bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of NOX1 Mitigates Blood Pressure Increases in Elastin Insufficiency
Authors: Troia Angela , Knutsen Russell H , Halabi Carmen M , Malide Daniela , Yu Zu Xi , Wardlaw-Pickett Amanda , Kronquist Elise K , Tsang Kit Man , Kovacs Attila , Mecham Robert P , Kozel Beth A 
Published: March 2021

Abstract
Elastin (ELN) insufficiency leads to the cardiovascular hallmarks of the contiguous gene deletion disorder, Williams–Beuren syndrome, including hypertension and vascular stiffness. Previous studies showed that Williams–Beuren syndrome deletions, which extended to include the NCF1 gene, were associated with lower blood pressure (BP) and reduced vascular stiffness. NCF1 encodes for p47phox, the regulatory component of the NOX1 NADPH oxidase complex that generates reactive oxygen species (ROS) in the vascular wall. Dihydroethidium and 8-hydroxyguanosine staining of mouse aortas confirmed that Eln heterozygotes (Eln+/−) had greater ROS levels than the wild-types (Eln+/+), a finding that was negated in vessels cultured without hemodynamic stressors. To analyze the Nox effect on ELN insufficiency, we used both genetic and chemical manipulations. Both Ncf1 haploinsufficiency (Ncf1+/−) and Nox1 insufficiency (Nox1−/y) decreased oxidative stress and systolic BP in Eln+/− without modifying vascular structure. Chronic treatment with apocynin, a p47phox inhibitor, lowered systolic BP in Eln+/−, but had no impact on Eln+/+ controls. In vivo dosing with phenylephrine (PE) produced an augmented BP response in Eln+/− relative to Eln+/+, and genetic modifications or drug-based interventions that lower Nox1 expression reduced the hypercontractile response to PE in Eln+/− mice to Eln+/+ levels. These results indicate that the mechanical and structural differences caused by ELN insufficiency leading to oscillatory flow can perpetuate oxidative stress conditions, which are linked to hypertension, and that by lowering the Nox1-mediated capacity for vascular ROS production, BP differences can be normalized.
Long noncoding RNA regulation of spermatogenesis via the spectrin cytoskeleton in Drosophila
Authors: Bouska Mark J , Bai Hua 
Published: March 2021

Abstract
The spectrin cytoskeleton has been shown to be critical in diverse processes such as axon development and degeneration, myoblast fusion, and spermatogenesis. Spectrin can be modulated in a tissue specific manner through junctional protein complexes, however, it has not been shown that long noncoding RNAs (lncRNAs) interact with and modulate spectrin. Here, we provide evidence of a lncRNA CR45362 that interacts with α-Spectrin, is required for spermatid nuclear bundling during Drosophila spermatogenesis. We observed that CR45362 showed high expression in the cyst cells at the basal testis, and CRISPR-mediated knockout of CR45362 led to sterile male, unbundled spermatid nuclei, and disrupted actin cones. Through chromatin isolation by RNA precipitation—mass spectrometry (ChIRP-MS), we identified actin-spectrin cytoskeletal components physically interact with the lncRNA CR45362. Genetic screening on identified cytoskeletal factors revealed that cyst cell-specific knockdown of α-Spectrin phenocopied CR45362 mutants and resulted in spermatid nuclear bundle defects. Consistently, CR45362 knockout disrupted the co-localization of α-Spectrin and spermatid nuclear bundles in the head cyst cells at the basal testis. Thus, we uncovered a novel lncRNA CR45362 that interacts with α-Spectrin to stabilize spermatid nuclear bundles during spermatid maturation.
Robust, flexible, and scalable tests for Hardy–Weinberg equilibrium across diverse ancestries
Authors: Kwong Alan M , Blackwell Thomas W , LeFaive Jonathon , de Andrade Mariza , Barnard John , Barnes Kathleen C , Blangero John , Boerwinkle Eric , Burchard Esteban G , Cade Brian E , Chasman Daniel I , Chen Han , Conomos Matthew P , Cupples L Adrienne , Ellinor Patrick T , Eng Celeste , Gao Yan , Guo Xiuqing , Irvin Marguerite Ryan , Kelly Tanika N , Kim Wonji , Kooperberg Charles , Lubitz Steven A , Mak Angel C Y , Manichaikul Ani W , Mathias Rasika A , Montasser May E , Montgomery Courtney G , Musani Solomon , Palmer Nicholette D , Peloso Gina M , Qiao Dandi , Reiner Alexander P , Roden Dan M , Shoemaker M Benjamin , Smith Jennifer A , Smith Nicholas L , Su Jessica Lasky , Tiwari Hemant K , Weeks Daniel E , Weiss Scott T ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Analysis Working Group, Scott Laura J , Smith Albert V , Abecasis Gonçalo R , Boehnke Michael , Kang Hyun Min 
Published: March 2021

