Miracle-dz/UniFAR-FTUs huggingface dataset:
Review: The Interleukin‐23/Interleukin‐17 Axis in Spondyloarthritis Pathogenesis: Th17 and Beyond

Spondyloarthritis (SpA) represents a group of immune-mediated inflammatory diseases that exhibit overlapping clinical features, genetic predisposition, and pathogenic mechanisms (1), and affect 0.5–1.5% of the population (2). Disease can be undifferentiated, or manifest as reactive arthritis, psoriatic arthritis (PsA), arthritis associated with inflammatory bowel disease (IBD), or ankylosing spondylitis (AS). Enthesitis is an important pathologic feature of SpA, and contributes to both axial and peripheral arthritis, although synovitis also occurs. Structural damage in AS is dominated by new bone formation that can result in spinal fusion and marked functional limitation. Trabecular bone loss is also prominent, and paradoxically, occurs in close proximity to vertebral osteoproliferation. It can take years from the onset of symptoms to fulfill modified New York criteria for AS. Consequently, newer classification systems have been developed to identify individuals with early axial SpA (3,4) who may benefit from aggressive treatment. Tumor necrosis factor inhibitors (TNFi) have had a major impact on the treatment of SpA (5). Their ability to reduce new bone formation in AS continues to be debated (6), although recent results are encouraging (7). TNFi are not beneficial in all patients, and thus there is a need for greater understanding of pathogenic mechanisms and translation of this knowledge into more effective therapies. Over the last decade our knowledge of the role of IL-23 and IL-17 cytokine pathways in immunity and immune-mediated inflammatory diseases, from multiple sclerosis (MS) to IBD, arthritis, and psoriasis has grown exponentially (8–11). For SpA, there has been a striking convergence of evidence from genetic studies (12–15), animal models (16–19), translational studies (20–23), and now a therapeutic trial (24) firmly implicating the IL-23/IL-17 axis in pathogenesis (25). In this review we outline key evidence accumulated over the last several years that forms the basis for this conclusion, and provides a background on which to build and refine models of pathogenesis, from inflammation to dysregulated bone formation. These developments, together with the availability of biologics and small molecules that target the IL-23/IL-17 axis, provide an unprecedented opportunity for advances in the treatment of SpA.
Region-Specific Gene Expression Profiling: Novel Evidence for Biological Heterogeneity of the Human Amnion1

Abstract The amnion plays an important role during pregnancy and parturition. Though referred to as a single structure, this fetal tissue is regionally divided into placental amnion, reflected amnion, and umbilical amnion. Histological differences between placental amnion and reflected amnion led us to hypothesize that the amnion is biologically heterogeneous. The gene expression profiles of placental amnion and reflected amnion were compared in patients at term with no labor (TNL; n = 10) and in labor (TIL; n = 10). Real-time quantitative RT-PCR revealed a higher expression of IL1B mRNA in reflected amnion than in placental amnion in TNL cases but not in TIL cases. Extended screening using microarrays showed differential expression of 17 genes in labor, regardless of the region. Interestingly, 839 genes were differentially expressed between placental amnion and reflected amnion. Pathway analysis identified 19 signaling pathways, such as mitogen-activated protein kinase and transforming growth factor beta pathways, associated with region. Lipopolysaccharide (LPS) treatment of the amnion explants showed more robust activation of mitogen-activated protein kinase 3/1 (extracellular signal-regulated kinase 1/2) in placental amnion of TNL but not in TIL cases. Placental amnion from TNL and TIL cases showed a significant difference in the amplitude of IL1B mRNA induction by LPS. We report that the anatomical region has a substantial impact on the transcriptional program and the biological properties of the amnion. Labor-associated switching to a proinflammatory signature is a feature particular to placental amnion. The novel observations herein strongly suggest that the seemingly homogeneous amnion is biologically heterogeneous and compartmentalized, with implications for the physiology of pregnancy and parturition.
A POSSIBLE SIGNATURE OF LENSE–THIRRING PRECESSION IN DIPPING AND ECLIPSING NEUTRON-STAR LOW-MASS X-RAY BINARIES

Relativistic Lense–Thirring precession of a tilted inner accretion disk around a compact object has been proposed as a mechanism for low-frequency (∼0.01–70 Hz) quasi-periodic oscillations (QPOs) in the light curves of X-ray binaries. A substantial misalignment angle (∼15°–20°) between the inner-disk rotation axis and the compact-object spin axis is required for the effects of this precession to produce observable modulations in the X-ray light curve. A consequence of this misalignment is that in high-inclination X-ray binaries the precessing inner disk will quasi-periodically intercept our line of sight to the compact object. In the case of neutron-star systems, this should have a significant observational effect, since a large fraction of the accretion energy is released on or near the neutron-star surface. In this Letter, I suggest that this specific effect of Lense–Thirring precession may already have been observed as ∼1 Hz QPOs in several dipping/eclipsing neutron-star X-ray binaries.
Alcohol dehydrogenase genetic polymorphisms, low-to-moderate alcohol consumption, and risk of breast cancer.

