bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact and risk factors of cancer‐associated thrombosis events in stage‐IV cancer patients treated with immune checkpoint inhibitors
Authors: Kewan Tariq , Ko Taeyeong , Flores Monica , Sallam Yacoub , Haddad Abdo , Daw Hamed 
Published: February 2021

AbstractBackgroundCancer‐associated thrombosis (CAT) is a major cause of mortality in cancer patients. Immune checkpoint inhibitors (ICIs) have been associated with multiple side effects including CAT. The aim of this study is to investigate risk factors and prognostic impact associated with CAT events during ICIs treatment.MethodsThis is a multi‐center retrospective study that included stage IV cancer patients treated with ICIs.ResultsWe identified 552 cancer patients treated with ICIs. During follow‐up time, 58 (10.5%) patients developed 67 venous thromboembolism (VTE) events while on ICIs. Anticoagulation use at the time of ICIs treatment start was associated with significantly higher VTE incidence rate (IRR: 2.23). No significant difference in VTE IRR was observed depending on response to ICIs treatment, aspirin use, or Khorana VTE risk score. Melanoma as primary cancer, Khorana score, ECOG status, and anemia at baseline were able to predict mortality.ConclusionsThe incidence of CAT in stage‐IV cancer patients treated with ICIs was higher in our study compared to previous reports. Control group of patients who did not receive ICIs is needed for better identification of CAT risk factors. Khorana score was a good predictor of mortality but not CAT risk and needs to be further validated in a homogenous group of patients.
Propagation and update of auditory perceptual priors through alpha and theta rhythms
Authors: Ho Hao Tam , Burr David C. , Alais David , Morrone Maria Concetta 
Published: February 2021

AbstractTo maintain a continuous and coherent percept over time, the brain makes use of past sensory information to anticipate forthcoming stimuli. We recently showed that auditory experience of the immediate past is propagated through ear‐specific reverberations, manifested as rhythmic fluctuations of decision bias at alpha frequencies. Here, we apply the same time‐resolved behavioural method to investigate how perceptual performance changes over time under conditions of stimulus expectation and to examine the effect of unexpected events on behaviour. As in our previous study, participants were required to discriminate the ear‐of‐origin of a brief monaural pure tone embedded in uncorrelated dichotic white noise. We manipulated stimulus expectation by increasing the target probability in one ear to 80%. Consistent with our earlier findings, performance did not remain constant across trials, but varied rhythmically with delay from noise onset. Specifically, decision bias showed a similar oscillation at ~9 Hz, which depended on ear congruency between successive targets. This suggests rhythmic communication of auditory perceptual history occurs early and is not readily influenced by top‐down expectations. In addition, we report a novel observation specific to infrequent, unexpected stimuli that gave rise to oscillations in accuracy at ~7.6 Hz one trial after the target occurred in the non‐anticipated ear. This new behavioural oscillation may reflect a mechanism for updating the sensory representation once a prediction error has been detected.
Detection of the deep biosphere in metamorphic rocks from the Chinese continental scientific drilling
Authors: Dai Xin , Wang Yuanliang , Luo Liqiang , Pfiffner Susan M. , Li Guangyu , Dong Zhiyang , Xu Zhiqin , Dong Hailiang , Huang Li 
Published: February 2021

AbstractIt is generally accepted that there is a vast, well‐populated biosphere in the subsurface, but the depth limit of the terrestrial biosphere has yet to be determined, largely because of the lack of access to the subsurface. Here as part of the Chinese Continental Scientific Drilling (CCSD) project in eastern China, we acquired continuous rock cores and endeavored to probe the depth limit of the biosphere and the depth‐dependent distribution of microorganisms at a geologically unique site, that is, a convergent plate boundary. Microbiological analyses of ultra‐high‐pressure metamorphic rock cores taken from the ground surface to 5,158‐meter reveal that microbial distribution was continuous up to a depth of ~4,850 m, where temperature was estimated to be ~137°C. The metabolic state of these organisms at such great depth remains to be determined. Microbial abundance, ranging from 103 to 108 cells/g, was also related to porosity, but not to the depth and rock composition. In addition, microbial diversity systematically decreased with depth. Our results support the notion that temperature is a key factor in determining the lower limit of the biosphere in the continental subsurface.
The technocratic tendencies of economists in government bureaucracy
Authors: Christensen Johan , Mandelkern Ronen 
Published: February 2021

