bluuebunny/crossref_metadata_2025 huggingface dataset:
全谷物食品开发技术解决方案
Authors: Bin Tan , Nana Wu , Xiaotong Zhai
Published: June 2020

鉴于全谷物的健康益处，全球范围内一直在致力于增加其消费量，许多国家都在制定关于全谷物推荐摄入量的膳食指南。在中国，全谷 物的摄入不足，部分原因是由于全谷物食品开发的技术障碍。本文重 点介绍了在全产业链中潜在的全谷物食品开发解决方案，以及新食品 技术在全谷物食品开发中的应用，使全谷物具有优良口感、安全性、同 时尽可能保留其中的生物活性物质。
Too Few, Too Little: Parliaments’ Response to Sexism and Sexual Harassment
Authors: Verge Tània
Published: June 2020

Despite the increasingly reported incidence of sexual harassment among female elected representatives and staff members around the world, many more cases may not surface due to the power asymmetries, partisan logics and male organisational culture underpinning parliaments. No workplace is immune to sexual harassment, but when such misconducts occur in parliaments women’s right to fully and equally participate in political life is severely infringed. While international organisations have issued numerous resolutions calling parliaments to take action, this article shows that most legislative chambers in Europe and the Americas lag behind the adoption of adequate preventative measures, complaint mechanisms and reparation measures.
Comparing the accuracy of lay diagnosis of childhood malaria and pneumonia with that of the revised IMCI guidelines in Nigeria
Authors: Elimian K O , Myles P R , Phalkey R , Sadoh A , Pritchard C
Published: June 2020

Background

Improving caregivers’ recognition of childhood malaria and pneumonia is crucial to early treatment and improving outcomes. The objective of this study was to assess the accuracy and reliability of caregivers’ recognition of malaria and pneumonia (lay diagnosis) as compared to the revised IMCI guidelines.

Methods

A cross-sectional study design was used to recruit 903 children aged 2–59 months who were assessed for malaria and pneumonia by health workers at five primary healthcare centres in Benin City, Nigeria. Accuracy of lay diagnosis as compared to the revised IMCI guidelines was assessed using sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic curve (AUROC) values.

Results

The accuracy of caregivers’ ability to recognise malaria (AUROC: 0.60; 95% CI: 0.57–0.64) and pneumonia (AUROC: 0.54; 95% CI: 0.50–0.58) was, respectively, moderate and poor as compared to the IMCI guidelines. Caregivers were better able to identify children without than those with malaria and pneumonia. Agreement between caregivers and the IMCI guidelines for malaria and pneumonia diagnosis was poor (k = 0.14, 95% CI: 0.09–0.19; P = 0.0001).

Conclusion

Caregivers’ ability to recognise these childhood diseases as compared to the IMCI guidelines was poor overall, which was partly due to the approach used to ascertain lay diagnosis.
Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan
Authors: Sawano T , Kotera Y , Ozaki A , Murayama A , Tanimoto T , Sah R , Wang J
Published: June 2020

Background

Under the unique Japanese policy to restrict reverse transcriptase–polymerase chain reaction (RT-PCR) testing against severe acute respiratory syndrome coronavirus 2, a nationwide number of its confirmed cases and mortality remains to be low. Yet the information is lacking on geographical differences of these measures and their associated factors.

Aim

Evaluation of prefecture-based geographical differences and associated predictors for the incidence and number of RT-PCR tests for coronavirus disease 2019 (COVID-19).

Design

Cross-sectional study using regression and correlation analysis.

Methods

We retrieved domestic laboratory-confirmed cases, deaths and the number of RT-PCR testing for COVID-19 from 15 January to 6 April 2020 in 47 prefectures in Japan, using publicly available data by the Ministry of Health, Labour and Welfare. We did descriptive analyses of these three measures and identified significant predictors for the incidence and RT-PCR testing through multiple regression analyses and correlates with the number of deaths through correlation analysis.

Results

The median prefectural-level incidence and number of RT-PCR testing per 100 000 population were 1.14 and 38.6, respectively. Multiple regression analyses revealed that significant predictors for the incidence were prefectural-level population (P < 0.001) and the number of RT-PCR testing (P = 0.03); and those for RT-PCR testing were the incidence (P = 0.025), available beds (P = 0.045) and cluster infections (P = 0.034).

Conclusion

Considering bidirectional association between the incidence and RT-PCR testing, there may have been an underdiagnosed population for the infection. The restraint policy for RT-PCR testing should be revisited to meet the increasing demand under the COVID-19 epidemic.
Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma
Authors: Martini Giorgia , Saggioro Laura , Culpo Roberta , Vittadello Fabio , Meneghel Alessandra , Zulian Francesco
Published: June 2020

Objectives

To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma.

Methods

Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan–Meier analysis.

Results

MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy.

