bluuebunny/crossref_metadata_2025 huggingface dataset:
POTENTIAL ENVIRONMENTAL HAZARD TO THE PUBLIC FROM THE OPERATION OF URANIUM MINING AND MILLING FACILITY
Authors: Rweyemamu Mujuni , Kim Juyoul
Published: November 2020

Mining and milling processes could cause potential radiological exposures to the public. The objective of this study was to estimate the off-site radiological doses expected to be received by the public as a result of uranium mining and milling activities at Mkuju River Project in the United Republic of Tanzania. MILDOS-AREA was used to estimate off-site doses along with RESRAD-OFFSITE for comparison and verification. Since the mining has not yet started, the conceptual scenario was chosen. Using the concept of the most exposed individual, the location of the nearest residence (receptor) was chosen at 2.5 km from the site with other receptors being the fence boundary and grazing area being at 1.0 and 1.8 km, respectively. Yellowcake stack (point source), ore pad and two tailing piles where each had an area of 2.5 × 105 m2 were chosen to be the source of radiological contamination. The radiological source term was obtained from the concentration of 226Ra and 232Th in soil obtained from the previous studies of environmental impact assessments. Meteorological and site-specific data were used for this analysis. The estimated total effective dose equivalent (TEDE) for the nearest residence which was calculated by MILDOSE-AREA ranged from 2.5 × 10−2 to 4.45 × 10−2 mSv/y during the operation of 13 y. The result of RESRAD-OFFSITE ranged from 7.19 × 10−2 mSv/y for the first year to 7.43 × 10−2 mSv/y in the final year. This implied all the estimated TEDEs were below the dose limit and dose constraint of 1 and 0.3 mSv/y, respectively, as suggested by the International Atomic Energy Agency. Hence, it was found that there was no potential radiological concern of uranium mining at Mkuju River Project. It was found that using MILDOS-AREA it is possible to estimate dose at different distances from the facility. Therefore, this study apart from estimating the off-site doses, it can be used for planning of public and social premises before the commencement of the project. That is the distance from the facility where the public should be located as well as other locations for social activities.
The energy requirements of racehorses in training
Authors: Ebert Mark , Moore-Colyer Meriel J S
Published: November 2020

The aim of this study was to estimate the energy requirements of Thoroughbred racehorses in active training for flat racing. Twenty-two Thoroughbred racehorses in England were measured over periods from 6 to 15 wk, which included periods of active race training and temporarily reduced training. Energy intake was determined by measuring daily feed consumption. Energy output was measured using heart rate monitors during 730 training sessions, relating heart rate (HR) to oxygen consumption (VO2) and converting VO2 to energy. Field maintenance requirements were calculated by deducting the marginal energy cost of training from energy input. The mean field maintenance expenditure during periods of active race training was 0.1731 megajoules (MJ) of metabolizable energy (ME)/kg of bodyweight (BW)/d (SD = 0.0174, CI = 0.0073, n = 22 horses, 193 wk). This result is 11% to 66% greater than the official guidance found in the United States, France, Germany, and the Netherlands. Heart rate monitoring revealed a mean energy expenditure for exercise of 0.0212 MJ ME/d (SD = 0.0049, CI = 0.0007, n = 22 horses) for racehorses in active race training, a result 70% to 82% below the official guidance. The total mean energy expenditure for racehorses in active race training was 0.1943 MJ ME/kg/d (SD = 0.0177, CI = 0.0078, n = 20 horses 193 wk), 4% to 22% less than the official guidance. Horses actively racing had a 12% higher maintenance requirement than those in training but not yet racing (P = 0.01). The 2- and 3-yr-old horses did not gain weight during active race training, but grew slowly during breaks in training. This study explores the factors affecting energy balance in racehorses, and provides updated findings for their maintenance and training requirements.
Genome-Wide Mapping of Loci for Adult-Plant Resistance to Stripe Rust in Durum Wheat Svevo Using the 90K SNP Array
Authors: Zhou Xinli , Zhong Xiao , Roter Jonatan , Li Xin , Yao Qiang , Yan Jiahui , Yang Suizhuang , Guo Qingyun , Distelfeld Assaf , Sela Hanan , Kang Zhensheng
Published: November 2020

Stripe rust is a foliar disease in wheat caused by Puccinia striiformis f. tritici. The best way to protect wheat from this disease is by growing resistant cultivars. Tetraploid wheat can serve as a good source of valuable genetic diversity for various traits. Here, we report the mapping of nine stripe rust resistance quantitative trait loci (QTL) effective against P. striiformis f. tritici in China and Israel. We used recombinant inbred lines (RILs) developed from a cross between the durum wheat cultivar Svevo and Triticum dicoccoides accession Zavitan. By genotyping the RIL population of 137 lines using the wheat 90K single-nucleotide polymorphism array, we mapped an adult-plant resistance locus QYrsv.swust-1BL.1, the most effective QTL, within a 0.75-centimorgan region in T. turgidum subsp. durum ‘Svevo’ on chromosome arm 1BL, corresponding to the region of 670.7 to 671.5 Mb on the Chinese Spring chromosome arm 1BL. Of the other eight minor-effect stripe rust QTL, seven were from Svevo and mapped on chromosomes 1A, 1B, 2B, 3A, 4A, and 5A, and one was from Zavitan and mapped on chromosome 2A. Several QTL with epistatic effects were identified as well. The markers linked to the resistance QTL can be useful in marker-assisted selection for incorporation of these resistance QTL into both durum and common wheat cultivars.
Genetics of Partial Resistance AgainstVerticillium dahliaeRace 2 in Wild and Cultivated Lettuce
Authors: Sandoya Germán V. , Truco Maria José , Bertier Lien D. , Subbarao Krishna V. , Simko Ivan , Hayes Ryan J. , Michelmore Richard W.
Published: November 2020

