Miracle-dz/UniFAR-FTUs huggingface dataset:
Stroke recurrence in patients with patent foramen ovale

Patent foramen ovale (PFO) is more common in patients with stroke than in matched controls, but the stroke mechanism and late prognosis are not well known. We studied features, coexisting causes, and recurrences of stroke in 140 consecutive patients (mean age 44 ± 14 years) with stroke and PFO admitted to a population-based primary-care center. We selected the patients from 340 patients (41%) aged 560 years with acute stroke. The initial event was brain infarction in 118 patients (84%) and TIA in 22 (16%). Intracranial embolic occlusions were present on angiography or transcranial Doppler in most patients admitted within 12 hours of onset, whereas a venous source was clinically apparent in only six patients (5.5%). Pulmonary embolism, Valsalva maneuver at onset, and coagulation abnormalities were rare, but one-fourth of the patients had an interatrial septum aneurysm (ISA) that coexisted with PFO. An alternative cause of stroke was present in only 22 patients (16%), usually cardiac (atrial fibrillation, severe mitral valve prolapse, akinetic left ventricular segment). During a mean follow-up of 3 years, the stroke or death rate was 2.4% per year, but only eight patients had a recurrent infarct (1.9% per year). This low rate of recurrence contrasted with the severity of initial stroke, which left disabling sequelae in one-half the patients. Multivariate analysis showed that interatrial communication, a history of recent migraine, posterior cerebral artery territory infarct, and a coexisting cause of stroke were associated with recurrence, whereas ISA and treatment type (coagulant or antiaggregant therapy, surgical closure of PFO) were not. However, given the low number of events, these findings must be taken with caution. In conclusion, our study shows that stroke associated with PFO with or without ISA is not commonly due to a coexisting cause of stroke. It is usually embolic, although a definite source cannot often be demonstrated. The presenting stroke is often severe, but recurrence is uncommon. The demonstration of factors associated with a higher risk of recurrence in subgroups of patients is critical for the long-term management of these patients.
Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2)

The mechanistic target of rapamycin (mTOR) exists in two complexes that regulate diverse cellular processes. mTOR complex 1 (mTORC1), the canonical target of rapamycin, has been well studied, whereas the physiological role of mTORC2 remains relatively uncharacterized. In mice in which the mTORC2 component Rictor is deleted in liver [Rictor‐knockout (RKO) mice], we used genomic and phosphoproteomic analyses to characterize the role of hepatic mTORC2 in vivo. Overnight food withdrawal followed by refeeding was used to activate mTOR signaling. Rapamycin was administered before refeeding to specify mTORC2‐mediated events. Hepatic mTORC2 regulated a complex gene expression and post‐translational network that affects intermediary metabolism, ribosomal biogenesis, and proteasomal biogenesis. Nearly all changes in genes related to intermediary metabolic regulation were replicated in cultured fetal hepatocytes, indicating a cell‐autonomous effect of mTORC2 signaling. Phosphoproteomic profiling identified mTORC2‐related signaling to 144 proteins, among which were metabolic enzymes and regulators. A reduction of p38 MAPK signaling in the RKO mice represents a link between our phosphoproteomic and gene expression results. We conclude that hepatic mTORC2 exerts a broad spectrum of biological effects under physiological conditions. Our findings provide a context for the development of targeted therapies to modulate mTORC2 signaling. —Lamming, D. W. , Demirkan, G. , Boylan, J. M. , Mihaylova, M. M. , Peng, T. , Ferreira, J., Neretti, N. , Salomon, A. , Sabatini, D. M. , Gruppuso, P. A. Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2). FASEB J. 28, 300–315 (2014). www.fasebj. org
PRENATAL DIAGNOSIS OF β-THALASSEMIA MAJOR BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY ANALYSIS OF HEMOGLOBINS IN FETAL BLOOD SAMPLES

