Miracle-dz/UniFAR-FTUs huggingface dataset:
Carotid artery and heart disease in subtypes of cerebral infarction.

BACKGROUND AND PURPOSE The aim of the study was to determine the prevalences of carotid artery disease and major and minor potential cardioembolic sources (1) in patients with cerebral infarction and age-matched control subjects and (2) in different clinical subtypes of cerebral infarction. METHODS A series of 166 consecutive patients with cerebral infarction and 59 control subjects was examined. The study protocol included clinical subtyping of the cerebral infarctions, ultrasonography of the carotid arteries, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), ECG, and examination of the brain with computed tomography, magnetic resonance imaging, or autopsy. RESULTS Carotid artery stenosis > or = 80% or occlusion was present in 35 (21%) patients but in no control subjects (P < .001; chi 2 test). A major potential cardioembolic source was detected in 65 (39%) patients and 3 (5%) control subjects. Atrial fibrillation was present in 35 (21%) patients and 3 (5%) control subjects at initial ECG (P < .01) and in 47 (28%) patients at repeat examination; 17 patients had paroxysmal atrial fibrillation. Sinus rhythm and a major potential cardioembolic source were detected in 18 (11%) patients but in no control subjects (P < .01) at TTE (all patients and control subjects examined) or TEE (118 patients and 52 control subjects examined). The frequency of a minor potential cardioembolic source detectable at TTE or TEE was similar in the patient and control groups (51% and 53%, respectively [NS]) and increased significantly with age. A finding of carotid artery stenosis > or = 80% or occlusion, atrial fibrillation, or a major cardioembolic source detected at TTE or TEE was more frequent among patients with cortical symptoms from anterior or middle cerebral artery territories than among those with lacunar syndromes (66% versus 22%, respectively). The probable source of cerebral infarction was identified in most of the 166 patients: cardiac embolism in 28% of cases (n = 46), carotid artery disease in 8% (n = 14), both cardiac embolism and carotid artery disease in 7% (n = 11), and lacunar infarction in 23% (n = 38). In 57 (34%) of the patients no unequivocal cause of the cerebral infarction was found. CONCLUSIONS The prevalences of carotid artery and heart disease differ significantly between clinical subtypes of cerebral infarction. The cause of cerebral infarction remains uncertain in one third of patients. Because a minor potential cardioembolic source occurs in about 50% of both patients and control subjects, this finding is of questionable value as a risk factor for stroke in the elderly.
Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis

Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of connective tissue metamorphosis. It is characterized by malformation of the great (big) toes during embryonic skeletal development and by progressive heterotopic endochondral ossification (HEO) postnatally, which leads to the formation of a second skeleton of heterotopic bone. Individuals with these classic clinical features of FOP have the identical heterozygous activating mutation (c.617G>A; R206H) in the gene encoding ACVR1 (also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Disease activity caused by this ACVR1 mutation also depends on altered cell and tissue physiology that can be best understood in the context of a high-fidelity animal model. Recently, we developed such a knock-in mouse model for FOP (Acvr1R206H/+) that recapitulates the human disease, and provides a valuable new tool for testing and developing effective therapies. The FOP knock-in mouse and other models in Drosophila, zebrafish, chickens and mice provide an arsenal of tools for understanding BMP signaling and addressing outstanding questions of disease mechanisms that are relevant not only to FOP but also to a wide variety of disorders associated with regenerative medicine and tissue metamorphosis.
Effects on Locomotion, Muscle, Bone, and Blood Induced by a Combination Therapy Eliciting Weight-Bearing Stepping in Nonassisted Spinal Cord–Transected Mice

Background. The health benefits associated with physical activity–based rehabilitation in patients with no lower-extremity motor function after a spinal cord injury (SCI) is uncertain. Methods. The authors assessed signs of efficacy, safety, and utility associated with a novel pharmacological combination therapy to activate central pattern generator (CPG) activity and corresponding locomotor activity in complete thoracic Th9/10-transected mice. Results. Subcutaneous administration 4 times per week for 1 month of 1.5 mg/kg buspirone, 1.5 mg/kg apomorphine, 12.5 mg/kg benserazide, and 50 mg/kg L-DOPA induced episodes of weight-bearing stepping on a treadmill in nonassisted paraplegic mice for 45-minute sessions. Hindlimb muscle cross-sectional area and fiber area values as well as several blood cell constituent levels assessed at 30 days postinjury were positively affected by the combination therapy, as compared with controls. Episodes of locomotion remained effective on each treatment. Femoral bone mineral density loss was not prevented by triple therapy. Conclusion. Although translation of these findings needs further experimentation, similar pharmacological activation of the CPG offers a novel therapeutic target to provide some health benefits in motor-complete SCI patients.
Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase

