in multivariate 5-year disease-free survival analysis (P<0.001). Overall, we describe an integrated morphomolecular classification system for gastric carcinomas to effectively predict patient outcomes. This system is cost-effective and reliable and can help select target therapeutics and facilitate clinical management.
Inflammatory Myofibroblastic Tumor of the Uterus
Authors: Bennett Jennifer A. , Croce Sabrina , Pesci Anna , Niu Nifang , Van de Vijver Koen , Burks Eric J. , Burandt Eike , Zannoni Gian Franco , Rabban Joseph T. , Oliva Esther
Published: June 2020

Inflammatory myofibroblastic tumors (IMT) of the uterus may be underrecognized as their morphology and immunophenotype may overlap with myxoid variants of uterine smooth muscle tumors and endometrial stromal tumors. Although ALK is a helpful biomarker, not all uterine IMTs are ALK-rearranged, and a small subset of myxoid leiomyosarcomas is ALK-positive. Herein, we evaluated a series of 23 IMTs for the novel endometrial stromal markers interferon-inducible transmembrane protein-1 (IFITM1) and BCOR, the novel myoid marker transgelin, and possible predictive markers p16 and p53 by immunohistochemistry to determine their expression profile and potential prognostic value. Patients’ ages ranged from 8 to 59 (mean 39) years and tumors from 2 to 20 (mean 8.2) cm. Follow-up was available for 12/23 (52%) patients; 9/12 (75%) without evidence of disease, 2/12 (17%) alive with disease, and 1/12 (8%) dead from disease. Four IMTs were classified as malignant due to extrauterine disease at diagnosis and/or recurrence. IFITM1 was positive (combined score>2) in 19/23 (83%), BCOR in 8/20 (40%), and transgelin in 22/23 (96%) of tumors. IFITM1 and BCOR were more often expressed in the myxoid component, and transgelin in the compact areas. p16 expression was absent in 5/23 (22%) of IMTs, while p53 was wildtype in all tumors. p16-negative IMTs included all 4 classified as malignant and one where the patient was lost to follow-up. Molecular data were available in 2 malignant IMTs, both of which harbored CDKN2A deletions. We conclude that caution is advised when using IFITM1, BCOR, and transgelin as markers for endometrial and smooth muscle tumors, as these are commonly expressed in IMTs. However, we did identify an association among lack of p16 staining, CKDN2A deletions, and aggressive behavior that merits corroboration by other studies. As a result of this finding, we recommend the use of p16 in the diagnostic work-up of uterine IMTs due to its potential prognostic significance.
Medications for Children Receiving Intensive Care: A National Sample
Authors: Heneghan Julia A. , Trujillo Rivera Eduardo A. , Zeng-Treitler Qing , Faruqe Farhana , Morizono Hiroki , Bost James E. , Pollack Murray M. , Patel Anita K.
Published: June 2020

Objective:

To examine medication administration records through electronic health record data to provide a broad description of the pharmaceutical exposure of critically ill children.

Design:

Retrospective cohort study using the Cerner Health Facts database.

Setting:

United States.

Patients:

A total of 43,374 children 7 days old to less than 22 years old receiving intensive care with available pharmacy data.

Interventions:

None.

Measurements and Main Results:

A total of 907,440 courses of 1,080 unique medications were prescribed with a median of nine medications (range, 1–99; 25–75th percentile, 5–16) per patient. The most common medications were acetaminophen, ondansetron, and morphine. Only 45 medications (4.2%) were prescribed to more than 5% of patients, and these accounted for 442,067 (48.7%) of the total courses of medications. Each additional medication was associated with increased univariate risk of mortality (odds ratio, 1.05; 95% CI, 1.05–1.06; p < 0.001).

Conclusions:

Children receiving intensive care receive a median of nine medications per patient and one quarter are prescribed at least than 16 medications. Only 45 medications were prescribed to more than 5% of patients, but these accounted for almost half of all medication courses.
Underlying Mechanisms of Psychological Interventions in Magnetic Resonance Imaging and Image-Guided Radiology Procedures
Authors: Chadderdon Alexandra L. , Carns Danielle R. , Pudalov Lauren R. , McKernan Lindsey C. , Honce Justin M.
Published: June 2020

Positive patient care and healthcare facility outcomes are associated with using various psychological interventions during magnetic resonance imaging and interventional radiology procedures. Interventions such as hypnosis, relaxation, guided imagery, and empathic communication can improve anxiety, pain, and hemodynamic stability during procedures, as well as improve claustrophobia and anxiety during magnetic resonance imaging. Little is understood as to the potential underlying mechanisms of how these interventions operate and contribute to positive outcomes. Thus, this article seeks to address that question by integrating autonomic nervous system functioning, neuropsychological concepts, and common factors theory of psychotherapy as potential underlying mechanisms. Opportunities for future directions in the field are also included.
Tissue Expander–Based Breast Reconstruction in the Prepectoral Versus Subpectoral Plane
Authors: Kraenzlin Franca , Darrach Halley , Khavanin Nima , Kokosis George , Aliu Oluseyi , Broderick Kristen , Rosson Gedge D. , Manahan Michele A. , Sacks Justin M.
Published: June 2020

Background

Breast reconstruction is becoming an increasingly important and accessible component of breast cancer care. We hypothesize that prepectoral patients benefit from lower short-term complications and shorter periods to second-stage reconstruction compared with individuals receiving reconstruction in the subpectoral plane.

