bluuebunny/crossref_metadata_2025 huggingface dataset:
Human immunodeficiency virus infection and risks of morbidity and death in adults with incident heart failure
Authors: Avula Harshith R , Ambrosy Andrew P , Silverberg Michael J , Reynolds Kristi , Towner William J , Hechter Rulin C , Horberg Michael , Vupputuri Suma , Leong Thomas K , Leyden Wendy A , Harrison Teresa N , Lee Keane K , Sung Sue Hee , Go Alan S
Published: December 2021

Aims

Human immunodeficiency virus (HIV) increases the risk of heart failure (HF), but whether it influences subsequent morbidity and mortality remains unclear.

Methods and results

We investigated the risks of hospitalization for HF, HF-related emergency department (ED) visits, and all-cause death in an observational cohort of incident HF patients with and without HIV using data from three large US integrated healthcare delivery systems. We estimated incidence rates and adjusted hazard ratios (aHRs) by HIV status at the time of HF diagnosis for subsequent outcomes. We identified 448 persons living with HIV (PLWH) and 3429 without HIV who developed HF from a frequency-matched source cohort of 38 868 PLWH and 386 586 without HIV. Mean age was 59.5 ± 11.3 years with 9.8% women and 31.8% Black, 13.1% Hispanic, and 2.2% Asian/Pacific Islander. Compared with persons without HIV, PLWH had similar adjusted rates of HF hospitalization [aHR 1.01, 95% confidence interval (CI): 0.81–1.26] and of HF-related ED visits [aHR 1.22 (95% CI: 0.99–1.50)], but higher adjusted rates of all-cause death [aHR 1.31 (95% CI: 1.08–1.58)]. Adjusted rates of HF-related morbidity and all-cause death were directionally consistent across a wide range of CD4 counts but most pronounced in the subset with a baseline CD4 count <200 or 200–499 cells/μL.

Conclusion

In a large, diverse cohort of adults with incident HF receiving care within integrated healthcare delivery systems, PLWH were at an independently higher risk of all-cause death but not HF hospitalizations or HF-related ED visits. Future studies investigating modifiable HIV-specific risk factors may facilitate more personalized care to optimize outcomes for PLWH and HF.
Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990–2019
Authors: Safiri Saeid , Karamzad Nahid , Singh Kuljit , Carson-Chahhoud Kristin , Adams Cobi , Nejadghaderi Seyed Aria , Almasi-Hashiani Amir , Sullman Mark J M , Mansournia Mohammad Ali , Bragazzi Nicola Luigi , Kaufman Jay S , Collins Gary S , Kolahi Ali-Asghar
Published: December 2021

Aims

To report the prevalence, deaths, and disability-adjusted life years (DALYs) associated with ischemic heart disease (IHD) and its attributable risk factors in 204 countries and territories from 1990 to 2019, by age, sex, and socio-demographic index (SDI).

Methods and results

Ischemic heart disease was defined as acute myocardial infarction (MI) and chronic IHD (angina; asymptomatic IHD following MI). Cause of death ensemble modelling was used to produce fatality estimates. The prevalence of the non-fatal sequalae of IHD was estimated using DisMod MR 2.1. All estimates were presented as counts and age-standardized rates per 100 000 population. In 2019, IHD accounted for 197.2 million (177.7–219.5) prevalent cases, 9.1 million (8.4–9.7) deaths, and 182.0 million (170.2–193.5) DALYs worldwide. There were decreases in the global age-standardized prevalence rates of IHD [−4.6% (−5.7, −3.6)], deaths [−30.8% (−34.8, −27.2)], and DALYs [−28.6% (−33.3, −24.2)] from 1990 to 2019. In 2019, the global prevalence and death rates of IHD were higher among males across all age groups, while the death rate peaked in the oldest group for both sexes. A negative association was found between the age-standardized DALY rates and SDI. Globally, high systolic blood pressure (54.6%), high low-density lipoprotein cholesterol (46.6%), and smoking (23.9%) were the three largest contributors to the DALYs attributable to IHD.

Conclusion

Although the global age-standardized prevalence, death, and DALY rates all decreased. Prevention and control programmes should be implemented to reduce population exposure to risk factors, reduce the risk of IHD in high-risk populations, and provide appropriate care for communities.
Variation in genomic traits of microbial communities among ecosystems
Authors: Chuckran Peter F , Hungate Bruce A , Schwartz Egbert , Dijkstra Paul
Published: December 2021

