CWAS-Plus: estimating category-wide association of rare noncoding variation from whole-genome sequencing data with cell-type-specific functional data.

Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer's disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus's utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Serum phosphorus and subclinical coronary atherosclerosis in asymptomatic subjects without kidney dysfunction.

BACKGROUND AND AIMS: There is limited data on the association between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in low-risk asymptomatic subjects without kidney dysfunction. MATERIALS AND METHODS: We retrospectively analyzed 1,636 Korean individuals (mean age 52.6 ± 7.6 years; males: 712 (43.5%)) without traditional cardiovascular risk factors (CVRFs) and kidney dysfunction who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Traditional CVRFs were defined as follows: systolic/diastolic blood pressure ≥ 140/90 mmHg, fasting blood glucose ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5%, total cholesterol ≥ 240 mg/dL, low-density lipoprotein cholesterol ≥ 160 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, body mass index ≥ 25.0 kg/m2, currently smoking, and medical history of hypertension, diabetes, and hyperlipidemia. Study participants were stratified into tertiles according to their SPC levels (≤ 3.2, 3.3 - 3.6, and ≥ 3.7 mg/dL). RESULTS: 297 (18.2%) study participants had subclinical coronary atherosclerosis, characterized by any coronary plaque on CCTA. In multivariable regression analysis, the risk of subclinical coronary atherosclerosis increased in the second (odds ratio (OR): 1.629; 95% confidence interval (CI): 1.149 - 2.308; p = 0.006) and third (OR: 1.645; 95% CI: 1.093 - 2.476; p = 0.017) SPC tertiles compared to the first SPC tertile. In addition, the risk of calcified plaque increased in the second (OR: 1.605; 95% CI: 1.124 - 2.292; p = 0.009) and third (OR 1.790; 95% CI 1.179 - 2.716; p = 0.006) SPC tertiles. CONCLUSION: In low-risk asymptomatic Korean individuals without kidney dysfunction, a higher SPC level was an independent predictor of subclinical coronary atherosclerosis.

Missed Diagnosis of Anaphylaxis in Patients With Pediatric Urticaria in the Emergency Department.

OBJECTIVES: This study was to determine the characteristics of missed diagnosis of pediatric anaphylaxis that were registered as urticaria only at the emergency department (ED) by comparing those who had only urticaria symptoms with those who had both anaphylaxis and urticaria symptoms. METHODS: Subjects were classified into missed anaphylaxis and urticaria group according to whether satisfied anaphylaxis diagnostic criteria or not. Anaphylaxis group, those who were initially registered as anaphylaxis with urticaria and anaphylaxis symptoms simultaneously, were further investigated. RESULTS: The missed anaphylaxis group included 37 patients of 1051 pediatric urticaria patients. The anaphylaxis group included 11 patients. The time from symptom onset to ED arrival in the missed anaphylaxis group was shorter than the urticaria group. More patients in the missed anaphylaxis group had a history of past food allergy. Seafood, egg, and milk were more common causes of allergy in the missed anaphylaxis group; however, idiopathic causes were more common in the urticaria group. Symptom was more severe in the missed anaphylaxis group than the urticaria group. More treatments except antihistamine were performed at ED in the missed anaphylaxis group. Cardiovascular symptoms were more common in the anaphylaxis group than the missed anaphylaxis group. CONCLUSIONS: Of all pediatric urticaria patients, 3.5% of patients were not registered as anaphylaxis although they had anaphylaxis symptoms. Missed diagnosis of anaphylaxis in pediatric urticaria patients at ED was associated with a history of past food allergy, milk, egg, and seafood as causes of allergy, treated with fluid administration, steroid, and epinephrine.

Germinated Rhynchosia nulubilis Fermented with Lactobacillus pentosus SC65 Reduces Particulate Matter Induced Type II Alveolar Epithelial Apoptotic Cell Death.