Methods

An institutional review board–approved retrospective review of all adult postmastectomy patients receiving tissue expanders (TEs) was completed for a 21-month period (n = 286).

Results

A total of 286 patients underwent mastectomy followed by TE placement, with 59.1% receiving prepectoral TEs and 40.9% receiving subpectoral TEs. Participants receiving prepectoral TEs required fewer clinic visits before definitive reconstruction (6.4 vs 8.8, P <0.01) and underwent definitive reconstruction 71.6 days earlier than individuals with subpectoral TE placement (170.8 vs 242.4 days, P < 0.01). Anesthesia time was significantly less for prepectoral TE placement, whether bilateral (68.0 less minutes, P < 0.01) or unilateral (20.7 minutes less, P < 0.01). Operating room charges were higher in the prepectoral subgroup ($31,276.8 vs $22,231.8, P < 0.01). Partial necrosis rates were higher in the prepectoral group (21.7% vs 10.9%, P < 0.01).

Conclusions

Patients undergoing breast reconstruction using prepectoral TE-based reconstruction benefit from less anesthesia time, fewer postoprative clinic visits, and shorter time to definitive reconstruction, at the compromise of higher operating room charges.
A Free Tool for Breast Aesthetic Scale Computation
Authors: Monton Javier , Kenig Nitzan , Chang-Azancot Luis , Jordan Joaquin , Insausti Ricardo
Published: June 2020

Background

Our work describes the concept of Breast Aesthetic Scale (BAS) as a score for quick and simple objective assessment of results in cosmetic breast surgery. It is obtained by running a software program that we created, based on the previous concept of Objective Breast Cosmesis Scale (OBCS). This was previously described to be used in the context of conservative breast cancer treatment to objectively assess the degree of asymmetry. We describe the implementation of BAS algorithm and study its reproducibility in a set of images.

Methods

A new multiplatform software was developed by us and named Breast Aesthetic Scale Calculator (BAS-Calc), which can be executed on Windows Mac, and Linux. A set of 25 photographs were studied with this software twice by 2 different surgeons. Intrarater and interrater variability were studied, as well as concordance with categorization by another symmetry assessment software available called Breast Analyzing Tool®.

Results

Concordance among raters was excellent (intraclass correlation coefficient = 0.953; Lin concordance and correlation coefficient = 0.950), as well as intrarater (0.952 and 0.965). Categorization of both systems (Breast Analyzing Tool and BAS-Calc) showed almost perfect concordance (Cohen κ = 0.920).

Conclusions

Objective estimation of symmetry after breast surgery can be assessed with BAS-Calc. The “symmetric” and “asymmetric” categories are accurately discriminated by this free software, and it can be used by surgeons as a simple method for objective assessment of results in cosmetic breast surgery.
Fronto-Orbital Advance in a Patient With Roberts Syndrome
Authors: Alvarez Jaime Andres Jimenez , Chacon Leonardo Andres , Montealegre Jesus Andres Duque , Reyes José Manuel Valdés , Cataño Carlos Perez
Published: June 2020

Roberts Syndrome is an extremely rare syndrome reporting about 150 cases in the literature, with a very low survival rate. The authors present a case of a female patient with Roberts Syndrome who also had a coronal craniosynostosis. The aim of this case report is to present a case of a patient with Roberts Syndrome with a brachycephaly that required management of fronto-orbital advancement. In conclusion Roberts Syndrome is a rare disease, which can have different skeletal variations. This syndrome can manifest itself with craniosynostosis, with the requirement of a comprehensive management to correct it and avoid compression of the brain with endocranial hypertension.
Outcomes of Pneumatic Lithotripsy Versus Holmium Laser-Assisted Lithotripsy With Sialendoscopy in Management of Submandibular Sialolithiasis
Authors: Ozdemir Suleyman
Published: June 2020

Objective:

This study aimed to comparatively analyze the indications, treatment outcomes, and reliability levels of the intraductal pneumatic lithotripsy (IPL) and holmium laser-assisted lithotripsy (HLL) methods that are used to sialendoscopically separate stones into smaller pieces in submandibular gland sialolithiasis (SMGS) patients. To the best of the author's knowledge, there is no study that compared these 2 methods in the literature in English.

Methods:

The retrospectively designed study included 51 patients with SMGS. The IPL was used to break up 32 stones in 28 patients, while HLL was used to break up 28 stones in 23 patients.

