bluuebunny/crossref_metadata_2025_split huggingface dataset:
A generalised analysis of similarities (ANOSIM) statistic for designs with ordered factors
Authors: Somerfield Paul J. , Clarke K. Robert , Gorley Ray N. 
Published: June 2021

AbstractIn the study of multivariate data, for example of change in ecological communities, ANOSIM is a robust non‐parametric hypothesis‐testing framework for differences in resemblances among groups of samples. RELATE is a non‐parametric Mantel test of the hypothesis of no relationship between two resemblance matrices. Details are given of the explicit link between the RELATE statistic, a Spearman rank correlation (ρ) between corresponding elements in the two resemblance matrices, and the ANOSIM statisticR, a scaled contrast between the among‐ and within‐group ranks. It is seen thatRcan equivalently be defined as the slope of the linear regression of ranked resemblances from observations against ranked distances among samples, the latter from a simple model matrix assigning the values 1 and 0 to between‐ and within‐group distances, respectively. Re‐defining this model matrix to represent ordered distances among groups leads naturally to a generalised ANOSIM statistic,RO, suitable for testing, for example, ordered factor levels in space or time, or an environmental or pollution gradient. Two variants of the generalised ANOSIM statistic are described, namelyROcwhere there are replicates within groups, andROswhere there are only single samples (no replicates) within groups, for which an ANOSIM test was not previously available. Three marine ecological examples using ANOSIM to analyse an ordered factor in one‐way designs are provided. These are: (1) changes in macrofaunal composition with increasing distance from an oil rig; (2) differences in phytal meiofaunal community composition with increasing macroalgal complexity; and (3) changes in average community composition of free‐living nematodes along a long‐term heavy metal gradient. Incorporating knowledge of an ordering structure is seen to provide more focussed, and thus stronger, ANOSIM tests, but inevitably risks losing power if that prior knowledge is incorrect or inappropriate.
Simulation‐based estimators of analytically intractable causal effects
Authors: Linero Antonio R. 
Published: June 2021

AbstractIn causal inference problems, one is often tasked with estimating causal effects which are analytically intractable functionals of the data‐generating mechanism. Relevant settings include estimating intention‐to‐treat effects in longitudinal problems with missing data or computing direct and indirect effects in mediation analysis. One approach to computing these effects is to use the g‐formula implemented via Monte Carlo integration; when simulation‐based methods such as the nonparametric bootstrap or Markov chain Monte Carlo are used for inference, Monte Carlo integration must be nested within an already computationally intensive algorithm. We develop a widely‐applicable approach to accelerating this Monte Carlo integration step which greatly reduces the computational burden of existing g‐computation algorithms. We refer to our method as accelerated g‐computation (AGC). The algorithms we present are similar in spirit to multiple imputation, but require removing within‐imputation variance from the standard error rather than adding it. We illustrate the use of AGC on a mediation analysis problem using a beta regression model and in a longitudinal clinical trial subject to nonignorable missingness using a Bayesian additive regression trees model.
Connexin32 activates necroptosis through Src‐mediated inhibition of caspase 8 in hepatocellular carcinoma
Authors: Xiang Yu‐ke , Peng Fu‐hua , Guo Yun‐quan , Ge Hui , Cai Shao‐yi , Fan Li‐xia , Peng Yue‐xia , Wen Hao , Wang Qin , Tao Liang 
Published: June 2021

