Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive Function of Elderly Persons in Japanese Neighborhoods: The Role of Street Layout

Objectives: The aims of this study were to examine (a) associations of two metric and space syntax measures of street layout with the cognitive function of Japanese older adults and (b) the extent to which objectively assessed physical activity mediated such associations. Methods: Cross-sectional data from 277 older adults who lived in Japan were used. Street layout attributes were objectively calculated for each participant’s geocoded home location. The Mini-Mental State Examination was used to evaluate cognitive function. Physical activity was objectively assessed with accelerometers. Results: There was a statistically significant negative association between street integration and the odds of having cognitive impairment. Objectively assessed physical activity did not attenuate this relationship. Conclusions: Our findings provide unique evidence regarding the importance of the topological aspects of street layouts in (re)designing neighborhoods to support mental illness.
Radical prostatectomy or radiotherapy for high‐ and very high‐risk prostate cancer: a multidisciplinary prostate cancer clinic experience of patients eligible for either treatment

To compare radical prostatectomy (RP) vs radiotherapy (RT) with androgen‐deprivation therapy (ADT) in the setting of patients with high‐risk and very high‐risk (VHR) prostate cancer who were deemed eligible for either therapy and made a treatment choice after consultation in a multidisciplinary prostate cancer clinic (MDPCC), and to compare the MDPCC patients’ outcomes to a matched Surveillance, Epidemiology and End Results (SEER) cohort.
Columnar connectome: toward a mathematics of brain function

Understanding brain networks is important for many fields, including neuroscience, psychology, medicine, and artificial intelligence. To address this fundamental need, there are multiple ongoing connectome projects in the United States, Europe, and Asia producing brain connection maps with resolutions at macro- and microscales. However, still lacking is a mesoscale connectome. This viewpoint (1) explains the need for a mesoscale connectome in the primate brain (the columnar connectome), (2) presents a new method for acquiring such data rapidly on a large scale, and (3) proposes how one might use such data to achieve a mathematics of brain function.
Lactation induces increased IPSC bursting in oxytocinergic neurons

Hypothalamic magnocellular neurosecretory cells (MNCs) undergo dramatic structural reorganization during lactation in female rats that is thought to contribute to the pulsatile secretion of oxytocin critical for milk ejection. MNCs from male rats generate robust bursts of GABAergic synaptic currents, a subset of which are onset‐synchronized between MNC pairs, but the functional role of the IPSC bursts is not known. To determine the physiological relevance of IPSC bursts, we compared MNCs from lactating and non–lactating female rats using whole–cell recordings in brain slices. We recorded a sixfold increase in the incidence of IPSC bursts in oxytocin (OT)‐MNCs from lactating rats compared to non–lactating rats, whereas there was no change in IPSC bursts in vasopressin (VP)‐MNCs. Synchronized bursts of IPSCs were observed in pairs of MNCs in slices from lactating rats. Our data indicate, therefore, that IPSC bursts are upregulated specifically in OT‐MNCs during lactation, and may, therefore, contribute via rebound depolarization to the spike trains in OT neurons that lead to reflex milk ejection.
Disruption of valosin-containing protein activity causes cardiomyopathy and reveals pleiotropic functions in cardiac homeostasis

Valosin-containing protein (VCP), also known as p97, is an ATPase with diverse cellular functions, although the most highly characterized is targeting of misfolded or aggregated proteins to degradation pathways, including the endoplasmic reticulum–associated degradation (ERAD) pathway. However, how VCP functions in the heart has not been carefully examined despite the fact that human mutations in VCP cause Paget disease of bone and frontotemporal dementia, an autosomal dominant multisystem proteinopathy that includes disease in the heart, skeletal muscle, brain, and bone. Here we generated heart-specific transgenic mice overexpressing WT VCP or a VCPK524A mutant with deficient ATPase activity. Transgenic mice overexpressing WT VCP exhibit normal cardiac structure and function, whereas mutant VCP-overexpressing mice develop cardiomyopathy. Mechanistically, mutant VCP-overexpressing hearts up-regulate ERAD complex components and have elevated levels of ubiquitinated proteins prior to manifestation of cardiomyopathy, suggesting dysregulation of ERAD and inefficient clearance of proteins targeted for proteasomal degradation. The hearts of mutant VCP transgenic mice also exhibit profound defects in cardiomyocyte nuclear morphology with increased nuclear envelope proteins and nuclear lamins. Proteomics revealed overwhelming interactions of endogenous VCP with ribosomal, ribosome-associated, and RNA-binding proteins in the heart, and impairment of cardiac VCP activity resulted in aggregation of large ribosomal subunit proteins. These data identify multifactorial functions and diverse mechanisms whereby VCP regulates cardiomyocyte protein and RNA quality control that are critical for cardiac homeostasis, suggesting how human VCP mutations negatively affect the heart.
Variance component tests of multivariate mediation effects under composite null hypotheses

