Miracle-dz/UniFAR-FTUs huggingface dataset:
Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid β‐Peptide Toxicity in Hippocampal Neurons

Abstract: Steroid hormones, particularly estrogens and glucocorticoids, may play roles in the pathogenesis of neurodegenerative disorders, but their mechanisms of action are not known. We report that estrogens protect cultured hippocampal neurons against glutamate toxicity, glucose deprivation, FeSO4 toxicity, and amyloid β‐peptide (Aβ) toxicity. The toxicity of each insult was significantly attenuated in cultures pretreated for 2 h with 100 nM‐10 µM 17β‐estradiol, estriol, or progesterone. In contrast, corticosterone exacerbated neuronal injury induced by glutamate, FeSO4, and Aβ. Several other steroids, including testosterone, aldosterone, and vitamin D, had no effect on neuronal vulnerability to the different insults. The protective actions of estrogens and progesterone were not blocked by actinomycin D or cycloheximide. Lipid peroxidation induced by FeSO4 and Aβ was significantly attenuated in neurons and isolated membranes pretreated with estrogens and progesterone, suggesting that these steroids possess antioxidant activities. Estrogens and progesterone also attenuated Aβ‐ and glutamate‐induced elevation of intracellular free Ca2+ concentrations. We conclude that estrogens, progesterone, and corticosterone can directly affect neuronal vulnerability to excitotoxic, metabolic, and oxidative insults, suggesting roles for these steroids in several different neurodegenerative disorders.
Pharmacological studies of ethanolic extracts of Maytenus rigida Mart (Celastraceae) in animal models

The crude ethanol extract (EEOH) of the bark of Maytenus rigida Mart (Celastraceae) a plant used in Brazil herbal traditional medicine, was tested for anti-inflammatory, antiulcer and antidiarrhoeal activities in animal models. No acute toxicological sign was observed in animals treated with the highest dose (5000 mg/kg, p.o. or 2000 mg/kg i.p.) of EEOH. The extract doses of 250, 500 or 750 mg/kg revealed a significant inhibitory effect (P < 0,01) in carrageenin-induced rat paw oedema and exhibited ulcer-protective properties against ethanol-induced ulceration in rats. An anti-diarrhoeal activity (P < 0.01) was also observed in castor-oil-induced diarrhoeal in mice. The intestinal transit was significantly (P < 0.01) reduced, however the pretreatment did not reduce the weight of intestinal contents. These results support the popular applications of Maytenus rigida for the treatment of inflammation, ulcer and diarrhoea in Brazil herbal traditional medicine.
'Got to Be in it to Win It': Impact of Individual Risk Aversion on Ability to Monetize Profitable Investment Opportunities

This research note is inspired by a simple but illuminating behavioural finance experiment by Victor Haghani and Richard Dewey, built around flipping for profit an unfair coin with known heads/tails probabilities. Using this elementary framework with fully known game parameters and well-understood win/loss probabilities the paper shows that our ability to take advantage of this clearly profitable opportunity greatly depends on our attitude to risk, our outside financial resources as well as on financial strength of “the house” (i.e. the game organizer). The paper then generalizes this intuition for real-life situations and suggests ways to improve our ability to profit from risky investment opportunities.
Dexamphetamine Improves Upper Extremity Outcome During Rehabilitation After Stroke

Background. For early inpatient stroke rehabilitation, the effectiveness of amphetamine combined with physiotherapy varies across studies. Objective. To investigate whether the recovery of activities of daily living (ADL, primary outcome) and motor function (secondary outcome) can be improved by dexamphetamine added to physiotherapy. Methods. In a double-blind, placebo-controlled trial, 16 patients, from 918 who were screened, were randomized to the experimental group (EG, dexamphetamine + physiotherapy) or control group (CG, placebo + physiotherapy). Both groups received multidisciplinary inpatient rehabilitation. Dexamphetamine (10 mg oral) or placebo was administered 2 days per week before physiotherapy. ADL and motor function were measured using the Chedoke–McMaster Stroke Assessment (CMSA) twice during baseline, every week during the 5-week treatment period, and at follow-up 1 week, 6 months, and 12 months after intervention. Results. The majority of ineligible patients had too little paresis, were on anticoagulants, or had a stroke >60 days prior to entry. Participants (EG, n = 7, age 70.3 ± 10 years, 5 women, 37.9 ± 9 days after stroke; CG, n = 9, age 65.2 ± 17 years, 3 women, 40.3 ± 9 days after stroke) did not differ at baseline except for the leg subscale. Analysis of variance from baseline to 1 week follow-up revealed significant improvements in favor of EG for subscales ADL (P = .023) and arm function (P = .020) at end of treatment. No adverse events were detected. Conclusion. In this small trial that was based on prior positive trials, significant gains in ADL and arm function suggest that the dose and timing of dexamphetamine can augment physiotherapy. Effect size calculation suggests inclusion of at least 25 patients per group in future studies (ClinicalTrials.gov number: NCT00572767).
Association among individual deprivation, glycemic control, and diabetes complications: the EPICES score.