Free-living bacteria in nutrient limited environments often exhibit traits which may reduce the cost of reproduction, such as smaller genome size, low GC content and fewer sigma (σ) factor and 16S rRNA gene copies. Despite the potential utility of these traits to detect relationships between microbial communities and ecosystem-scale properties, few studies have assessed these traits on a community-scale. Here, we analysed these traits from publicly available metagenomes derived from marine, soil, host-associated and thermophilic communities. In marine and thermophilic communities, genome size and GC content declined in parallel, consistent with genomic streamlining, with GC content in thermophilic communities generally higher than in marine systems. In contrast, soil communities averaging smaller genomes featured higher GC content and were often from low-carbon environments, suggesting unique selection pressures in soil bacteria. The abundance of specific σ-factors varied with average genome size and ecosystem type. In oceans, abundance of fliA, a σ-factor controlling flagella biosynthesis, was positively correlated with community average genome size—reflecting known trade-offs between nutrient conservation and chemotaxis. In soils, a high abundance of the stress response σ-factor gene rpoS was associated with smaller average genome size and often located in harsh and/or carbon-limited environments—a result which tracks features observed in culture and indicates an increased capacity for stress response in nutrient-poor soils. This work shows how ecosystem-specific constraints are associated with trade-offs which are embedded in the genomic features of bacteria in microbial communities, and which can be detected at the community level, highlighting the importance of genomic features in microbial community analysis.
Microbiological characteristics of bacteremias among COVID-19 hospitalized patients in a tertiary referral hospital in Northern Greece during the second epidemic wave
Authors: Protonotariou Efthymia , Mantzana Paraskevi , Meletis Georgios , Tychala Areti , Kassomenaki Angeliki , Vasilaki Olga , Kagkalou Georgia , Gkeka Ioanna , Archonti Maria , Kati Styliani , Metallidis Simeon , Skoura Lemonia
Published: December 2021

Northern Greece was struck by an intense second COVID-19 (coronavirus disease 2019) epidemic wave during the fall of 2020. Because of the coinciding silent epidemic of multidrug-resistant organisms, the handling of COVID-19 patients became even more challenging. In the present study, the microbiological characteristics of bacteremias in confirmed cases of hospitalized COVID-19 patients were determined. Data from 1165 patients hospitalized between September and December 2020 were reviewed regarding the frequency of bloodstream infections, the epidemiology and the antibiotic susceptibility profiles of the causative bacteria. The hospital's antibiotic susceptibility data for all major nosocomial pathogens isolated from bacteremias of COVID-19 patients between September and December 2020 versus those between September and December 2019 were also compared. Overall, 122 patients developed bacteremia (10.47%). The average of time interval between hospitalization date and development of bacteremia was 13.98 days. Admission to ICU occurred in 98 out of 122 patients with an average stay time of 15.85 days and 90.81% in-hospital mortality. In total, 166 pathogens were recovered including 114 Gram-negative bacteria and 52 Gram-positive cocci. Acinetobacter baumannii was the most frequent (n = 51) followed by Klebsiella pneumoniae (n = 45) and Enterococcus faecium (n = 31). Bacteremias in hospitalized COVID-19 patients were related with prolonged time of hospitalization and higher in-hospital mortality, and the isolated microorganisms represented the bacterial species that were present in our hospital before the COVID-19 pandemic. Worryingly, the antibiotic resistance rates were increased compared with the pre-pandemic era for all major opportunistic bacterial pathogens. The pandemic highlighted the need for continuous surveillance of patients with prolonged hospitalization.
Cytokine and Nitric Oxide-Dependent Gene Regulation in Islet Endocrine and Nonendocrine Cells
Authors: Stancill Jennifer S , Kasmani Moujtaba Y , Khatun Achia , Cui Weiguo , Corbett John A
Published: December 2021

While exposure to inflammatory cytokines is thought to contribute to pancreatic β-cell damage during diabetes, primarily because cytokine-induced nitric oxide impairs β-cell function and causes cell death with prolonged exposure, we hypothesize that there is a physiological role for cytokine signaling that protects β-cells from a number of environmental stresses. This hypothesis is derived from the knowledge that β-cells are essential for survival even though they have a limited capacity to replicate, yet they are exposed to high cytokine levels during infection as most of the pancreatic blood flow is directed to islets. Here, mouse islets were subjected to single-cell RNA sequencing following 18-h cytokine exposure. Treatment with IL-1β and IFN-γ stimulates expression of inducible nitric oxide synthase (iNOS) mRNA and antiviral and immune-associated genes as well as repression of islet identity factors in a subset of β- and non-β-endocrine cells in a nitric oxide-independent manner. Nitric oxide-dependent expression of genes encoding heat shock proteins was observed in both β- and non-β-endocrine cells. Interestingly, cells with high expression of heat shock proteins failed to increase antiviral and immune-associated gene expression, suggesting that nitric oxide may be an internal “off switch” to prevent the negative effects of prolonged cytokine signaling in islet endocrine cells. We found no evidence for pro-apoptotic gene expression following 18-h cytokine exposure. Our findings suggest that the primary functions of cytokines and nitric oxide are to protect islet endocrine cells from damage, and only when regulation of cytokine signaling is lost does irreversible damage occur.
Calcium Signaling in the Photodamaged Skin: In Vivo Experiments and Mathematical Modeling
Authors: Donati Viola , Peres Chiara , Nardin Chiara , Scavizzi Ferdinando , Raspa Marcello , Ciubotaru Catalin D , Bortolozzi Mario , Pedersen Morten Gram , Mammano Fabio
Published: December 2021