In Thailand and adjacent countries, most of the β-thalassemia genes are β0-thalassemia mutations that prevent the production of Hb A. We propose the quantitation of the Hb A fraction in fetal blood in the mid-trimester of pregnancy by automated high performance liquid chromatography as a reasonable prenatal diagnostic method to be applied in areas with limited laboratory facilities. Forty pregnant women at risk of delivering a child with β-thalassemia major were identified using an erythrocyte osmotic fragility test and quantitation of Hb A2. Cordocentesis was performed at the gestational age of 18–22 weeks and fetal blood was analyzed for hemoglobin fractions by automated high performance liquid chromatography. The β-globin gene mutations were characterized by β-globin gene sequencing. The 4 bp deletion at codons 41/42 (−TTCT) was the most frequent of the 40 β-thalassemia mutations observed (20/40 = 50%), followed by the splice site mutation IVS-I-1 (G → T) (7/40 = 17.5%), the nonsense mutation at codon 17 (A → T) (7/40 = 17.5%), the nonsense mutation at codon 35 (C → A) (3/40 = 7.5%), and the β+ -thalassemia promoter mutation at −28 (A → G) (3/40 = 7.5%). High performance liquid chromatography revealed nine fetuses which had only Hb F and no Hb A. All were homozygotes or compound heterozygotes for β0-thalassemia mutations. In the remaining 31 fetuses, a Hb A peak was present in the chromatograms. One fetus with 0.5% Hb A was a compound heterozygote for the −28 (A → G) and codons 41/42 (−TTCT) mutations. In the remaining 30 fetuses, the Hb A values ranged between 0.8 and 7.4%. Twenty of these, with a Hb A concentration of 1.82 ± 0.49% (range 0.8–2.8%), were β-thalassemia heterozygotes. The remaining 10 fetuses had Hb A values of 4.89 ± 1.47% (range 2.9–7.4%) and normal β-globin genes. The absence of Hb A in homozygotes or compound heterozygotes for β0-thalassemia mutations and the presence of measurable amounts of Hb A in heterozygotes and normal homozygotes, permits the diagnosis of fetuses expected to develop postnatal β-thalassemia major.
Evidence Based Health Benefits Management

OBJECTIVE To review how evidence-based principles can be applied to benefit design, specialty network management, and medication therapy management to successfully manage pharmaceutical benefits for patients infected with human immunodeficiency virus (HIV). SUMMARY The most critical barrier to successfully managing HIV disease is suboptimal patient adherence to antiretroviral therapy. Managing HIV infection is unique in that the risk of treatment failure increases remarkably with even relatively minor lapses in patient adherence. The incremental cost of HIV treatment failure has been approximated at $26,000 per patient per year. Treatment failure, of course, also drives mortality related to HIV and acquired immunodeficiency syndrome (AIDS). Benefit design, specialty medication management strategies, and care management programs can be integrated to deliver high-quality, efficient care that optimizes clinical outcomes for populations of HIV-infected individuals. CONCLUSION Managed care programs can be structured to provide HIV care that allows optimal patient adherence and clinical outcomes.
The parkinsonian phenotype of spinocerebellar ataxia type 2.

BACKGROUND We recently reported that spinocerebellar ataxia type 2 (SCA2) caused familial parkinsonism in 2 brothers with predominant symptoms of resting tremor, rigidity, and bradykinesia that responded to levodopa. OBJECTIVE To investigate SCA2 as the possible cause of familial parkinsonism in our series and subsequently to analyze the correlation between the clinical manifestation and CAG repeat size in the ataxin-2 gene product. PATIENTS One hundred thirty patients from 41 families with familial parkinsonism were examined for SCA2. Another 8 patients with the classic ataxic phenotype of SCA2 from 6 families were the control group. DESIGN The length of expanded CAG repeat was analyzed by means of polymerase chain reaction. The clinical data and genetic findings in the parkinsonian phenotype were then compared with those in the ataxic phenotype. RESULTS We found expanded CAG repeats in the ataxin-2 gene product in 7 patients from 4 families with parkin-sonism, which was about 10% of our familial parkinsonism series. The parkinsonian phenotype was characterized by resting tremor, rigidity, and bradykinesia. Only mild dysarthria, ataxic gait, and instability were noted, particularly in the late stage. Patients with the parkinsonian phenotype had an older mean +/- SD age of symptom onset (45.8 +/- 13.9 years) and shorter mean +/- SD abnormal CAG length (36.2 +/- 1.1 repeats) than did those with the ataxic phenotype (26.9 +/- 11.0 years and 43.1 +/- 3.2 repeats). Parkinsonian SCA2 responded well to levodopa. CONCLUSIONS We conclude that SCA2 is a minor cause of familial parkinsonism, particularly in Taiwan. The parkinsonian phenotype is associated predominantly with a shorter abnormal range of CAG repeat lengths and older onset age. Because of the clinical resemblance among familial parkinsonisms, we suggest that SCA2 should be excluded in cases of familial parkinsonism.
The performance of thin film solar cells employing photovoltaic ZnSe/CdTe, CdS/CdTe and ZnTe/CdTe heterojunctions