AbstractTraditional Hardy–Weinberg equilibrium (HWE) tests (the χ2 test and the exact test) have long been used as a metric for evaluating genotype quality, as technical artifacts leading to incorrect genotype calls often can be identified as deviations from HWE. However, in data sets composed of individuals from diverse ancestries, HWE can be violated even without genotyping error, complicating the use of HWE testing to assess genotype data quality. In this manuscript, we present the Robust Unified Test for HWE (RUTH) to test for HWE while accounting for population structure and genotype uncertainty, and to evaluate the impact of population heterogeneity and genotype uncertainty on the standard HWE tests and alternative methods using simulated and real sequence data sets. Our results demonstrate that ignoring population structure or genotype uncertainty in HWE tests can inflate false-positive rates by many orders of magnitude. Our evaluations demonstrate different tradeoffs between false positives and statistical power across the methods, with RUTH consistently among the best across all evaluations. RUTH is implemented as a practical and scalable software tool to rapidly perform HWE tests across millions of markers and hundreds of thousands of individuals while supporting standard VCF/BCF formats. RUTH is publicly available at https://www.github.com/statgen/ruth.
Robust nonconforming virtual element methods for general fourth-order problems with varying coefficients
Authors: Dedner Andreas , Hodson Alice 
Published: March 2021

Abstract
We present a class of nonconforming virtual element methods for general fourth-order partial differential equations in two dimensions. We develop a generic approach for constructing the necessary projection operators and virtual element spaces. Optimal error estimates in the energy norm are provided for general linear fourth-order problems with varying coefficients. We also discuss fourth-order perturbation problems and present a novel nonconforming scheme which is uniformly convergent with respect to the perturbation parameter without requiring an enlargement of the space. Numerical tests are carried out to verify the theoretical results. We conclude with a brief discussion on how our approach can easily be applied to nonlinear fourth-order problems.
Rapidly Increasing Severe Acute Respiratory Syndrome Coronavirus 2 Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected During the 2020 Pandemic
Authors: Farcet Maria R , Karbiener Michael , Schwaiger Julia , Ilk Reinhard , Kreil Thomas R 
Published: March 2021

Abstract
Immunoglobulin lots (N = 176) released since March 2020 were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies, with first positive results for September 2020 lots (mean, 1.7 IU/mL; 46% of lots positive). From there, values steadily increased, in correlation with the cumulative coronavirus disease 2019 (COVID-19) incidence, to reach a mean of 31.2 IU/mL and 93% of lots positive by January 2021. Extrapolating the correlation, immunoglobulins could reach an anti–SARS-CoV-2 potency of approximately 345 IU/mL by July 2021. At that stage, prophylactic immunoglobulin treatment for primary/secondary immunodeficiency could contain similar doses of anti–SARS-CoV-2 as convalescent plasma that is used for treatment of COVID-19.
Targeting Nrf2-antioxidant signalling reverses acquired cabazitaxel resistance in prostate cancer cells
Authors: Endo Satoshi , Kawai Mina , Hoshi Manami , Segawa Jin , Fujita Mei , Matsukawa Takuo , Fujimoto Naohiro , Matsunaga Toshiyuki , Ikari Akira 
Published: March 2021

