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This paper examines housing accessibility to public–community facilities (PCFs) using geographical information systems (GIS) for four county–wide metropolitan areas in North Carolina with population ranging from 90,000 to 700,000. An optimization–based assignment model is developed and implemented in ArcView GIS. Rather than using the conventional and less accurate traffic analysis zone (TAZ) or census geography, this research uses detailed county–wide building and parcel databases to estimate direct distances, hence accessibility, from homes (i.e., apartment, manufactured home, and single–family house) to PCF (i.e., office, shopping center, school). The results indicate that distinct housing accessibility patterns exist. In general, multi–family housing such as apartment and townhouse enjoys higher accessibility to positive (desirable) PCFs, followed by single–family detached housing. Manufactured housing has been placed further away from most positive PCFs, but closer to some negative (undesirable) ones. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the associations between physical activity (PA) intensity, occupational PA engagement, and sarcopenia in younger adults., Methods: Data from the National Health and Nutrition Examination Survey (NHANES) (from 2011 to 2018) were used for the study. PA data were extracted for the Global Physical Activity Questionnaire, and the ratio of limb muscle mass (ALM) to body mass index (BMI) was used to determine sarcopenia. Multiple logistic regression was performed, and dose-response curves were drawn to evaluate the associations., Results: Of the 8802 adults aged 20 to 59 years, 770 (8.7%) were identified as having sarcopenia. Compared to those in the reference group, the participants in the "low", "moderate", and "high" total METs groups had lower risks of sarcopenia (low: OR = 0.730, 95% CI = 0.583; 0.915; moderate: OR = 0.643, 95% CI = 0.485; 0.853; high: OR = 0.560, 95% CI = 0.457; 0.687). The risk of sarcopenia decreased in the high-intensity recreational PA group; however, such a significant association was observed only in the high-intensity occupational PA group. The relationship between total METs and sarcopenia showed a nonlinear U-shaped trend., Conclusions: A greater intensity of PA is associated with a lower risk of sarcopenia among younger adults, regardless of whether moderate or vigorous PA is performed. Moreover, recreational PA may particularly advantageously contrast with occupational PA in lowering the risk of sarcopenia., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted according to the guideline laid down in the Declaration of Helsinki. All procedures performed in the study involving human participants were approved by the Ethics Review Committee of the National Center for Health Statistics (available at https://www.cdc.gov/nchs/nhanes/irba98.htm), and the data were free and publicly available. The information of each participant in the NHANES was collected after providing informed consent. The NHANES website provides detailed information on ethical declaration and written informed consent. Consent for publication Not applicable. Conflict of interest None declared. The research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© 2024. The Author(s).)

Purpose: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine., Methods: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale., Results: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles., Conclusions: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Alopecia areata (AA) is an autoimmune disorder characterized by hair loss on the scalp, face, and other body areas. Despite affecting approximately 2% of the global population, there has been no previous bibliometric analysis specifically focusing on AA treatment that can guide researchers in exploring promising treatment options and directing future research efforts., Summary: This study conducted a bibliometric analysis of AA treatment research, encompassing publications from 2003 to 2022. A total of 1,323 papers from 65 countries, predominantly led by the USA and China, were included in the analysis. The number of publications related to AA treatment showed a notable increase over the years. Prominent research institutions included the University of Manchester, Icahn School of Medicine at Mount Sinai, University of Miami, and Columbia University. Among the journals, Dermatologic Therapy stood out as the most popular, while the Journal of the American Academy of Dermatology appeared as the most frequently co-cited publication., (© 2023 S. Karger AG, Basel.)

