bluuebunny/crossref_metadata_2025_split huggingface dataset:
f‐Statistics estimation and admixture graph construction with Pool‐Seq or allele count data using the R package poolfstat
Authors: Gautier Mathieu , Vitalis Renaud , Flori Laurence , Estoup Arnaud 
Published: November 2021

AbstractBy capturing various patterns of the structuring of genetic variation across populations, ‐statistics have proved highly effective for the inference of demographic history. Such statistics are defined as covariances of SNP allele frequency differences among sets of populations without requiring haplotype information and are hence particularly relevant for the analysis of pooled sequencing (Pool‐Seq) data. We here propose a reinterpretation of the (and ) parameters in terms of probability of gene identity and derive from this unified definition unbiased estimators for both Pool‐Seq data and standard allele count data obtained from individual genotypes. We implemented these estimators in a new version of the R package poolfstat, which now includes a wide range of inference methods: (i) three‐population test of admixture; (ii) four‐population test of treeness; (iii) ‐ratio estimation of admixture rates; and (iv) fitting, visualization and (semi‐automatic) construction of admixture graphs. A comprehensive evaluation of the methods implemented in poolfstat on both simulated Pool‐Seq (with various sequencing coverages and error rates) and allele count data confirmed the accuracy of these approaches, even for the most cost‐effective Pool‐Seq design involving relatively low sequencing coverages. We further analysed a real Pool‐Seq data made of 14 populations of the invasive species Drosophila suzukii, which allowed refining both the demographic history of native populations and the invasion routes followed by this emblematic pest. Our new package poolfstat provides the community with a user‐friendly and efficient all‐in‐one tool to unravel complex population genetic histories from large‐size Pool‐Seq or allele count SNP data.
Chromosome‐level de novo genome assembly and whole‐genome resequencing of the threatened species Acanthochlamys bracteata (Velloziaceae) provide insights into alpine plant divergence in a biodiversity hotspot
Authors: Xu Bo , Liao Min , Deng Heng‐ning , Yan Chao‐chao , Lv Yun‐yun , Gao Yun‐dong , Ju Wen‐bin , Zhang Jun‐yi , Jiang Li‐sha , Li Xiong , Gao Xin‐fen 
Published: November 2021

AbstractThe Hengduan Mountains region is an important hotspot of alpine plant diversity and endemism. Acanthochlamys bracteata is a species of a threatened monotypic genus endemic to the Hengduan Mountains. In this study, we present a high‐quality, chromosome‐level reference genome for A. bracteata, constructed using long reads, short reads and Hi‐C technology. We characterized its genetic diversity, population structure, demographic history and gene flow by resequencing individuals collected across its distribution. Comparative genomics analyses based on sequence information from single‐copy orthologous genes revealed that A. bracteata and Dioscorea rotundata diverged ~104.5 million years ago. Whole‐genome resequencing based on population genetic analysis revealed that the division of the 14 populations into 10 distinct clusters reflected geographical divergence, and three separate high levels of gene flow occurred sequentially between isolated populations of the Hengduan Mountains, a finding which is consistent with the turnover between ice ages and interglacial periods. Our findings indicate that Quaternary climatic changes played an important role in shaping the genetic structure and demographic trajectories of A. bracteata, and provide critical insights into the genetic status and evolutionary history of this poorly understood species, and possibly other alpine plants with a similar distribution. This study demonstrates the usefulness of population genomics for evaluating the effects of past climatic changes and identifying conservation units for the conservation and management of threatened species. Our high‐quality genome represents a valuable resource for future studies of the underlying molecular mechanisms of adaptive evolution and provides insight for further comparative genomic analysis with other Velloziaceae species.
Clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in advanced ALK+NSCLC: A multicenter retrospective analysis in China
Authors: Zou Zihua , Hao Xuezhi , Zhang Cuiying , Li Haojing , Dong Guilan , Peng Yumei , Ma Kewei , Guo Ye , Shan Li , Zhang Yan , Liang Li , Gu Yangchun , Xing Puyuan , Li Junling 
Published: December 2021