Lettuce (Lactuca sativa) is one of the most economically important vegetables in the United States, with approximately 50% of the domestic production concentrated in the Salinas Valley of California. Verticillium wilt, caused by races 1 and 2 of the fungal pathogen Verticillium dahliae, poses a major threat to lettuce production in this area. Although resistance governed by a single dominant gene against race 1 has previously been identified and is currently being incorporated into commercial cultivars, identification of resistance against race 2 has been challenging and no lines with complete resistance have been identified. In this study, we screened germplasm for resistance and investigated the genetics of partial resistance against race 2 using three mapping populations derived from crosses involving L. sativa × L. sativa and L. serriola × L. sativa. The inheritance of resistance in Lactuca species against race 2 is complex but a common quantitative trait locus (QTL) on linkage group 6, designated qVERT6.1 (quantitative Verticillium dahliae resistance on LG 6, first QTL), was detected in multiple populations. Additional race 2 resistance QTLs located in several linkage groups were detected in individual populations and environments. Because resistance in lettuce against race 2 is polygenic with a large genotype by environment interaction, breeding programs to incorporate these resistance genes should be aware of this complexity as they implement strategies to control race 2.
Clinical Significance of Immunohistochemical Expression of Neuropeptide Y1 Receptor in Patients With Breast Cancer in Egypt
Authors: Dawoud Marwa M. , Abdelaziz Khaled K.-E. , Alhanafy Alshimaa M. , Ali Manar S. E.-d. , Elkhouly Enas Ab. B.
Published: November 2020

Breast cancer (BC) is the most common malignancy in female individuals worldwide. It constitutes about 38.8% of all malignant tumors among Egyptian female individuals. Neuropeptide Y1 receptor (NPY1R) is one of the most abundant peptides in the central and peripheral nervous systems of mammals. It has been found to promote proliferation, vascularization, and stimulate migration in several cell types and tissues and some types of tumor. This the first immunohistochemical study to evaluate the expression of NPY1R in BC and its correlation with clinicopathologic parameters and patient survival. This study included 92 patients with BC. Immunohistochemical staining for NPY1R was done on paraffin-embedded formalin-fixed tissue sections. Statistically significant increases in NPY1R expression was seen in malignant (46/92; 50%) versus non-neoplastic tissue (12/29; 20.7%) (P<0.001). The receiver operating characteristic curve showed that NPY1R is a poor diagnostic test for BC (P<0.001, area under the curve=0.686) in breast tissue. Membranous was the most common pattern of positivity in carcinoma cases (24/46; 52.2%). Statistically significant associations were found between positive NPY1R expression and the presence of metastatic disease (P<0.001), clinical stage (P=0.0003), perineurial invasion (P=0.003), estrogen receptor expression (P=0.004), molecular subtype (P=0.015), Nottingham Prognostic Index risk group (P=0.04), radiotherapy treatment (P=0.01), hormonal treatment (P=0.015), and type of endocrine therapy (P=0.011). Although no significant association was detected between NPY1R-positive and NPY1R-negative cases regarding overall survival and progression-free survival, cases with non-nuclear (membranous+cytoplasmic) expression showed near significantly shorter survival (P=0.063). This study shows that NPY1R was identified in about 50% of malignant BC cases. Its expression correlates with some features of the aggressive disease being associated with metastasis, perineurial invasion, advanced stages, and poor Nottingham Prognostic Index. This suggests a potential prognostic role of NPY1R in BC. Non-nuclear expression of NPY1R seems to be more important in terms of prognosis of BC.
Asymptomatic bacteriuria and urinary tract infections in kidney transplant recipients
Authors: Coussement Julien , Kaminski Hannah , Scemla Anne , Manuel Oriol
Published: November 2020

Purpose of review

Urinary tract infection (UTI) is the most common infection in kidney transplant recipients (KTRs). Several elements increase the risk of UTI and/or modify its clinical presentation among KTRs (e.g. immunosuppressive therapy, kidney allograft denervation, and use of urinary catheters). Also, KTRs may have UTIs because of difficult-to-identify and/or difficult-to-treat organisms. We provide an overview of the current knowledge regarding bacterial UTIs in KTRs, with a focus on recent findings.

