Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiology and pathophysiology of canonical transient receptor potential channels

The existence of a mammalian family of TRPC ion channels, direct homologues of TRP, the visual transduction channel of flies, was discovered during 1995‐1996 as a consequence of research into the mechanism by which the stimulation of the receptor‐Gq‐phospholipase Cβ signaling pathway leads to sustained increases in intracellular calcium. Mammalian TRPs, TRPCs, turned out to be nonselective, calcium‐permeable cation channels, which cause both a collapse of the cell's membrane potential and entry of calcium. The family comprises 7 members and is widely expressed. Many cells and tissues express between 3 and 4 of the 7 TRPCs. Despite their recent discovery, a wealth of information has accumulated, showing that TRPCs have widespread roles in almost all cells studied, including cells from excitable and nonexcitable tissues, such as the nervous and cardiovascular systems, the kidney and the liver, and cells from endothelia, epithelia, and the bone marrow compartment. Disruption of TRPC function is at the root of some familial diseases. More often, TRPCs are contributing risk factors in complex diseases. The present article reviews what has been uncovered about physiological roles of mammalian TRPC channels since the time of their discovery. This analysis reveals TRPCs as major and unsuspected gates of Ca2+ entry that contribute, depending on context, to activation of transcription factors, apoptosis, vascular contractility, platelet activation, and cardiac hypertrophy, as well as to normal and abnormal cell proliferation. TRPCs emerge as targets for a thus far nonexistent field of pharmacological intervention that may ameliorate complex diseases. — Abramowitz, J., Birnbaumer, L. Physiology and patho‐physiology of canonical transient receptor potential channels. FASEB J. 23, 297‐328 (2009)
Expression of cyclooxygenase-1 and -2 in normal and glaucomatous human eyes.

PURPOSE Primary open-angle glaucoma (POAG) is the predominant form of chronic glaucoma, but the underlying pathologic mechanisms are largely unknown. Because prostaglandins (PGs) have been introduced into POAG treatment with remarkable success, this study was undertaken to investigate whether a change in the expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be involved in the pathogenesis of POAG. METHODS Expression of COX-1 and -2 was assessed by confocal laser microscopy, immunohistochemistry, Western blot analysis, and real-time RT-PCR in human eyes with different forms of glaucoma (primary open-angle, angle-closure, congenital juvenile, and steroid-induced), as well as in age-matched control eyes. Additionally, PGE2 was measured in aqueous humor by means of an enzyme-linked immunoassay as a product of COX activity. RESULTS In normal eyes, ocular COX-1 and -2 expression were largely confined to the nonpigmented secretory epithelium of the ciliary body. By immunohistochemistry and real-time RT-PCR, COX-2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end-stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistry, in the ciliary bodies of eyes in five patients with diagnosis of early POAG, eyes in two had complete loss of COX-2 expression and in three showed only a few remaining scattered COX-2-expressing cells. COX-2 expression in the ciliary body was also lost in patients with steroid-induced glaucoma and was reduced in patients receiving topical steroid treatment. Eyes of patients with either congenital juvenile or angle-closure glaucoma showed COX-2 expression indistinguishable from control eyes. Aqueous humor of eyes with POAG contained significantly less PGE2 than control eyes. CONCLUSIONS Both cyclooxygenase isoforms are constitutively expressed in the normal human eye. Specific loss of COX-2 expression in the nonpigmented secretory epithelium of the ciliary body appears to be linked to the occurrence of POAG and steroid-induced glaucoma.
Benchmark of structured machine learning methods for microbial identification from mass-spectrometry data

Microbial identification is a central issue in microbiology, in particular in the fields of infectious diseases diagnosis and industrial quality control. The concept of species is tightly linked to the concept of biological and clinical classification where the proximity between species is generally measured in terms of evolutionary distances and/or clinical phenotypes. Surprisingly, the information provided by this well-known hierarchical structure is rarely used by machine learning-based automatic microbial identification systems. Structured machine learning methods were recently proposed for taking into account the structure embedded in a hierarchy and using it as additional a priori information, and could therefore allow to improve microbial identification systems. We test and compare several state-of-the-art machine learning methods for microbial identification on a new Matrix-Assisted Laser Desorption/Ionization Time-of-Flight mass spectrometry (MALDI-TOF MS) dataset. We include in the benchmark standard and structured methods, that leverage the knowledge of the underlying hierarchical structure in the learning process. Our results show that although some methods perform better than others, structured methods do not consistently perform better than their "flat" counterparts. We postulate that this is partly due to the fact that standard methods already reach a high level of accuracy in this context, and that they mainly confuse species close to each other in the tree, a case where using the known hierarchy is not helpful.
Differential Effects of Nitrogen Limitation on Photosynthetic Efficiency of Photosystems I and II in Microalgae