AbstractEconomists are by many accounts the most influential group of experts in contemporary political decision‐making. While the literature on the power of economists mostly focuses on the policy ideas of economic experts, some recent studies suggest that economists also hold particular technocratic ideas about the policy process. The article systematically tests this argument. Focusing on economists within government bureaucracy, the study is based on a quantitative analysis of a large‐scale survey of Norwegian ministerial civil servants. It finds that economists are more likely to hold technocratic role perceptions than officials with other educational backgrounds only if they work in the finance ministry or in higher administrative grades. The findings contribute to scholarship on the political sway of economists and to debates about technocracy and the technocratic views of civil servants.
Baseline CHA2DS2‐VASc score and prognosis in octogenarians with non‐ST segment elevation acute coronary syndrome
Authors: Díez‐Villanueva Pablo , Vera Alberto , Ariza‐Solé Albert , Formiga Francesc , Martínez‐Sellés Manuel , Alegre Oriol , Sanchís Juan , Marín Francisco , Vidán Maite , López‐Palop Ramon , Abu‐Assi Emad , Bueno Héctor , Alfonso Fernando ,   the LONGEVO‐SCA registry investigators
Published: February 2021

AbstractBackgroundCHA2DS2‐VASc Score is widely used to predict thromboembolic risk in patients with Atrial Fibrillation (AF). We sought to study if this score predicts outcomes in elderly patients with Non‐ST segment Elevation Acute Coronary Syndromes (NSTEACS).MethodsThe multicenter LONGEVO‐SCA prospective registry included 532 unselected patients with NSTEACS aged ≥80 years. Data to calculate CHA2DS2‐VASc Score were available in 523 patients (98.3%). They were classified according to CHA2DS2‐VASc Score: group 1 (score ≤ 4), and 2 (5‐9). We studied outcomes in terms of mortality or readmission at 6 months follow‐up.ResultsA total of 266 patients (51%) had a high CHA2DS2‐VASc Score (group 2). They were more often women, with more cardiovascular risk factors, such as hypertension or diabetes mellitus, and history of previous stroke and cardiovascular disease and heart failure (all, P = .001). Geriatric syndromes (Barthel Index, Lawton Brody, cognitive impairment, and frailty) and Charlson Index were worse in this group (all, P = .001). They had poorer clinical status on admission, with worse Killip class and lower left ventricle ejection fraction (all, P = .001), and developed new‐onset AF more often during admission (12.4% vs. 6.6%, P = .024). At six months follow‐up, patients in group 2 had higher reinfarction, all‐cause mortality, and mortality or readmission rates. A CHA2DS2‐VASc Score > 4 was associated with mortality or readmission at 6 months (HR 2.07, P < .001). However, after adjusting for potential confounders, this last association was not significant (P = .175).ConclusionsA CHA2DS2‐VASc Score > 4 is present in half of octogenarians with NSTEACS and is associated with poorer outcomes. However, it is not an independent predictor of events and should not replace recommended tools for risk prediction in this setting.
Ontogeny and heterogeneity of innate lymphoid cells and the noncoding genome
Authors: Michieletto Michaël F. , Henao‐Mejia Jorge 
Published: February 2021