Abstract
Prostate cancer is known to have a relatively good prognosis, but long-term hormone therapy can lead to castration-resistant prostate cancer (CRPC). Cabazitaxel, a second-generation taxane, has been used for the CRPC treatment, but its tolerance is an urgent problem to be solved. In this study, to elucidate the acquisition mechanism of the cabazitaxel-resistance, we established cabazitaxel-resistant prostate cancer 22Rv1 (Cab-R) cells, which exhibited ∼sevenfold higher LD50 against cabazitaxel than the parental 22Rv1 cells. Cab-R cells showed marked increases in nuclear accumulation of NF-E2 related factor 2 (Nrf2) and expression of Nrf2-inducible antioxidant enzymes compared to 22Rv1 cells, suggesting that Nrf2 signalling is homeostatically activated in Cab-R cells. The cabazitaxel sensitivity of Cab-R cells was enhanced by silencing of Nrf2, and that of 22Rv1 cells was reduced by activation of Nrf2. Halofuginone (HF) has been recently identified as a potent Nrf2 synthetic inhibitor, and its treatment of Cab-R cells not only suppressed the Nrf2 signalling by decreasing both nuclear and cytosolic Nrf2 protein levels, but also significantly augmented the cabazitaxel sensitivity. Thus, inhibition of Nrf2 signalling may be effective in overcoming the cabazitaxel resistance in prostate cancer cells.
Epigenetic effects induced by the ectopic expression of Pax7 in 3T3-L1
Authors: Elgaabari Alaa , Miyawaki-Kuwakado Atsuko , Tomimatsu Kosuke , Wu Qianmei , Tokunaga Kosuke , Izumi Wakana , Suzuki Takahiro , Tatsumi Ryuichi , Nakamura Mako 
Published: March 2021

Abstract
Although skeletal muscle cells and adipocytes are derived from the same mesoderm, they do not transdifferentiate in vivo and are strictly distinct at the level of gene expression. To elucidate some of the regulatory mechanisms underlying this strict distinction, Pax7, a myogenic factor, was ectopically expressed in 3T3-L1 adipose progenitor cells to perturb their adipocyte differentiation potential. Transcriptome analysis showed that ectopic expression of Pax7 repressed the expression of some adipocyte genes and induced expression of some skeletal muscle cell genes. We next profiled the epigenomic state altered by Pax7 expression using H3K27ac, an activating histone mark, and H3K27me3, a repressive histone mark, as indicators. Our results show that ectopic expression of Pax7 did not result in the formation of H3K27ac at loci of skeletal muscle-related genes, but instead resulted in the formation of H3K27me3 at adipocyte-related gene loci. These findings suggest that the primary function of ectopic Pax7 expression is the formation of H3K27me3, and muscle gene expression results from secondary regulation.
Emergence and Infestation Level of Hypothenemus hampei (Coleoptera: Curculionidae) on Coffee Berries on the Plant or on the Ground During the Post-harvest Period in Brazil
Authors: Pereira Adriano E , Gontijo Pablo C , Fantine Andreza K , Tinoco Ricardo S , Ellersieck Mark R , Carvalho Geraldo A , Zanuncio José C , Vilela Evaldo F 
Published: March 2021

Abstract
The coffee berry borer (CBB), Hypothenemus hampei Ferrari (Coleoptera: Curculionidae), is the most important coffee pest in most of the coffee growing countries. CBB females leave old dry berries after harvest and search for dry noninfested berries on the plant or on the ground to lay eggs or to use as refuge until new berries are available on the coffee trees in the following season. The CBB infestation level and emergence from berries on the ground or on the plants were evaluated in two fields post-harvest in the Spring in Brazil over two seasons. Twenty infested or noninfested berries in separate cages (250 ml plastic cups) were placed on the plants or on the ground under the tree canopy, in each field. The number of infested berries and CBB females that emerged from the infested berries were recorded weekly. CBB emergence was higher from berries on the ground than those on the coffee trees in both seasons, whereas CBB infestation was higher on coffee berries on the plants than those on the ground in season I. Insolation (hours of sunlight) and temperature were the main covariates that affected emergence and infestation by this insect. The results are discussed for monitoring CBB during the time of dispersal with implications on integrated management of this pest.
Breast Cancer–Related Employment Disruption and Financial Hardship in the Sister Study
Authors: Meernik Clare , Sandler Dale P , Peipins Lucy A , Hodgson M Elizabeth , Blinder Victoria S , Wheeler Stephanie B , Nichols Hazel B 
Published: March 2021

Abstract

Background
More than one-half of breast cancer cases are diagnosed among women aged younger than 62 years, which may result in employment challenges. This study examined whether cancer-related employment disruption was associated with increased financial hardship in a national US study of women with breast cancer.

Methods
Women with breast cancer who were enrolled in the Sister or Two Sister Studies completed a survivorship survey in 2012. Employment disruption was defined as stopping work completely or working fewer hours after diagnosis. Financial hardship was defined as: 1) experiencing financial problems paying for cancer care, 2) borrowing money or incurring debt, or 3) filing for bankruptcy because of cancer. Prevalence ratios and 95% confidence intervals for the association between employment disruption and financial hardship were estimated using multivariable Poisson regression with robust variance.

