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Background: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. Methods: We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study (n = 6144 participants of European ancestry and n = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC. Results: We identified genome-wide significant associations for CAC in the chromosome 9p21 region [CDKN2B-AS1] among all COPDGene participants (p = 7.1 × 10-14) and among males (p = 1.0 × 10-9), but the signal was not genome-wide significant among females (p = 6.4 × 10-6). For the sex stratified GWA analyses among females, the chromosome 6p24 region [PHACTR1] had a genome-wide significant association (p = 4.4 × 10-8) with CAC, but this signal was not genome-wide significant among all COPDGene participants (p = 1.7 × 10-7) or males (p = 0.03). There was a significant interaction for the SNP rs9349379 in PHACTR1 with sex (p = 0.02), but the interaction was not significant for the SNP rs10757272 in CDKN2B-AS1 with sex (p = 0.21). In addition, PHACTR1 had a stronger association with CAC among current smokers (p = 6.2 × 10-7) than former smokers (p = 7.5 × 10-3) and the SNP by smoking status interaction was marginally significant (p = 0.03). CDKN2B-AS1 had a strong association with CAC among both former (p = 7.7 × 10-8) and current smokers (p = 1.7 × 10-7) and the SNP by smoking status interaction was not significant (p = 0.40). Conclusions: Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [PHACTR1] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC.

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

RATIONALE & OBJECTIVE: In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect. STUDY DESIGN: Randomized controlled trial. SETTING & POPULATION: A total of 1,381 sedentary adults aged 70-89 years enrolled in the LIFE trial. INTERVENTION: Structured, 2-year, moderate-intensity exercise intervention versus health education. OUTCOMES: Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure. RESULTS: Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (≥3,470 vs

Living alone, particularly for individuals with poor physical health, can increase the likelihood of mortality. This study aimed to explore the individual and joint associations of living alone and physical health with overall mortality among breast cancer survivors in the Women's Healthy Eating and Living (WHEL). We collected baseline, 12-month and 48-month data among 2869 women enrolled in the WHEL cohort. Living alone was assessed as a binary variable (Yes, No), while scores of physical health were measured using the RAND Short Form-36 survey (SF-36), which include four domains (physical function, role limitation, bodily pain, and general health perceptions) and an overall summary score of physical health. Cox proportional hazard models were used to evaluate associations. No significant association between living alone and mortality was observed. However, several physical health measures showed significant associations with mortality (p-values < 0.05). For physical function, the multivariable model showed a hazard ratio (HR) of 2.1 (95% CI = 1.02-4.23). Furthermore, the study examined the joint impact of living alone and physical health measures on overall mortality. Among women with better physical function, those living alone had a 3.6-fold higher risk of death (95% CI = 1.01-12.89) compared to those not living alone. Similar trends were observed for pain. However, regarding role limitation, the pattern differed. Breast cancer survivors living alone with worse role limitations had the highest mortality compared to those not living alone but with better role limitations (HR = 2.6, 95% CI = 1.11-5.95). Similar trends were observed for general health perceptions. Our findings highlight that living alone amplifies the risk of mortality among breast cancer survivors within specific health groups.

Breast cancer survivors often have a reduced digestive capacity to digest whole grains due to cancer treatment. The purpose of this study was to investigate the independent and joint associations of whole grain and refined grain consumption with total mortality among breast cancer survivors. We studied a cohort of 3081 female breast cancer survivors who provided demographic, dietary, and lifestyle data at baseline, year 1 and year 4. Mortality was assessed via semi-annual telephone interviews and confirmed by the National Death Index (NDI) and death certificates. We assessed the associations of whole grain and refined grain with incident of mortalities using Cox proportional hazards models. Increased whole grain consumption was marginally associated with an increased risk of total mortality (p = 0.07) but was not significantly associated with breast cancer-specific mortality (p = 0.55). An increased intake of refined grains was associated with an increased risk of both total (HR = 1.74; 95% CI,1.17 to 2.59) and breast cancer-specific mortality (HR = 1.16; 95% CI, 1.08 to 1.26). Furthermore, we examined the joint associations of whole grain and refined grain with total mortality. Among those with a high consumption of refined grain, those with high consumption of whole grain had a higher risk of total mortality (HR = 1.52, 95% CI, 1.07 to 2.14) than those with a low consumption of whole grain. Increased consumption of whole grains may exacerbate the adverse associations of refined grain with mortality among breast cancer survivors. Our findings indicate the need to revisit current dietary guidelines for breast cancer survivors regarding whole grain intake.