Results:

The stones could be completely extracted in 95.6% of the patients in the HLL group, 92.8% of those in the IPL group and 94.1% of all patients. The complete and partial recovery rates of the patients were respectively 91.3% and 8.7% in the HLL group and 92.8% and 7.2% in the IPL group. There was no significant difference based on the lithotripsy method that was used in the patients’ laterality of stones, location of stones, stone diameter, operation time, need of papillotomy and silicone stent, complete removal status of stones and the symptomatic assessments of the patients in the 6th postoperative month.

Conclusion:

This study showed that both HLL and IPL treatments are effective, minimally invasive, and promising methods in difficult/complex SMGS treatments which may provide success rates of higher than 90% when they are performed by an experienced surgeon and by selection of appropriate patients.
Assessment of the Optic Foramen Shape and Size in Human Fetuses
Authors: Beger Orhan
Published: June 2020

Objective:

This study was aimed to obtain data on the dimensions of the optic foramen in human fetuses for early childhood surgeries.

Methods:

Twenty-five formalin-fixed fetuses (16 boys and 9 girls) with average age 21.68 ± 3.12 gestational weeks (range, 16–28 weeks) in the inventory of Anatomy Department, Faculty of Medicine were included in the study. The surface area, width, and height of the optic foramen were bilaterally measured using a digital image analysis software.

Results:

The forms of the optic foramen were described as oval shaped (72%, 36 foramina) and round shaped (28%, 14 foramina). The surface area, width, and height of the optic foramen were found as 2.40 ± 1.02 mm2, 1.83 ± 0.59 mm, and 1.58 ± 0.36 mm, respectively. The measurements of the parameters related to the optic foramen were not statistically different in terms of sides and sexes (P > 0.05). Linear functions for the height, width and surface area of the optic foramen were calculated as: y = 0.711 + 0.040 × weeks, y = −0.019 + 0.086 × weeks, and y = −0.400 + 0.129 × weeks, respectively.

Conclusion:

The linear functions in this study can be used to estimate the dimensions of the optic foramen. The calculated regression equations, representing the growth dynamic of the optic foramen showed that the surface area, width, and height were increasing according to gestational ages between 16 and 28 weeks. Microanatomical knowledge related to the optic foramen may be beneficial for surgeons to avoid iatrogenic injury in infants and for anatomists to understand the development of the fetal skull base.
Branching Patterns of Mental Nerve in Newborns
Authors: Çorumlu Ufuk , Kopuz Cem , Aydar Yüksel
Published: June 2020

In classical textbooks of Anatomy, the mental nerve is considered to be the terminal or main branch of the inferior alveolar nerve, especially trifurcate with no designated names as soon as it emerges from the mental foramen. The textbooks define the innervation area of the mental nerve regionally without naming its terminal branches. Nomina Anatomica designates 3 terminal branches of mental nerve as “labial, gingival, and mental branch” but offers no description about their distribution on the mandible. In the present study, bilateral dissections were performed on the lower lip specimens of 20 newborns for 40 mental nerves to determine the branching types of mental nerve. Although anatomy textbooks indicate that mental nerve divides into 3 branches, the authors noted that mental nerve branched into 1, 2, or 3 branches at or right after its exit from the mental foramen. Branching patterns were typed in 13 different subclasses under 3 main groups (Form I-II-III). Moreover, the branching patterns that could not be included in one of these 3 main groups were defined as “Complex Form.” The most common type of branching that the authors observed was Form II, which had 2 terminal branches with an incidence of 41.9% (16 specimens). The next frequently encountered type was Form III, having 3 terminal branches, and it was detected in 32.0% of patients (12 specimens). The least common form was Form I, which had 1 terminal branch with a frequency of 15.8% (6 specimens). The unclassified group, Complex Form, was found 10.5% (4 specimens).
When Is a Critically Ill Cirrhotic Patient Too Sick to Transplant? Development of Consensus Criteria by a Multidisciplinary Panel of 35 International Experts
Authors: Weiss Emmanuel , Saner Fuat , Asrani Sumeet K. , Biancofiore Gianni , Blasi Annabel , Lerut Jan , Durand François , Fernandez Javier , Findlay James Y. , Fondevila Constantino , Francoz Claire , Gustot Thierry , Jaber Samir , Karvellas Constantine , Kronish Kate , Laleman Wim , Laterre Pierre François , Levesque Eric , Mandell M. Susan , Mc Phail Mark , Muiesan Paolo , Olson Jody C. , Olthoff Kim , Daniele Pinna Antonio , Reiberger Thomas , Reyntjens Koen , Saliba Faouzi , Scatton Olivier , Simpson Kenneth J. , Soubrane Olivier , Subramanian Ram M. , Tacke Frank , Tomescu Dana , Xia Victor , Wagener Gebhard , Paugam-Burtz Catherine
Published: June 2020

Background.

Critically ill cirrhotic patients are increasingly transplanted, but there is no consensus about futile liver transplantation (LT). Therefore, the decision to delay or deny LT is often extensively debated. These debates arise from different opinions of futility among transplant team members. This study aims to achieve a multinational and multidisciplinary consensus on the definition of futility in LT and to develop well-articulated criteria for not proceeding with LT due to futility.