AbstractNecroptosis is an alternative form of programmed cell death that generally occurs under apoptosis‐deficient conditions. Our previous work showed that connexin32 (Cx32) promotes the malignant progress of hepatocellular carcinoma (HCC) by enhancing the ability of resisting apoptosis in vivo and in vitro. Whether triggering necroptosis is a promising strategy to eliminate the apoptosis‐resistant HCC cells with high Cx32 expression remains unknown. In this study, we found that Cx32 expression was positively correlated with the expression of necroptosis protein biomarkers in human HCC specimens, cell lines, and a xenograft model. Treatment with shikonin, a well‐used necroptosis inducer, markedly caused necroptosis in HCC cells. Interestingly, overexpressed Cx32 exacerbated shikonin‐induced necroptosis, but downregulation of Cx32 alleviated necroptosis in vitro and in vivo. Mechanistically, Cx32 was found to bind to Src and promote Src‐mediated caspase 8 phosphorylation and inactivation, which ultimately reduced the activated caspase 8‐mediated proteolysis of receptor‐interacting serine‐threonine protein kinase 1/3, the key molecule for necroptosis activation. In conclusion, we showed that Cx32 contributed to the activation of necroptosis in HCC cells through binding to Src and then mediating the inactivation of caspase 8. The present study suggested that necroptosis inducers could be more favorable than apoptosis inducers to eliminate HCC cells with high expression of Cx32.
Rational design of novel N‐alkyl amine analogues of noscapine, their chemical synthesis and cellular activity as potent anticancer agents
Authors: Meher Rajesh Kumar , Pragyandipta Pratyush , Pedapati Ravi K. , Nagireddy Praveen K. R. , Kantevari Srinivas , Nayek Arnab K. , Naik Pradeep K. 
Published: June 2021

AbstractThe scaffold structure of noscapine (an antitussive plant alkaloid) was modified by inducting N‐aryl methyl pharmacophore at C‐9 position of the isoquinoline ring to rationally design and screened three novel 9‐(N‐arylmethylamino) noscapinoids, 15–17 with robust binding affinity with tubulin. The selected 9‐(N‐arylmethylamino) noscapinoids revealed improved predicted binding energy of −6.694 kcal/mol for 15, −7.118 kcal/mol for 16 and −7.732 kcal/mol for 17, respectively in comparison to the lead molecule (−5.135 kcal/mol). These novel derivatives were chemically synthesized and validated their anticancer activity based on cellular studies using two human breast adenocarcinoma, MCF‐7 and MDA‐MB‐231, as well as with a panel of primary breast tumor cells. These derivatives inhibited cellular proliferation in all the cancer cells that ranged between 3.2 and 32.2 μM, which is 11.9 to 1.8 fold lower than that of noscapine. These novel derivatives effectively arrest the cell cycle in the G2/M phase followed by apoptosis and appearance of apoptotic cells. Thus, we conclude that 9‐(N‐arylmethyl amino) noscapinoids, 15–17 have a high probability to be a novel therapeutic agent for breast cancers.
State of the Art on Computational Design of Assemblies with Rigid Parts
Authors: Wang Ziqi , Song Peng , Pauly Mark 
Published: June 2021

AbstractAn assembly refers to a collection of parts joined together to achieve a specific form and/or functionality. Designing assemblies is a non‐trivial task as a slight local modification on a part's geometry or its joining method could have a global impact on the structural and/or functional performance of the whole assembly. Assemblies can be classified asstructuresthat transmit force to carry loads andmechanismsthat transfer motion and force to perform mechanical work. In this state‐of‐the‐art report, we focus on computational design of structures with rigid parts, which generally can be formulated as a geometric modeling and optimization problem. We broadly classify existing computational design approaches, mainly from the computer graphics community, according to high‐level design objectives, including fabricability, structural stability, reconfigurability, and tileability. Computational analysis of various aspects of assemblies is an integral component in these design approaches. We review different classes of computational analysis and design methods, discuss their strengths and limitations, make connections among them, and propose possible directions for future research.
A Survey on Bounding Volume Hierarchies for Ray Tracing
Authors: Meister Daniel , Ogaki Shinji , Benthin Carsten , Doyle Michael J. , Guthe Michael , Bittner Jiří 
Published: June 2021

AbstractRay tracing is an inherent part of photorealistic image synthesis algorithms. The problem of ray tracing is to find the nearest intersection with a given ray and scene. Although this geometric operation is relatively simple, in practice, we have to evaluate billions of such operations as the scene consists of millions of primitives, and the image synthesis algorithms require a high number of samples to provide a plausible result. Thus, scene primitives are commonly arranged in spatial data structures to accelerate the search. In the last two decades, the bounding volume hierarchy (BVH) has become the de facto standard acceleration data structure for ray tracing‐based rendering algorithms in offline and recently also in real‐time applications. In this report, we review the basic principles of bounding volume hierarchies as well as advanced state of the art methods with a focus on the construction and traversal. Furthermore, we discuss industrial frameworks, specialized hardware architectures, other applications of bounding volume hierarchies, best practices, and related open problems.
TROAP regulates cell cycle and promotes tumor progression through Wnt/β‐Catenin signaling pathway in glioma cells
Authors: Zhao Zong‐qing , Wu Xiu‐jie , Cheng Yan‐hao , Zhou Yun‐fei , Ma Xi‐meng , Zhang Jian , Heng Xue‐yuan , Feng Fan 
Published: June 2021