BACKGROUND In vitro, human isoenzymes encoded by genes homozygous for the ADH1C*1 or ADH1B*2 alleles metabolize ethanol to acetaldehyde at a faster rate than those homozygous for the ADH1C*2 or ADH1B*1 allele. Because alcohol is a known risk factor for breast cancer, we evaluated the joint association of genetic variants in ADH and alcohol consumption in relation to breast cancer. METHODS A nested case-control study of 321 cases and matched controls was conducted. Five single nucleotide polymorphisms (SNPs) in the ADH1C and ADH1B genes were genotyped. Logistic regression was used to assess odds ratios (ORs) and 95% confidence limits (CIs) for each SNP. Haplotype analysis of all 5 SNPs was also undertaken. RESULTS Among drinkers, the median intake of total alcohol was 13 g/wk (10th-90th percentiles; 4.5-135.9) in cases and 18 g/wk (10th-90th percentiles; 4.5-104.1) in controls. Women who drank alcohol tended to be at an increased risk of developing breast cancer compared with those who did not drink (OR=1.40%, 95% CI 0.97-2.03), particularly those who were premenopausal at the time of breast cancer diagnosis (OR=2.69%, 95% CI: 1.00-7.26). Of the known functional alleles, breast cancer risk was not significantly increased among carriers of at least 1 ADH1C*1 or ADH1B*2 allele, when compared with those homozygous for the genotype at each locus. However, breast cancer risk tended to be lower among women who inherited the G allele at ADH1B IVS1+896A>G (OR=0.62, 95% CI 0.37-1.04). Overall haplotype frequencies were not significantly different between cases and controls. CONCLUSIONS In this study low levels of alcohol are associated with a modest increase in breast cancer risk that is not altered by known functional allelic variants of the ADH1B and 1C gene. The protective association conferred by the G allele at ADH1B IVS1+896A>G needs further evaluation.
Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2.

BACKGROUND Genome-wide association studies have identified multiple genetic variants associated with susceptibility to prostate cancer (PrCa). In the two-stage Cancer Genetic Markers of Susceptibility prostate cancer scan, a single-nucleotide polymorphism (SNP), rs10486567, located within intron 2 of JAZF1 gene on chromosome 7p15.2, showed a promising association with PrCa overall (P=2.14x10(-6)), with a suggestion of stronger association with aggressive disease (P=1.2x10(-7)). METHODS In the third stage of genome-wide association studies, we genotyped 106 JAZF1 SNPs in 10,286 PrCa cases and 9,135 controls of European ancestry. RESULTS The strongest association was observed with the initial marker rs10486567, which now achieves genome-wide significance [P=7.79x10(-11); ORHET, 1.19 (95% confidence interval, 1.12-1.27); ORHOM, 1.37 (95% confidence interval, 1.20-1.56)]. We did not confirm a previous suggestion of a stronger association of rs10486567 with aggressive disease (P=1.60x10(-4) for aggressive cancer, n=4,597; P=3.25x10(-8) for nonaggressive cancer, n=4,514). Based on a multilocus model with adjustment for rs10486567, no additional independent signals were observed at chromosome 7p15.2. There was no association between PrCa risk and SNPs in JAZF1 previously associated with height (rs849140; P=0.587), body stature (rs849141, tagged by rs849136; P=0.171), and risk of type 2 diabetes and systemic lupus erythematosus (rs864745, tagged by rs849142; P=0.657). CONCLUSION rs10486567 remains the most significant marker for PrCa risk within JAZF1 in individuals of European ancestry. IMPACT Future studies should identify all variants in high linkage disequilibrium with rs10486567 and evaluate their functional significance for PrCa.
Influence of Insertion of the Last Sense Codon on Expression Efficiency of Green Fluorescent Protein Gene in Escherichia coli

We studied the relationship between insertion of the last sense codon (i.e., the codon preceding the stop codon) and the efficiency of gene expression. We inserted 64 kinds of last sense codon at the 5’ end of the stop codon of the green fluorescent protein (GFP) gene and introduced the modified GFP genes into Escherichia coli (E. coli). Measuring the fluorescence intensity of the GFP produced in E. coli showed that the last sense codon influenced GFP gene expression and when CCG was inserted as the last sense codon, fluorescence intensity of E. coli was increased to 2.09 fold. On the other hand, insertion of CUA caused decrease of fluorescence intensity to 0.33 fold. We hope that our findings, which may be applicable to gene engineering, will be useful for further studies of protein expression.
Behavioral/systems/cognitive Functional but Not Structural Networks of the Human Laryngeal Motor Cortex Show Left Hemispheric Lateralization during Syllable but Not Breathing Production