The epidermis forms an essential barrier against a variety of insults. The overall goal of this study was to shed light not only on the effects of accidental epidermal injury, but also on the mechanisms that support laser skin resurfacing with intra-epidermal focal laser-induced photodamage, a widespread medical practice used to treat a range of skin conditions. To this end, we selectively photodamaged a single keratinocyte with intense, focused and pulsed laser radiation, triggering Ca2+ waves in the epidermis of live anesthetized mice with ubiquitous expression of a genetically encoded Ca2+ indicator. Waves expanded radially and rapidly, reaching up to eight orders of bystander cells that remained activated for tens of minutes, without displaying oscillations of the cytosolic free Ca2+ concentration (${[ {{\rm{C}}{{\rm{a}}^{2 + }}} ]_c}$). By combining in vivo pharmacological dissection with mathematical modeling, we demonstrate that Ca2+ wave propagation depended primarily on the release of ATP, a prime damage-associated molecular patterns (DAMPs), from the hit cell. Increments of the ${[ {{\rm{C}}{{\rm{a}}^{2 + }}} ]_c}$ in bystander cells were chiefly due to Ca2+ release from the endoplasmic reticulum (ER), downstream of ATP binding to P2Y purinoceptors. ATP-dependent ATP release though connexin hemichannels (HCs) affected wave propagation at larger distances, where the extracellular ATP concentration was reduced by the combined effect of passive diffusion and hydrolysis due to the action of ectonucleotidases, whereas pannexin channels had no role. Bifurcation analysis suggests basal keratinocytes have too few P2Y receptors (P2YRs) and/or phospholipase C (PLC) to transduce elevated extracellular ATP levels into inositol trisphosphate (IP3) production rates sufficiently large to sustain ${[ {{\rm{C}}{{\rm{a}}^{2 + }}} ]_c}$ oscillations.
Efficient approaches for large-scale GWAS with genotype uncertainty
Authors: Jørsboe Emil , Albrechtsen Anders
Published: December 2021

Association studies using genetic data from SNP-chip-based imputation or low-depth sequencing data provide a cost-efficient design for large-scale association studies. We explore methods for performing association studies applicable to such genetic data and investigate how using different priors when estimating genotype probabilities affects the association results. Our proposed method, ANGSD-asso’s latent model, models the unobserved genotype as a latent variable in a generalized linear model framework. The software is implemented in C/C++ and can be run multi-threaded. ANGSD-asso is based on genotype probabilities, which can be estimated using either the sample allele frequency or the individual allele frequencies as a prior. We explore through simulations how genotype probability-based methods compare with using genetic dosages. Our simulations show that in a structured population using the individual allele frequency prior has better power than the sample allele frequency. In scenarios with sequencing depth and phenotype correlation ANGSD-asso’s latent model has higher statistical power and less bias than using dosages. Adding additional covariates to the linear model of ANGSD-asso’s latent model has higher statistical power and less bias than other methods that accommodate genotype uncertainty, while also being much faster. This is shown with imputed data from UK Biobank and simulations.
Next-generation sequencing-based bulked segregant analysis without sequencing the parental genomes
Authors: Zhang Jianbo , Panthee Dilip R
Published: December 2021

Genomic regions that control traits of interest can be rapidly identified using BSA-Seq, a technology in which next-generation sequencing is applied to bulked segregant analysis (BSA). We recently developed the significant structural variant method for BSA-Seq data analysis that exhibits higher detection power than standard BSA-Seq analysis methods. Our original algorithm was developed to analyze BSA-Seq data in which genome sequences of one parent served as the reference sequences in genotype calling and, thus, required the availability of high-quality assembled parental genome sequences. Here, we modified the original script to effectively detect the genomic region–trait associations using only bulk genome sequences. We analyzed two public BSA-Seq datasets using our modified method and the standard allele frequency and G-statistic methods with and without the aid of the parental genome sequences. Our results demonstrate that the genomic region(s) associated with the trait of interest could be reliably identified via the significant structural variant method without using the parental genome sequences.
Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids
Authors: Larson Erica L , Kopania Emily E K , Hunnicutt Kelsie E , Vanderpool Dan , Keeble Sara , Good Jeffrey M
Published: December 2021

Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of meiotic sex chromosome inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X- and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes await further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.
Restricted maximum-likelihood method for learning latent variance components in gene expression data with known and unknown confounders
Authors: Malik Muhammad Ammar , Michoel Tom
Published: December 2021

Random effects models are popular statistical models for detecting and correcting spurious sample correlations due to hidden confounders in genome-wide gene expression data. In applications where some confounding factors are known, estimating simultaneously the contribution of known and latent variance components in random effects models is a challenge that has so far relied on numerical gradient-based optimizers to maximize the likelihood function. This is unsatisfactory because the resulting solution is poorly characterized and the efficiency of the method may be suboptimal. Here, we prove analytically that maximum-likelihood latent variables can always be chosen orthogonal to the known confounding factors, in other words, that maximum-likelihood latent variables explain sample covariances not already explained by known factors. Based on this result, we propose a restricted maximum-likelihood (REML) method that estimates the latent variables by maximizing the likelihood on the restricted subspace orthogonal to the known confounding factors and show that this reduces to probabilistic principal component analysis on that subspace. The method then estimates the variance–covariance parameters by maximizing the remaining terms in the likelihood function given the latent variables, using a newly derived analytic solution for this problem. Compared to gradient-based optimizers, our method attains greater or equal likelihood values, can be computed using standard matrix operations, results in latent factors that do not overlap with any known factors, and has a runtime reduced by several orders of magnitude. Hence, the REML method facilitates the application of random effects modeling strategies for learning latent variance components to much larger gene expression datasets than possible with current methods.
The relative impact of evolving pleiotropy and mutational correlation on trait divergence
Authors: Chebib Jobran , Guillaume Frédéric
Published: December 2021

