bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction
Authors: Arulalan Karthik Suresh , Huayta Javier , Stallrich Jonathan W , San-Miguel Adriana 
Published: November 2021

Abstract
Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically include multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematode Caenorhabditis elegans, by quantitatively assessing levels of gst-4 expression. Our results indicate that naphthoquinone mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted by C. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics are confounded by environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments (DoE) approaches as they can greatly expand the experimental space probed in noisy biological readouts, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated DoE approaches to identify significant interactions.
A conserved behavioral role for a nematode interneuron neuropeptide receptor
Authors: Chai Cynthia M , Chen Wen , Wong Wan-Rong , Park Heenam , Cohen Sarah M , Wan Xuan , Sternberg Paul W 
Published: November 2021

Abstract
Neuropeptides are evolutionarily conserved modulators of many aspects of animal behavior and physiology, and expand the repertoire of processes that can be controlled by a limited number of neurons. Deciphering the neuropeptidergic codes that govern distinct processes requires systematic functional analyses of neuropeptides and their cognate receptors. Even in well-studied model organisms like Caenorhabditis elegans, however, such efforts have been precluded by a lack of mutant reagents. Here, we generated and screened 21 C. elegans neuropeptide G-protein coupled receptor mutants with no pre-existing reagents for the touch-evoked escape response, and implicated six receptors expressed in diverse neuron classes representing multiple circuit levels in this behavior. We further characterized the mutant with the most severe phenotype, frpr-14, which was defective in multiple behavioral paradigms. We leveraged this range of phenotypes to reveal that FRPR-14 modulation of different precommand interneuron classes, AVH and AIB, can drive distinct behavioral subsets, demonstrating cellular context-dependent roles for FRPR-14 signaling. We then show that Caenorhabditis briggsae CBR-FRPR-14 modulates an AVH-like interneuron pair to regulate the same behaviors as C. elegans but to a smaller extent. Our results also suggest that differences in touch-evoked escape circuit architecture between closely related species results from changes in neuropeptide receptor expression pattern, as opposed to ligand–receptor pairing. This study provides insights into the principles utilized by a compact, multiplexed nervous system to generate intraspecific behavioral complexity and interspecific variation.
Age-Related Sexual Dimorphism on the Longitudinal Progression of Blood Immune Cells in BALB/cByJ Mice
Authors: Serre-Miranda Cláudia , Roque Susana , Barreira-Silva Palmira , Nobrega Claudia , Vieira Neide , Costa Patrício , Almeida Palha Joana , Correia-Neves Margarida 
Published: November 2021

Abstract
The study of immune system aging is of relevance, considering its myriad of interactions and role in protecting and maintaining body homeostasis. While mouse models have been extensively used to study immune system aging, little is known on how the main immune populations progress over time and what is the impact of sex. To contribute to filling this gap, male and female BALB/cByJ mice were longitudinally evaluated, from 3 to 18 months old, for the main blood populations, assessed by flow cytometry. Using linear mixed-effect models, we observed that the percentages of neutrophils, monocytes, eosinophils, and total natural killer (NK) cells increase with aging, while those of B cells, T cells (including CD4+ and CD8+ subsets), and Ly6C+ NK cells decrease. Males present higher percentages of neutrophils and classical monocytes Ly6Chigh over time, while females present higher percentages of total T cells, both CD4+ and CD8+, eosinophils, and NK cells. Males and females display similar percentages of B cells, even though with opposite accelerated progressions over time. This study revealed that mouse models recapitulate what is observed in humans during aging: an overall proportional decrease in the adaptive and an increase in the innate immune cells. Additionally, it uncovers an age-related sexual dimorphism in the proportion of immune cells in circulation, further strengthening the need to explore the impact of sex when addressing immune system aging using mouse models.
Urinary Incontinence and Depressive Symptoms: The Mediating Role of Physical Activity and Social Engagement
Authors: Park Gum-Ryeong , Park Sujeong , Kim Jinho 
Published: November 2021

Abstract

Objectives
This study investigates longitudinal within-person associations between urinary incontinence (UI) and depressive symptoms among older women. Drawing on activity theory, this study also adds to limited knowledge about the mediating role of physical activity and social engagement in the association between UI and depressive symptoms.