AbstractBackgroundThere is limited data on the clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in a real‐world setting for Chinese patients with advanced ALK+ NSCLC.MethodsThe medical records of patients who received sequential therapy with first‐line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK‐TKIs) were collected from six centers in China. Combined time treatment to failure (C‐TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause.ResultsA total of 61 patients were included in our study. Fifty‐two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK‐TKIs compared with those without (10.4 vs. 3.1 m, p = 0.0018, HR = 0.08). With a median follow‐up of 34.3 months, C‐TTF was 39.2 months and estimated 5‐year OS was 68.6% in the overall population.ConclusionSequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.
Product Market Competition and Voluntary Corporate Social Responsibility Disclosures†
Authors: Ryou Ji Woo , Tsang Albert , Wang Kun Tracy 
Published: November 2021

ABSTRACTThis study examines whether and how firms' voluntary forward‐looking nonfinancial disclosure, specifically their corporate social responsibility (CSR) disclosure, is associated with the intensity of product market competition (PMC). Despite the importance of the proprietary cost argument in explaining corporate disclosure incentives, there is little empirical evidence of the relationship between firms' proprietary cost concerns and their voluntary nonfinancial disclosure decisions. Using a reduction in industry‐level import tariffs as an exogenous shock to competition intensity, we find that the likelihood, frequency, and length of stand‐alone CSR reports decrease in response to heightened PMC. We also find that higher PMC intensity is associated with a reduced likelihood of CSR disclosure with external assurance, CSR disclosure in accordance with the Global Reporting Initiative guidelines, and CSR disclosure integrated with financial statements. Our results are robust to multiple alternative measures of PMC—namely, the level of nonprice competition, product similarity, and managers' perceptions of competition. Further analysis suggests that firms facing intense competition tend to commit more resources to advertising activities after reducing their CSR disclosure, presumably to mitigate the effect of this reduction. Overall, our findings suggest that proprietary cost concerns reduce firms' incentive to report their competition‐sensitive CSR activities.
Relationship between electrocardiogram‐based features and personality traits: Machine learning approach
Authors: Boljanić Tanja , Miljković Nadica , Lazarevic Ljiljana B. , Knezevic Goran , Milašinović Goran 
Published: November 2021

AbstractBackgroundBased on the known relationship between the human emotion and standard surface electrocardiogram (ECG), we explored the relationship between features extracted from standard ECG recorded during relaxation and seven personality traits (Honesty/humility, Emotionality, eXtraversion, Agreeableness, Conscientiousness, Openness, and Disintegration) by using the machine learning (ML) approach which learns from the ECG‐based features and predicts the appropriate personality trait by adopting an automated software algorithm.MethodsA total of 71 healthy university students participated in the study. For quantification of 62 ECG‐based parameters (heart rate variability, as well as temporal and amplitude‐based parameters) for each ECG record, we used computation procedures together with publicly available data and code. Among 62 parameters, 34 were segregated into separate features according to their diagnostic relevance in clinical practice. To examine the feature influence on personality trait classification and to perform classification, we used random forest ML algorithm.ResultsClassification accuracy when clinically relevant ECG features were employed was high for Disintegration (81.3%) and Honesty/humility (75.0%) and moderate to high for Openness (73.3%) and Conscientiousness (70%), while it was low for Agreeableness (56.3%), eXtraversion (47.1%), and Emotionality (43.8%). When all calculated features were used, the classification accuracies were the same or lower, except for the eXtraversion (52.9%). Correlation analysis for selected features is presented.ConclusionsResults indicate that clinically relevant features might be applicable for personality traits prediction, although no remarkable differences were found among selected groups of parameters. Physiological associations of established relationships should be further explored.
Perinatal outcome and need of care for term asphyxiated newborns without moderate or severe hypoxic‐ischemic encephalopathy
Authors: Bower Alexandra , Lorain Perrine , Kayem Gilles , Dommergues Marc , Foix‐L’Hélias Laurence , Guellec Isabelle 
Published: November 2021

