bluuebunny/crossref_metadata_2025_split huggingface dataset:
Projecting introgression from domestic cats into European wildcats in the Swiss Jura
Authors: Quilodrán Claudio S. , Nussberger Beatrice , Macdonald David W. , Montoya‐Burgos Juan I. , Currat Mathias 
Published: April 2020

AbstractHybridization between wild and domesticated organisms is a worldwide conservation issue. In the Jura Mountains, threatened European wildcats (Felis silvestris) have been demographically spreading for approximately the last 50 years, but this recovery is coupled with hybridization with domestic cats (Felis catus). Here, we project the pattern of future introgression using different spatially explicit scenarios to model the interactions between the two species, including competition and different population sizes. We project the fast introgression of domestic cat genes into the wildcat population under all scenarios if hybridization is not severely restricted. If the current hybridization rate and population sizes remain unchanged, we expect the loss of genetic distinctiveness between wild and domestic cats at neutral nuclear, mitochondrial and Y chromosome markers in one hundred years. However, scenarios involving a competitive advantage for wildcats and a future increase in the wildcat population size project a slower increase in introgression. We recommend that future studies assess the fitness of these hybrids and better characterize their ecological niche and their ecological interactions with parental species to elucidate effective conservation measures.
Cardiac and arrhythmic complications in patients with COVID‐19
Authors: Kochi Adriano Nunes , Tagliari Ana Paula , Forleo Giovanni Battista , Fassini Gaetano Michele , Tondo Claudio 
Published: April 2020

AbstractIn December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.
The Relationship Between First and Second Language Writing: Investigating the Effects of First Language Complexity on Second Language Complexity in Advanced Stages of Learning
Authors: Ströbel Marcus , Kerz Elma , Wiechmann Daniel 
Published: April 2020

AbstractRecent studies have uncovered substantial individual differences in first language (L1) language attainment across the lifespan and across multiple components of language. The existence of such variability raises the question of its role in second language (L2) learning. The existing body of research on L1–L2 relationships has primarily targeted reading comprehension by means of controlled experimental designs. This study extended existing research by investigating L1–L2 relationships in writing through the automatic analysis of linguistic complexity in paired samples of authentic production data. For each writing sample, a series of measurements of 12 indicators was obtained using a computational tool that implements a sliding‐window approach. Results from mixed‐effects modeling revealed significant relationships between L1 complexity and L2 complexity for all but one measure, indicating that an L1 effect is robust across different levels of linguistic description.
Is left bundle branch block pattern on the ECG caused by variable ventricular activation sequence?
Authors: Riedlbauchová Lucie , Adla Theodor , Suchánek Vojtěch , Ložek Miroslav , Tomis Jan , Hozman Jiří , Tomek Viktor , Veselka Josef , Janoušek Jan 
Published: April 2020

AbstractBackgroundThe presence and extent of ventricular dyssynchrony are currently assessed from the QRS complex morphology and width. However, similar electrocardiography (ECG) pattern may be caused by variable ventricular activation sequence. This may then contribute to interindividually different response to cardiac resynchronization therapy (CRT).MethodsElectroanatomical mapping and magnetic resonance imaging scan were performed in 11 patients with left bundle branch block (LBBB, QRS 170 ± 14 ms) and heart failure of ischemic (coronary artery disease (CAD), n = 2) and nonischemic (dilated cardiomyopathy (DCM), n = 9) etiology. Ventricular activation sequence was studied during LBBB and final CRT programming. Presence and extent of scarring were analyzed in the 17‐segment left‐ventricular (LV) model.ResultsRegardless of etiology, presence of typical LBBB was associated with diffuse prolongation of impulse conduction with right‐to‐left activation sequence. Basal lateral wall was constant site of late activation. This activation pattern was present in “true LBBB,” but also in LBBB‐like pattern (persistent S wave in V5‐6) and left axis deviation. Activation started in right vetricular (RV) apex in patients with left axis deviation at RV free wall in normal axis. Individuals with CAD and DCM patient displayed focal scar. Despite that they exhibited typical LBBB and activation sequence mirrored findings in other LBBB individuals. Reverse remodeling (∆LVESV > 15% after 6 months) was evident in 10 patients.ConclusionsBoth typical LBBB and LBBB‐like pattern might be associated with constant activation sequence regardless of etiology and scar localization. Activation initiation in RV apex, not LV activation sequence can be surrogate for left axis deviation. CRT caused inter‐ and intraventricular LV resynchronization without significantly changed RV activation sequence and duration.
The effects of the integration of an economic strengthening and HIV prevention education programme on the prevalence of sexually transmitted infections and savings behaviours among adolescents: a full-factorial randomised controlled trial in South Africa
Authors: Burke Holly M , Chen Mario , Murray Kate , Bezuidenhout Charl , Ngwepe Phuti , Bernholc Alissa , Medina-Marino Andrew 
Published: April 2020