Results
We analyzed data from women employed at diagnosis (n = 1628). Women were a median age of 48 years at diagnosis and 5.6 years from diagnosis at survey completion. Overall, 27.3% of women reported employment disruption (15.4% stopped working; 11.9% reduced hours), and 21.0% experienced financial hardship (16.0% had difficulty paying for care; 12.6% borrowed money or incurred debt; 1.8% filed for bankruptcy). In adjusted analysis, employment disruption was associated with nearly twice the prevalence of financial hardship (prevalence ratio = 1.93, 95% confidence interval = 1.58 to 2.35).

Conclusions
Women experiencing employment disruptions after breast cancer may be more vulnerable to financial hardship. Findings highlight the need to target risk factors for employment disruption, facilitate return to work or ongoing employment, and mitigate financial consequences after cancer.
Light-emitting self-assembled metallacages
Authors: Zhao Jun , Zhou Zhixuan , Li Guangfeng , Stang Peter J , Yan Xuzhou 
Published: March 2021

Abstract
Coordination-driven self-assembly of metallacages has garnered significant interest because of their 3D layout and cavity-cored nature. The well-defined, highly tunable metallacage structures render them particularly attractive for investigating the properties of luminophores, as well as for inducing novel photophysical characters that enable widespread applications. In this review, we summarize the recent advances in synthetic methodologies for light-emitting metallacages, and highlight some representative applications of these metallacages. In particular, we focus on the favorable photophysical properties—including high luminescence efficiency in various physical states, good modularity in photophysical properties and stimulus responsiveness—that have resulted from incorporating ligands displaying aggregation-induced emission (AIE) into metallacages. These features show that the synergy between carrying out coordination-driven self-assembly and using luminophores with novel photophysical characteristics like AIE could stimulate the development of supramolecular luminophores for applications in fields as diverse as sensing, biomedicine and catalysis.
Motor Evoked Potential Recordings During Segmented Deep Brain Stimulation—A Feasibility Study
Authors: Shils Jay , Kochanski Ryan B , Borghei Alireza , Candocia Alexander , Pal Gian D , Afshari Mitra , Verhagen Leonard Metman , Sani Sepehr 
Published: March 2021

Abstract

BACKGROUND
Segmented deep brain stimulation (DBS) leads, which are capable of steering current in the direction of any 1 of 3 segments, can result in a wider therapeutic window by directing current away from unintended structures, particularly, the corticospinal tract (CST). It is unclear whether the use of motor evoked potentials (MEPs) is feasible during DBS surgery via stimulation of individual contacts/segments in order to quantify CST activation thresholds and optimal contacts/segments intraoperatively.

OBJECTIVE
To assess the feasibility of using MEP to identify CST thresholds for ring and individual segments of the DBS lead under general anesthesia.

METHODS
MEP testing was performed during pulse generator implantation under general anesthesia on subjects who underwent DBS lead implantation into the subthalamic nucleus (STN). Stimulation of each ring and segmented contacts of the directional DBS lead was performed until CST threshold was reached. Stereotactic coordinates and thresholds for each contact/segment were recorded along with the initially activated muscle group.

RESULTS
A total of 34 hemispheres were included for analysis. MEP thresholds were recorded from 268 total contacts/segments. For segmented contacts (2 and 3, respectively), the mean highest CST thresholds were 2.33 and 2.62 mA, while the mean lowest CST thresholds were 1.7 and 1.89 mA, suggesting differential thresholds in relation to CST. First dorsal interosseous and abductor pollicis brevis (34% each) were the most commonly activated muscle groups.

CONCLUSION
MEP threshold recording from segmented DBS leads is feasible. MEP recordings can identify segments with highest CST thresholds and may identify segment orientation in relation to CST.
Finding the strongest stable massless column with a follower load and relocatable concentrated masses
Authors: Kirillov Oleg N , Overton Michael L 
Published: March 2021

