bluuebunny/crossref_metadata_2025_split huggingface dataset:
WELCOME-GP: A randomised controlled trial of the effectiveness of a targeted postal cancer awareness intervention for increasing attendance at general practice
Authors: Laake Jean-Pierre , Vulkan Daniel , Quaife Samantha L , Hamilton William T , Martins Tanimola , Waller Jo , Parmar Dharmishta , Sasieni Peter , Duffy Stephen W 
Published: June 2020

ABSTRACTObjectiveTo assess the effectiveness of a targeted postal promotion for improving cancer symptom awareness and increasing help-seeking in general practice, on subsequent general practitioner (GP) consultation rates in a population which has made infrequent use of consultations at their local practice.Setting23 general practices in England.DesignRandomised controlled trial comparing a mailed leaflet providing information on six key cancer symptoms plus a covering letter signed by their general practitioner designed to reduce barriers to primary care help-seeking (intervention arm), with usual care (control arm).Participants1,513 adults aged 50-84 years (783 individually randomised to the intervention arm and 730 individually randomised to the control arm) who had not consulted their GP in the last 12 months and had at least two other risk factors for late presentation with cancer, identified by practice staff between November 2016 and May 2017. 749 individuals in the intervention arm and 705 in the control arm were included in the intention to treat analyses.Outcome measureThe primary outcome was number of GP consultations in the six months subsequent to mailing of the intervention.ResultsThere was a significantly higher rate of consultation in the intervention arm: 436 consultations compared to 335 in the control arm (RR = 1.40, 95% CI 1.11-1.77, p=0.004). However, there was no difference in the numbers of persons consulting their GP, with 165 in each group.ConclusionsTargeted interventions of this nature can change behaviour. This intervention stimulated a greater number of consultations but not a greater number of patients consulting. There is a need to develop interventions which can be more effective on the broader less engaged population.Trial registrationThe trial was registered prospectively on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (ISRCTN95610478).FundingThis research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis, 106/0001. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Additional support, including NHS service support costs, were provided by the National Institute for Health Research Clinical Research Network (NIHR CRN) (UKCRN ID 31163).
Initial Whole Genome Sequencing and Analysis of the Host Genetic Contribution to COVID-19 Severity and Susceptibility
Authors: Wang Fang , Huang Shujia , Gao Rongsui , Zhou Yuwen , Lai Changxiang , Li Zhichao , Xian Wenjie , Qian Xiaobo , Li Zhiyu , Huang Yushan , Tang Qiyuan , Liu Panhong , Chen Ruikun , Liu Rong , Li Xuan , Tong Xin , Zhou Xuan , Bai Yong , Duan Gang , Zhang Tao , Xu Xun , Wang Jian , Yang Huanming , Liu Siyang , He Qing , Jin Xin , Liu Lei 
Published: June 2020

AbstractThe COVID-19 pandemic has accounted for more than five million infections and hundreds of thousand deaths worldwide in the past six months. The patients demonstrate a great diversity in clinical and laboratory manifestations and disease severity. Nonetheless, little is known about the host genetic contribution to the observed inter-individual phenotypic variability. Here, we report the first host genetic study in China by deeply sequencing and analyzing 332 COVID-19 patients categorized by varying levels of severity from the Shenzhen Third People’s Hospital. Upon a total of 22.2 million genetic variants, we conducted both single-variant and gene-based association tests among five severity groups including asymptomatic, mild, moderate, severe and critical ill patients after the correction of potential confounding factors. The most significant gene locus associated with severity is located in TMEM189-UBE2V1 involved in the IL-1 signaling pathway. The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population. We also identified that the HLA-A*11:01, B*51:01 and C*14:02 alleles significantly predispose the worst outcome of the patients. This initial study of Chinese patients provides a comprehensive view of the genetic difference among the COVID-19 patient groups and highlighted genes and variants that may help guide targeted efforts in containing the outbreak. Limitations and advantages of the study were also reviewed to guide future international efforts on elucidating the genetic architecture of host-pathogen interaction for COVID-19 and other infectious and complex diseases.
An Ensembled Deep Learning Model Outperforms Human Experts in Diagnosing Biliary Atresia from Sonographic Gallbladder Images
Authors: Zhou Wenying , Yang Yang , Yu Cheng , Liu Juxian , Duan Xingxing , Weng Zongjie , Chen Dan , Liang Qianhong , Qing Fang , Zhou Jiaojiao , Ju Hao , Luo Zhenhua , Guo Weihao , Ma Xiaoyan , Xie Xiaoyan , Wang Ruixuan , Zhou Luyao 
Published: June 2020