Objective: To assess the feasibility of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) in children. Methods: Clinical data and follow-up information of 4 AIS children who received EVT in the Department of Intervention & Hemangioma at the Children's Hospital of the Capital Institute of Pediatrics from December 2020 to June 2021 were collected retrospectively. The vascular recanalization after EVT was assessed by the modified thrombolysis in cerebral infarction (mTICI) score. Efficacy outcomes were assessed with initial and postprocedural Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score, and the modified Rankin scale (mRS) score at 3 and 6 months after treatment. Safety assessments included perioperative complications and intracranial hemorrhage post-treatment. Results: A total of 5 EVT treatment were performed on 4 children with AIS, of whom 3 were male. The age of onset was 4.6, 13.8, 7.8, 8.0, 8.9 years, respectively. The time from symptom onset to initiation of EVT was 19.0, 25.0, 22.0, 4.0, 16.5 hours, respectively and all patients achieved successful recanalization of the vessel after EVT (mTICI≥2b). The PedNIHSS score was 39, 14, 25, 39, 24 before treatment and decreased to 8, 1, 12, 39, 5 at discharge. All the procedures were performed with no perioperative complications. Only 1 patient with congenital heart disease had a recurrent AIS with malignant brain oedema and brain hernia. Although the occluded vessels were successfully recanalized,the symptoms were not improved and this patient died after treatment abandonment. The other 3 patients achieved good recovery at 6 months postoperatively. The mRS score of 3 patients was 3, 1, 2 at 3 months after EVT and decreased to 2, 1, 1 at 6 months. Conclusion: EVT treatment may be feasible and safe for pediatric AIS due to large vessel occlusion even when the treatment was initiated 6 hours post stroke, but children with heart disease may have a dismal prognosis.

Introduction: African American English (AAE) has never been examined through neurophysiological methods in investigations of dual-language variety processing. This study examines whether contrastive and non-contrastive morphosyntactic features in sentences with and without AAE constructions elicit differing neural and/or behavioral responses in bidialectal speakers of AAE and Mainstream American English (MAE), compared to monodialectal MAE speakers. We compared electroencephalographic (EEG) and behavioral (grammatical acceptability judgment) data to determine whether two dialects are processed similarly to distinct languages, as seen in studies of bilingual codeswitching where the P600 event related potential (ERP) has been elicited when processing a switch between language varieties., Methods: Bidialectal AAE-MAE speakers (n = 15) and monodialectal MAE speakers (n = 12) listened to sentences in four conditions, while EEG was recorded to evaluate time-locked brain responses to grammatical differences between sentence types. The maintained verb form in the present progressive tense sentences (e.g., The black cat lap/s the milk) was the morphosyntactic feature of interest for comparing P600 responses as an indicator of error detection. Following each trial, responses and reaction times to a grammatical acceptability judgment task were collected and compared., Results: Findings indicate distinct neurophysiological profiles between bidialectal and monodialectal speakers. Monodialectal speakers demonstrated a P600 response within 500-800ms following presentation of an AAE morphosyntax feature, indicating error detection; this response was not seen in the bidialectal group. Control sentences with non-contrasting grammar revealed no differences in ERP responses between groups. Behaviorally, bidialectal speakers showed greater acceptance of known dialectal variation and error (non-contrastive) sentence types compared to the monodialectal group., Conclusions: ERP and behavioral responses are presented as preliminary evidence of dual-language representation in bidialectal speakers. Increased consideration of AAE language processing would enhance equity in the study of language at large, improving the work of clinicians, researchers, educators and policymakers alike., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To detect pathogenic variant in a child featuring Usher syndrome type II., Methods: Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes. The findings were verified in 100 individuals with normal hearing., Results: The child was found to harbor compound heterozygous variants of the USH2A gene, namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X) in exon 28, which were inherited respectively from his mother and father. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.8224-1G>C and c.5678C>G(p.Ser1893X) variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3)., Conclusion: The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child. Above finding has enriched the spectrum of USH2A gene variants.

Background: Given the fat redistribution in later stages of life, how the associations between abdominal obesity and the risk of morbidity and mortality have changed with age have not been elucidated, especially for waist to height ratio (WHtR)., Objective: To compare the strength of association between obesity indices and chronic diseases at baseline, and the subsequent mortality risk among US adults., Methods: We included 21 109 participants from National Health and Nutrition Examination Survey 1999-2014. We performed logistic regression and receiver operating curve analysis to examine the discriminatory power of obesity indicators on cardiometabolic diseases and cancer at baseline. Sex-stratified and age-stratified Cox models were constructed to explore the prospective association between obesity indices and all-cause, cardiovascular and cancer mortality., Results: Elevated WHtR, elevated waist circumference (WC) and body mass index (BMI)-classified obesity are associated with higher odds of hypertension (OR: 1.37-2.13), dyslipidemia (OR: 1.06 to 1.75, all p<0.05) and diabetes (OR: 1.40-3.16, all p<0.05). WHtR had significantly better discriminatory power to predict cardiometabolic health than BMI, especially for diabetes (area under the curve: 0.709 vs 0.654). After multivariable adjustment, all obesity indicators are associated with lower risk of all-cause mortality among females aged ≥65 years (HR: 0.64 to 0.85), but the association was only significant for BMI when obesity indicators were mutually adjusted (HR: 0.79)., Conclusions: WHtR and WC appeared to be the better indicators for cardiometabolic health than BMI. However, BMI had a stronger and inverse association with a greater risk of all-cause mortality among older females., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The FDA-approved entrectinib on August 15, 2019, for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. Approval was based on demonstration of a durable overall response rate of 57% (95% confidence interval: 43-71), including a complete response rate of 7%, among 54 entrectinib-treated patients with 10 different tumor types harboring an NTRK fusion enrolled in one of three single-arm clinical trials. The durations of response ranged from 2.8 months to 26.0+ months; 68% of responses lasted ≥ 6 months. The most serious toxicities of entrectinib are congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, and vision disorders. Adverse reactions were manageable through dose interruptions (46%), dose reductions (29%), or discontinuation of entrectinib (9%). This is the third approval of a cancer drug for treatment of a tissue agnostic, biomarker-defined cancer., (©2020 American Association for Cancer Research.)