Mediation effects of multiple mediators are determined by two associations: one between an exposure and mediators ( S ‐ M ) and the other between the mediators and an outcome conditional on the exposure ( M ‐ Y ). The test for mediation effects is conducted under a composite null hypothesis, that is, either one of the S ‐ M and M ‐ Y associations is zero or both are zeros. Without accounting for the composite null, the type 1 error rate within a study containing a large number of multimediator tests may be much less than the expected. We propose a novel test to address the issue. For each mediation test j , j = 1 , … , J , we examine the S ‐ M and M ‐ Y associations using two separate variance component tests. Assuming a zero‐mean working distribution with a common variance for the element‐wise S ‐ M (and M ‐ Y ) associations, score tests for the variance components are constructed. We transform the test statistics into two normally distributed statistics under the null. Using a recently developed result, we conduct J hypothesis tests accounting for the composite null hypothesis by adjusting for the variances of the normally distributed statistics for the S ‐ M and M ‐ Y associations. Advantages of the proposed test over other methods are illustrated in simulation studies and a data application where we analyze lung cancer data from The Cancer Genome Atlas to investigate the smoking effect on gene expression through DNA methylation in 15 114 genes.
Smartphone Apps Targeting Alcohol and Illicit Substance Use: Systematic Search in in Commercial App Stores and Critical Content Analysis

Background Smartphone apps promise to enhance the reach of evidence-based interventions (cognitive behavior therapy, contingency management and therapeutic education system) for populations with substance use disorders, with minimal disruption to health systems. However, further studies are needed to systematically evaluate smartphone apps targeting alcohol and illicit substances. Objective The aim of this study was to evaluate the functionality, aesthetics, and quality of information of free or low-cost apps claiming to target alcohol, benzodiazepine, cocaine, crack/cocaine, crystal methamphetamine, and heroin use using the validated Mobile App Rating Scale (MARS) and critical content analysis. Methods A systematic search of iTunes and Google Play app stores for free or low-cost apps facilitating recovery was conducted in March 2018 and yielded 904 apps using the keywords described in previous studies (eg, recovery, sobriety, sober, alcohol, and heroin). An interdisciplinary team of clinicians, behavioral informatics, and public health reviewers trained in substance use disorders conducted a descriptive analysis of 74 apps categorized as reducing use. In addition to the MARS scale, a descriptive analysis of relevant apps was conducted by the study team to assess for quality indicators emphasized by expert guidelines and review articles. Results Most apps (n=74) claimed to reduce use or promote abstinence and yielded an overall low median MARS score of 2.82 (0.55) and a wide range of scores (1.64, 4.20). Ratings were also low for engagement (2.75 (0.72)), functionality (3.64 (0.78)), aesthetics (3.03 (0.87)), information (2.82 (0.62)), and satisfaction (1.76 (0.67)) subdomains. Innovative design and content features elicited in the review included initial assessments of substance use following app download, tracking substance use, and related consequences (eg, cost or calorie intake), remote and proximate peer support per geospatial positioning, and allowing users and family members of individuals with substance use disorders to locate 12-step meetings, treatment programs, and mental health services. Few apps integrated evidence-based psychotherapeutic (eg, cognitive behavioral therapy [CBT] or motivational interviewing) and pharmacologic interventions (eg, naloxone or buprenorphine). Conclusions Few commercially available apps yielded in our search integrated evidence-based interventions (eg, extended-release naltrexone, buprenorphine, naloxone, Self-Management and Recovery Training recovery, or CBT), and a concerning number of apps promoted harmful drinking and illicit substance use.
Temperament, executive function, and attention-deficit/hyperactivity disorder (ADHD) in adolescents: The mediating role of effortful control

ABSTRACT Introduction: Temperament dimensions may be related to executive functions (EF) and may be involved in the expression and maintenance of symptoms of attention-deficit/hyperactivity disorder (ADHD). The current study aimed to assess whether effortful control (EC) mediates the relationship between EF and inattentive symptoms, and whether surgency (S) and negative affectivity (NA) mediate the relationships between EF and hyperactive–impulsive ADHD symptoms in adolescents. Method: Working individually, participants aged between 12 and 16 years (N = 118; 75 with ADHD) performed tests of cognitive EF (working memory, planning, flexibility, and inhibition), and parents and teachers completed a multi-informant assessment focusing on measures of ADHD symptoms and temperament dimensions (EC, S, and NA). Results: There were significant differences between ADHD and control participants in EF and temperament dimensions. ADHD participants had lower scores than controls in working memory, planning, and inhibition EF; they also had lower scores in EC and higher scores in S and NA. Structural equation modeling indicated differential associations between EC, S, and NA temperament dimensions, and working memory, planning and inhibition EF, and ADHD symptoms. Mediation analysis suggested that EF exerted indirect effects on the inattentive and hyperactive–impulsive symptoms, via EC; higher EF abilities were related to higher levels of EC, which in turn were related to lower scores of inattentive and hyperactive–impulsive ADHD symptoms. S and NA did not mediate relations among EF and hyperactive–impulsive symptoms. Conclusion: The findings expand on those of previous studies of the complex relationship between temperament dimensions and EF and confirm the differential association between impairments in some EF, low EC, and the expression of inattentive and hyperactive–impulsive symptoms in adolescents, which may account for the ADHD–control group differences.
Impact of age , leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era : results of the FRALLE 93 study

