Network medicine-based epistasis detection in complex diseases: ready for quantum computing.

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs) (1-3). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs. With NeEDL (network-based epistasis detection via local search), we leverage network medicine to inform the selection of EIs that are an order of magnitude more statistically significant compared to existing tools and consist, on average, of five SNPs. We further show that this computationally demanding task can be substantially accelerated once quantum computing hardware becomes available. We apply NeEDL to eight different diseases and discover genes (affected by EIs of SNPs) that are partly known to affect the disease, additionally, these results are reproducible across independent cohorts. EIs for these eight diseases can be interactively explored in the Epistasis Disease Atlas (https://epistasis-disease-atlas.com). In summary, NeEDL demonstrates the potential of seamlessly integrated quantum computing techniques to accelerate biomedical research. Our network medicine approach detects higher-order EIs with unprecedented statistical and biological evidence, yielding unique insights into polygenic diseases and providing a basis for the development of improved risk scores and combination therapies.

Overcoming Barriers to Latino Participation in Alzheimer's Disease Research.

There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

Admixture mapping of cognitive function in diverse Hispanic and Latino adults: Results from the Hispanic Community Health Study/Study of Latinos.

INTRODUCTION: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities. METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts. RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13. DISCUSSION: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies. HIGHLIGHTS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

Rational use of short-term anorectic drugs for one-year effective treatment of obesity: An analysis of four studies.

BACKGROUND: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity. OBJECTIVE: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed. MATERIALS AND METHODS: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation. RESULTS: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%. CONCLUSION: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.

A leucine-rich repeat receptor kinase as a regulator in the cuticular wax deposition in sorghum.

Cuticular wax (CW) is the first defensive barrier of plants that forms a waterproof barrier, protects the plant from desiccation, and defends against insects, pathogens, and UV radiation. Sorghum, an important grass crop with high heat and drought tolerance, exhibits a much higher wax load than other grasses and the model plant Arabidopsis. In this study, we explored the regulation of sorghum CW biosynthesis using a bloomless mutant. The CW on leaf sheaths of bloomless 41 (bm41) mutant showed significantly reduced very long-chain fatty acids (VLCFAs), triterpenoids, alcohols, and other wax components, with an overall 86% decrease in total wax content compared to the wild-type. Notably, the 28-carbon and 30-carbon VLCFAs were decreased in the mutants. Using bulk segregant analysis, we identified the causal gene of the bloomless phenotype as a leucine-rich repeat transmembrane protein kinase. Transcriptome analysis of the wild-type and bm41 mutant leaf sheaths revealed BM41 as a positive regulator of lipid biosynthesis and steroid metabolism. BM41 may regulate CW biosynthesis by regulating the expression of the gene encoding 3-ketoacyl-CoA synthase 6. Identification of BM41 as a new regulator of CW biosynthesis provides fundamental knowledge for improving grass crops' heat and drought tolerance by increasing CW.

Neurocognitive profiles are associated with subsequent brain integrity in a sample of Hispanics/Latinos: Findings from the SOL-INCA-MRI study (HCHS/SOL).

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration. Highlights: Cognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.

Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos.

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008-2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2',4,4',5,5'-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015-2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (ßs range:-0.053 to -0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

Gut Microbiome Multi-Omics and Cognitive Function in the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging.

INTRODUCTION: We conducted a study within the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging (HCHS/SOL-INCA) cohort to examine the association between gut microbiome and cognitive function. METHODS: We analyzed the fecal metagenomes of 2,471 HCHS/SOL-INCA participants to, cross-sectionally, identify microbial taxonomic and functional features associated with global cognitive function. Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition. RESULTS: Eubacterium species( E. siraeum and E. eligens ), were associated with better cognition. Several KEGG modules, most strongly Ornithine, Serine biosynthesis and Urea Cycle, were associated with worse cognition. DISCUSSION: In a large Hispanic/Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

Neonatal screening of ABO/RhD blood group and direct antiglobulin Coombs test. Experience of a single institution.

BACKGROUND: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth. METHODS: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR). RESULTS: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95% CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1). DISCUSSION: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination.