Particulate matter (PM) is a significant environmental pollutant that promotes respiratory diseases, including lung injury and inflammation, by inducing oxidative stress. Rhynchosia nulubilis (black soybean) is traditionally used to prevent chronic respiratory disease via inducing antioxidant and anti-inflammatory effects. To investigate the effects of Lactobacillus pentosus SC65 fermented GR (GR-SC65) and Pediococcus pentosaceus ON81A (GR-ON81A) against PM-induced oxidative stress and cell death in A549 cells, we performed the 2-7-dichlorodihydrofluorescein diacetate and cell counting kit-8 assays, as well as Hoechst 33342 and propidium iodide staining and western blotting. GR-SC65 showed the highest total polyphenolic contents and 1,1-diphenyl-2-picrylidrazil radical scavenging activity among lactic acid bacteria-fermented GRs (p < 0.001 vs. GR). Four soy peptides, ß-conglycinin breakdowns (INAENNQRNF, ISSEDKPFN, LAFPGSAQAVEK, and LAFPGSAKDIEN), were detected in GR-SC65, but not in GR. In GR-SC65, PM-induced A549 cell death was less than that observed in GR-ON81A and GR (p < 0.001 vs. PM-treated group). GR-SC65 significantly decreased intracellular reactive oxidative species (ROS) when compared with PM (*** p < 0.001 vs. PM). GR-SC65 decreased the levels of BAX, active caspase-9, -3, and poly ADP-ribose polymerase (PARP) proteins (#p < 0.01, ###p < 0.001 vs. PM), while increasing the level of BCL-2 protein, a mitochondrial anti-apoptotic protein (###p < 0.001 vs. PM). Our findings indicate that GR-SC65 inhibited PM-induced cell death by suppressing the levels of ROS, active caspase-9 and -3, and PARP proteins, while enhancing the level of BCL-2 protein in type II alveolar epithelial A549 cells. Therefore, GR-SC65 might be a potential therapeutic and preventive agent against PM-induced lung injury.

Occupational post-traumatic stress disorder: an updated systematic review.

BACKGROUND: Although numerous studies on occupational post-traumatic stress disorder (PTSD) have been conducted prior to the 1950-2010 seminal systematic review by Skogstad et al., the prevalence, risk factors, and impact of this disorder following traumatic events in occupational settings remain unclear. This study aims to address this knowledge gap by reviewing the literature published after 2010. METHODS: We reviewed literature from databases such as PubMed and Google Scholar using PRISMA guidelines to identify studies that address occupational PTSD and examined the status (prevalence or incidence), the risk factors, and the health effects of PTSD among workers. RESULTS: In total, 123 articles were identified, and finally, 31 (25.2%) articles were selected after excluding duplicates. Various occupational traumatic physical events were reported such as natural or manmade disaster, explosion, accident, handling refugee corpses, or bullying at work. Risk of PTSD was closely associated with working conditions, severity of injury, history of mental disorder, occurrence of psychiatric symptoms at the time of the event, personality, interpersonal relationships, etc. Workers with PTSD were likely to experience a deterioration of physical and psychological health and impairment of social and occupational functioning. CONCLUSIONS: Our review suggests that many workers remain highly vulnerable to occupational PTSD and its consequences.

High-Flow Nasal Cannula Oxygen Therapy Can Be Effective for Patients in Acute Hypoxemic Respiratory Failure with Hypercapnia: a Retrospective, Propensity Score-Matched Cohort Study.

BACKGROUND: Usually, high-flow nasal cannula (HFNC) therapy is indicated for de novo acute hypoxemic respiratory failure (AHRF). Although only a few researches have examined the effectiveness of HFNC therapy for respiratory failure with hypercapnia, this therapy is often performed under such conditions for various reasons. We investigated the effectiveness of HFNC therapy for AHRF patients with hypercapnia compared to those without hypercapnia. METHODS: All consecutive patients receiving HFNC therapy between January 2012 and June 2018 at a university hospital were enrolled and classified into nonhypercapnic and hypercapnic groups. We compared the outcomes of both groups and adjusted the outcomes with propensity score matching. RESULTS: A total of 862 patients were enrolled, of which 202 were included in the hypercapnic group. HFNC weaning success rates were higher, and intensive care unit (ICU) and hospital mortality was lower in the hypercapnic group than in the nonhypercapnic group (all P < 0.05). However, no statistical differences in HFNC weaning success (adjusted P = 0.623, matched P = 0.593), ICU mortality (adjusted P = 0.463, matched P = 0.195), and hospital mortality (adjusted P = 0.602, matched P = 0.579) were noted from the propensity-adjusted and propensity-matched analyses. Additionally, in the propensity score-matched subgroup analysis (according to chronic lung diseases and causes of HFNC application), there was also no significant difference in outcomes between the two groups. CONCLUSION: In AHRF with underlying conditions, HFNC therapy might be helpful for patients with hypercapnia. Large prospective and randomized controlled trials are required for firm conclusions.