Summary
We consider the problem of optimal placement of concentrated masses along a massless elastic column that is clamped at one end and loaded by a nonconservative follower force at the free end. The goal is to find the largest possible interval such that the variation in the loading parameter within this interval preserves stability of the structure. The stability constraint is nonconvex and nonsmooth, making the optimization problem quite challenging. We give a detailed analytical treatment for the case of two masses, arguing that the optimal parameter configuration approaches the flutter and divergence boundaries of the stability region simultaneously. Furthermore, we conjecture that this property holds for any number of masses, which in turn suggests a simple formula for the maximal load interval for $n$ masses. This conjecture is strongly supported by extensive computational results, obtained using the recently developed open-source software package granso (GRadient-based Algorithm for Non-Smooth Optimization) to maximize the load interval subject to an appropriate formulation of the nonsmooth stability constraint. We hope that our work will provide a foundation for new approaches to classical long-standing problems of stability optimization for nonconservative elastic systems arising in civil and mechanical engineering.
Germs, Social Networks, and Growth
Authors: Fogli Alessandra , Veldkamp Laura 
Published: March 2021

Abstract
Does the pattern of social connections between individuals matter for macroeconomic outcomes? If so, where do differences in these patterns come from and how large are their effects? Using network analysis tools, we explore how different social network structures affect technology diffusion and thereby a country’s rate of growth. The correlation between high-diffusion networks and income is strongly positive. But when we use a model to isolate the effect of a change in social networks on growth, the effect can be positive, negative, or zero. The reason is that networks diffuse both ideas and disease. Low-diffusion networks have evolved in countries where disease is prevalent because limited connectivity protects residents from epidemics. But a low-diffusion network in a low-disease environment compromises the diffusion of good ideas. In general, social networks have evolved to fit their economic and epidemiological environment. Trying to change networks in one country to mimic those in a higher-income country may well be counterproductive.
Models of supportive care in oncology
Authors: Hui David , Hoge Geordyn , Bruera Eduardo 
Published: March 2021

Purpose of review
Supportive care services have evolved overtime to meet the growing supportive care need of patients with cancer and their families. In this review, we summarize existing definitions of supportive care, highlight empiric studies on supportive care delivery, and propose an integrated conceptual framework on supportive cancer care.

Recent findings
Supportive care aims at addressing the patients’ physical, emotional, social, spiritual, and informational needs throughout the disease trajectory. Interdisciplinary teams are needed to deliver multidimensional care. Oncology teams have an important role providing supportive care in the front lines and referring patients to supportive care services such as palliative care, social work, rehabilitation, psycho-oncology, and integrative medicine. However, the current model of as needed referral and siloed departments can lead to heterogeneous access and fragmented care. To overcome these challenges, we propose a conceptual model in which supportive care services are organized under one department with a unified approach to patient care, program development, and research. Key features of this model include universal referral, systematic screening, tailored specialist involvement, streamlined care, collaborative teamwork, and enhanced outcomes.

Summary
Further research is needed to develop and test innovative supportive care models that can improve patient outcomes.
Sarcopenia is a Predictor for Adverse Clinical Outcome in Pediatric Inflammatory Bowel Disease
Authors: Atlan Lilian , Cohen Shlomi , Shiran Shelly , Sira Liat Ben , Pratt Li‐Tal , Yerushalmy‐Feler Anat 
Published: March 2021

ABSTRACTObjectives:Inflammatory bowel disease (IBD) has a high impact on nutritional status. Sarcopenia is related to higher risk of surgery and rescue therapy in adults with IBD; however, comparable data in pediatric populations are scarce. We evaluated muscle mass as a predictor of disease outcome in pediatric IBD.Methods:All pediatric IBD patients who underwent magnetic resonance enterography (MRE) during 2008 to 2019 were included. Muscle mass was assessed by measuring the area of the psoas muscle at the upper level of L3 on MRE. The psoas area divided by the body surface area (BSA) yielded the psoas index. Clinical and radiological data, including disease location, activity, course, and medications were documented. The control group included non‐IBD children who underwent an MR imaging study.Results:We enrolled 101 IBD patients, 69 (68.3%) with Crohn disease (CD) and 32 (31.7%) with ulcerative colitis (UC) (mean age 15.03 ± 3.27 years). The psoas index was significantly lower in the IBD patients compared with the 87 controls (326 vs 528, respectively, P < 0.001). Patients with a psoas index in the lowest quartile had significantly higher risk for biologic therapy (multivariate analysis, hazard ratio [HR] = 12.1, P = 0.046) and disease exacerbation (HR = 9, P = 0.047) independently of body mass index, compared with patients with a psoas index in the uppermost quartile.Conclusions:Sarcopenia correlates with the radiological severity of pediatric IBD and serves as a predictor for adverse clinical disease outcome. Muscle mass measurement in MRE studies may serve as a possible marker for disease outcome in this population.