Both pleiotropic connectivity and mutational correlations can restrict the decoupling of traits under divergent selection, but it is unknown which is more important in trait evolution. To address this question, we create a model that permits within-population variation in both pleiotropic connectivity and mutational correlation, and compare their relative importance to trait evolution. Specifically, we developed an individual-based stochastic model where mutations can affect whether a locus affects a trait and the extent of mutational correlations in a population. We find that traits can decouple whether there is evolution in pleiotropic connectivity or mutational correlation, but when both can evolve, then evolution in pleiotropic connectivity is more likely to allow for decoupling to occur. The most common genotype found in this case is characterized by having one locus that maintains connectivity to all traits and another that loses connectivity to the traits under stabilizing selection (subfunctionalization). This genotype is favored because it allows the subfunctionalized locus to accumulate greater effect size alleles, contributing to increasingly divergent trait values in the traits under divergent selection without changing the trait values of the other traits (genetic modularization). These results provide evidence that partial subfunctionalization of pleiotropic loci may be a common mechanism of trait decoupling under regimes of corridor selection.
Skulls and Stories: Creating the Value of Bones in Johann Friedrich Blumenbach’s Collection
Authors: Schober Sarah-Maria
Published: December 2021

This article focuses on the famous skull collection of the German naturalist Johann Friedrich Blumenbach (1752–1840) to demonstrate that human remains in early modern scientific collections possessed an important but often underestimated economic value in addition to their well-known scientific and social worth. Blumenbach’s skulls are thus presented as a part of a vigorous early modern ‘necro-economy’ and as a product of its networks. The article highlights three strategies of enrichment which were used to create the value of these bones: reference to scientific values, the use of emotions and story-telling. The last two strategies in particular are relevant to present-day debates concerning the restitution of musealized human remains, for their analysis helps us deconstruct a perceptual bias that tends to contrast a Western and predominantly ‘scientific’ (and thus seemingly universal) value of collected human remains with theoretically ‘softer’ cultural values allegedly attributed to them in their countries of origin.
Reduced Electroencephalogram Complexity in Postoperative Delirium
Authors: Tanabe Sean , Parker Maggie , Lennertz Richard , Pearce Robert A , Banks Matthew I , Sanders Robert D
Published: December 2021

Delirium is associated with electroencephalogram (EEG) slowing and impairments in connectivity. We hypothesized that delirium would be accompanied by a reduction in the available cortical information (ie, there is less information processing occurring), as measured by a surrogate, Lempil-Ziv Complexity (LZC), a measure of time-domain complexity. Two ongoing perioperative cohort studies (NCT03124303, NCT02926417) contributed EEG data from 91 patients before and after surgery; 89 participants were used in the analyses. After cleaning and filtering (0.1–50Hz), the perioperative change in LZC and LZC normalized (LZCn) to a phase-shuffled distribution were calculated. The primary outcome was the correlation of within-patient paired changes in delirium severity (Delirium Rating Scale-98 [DRS]) and LZC. Scalp-wide threshold-free cluster enhancement was employed for multiple comparison correction. LZC negatively correlated with DRS in a scalp-wide manner (peak channel r2 = .199, p < .001). This whole brain effect remained for LZCn, though the correlations were weaker (peak channel r2 = .076, p = .010). Delirium diagnosis was similarly associated with decreases in LZC (peak channel p < .001). For LZCn, the topological significance was constrained to the midline posterior regions (peak channel p = .006). We found a negative correlation of LZC in the posterior and temporal regions with monocyte chemoattractant protein-1 (peak channel r2 = .264, p < .001, n = 47) but not for LZCn. Complexity of the EEG signal fades proportionately to delirium severity implying reduced cortical information. Peripheral inflammation, as assessed by monocyte chemoattractant protein-1, does not entirely account for this effect, suggesting that additional pathogenic mechanisms are involved.
Loss of Natriuretic Peptide Receptor C Enhances Sinoatrial Node Dysfunction in Aging and Frail Mice
Authors: Jansen Hailey J , Moghtadaei Motahareh , Rafferty Sara A , Belke Darrell D , Rose Robert A
Published: December 2021