Hair Growth Promoting Effect of 4HGF Encapsulated with PGA Nanoparticles (PGA-4HGF) by ß-Catenin Activation and Its Related Cell Cycle Molecules.

Poly-γ-glutamic acid (γ-PGA)-based nanoparticles draw remarkable attention as drug delivery agents due to their controlled release characteristics, low toxicity, and biocompatibility. 4HGF is an herbal mixture of Phellinus linteus grown on germinated brown rice, Cordyceps militaris grown on germinated soybeans, Polygonum multiflorum, Ficus carica, and Cocos nucifera oil. Here, we encapsulated 4HGF within PGA-based hydrogel nanoparticles, prepared by simple ionic gelation with chitosan, to facilitate its penetration into hair follicles (HFs). In this study, we report the hair promoting activity of 4HGF encapsulated with PGA nanoparticles (PGA-4HGF) and their mechanism, compared to 4HGF alone. The average size of spherical nanoparticles was ~400 nm in diameter. Continuous release of PGA-4HGF was observed in a simulated physiological condition. As expected, PGA-4HGF treatment increased hair length, induced earlier anagen initiation, and elongated the duration of the anagen phase in C57BL/6N mice, compared with free 4HGF treatment. PGA-4HGF significantly increased dermal papilla cell proliferation and induced cell cycle progression. PGA-4HGF also significantly increased the total amount of ß-catenin protein expression, a stimulator of the anagen phase, through induction of cyclinD1 and CDK4 protein levels, compared to free 4HGF treatment. Our findings underscore the potential of PGA nanocapsules to efficiently deliver 4HGF into HFs, hence promoting hair-growth. Therefore, PGA-4HGF nanoparticles may be promising therapeutic agents for hair growth disorders.

Minimum InDel pattern analysis of the Zika virus.

BACKGROUND: The Zika virus (ZIKV) can cause microcephaly and congenital abnormalities in the foetus. Recent studies have provided insights into the evolution of ZIKV from the current and previous outbreaks, but the types have not been determined. RESULTS: We analysed the insertions and deletions (InDels) in 212 ZIKV polyproteins and 5 Dengue virus (DENV) reference sequences. Spearman correlation tests for the minimum InDel (minInDel) patterns were used to assess the type of polyprotein. Using the minInDel frequencies calculated from polyproteins with 11 elements, likelihood estimation was conducted to correct the evolutionary distance. The minInDel-corrected tree topology clearly distinguished between the ZIKV types (I and II) with a unique minInDel character in the E protein. From the 10-year average genetic distance, the African and Asian lineages of ZIKV-II were estimated to have occurred ~ 270 years ago, which is unlikely for ZIKV-I. CONCLUSIONS: The minInDel pattern analysis showed that the minInDel in the E protein is targetable for the rapid detection and determination of the virus types.

High-pressure oxygen annealing of Al2O3 passivation layer for performance enhancement of graphene field-effect transistors.

High-pressure annealing in oxygen ambient at low temperatures (∼300 °C) was effective in improving the performance of graphene field-effect transistors. The field-effect mobility was improved by 45% and 83% for holes and electrons, respectively. The improvement in the quality of Al2O3 and the reduction in oxygen-related charge generation at the Al2O3-graphene interface, are suggested as the reasons for this improvement. This process can be useful for the commercial implementation of graphene-based electronic devices.

Severe Injuries from Low-height Falls in the Elderly Population.