AbstractIt is still difficult to make accurate diagnosis of biliary atresia (BA) by sonographic gallbladder images particularly in rural area lacking relevant expertise. To provide an artificial intelligence solution to help diagnose BA based on sonographic gallbladder images, an ensembled deep learning model was developed based on a small set of sonographic images. The model yielded a patient-level sensitivity 93.1% and specificity 93.9% (with AUROC 0.956) on the multi-center external validation dataset, superior to that of human experts. With the help of the model, the performance of human experts with various levels would be improved further. Moreover, the diagnosis based on smartphone photos of sonographic gallbladder images through a smartphone app and based on video sequences by the model still yielded expert-level performance. Our study provides a deep learning solution to help radiologists improve BA diagnosis in various clinical application scenarios, particularly in rural and undeveloped regions with limited expertise.
TMPRSS2 variants and their susceptibility to COVID-19: focus in East Asian and European populations
Authors: dos Santos Ney Pereira Carneiro , Khayat André Salim , Gomes Rodrigues Juliana Carla , Pinto Pablo , de Araújo Gilderlanio Santana , Pastana Lucas Favacho , Medeiros Jéssyca Amanda Gomes , Fernandes Marianne Rodrigues , Ribeiro-dos-Santos Arthur , Meireles Khayat Bruna Claudia , Moreira Fabiano Cordeiro , Ribeiro-dos-Santos André Maurício , de Assumpção Paula Baraúna , Ribeiro-dos-Santos Ândrea , Assumpção Paulo Pimentel de , Santos Sidney 
Published: June 2020

AbstractThe manifestation of the COVID-19 varies from absence of symptoms to Severe Acute Respiratory Syndrome. The epidemiological data indicate that infection and mortality rates are greater in European populations in comparison with eastern Asians. To test if epidemiological patterns may be partly determined by human genetic variation, we investigated, by exomic and databank analyses, the variability found in the TMPRSS2 gene in populations from different continents, since this gene is fundamental to virus access into human cells. The functional variants revealed low diversity. The analyses of the variation in the modifiers of gene expression indicate that the European populations may have much higher levels of pulmonary expression of the TMPRSS2 gene and would be more vulnerable to infection by SARS-CoV-2. By contrast, the pulmonary expression of the TMPRSS2 may be reduced in the populations from East Asia, which implies that they are less susceptible to the virus infection and, these genetic features might also favor their better outcomes. The presented data, if confirmed, indicates a potential genetic contribution of TMPRSS2 to individual susceptibility to viral infection, and might also influence COVID-19 outcome.
Work-related and Personal Factors Associated with Mental Well-being during COVID-19 Response: A Survey of Health Care and Other Workers
Authors: Evanoff Bradley A. , Strickland Jaime R. , Dale Ann Marie , Hayibor Lisa , Page Emily , Duncan Jennifer G. , Kannampallil Thomas , Gray Diana L. 
Published: June 2020