Recent findings

There is accumulating evidence from clinical trials that screening for and treating asymptomatic bacteriuria is not beneficial in most KTRs (i.e. those who are ≥1–2 months posttransplant and do not have a urinary catheter). These patients have a point-prevalence of asymptomatic bacteriuria of only 3% and treating asymptomatic bacteriuria probably does not improve their outcomes. There is no clinical trial evidence to guide the management of symptomatic UTI in KTRs. Several important clinical questions remain unanswered, especially regarding the management of posttransplant pyelonephritis and the prevention of UTI in KTRs.

Despite its frequency and associated morbidity, UTI after kidney transplantation is an understudied infection. In an era of increasing antimicrobial resistance and limited resources, further research is needed to ensure optimal use of antimicrobials in KTRs with UTI.
Inflammatory Myofibroblastic Tumor of the Liver Mimicking Metastasis on 18F-FDG PET/CT
Authors: Raad Roy A. , Haddad Laura , Jabbour Teddy , El-Rassi Ziad
Published: November 2020

A 62-year-old woman with history of stage III endometrial cancer was found to have a small enhancing liver lesion on follow-up abdominal CT and MRI, suspicious for metastasis. Subsequent 18F-FDG PET/CT was performed, demonstrating intense uptake within the liver lesion, consistent with metastasis. Subsequently, laparoscopic wedge liver lesion resection was performed. Histopathologic examination confirmed the diagnosis of inflammatory myofibroblastic tumor (IMT) with predominant inflammatory cells. Although solitary liver IMTs are rare occurrences with imaging features overlapping with malignancy, IMT should be considered in the differential diagnosis of suspicious liver lesions, especially when the pattern of spread is unusual.
FDG-Avid Pulmonary Nodules and Tracheobronchial Mural Inflammation in IgG4-Related Disease
Authors: Namireddy Meera K. , Consul Nikita , Sher Andrew C.
Published: November 2020

We report the case of a 9-year-old girl who presented with acute fevers, cough, and epistaxis with nasal swelling, and found to have a nasal mass. On 18F-FDG PET/CT, she was found to have marked nodal and pulmonary parenchymal disease with diffuse and symmetrical mural FDG uptake within the trachea and bronchial tree. The differential diagnosis was broad, and she was diagnosed with IgG4-RD (IgG4-related disease) and improved on appropriate treatment. To our knowledge, there are only 2 other pediatric cases of IgG4-related pulmonary disease in the literature, and our case serves as a unique constellation of intrapulmonary IgG4-RD imaging findings.
Intravenous Recombinant Tissue-Type Plasminogen Activator Thrombolysis for Acute Central Retinal Artery Occlusion
Authors: Wang Xiaotang , Liu Yong , Suo Yan , Qin Dan , Ren Meixia , Lei Runjia , Zhang Yanchun , Wang Ying
Published: November 2020

Introduction:

Central retinal artery occlusion (CRAO), an ocular stroke, causes severe and permanent visual impairment. Thrombolytic therapy is currently the main treatment option for CRAO. Intravenous thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) has been extensively applied in the treatment of CRAO with the proven advantages of effectiveness and safety. This meta-analysis aimed to assess the efficacy of intravenous rt-PA thrombolysis for the management of CRAO by evaluating the pooled evidence.

Methods:

A comprehensive literature search of electronic databases including PubMed, OVID, and Cochrane Library was conducted up to and including March 2019. All studies reporting visual outcomes after CRAO with thrombolytic therapy were collected. Data on visual acuity and adverse events were recorded and assessed in this analysis. Data were inputted into the statistical software of STATA. The studies were weighed by the inverse of the variance and merged in a random-effects model.

Results:

The systematic review process yielded 7 eligible studies including 121 patients with CRAO who received the intravenous rt-PA treatment. Sixty-two patients showed improvement in visual acuity (52.0%; 95% CI, 34.0%–70.0%) following rt-PA intravenous thrombolytic therapy. The observed improvement rate in the intravenous rt-PA treatment group was significantly higher than the conservative treatment group (40.4% vs. 13.0%; OR = 5.16; 95% CI, 1.90–14.05). The incidence rate of complications was relatively low (11 out of the 121 patients). Hemorrhage (9/11) was the major reported complication. Mortality was zero.

Discussion:

This meta-analysis indicated that intravenous rt-PA thrombolysis could be an effective and safe strategy for the management of CRAO. However, a more detailed large-scale clinical trial is warranted to strengthen the evidence-based therapeutic guidance.
Role of Von Willebrand Factor after Injury: It May Do More Than We Think
Authors: Zeineddin Ahmad , Dong Jing-Fei , Wu Feng , Terse Pranaya , Kozar Rosemary A.
Published: November 2020