BACKGROUND: Falls from low-height can cause severe injuries in the elderly population. This study was conducted to determine characteristics of injuries from low-height falls. METHODS: We retrospectively review surveillance data on injured patients who presented to six emergency departments from January 2011 to December 2015. Study subjects were divided into severe group and non-severe group based on severity of injury. The general and clinical characteristics were compared between the two groups and analyzed factors related with severe injuries. RESULTS: Of 1,190 elderly patients, severe group comprised 82 patients (7%). The severe group was 2 years younger than the non-severe group. In the severe group, 61% was men and 34% in the non-severe group. In the non-severe, the injuries more commonly occurred at residential facilities and indoors than those in the severe group. Paid work during injury occurrence was 15%, and the more patients presented with non-alert consciousness in the severe group. The most common regions of major injury were head and neck in the severe group. CONCLUSION: Paid work, non-alert consciousness, and major injury to head and neck are relating factors to severe injuries in the elderly population.

Pediococcus pentosaceus-Fermented Cordyceps militaris Inhibits Inflammatory Reactions and Alleviates Contact Dermatitis.

Cordyceps militaris is a medicinal mushroom used to treat immune-related diseases in East Asia. We investigated the anti-inflammatory effect of the extract of C. militaris grown on germinated Rhynchosia nulubilis (GRC) fermented with Pediococcus pentosaceus ON89A isolated from onion (GRC-ON89A) in vivo as well as in vitro. The anti-inflammatory effect of GRC-ON89A was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The total polyphenol content (TPC) and total flavonoid content (TFC) in the GRC-ON89A ethanol extract were significantly increased compared to that in GRC. GRC-ON89A hexane fraction (GRC-ON89A-Hex) inhibited the release of nitric oxide (NO) compared to that of the LPS-treated control without cytotoxicity in LPS-stimulated RAW 264.7 macrophages. GRC-ON89A-Hex decreased the inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and tumor necrosis factor (TNF)-α mRNA expression in LPS-stimulated RAW 264.7 macrophages. In addition, pre-treatment with GRC-ON89A-Hex significantly inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. To induce allergic contact dermatitis (ACD), 1-fluoro-2, 4-dinitrofluorobenzene (DNFB) was applied to the surface of the right ears of C57BL/6N mice. GRC-ON89A reduced the ear swelling and thickness in DNFB-induced ACD mice. This study demonstrates the potential usefulness of GRC-ON89A as an anti-inflammatory dietary supplement or drug.

Feasibility and Safety of Mild Therapeutic Hypothermia in Poor-Grade Subarachnoid Hemorrhage: Prospective Pilot Study.

Therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic brain injury. We studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after successful treatment. Patients were allocated randomly to either the TH group (34.5°C) or control group after successful clipping or coil embolization. Eleven patients received TH for 48 hours followed by 48 hours of slow rewarming. Vasospasm, delayed cerebral ischemia (DCI), functional outcome, mortality, and safety profiles were compared between groups. We enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4, 5 and modified Fisher Scale 3, 4). In the TH group, 10 of 11 (90.9%) patients had a core body temperature of < 36°C for > 95% of the 48-hour treatment period. Fewer patients in the TH than control group (n = 11, each) had symptomatic vasospasms (18.1% vs. 36.4%, respectively) and DCI (36.3% vs. 45.6%, respectively), but these differences were not statistically significant. At 3 months, 54.5% of the TH group had a good-to-moderate functional outcome (0-3 on the modified Rankin Scale [mRS]) compared with 9.0% in the control group (P = 0.089). Mortality at 1 month was 36.3% in the control group compared with 0.0% in the TH group (P = 0.090). Mild TH is feasible and can be safely used in patients with poor-grade SAH. Additionally, it may reduce the risk of vasospasm and DCI, improving the functional outcomes and reducing mortality. A larger randomized controlled trial is warranted.

Reproductive disorders among cosmetologists and hairdressers: a meta-analysis.

PURPOSE: Occupational risks for reproductive disorders among hairdressers and cosmetologists have been examined in numerous epidemiological studies, although the results of those studies have been inconsistent. Therefore, we conducted a meta-analysis of published studies to evaluate the risks of reproductive disorders among cosmetologists and hairdressers. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Library databases, as well as the reference lists of relevant publications, to identify studies for our analysis. After careful consideration, 19 eligible studies were included in the meta-analysis. We also performed systematic evaluations of publication bias, heterogeneity, and publication quality. RESULTS: Study-specific odds ratios (ORs) were weighted using the inverse of their variance to calculate fixed- and random-effect pooled estimates. The meta-analysis revealed a significantly increased risk of infertility (OR 1.15, 95 % CI 1.03-1.28), fetal death (OR 1.14, 95 % CI 1.04-1.24), and preterm delivery (OR 1.04, 95 % CI 1.00-1.07) among hairdressers and cosmetologists. CONCLUSION: These findings indicate that hairdressers and cosmetologists have a higher risk of reproductive disorders, compared to the general population.

