bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of emergency medical system transport time on in route clinical decline in a rural system
Authors: Kai Taylor R. , Broady Marlene J. , Davenport Daniel L. , Bernard Andrew C. 
Published: April 2020

BACKGROUND
The emergency medical system (EMS) Field Triage Decision Scheme (FTDS) exists to direct certain injured patients to high-level care facilities. In rural states, this may require long transport durations, with uncertainty about the effects on clinical decline. We investigate adherence to the FTDS and the effect of transport duration on clinical decline in helicopter emergency medical system (HEMS) and ground emergency medical system (GEMS) transport in the Commonwealth of Kentucky.

METHODS
This institutional review board–approved study retrospectively analyzed deidentified data from the 2017 National EMS Information System for Kentucky. Patients were classified using step 1 FTDS criteria (respiratory rate [RR], <10 or >29 breaths per minute; systolic blood pressure (SBP), <90 mm Hg; or Glasgow Coma Scale [GCS] score, <14 points), by mode of transport (HEMS or GEMS), and by arrival at an appropriate center (levels I–III trauma center). Clinical decline was defined in both groups as an in route decrease in GCS of 2 points or greater, a SBP decrease of 1 SD or greater into or within the low range, an RR increase of 1 SD or greater into or within the high range, or an RR decrease of 1 SD or greater into or within the low range.

RESULTS
Almost half (46.3%) of step 1 patients were transported to an inappropriate center; the most common reason recorded was “closest facility” (57.8%). The percent of step 1 patients who declined in route increased with prehospital time in both HEMS and GEMS (p < 0.001). Overall, 12.2% of step 1 patients declined during transport, most commonly because of decreasing GCS (median change, −5 points; interquartile range, −3 to −9, in GCS declining patients). Helicopter EMS patients were more likely to meet step 1 criteria at the scene (29.9% vs. 5.8% GEMS, p < 0.001) and to decline (27.8% vs. 6.1% GEMS, p < 0.001).

CONCLUSION
This study demonstrates that, in a rural state, injured patients meeting FTDS step 1 criteria reach levels I to III trauma centers only about half the time. The FTDS step 1 criteria identified patients at higher risk of further prehospital clinical decline. Rather than decline after 1 hour, these data show that an increasing proportion of patients experience clinical decline throughout prehospital transport.

LEVEL OF EVIDENCE
Therapeutic, Level IV.
Use of multiple potency assays to evaluate human mesenchymal stromal cells
Authors: Christy Barbara A. , Herzig Maryanne C. , Delavan Christopher P. , Abaasah Isaac , Cantu Carolina , Salgado Christi , Lovelace Sarah , Garcia Laurynn , Jensen Katherine , Montgomery Robbie , Cap Andrew P. , Bynum James A. 
Published: April 2020

BACKGROUND
There is broad interest in the use of cell therapies and cell products for treatment of a variety of diseases and problems. Of interest to the military, cellular therapies have the potential to confer tremendous benefit for treatment of both acute and chronic injuries. Although many different cell therapy products are currently under investigation, mesenchymal stromal cells (MSCs) are good candidates, based on their ability to respond to inflammation, limit vascular permeability, and modulate immune responses to injury. Although a large number of clinical trials utilize MSCs or their products, there is no firm consensus defining the characteristics and activities of a good MSC product. Here, we test multiple human MSCs in several assays designed to test potency, to determine if functionally relevant differences between MSCs can be defined using in vitro assays, allowing identification of superior MSC products for preclinical or clinical testing.

METHODS
Human MSCs derived from several tissue sources (adipose, bone marrow, umbilical cord) were evaluated for their ability to respond to inflammatory signaling by upregulating indoleamine-2,3-dioxygenase and TSG6, suppress lymphocyte proliferation, alter the polarization of macrophages, and affect tube formation by endothelial cells.

RESULTS
All MSCs tested displayed activity in the functional assays utilized, but differences in potency were observed in each assay.