Heart rate (HR) is controlled by the sinoatrial node (SAN). SAN dysfunction is highly prevalent in aging; however, not all individuals age at the same rate. Rather, health status during aging is affected by frailty. Natriuretic peptides regulate SAN function in part by activating natriuretic peptide receptor C (NPR-C). The impacts of NPR-C on HR and SAN function in aging and as a function of frailty are unknown. Frailty was measured in aging wild-type and NPR-C knockout (NPR-C−/−) mice using a mouse clinical frailty index (FI). HR and SAN structure and function were investigated using intracardiac electrophysiology in anesthetized mice, high-resolution optical mapping in intact atrial preparations, histology, and molecular biology. NPR-C−/− mice rapidly became frail leading to shortened life span. HR was reduced and SAN recovery time was increased in older versus younger mice, and these changes were exacerbated in NPR-C−/− mice; however, there was substantial variability among age groups and genotypes. HR and SAN recovery time were correlated with FI score and fell along a continuum regardless of age or genotype. Optical mapping demonstrates impairments in SAN function that were also correlated with FI score. SAN fibrosis was increased in aged and NPR-C−/− mice and was graded by FI score. Loss of NPR-C results in accelerated aging and rapid decline in health status in association with impairments in HR and SAN function. Frailty assessment was effective and better able to distinguish aging-dependent changes in SAN function in the setting of shortened life span due to loss of NPR-C.
Antecedent Metabolic Health and Metformin (ANTHEM) Aging Study: Rationale and Study Design for a Randomized Controlled Trial
Authors: Kumari Santosh , Bubak Matthew T , Schoenberg Hayden M , Davidyan Arik , Elliehausen Christian J , Kuhn Katrin G , VanWagoner Timothy M , Karaman Rowan , Scofield Robert Hal , Miller Benjamin F , Konopka Adam R
Published: December 2021

The antidiabetic medication metformin has been proposed to be the first drug tested to target aging and extend healthspan in humans. While there is extensive epidemiological support for the health benefits of metformin in patient populations, it is not clear if these protective effects apply to those free of age-related disease. Our previous data in older adults without diabetes suggest a dichotomous change in insulin sensitivity and skeletal muscle mitochondrial adaptations after metformin treatment when co-prescribed with exercise. Those who entered the study as insulin-sensitive had no change to detrimental effects while those who were insulin-resistant had positive changes. The objective of this clinical trial is to determine if (a) antecedent metabolic health and (b) skeletal muscle mitochondrial remodeling and function mediate the positive or detrimental effects of metformin monotherapy, independent of exercise, on the metabolism and biology of aging. In a randomized, double-blind clinical trial, adults free of chronic disease (n = 148, 40–75 years old) are stratified as either insulin-sensitive or resistant based on homeostatic model assessment of insulin resistance (≤2.2 or ≥2.5) and take 1 500 mg/day of metformin or placebo for 12 weeks. Hyperinsulinemic-euglycemic clamps and skeletal muscle biopsies are performed before and after 12 weeks to assess primary outcomes of peripheral insulin sensitivity and mitochondrial remodeling and function. Findings from this trial will identify clinical characteristics and cellular mechanisms involved in modulating the effectiveness of metformin treatment to target aging that could inform larger Phase 3 clinical trials aimed at testing aging as a treatment indication for metformin.

Clinical Trials Registration Number: NCT04264897.
Effects of Stress Exposure Versus Appraisal on Episodic Memory Trajectories: Evidence for Risk and Resilience Among Black Older Adults
Authors: Morris Emily P , Brown Lauren L , Zaheed Afsara B , Palms Jordan D , Sol Ketlyne , Martino Alexa , Zahodne Laura B
Published: December 2021

Objectives

Chronic stressors, experienced disproportionately by Black older adults, are a risk factor for memory impairment. Racially patterned stress exposure may contribute to higher rates of Alzheimer’s disease and related dementias (ADRD) among Black older adults compared with Whites, but less is known about the role of stress appraisal. This study examined whether chronic stress exposure mediates racial disparities in memory and whether stress appraisal moderates these associations.

Methods

Participants included 16,924 older adults (Mage = 67.39, 21% Black) from the 2010 and 2012 waves of the Health and Retirement Study who completed measures of chronic stress exposure (health, financial, housing, relationships, and caregiving) and appraisal. Latent growth curves modeled longitudinal performance on a word list memory task over 6 years.

Results

Black older adults reported greater stress exposure than Whites, and greater stress exposure partially mediated Black–White disparities in initial memory (standardized indirect effect = −0.002, p = .009). However, Black older adults appraised stressors as less upsetting than Whites. While stress appraisal did not moderate links between stress exposure and memory, appraising stressors as less upsetting was independently associated with better initial memory. Thus, Black–White disparities in initial memory was partially offset by Black participants’ appraisal of stressors as less upsetting (standardized indirect effect = 0.002, p = .016).

Discussion

Reducing chronic stress exposure may reduce racial disparities in ADRD risk. The counteractive effect of stress appraisal on Black–White disparities in episodic memory highlights resilience factors among Black older adults that should be characterized in future research to move beyond deficit models of ADRD inequality.
Toward Responsible Artificial Intelligence in Long-Term Care: A Scoping Review on Practical Approaches
Authors: Lukkien Dirk R M , Nap Henk Herman , Buimer Hendrik P , Peine Alexander , Boon Wouter P C , Ket Johannes C F , Minkman Mirella M N , Moors Ellen H M
Published: December 2021

Background and Objectives

Artificial intelligence (AI) is widely positioned to become a key element of intelligent technologies used in the long-term care (LTC) for older adults. The increasing relevance and adoption of AI has encouraged debate over the societal and ethical implications of introducing and scaling AI. This scoping review investigates how the design and implementation of AI technologies in LTC is addressed responsibly: so-called responsible innovation (RI).