Production of aglycone protopanaxatriol from ginseng root extract using Dictyoglomus turgidum ß-glycosidase that specifically hydrolyzes the xylose at the C-6 position and the glucose in protopanaxatriol-type ginsenosides.

The hydrolytic activity of a recombinant ß-glycosidase from Dictyoglomus turgidum that specifically hydrolyzed the xylose at the C-6 position and the glucose in protopanaxatriol (PPT)-type ginsenosides followed the order Rf > Rg1 > Re > R1 > Rh1 > R2. The production of aglycone protopanaxatriol (APPT) from ginsenoside Rf was optimal at pH 6.0, 80 °C, 1 mg ml⁻¹ Rf, and 10.6 U ml⁻¹ enzyme. Under these conditions, D. turgidum ß-glycosidase converted ginsenoside R1 to APPT with a molar conversion yield of 75.6 % and a productivity of 15 mg l⁻¹ h⁻¹ after 24 h by the transformation pathway of R1 → R2 → Rh1 → APPT, whereas the complete conversion of ginsenosides Rf and Rg1 to APPT was achieved with a productivity of 1,515 mg l⁻¹ h⁻¹ after 6.6 h by the pathways of Rf → Rh1 → APPT and Rg1 → Rh1 → APPT, respectively. In addition, D. turgidum ß-glycosidase produced 0.54 mg ml⁻¹ APPT from 2.29 mg ml⁻¹ PPT-type ginsenosides of Panax ginseng root extract after 24 h, with a molar conversion yield of 43.2 % and a productivity of 23 mg l⁻¹ h⁻¹, and 0.62 mg ml⁻¹ APPT from 1.35 mg ml⁻¹ PPT-type ginsenosides of Panax notoginseng root extract after 20 h, with a molar conversion yield of 81.2 % and a productivity of 31 mg l⁻¹ h⁻¹. This is the first report on the APPT production from ginseng root extract. Moreover, the concentrations, yields, and productivities of APPT achieved in the present study are the highest reported to date.

Characteristics of consecutive versus non-consecutive frequent emergency medical services transport to a single emergency department.

OBJECTIVE: This study was to examine characteristics concerning frequent users of emergency medical services (EMS) transport by comparing patients who used EMS transport frequently for one year and those who used EMS transport for more than two years consecutively. METHODS: A retrospective review for frequent use of EMS transport was conducted. The patients from the fire stations that transported more than 70% of all EMS transport to the study hospital emergency department (ED) were included. The study subjects were divided into consecutive group (frequent EMS transport for ≥ two years consecutively) and non-consecutive group (frequent EMS transport for only one year). Characteristics of patients who were frequent users of EMS transport and those of all cases with EMS transport were examined. RESULTS: Of the total 205 patients and 1204 cases of frequent EMS transport, 85 (42%) patients and 755 (63%) cases were in the consecutive group. Patients in the consecutive group were more likely to have risky alcohol use, unemployed state, and medical aid type of payment for ED treatment than those in the non-consecutive group. More patients had previous experience of EMS transport to the study hospital ED in the consecutive group and the number of cases with alcohol ingestion was higher in the consecutive group. Elapsed time from EMS call to ED arrival was longer for the consecutive group. CONCLUSION: Risky alcohol use, unemployed state, and previous experience of EMS transport were associated with consecutive and frequent use of EMS transport in frequent users of EMS transport.

Alleviation of Menopausal Symptoms by Yam (Dioscorea japonica Thunb.) and Gromwell (Lithospermum erythrorhizon Sieb. Et Zucc.) Extracts in Ovariectomized Mice.