AbstractAimsExperimental evidence demonstrated a crucial role of TROAP (Trophinin‐associated protein) in regulating the cell proliferation of multiple tumors, while TROAP expression and function were largely unknown in glioma. We aimed to investigate the oncogenic role of TROAP and its potential mechanisms in gliomagenesis.MethodsFour gene expression databases (GEO, TCGA, GTEx and CCLE) were enrolled in our study and used for TROAP expression and survival analysis. TROAP expression was quantified by qRT‐PCR, western blot and immunohistochemistry assays in glioma tissues and cell lines. TROAP knockdown and overexpression vector were constructed and transfected into glioma cells. CCK‐8, colony formation, transwell, and wound healing assays were used to evaluate cell viability, migration and invasion, flow cytometry to determine cell cycle arrest. Gene set enrichment analysis (GSEA) was conducted to screen the pathway involved in TROAP‐high phenotype. The expression of cell cycle and Wnt/β‐Catenin signaling proteins were analyzed by immunofluorescence and western blot.ResultsBased on the bioinformatic analysis and a series of functional assays, we found the TROAP was enriched in glioma tissues and cell lines, its overexpression was correlated with the clinicopathologic characteristics and poor prognosis. TROAP knockdown inhibited cell proliferation, migration, invasion, and G1/S cell cycle arrest compared with control group in glioma. Mechanism analysis revealed that TROAP activated Wnt/β‐Catenin pathway and upregulated its downstream targets expression, while silencing β‐Catenin or Axin2 could reverse the tumor‐promoting effects caused by TROAP, confirming that TROAP‐induced malignant phenotype and tumorigenesis via Wnt/β‐Catenin signaling pathway.ConclusionThe present study found that TROAP accelerated the progression of gliomagenesis through Wnt/β‐Catenin pathway, and TROAP might be considered as a novel target for glioma therapy.
Perioperative instrumental swallowing evaluation in adult airway reconstruction: A retrospective observational cohort study
Authors: Haywood Matthew , Lovell Lindsay , Roe Justin , Clunie Gemma , Sandhu Guri , Al Yaghchi Chadwan 
Published: June 2021

AbstractObjectivesAirway reconstruction for laryngotracheal stenosis (LTS) encompasses several procedures. Dysphagia is a well‐recognised sequela of LTS and airway surgery, however studies have employed mostly non‐validated assessments post‐operatively in small, heterogenous samples, perpetuating uncertainty around the contributions of LTS and its management to impaired deglutition. Consequently, considerable variation in LTS perioperative nutritional management exists. Our objective was to characterise baseline and post‐operative dysphagia with instrumental assessment in an LTS cohort undergoing airway reconstruction and provide a gold‐standard management framework for its management.Design, setting, participants and main outcome measuresWe performed a retrospective cohort study of adult airway reconstruction procedures from 2016‐2020 at our quaternary centre. Patient background, LTS aetiology, procedure type, tube feeding duration, length of stay and serial Functional Oral Intake Scale (FOIS) and International Dysphagia Diet Standardisation Initiative (IDDSI) scores were noted. Baseline, post‐operative day one and post‐stent removal Fibreoptic Endoscopic Evaluation of Swallow (FEES) generated Penetration Aspiration Scale (PAS) scores.ResultsForty‐four patients underwent forty‐six reconstructions. Baseline incidence of penetration‐aspiration was considerably higher than the general population and worsened in the immediate post‐operative period, however FOIS and PAS scores generally returned to baseline by discharge. Post‐operative FOIS correlated negatively with tracheostomy or airway stent placement. At discharge, 80% tolerated soft or normal diet and 93% were feeding tube independent.ConclusionsWe present the largest adult airway reconstruction cohort with instrumental swallow assessment perioperatively. LTS patients have a higher incidence of underlying dysphagia but swallowing tends to return to baseline with appropriate postoperative rehabilitation. Such practice may avoid the complications, costs and morbidity of prolonged nutritional support.
Prediction of human pharmacokinetics for low‐clearance compounds using pharmacokinetic data from chimeric mice with humanized livers
Authors: Yoshida Kosuke , Doi Yuki , Iwazaki Norihiko , Yasuhara Hidenori , Ikenaga Yuka , Shimizu Hidetoshi , Nakada Tomohisa , Watanabe Tomoko , Tateno Chise , Sanoh Seigo , Kotake Yaichiro 
Published: June 2021