Methods
Using 6 waves of a nationally representative longitudinal study of older adults in Korea between 2008 and 2018, this study examined the relationship between UI and depressive symptoms among women aged 70 and older. Fixed effects models were estimated to account for unobserved time-invariant confounding factors. Sobel mediation tests were conducted to formally test for mediation.

Results
Fixed effects estimates showed that, after adjusting for a wide array of time-varying covariates, having UI is positively associated with depressive symptoms among older women (b = 0.238, p &lt; .05). Results revealed that individuals who begin to experience UI tend to have less frequent social interactions and participate in fewer social activities. UI, however, is only marginally associated with a decrease in physical activity. Reductions in physical activity, social connections, and social activities jointly explain about 22% of the association between UI and depressive symptoms, rendering it statistically insignificant.

Discussion
UI poses a threat to psychological well-being among older women. This is partly explained by a decrease in physical activity and disruption in social engagement. This study reaffirms the significance of the programs that promote physical and social activity among older adults.
Feeding of a magma chamber by an ascending magma bubble
Authors: Dragoni Michele 
Published: November 2021

SUMMARY
There is evidence that magma chambers are not fed by a continuous flow, but in the form of discrete magma batches. The possibility is considered that the chamber is fed by a magma bubble ascending through the region underneath, driven by buoyancy force. Due to the high ambient temperatures, it is assumed that the bubble moves through a viscoelastic medium with temperature-dependent viscosity. The motion of a spherical magma bubble and its inflow into the chamber are studied. The bubble volume is assumed to be at least equal to magma volumes in typical effusive eruptions on Mount Etna, corresponding to bubble radii of a few hundred metres. Under some simplifying assumptions, the problem is solved analytically. The bubble velocity is directly proportional to the square of its radius and inversely to the viscosity of surrounding rocks, but it is independent of magma viscosity. Velocity can reach values of the order of tens of metres per year in the proximity of the chamber. Since the characteristic time for heat diffusion is several hundred years, the bubble can cover several kilometres with only moderate cooling. During ascent, forced convection takes place in the bubble. Equations for convection streamlines are obtained and traveltimes of magma are calculated, giving a mixing time of the order of hundred years below the chamber. Inflow of the bubble in the magma chamber produces a pulse in flow rate. Under reasonable assumptions, pulse shape and duration are calculated analytically. Pulse duration can be several tens of years and can give rise to a sequence of eruptions, depending on the size of the bubble and the critical overpressure for eruption.
Anti-Suit Injunctions, FRAND Policies and the Conflict between Overlapping Jurisdictions
Authors: Haedicke Maximilian 
Published: November 2021

Abstract
Numerous courts worldwide consider themselves competent to determine the FRAND compliance of global SEP license agreements and to set worldwide FRAND rates. A court deciding a FRAND case involving a global FRAND rate may issue an injunction which prohibits the filing or enforcement of an action in another jurisdiction (anti-suit injunction, hereinafter ‘ASI’). The parties litigating in the courts of another country may request this court to enjoin the filing or execution of the ASI – (anti-anti-suit injunction, hereinafter ‘AASI’). This article argues that the extraterritorial effects of both ASIs and AASIs may unduly impede court proceedings. However, ASIs and AASIs may in certain cases legitimately protect the interests that sovereign states have in undisturbed court proceedings. Self-restraint should be exercised because each ASI/AASI contains the risk of escalation. The article gives guidelines as to under which conditions ASIs/AASIs may be issued and accepted by the courts. It also aims to raise awareness among policymakers so that internationally binding rules which ease the conflicts may be implemented.
Follow-up Interactive Long-Term Expert Ranking (FILTER): a crowdsourcing platform to adjudicate risk for survivorship care
Authors: Cheng Alex C , Wen Li , Li Yanwei , Koyama Tatsuki , Berry Lynne D , Pal Tuya , Friedman Debra L , Osterman Travis J 
Published: November 2021

Abstract

Objectives
To develop an online crowdsourcing platform where oncologists and other survivorship experts can adjudicate risk for complications in follow-up.

