bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definitive Chemoradiotherapy Compared to Neoadjuvant Chemoradiotherapy With Esophagectomy for Locoregional Esophageal Cancer
Authors: Kamarajah Sivesh K. , Phillips Alexander W. , Hanna George B. , Low Donald , Markar Sheraz R. 
Published: May 2020

Aim:
Ongoing randomized controlled trials seek to evaluate the potential organ-preservation strategy of definitive chemoradiotherapy as a primary treatment for esophageal cancer. This population-based cohort study aimed to assess survival following definitive chemoradiotherapy (DCR) with or without salvage esophagectomy (SALV) in the treatment of esophageal cancer.

Patients and Methods:
Data from the National Cancer Database (NCDB) from 2004 to 2015, was used to identify patients with nonmetastatic esophageal cancer receiving either DCR (n = 5977) or neoadjuvant chemoradiotherapy with planned esophagectomy (NCRS) (n = 13,555). Propensity score matching and multivariable analyses were used to account for treatment selection bias. Subset analyses compared patients receiving SALV after DCR with NCRS.

Results:
Comparison of baseline demographics of the unmatched cohort revealed that patients receiving NCRS were younger, had a lower burden of medical comorbidities, lower proportion of squamous cell carcinoma (SCC), and more positive lymph nodes. Following matching, NCRS was associated with significantly improved survival compared with DCR [hazard ratio (HR): 0.60, 95% confidence Interval (CI): 0.57–0.63, P < 0.001], which persisted in subset analyses of patients with adenocarcinoma (HR: 0.60, 95% CI: 0.56–0.63, P < 0.001) and SCC (HR: 0.58, 95% CI: 0.53–0.63, P < 0.001). Of 829 receiving SALV after DCR, 823 patients were matched to 1643 NCRS. There was no difference in overall survival between SALV and NCRS (HR: 1.00, 95% CI: 0.90–1.11, P = 1.0).

Conclusions:
Surgery remains an integral component of the management of patients with esophageal cancer. Neoadjuvant therapy followed by planned esophagectomy appears to remain the optimum curative treatment regime in patients with locoregional esophageal cancer.
Manifestations of mortality based global data of COVID-19; unifying global model through single parameter
Authors: Jindal V.K. 
Published: May 2020

AbstractCritical inspection of the world data of COVID-19 mortality rates per population number has been made and used to express extensive variations in mortality over the globe in terms of a powered parameter λ varying from 0 to 1.2 expressed as a measure of strength of primary infection, originating from China source. The copying process is degenerating successively while infection is passed on to secondary subjects. We have been able to correlate global data through this parameter; any value close to or less than 1 shows significant impact of diluted multiple secondary effect. Further, the scatter diagram shows no effect of temperature of the geographical location and so is likely as the virus is only being spread from either contact or close proximity – the virus does not need to face highs and lows of temperatures of the environment. It stays only in the range of human body temperature and appears to be stable in 36–40°C range. If it faces the environmental temperatures it is possible for its quicker deactivation but that situation never arises for this virus except when it spreads from surfaces.
The infection fatality rate of COVID-19 inferred from seroprevalence data
Authors: Ioannidis John P.A. 
Published: May 2020

ABSTRACTObjectiveTo estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies.MethodsPopulation studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of July 11, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Secondarily, results from national studies were also examined from preliminary press releases and reports whenever a country had no other data presented in full papers of preprints.Results36 studies (43 estimates) were identified with usable data to enter into calculations and another 7 preliminary national estimates were also considered for a total of 50 estimates. Seroprevalence estimates ranged from 0.222% to 47%. Infection fatality rates ranged from 0.00% to 1.63% and corrected values ranged from 0.00% to 1.31%. Across 32 different locations, the median infection fatality rate was 0.27% (corrected 0.24%). Most studies were done in pandemic epicenters with high death tolls. Median corrected IFR was 0.10% in locations with COVID-19 population mortality rate less than the global average (<73 deaths per million as of July 12, 2020), 0.27% in locations with 73-500 COVID-19 deaths per million, and 0.90% in locations exceeding 500 COVID-19 deaths per million. Among people <70 years old, infection fatality rates ranged from 0.00% to 0.57% with median of 0.05% across the different locations (corrected median of 0.04%).ConclusionsThe infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.
COVID-19 FATALITY RISK: WHY IS AUSTRALIA’S LOWER THAN SOUTH KOREA?
Authors: Collignon Peter , Beggs John J. 
Published: May 2020

