bluuebunny/crossref_metadata_2025_split huggingface dataset:
PWD/Ph-Encoded Genetic Variants Modulate the Cellular Wnt/β-Catenin Response to Suppress ApcMin-Triggered Intestinal Tumor Formation
Authors: Farrall Alexandra L. , Lienhard Matthias , Grimm Christina , Kuhl Heiner , Sluka Susanna H.M. , Caparros Marta , Forejt Jiri , Timmermann Bernd , Herwig Ralf , Herrmann Bernhard G. , Morkel Markus 
Published: November 2020

Abstract

Genetic predisposition affects the penetrance of tumor-initiating mutations, such as APC mutations that stabilize β-catenin and cause intestinal tumors in mice and humans. However, the mechanisms involved in genetically predisposed penetrance are not well understood. Here, we analyzed tumor multiplicity and gene expression in tumor-prone ApcMin/+ mice on highly variant C57BL/6J (B6) and PWD/Ph (PWD) genetic backgrounds. (B6 × PWD) F1 APCMin offspring mice were largely free of intestinal adenoma, and several chromosome substitution (consomic) strains carrying single PWD chromosomes on the B6 genetic background displayed reduced adenoma numbers. Multiple dosage-dependent modifier loci on PWD chromosome 5 each contributed to tumor suppression. Activation of β-catenin–driven and stem cell–specific gene expression in the presence of ApcMin or following APC loss remained moderate in intestines carrying PWD chromosome 5, suggesting that PWD variants restrict adenoma initiation by controlling stem cell homeostasis. Gene expression of modifier candidates and DNA methylation on chromosome 5 were predominantly cis controlled and largely reflected parental patterns, providing a genetic basis for inheritance of tumor susceptibility. Human SNP variants of several modifier candidates were depleted in colorectal cancer genomes, suggesting that similar mechanisms may also affect the penetrance of cancer driver mutations in humans. Overall, our analysis highlights the strong impact that multiple genetic variants acting in networks can exert on tumor development.

Significance:
These findings in mice show that, in addition to accidental mutations, cancer risk is determined by networks of individual gene variants.
Regulatory T Cells Play an Important Role in the Prevention of Murine Melanocytic Nevi and Melanomas
Authors: Nasti Tahseen H. , Yusuf Nabiha , Sherwani Mohammad Asif , Athar Mohammad , Timares Laura , Elmets Craig A. 
Published: November 2020

Abstract
Melanocytic nevi are benign proliferations of pigment cells that can occasionally develop into melanomas. There is a significant correlation between increased nevus numbers and melanoma development. Our previous reports revealed that 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced dysplastic nevi in C3H/HeN mice, with a potential to transform into melanomas. To understand the immune mechanisms behind this transformation, we applied increasing DMBA doses followed by TPA to the skin of C3H/HeN mice. We observed that increased doses of DMBA correlated well with increased numbers of nevi. The increased DMBA dose induced diminished immune responses and promoted the expansion of regulatory T cells (Treg) that resulted in increased IL10 and reduced IFNγ levels. Mice with increased nevus numbers had loss of p16 expression. These mice had increased migration of melanocytic cells to lymph nodes (LN) and a greater percent of LNs produced immortalized melanocytic cell lines. DMBA-induced immunosuppression was lost in CD4-knockout (KO) mice. Lymphocytes in the CD4KO mice produced less IL10 than CD8KO mice. Furthermore, CD4KO mice had significantly reduced nevus numbers and size compared with wild-type and CD8KO mice. These results suggest that Tregs play a vital role in the incidence of nevi and their progression to melanoma.
Prevention Relevance: There has been little progress in developing novel strategies for preventing premalignant dysplastic nevi from becoming melanomas. In this study in mice, regulatory-T cells enhanced progression of benign nevi to malignant melanomas; and by inhibiting their activity, melanomas could be retarded. The findings identify new possibilities for melanoma prevention in high risk individuals.
Residenciais de idosos durante a crise do COVID-19
Authors: Blasco Pablo González , Levites Marcelo Rozenfeld , Moreto Graziela , Janaudis Marco Aurelio , De Benedetto Maria Auxiliadora Craice 
Published: November 2020

