Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in experimental autoimmune encephalomyelitis

PDE4 inhibition suppresses experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, side effects hinder PDE4 inhibitors clinical use. PDE7 inhibition might constitute an alternative therapeutic strategy, but few data about the anti‐inflammatory potential of PDE7 inhibitors are currently available. We have used the EAE model to perform a comparative evaluation of PDE4 and PDE7 inhibition as strategies for MS treatment.
Drug-Induced Headache: Long-Term Results of Stationary Versus Ambulatory Withdrawal Therapy

Drug-induced headache is a well-known complication of the treatment of primary headache disorders, and its successful management is only possible by withdrawal therapy. However, it is unknown whether ambulatory or stationary withdrawal is the therapy preferred. We conducted a prospective study on the outcome of stationary versus ambulatory withdrawal therapy in patients with drug-induced headache according to the International Headache Society criteria. Out of 257 patients with the diagnosis of drug-induced headache during the study period, 101 patients (41 after ambulatory and 60 after stationary withdrawal therapy) could be followed up for 5.9 ± 4.0 years. The total relapse rate after successful withdrawal therapy was 20.8% (14.6% after ambulatory and 25.0% after stationary withdrawal therapy, p <0.2). The main risk factors for a relapse were male sex (OR=3.9, CI=1.3-11.6), intake of combined analgesic drugs (OR=3.8, CI=1.4-10.3), administration of naturopathy (OR=6.0, CI=1.2-29.3), and a trend to tension-type headache as the primary headache disorder (OR=1.9, CI=0.6-53.0). Our data suggest that neither the method of withdrawal therapy nor the kind of analgesic and other antimigraine drugs has a major impact on the long-term result after successful withdrawal therapy. Patients with risk factors according to our findings should be informed and monitored regularly, and combined drugs should be avoided. Furthermore, our data suggest that there is a need for research on individual psychological and behavioral risk factors for relapse after successful withdrawal therapy in drug-induced headache.
Individual and familial predictors of impairment in childhood anxiety disorders.

OBJECTIVE To determine which correlates of childhood anxiety disorders are predictive of impaired functioning as judged by clinicians. METHOD Seventy-four families of children with anxiety disorders attending a hospital outpatient clinic completed questionnaires measuring child symptoms of anxiety and depression, maternal psychopathology, maternal ratings of child psychopathology, and developmental and environmental difficulties. Clinicians completed the Global Assessment of Functioning (GAF) for each child, and correlations between it and the other measures were ascertained. RESULTS Maternal ratings of child conduct problems, child symptoms of depression, maternal phobic anxiety, developmental difficulties, and psychosocial adversity were significantly correlated with GAF. Results of a multiple regression analysis revealed that these variables accounted for 25% of the variance in GAF scores. The first four variables were significant predictors of impairment in children with phobic disorders. Psychosocial adversity was the only significant predictor of impairment in children with generalized anxiety disorder. CONCLUSIONS In addition to child depression and developmental or psychosocial adversity, impairment in childhood anxiety disorders appears to be related to parental anxiety and behavior management difficulties, particularly in phobic disorders. Addressing the latter factors may enhance treatment efficacy.
Effect of number of fins on input impedance in MIGFET using TCAD simulations

This work analyses the effects of the number of fins and fin structure on the device input impedance (both real part and imaginary part) of multifin double gate fin field effect transistors (DG-FinFET). In order to have fair comparison, when the number of fins increases, the fin height is reduced to have the same drive current (ION). The real part of the input impedance remains unchanged with increase in number of fins, whereas the imaginary part decreases with the number of fins. An empirical model is developed for imaginary part of input impedance in terms of number of fins. Simulation results obtained from TCAD simulator matches well with the model developed.
Investigation of ZVS condition for dual-active-bridge converter using dual-phase-shift modulation

This paper investigates the operation principle of Dual-Active-Bridge (DAB) converter using Dual-Phase-Shift modulation. All eight operation modes are examined in order to find out the limitation for Zero Voltage Switch (ZVS) achievement. Some constraints are established to identify the ZVS region. Simulation results affirm that if the modulation is taken inside the region, lower switching dissipation could be attained. Especially, at the boundary of that region, the switching devices could obtain not only ZVS but also ZCS characteristic.
The Digital Divide and Patient Portals: Internet Access Explained Differences in Patient Portal Use for Secure Messaging by Age, Race, and Income