BackgroundMultisectoral approaches are thought necessary to prevent HIV among adolescents. We examined whether an economic strengthening (ES) and an HIV-prevention education intervention improved outcomes when combined versus separately.MethodsWe conducted a full-factorial randomised controlled study to randomise participants into all possible intervention groups based on the two interventions: economic strengthening only (ES-only), HIV-prevention only (HIV-only), both interventions combined (ES+HIV) and no intervention (control). We measured sexually transmitted infections (STIs), self-reported economic and sexual behaviours/knowledge, and pregnancy at a pre-intervention and two post-intervention assessments. Eligible participants were adolescents 14 to 17 years old from a programme supporting vulnerable families in Gauteng Province, South Africa. We estimated intervention effects using repeated measures, generalised linear mixed models.ResultsA total of 1773 adolescents participated (57% female). ES+HIV adolescents had the lowest STI prevalence at first endline; however, the comparison with the control was not significant (OR 0.62, 95% CI 0.27 to 1.41). ES-only or HIV-only groups were not significantly better than the control on STI prevalence (OR 1.53, 95% CI 0.73 to 3.20 and OR 1.47, 95% CI 0.69 to 3.12, respectively). STI prevalence became more similar among the groups at second endline.ES-only adolescents were more likely to participate in savings groups (p=0.004) and plan to save for education (p=0.001) versus the control. ES+HIV adolescents were more likely to plan to save for education versus the control (p=0.001) and HIV-only groups (p=0.002) but did not differ significantly from the ES-only group (p=0.803). The ES+HIV intervention’s effect on HIV knowledge was significant compared with the control (p=0.03) and ES-only groups (p<0.001), but not when compared with the HIV-only group (p=0.091). Effects on pregnancy, sexual behaviours or other economic behaviours were not significant.ConclusionsWe could not confirm the ES and HIV interventions, separately or combined, were effective to reduce STI prevalence. Evaluations of multicomponent interventions should use full-factorial designs to fully assess effects.Trial registration numberNCT02888678
Phosphorus supplementation raised the heart rate of male water polo players during a randomised graded dryland exercise test
Authors: Elhusseini Rami , Fares Elie-Jacques , Obeid Omar 
Published: April 2020

ObjectiveThe impact of phosphorus supplementation on athletic performance is unclear. Ingestion of phosphorus for several days has been reported to increase cardiac capacity, improve oxygen muscle kinetics and enhance lactate buffering capacity. Recent studies have shown that phosphorus ingestion with a meal increases postprandial glucose uptake and thermogenesis. The present study aimed to assess the effect of acute phosphorus ingestion with a meal on specific workload parameters.MethodsA double-blind, crossover trial of 12 male water polo players between 18 and 22 years old was conducted. Overnight fasted subjects were asked to cycle for 20 min before ingesting 100 g of glucose with phosphorus or placebo (400 mg). Three hours later, they were asked to perform a graded cycling exercise for 25 min.ResultsExpenditure, respiratory quotient, perception of fatigue and exercise efficiency were similar between treatments. However, heart rate was significantly higher in the phosphorus group (142±10 beats/min) compared with placebo (135±10 beats/min).ConclusionExercise performance 3 hours after the coingestion of glucose with phosphorus did not affect substrate use, while heart rate was increased. The heart rate increase could be attributed to a rise in core body temperature.Trial registration numberNCT03101215.
First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach
Authors: Schaller Teilo H , Snyder David J , Spasojevic Ivan , Gedeon Patrick C , Sanchez-Perez Luis , Sampson John H 
Published: April 2020