A atual pandemia pelo COVID-19 nos faz viver tempos difíceis e inéditos. Os esforços de todos os profissionais de saúde, cada um nas suas competências, são essenciais. Enquanto pesquisadores e cientistas se debatem procurando recursos terapêuticos eficazes, aqueles que estão na linha de frente devotam seus melhores esforços no cuidado clinico dos pacientes afetados. A cada dia que passa mostra-se imprescindível o cuidado da própria equipe de saúde. Não apenas o cuidado físico (para o qual se tomam todas as providências possíveis em cada caso) mas também da saúde mental. Um elemento da equipe de saúde desanimado, pessimista, sem perspectiva é também um fator de crise, provoca insegurança nos pacientes e nas famílias -mais ainda da que lhes chega habitualmente da mídia - e nada ajuda na equipe de saúde. Torna-se preciso levantar o moral dos que lidam diariamente com esta ameaça de proporções antes nunca vistas.
Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease
Authors: Gendron Nicolas , Rosa Mickael , Blandinieres Adeline , Sottejeau Yoann , Rossi Elisa , Van Belle Eric , Idelcadi Salim , Lecourt Séverine , Vincentelli André , Cras Audrey , Jashari Ramadan , Chocron Richard , Baudouin Yaël , Pamart Thibault , Bièche Ivan , Nevo Nathalie , Cholley Bernard , Rancic Jeanne , Staels Bart , Gaussem Pascale , Dupont Annabelle , Carpentier Alain , Susen Sophie , Smadja David M. 
Published: November 2020

Objective:
The study’s aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis.

Approach and Results:

VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC
p
) mesenchymal-like phenotype was confirmed by CD90
+
/CD73
+
/CD44
+
expression and multipotent-like differentiation ability. When VIC
p
were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC
p
and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC
p
-conditioned media and confirmed at the mRNA level in VIC
p
compared with control VIC. Conditioned media from VIC
p
induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC
p
involvement in angiogenesis by a VEGF-A dependent mechanism.

Conclusions:

We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC
p
in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
Sensitivity of the Edinburgh Criteria for Lobar Intracerebral Hemorrhage in Hereditary Cerebral Amyloid Angiopathy
Authors: van Etten Ellis S. , Kaushik Kanishk , van Zwet Erik W. , Voigt Sabine , van Walderveen Marianne A.A. , van Buchem Mark A. , Terwindt Gisela M. , Wermer Marieke J.H. 
Published: November 2020

Background and Purpose:
The Edinburgh computed tomography and genetic criteria enable diagnosis of cerebral amyloid angiopathy (CAA) associated lobar intracerebral hemorrhage (ICH) but have not been validated in living patients. We assessed the sensitivity of the Edinburgh criteria in patients with acute lobar ICH due to Dutch-type hereditary CAA; a genetic and pure form of CAA.

Methods:
We retrospectively analyzed computed tomography-scans from a cohort of consecutive Dutch-type hereditary CAA patients who presented with ≥1 episode(s) of acute lobar ICH at the Leiden University Medical Center. Presence of subarachnoid hemorrhage (SAH) and finger-like projections (FLP) were determined. Association of SAH and FLP with ICH volume was analyzed using multivariate linear regression.

Results:

We included 55 Dutch-type hereditary CAA patients (mean age 56 years, 55% men) with a total of 107 episodes of acute lobar ICH. SAH was present in 82/107 (76%) and FLP in 62/107 (58%), resulting in a sensitivity of 76% for SAH and 58% for FLP. In 56 (52%), both markers were present. Nineteen (18%) lobar ICH showed no SAH extension or FLP. ICH volume was significantly associated with presence of SAH (median volume 4 versus 28 mL;
P
=0.001) and presence of FLP (median volume 7 versus 39 mL;
P
<0.001). With an ICH volume of ≥40 mL, the sensitivity of the presence of both SAH and FLP was >81% (95% CI, 70%–92%), whereas in ICH volumes <15 mL the sensitivity was <50%.

Conclusions:
The computed tomography-based Edinburgh criteria seem to be a sensitive diagnostic test for CAA-associated lobar ICH, although they should be used with caution in small-sized lobar ICH.
Expansive Legal Interpretation and Muslim Judges’ Approach to Polygamy in Indonesia
Authors: Nurlaelawati Euis 
Published: November 2020

Abstract
Similar to other Muslim-majority countries, Indonesia has undertaken legislative changes in the domain of family law, including on polygamy. In practice, however, these legal reforms continue to be challenged by a number of judges, specifically those regarding polygamy. This paper looks at the extent to which judges meet husbands’ proposals for polygamy. It investigates judges’ legal interpretation of the legal grounds specified for polygamous marriage and how judges have deployed the notions of maslahah (public good) and mafsadah (harm), with a view to fortifying their legal decisions. It will be argued that the judges’ approach remains shaped by classical Islamic legal doctrine and that they subscribe to free and supplementary legal interpretation, or ijtihad, as well as contemporary notions of maslahah, resulting in conservative legal decisions that uphold gender asymmetries. It is also found that, even though many women may choose to share husbands rather than to be divorced, judges seem to ignore the fact that the practice of polygamy is detrimental to the dissolution of the marriage through wife-petitioned divorce.
Empirical foundations for an integrated study of language evolution
Authors: Roberts Gareth , Sneller Betsy 
Published: November 2020