Objectives: The association between telomeres length (TL) and cancer mortality is uncertain. We tested the hypotheses that long TL are associated with reduced cancer mortality., Design: Prospective cohort study., Setting: the National Health and Nutrition Survey (NHANES, 1999-2002)., Participants: The analytic sample included adults (n = 7183) who had TL measurements., Measurements: DNA was obtained via blood samples. Telomere length was assessed using the quantitative polymerase chain reaction method., Results: During follow-up (0.08-12.7 person-years, median = 9.5 years), we observed 195 participants had cancer as causes of death. TL was negatively corelated with age, body mass index (BMI), systolic blood pressure (SBP), C-reactive protein (CRP), race, diabetes, hypertension, cardiovascular diseases (CVD) and cancer mortality, conversely, positively corelated with alcohol use, but not related to diastolic blood pressure (DBP) and smoking. Kaplan-Meier analysis revealed that TL was significantly associated with cancer mortality (log-rank, P <0.001)., Conclusions: Our study expands upon previous evidence of a relationship between TL and cancer mortality. TL may be a useful tool for evaluating risk of cancer mortality in American adults., Competing Interests: The author has no conflicts of interests to report.

Coronary artery disease (CAD) is the leading cause of death worldwide. Recent genome-wide association studies (GWAS) identified >50 common variants associated with CAD or its complication myocardial infarction (MI), but collectively they account for <20% of heritability, generating a phenomena of "missing heritability". Rare variants with large effects may account for a large portion of missing heritability. Genome-wide linkage studies of large families and follow-up fine mapping and deep sequencing are particularly effective in identifying rare variants with large effects. Here we show results from a genome-wide linkage scan for CAD in multiplex GeneQuest families with early onset CAD and MI. Whole genome genotyping was carried out with 408 markers that span the human genome by every 10 cM and linkage analyses were performed using the affected relative pair analysis implemented in GENEHUNTER. Affected only nonparametric linkage (NPL) analysis identified two novel CAD loci with highly significant evidence of linkage on chromosome 3p25.1 (peak NPL  = 5.49) and 3q29 (NPL  = 6.84). We also identified four loci with suggestive linkage on 9q22.33, 9q34.11, 17p12, and 21q22.3 (NPL  = 3.18-4.07). These results identify novel loci for CAD and provide a framework for fine mapping and deep sequencing to identify new susceptibility genes and novel variants associated with risk of CAD.

Extending research on self-other differences in perception to a global health risk, this study compares U.S. and Chinese college students' perceived H1N1 flu risk at four levels: personal, group, societal, and global. It also examines how personal experience, interpersonal communication, traditional and Internet-based media, and self-efficacy affect perception at four levels, as well as the self-other differences between the personal level and each of the other three levels. An online survey in both countries reveals an "ascending pattern," showing higher perceived risk for others than for selves. Chinese respondents perceive higher risk than U.S. respondents at all levels. Interpersonal communication predicts risk perception at four levels in the United States and at the group and societal levels in China. New media exposure exerts influence on all but the group level in China, while social networking sites (SNS) exposure predicts group- and societal-level risk perception in the United States. The overall attention paid to H1N1 information in the media affects all levels in both countries. Interaction between media exposure and attention is influential at all levels in the United States. Self-efficacy is negatively associated with risk perception in China except at the global level. Attention to media in the United States, and SNS exposure in China, explain the self-other differences in three comparisons, along with self-efficacy, which decreases the self-other gap in the United States while increasing the gap in China.