INTRODUCCIÓN: La determinación del grupo sanguíneo ABO/RhD y la prueba directa de Coombs (PDC) al nacimiento son una práctica recomendada, pero existe variabilidad en su implementación universal. Se presentan los resultados de la determinación al nacimiento del grupo ABO/RhD y la PDC en una cohorte institucional. MÉTODOS: Se incluyeron los recién nacidos entre 2017 y 2020 en un hospital de atención a embarazos de alto riesgo. Se determinó el grupo ABO/RhD y se realizó la PDC en muestras de cordón umbilical o en las primeras 24 horas de vida. Se registraron las variables demográficas, maternas y neonatales. Se estimó la asociación entre las variables mediante la razón de probabilidad (OR). RESULTADOS: Se incluyeron 8721 binomios. La PDC fue positiva en 239 recién nacidos (2.7%), siendo las variables asociadas a la PDC positiva la edad materna > 40 años (OR: 1.5;IC95%: 1.0-2.3), el nacimiento por vía cesárea (1.4; 1.1-2.0), la madre del grupo O (6.4; 3.8-11.8), la prematuridad (3.6; 2.6-5.0); el peso al nacer < 2500 g (2.1; 1.6-2.8); el neonato del grupo A (15.7; 10.7-23.1) o del grupo B (17.6; 11.4-27.2), la hemoglobina al nacer < 13.5 g/dl (4.5; 2.8-7.1) y la reticulocitosis > 9% (1.9; 1.2 a 3.1). DISCUSIÓN: La frecuencia de PDC positiva neonatal es del 2.7%, con asociación significativa la incompatibilidad materna/neonatal al grupo ABO y RhD, con impacto significativo en diversas variables neonatales. Estos resultados apoyan la política de implementación universal al nacimiento de la determinación de ABO/RhD y PDC.

Associations of Allostatic Load with Level of and Change in Cognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. Methods: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.

Sleep-wake behaviors associated with cognitive performance in middle-aged participants of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVES: Many sleep-wake behaviors have been associated with cognition. We examined a panel of sleep-wake/activity characteristics to determine which are most robustly related to having low cognitive performance in midlife. Secondarily, we evaluate the predictive utility of sleep-wake measures to screen for low cognitive performance. METHODS: The outcome was low cognitive performance defined as being >1 standard deviation below average age/sex/education internally normalized composite cognitive performance levels assessed in the Hispanic Community Health Study/Study of Latinos. Analyses included 1006 individuals who had sufficient sleep-wake measurements about 2years later (mean age=54.9, standard deviation= 5.1; 68.82% female). We evaluated associations of 31 sleep-wake variables with low cognitive performance using separate logistic regressions. RESULTS: In individual models, the strongest sleep-wake correlates of low cognitive performance were measures of weaker and unstable 24-hour rhythms; greater 24-hour fragmentation; longer time-in-bed; and lower rhythm amplitude. One standard deviation worse on these sleep-wake factors was associated with ∼20%-30% greater odds of having low cognitive performance. In an internally cross-validated prediction model, the independent correlates of low cognitive performance were: lower Sleep Regularity Index scores; lower pseudo-F statistics (modellability of 24-hour rhythms); lower activity rhythm amplitude; and greater time in bed. Area under the curve was low/moderate (64%) indicating poor predictive utility. CONCLUSION: The strongest sleep-wake behavioral correlates of low cognitive performance were measures of longer time-in-bed and irregular/weak rhythms. These sleep-wake assessments were not useful to identify previous low cognitive performance. Given their potential modifiability, experimental trials could test if targeting midlife time-in-bed and/or irregular rhythms influences cognition.

Career Trajectory After General Surgery Residency: Do Academic Program Graduates Pursue Academic Surgery?

OBJECTIVE: Determine the proportion of contemporary US academic general surgery residency program graduates who pursue academic careers and identify factors associated with pursuing academic careers. SUMMARY BACKGROUND DATA: Many academic residency programs aim to cultivate academic surgeons, yet the proportion of contemporary graduates who choose academic careers is unclear. The potential determinants that affect graduates' decisions to pursue academic careers remain underexplored. METHODS: We collected program and individual-level data on 2015 and 2018 graduates across 96 US academic general surgery residency programs using public resources. We defined those pursuing academic careers as faculty within US allopathic medical school-affiliated surgery departments who published two or more peer-reviewed publications as the first or senior author between 2020-2021. After variable selection using sample splitting LASSO regression, multivariable regression evaluated association with pursuing academic careers among all graduates, and graduates of top-20 residency programs. Secondary analysis using multivariable ordinal regression explored factors associated with high research productivity during early faculty years. RESULTS: Among 992 graduates, 166 (17%) were pursuing academic careers according to our definition. Graduating from a top-20 ranked residency program (OR[95%CI]: 2.34[1.40-3.88]), working with a longitudinal research mentor during residency (OR[95%CI]: 2.21[1.24-3.95]), holding an advanced degree (OR[95%CI]: 2.20[1.19-3.99]), and the number of peer-reviewed publications during residency as first or senior author (OR[95%CI]: 1.13[1.07-1.20]) were associated with pursuing an academic surgery career, while the number of peer-reviewed publications before residency was not (OR[95%CI]: 1.08[0.99-1.20]). Among top 20 program graduates, working with a longitudinal research mentor during residency (OR[95%CI]: 0.95[0.43-2.09]) was not associated with pursuing an academic surgery career. The number of peer-reviewed publications during residency as first or senior author was the only variable associated with higher productivity during early faculty years (OR[95%CI]: 1.12[1.07-1.18]). CONCLUSIONS: Our findings suggest programs that aim to graduate academic surgeons may benefit from ensuring trainees receive infrastructural support and demonstrate sustained commitment to research throughout residency. Our results should be interpreted cautiously as the impact of unmeasured confounders is unclear.