The effects of nitrogen starvation on photosynthetic efficiency were examined in three unicellular algae by measuring changes in the quantum yield of fluorescence with a pump-and-probe method and thermal efficiency (i.e. the percentage of trapped energy stored photochemically) with a pulsed photoacoustic method together with the inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea to distinguish photosystems I and II (PSI and PSII). Measured at 620 nm, maximum thermal efficiency for both photosystems was 32% for the diatom Thalassiosira weissflogii (PSII:PSI ratio of 2:1), 39% for the green alga Dunaliella tertiolecta (PSII:PSI ratio of 1:1), and 29% for the cyanobacterium Synechococcus sp. PCC 7002 (PSII:PSI ratio of 1:2). Nitrogen starvation decreased total thermal efficiency by 56% for T. weissflogii and by 26% for D. tertiolecta but caused no change in Synechococcus. Decreases in the number of active PSII reaction centers (inferred from changes in variable fluorescence) were larger: 86% (T. weissflogii), 65% (D. tertiolecta), and 65% (Synechococcus). The selective inactivation of PSII under nitrogen starvation was confirmed by independent measurements of active PSII using oxygen flash yields and active PSI using P700 reduction. Relatively high thermal efficiencies were measured in all three species in the presence of the PSII inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea, suggesting the potential for significant cyclic electron flow around PSI. Fluorescence or photoacoustic data agreed well; in T. weissflogii, the functional cross-sectional area of PSII at 620 nm was estimated to be the same using both methods (approximately 1.8 x 102 A2). The effects of nitrogen starvation occur mainly in PSII and are well represented by variable fluorescence measurements.
Eliciting thematic reanalysis effects: The role of syntax-independent information during parsing

In this paper, we present experimental evidence for the existence of syntax-independent (viz. thematic) reanalysis effects. In an experiment using event-related brain potentials (ERPs), we manipulated the thematic structure of the verb in transitive, unambiguously case marked German verb-final clauses such that the processing of this verb either confirmed the "canonical" hierarchical thematic ordering between the sentential arguments (active verbs) or required a reversal of this ordering (object-experiencer verbs). The latter elicited a parietal positivity between 300 and 600 ms post onset, which, as we argue, must be interpreted as reflecting a thematic reanalysis. The second experimental manipulation, i.e., a variation of word order (SO vs. OS), revealed an early positivity at the position of the second NP in dative-nominative (OS) structures. Again, we account for this effect in terms of a thematic reanalysis, which becomes necessary when the original interpretation of the initial argument as thematically highest-ranking must be revised. We conclude from our data that case marking languages such as German may employ non-syntactic processing routes to determine the thematic interpretation of a sentence.
Sleep Problems/Habits and School Performance in Elementary School Children

No previous studies have assessed the relationship between sleep problems/habits and school performance in Saudi school children. Therefore, we surveyed parents of a sample of elementary school children in Riyadh to assess the relation between sleep problems/habits and school performance in this age group. The study was conducted in Riyadh city among elementary school children (boys and girls) during springtime of the year 1999. Questionnaires were distributed by trained medical students according to the sampling process and parents were asked to score each item that describes the child behavior within the past 6 months. School performance was assessed using the latest monthly evaluation report provided by the school. Students’ performance was stratified as “excellent students” (≥85%) or “average students” (<85%). Completed questionnaires were returned from the households of 1012 students. Boys were 511 (50.5%) and girls 501 (49.5%). The mean age was 9.5±1.9 years ranging from 5 to 13 years. Six hundred and forty nine students (64.1%) of students had “excellent” performance and 363 students (35.9%) had “average” performance. School performance was significantly associated with children’s age, gender, father’s educational level, and mother’s educational level. It was evident that the presence of sleep problems, poor sleep habits, or shortened total sleep time was affecting the students’ school performance. Sleep problems and habits may negatively affect school performance. Schools, parents, and pediatricians needs to take an active role to consider sleep and sleep disorders in the context of school performance and daytime functioning. (Sleep and Hypnosis 2006;8(1):13-19)
Static vs. Dynamic Impacts of Unbundling – Electricity Markets in South America

Ownership unbundling and third party access are discussed as two options of unbundling in both the literature and political discussions. Focusing on the South American electricity sector, I contrast static and dynamic impacts of ownership unbundling and third party access regimes on customer prices. Substantially different results are found using dynamic rather than static analysis. In particular, negative short term effects of ownership unbundling found in static models are approximately cancelled out by subsequent positive impacts in the dynamic model. Third party access seems to allow for similar benefits while avoiding the (restructuring) costs of ownership unbundling. Previously estimated static models thus appear to suffer from either omitted variable biases or endogeneity problems of static non-difference models.
Epigenetic malprogramming of the insulin receptor promoter due to developmental overfeeding

