Miracle-dz/UniFAR-FTUs huggingface dataset:
Soy Intake is Associated with Increased 2-Hydroxylation and Decreased 16α-Hydroxylation of Estrogens in Asian-American Women

Introduction: In Asian and Asian-American women, soy consumption is associated with reduced breast cancer risk, perhaps due to its effects on estrogen production or metabolism. In a sample of Asian-American women, we investigated the associations of usual adult soy intake with the urinary concentrations of 15 estrogens and estrogen metabolites (EM) measured using liquid chromatography-tandem mass spectrometry. Methods: Participants included 430 Chinese-American, Japanese-American, and Filipino-American women, ages 20 to 55 years, and living in San Francisco-Oakland (California), Los Angeles (California), or Oahu (Hawaii). They were postmenopausal (n = 167) or premenopausal in luteal phase (n = 263) when 12-hour urine samples were collected. Robust linear regression was used to assess soy tertiles as predictors of log-transformed EM measures. Individual and grouped EM were considered as concentrations (pmol/mg creatinine) and as percentages of total EM (%EM). Results: Factor analysis confirmed that EM groups defined by metabolic pathways appropriately captured covariation in EM profiles. Total EM concentrations were not significantly associated with soy in premenopausal or postmenopausal women. Among all women, %2-hydroxylated EM and %4-hydroxylation pathway EM were 16% higher (Ptrend = 0.02) and 19% higher (Ptrend = 0.03) in the highest versus lowest soy tertiles, respectively. In contrast, 16% hydroxylated EM were 11% lower (Ptrend < 0.01). Results were consistent across ethnic and menopausal groups and after adjustment for westernization measured by birthplace (Asia or United States). Discussion: Findings suggest that regular soy intake is associated with increased ratios of 2:16-pathway EM and with higher relative levels of 4-hydroxylated EM. The observed variations in estrogen metabolism might modify breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2751–60)
Predicting Health-related Quality of Life in Myocardial Infarction Patients

Goal theory suggests that both goal attainment and psychological processes concerning goal pursuit can influence a patient’s (health-related) quality of life (HRQL) (e.g. Carver & Scheier, 1999). In the present longitudinal study, 46 MI patients completed questionnaires shortly after hospitalization and four months later, assessing a health, social and individual goal for the coming year, goal conflict, goal self-efficacy, goal attainment and HRQL. The results of a multiple regression analysis suggest that both goal conflict and goal self-efficacy predict goal attainment. Furthermore, goal self-efficacy appeared to be an independent predictor of physical and social HRQL. Goal attainment had a medium effect on social HRQL, but its effect was mediated by goal conflict and goal self-efficacy. A goal theory perspective seems to offer additional insights into HRQL after an MI.
Preferential Use of CXCR4 by R5X4 Human Immunodeficiency Virus Type 1 Isolates for Infection of Primary Lymphocytes

ABSTRACT Coreceptor specificity of human immunodeficiency virus type 1 (HIV-1) strains is generally defined in vitro in cell lines expressing CCR5 or CXCR4, but lymphocytes and macrophages are the principal targets in vivo. CCR5-using (R5) variants dominate early in infection, but strains that use CXCR4 emerge later in a substantial minority of subjects. Many or most CXCR4-using variants can use both CXCR4 and CCR5 (R5X4), but the pathways that are actually used to cause infection in primary cells and in vivo are unknown. We examined several R5X4 prototype and primary isolates and found that they all were largely or completely restricted to CXCR4-mediated entry in primary lymphocytes, even though lymphocytes are permissive for CCR5-mediated entry by R5 strains. In contrast, in primary macrophages R5X4 isolates used both CCR5 and CXCR4. The R5X4 strains were also more sensitive than R5 strains to CCR5 blocking, suggesting that interactions between the R5X4 strains and CCR5 are less efficient. These results indicate that coreceptor phenotyping in transformed cells does not necessarily predict utilization in primary cells, that variability exists among HIV-1 isolates in the ability to use CCR5 expressed on lymphocytes, and that many or most strains characterized as R5X4 are functionally X4 in primary lymphocytes. Less efficient interactions between R5X4 strains and CCR5 may be responsible for the inability to use CCR5 on lymphocytes, which express relatively low CCR5 levels. Since isolates that acquire CXCR4 utilization retain the capacity to use CCR5 on macrophages despite their inability to use it on lymphocytes, these results also raise the possibility that a CCR5-mediated macrophage reservoir is required for sustained infection in vivo.
Rule-violations sensitise towards negative and authority-related stimuli

