bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Aerobic or Resistance Exercise, or Both, on Intermuscular and Visceral Fat and Physical and Metabolic Function in Older Adults With Obesity While Dieting
Authors: Waters Debra L , Aguirre Lina , Gurney Burke , Sinacore David R , Fowler Kenneth , Gregori Giulia , Armamento-Villareal Reina , Qualls Clifford , Villareal Dennis T 
Published: April 2021

Abstract

Background
Obesity exacerbates age-related effects on body composition and physical and metabolic function. Which exercise mode is most effective in mitigating these deleterious changes in dieting older adults with obesity is unknown.

Methods
In a randomized controlled trial, we performed a head-to-head comparison of aerobic (AEX), resistance (REX), or combination (COMB) exercise during matched ~10% weight loss in 160 obese older adults. Prespecified analyses compared 6-month changes in intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) assessed using MRI, insulin sensitivity index (ISI) by oral glucose tolerance test, physical function using Modified Physical Performance Test (PPT), VO2peak, gait speed, and knee strength by dynamometry.

Results
IMAT and VAT decreased more in COMB than AEX and REX groups (IMAT; −41% vs −28% and −23% and VAT: −36% vs −19% and −21%; p = .003 to .01); IMAT and VAT decreased in all groups more than control (between-group p &lt; .001). ISI increased more in COMB than AEX and REX groups (86% vs 50% and 39%; p = .005 to .03). PPT improved more in COMB than AEX and REX groups, while VO2peak improved more in COMB and AEX than REX group (all p &lt; .05). Knee strength improved more in COMB and REX than AEX group (all p &lt; .05). Changes in IMAT and VAT correlated with PPT (r = −0.28 and −0.39), VO2peak (r = −0.49 and −0.52), gait speed (r = −0.25 and −0.36), and ISI (r = −0.49 and −0.52; all p &lt; .05).

Conclusions
Weight loss plus combination aerobic and resistance exercise was most effective in improving ectopic fat deposition and physical and metabolic function in older adults with obesity.
Political integration and the career opportunities of immigrants in political parties: Experiences from Swedish party organisations
Authors: Soininen Maritta , Qvist Martin 
Published: April 2021

Abstract
Political parties are an important part of the institutional framework for migrants’ political integration, but remain an underdeveloped area of research in the literature on political opportunity structures (POS) for migrants. Departing from the POS framework, this article addresses the question of what role the intra-party structure of candidate recruitment has for enabling the political career path of people with migrant background. It focuses on the case of Sweden, which has one of the most open POS in terms of formal political rights. Based on an interview study with party officials and political candidates with migrant background, we identify a number of party-internal factors in this POS. The empirical analysis combines two approaches in institutional theory in order to differentiate between ‘thresholds’ related to strategic considerations and short-term vote-maximisation, and ‘barriers’ embedded in roles, identities and organisational practices. In addition to making a contribution to research on the responsiveness of political systems in open-POS countries, the article discusses how the institutional approach can be useful for identifying possible solutions for supporting the political career of immigrants.
Measuring cosmological distances using cluster edges as a standard ruler
Authors: Wagoner Erika L , Rozo Eduardo , Aung Han , Nagai Daisuke 
Published: April 2021

ABSTRACT
The line-of-sight velocity dispersion profile of galaxy clusters exhibits a ‘kink’ corresponding to the spatial extent of orbiting galaxies. Because the spatial extent of a cluster is correlated with the amplitude of the velocity dispersion profile, we can utilize this feature as a gravity-calibrated standard ruler. Specifically, the amplitude of the velocity dispersion data allows us to infer the physical cluster size. Consequently, observations of the angular scale of the ‘kink’ in the profile can be translated into a distance measurement to the cluster. Assuming the relation between cluster radius and cluster velocity dispersion can be calibrated from simulations, we forecast that with existing data from the Sloan Digital Sky Survey we will be able to measure the Hubble constant with 3.0 per cent precision. Implementing our method with data from the Dark Energy Spectroscopic Instrument (DESI) will result in a 1.3 per cent measurement of the Hubble constant. Adding cosmological supernova data improves the uncertainty of the DESI measurement to 0.7 per cent. While these error estimates are statistical only, they provide strong motivation for pursuing the necessary simulation program required to characterize and calibrate the systematic uncertainties impacting our proposed measurement. Whether or not our proposed measurement can in fact result in competitive H0 constraints will depend on what the eventual systematics floor for this method is.
PARP-1 overexpression does not protect HaCaT cells from DNA damage induced by SiO2 nanoparticles
Authors: Gong Chun-Mei , Xu Yuan-Fei , Liang Xiong-Shun , Mo Jun-Luan , Zhuang Zhi-Xiong 
Published: April 2021