Abstract
Half a century ago, Uriel Weinreich, William Labov, and Marvin Herzog laid out a programmatic vision for the study of language change. This included establishing five fundamental problems for the field and a radical shift from a focus on idiolects to a focus on population-level change (grounded in their concept of orderly heterogeneity). They also expressed an explicit desire to see an integrated evolutionary study of language change. In spite of this, the newer fields of language evolution and cultural evolution make little contact with the field of sociolinguistics that emerged out of their work. Here we lay out a program, grounded in their five problems, for a more integrated future. We situate each problem in modern sociolinguistics and identify promising points for theoretical exchange, making comparisons with Tinbergen’s four questions, which play a similar role in the evolutionary sciences. Finally, we propose cultural-evolutionary experiments for making empirical progress.
Networked Pantheon: a Relational Database of Globally Famous People
Authors: Beytía Pablo , Schobin Janosch 
Published: November 2020

Abstract
This article presents the Networked Pantheon, a relational database of biographies of globally famous people spanning the last 5,500 years of human history. This information source is intended to complement Pantheon 1.0 (Yu et al., 2016), a dataset that includes temporal, spatial, gender, and occupational information on 11,341 world-renowned people – defined as those who have biographies available in more than 25 languages on Wikipedia. The Networked Pantheon adds information about the biographical links between these historical figures, compiled from hyperlinks between the biographies in the English Wikipedia. This digital method enables techniques from network analysis to be used in studying the biographical relationships between globally famous people. Thus, distinct measures of historical centrality can be calculated for individuals, cities, countries, genders, and occupations. The Networked Pantheon includes indicators of figure centrality in the network of biographical references and provides an approximation of the information flows between various territories, genders, and occupations of famous people over time.
The Post-Apartheid Labour Market Series
Authors: Kerr Andrew , Wittenberg Martin 
Published: November 2020

Abstract
The Post-Apartheid Labour Market Series (palms) is a compilation of microdata from 69 household surveys conducted in South Africa. The dataset and the code used to create the data are publicly available from DataFirst, a data repository at the University of Cape Town (www.doi.org/10.25828/gtr1-8r20). To harmonise the data required understanding the differences across the surveys, which has generated new knowledge about the South African labour market.
R2D2: A Region-Based Recursive Doppler Dealiasing Algorithm for Operational Weather Radar
Authors: Feldmann Monika , James Curtis N. , Boscacci Marco , Leuenberger Daniel , Gabella Marco , Germann Urs , Wolfensberger Daniel , Berne Alexis 
Published: November 2020

AbstractRegion-based Recursive Doppler Dealiasing (R2D2) is a novel dealiasing algorithm to unfold Doppler velocity fields obtained by operational radar measurements. It specializes in resolving issues when the magnitude of the gate-to-gate velocity shear approaches or exceeds the Nyquist velocity. This occurs either in highly sheared situations, or when the Nyquist velocity is low. Highly sheared situations, such as convergence lines or mesocyclones, are of particular interest for nowcasting and warnings. R2D2 masks high-shear areas and adds a spatial buffer around them. The areas between the buffers are then identified as continuous regions that lie within the same Nyquist interval. Each region subsequently is assigned its most likely Nyquist interval by applying vertical and temporal continuity constraints, as well as supplemental wind information from an operational mesoscale model. The shear zones are then resolved using 2D continuity in azimuth and range. This 4D procedure is repeated until no further improvement can be achieved. Each iteration with fewer folds identifies fewer but larger continuous regions and less shear zones until an optimum is reached. Residual errors, often related to shear greater than the Nyquist velocity, are contained to small areas within the buffer zones. This approach maximizes operational performance in high-shear situations and restricts errors to minimal areas to mitigate error propagation.
Gender Differences in Endothelial Function and Coronary Vasomotion Abnormalities
Authors: Godo Shigeo , Shimokawa Hiroaki 
Published: November 2020

