bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2
Authors: Sung Pei-Shan , Huang Tur-Fu , Hsieh Shie-Liang 
Published: June 2019

AbstractPlatelet-leukocyte interactions amplify inflammatory reactions, but the underlying mechanism is still unclear. CLEC5A and CLEC2 are spleen tyrosine kinase (Syk)-coupled C-type lectin receptors, abundantly expressed by leukocytes and platelets, respectively. Whereas CLEC5A is a pattern recognition receptor (PRR) to flaviviruses and bacteria, CLEC2 is the receptor for platelet-activating snake venom aggretin. Here we show that dengue virus (DV) activates platelets via CLEC2 to release extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles (MVs). DV-induced EXOs (DV-EXOs) and MVs (DV-MVs) further activate CLEC5A and TLR2 on neutrophils and macrophages, thereby induce neutrophil extracellular trap (NET) formation and proinflammatory cytokine release. Compared to stat1−/− mice, simultaneous blockade of CLEC5A and TLR2 effectively attenuates DV-induced inflammatory response and increases survival rate from 30 to 90%. The identification of critical roles of CLEC2 and CLEC5A/TLR2 in platelet-leukocyte interactions will support the development of novel strategies to treat acute viral infection in the future.
Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations
Authors: Birkinshaw Richard W. , Gong Jia-nan , Luo Cindy S. , Lio Daisy , White Christine A. , Anderson Mary Ann , Blombery Piers , Lessene Guillaume , Majewski Ian J. , Thijssen Rachel , Roberts Andrew W. , Huang David C. S. , Colman Peter M. , Czabotar Peter E. 
Published: June 2019

AbstractVenetoclax is a first-in-class cancer therapy that interacts with the cellular apoptotic machinery promoting apoptosis. Treatment of patients suffering chronic lymphocytic leukaemia with this BCL-2 antagonist has revealed emergence of a drug-selected BCL-2 mutation (G101V) in some patients failing therapy. To understand the molecular basis of this acquired resistance we describe the crystal structures of venetoclax bound to both BCL-2 and the G101V mutant. The pose of venetoclax in its binding site on BCL-2 reveals small but unexpected differences as compared to published structures of complexes with venetoclax analogues. The G101V mutant complex structure and mutant binding assays reveal that resistance is acquired by a knock-on effect of V101 on an adjacent residue, E152, with venetoclax binding restored by a E152A mutation. This provides a framework for considering analogues of venetoclax that might be effective in combating this mutation.
Single particle cryo-EM reconstruction of 52 kDa streptavidin at 3.2 Angstrom resolution
Authors: Fan Xiao , Wang Jia , Zhang Xing , Yang Zi , Zhang Jin-Can , Zhao Lingyun , Peng Hai-Lin , Lei Jianlin , Wang Hong-Wei 
Published: June 2019

AbstractThe fast development of single-particle cryogenic electron microscopy (cryo-EM) has made it more feasible to obtain the 3D structure of well-behaved macromolecules with a molecular weight higher than 300 kDa at ~3 Å resolution. However, it remains a challenge to obtain the high-resolution structures of molecules smaller than 200 kDa using single-particle cryo-EM. In this work, we apply the Cs-corrector-VPP-coupled cryo-EM to study the 52 kDa streptavidin (SA) protein supported on a thin layer of graphene and embedded in vitreous ice. We are able to solve both the apo-SA and biotin-bound SA structures at near-atomic resolution using single-particle cryo-EM. We demonstrate that the method has the potential to determine the structures of molecules as small as 39 kDa.
Feed-forward regulation adaptively evolves via dynamics rather than topology when there is intrinsic noise
Authors: Xiong Kun , Lancaster Alex K. , Siegal Mark L. , Masel Joanna 
Published: June 2019

