Miracle-dz/UniFAR-FTUs huggingface dataset:
Paternal age and common mental disorders

Introduction. There is evidence in the literature that there are associations between advancing paternal age and psychosis or more specifically schizophrenia, but not enough to support a strong link between advancing paternal age and common mental disorders. Objective. This study aims to explain the association between paternal age at birth and common mental disorders in progeny during their adulthood. Methodology. This is a sub-study from a larger survey which was planned to study the epidemiology of mental disorders in Malaysia. Respondents who could remember the age of parents at birth were included in the study. The diagnosis of common mental disorders (CMD) was made using the CIS-R (Clinical Interview Schedule-Revised) instrument in the PROQSY (Programmed Questionnaire System) format. Association between paternal age at birth and CMD was studied using logistic regression, after controlling for age, gender, ethnicity and presence of family history of mental disorders. Results. Respondents with paternal age at birth of 19 and below and 50 above and had higher rates of 10 and 25% for common mental disorders (χ2=7.007, P=0.072) with odds ratios of 2.89 (95% CI of OR = 1.1–7.6) and 4.28 (1.4–12.7). Discussion. Progenies of fathers under 20 and over 50 had higher risk for mental disorders. Factors such as immaturity in sperm of teenage fathers, mutation in germ line of older fathers, environmental and psychosocial factors could have contributed to increased prevalence of common mental disorders in the progeny.
Sex differences between parental pregnancy characteristics and nonalcoholic fatty liver disease in adolescents

Nonalcoholic fatty liver disease (NAFLD) is a complex chronic liver disorder. Examination of parental pregnancy‐related characteristics may provide insights into the origins of risk of NAFLD in offspring. We examined relationships between parental pregnancy‐related characteristics and NAFLD in 1,170 adolescent offspring aged 17 years participating in the Western Australian Pregnancy (Raine) Cohort Study. Fatty liver was diagnosed using liver ultrasound. NAFLD was diagnosed in 15.2% of adolescents at age 17 years. In univariate analysis, maternal factors associated with NAFLD in female offspring were younger maternal age (P = 0.02), higher maternal prepregnancy BMI (P < 0.001), higher maternal weight gain by 18 weeks' gestation (P < 0.001), and maternal smoking during pregnancy (P = 0.04). Paternal age or body mass index (BMI) were not associated with NAFLD in female offspring. In contrast, higher paternal BMI (P < 0.001), maternal prepregnancy BMI (P < 0.001), and lower family socioeconomic status (SES) at time of birth (P = 0.001), but not parental age nor maternal gestational weight gain, were associated with NAFLD in male offspring. Using multivariate logistic regression, factors independently associated with NAFLD after adjusting for obesity in adolescent females included maternal obesity (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.49‐8.05; P = 0.004) and maternal weight gain ≥6.0 kg by the 18th week of gestation (OR, 1.10; 95% CI, 1.04‐1.15; P < 0.001). In adolescent males, family SES at the time of birth (OR, 9.07; 95% CI, 1.54‐53.29; P = 0.02) remained significantly associated with NAFLD after multivariate modeling adjusted for adolescent obesity. Conclusion: Early‐life contributors to NAFLD show considerable sexual dimorphism. Maternal obesity and higher early‐mid gestational weight gain were associated with NAFLD in female offspring, whereas lower family SES at birth was associated with NAFLD in male offspring independent of adolescent obesity. (Hepatology 2018;67:108‐122).
Expression and methylation of BDNF in the human brain in schizophrenia

Abstract Objectives: To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene. Methods: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia. Results: There was 43% more of the BDNF V-VIII-IX transcript in schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally significant positive correlation with mRNA expression in schizophrenia subjects. Conclusions: Schizophrenia risk was not associated with differential BDNF mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.
β‐Catenin regulation of farnesoid X receptor signaling and bile acid metabolism during murine cholestasis