Background:Online access to health records and the ability to exchange secure messages with physicians can improve patient engagement and outcomes; however, the digital divide could limit access to web-based portals among disadvantaged groups. Objectives:To understand whether sociodemographic differences in patient portal use for secure messaging can be explained by differences in internet access and care preferences. Research Design:Cross-sectional survey to examine the association between patient sociodemographic characteristics and internet access and care preferences; then, the association between sociodemographic characteristics and secure message use with and without adjusting for internet access and care preference. Subjects:One thousand forty-one patients with chronic conditions in a large integrated health care delivery system (76% response rate). Measures:Internet access, portal use for secure messaging, preference for in-person or online care, and sociodemographic and health characteristics. Results:Internet access and preference mediated some of the differences in secure message use by age, race, and income. For example, using own computer to access the internet explained 52% of the association between race and secure message use and 60% of the association between income and use (Sobel-Goodman mediation test, P<0.001 for both). Education and sex-related differences in portal use remained statistically significant when controlling for internet access and preference. Conclusions:As the availability and use of patient portals increase, it is important to understand which patients have limited access and the barriers they may face. Improving internet access and making portals available across multiple platforms, including mobile, may reduce some disparities in secure message use.
EEG–fMRI Bayesian framework for neural activity estimation: a simulation study

Objective. Due to the complementary nature of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), and given the possibility of simultaneous acquisition, the joint data analysis can afford a better understanding of the underlying neural activity estimation. In this simulation study we want to show the benefit of the joint EEG–fMRI neural activity estimation in a Bayesian framework. Approach. We built a dynamic Bayesian framework in order to perform joint EEG–fMRI neural activity time course estimation. The neural activity is originated by a given brain area and detected by means of both measurement techniques. We have chosen a resting state neural activity situation to address the worst case in terms of the signal-to-noise ratio. To infer information by EEG and fMRI concurrently we used a tool belonging to the sequential Monte Carlo (SMC) methods: the particle filter (PF). Main results. First, despite a high computational cost, we showed the feasibility of such an approach. Second, we obtained an improvement in neural activity reconstruction when using both EEG and fMRI measurements. Significance. The proposed simulation shows the improvements in neural activity reconstruction with EEG–fMRI simultaneous data. The application of such an approach to real data allows a better comprehension of the neural dynamics.
Discontinuation of and changes in treatment after start of new courses of antihypertensive drugs: a study of a United Kingdom population

Abstract Objective: To evaluate the incidence of discontinuation of and changes in treatment after newly prescribed courses of antihypertensive drugs of the four primary therapeutic classes: ß blocker, calcium channel blocker, and angiotensin converting enzyme inhibitor. Design: A retrospective analysis of patients on an automated database of 1.2 million patients was conducted on visits between 1 October 1992 and 30 September 1993. Setting: General practices in the United Kingdom. Subjects: 37643 patients with hypertension receiving a relevant drug in the time period were identified. A new course of treatment in at least one of the four therapeutic classes, defined as a drug not prescribed in the previous four months, was observed in 10222 patients aged >/=40 years. Main outcome measures: Patients changing to other treatment or discontinuing after initiating a new course of treatment, defined as the absence of a refill prescription for the new drug or another in its category within a six month observation period. Results: Changes in or discontinuation of treatment were frequently observed, and by month six continuation rates ranged between 40% to 50% for all four classes of drugs. Conclusion: Low rates of continuation with a newly prescribed antihypertensive drug exist regardless of which drug is prescribed.
Caspase-12 and Caspase-4 Are Not Required for Caspase-dependent Endoplasmic Reticulum Stress-induced Apoptosis*

Alterations in cellular homeostasis that affect protein folding in the endoplasmic reticulum (ER) trigger a signaling pathway known as the unfolded protein response (UPR). The initially cytoprotective UPR will trigger an apoptotic cascade if the cellular insult is not corrected; however, the proteins required to initiate this cell death pathway are poorly understood. In this study, we show that UPR gene expression is induced in cells treated with ER stress agents in the presence or absence of murine caspase-12 or human caspase-4 expression and in cells that overexpress Bcl-xL or a dominant negative caspase-9. We further demonstrate that ER stress-induced apoptosis is a caspase-dependent process that does not require the expression of caspase-12 or caspase-4 but can be inhibited by overexpression of Bcl-xL or a dominant negative caspase-9. Additionally, treatment of human and murine cells with ER stress agents led to the cleavage of the caspase-4 fluorogenic substrate, LEVD-7-amino-4-trifluoromethylcoumarin, in the presence or absence of caspase-12 or caspase-4 expression, whereas Bcl-xL or a dominant negative caspase-9 overexpression inhibited LEVD-7-amino-4-trifluoromethylcoumarin cleavage. These data suggest that caspase-12 and caspase-4 are not required for the induction of ER stress-induced apoptosis and that caspase-4-like activity is not always associated with an initiating event.
Understanding Role of Market-orientated IT Competence and Knowledge Sharing Mechanism in Gaining Competitive Advantage

Contemporary research on start-up firms primarily focuses on business ecosystem and assessing its contribution into the mainstream business economies. Research featuring investments in information technology (IT) and market-oriented IT (MOIT) competence to facilitate the flow of firm innovativeness (FI) across multisectoral start-ups is yet to be identified. Further, the role of innovation orientation (IO)-enabled firm innovativeness (FI) on sustainable competitive advantage (SCA) needs further exploration in the light of customer orientation (CO) of the enterprise. It is partially because the underlying mechanism remains largely unexplored in the context of rippling start-ups. In the current research, we conceptualized and tested a model that examines the role of MOIT competence and knowledge sharing mechanism (KSM) on FI and SCA, in the light of Resource Advantage (R-A) theory and SD logic (SDL) framework. This model also proposes and establishes IO as an important enabler for firm’s competitive advantage. Using a sample of 267 start-up ventures registered under Start-up India Programme (DIPP, Ministry of Commerce and Industry, Government of India), we tested above-mentioned relationship using SPSS AMOS 22. Results show that MOIT competence is an important enabler for FI and in turn SCA of the firm. CO strongly moderates the role of IO on firm’s competitive advantage.
Robust speaker localization in a disturbance noise environment using a distributed microphone system