Materials and Methods
This platform, called Follow-up Interactive Long-Term Expert Ranking (FILTER), prompts participants to adjudicate risk between each of a series of pairs of synthetic cases. The Elo ranking algorithm is used to assign relative risk to each synthetic case.

Results
The FILTER application is currently live and implemented as a web application deployed on the cloud.

Discussion
While guidelines for following cancer survivors exist, refinement of survivorship care based on risk for complications after active treatment could improve both allocation of resources and individual outcomes in long-term follow-up.

Conclusion
FILTER provides a means for a large number of experts to adjudicate risk for survivorship complications with a low barrier of entry.
Effect of aspirin to intentionally induce leaky gut on performance, inflammation, and carcass characteristics of feedlot cattle
Authors: Briggs Nathan G , Silva Breno C , Godoi Letícia A , Schoonmaker Jon P 
Published: November 2021

Abstract
The negative impacts of stress on gastrointestinal tract (GIT) barrier function can result in compromised animal growth and health. Aspirin is known to cause mucosal injury leading to increased gut permeability and tight junction damage and can be used as a model to study leaky gut in cattle. The objective of this study was to determine the long-term impact of aspirin-induced chronic leaky gut on cattle growth and carcass attributes. Two treatments were evaluated in two studies: control (no aspirin) or 0.25% of the diet dry matter (DM) aspirin fed daily. Diets consisted of 50% corn, 24% dried distillers grains, 20% corn silage, and 6% supplement on a DM basis. In experiment 1, sixteen Angus × Simmental heifers, allotted by body weight (BW) and breed composition, were fed diets for 154 d. On day 155, heifers were dosed with 1 liter of a 180-mM Cr–ethylenediaminetetraacetic acid solution using an esophageal tube and had urine collected every 1.5 to 3 h for 48 h for analysis of Cr as a measure of gut leakiness. In experiment 2, ninety-six Simmental × Angus steers (355.0 ± 14.8 kg) were allotted by BW and breed composition and fed treatment diets for 159 d. Weight was recorded monthly and serum was collected on day 159 and analyzed for lipopolysaccharide-binding protein (LBP), interleukin-6 (IL-6), serum amyloid A (SAA), haptoglobin, and aspartate aminotransferase (AST). Data were analyzed using the MIXED procedure of SAS. Heifers fed 0.25% aspirin in experiment 1 excreted more Cr into urine compared with heifers not fed aspirin (overall treatment effect, P = 0.01). In experiment 2, aspirin tended to increase serum LBP (P = 0.06) but had no effect on concentrations of IL-6, haptoglobin, SAA, or AST (P ≥ 0.25). Aspirin tended to decrease average daily gain (P = 0.10), decreased hot carcass weight and rib-eye area (P ≤ 0.05), and increased fat thickness, marbling score, and yield grade (P ≤ 0.02). Aspirin tended to increase kidney, pelvic, and heart fat percentage (P = 0.10) and had no effect on liver abscesses (P ≥ 0.80). This study indicates that leaky gut induced by long-term administration of aspirin has negative impacts on feedlot performance and carcass composition. The negative impact of aspirin-induced leaky gut on animal performance suggests that chronic leaky gut caused by other factors (subacute acidosis, stress) may be a significant problem for the feedlot industry.
Volume as an Indicator for Outcomes for Severe Maternal Morbidity in the Military Health System
Authors: Hunter Aimee , Banaag Amanda , Lutgendorf Monica A , Staat Col Barton , Koehlmoos Tracey P 
Published: November 2021

ABSTRACT

Background
Maternal obstetric morbidity is a growing concern in the USA, where rates of maternal morbidity exceed Europe and most developed countries. Prior studies have found that obstetric case volume affects maternal morbidity, with low-volume facilities having higher rates of morbidity. However, these studies were done in civilian healthcare systems that are different from the Military Health System (MHS). This study evaluates whether obstetric case volume impacts severe maternal morbidity (SMM) in military hospitals located in the continental United States.