Cholestatic liver diseases result from impaired bile flow and are characterized by inflammation, atypical ductular proliferation, and fibrosis. The Wnt/β‐catenin pathway plays a role in bile duct development, yet its role in cholestatic injury remains indeterminate. Liver‐specific β‐catenin knockout mice and wild‐type littermates were subjected to cholestatic injury through bile duct ligation or short‐term exposure to 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine diet. Intriguingly, knockout mice exhibit a dramatic protection from liver injury, fibrosis, and atypical ductular proliferation, which coincides with significantly decreased total hepatic bile acids (BAs). This led to the discovery of a role for β‐catenin in regulating BA synthesis and transport through regulation of farnesoid X receptor (FXR) activation. We show that β‐catenin functions as both an inhibitor of nuclear translocation and a nuclear corepressor through formation of a physical complex with FXR. Loss of β‐catenin expedited FXR nuclear localization and FXR/retinoic X receptor alpha association, culminating in small heterodimer protein promoter occupancy and activation in response to BA or FXR agonist. Conversely, accumulation of β‐catenin sequesters FXR, thus inhibiting its activation. Finally, exogenous suppression of β‐catenin expression during cholestatic injury reduces β‐catenin/FXR complex activation of FXR to decrease total BA and alleviate hepatic injury. Conclusion: We have identified an FXR/β‐catenin interaction whose modulation through β‐catenin suppression promotes FXR activation and decreases hepatic BAs, which may provide unique therapeutic opportunities in cholestatic liver diseases. (Hepatology 2018;67:955–971)
Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression

Abstract Objectives: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients. Methods: All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele. Results: In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders. Conclusions: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.
An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice

Hepatocellular carcinoma (HCC) is the third leading cause of cancer–related deaths worldwide, mainly because of its poor prognosis. A valid mechanism‐based prognostic biomarker is urgently needed. γ‐hydroxy‐1,N2‐propanodeoxyguanosine (γ‐OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation. We examined the relationship of γ‐OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in xeroderma pigmentosum group A knockout mice and diethylnitrosamine‐injected mice, both prone to HCC development. γ‐OHPdG levels in the livers of these animals were determined. The effects of antioxidant treatments on γ‐OHPdG and hepatocarcinogenesis were examined. Using two independent sets of HCC specimens from patients, we examined the relationship between γ‐OHPdG and survival or recurrence‐free survival. γ‐OHPdG levels in liver DNA showed an age‐dependent increase and consistently correlated with HCC development in all three animal models. Theaphenon E treatment significantly decreased γ‐OHPdG levels in the liver DNA of xeroderma pigmentosum group A knockout mice and remarkably reduced HCC incidence in these mice to 14% from 100% in the controls. It also effectively inhibited HCC development in the diethylnitrosamine‐injected mice. Using clinical samples from two groups of patients, our study revealed that higher levels of γ‐OHPdG are strongly associated with low survival (P < 0.0001) and low recurrence‐free survival (P = 0.007). Conclusion: These results support γ‐OHPdG as a mechanism‐based, biologically relevant biomarker for predicting the risk of HCC and its recurrence. (Hepatology 2018;67:159‐170).
Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia

Abstract Objectives: Accelerated intermittent theta-burst stimulation (aiTBS) anti-depressive working mechanisms are still unclear. Because aiTBS may work through modulating the reward system and the level of anhedonia may influence this modulation, we investigated the effect of aiTBS on reward responsiveness in high and low anhedonic MDD patients. Methods: In this registered RCT (NCT01832805), 50 MDD patients were randomised to a sham-controlled cross-over aiTBS treatment protocol over the left dorsolateral prefrontal cortex (DLPFC). Patients performed a probabilistic learning task in fMRI before and after each week of stimulation. Results: Task performance analyses did not show any significant effects of aiTBS on reward responsiveness, nor differences between both groups of MDD patients. However, at baseline, low anhedonic patients displayed higher neural activity in the caudate and putamen. After the first week of aiTBS treatment, in low anhedonic patients we found a decreased neural activity within the reward system, in contrast to an increased activity observed in high anhedonic patients. No changes were observed in reward related neural regions after the first week of sham stimulation. Conclusions: Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.
RETRACTED ARTICLE: Biofeedback for Pain Management in Traumatised Refugees

Chronic pain (CP) and posttraumatic stress disorder (PTSD) are both frequent and often comorbid in refugees. To date, few controlled trials have studied the efficacy of treatments targeting this comorbidity; no treatment guidelines yet exist. The authors examined the feasibility and efficacy of short-term cognitive behavioural biofeedback (BF) addressing CP in traumatised refugees. The sample comprised 11 severely traumatised refugees with CP and PTSD (mean age = 36 years, SD = 6), who underwent assessment with the Mini International Neuropsychiatric Interview, Posttraumatic Diagnostic Scale, Pain Disability Index, and Visual Rating Scale. Additionally, coping with pain and psychotherapy tolerance were assessed. Acceptance of BF was high. Pre-post effects were small to medium for increased pain management and associated heart rate reactivity but large for coping with pain. The results encourage further research to confirm whether BF is indicated as a treatment component, but not a stand-alone treatment, for traumatised refugees with comorbid CP and PTSD.
Korea: trends in four national KAP surveys 1964-67.