Conclusion

The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment.
Comparison of three different definitions of low disease activity in patients with systemic lupus erythematosus and their prognostic utilities
Authors: Kang Ji-Hyoun , Shin Min-Ho , Choi Sung-Eun , Xu Haimuzi , Park Dong-Jin , Lee Shin-Seok
Published: June 2020

Objectives

Three definitions of low-level disease activity in patients with SLE have been proposed by different groups. These include minimal disease activity (MDA), low disease activity (LDA) and the lupus low disease activity state (LLDAS). We investigated the performance of these definitions in SLE patients.

Methods

We recruited 299 SLE patients who were followed up annually for 4 consecutive years. We compared the three definitions of low disease activity via longitudinal analysis; we used a generalized, linear-mixed effects model and generalized estimating equations.

Results

The LLDAS was significantly associated with a lower SLICC/ACR damage index (β coefficient=−0.064, 95% CI: −0.129, −0.002, P=0.050), reduced flare (odds ratio = 0.090, 95% CI: 0.034, 0.239, P<0.001), an improved SF-36 physical component score (β coefficient=0.782, 95% CI: 0.046, 1.519, P=0.037), and an improved SF-36 mental component score (β coefficient=1.522, 95% CI: 0.496, 2.547, P=0.004). Neither the MDA nor the LDA were associated with these variables.

Conclusion

The LLDAS definition performs better than the MDA and LDA definitions, showing that LLDAS is associated with less organ damage and flare, and a better quality of life, during follow-up.
Quantifying the Core Deficit in Classical Schizophrenia
Authors: Rathnaiah Mohanbabu , Liddle Elizabeth B , Gascoyne Lauren , Kumar Jyothika , Zia Ul Haq Katshu Mohammad , Faruqi Catherine , Kelly Christina , Gill Malkeet , Robson Sian , Brookes Matt , Palaniyappan Lena , Morris Peter , Liddle Peter F
Published: June 2020

In the classical descriptions of schizophrenia, Kraepelin and Bleuler recognized disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganization, mental impoverishment, impaired cognition, and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from 3 commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit. Persisting brain disorders are associated with a reduction in post-movement beta rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score. While the symptoms constituting impoverished and disorganized mental activity are dissociable in schizophrenia, nonetheless, the variance that these 2 symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia.
Reorganizing a Medicine Residency Program in Response to the COVID-19 Pandemic in New York
Authors: Manson Daniel K. , Shen Sherry , Lavelle Michael P. , Lumish Heidi S. , Chong David H. , De Miguel Maria H. , Christianer Kaylan , Burnett Eric J. , Nickerson Katherine G. , Chandra Subani
Published: June 2020

The COVID-19 pandemic has been particularly severe in New York City, resulting in a rapid influx of patients into New York–Presbyterian Hospital/Columbia University Irving Medical Center. The challenges precipitated by this pandemic have required urgent changes to existing models of care. Internal medicine residents are at the forefront of caring for patients with COVID-19, including the critically ill. This article describes the exigent restructuring of the New York–Presbyterian Hospital/Columbia University Internal Medicine Residency Program. Patient care and educational models were fundamentally reconceptualized, which required a transition away from traditional hierarchical team structures and a significant expansion in the program’s capacity and flexibility to care for large numbers of patients with disproportionately high levels of critical illness. These changes were made while the residency program maintained the priorities of patient care and safety, resident safety and well-being, open communication, and education. The process of adapting the residency program to the demands of the pandemic was iterative given the unprecedented nature of this crisis. The goal of this article is to share the experiences and lessons learned from this crisis, communicate the solutions that were designed, and inform others who may be facing the prospect of creating similar disaster response measures.
Characteristics and Outcomes of 241 Births to Women With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers
Authors: Khoury Rasha , Bernstein Peter S. , Debolt Chelsea , Stone Joanne , Sutton Desmond M. , Simpson Lynn L. , Limaye Meghana A. , Roman Ashley S. , Fazzari Melissa , Penfield Christina A. , Ferrara Lauren , Lambert Calvin , Nathan Lisa , Wright Rodney , Bianco Angela , Wagner Brian , Goffman Dena , Gyamfi-Bannerman Cynthia , Schweizer William E. , Avila Karina , Khaksari Bijan , Proehl Meghan , Heitor Fabiano , Monro Johanna , Keefe David L. , D'Alton Mary E. , Brodman Michael , Makhija Sharmila K. , Dolan Siobhan M.
Published: June 2020

OBJECTIVE:

To describe the characteristics and birth outcomes of women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as community spread in New York City was detected in March 2020.

METHODS:

We performed a prospective cohort study of pregnant women with laboratory-confirmed SARS-CoV-2 infection who gave birth from March 13 to April 12, 2020, identified at five New York City medical centers. Demographic and clinical data from delivery hospitalization records were collected, and follow-up was completed on April 20, 2020.