AbstractDevelopment of low‐clearance (CL) compounds that are slowly metabolized is a major goal in the pharmaceutical industry. However, the pursuit of low intrinsic CL (CLint) often leads to significant challenges in evaluating the pharmacokinetics of such compounds. Although in vitro–in vivo extrapolation is widely used to predict human CL, its application has been limited for low‐CLint compounds because of the low turnover of parent compounds in metabolic stability assays. To address this issue, we focused on chimeric mice with humanized livers (PXB‐mice), which have been increasingly reported to accurately predict human CL in recent years. The predictive accuracy for nine low‐CLint compounds with no significant turnover in a human hepatocyte assay was investigated using PXB‐mouse methods, such as single‐species allometric scaling (PXB‐SSS) approach and a novel physiologically based scaling (PXB‐PBS) approach that assumes that the CLint per hepatocyte is equal between humans and PXB‐mice. The percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CLint compounds were 89% and 100%, respectively, for both PXB‐SSS and PXB‐PBS approaches. Moreover, the predicted CL was mostly consistent among the methods. Conversely, the percentages of compounds with predicted CL within 2‐ and 3‐fold ranges of the observed CL for low‐CLint compounds were 50% and 63%, respectively, for multispecies allometric (MA) scaling. Overall, these PXB‐mouse methods were much more accurate than conventional MA scaling approaches, suggesting that PXB‐mice are useful tools for predicting the human CL of low‐CLint compounds that are slowly metabolized.
The effect of age on blood pressure response by 4‐week treatment perindopril: A pooled sex‐specific analysis of the EUROPA, PROGRESS, and ADVANCE trials
Authors: Schreuder Michelle M. , Mirabito Colafella Katrina M. , Boersma Eric , Brugts Jasper J. , Roeters van Lennep Jeanine E. , Versmissen Jorie 
Published: June 2021

AbstractPrevious studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron‐MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4‐week run‐in phase in which all patients were treated with the perindopril‐based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1–5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55–65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55–65: 2.8 mmHg [95% CI = 1.8–3.7], p < 0.001, >65: 3.7 mmHg [95% CI = 2.7–4.7], p < 0.001). A trend of less blood pressure reduction was seen with ageing in both men and women (p < 0.001). To conclude, we observed that in both women and men the perindopril leads to less SBP reduction with increasing age, whereas the DBP reduction increases with age. More research is needed to determine whether it would be beneficial to use age‐adjusted perindopril dosages.
Rewiring of chromatin state and gene expression by transposable elements
Authors: Ohtani Hitoshi , Iwasaki Yuka W. 
Published: June 2021

AbstractTransposable elements form a major fraction of the genome in various eukaryotic species. Although deleterious effects of transpositions within the genome have been reported, recent findings suggest that transposable elements can function as novel regulatory elements to fine‐tune gene expression. Transposable elements can impact the chromatin state through processes such as heterochromatin formation, enhancer–promoter interactions, and chromatin boundary formation, mainly because of the functions of chromatin‐based pathways that regulate the expression of transposable elements via DNA methylation and repressive histone modification. Therefore, transposable elements can rewire the chromatin state and gene expression depending on their insertions. Here, we review the findings that reveal the role of transposable elements as modifiers of the chromatin state and gene expression as well as the molecular mechanisms capable of inducing these changes.
Does autoimmune vitiligo protect against COVID‐19 disease?
Authors: Post Nicoline F. , Luiten Rosalie M. , Wolkerstorfer Albert , Bekkenk Marcel W. , Böhm Markus 
Published: June 2021