Acute traumatic coagulopathy is a complex phenomenon following injury and a main contributor to hemorrhage. It remains a leading cause of preventable death in trauma patients. This phenomenon is initiated by systemic injury to the vascular endothelium that is exacerbated by hypoperfusion, acidosis, and hypothermia and leads to systemic activation of the coagulation cascades and resultant coagulopathy. Many previous studies have focused on endotheliopathy with targeted markers such as syndecan-1, soluble thrombomodulin, and plasma adrenaline as potential culprits for initiation and propagation of this state. However, in more recent studies, hyperadhesive von Willebrand factor (VWF), which is released following endothelial injury, and its cleaving metalloprotease ADAMTS13 have emerged as significant targets of the downstream effect of endothelial breakdown and coagulation dysregulation. Elucidation of the mechanism by which the dysregulated VWF-ADAMTS13 axis leads to endothelial dysfunction and coagulopathy after trauma can help identify new targets for therapy and sites for intervention. Much of what is known mechanistically regarding VWF stems from work done in traumatic brain injury. Following localized brain injury, brain-derived extracellular vesicles are released into circulation where they induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. VWF released from injured endothelial cells binds to these extracellular vesicles to enhance their activity in promoting coagulopathy and increasing endothelial permeability. However, there are numerous gaps in our knowledge of VWF following injury, providing a platform for further investigation.
Clinical Magnetoencephalography Practice in the United States Ten Years Later: A Survey-Based Reappraisal
Authors: Bagić Anto I. , Burgess Richard C.
Published: November 2020

Purpose:

Broader utilization of magnetoencephalography (MEG) and optimization of clinical practice remain strategic goals of the American Clinical Magnetoencephalography Society. Despite the implementation of the first MEG Clinical Practice Guidelines, clinical adoption has been less than expected, prompting a reassessment.

Methods:

Twenty-five clinical MEG centers were invited to participate anonymously in a survey of clinical practice.

Results:

Centers (N= 18) mostly operated within an academic medical center (10/18), were owned by the “hospital” (10/18), associated with a level 4 National Association of Epilepsy center (15/18), and directed by neurologists (10/18). A total of 873 (median 59) epilepsy studies, 1,179 evoked fields (of all types), and 1,607 (median 30) research MEG studies were reported. Fourteen of 17 centers serve children (median 35%), but only 5 of 14 sedate children for MEG. All (N= 14) centers record EEG simultaneous with MEG, and 57% used dipole source localization. The median reporting time for epilepsy studies was 12 and 10 days for presurgical mapping studies. Most (12/14) were favorable toward the Clinical Practice Guidelines and “formalized certification” but were against mandating the latter.

Conclusions:

A plateau in MEG volumes suggests that MEG has not become a part of the standard of care, and correspondingly, the Clinical Practice Guidelines appeared to have had little impact on clinical practice. The American Clinical Magnetoencephalography Society must continue to engage magnetoencephalographers, potential referrers, and vendors.
Effect of control measure on the development of new COVID-19 cases through SIR model simulation
Authors: L. Clara , Liu Fei
Published: November 2020

In December 2019, the outbreak of corona virus disease, also known as COVID-19, was first reported in Wuhan, China [1]. Within only one month, the disease quickly spread to the United States through the transmission of respiratory droplets released when an infected individual sneezes or coughs [2]. Throughout the course of 9 months, the US reported over 8 million cases and 204,000 deaths, affecting the daily lives of American citizens [3]. As trends in corona virus cases are changing daily, it’s important to monitor these trends and observe the causes for the increase and decrease in new cases. The trends in new corona virus cases in the US as well as New Jersey are simulated using a modified Susceptible-Infected-Recovered (SIR) model. The new case graphs from the simulations reflect the new case trends in both the US and New Jersey and can be used to understand the mechanism behind the rates of corona virus infection as well as predict future corona virus trends. Comparisons between the results of the simulations and observed data show the effectiveness of control measures such as quarantine, physical distancing, and wearing masks. The extended time period of control measures taken in New Jersey led to a gradual decline in new cases reported daily while the US new cases showed a second wave of growth after control measures were implemented to a lesser extent.
External validation of a claims-based model to predict left ventricular ejection fraction class in patients with heart failure
Authors: Mahesri Mufaddal , Chin Kristyn , Kumar Abheenava , Barve Aditya , Studer Rachel , Lahoz Raquel , Desai Rishi J.
Published: November 2020

BACKGROUND

Ejection fraction (EF) is an important prognostic factor in heart failure (HF), but administrative claims databases lack information on EF. We previously developed a model to predict EF class from Medicare claims. Here, we evaluated the performance of this model in an external validation sample of commercial insurance enrollees.

METHOD

Truven MarketScan claims linked to electronic medical records (EMR) data (IBM Explorys) containing EF measurements were used to identify a cohort of US patients with HF between 01-01-2012 and 10-31-2019. By applying the previously developed model, patients were classified into HF with reduced EF (HFrEF) or preserved EF (HFpEF). EF values recorded in EMR data were used to define gold-standard HFpEF (LVEF ≥45%) and HFrEF (LVEF<45%). Model performance was reported in terms of overall accuracy, positive predicted values (PPV), and sensitivity for HFrEF and HFpEF.

RESULTS

A total of 7,001 HF patients with an average age of 71 years were identified, 1,700 (24.3%) of whom had HFrEF. An overall accuracy of 0.81 (95% CI: 0.80-0.82) was seen in this external validation sample. For HFpEF, the model had sensitivity of 0.96 (95%CI, 0.95-0.97) and PPV of 0.81 (95% CI, 0.81-0.82); while for HFrEF, the sensitivity was 0.32 (95%CI, 0.30-0.34) and PPV was 0.73 (95%CI, 0.69-0.76). These results were consistent with what was previously published in US Medicare claims data.