Methods.

Thirty-five international experts from anesthesiology/intensive care, hepatology, and transplant surgery were surveyed using the Delphi method. More than 70% of similar answers to a question were necessary to define agreement.

Results.

The panel recommended patient and graft survival at 1 year after LT to define futility. Severe frailty and persistent fever or <72 hours of appropriate antimicrobial therapy in case of ongoing sepsis were considered reasons to delay LT. A simple assessment of the number of organs failing was considered the most appropriate way to decide whether LT should be delayed or denied, with respiratory, circulatory and metabolic failures having the most influence in this decision. The thresholds of severity of organ failures contraindicating LT for which a consensus was achieved were a Pao
2/FiO2 ratio<150 mm Hg, a norepinephrine dose >1 μg/kg per minute and a serum lactate level >9 mmol/L.

Conclusions.

Our expert panel provides a consensus on the definition of futile LT and on specific criteria for postponing or denying LT. A framework that may facilitate the decision if a patient is too sick for transplant is presented.
Halobacterium bonnevillei sp. nov., Halobaculum saliterrae sp. nov. and Halovenus carboxidivorans sp. nov., three novel carbon monoxide-oxidizing Halobacteria from saline crusts and soils
Authors: Myers Marisa R. , King G.M.
Published: June 2020

Three novel carbon monoxide-oxidizing Halobacteria were isolated from Bonneville Salt Flats (Utah, USA) salt crusts and nearby saline soils. Phylogenetic analysis of 16S rRNA gene sequences revealed that strains PCN9T, WSA2Tand WSH3Tbelong to the generaHalobacterium,HalobaculumandHalovenus, respectively. Strains PCN9T, WSA2Tand WSH3Tgrew optimally at 40 °C (PCN9T) or 50 °C (WSA2T, WSH3T). NaCl optima were 3 M (PCN9T, WSA2T) or 4 M NaCl (WSH3T). Carbon monoxide was oxidized by all isolates, each of which contained a molybdenum-dependent CO dehydrogenase. G+C contents for the three respective isolates were 66.75, 67.62, and 63.97 mol% as derived from genome analyses. The closest phylogenetic relatives for PCN9T, WSA2Tand WSH3TwereHalobacterium noricenseA1T,Halobaculum roseumD90TandHalovenus aranensisEB27Twith 98.71, 98.19 and 95.95 % 16S rRNA gene sequence similarities, respectively. Genome comparisons of PCN9TwithHalobacterium noricenseA1Tyielded an average nucleotide identity (ANI) of 82.0% and a digital DNA–DNA hybridization (dDDH) value of 25.7 %; comparisons of WSA2TwithHalobaculum roseumD90Tyielded ANI and dDDH values of 86.34 and 31.1 %, respectively. The ANI value for a comparison of WSH3TwithHalovenus aranensisEB27Twas 75.2 %. Physiological, biochemical, genetic and genomic characteristics of PCN9T, WSA2Tand WSH3Tdifferentiated them from their closest phylogenetic neighbours and indicated that they represent novel species for which the namesHalobaculum bonnevillei,Halobaculum saliterraeandHalovenus carboxidivoransare proposed, respectively. The type strains are PCN9T(=JCM 32472=LMG 31022=ATCC TSD-126), WSA2T(=JCM 32473=ATCC TSD-127) and WSH3T(=JCM 32474=ATCC TSD-128).
Hepatitis B virus X protein stimulates cell growth by downregulating p16 levels via PA28γ-mediated proteasomal degradation
Authors: Cha Sungkyung , Jang Kyung Lib
Published: June 2020

Proteasomal activator 28 gamma (PA28γ), an essential constituent of the 20S proteasome responsible for ubiquitin-independent degradation of target proteins, is frequently overexpressed in hepatocellular carcinoma. Recently, we have reported that hepatitis B virus (HBV) X protein (HBx) activates PA28γ expression in human hepatocytes via upregulation of p53 levels; however, its role in HBV tumorigenesis remains unknown. Here, we found that HBx-activated PA28γ downregulates p16 levels via ubiquitin-independent proteasomal degradation. As a result, HBx activated the Rb-E2F pathway and stimulated G1/S cell cycle progression, resulting in an increase in cell proliferation. The potential of HBx to induce these effects was reproduced in a 1.2-mer HBV replicon and in in vitro HBV infection systems and was almost completely abolished by either PA28γ knockdown or p16 overexpression, demonstrating the critical role of the PA28γ-mediated p16 degradation in HBV tumorigenesis.
COVID-19 Outpatient Screening: a Prediction Score for Adverse Events
Authors: Sun Haoqi , Jain Aayushee , Leone Michael J. , Alabsi Haitham S. , Brenner Laura , Ye Elissa , Ge Wendong , Shao Yu-Ping , Boutros Christine , Wang Ruopeng , Tesh Ryan , Magdamo Colin , Collens Sarah I. , Ganglberger Wolfgang , Bassett Ingrid V. , Meigs James B. , Kalpathy-Cramer Jayashree , Li Matthew D. , Chu Jacqueline , Dougan Michael L. , Stratton Lawrence , Rosand Jonathan , Fischl Bruce , Das Sudeshna , Mukerji Shibani , Robbins Gregory K. , Westover M. Brandon
Published: June 2020

Background

We sought to develop an automatable score to predict hospitalization, critical illness, or death in patients at risk for COVID-19 presenting for urgent care during the Massachusetts outbreak.

