Miracle-dz/UniFAR-FTUs huggingface dataset:
Bringing Critical Race Praxis Into the Study of Electrophysiological Substrate of Sudden Cardiac Death: The ARIC Study

Background Race is an established risk factor for sudden cardiac death (SCD). We sought to determine whether the association of electrophysiological substrate with SCD varies between black and white individuals. Methods and Results Participants from the ARIC (Atherosclerosis Risk in Communities) study with analyzable ECGs (n=14 408; age, 54±6 years; 74% white) were included. Electrophysiological substrate was characterized by ECG metrics. Two competing outcomes were adjudicated: SCD and non‐SCD. Interaction of ECG metrics with race was studied in Cox proportional hazards and Fine‐Gray competing risk models, adjusted for prevalent cardiovascular disease, risk factors, and incident nonfatal cardiovascular disease. At the baseline visit, adjusted for age, sex, and study center, blacks had larger spatial ventricular gradient magnitude (0.30 mV; 95% CI, 0.25–0.34 mV), sum absolute QRST integral (18.4 mV*ms; 95% CI, 13.7–23.0 mV*ms), and Cornell voltage (0.30 mV; 95% CI, 0.25–0.35 mV) than whites. Over a median follow‐up of 24.4 years, SCD incidence was higher in blacks (2.86 per 1000 person‐years; 95% CI, 2.50–3.28 per 1000 person‐years) than whites (1.37 per 1000 person‐years; 95% CI, 1.22–1.53 per 1000 person‐years). Blacks with hypertension had the highest rate of SCD: 4.26 (95% CI, 3.66–4.96) per 1000 person‐years. Race did not modify an association of ECG variables with SCD, except QRS‐T angle. Spatial QRS‐T angle was associated with SCD in whites (hazard ratio, 1.38; 95% CI, 1.25–1.53) and hypertension‐free blacks (hazard ratio, 1.52; 95% CI, 1.09–2.12), but not in blacks with hypertension (hazard ratio, 1.15; 95% CI, 0.99–1.32) (P‐interaction=0.004). Conclusions Race did not modify associations of electrophysiological substrate with SCD and non‐SCD. Electrophysiological substrate does not explain racial disparities in SCD rate.
Using social return on investment analysis to calculate the social impact of modified vehicles for people with disability

Abstract Introduction Returning to driving is often a goal for people with acquired disabilities. Vehicle modifications make it possible for people with both acquired and lifelong disabilities to drive yet can be costly. There has been no financial evaluation of vehicle modifications in Australia or internationally. Methods A social return on investment analysis of vehicle modifications was undertaken. Primary data were collected via qualitative interviews with consumers and other stakeholders (e.g. driver‐trained occupational therapists, rehabilitation physicians, driving instructors, vehicle modifiers) (n = 23). Secondary data were collected from literature searches and used to identify suitable financial proxies and make estimations of the proportion of drivers with vehicle modifications experiencing each outcome. A co‐investment model was adopted to estimate social return on investment and payback period for funder and consumer. Five scenarios were developed to illustrate social return for low‐cost modifications (Scenario 1) through to high‐cost modifications (Scenario 5). Results Social return on investment ratios was positive for funder and consumer investment in all five scenarios. Social return on investment calculations based on co‐investment ranged from $17.32 for every $1 invested (Scenario 1) to $2.78 for every $1 invested (Scenario 5). Consumers' payback periods were between 5.4 and 7.1 months, and funders between 3.5 weeks and 2 years 8.4 months. Conclusion Vehicle modifications represent sound investments for both funders and consumers. Given the short payback periods, funders should reconsider age restrictions on vehicles considered suitable for modifications, especially for low‐ to medium‐cost modifications.
Secukinumab Efficacy in Psoriatic Arthritis