AbstractThe SARS‐CoV‐2 pandemic has evolved to a global health problem with a dramatic morbidity and mortality rate impacting our daily life and those of many patients. While there is evidence that some diseases are associated with an increased risk for development of a more severe course of COVID‐19, little is known on protective conditions. Importantly, clearance of viral infection and protection against disease manifestation crucially depends on functional innate and adaptive immunity and the interferon signalling axis. Here, we hypothesize that patients with non‐segmental vitiligo (NSV), an autoimmune skin (and mucosal) disorder, may clear SARS‐CoV‐2 infection more efficiently and have a lower risk of COVID‐19 development. Conversely, in case of COVID‐19 development, vitiligo autoimmunity may influence the cytokine storm‐related disease burden. In addition, immune activation during SARS‐CoV‐2 infection or COVID‐19 disease might increase vitiligo disease activity. Our hypothesis is based on the shift of the immune system in NSV towards adaptive type 1 (IFNγ and CD8 T cells) and innate immune responses. Identified susceptibility genes of NSV patients may further confer increased antiviral activity. To validate our hypothesis, we suggest an international consortium to perform a retrospective data registry and patient‐reported study on a large number of NSV patients worldwide during the COVID‐19 pandemic.
HUMBOLDT IN VENEZUELA AND CUBA: THE ‘SECOND SLAVERY’
Authors: Zeuske Michael 
Published: June 2021

ABSTRACTThe reception of Humboldt's work now spans more than 200 years. It began with the publication of the texts that form his Opus Americanum (1808–31). Among these works, it was in the Political Essay on Cuba, where a chapter was devoted to the demography of the slave trade from Africa to Cuba, that became a cornerstone of the global historical significance of Humboldt's oeuvre. It can be argued that during the past 200 years the same clichés and slogans of liberal abolitionism (or its opponents, such as J. S. Thrasher) have been heard over and over again, without researchers having taken the trouble to investigate the biographical‐historical and micro‐historical origins of Humboldt's attitude to slavery, the slave trade and its sources. This article aims to show what Humboldt really could (and wanted to) know about slavery and the slave trade, by means of a micro‐distance and a micro‐point, the 25‐day crossing from Nueva Barcelona, in present‐day Venezuela, to Havana in Cuba in November/December 1800, as well as Humboldt's stay at the home of slave trader, Don Juan Luis de la Cuesta, in Havana (1800/1 and 1804). Die Humboldt‐Rezeption umfasst ca. 200 Jahre. Sie begann mit den Publikationen der Werke des Opus Americanum (1808–31). In Bezug auf eines dieser Werke, den Politischen Essay über die Insel Kuba, steht fest, dass die Demografie des Sklavenhandels von Afrika nach Kuba (und in der Karibik) sowie das Kapitel ʻÜber das Sklavenwesenʼ Eckpunkte oder auch Säulen der globalhistorischen Bedeutung des humboldtschen Werkes darstellen. In der Rezeption von Humboldts Werk, und vor allem dieser Eckpunkte/Säulen sind über 200 Jahre eigentlich immer wieder die gleichen Klischees und Fahnenworte des liberalen Abolitionismus benutzt worden (oder seiner Gegner, wie J. S. Thrasher), ohne dass sich Rezipienten die Mühe gemacht hätten, die lebensgeschichtliche und mikrohistorische Entstehung der Haltung Humboldts zu Sklaverei und Sklavenhandel und seine Quellen zu erforschen. Der Beitrag will an einer Mikrostrecke und einem Mikropunkt, der 25‐tägigen Überfahrt von Nueva Barcelona im heutigen Venezuela nach Havanna auf Kuba im November/Dezember 1800 und Humboldts Beherbergung durch den Sklavenhändler Don Juan Luis de la Cuesta in Havanna (1800/1 und 1804), zeigen, was Humboldt realhistorisch zu Sklaverei und Sklavenhandel wissen konnte (und wollte).