This paper focuses on the photovoltaic parameters of ZnSe/CdTe, CdS/CdTe, and ZnTe/CdTe thin film heterojunction solar cells. ZnSe/CdTe, CdS/CdTe, and ZnTe/CdTe thin film heterojunction solar cells were fabricated by Close Space Sublimation (CSS) on TCO-coated glass substrates. All types of solar cells were fabricated in a superstrate configuration. The thickness of ZnSe and ZnTe layers was varied in order to adjust the solar cell performance. A similar cadmium chloride solution for the treatment of a CdTe layer with an elevated temperature air annealing of the completed devices before the back contact deposition was applied to ZnSe/CdTe and CdS/CdTe thin film heterojunctions solar cells with exception of ZnTe/CdTe. All cells were characterized through light and dark current density-voltage (J-V) measurements and quantum efficiency (QE) measurements. The saturation current, ideality factor and photovoltaic parameters for all thin film heterojunction solar cells are presented. The investigation at the room temperature under illumination of 100 mW/cm2 through the wide gap components of ZnSe/CdTe, CdS/CdTe, and ZnTe/CdTe heterojunctions showed a value of conversion efficiency (η) of solar energy to electric energy about 4.7%, 9.9%, and 1.3%, respectively. The incorporation of Zn at the ZnSe and CdTe interface doubles the short circuit current density and improves the performance of ZnSe/CdTe thin film heterojunction solar cells.
The effects of high‐intensity interval training on glucose regulation and insulin resistance: a meta‐analysis

The aim of this meta‐analysis was to quantify the effects of high‐intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = −0.49, confidence intervals [CIs] −0.87 to −0.12, P = 0.009; CT: SMD = −0.35, −0.68 to −0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (−0.36 to −0.03, P = 0.021) and body weight decreased by 1.3 kg (−1.9 to −0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (−0.92 mmol L−1, −1.22 to −0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta‐analysis are required to confirm these results.
The involvement of lipid rafts in Alzheimer's disease (Review)

The amyloidogenesis occurring in Alzheimer's disease represents a fundamental membrane-related pathology involving a membrane-bound substrate metabolized by integral membrane proteases (secretases). Thus, the amyloid-β peptide (Aβ), which accumulates extracellularly as plaques in the brains of Alzheimer's disease patients, is derived by sequential proteolytic cleavage of the integral transmembrane amyloid precursor protein (APP). Beta-Secretase or BACE-1 (β-site APP cleaving enzyme) is a transmembrane aspartic protease responsible for the first of these cleavage events, generating the soluble APP ectodomain sAPPβ, and a C-terminal fragment CTFβ. CTFβ is subsequently cleaved by the γ-secretase complex, of which presenilin is the catalytic core, to produce Aβ. A variety of studies indicate that cholesterol is an important factor in the regulation of Aβ production, with high cholesterol levels being linked to increased Aβ generation and deposition. However, the mechanism(s) underlying this effect are unclear at present. Recent evidence suggests that amyloidogenic APP processing may preferentially occur in the cholesterol-rich regions of membranes known as lipid rafts, and that changes in cholesterol levels could exert their effects by altering the distribution of APP-cleaving enzymes within the membrane. Rafts may be involved in the aggregation of Aβ and also in its clearance by amyloid-degrading enzymes such as plasmin or possibly neprilysin (NEP).
Health inequalities in Korea: age- and sex-specific educational differences in the 10 leading causes of death.