CONCLUSION
The indoleamine-2,3-dioxygenase enzyme activity assay represents a simple way to screen multiple samples. The mixed lymphocyte reaction and monocyte assays used to test interactions between MSCs and immune cells are more involved but give direct information on immunomodulation potential. The endothelial cell tube formation assay is relatively simple to perform but a large number of images must be generated and analyzed. However, it tests a functional activity other than immunomodulation and, therefore, adds another facet to MSC evaluation.
Effects of parity on the age at menopause and menopausal syndrome: a cross-sectional study in Northwest China
Authors: Sun Xiaoyan , Li Weiguo , Zhang Rui , Wang Lirong , Shen Xiping , Lu Yongbin , An Junxia , Wang Liyan , Wang Yiqing , Luo Xiaorong , Zhu Haiying , Zhang Xuehong 
Published: April 2020

AbstractObjectiveThis study evaluated the relationship between the number of births and the age at menopause and menopausal syndrome among Chinese women in Gansu.MethodsA cross-sectional study was conducted by a local university from March to November in 2016. A total of 7236 women aged 40–55 years met study eligibility criteria. The modified KMI was used to assess the menopausal syndrome. Cox regression was applied to estimate HR and 95% CI of the relationship between parity and age at menopause. Logistic regression was performed to calculate OR and CI of the effects of birth times on the menopausal syndrome.Outcome measureThe relationship between the parity and the age at menopause and menopausal syndrome in mid-life northwest Chinese women was analyzed.ResultsThe mean age at menopause was 47.91 ± 3.31 years. The relationships between parity and age at menopause were not significant by applying Cox regression (P = 0.488). Women with nulliparity and more births (3 and ≥4) seemed to have higher risks of moderate and severe menopausal syndrome. In addition, the potential beneficial effects of 1 or 2 births on menopausal syndrome were still observed by applying the multivariable logistic regression analysis, particularly in urogenital symptoms.ConclusionsNo obvious relationship was found between parity and age at menopause among Chinese women in Gansu. Women with nulliparity and more births appeared to be at the increased risk of menopause syndrome compared with women with 1 and 2 births. The underlying mechanisms were not assessed and deserved further investigation.Highlight. The mean age at menopause was lower among Chinese women in Gansu than developed countries and regions.. There is no obvious relationship between parity and age at menopause.. Women with nulliparity and more births (3 and ≥4) appeared to be at the increased risk of menopause syndrome, particularly in urogenital symptoms.
Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA
Authors: Hasan Mohammad Rubayet , Mirza Faheem , Al-Hail Hamad , Sundararaju Sathyavathi , Xaba Thabisile , Iqbal Muhammad , Alhussain Hashim , Yassine Hadi Mohamad , Lopez Andres Perez , Tang Patrick 
Published: April 2020

AbstractTo circumvent the limited availability of RNA extraction reagents, we aimed to develop a protocol for direct RT-qPCR to detect SARS-CoV-2 in nasopharyngeal swabs without RNA extraction. Nasopharyngeal specimens positive for SARS-CoV-2 and other coronaviruses collected in universal viral transport (UVT) medium were pre-processed by several commercial and laboratory-developed methods and tested by RT-qPCR assays without RNA extraction using different RT-qPCR master mixes. The results were compared to that of standard approach that involves RNA extraction. Incubation of specimens at 65°C for 10 minutes along with the use of TaqPath™ 1-Step RT-qPCR Master Mix provides higher analytical sensitivity for detection of SARS-CoV-2 RNA than many other conditions tested. The optimized direct RT-qPCR approach demonstrated a limit of detection of 6.6×103 copy/ml and high reproducibility (co-efficient of variation = 1.2%). In 132 nasopharyngeal specimens submitted for SARS-CoV-2 testing, the sensitivity, specificity and accuracy of our optimized approach were 95%, 99% and 98.5%, respectively, with reference to the standard approach. Also, the RT-qPCR CT values obtained by the two methods were positively correlated (Pearson correlation coefficient r=0.6971, p=0.0013). The rate of PCR inhibition by the direct approach was 8% compared to 9% by the standard approach. Our simple approach to detect SARS-CoV-2 RNA by direct RT-qPCR may help laboratories continue testing for the virus despite reagent shortages or expand their testing capacity in resource limited settings.
Analysis of the impact of lockdown on the reproduction number of the SARS-Cov-2 in Spain
Authors: Hyafil Alexandre , Moriña David 
Published: April 2020