AbstractAimBirth asphyxia can lead to organ dysfunction, varying from isolated biological acidosis to hypoxic‐ischemic encephalopathy (HIE). Pathophysiology of moderate or severe HIE is now well known and guidelines exist regarding the care required in this situation. However, for newborns without moderate or severe HIE, no consensus is available. Our objective was to describe the immediate neonatal consequences and need for care of asphyxiated newborns without moderate or severe HIE.MethodsMulticentre retrospective study from January 2015 to December 2017 in two academic centres, including neonates ≥37 gestational weeks with pathological foetal acidemia (umbilical arterial pH<7.00 and/or lactate≥10 mmol/L).ResultsAmong 18 550 births, 161 (0.9%) had pathological foetal acidemia. 142 (88.0%) were not diagnosed with moderate or severe HIE. Among them, 82 (58.0%) were hospitalised. 13 (9.0%) had respiratory failure and required nutritional support. 100 (70.0%) underwent blood sampling, which showed at least one biological anomaly in 66 (66.0%) of cases.ConclusionNewborns born with pathological foetal acidemia without the occurrence of moderate or severe HIE had metabolic disorders and could need organ support. A prospective study describing this vulnerable population would help to establish consensus guidelines for the management of this population.
High anticholinergic burden at admission associated with in‐hospital mortality in older patients: A comparison of 19 different anticholinergic burden scales
Authors: Lisibach Angela , Gallucci Giulia , Beeler Patrick E. , Csajka Chantal , Lutters Monika 
Published: November 2021

AbstractAlthough no gold standard exists to assess a patient's anticholinergic burden, a review identified 19 anticholinergic burden scales (ABSs). No study has yet evaluated whether a high anticholinergic burden measured with all 19 ABSs is associated with in‐hospital mortality and length of stay (LOS). We conducted a cohort study at a Swiss tertiary teaching hospital using patients' electronic health record data from 2015–2018. Included were patients aged ≥65 years, hospitalised ≥48 h without stays and >24 h in intensive care. Patients' cumulative anticholinergic burden score was classified using a binary (<3: low, ≥3: high) and categorical approach (0: no, 0.5–3: low, ≥3: high). In‐hospital mortality and LOS were analysed using multivariable logistic and linear regression, respectively. We included 27,092 patients (mean age 78.0 ± 7.5 years, median LOS 6 days). Of them, 913 died. Depending on the evaluated ABS, 1370 to 17,035 patients were exposed to anticholinergics. Patients with a high burden measured by all 19 ABSs were associated with a 1.32‐ to 3.03‐fold increase in in‐hospital mortality compared with those with no/low burden. We obtained similar results for LOS. To conclude, discontinuing drugs with anticholinergic properties (score ≥3) at admission might be a targeted intervention to decrease in‐hospital mortality and LOS.
Risk factors and natural history of parastomal hernia after radical cystectomy and ileal conduit
Authors: Ghoreifi Alireza , Allgood Evan , Whang Gilbert , Douglawi Antoin , Yu Wenhao , Cai Jie , Miranda Gus , Aron Monish , Schuckman Anne , Desai Mihir , Gill Inderbir , Daneshmand Siamak , Duddalwar Vinay , Djaladat Hooman 
Published: November 2021

ObjectiveTo investigate the incidence, risk factors and natural history of parastomal hernia (PSH).Materials and MethodsWe reviewed the records of patients who underwent radical cystectomy (RC) and ileal conduit (IC) procedure between 2007 and 2020. Patients who had available follow‐up computed tomography (CT) imaging were included in this study. All CT scans were re‐reviewed for detection of PSH according to Moreno‐Matias classification. Patients who developed hernia were followed up and classified into stable or progressive (defined as radiological upgrading and/or need for surgical intervention) groups. Multivariable Cox regression was performed to identify independent predictors of hernia development and progression.ResultsA total of 361 patients were included in this study. The incidence of radiological PSH was 30%, graded as I (56.5%), II (12%) and III (31.5%). The median (interquartile range [IQR]) time to radiological hernia was 8 (5–15) months. During the median (IQR) follow‐up of 27 (13–47) months in 108 patients with a hernia, 26% patients progressed. The median (IQR) time to progression was 12 (6–21) months. On multivariable analysis, female gender (hazard ratio [HR] 1.86), diabetes (HR 1.81), chronic obstructive pulmonary disease (COPD; HR 1.78) and higher body mass index (BMI; HR 1.07 for each unit) were independent predictors for radiological PSH development. No significant factor was found to be associated with hernia progression.ConclusionRadiological PSH after RC and IC occurred in 30% of patients, a quarter of whom progressed in a median time of 12 months. Female gender, diabetes, COPD and high BMI were independent predictors for radiological hernia development.
Establishing a sustainable healthcare environment in low‐ and middle‐income countries
Authors: Aslam Muhammad Z. , Trail Matthew , Cassell Ayun K. , Khan Abdul B. , Payne Steven 
Published: November 2021