SCOPE: The decline in estrogen during menopause contributes to a variety of menopausal symptoms, for which hormone replacement therapy (HRT) has been extensively applied. Regarding side effects and limited effectiveness of HRT for specific individuals, there is a growing interest in safe alternatives such as phytoestrogens which are structurally analogous to estrogens. This study aims to investigate the efficacy of yam and gromwell extracts, rich in bioactive compounds, and the synergistic effect of extracts on symptoms induced by estrogen deficiency in ovariectomized (OVX) mice. METHODS AND RESULTS: OVX mice receive dietary intervention of either yam, gromwell extract, or their mixture for 14 weeks. Sham-operated mice and E2-injected OVX mice serve as positive controls. Following 14 weeks of oral administration, blood, adipose tissue, vagina, uterus, femurs, and tibias are harvested for further investigation. Consequently, yam and gromwell extracts ameliorate menopausal conditions such as weight gain, glucose intolerance, dyslipidemia, and osteoporosis in estrogen-deficient OVX mice. In addition, the mixture of yam and gromwell extracts synergistically aids in the relief of the indications. CONCLUSION: These results indicate the potential use of yam and gromwell extracts, as well as their mixture, for the development of healthy functional foods to modulate menopausal symptoms.

Chemical Structure-Physicochemical Property Relationships of Copolymers Utilizable for Negative-Tone Photoimaging via Chemical Amplification.

We demonstrate an understanding of different physicochemical properties of copolymers induced by systematic changes in their structural parameters, i.e., the chemical structure of the comonomer unit, composition, molecular weight, and dispersity. The terpolymers were designed to be implemented in a chemically amplified resist (CAR) to form negative-tone patterns. With two basic repeating units of 4-hydroxystyrene and 2-ethyl-2-methacryloxyadamantane as monomers for conventional CARs, the pendant group of the third methacrylate comonomer was varied from aromatic, aliphatic lactone to lactone rings to modulate the interaction capability of the copolymer chains with n-butyl acetate, which is a negative-tone developer. Along with these structures, the monomer composition, molecular weight, and dispersity were also controlled. Physicochemical properties of the synthesized copolymers having controlled structures, i.e., dissolution behaviors and quantified Hansen solubility parameters, surface wetting characteristics, and surface roughness, which can be important properties affecting patterning capability in high-resolution lithography, were explored. Furthermore, the feasibility to use experimentally determined Hansen solubility parameters of the copolymers for the prediction of pattern formation using a coarse-grained model was assessed. Our comprehensive studies on the correlation of the structural parameters of the copolymers with final properties offer fundamental avenues to attain effective designs of the complex CAR system toward the lithographic process to achieve a sub-10 nm dimension, which is close to a single-chain dimension.

CWAS-Plus: Estimating category-wide association of rare noncoding variation from whole-genome sequencing data with cell-type-specific functional data.

Variants in cis-regulatory elements link the noncoding genome to human brain pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS) employs both whole-genome sequencing and user-provided functional data to enhance noncoding variant analysis, with a faster and more efficient execution of the CWAS workflow. Here, we used single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type specific enhancers and promoters. Examining autism spectrum disorder whole-genome sequencing data (n = 7,280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer's disease whole-genome sequencing data (n = 1,087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus's utility in genomic disorders and scalability for processing large-scale whole-genome sequencing data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

Piezoelectric Nanogenerators Fabricated Using Spin Coating of Poly(vinylidene fluoride) and ZnO Composite.

In this context, the open-circuit voltage generated by either poly (vinylidene fluoride) or PVDF and ZnO composite sample before being enhanced to 4.2 V compared to 1.2 V for the samples of pure PVDF. The spin coating method was used to create a composite film, which served as a piezoelectric nanogenerator (PNG). Zinc oxide (ZnO) nanoparticles and PVDF serve as the matrix for the coating structure. Thin films were created that employed the spin coating method to achieve the desired results of ZnO's non-brittle outcome and piezoelectric characteristics, as well as PVDF for use in self-powered devices. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and fourier transform infrared (FT-IR) were used to evaluate the properties of these formations. The electrical properties of the film were measured using an oscilloscope. Results indicated that by adding ZnO nanoparticles to the PVDF samples, piezoelectric capabilities were enhanced compared to samples containing PVDF only. These results point to promising uses for various wearable devices, such as water strider robot systems and self-operating equipment.