ABSTRACT Rule violations have usually been studied from a third-person perspective, identifying situational factors that render violations more or less likely. A first-person perspective of the agent that actively violates the rules, on the other hand, is only just beginning to emerge. Here we show that committing a rule violation sensitises towards subsequent negative stimuli as well as subsequent authority-related stimuli. In a Prime-Probe design, we used an instructed rule-violation task as the Prime and a word categorisation task as the Probe. Also, we employed a control condition that used a rule inversion task as the Prime (instead of rule violations). Probe targets were categorised faster after a violation relative to after a rule-based response if they related to either, negative valence or authority. Inversions, however, primed only negative stimuli and did not accelerate the categorisation of authority-related stimuli. A heightened sensitivity towards authority-related targets thus seems to be specific to rule violations. A control experiment showed that these effects cannot be explained in terms of semantic priming. Therefore, we propose that rule violations necessarily activate authority-related representations that make rule violations qualitatively different from simple rule inversions.
Differences in the profiles of DSM-IV and DSM-5 alcohol use disorders: implications for clinicians.

BACKGROUND Existing information on consequences of the DSM-5 revision for the diagnosis of alcohol use disorders (AUD) has gaps, including missing information critical to understanding implications of the revision for clinical practice. METHODS Data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used to compare AUD severity, alcohol consumption and treatment, sociodemographic and health characteristics, and psychiatric comorbidity among individuals with DSM-IV abuse versus DSM-5 moderate AUD and DSM-IV dependence versus DSM-5 severe AUD. For each pair of disorders, we additionally compared 3 mutually exclusive groups: individuals positive solely for the DSM-IV disorder, those positive solely for the DSM-5 disorder, and those positive for both. RESULTS Whereas 80.5% of individuals positive for DSM-IV dependence were positive for DSM-5 severe AUD, only 58.0% of those positive for abuse were positive for moderate AUD. The profiles of individuals with DSM-IV dependence and DSM-5 severe AUD were almost identical. The only significant (p < 0.005) difference, more AUD criteria among the former, reflected the higher criterion threshold (≥ 4 vs. ≥ 3) for severe AUD relative to dependence. In contrast, the profiles of individuals with DSM-5 moderate AUD and DSM-IV abuse differed substantially. The former endorsed more AUD criteria, had higher rates of physiological dependence, were less likely to be White individuals and men, had lower incomes, were less likely to have private and more likely to have public health insurance, and had higher levels of comorbid anxiety disorders than the latter. CONCLUSIONS Similarities between the profiles of DSM-IV and DSM-5 AUD far outweigh differences; however, clinicians may face some changes with respect to appropriate screening and referral for cases at the milder end of the AUD severity spectrum, and the mechanisms through which these will be reimbursed may shift slightly from the private to public sector.
Socio-emotional and clinical profile of bullied youth in a clinic setting: assessing bullying-related functional impairment

Community and school research has identified bullying as a pervasive and significant problem for school-age youth. Less emphasis has been placed on bullying-related impairment in clinic settings, but treatment-seeking youth with a history of bullying may have specific needs that deserve attention. Limited information regarding the clinical profile and socio-emotional functioning of bullied youth leave clinicians with little information to guide treatment planning and services. The present study completed retrospective interviews with youth and young adults who had previously sought treatment for anxiety and/or depression at a university-based outpatient clinic. Participants (N=85; youth = 60; adults = 25) completed diagnostic and symptom assessment at the original point of clinic contact and completed bullying-specific interview procedures nine months to eight years after clinic contact (M = 4.23 years). The majority of participants (51.7%) endorsed being bullied at least once or twice in the year prior to seeking mental health services. However, bullied and non-bullied youth did not differ on most measures of anxiety and depression symptoms, according to youth, father, and mother reports. This study also examined the psychometric properties of the Multidimensional Bullying Impairment Scale (MBIS), a self-report scale designed to assess functional impairment related to bullying. Results suggested the MBIS and its a priori subscales had strong internal reliability. Exploratory factor analysis supported a five-factor model, but further analysis suggested that a single total score might represent the construct best. Correlations amongst functional impairment and anxiety and depression symptoms highlighted interesting patterns. Functional impairment was found to be strongly related to depression and moderately correlated with anxiety symptoms. As predicted, bullying related impairment was not found to be positively correlated with externalizing symptoms. Together, results suggest the MBIS may be a promising tool to evaluate
An anthropometric survey of US pre-term and full-term neonates