Supplemental digital content is available in the text. Background Using a machine learning approach, the study investigated if specific baseline characteristics could predict which psoriatic arthritis (PsA) patients may gain additional benefit from a starting dose of secukinumab 300 mg over 150 mg. We also report results from individual patient efficacy meta-analysis (IPEM) in 2049 PsA patients from the FUTURE 2 to 5 studies to evaluate the efficacy of secukinumab 300 mg, 150 mg with and without loading regimen versus placebo at week 16 on achievement of several clinically relevant difficult-to-achieve (higher hurdle) endpoints. Methods Machine learning employed Bayesian elastic net to analyze baseline data of 2148 PsA patients investigating 275 predictors. For IPEM, results were presented as difference in response rates versus placebo at week 16. Results Machine learning showed secukinumab 300 mg has additional benefits in patients who are anti–tumor necrosis factor–naive, treated with 1 prior anti–tumor necrosis factor agent, not receiving methotrexate, with enthesitis at baseline, and with shorter PsA disease duration. For IPEM, at week 16, all secukinumab doses had greater treatment effect (%) versus placebo for higher hurdle endpoints in the overall population and in all subgroups; 300-mg dose had greater treatment effect than 150 mg for all endpoints in overall population and most subgroups. Conclusions Machine learning identified predictors for additional benefit of secukinumab 300 mg compared with 150 mg dose. Individual patient efficacy meta-analysis showed that secukinumab 300 mg provided greater improvements compared with 150 mg in higher hurdle efficacy endpoints in patients with active PsA in the overall population and most subgroups with various levels of baseline disease activity and psoriasis.
Total Sugar Intake and Macro and Micronutrients in Children Aged 6–8 Years: The ANIVA Study

The objective of this study was to study the association between total sugar intake (TSI) levels of children aged 6–8 years old, nutrient intake and anthropometry. Food and beverage intakes were collected by a prospective three-day recall questionnaire. The 2237 children were distributed into three groups according to TSI percentiles. Mean TSI was 93.77 ± 25.72 g/day, 22%–25% of total caloric intake, with boys presenting an intake of 96.24 ± 24.34 g/day and girls 91.38 ± 26.78 g/day. Greater TSI was associated with higher body fat, parental education, energy intake, nutrients/1000 kcal, and lower weight z-scores, BMI z-scores, waist circumferences, and hip circumferences. Weight, height, and waist circumference had the highest R2 while body fat had the lowest. The percentage of total energy derived (%E) from protein decreased as the %E from TSI increased, while the opposite was true for carbohydrates and saccharides, while for fiber intake, the medium groups presented the highest intake/1000 kcal. For the remaining macronutrients studied, intake/1000 kcal decreased when the %E from TSI increased. Calcium, iodine, magnesium, vitamin B2, folate, and vitamin C intake increased as the %E from TSI increased, while the opposite was true for vitamin B12. Fiber, ω-6 PUFA, iodine, folate, vitamin D, and vitamin E intakes were insufficient across most of the sample. TSI levels in children were identified to exceed adult recommendations. It is not clear what the effect of up to an average of 21% of energy coming from total sugars has on childhood obesity and further research is needed in the pediatric population, however, opportunities exist to improve sugar intake patterns.
Increased Urinary 3-Mercaptolactate Excretion and Enhanced Passive Systemic Anaphylaxis in Mice Lacking Mercaptopyruvate Sulfurtransferase, a Model of Mercaptolactate-Cysteine Disulfiduria

Mercaptopyruvate sulfurtransferase (Mpst) and its homolog thiosulfate sulfurtransferase (Tst = rhodanese) detoxify cyanide to thiocyanate. Mpst is attracting attention as one of the four endogenous hydrogen sulfide (H2S)/reactive sulfur species (RSS)-producing enzymes, along with cystathionine β-synthase (Cbs), cystathionine γ-lyase (Cth), and cysteinyl-tRNA synthetase 2 (Cars2). MPST deficiency was found in 1960s among rare hereditary mercaptolactate-cysteine disulfiduria patients. Mpst-knockout (KO) mice with enhanced liver Tst expression were recently generated as its model; however, the physiological roles/significances of Mpst remain largely unknown. Here we generated three independent germ lines of Mpst-KO mice by CRISPR/Cas9 technology, all of which maintained normal hepatic Tst expression/activity. Mpst/Cth-double knockout (DKO) mice were generated via crossbreeding with our previously generated Cth-KO mice. Mpst-KO mice were born at the expected frequency and developed normally like Cth-KO mice, but displayed increased urinary 3-mercaptolactate excretion and enhanced passive systemic anaphylactic responses when compared to wild-type or Cth-KO mice. Mpst/Cth-DKO mice were also born at the expected frequency and developed normally, but excreted slightly more 3-mercaptolactate in urine compared to Mpst-KO or Cth-KO mice. Our Mpst-KO, Cth-KO, and Mpst/Cth-DKO mice, unlike semi-lethal Cbs-KO mice and lethal Cars2-KO mice, are useful tools for analyzing the unknown physiological roles of endogenous H2S/RSS production.
Cardiovascular Risk Factors in Patients for Vascular Surgery