Insomnia is prevalent in up to 40% of breast cancer survivors. Few studies have examined pessimism and dietary factors as risk factors for insomnia among breast cancer survivors. We leveraged a cohort of 2944 breast cancer survivors who enrolled in the Women’s Healthy Eating and Living study; these survivors provided dietary, insomnia, mental health, demographic, and lifestyle information at baseline and at 1- and 4-year follow-up assessments. Insomnia symptoms were assessed using the Women’s Health Initiative (WHI)-Insomnia Rating Scale, and pessimism was assessed using the Life Orientation Test Revised (LOT-R). Total calorie intake and acid-producing diets were assessed using 24 h dietary recalls. Multivariable-adjusted generalized estimating equation (GEE) models were used to test the independent and joint effects of psychological and dietary factors on insomnia. In the multivariable model, women in the third tertile of pessimism had greater odds (OR = 1.57 95% CI [1.37−1.79]) of insomnia when compared to women in the lowest tertile. Total calorie intake and acid-producing diets were each independently and significantly associated with insomnia symptoms. Further, pessimism and calorie intake/acid-producing diets were jointly associated with insomnia. For instance, women with pessimism scores in tertile 3 and total calorie intakes < median reported 2 times the odds (OR = 2.09; 95% CI [1.51−3.47]) of insomnia compared to women with pessimism score in tertile 1 and calorie intakes < median. Our results highlight the need for patient care regarding mental health, and recommendations of healthy dietary intakes for breast cancer survivors.

Triboelectric nanogenerators (TENGs) have revealed fascinating potential in multifaceted wearables. However, their reliance on physical contact and separation from human bodies presents drawbacks for efficient energy collection, especially over large areas. Herein, the first stretchable non‐contact TENG textile is proposed using a topological insulator nanocomposite coating (triboelectric layer) and a graphite‐like fabric (tribo‐charges reservoir). This design encompasses the capture, transporting, and storage of tribo‐charges, leading to enhanced device performance (452 V, 1.96 mA m−2, and 179 mW m−2) and prolonged tribo‐charges retention time (5000 min). During non‐contact operation, the output remained at 382 V (318 µA m−2), 123 V (59 µA m−2), and 94 V (23 µA m−2) for separation distances of 0.1, 0.5, and 1 cm, respectively. Additionally, it exhibits excellent stretchability (>100% strain). Notably, its performance during non‐contact operation and mechanical freedom surpasses those of previous reports, enabling both wearable non‐contact biomechanical energy harvesting and deformable self‐powered proximity sensing. Its applicability is comprehensively examined for non‐contact harvesting of body‐motion energy in garments and driving electronics. Finally, its application as a self‐powered touchless interface for system‐level applications is demonstrated. These results provide new directions for developing non‐contact biomechanical energy harvesting and sensing, enabling advancements in autonomous wearables and Metaverse applications. [ABSTRACT FROM AUTHOR]

We demonstrate highly sensitive, efficient, ambient-stable organic photodetectors (OPDs) in an inverted platform. The bilayer structure of poly{[N,N′′-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′bithiophene)}/poly[9,9-bis(6′-(N,N-diethylamino)propyl)-fluorene-alt-9,9-bis-(3-ethyl(oxetane-3-ethyloxy)-hexyl)-fluorene] (N2200/PFN-OX) with hydrophobic surface characteristics is implemented as an electron-transport layer (ETL) for the fabrication of ITO/N2200/PFN-OX/P3HT:PCBM/MoO3/Ag bulk heterojunction type OPDs. Devices with a 15-nm-thick N2200/PFN-OX layer are able to produce an ultra-low dark current density of 1.58 × 10−11 A cm−2 at 0 V, a faster response time of 4.9 μs, a wide linear dynamic range (LDR) value of >138 dB, and an impressive detectivity of 1.20 × 1014 cm Hz1/2 W−1. Additionally, after 63 days, the OPDs retain 85% and 70% of their initial responsivity and detectivity, respectively, in contrast to those with hydrophilic ZnO as the ETL having 70% and 30% residuals, respectively. The superior performance of the proposed OPDs can be attributed to the hydrophobic surface characteristics of the polymer bilayer, which enables the formation of an excellent interface with the photoactive layer to facilitate charge transport and minimize the influence of water molecules. Our approach is very useful and can be generalized to other highly efficient photoactive blends and even other organic optoelectronic devices for developing high-performance, ambient-stable devices. [ABSTRACT FROM AUTHOR]

Hyperbolic metamaterials (HMMs) are known for their robust light–matter interaction and ability to generate volume plasmon polaritons (VPPs). Au nanoparticles (Au NPs) enable to enhance this interaction through localized surface plasmon resonance (LSPR), creating intense local electric fields. However, combining LSPR and VPPs in one device remains unexplored. This study proposes and demonstrates Au NP‐coupled‐HMMs (NPCHMMs), integrating Au NPs with HMMs to enhance random laser action and lower the lasing threshold. NPCHMMs boost emission intensity by ≈6 times compared to pure HMMs, with a ≈47% reduction in lasing threshold. Based on Fermi's golden rule, the calculated transition rate in NPCHMMs surpasses the algebraic sum of the individual transition rates derived from HMMs and Au NPs. It reveals the effect of the coherent coupling between the transition matrix elements of VPP and LSPR. This research indicates that NPCHMMs are a promising platform to create high‐performance optical and optoelectronic devices, such as lasers and phototransistors, for a wide range of application in many fields. [ABSTRACT FROM AUTHOR]