AbstractBackgroundAs the Covid-19 virus epidemic spreads, it is important to establish reliable estimates of fatality hazard rates. Australia and South Korea are ideal candidates for detailed consideration. Both have completed the first wave of the epidemic, they have extensive Covid-19 testing and tracking programs so that confirmed case load data are reliable, and neither country has had any significant case load stress in their hospital systems.MethodsFor each country, mortality hazard models were estimated using a parameterized distributed lag model where the number of daily deaths was dependent on the number of confirmed cases in each of the preceding six weeks. Age cohort CFRs were also examined.FindingsWe observed major difference in the mortality rates when comparing South Korea to Australia in both the simple age adjusted fatality rates and in the disease hazard curve. On a like-for-like basis, the CFR for South Korea appears to be close to double the Australian rate (aggregate; 2.4% vs 1.4%).InterpretationNeither differences in the time pattern of the peaking of the case load of confirmed cases, nor differences in the size of age cohorts of confirmed cases explain the difference in mortality observed. We discuss possible explanations that point the way for further investigation.Fundingnil.
A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems
Authors: Denaxas Spiros , Shah Anoop D. , Mateen Bilal A. , Kuan Valerie , Quint Jennifer K. , Fitzpatrick Natalie , Torralbo Ana , Fatemifar Ghazaleh , Hemingway Harry 
Published: May 2020

AbstractObjectivesThe UK Biobank (UKB) is making primary care Electronic Health Records (EHR) for 500,000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers.Materials and MethodsWe describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving a) bootstrapping definitions using existing phenotypes, b) excluding generic, rare or semantically distant terms, c) forward-mapping terminology terms, d) expert review, and e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models.ResultsWe created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID–19 complications e.g. diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38,190,682 events and identified 220,978 participants with at least one biomarker measured.Discussion and conclusionBootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.
Flatten the Curve! Modeling SARS-CoV-2/COVID-19 Growth in Germany at the County Level
Authors: Wieland Thomas 
Published: May 2020

AbstractSince the emerging of the “novel coronavirus” SARS-CoV-2 and the corresponding respiratory disease COVID-19, the virus has spread all over the world. Being one of the most affected countries in Europe, in March 2020, Germany established several nonpharmaceutical interventions to contain the virus spread, including the closure of schools and child day care facilities (March 16-18, 2020) as well as a full “lockdown” with forced social distancing and closures of “nonessential” services (March 23, 2020). The present study attempts to analyze whether these governmental interventions had an impact on the declared aim of ‘’flattening the curve”, referring to the epidemic curve of new infections. This analysis is conducted from a regional perspective. On the level of the 412 German counties, logistic growth models were estimated based on daily infections (estimated from reported cases), aiming at determining the regional growth rate of infections and the point of inflection where infection rates begin to decrease and the curve flattens. All German counties exceeded the peak of new infections between the beginning of March and the middle of April. In a large majority of German counties, the epidemic curve has flattened before the “lockdown” was established. In a minority of counties, the peak was already exceeded before school closures. The growth rates of infections vary spatially depending on the time the virus emerged. Counties belonging to states which established an additional curfew show no significant improvement with respect to growth rates and mortality. Furthermore, mortality varies strongly across German counties, which can be attributed to infections of people belonging to the “risk group”, especially residents of retirement homes. The results raise the question whether social ban measures and curfews really contribute to curve flattening within a pandemic.
A Model-Based Approach for Pulse Selection from Electrodermal Activity
Authors: Subramanian Sandya , Purdon Patrick L. , Barbieri Riccardo , Brown Emery N. 
Published: May 2020