AbstractObjectiveThe late 2019 Covid-19 disease outbreak has put the health systems of many countries to the limit of their capacity. The most affected European countries are, so far, Italy and Spain. In both countries (and others), the authorities decreed a lockdown, with local specificities. The objective of this work is to evaluate the impact of the measures undertaken in Spain to deal with the pandemic.MethodWe estimated the number of cases and the impact of lockdown on the reproducibility number based on the hospitalization reports up to April 15th 2020.ResultsThe estimated number of cases shows a sharp increase until the lockdown, followed by a slowing down and then a decrease after full quarantine was implemented. Differences in the basic reproduction ratio are also very significant, dropping from de 5.89 (95% CI: 5.46-7.09) before the lockdown to 0.48 (95% CI: 0.15-1.17) afterwards.ConclusionsHandling a pandemic like Covid-19 is very complex and requires quick decision making. The large differences found in the speed of propagation of the disease show us that being able to implement interventions at the earliest stage is crucial to minimise the impact of a potential infectious threat. Our work also stresses the importance of reliable up to date epidemiological data in order to accurately assess the impact of Public Health policies on viral outbreak.
Early Evidence and Predictors of Mental Distress of Adults One Month in the COVID-19 Epidemic in Brazil
Authors: Zhang Stephen Xu , Wang Yifei , Jahanshahi Asghar Afshar , Li Jizhen , Schmitt Valentina Gomes Haensel 
Published: April 2020

ABSTRACTObjectiveWe aim to provide early evidence of mental distress and its associated predictors among adults one month into the COVID-19 crisis in Brazil.MethodsWe conducted an online survey of 638 adults in Brazil on March 25–28, 2020, about one month (32 days) cross-sectionally after the first COVID-19 case in South America was confirmed in São Paulo. The 638 adults were in 25 states out of the 26 Brazilian states, with the only exception being Roraima, the least populated state in the Amazon. Of all the participating adults, 24%, 20%, and 18% of them were located in Rio de Janeiro state, Santa Catarina state, and São Paulo state respectively.ResultsIn Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less reported higher levels of distress. Each individual’s distance from the Brazilian epicenter of São Paulo interacted with age and workplace attendance to predict the level of distress. The “typhoon eye effect” was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey.ConclusionIdentifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis.
Ongoing outbreak of COVID-19 in Iran: challenges and signs of concern with under-reporting of prevalence and deaths
Authors: Ghafari Mahan , Hejazi Bardia , Karshenas Arman , Dascalu Stefan , Kadvidar Alireza , Khosravi Mohammad A. , Abbasalipour Maryam , Heydari Majid , Zeinali Sirous , Ferretti Luca , Ledda Alice , Katzourakis Aris 
Published: April 2020