BACKGROUND An ideological climate has persisted in Korea that has discouraged public discussion of social inequalities. Thus studies on inequalities in mortality remain undeveloped. This study is to examine age- and cause-specific socioeconomic mortality differentials for both men and women representative of the Korean population. METHODS Using Korea's 1995 Census and 1995-2000 Death Certificate data, age-, sex-, and education-specific mortality rates were measured, after which education-specific rate ratios, and relative indices of inequality were calculated. RESULTS Graded educational differentials in mortality were observed among both sexes with higher mortality rates related to lower educational attainment in most causes of death. However, positive associations were identified between education levels and mortality rates with respect to ischaemic heart disease among older males and breast cancer among older females. The magnitude of educational inequality in mortality was not constant across causes and in some cases differed by sex. CONCLUSIONS The changing relation between educational attainment and mortality rates from ischaemic heart disease and breast cancer likely reflects changes in the social distribution of risk factors that emerged in the process of Korea's rapid economic development. Studies on specific exposures over the life course influencing the occurrence of and survival after specific diseases would help provide a more complete understanding of patterns and trends in socioeconomic mortality differentials in Korea.
Randomized Comparison of a Titanium-Nitride-Oxide–Coated Stent With a Stainless Steel Stent for Coronary Revascularization: The TiNOX Trial

Background—Stent coating with titanium-nitride-oxide has been shown to reduce neointimal hyperplasia in the porcine restenosis model. We designed a prospective, randomized, clinical study to investigate the safety and efficacy of titanium-nitride-oxide–coated stents compared with stainless steel stents. Methods and Results—Ninety-two patients with de novo lesions were randomly assigned to treatment with titanium-nitride-oxide–coated stents (n=45) or stainless steel stents of otherwise identical design (n=47; control). Baseline characteristics were similar in both groups. At 30 days, no stent thromboses or other adverse events had occurred in either group. Quantitative coronary angiography at 6 months revealed lower late loss (0.55±0.63 versus 0.90±0.76 mm, P=0.03) and percent diameter stenosis (26±17% versus 36±24%, P=0.04) in lesions treated with titanium-nitride oxide–coated than in control stents. Binary restenosis was reduced from 33% in the control group to 15% in the titanium-nitride oxide–coated stent group (P=0.07). Intravascular ultrasound studies at 6 months showed smaller neointimal volume in titanium-nitride-oxide–coated stents than in control stents (18±21 versus 48±28 mm3, P<0.0001). Major adverse cardiac events at 6 months were less frequent in titanium-nitride-oxide–coated stents than in control stent–treated patients (7% versus 27%, P=0.02), largely driven by a reduced need for target-lesion revascularization (7% versus 23%, P=0.07). Conclusions—Revascularization with titanium-nitride-oxide–coated stents is safe and effective in patients with de novo native coronary artery lesions. Titanium-nitride-oxide–coated stents reduce restenosis and major adverse cardiac events compared with stainless steel stents of otherwise identical design.
Expression of Cell Cycle–Related Gene Products in Langerhans Cell Histiocytosis

Background The pathogenesis of Langerhans cell histiocytosis (LCH), a disease characterized by an abnormal accumulation of the dendritic Langerhans cells, is still unknown. Based on the monoclonality of the CD1a+ cell and reports of familial clustering, it is hypothesized that a genetic alteration at a cellular level may be causative. This genetic change may have an effect on the cellular mechanisms controlling proliferation and apoptosis. Materials and Methods LCH-lesions were studied for the expression of Ki-67, present in the nucleus of proliferating cells. Furthermore, the expression of cell cycle-related gene products TGF-&bgr; receptor I and II, MDM2, p53, p21, p16, Rb, and Bcl2 were studied. The TGF-&bgr;R genes play a role in tumor suppression, whereas Bcl2 inhibits apoptosis. The remaining genes are part of either the p53-p21 and/or p16-Rb pathways, which induce cell cycle arrest or apoptosis in response to DNA damage. Results In 30 biopsies the diagnosis of LCH could be confirmed on the basis of CD1a positivity (27 bone and 3 skin). All cases showed scattered nuclear-positive staining for the proliferation marker Ki-67. In more than 90% (n ≥27) of these cases, expression of TGF&bgr; receptor I and II, MDM2, p53, p21, p16, Rb, and Bcl2 was detected in lesional LCH cells. The overexpression was in general heterogeneous, ranging from limited focal staining of scattered cells within the lesion to strong diffuse staining. Conclusions These findings suggest that the cellular mechanisms that sense and respond to DNA-damage, namely the p53-p21 pathway and the p16-Rb pathway, are activated. The expression of Ki-67 indicates that the cells in LCH are proliferating. The observed overexpression of Bcl2 may play a role in the activation of p53 and p16 and/or the arrest of apoptosis.
A Long-Distance Translocatable Phloem Protein from Cucumber Forms a Ribonucleoprotein Complex In Vivo with Hop Stunt Viroid RNA