Unlocking the nanoparticle emission potential: a study of varied filaments in 3D printing.

This study investigates nanoparticle emission during 3D printing processes, assessing various filament materials' impact on air quality. Commonly used 3D printers, including both filament and resin-based types, were examined. The study's scope encompasses diverse filament materials like ABS (acrylonitrile butadiene styrene), PLA (polylactic acid), PETG (polyethylene terephthalate glycol), ASA (acrylonitrile styrene acrylate), TPU (thermoplastic polyurethane), PP (polypropylene), nylon, and wood-based variants, alongside three types of resins. The research delves into the relationship between the type of material and nanoparticle emissions, emphasizing temperature's pivotal role. Measurement instruments were employed for nanoparticle quantification, including an engine exhaust particle sizer spectrometer, condensation particle counter, and nanozen dust counters. Notably, results reveal substantial variations in nanoparticle emissions among different filament materials, with ASA, TPU, PP, and ABS showing considerably elevated emission levels and characteristic particle size distribution patterns. The findings prompt practical recommendations for reducing nanoparticle exposure, emphasizing printer confinement, material selection, and adequate ventilation. This study offers insights into potential health risks associated with 3D printing emissions and provides a basis for adopting preventive measures.

Association between anti-PL7 antibodies and increased fibrotic component in patients with antisynthetase syndrome and interstitial lung disease: a cross-sectional study.

OBJECTIVE: To evaluate whether anti-PL7 and anti-PL12 autoantibodies are associated with a greater extent of the fibrotic component of ILD in ASSD patients. METHODS: Patients with ILD-ASSD who were positive for one of the following autoantibodies: anti-Jo1, anti-PL7, anti-PL12, and anti-EJ were included. Clinical manifestations, CPK levels, pulmonary function tests, and HCRT assessments were prospectively collected according to the Goh index. The fibrotic, inflammatory, and overall extension of the Goh index and DLCO were assessed by multiple linear analyses and compared between ASSD antibody subgroups. RESULTS: Sixty-six patients were included; 17 were positive for anti-Jo1 (26%), 17 for anti-PL7 (26%), 20 for anti-PL12 (30%), and 9 (14%) for anti-EJ. Patients with anti-PL7 and anti-PL12 had a more extensive fibrotic component than anti-Jo1. Anti-PL7 patients had a 7.9% increase in the fibrotic extension (cß = 7.9; 95% CI 1.863, 13.918), and the strength of the association was not modified after controlling for sex, age, and time of disease evolution (aß = 7.9; 95% CI 0.677, 15.076) and also was associated with an increase in ILD severity after adjusting for the same variables, denoted by a lower DLCO (aß = - 4.47; 95% CI - 8.919 to - 0.015). CONCLUSIONS: Anti-PL7-positive ASSD patients had more extensive fibrosis and severe ILD than the anti-Jo1 subgroup. This information is clinically useful and has significant implications for managing these patients, suggesting the need for early consideration of concurrent immunosuppressive and antifibrotic therapy.

Characterizing cognitive profiles in diverse middle-aged and older Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL).

Introduction: We investigated cognitive profiles among diverse, middle-aged and older Hispanic/Latino adults in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) cohort using a cross-sectional observational study design. Methods: Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL-INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results: Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average-to-high-average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average-to-low-average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low-average-to-mildly impaired across all cognitive/IADL tests (12.1%). Discussion: Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community-dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights: The present study characterized cognitive profiles among diverse middle-aged and older Hispanic/Latino adults.Latent profile analysis of neurocognitive test scores was the primary analysis conducted.The target population consists of middle-aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos - Investigation of Neurocognitive Aging.