AbstractMany countries with an early outbreak of SARS-CoV-2 struggled to gauge the size and start date of the epidemic mainly due to limited testing capacities and a large proportion of undetected asymptomatic and mild infections. Iran was among the first countries with a major outbreak outside China. Using all genomic sequences collected from patients with a travel link to Iran, we estimate that the epidemic started on 21/01/2020 (95% HPD: 05/12/2019 – 14/02/2020) with a doubling time of 3 days (95% HPD: 1.68 – 16.27). We also show, using air travel data from confirmed exported cases, that from late February to early March the number of active cases across the country were more than a hundred times higher than the reported cases at the time. A detailed province-level analysis of all-cause mortality shows 20,718 (CI 95%: 18,859 – 22,576) excess deaths during winter and spring 2020 compared to previous years, almost twice the number of reported COVID-19-related deaths at the time. Correcting for under-reporting of prevalence and deaths, we use an SEIR model to reconstruct the outbreak dynamics in Iran. Our model forecasted the second epidemic peak and suggests that by 14/07/2020 a total of 9M (CI 95%: 118K – 44M) have recovered from the disease across the country. These findings have profound implications for assessing the stage of the epidemic in Iran and shed light on the dynamics of SARS-CoV-2 transmissions in Iran and central Asia despite significant levels of under-reporting.One Sentence SummaryWe use epidemiological and genetic data to investigate the origins of the SARS-CoV-2 outbreak in Iran and assess the degree of under-reporting in prevalence and deaths.
Towards harmonizing subtyping methods for neuroimaging studies in Alzheimer’s disease
Authors: Mohanty Rosaleena , Mårtensson Gustav , Poulakis Konstantinos , Muehlboeck J-Sebastian , Rodriguez-Vieitez Elena , Chiotis Konstantinos , Grothe Michel J. , Nordberg Agneta , Ferreira Daniel , Westman Eric 
Published: April 2020

ABSTRACTBackgroundBiological subtypes in Alzheimer’s disease (AD), originally identified on neuropathological data, have been translated toin vivobiomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within AD. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context.MethodsWe compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive (Aβ+) AD dementia patients (reference group: 70 Aβ-healthy individuals; HC) using sMRI. Secondly, we extended and applied the subtyping methods to 53 Aβ+ prodromal AD and 30 Aβ+ AD dementia patients (reference group: 200 Aβ-HC) using both sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed.ResultsEach individual method was replicated and the proof-of-concept was established. All methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar maps of cortical thinning and tau PET uptake, at the group level. However, large disagreements were found at the individual level.ConclusionsAlthough characteristics of subtypes may be comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.
Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients
Authors: Hadjadj Jérôme , Yatim Nader , Barnabei Laura , Corneau Aurélien , Boussier Jeremy , Péré Hélène , Charbit Bruno , Bondet Vincent , Chenevier-Gobeaux Camille , Breillat Paul , Carlier Nicolas , Gauzit Rémy , Morbieu Caroline , Pène Frédéric , Marin Nathalie , Roche Nicolas , Szwebel Tali-Anne , Smith Nikaïa , Merkling Sarah H , Treluyer Jean-Marc , Verer David , Mouthon Luc , Blanc Catherine , Tharaux Pierre-Louis , Rozenberg Flore , Fischer Alain , Duffy Darragh , Rieux-Laucat Frédéric , Kernéis Solen , Terrier Benjamin 
Published: April 2020

AbstractBackgroundCoronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known.MethodsWe performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy.ResultsA unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFĸB. It was also characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines.ConclusionWe propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF-α in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.
COVID-19 Asymptomatic Infection Estimation
Authors: Yu Yang , Liu Yu-Ren , Luo Fan-Ming , Tu Wei-Wei , Zhan De-Chuan , Yu Guo , Zhou Zhi-Hua 
Published: April 2020