AbstractIn transcriptional regulatory networks (TRNs), a canonical 3-node feed-forward loop (FFL) is hypothesized to evolve to filter out short spurious signals. We test this adaptive hypothesis against a novel null evolutionary model. Our mutational model captures the intrinsically high prevalence of weak affinity transcription factor binding sites. We also capture stochasticity and delays in gene expression that distort external signals and intrinsically generate noise. Functional FFLs evolve readily under selection for the hypothesized function but not in negative controls. Interestingly, a 4-node “diamond” motif also emerges as a short spurious signal filter. The diamond uses expression dynamics rather than path length to provide fast and slow pathways. When there is no idealized external spurious signal to filter out, but only internally generated noise, only the diamond and not the FFL evolves. While our results support the adaptive hypothesis, we also show that non-adaptive factors, including the intrinsic expression dynamics, matter.
Room temperature terahertz semiconductor frequency comb
Authors: Lu Quanyong , Wang Feihu , Wu Donghai , Slivken Steven , Razeghi Manijeh 
Published: June 2019

AbstractA terahertz (THz) frequency comb capable of high-resolution measurement will significantly advance THz technology application in spectroscopy, metrology and sensing. The recently developed cryogenic-cooled THz quantum cascade laser (QCL) comb has exhibited great potentials with high power and broadband spectrum. Here, we report a room temperature THz harmonic frequency comb in 2.2 to 3.3 THz based on difference-frequency generation from a mid-IR QCL. The THz comb is intracavity generated via down-converting a mid-IR comb with an integrated mid-IR single mode based on distributed-feedback grating without using external optical elements. The grating Bragg wavelength is largely detuned from the gain peak to suppress the grating dispersion and support the comb operation in the high gain spectral range. Multiheterodyne spectroscopy with multiple equally spaced lines by beating it with a reference Fabry-Pérot comb confirms the THz comb operation. This type of THz comb will find applications to room temperature chip-based THz spectroscopy.
Posterior samples of the parameters of binary black holes from Advanced LIGO, Virgo’s second observing run
Authors: De Soumi , Biwer Christopher M. , Capano Collin D. , Nitz Alexander H. , Brown Duncan A. 
Published: June 2019

AbstractThis paper presents a parameter estimation analysis of the seven binary black hole mergers—GW170104, GW170608, GW170729, GW170809, GW170814, GW170818, and GW170823—detected during the second observing run of the Advanced LIGO and Virgo observatories using the gravitational-wave open data. We describe the methodology for parameter estimation of compact binaries using gravitational-wave data, and we present the posterior distributions of the inferred astrophysical parameters. We release our samples of the posterior probability density function with tutorials on using and replicating our results presented in this paper.
M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis
Authors: Essone Paulin N. , Leboueny Marielle , Maloupazoa Siawaya Anicet Christel , Alame-Emane Amel Kévin , Aboumegone Biyogo Oriane Cordelia , Dapnet Tadatsin Patrice Hemery , Mveang Nzoghe Amandine , Essamazokou Dimitri Ulrich , Mvoundza Ndjindji Ofilia , Padzys Guy-Stéphane , Agnandji Selidji Todagbe , Takiff Howard , Gicquel Brigitte , Djoba Siawaya Joel Fleury 
Published: June 2019

AbstractTuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response toM.tuberculosisinfection, we conducted a cross-sectional study investigatingM.tuberculosisinfection status and comparing the release profiles of cytokines GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, TNF-α, in community controls (CCs) and healthy healthcare workers (HCWs) highly exposed to TB. Among HCWs and CCs, the probability of latentM.tuberculosis(LTB+) infection was respectively 5.4 (p = 0.002) and 3.4 (p = 0.006) times higher in men than women. The odds ratio of LTB infection was 4 times higher among HCWs in direct contact with active TB patients than other HCW (p = 0.01). Whole blood supernatant cytokine responses toM.tuberculosisantigens showed differential pro-inflammatory responses between HCWs and CCs. CCsLTB−had higher IL-1β responses than HCWsLTB−(p = 0.002). HCWsLTB+had significantly higher IL-8 responses toM.tuberculosisantigens than HCWsLTB−(p = 0.003) and CCsLTB−(p = 0.015). HCWsLTB+/−showed weak but positive TNF-α responses toM.tuberculosisantigen stimulation compared to CCsLTB+/−(p ≤ 0.015). Looking at T-helper (1 and 2) responses, HCWsLTB+and CCsLTB+had significantly higher IFN-γ and IL-2 responses compared to HCWsLTB−and CCsLTB−(p < [0.0001–0.003]). Also, TB antigen induced IL-5 secretion was significantly higher in HCWsLTB+and CCsLTB+than in non-infected CCsLTB−(p < [0.005–0.04]).M.tuberculosisantigen specific responses in HCWsLTB+varied based on active TB exposure gradient. HCWsLTB+who were highly exposed to active TB (≥3 hours per day) had significantly higher IFN-γ and IL-8 responses (p ≤ 0.02) than HCWsLTB+not in direct contact with active TB patients. HCWsLTB+working with active TB patients for 5 to 31 years had a significantly enhanced secretion of proinflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF-α) compared to HCWsLTB−(p < [0.0001–0.01]). Secretion of anti-inflammatory/Th2 cytokines IL-5 and IL-10 was also higher in HCWsLTB+than HCWsLTB−. In conclusion, LTBI individuals controlling theM.tuberculosisinfection have an enhanced TB specific Th1-cytokines/proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.
The association between physical activity and low back pain: a systematic review and meta-analysis of observational studies
Authors: Alzahrani Hosam , Mackey Martin , Stamatakis Emmanuel , Zadro Joshua Robert , Shirley Debra 
Published: June 2019

AbstractThe aim of this review was to investigate the association between total and domain-specific physical activity (PA) and non-specific low back pain (LBP) in adults. Seven databases were searched for cohort and cross-sectional studies. Pooled estimates of the association of medium and high levels PA and LBP, using the generic inverse-variance method with fixed- and random-effects models were calculated. Twenty-four studies (15 cohort and nine cross-sectional; 95,796 participants) were included. The pooled fully adjusted risk ratios (RR) from cohort studies comparing medium with lowest activity levels were 0.90 (95%CI 0.85 to 0.96) for total PA, and 0.90 (95%CI 0.85 to 0.96) for leisure-time PA (LTPA). The pooled RR comparing highest with lowest activity levels were 1.00 (95%CI 0.92 to 1.08) for total PA, and 1.01 (95%CI 0.93 to 1.10) for LTPA. The pooled fully adjusted odds ratios (OR) from cross-sectional studies comparing medium with lowest activity levels were 0.93 (95%CI 0.65 to 1.32) for total PA, and 0.77 (95%CI 0.62 to 0.96) for LTPA. The pooled OR comparing highest with lowest activity levels were 1.05 (95%CI 0.89 to 1.23) for total PA, and 0.85 (95%CI 0.79 to 0.93) for LTPA. PA seems to be associated with lower prevalence of LBP.
Social and Physiological Context can Affect the Meaning of Physiological Synchrony
Authors: Danyluck Chad , Page-Gould Elizabeth 
Published: June 2019

AbstractSurvival of many species, from insects and birds to human and non-human mammals, requires synchronized activity. Among humans, synchrony occurs even at the level of autonomic functioning; people interacting often show mutual, simultaneous changes in activity of the sympathetic or parasympathetic branches of the autonomic nervous system. Critically, autonomic reactivity predicts many mental states and, when synchronized, may reflect higher-order social processes like affiliation. Here, using data from 134 strangers interacting in pairs, we manipulated two features of social context to test their impact on synchrony in sympathetic and parasympathetic reactivity. Participants completed a knot-tying task within a collective reward (“cooperation”) or individual reward (“competition”) framework while conversing or not (“talking” condition). Autonomic reactivity varied by features of social context. Synchrony occurred across social contexts in both autonomic branches. We then examined how synchrony predicted affiliation. Sympathetic synchrony alone predicted affiliation yet social context and parasympathetic reactivity moderated associations between parasympathetic synchrony and affiliation. Thus, social and physiological context of parasympathetic synchrony predicted affiliation better than parasympathetic synchrony alone. We argue that social context and the degree of physiological reactivity underlying physiological synchrony, not the mere existence of physiological synchrony, are key to interpreting physiological synchrony as a social process.
Hurricane stalling along the North American coast and implications for rainfall
Authors: Hall Timothy M. , Kossin James P. 
Published: June 2019