CONCLUSIONS

The successful validation of the Medicare claims-based model provides evidence that this model may be used to identify patient subgroups with specific EF class in commercial claims databases as well.
A longitudinal comparison of spike and nucleocapsid SARS-CoV-2 antibody responses in a tertiary hospital’s laboratory workers with validation of DBS specimen analysis
Authors: Murrell I , Forde D , Tyson L , Chichester L , Garratt A , Vineall O , Palmer N , Jones R , Moore C
Published: November 2020

There is a requirement for easily accessible, high throughput serological testing as part of the SARS-CoV-2 pandemic response. Whilst of limited diagnostic use in an acute individual setting, its use on a population level is key to informing a coherent public health response. As experience of commercial assays increases, so too does knowledge of their precision and limitations. Here we present our experience of these systems thus far. We perform a spot sero-prevalence study amongst staff in a tertiary hospital’s clinical microbiology laboratory, before undertaking validation of DBS serological testing as an alternate specimen for analysis. Finally, we characterise the spike and nucleocapsid antibody response over 160 days post a positive PCR test in nine non-hospitalised staff members.

Amongst a cohort of 195 staff, 17 tested positive for SARS-CoV-2 antibodies (8.7%). Self-reporting of SARS-CoV2 infection (P=<0.0001) and testing of a household contact (P = 0.027) were significant variables amongst the positive and negative sub-groups. Testing of 28 matched serum and DBS samples demonstrated 96% accuracy between the sample types. A differential rate of decline of SARS-CoV-2 antibodies against nucleocapsid or spike protein was observed. At 4 months post a positive PCR test 7/9 (78%) individuals had detectable antibodies against spike protein, but only 2/9 (22%) had detectable antibodies against nucleocapsid protein. This study reveals a broad agreement amongst commercial platforms tested and suggests the use of DBS as an alternate specimen option to enable widespread population testing for SARS-CoV-2 antibodies. These results suggest potential limitations of these platforms in estimating historical infection. By setting this temporal point of reference for this cohort of non-patient facing laboratory staff, future exposure risks and mitigation strategies can be evaluated more fully.
Identification of metabolomics biomarkers for type 2 diabetes: triangulating evidence from longitudinal and Mendelian randomization analyses
Authors: Porcu Eleonora , Gilardi Federica , Darrous Liza , Yengo Loic , Bararpour Nasim , Gasser Marie , Vidal Pedro Marques , Froguel Philippe , Waeber Gerard , Thomas Aurelien , Kutalik Zoltán
Published: November 2020

The number of people affected by Type 2 Diabetes Mellitus (T2DM) is close to half a billion and is on a sharp rise, representing a major and growing public health burden. As the case for many other complex diseases, early diagnosis is key to prevent irreversible end-organ damages. However, given its mild initial symptoms, T2DM is often diagnosed several years after its onset, leaving half of diabetic individuals undiagnosed. While several classical clinical and genetic biomarkers have been identified, improving early diagnosis by exploring other kinds of omics data remains crucial. In this study, we have combined longitudinal data from two population-based cohorts CoLaus and DESIR (comprising in total 493 incident cases vs 1’360 controls) to identify new or confirm previously implicated metabolomic biomarkers predicting T2DM incidence more than five years ahead of clinical diagnosis. Our longitudinal data have shown robust evidence for valine, leucine, carnitine and glutamic acid being predictive of future conversion to T2DM, and also confirmed to be causal by 2-sample Mendelian randomisation (based on independent data). Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. These findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.
Quantification of occupational and community risk factors for SARS-CoV-2 seropositivity among healthcare workers in a large U.S. healthcare system
Authors: Baker Julia M. , Nelson Kristin N. , Overton Elizabeth , Lopman Benjamin A. , Lash Timothy L. , Photakis Mark , Jacob Jesse T. , Roback John , Fridkin Scott K. , Steinberg James P.
Published: November 2020

Background

Quantifying occupational risk factors for SARS-CoV-2 infection among healthcare workers can inform efforts to improve healthcare worker and patient safety and reduce transmission. This study aimed to quantify demographic, occupational, and community risk factors for SARS-CoV-2 seropositivity among healthcare workers in a large metropolitan healthcare system.

Methods

We analyzed data from a cross-sectional survey conducted from April through June of 2020 linking risk factors for occupational and community exposure to COVID-19 with SARS-CoV-2 seropositivity. A multivariable logistic regression model was fit to quantify risk factors for infection. Participants were employees and medical staff members who elected to participate in SARS-CoV-2 serology testing offered to all healthcare workers as part of a quality initiative, and who completed a survey on exposure to COVID-19 and use of personal protective equipment. Exposures of interest included known demographic risk factors for COVID-19, residential zip code incidence of COVID-19, occupational exposure to PCR test-positive healthcare workers or patients, and use of personal protective equipment. The primary outcome of interest was SARS-CoV-2 seropositivity.