RESULTS:

Among this cohort (241 women), using evolving criteria for testing, 61.4% of women were asymptomatic for coronavirus disease 2019 (COVID-19) at the time of admission. Throughout the delivery hospitalization, 26.5% of women met World Health Organization criteria for mild COVID-19, 26.1% for severe, and 5% for critical. Cesarean birth was the mode of delivery for 52.4% of women with severe and 91.7% with critical COVID-19. The singleton preterm birth rate was 14.6%. Admission to the intensive care unit was reported for 17 women (7.1%), and nine (3.7%) were intubated during their delivery hospitalization. There were no maternal deaths. Body mass index (BMI) 30 or higher was associated with COVID-19 severity (P=.001). Nearly all newborns tested negative for SARS-CoV-2 infection immediately after birth (97.5%).

CONCLUSION:

During the first month of the SARS-CoV-2 outbreak in New York City and with evolving testing criteria, most women with laboratory-confirmed infection admitted for delivery did not have symptoms of COVID-19. Almost one third of women who were asymptomatic on admission became symptomatic during their delivery hospitalization. Obesity was associated with COVID-19 severity. Disease severity was associated with higher rates of cesarean and preterm birth.
The Use of Nitinol Compression Staple Fixation and Bone Graft for Scaphoid Waist Fractures and Nonunion: A Surgical Technique
Authors: Congiusta Dominick V. , Basyuk Yaroslav , Vosbikian Michael M. , Ahmed Irfan H. , Kirschenbaum Abram
Published: June 2020

In the management of scaphoid fractures, nonunion is an important complication that can lead to carpal instability and early-onset arthritis. Various techniques have been described to treat scaphoid nonunions, yet a clear consensus on the superiority of one method is not yet established. The use of compression staple fixation has been described in the literature and may be a viable alternative to other fixation techniques. Volar Nitinol staple fixation avoids damage to the trapezium during retrograde fixation with a screw. It also avoids damage to the proximal dorsal cartilage, which occurs during anterograde screw fixation. Because of its shape and position on the volar aspect of the scaphoid, staple fixation provides compression, prevents graft extrusion, and avoids taking up space in the medullary canal of the scaphoid. Moreover, it may be technically easier than screw fixation. Despite these advantages, this technique has not been widely adopted. We describe the technique for utilizing Nitinol compression staples and bone grafting in the treatment of scaphoid nonunion.
Changes in kidney function during the menopausal transition: the Study of Women's Health Across the Nation (SWAN) – Michigan site
Authors: Kim Catherine , Saran Rajiv , Hood Michelle , Karvonen-Gutierrez Carrie , Peng Mia Q. , Randolph John F. , Harlow Siobán D.
Published: June 2020

Objective:

The aim of the study was to examine changes in kidney function during the menopausal transition (MT) and associations with levels of sex hormones (follicle stimulating hormone [FSH], sex hormone binding globulin [SHBG], estradiol, and testosterone).

Methods:

We used data from the Michigan site of Study of the Women's Health Across the Nation, a longitudinal study of the MT. For this analysis, we included women who had at least one creatinine measure before the final menstrual period (FMP) and at least one creatinine measure after the FMP (n = 101 women with 440 observations). To determine whether the declines in estimated glomerular filtration rate (eGFR) remained constant during the MT, we used local weighted regression curves to fit eGFR estimates. We examined the association between sex hormones and eGFR with longitudinal mixed models adjusting for baseline age, day of menstrual cycle, and time from FMP.

Results:

At baseline, women had a mean age of 45.4 ± 2.5 years; 54% were African-American and 46% were white. Although eGFR declined significantly over time, declines were linear, consistent with declines in eGFR due to age alone rather than the MT. Total testosterone, estradiol, ratio of testosterone:estradiol, and free androgen index were not significantly associated with eGFR, whereas lower FSH (−0.039, 95% confidence interval [CI] −0.067 to −0.012) and higher SHBG (0.050, 95% CI 0.004-0.096) were associated with higher eGFR.

Conclusions:

Kidney function declines during the MT. Although associated with levels of FSH and SHBG, the rate of decline in eGFR is consistent with what would be expected of age alone.
Complications of appendectomy and cholecystectomy in acute care surgery: A systematic review and meta-analysis
Authors: Al Busaidi Omar , Lee Seungwon , Kortbeek John B. , Turin Tanvir C. , Stelfox Henry T. , Austen Lea , Ball Chad G.
Published: June 2020

INTRODUCTION

Acute care surgery (ACS) was initiated two decades ago to address timeliness and quality in emergency general surgery. We hypothesized that ACS has improved the management of acute appendicitis and biliary disease.

METHODS

A comprehensive systematic review and meta-analysis of outcome studies for emergent appendectomy and cholecystectomy from 1966 to 2017, comparing studies prior to and following ACS implementation, were performed.

