Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk Factors, Vascular Lesion Distribution, Outcome and Recurrence of Strokes Due to Intracranial Atherosclerosis: One Year Data from Hyderabad Stroke Registry

Background: Intracranial atherosclerotic stenosis (ICAS) is a common cause of ischemic stroke in Asian countries and probably in India. Aim: The aim of this study was to describe the risk factors, distribution of vascular lesions, recurrence and outcome of stroke due to ICAS. Methodology: A total of 100 consecutive patients of ischemic stroke due to ICAS were enrolled prospectively from January 1, 2015, to December 31, 2015, and followed for 1 year for treatment compliance and recurrence. The details about demographics, risk factors, and vascular lesions were noted. Results: There were 68 males and 32 females. Hypertension (HTN), diabetes, alcohol, smoking, hyperlipidemia, and hyperhomocysteinemia was present in 82%, 52%, 34%, 33%, 28%, and 23%, respectively. The number of arteries involved were middle cerebral artery, 53 (37.3%); posterior cerebral artery, 24 (16.9%); internal cerebral artery, 21 (14.8%); vertebral artery, 18 (12.7%); basilar artery, 6 (4.2%); and anterior cerebral artery, 6 (4.2%). Seventeen (17%) patients had a recurrent stroke during 1 year follow-up. The presence of uncontrolled HTN and diabetes mellitus after discharge were significantly associated with stroke recurrence (P < 0.05). The use of dual antiplatelet agents and statins was found to have a significant effect in the prevention of recurrent stroke (P < 0.05). Severe stroke at presentation and presence of hemiparesis were the predictors for unfavorable outcome at 3 months (P < 0.05). Conclusion: Risk factors, distribution of vascular lesions and high recurrence of stroke due to ICAS in this study is similar to that reported from other Asian countries. Aggressive medical management and risk factor control remains the best strategy for preventing recurrence.
Pathogenesis of chronic active Epstein‐Barr virus infection: Is this an infectious disease, lymphoproliferative disorder, or immunodeficiency?

Chronic active Epstein‐Barr virus infection (CAEBV) is characterised by chronic or recurrent infectious mononucleosis‐like symptoms, such as fever, hepatosplenomegaly, persistent hepatitis and extensive lymphadenopathy. Patients with CAEBV have high viral loads in their peripheral blood and/or an unusual pattern of EBV‐related antibodies. This disease is rare but severe with high morbidity and mortality. Nearly three decades have passed since this disease was first identified, and recent advances in technology have increased our understanding of CAEBV pathophysiology. There is accumulating evidence that the clonal expansion of EBV‐infected T or natural killer (NK) cells plays a central role in the pathogenesis of CAEBV. However, it remains unclear whether CAEBV is truly a monoclonal lymphoproliferative disorder. EBV‐infected T or NK cells are able to evade the host cellular immune system due to the limited expression of viral proteins of reduced antigenicity. Recent studies suggest that infection of T or NK cells is a common event during primary EBV infection. A defect or single nucleotide polymorphism in host immune‐modulating genes may allow for the expansion of virus infected cells giving rise to CAEBV. In this review, I summarise our current understanding of the pathogenesis of CAEBV and propose a model of CAEBV pathogenicity. Copyright © 2006 John Wiley & Sons, Ltd.
Social Participation and Cognitive Decline Among Community-dwelling Older Adults: A Community-based Longitudinal Study

Objective To examine whether social participation (SP) by older individuals is associated with cognitive decline (CD). Method Participants were community-dwelling older adults aged 65 or older with both independent activities of daily living and normal cognitive performance at baseline (2,768 men and 3,325 women). CD was evaluated using the Cognitive Performance Scale. Logistic regression analysis stratified by gender was used to examine CD in relation to SP, with nonparticipation as reference. Age, family, body mass index, pensions, comorbidities, medications, alcohol, smoking, depression, self-rated health, and instrumental activities of daily living were used as covariates. Results During the 3-year follow-up, 16.7% of eligible participants reported CD. After covariate adjustments, greater social group participation was associated with CD prevention for women only. Lessened negative CD effects were found in respondents active in these particular types of social outlets: neighborhood associations (odds ratio = 0.81, 95% confidence interval = 0.66-0.99) and local event groups (0.79, 0.63-0.99) for men, and hobby groups (0.70, 0.54-0.91) and volunteer groups (0.66, 0.45-0.96) for women. Discussion Our results suggest that greater social group participation prevents CD in women, while the beneficial effect of each type of SP on cognition differs between genders. Determining which types of social groups are best for community-dwelling older people's participation based on gender may help them maintain their cognitive functioning abilities.
The ocular albinism type 1 (OA1) gene controls melanosome maturation and size.