Research Design and Methods

We conducted a systematic literature search in 5 electronic databases using concepts related to LTC, AI, and RI. We then performed a descriptive and thematic analysis to map the key concepts, types of evidence, and gaps in the literature.

Results

After reviewing 3,339 papers, 25 papers were identified that met our inclusion criteria. From this literature, we extracted 3 overarching themes: user-oriented AI innovation; framing AI as a solution to RI issues; and context-sensitivity. Our results provide an overview of measures taken and recommendations provided to address responsible AI innovation in LTC.

Discussion and Implications

The review underlines the importance of the context of use when addressing responsible AI innovation in LTC. However, limited empirical evidence actually details how responsible AI innovation is addressed in context. Therefore, we recommend expanding empirical studies on RI at the level of specific AI technologies and their local contexts of use. Also, we call for more specific frameworks for responsible AI innovation in LTC to flexibly guide researchers and innovators. Future frameworks should clearly distinguish between RI processes and outcomes.
Profile of the current psychiatrist workforce in South Africa: establishing a baseline for human resource planning and strategy
Authors: Janse van Rensburg Bernard , Kotzé Carla , Moxley Karis , Subramaney Ugasvaree , Zingela Zukiswa , Seedat Soraya
Published: December 2021

The World Health Organization Global Health Observatory Data Repository reports South Africa with 1.52 psychiatrists per 100 000 of the population among other countries in Africa with 0.01 psychiatrists per 100 000 (Chad, Burundi and Niger) to more than 30 per 100 000 for some countries in Europe. The overall situation, while being cognizant that mental health care is not only provided by specialist psychiatrists and that the current treatment gap may have to be addressed by strategies such as appropriate task sharing, suggests that there are actually too few psychiatrists to meet the country’s mental health care needs. To address the need to develop a strategy to increase the local specialist training and examination capacity, a situational review of currently practicing psychiatrists was undertaken by the [BLINDED] and the [BLINDED] using the South African Society of Psychiatrists membership database. The number, distribution and attributes of practicing psychiatrists were compared with international figures on the ratio of psychiatrists per 100 000 population. In April 2019, there were 850 qualified psychiatrists actively practicing in the country and based on the national population figure of 55.6 million people (2016 Census), the psychiatrists per 100 000 ratio was 1.53. This indicates no improvement between 2016 to 2019. From the South African Society of Psychiatrists database, we determined that about 80% of psychiatrists are working in the private sector—a much higher proportion than is usually quoted. As the vast majority of psychiatrists are practicing in urban areas in two provinces, Gauteng (n = 350) and Western Cape (n = 292), the ratio of psychiatrists per 100 000 in these areas is relatively higher at 2.6 and 5.0, respectively, whereas rural areas in South Africa are largely without specialist mental health expertise at a rate of 0.03 per 100 000 population. This investigation provides a discipline-specific situational review of the attributes and distribution of the current workforce of specialists in the country.
A “Priesthood of Knowledge”: The International Thought of Henri de Saint-Simon
Authors: Eijking Jan
Published: December 2021

The French political theorist Henri de Saint-Simon is largely absent from historical International Relations (IR). This article shows why this is unwarranted and introduces him as an international thinker who made lasting contributions to IR's modern conceptual imagination. Largely responding to the French Revolution Saint-Simon rethought the parameters of international order, imagining the international as a realm separable from national politics and conformable to human agency. International order, on his account, could be actively created. This could take the shape of legislation, trade, or large-scale engineering projects: of new methods of governance. Based on a close reading of texts rarely brought into IR’s focus, this article introduces Saint-Simon as a thinker who cut across traditional IR divides and developed a central actor category of international order: impartial, knowledge-based agents of change. His understanding of international reform not only made it possible to theorize and experiment with a role in global governance for technical experts but also masked the imperial underpinnings of the international projects these experts facilitated. The article makes the case that Saint-Simon deserves a firm place in historical IR, that his thought presents an opportunity for revisiting widely held assumptions about international authority, and that a discernible Saint-Simonian strand of international thought puts typically liberal histories of global governance in question.
Development of a repository of computable phenotype definitions using the clinical quality language
Authors: Brandt Pascal S , Pacheco Jennifer A , Rasmussen Luke V
Published: December 2021

Objective

The objective of this study is to create a repository of computable, technology-agnostic phenotype definitions for the purposes of analysis and automatic cohort identification.

Materials and Methods

We selected phenotype definitions from PheKB and excluded definitions that did not use structured data or were not used in published research. We translated these definitions into the Clinical Quality Language (CQL) and Fast Healthcare Interoperability Resources (FHIR) and validated them using code review and automated tests.

Results

A total of 33 phenotype definitions met our inclusion criteria. We developed 40 CQL libraries, 231 value sets, and 347 test cases. To support these test cases, a total of 1624 FHIR resources were created as test data.