RESULTS

Of 1,704 studies, 27 were selected for analysis (appendicitis, 16; biliary pathology, 7; both, 4). Following ACS introduction, the complication rate was significantly reduced in both appendectomy and cholecystectomy (risk ratios, 0.70; 95% confidence interval [CI], 0.57–0.85;I2= 9.2% and relative risk, 0.62; 95% CI, 0.41–0.94;I2= 63.5%) respectively. There was a significant reduction in the time from arrival in emergency until admission and from admission to operation (−1.37 hours: 95% CI, −1.93 to −0.80; −2.51 hours: 95% CI, −4.44 to −0.58) in the appendectomy cohort. Time to operation was shorter in the cholecystectomy group (−6.46 hours; 95% CI, −9.54 to −3.4). Length of hospital stay was reduced in both groups (appendectomy, −0.9 day; cholecystectomy, −1.09 day). There was a reduction in overall cost in cholecystectomy group (−US $854.37; 95% CI, –1,554.1 to −154.05). No statistical significance was detected for wound infection, abscess, conversion of laparoscopy to open technique, rate of negative appendectomy, after hours, readmission, and cost.

CONCLUSION

The implementation of ACS models in general surgery emergency care has significantly improved system and patient outcomes for appendicitis and biliary pathology.

LEVEL OF EVIDENCE

Systematic review and meta-analysis of a retrospective study, level III.
Globally invasive populations of the clonal raider ant are derived from Bangladesh
Authors: Trible Waring , McKenzie Sean K. , Kronauer Daniel J. C.
Published: June 2020

Identifying the native range of invasive species is useful to understand their evolution and natural history, as well as to develop new methods to control potentially harmful introduced organisms. The clonal raider ant,Ooceraea biroi, is an introduced species and an increasingly important social insect model organism, but its native range remains unknown. Here, we report a new series ofO. biroicollections from Bangladesh, Singapore, Vietnam and China. We use a molecular phylogeny constructed with five gene fragments from 27 samples to determine that invasive lineages ofO. biroioriginated in Bangladesh. These lineages may have spread from Bangladesh via the historically significant Bay of Bengal shipping ports.Ooceraea biroishares multiple features of its biology with other introduced ants, including parthenogenesis, retention of heterozygosity and presence of multiple egg-layers in the colony. Using laboratory rearing and microsatellite markers, we show that colonies collected from disturbed habitat in Bangladesh have these traits in common with colonies from the invasive range. Ancestral populations with sexual reproduction in primary habitats either remain to be discovered or have gone extinct. Our findings advance our understanding of the global spread of the clonal raider ant and highlight a suite of general traits that make certain ants prone to becoming invasive.
Early Prediction of Alzheimer’s Disease and Related Dementias Using Electronic Health Records
Authors: Yang Xi , Li Qian , Wu Yonghui , Bian Jiang , Lyu Tianchen , Guo Yi , Marra David , Miller Amber , Shenkman Elizabeth , Maraganore Demetrius
Published: June 2020

Alzheimer’s disease (AD) and AD-related dementias (ADRD) are a class of neurodegenerative diseases affecting about 5.7 million Americans. There is no cure for AD/ADRD. Current interventions have modest effects and focus on attenuating cognitive impairment. Detection of patients at high risk of AD/ADRD is crucial for timely interventions to modify risk factors and primarily prevent cognitive decline and dementia, and thus to enhance the quality of life and reduce health care costs. This study seeks to investigate both knowledge-driven (where domain experts identify useful features) and data-driven (where machine learning models select useful features among all available data elements) approaches for AD/ADRD early prediction using real-world electronic health records (EHR) data from the University of Florida (UF) Health system. We identified a cohort of 59,799 patients and examined four widely used machine learning algorithms following a standard case-control study. We also examined the early prediction of AD/ADRD using patient information 0-years, 1-year, 3-years, and 5-years before the disease onset date. The experimental results showed that models based on the Gradient Boosting Trees (GBT) achieved the best performance for the data-driven approach and the Random Forests (RF) achieved the best performance for the knowledge-driven approach. Among all models, GBT using a data-driven approach achieved the best area under the curve (AUC) score of 0.7976, 0.7192, 0.6985, and 0.6798 for 0, 1, 3, 5-years prediction, respectively. We also examined the top features identified by the machine learning models and compared them with the knowledge-driven features identified by domain experts. Our study demonstrated the feasibility of using electronic health records for the early prediction of AD/ADRD and discovered potential challenges for future investigations.
Random time transformation analysis of Covid19 2020
Authors: Alon Nitay , Meilijson Isaac
Published: June 2020

The SIR epidemiological equations model new affected and removed cases as roughly proportional to the current number of infected cases. The present report adopts an alternative that has been considered in the literature, in which the number of new affected cases is proportional to the α ≤ 1 power of the number of infected cases. After arguing that α = 1 models exponential growth while α < 1 models polynomial growth, a simple method for parameter estimation in differential equations subject to noise, the random-time transformation RTT of Bassan, Meilijson, Marcus and Talpaz 1997, will be reviewed and compared with stochastic differential equations. Both methods are applied in an attempt to uncover the growth pattern of Covid19.
A population-based study of the prevalence of COVID-19 infection in Espírito Santo, Brazil: methodology and results of the first stage
Authors: Gomes Cristiana Costa , Cerutti Crispim , Zandonade Eliana , Noia Maciel Ethel Leonor , de Alencar Filomena Euridice Carvalho , Almada Gilton Luiz , Cardoso Orlei Amaral , Jabor Pablo Medeiros , Zanotti Raphael Lubiana , Reuter Tania Queiroz , de Andrade Vera Lucia Gomes , Bastos Whisllay Maciel , de Medeiros Nésio Fernandes
Published: June 2020

BACKGROUND

COVID-19 is affecting almost the entire world, causing more than four hundred thousand deaths and undermining the health care systems, as much as the economy, of the afflicted countries. The strategies for prevention depend on largely lacking information, as infection prevalence and virus pathogenicity. This study aimed to determine the prevalence, the pathogenicity, and the speed of infection spreading in a large population in Brazil.