The laryngeal motor cortex (LMC) is indispensible for the vocal motor control of speech and song production. Patients with bilateral lesions in this region are unable to speak and sing, although their nonverbal vocalizations, such as laughter and cry, are preserved. Despite the importance of the LMC in the control of voluntary voice production in humans, the literature describing its connections remains sparse. We used diffusion tensor probabilistic tractography and functional magnetic resonance imaging-based functional connectivity analysis to identify LMC networks controlling two tasks necessary for speech production: voluntary voice as repetition of two different syllables and voluntary breathing as controlled inspiration and expiration. Peaks of activation during all tasks were found in the bilateral ventral primary motor cortex in close proximity to each other. Functional networks of the LMC during voice production but not during controlled breathing showed significant left-hemispheric lateralization (p Ͻ 0.0005). However, structural networks of the LMC associated with both voluntary voice production and controlled breathing had bilateral hemispheric organization. Our findings indicate the presence of a common bilateral structural network of the LMC, upon which different functional networks are built to control various voluntary laryngeal tasks. Bilateral organization of functional LMC networks during controlled breathing supports its indispensible role in all types of laryngeal behaviors. Significant left-hemispheric lateralization of functional networks during simple but highly learned voice production suggests the readiness of the LMC network for production of a complex voluntary behavior, such as human speech.
Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma.

PURPOSE We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. PATIENTS AND METHODS Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL) -2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m(2)). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. RESULTS Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 +/- 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. CONCLUSION Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma.
Traditional healers for mental health care in Africa

Global mental health is primarily concerned with reducing inequalities in the access to health care and health outcomes for people with mental illness within and between countries (1). Reducing the vast treatment gap and promoting the rights of people with mental illness to live with dignity are major goals of adherents of the field such as the Movement for Global Mental Health (www.globalmentalhealth.org). In this context, the thesis by Abbo summarised in her PhD Review paper in Global Health Action (2) is a timely reminder of the role of a key player in the mental health care system in African countries where the biomedical treatment gap is notably large - the traditional healer. Her series of studies in Uganda show that a variety of indigenous labels are used by traditional healers to describe what biomedical psychiatry categorises as psychotic disorders and that these are associated with a range of explanatory models, from supernatural/spiritual causes to somatic causes such as HIV. The prevalence of any mental illness amongst patients seeking help from traditional healers is very high and, notably, the vast majority of persons with psychotic disorders were also concurrently seeking help from the biomedical sector. There was a strong association of mental illness with indicators suggestive of poverty, such as lack of food or indebtedness and, amongst those patients who had a psychotic disorder, being in debt was associated with poorer outcomes. These findings serve to replicate a rich record of evidence from several countries in the region, going back several decades that testify to three major findings: severe mental illness is clearly recognised as causes of illness and suffering by indigenous communities, poverty and mental illness frequently co-exist, and traditional healers plays a prominent role in mental health care. Each of these findings has important implications for global mental health. (Published: 2 August 2011) Citation: Global Health Action 2011, 4 : 7956 - DOI: 10.3402/gha.v4i0. 7956
The resilience of ethnic minority parties in the face of strategic voting incentives

Recent research has indicated that social heterogeneity impacts party system size, even in restrictive settings. This research as yet has not established whether it is minority or majority voters who are behaving outside Duvergerian expectations. This study argues that it is ethnic voters that seem to defect from their parties at lower rates, which explains why small parties proliferate and persist in heterogeneous states. This hypothesis is tested on party-in-district level election returns in the German lander Schleswig-Holstein. The results show that small ethnic parties suffer notably less defection than small non-ethnic parties. The study proposes a number of potential causal mechanisms that could be driving ethnic voters, as a group, to defect at lower rates than non-ethnic voters.
Hidden From Happiness: Structural Stigma, Sexual Orientation Concealment, and Life Satisfaction Across 28 Countries