Background: We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors. Methods: Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLAmatched sibling. Results: Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 Published: 13 January 2009 BMC Cancer 2009, 9:14 doi:10.1186/1471-2407-9-14 Received: 15 September 2008 Accepted: 13 January 2009 This article is available from: http://www.biomedcentral. com/1471-2407/9/14 © 2009 Gandemer et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Cr isotopic insights into ca. 1.9 Ga oxidative weathering of the continents using the Beaverlodge Lake paleosol, Northwest Territories, Canada

The ca. 1.9 Ga Beaverlodge Lake paleosol was studied using redox‐sensitive Cr isotopes in order to determine the isotopic response to paleoweathering of a rhyodacite parent rock 500 million years after the Great Oxidation Event. Redox reactions occurring in modern weathering environments produce Cr(VI) that is enriched in heavy Cr isotopes compared to the igneous inventory. Cr(VI) species are soluble and easily leached from soils into streams and rivers, thus, leaving particle‐reactive and isotopically light Cr(III) species to build up in soils. The Beaverlodge Lake paleosol and two other published weathering profiles of similar age, the Flin Flon and Schreiber Beach paleosols, are not as isotopically light as modern soils, indicating that rivers were not as isotopically heavy at that time. Considering that the global average δ53Cr value for the oxidative weathering flux of Cr to the oceans today is just 0.27 ± 0.30‰ (1σ) based on a steady‐state analysis of the modern ocean Cr cycle, the oxidative weathering flux of Cr to the oceans at ca. 1.9 Ga would have likely been shifted to lower δ53Cr values, and possibly lower than the igneous inventory (–0.12 ± 0.10‰, 2σ). Mn oxides are the main oxidant of Cr(III) in modern soils, but there is no evidence that they formed in the studied paleosols. Cr(VI) may have formed by direct oxidation of Cr(III) using molecular oxygen or H2O2, but neither pathway is as efficient as Mn oxides for producing Cr(VI). The picture that emerges from this and other studies of Cr isotope variation in ca. 1.9 Ga paleosols is of atmospheric oxygen concentrations that are high enough to oxidize iron, but too low to oxidize Mn, resulting in low Cr(VI) inventories in Earth surface environments.
The MTHFR 677C>T polymorphism is associated with unmetabolized folic acid in breast milk in a cohort of Canadian women.

BACKGROUND Maternal nutrition and genetics are determinants of breast-milk nutrient composition and, as such, are determinants of the nutritional exposure of breastfed infants. OBJECTIVES The aim of this study was to determine whether common maternal single nucleotide polymorphisms (SNPs) in folate-dependent enzymes are associated with breast-milk folate content in a cohort of mothers enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. METHODS The MIREC study is a Canadian prospective pregnancy cohort study that recruited 2001 participants between 2008 and 2011. Five folate-related SNPs-MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), MTHFR 1793G>A (rs2274976), MTR 2756A>G (rs1805087), and MTRR 66A>G (rs1801394)-were genotyped. Breast milk was sampled ∼1 mo postpartum, and tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF, 5,10-methenyl-THF, and unmetabolized folic acid (UMFA) were measured using liquid chromatography-tandem mass spectrometry in a subset of participants (n = 551). Associations were assessed using Wald's test. Associations were considered significant if P ≤ 0.01 (Bonferroni correction for multiple testing). RESULTS None of the SNPs were associated with total breast-milk folate. However, the MTHFR 677C>T SNP was associated with breast-milk UMFA (R2 = 0.01; unadjusted P = 0.004), explaining a small portion of total variance; this association remained significant when adjusted for other covariates, including supplemental folic acid consumption. The MTHFR 1793G>A and MTRR 66A>G SNPs tended to be associated with 5-methyl-THF (R2 = 0.008, P = 0.04) and reduced folates (THF + 5-methyl-THF + 5-formyl-THF + 5,10-methenyl-THF; R2 = 0.01, P = 0.02), respectively. CONCLUSIONS We found that total breast-milk folate content was not associated with any of the folate-related SNPs examined. The association between the MTHFR 677C>T SNP and breast-milk UMFA, albeit modest, highlights the need to better understand the determinants of breast-milk folate and the impact they might have on milk folate bioavailability.
Bycatch and discard mortality in commercially caught blue sharks Prionace glauca assessed using archival satellite pop-up tags