Sugar-sweetened beverage (SSB) and fruit juice (FJ) consumption may promote lipid abnormalities in childhood. We examined the association between SSB/FJ intake and lipid levels using electronic health record data for 2816 adolescents. Multivariable logistic regression models treated clinical cutpoints for abnormal lipid levels (triglycerides [TG], high-density lipoprotein (HDL), low-density lipoprotein [LDL], and total cholesterol) as dependent variables. In models not adjusted for adiposity, elevated SSB and FJ consumption was associated with increased odds of having abnormally high TG (SSB: odds ratio [OR] = 1.28 (95% confidence interval [CI] = [1.07-1.52], P =.007); FJ: 1.35 ([1.09-1.69], P =.007)) and abnormally low HDL (SSB: 1.47 ([1.17-1.86], P =.001); FJ: 1.35 ([1.02-1.78], P =.03)). Adjusting for adiposity, a likely mediator of the relationship, attenuated these associations. These findings support the need for identifying unhealthy beverage consumption habits during childhood health care visits as a modifiable behavior associated with cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Because many genes associate with DKD, multiomics approaches were used to narrow the list of functional genes, gene products, and related pathways providing insights into the pathophysiological mechanisms of DKD. The Kidney Precision Medicine Project human kidney single-cell RNA-sequencing (scRNA-seq) data set and Mendeley Data on human kidney cortex biopsy proteomics were used. The R package Seurat was used to analyze scRNA-seq data and data from a subset of proximal tubule cells. PathfindR was applied for pathway analysis in cell type–specific differentially expressed genes and the R limma package was used to analyze differential protein expression in kidney cortex. A total of 790 differentially expressed genes were identified in proximal tubule cells, including 530 upregulated and 260 downregulated transcripts. Compared with differentially expressed proteins, 24 genes or proteins were in common. An integrated analysis combining protein quantitative trait loci, genome-wide association study hits (namely, estimated glomerular filtration rate), and a plasma metabolomics analysis was performed using baseline metabolites predictive of DKD progression in our longitudinal Diabetes Heart Study samples. The aldo-keto reductase family 1 member A1 gene (AKR1A1) was revealed as a potential molecular hub for DKD cellular dysfunction in several cross-linked pathways featured by deficiency of this enzyme. Article Highlights: It is critical to identify credible biomarkers for progression of diabetic kidney disease (DKD) useful in clinical practice. We used multiomics approaches to uncover and cross-verify DKD biomarkers using publicly available genomics, single-cell transcriptomics, and proteomics data, as well as our unique immunofluorescence microscopy and metabolomics data. We found that the aldo-keto reductase family-1 member A1 (AKR1A1) transcript and protein/enzyme level was significantly lower in proximal tubule cells of patients with DKD than in those of control cells. DKD progression was supported by higher plasma metabolic end products catalyzed by AKR1A1. Our results suggest AKR1A1 and/or its metabolic end products may serve as biomarkers for DKD. [ABSTRACT FROM AUTHOR]

On‐skin electronics can be conformably deployed on body for health monitoring, assisted living, and human/computer interfaces. However, developing corresponding energy devices is a critical challenge. Herein, a permeable and stretchable multifunctional liquid‐metal electronic skin that can generate electricity by recovering ambient electromagnetic pollution (from surrounding electrical appliances) and biomechanical energy (from body movements) is presented for epidermal energy and self‐powered sensing applications. To the best of the authors' knowledge, this is the first demonstration that a breathable on‐skin device can convert ambient electromagnetic pollution into useful electricity. The device is constructed using two stretchable microfibrous films sandwiching self‐organized mesh‐like and wrinkled liquid‐metal that affords electricity via induced electrification (±9.3 V, ±1.7 µA; 60 Hz) and triboelectricity (205.6 V, ±2.3 µA; 4 Hz). Its applicability in powering electronic devices is demonstrated. Moreover, it can serve as an epidermal self‐powered sensor for continuously monitoring whole‐body physiological signals and motions of the eyelids, face, throat, chest, and limbs, thus demonstrating its potential to remotely collect clinical and biomechanical information. Finally, it is used as an interface in diverse system‐level applications. These results shed light on new directions in on‐skin energy and sensing, enabling to usher electronics toward untethered and diversified applications. [ABSTRACT FROM AUTHOR]

We measured neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cohort of 235 convalescent patients (representing 384 analytic samples). They were followed for up to 588 days after the first report of onset in Taiwan. A proposed Bayesian approach was used to estimate nAb dynamics in patients postvaccination. This model revealed that the titer reached its peak (1819.70 IU/mL) by 161 days postvaccination and decreased to 154.18 IU/mL by day 360. Thus, the nAb titers declined in 6 months after vaccination. Protection, against variant B.1.1.529 (ie, Omicron) may only occur during the peak period. [ABSTRACT FROM AUTHOR]