Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment

Background Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. Methods We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). Results Excessive cortical volume reductions were observed in patients [−4.6 (6.6)%] v. controls [−1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. Conclusions Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.
Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.
Long-term overall and disease-specific mortality associated with benign gynecologic surgery performed at different ages

ObjectiveAs bilateral salpingo-oophorectomy is frequently performed with hysterectomy for nonmalignant conditions, defining health outcomes associated with benign bilateral salpingo-oophorectomy performed at different ages is critical. MethodsWe assessed mortality risk associated with benign total abdominal hysterectomy or bilateral salpingo-oophorectomy among 52,846 Breast Cancer Detection Demonstration Project follow-up study participants. Surgery and risk factor data were ascertained via baseline interview (1979-1986) and three questionnaires (1987-1998). During follow-up through December 2005 (mean, 22.1 y), 13,734 deaths were identified. We estimated hazard ratios (HRs) and 95% CIs for overall and disease-specific mortality for total abdominal hysterectomy or bilateral salpingo-oophorectomy performed by age 35, 40, 45, 50, or 55 years, compared with not having surgery, using landmark analyses and multivariable Cox regression. ResultsUndergoing bilateral salpingo-oophorectomy by age 35 years was associated with increased mortality risk (HR35 y, 1.20; 95% CI, 1.08-1.34), which decreased with age (HR40 y, 1.12; 95% CI, 1.04-1.21; HR45 y, 1.10; 95% CI, 1.03-1.17). Total abdominal hysterectomy alone performed by age 40 years was associated with increased mortality risk to a lesser extent (HR40 y, 1.08; 95% CI, 1.01-1.15). Analyses based on matched propensity scores related to having gynecologic surgery yielded similar results. Elevated mortality risks were largely attributable to noncancer causes. ConclusionsBenign gynecologic surgeries among young women are associated with increased mortality risk, which attenuates with age.
The LDL Receptor-Related Protein 1: At the Crossroads of Lipoprotein Metabolism and Insulin Signaling

The metabolic syndrome is an escalating worldwide public health concern. Defined by a combination of physiological, metabolic, and biochemical factors, the metabolic syndrome is used as a clinical guideline to identify individuals with a higher risk for type 2 diabetes and cardiovascular disease. Although risk factors for type 2 diabetes and cardiovascular disease have been known for decades, the molecular mechanisms involved in the pathophysiology of these diseases and their interrelationship remain unclear. The LDL receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is widely expressed in several tissues. As a member of the LDL receptor family, LRP1 is involved in the clearance of chylomicron remnants from the circulation and has been demonstrated to be atheroprotective. Recently, studies have shown that LRP1 is involved in insulin receptor trafficking and regulation and glucose metabolism. This review summarizes the role of tissue-specific LRP1 in insulin signaling and its potential role as a link between lipoprotein and glucose metabolism in diabetes.
Adherence partners are an acceptable behaviour change strategy to support calcium and iron‐folic acid supplementation among pregnant women in Ethiopia and Kenya

Antenatal calcium and iron-folic acid (IFA) supplementation can reduce maternal mortality and morbidity. Yet, even when pregnant women have a stable supply of supplements, forgetting is often a barrier to adherence. We assessed the acceptability of adherence partners to support calcium and IFA supplementation among pregnant women in Kenya and Ethiopia. Adherence partners are a behaviour change strategy to improve adherence, where pregnant women are counselled to select a partner (e.g. spouse, relative) to remind them to take their supplements. We conducted trials of improved practices, a formative research method that follows participants over time as they try a new behaviour. We provided pregnant women in Ethiopia (n = 50) and Kenya (n = 35) with calcium and IFA supplements and counselling, and suggested selecting an adherence partner. For each participant, we conducted semi-structured interviews about acceptability and adherence during four interviews over six weeks. We analysed interview transcripts thematically and tallied numerical data. In Kenya, 28 of 35 women agreed to try an adherence partner; almost all selected their husbands. In Ethiopia, 42 of 50 women agreed to try an adherence partner; half asked their husbands, others asked children or relatives. Most women who did not select adherence partners reported not needing help or not having anyone to ask. Participants reported adherence partners reminded and encouraged them, brought supplements, provided food and helped address side-effects. Almost all women with adherence partners would recommend this strategy to others. Adherence partners are an acceptable, low-cost strategy with the potential to support antenatal micronutrient supplementation adherence.
The Sequence Read Archive