AbstractThe dynamics of disease prevalence and healthcare systems continue to change dramatically in low‐ and middle‐income countries (LMICs). This is a result of multiple factors including the demands of an ageing population in the context of increasing life expectancy and the rise of non‐communicable diseases putting an additional burden on an already weak healthcare system. Further healthcare deficiency is attributable to additional factors such as low financial budgets, political conflicts and civil war, as well as continuing burden of communicable diseases, which are known to be the major risk to health in LMICs. Surgical needs largely remain unmet despite a Lancet report published in 2015. Various deficient aspects of healthcare systems need to be addressed immediately to provide any hope of creating a sustainable healthcare environment in the coming decades. These include developing strong primary and secondary care structures as well as strengthening tertiary care hospitals with an adequately trained healthcare workforce. The facilities required to improve patients’ access to healthcare cannot be developed and sustained solely within the local budget allocation and require major input from international organizations such as the World Bank and the World Health Organization as well as a chain of donor networks. To create and retain a local healthcare workforce, improved training and living conditions and greater financial security need to be provided. Finally, healthcare economics need to be addressed with financial models that can provide insurance and security to the underprivileged population to achieve universal health coverage, which remains the goal of several global organizations promoting equity in high‐standard healthcare provision.
A new class of 5‐HT2A/5‐HT2C receptor inverse agonists: Synthesis, molecular modeling, in vitro and in vivo pharmacology of novel 2‐aminotetralins
Authors: Casey Austen B. , Mukherjee Munmun , McGlynn Ryan P. , Cui Meng , Kohut Stephen J. , Booth Raymond G. 
Published: November 2021

Background and PurposeThe 5‐HT receptor subtypes 5‐HT2A and 5‐HT2C are important neurotherapeutic targets, though, obtaining selectivity over 5‐HT2B and H1 receptors is challenging. Here, we delineated molecular determinants of selective binding to 5‐HT2A and 5‐HT2C receptors for novel 4‐phenyl‐2‐dimethylaminotetralins (4‐PATs).Experimental ApproachWe synthesized 42 novel 4‐PATs with halogen or aryl moieties at the C(4)‐phenyl meta‐position. Affinity, function, molecular modeling and 5‐HT2A receptor mutagenesis studies were performed to understand structure–activity relationships at 5‐HT2‐type and H1 receptors. Lead 4‐PAT‐type 5‐HT2A/5‐HT2C receptor inverse agonists were compared with pimavanserin, a selective 5‐HT2A/5‐HT2C receptor inverse agonist approved to treat Parkinson's disease‐related psychosis, in the mouse head twitch response and locomotor activity assays, models relevant to antipsychotic drug development.Key ResultsMost 4‐PAT diastereomers in the (2S,4R)‐configuration bound non‐selectively to 5‐HT2A, 5‐HT2C and H1 receptors, with >100‐fold selectivity over 5‐HT2B receptors, whereas diastereomers in the (2R,4R)‐configuration bound preferentially to 5‐HT2A over 5‐HT2C receptors and had >100‐fold selectivity over 5‐HT2B and H1 receptors. Results suggest that G2385.42 and V2355.39 in 5‐HT2A receptors (conserved in 5‐HT2C receptors) are important for high affinity binding, whereas interactions with T1945.42 and W1584.56 determine H1 receptor affinity. The 4‐PAT analog (2S,4R)‐4‐(4'‐(dimethylamino)‐[1,1'‐biphenyl]‐3‐yl)‐N,N‐dimethyl‐1,2,3,4‐tetrahydronaphthalen‐2‐amine, (2S,4R)‐2k, a potent and selective 5‐HT2A/5‐HT2C receptor inverse agonist, had activity like pimavanserin in the mouse head twitch response assay but was distinct in not suppressing locomotor activity.Conclusions and ImplicationsThe novel 4‐PAT chemotype can yield selective 5‐HT2A/5‐HT2C receptor inverse agonists for antipsychotic drug development by optimizing ligand–receptor interactions in transmembrane domain 5. Chirality can be exploited to attain selectivity over H1 receptors, which may circumvent sedative effects.
Conservative Meshlet Bounds for Robust Culling of Skinned Meshes
Authors: Unterguggenberger J. , Kerbl B. , Pernsteiner J. , Wimmer M. 
Published: November 2021