ABSTRACTObjectiveMeasure the prevalence of stress, anxiety, depression, work-exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic, and describe work-related and personal factors associated with mental health and well-being.DesignObservational cohort study conducted between April 17 and May 1, 2020 using a web-based questionnaire.SettingMedical and main campuses of a university.ParticipantsAll faculty, staff, and post-doctoral fellows.ExposuresWork factors including supervisor support and exposure to high-risk clinical settings; personal factors including demographics and family/home stressors.Main Outcomes and MeasuresStress, anxiety, depression, work exhaustion, burnout, and decreased well-being.ResultsThere were 5550 respondents (overall response rate of 34.3%). 38% of faculty and 14% of staff (n=915) were providing clinical care, while 57% of faculty and 77% of staff were working from home. The prevalence of anxiety, depression, and work exhaustion were somewhat higher among clinicians than non-clinicians. Among all workers, anxiety, depression, and high work exhaustion were independently associated with community or clinical exposure to COVID-19 [Prevalence Ratios and 95% confidence intervals 1.37(1.09- 1.73), 1.28(1.03 - 1.59), and 1.24(1.13 - 1.36) respectively]. Poor family supportive behaviors by supervisors were also associated with these outcomes [1.40 (1.21 - 1.62), 1.69 (1.48 - 1.92), 1.54 (1.44 - 1.64)]. Age below 40 and a greater number of family/home stressors were also associated with poorer outcomes. Among the subset of clinicians, caring for patients with COVID-19 and work in high-risk clinical settings were additional risk factors.Conclusions and ImplicationsOur findings suggest that the pandemic has had negative effects on mental health and well-being among both clinical and non-clinical employees. Prevention of exposure to COVID-19 and increased supervisor support are modifiable risk factors that may protect mental health and well-being.
What does and does not correlate with COVID-19 death rates
Authors: Knittel Christopher R. , Ozaltun Bora 
Published: June 2020

AbstractWe correlate county-level COVID-19 death rates with key variables using both linear regression and negative binomial mixed models, although we focus on linear regression models. We include four sets of variables: socio-economic variables, county-level health variables, modes of commuting, and climate and pollution patterns. Our analysis studies daily death rates from April 4, 2020 to May 27, 2020. We estimate correlation patterns both across states, as well as within states. For both models, we find higher shares of African American residents in the county are correlated with higher death rates. However, when we restrict ourselves to correlation patterns within a given state, the statistical significance of the correlation of death rates with the share of African Americans, while remaining positive, wanes. We find similar results for the share of elderly in the county. We find that higher amounts of commuting via public transportation, relative to telecommuting, is correlated with higher death rates. The correlation between driving into work, relative to telecommuting, and death rates is also positive across both models, but statistically significant only when we look across states and counties. We also find that a higher share of people not working, and thus not commuting either because they are elderly, children or unemployed, is correlated with higher death rates. Counties with higher home values, higher summer temperatures, and lower winter temperatures have higher death rates. Contrary to past work, we do not find a correlation between pollution and death rates. Also importantly, we do not find that death rates are correlated with obesity rates, ICU beds per capita, or poverty rates. Finally, our model that looks within states yields estimates of how a given state’s death rate compares to other states after controlling for the variables included in our model; this may be interpreted as a measure of how states are doing relative to others. We find that death rates in the Northeast are substantially higher compared to other states, even when we control for the four sets of variables above. Death rates are also statistically significantly higher in Michigan, Louisiana, Iowa, Indiana, and Colorado. California’s death rate is the lowest across all states.It is important to understand that this research, and other observational analyses like it, only identify correlations: these relationships are not necessarily causal. However, these correlations may help policy makers identify variables that may potentially be causally related to COVID-19 death rates and adopt appropriate policies after understanding the causal relationship.
Association between use of aspirin use before hospital admission and sepsis outcomes: a population-based cohort study
Authors: Hsu Wan-Ting , Porta Lorenzo , Hsu Tzu-Chun , Chen Shyr-Chyr , Lee Chien-Chang 
Published: June 2020