AbstractSince their discovery a decade ago, it has become evident that innate lymphoid cells (ILCs) play critical roles in protective immune responses against intracellular and extracellular pathogens but are also central regulators of epithelial barrier integrity and tissue homeostasis. ILCs populate almost every tissue in mammalian organisms; therefore, not surprisingly, dysregulation of their functions contributes to the development and progression of multiple inflammatory and metabolic diseases. Our knowledge of the transcriptional programs governing the development, differentiation, and functions of the different groups of ILCs has increased dramatically in the last ten years. However, with the advent of new technologies, an unprecedented level of heterogeneity, plasticity, and developmental complexity has started to be revealed. In this review, we highlight recent advances in our understanding of ILC development and their biological functions. In particular, we aim to emphasize how our increasing knowledge of the chromatin landscape and the noncoding genome of these innate lymphocytes is allowing us to better understand their development and functions in different contexts during homeostasis and inflammation. Moreover, we propose that the design of more refined genetic tools to study tissue‐specific ILCs and their functions can be accomplished by leveraging our understanding of how specific noncoding elements of the genome regulate gene expression in ILCs.
Not too fat to fight: The emerging role of macrophage fatty acid metabolism in immunity to Mycobacterium tuberculosis
Authors: Laval Thomas , Chaumont Lise , Demangel Caroline 
Published: February 2021

AbstractWhile the existence of a special relationship between Mycobacterium tuberculosis (Mtb) and host lipids has long been known, it remains a challenging enigma. It was clearly established that Mtb requires host fatty acids (FAs) and cholesterol to produce energy, build its distinctive lipid‐rich cell wall, and produce lipid virulence factors. It was also observed that in infected hosts, Mtb constantly resides in a FA‐rich environment that the pathogen contributes to generate by inducing a lipid‐laden “foamy” phenotype in host macrophages. These observations and the proximity between lipid droplets and phagosomes containing bacteria within infected macrophages gave rise to the hypothesis that Mtb reprograms host cell lipid metabolism to ensure a continuous supply of essential nutrients and its long‐term persistence in vivo. However, recent studies question this principle by indicating that in Mtb‐infected macrophages, lipid droplet formation prevents bacterial acquisition of host FAs while supporting the production of FA‐derived protective lipid mediators. Further, in vivo investigations reveal discrete macrophage phenotypes linking the FA metabolisms of host cell and intracellular pathogen. Notably, FA storage within lipid droplets characterizes both macrophages controlling Mtb infection and dormant intracellular Mtb. In this review, we integrate findings from immunological and microbiological studies illustrating the new concept that cytoplasmic accumulation of FAs is a metabolic adaptation of macrophages to Mtb infection, which potentiates their antimycobacterial responses and forces the intracellular pathogen to shift into fat‐saving, survival mode.
A decision tool based on bilevel optimization for the allocation of water resources in a hierarchical system
Authors: Calvete Herminia I. , Galé Carmen , Iranzo José A. , Mateo Pedro M. 
Published: February 2021

AbstractThis paper addresses the optimal allocation of water among competing stakeholders during a finite planning horizon. We focus on those water systems where there are two levels of decision making organized according to a hierarchical framework. At the upper level, a central authority allocates water to demand points having regard to environmental and sustainability issues as well as balancing water users' supply/demand. At the lower level of the hierarchy, demand point managers allocate water to users prioritizing economic strategies. On the other hand, when it comes to allocating limited resources that affect public welfare, the authority in charge can also use different political instruments such as fees to influence the decisions made at those levels of decision making that are not directly within its competence. We propose a multiobjective multifollower bilevel optimization problem that aims to fulfill the central authority goals while including the reaction of the demand point managers in terms of optimization problems as constraints. Using the well‐known Karush–Kuhn–Tucker approach, we transform the bilevel model into an equivalent multiobjective mixed‐integer single‐level model for which we provide tight big‐M values. For the purpose of showing the versatility of the model, extensive computational experiments on a set of instances have been carried out. The results show that the optimization problem can be solved to optimality in small computing times using off‐the‐shelf mixed‐integer solvers even for complex water systems and long planning periods. In addition, they illustrate the effect of imposing fees on the achievement of the central authority's objectives.
Efficacy of medical and ablation therapy for inappropriate sinus tachycardia: A single‐center experience
Authors: Shabtaie Samuel A. , Witt Chance M. , Asirvatham Samuel J. 
Published: February 2021