Abstract Background: Anthropometric data prove valuable for screening and monitoring various medical conditions. In young infants, however, only weight, length and head circumference are represented in publicly accessible databases. Aim: To characterise length and circumferential measures in pre-term and full-term infants up to 90 days post-natal. Subjects and methods: In eight US medical centres, trained raters recorded humeral, ulnar, femoral, tibial and fibular lengths along with mid-upper arm, mid-thigh, chest, abdominal and neck circumference. Data were pooled by post-menstrual age into 1-week intervals and population curves created using the lambda, mu and sigma (LMS) method. Goodness-of-fit was assessed by examining de-trended quantile-quantile plots, Q statistics and fitted centiles overlaid on empirical centiles. Results: In total, 2097 infants were enrolled in this study with a mean ± SD gestational age and post-natal age of 37.1 ± 3.3 weeks and 27.3 ± 25.3 days, respectively. A re-scale option was used to describe all curves. The resultant models reliably characterised anthropometric measures from 33–52 weeks PMA, with less certainty at the extremes (27–55 weeks). Conclusion: The population curves generated under this investigation expand existing reference data on a comprehensive set of anthropometric traits in infants through the first 90 days post-natal.
Intraprotomer masking of third variable loop (V3) epitopes by the first and second variable loops (V1V2) within the native HIV-1 envelope glycoprotein trimer

Within the trimeric HIV-1 envelope (Env) spike, the first and second variable loops (V1V2 region) and the third variable loop (V3) of the gp120 subunit play dual roles in antibody recognition, because they contain neutralization epitopes and also participate in epitope masking. The spatial relationships between V1V2 and V3 and the associated mechanisms of epitope masking remain unclear. Here we investigated interactions between these domains using two monoclonal antibodies recognizing distinct conserved linear epitopes that are subject to masking in the functional trimer, which limits their neutralizing activities. Using Env pseudotype virus infection assays, we found that deleting the V1V2 region greatly enhanced neutralization by both antibodies, leading us to consider two alternative models: V1V2 on one gp120 protomer masks V3 on the same protomer (intraprotomer or cis masking) versus on an adjacent protomer (interprotomer or trans masking). Our experimental approach exploited a previously described complementation system wherein two variant Envs harboring different inactivating mutations (one in gp120, the other in gp41) are coexpressed in the same cell; functional Env results only from cooperative interactions within mixed trimers, thereby enabling selective examination of mixed trimer activity. We introduced additional mutations that either promoted (V1V2 deletion, i.e., unmasking) or prevented (GPGR to GPGQ mutation, i.e., epitope destruction) interaction with the antibodies. The observed neutralization sensitivities of mixed trimers produced from various combinations of constructs support the intraprotomer (cis) model of V1V2 masking of V3 epitopes.
Target-Specific Suppression of GABA Release from Parvalbumin Interneurons in the Basolateral Amygdala by Dopamine

Dopamine (DA) in the basolateral amygdala (BLA) promotes fear learning by disinhibiting principal neurons (PNs) and enabling synaptic plasticity in their sensory inputs. While BLA interneurons (INs) are heterogeneous, it is unclear which interneuron subtypes decrease GABAergic input to PNs in the presence of DA. Here, using cell type-selective photostimulation by channelrhodopsin 2 in BLA slices from mouse brain, we examined the role of parvalbumin-positive INs (PV-INs), the major interneuronal subpopulation in BLA, in the disinhibitory effect of DA. We found that DA selectively suppressed GABAergic transmission from PV-INs to PNs by acting on presynaptic D2 receptors, and this effect was mimicked by Rp-cAMP, an inhibitor of cAMP-dependent signaling. In contrast, DA did not alter GABA release from PV-INs to INs. Furthermore, neither suppressing cAMP-dependent signaling by Rp-cAMP nor enhancing it by forskolin altered GABA release from PV-INs to BLA INs. Overall, DA disinhibits BLA, at least in part, by suppressing GABA release from PV-INs in the target cell-specific manner that results from differential control of this release by cAMP-dependent signaling.
Estimated phytanic acid intake and prostate cancer risk: A prospective cohort study