Introduction: Structural and functional abnormalities of coronary microvasculature, referred to as coronary microvascular dysfunction (CMD), have been implicated in a wide range of cardiovascular diseases and have gained growing attention in patients with chest pain with no obstructive coronary artery disease, especially in females. The central mechanisms of coronary vasomotion abnormalities encompass enhanced coronary vasoconstrictive reactivity (ie, coronary spasm), reduced endothelium-dependent and -independent coronary vasodilator capacities, and increased coronary microvascular resistance. The 2 major endothelium-derived relaxing factors, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factors, modulate vascular tone in a distinct vessel size–dependent manner; NO mainly mediates vasodilatation of relatively large, conduit vessels, while EDH factors in small resistance vessels. Endothelium-dependent hyperpolarization–mediated vasodilatation is more prominent in female resistance arteries, where estrogens exert beneficial effects on endothelium-dependent vasodilatation via multiple mechanisms. In the clinical settings, therapeutic approaches targeting NO are disappointing for the treatment of various cardiovascular diseases, where endothelial dysfunction and CMD are substantially involved. Significance: In this review, we will discuss the current knowledge on the pathophysiology and molecular mechanisms of endothelial function and coronary vasomotion abnormalities from bench to bedside, with a special reference to gender differences. Results: Recent experimental and clinical studies have demonstrated distinct gender differences in endothelial function and coronary vasomotion abnormalities with major clinical implications. Moreover, recent landmark clinical trials regarding the management of stable coronary artery disease have questioned the benefit of percutaneous coronary intervention, supporting the importance of the coronary microvascular physiology. Conclusion: Further characterization and a better understanding of the gender differences in basic vascular biology as well as those in cardiovascular diseases are indispensable to improve health care and patient outcomes in cardiovascular medicine.
A New Method for Type Synthesis of 2R1T and 2T1R 3-DOF Redundant Actuated Parallel Mechanisms with Closed Loop Units
Authors: Li Yongquan , Zhang Yang , Zhang Lijie 
Published: November 2020

AbstractThe current type synthesis of the redundant actuated parallel mechanisms is adding active-actuated kinematic branches on the basis of the traditional parallel mechanisms, or using screw theory to perform multiple getting intersection and union to complete type synthesis. The number of redundant parallel mechanisms obtained by these two methods is limited. In this paper, based on Grassmann line geometry and Atlas method, a novel and effective method for type synthesis of redundant actuated parallel mechanisms (PMs) with closed-loop units is proposed. Firstly, the degree of freedom (DOF) and constraint line graph of the moving platform are determined successively, and redundant lines are added in constraint line graph to obtain the redundant constraint line graph and their equivalent line graph, and a branch constraint allocation scheme is formulated based on the allocation criteria. Secondly, a scheme is selected and redundant lines are added in the branch chains DOF graph to construct the redundant actuated branch chains with closed-loop units. Finally, the branch chains that meet the requirements of branch chains configuration criteria and F&C (degree of freedom & constraint) line graph are assembled. In this paper, two types of 2 rotational and 1 translational (2R1T) redundant actuated parallel mechanisms and one type of 2 translational and 1 rotational (2T1R) redundant actuated parallel mechanisms with few branches and closed-loop units were taken as examples, and 238, 92 and 15 new configurations were synthesized. All the mechanisms contain closed-loop units, and the mechanisms and the actuators both have good symmetry. Therefore, all the mechanisms have excellent comprehensive performance, in which the two rotational DOFs of the moving platform of 2R1T redundant actuated parallel mechanism can be independently controlled. The instantaneous analysis shows that all mechanisms are not instantaneous, which proves the feasibility and practicability of the method.
In vitro differentiation of W8B2+ human cardiac stem cells: gene expression of ionic channels and spontaneous calcium activity
Authors: Ayad Oualid , Al Sayed Zeina R. , Sebille Stéphane , Magaud Christophe , Chapotte-Baldacci Charles-Albert , Jayle Christophe , Faivre Jean-François , Gaborit Nathalie , Chatelier Aurélien , Bois Patrick 
Published: November 2020

AbstractBackgroundHuman cardiac stem cells expressing the W8B2 marker (W8B2+CSCs) were recently identified and proposed as a new model of multipotent CSCs capable of differentiating into smooth muscle cells, endothelial cells and immature myocytes. Nevertheless, no characterization of ion channel or calcium activity during the differentiation of these stem cells has been reported.MethodsThe objectives of this study were thus to analyze (using the TaqMan Low-Density Array technique) the gene profile of W8B2+CSCs pertaining to the regulation of ion channels, transporters and other players involved in the calcium homeostasis of these cells. We also analyzed spontaneous calcium activity (via the GCaMP calcium probe) during the in vitro differentiation of W8B2+CSCs into cardiac myocytes.ResultsOur results show an entirely different electrophysiological genomic profile between W8B2+CSCs before and after differentiation. Some specific nodal genes, such as Tbx3, HCN, ICaT, L, KV, and NCX, are overexpressed after this differentiation. In addition, we reveal spontaneous calcium activity or a calcium clock whose kinetics change during the differentiation process. A pharmacological study carried out on differentiated W8B2+CSCs showed that the NCX exchanger and IP3 stores play a fundamental role in the generation of these calcium oscillations.ConclusionsTaken together, the present results provide important information on ion channel expression and intrinsic calcium dynamics during the differentiation process of stem cells expressing the W8B2 marker.