The national surveys conducted every year in Korea give an unmatched glimpse into historic changes. The first survey was taken in early 1964 a perfectly-timed baseline in the national campaign of education and service that was launched that spring. It and subsequent surveys all of similar methodology show marked rises in critical indicators especially in knowledge and use of the intrauterine device (IUD) and in the proportion protected against pregnancy. This report is a summary of the latest KAP publication with certain unpublished material added. (excerpt)
Brain Injury Vision Symptom Survey (BIVSS) Questionnaire.

PURPOSE Validation of the Brain Injury Vision Symptom Survey (BIVSS), a self-administered survey for vision symptoms related to traumatic brain injury (TBI). METHODS A 28-item vision symptom questionnaire was completed by 107 adult subjects (mean age 42.1, 16.2 SD, range 18-75) who self-reported as having sustained mild-to-moderate TBI and two groups of reference adult subjects (first-year optometry students: mean age 23.2, 2.8 SD, range 20-39; and 71 third-year optometry students: mean age 26.0, 2.9 SD, range 22-42) without TBI. Both a Likert-style method of analysis with factor analysis and a Rasch analysis were used. Logistic regression was used to determine sensitivity and specificity. RESULTS At least 27 of 28 questions were completed by 93.5% of TBI subjects, and all 28 items were completed by all of the 157 reference subjects. BIVSS sensitivity was 82.2% for correctly predicting TBI and 90.4% for correctly predicting the optometry students. Factor analysis identified eight latent variables; six factors were positive in their risk for TBI. Other than dry eye and double vision, the TBI patients were significantly more symptomatic than either cohort of optometry students by at least one standard deviation (p < 0.001). Twenty-five of 28 questions were within limits for creating a single-dimension Rasch scale. CONCLUSIONS Nearly all of the adult TBI subjects were able to self-complete the BIVSS, and there was significant mean score separation between TBI and non-TBI groups. The Rasch analysis revealed a single dimension associated with TBI. Using the Likert method with the BIVSS, it may be possible to identify different vision symptom profiles with TBI patients. The BIVSS seems to be a promising tool for better understanding the complex and diverse nature of vision symptoms that are associated with brain injury.
Cystathionine β‐synthase is required for body iron homeostasis

Cystathionine β‐synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin‐6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS−/−) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis‐like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin‐6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2–related factor‐2 and an up‐regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS‐overexpressing adenovirus into CBS mutant mice could partially reverse the iron‐related phenotype. Conclusion: Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis‐like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS. (Hepatology 2018;67:21‐35)
Changes in Catastrophizing and Depressed Mood During and After Early Cognitive Behaviorally Oriented Interventions for Pain

Catastrophizing and depressed mood are risk factors for poor outcome in treatments for pain and appear to act as mediators for favorable outcome. However, little is known about how catastrophizing and depressed mood co-occur within individuals and how these patterns change during treatment, which is the focus of the current study. The study uses data from a randomized controlled trial about early cognitive behaviorally oriented interventions for patients with nonspecific spinal pain (N = 84). Cluster analyses were used to extract subgroups of individuals with similar scoring patterns on catastrophizing and depressed mood at pretreatment, mid-treatment, posttreatment, and at 6 months' follow-up. To track individual progress, the clusters were linked over time. The analyses revealed four clusters: “low depression and catastrophizing”, “high depression and catastrophizing”, “high depression”, and “high catastrophizing”. There was little individual transition from one scoring pattern to another across time, not at least for those scoring high on both depressed mood and catastrophizing. Moreover, high stability within this cluster was related to low levels of psychological flexibility at baseline. It is concluded that catastrophizing and depressed mood at the start of treatment were likely to remain high despite a cognitive behavioral intervention and that a lack of psychological flexibility may have a role.
Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events