Various attempts have made been made to quantify the cardiovascular risk factors associated with anaesthesia and surgery. Two such schemes are the “Multifactorial Index of Cardiac Risk” developed by Goldman et al., and the one devised by Cooperman et al. The validity of these two schemes in relation to anaesthesia for vascular surgery was investigated by carrying out a prospective study of 100 patients. Cooperman's scheme was found to be much more accurate than Goldman's scheme in assessing patient risk. The study confirms the impression that the vascular patient falls into a higher risk group than most other surgical patients with regard to cardiovascular complications.
A histopathological, immunohistochemical and biochemical investigation of the antidiabetic effects of the Pistacia terebinthus in diabetic rats

ABSTRACT We investigated the antidiabetic activity of Pistacia terebinthus (PT) extracts in streptozotocin (STZ) induced diabetic rats. We used 40 Wistar albino male rats divided into five groups: control (C), diabetes (DM), diabetes + acarbose (DM + AC), diabetes + PT (DM + PT) and PT. DM was established by intraperitoneal injection of STZ. Immunohistochemistry revealed that STZ reduced insulin immunoreactivity in the pancreas of the diabetic rats. To the contrary, insulin immunoreactivity in the pancreatic β cells of PT treated diabetic rats was increased significantly. Decreased levels of blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glucose, total triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were found in the PT supplemented diabetic group. Also, malondialdehyde (MDA) and antioxidant defense system enzyme levels were normalized in the DM + PT group. PT exhibited a protective effect on liver, kidney and pancreas that had been damaged by STZ induced DM.
Concentration-Dependent Recruitment of Mammalian Odorant Receptors

Abstract A fundamental challenge in studying principles of organization used by the olfactory system to encode odor concentration information has been identifying comprehensive sets of activated odorant receptors (ORs) across a broad concentration range inside freely behaving animals. In mammals, this has recently become feasible with high-throughput sequencing-based methods that identify populations of activated ORs in vivo. In this study, we characterized the mouse OR repertoires activated by the two odorants, acetophenone (ACT) and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), from 0.01% to 100% (v/v) as starting concentrations using phosphorylated ribosomal protein S6 capture followed by RNA-Seq. We found Olfr923 to be one of the most sensitive ORs that is enriched by ACT. Using a mouse line that genetically labels Olfr923-positive axons, we provided evidence that ACT activates the Olfr923 glomeruli in the olfactory bulb. Through molecular dynamics stimulations, we identified amino acid residues in the Olfr923 binding cavity that facilitate ACT binding. This study sheds light on the active process by which unique OR repertoires may collectively facilitate the discrimination of odorant concentrations.
Cardiopharyngeal mesoderm origins of musculoskeletal and connective tissues in the mammalian pharynx

ABSTRACT Cardiopharyngeal mesoderm (CPM) gives rise to muscles of the head and heart. Using genetic lineage analysis in mice, we show that CPM develops into a broad range of pharyngeal structures and cell types encompassing musculoskeletal and connective tissues. We demonstrate that CPM contributes to medial pharyngeal skeletal and connective tissues associated with both branchiomeric and somite-derived neck muscles. CPM and neural crest cells (NCC) make complementary mediolateral contributions to pharyngeal structures, in a distribution established in the early embryo. We further show that biallelic expression of the CPM regulatory gene Tbx1, haploinsufficient in 22q11.2 deletion syndrome patients, is required for the correct patterning of muscles with CPM-derived connective tissue. Our results suggest that CPM plays a patterning role during muscle development, similar to that of NCC during craniofacial myogenesis. The broad lineage contributions of CPM to pharyngeal structures provide new insights into congenital disorders and evolution of the mammalian pharynx. Summary: Cardiopharyngeal mesoderm, source of heart and head muscles, unexpectedly gives rise to a broad range of pharyngeal structures implicated in muscle patterning, pharyngeal pathology and evolution.
Reconstituting the Mammalian Apoptotic Switch in Yeast