Discussion and Conclusion

Although a number of challenges were encountered while translating the phenotypes into structured form, such as requiring specialized knowledge, or imprecise, ambiguous, and conflicting language, we have created a repository and a development environment that can be used for future research on computable phenotypes.
Effects of dietary leucine and tryptophan on serotonin metabolism and growth performance of growing pigs
Authors: Kwon Woong B , Soto Jose A , Stein Hans H
Published: December 2021

An experiment was conducted to test the hypothesis that increased dietary Trp is needed in high-Leu diets for growing pigs to prevent a drop in plasma serotonin and hypothalamic serotonin concentrations and to maintain growth performance of animals. A total of 144 growing pigs (initial weight: 28.2 ± 1.9 kg) were assigned to 9 treatments in a randomized complete block design with 2 blocks, 2 pigs per pen, and 8 replicate pens per treatment. The 9 diets were formulated in a 3 × 3 factorial with 3 levels of dietary Leu (101%, 200%, or 299% standardized ileal digestible [SID] Leu:Lys), and 3 levels of dietary Trp (18%, 23%, or 28% SID Trp:Lys). A basal diet that met requirements for SID Leu and SID Trp was formulated and 8 additional diets were formulated by adding crystalline L-Leu and (or) L-Trp to the basal diet. Individual pig weights were recorded at the beginning of the experiment and at the conclusion of the 21-d experiment. On the last day of the experiment, 1 pig per pen was sacrificed, and blood and hypothalamus samples were collected to measure plasma urea N, plasma serotonin, and hypothalamic serotonin concentrations. Results indicated that increasing dietary Trp increased (P < 0.05) hypothalamic serotonin, whereas increases (P < 0.05) in average daily gain (ADG) and average daily feed intake (ADFI) were observed only in pigs fed diets containing excess Leu. Increasing dietary Leu reduced (P < 0.05) ADG, ADFI, and hypothalamic serotonin. However, the increase in ADG and ADFI caused by dietary Trp was greater if 299% SID Leu:Lys was provided than if 101% SID Leu:Lys was provided (interaction, P < 0.05). Plasma Leu concentration was positively affected by dietary Leu and negatively affected by dietary Trp, but the negative effect of Trp was greater if 299% SID Leu:Lys was provided than if 101% SID Leu:Lys was provided (interaction, P < 0.05). Plasma concentration of Trp was positively affected by increased dietary Trp and increased dietary Leu, but the increase in plasma concentration of Trp was greater if Leu level was at 101% SID Leu:Lys ratio than at 299% SID Leu:Lys ratio (interaction, P < 0.05). In conclusion, increased dietary Leu reduced ADG, ADFI, and hypothalamic serotonin concentration, and influenced metabolism of several indispensable amino acids, but Trp supplementation partly overcame the negative effect of excess Leu. This demonstrates the importance of Trp in regulation of hypothalamic serotonin, and therefore, feed intake of pigs.
Effects of housing beef cow–calf pairs on drylot or pasture in the Midwest on production parameters and calf behavior through feedlot receiving
Authors: Myerscough Megan E , Neira Lucas T , Sexton Keifer H , Hofer Lucas S , Trennepohl Keela M , Meteer William T , Chapple Wesley P , McCann Josh C , Shike Daniel W
Published: December 2021

The objectives were to analyze the effects of housing cow–calf pairs in drylots (DL) or pasture (PAST) on cow performance and reproduction as well as calf performance and behavior through feedlot receiving. Simmental × Angus (2 yr; 108/yr; 81 ± 15.3 d postpartum) spring-calving cows were stratified by age, body weight (BW), body condition score (BCS), and calf sex and allotted to six groups per year. Groups were randomly assigned to one of two treatments: DL or PAST. Cows in DL were limit-fed at maintenance and calves had ad libitum access to the cow diet in an adjacent pen. Pairs on PAST were rotationally grazed and calves received creep ad libitum 3 wk prior to weaning. On day 110, calves were fence-line weaned and behavior was observed on days 111 and 112. On day 116, calves were transported 272 km to a feedlot for a 42-d receiving period. Behavior was evaluated again on days 117 and 118. Data were analyzed using the MIXED procedure of SAS except reproductive data which was analyzed using the GLIMMIX procedure. Cows on DL had greater (P ≤ 0.01) BW and BCS at weaning. There were no differences (P ≥ 0.42) detected in reproductive data. Cows on DL had greater (P = 0.02) milk production. Calves on DL had greater BW (P ≤ 0.01) on day 55 and at weaning and greater preweaning average daily gain (ADG). There were treatment × time effects (P = 0.01) for lying and eating on days 111 and 112. More DL calves were eating in the morning and lying in the evening. More (P < 0.01) PAST calves were walking on day 111. Pasture calves vocalized more (P ≤ 0.01) on day 112. On day 117, more (P ≤ 0.05) pasture calves were lying and eating, and DL vocalized more. On day 118, treatment × time and treatment effects were detected (P ≤ 0.02) for lying and walking. More PAST calves were lying and more DL calves were walking. Drylot calves had greater (P ≤ 0.02) BW at the beginning and end of the receiving phase. Pasture calves had greater (P < 0.01) ADG and tended (P = 0.10) to have greater gain efficiency during feedlot receiving phase. In conclusion, housing cow–calf pairs in drylots improved BW, BCS, and milk production of cows but did not affect reproductive performance. Drylot calves had increased BW and ADG during the preweaning phase. Calf behavior at weaning and receiving was influenced by preweaning housing. Pasture calves had improved receiving phase ADG and feed efficiency but were still lighter than drylot calves after 42-d receiving phase.
Intermittent maternofetal oxygenation during late gestation improved birthweight, neonatal growth, body symmetry, and muscle metabolism in intrauterine growth-restricted lambs
Authors: Cadaret Caitlin N , Posont Robert J , Swanson Rebecca M , Beard Joslyn K , Gibbs Rachel L , Barnes Taylor L , Marks-Nelson Eileen S , Petersen Jessica L , Yates Dustin T
Published: December 2021