OBJECTIVE Previous studies have related poor glycemic control and/or some diabetes complications to low socioeconomic status. Some aspects of socioeconomic status have not been assessed in these studies. In the present study, we used an individual index of deprivation, the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé (Evaluation of Precarity and Inequalities in Health Examination Centers [EPICES]) score, to determine the relationship among glycemic control, diabetes complications, and individual conditions of deprivation. RESEARCH DESIGN AND METHODS We conducted a cross-sectional prevalence study in 135 consecutive diabetic patients (age 59.41 +/- 13.2 years [mean +/- SD]) admitted in the hospitalization unit of a French endocrine department. Individual deprivation was assessed by the EPICES score, calculated from 11 socioeconomic questions. Glycemic control, lipid levels, blood pressure, retinopathy, neuropathy, and nephropathy were assessed. RESULTS HbA(1c) level was significantly correlated with the EPICES score (r = 0.366, P < 0.001). The more deprived patients were more likely than the less deprived patients to have poor glycemic control (beta = 1.984 [SE 0.477], P < 0.001), neuropathy (odds ratio 2.39 [95% CI 1.05-5.43], P = 0.037), retinopathy (3.66 [1.39-9.64], P = 0.009), and being less often admitted for 1-day hospitalization (0.32 [0.14-0.74], P = 0.008). No significant relationship was observed with either nephropathy or cardiovascular risk factors. CONCLUSIONS Deprivation status is associated with poor metabolic control and more frequent microvascular complications, i.e., retinopathy and neuropathy. The medical and economic burden of deprived patients is high.
Upper Eyelid Blepharoplasty: Evaluation, Treatment, and Complication Minimization

Abstract Upper eyelid blepharoplasty is one of the most common procedures performed worldwide for both functional and cosmetic indications. There is a high rate of patient satisfaction; however, in this era of social media, patient expectations are higher than ever. Today's digitally savvy patients expect perfect outcomes with no complications and rapid recovery. To achieve optimal results, a careful preoperative evaluation and sound surgical technique is essential for minimizing complications. Here the authors review their approach to the management of the blepharoplasty patient.
An efficient spectrum mobility management strategy in cognitive radio networks

In this paper, we propose to design a spectrum mobility strategy using Fuzzy Logic System for cognitive radio networks (CRN). The proposed strategy enables cognitive radios (CR) to vacate the spectrum if primary user (PU) needs it back or to adjust its transmit power in order to avoid interference with PU or nearby CR. Using our scheme, CR switches between the bands only if it is not able to modify its transmit power within the tolerable interference limits. Thus, our work is divided in two modules, one with the priority to control CR transmit power within tolerable range and second to switch to another frequency band in order to avoid interference. Simulated results show that using our proposed fuzzy power control scheme, we can decrease transmit power consumption and achieve lower number of spectrum handovers.
Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.

BACKGROUND In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. METHODS We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. RESULTS A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P=0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. CONCLUSIONS Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response. (Funded by AbbVie; SAPPHIRE-II ClinicalTrials.gov number, NCT01715415.).
Water balance in embryos of Fundulus heteroclitus and F. bermudae in seawater.

The purpose of this study is to examine the mechanisms of osmoregulation in embryos of Fundulus heteroclitus and F. bermudae. The turnover rate of tritiated water in intact embryos of F. heteroclitus increases from 0.05 to 0.013 h-1 at 4 days to 0.12 +/- 0.030 h-1 at 7 days and to 0.18 +/- 0.060 h-1 at 10 days, corresponding to estimated diffusional water permeabilities of 0.4, 1.0, and 1.6 x 10(-6) cm . s-1, respectively. These values are low when compared to other organisms but not sufficiently low to maintain embryos in water balance. The osmolality of the embryonic extracellular fluids decreases during development from 362 +/- 9.2 mosmol . kg-1 at 4 days to 344 +/- 6.9 mosmol . kg-1 at 10 days. Water loss is balanced by drinking seawater at a rate of 600 pl . mg-1 . h-1 for 7- to 8-day embryos. The embryo possesses a pair of branchial chambers that communicate anteriorly with the pharynx through embryonic gill slits and posteriorly with the perivitelline space by means of pores. In the absence of a mouth it is probably through these pores that seawater is injested.
Inhibitory effect of E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil on herpes simplex virus replication and DNA synthesis

The effect of E-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) on herpes simplex virus (HSV) replication was examined and compared with that of E-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd). The 50% inhibitory dose against HSV type 1 (HSV-1) was 0.1 microgram/ml compared with 0.008 microgram/ml for BVdUrd; the antimetabolic 50% inhibitory dose of BVaraU ranged from 20 to 95 micrograms/ml. The addition of 50 micrograms of BVaraU per ml to HSV-1-infected Vero cells decreased the synthesis of viral and cellular DNA by 37 and 28%, respectively. The 5'-triphosphate (BVaraUTP) competed with dTTP in DNA synthesis by the herpes-viral and cellular DNA polymerases; the apparent Ki values of HSV-1 DNA polymerase, DNA polymerase alpha, and DNA polymerase beta were 0.14, 0.32, and 5 microM, respectively. Thus, BVaraU was a less effective antiherpesvirus agent than BVdUrd; unlike BVdUrd, it did not appear to be internally incorporated into replicating DNA in virus-infected cells.
Shear stress is associated with markers of plaque vulnerability and MMP-9 activity.

BACKGROUND Vulnerable plaque has been associated with local macrophage accumulation and local high matrix metalloproteinase-2 (MMP-2) and MMP-9 activity. Since shear stress is a known local modulator of plaque location, we have determined whether local shear stress was associated with local plaque composition and with local MMP activity. METHODS AND RESULTS In 17 NZW rabbits plaque was generated by denudation of the infrarenal aorta over a region of 5 cm and feeding them a high cholesterol diet for 2 months. After 2 months, a motorised IVUS pullback of the infrarenal aorta was performed with a 40 MHz IVUS catheter (CVIS, Boston Scientific, USA). IVUS derived vessel wall-lumen contours were reconstructed in 3D with in-house developed software. These reconstructions served as an input for a computational fluid dynamics technique, from which the 3-D shear stress field was calculated. Plaque regions were divided in 5 regions (n=8) to identify the location of highest macrophage accumulation or selected on basis of shear stress to identify whether high shear stress selects macrophage accumulation (n=8). In a second series, shear stress values were used to select regions -containing both latent and active MMP-2 and MMP-9. Segments were sectioned with a microtome and stained for smooth muscle cells (SMC), macrophages (MPhi) and collagen (COL). MPhi, displayed the highest density upstream of the plaque (6.9+/-2.4%, p<0.05), while SMC accumulated downstream (74.8+/-1.9%) of the plaque. High shear stress was associated with MPhi accumulation and MMP-9 activity (p<0.05). CONCLUSION Upstream location of macrophages in plaques is associated with high shear stress and MMP-9 accumulation. These findings are discussed in relation to rheological theories reported previously in atherosclerosis.
Single nucleotide polymorphism at exon 7 splice acceptor site of OAS1 gene determines response of hepatitis C virus patients to interferon therapy

Background and Aim: Response to interferon therapy and disease progression in hepatitis C virus (HCV) infected patients differs among individuals, suggesting a possibility of a contribution of host genetic factors. 2′‐5′‐oligoadenylate synthetase 1 (OAS1), an important component of the innate immune system with a proven antiviral function, may therefore have a relationship with the response to interferon therapy and clinical course of HCV disease. Our aim was to determine the frequency of single nucleotide polymorphism (SNP) at exon 7 splice acceptor site (SAS) of the OAS1 gene in relation to the interferon response and status of HCV infection.
Proposal of two-stage patent retrieval method considering the claim structure