Abstract
Nano-SiO2 is increasingly used in diagnostic and biomedical research because of its ease of production and relatively low cost and which is generally regarded as safe and has been approved for use as a food or animal feed ingredient. Although recent literature reveals that nano-SiO2 may present toxicity and DNA damage, however, the underlying mechanism remains poorly understood. Since in previous studies, we found that nano-SiO2 treatment down-regulated the expression of the poly(ADP-ribose) polymerases-1 (PARP-1), a pivotal DNA repair gene, in human HaCaT cells and PAPR-1 knockdown can aggravate DNA damage induced by nano-SiO2. Therefore, we speculate whether PARP-1 overexpression can protect DNA from damage induced by nano-SiO2. However, our data demonstrated that overexpression of PARP-1 in HaCaT cells slightly enhanced the cellular proliferation of undamaged cells, when compared with both empty vector control cells and parental cells, but had drastic consequences for cells treated with nano-SiO2. The PARP-1 overtransfected cells were sensitized to the cytotoxic effects and DNA damage of nano-SiO2 compared with control parental cells. Meanwhile, flow cytometric analysis of nano-SiO2 stimulated poly(ADP-ribose) synthesis revealed consistently larger fractions of cells positive for this polymer in the PARP-1 overexpression cells than in control clones. Combining our previous research on PARP-1 knockdown HaCaT cells, we hypothesize that an optimal level of cellular poly(ADP-ribose) accumulation exists for the cellular recovery from DNA damage.
Modelling the impact of extending dose intervals for COVID-19 vaccines in Canada
Authors: Nam Austin , Ximenes Raphael , Yeung Man Wah , Mishra Sharmistha , Wu Jianhong , Tunis Matthew , Sander Beate 
Published: April 2021

AbstractBackgroundDual dose SARS-CoV-2 vaccines demonstrate high efficacy and will be critical in public health efforts to mitigate the COVID-19 pandemic and its health consequences; however, many jurisdictions face very constrained vaccine supply. We examined the impacts of extending the interval between two doses of mRNA vaccines in Canada in order to inform deliberations of Canada’s National Advisory Committee on Immunization.MethodsWe developed an age-stratified, deterministic, compartmental model of SARS-CoV-2 transmission and disease to reproduce the epidemiologic features of the epidemic in Canada. Simulated vaccination comprised mRNA vaccines with explicit examination of effectiveness against disease (67% [first dose], 94% [second dose]), hospitalization (80% [first dose], 96% [second dose]), and death (85% [first dose], 96% [second dose]) in adults aged 20 years and older. Effectiveness against infection was assumed to be 90% relative to the effectiveness against disease. We used a 6-week mRNA dose interval as our base case (consistent with early program rollout across Canadian and international jurisdictions) and compared extended intervals of 12 weeks, 16 weeks, and 24 weeks. We began vaccinations on January 1, 2021 and simulated a third wave beginning on April 1, 2021.ResultsExtending mRNA dose intervals were projected to result in 12.1-18.9% fewer symptomatic cases, 9.5-13.5% fewer hospitalizations, and 7.5-9.7% fewer deaths in the population over a 12-month time horizon. The largest reductions in hospitalizations and deaths were observed in the longest interval of 24 weeks, though benefits were diminishing as intervals extended. Benefits of extended intervals stemmed largely from the ability to accelerate coverage in individuals aged 20-74 years as older individuals were already prioritized for early vaccination. Conditions under which mRNA dose extensions led to worse outcomes included: first-dose effectiveness < 65% against death; or protection following first dose waning to 0% by month three before the scheduled 2nd dose at 24-weeks. Probabilistic simulations from a range of likely vaccine effectiveness values did not result in worse outcomes with extended intervals.ConclusionUnder real-world effectiveness conditions, our results support a strategy of extending mRNA dose intervals across all age groups to minimize symptomatic cases, hospitalizations, and deaths while vaccine supply is constrained.
Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia
Authors: Abuga Kelvin M. , Muriuki John Muthii , Uyoga Sophie M. , Mwai Kennedy , Makale Johnstone , Mogire Reagan , Macharia Alex W. , Mohammed Shebe , Mwarumba Salim , Mturi Neema , Bejon Philip , Scott J. Anthony G. , Nairz Manfred , Williams Thomas N. , Atkinson Sarah H. 
Published: April 2021