AbstractFollowing recent advances in GPU hardware development and newly introduced rendering pipeline extensions, the segmentation of input geometry into small geometry clusters—so‐called meshlets—has emerged as an important practice for efficient rendering of complex 3D models. Meshlets can be processed efficiently using mesh shaders on modern graphics processing units, in order to achieve streamlined geometry processing in just two tightly coupled shader stages that allow for dynamic workload manipulation in‐between. The additional granularity layer between entire models and individual triangles enables new opportunities for fine‐grained visibility culling methods. However, in contrast to static models, view frustum and backface culling on a per‐meshlet basis for skinned, animated models are difficult to achieve while respecting the conservative spatio‐temporal bounds that are required for robust rendering results. In this paper, we describe a solution for computing and exploiting relevant conservative bounds for culling meshlets of models that are animated using linear blend skinning. By enabling visibility culling for animated meshlets, our approach can help to improve rendering performance and alleviate bottlenecks in the notoriously performance‐ and memory‐intensive skeletal animation pipelines of modern real‐time graphics applications.
Neural Sequence Transformation
Authors: Mukherjee Sabyasachi , Mukherjee Sayan , Hua Binh‐Son , Umetani Nobuyuki , Meister Daniel 
Published: November 2021

AbstractMonte Carlo integration is a technique for numerically estimating a definite integral by stochastically sampling its integrand. These samples can be averaged to make an improved estimate, and the progressive estimates form a sequence that converges to the integral value on the limit. Unfortunately, the sequence of Monte Carlo estimates converges at a rate of O(), where n denotes the sample count, effectively slowing down as more samples are drawn. To overcome this, we can apply sequence transformation, which transforms one converging sequence into another with the goal of accelerating the rate of convergence. However, analytically finding such a transformation for Monte Carlo estimates can be challenging, due to both the stochastic nature of the sequence, and the complexity of the integrand. In this paper, we propose to leverage neural networks to learn sequence transformations that improve the convergence of the progressive estimates of Monte Carlo integration. We demonstrate the effectiveness of our method on several canonical 1D integration problems as well as applications in light transport simulation.
Optimizing Ray Tracing of Trimmed NURBS Surfaces on the GPU
Authors: Sloup J. , Havran V. 
Published: November 2021

AbstractThe representation of geometric models by trimmed NURBS surfaces has become a standard in the CAD industry. In CAD applications, the rendering of surfaces is usually solved by tessellation followed up by z‐buffer rendering. Ray tracing of NURBS surfaces has not been widely used in industry due to its computational complexity that hinders achieving real‐time performance in practice. We propose novel methods achieving faster point location search needed by trimming in the context of ray tracing trimmed NURBS surfaces. The proposed 2D data structure based on kd‐trees allows for faster ray tracing while it requires less memory for its representation and less preprocessing time than previously published methods. Further, we show the current state of the art for ray tracing trimmed NURBS surfaces on a GPU. With careful design and implementation, the number of rays cast on a GPU may reach real‐time performance in the order of tens to hundreds of million rays per second for moderately to large complex scenes containing hundreds of thousands of NURBS surfaces and trimming curves.