BackgroundFirst-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with the advent of target-specific and highly active immunotherapeutics, both the Food and Drug Administration and the European Medicines Agency have provided guidance that recommend determining a safe starting dose based on a minimum anticipated biological effect level (MABEL) approach.MethodsWe recently developed a T cell activating bispecific antibody that effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma in mice (hEGFRvIII:CD3 bi-scFv). hEGFRvIII:CD3 bi-scFv is comprized of two single chain antibody fragments (bi-scFvs) that bind mutant epidermal growth factor receptor variant III (EGFRvIII), a mutation frequently seen in malignant glioma, and human CD3ε on T cells, respectively. In order to establish a FIH dose, we used a MABEL approach to select a safe starting dose for hEGFRvIII:CD3 bi-scFv, based on a combination of in vitro data, in vivo animal studies, and theoretical human receptor occupancy modeling.ResultsUsing the most conservative approach to the MABEL assessment, a dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/kg body weight was selected as a safe starting dose for a FIH clinical study.ConclusionsThe comparison of our MABEL-based starting dose to our in vivo efficacious dose and the theoretical human receptor occupancy strongly supports that our human starting dose of 57.4 ng hEGFRvIII:CD3 bi-scFv/patient kg will be safe.
Serum neuronal exosomes predict and differentiate Parkinson’s disease from atypical parkinsonism
Authors: Jiang Cheng , Hopfner Franziska , Katsikoudi Antigoni , Hein Robert , Catli Candan , Evetts Samuel , Huang Yongzhi , Wang Hong , Ryder John W , Kuhlenbaeumer Gregor , Deuschl Guenther , Padovani Alessandro , Berg Daniela , Borroni Barbara , Hu Michele T , Davis Jason J , Tofaris George K 
Published: April 2020

ObjectiveParkinson’s disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or distinguish Parkinson’s from atypical parkinsonian syndromes. We assessed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson’s disease, multiple system atrophy and other proteinopathies.MethodsWe performed a cross-sectional study of 664 serum samples from the Oxford, Kiel and Brescia cohorts consisting of individuals with rapid eye movement sleep behavioural disorder, Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome and controls. Longitudinal samples were analysed from Parkinson’s and control individuals. We developed poly(carboxybetaine-methacrylate) coated beads to isolate L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles with characteristics of exosomes and used mass spectrometry or multiplexed electrochemiluminescence to measure exosomal proteins.ResultsMean neuron-derived exosomal α-synuclein was increased by twofold in prodromal and clinical Parkinson’s disease when compared with multiple system atrophy, controls or other neurodegenerative diseases. With 314 subjects in the training group and 105 in the validation group, exosomal α-synuclein exhibited a consistent performance (AUC=0.86) in separating clinical Parkinson’s disease from controls across populations. Exosomal clusterin was elevated in subjects with non-α-synuclein proteinopathies. Combined neuron-derived exosomal α-synuclein and clusterin measurement predicted Parkinson’s disease from other proteinopathies with AUC=0.98 and from multiple system atrophy with AUC=0.94. Longitudinal sample analysis showed that exosomal α-synuclein remains stably elevated with Parkinson’s disease progression.ConclusionsIncreased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson’s disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson’s disease from atypical parkinsonism.
Stable Boundary Layer Regimes in Single-Column Models
Authors: Costa Felipe D. , Acevedo Otávio C. , Medeiros Luiz E. , Maroneze Rafael , Puhales Franciano S. , Carvalho Jr. Arlindo D. , Camponogara Luis F. , dos Santos Daniel M. , Mortarini Luca 
Published: April 2020

AbstractTwo contrasting flow regimes exist in the stable boundary layer (SBL), as evidenced from both observational and modeling studies. In general, numerical schemes such as those used in numerical weather prediction and climate models (NWPCs) reproduce a transition between SBL regimes. However, the characteristics of such a transition depend on the turbulence parameterizations and stability functions used to represent the eddy diffusivity in the models. The main goal of the present study is to detail how the two SBL regimes occur in single-column models (SCMs) by analyzing the SBL structure and its dependence on external parameters. Two different turbulence closure orders (first order and an E–l model) and two types of stability functions (short and long tail) are considered. The control exerted by the geostrophic wind and the surface cooling rate on the model SBL regimes is addressed. The model flow presents a three-layer structure: a fully turbulent, weakly stable layer (WSL) next to the surface; a very stable layer (VSL) above that; and a laminar layer above the other two and toward the domain top. It is shown that the WSL and VSL are related to both SBL regimes, respectively. Furthermore, the numerically simulated SBL presents the two-layer structure regardless of the turbulence parameterization order and stability function used. The models also reproduce other features reported in recent observational studies: an S-shaped dependence of the thermal gradient on the mean wind speed and an independence of the vertical gradient of friction velocity on the mean wind speed.
Time Scales and Mechanisms for the Tropical Pacific Response to Global Warming: A Tug of War between the Ocean Thermostat and Weaker Walker
Authors: Heede Ulla K. , Fedorov Alexey V. , Burls Natalie J. 
Published: April 2020