PURPOSE The authors took advantage of the Oa1 mutant mouse in combination with other albinism mouse models (i.e., Tyrosinase and membrane-associated transporter protein [Matp]) to study the function of Oa1, the gene mutated in ocular albinism type 1, in the RPE during development and after birth. METHODS Enzyme activity and protein localization were analyzed by immunohistochemistry of tyrosinase (Tyr) in Oa1-null mice. Ultrastructural analysis and morphometry were performed by electron microscopy, of the RPE in Oa1-knockout mouse and double-mutant mice of Oa1 with either Tyr or Matp. RESULTS Differently from other albinism models, Tyr activity was not impaired in Oa1-/- eyes. Hypopigmentation of the RPE in Oa1-/- mice is due to a reduced number of melanosomes. Analysis of Oa1-/-;Tyr(c-2J)/Tyr(c-2J) and Oa1-/-;Matp(uw)/Matp(uw) double-knockout mice, which display a block at stages II and III of melanosome maturation, respectively, revealed that Oa1 controls the rate of melanosome biogenesis at early stages of the organellogenesis, whereas the control on the organelle size is exerted at the final stage of melanosome development (stage IV). CONCLUSIONS The findings indicate that Oa1 is involved in the regulation of melanosome maturation at two steps. Acting at early maturation stages, Oa1 controls the abundance of melanosomes in RPE cells. At later stages, Oa1 has a function in the maintenance of a correct melanosomal size. This study helps to define ocular albinism type 1 as a defect in melanosome organellogenesis and not in melanin production.
Phosphodiesterase 4D and heart failure: a cautionary tale

Stimulation of several G-protein-coupled receptors (GPCRs) promotes intracellular production of cyclic adenosine 3′,5′-monophosphate (cAMP) and subsequently activates protein kinase A (PKA). In the heart, β-adrenergic receptor (β-AR) stimulation increases contractile performance and heart rate as part of the ‘fight-or-flight’ stress response. Molecular organisation of PKA-effector association occurs by A kinase anchoring proteins (AKAPs), which target kinase action to specific intracellular sites. Some AKAPs interact directly with specific cAMP-hydrolysing phosphodiesterase (PDE) isoforms allowing for the assembly of multi-protein complexes that create focal points of intracellular cAMP signalling. Certain PDE isoforms co-localise with PKA as part of negative feedback mechanisms which may protect from excess β-AR stimulation of Ca2+ transporters during cardiac excitation–contraction coupling. Pharmacological PDE inhibition increases intracellular cAMP concentrations and augments excitation–contraction coupling in heart failure. However, chronic PDE inhibitor treatment causes severe cardiac side effects and increases mortality. Moreover, cAMP hydrolysing PDE activity was found decreased in heart failure which may contribute to disease progression via chronic PKA-dependent dysregulation of Ca2+ transport proteins. The authors review the contribution of PDE activity in the heart to contractile stress adaptation, the significance of altered cAMP signalling in heart failure, and the effects of PDE inhibition in heart disease.
Evaluation of HIV serial and parallel serologic testing algorithms in Abidjan, Côte d'Ivoire.

OBJECTIVE To evaluate HIV serologic testing algorithms based on a combination of three enzyme linked immunosorbent assays (ELISA) for the confirmation of HIV infection in Abidjan, Côte d'Ivoire, where HIV-2 and HIV-1 non-B subtypes are prevalent. METHODS A total of 1069 human sera with known serologic status, in addition to a seroconversion and low titer antibody panel were initially tested by six ELISA to determine the sensitivity, specificity and delta values of the assays. On the basis of the performance of the assays, three ELISA (Enzygnost, ICE 1.0.2, and Vironostika) were selected for use in a parallel and serial testing algorithm in analyzing 8283 consecutively collected sera. In the parallel testing algorithm, sera concordantly reactive or non-reactive by Enzygnost and ICE 1.0. 2 were considered as true positive or true negative, respectively. In the serial algorithm, sera reactive by Enzygnost were retested by ICE 1.0. 2. Sera with discordant results were tested by Vironostika, and the results was considered definitive. All reactive sera, plus a random sample of negative sera were tested for confirmation by Peptilav. In addition, a random sample of reactive sera was tested by Western blot. RESULTS All ELISA had 100% sensitivity; specificities ranged from 96.8 to 100%. Positive and negative delta values of the ELISA were high (range, 6.89 to 46.07 and -2.05 to -5.75, respectively). Of the 8283 sera, 2054 were considered true positives and were correctly classified by the parallel testing algorithm (sensitivity, 100%). Of the 6229 true negative sera, 6226 were negative by the parallel testing algorithm (specificity, 99.95%). The sensitivity of the serial algorithm was 99.96%, and specificity was 99.95%. None of the 250 concordant ELISA-negative sera in the algorithm that were randomly tested in Peptilav was positive; similarly, all of the 103 concordant ELISA-positive sera were confirmed by Western blot. The three-ELISA algorithm resulted in reagent cost-savings of at least 50% compared with the Peptilav-based algorithm. CONCLUSION These results suggest that a combination of ELISA using different principles or antigens in a serial or parallel algorithm is an efficient and cost-effective alternative to the standard algorithm in areas where HIV-1 and HIV-2 are prevalent.
Isometric and isokinetic muscle strength in the upper extremity can be reliably measured in persons with chronic stroke.