ABSTRACTObjectiveThe goal of this work was to develop a physiology-based paradigm for pulse selection from electrodermal activity (EDA) data.MethodsWe aimed to use insight about the integrate-and-fire physiology of sweat gland bursts, which predicts inverse Gaussian inter-pulse interval structure. At the core of our paradigm is a subject-specific amplitude threshold selection process for pulses based on the statistical properties of four right-skewed models including the inverse Gaussian. These four models differ in their tail behavior, which reflects sweat gland physiology to varying degrees. By screening across thresholds and fitting all four models, we selected for heavier tails that reflect inverse Gaussian-like structure and verified the pulse selection with a goodness-of-fit analysis.ResultsWe tested our paradigm on two different subject cohorts recorded during different experimental conditions and using different equipment. In both cohorts, our method robustly and consistently recovered pulses that captured the inverse Gaussian-like structure predicted by physiology, despite large differences in noise level of the data. In contrast, an established EDA analysis paradigm, which assumes a constant amplitude threshold across all data, was unable to separate pulses from noise.ConclusionWe present a computationally efficient, statistically rigorous, and physiology-informed paradigm for pulse selection from EDA data that is robust across individuals and experimental conditions yet adaptable to changes in noise level.SignificanceThe robustness of our paradigm and its basis in physiology move EDA closer to serving as a clinical marker for sympathetic activity in diverse conditions such as pain, anxiety, depression, and sleep.
Does chronic systemic injection of the DREADD agonists clozapine-N-oxide or compound 21 change behavior relevant to locomotion, exploration, anxiety, and depression in male non-DREADD-expressing mice?
Authors: Tran Fionya H. , Spears Stella L. , Ahn Kyung J. , Eisch Amelia J. , Yun Sanghee 
Published: May 2020

AbstractDesigner Receptors Exclusively Activated by Designer Drugs (DREADDs) are chemogenetic tools commonly-used to manipulate brain activity. The most widely-used synthetic DREADD ligand, clozapine-N-oxide (CNO), is back-metabolized to clozapine which can itself activate endogenous receptors. Studies in non-DREADD-expressing rodents suggest CNO or a DREADD agonist that lacks active metabolites, such as Compound 21 (C21), change rodent behavior (e.g. decrease locomotion), but chronic injection of CNO does not change locomotion. However, it is unknown if chronic CNO changes behaviors relevant to locomotion, exploration, anxiety, and depression, or if chronic C21 changes any aspect of mouse behavior. Here non-DREADD-expressing mice received i.p. Vehicle (Veh), CNO, or C21 (1mg/kg) 5 days/week for 16 weeks and behaviors were assessed over time. Veh, CNO, and C21 mice had similar weight gain over the 16-week-experiment. During the 3rd injection week, CNO and C21 mice explored more than Veh mice in a novel context and had more open field center entries; however, groups were similar in other measures of locomotion and anxiety. During the 14th-16th injection weeks, Veh, CNO, and C21 mice had similar locomotion and anxiety-like behaviors. We interpret these data as showing chronic Veh, CNO, and C21 injections given to male non-DREADD-expressing mice largely lack behavioral effects. These data may be helpful for behavioral neuroscientists when study design requires repeated injection of these DREADD agonists.HighlightsAcute injection of CNO changes behavior of non-DREADD-expressing miceIt’s not known if chronic CNO or alternative agonist C21 also changes mouse behaviorDREADD agonists or Veh were given chronically to non-DREADD-expressing miceCNO and C21 don’t change locomotion and have a mixed effect on anxiety-like behavior1 mg/kg CNO and C21 can be injected repeatedly without non-specific behavior effects
Endocannabinoids and dopamine balance basal ganglia output
Authors: Gorodetski Lilach , Loewenstern Yocheved , Faynveitz Anna , Bar-Gad Izhar , Blackwell Kim T. , Korngreen Alon 
Published: May 2020

AbstractThe entopeduncular nucleus is one of the basal ganglia’s output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the striatum and the globus pallidus and glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all the primary afferents to the entopeduncular nucleus. Our results suggest that dopamine-endocannabinoids interplay determines the balance of the direct or indirect dominance of entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoids diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.
Th2-like T-follicular helper cells promote functional antibody production duringPlasmodium falciparuminfection
Authors: Chan Jo-Anne , Rivera Fabian de Labastida , Loughland Jessica , Engel Jessica A , Lee Hyun Jae , SheelaNair Arya , Wines Bruce D , Amante Fiona H , Webb Lachlan , Mukhopadhyay Pamela , Patch Ann-Marie , Hogarth P. Mark , Beeson James G , McCarthy James S , Haque Ashraful , Engwerda Christian R , Boyle Michelle J 
Published: May 2020