MATERIALS AND METHODS

This is a serial cross-sectional study designed on a population basis and structured over houses as the sampling units. The sampling consisted of four visits at 15 days intervals in randomly selected census-designated sectors of the State major municipalities (reference municipalities) and two visits at 30 days intervals in smaller municipalities of the same regions of those of reference. At each visit, the investigators sampled houses and sampled one individual in each house for data collection. After the informed consent, the investigators performed a rapid antibody detection test (Celer Technology, Inc) and applied a questionnaire containing clinical and demographic questions.

RESULTS

From May 13th to 15th, the investigators performed 6,393 rapid tests in 4,612 individuals of the reference municipalities, 1,163 individuals of the smaller municipalities, and 166 contacts of the positive individuals. Ninety-seven dwellers were positive in the reference municipalities, giving a prevalence of 2.1% (CI 95%: 1.67-2.52%). In the smaller municipalities, the figure was 0.26% (CI 95%: 0.05%-0.75%) (three positives). There was an association of the positive result with female sex (p = 0.013) and houses with five dwellers or more (p = 0.003). Seventy-eight positive individuals reported symptoms in the previous 15 days (80.4%), being anosmia (45.4%), cough (40.2%), and myalgia (38.1%) the more frequent. About one-third of them reported fever (28.9%).

CONCLUSIONS

The results reveal a still small prevalence of infection in the study area, despite the significant number of sick people overloading the health system. The figures indicate an important underreporting in the area and a frequency that still can grow, making necessary public health actions for the containment of the transmission.
Modeling the dynamics of COVID19 spread during and after social distancing: interpreting prolonged infection plateaus
Authors: Komarova Natalia L. , Wodarz Dominik
Published: June 2020

Non-pharmaceutical intervention measures, such as social distancing, have so far been the only means to slow the spread of COVID19. In the United States, strict social distancing has resulted in different types infection dynamics. In some states, such as New York, extensive infection spread was followed by a pronounced decline of infection levels. In other states, such as California, less infection spread occurred before strict social distancing, and a different pattern was observed. Instead of a pronounced infection decline, a long-lasting plateau is evident, characterized by similar daily new infection levels. While these plateau dynamics cannot be readily reproduced with standard SIR infection models, we show that network models, in which individuals and their social contacts are explicitly tracked, can reproduce the plateau if network connections are cut due to social distancing measures. The reason is that in networks characterized by a 2D spatial structure, infection tends to spread quadratically with time, but as edges are randomly removed, the infection spreads along nearly one-dimensional infection “corridors”, resulting in plateau dynamics. Interestingly, the plateau dynamics are predicted to eventually transition into an infection decline phase without any further increase in social distancing measures. Additionally, the models suggest that a potential second wave becomes significantly less pronounced if social distancing is only relaxed once the dynamics have transitioned to the decline phase. The network models analyzed here allow us to interpret and reconcile different infection dynamics during social distancing observed in various US states.
Covid-19 in Chile. The experience of a Regional reference Center. Preliminary report
Authors: Olivares Felipe , Muñoz Daniel , Fica Alberto , Delama Ignacio , Alvarez Ignacia , Navarrete Maritza , Blackburn Eileen , Garrido Pamela , Grandjean Juan
Published: June 2020

During the first pandemic wave Covid-19 reached Latin America cities.

Aim

To report clinical features and outcomes associated to Covid-19 in a group of patients admitted during the first wave in a regional reference Center in southern Chile designated to severe and critical cases.

Methods

Cases were identified by a compatible clinical picture associated to positive RT-PCR or serological testing. A standard protocol was applied.

Results

21 adult patients (20 diagnosed by PCR, one by serology) were admitted between epidemiological weeks 13 to 20, involving 8.8% of total regional cases. Hospitalization occurred at a median of 11 days after symptoms onset. Patients ≥60 years old predominated (57.1%). Hypertension (61.9%), obesity (57.1%) and diabetes mellitus 2 (38.1%) were prevalent but 19% had no comorbid conditions nor were elderly. Two cases involved second-trimester pregnant women. Positive IgM or IgM/IgG results obtained by rapid serological testing were limited (19% at 1st week; 42.9% at 2nd week). Nine patients (42.9%, critical group) were transferred to ICU and connected to mechanical ventilation due to respiratory failure. By univariate analysis admission to ICU was significantly associated to tachypnea and higher plasmatic LDH values. One pregnant woman required urgent cesarean section given birth to a premature neonate without vertical transmission. Two patients died (in-hospital mortality 9.5%) and length of stay was ≥ 14 days in 57.9% of patients.