Introduction: Orthodontics in China has developed rapidly, but there is no standard index of treatment outcomes. We assessed the validity of the American Board of Orthodontics Objective Grading System (ABO-OGS) for the classification of treatment outcomes in Chinese patients., Methods: We randomly selected 108 patients who completed treatment between July 2005 and September 2008 in 6 orthodontic treatment centers across China. Sixty-nine experienced Chinese orthodontists made subjective assessments of the end-of-treatment casts for each patient. Three examiners then used the ABO-OGS to measure the casts. Pearson correlation analysis and receiver operating characteristic curve analysis were conducted to evaluate the correspondence between the ABO-OGS cast measurements and the orthodontists' subjective assessments., Results: The average subjective grading scores were highly correlated with the ABO-OGS scores (r = 0.7042). Four of the 7 study cast components of the ABO-OGS score-occlusal relationship, overjet, interproximal contact, and alignment-were statistically significantly correlated with the judges' subjective assessments. Together, these 4 accounted for 58% of the variability in the average subjective grading scores. The ABO-OGS cutoff score for cases that the judges deemed satisfactory was 16 points; the corresponding cutoff score for cases that the judges considered acceptable was 21 points., Conclusions: The ABO-OGS is a valid index for the assessment of treatment outcomes in Chinese patients. By comparing the objective scores on this modification of the ABO-OGS with the mean subjective assessment of a panel of highly qualified Chinese orthodontists, a cutoff point for satisfactory treatment outcome was defined as 16 points or fewer, with scores of 16 to 21 points denoting less than satisfactory but still acceptable treatment. Cases that scored greater than 21 points were considered unacceptable., (Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

Genome-wide association studies have separately identified four single nucleotide polymorphisms (SNPs) on chromosome 9p21 that confer susceptibility to coronary artery disease (CAD) and myocardial infarction (MI). This study presents the first analysis of these SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) in a premature, familial CAD/MI population (GeneQuest). We performed a case-control analysis of the GeneQuest Caucasian population with 310 cases with premature CAD and MI (average age at onset of 40.3 +/- 5.1) and 560 non-CAD controls to determine if these SNPs are associated with risk of CAD using both the population-based and family-based association study designs. The four SNPs are significantly associated with premature and familial MI and CAD in the GeneQuest Caucasian population (allelic P= 6.61 x 10(-7) to 1.87 x 10(-8)). Sib-TDT analysis showed that three of the four SNPs could confer significant susceptibility to premature CAD and MI. These results indicate that the four SNPs on chromosome 9p21 are also associated with premature, familial CAD.

Objectives: The objectives of this study were to determine growth status and to identify malnutrition with various anthropometric indicators in children with cystic fibrosis (CF) based on cross-sectional analysis of the 1993 National CF Patient Registry data., Methods: Heights and weights of 13,116 children with CF were evaluated with percentile, percent of reference median, Z-score, and percent ideal weight-for-height based on National Center for Health Statistics/Centers for Disease Control growth references. Malnutrition was defined by four criteria: (1) height-for-age <5th percentile ("stunting") or weight-for-age <5th percentile ("wasting") (2) height-for-age <90% of reference median or weight-for-age <80% of reference median, (3) height-for-age <5th percentile or percent ideal weight-for-height <85%, and (4) height-for-age <90% of reference median or weight-for-height <85% of reference median., Results: Mean and median height- and weight-for-age were found to be at the 30th and 20th percentiles in children with CF. Malnutrition (height- or weight-for-age <5th percentile) was particularly pronounced in infants (47%) and adolescents (34%) and patients with newly diagnosed CF (44%). A significant sex difference (p < 0.01) in the occurrence of stunting (height-for-age <5th percentile) was observed during adolescence: boys 11 to 14 years of age showed lower occurrence of stunting (19%) compared with girls (29%), whereas the opposite trend was observed at 15 to 18 years (34% in male patients vs 28% in female patients)., Conclusion: Twenty percent of all children in the 1993 National CF Patient Registry were <5th percentile for height- or weight-for-age. A significant discrepancy was found when different criteria were used to distinguish "stunting" versus "wasting" in malnourished children with CF.

The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones.