Miracle-dz/UniFAR-FTUs huggingface dataset:
The WI-1 Adhesin Blocks Phagocyte TNF-α Production, Imparting Pathogenicity on Blastomyces dermatitidis1

The WI-1 adhesin is indispensable for pathogenicity of Blastomyces dermatitidis and is thought to promote pulmonary infection by fixing yeast to lung tissue and cells. Recent findings suggest that WI-1 confers pathogenicity by mechanisms in addition to adherence. Here, we investigated whether WI-1 modulates host immunity by altering production of pro-inflammatory cytokines. Production of TNF-α in lung alveolar fluids of mice infected with B. dermatitidis was severalfold higher for WI-1 knockout yeast compared with wild-type yeast, and in vitro coculture of unseparated lung cells with these isogenic yeast disclosed similar differences. Upon coculture with purified macrophages and neutrophils, wild-type yeast blocked TNF-α production, yet WI-1 knockout yeast stimulated production. Coating knockout yeast with purified WI-1 converted them from stimulating TNF-α production to inhibiting production. Addition of purified WI-1 into stimulated phagocyte cultures led to concentration-dependent inhibition of TNF-α production. Neutralization of TNF-α in vivo exacerbated experimental pulmonary infection, particularly for the nonpathogenic WI-1 knockout yeast. Inducing increased TNF-α levels in the lung by adenovirus-vectored gene therapy controlled infection with wild-type yeast. Thus, the WI-1 adhesin on yeast modulates host immunity through blocking TNF-α production by phagocytes, which fosters progression of pulmonary infection.
Homework assignments in cognitive and behavioral therapy: a meta-analysis.

This meta-analysis (27 studies, N= 1702) examined (a) the effects of homework assignments on treatment outcome and (b) the relationship between homework compliance and therapy outcome. Results of the primary meta-analyses indicated a weighted mean effect size (r) of . 36 for homework effects and . 22 for homework compliance. A moderator analysis (chosen on a priori grounds) was also conducted by partitioning the sample of effect size estimations first according to the sample problem type, according to the type of homework activity administered, and according to the source and time of homework compliance assessment. We hope that the focus of future research will now be diverted from general questions of the benefit of including homework in therapy, to more specific questions regarding the relative effectiveness of different types of homework assignments for different client problems.
Amino acid catabolism and antibiotic synthesis: valine is a source of precursors for macrolide biosynthesis in Streptomyces ambofaciens and Streptomyces fradiae

Targeted inactivation of the valine (branched-chain amino acid) dehydrogenase gene (vdh) was used to study the role of valine catabolism in the production of tylosin in Streptomyces fradiae and spiramycin in Streptomyces ambofaciens. The deduced products of the vdh genes, cloned and sequenced from S. fradiae C373.1 and S. ambofaciens ATCC 15154, are approximately 80% identical over all 363 amino acids and 96% identical over a span of the first N-terminal 107 amino acids, respectively, to the deduced product of the Streptomyces coelicolor vdh gene. The organization of the regions flanking the vdh genes is the same in all three species. Inactivation of the genomic copy of the vdh gene in S. fradiae and S. ambofaciens by insertion of a hygromycin resistance (hyg) gene caused loss of the valine dehydrogenase (Vdh) activity, and thus only one enzyme is responsible for the Vdh activity in these organisms. Analysis of the culture broth by bioassay revealed that the vdh::hyg mutants produce an approximately sixfold-lower level of tylosin and an approximately fourfold-lower level of spiramycin than the wild-type S. fradiae and S. ambofaciens strains, while maintaining essentially identical growth in a defined minimal medium with either 25 mM ammonium ion or 0.05% asparagine as the nitrogen source. The addition of the valine catabolite, propionate or isobutyrate, and introduction of the wild-type vdh gene back to each vdh::hyg mutant reversed the negative effect of the vdh::hyg mutation on spiramycin and tylosin production. These data show that the catabolism of valine is a major source of fatty acid precursors for macrolide biosynthesis under defined growth conditions and imply that amino acid catabolism is a vital source of certain antibiotic precursors in actinomycetes.
CCL 18 as an Indicator of Pulmonary Fibrotic Activity in Idiopathic Interstitial Pneumonias and Systemic Sclerosis

Objective. In diffuse parenchymal lung diseases, the evolution of pulmonary fibrosis is often devastating and may result in death. In this study the role of CCL18 as a biomarker of disease activity in idiopathic interstitial pneumonias (IIPs) and systemic sclerosis (SSc) with lung involvement was evaluated. Methods. CCL18 was assessed in supernatants of cultured bronchoalveolar lavage (BAL) cells as well as BAL fluid and serum samples from 43 patients with IIPs, 12 patients with SSc, and 23 healthy control subjects. Concentrations of CCL18 were measured by enzyme-linked immunosorbent assay, and expression of CCL18 was assessed by flow cytometry. Results. CCL18 concentrations were statistically significantly increased in all patients with fibrotic lung diseases. Spontaneous CCL18 production by BAL cells was negatively correlated with total lung capacity and the diffusion capacity for carbon monoxide, whereas there was a positive correlation of CCL18 concentrations with BAL neutrophil and eosinophil cell counts. Flow cytometry revealed an increase in the percentage of CCL18-positive alveolar macrophages and an increase in the CCL18 fluorescence intensity per cell in patients with fibrotic lung diseases. In a cohort of patients who were followed up for at least 6 months (n 40), a close negative correlation was observed between changes in the predicted total lung capacity and changes in CCL18 serum concentrations. Conclusion. These findings suggest that CCL18 production by BAL cells and serum CCL18 concentrations reflect pulmonary fibrotic activity in patients with IIPs and those with SSc. Monitoring changes in CCL18 production might be an extraordinarily useful tool in clinical practice and in studies aimed at evaluating new approaches for treatment of fibrotic lung diseases.
Learning and memory of cue–reward association meaning by modifications of synaptic efficacy in dentate gyrus and piriform cortex

This article begins with a review of recent experiments investigating the synaptic efficacy changes occurring in rat dentate gyrus and piriform cortex during an associative olfactory task. In all these experiments, animals were trained to discriminate among an artificial cue, a patterned electrical stimulation distributed to the lateral olfactory tract associated with a water reward, and a natural odor associated with a flash of light. Monosynaptic field potential responses evoked by single electrical stimuli to the lateral olfactory tract were recorded in the ipsilateral piriform cortex before and just after each training session. Monosynaptic field and polysynaptic field potentials evoked by single electrical stimuli applied respectively to the lateral perforant pathway and lateral olfactory tract were also recorded in ipsilateral dentate gyrus. The results showed an increase in synaptic efficacy subsequent to the first training session in the dentate gyrus network when compared with piriform cortex at the later stage of the learning. The early increase of monosynaptic response in the dentate gyrus was observed immediately after the first learning session but disappeared 24 h later. Inversely, a synaptic depression developed across sessions, becoming significant at the onset of the last (fifth) session. The polysynaptic potential recorded in this structure increased substantially when rats began to discriminate the learning cues, usually after the second or third learning session. Then, from the third to the fifth session, an LTP like‐phenomenon appeared in piriform cortex when rats perfectly mastered the associations. Experiments using high‐frequency stimulation to prevent changes in gyrus dentatus indicated that the onset of the observed depression was necessary for the learning of the olfactory associations. The fact that hippocampal and cortical neuronal networks exhibited different timing in synaptic efficacy changes could physiologically explain learning and memory processes. Hippocampus 2002;12:600–608. © 2002 Wiley‐Liss, Inc.
Metalloprotease‐mediated OPA1 processing is modulated by the mitochondrial membrane potential

Background information. Human OPA1 (optic atrophy type 1) is a dynamin‐related protein of the mitochondrial IMS (intermembrane space) involved in membrane fusion and remodelling. Similarly to its yeast orthologue Mgm1p that exists in two isoforms generated by the serine protease Pcp1p/Rbd1p, OPA1 exists in various isoforms generated by alternative splicing and processing. In the present paper, we focus on protease processing of OPA1.
Kinetics of the Tau PET Tracer 18F-AV-1451 (T807) in Subjects with Normal Cognitive Function, Mild Cognitive Impairment, and Alzheimer Disease