The combination of significantly lower cost and increased speed of sequencing has resulted in an explosive growth of data submitted into the primary next-generation sequence data archive, the Sequence Read Archive (SRA). The preservation of experimental data is an important part of the scientific record, and increasing numbers of journals and funding agencies require that next-generation sequence data are deposited into the SRA. The SRA was established as a public repository for the next-generation sequence data and is operated by the International Nucleotide Sequence Database Collaboration (INSDC). INSDC partners include the National Center for Biotechnology Information (NCBI), the European Bioinformatics Institute (EBI) and the DNA Data Bank of Japan (DDBJ). The SRA is accessible at http://www.ncbi. nlm.nih. gov/Traces/sra from NCBI, at http://www.ebi. ac.uk/ena from EBI and at http://trace.ddbj. nig.ac. jp from DDBJ. In this article, we present the content and structure of the SRA, detail our support for sequencing platforms and provide recommended data submission levels and formats. We also briefly outline our response to the challenge of data growth.
Chronic Bronchitis Among Nonsmoking Farm Women in the Agricultural Health Study

Objective: The purpose of this study was to examine agricultural risk factors for chronic bronchitis among nonsmoking farm women. Methods: We used self-reported enrollment data from the 21,541 nonsmoking women in the Agricultural Health Study to evaluate occupational risk factors for prevalent chronic bronchitis among farm women. Odds ratios (ORs) for chronic bronchitis for occupational exposures were adjusted for age, state, and related agricultural exposures. Results: Applying manure and driving combines were independently associated with chronic bronchitis. Off-farm job exposures associated with chronic bronchitis were organic dusts, asbestos, gasoline, and solvents. Five pesticides were associated with chronic bronchitis after multivariate adjustment and sensitivity analyses: dichlorvos (OR = 1.63, 95% CI = 1.01, 2.61), DDT (OR = 1.67, 95% CI = 1.13, 2.47), cyanazine (OR = 1.88, 95% CI = 1.00, 3.54), paraquat (OR = 1.91, 95% CI = 1.02, 3.55), and methyl bromide (OR = 1.82, 95% CI = 1.02, 3.24). Conclusion: Pesticides as well as grain and dust exposures were associated with chronic bronchitis among nonsmoking farm women.
Premeditation and Sensation Seeking Moderate the Reasoned Action and Social Reaction Pathways in the Prototype/Willingness Model of Alcohol Use

ABSTRACT Background: Drinking can occur because of expectations to drink (reasoned pathway) or because of willingness to drink under certain circumstances (reactive pathway). These pathways are thought to be influenced by different cognitions such as alcohol-related attitudes, norms, or drinking prototypes (Gerrard et al., 2008). Impulsive traits reflect individual differences in the influence of reasoned or reactive factors, however little research has investigated whether impulsivity moderates the effects of cognitive factors predicting alcohol use. Objectives: We tested whether differences in three impulsivity traits (premeditation, sensation seeking and negative urgency) moderated associations of reasoned (risk/disapproval attitudes and social norms) and reactive (prototype) pathway variables on expectation/willingness to drink and recent alcohol use. Methods: We collected data from n = 409 college students; the sample was 67% female, 43% Asian American, with Mdnage = 19. Hypotheses were tested using multiple regression. Results: Premeditation and sensation seeking moderated reasoned variable effects on expectation and drinking. Among those low on premeditation, risk attitudes were most associated with drinking expectation, with alcohol prototypes most related to recent drinking. These effects declined at higher premeditation levels. Among those high on sensation seeking, risk attitudes were most associated with expectation and drinking, declining at lower sensation seeking levels. There was little evidence of moderation predicting drinking willingness. Conclusions/Importance: Findings imply personality differences may explain association strength between reasoned but not reactive risk behavior pathways with alcohol outcomes. They have ramifications for personalized prevention programs to reduce drinking through cognition change, as alcohol-related cognition influence may differ depending on personality characteristics.
Cumulative life course and adult socioeconomic status and markers of inflammation in adulthood

Objective: To examine the association between cumulative life course and adult socioeconomic status (SES) and adult levels of inflammatory risk markers (fibrinogen, white blood cell count (WBC), C-reactive protein (CRP), von Willebrand factor (vWF) and an overall inflammatory score). Design: Retrospective cohort study. Setting: 12 681 white and African-American participants in the Atherosclerosis Risk in Communities (ARIC) study and two ancillary studies. Methods: Participants provided information on SES and place of residence in childhood and young (30–40 years) and mature (45+) adulthood. Residences were linked to census data for neighbourhood SES information. Multiple imputation (MI) was used for missing data. Linear regression and adjusted geometric means were used to estimate the effects of SES on inflammatory risk marker levels. Results: Graded, statistically significant associations were observed between greater cumulative life-course exposure to low education and social class and elevated levels of fibrinogen and WBC among white participants. Stronger graded, statistically significant associations were observed between low adult education, social class and neighbourhood SES and elevated inflammatory levels. Associations were weaker and less consistent in African-Americans. Covariate adjustment attenuated results but many associations remained strong. Conclusions: Our results suggest that cumulative exposure to adverse SES conditions across the life course and low adult SES are associated with an elevated systemic inflammatory burden in adulthood. Chronic systemic inflammation may be one pathway linking low life-course SES and elevated cardiovascular disease risk.
Dynamic Light Scattering Microrheology Reveals Multiscale Viscoelasticity of Polymer Gels and Precious Biological Materials

The development of experimental techniques capable of probing the viscoelasticity of soft materials over a broad range of time scales is essential to uncovering the physics that governs their behavior. In this work, we develop a microrheology technique that requires only 12 μL of sample and is capable of resolving dynamic behavior ranging in time scales from 10–6 to 10 s. Our approach, based on dynamic light scattering in the single-scattering limit, enables the study of polymer gels and other soft materials over a vastly larger hierarchy of time scales than macrorheology measurements. Our technique captures the viscoelastic modulus of polymer hydrogels with a broad range of stiffnesses from 10 to 104 Pa. We harness these capabilities to capture hierarchical molecular relaxations in DNA and to study the rheology of precious biological materials that are impractical for macrorheology measurements, including decellularized extracellular matrices and intestinal mucus. The use of a commercially available benchtop setup that is already available to a variety of soft matter researchers renders microrheology measurements accessible to a broader range of users than existing techniques, with the potential to reveal the physics that underlies complex polymer hydrogels and biological materials.
Changes in Nasal Configuration following Primary Rhinoplasty: Direct Anthropometric Measurement in Patients with Complete Unilateral Cleft Lip and Palate

Background With the recent advances of surgical adjuncts including presurgical naso-alveolar molding and postoperative nasal stenting, information on the anthropometric evaluation of cleft lip nasal symmetry after primary rhinoplasty is lacking. Method Twenty-nine nonsyndromic patients with complete unilateral cleft lip and palate undergoing modified rotation advancement cheiloplasty with synchronous primary rhinoplasty in our center were prospectively recruited in our study. All of them received our center's perioperative management protocol, including presurgical naso-alveolar molding and postoperative nasal stenting. Direct anthropometric measurements of their nasal configuration were documented when they were anesthetized for primary lip repair at 3 months of age and for the primary palate repair at 12 months of age. Their nasal configurations were analyzed before primary rhinoplasty and at 9 months after rhinoplasty. Results There is a statistically significant change in nasal symmetry at 9 months after the primary rhinoplasty. There is no significant correlation between the nasal configuration before and at 9 months after the primary rhinoplasty. Conclusions With significant relapse of nasal deformity at 9 months after the primary rhinoplasty despite the use of presurgical naso-alveolar molding and postoperative nasal stenting, overcorrection of the nasal configuration at primary rhinoplasty should be considered for optimal long-term nasal symmetrical outcome.
Attenuated airway hyperresponsiveness and mucus secretion in HDM‐exposed Igf1r‐deficient mice

Asthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR), and airway inflammation. IGFs have been reported to play a role in asthma, but little is known about how the insulin‐like growth factor 1 receptor (IGF1R) affects asthma pathobiology.
Analysis of factors influencing survival in patients with severe acute pancreatitis

Abstract Objective: Acute pancreatitis (AP) ranges from a mild and self-limiting disease to a fulminant illness with significant morbidity and mortality. Severe acute pancreatitis (SAP) is defined as persistent organ failure lasting for 48 h. We aimed to determine the factors that predict survival and mortality in patients with SAP. Methods: We reviewed a consecutive series of patients who were admitted with acute pancreatitis between January 2003 and January 2013. A total of 1213 cases involving 660 patients were evaluated, and 68 cases with SAP were selected for the study. Patients were graded based on the Computer Tomography Severity Index (CTSI), the bedside index for severity (BISAP), and Ranson’s criteria. Results: The frequency of SAP was 5.6% (68/1213 cases). Among these patients, 17 died due to pancreatitis-induced causes. We compared several factors between the survivor (n = 51) and non-survivor (n = 17) groups. On multivariate analysis, there were significant differences in the incidence of diabetes mellitus (p = .04), Ranson score (p = .03), bacteremia (p = .05) and body mass index (BMI) (p = .02) between the survivor and non-survivor groups. Conclusions: Bacteremia, high Ranson score, DM, and lower BMI were closely associated with mortality in patients with SAP. When patients with SAP show evidence of bacteremia or diabetes, aggressive treatment is necessary. For the prediction of disease mortality, the Ranson score might be a useful tool in SAP.
Association of MIR-499a expression and seed region variant (rs3746444) with cardiovascular disease in Egyptian patients

Abstract Background: Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population. Methods: Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay. Results: Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile. Conclusions: Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.
A Role for Sigma Receptors in Stimulant Self Administration and Addiction

Sigma1 receptors (σ1Rs) represent a structurally unique class of intracellular proteins that function as chaperones. σ1Rs translocate from the mitochondria-associated membrane to the cell nucleus or cell membrane, and through protein-protein interactions influence several targets, including ion channels, G-protein-coupled receptors, lipids, and other signaling proteins. Several studies have demonstrated that σR antagonists block stimulant-induced behavioral effects, including ambulatory activity, sensitization, and acute toxicities. Curiously, the effects of stimulants have been blocked by σR antagonists tested under place-conditioning but not self-administration procedures, indicating fundamental differences in the mechanisms underlying these two effects. The self administration of σR agonists has been found in subjects previously trained to self administer cocaine. The reinforcing effects of the σR agonists were blocked by σR antagonists. Additionally, σR agonists were found to increase dopamine concentrations in the nucleus accumbens shell, a brain region considered important for the reinforcing effects of abused drugs. Although the effects of the σR agonist, DTG, on dopamine were obtained at doses that approximated those that maintained self administration behavior those of another agonist, PRE-084 required higher doses. The effects of DTG were antagonized by non-selective or a preferential σ2R antagonist but not by a preferential σ1R antagonist. The effects of PRE-084 on dopamine were insensitive to σR antagonists. The data suggest that the self administration of σR agonists is independent of dopamine and the findings are discussed in light of a hypothesis that cocaine has both intracellular actions mediated by σRs, as well as extracellular actions mediated through conventionally studied mechanisms. The co-activation and potential interactions among these mechanisms, in particular those involving the intracellular chaperone σRs, may lead to the pernicious addictive effects of stimulant drugs.