Methods

Single-center study of adult outpatients seen in respiratory illness clinics (RICs) or the emergency department (ED), including development (n = 9381, March 7-May 2) and prospective (n = 2205, May 3-14) cohorts. Data was queried from Partners Enterprise Data Warehouse. Outcomes were hospitalization, critical illness or death within 7 days. We developed the COVID-19 Acuity Score (CoVA) using automatically extracted data from the electronic medical record and learning-to-rank ordinal logistic regression modeling. Calibration was assessed using predicted-to-observed ratio (E/O). Discrimination was assessed by C-statistics (AUC).

Results

In the development cohort, 27.3%, 7.2%, and 1.1% of patients experienced hospitalization, critical illness, or death, respectively; and in the prospective cohort, 26.1%, 6.3%, and 0.5%. CoVA showed excellent performance in the development cohort (concurrent validation) for hospitalization (E/O: 1.00, AUC: 0.80); for critical illness (E/O: 1.00, AUC: 0.82); and for death (E/O: 1.00, AUC: 0.87). Performance in the prospective cohort (prospective validation) was similar for hospitalization (E/O: 1.01, AUC: 0.76); for critical illness (E/O 1.03, AUC: 0.79); and for death (E/O: 1.63, AUC=0.93). Among 30 predictors, the top five were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate.

Conclusions

CoVA is a prospectively validated automatable score to assessing risk for adverse outcomes related to COVID-19 infection in the outpatient setting.
Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infections
Authors: Thair Simone A. , He Yudong D. , Hasin-Brumshtein Yehudit , Sakaram Suraj , Pandya Rushika , Toh Jiaying , Rawling David , Remmel Melissa , Coyle Sabrina , Dalekos George N. , Koutsodimitropoulos Ioannis , Vlachogianni Glykeria , Gkeka Eleni , Karakike Eleni , Damoraki Georgia , Antonakos Nikolaos , Khatri Purvesh , Giamarellos-Bourboulis Evangelos J , Sweeney Timothy E
Published: June 2020

COVID-19 is a pandemic that shares certain clinical characteristics with other acute viral infections. Here, we studied the whole-blood transcriptomic host response to SARS-CoV-2 and compared it with other viral infections to understand similarities and differences in host response. Using RNAseq we profiled peripheral blood from 24 healthy controls and 62 prospectively enrolled patients with community-acquired lower respiratory tract infection by SARS-Cov-2 within the first 24 hours of hospital admission. We also compiled and curated 23 independent studies that profiled 1,855 blood samples from patients with one of six viruses (influenza, RSV, HRV, ebola, Dengue, and SARS-CoV-1). We show gene expression changes in peripheral blood in patients with COVID-19 versus healthy controls are highly correlated with changes in response to other viral infections (r=0.74, p<0.001). However, two genes, ACO1 and ATL3, show significantly opposite changes between conditions. Pathway analysis in patients with COVID-19 or other viral infections versus healthy controls identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection, and cytokine production for over-expressed genes. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and T cell activation. When comparing transcriptome profiles of patients with COVID-19 directly with those with other viral infections, we found 114 and 302 genes were over- or under-expressed, respectively, during COVID-19. Pathways analysis did not identify any significant pathways in these genes, suggesting novel responses to further study. Statistical deconvolution using immunoStates found that M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells, and total B cells showed change consistently in the same direction across all viral infections including COVID-19. Those that increased in COVID-19 but decreased in non-COVID-19 viral infections were CD56bright NK cells, M2 macrophages, and total NK cells. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of COVID-19 versus other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2.
Management strategies and prediction of COVID-19 by a fractional order generalized SEIR model
Authors: Guo Lihong , Zhao Yanting , Chen YangQuan
Published: June 2020

In this project, we study a class of fractional order generalized SEIR epidemic models. Based on the public data from Jan. 22th to May 15th, 2020, we reliably estimate key epidemic parameters and make predictions on the peak point and possible ending time for the target region. We analyze the current management strategy and predict the future implementation of different management strategies. Numerical simulations which support our analysis are also given.
Are men who smoke at higher risk for a more severe case of COVID-19 than women who smoke? A Systematic Review
Authors: Rodgers Aoife , Indreberg Emilie Kruke , Alfallaj Lenah , Nadkarni Manasi , Kabir Zubair
Published: June 2020

Background

The novelty of the Covid-19 pandemic is reflected in the lack of literature available for the impact of smoking on the intensity of the COVID-19 clinical manifestations. Our study tries to address this gap.

Method

Six cohorts from China were analysed and a crude odds ratio was manually calculated.