AbstractThe average speed of tropical cyclone (TC) translation has slowed since the mid 20th century. Here we report that North Atlantic (NA) TCs have become increasingly likely to “stall” near the coast, spending many hours in confined regions. The stalling is driven not only by slower translation, but also by an increase in abrupt changes of direction. We compute residence-time distributions for TCs in confined coastal regions, and find that the tails of these distributions have increased significantly. We also show that TCs stalling over a region result in more rain on the region. Together, increased stalling and increased rain during stalls imply increased coastal rainfall from TCs, other factors equal. Although the data are sparse, we do in fact find a significant positive trend in coastal annual-mean rainfall 1948–2017 from TCs that stall, and we verify that this is due to increased stalling frequency. We make no attribution to anthropogenic climate forcing for the stalling or rainfall; the trends could be due to low frequency natural variability. Regardless of the cause, the significant increases in TC stalling frequency and high potential for associated increases in rainfall have very likely exacerbated TC hazards for coastal populations.
Best practices for analyzing large-scale health data from wearables and smartphone apps
Authors: Hicks Jennifer L. , Althoff Tim , Sosic Rok , Kuhar Peter , Bostjancic Bojan , King Abby C. , Leskovec Jure , Delp Scott L. 
Published: June 2019

AbstractSmartphone apps and wearable devices for tracking physical activity and other health behaviors have become popular in recent years and provide a largely untapped source of data about health behaviors in the free-living environment. The data are large in scale, collected at low cost in the “wild”, and often recorded in an automatic fashion, providing a powerful complement to traditional surveillance studies and controlled trials. These data are helping to reveal, for example, new insights about environmental and social influences on physical activity. The observational nature of the datasets and collection via commercial devices and apps pose challenges, however, including the potential for measurement, population, and/or selection bias, as well as missing data. In this article, we review insights gleaned from these datasets and propose best practices for addressing the limitations of large-scale data from apps and wearables. Our goal is to enable researchers to effectively harness the data from smartphone apps and wearable devices to better understand what drives physical activity and other health behaviors.
Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis
Authors: Shi Han , He Hongyan , Ojha Suvash Chandra , Sun Changfeng , Fu Juan , Yan Mao , Deng Cunliang , Sheng Yunjian 
Published: June 2019

Abstract
Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA&lt;0.01) and chronic hepatitis B (CHB)-related HCC (PA&lt;0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.
Near-Earth asteroids spectroscopic survey atIsaac NewtonTelescope
Authors: Popescu M. , Vaduvescu O. , de León J. , Gherase R. M. , Licandro J. , Boacă I. L. , Şonka A. B. , Ashley R. P. , Močnik T. , Morate D. , Predatu M. , De Prá M. , Fariña C. , Stoev H. , Díaz Alfaro M. , Ordonez-Etxeberria I. , López-Martínez F. , Errmann R. 
Published: June 2019

Context.The population of near-Earth asteroids (NEAs) shows a large variety of objects in terms of physical and dynamical properties. They are subject to planetary encounters and to strong solar wind and radiation effects. Their study is also motivated by practical reasons regarding space exploration and long-term probability of impact with the Earth.Aims.We aim to spectrally characterize a significant sample of NEAs with sizes in the range of ~0.25–5.5 km (categorized as large), and search for connections between their spectral types and the orbital parameters.Methods.Optical spectra of NEAs were obtained using theIsaac NewtonTelescope (INT) equipped with the IDS spectrograph. These observations are analyzed using taxonomic classification and by comparison with laboratory spectra of meteorites.Results.A total number of 76 NEAs were observed. We spectrally classified 44 of them as Q/S-complex, 16 as B/C-complex, eight as V-types, and another eight belong to the remaining taxonomic classes. Our sample contains 27 asteroids categorized as potentially hazardous and 31 possible targets for space missions including (459872) 2014 EK24, (436724) 2011 UW158, and (67367) 2000 LY27. The spectral data corresponding to (276049) 2002 CE26 and (385186) 1994 AW1 shows the 0.7μm feature which indicates the presence of hydrated minerals on their surface. We report that Q-types have the lowest perihelia (a median value and absolute deviation of 0.797 ± 0.244 AU) and are systematically larger than the S-type asteroids observed in our sample. We explain these observational evidences by thermal fatigue fragmentation as the main process for the rejuvenation of NEA surfaces.Conclusions.In general terms, the taxonomic distribution of our sample is similar to the previous studies and matches the broad groups of the inner main belt asteroids. Nevertheless, we found a wide diversity of spectra compared to the standard taxonomic types.
Umgang mit Spannungen und Krisen in der therapeutischen Beziehung: Erste Erfahrungen mit einem handlungsorientierten Ausbildungs- und Supervisionskonzept
Authors: Gumz Antje , Reuter Laurence , Flückiger Christoph , Marx Christopher , Rugenstein Kai , Schlipfenbacher Carina , Schmidt Lisa , Munder Thomas 
Published: June 2019