The clinical benefit of sorafenib in patients with hepatocellular carcinoma (HCC) has been undervalued due to the absence of complete responses, even though patients who develop early dermatologic reactions have shown to have a positive outcome. In addition, sorafenib is described as an antiangiogenic drug, but it also acts on immunological cells. Thus, the goal of this study was to assess the complete response rate in a retrospective cohort of HCC patients treated with sorafenib and to describe the profile of the patients who achieve complete response for identifying factors related to this event and their connection with the immunological profile of sorafenib. Ten Spanish centers submitted cases of complete response under sorafenib. The baseline characteristics, development of early dermatologic reactions, and cause of treatment discontinuation were annotated. Radiological images taken before starting sorafenib, at first control, after starting sorafenib, at the time of complete response, and at least 1 month after treatment were centrally reviewed. Of the 1119 patients studied, 20 had been classified as complete responders by the centers, but eight of these patients were excluded after central review. Ten patients had complete disappearance of all tumor sites, and two had just a small residual fibrotic scar. Thus, 12 patients were classified as complete responders (58% HCV, median age 59.7 years, 83.4% Child‐Pugh class A, Eastern Cooperative Oncology Group performance status 0 91.7%, and Barcelona Clinic Liver Cancer stage C 83.3%). The median overall survival and treatment duration were 85.8 and 40.1 months, respectively. All but one patient developed early dermatologic reactions, and seven patients discontinued sorafenib after achieving complete response due to adverse events, patient decision, or liver decompensation. Conclusion: Complete response affects 1% of patients with HCC who are treated with sorafenib. The association of complete response with early dermatologic reactions supports the role of a specific immune/inflammatory patient profile in the improved response to sorafenib. (Hepatology 2018;67:612‐622).
Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: A 20 year‐community study

Recent population‐based data on nonalcoholic fatty liver disease (NAFLD) epidemiology in general, and incidence in particular, are lacking. We examined trends in NAFLD incidence in a U.S. community and the impact of NAFLD on incident metabolic comorbidities (MCs), cardiovascular (CV) events, and mortality. A community cohort of all adults diagnosed with NAFLD in Olmsted County, Minnesota, between 1997 and 2014 was constructed using the Rochester Epidemiology Project database. The yearly incidence rate were calculated. The impact of NAFLD on incident MCs, CV events, and mortality was studied using a multistate model, with a 4:1 age‐ and sex‐matched general population as a reference. We identified 3,869 NAFLD subjects (median age, 53; 52% women) and 15,209 controls; median follow‐up was 7 (1‐20) years. NAFLD incidence increased 5‐fold, from 62 to 329 in 100,000 person‐years. The increase was highest (7‐fold) in young adults, aged 18‐39 years. The 10‐year mortality was higher in NAFLD subjects (10.2%) than controls (7.6%; P < 0.0001). NAFLD was an independent risk factor for incident MCs and death. Mortality risk decreased as the number of incident MCs increased: relative risk (RR) = 2.16 (95% confidence [CI], 1.41‐3.31), 1.99 (95% CI, 1.48‐2.66), 1.75 (95% CI, 1.42‐2.14), and 1.08 (95% CI, 0.89‐1.30) when 0, 1, 2, or 3 MCs were present, respectively. The NAFLD impact on CV events was significant only in subjects without MCs (RR = 1.96; 95% CI = 1.35‐2.86). NAFLD reduced life expectancy by 4 years, with more time spent in high metabolic burden. Conclusion: Incidence of NAFLD diagnosis in the community has increased 5‐fold, particularly in young adults. NAFLD is a consequence, but also a precursor of MC. Incident MC attenuates the impact of NAFLD on death and annuls its impact on CV disease. (Hepatology 2018;67:1726‐1736).
App-guided exposure and response prevention for obsessive compulsive disorder: an open pilot trial

Abstract Although effective treatments for obsessive–compulsive disorder (OCD) exist, there are significant barriers to receiving evidence-based care. Mobile health applications (Apps) offer a promising way of overcoming these barriers by increasing access to treatment. The current study investigated the feasibility, acceptability, and preliminary efficacy of LiveOCDFree, an App designed to help OCD patients conduct exposure and response prevention (ERP). Twenty-one participants with mild to moderate symptoms of OCD were enrolled in a 12-week open trial of App-guided self-help ERP. Self-report assessments of OCD, depression, anxiety, and quality of life were completed at baseline, mid-treatment, and post-treatment. App-guided ERP was a feasible and acceptable self-help intervention for individuals with OCD, with high rates of retention and satisfaction. Participants reported significant improvement in OCD and anxiety symptoms pre- to post-treatment. Findings suggest that LiveOCDFree is a feasible and acceptable self-help intervention for OCD. Preliminary efficacy results are encouraging and point to the potential utility of mobile Apps in expanding the reach of existing empirically supported treatments.