Methods
This cross-sectional study included all military treatment facilities (MTFs) (n = 35) that performed obstetric deliveries (n = 102,959) from October 2015 to September 2018. Data were collected from the MHS Data Repository and identified all deliveries for the study time period. Severe maternal morbidity was defined by the Centers for Disease Control. The 30-day readmission rates were also included in analysis. Military treatment facilities were separated into volume quartiles for analysis. Univariate logistic regressions were performed to determine the impact of MTF delivery volume on the probability of SMM and 30-day maternal readmissions.

Results
The results for all regression models indicate that the MTF delivery volume had no significant impact on the probability of SMM. With regard to 30-day maternal readmissions, using the upper middle quartile as the comparison group due to the largest number of deliveries, MTFs in the lower middle quartile and in the highest quartile had a statistically significant higher likelihood of 30-day maternal readmissions.

Conclusion
This study shows no difference in SMM rates in the MHS based on obstetric case volume. This is consistent with previous studies showing differences in MHS patient outcomes compared to civilian healthcare systems. The MHS is unique in that it provides families with universal healthcare coverage and access and provides care for approximately 40,000 deliveries annually. There may be unique lessons on volume and outcomes in the MHS that can be shared with healthcare planners and decision makers to improve care in the civilian setting.
Acceleration and clustering of cosmic dust in a gravoturbulent gas I. Numerical simulation of the nearly Jeans-unstable case
Authors: Mattsson Lars , Hedvall Robert 
Published: November 2021

ABSTRACT
We investigate the dynamics of interstellar dust particles in moderately high resolution (5123 grid points) simulations of forced compressible transonic turbulence including self-gravity of the gas. Turbulence is induced by stochastic compressive forcing which is delta-correlated in time. By considering the nearly Jeans-unstable case, where the scaling of the simulation is such that a statistical steady state without any irreversible collapses is obtained, we obtain a randomly varying potential, acting as a second stochastic forcing. We show that, in this setting, low-inertia grains follow the gas flow and cluster in much the same way as in a case of statistical steady-state turbulence without self-gravity. Large, high-inertia grains, however, are accelerated to much higher mean velocities in the presence of self-gravity. Grains of intermediate size also show an increased degree of clustering. We conclude that self-gravity effects can play an important role for aggregation/coagulation of dust even in a turbulent system which is not Jeans-unstable. In particular, the collision rate of large grains in the interstellar medium can be much higher than predicted by previous work.
The Emergence of the Spike Furin Cleavage Site in SARS-CoV-2
Authors: Chan Yujia Alina , Zhan Shing Hei 
Published: November 2021

Abstract
Compared with other SARS-related coronaviruses (SARSr-CoVs), SARS-CoV-2 possesses a unique furin cleavage site (FCS) in its spike. This has stimulated discussion pertaining to the origin of SARS-CoV-2 because the FCS has been observed to be under strong selective pressure in humans and confers the enhanced ability to infect some cell types and induce cell–cell fusion. Furthermore, scientists have demonstrated interest in studying novel cleavage sites by introducing them into SARSr-CoVs. We review what is known about the SARS-CoV-2 FCS in the context of its pathogenesis, origin, and how future wildlife coronavirus sampling may alter the interpretation of existing data.
Xpert MTB/RIF Use Is Associated With Earlier Treatment Initiation and Culture Conversion Among Patients With Sputum Smear-Negative Multidrug-Resistant Tuberculosis
Authors: Kipiani Maia , Graciaa Daniel S , Buziashvili Mariana , Darchia Lasha , Avaliani Zaza , Tabagari Nino , Mirtskhulava Veriko , Kempker Russell R 
Published: November 2021