Blue sharks Prionace glauca are the most frequently discarded fish species during com- mercial pelagic longline fishing operations worldwide, yet their post-release mortality rate has never been measured. A generalized linear model of 12 404 blue sharks observed during the Canadian Atlantic pelagic longline swordfishery suggested a hooking mortality of 12 to 13%, yet scientific examination of 902 of these sharks indicated that hooking mortality was actually higher. A random sample of 40 of these blue sharks were tagged with satellite pop-up archival transmission (PAT) tags, then monitored for periods of up to 6 mo after release. All of the surviving sharks exhibited a depth- holding recovery behaviour for a period of 2 to 7 d after release. All healthy sharks survived, while 33% of those that were badly injured or gut hooked subsequently died. Overall blue shark bycatch mortality in the pelagic longline fishery was estimated at 35%, while the estimated discard mortality for sharks that were released alive was 19%. Survival time models indicated that 95% of the mortal- ity occurred within 11 d of release, indicative of death by trauma rather than starvation. The annual blue shark catch in the North Atlantic was estimated at about 84 000 t, of which 57 000 t is discarded. A preliminary estimate of 20 000 t of annual dead discards for North Atlantic blue sharks is similar to that of the reported nominal catch, and could substantially change the perception of population health if incorporated into a population-level stock assessment.
Shared Genetic Etiology of Hwabyung (Anger Syndrome) and Somatization Symptoms in South Korean Adolescent and Young Adult Twins

Abstract Somatization is known to be more prevalent in Asian than in Western populations. Using a South Korean adolescent and young adult twin sample (N = 1754; 367 monozygotic male, 173 dizygotic male, 681 monozygotic female, 274 dizygotic female and 259 opposite-sex dizygotic twins), the present study aimed to estimate heritability of somatization and to determine common genetic and environmental influences on somatization and hwabyung (HB: anger syndrome). Twins completed self-report questionnaires of the HB symptoms scale and the somatization scale via a telephone interview. The results of the general sex-limitation model showed that 43% (95% CI [36, 50]) of the total variance of somatization was attributable to additive genetic factors, with the remaining variance, 57% (95% CI [50, 64]), being due to individual-specific environmental influences, including measurement error. These estimates were not significantly different between the two sexes. The phenotypic correlation between HB and somatization was . 53 (p < .001). The bivariate model-fitting analyses revealed that the genetic correlation between the two symptoms was . 68 (95% CI [.59, .77]), while the individual-specific environmental correlation, including correlated measurement error, was . 41 (95% CI [.34, .48]). Of the additive genetic factors of 43% that influence somatization, approximately half (20%) were associated with those related to HB, with the remainder being due to genes unique to somatization. A substantial part (48%) of individual environmental variance in somatization was unrelated to HB; only 9% of the environmental variance was shared with HB. Our findings suggest that HB and somatization have shared genetic etiology, but environmental factors that precipitate the development of HB and somatization may be largely independent from each other.
Medical students’ perceptions of stress due to academic studies and its interrelationships with other domains of life: a qualitative study

ABSTRACT Background: Medical students have been found to experience considerable stress due to their academic studies. The high demands associated with academic studies may interfere with demands in other domains of life. Conversely, demands in those other domains of life may conflict with academic studies. Objective: We aimed to better understand the potential inter-relationships between the demands related to academic studies and in other domains of life. Design: A total of 68 medical students from a medical school in Germany participate in eight focus groups. Sessions were structured by a topic guide and were recorded, transcribed and content-analyzed. Results: Embarking on one’s medical studies was perceived to be associated with important personal challenges, such as living alone for the first time and finding a new social role in one’s peer group. Permanent stress was perceived to result in emotional exhaustion, which spilled over in other domains of life. Students reported to feel guilty if they did not spend their limited spare time on learning. Consequently, they felt to have little time for leisure time activities and a healthy lifestyle. Feelings of social isolation, especially during exam phases, were reported. Leisure activities were perceived to facilitate recovery from academic stress. Social ties were subjectively able to reduce stress, but also to increase stress due to demands. Side jobs were perceived to increase stress and to be time-consuming and were thus perceived to result in poorer academic performance. Certain personality characteristics seemed to amplify those perceptions. For instance, high levels of conscientiousness were felt to relate to higher expectations regarding one’s academic performance and thus increased stress. Conclusion: The demands associated with medical studies, the demands in private life, lacking resources for recovery and certain personal traits as well as interactions between those domains can contribute to stress among medical students and reduce well-being.