Results

Patients with a smoking history were approximately 2 times (95% CI= 1.036-1.883) as likely to suffer from severe clinical manifestations of COVID-19 compared to patients without a smoking history. A higher percentage of males suffer more severe symptoms of COVID-19 in comparison to females, but this could be associated with the gender specific smoking trends observed in China.

Conclusion

The gender specific smoking trends could be associated with the increased severity of COVID-19 disease manifestations in the male population.
A Computational Study for Identifying Agronomically Essential Biomarkers Using nsSNP Data of Korean Soybeans
Authors: Jung Yongwoon , You Nahyun , Nam Sangyong
Published: June 2020

Soybean is a highly nutritious legume grown globally as a food and feed crop. An examination of a collection of 10 cultivated and 6 wild Korean soybean varieties showed that there is phenotypic variability notable in different soybeans. Therefore, to develop a list of biomarker candidates useful for growing soybeans of better quality and quantity, The genes of 16 Korean soybean varieties were compared with those of the reference Glycine max var. Williams 82. The comparison was made through gene sequencing to facilitate selection of nsSNPs. The objective of the study was to find out the structural and functional variations caused by nsSNPs and discuss whether the collection of Korean soybean varieties qualifies as biomarkers based on their phenotypic traits.

Analysis of the data collected was done using four software: SIFT, Polyphen, PANTHER, and I-mutant 2.0, which are designed to detect the rate of functional and structural variations caused by the nsSNPs in cultivated and wild soybean varieties. Genotypic information obtained in the analysis was used to develop a core collection of biomarkers based on whether nsSNP content was found in more than half of the 16 samples. Therefore, the list of biomarker candidates developed from this study showed that Korean soybean could provide valuable information needed in both future crop genetic research and identification of biomarkers.
Anti-IL-6versusAnti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice: Potential Implications for Treating Cytokine Release Syndrome
Authors: Rubsamen Reid , Burkholz Scott , Massey Christopher , Brasel Trevor , Hodge Tom , Wang Lu , Herst Charles , Carback Richard , Harris Paul
Published: June 2020

Cytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus and coronavirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity and important for the host response to an acute viral infection. Clinical studies are now being conducted by various researchers to evaluate the possible role of IL-6 blockers to improve outcomes in critically ill patients with CRS. Most of these studies involve the use of anti-IL-6R monoclonal antibodies (α-IL-6R mAbs). We present data showing that direct neutralization of IL-6 with an α-IL-6 mAb in a BALB/c Ebolavirus (EBOV) challenge model produced a statistically significant improvement in outcome compared with controls when administered within the first 24 hours of challenge and repeated every 72 hours. A similar effect was seen in mice treated with the same dose of α-IL-6R mAb when the treatment was delayed 48 hrs post-challenge. These data suggest that direct neutralization of IL-6, early during the course of infection, may provide additional clinical benefits to IL-6 receptor blockade alone during treatment of patients with virus-induced CRS.
An Analysis of SARS-CoV-2 Using ViReport
Authors: Song Miranda , Moshiri Niema
Published: June 2020

The ongoing outbreak ofsevere acute respiratory syndrome coronavirus 2(SARS-CoV-2) has resulted in millions of cases and hundreds of thousands of deaths. Given the current lack of treatments or vaccines available, it may be useful to trace the evolu-tion and spread of the virus to better develop methods of preventative intervention. In this study, we analyzed over 4,000 full genome sequences of human SARS-CoV-2 using novel tool ViReport [13], an automated workflow for performing phylogenetic analyses on viral sequences and generating comprehensive molecular epidemiologi-cal reports. The complete ViReport output can be found athttps://github.com/mirandajsong/ViReport-SARS-CoV-2.
Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the “confined virus”?
Authors: Alouane Tarek , Laamarti Meriem , Essabbar Abdelomunim , Hakmi Mohammed , Bouricha EL Mehdi , Chemao-Elfihri M.W. , Kartti Souad , Boumajdi Nasma , Bendani Houda , Laamarti Rokia , Ghrifi Fatima , Allam Loubna , Aanniz Tarik , Ouadghiri Mouna , El Hafidi Naima , Jaoudi Rachid EL , Benrahma Houda , Elattar Jalil , Mentag Rachid , Sbabou Laila , Nejjari Chakib , Amzazi Saaid , Belyamani Lahcen , Ibrahimi Azeddine
Published: June 2020

The COVID-19 pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. Understanding and monitoring the genetic evolution of the virus, its geographical characteristics, and its stability are particularly important for controlling the spread of the disease and especially for the development of a universal vaccine covering all circulating strains. From this perspective, we analyzed 30,983 complete SARS-CoV-2 genomes from 79 countries located in the six continents and collected from December 24, 2019, to May 13, 2020, according to the GISAID database. Our analysis revealed the presence of 3,206 variant sites, with a uniform distribution of mutation types in different geographic areas. Remarkably, a low frequency of recurrent mutations has been observed; only 169 mutations (5.27%) had a prevalence greater than 1% of genomes. Nevertheless, fourteen non-synonymous hotspot mutations (> 10%) have been identified at different locations along the viral genome; eight in ORF1ab polyprotein (in nsp2, nsp3, transmembrane domain, RdRp, helicase, exonuclease, and endoribonuclease), three in nucleocapsid protein and one in each of three proteins: spike, ORF3a, and ORF8. Moreover, 36 non-synonymous mutations were identified in the RBD of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor. These results along with mutational frequency dissimilarity and intra-genomic divergence of SARS-CoV-2 could indicate that the SARS-CoV-2 is not yet adapted to its host. Unlike the influenza virus or HIV viruses, the low mutation rate of SARS-CoV-2 makes the development of an effective global vaccine very likely.
Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins
Authors: Singh Nilmani , Reyes-Ordoñez Adriana , Compagnone Michael A. , Moreno Castillo Jesus F. , Leslie Benjamin J. , Ha Taekjip , Chen Jie
Published: June 2020

Pleckstrin homology (PH) domains are presumed to bind phosphoinositides (PIPs), but specific interaction with and regulation by PIPs for most PH domain-containing proteins are unclear. Here we employed a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates. Of 67 human PH domaincontaining proteins examined, 36 (54%) were found to have affinity for PIPs with various specificity, the majority of which had not been reported before. Further investigation of ARHGEF3 revealed structural requirements and functional relevance of its newly discovered PI(4,5)P2binding. A recursive-learning algorithm based on the assay results of the 67 proteins was generated to analyze the sequences of 246 human PH domains, which predicted 48% of them to bind PIPs. A collection of the predicted PIP-binding proteins was assayed, with the vast majority found to bind PIPs. Collectively, our findings reveal unexpected lipid-binding specificity of PH domain-containing proteins.
Compartment-specific opioid receptor signaling is selectively modulated by Dynorphin subtypes
Authors: Kunselman Jennifer M. , Gupta Achla , Gomes Ivone , Devi Lakshmi A. , Puthenveedu Manoj A.
Published: June 2020

Many signal transduction systems have an apparent redundancy built into them, where multiple physiological agonists activate the same receptors. Whether this is true redundancy, or whether this provides as-yet unrecognized specificity in downstream signaling, is not well understood. We address this question using the kappa opioid receptor (KOR), a physiologically relevant G protein-coupled receptor (GPCR) that is activated by multiple members of the Dynorphin family of opioid peptides. We show that, although highly related Dynorphins bind and activate KOR to similar extents on the cell surface, they localize KOR to distinct subcellular compartments, dictate different post-endocytic fates of the receptor, and differentially induce KOR signaling from the degradative pathway. Our results show that seemingly redundant endogenous opioid peptides that are often co-released can in fact fine-tune signaling by differentially regulating the subcellular spatial profile of GPCR localization and signaling.
ASpli2: Integrative analysis of splicing landscapes through RNA-Seq assays
Authors: Mancini Estefania , Rabinovich Andres , Iserte Javier , Yanovsky Marcelo , Chernomoretz Ariel
Published: June 2020

Genome-wide analysis of alternative splicing has been a very active field of research since the early days of NGS (Next generation sequencing) technologies. Since then, ever-growing data availability and the development of increasingly sophisticated analysis methods have uncovered the complexity of the general splicing repertoire. However, independently of the considered quantification methodology, very often changes in variant concentration profiles can be hard to disentangle. In order to tackle this problem we present ASpli2, a computational suite implemented in R, that allows the identification of changes in both, annotated and novel alternative splicing events, and can deal with complex experimental designs.

Our analysis workflow relies on the analysis of differential usage of subgenic features in combination with a junction-based description of local splicing changes. Analyzing simulated and real data we found that the consolidation of these signals resulted in a robust proxy of the occurrence of splicing alterations. While junction-based signals allowed us to uncover annotated as well and non-annotated events, bin-associated signals notably increased recall capabilities at a very competitive performance in terms of precision.
Iron limitation by transferrin promotes simultaneous cheating of pyoverdine and exoprotease inPseudomonas aeruginosa
Authors: Tostado-Islas Oswaldo , Mendoza-Ortiz Alberto , Ramírez-García Gabriel , Cabrera-Takane Isamu Daniel , Loarca Daniel , Pérez-González Caleb , Jasso-Chavez Ricardo , Jiménez-Cortés J Guillermo , Hoshiko Yuki , Maeda Toshinari , Cazares Adrian , García-Contreras Rodolfo
Published: June 2020