Abstract Aim: Prenatal and neonatal overfeeding programs a permanent obesity and diabetes disposition, e.g., due to induction of hypothalamic insulin resistance. We investigated acquired alterations of the DNA methylation pattern of the hypothalamic insulin receptor promoter (IRP) which might be an underlying molecular mechanism. Methods: Neonatal overfeeding was induced by rearing Wistar rats in small litters (SL). Methylation of CpG-dinucleotides of the hypothalamic IRP was mapped using bisulfite sequencing. Results: Neonatal overfeeding led to rapid early weight gain, resulting in a metabolic syndrome phenotype, i.e., obesity, hyperleptinemia, hyperglycemia, hyperinsulinemia, and increased insulin/glucose-ratio. The proportion of animals carrying any methylated CpG residue in the 322 bp CpG island of the IRP was increased in neonatally overfed SL rats (n=8), as compared to controls (n=8; P=0.04). Moreover, the mean percentage of methylated CpG positions was also higher in SL rats (P=0.01). Over both groups, neonatal blood glucose levels were positively correlated to the extent of promoter methylation (r=0.52; P=0.04). Conclusions: This study characterizes for the first time the IRP epigenomically in any species and tissue. Our data reveal that the IRP is vulnerable to hypermethylation due to overnutrition, probably especially glucose-dependent in a dose-response manner. This paradigmatically indicates the impact of nutrient-dependent epigenetic malprogramming, leading to a “diabesity” disposition which may become pathogenic throughout life.
Epidemiology of Wegener's granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome.

The primary systemic vasculitides (PSV— Wegener’s granulomatosis [WG], Churg-Strauss syndrome [CSS], microscopic polyangiitis [MPA], polyarteritis nodosa [PAN]) are a group of uncommon diseases. The etiology of vasculitis is unknown but is clearly multifactorial; among the influences on disease expression are ethnicity, genes (HLA and others), gender, and environment (infections, toxins, drugs, allergy, smoking, UV light). There are sufficient differences, even with the limited epidemiological data available, to suggest that not all these factors work in the same direction in the various vasculitic syndromes described. The lack of any clear understanding of the etiology of the systemic vasculitides and universally accepted classification systems hampered accurate epidemiological studies until the 1990s.
The four community dimensions of primary care practice.

BACKGROUND Despite the growing belief that "the community" should play a larger role in the work of physicians, there is no clear understanding of exactly how physicians should participate in their communities. The primary goals of this study were to propose and test an organizing framework that identified four distinct categories of activities whereby physicians can interact with their communities: (1) identifying and intervening in the community's health problems; (2) responding to the particular health issues of local cultural groups when caring for patients; (3) coordinating local community health resources in the care of patients; and (4) assimilating into the community and its organizations. Other goals were to characterize physicians' level of involvement in each of these four types of community activities, and to identify the correlates of greater and lesser involvement. METHODS A questionnaire was mailed to a random sample of 500 young primary care physicians in the United States. The response rate was 66.6%. Physicians reported how confident they were in performing each of 15 specific community-relevant activities. Confidence ratings were factor-analyzed to test the hypothesis that physician involvement in community activities can be organized into the four proposed categories. Physicians also self-rated their involvement in various community activities within each of these four categories, and predictors of involvement were identified through ordinary least-squares regression models. RESULTS Using factor analysis, the community activities sorted cleanly into the four postulated community dimensions of medical practice, providing a measure of validation for the distinctiveness of the four dimensions. Physicians reported active involvement in some activities (eg, speaking to community groups and gaining acceptance in their communities) and little involvement in other activities (eg, working with community groups to address local health problems, familiarity with local women's shelters). Contrary to expectations, physicians who worked with minority and poorer patient populations and counties generally reported less community involvement. Physicians caring for more patients covered by HMO or capitated health insurance plans also reported lower participation in their communities. CONCLUSIONS This study provides support for the hypothesis that the community plays a role in the work of physicians that can be categorized into four types of activities. This framework may help physicians and practices recognize the breadth of ways they can meet the growing demand that they approach their work with a community perspective.
The bidirectional relationship between gambling and addictive substances

This study aims to analyse the co-occurrence of gambling activity and the consumption of addictive substances, such as tobacco, alcohol and drugs. By using a sample of 709 gamblers in Sardinia (Italy), a multivariate probit approach is proposed since it allows simultaneous study of the extent of correlation between the consumption of different substances. Our findings document that, on the one hand, betting more money leads to an increase in the propensity to consume tobacco in the middle of the game, and, on the other hand, the simultaneous co-occurrence of smoking, alcohol and drugs drives up the probability of getting more involved in gambling activity. Knowing the positive reinforcing effects of addictive substances is the first step towards implementing the most effective prevention and treatment modalities for problem/pathological gamblers.
Regulatory T Cell Vaccination without Autoantigen Protects against Experimental Autoimmune Encephalomyelitis1