Conclusion

In our regional Center, Covid 19 was associated to known risk factors, had a prolonged stay and in-hospital mortality. Tachypnea ≥30/min is predictive of transfer to ICU.
Bacterial mobbing behavior: coordinated communal attack ofPseudomonas aeruginosaon a protozoan predator
Authors: Shteindel N. , Gerchman Y.
Published: June 2020

Mobbing, a group attack of prey on predator, is a strategy enacted by many animal species. Here we report bacterial mobbing carried out by the bacteriumPseudomonas aeruginosatowardsAcanthamoeba castellanii, a common bacterivore. This behavior consists of bacterial taxis towards the amoebae, adhesion en masse to amoebae cells, and eventual killing of the amoebae. Mobbing behavior transpires in second’s timescale and responds to predator population density. A mutant defective in the production of a specific quorum sensing signal displays reduced adhesion to amoeba cells. This deficiency ameliorated by external addition of the missing signal molecule. The same quorum sensing mutant also expresses long term deficiency in its ability to cause amoeba death and shows higher susceptibility to predation, highlighting the importance of group coordination to mobbing and predation avoidance. These findings portray bacterial mobbing as a regulated and dynamic group behavior.
Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera
Authors: Pape Constantin , Remme Roman , Wolny Adrian , Olberg Sylvia , Wolf Steffen , Cerrone Lorenzo , Cortese Mirko , Klaus Severina , Lucic Bojana , Ullrich Stephanie , Anders-Össwein Maria , Wolf Stefanie , Cerikan Berati , Neufeldt Christopher J. , Ganter Markus , Schnitzler Paul , Merle Uta , Lusic Marina , Boulant Steeve , Stanifer Megan , Bartenschlager Ralf , Hamprecht Fred A. , Kreshuk Anna , Tischer Christian , Kräusslich Hans-Georg , Müller Barbara , Laketa Vibor
Published: June 2020

Emergence of the novel pathogenic coronavirus SARS-CoV-2 and its rapid pandemic spread presents numerous questions and challenges that demand immediate attention. Among these is the urgent need for a better understanding of humoral immune response against the virus as a basis for developing public health strategies to control viral spread. For this, sensitive, specific and quantitative serological assays are required. Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in specific, sensitive and unbiased assay which complements the portfolio of SARS-CoV-2 serological assays. The procedure described here has been used for clinical studies and provides a general framework for the application of quantitative high-throughput microscopy to rapidly develop serological assays for emerging virus infections.
Metabolic but not transcriptional regulation by PKM2 is important for Natural Killer cell responses
Authors: Walls Jessica F. , Subleski Jeff J. , Palmieri Erika M. , Cotto Marieli Gonzalez , Gardiner Clair M. , McVicar Daniel W. , Finlay David K.
Published: June 2020

Natural Killer (NK) cells have an important role in immune responses to viruses and tumours. Integrating changes in signal transduction pathways and cellular metabolism is essential for effective NK cells responses. The PKM2 isoform of the glycolytic enzyme Pyruvate Kinase Muscle has described roles in regulating glycolytic flux and signal transduction, especially gene transcription. While PKM2 expression is robustly induced in activated NK cells, mice lacking PKM2 in NK cells showed no defect in NK cell metabolism or anti-viral responses to MCMV infection. This maintenance of function is explained by compensatory PKM1 expression in PKM2-null NK cell cells demonstrating that PKM2 is not a signalling molecule in this immune cell type. To further investigate the role of PKM2 we forced the tetramerization of the protein with TEPP-46, which increases its catalytic activity while inhibiting any signalling functions mediated by mono/dimeric conformations. NK cells activated with TEPP-46 had reduced effector function due to TEPP-46-induced increases in oxidative stress. Overall, PKM2-regulated glycolytic metabolism and redox status, not transcriptional control, facilitate optimal NK cells responses.
Interfacial Water Molecules Make RBD of SPIKE Protein and Human ACE2 to Stick Together
Authors: Malik Ashish , Prahlad Dwarakanath , Kulkarni Naveen , Kayal Abhijit
Published: June 2020

A novel coronavirus (SARS-CoV-2; COVID-19) that initially originates from Wuhan province in China has emerged as a global pandemic, an outbreak that started at the end of 2019 which claims 431,192 (Date: 15th June 2020 (https://covid19.who.in) life till now. Since then scientists all over the world are engaged in developing new vaccines, antibodies, or drug molecules to combat this new threat. Here in this work, we performed an in-silico analysis on the protein-protein interactions between the receptor-binding (RBD) domain of viral SPIKE protein and human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between these two viruses by using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations show SARS-CoV-2 binds little more firmly to the hACE2 receptor than that of SARS-CoV. Analysis of simulation trajectories reveals that enhanced hydrophobic contacts or the van der Waals interaction play a major role in stabilizing the protein-protein interface. The major finding obtained from molecular dynamics simulations is that the RBD-ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. We also emphasize that the interfacial water molecules play a critical role in binding and maintaining the stability of the RBD/hACE2 complex. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.
piRNAs prevent runaway amplification of siRNAs from ribosomal RNAs and histone mRNAs
Authors: Montgomery Brooke E. , Vijayasarathy Tarah , Marks Taylor N. , Reed Kailee J. , Montgomery Taiowa A.
Published: June 2020