AbstractThe most advanced malaria vaccine only has approximately 30% efficacy in target populations, and avenues to improve next generation vaccines need to be identified. Functional antibodies are key effectors of both vaccine induced and naturally acquired immunity, with induction driven by T-follicular helper cells (TfH) CD4+ T cells. We assessed circulating TfH (cTfH) responses and functional antibody production in human volunteers experimentally infected withPlasmodium falciparum. Longitudinal single-cell RNA-sequencing of cTfH revealed peak transcriptional activation and clonal expansion of major cTfH subsets occurred at day 8 following infection and a population structure of cTfH capturing phenotypical subsets of Th1- and Th2-like cells. Among 40 volunteers, infection resulted in the emergence of activated ICOS+ cTfH cells. During peak infection, activation was restricted to Th2-like cTfH cells, while Th1-like cTfH cell activation occurred one week after treatment. To link cTfH activation to antibody induction, we assessed the magnitude and function of anti-malarial IgM and IgG after infection. The functional breadth and magnitude of parasite-specific antibodies was positively associated with Th2-cTfH activation. In contrast, Th1-cTfH activation was associated with the induction of plasma cells, which we have previously shown have a detrimental role in germinal cell formation and antibody development. Thus, we identified that duringP. falciparummalaria infection in humans, the activation of Th2-cTfH but not other subsets correlates with the development of functional antibodies required for protective immunity. Data for the first time identify a specific cellular response that can be targeted by future malaria vaccines to improve antibody induction.
The microbial metabolitep-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota
Authors: Bermudez-Martin P. , Becker J. A. J. , Caramello N. , Fernandez S. P. , Costa-Campos R. , Canaguier J. , Barbosa S. , Martinez-Gili L. , Myridakis A. , Dumas M.-E. , Bruneau A. , Cherbuy C. , Langella P. , Callebert J. , Launay J.-M. , Chabry J. , Barik J. , Le Merrer J. , Glaichenhaus N. , Davidovic L. 
Published: May 2020

ABSTRACTBackgroundAutism Spectrum Disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis resulting in changes in microbiota composition as well as fecal, serum and urine levels of microbial metabolites. Yet, a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolitep-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.ResultsMice exposed top-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced byp-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further,p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred fromp-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota ofp-Cresol-treated mice exhibited increased fecalp-Cresol levels compared to mice transplanted with the microbiota of control mice and identified possiblep-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability and fecalp-Cresol levels when transplanted top-Cresol-treated mice.ConclusionsThe microbial metabolitep-Cresol induces ASD core behavioral symptoms in mice via a gut microbiota-dependent mechanism. Our study paves the way for therapeutic interventions targeting the microbiota to treat patients with ASD.
Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?
Authors: Pique-Regi Roger , Romero Roberto , Tarca Adi L. , Luca Francesca , Xu Yi , Alazizi Adnan , Leng Yaozhu , Hsu Chaur-Dong , Gomez-Lopez Nardhy 
Published: May 2020

ABSTRACTThe pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 3.8 million people, including pregnant women. To date, no consistent evidence of vertical transmission for SARS-CoV-2 exists. This new coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. Herein, building upon our previous single cell study of the placenta (Pique-Regi, 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy as well as in third-trimester chorioamniotic membranes. We report that co-transcription of ACE2 and TMPRSS2 is negligible, thus not a likely path of vertical transmission for SARS-CoV-2 at any stage of pregnancy. In contrast, receptors for Zika virus and cytomegalovirus which cause congenital infections are highly expressed by placental cell types. These data suggest that SARS-CoV-2 is unlikely to infect the human placenta through the canonical cell entry mediators; yet, other interacting proteins could still play a role in the viral infection.
SARS-CoV2 infection in farmed mink, Netherlands, April 2020
Authors: Oreshkova Nadia , Molenaar Robert-Jan , Vreman Sandra , Harders Frank , Munnink Bas B. Oude , Hakze Renate , Gerhards Nora , Tolsma Paulien , Bouwstra Ruth , Sikkema Reina , Tacken Mirriam , de Rooij Myrna M.T. , Weesendorp Eefke , Engelsma Marc , Bruschke Christianne , Smit Lidwien A.M. , Koopmans Marion , van der Poel Wim H.M. , Stegeman Arjan 
Published: May 2020

AbstractIn April 2020, respiratory disease and increased mortality were observed in farmed mink on two farms in the Netherlands. In both farms, at least one worker had been found positive for SARS-CoV-2. Necropsies of the mink revealed interstitial pneumonia, and organ and swab samples tested positive for SARS-CoV-2 RNA by qPCR. Variations in viral genomes point at between-mink transmission on the farms and lack of infection link between the farms. Inhalable dust in the mink houses contained viral RNA, indicating possible exposure of workers.