Abstract

Background
Although rapid molecular diagnostic tests for tuberculosis (TB) have decreased detection time of Mycobacterium tuberculosis and drug resistance, whether their use improves clinical care and outcomes is uncertain. To address these knowledge gaps, we evaluated whether use of the Xpert MTB/RIF assay impacts treatment and clinical outcome metrics among patients treated for sputum smear-negative multidrug-resistant (MDR)-TB.

Methods
We conducted a retrospective cohort study of adult patients initiating treatment for sputum smear-negative MDR-TB at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia from 2011 to 2016. The Xpert MTB/RIF was introduced in Georgia in 2010 and implemented into programmatic use in 2014. Exposure was availability of an Xpert result at time of diagnosis. Time to second-line treatment initiation, sputum culture conversion, and end-of-treatment outcomes were determined. Time to event was compared using a Cox proportional hazards model.

Results
Among 151 patients treated for sputum smear-negative MDR-TB (96% culture positive), the Xpert was utilized in the clinical management of 78 (52%) patients and not used in 73 (48%). An adjusted analysis controlling for potential confounders found that patients in the Xpert group had shorter median time to second-line treatment (13 vs 56 days; adjusted hazard ratio [aHR], 10.21; P &lt; .0001) and culture conversion (61 vs 93 days; aHR, 1.93; P &lt; .001). There was no difference in treatment outcomes.

Conclusions
Use of the Xpert in the management of sputum smear-negative MDR-TB decreases time to second-line therapy and sputum culture conversion, providing evidence of its clinical impact and supporting its programmatic utility.
Characterization of Heavily Treatment-Experienced People With HIV and Impact on Health Care Resource Utilization in US Commercial and Medicare Advantage Health Plans
Authors: Priest Julie , Hulbert Erin , Gilliam Bruce L , Burton Tanya 
Published: November 2021

Abstract

Background
This retrospective administrative claims study aimed to describe clinical characteristics, health care resource utilization (HCRU), and costs of people with HIV (PWH) in US commercial and Medicare Advantage health plans by antiretroviral treatment (ART) experience and CD4+ cell count.

Methods
Data from the national Optum Research Database between January 1, 2014, and March 31, 2018, for adult PWH continuously enrolled 6 months before and ≥12 months after the first ART identified (follow-up) were summarized by treatment (heavily treatment-experienced [HTE] with limited remaining ART options, treatment-experienced but not HTE [non-HTE], or treatment-naive starting a first antiretroviral regimen) and index CD4+ cell count (&lt;200, 200–500, or &gt;500 cells/mm3).

Results
Compared with non-HTE (n=7604) and treatment-naive PWH (n=4357), HTE PWH (n=2297) were older (53.5 vs 48.8 and 42.3 years), were more likely to have HIV-related emergency department visits (22.3% vs 12.4% and 18.6%) and inpatient stays (15.8% vs 7.1% and 10.3%), and had a higher mean (SD) daily pill burden (9.7 [7.7] vs 5.1 [5.9] and 3.6 [5.3] pills/d) and a higher mortality rate (5.9% vs 2.9% and 2.3%) during follow-up (all P&lt;.001). More HTE (21.8%) and treatment-naive PWH (27.0%) had &lt;200 CD4+ cells/mm3 vs non-HTE PWH (8.0%; P&lt;.001). All-cause and HIV-related costs were higher among HTE PWH in all CD4+ cell count strata and treatment-naive PWH with CD4+ cell counts &lt;200 cells/mm3 vs non-HTE PWH in all CD4+ cell count strata.

Conclusions
Improved support and clinical monitoring of HTE PWH are needed to prevent worsening outcomes and increased costs.