ABSTRACT Viroids are highly structured plant pathogenic RNAs that do not code for any protein, and thus, their long-distance movement within the plant must be mediated by direct interaction with cellular factors, the nature of which is presently unknown. In addition to this type of RNAs, recent evidence indicates that endogenous RNAs move through the phloem acting as macromolecular signals involved in plant defense and development. The form in which these RNA molecules are transported to distal parts of the plant is unclear. Viroids can be a good model system to try to identify translocatable proteins that could assist the vascular movement of RNA molecules. Here, we demonstrate by use of immunoprecipitation experiments, that the phloem protein 2 from cucumber (CsPP2) is able to interact in vivo with a viroid RNA. Intergeneric graft assays revealed that both the CsPP2 and the Hop stunt viroid RNA were translocated to the scion. The translocated viroid is symptomatic in the nonhost scion, indicating that the translocated RNA is functional. The CsPP2 gene was cloned and sequenced. The analysis of its primary structure revealed the existence of a potential double-spaced-RNA-binding motif, previously identified in a set of proteins that bind to highly structured RNAs, which could explain its RNA-binding properties. The possible involvement of this phloem protein in assisting the long-distance movement of the viroid RNA within the plant is discussed.
Insulin-Like Growth Factor-I Induces Oocyte Maturational Competence but Not Meiotic Resumption in White Bass (Morone chrysops) Follicles In Vitro: Evidence for Rapid Evolution of Insulin-Like Growth Factor Action1

Abstract A combination of recombinant human (rh) insulin-like growth factor-I (IGF-I) (25 nM) and the maturation-inducing hormone (MIH), 17,20β,21-trihydroxy-4-pregnen-3-one (20β-S; 72.5 nM), induced germinal vesicle breakdown (GVBD) in ovarian follicles of white bass incubated in vitro, whereas a four times greater concentration of each hormone was ineffective alone. These results indicate that IGF-I induces oocyte maturational competence (OMC) but not meiotic resumption in white bass. Culture medium concentrations of 20β-S remained below detection limits for ovarian fragments incubated with rhIGF-I. Actinomycin D blocked GVBD in response to hCG but not to rhIGF-I plus 20β-S, suggesting that IGF-I requires de novo translation but not transcription to induce OMC. Gap junction uncouplers, 1-octanol and 1-heptanol, and the phosphatidylinositiol 3-kinase (PI 3-K) inhibitors, wortmannin and LY 294002, attenuated hCG-, 20β-S-, and rhIGF-I plus 20β-S-induced GVBD. Although these inhibitors reduced hCG-induced progestin release, PI 3-K inhibitors did not alter MIH synthesis in some incubations and addition of 20β-S to the incubations did not fully overcome the effects of either class of inhibitors, suggesting that decreasing MIH production is not their only inhibitory effect on gonadotropin (GtH) action. Our data suggest that gap junctions and PI 3-K activity are necessary for GtH and IGF-I to induce and maintain OMC in white bass. The induction of OMC but not meiotic resumption by IGF-I in white bass, compared with the induction of meiotic resumption but not OMC by IGF-I discovered in the congeneric striped bass suggests rapid evolution of the reproductive actions of IGF-I among temperate basses (genus Morone).