Results

SARS-CoV-2 seropositivity was estimated to be 5.7% (95% CI: 5.2%-6.1%) among 10,275 healthcare workers. Community contact with a person known or suspected to have COVID-19 (aOR=1.9, 95% CI:1.4-2.5) and zip code level COVID-19 incidence (aOR: 1.4, 95% CI: 1.0-2.0) increased the odds of infection. Black individuals were at high risk (aOR=2.0, 95% CI:1.6-2.4). Overall, occupational risk factors accounted for 27% (95% CI: 25%-30%) of the risk among healthcare workers and included contact with a PCR test-positive healthcare worker (aOR=1.2, 95% CI:1.0-1.6).

Conclusions

Community risk factors, including contact with a COVID-19 positive individual and residential COVID-19 incidence, are more strongly associated with SARS-CoV-2 seropositivity among healthcare workers than exposure in the workplace.
COVID-19, a social disease in Paris: a socio-economic wide association study on hospitalized patients highlights low-income neighbourhood as a key determinant of severe COVID-19 incidence during the first wave of the epidemic
Authors: Jannot Anne-Sophie , Coutouris Hector , Burgun Anita , Katsahian Sandrine , Rance Bastien
Published: November 2020

Background

Studies have already shown that many environmental factors are associated with COVID-19 incidence. However, none have studied a very large set of socio-economic indicators and analysed to what extent these factors could highlight populations at high risk for COVID-19. We propose here a new approach, a socio-economic wide study, to pinpoint subgroups with a high incidence of COVID-19, and illustrated this approach using hospitalized cases in Paris area.

Methods

We extracted 303 socio-economic indicators from French census data for the 855 residential units in Paris and assessed their association with COVID-19 hospitalization risk. We then fitted a predictive model using a penalized regression on these indicators to predict the incidence of patient hospitalization for COVID-19 in Paris.

Findings

The most associated indicator was income, corresponding to the 3rd decile of the population (OR= 0.11, CI95% [0.05; 0.20]). A model including only income achieves a high performance in both the training set (AUC=0.78, CI95%: 0.72-0.85) and the test set (AUC=0.79 (CI95%: 0.71-0.87). Overall, the 45% most deprived areas gathered 86% of the areas with a high incidence of COVID-19 hospitalized cases.

Interpretation

During the first wave of the epidemic, income predicted Paris areas at risk for a high incidence of patients hospitalized for COVID-19 with a high performance. Socio-economic wide association studies, collecting passively data from hospitalized cases, therefore not necessitating any effort for health caregivers, is of particular interest in such a period of hospital overcrowding as it provides real-time indirect information on populations having high COVID-19 incidence.
Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection
Authors: Zuo J , Dowell A , Pearce H , Verma K , Long HM , Begum J , Aiano F , Amin-Chowdhury Z , Hallis B , Stapley L , Borrow R , Linley E , Ahmad S , Parker B , Horsley A , Amirthalingam G , Brown K , Ramsay ME , Ladhani S , Moss P
Published: November 2020

The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT and/or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.
Conditional distribution modeling as an alternative method for covariates simulation: comparison with joint multivariate normal and bootstrap techniques
Authors: Smania Giovanni , Jonsson E. Niclas
Published: November 2020

Clinical trial simulation (CTS) is a valuable tool in drug development. To obtain realistic scenarios, the subjects included in the CTS must be representative of the target population. Common ways of generating virtual subjects are based upon bootstrap (BS) procedures or multivariate normal distributions (MVND). Here, we investigated the performance of an alternative method based on conditional distributions (CD). Covariates data from a hypertension drug development program were used. The methods were evaluated based on the original dataset (internal evaluation) and on their ability to reproduce an older, unobserved population (extrapolation). Similar results were obtained in the internal evaluation for summary statistics, yet BS was able to preserve the correlation structure of the empirical distribution, which was not adequately reproduced by MVND; CD was in between BS and MVND. BS does not allow to extrapolate to an unobserved population. When the dataset used to inform the extrapolation was well approximated by a MVND, the results from CD and MVND were comparable. However, improved extrapolation performance was observed for CD when deviations from normality assumptions occurred. If CTS is used to simulate within the observed distribution, BS is the preferred method. When extrapolating to new populations, a parametric method like CD/MVND is needed. In case the empirical multivariate distribution is characterized by linearly related covariates and unimodal marginal distributions, MVND can be used because of the simpler statistical framework and well-established use; however, if uncertainty about the MVND assumptions exists, CD will increase the confidence in the simulations compared to MVND.
Bioassemblying Macro-Scale, Lumnized Airway Tubes of Defined Shape via Multi-Organoid Patterning and Fusion
Authors: Liu Ye , Dabrowska Catherine , Mavousian Antranik , Strauss Bernhard , Meng Fanlong , Mazzaglia Corrado , Ouaras Karim , Macintosh Callum , Terentjev Eugene , Lee Joo-Hyeon , Huang Yan Yan Shery
Published: November 2020