We report kinetic modeling results of dynamic acquisition data from 0 to 100 min after injection with the tau PET tracer 18F-AV-1451 in 19 subjects. Methods: Subjects were clinically diagnosed as 4 young cognitively normal, 5 old cognitively normal, 5 mild cognitive impairment, and 5 Alzheimer disease (AD). Kinetic modeling was performed using Logan graphical analysis with the cerebellum crus as a reference region. Voxelwise binding potential (BP) and SUV ratio (SUVR80−100) images were compared. Results: In AD subjects, slower and spatially nonuniform clearance from cortical regions was observed as compared with the controls, which led to focal uptake and elevated retention in the imaging data from 80 to 100 min after injection. BP from the dynamic data from 0 to 100 min correlated strongly (R2 > 0.86) with corresponding regional SUVR80−100−1 values. In the putamen, the observed kinetics (positive SUVR1−5−1 at the tracer delivery stage and plateauing time–SUVR curves for all diagnostic categories) may suggest either additional off-target binding or a second binding site with different kinetics. Conclusion: The kinetics of the 18F-AV-1451 tracer in cortical areas, as examined in this small group of subjects, differed by diagnostic stage. A delayed 80- to 100-min scan provided a reasonable substitute for a dynamic 0- to 100-min acquisition for cortical regions although other windows (e.g., 75–105 min) may be useful to evaluate.
Screening for Hypertension in High School

Arterial hypertension is a major risk factor for atherosclerotic ischemic heart disease and cerebrovascular stroke. Blood pressure measurements were taken in the supine position in 6,282 healthy adolescents (3073 boys, 3209 girls) aged 13-17 years of both sexes. Forty-eight subjects were found to have hypertension: 35 idopathic and 13 secondary to reflux nephropathy, chronic glomerulonephritis, coarctation of the aorta, and hemolytic uremic syndrome. Systolic blood pressure was significantly higher among males than females at ages 15-17 years (p<0.001); diastolic blood pressure was higher among males at age 17 years only (p<0.05). Males with BMI>17 exhibited higher systolic blood pressure than females. Prevalence of hypertension, mostly primary, in a large cohort of students was 0.76%. Early screening is important for early interventions and reducing cardiovascular morbidity and mortality in adulthood.
A proposed chronology of events for forward head posture.

AbstractThe purpose of this article is to attempt to organize some of the many ramifications of the position referred to as forward head posture (FHP). It will present a proposed chronology of events and attempt to explain why patients with masticatory disorders may also demonstrate other symptoms in anatomical locations that are not directly connected with the masticatory mechanism. Abnormal posture affects muscle length/tension relationships and joint biomechanics, and this may cause pain. Many of the observations made in this article are derived from clinical settings, while other observations are ones that have been documented throughout medical and dental literature.
Functional CLOCK gene rs1554483 G/C polymorphism is associated with susceptibility to Alzheimer's disease in the Chinese population

Objective To examine the association between the circadian locomotor output cycles kaput (CLOCK) gene rs1554483 G/C polymorphism and susceptibility to Alzheimer's disease in Chinese people. Methods This case–control study determined apolipoprotein E (APOE) and CLOCK rs1554483 G/C genotypes using polymerase chain reaction restriction fragment length polymorphism. Results Unrelated patients with Alzheimer's disease (n = 130) and healthy controls (n = 188) were analysed for an association between the CLOCK gene rs1554483 G/C polymorphism and susceptibility to Alzheimer's disease. In the whole sample and in APOE ɛ4 isoform noncarriers, the prevalence of CLOCK gene rs1554483 G allele carriers was significantly higher in patients with Alzheimer's disease than in controls. Among APOE ɛ4 carriers, the prevalence of CLOCK rs1554483 G allele carriers was not significantly different between patients with Alzheimer's disease and controls. Conclusion Among APOE ɛ4 noncarriers, but not APOE ɛ4 carriers, the CLOCK rs1554483 G allele was associated with increased susceptibility to Alzheimer's disease.
Validity of Arabic Version of Beliefs About Medication Questionnaire

To assess the validity and reliability of the Arabic version of the Beliefs About Medication Questionnaire, a cross-sectional design was used and the data were collected from 605 patients with chronic diseases. The study was conducted between July 2013 and December 2013. The results showed that the Cronbach’s alpha coefficient (.71) was satisfactory. There was a significant strong positive correlation between test–retest for the same group subsample, with a correlation coefficient range of . 45 to . 78. There were no statistically significant differences between retest subgroups and remaining samples in the questionnaire subscales. The percentage of missing value was around 0.03, which confirmed the feasibility of the Arabic version of the questionnaire. These findings suggested that having a culturally acceptable, valid and reliable instrument to identify patients’ beliefs toward medication in Jordan will play an important role in tailoring appropriate intervention to enhance patient compliance with their prescribed medication.
Molecular basis of vertebrate limb patterning.

Mechanisms of limb development are common to all higher vertebrates. The current understanding of how vertebrate limbs develop comes mainly from studies on chick embryos, which are classical models for experimental manipulation, and mouse embryos, which can be genetically manipulated. Work on chick and mouse embryos is often complementary and has direct implications for human limb development. Analysis has moved to the molecular level, which allows direct links to genetics. Even though genes involved in limb development have been discovered by basic scientists through different routes to that taken by clinical geneticists, many of the same genes have been identified. Thus, the fields of embryology and clinical medicine increasingly converge. The next challenge will be to go back to animal models to begin to dissect how particular gene mutations lead to specific limb phenotypes.
An Investigation into the Social Construction and Consequences of the Label Epilepsy

This research was never conceived within a formal theoretical framework though of course there were, and are, sensitizing concepts which have guided the investigation and directed attention towards particular kinds of issue. I make no apologies for this but rather suggest that early reservations about too neat a theoretical package have been amply substantiated during the course of field-work and analysis. In short, I have been continually forced' back to the data to reconsider interpretations which at one time at least seemed less problematic. Essentially, the problem revolves round the distinction between the content of accounts, which at face value might be used to support Various propositions, and what peoide are 'doing' with their talk. The dilemma remains and I suspect I move uneasily from one position to the other, but perhaps both can be employed to advantage; the former by invoking some notion of validity or plausibility established by Denzin's principle of 'triangulationV the latter by recognizing the situated nature of accounts and treating them as procedures, resources or methods by which people *do' interpretative work within particular contexts. ' Though necessarily selective, I want to present a biography of the research which principally focusses on 24 families with an epileptic child, to illustrate changing perspectives, emergent problems and some of the solutions, or attempted solutions, to overcome them, indicating my position then as it was; and how, in the light <tf an examination of the data, revisions in procedures and interpretations were required. In particular, the paper focusses on the problems of making sense of extensive data, much of which is biografdiical, collected on one of these families. Analysis of these accounts suggests
Forkhead box A 1 transcriptional pathway in KRT 7-expressing esophageal squamous cell carcinomas with extensive lymph node metastasis

Prognosis of cancers with lymph node metastasis is known to be very poor; however, it is still controversial whether metastatic potential can be evaluated by expression profiles of primary tumors. Therefore, to address this issue, we compared gene expression profiles of 24 esophageal squamous cell carcinomas (ESCCs) with extensive lymph node metastasis and 11 ESCCs with no metastatic lymph node. However, there was no gene cluster distinguishing these two groups, suggesting that lymph node metastasisassociated genes are varied depending on cases or subgroups. Therefore, we applied a recently developed filtering method (S2N') to identify such genes, and successfully extracted 209 genes associated with node status. Among them, overexpression of CALB1, KRT7/CK7, MUC1 and CEA/CEACAM5 in poor prognostic cases with metastatic lymph nodes was confirmed in two sets of ESCCs by RT-PCR. Each often seemed to have glandular cell type-characteristics in both the gene expression and morphology. It was also revealed that FOXA1 siRNA treatment of esophageal cancer cells reduced the mRNA level of both KRT7 and a stabilizer of epithelialmesenchymal transition (EMT) regulator LOXL2, and that both FOXA1 and LOXL2 siRNAs reduced invasion and migration of ESCC cells. In 15 KRT7-expressing ESCCs with metastatic lymph nodes, 60% expressed FOXA1 and 33% expressed both FOXA1 and LOXL2. These results suggest that FOXA1 induces not only KRT7 but also LOXL2 in a subset of poor prognostic ESCCs with metastatic lymph nodes, and it is also plausible, that other FOXA1 downstream genes could be therapeutic targets of poor prognostic ESCCs.
Very Large Database of Lipids: Rationale and Design