The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (TFH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in TFH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4+ T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key TFH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of TFH and suggest that CD28 and ICOS play differential roles during a multistep process of TFH differentiation.
An association study between Heme oxygenase-1 genetic variants and Parkinson's disease

The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT)n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT)n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk.
Silver-enhanced In Situ Hybridization for Detection of Polyomavirus DNA in Patients With BK Virus Nephropathy

BK virus nephropathy is not an infrequent complication of renal transplantation associated with high rates of graft loss. Although antibodies against SV40 antigen detect different viruses of the polyomavirus family, immunohistochemistry is widely used to confirm the diagnosis of BK virus nephropathy in renal biopsies. Here we aimed to validate the novel silver-enhanced in situ hybridization (SISH) technique for the automated detection of BK virus in renal transplant biopsies. Two different patient cohorts were included. Twenty-nine consecutive patients suspicious for BK virus infection were investigated by SISH and chromogenic in situ hybridization. An additional 26 renal biopsies positive by SV40 immunohistochemistry from 19 patients were analyzed by SISH. Polyomavirus DNA serum levels, as determined by nested PCR analysis, were available for all of these patients. The presence of BK virus DNA in renal tubular cells was identified in 5 of the suspicious cases by both, SISH and chromogenic in situ hybridization . One additional patient was only positive in the SISH. In the second cohort, SISH was positive in all SV40 positive biopsies, but SISH signals were less extensive than SV40 immunohistochemistry. Our results show that the BK virus SISH is an ancillary tool for the detection of polyomavirus DNA in renal biopsies using bright-field microscopy. However, its diagnostic value in comparison with standard immunohistochemistry seems to be limited.
The Effect of Race and Chronic Obstructive Pulmonary Disease on Long-Term Survival after Coronary Artery Bypass Grafting

Background: Chronic obstructive pulmonary disease (COPD) is a known predictor of decreased long-term survival after coronary artery bypass grafting (CABG). Differences in survival by race have not been examined. Methods: A retrospective cohort study was conducted of CABG patients between 2002 and 2011. Long-term survival was compared in patients with and without COPD and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. Results: A total of 984 (20%) patients had COPD (black n = 182; white n = 802) at the time of CABG (N = 4,801). The median follow-up for study participants was 4.4 years. COPD was observed to be a statistically significant predictor of decreased survival independent of race following CABG (no COPD: HR = 1.0; white COPD: adjusted HR = 1.9, 95% CI = 1.7–2.3; black COPD: adjusted HR = 1.6, 95% CI = 1.1–2.2). Conclusion: Contrary to the expected increased risk of mortality among black COPD patients in the general population, a similar survival disadvantage was not observed in our CABG population.
The Interaction of Polyene Antibiotics with Thin Lipid Membranes

Optically black, thin lipid membranes prepared from sheep erythrocyte lipids have a high dc resistance (Rm ≅ 108 ohm-cm2) when the bathing solutions contain NaCl or KCl. The ionic transference numbers (Ti) indicate that these membranes are cation-selective (T Na ≅ 0.85; T Cl ≅ 0.15). These electrical properties are independent of the cholesterol content of the lipid solutions from which the membranes are formed. Nystatin, and probably amphotericin B, are cyclic polyene antibiotics containing ≈36 ring atoms and a free amino and carboxyl group. When the lipid solutions used to form membranes contained equimolar amounts of cholesterol and phospholipid, these antibiotics reduced Rm to ≈102 ohm-cm2; concomitantly, T Cl became ≅0.92. The slope of the line relating log Rm and log antibiotic concentration was ≅4.5. Neither nystatin (2 x 10-5 M) nor amphotericin B (2 x 10-7 M) had any effect on membrane stability. The antibiotics had no effect on Rm or membrane permselectivity when the lipids used to form membranes were cholesterol-depleted. Filipin (10-5 M), an uncharged polyene with 28 ring atoms, produced striking membrane instability, but did not affect Rm or membrane ionic selectivity. These data suggest that amphotericin B or nystatin may interact with membrane-bound sterols to produce multimolecular complexes which greatly enhance the permeability of such membranes for anions (Cl-, acetate), and, to a lesser degree, cations (Na+, K+, Li+).
Isolation and characterization of a nitrite reductase gene and its use as a probe for denitrifying bacteria