Piwi-interacting RNAs (piRNAs) are a largely germline-specific class of small RNAs found in animals. Although piRNAs are best known for silencing transposons, they regulate many different biological processes. Here we identify a role for piRNAs in preventing runaway amplification of small interfering RNAs (siRNAs) from certain genes, including ribosomal RNAs (rRNAs) and histone mRNAs. InCaenorhabditis elegans, rRNAs and some histone mRNAs are heavily targeted by piRNAs, which facilitates their entry into an endogenous RNA interference (RNAi) pathway involving a class of siRNAs called 22G-RNAs. Under normal conditions, rRNAs and histone mRNAs produce relatively low levels of 22G-RNAs. But if piRNAs are lost, 22G-RNA production is highly elevated. We show that 22G-RNAs produced downstream of piRNAs likely function in a feed-forward amplification circuit. Thus, our results suggest that piRNAs facilitate low-level 22G-RNA production while simultaneously obstructing the 22G-RNA machinery to prevent runaway amplification from certain RNAs. Histone mRNAs and rRNAs are unique from other cellular RNAs in lacking polyA tails, which may promote feed-forward amplification of 22G-RNAs. In support of this, we show that the subset of histone mRNAs that contain polyA tails are largely resistant to silencing in piRNA mutants.
Dissecting Autism Genetic Risk Using Single-cell RNA-seq Data
Authors: Chen Siying , Zhou Xueya , Byington Eve , Bruce Samuel L. , Zhang Haicang , Shen Yufeng
Published: June 2020

Autism spectrum disorder (autism) is a condition with strong but heterogenous genetic contribution. Recent exome and genome sequencing studies have uncovered many new risk genes throughde novovariants. However, a large fraction of enrichment ofde novovariants observed in cases are not accounted for by known or candidate risk genes, suggesting that the majority of risk genes are still unknown. Here we hypothesize that autism risk genes share a few common cell-type specific gene expression patterns during brain development, and such information can be quantified to improve statistical power of detecting new risk genes. We obtained large-scale single-cell RNA-seq data from human fetal brain collected through a range of developmental stages, and developed a supervised machine-learning approach “A-risk” (Autism risk), to predict the plausibility of autism risk genes across the genome. Using data from recent exome sequencing studies of autism, A-risk achieves better performance in prioritizingde novovariants than other methods, especially for genes that are less intolerant of loss of function variants. We stratified genes based on A-risk and mutation intolerance metrics to improve estimation of priors in extTADA and identified 71 candidate risk genes. In particular,CLCN4, PRKAR1B, and NR2F1are potentially new risk genes with further support from neurodevelopmental disorders. Expression patterns of both known and candidate risk genes reveals the important role of deep-layer excitatory neurons from adult human cortex in autism etiology. With the unprecedented revolution of single-cell transcriptomics and expanding autism cohorts with exome or genome sequencing, our method will facilitate systematic discovery of novel risk genes and understanding of biological pathogenesis in autism.
A molecular lid mechanism of K+channel blocker action revealed by a cone peptide
Authors: Saikia Chandamita , Dym Orly , Altman-Gueta Hagit , Gordon Dalia , Reuveny Eitan , Karbat Izhar
Published: June 2020

Many venomous organisms carry in their arsenal short polypeptides that block K+channels in a highly selective manner. These toxins may compete with the permeating ions directly via a “plug” mechanism or indirectly via a “pore-collapse” mechanism. An alternative “lid” mechanism was proposed but remained poorly defined. Here we study the block of the Drosophila Shaker channel by Conknunitzin-S1 and Conkunitzin-C3, two highly similar toxins derived from cone venom. Despite their similarity, the two peptides exhibited differences in their binding poses and in biophysical assays, implying discrete modes of action. We show that while Conknunitzin-S1 binds tightly to the channel turret and acts via a “pore-collapse” mechanism, Conkunitzin-C3 does not contact this region. Instead, Conk-C3 uses a non-conserved Arg to divert the permeant ions and trap them in off-axis cryptic sites above the SF, a mechanism we term a “molecular-lid”. Our study provides an atomic description of the “lid” K+blocking mode and offers valuable insights for the design of therapeutics based on venom peptides.
The ribbon-helix-helix domain proteins CdrS and CdrL regulate cell division in archaea
Authors: Darnell Cynthia L. , Zheng Jenny , Wilson Sean , Bertoli Ryan M. , Bisson-Filho Alexandre W. , Garner Ethan C. , Schmid Amy K.
Published: June 2020