Phytanic acid is a saturated fatty acid found predominantly in red meat and dairy products and may contribute to increases in prostate cancer risk that are observed with higher intakes of these foods. We constructed a novel summary measure of phytanic acid intake and prospectively examined its association with prostate cancer risk in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study—a cohort of Finnish male smokers aged 50–69 years. Diet was assessed at baseline in 27,111 participants using a validated 276‐item dietary questionnaire. Since phytanic acid is not currently included in food composition tables, we used the published phytanic acid content of 151 major food items to estimate total daily intake. During up to 21 years of follow‐up, a total of 1,929 incident prostate cancer cases (including 438 advanced cases) were identified. Higher phytanic acid intake, though unrelated to the risk of localized disease [relative risks (RR) and 95% confidence intervals (CI) for increasing quartiles of intake = 1.00 (ref), 0.83 (0.68–1.01), 0.76 (0.62–0.94) and 0.91 (0.74–1.13); p trend = 0.23], was associated with increased risks of advanced prostate cancer [RR and 95% CI = 1.00 (ref), 1.43 (1.09–1.89), 1.31 (0.99–1.75) and 1.38 (1.02–1.89); p trend = 0.06]. This association appeared to be driven predominantly by phytanic acid obtained from dairy products (particularly butter). Our study indicates that phytanic acid may contribute to previously observed associations between high‐fat animal foods (particularly dairy products) and prostate cancer risk, although some caution is warranted as it may be acting as a surrogate marker of dairy fat.
Statistical considerations for a trial of Ebola virus disease therapeutics

The 2014 West African outbreak of Ebola virus ravaged Liberia, Sierra Leone, and Guinea, causing hemorrhagic fever and death. The need to identify effective therapeutics was acute. The usual drug development paradigm of phase I, followed by phase II, and then phase III trials would take too long. These and other factors led to the design of a clinical trial of Ebola virus disease therapeutics that differs from more conventional clinical trial designs. This article describes the Ebola virus disease medical countermeasures trial design and the thinking behind it.
The emotions of romantic relationships: Do they wreak havoc on adolescents?

Romantic emotions can grip adolescents' lives. A 14-year-old reports feeling so in love that he can think of nothing else. A 15-year-old is distressed that “everyone has a boyfriend but me” and broods for hours in her room. Another girl finds herself in a passionate lesbian relationship and feels elated, affirmed, and “chosen. ” And a boy reports feeling so enraged by the betrayal of his girlfriend that he is obsessed with thinking up ways to hurt her. Western thought has long been ambivalent about the role of emotion in human behavior. On the one hand, we have praised and idealized deep feeling. It is the motif for much of our entertainment in novels, television, and film. On the other hand, we have been suspicious about emotions and the disruptive effects they are believed to inflict upon rational thought and action; Kant (1798/1978), for example, referred to emotions as “diseases of the mind. ” This same ambivalence is manifest in our society's attitudes toward adolescent romance and the emotions that surround it. We sentimentalize young love and the joys and pains that accompany it, yet we also view it with suspicion as a set of affairs that can play havoc with young people's lives. What is indisputable is that emotions related to romantic relationships constitute a substantial part of adolescents' day-to-day emotional lives, at least in the United States.
Elevated prefrontal cortex γ-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy.

CONTEXT Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. OBJECTIVE To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. DESIGN Case-control study. SETTING Inpatient psychiatric research unit and associated outpatient clinic. PARTICIPANTS Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. METHODS Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. MAIN OUTCOME MEASURES The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. RESULTS In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. CONCLUSIONS To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.
PE-Probe: Leveraging Packer Detection and Structural Information to Detect Malicious Portable Executables

The number of executable malware and the sophistication of their destructive ability has exponentially increased in past couple of years. Malware writers use sophisticated code obfuscation and encryption (a.k.a. packing) techniques to circumvent signatures ‐ derived from the code of the malware for detection ‐ stored in the signatures’ database of commercial off-the-shelf anti-virus software. In fact, it is claimed that more than half of new malware are created by simply re-packing the existing malware. Malware packing can undoubtedly be considered as the most challenging problem faced by anti-virus vendors nowadays. In this paper we present a novel scheme ‐ PE-Probe ‐ which has the ability to detect packed files and uses structural information of portable executables to detect zero-day (i.e. previously unseen) malicious executables. As a result, our proposed scheme is fully robust to code obfuscation and packing techniques. PE-Probe functions in two phases: (1) it classifies a given executable as packed or non-packed by employing well-studied heuristics, and (2) it invokes specialized structural models ‐ separately developed for packed and non-packed executables ‐ for malware detection on the basis of the outcome of the previous step. PE-Probe is real-time deployable as its scanning time is, on the average, less than quarter of a second per executable. We have carefully designed experiments ‐ keeping in view the stringent testing scenarios ‐ to analyze the reliability and robustness of our scheme to packing and obfuscation techniques. We report our experiments on a recently obtained malware dataset from OffensiveComputing.net, which contains more than half a million malicious executables.