The dissimilatory nitrite reductase gene (nir) from denitrifying bacterium Pseudomonas stutzeri JM300 was isolated and sequenced. In agreement with recent sequence information from another strain of P. stutzeri (strain ZoBell), strain JM300 nir is the first gene in an operon and is followed immediately by a gene which codes for a tetraheme protein; 2.5 kb downstream from the nitrite reductase carboxyl terminus is the cytochrome c551 gene. P. stutzeri JM300 nir is 67% homologous to P. aeruginosa nir and 88% homologous to P. stutzeri ZoBell nir. Within the nitrite reductase promoter region is an fnr-like operator very similar to an operator upstream of a separate anaerobic pathway, that for arginine catabolism in P. aeruginosa. The denitrification genes in P. stutzeri thus may be under the same regulatory control as that found for other anaerobic pathways of pseudomonads. We have generated gene probes from restriction fragments within the nitrite reductase operon to evaluate their usefulness in ecology studies of denitrification. Probes generated from the carboxyl terminus region hybridized to denitrifying bacteria from five separate genera and did not cross-hybridize to any nondenitrifying bacteria among six genera tested. The denitrifier probes were successful in detecting denitrifying bacteria from samples such as a bioreactor consortium, aquifer microcosms, and denitrifying toluene-degrading enrichments. The probes also were used to reveal restriction fragment length polymorphism patterns indicating the diversity of denitrifiers present in these mixed communities.
Duplicated genes with split functions: independent roles of protocadherin15 orthologues in zebrafish hearing and vision

In the sensory receptors of both the eye and the ear, specialized apical structures have evolved to detect environmental stimuli such as light and sound. Despite the morphological divergence of these specialized structures and differing transduction mechanisms, the receptors appear to rely in part on a shared group of genes for function. For example, mutations in Usher (USH) genes cause a syndrome of visual and acoustic-vestibular deficits in humans. Several of the affected genes have been identified, including the USH1F gene, which encodes protocadherin 15 (PCDH15). Pcdh15 mutant mice also have both auditory and vestibular defects, although visual defects are not evident. Here we show that zebrafish have two closely related pcdh15 genes that are required for receptor-cell function and morphology in the eye or ear. Mutations in pcdh15a cause deafness and vestibular dysfunction, presumably because hair bundles of inner-ear receptors are splayed. Vision, however, is not affected in pcdh15a mutants. By contrast, reduction of pcdh15b activity using antisense morpholino oligonucleotides causes a visual defect. Optokinetic and electroretinogram responses are reduced in pcdh15b morpholino-injected larvae. In electron micrographs, morphant photoreceptor outer segments are improperly arranged, positioned perpendicular to the retinal pigment epithelium and are clumped together. Our results suggest that both cadherins act within their respective transduction organelles: Pcdh15a is necessary for integrity of the stereociliary bundle, whereas Pcdh15b is required for alignment and interdigitation of photoreceptor outer segments with the pigment epithelium. We conclude that after a duplication of pcdh15, one gene retained an essential function in the ear and the other in the eye.
Hypertension Improvement Project (HIP) Latino: results of a pilot study of lifestyle intervention for lowering blood pressure in Latino adults

Objectives. To assess the feasibility of a culturally tailored behavioral intervention for improving hypertension-related health behaviors in Hispanic/Latino adults. Design. Feasibility pilot study in a community health center and a Latino organization in Durham, North Carolina. Intervention. The culturally adapted behavioral intervention consisted of six weekly group sessions incorporating motivational interviewing techniques. Goals included weight loss if overweight, adoption of the Dietary Approaches to Stop Hypertension dietary pattern, and increased physical activity. Participants were also encouraged to monitor their daily intake of fruits, vegetables, dairy and fat, and to record physical activity. Cultural adaptations included conducting the study in familiar places, using Spanish-speaking interventionist, culturally appropriate food choices, and physical activity. Main outcomes. Systolic blood pressure (BP), weight, body mass index (BMI), exercise, and dietary pattern were measured at baseline and at 6 weeks follow-up. Qualitative evaluations of the recruitment process and the intervention were also conducted. Results. There were 64 potential participants identified via healthcare provider referrals (33%), printed media (23%), and direct contact (44%). Seventeen participants completed the intervention and had main outcome data available. Participants ‘strongly agreed/agreed’ that the group sessions provided them with the tools they needed to achieve weight loss, BP control, and the possibility of sustaining the lifestyle changes after completing the intervention. At the end of the intervention, all physiological, diet, and exercise outcomes were more favorable, with the exception of fat. After 6 weeks, systolic BP decreased an average of −10.4±10.6 mmHg, weight decreased 1.5±3.2 lbs, BMI decreased 0.3±0.5, and physical activity increased 40 minutes per week. Conclusion. Our findings suggest that lifestyle interventions for preventing and treating hypertension are feasible and potentially effective in the Hispanic/Latino population.
An arithmetical hierarchy of the law of excluded middle and related principles