Regulatory T (Treg) cells show promise for treating autoimmune diseases, but their induction to elevated potency has been problematic when the most optimally derived cells are from diseased animals. To circumvent reliance on autoantigen-reactive Treg cells, stimulation to myelin-independent Ags may offer a viable alternative while maintaining potency to treat experimental autoimmune encephalomyelitis (EAE). The experimental Salmonella vaccine expressing colonization factor Ag I possesses anti-inflammatory properties and, when applied therapeutically, reduces further development of EAE in SJL mice. To ascertain Treg cell dependency, a kinetic analysis was performed showing increased levels of FoxP3+CD25+CD4+ T cells. Inactivation of these Treg cells resulted in loss of protection. Adoptive transfer of the vaccine-induced Treg cells protected mice against EAE with greater potency than naive or Salmonella vector-induced Treg cells, and cytokine analysis revealed enhanced production of TGF-β, not IL-10. The development of these Treg cells in conjunction with immune deviation by Th2 cells optimally induced protective Treg cells when compared those induced in the absence of Th2 cells. These data show that Treg cells can be induced to high potency to non-disease-inducing Ags using a bacterial vaccine.
Cost and affordability of non-communicable disease screening, diagnosis and treatment in Kenya: Patient payments in the private and public sectors

Introduction The prevalence of non-communicable diseases (NCDs) is rising in low- and middle-income countries, including Kenya, disproportionately to the rest of the world. Our objective was to quantify patient payments to obtain NCD screening, diagnosis, and treatment services in the public and private sector in Kenya and evaluate patients’ ability to pay for the services. Methods and findings We collected payment data on cardiovascular diseases, diabetes, breast and cervical cancer, and respiratory diseases from Kenyatta National Hospital, the main tertiary public hospital, and the Kibera South Health Center—a public outpatient facility, and private sector practitioners and hospitals. We developed detailed treatment frameworks for each NCD and used an itemization cost approach to estimate payments. Patient affordability metrics were derived from Kenyan government surveys and national datasets. Results compare public and private costs in U.S. dollars. NCD screening costs ranged from $4 to $36, while diagnostic procedures, particularly for breast and cervical cancer, were substantially more expensive. Annual hypertension medication costs ranged from $26 to $234 and $418 to $987 in public and private facilities, respectively. Stroke admissions ($1,874 versus $16,711) and dialysis for chronic kidney disease ($5,338 versus $11,024) were among the most expensive treatments. Cervical and breast cancer treatment cost for stage III (curative approach) was about $1,500 in public facilities and more than $7,500 in the private facilities. A large proportion of Kenyans aged 15 to 49 years do not have health insurance, which makes NCD services unaffordable for most people given the overall high cost of services relative to income (average household expenditure per adult is $413 per annum). Conclusions There is substantial variation in patient costs between the public and private sectors. Most NCD diagnosis and treatment costs, even in the public sector, represent a substantial economic burden that can result in catastrophic expenditures.
Prevalence of hepatitis B surface antigen carrier state in patients with lichen planus--report of 200 cases from Lahore, Pakistan.

BACKGROUND To determine the prevalence of hepatitis B surface antigen carrier state in patients with lichen planus. METHODS A quasi experimental cross sectional study was done at Department of Dermatology, Shaikh Zayed Federal Postgraduate Medical Institute, Lahore, Pakistan, from April 2003 to March 2005. Two hundred clinically diagnosed cases of LP and equal number of patients with other dermatoses not reportedly associated with hepatitis B virus (HBV) infection (control group) were collected from Skin Out Patient Department. They were screened for hepatitis B surface antigen (HBsAg) by Enzyme Linked Immunosorbent Assay (ELISA). Statistical analysis was done by using SPSS package version 11. RESULTS Out of 200 patients of each group, three patients with LP and seven patients from control group were positive for HBsAg. The test of significance for proportions revealed that there was no significant difference (p > 0.1) between two groups. CONCLUSION No association between HBsAg carrier state and LP was found in our study.
Culture and Contact in the Promotion and Reduction of Anti-Gay Prejudice: Evidence from Jamaica and Britain

Jamaica has been called “the most homophobic place on Earth” (Padgett, 2006, p. 1), and has been involved in numerous international incidents with Britain, and other countries, concerning anti-gay prejudice. However, neither the severity of Jamaican anti-gay prejudice, nor any means of reducing this prejudice has ever been empirically investigated. Intergroup contact—social interaction with a person from another group—is one of the most successful and widely used social–psychological interventions to reduce prejudice and improve intergroup relations. In this article, we compared sexual prejudice in Jamaica to that in Britain and investigated the relationship between contact and sexual prejudice in both countries. Jamaican participants reported more negative attitudes toward gay men than did British participants, but contact was more strongly associated with reduced sexual prejudice for Jamaican participants than for British participants. Implications for reducing Jamaican sexual prejudice are discussed.