AbstractBackgroundSevere malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth, within the Salmonella-containing vacuole.MethodsWe first investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged ≤5 years between August 1998 and October 2019 (n=75,015). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malaria anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA alone (n=33); (3) NTS alone (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children.ResultsIn hospitalized children SMA, but not other malaria phenotypes, was associated with an increased risk of NTS (adjusted OR 2.88 [95% CI 1.97, 4.23]; P<0.0001). Risk of NTS increased by 30% with each 1g/dl decrease in hemoglobin concentrations. In hospitalized children median hepcidin levels were lower in the SMA+NTS (9.3 ng/mL [interquartile range 4.7, 49.8]) and SMA (31.1 ng/mL [5.5, 61.2]) groups, compared to levels in those with CM (90.7 ng/mL [38.7, 176.1]) or NTS (105.8 ng/mL [17.3, 233.3]), despite similar ferritin and CRP levels. Soluble transferrin receptor levels were lower in the CM group compared to the other hospitalized groups.ConclusionSMA was associated with increased risk of NTS and with reduced hepcidin levels. We hypothesized that reduced hepcidin might allow increased movement of iron into the Salmonella-containing vacuole favoring bacterial growth.
Involvement of the habenula in the pathophysiology of autism spectrum disorder
Authors: Germann Jürgen , Gouveia Flavia Venetucci , Brentani Helena , Bedford Saashi A. , Tullo Stephanie , Chakravarty M. Mallar , Devenyi Gabriel A. 
Published: April 2021

AbstractThe habenula is a small epithalamic structure that has rich widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder is characterized by social communication deficits, restricted interests and repetitive behaviors, and frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in children and adults with ASD compared to age matched controls. The present study is first to provide evidence of the involvement of the Hb in the pathophysiology of ASD.
Proof-of-principle neural network models for classification, attribution, creation, style-mixing, and morphing of image data for genetic conditions
Authors: Duong Dat , Waikel Rebekah L. , Hu Ping , Tekendo-Ngongang Cedrik , Solomon Benjamin D. 
Published: April 2021

AbstractNeural networks have shown strong potential to aid the practice of healthcare. Mainly due to the need for large datasets, these applications have focused on common medical conditions, where much more data is typically available. Leveraging publicly available data, we trained a neural network classifier on images of rare genetic conditions with skin findings. We used approximately100 images per condition to classify 6 different genetic conditions. Unlike other work related to these types of images, we analyzed both preprocessed images that were cropped to show only the skin lesions, as well as more complex images showing features such as the entire body segment, patient, and/or the background. The classifier construction process included attribution methods to visualize which pixels were most important for computer-based classification. Our classifier was significantly more accurate than pediatricians or medical geneticists for both types of images. Next, we trained two generative adversarial networks to generate new images. The first involved all of the genetic conditions and was used for style-mixing to demonstrate how the diversity of small datasets can be increased. The second focused on different disease stages for one condition and depicted how morphing can illustrate the disease progression of this condition. Overall, our findings show how computational techniques can be applied in multiple ways to small datasets to enhance the study of rare genetic diseases.
Variant Creutzfeldt-Jakob Disease: The Challenge of Preventing a Rare but Potentially Devastating Exposure
Authors: Pandey Ritambhara , Rai Devesh , Giles Julie , Laguio-Vila Maryrose , Lesho Emil 
Published: April 2021

AbstractAlthough rare, patients with variant Creutzfeldt-Jakob Disease (vCJD) in their differential diagnosis of progressive dementia and movement disorder could continue to present to hospitals for care. However, U.S.-based infection control guidelines do not fully address the possibility of vCJD. After near-misses involving increasing numbers of patients with clinical findings and epidemiologic risks compatible with vCJD, or exposures to chronic wasting disease, we sought to improve recognition and prevention of iatrogenic spread of these prion-related diseases.
A CROSS-SECTIONAL SURVEY OF THE PREVALENCE AND THE RISK FACTORS OF TOBACCO USE AMONGST CONSTRUCTION ARTISANS IN EKITI STATE, NIGERIA
Authors: Olomofe Charles Oluwatemitope , Benyon Caryl M , Durowade Kabir Adekunle , Olomofe Oluwafunmike Ruth 
Published: April 2021

ABSTRACTBackgroundConstruction artisans are those who perform skilled work relating to the erection or assembly of a large structure. These artisans are prone to tobacco use. This study aims to assess the prevalence and the associated risk factors of tobacco use amongst construction artisans in Ekiti State, Nigeria.Materials and MethodsThis cross-sectional study employed a multi-stage sampling technique to select participants (carpenters and bricklayers) artisans, journeymen, and their apprentices who were working in Ekiti State. Chi-square and logistic regression were used to test for association in bivariate and multivariate analyses respectively.ResultsThe prevalence of ever-smoke amongst respondents was 19.3%. Multivariate analysis showed that artisans who were within the age range 31-40 years were four times more likely to use tobacco (OR=3.410; CI=1.476-7.878). Similarly, being in school and divorced/separated were associated with tobacco use.ConclusionNoting the increased prevalence of tobacco use among construction artisans when compared to the general population, and few self-reported cases of addiction amongst users demands action from communities and government at all levels.
Atypical N-glycosylation of SARS-CoV-2 impairs the efficient binding of Spike-RBM to the human-host receptor hACE2
Authors: Gámez Gustavo , Hermoso Juan A. , Carrasco-López César , Gómez-Mejia Alejandro , Muskus Carlos E. , Hammerschmidt Sven 
Published: April 2021