AbstractBackgroundMounting evidence suggests that there is an undetected pool of COVID-19 asymptomatic but infectious cases. Estimating the number of asymptomatic infections has been crucial to understand the virus and contain its spread, which is, however, hard to be accurately counted.MethodsWe propose an approach of machine learning based fine-grained simulator (ML-Sim), which integrates multiple practical factors including disease progress in the incubation period, cross-region population movement, undetected asymptomatic patients, and prevention and containment strength. The interactions among these factors are modeled by virtual transmission dynamics with several undetermined parameters, which are determined from epidemic data by machine learning techniques. When MLSim learns to match the real data closely, it also models the number of asymptomatic patients. MLSim is learned from the open Chinese global epidemic data.FindingsMLSim showed better forecast accuracy than the SEIR and LSTM-based prediction models. The MLSim learned from the data of China’s mainland reveals that there could have been 150,408 (142,178-157,417) asymptomatic and had self-healed patients, which is 65% (64% – 65%) of the inferred total infections including undetected ones. The numbers of asymptomatic but infectious patients on April 15, 2020, were inferred as, Italy: 41,387 (29,037 – 57,151), Germany: 21,118 (11,484 – 41,646), USA: 354,657 (277,641 – 495,128), France: 40,379 (10,807 – 186,878), and UK: 144,424 (127,215 – 171,930). To control the virus transmission, the containment measures taken by the government were crucial. The learned MLSim also reveals that if the date of containment measures in China’s mainland was postponed for 1, 3, 5, and 7 days later than Jan. 23, there would be 109,039 (129%), 183,930 (218%), 313,342 (371%), 537,555 (637%) confirmed cases on June 12.ConclusionsMachine learning based fine-grained simulators can better model the complex real-world disease transmission process, and thus can help decision-making of balanced containment measures. The simulator also revealed the potential great number of undetected asymptomatic infections, which poses a great risk to the virus containment.FundingNational Natural Science Foundation of China.
Reduced expression of COVID-19 host receptor,ACE2is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn’s disease
Authors: Potdar Alka A. , Dube Shishir , Naito Takeo , Botwin Gregory , Haritunians Talin , Li Dalin , Yang Shaohong , Bilsborough Janine , Denson Lee A. , Daly Mark , Targan Stephan R. , Fleshner Phillip , Braun Jonathan , Kugathasan Subra , Stappenbeck Thaddeus S. , McGovern Dermot P.B. 
Published: April 2020

AbstractAngiotensin-Converting Enzyme 2 (ACE2) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. Utilizing transcriptomic data from four cohorts taken from Crohn’s disease (CD) and non-inflammatory bowel disease (IBD) subjects, we observed evidence of increasedACE2mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI.ACE2was downregulated in CD compared to controls in independent cohorts. Within CD,ACE2expression was reduced in inflamed ileal tissue and also remarkably, from un-involved tissue in patients with a worse prognosis in both adult and pediatric cohorts. In active CD, small bowelACE2expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest thatACE2downregulation is associated with inflammation and worse outcomes in CD.
The Novel Coronavirus Disease (COVID-19): A PRISMA Systematic Review and Meta-analysis of Clinical and Paraclinical characteristics
Authors: Hasani Hamidreza , Mardi Shayan , Shakerian Sareh , Taherzadeh-Ghahfarokhi Nooshin , Mardi Parham 
Published: April 2020

AbstractAn outbreak of pneumonia, caused by a novel coronavirus (COVID-19) was Identified in China in Dec 2019. This virus expanded worldwide, causing global concern. Clinical, laboratory and imaging features of this infection are characterized in some observational studies. We undertook a systematic review and meta-analysis to assess the frequency of clinical, laboratory, and CT features in COVID-19 patients.We did a systematic review and meta-analysis using three databases to identify clinical, laboratory, and CT features of rRT-PCR confirmed cases of COVID-19. Data for 3420 patients from 30 observational studies were included.Overall, the results showed that fever (84.2%, 95%CI 82.6-85.7), cough (62%, 95%CI 60-64), and fatigue (39.4%, 95%CI 37.2-41.6%) were the most prevalent symptoms in COVID-19 patients. Increased CRP level, decreased lymphocyte count, and increased D-dimer level were the most common laboratory findings. Among COVID-19 patients, 92% had a positive CT finding, most prevalently GGO (60%, 95%CI 58-62) and peripheral distribution (64%, 95%CI 60-69).These results demonstrate the clinical, paraclinical, and imaging features of COIVD-19.