The topic of this paper is relative constructivism. We are concerned with classifying nonconstructive principles from the constructive viewpoint. We compare, up to provability in intuitionistic arithmetic, subclassical principles like Markov's principle, (a function-free version of) weak Konig's lemma, Post's theorem, excluded middle for simply existential and simply universal statements, and many others. Our motivations are rooted in the experience of one of the authors with an extended program extraction and of another author with bound extraction from classical proofs.
Low distortion spanners

A <i>spanner</i> of an undirected unweighted graph is a subgraph that approximates the distance metric of the original graph with some specified accuracy. Specifically, we say <i>H</i> ⊆ <i>G</i> is an <i>f</i>-spanner of <i>G</i> if any two vertices <i>u</i>,<i>v</i> at distance <i>d</i> in <i>G</i> are at distance at most <i>f</i>(<i>d</i>) in <i>H</i>. There is clearly some trade-off between the sparsity of <i>H</i> and the <i>distortion</i> function <i>f</i>, though the nature of the optimal trade-off is still poorly understood. In this article we present a simple, modular framework for constructing sparse spanners that is based on interchangable components called <i>connection schemes</i>. By assembling connection schemes in different ways we can recreate the additive 2- and 6-spanners of Aingworth et al. [1999] and Baswana et al. [2009], and give spanners whose multiplicative distortion quickly tends toward 1. Our results rival the simplicity of all previous algorithms and provide substantial improvements (up to a doubly exponential reduction in edge density) over the comparable spanners of Elkin and Peleg [2004] and Thorup and Zwick [2006].
Moderate Calcium Channel Dysfunction in Adult Mice with Inducible Cardiomyocyte-specific Excision of the cacnb2 Gene*

The major L-type voltage-gated calcium channels in heart consist of an α1C (CaV1.2) subunit usually associated with an auxiliary β subunit (CaVβ2). In embryonic cardiomyocytes, both the complete and the cardiac myocyte-specific null mutant of CaVβ2 resulted in reduction of L-type calcium currents by up to 75%, compromising heart function and causing defective remodeling of intra- and extra-embryonic blood vessels followed by embryonic death. Here we conditionally excised the CaVβ2 gene (cacnb2) specifically in cardiac myocytes of adult mice (KO). Upon gene deletion, CaVβ2 protein expression declined by >96% in isolated cardiac myocytes and by >74% in protein fractions from heart. These latter protein fractions include CaVβ2 proteins expressed in cardiac fibroblasts. Surprisingly, mice did not show any obvious impairment, although cacnb2 excision was not compensated by expression of other CaVβ proteins or changes of CaV1.2 protein levels. Calcium currents were still dihydropyridine-sensitive, but current density at 0 mV was reduced by <29%. The voltage for half-maximal activation was slightly shifted to more depolarized potentials in KO cardiomyocytes when compared with control cells, but the difference was not significant. In summary, CaVβ2 appears to be a much stronger modulator of L-type calcium currents in embryonic than in adult cardiomyocytes. Although essential for embryonic survival, CaVβ2 down-regulation in cardiomyocytes is well tolerated by the adult mice.
Some trade-off results for polynomial calculus: extended abstract

We present size-space trade-offs for the polynomial calculus (PC) and polynomial calculus resolution (PCR) proof systems. These are the first true size-space trade-offs in any algebraic proof system, showing that size and space cannot be simultaneously optimized in these models. We achieve this by extending essentially all known size-space trade-offs for resolution to PC and PCR. As such, our results cover space complexity from constant all the way up to exponential and yield mostly superpolynomial or even exponential size blow-ups. Since the upper bounds in our trade-offs hold for resolution, our work shows that there are formulas for which adding algebraic reasoning on top of resolution does not improve the trade-off properties in any significant way. As byproducts of our analysis, we also obtain trade-offs between space and degree in PC and PCR exactly matching analogous results for space versus width in resolution, and strengthen the resolution trade-offs in [Beame, Beck, and Impagliazzo '12] to apply also to k-CNF formulas.