AbstractDifferent oceanic and atmospheric mechanisms have been proposed to describe the response of the tropical Pacific to global warming, yet large uncertainties persist on their relative importance and potential interaction. Here, we use idealized experiments forced with a wide range of both abrupt and gradual CO2 increases in a coupled climate model (CESM) together with a simplified box model to explore the interaction between, and time scales of, different mechanisms driving Walker circulation changes. We find a robust transient response to CO2 forcing across all simulations, lasting between 20 and 100 years, depending on how abruptly the system is perturbed. This initial response is characterized by the strengthening of the Indo-Pacific zonal SST gradient and a westward shift of the Walker cell. In contrast, the equilibrium response, emerging after 50–100 years, is characterized by a warmer cold tongue, reduced zonal winds, and a weaker Walker cell. The magnitude of the equilibrium response in the fully coupled model is set primarily by enhanced extratropical warming and weaker oceanic subtropical cells, reducing the supply of cold water to equatorial upwelling. In contrast, in the slab ocean simulations, the weakening of the Walker cell is more modest and driven by differential evaporative cooling along the equator. The “weaker Walker” mechanism implied by atmospheric energetics is also observed for the midtroposphere vertical velocity, but its surface manifestation is not robust. Correctly diagnosing the balance between these transient and equilibrium responses will improve understanding of ongoing and future climate change in the tropical Pacific.
Morphological changes of the thyroid gland as a new radiographic marker for lung cancer treatment efficacy of immune checkpoint inhibitors
Authors: Itonaga Tomohiro , Saito Kazuhiro , Ikeda Norihiko , Mikami Ryuji 
Published: April 2020

Background Fully human IgG4 programmed cell death-1 (PD-1) immune checkpoint inhibitors are effective against non-small-cell lung cancer (NSCLC). PD-1-targeted antibodies induce autoimmune adverse events that are not caused by conventional chemotherapy. Purpose To clarify the association between morphological changes of the thyroid gland and the efficacy of PD-1 immune checkpoint inhibitor treatment for lung cancer. Material and Methods The study enrolled 29 patients who received PD-1 immune checkpoint inhibitor treatment. The thyroid volume was measured using computed tomography (CT) at the following three timepoints: pre-treatment (baseline); three months after the initial administration (early treatment); and at the last CT scan during the observation period (late treatment). Thyroid volume ratios were calculated as follows: early treatment/baseline thyroid volume at CT (E/B-CT ratio) and late treatment/baseline thyroid volume at CT (L/B-CT ratio). Thyroid dysfunction was assessed according to thyroid hormone levels. Results The E/B-CT ratio was significantly higher in patients with adverse events of grade 3 or higher than in the other patients ( P = 0.013). The L/B-CT ratio was significantly lower in patients with thyroid dysfunction than in those without thyroid dysfunction ( P = 0.001). Complete response (CR) was achieved in three patients at the time of the final CT. The E/B-CT ratio was significantly higher in patients with CR than in the other patients (1.48 vs. 0.99, P = 0.029). Conclusion Changes in thyroid volume after administration of PD-1 immune checkpoint inhibitors might be a useful radiographic marker of therapeutic efficacy in patients with lung cancer.
Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea
Authors: Powell Jason , Piszczatoski Chris , Garland Scott 
Published: April 2020

Objective: The purpose of this article is to review the available clinical trial data that led to the Food and Drug Administration (FDA) approval of solriamfetol as well as its role in clinical practice. Data Sources: A MEDLINE/PubMed search was conducted (January 2000 to February 2020) using the keyword solriamfetol to discover appropriate clinical trials. Study Selection and Data Extraction: Articles were included that were published in the English language and related to the FDA approval of solriamfetol or provided novel information regarding this drug entity. Data Synthesis: The findings of the review show that solriamfetol may be a safe and effective option for the treatment of excessive sleepiness (ES) related to narcolepsy and obstructive sleep apnea (OSA). Relevance to Patient Care and Clinical Practice: Solriamfetol is distinguished from other stimulants in that it has lower binding affinity to dopamine and norepinephrine transporters and does not have the monoamine-releasing effects of amphetamines at usual therapeutic doses. Because of solriamfetol’s unique mechanism of action, there may be a reduction in abuse potential compared with the other currently FDA-approved options. Conclusions: In clinical trials, solriamfetol has shown dose-dependent improvement in wakefulness over placebo and adds another option for clinicians when treating ES in narcolepsy and OSA.