Pseudomonas aeruginosais the main bacterial model to study cooperative behaviors, since it yields exoproducts such as exoproteases and siderophores that act as public goods and can be exploited by selfish non-producers that behave as social cheaters. Non-producers of the siderophore pyoverdine are typically isolated in media with low free iron, mainly casamino acids medium supplemented with transferrin. Nevertheless, using a protein as the iron chelator could additionally select mutants unable to produce exoproteases that degrade the transferrin to facilitate iron release. Here, we investigated the dynamics of pyoverdine and exoprotease production in media in which iron was limited by using either transferrin or a cation chelating resin. Our experiments show that concomitant loss of pyoverdine and exoprotease production readily develops in media with transferrin whereas only lack of pyoverdine emerges in medium treated with the resin. Genomic characterization of the exoprotease- and pyoverdine-less mutants revealed large deletions (13 to 33 Kb) including Quorum Sensing (lasR, rsal and lasl) and flagellar genes. Complementation experiments, PCR and motility tests confirmed the deletions. Our work shows that using transferrin as an iron chelator imposes simultaneous selective pressure for the loss of pyoverdine and exoprotease production. The unintended effect of transferrin observed in our experiment settings can help revisiting or informing the design of similar studies.
A general role for ventral white matter pathways in morphological processing: going beyond reading
Authors: Yablonski Maya , Menashe Benjamin , Ben-Shachar Michal
Published: June 2020

The ability to recognize the structural components of words, known as morphological processing, was recently associated with the bilateral ventral white matter pathways, across different writing systems. However, it remains unclear whether these associations are specific to the context of reading. To shed light on this question, in the current study we investigated whether the ventral pathways are associated with morphological processing in an oral word production task that does not involve reading. Forty-five participants completed a morpheme-based fluency task in Hebrew, as well as diffusion MRI (dMRI) scans. We used probabilistic tractography to segment the major ventral and dorsal white matter pathways, and assessed the correlations between their microstructural properties and performance on the morpheme-based fluency task. We found significant correlations between morpheme-based fluency and properties of the bilateral ventral tracts, suggesting that the involvement of these tracts in morphological processing extends beyond the reading modality. In addition, significant correlations were found in the frontal aslant tract (FAT), a dorsal tract associated with oral fluency and speech production. Together, our findings emphasize that neurocognitive associations reflect both the cognitive construct under investigation as well as the task used for its assessment. Lastly, to elucidate the biological factors underlying these correlations, we incorporated the composite hindered and restricted model of diffusion (CHARMED) framework, measured in independent scans. We found that only some of our findings could be attributed to variation in a CHARMED-based estimate of fiber density. Further, we were able to uncover additional correlations that could not be detected using traditional dMRI indices. In sum, our results show that the involvement of the ventral tracts in morphological processing extends to the production domain, and demonstrate the added value of including sensitive structural measurements in neurocognitive investigations.
Baseline survey of the fish and invertebrate fauna of Hill Inlet, the northernmost estuary in south-western Australia
Authors: Tweedley James R. , Sama Ayme , Poh Brian , Lonergan Neil R.
Published: June 2020

Microtidal estuaries in Mediterranean climates are particularly vulnerable to the effects of anthropogenic degradation. This study provides the first data on the fish and benthic macroinvertebrate fauna of Hill Inlet, the northernmost estuary in south-western Australia. Sampling was conducted in June 2019 (Austral winter), when water levels were very high due to recent heavy rainfall and the bar at the mouth of the estuary was intact. Surface salinities were oligohaline and declined along the longitudinal axis, ranging from 12 to 3. A marked halocline was present at most sites, resulting in pronounced hypoxia. High water levels precluded the use of a seine net at some sites to sample the nearshore fish fauna, however, two species were recorded (Pseudogobius olorumandAcanthopagrus butcheri), both of which complete their life-cycle within the estuary. Deeper, offshore waters, sampled using gill nets, yielded only four species (Mugil cephalus, A. butcheri, Adrichetta forsteriandPomatomus saltatrix), due to the bar at the mouth of the estuary being closed prior to sampling thus limiting recruitment from marine species. Ten benthic macroinvertebrates species were collected, representing mainly polychaetes, molluscs and crustaceans. The low number of species was likely caused by the hypoxia present throughout most of the bottom waters. Although these data represent a benchmark against which future changes can be detected, it is recommended that additional sampling is conducted when water levels are lower and the bar has been open to provide a more holistic assessment of the fauna of Hill Inlet.
Characterizing transcriptional regulatory sequences in coronaviruses and their role in recombination
Authors: Yang Yiyan , Yan Wei , Hall A. Brantley , Jiang Xiaofang
Published: June 2020

Novel coronaviruses, including SARS-CoV-2, SARS, and MERS, often originate from recombination events. The mechanism of recombination in RNA viruses is template switching. Coronavirus transcription also involves template switching at specific regions, called transcriptional regulatory sequences (TRS). It is hypothesized but not yet verified that TRS sites are prone to recombination events. Here, we developed a tool called SuPER to systematically identify TRS in coronavirus genomes and then investigated whether recombination is more common at TRS. We ran SuPER on 506 coronavirus genomes and identified 465 TRS-L and 3509 TRS-B. We found that the TRS-L core sequence (CS) and the secondary structure of the leader sequence are generally conserved within coronavirus genera but different between genera. By examining the location of recombination breakpoints with respect to TRS-B CS, we observed that recombination hotspots are more frequently co-located with TRS-B sites than expected.