Zusammenfassung
Ziele Das allianzfokussierte Training (AFT) 1 schult therapeutische Kompetenzen, die für den Umgang mit Spannungen und Krisen in der therapeutischen Beziehung hilfreich sind unter Einsatz von Videoaufzeichnungen und Rollenspielen. Ziel der von der Heigl-Stiftung geförderten Pilotstudie war es, erste klinische Erfahrungen und Ergebnisse mit AFT im deutschsprachigen Raum vorzustellen und eine RCT-Folgestudie vorzubereiten.
Methoden 7 Ausbildungskandidaten nahmen teil. Therapien von 15 Patienten mit depressiver Störung wurden analysiert.
Ergebnisse und Schlussfolgerung AFT wurde als sehr hilfreich für die professionelle Entwicklung und den Umgang mit Spannungen und Krisen erlebt. Die therapeutische Kompetenz verbesserte sich signifikant im Selbsterleben und aus Beobachterperspektive. Die Ergebnisse sprechen dafür, dass AFT eine vielversprechende Möglichkeit zur Verbesserung der Psychotherapieausbildung ist und sich die Durchführung eines RCT zum Nachweis der Wirksamkeit lohnt.
Nonthyroidal Illness Syndrome in Ischaemic Stroke Patients is
Associated with Increased Mortality
Authors: Taroza Saulius , Rastenytė Daiva , Podlipskytė Aurelija , Kazlauskas Henrikas , Mickuvienė Narseta 
Published: June 2019

Abstract
Background Results of studies on associations between triiodothyronine
serum levels and mortality after acute ischemic stroke (AIS) are inconsistent.
Therefore, the aim of this prospective study was to evaluate links between serum
levels of thyroid axis associated hormones and all-cause mortality during 1 year
after AIS.
Methods and results This study involved 255 patients with AIS. Patients
were divided into two groups: those who survived 1 year after their index stroke
and those who not, and by quartiles of free triiodothyronine (FT3) and
ΔFT3 (difference between basal FT3 and repeated FT3 on discharge)
hormone serum concentrations. To assess serum levels of thyroid stimulating
hormone (TSH), FT3 and free tetraiodothyronine (FT4), venous blood was taken
from all included patients on admission to hospital. On discharge, blood tests
were repeated for 178 (69.8%) patients. Study endpoints were overall
mortality within 30, 90 and 365 days after AIS.
Results Compared with the survivals, those who died had significantly
lower mean FT3, FT3/FT4 ratio in all periods and lower median TSH within
30 days. Higher FT3 serum levels versus lower, even after adjustment for
included important variables, remained significant for lower odds of death
within 365 days after AIS (OR=0.57; 95% CI: 0.33–0.97,
p=0.04), but added insignificant additional predictive value
to the NIHSS score or age. Kaplan–Meier survival curves demonstrated
that the first FT3 quartile was significantly associated with increased
mortality compared with all other quartiles within 365 days after AIS. With
ΔFT3 quartiles no such association was found.
Conclusions. Higher FT3 levels on admission versus lower are
significantly associated with lower mortality within 365 days after AIS. FT3
serum levels changes over time didn’t show any association with
mortality within first year.