AbstractBackgroundEffective therapy for inappropriate sinus tachycardia (IST) remains challenging with high rates of treatment failure and symptom recurrence. It is uncertain how effective pharmacotherapy and procedural therapy are long‐term, with poor response to medical therapy in general.MethodsWe retrospectively reviewed all patients with the diagnosis of IST at a tertiary academic medical center from 1998 to 2018. We extracted data related to prescribing patterns and symptom response to medical therapy and sinus node modification (SNM), assessing efficacy and periprocedural complication rates.ResultsA total of 305 patients with a formal diagnosis of IST were identified, with 259 (84.9%) receiving at least one prescription medication related to the condition. Beta‐blockers were the most commonly used medication (n = 245), with a majority of patients reporting no change or worsening of symptoms, and poor response was seen to other medication classes. Improvement was seen significantly more often with ivabradine than beta blockers, though the sample size was limited (p = .003). Fifty‐five patients (18.0% of all IST patients), mean age 32.0 ± 9.1 years, underwent a SNM procedure, with an average of 1.8 ± 0.9 procedures per patient. Acute symptomatic improvement (<6 months) was seen in 58.2% of patients. Long‐term complete resolution of symptoms was seen in 5.5% of patients, modest improvement in 29.1%, and no long‐term benefit was seen in 65.5% of patients.ConclusionsAmong all medical therapies, there were high rates of treatment failure or symptom worsening in over three‐quarters of patients in our study. Ivabradine was most beneficial, though the sample size was small. While most patients receiving SNM ablation for IST perceive an acute symptomatic improvement, almost two‐thirds of patients have no long‐term improvement, and resolution of symptoms is quite rare. AV node ablation with pacemaker implantation following lack of response to SNM offered increased success, though the sample size was limited.
Association of plant‐based diet and type 2 diabetes mellitus in Chinese rural adults: The Henan Rural Cohort Study
Authors: Yang Xiu , Li Yuqian , Wang Chongjian , Mao Zhenxing , Chen Yu , Ren Pengfei , Fan Mengying , Cui Songyang , Niu Kailin , Gu Ruohua , Li Linlin 
Published: February 2021

AbstractAims/IntroductionStudies have found that a plant‐based diet was associated with a lower risk of type 2 diabetes, but evidence is scarce on such associations in China. The aim of this study was to investigate whether a plant‐based diet is related to a lower risk of type 2 diabetes among Chinese adults.Materials and MethodsA total of 37,985 participants were enrolled from the Henan Rural Cohort Study. An overall plant‐based diet index (PDI) was created by assigning positive and reverse scores to 12 commonly consumed food groups. Multivariate logistic regression models and restricted cubic spline analysis were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI).ResultsAfter multivariable adjustment, the risk of type 2 diabetes was inversely associated with the PDI (extreme‐quartile OR = 0.88, 95% CI: 0.79–0.98; P = 0.027), the risk associated with a 1 standard deviation (SD) increase in PDI was 4% lower (95% CI, 0.93–1.00; P trend = 0.043) for type 2 diabetes. Moreover, the odds of type 2 diabetes was decreased with an increment of PDI after fitting restricted cubic splines (P trend < 0.01).ConclusionsAmong Chinese populations, diets higher in plant foods and lower in animal foods were associated with a reduced risk of type 2 diabetes.
Relationship between sensitive skin and sleep disorders, fatigue, dust, sweating, food, tobacco consumption or female hormonal changes: Results from a worldwide survey of 10 743 individuals
Authors: Misery L. , Morisset S. , Séité S. , Brenaut E. , Ficheux A.‐S. , Fluhr J. W. , Delvigne V. , Taieb C. 
Published: February 2021