Precise control of the cell cycle is central to the physiology of all cells. In prior work we demonstrated that archaeal cells maintain a constant size; however, the regulatory mechanisms underlying the cell cycle remain unexplored in this domain of life. Here we use genetics, functional genomics, and quantitative imaging to identify and characterize the novel CdrSL gene regulatory network in a model species of archaea. We demonstrate the central role of these ribbon-helix-helix family transcription factors in the regulation of cell division through specific transcriptional control of the gene encoding FtsZ2, a putative tubulin homolog. Using time lapse fluorescence microscopy in live cells cultivated in microfluidics devices, we further demonstrate that FtsZ2 is required for cell division but not elongation. The cdrS-ftsZ2 locus is highly conserved throughout the archaeal domain, and the central function of CdrS in regulating cell division is conserved across hypersaline adapted archaea. We propose that the CdrSL-FtsZ2 transcriptional network coordinates cell division timing with cell growth in archaea.

Importance

Healthy cell growth and division are critical for individual organism survival and species long-term viability. However, it remains unknown how cells of the domain Archaea maintain a healthy cell cycle. Understanding archaeal cell cycle is of paramount evolutionary importance given that an archaeal cell was the host of the endosymbiotic event that gave rise to eukaryotes. Here we identify and characterize novel molecular players needed for regulating cell division in archaea. These molecules dictate the timing of cell septation, but are dispensable for growth between divisions. Timing is accomplished through transcriptional control of the cell division ring. Our results shed light on mechanisms underlying the archaeal cell cycle, which has thus far remained elusive.
Arabidopsis mTERF9 protein promotes chloroplast ribosomal assembly and translation by establishing ribonucleoprotein interactionsin vivo
Authors: Méteignier Louis-Valentin , Ghandour Rabea , Zimmerman Aude , Kuhn Lauriane , Meurer Jörg , Zoschke Reimo , Hammani Kamel
Published: June 2020

The mitochondrial transcription termination factor proteins are nuclear-encoded nucleic acid binders defined by degenerate tandem helical-repeats of ~30 amino acids. They are found in metazoans and plants where they localize to mitochondria or chloroplasts. In higher plants, the mTERF family comprises ~30 members and several of these have been linked to plant development and response to abiotic stress. However, knowledge of the molecular basis underlying these physiological effects is scarce. We show that the Arabidopsis mTERF9 protein promotes the accumulation of the16Sand23SrRNAs in chloroplasts, and interacts predominantly with the16SrRNAin vivoandin vitro. Furthermore, mTERF9 is found in large complexes containing ribosomes and polysomes in chloroplasts. The comprehensive analysis of mTERF9in vivoprotein interactome identified many subunits of the 70S ribosome whose assembly is compromised in the nullmterf9mutant, putative ribosome biogenesis factors and CPN60 chaperonins. Protein interaction assays in yeast revealed that mTERF9 directly interact with these proteins. Our data demonstrate that mTERF9 integrates protein-protein and protein-RNA interactions to promote chloroplast ribosomal assembly and translation. Besides extending our knowledge of mTERF functional repertoire in plants, these findings provide an important insight into the chloroplast ribosome biogenesis.
A helium mini-cryostat for the nanoprobe beamline ID16B at ESRF: characteristics and performance
Authors: Steinmann Ricardo G. , Martinez-Criado Gema , Salomon Damien , Vitoux Hugo , Tucoulou Remi , Villanova Julie , Laboure Sylvain , Eymery Joel , Segura-Ruiz Jaime
Published: June 2020

A helium mini-cryostat has been developed for the hard X-ray nanoprobe ID16B of the European Synchrotron to collect X-ray excited optical luminescence and X-ray fluorescence at low temperature (<10 K). The mini-cryostat has been specifically designed to fit within the strong space restrictions and high-demanding mechanical constraints imposed by the beamline to provide vibration-free operation and maximal thermal stability. This paper reports the detailed design, architecture and technical requirements of the mini-cryostat, and presents the first experimental data measured using the cryogenic equipment. The resulting cryo-system features ultimate thermal stability, fast cool-down and ultra-low vibrations. The simultaneous X-ray fluorescence and X-ray excited optical luminescence data acquired from bulk GaN and core/shell InGaN/GaN multi-quantum wells validated the excellent performance of the cryostat with ultimate resolution, stability and sensitivity.
(E)-3-{4,6-Dimethoxy-2-[(E)-4-methoxystyryl]-3-methylphenyl}-1-(2-hydroxy-5-methoxyphenyl)prop-2-en-1-one
Authors: Yoo Miri , Koh Dongsoo
Published: June 2020

In the title compound, C28H28O6, the benzene rings in the resveratrol moiety are connected by a trans C=C double bond, and the hydroxyl group containing a benzene ring and the central benzene ring are linked through a C=(O)—C=C (enone) moiety to form a chalcone unit. An intramolecular O—H...O hydrogen bond generates an S(6) ring motif. In the crystal, pairs of C—H...O hydrogen bonds generate dimers and additional weak C—H...O interactions link the dimers into chains propagating along the b-axis direction.