In humans and animals, intrauterine growth restriction (IUGR) results from fetal programming responses to poor intrauterine conditions. Chronic fetal hypoxemia elevates circulating catecholamines, which reduces skeletal muscle β2 adrenoceptor content and contributes to growth and metabolic pathologies in IUGR-born offspring. Our objective was to determine whether intermittent maternofetal oxygenation during late gestation would improve neonatal growth and glucose metabolism in IUGR-born lambs. Pregnant ewes were housed at 40 °C from the 40th to 95th day of gestational age (dGA) to produce IUGR-born lambs (n = 9). A second group of IUGR-born lambs received prenatal O2 supplementation via maternal O2 insufflation (100% humidified O2, 10 L/min) for 8 h/d from dGA 130 to parturition (IUGR+O2, n = 10). Control lambs (n = 15) were from pair-fed thermoneutral ewes. All lambs were weaned at birth, hand-reared, and fitted with hindlimb catheters at day 25. Glucose-stimulated insulin secretion (GSIS) and hindlimb hyperinsulinemic-euglycemic clamp (HEC) studies were performed at days 28 and 29, respectively. At day 30, lambs were euthanized and ex vivo HEC studies were performed on isolated muscle. Without maternofetal oxygenation, IUGR lambs were 40% lighter (P < 0.05) at birth and maintained slower (P < 0.05) growth rates throughout the neonatal period compared with controls. At 30 d of age, IUGR lambs had lighter (P < 0.05) hindlimbs and flexor digitorum superficialis (FDS) muscles. IUGR+O2 lambs exhibited improved (P < 0.05) birthweight, neonatal growth, hindlimb mass, and FDS mass compared with IUGR lambs. Hindlimb insulin-stimulated glucose utilization and oxidation rates were reduced (P < 0.05) in IUGR but not IUGR+O2 lambs. Ex vivo glucose oxidation rates were less (P < 0.05) in muscle from IUGR but not IUGR+O2 lambs. Surprisingly, β2 adrenoceptor content and insulin responsiveness were reduced (P < 0.05) in muscle from IUGR and IUGR+O2 lambs compared with controls. In addition, GSIS was reduced (P < 0.05) in IUGR lambs and only modestly improved (P < 0.05) in IUGR+O2. Insufflation of O2 also increased (P < 0.05) acidosis and hypercapnia in dams, perhaps due to the use of 100% O2 rather than a gas mixture with a lesser O2 percentage. Nevertheless, these findings show that intermittent maternofetal oxygenation during late gestation improved postnatal growth and metabolic outcomes in IUGR lambs without improving muscle β2 adrenoceptor content.
Genetic diversity and detection of atypical porcine pestivirus infections
Authors: Sutton Kylee M , Eaton Christian W , Borza Tudor , Burkey Thomas E , Mote Benny E , Loy John Dustin , Ciobanu Daniel C
Published: December 2021

Atypical porcine pestivirus (APPV), an RNA virus member of the Flaviviridae family, has been associated with congenital tremor in newborn piglets. Previously reported quantitative polymerase chain reaction (qPCR)–based assays were unable to detect APPV in novel cases of congenital tremor originated from multiple farms from U.S. Midwest (MW). These assays targeted the viral polyprotein coding genes, which were shown to display substantial variation, with sequence identity ranging from 58.2% to 70.7% among 15 global APPV strains. In contrast, the 5′-untranslated region (5′ UTR) was found to have a much higher degree of sequence conservation. In order to obtain the complete 5′ UTR of the APPV strains originated from MW, the 5′ end of the viral cDNA was obtained by using template switching approach followed by amplification and dideoxy sequencing. Eighty one percent of the 5′ UTR was identical across 14 global and 5 MW strains with complete or relatively complete 5′ UTR. Notably, some of the most highly conserved 5′ UTR segments overlapped with potentially important regions of an internal ribosome entry site (IRES), suggesting their functional role in viral protein translation. A newly designed single qPCR assay, targeting 100% conserved 5′ UTR regions across 19 strains, was able to detect APPV in samples of well documented cases of congenital tremor which originated from five MW farm sites (1–18 samples/site). As these fully conserved 5′ UTR sequences may have functional importance, we expect that assays targeting this region would broadly detect APPV strains that are diverse in space and time.