AbstractSARS-CoV-2 internalization by human host cells relies on the molecular binding of its spike glycoprotein (SGP) to the angiotensin-converting-enzyme-2 (hACE2) receptor. It remains unknown whether atypical N-glycosylation of SGP modulates SARS-CoV-2 tropism for infections. Here, we address this question through an extensive bioinformatics analysis of publicly available structural and genetic data. We identified two atypical sequons (sequences of N-glycosylation: NGV 481-483 and NGV 501-503), strategically located on the receptor-binding motif (RBM) of SGP and facing the hACE2 receptor. Interestingly, the cryo-electron microscopy structure of trimeric SGP in complex with potent-neutralizing antibodies from convalescent patients revealed covalently-linked N-glycans in NGV 481-483 atypical sequons. Furthermore, NGV 501-503 atypical sequon involves the asparagine-501 residue, whose highly-transmissible mutation N501Y is present in circulating variants of major concerns and affects the SGP-hACE2 binding-interface through the well-knownhotspot-353. These findings suggest that atypical SGP post-translational modifications modulate the SGP-hACE2 binding-affinity affecting consequently SARS-CoV-2 transmission and pathogenesis.
Nonnegative matrix factorization integrates single-cell multi-omic datasets with partially overlapping features
Authors: Kriebel April R. , Welch Joshua D. 
Published: April 2021

AbstractSingle-cell genomic technologies provide an unprecedented opportunity to define molecular cell types in a data-driven fashion, but present unique data integration challenges. Integration analyses often involve datasets with partially overlapping features, including both shared features that occur in all datasets and features exclusive to a single experiment. Previous computational integration approaches require that the input matrices share the same number of either genes or cells, and thus can use only shared features. To address this limitation, we derive a novel nonnegative matrix factorization algorithm for integrating single-cell datasets containing both shared and unshared features. The key advance is incorporating an additional metagene matrix that allows unshared features to inform the factorization. We demonstrate that incorporating unshared features significantly improves integration of single-cell RNA-seq, spatial transcriptomic, SHARE-seq, and cross-species datasets. We have incorporated the UINMF algorithm into the open-source LIGER R package (https://github.com/welch-lab/liger).
Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques
Authors: King Hannah A. D. , Gordon Joyce M. , Naouar Ines Elakhal , Ahmed Aslaa , Cincotta Camila Macedo , Subra Caroline , Peachman Kristina K. , Hack Holly H. , Chen Rita E. , Thomas Paul V. , Chen Wei-Hung , Sankhala Rajeshwer S. , Hajduczki Agnes , Martinez Elizabeth J. , Peterson Caroline E. , Chang William C. , Choe Misook , Smith Clayton , Headley Jarrett A. , Elyard Hanne A. , Cook Anthony , Anderson Alexander , Wuertz Kathryn McGuckin , Dong Ming , Swafford Isabella , Case James B. , Currier Jeffrey R. , Lal Kerri G. , Amare Mihret F. , Dussupt Vincent , Molnar Sebastian , Daye Sharon P. , Zeng Xiankun , Barkei Erica K. , Alfson Kendra , Staples Hilary M. , Carrion Ricardo , Krebs Shelly J. , Paquin-Proulx Dominic , Karasavvas Nicos , Polonis Victoria R. , Jagodzinski Linda L. , Vasan Sandhya , Scott Paul T. , Huang Yaoxing , Nair Manoj S. , Ho David D. , de Val Natalia , Diamond Michael S. , Lewis Mark G. , Rao Mangala , Matyas Gary R. , Gromowski Gregory D. , Peel Sheila A. , Michael Nelson L. , Modjarrad Kayvon , Bolton Diane L. 
Published: April 2021

ABSTRACTEmergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 µg RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only ∼2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development.Significance StatementThe emergence of SARS-CoV-2 variants of concern (VOC) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 Spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation, efficacious vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses exceeding those of current vaccines in terms of breadth and potency and protects against high-dose respiratory tract challenge. Neutralization activity against the B.1.351 VOC within two-fold of wild-type virus and against SARS-CoV-1 indicate exceptional breadth. Our results support consideration of RFN for SARS-like betacoronavirus vaccine development.