Epithelial, stem-cell derived organoids are ideal building blocks for tissue engineering, however, scalable and shape-controlled bioassembly of epithelial organoids into larger and anatomical structures has yet to be achieved. Here, a robust organoid engineering approach, Multi-Organoid Patterning and Fusion (MOrPF), is presented to assemble individual airway organoids of different sizes into upscaled, scaffold-free airway tubes with pre-defined shapes. Multi-Organoid Aggregates (MOAs) undergo accelerated fusion in a matrix-depleted, free-floating environment, possess a continuous lumen and maintain prescribed shapes without an exogenous scaffold interface. MOAs in the floating culture exhibit a well-defined three-stage process of inter-organoid surface integration, luminal material clearance and lumina connection. The observed shape stability of patterned MOAs is confirmed by theoretical modelling based on organoid morphology and the physical forces involved in organoid fusion. Immunofluorescent characterization shows that fused MOA tubes possess an unstratified epithelium consisting mainly of tracheal basal stem cells. By generating large, shape-controllable organ tubes, MOrPF enables upscaled organoid engineering towards integrated organoid-devices and structurally complex organ tubes.
Functional brain network topology across the menstrual cycle is sex hormone dependent and correlates with the individual well-being
Authors: Liparoti Marianna , Lopez Emahnuel Troisi , Sarno Laura , Rucco Rosaria , Minino Roberta , Pesoli Matteo , Perruolo Giuseppe , Formisano Pietro , Lucidi Fabio , Sorrentino Giuseppe , Sorrentino Pierpaolo
Published: November 2020

The menstrual cycle is known to influence the behaviour. The neuronal bases of this phenomenon are poorly understood. We hypothesized that hormones, might affect the large-scale organization of the brain functional networks and that, in turn, such changes might have behavioural correlates in terms of the affective state. To test our hypothesis, we took advantage of magnetoencephalography to investigate brain topology in early follicular, ovulatory and luteal phases, in twenty-four naturally-cycling women without signs of anxiety and/or depression. We show that in the alpha band the betweenness centrality (BC) of the right posterior cingulate gyrus (PCG) during the ovulatory phase is increased and the rise is predicted by the levels of estradiol. We also demonstrate that the increase in the BC is related to improved subjective well-being that, in turn, is correlated to the estradiol levels. The increased topological centrality of the PCG during the ovulatory phase could have implications in reproductive psychology.
Photocatalyst under visible light irradiation inactivates SARS-CoV-2 on an abiotic surface
Authors: Uema Masashi , Yonemitsu Kenzo , Momose Yoshika , Ishii Yoshikazu , Tateda Kazuhiro , Inoue Takao , Asakura Hiroshi
Published: November 2020

There is a worldwide attempt to develop prevention strategies against SARS-CoV-2 transmission. Here we examined the effectiveness of visible light-responsive photocatalyst RENECAT™ on the inactivation of SARS-CoV-2 under different temperatures and exposure durations. The viral activation on the photocatalyst-coated glass slides decreased from 5.93±0.38 logTCID50/ml to 3.05±0.25 logTCID50/ml after exposure to visible light irradiation for 6h at 20°C. On the other hand, lighting without the photocatalyst, or the photocatalyst-coat without lighting retained viral stability. Immunoblotting and electron microscopic analyses showed the reduced amounts of spike protein on the viral surface after the photocatalyst treatment. Our data suggest a possible implication of the photocatalyst on the decontamination of the SARS-CoV-2 in indoor environments, thereby preventing indirect viral spread.
Phage Peptides Mediate Precision Base Editing with Focused Targeting Window
Authors: Jia Kun , Cui Yan-ru , Huang Shisheng , Yu Peihong , Lian Zhengxing , Ma Peixiang , Liu Jia
Published: November 2020

Cytidine base editors (CBE) are novel genome engineering tools that can generate C-to-T nucleotide substitutions without introducing double-stranded breaks (DSBs). Instead of generating single-point mutations, CBEs induce nucleotide substitutions at wobble positions within the 20-nucleotide target site. A variety of strategies have been developed to improve the targeting scope and window of CBEs. Among these strategies, molecular switches that can temporally control CBE activities represent compelling options. In this study, we investigated the feasibility of using a bacteriophage-derived peptide, referred to as G8PPD, as the off-switch of CBEs. We showed that G8PPDcould be employed to control the activities of and improve the targeting window of A3A and BE3 CBEs and adenine base editor 7.10 (ABE7.10). Notably, in a cell-based disease model of Marfan syndrome, G8PPDfacilitated A3A CBE-based gene correction with a more focused targeting window and improved the percentage of perfectly edited gene alleles from less than 4% to more than 38% of the whole population. Our study presents the first peptide off-switch that can improve the targeting scope of CBEs, thus highlighting the importance of the temporal control of BE activity for precision base editing.
Follicular fluid metabolome and cytokinome profiles in poor ovarian responders and the impact of dehydroepiandrosterone supplementation
Authors: Viardot-Foucault Veronique , Zhou Jieliang , Bi Dexi , Takinami Yoshihiko , Tan Heng Hao , Chan Jerry.K.Y. , Lee Yie Hou
Published: November 2020