ABSTRACTObjectivesAntiplatelet agents have been shown to reduce serum levels of inflammatory markers and may reduce sepsis mortality. A previous randomized clinical trial did not find that aspirin use after hospitalization, compared with placebo, improve acute respiratory distress syndrome within 7 days. We aimed to examine the association between preadmission use of aspirin and sepsis outcome.MethodsWe conducted a population-based cohort study based on the National Health Insurance Research Database of Taiwan. The association between aspirin use and 90-day mortality in sepsis patients was determined by Cox proportional hazard models, adjusting for either individual covariates or a propensity score. Restricted mean survival time (RMST) analysis was performed as a sensitivity analysis.ResultsOf 52,982 patients with sepsis, 12,776 received preadmission use of aspirin, while 39,081 did not receive any antiplatelets. Use of aspirin before sepsis admission was associated with a decreased risk of 90-day mortality (PS-adjusted HR: 0.89, 95% CI: 0.84-0.93). RMST analysis confirmed the beneficial effect of aspirin which was associated with a 2% increase in survival time (RMST ratio 1.02, 95% CI: 1.01-1.03), when compared to nonuse. On PS adjusted analysis, the odds ratios (OR) of respiratory failure with the preadmission use of aspirin was 0.98 (95% CI: 0.93-1.03), but we did not find any significant association between prior aspirin use and respiratory failure.ConclusionsOur study confirms that prehospital aspirin use was associated with a reduced 90-day mortality rate among sepsis patients, but we did not find any substantial association with respiratory or acute renal failure.
Child wasting and concurrent stunting in low- and middle-income countries
Authors: Mertens Andrew , Benjamin-Chung Jade , Colford John M , Hubbard Alan E , van der Laan Mark J , Coyle Jeremy , Sofrygin Oleg , Cai Wilson , Jilek Wendy , Rosete Sonali , Nguyen Anna , Pokpongkiat Nolan N , Djajadi Stephanie , Seth Anmol , Jung Esther , Chung Esther O , Malenica Ivana , Hejazi Nima , Li Haodong , Hafen Ryan , Subramoney Vishak , Häggström Jonas , Norman Thea , Christian Parul , Brown Kenneth H , Arnold Benjamin F. ,   members of the ki Child Growth Consortium
Published: June 2020

SummarySustainable Development Goal 2.2, to end malnutrition by 2030, includes elimination of child wasting, defined as weight-for-length more than 2 standard deviations below international standards. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery, and persistence — key features that inform preventive interventions and disease burden estimates. We analyzed 21 longitudinal cohorts to show wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. By age 24 months 29.2% of children had experienced at least one wasting episode, more than 5-fold higher than point prevalence (5.6%), demonstrating that wasting affects far more children than can be inferred through cross-sectional surveys. Children wasted before 6 months had faster recovery and shorter episodes than children wasted at older ages, but early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low height-for-age), increasing their risk of mortality. In diverse populations with high seasonal rainfall, population average weight-for-length varied substantially (>0.5 z in some cohorts), with the lowest mean Z-scores during the rainiest months, creating potential for seasonally targeted interventions. Our results elevate the importance of establishing interventions to prevent wasting from birth to age 6 months, likely through improved maternal nutrition, to complement current programs that focus on children ages 6-59 months.
Impact of COVID-19 pandemic on lung cancer treatment scheduling
Authors: Fujita Kohei , Ito Takanori , Saito Zentaro , Kanai Osamu , Nakatani Koichi , Mio Tadashi 
Published: June 2020

AbstractObjectiveCurrent pandemic of coronavirus disease 2019 (COVID-19) is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. Many patients with lung cancer are thought to be affected by this situation. Therefore, we aimed to evaluate the impact of COVID-19 pandemic on lung cancer treatment scheduling.Study designWe retrospectively reviewed the medical records of lung cancer patients who were undergoing anti-cancer treatment at the National Hospital Organization Kyoto Medical Center (600 beds) in Kyoto, Japan, between March 1, 2020 and May 31, 2020.MethodsAfter the medical records were reviewed, the patients were assigned to one of two groups, depending on whether their lung cancer treatment schedule was delayed. We assessed the characteristics, types of histopathology and treatment, and the reason for the delay.ResultsA total 15 (9.1%) patients experienced the delay of lung cancer treatment during COVID-19 pandemic. Patients with treatment delay received significantly more ICIs monotherapy than patients without treatment delay (p=0.0057). On the contrary, no patients receiving molecular target agents experienced treatment delay during COVID-19 pandemic period (p=0.0027). The treatments of most of the patients were delayed per their request.ConclusionWe revealed 9.1% lung cancer patients suffered anxiety and requested treatment delay during COVID-19 pandemic. Oncologists should keep in mind that patient with cancer have more anxiety than we expected under special occasions such as COVID-19 pandemic.
Causes and consequences of child growth faltering in low- and middle-income countries
Authors: Mertens Andrew , Benjamin-Chung Jade , Colford John M , Coyle Jeremy , van der Laan Mark J , Hubbard Alan E , Rosete Sonali , Malenica Ivana , Hejazi Nima , Sofrygin Oleg , Cai Wilson , Li Haodong , Nguyen Anna , Pokpongkiat Nolan N , Djajadi Stephanie , Seth Anmol , Jung Esther , Chung Esther O , Jilek Wendy , Subramoney Vishak , Hafen Ryan , Häggström Jonas , Norman Thea , Brown Kenneth H , Christian Parul , Arnold Benjamin F. ,   members of the ki Child Growth Consortium
Published: June 2020