Proteins of the Bcl-2 family regulate the permeabilization of the mitochondrial outer membrane that represents a crucial irreversible step in the process of induction of apoptosis in mammalian cells. The family consists of both proapoptotic proteins that facilitate the membrane permeabilization and antiapoptotic proteins that prevent it in the absence of an apoptotic signal. The molecular mechanisms, by which these proteins interact with each other and with the mitochondrial membranes, however, remain under dispute. Although yeast do not have apparent homologues of these apoptotic regulators, yeast cells expressing mammalian members of the Bcl-2 family have proved to be a valuable model system, in which action of these proteins can be effectively studied. This review focuses on modeling the activity of proapoptotic as well as antiapoptotic proteins of the Bcl-2 family in yeast.
The mediating effect of different exercise programs on the immune profile of frail older women with cognitive impairment.

BACKGROUND Frail individuals experience an accelerated immunosenescence, and exercise has been identified as a therapy to promote a better inflammatory environment. OBJECTIVE To analyze the effects of 28-weeks of two different exercise protocols on the functional fitness and immune profiles of institutionalized pre-frail and frail women with mild cognitive impairment. METHODS Participants residing in care homes (n=60, 81±7.84 years old) were randomized into three groups: a chair elastic band muscle-strength exercise (CSE, n=21; 81±4.79), a chair multimodal exercise (CME, n=20; 80±8.19) and a control non-exercise (CGne, n=19; 80±10.01). Both CME and CSE groups performed progressive circuit-training exercise sessions. The controls did not change their usual lifestyle. The Fried protocol and the Mini Mental State Examination questionnaire were used to identify the frail subgroups and the participants with mild cognitive impairment. Data for anti and pro-inflammatory markers and physical fitness were analyzed pre and post-interventions. RESULTS After the intervention, a significant effect of time and time by group for sIgA and time by group for IL-10 levels were found (p > 0.05). Within-group analysis showed a significant moderate decrease in the TNF-α to IL-10 ratio for the CME group and an increase in the controls (p > 0.05) and a slight reduction in the IL-6 and IL-1β concentrations. The controls showed a negative trend towards a decrease in physical fitness and a trend for increased levels in the pro-inflammatory markers IL-6 and IL-1β. CONCLUSIONS The evidence regarding the use of systematic and moderate long-term exercise as therapy for promoting a better balance between pro- and anti-inflammatory environments and a decrease in the inflammatory index for the CME group were the most promising results from this study.
Pseudomonas aeruginosa Alginate Benefits Staphylococcus aureus?

In this issue of Journal of Bacteriology, Price et al. show that the Pseudomonas aeruginosa-produced exopolysaccharide alginate protects Staphylococcus aureus by dampening the expression of P. aeruginosa virulence products that usually inhibit S. aureus respiration and cell membrane integrity when the two organisms compete in other environments (C. E. Price, D. G. Brown, D. H. Limoli, V. V. Phelan, and G. ABSTRACT In this issue of Journal of Bacteriology, Price et al. show that the Pseudomonas aeruginosa-produced exopolysaccharide alginate protects Staphylococcus aureus by dampening the expression of P. aeruginosa virulence products that usually inhibit S. aureus respiration and cell membrane integrity when the two organisms compete in other environments (C. E. Price, D. G. Brown, D. H. Limoli, V. V. Phelan, and G. A. O’Toole, J Bacteriol 202:e00559-19, 2020, https://doi.org/10.1128/jb.00559-19). This is the first report that exogenously added alginate affects P. aeruginosa competition and provides a partial explanation for S. aureus and P. aeruginosa coinfections in cystic fibrosis.
Predicting Cardiovascular Outcomes by Baseline Lipoprotein(a) Concentrations: A Large Cohort and Long‐Term Follow‐up Study on Real‐World Patients Receiving Percutaneous Coronary Intervention