AbstractBackgroundSensitive skin is related to environmental factors.ObjectivesWe aimed to investigate the roles of poorly known associated and triggering factors on sensitive skin in a large global population.MethodsA survey was administrated to a representative sample of the adult population aged 18–75 years in five different countries (Brazil, China, France Russia, and the United States). All participants answered a web‐based questionnaire on sociodemographic characteristics, sensitive skin and environmental factors.ResultsAmong the 10 743 included individuals (5285 men and 5458 women), 48.2% declared that they had sensitive skin. The group with sensitive skin reported significant increases in fatigue, dust or sweating and to a lesser extent food or tobacco consumption. The members of this group also declared that they experienced more sleep disorders than individuals without sensitive skin. Sensitive skin was very frequent in pregnant women, women with painful menstruations or women using contraceptive pills.ConclusionsThis large cohort study identified new factors, including female hormonal status, fatigue, sleep disorders and food, associated with sensitive skin. These associations suggest that sensitive skin is not restricted to an epidermal disorder but may be included in a larger context. The identified factors are potential upstream drivers of neurogenic inflammation in sensitive skin.
Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage
Authors: Vural S. , Baumgartner M. , Lichtner P. , Eckstein G. , Hariry H. , Chen W.C. , Ruzicka T. , Melnik B. , Plewig G. , Wagner M. , Giehl K.A. 
Published: February 2021

AbstractBackgroundHidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland‐bearing skin in the axilla, groin and under the breasts. Mutations of the gamma secretase gene complex, which is essential in the activation of Notch signalling pathways, were shown in some families with HS and in a few sporadic cases. Although an imbalance in Notch signalling is implicated in the pathogenesis, the exact mechanism of HS development is yet unknown.ObjectivesWe aim to investigate the genetic basis of HS by determining the presence of mutations of gamma secretase gene complex in a cohort of HS patients and by searching for a disease‐causing pathogenic variant in a multi‐generational HS family using parametric linkage analysis.MethodsThirty‐eight patients clinically diagnosed with HS were included in this study. All exons and exon–intron boundaries of the genes encoding gamma secretase complex consisting of six genes: APH1A, APH1B, PSENEN, NCSTN, PSEN1 and PSEN2 were sequenced by Sanger technique. Genetic mapping with parametric linkage analysis for the patients in the family was performed with eight affected and four healthy individuals. The logarithm of odds was calculated.ResultsIn a sporadic patient with early‐onset, severe lesions in axilla and groin, a novel single‐nucleotide deletion causing frameshift in exon 1 of the NCSTN gene was identified ((NM_015331.3): c.38delG, p.(Gly13Glufs*15)). The LOD score of 1.5 was never exceeded in any region of the genome, pointing towards intricate multi‐genic inheritance pattern within the affected family.ConclusionsThe gamma secretase gene complex mutations were rare in our cohort (3.2%). Besides, our analysis indicates a possible complex multi‐genic inheritance in a seemingly autosomal dominantly inherited large HS family. Genetics of both familial and sporadic HS may be complicated in most cases, and the role of other potential genes such as autoinflammatory and modifier genes as well as environmental factors may influence the pathogenesis.
High gene flow in polar cod (Boreogadus saida) from West‐Svalbard and the Eurasian Basin
Authors: Maes Sarah M. , Christiansen Henrik , Mark Felix C. , Lucassen Magnus , Van de Putte Anton , Volckaert Filip A.M. , Flores Hauke 
Published: February 2021

AbstractThe current and projected environmental change of the Arctic Ocean contrasts sharply with the limited knowledge of its genetic biodiversity. Polar cod Boreogadus saida (Lepechin, 1774) is an abundant circumpolar marine fish and ecological key species. The central role of polar cod in the Arctic marine food web warrants a better understanding of its population structure and connectivity. In this study, the genetic population structure of 171 juveniles, collected from several fjords off West‐Svalbard (Billefjorden, Hornsund and Kongsfjorden), the northern Sophia Basin and the Eurasian Basin of the Arctic Ocean, was analysed using nine DNA microsatellite loci. Genetic analyses indicated moderate to high genetic diversity, but absence of spatial population structure and isolation‐by‐distance, suggesting ongoing gene flow between the studied sampling regions. High levels of connectivity may be key for polar cod to maintain populations across wide spatial scales. The adaptive capacity of the species will be increasingly important to face challenges such as habitat fragmentation, ocean warming and changes in prey composition. In view of a limited understanding of the population dynamics and evolution of polar cod, a valuable next step to predict future developments should be an integrated biological evaluation, including population genomics, a life‐history approach, and habitat and biophysical dispersal modelling.