Objective: Although structural stigma (i.e., discriminatory laws, policies, and community attitudes) toward sexual minorities predicts adverse health and wellbeing, this association has typically only been examined within a single country and potential mechanisms remain unknown. Consequently, we examined the association between structural stigma and sexual minorities’ life satisfaction across 28 countries, identity concealment as a potential mechanism of this association, and, in high-stigma countries, the potential for concealment to protect sexual minorities from discrimination and victimization, and therefore even poorer life satisfaction than they would otherwise experience in those countries. Method: Sexual minority adults (n = 85,582) from 28 European countries responded to questions regarding sexual minority stigma, identity concealment, and life satisfaction. Structural stigma was assessed as national laws, policies, and attitudes affecting sexual minorities in each country. Results: Country-level structural stigma explained 60% of country-level variation in life satisfaction and more than 70% of country-level variation in sexual orientation concealment. Sexual orientation concealment mediated the association between structural stigma and life satisfaction. Especially in high-stigma countries, concealment also protected against even lower life satisfaction than would be experienced if a sexual minority individual did not conceal in those countries because it partially protected against discrimination and victimization. Conclusions: Sexual minorities’ life satisfaction varies greatly across countries largely due to the structural stigma of those countries and associated demands to conceal one’s sexual orientation. Findings highlight the importance of reducing structural stigma to promote equitable life satisfaction and tailoring affirmative psychotherapies to address the structural context surrounding sexual minorities who seek treatment.
Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study.

RATIONALE Basic research implicates alveolar endothelial cell apoptosis in the pathogenesis of chronic obstructive pulmonary disease (COPD) and emphysema. However, information on endothelial microparticles (EMPs) in mild COPD and emphysema is lacking. OBJECTIVES We hypothesized that levels of CD31(+) EMPs phenotypic for endothelial cell apoptosis would be elevated in COPD and associated with percent emphysema on computed tomography (CT). Associations with pulmonary microvascular blood flow (PMBF), diffusing capacity, and hyperinflation were also examined. METHODS The Multi-Ethnic Study of Atherosclerosis COPD Study recruited participants with COPD and control subjects age 50-79 years with greater than or equal to 10 pack-years without clinical cardiovascular disease. CD31(+) EMPs were measured using flow cytometry in 180 participants who also underwent CTs and spirometry. CD62E(+) EMPs phenotypic for endothelial cell activation were also measured. COPD was defined by standard criteria. Percent emphysema was defined as regions less than -950 Hounsfield units on full-lung scans. PMBF was assessed on gadolinium-enhanced magnetic resonance imaging. Hyperinflation was defined as residual volume/total lung capacity. Linear regression was used to adjust for potential confounding factors. MEASUREMENTS AND MAIN RESULTS CD31(+) EMPs were elevated in COPD compared with control subjects (P = 0.03) and were notably increased in mild COPD (P = 0.03). CD31(+) EMPs were positively related to percent emphysema (P = 0.045) and were inversely associated with PMBF (P = 0.047) and diffusing capacity (P = 0.01). In contrast, CD62E(+) EMPs were elevated in severe COPD (P = 0.003) and hyperinflation (P = 0.001). CONCLUSIONS CD31(+) EMPs, suggestive of endothelial cell apoptosis, were elevated in mild COPD and emphysema. In contrast, CD62E(+) EMPs indicative of endothelial activation were elevated in severe COPD and hyperinflation.
The Perception and Method in Teaching and Learning Islamic Education

The influence of Islam in West African education systems was significant. The transformation from traditional Qur'anic schools to more modern Islamic education was slow but evident. The objective of this paper is to determine the perception and the method in teaching Islamic education from the African teachers' opinion. The data was collected from a questionnaire survey that was distributed to African teachers from West Africa. The data were analyzed by using the descriptive statistics such as percentages and mean scores. The study revealed that the respondent agreed the Implementation of Teaching the Islamic education had subsequently improved. However, it need to be updated. This study found out that in term of teachers' opinion and perception the items resulted positively (65% and mean=3.751). Beside that, 7 methods of teaching (76.2%, mean=3.8847) showed that individual accountability did exist in many cooperative learning activities carried out by the teachers in the classroom. This study has several implications with regards to pedagogical modification of teaching methods of Islamic religious teachers in West Africa.
Efficacy and safety of a hexanic extract of Serenoa repens (Permixon®) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta‐analysis of randomised controlled trials and observational studies

To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon®; Pierre Fabre Médicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH).
Use of Self-Reported Adherence and Keeping Clinic Appointments as Predictors of Viremia in Routine HIV Care in the Gambia

We followed 205 HIV-infected adults on antiretroviral therapy for at least 12 weeks in a Gambian clinic, where routine viral load monitoring was performed. The 1- and 4-week self-reported adherence and timeliness in keeping to scheduled appointments were recorded at each visit. Seventy patients had measurable viremia between the 12th week and the 3rd year of therapy. Survival analysis of the first detectable viral load on therapy demonstrated an association with 4-week (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.5-4.3, P = .001) and 1-week (HR 1.9, 95% CI 1.1-3.3, P = .024) self-reported suboptimal adherence and with 1 to 15 days of late presentation for appointments (HR 1.6-1.8, P .027-.109). In a multiple regression model, only 4-week self-reported adherence remained as a significant predictor of viremia.