Blood lipids have major cardiovascular and public health implications. Lipid‐lowering drugs are prescribed based in part on categorization of patients into normal or abnormal lipid metabolism, yet relatively little emphasis has been placed on: (1) the accuracy of current lipid measures used in clinical practice, (2) the reliability of current categorizations of dyslipidemia states, and (3) the relationship of advanced lipid characterization to other cardiovascular disease biomarkers. To these ends, we developed the Very Large Database of Lipids (NCT01698489), an ongoing database protocol that harnesses deidentified data from the daily operations of a commercial lipid laboratory. The database includes individuals who were referred for clinical purposes for a Vertical Auto Profile (Atherotech Inc., Birmingham, AL), which directly measures cholesterol concentrations of low‐density lipoprotein, very low‐density lipoprotein, intermediate‐density lipoprotein, high‐density lipoprotein, their subclasses, and lipoprotein(a). Individual Very Large Database of Lipids studies, ranging from studies of measurement accuracy, to dyslipidemia categorization, to biomarker associations, to characterization of rare lipid disorders, are investigator‐initiated and utilize peer‐reviewed statistical analysis plans to address a priori hypotheses/aims. In the first database harvest (Very Large Database of Lipids 1.0) from 2009 to 2011, there were 1 340 614 adult and 10 294 pediatric patients; the adult sample had a median age of 59 years (interquartile range, 49–70 years) with even representation by sex. Lipid distributions closely matched those from the population‐representative National Health and Nutrition Examination Survey. The second harvest of the database (Very Large Database of Lipids 2.0) is underway. Overall, the Very Large Database of Lipids database provides an opportunity for collaboration and new knowledge generation through careful examination of granular lipid data on a large scale.
The Relationship between Exposure to Missiles and PTSD Symptoms as a Function of Hemispheric Preference in Israelis

ABSTRACT Recent research proposes that left hemispheric lateralization (HL) may protect against the effects of life events on mental distress. This study extends these findings by examining the protective role of left HL in the relationship between war threat (missile exposure) and PTSD symptoms. A sample of 186 Israelis, exposed to missile attacks, completed brief scales of self-reported missile exposure, a subjective and a neuropsychological HL measure, and of PTSD symptoms. The sample was split into right HL and left HL individuals on both HL measures. Self-reported missile exposure was positively associated with PTSD symptoms in right HL, but not in left HL individuals on both HL measures. These results replicate, extend our previous results and suggest that left HL may even protect against the effects of severe life threatening events. Results are discussed in relation to neuropsychological and neurophysiological differences between the hemispheres.
The toxicology of chlorine.

Chlorine is a reactive gas used by humanity for over two centuries. Exposure to chlorine has occurred in a number of situations, including as a chemical warfare agent, in industrial and domestic exposures, and as a result of accidents and spills. The toxicology of chlorine is related almost entirely to effects in the respiratory system. A consistent symptomology occurs in both animals and humans. This ranges from sensory irritation, to irritation and bronchospasm, to cellular changes to bronchioles and alveoli, to development of pulmonary disease. While full recovery from such injuries remains the most likely outcome, there is little doubt that permanent loss of function is possible in severe cases. In all industrial applications of chlorine, occupational exposures to chlorine should be controlled to at least the recommended exposure standard. However, a focus of activity on ensuring that excursions (such as leaks or "gassing" incidents) above these values do not occur is likely to be more beneficial. Treatment of chlorine exposure is essentially symptomatic, with the efficacy of some treatments (such as corticosteroid therapy) still not well established.