SummaryGrowth faltering (low length-for-age or weight-for-length) in the first 1000 days — from conception to two years of age — influences short and long-term health and survival. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Future preventive efforts will benefit from understanding age-windows and population subgroups in which to focus. Here, we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age Z of up to 0.40 and weight-for-length Z of up to 0.15 by age 24 months. Boys had consistently higher risk of all forms of growth faltering than girls. Early post-natal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits had higher mortality rates from birth to two years than those without deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes, and severe consequences for children who experienced early growth faltering, support a focus on pre-conception and pregnancy as key opportunities for new preventive interventions.
Identification of compounds producing non-visual photosensation via TRPA1 in zebrafish
Authors: Cheng Darya , McCarroll Matthew N , Taylor Jack C , Wu Taia , Kokel David 
Published: June 2020

ABSTRACTTRPA1 receptors sense chemical irritants, but they do not normally respond to light. Previous studies have identified compounds that confer photosensitivity onto vertebrate TRPA1. However, the pharmacology of TRPA1-mediated non-visual photosensation remains poorly understood. To identify novel compounds that affect this process, we screened a large chemical library for compounds that increased light-elicited motor activity in larval zebrafish. We found structurally diverse hit compounds that were photoreactive and produced specific behavioral phenotypes. A subset of these compounds required functional TRPA1 to produce behavioral phenotypes in vivo. These findings provide novel prototype compounds for controlling TRPA1 with light and improve our understanding of non-visual TRPA1-mediated photosensation.
Functional Analysis of Distinct Populations of Subthalamic Nucleus Neurons on Parkinson’s Disease and OCD-like Behaviors in Mice
Authors: Parolari Luca , Schneeberger Marc , Heintz Nathaniel , Friedman Jeffrey M. 
Published: June 2020

ABSTRACTThe Subthalamic Nucleus (STN) is a component of the basal ganglia and plays a key role to control movement and limbic-associative functions. STN modulation with Deep Brain Stimulation (DBS) improves the symptoms of Parkinson’s Disease (PD) and Obsessive-Compulsive Disorder (OCD) patients. However, DBS does not allow for cell-type specific modulation of the STN. While extensive work has focused on understanding STN functionality, the understanding of its cellular components is limited.Here, we first performed an anatomical characterization of molecular markers for specific STN neurons. These studies revealed that most STN neurons expressPitx2, and that different overlapping subsets expressGabrr3,NdnforNos1. Next, we used neuronal modulatory tools to demonstrate their roles in regulating locomotor and limbic functions in mice. Specifically, we showed that optogenetic photoactivation of STN neurons in Pitx2-Cre mice or of the Gabrr3-expressing subpopulation induces locomotor changes, and improves locomotion in a PD mouse model. Additionally, photoactivation of Pitx2 and Gabrr3 cells induced repetitive grooming, a phenotype associated with OCD. Repeated stimulation prompted a persistent increase in grooming that could be reversed by fluoxetine treatment, a first-line drug therapy for OCD. Conversely, repeated inhibition of STNGabrr3neurons suppressed grooming in Sapap3-KO mice, a model for OCD. Finally, circuit and functional mapping of STNGabrr3neurons showed that these effects are mediated via projections to the globus pallidus/entopeduncular nucleus and substantia nigra reticulata. Altogether, these data identify Gabrr3 neurons as a key population in mediating the beneficial effects of STN modulation thus providing a new molecular handle for PD and OCD drug discovery.