Background Although several studies have indicated that lipoprotein(a) is a useful prognostic predictor for patients following percutaneous coronary intervention (PCI), previous observations have somewhat been limited by either small sample size or short‐term follow‐up. Hence, this study aimed to evaluate the impact of lipoprotein(a) on long‐term outcomes in a large cohort of stable coronary artery disease patients after PCI. Methods and Results In this multicenter and prospective study, we consecutively enrolled 4078 stable coronary artery disease patients undergoing PCI from March 2011 to March 2016. They were categorized according to both the median of lipoprotein(a) levels and lipoprotein(a) values of <15 (low), 15 to 30 (medium), and ≥30 mg/dL (high). All patients were followed up for occurrence of cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and stroke. During an average of 4.9 years of follow‐up, 315 (7.7%) cardiovascular events occurred. The events group had significantly higher lipoprotein(a) levels than the nonevents group. Compared with the low lipoprotein(a) group, Kaplan–Meier analysis showed that the high lipoprotein(a) group had a significantly lower cumulative event‐free survival rate, and multivariate Cox regression analysis further revealed that the high lipoprotein(a) group had significantly increased cardiovascular events risk. Moreover, adding continuous or categorical lipoprotein(a) to the Cox model led to a significant improvement in C‐statistic, net reclassification, and integrated discrimination. Conclusions With a large sample size and long‐term follow‐up, our data confirmed that high lipoprotein(a) levels could be associated with a poor prognosis after PCI in stable coronary artery disease patients, suggesting that lipoprotein(a) measurements may be useful for patient risk stratification before selective PCI.
MiRNA‐137‐mediated modulation of mitochondrial dynamics regulates human neural stem cell fate

The role of miRNAs in determining human neural stem cell (NSC) fate remains elusive despite their high expression in the developing nervous system. In this study, we investigate the role of miR‐137, a brain‐enriched miRNA, in determining the fate of human induced pluripotent stem cells‐derived NSCs (hiNSCs). We show that ectopic expression of miR‐137 in hiNSCs reduces proliferation and accelerates neuronal differentiation and migration. TargetScan and MicroT‐CDS predict myocyte enhancer factor‐2A (MEF2A), a transcription factor that regulates peroxisome proliferator‐activated receptor‐gamma coactivator (PGC1α) transcription, as a target of miR‐137. Using a reporter assay, we validate MEF2A as a downstream target of miR‐137. Our results indicate that reduced levels of MEF2A reduce the transcription of PGC1α, which in turn impacts mitochondrial dynamics. Notably, miR‐137 accelerates mitochondrial biogenesis in a PGC1α independent manner by upregulating nuclear factor erythroid 2 (NFE2)‐related factor 2 (NRF2) and transcription factor A of mitochondria (TFAM). In addition, miR‐137 modulates mitochondrial dynamics by inducing mitochondrial fusion and fission events, resulting in increased mitochondrial content and activation of oxidative phosphorylation (OXPHOS) and oxygen consumption rate. Pluripotency transcription factors OCT4 and SOX2 are known to have binding sites in the promoter region of miR‐137 gene. Ectopic expression of miR‐137 elevates the expression levels of OCT4 and SOX2 in hiNSCs which establishes a feed‐forward self‐regulatory loop between miR‐137 and OCT4/SOX2. Our study provides novel molecular insights into NSC fate determination by miR‐137.
On Reproducible and Replicable Gerontology

Gerontological research focuses on longer timescales and different data sources than many other areas of behavioral and medical science. It is further important that gerontology rise to respond to the reproducibility revolution and engage in open and replicable science. However, most of the recent emphases on replication come from fields where data collection takes weeks or months, not the years or decades common to gerontological studies. The goal of this paper is to review existing recommendations for carrying out open science and tailor them to the needs of gerontological and longitudinal research. By being more transparent in our procedures and analytic decisions, replicating internally and externally to existing data, and better integrating our work with that of cutting-edge statistical methods, we can create more open and reproducible gerontological research. In doing so, our conclusions will be more accurate, more interpretable, and easier to disseminate to researchers and practitioners.
The Transcriptome of Hepatic Fibrosis Revealed by Single‐Cell RNA Sequencing

Signaling programs of hepatic disease have historically been studied by comparing bulk diseased and healthy liver tissue. As tissues contain heterogeneous cell mixtures, signals from less represented populations can be dampened however single cell RNA sequencing (scRNAseq) circumvents this. In revealing the transcriptomes of individual cells, scRNAseq has exposed the complex division of labor in normal hepatic homeostasis and led to conceptualization of the "fibrotic niche," regions of scarring composed of scar-associated cells, extracellular matrix and fibrotic programs.