The importance of patents is increasing in global society. In preparing a patent application, it is essential to search for related patents that may invalidate the invention. However, it is time-consuming to identify them among the millions of patents. This article proposes a patent-retrieval method that considers a claim structure for a more accurate search for invalidity. This method uses a claim text as input; it consists of two retrieval stages. In stage 1, general text analysis and retrieval methods are applied to improve recall. In stage 2, the top N documents retrieved in stage 1 are rearranged to improve precision by applying text analysis and retrieval methods using the claim structure. Our two-stage retrieval introduces five precision-oriented analysis and retrieval methods: query-term extraction from a portion of a claim text that describes the characteristics of a claim; query term-weighting without term frequency; query term-weighting with “measurement terms”; text retrieval using only claims as a target; and calculating the relevant score by “partially” adding scores in stage 2 to those in stage 1. Evaluation results using test sets of the NTCIR4 Patent Retrieval Task show that our methods are effective, though the degree of the effectiveness varies depending on the test sets.
Neuromuscular blockers in early acute respiratory distress syndrome.

BACKGROUND In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. METHODS In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)
Atomic Resolution X-ray Structure of the Substrate Recognition Domain of Higher Plant Ribulose-bisphosphate Carboxylase/Oxygenase (Rubisco) Activase*

Background: Rubisco activase has been linked to the inhibition of net photosynthesis upon warming. Results: The structure of the C-terminal domain adopts an unusually elongated shape. Conclusions: Reactivation of Rubisco may involve movement of a paddle-like extension. Significance: This work will aid in gaining a better understanding of Rubisco regulation. The rapid release of tight-binding inhibitors from dead-end ribulose-bisphosphate carboxylase/oxygenase (Rubisco) complexes requires the activity of Rubisco activase, an AAA+ ATPase that utilizes chemo-mechanical energy to catalyze the reactivation of Rubisco. Activase is thought to play a central role in coordinating the rate of CO2 fixation with the light reactions of photosynthesis. Here, we present a 1.9 Å crystal structure of the C-domain core of creosote activase. The fold consists of a canonical four-helix bundle, from which a paddle-like extension protrudes that entails a nine-turn helix lined by an irregularly structured peptide strand. The residues Lys-313 and Val-316 involved in the species-specific recognition of Rubisco are located near the tip of the paddle. An ionic bond between Lys-313 and Glu-309 appears to stabilize the glycine-rich end of the helix. Structural superpositions onto the distant homolog FtsH imply that the paddles extend away from the hexameric toroid in a fan-like fashion, such that the hydrophobic sides of each blade bearing Trp-302 are facing inward and the polar sides bearing Lys-313 and Val-316 are facing outward. Therefore, we speculate that upon binding, the activase paddles embrace the Rubisco cylinder by placing their hydrophobic patches near the partner protein. This model suggests that conformational adjustments at the remote end of the paddle may relate to selectivity in recognition, rather than specific ionic contacts involving Lys-313. Additionally, the superpositions predict that the catalytically critical Arg-293 does not interact with the bound nucleotide. Hypothetical ring-ring stacking and peptide threading models for Rubisco reactivation are briefly discussed.
[Prescription of non-steroidal anti-inflammatory drugs].

Non steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and largely used over the counter, especially for analgesic purposes in the most commonly nociceptive painful disorders. Unfortunately, NSAID use is associated with a high rate of side effects which account for 9% to 25% of the reports to the drug surveillance centres all over the world. Interestingly, severe adverse events are partly preventable provided some recommendations are followed. First, individual risk factors (old age, gastrointestinal history, possible drug interaction, .) should be carefully assessed in order to take particular preventive measures (coprescription of misoprostol or omeprazole, treatment of a preexisting dehydration, .) or ensure specific monitoring. Second, NSAIDs should be used at the lowest effective dosage after consideration of safer alternatives. Third, NSAIDs should be combined with other analgesics with the aim of reducing NSAID dosage. Finally, the patients should be informed about the main side effects of NSAIDs.