OBJECTIVE To evaluate the test-retest reliability of isometric and isokinetic muscle strength measurements in the upper extremity after stroke. DESIGN A test-retest design. SUBJECTS Forty-five persons with mild to moderate paresis in the upper extremity > 6 months post-stroke. METHODS Isometric arm strength (shoulder abduction, elbow flexion), isokinetic arm strength (elbow extension/flexion) and isometric grip strength were measured with electronic dynamometers. Reliability was evaluated with intra-class correlation coefficients (ICC), changes in the mean, standard error of measurements (SEM) and smallest real differences (SRD). RESULTS Reliability was high (ICCs: 0.92-0.97). The absolute and relative (%) SEM ranged from 2.7 Nm (5.6%) to 3.0 Nm (9.4%) for isometric arm strength, 2.6 Nm (7.4%) to 2.9 Nm (12.6%) for isokinetic arm strength, and 22.3 N (7.6%) to 26.4 N (9.2%) for grip strength. The absolute and relative (%) SRD ranged from 7.5 Nm (15.5%) to 8.4 Nm (26.1%) for isometric arm strength, 7.1 Nm (20.6%) to 8.0 Nm (34.8%) for isokinetic arm strength, and 61.8 N (21.0%) to 73.3 N (25.6%) for grip strength. CONCLUSION Muscle strength in the upper extremity can be reliably measured in persons with chronic stroke. Isometric measurements yield smaller measurement errors than isokinetic measurements and might be preferred, but the choice depends on the research question.
Cognitive dysfunction and health‐related quality of life in long‐term liver transplant survivors

Although several studies have investigated short‐term effects of liver transplantation on cognitive function and health‐related quality of life, there have been no studies looking at long‐term effects. Patients who received a single liver transplant at St James's University Hospital (Leeds, UK) before October 1, 1991, were invited to participate in this cross‐sectional study. Cognitive function was assessed using the Mini‐Mental State Examination, the Rey Auditory Verbal Learning Test, trail‐making tests, the Stroop test, and the Benton Visual Retention Test. Anxiety and depression were documented using the Hospital Anxiety and Depression Scale. Health‐related quality of life was assessed using the EuroQol. Twenty‐five healthy volunteers acted as controls. Thirty‐six patients had undergone transplantation before October 1, 1991. Thirteen patients (36%) had died, 6 patients had received more than one transplant, 2 patients did not speak English, and 3 patients did not want to participate, leaving 12 patients included in the study. Patients scored significantly lower on measures of health‐related quality of life than healthy controls, but there were no differences in levels of anxiety or depression. Patients scored significantly lower than controls across a wide range of cognitive functions, suggesting global cognitive impairment. We show that patients who survive for more than 10 years after liver transplantation have significant cognitive dysfunction and poor health‐related quality of life. Whether these patients never return to normal after transplantation or whether they experience an increased rate of decline in cognitive function and health‐related quality of life is uncertain and requires further study.
Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase (P≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals’ formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher Cmax of 0.74±0.15 µg/mL at a delayed Tmax of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration.
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle

The hepatitis C virus (HCV) life cycle involves multiple steps, but most current drug candidates target only viral replication. The inability to systematically discover inhibitors targeting multiple steps of the HCV life cycle has hampered antiviral development. We present a simple screen for HCV antivirals based on the alleviation of HCV-mediated cytopathic effect in an engineered cell line—n4mBid. This approach obviates the need for a secondary screen to avoid cytotoxic false-positive hits. Application of our screen to 1280 compounds, many in clinical trials or approved for therapeutic use, yielded >200 hits. Of the 55 leading hits, 47 inhibited one or more aspects of the HCV life cycle by >40%. Six compounds blocked HCV entry to levels similar to an antibody (JS-81) targeting the HCV entry receptor CD81. Seven hits inhibited HCV replication and/or infectious virus production by >100-fold, with one (quinidine) inhibiting infectious virus production by 450-fold relative to HCV replication levels. This approach is simple and inexpensive and should enable the rapid discovery of new classes of HCV life cycle inhibitors.
Subtype specificity of the ryanodine receptor for Ca2+ signal amplification in excitation‐contraction coupling.

In excitable cells membrane depolarization is translated into intracellular Ca2+ signals. The ryanodine receptor (RyR) amplifies the Ca2+ signal by releasing Ca2+ from the intracellular Ca2+ store upon receipt of a message from the dihydropyridine receptor (DHPR) on the plasma membrane in striated muscle. There are two distinct mechanisms for the amplification of Ca2+ signalling. In cardiac cells depolarization‐dependent Ca2+ influx through DHPR triggers Ca2+‐induced Ca2+ release via RyR, while in skeletal muscle cells a voltage‐induced change in DHPR is thought to be mechanically transmitted, without a requirement for Ca2+ influx, to RyR to cause it to open. In expression experiments using mutant skeletal myocytes lacking an intrinsic subtype of RyR (RyR‐1), we demonstrate that RyR‐1, but not the cardiac subtype (RyR‐2), is capable of supporting skeletal muscle‐type coupling. Furthermore, when RyR‐2 was expressed in skeletal myocytes, we observed depolarization‐independent spontaneous Ca2+ waves and oscillations, which suggests that RyR‐2 is prone to regenerative Ca2+ release responses. These results demonstrate functional diversity among RyR subtypes and indicate that the subtype of RyR is the key to Ca2+ signal amplification.
Structural Characterization of Amorphous Silicon

The structure of amorphous silicon (a-Si) has attracted wide interest over the recent decades. This substantial interest is twofold. Firstly, a-Si has many, highly significant, technological applications. Secondly, physically it is a fundamentally interesting material which has been regarded as a model system of a covalently bonded continuous random network (CRN). Such a CRN is a random network in which each atom has full four-fold coordination as the only specific structural feature. More recently, improvement of techniques has allowed greater insight into the structural properties of a-Si. Intriguing deviations, not only from the ideal CRN, but especially between different forms of a-Si have been observed. However, to date it remains unclear to what extent the formation method of a-Si influences its structural order. Another critically important parameter in the nature of a-Si is its thermal history. For example, a-Si formed by ion-implantation undergoes structural relaxation – or short-range ordering – upon thermal annealing to a new state that is close to an ideal CRN. It remains unclear however, if other forms of a-Si undergo structural relaxation to the same degree. Thus, despite its widespread use and decades of research, the exact nature of a-Si is still not fully understood and this thesis addresses this topic. Different forms of a-Si was prepared by deposition techniques, rapid quenching from the melt and solid-state amorphization. These different forms were investigated in their as-prepared state as well as in their thermally annealed. A combination of techniques was used, namely nanoindentation, electron-energy-loss spectroscopy, Raman microspectroscopy, electron diffraction and fluctuation electron microscopy. All forms of a-Si were first probed for their uniformity. Films prepared by plasma-enhanced chemical vapour deposition and by rapid quenching from the melt were found to contain voids and nanocrystals which prevented the study of their structural properties. More uniform films prepared by magnetron-sputtering, ion-implantation and the so-called pressure-induced (PI) a-Si however, were studied in depth for their structural properties. Each as-prepared form of a-Si was found to have a unique network with very different structural properties. The magnetron-sputtered a-Si was observed to have significant microstructure. The pure ion-implanted a-Si however, is free of such microstructure although some inhomogeneities are clearly present within the network. Interestingly, PI a-Si possesses very little order on the entire length-scale. Only uniform, pure forms of a-Si without any microstructure undergo structural relaxation upon annealing. In the case of the other forms of a-Si, the presence of voids and nanopores seems to prevent the formation of a more ideal CRN. Intriguingly, for the pure cases however, the structural relaxation results in essentially the same properties for both networks over the entire length-scale. These findings were used to build a framework for the understanding of the…