Poor ovarian responders (POR) are women undergoing in-vitro fertilization who respond poorly to ovarian stimulation, resulting in the retrieval of lower number of oocytes, and subsequently lower pregnancy rates. The follicular fluid (FF) provides a crucial microenvironment for the proper development of follicles and oocytes. Conversely, dysregulated FF metabolome and cytokinome could have detrimental effects on oocytes in POR. Androgens such as dehydroepiandrosterone (DHEA) have been proposed to alter the POR follicular microenvironment but its effects on the FF metabolome and cytokine profiles is unknown. In this study, untargeted LC-MS/MS metabolomics was performed on FF of POR patients with DHEA supplementation (DHEA+) and without (DHEA-) in a randomized clinical trial (N=52). Untargeted metabolomics identified 118 FF metabolites of diverse chemistries, which included lipids, steroids, amino acids, hormones, among others. FF metabolomes were different between DHEA+ and DHEA- groups. Specifically, glycerophosphocholine, linoleic acid, progesterone, and valine were significantly lower in DHEA+ relative to DHEA-. Among cytokines, MCP1, IFNγ, LIF and VEGF-D were significantly lower in DHEA+ relative to DHEA. Collectively, our data suggest a role of DHEA on these metabolic and cytokines pathways, and these FF metabolites could be used to guide future studies in DHEA supplementation regimen.
Demographic and psychological correlates of SARS-CoV-2 vaccination intentions in a sample of Canadian families
Authors: Lackner Christine L. , Wang Charles H.
Published: November 2020

The COVID-19 pandemic has been ongoing for close to a year, with second waves occurring presently and many viewing a vaccine as the most likely way to curb successive waves and promote herd immunity. Reaching herd immunity status likely necessitates that children, as well as their parents, receive a vaccine targeting SARS-CoV-2. In this exploratory study, we investigated the demographic, experiential, and psychological factors associated with the anticipated likelihood and speed of having children receive a SARS-CoV-2 vaccine in a sample of 455 Canadian families (857 children). Using linear mixed effects and proportional odds logistic regression models, we demonstrated that older parental age, living in the Prairies (relative to Central Canada), more complete child and parental vaccination history, more positive attitudes towards vaccines generally, higher psychological avoidance of the pandemic and a greater tendency to prioritize the risks of the disease relative to the risks of side effects (i.e., lower omission bias), were associated with higher likelihoods of intention to vaccinate participants’ children. In some models, subjective evaluations of proximal COVID-19 risk and higher levels of state anxiety were associated with increased likelihood of having children vaccinated. Faster speed of intended vaccination was predicted by a similar constellation of variables, with higher SES emerging as a trend-level predictor of vaccination speed. Results are discussed with respect to public health knowledge mobilization.
Localized Chemogenetic Silencing of Inhibitory Neurons: A novel Mouse Model of Focal Cortical Seizures
Authors: Goldenberg Adi Miriam , Schmidt Sarah , Mitelman Rea , Levy Dana Rubi , Katz Yonatan , Yizhar Ofer , Beck Heinz , Lampl Ilan
Published: November 2020

Focal cortical epilepsies are frequently refractory to available anticonvulsant drug therapies. One key factor contributing to this state is the limited availability of animal models that allow to reliably study focal cortical seizures and how they recruit surrounding brain areasin-vivo. In this study, we selectively expressed the inhibitory chemogenetic receptor, hM4D, in GABAergic neurons in focal cortical areas using viral gene transfer. Following focal silencing of GABAergic neurons by administration of Clozapine-N-Oxide (CNO), we demonstrated reliable induction of local epileptiform events in the electroencephalogram (EEG) signal of awake freely moving mice. Experiments in anesthetized mice showed consistent induction of focal seizures in two different brain regions – the barrel cortex (BC) and at the medial prefrontal cortex (mPFC). Seizures were accompanied by high frequency oscillations, a known characteristic of human focal seizures. Seizures propagated, but an analysis of seizure propagation revealed favored propagation pathways. CNO-induced epileptiform events propagated from the BC on one hemisphere to its counterpart and from the BC to the mPFC, but not vice-versa. Lastly, post-CNO epileptiform events in the BC could be triggered by sensory whisker-pad stimulation, indicating that this model, applied to sensory cortices, may be useful to study sensory-evoked seizures. Taken together, our results show that targeted chemogenetic inhibition of GABAergic neurons using hM4D can serve as a novel, versatile and reliable model of focal cortical epilepsy suitable to systematically study cortical ictogenesis in different cortical areas.

Significance Statement

Focal cortical epilepsies are often hard to alleviate using current anticonvulsant therapies while further drug discovery is impeded by the limited variety of suitable animal models. In this study, we established a novel model of focal cortical seizures induced by spatially-restricted chemogenetic silencing of cortical inhibitory neurons. We have shown this method to be effective at various cortical regions and reliably induce seizures that share key characteristics with known human epilepsy traits, including sensory triggering and seizure propagation. This model may thus be used to advance the discovery of new remedies for focal cortical epilepsies, as well as to improve our understanding of seizure spread along different cortical pathways.