Ambient noises and room reverberations seriously degrade the accuracy of speaker localization in real environments. In this paper we describe the localization of a speaker supposing that the speaker utters under a disturbance noise with large amplitude. Our algorithm localizes a sound source by finding the position that maximizes the accumulated correlation coefficient between multiple channel pairs. After the estimation of the first sound source, a typical pattern of the accumulated correlation for a single sound source is subtracted from the observed distribution of the accumulated correlation. Subsequently, the second sound source is searched again. To evaluate the effectiveness of the proposed method, experiments of speaker localization were carried out in an actual office room. The result shows that average error distances of the multiple sound sources are less than 10cm.
Sweetened Beverages Excise Tax Passthrough Rates: A Case Study in Philadelphia

ABSTRACT A 1.5 cent per ounce excise tax was implemented on all sweetened beverages (SBs) in Philadelphia County on January 1, 2017 at the distributor level. As the tax is on the distributor, retailers must determine the passthrough rate of this tax to the shelf price for SBs as well as determine the prices for SB substitutes. This paper investigates the pricing of SBs and their substitutes at retailers both inside and outside of Philadelphia County. Results suggest a 100% excise tax passthrough rate on SBs with almost no price change on substitute products.
Characterization of red wines from South America based on sensory properties and antioxidant activity.

BACKGROUND It is widely accepted that red wines constitute one of the most important sources of dietary polyphenolic antioxidants. However, it is still not known how some variables such as variety, vintage, country of origin, and retail price are associated with the antioxidant activity and sensory profile of South American red wines. In this regard, 80 samples produced in Brazil, Chile and Argentina were assessed in relation to their sensory properties, color and in vitro antioxidant activity, and results were subjected to multivariate statistical techniques. RESULTS Samples were grouped in clusters, characterized by high, intermediate and low in vitro antioxidant activity, sensory properties and prices. It was possible to observe that wines with high antioxidant activity were associated to high retail prices and overall perception of sensory quality. CONCLUSION South American wines produced from Vitis vinifera such as Syrah, Malbec and Cabernet Sauvignon had higher in vitro antioxidant activity and also higher sensory quality than wines produced from Vitis labrusca. This result was independent of vintage (2002-2010), corroborating the idea that the same grape varietal, even when produced in different years, displays similar sensory characteristics and antioxidant activity.
Comparison of Opioid Prescribing Patterns in the United States and Japan: Primary Care Physicians' Attitudes and Perceptions

Introduction: Far fewer opioids are prescribed in Japan than in the United States. Methods: We conducted an online physician survey assessing attitudes and perceptions that might influence prescribing. A Japanese version was distributed to members of the Japan Primary Care Association and an English version to members of the American Academy of Family Physicians practicing in Oregon. Results: We received 461 Japanese responses and 198 from the United States, though overall response rates were low (Japan: 10.1%, United States: 18.5%). Japanese respondents reported far less opioid prescribing than US respondents, especially for acute pain (acute pain: 49.4% vs 97.0%; chronic pain: 63.7% vs 90.9%; P < .001 for both). Almost half of respondents from both countries indicated that patient expectations and satisfaction were important factors that influence prescribing. US respondents were significantly more likely to identify medical indication and legal expectation as reasons to prescribe opioids for acute pain. Most US respondents (95.4%) thought opioids were used too often, versus 6.6% of Japanese respondents. Conclusions: Lower opioid use was reported in Japan, especially for acute pain, which may help minimize long-term use. Patient expectations and satisfaction seem to influence opioid prescribing in both countries. The United States could learn from Japanese regulatory and cultural perspectives.
Gaining comprehensive data about sexual knowledge through surveys

Background: Delivery of sexual health services rely on rigorous facts extracted from surveys, but often those facts cannot be available due to the lack of culturally-sensitive questionnaires. Objective: our aim was to show the validity and reliability of the Persian version of the Acquisition of Sexual Information Test (ASIT), a measure selected due to its assemblages with Iranian culture. Materials and Methods: Forward-backward procedure was applied to translate the questionnaire. Cross-sectional study was carried out and psychometric properties of the Iranian version were tested in a thirty sample of reproductive-age women. Face validity was assessed by qualitative and quantitative methods. Content validity was also assessed by calculating two quantitative indicators as content validity index (CVI) and content validity ratio (CVR). Reliability was assessed by test-retest analyses. Results: Impact score was 1.5, the majority of participants (83.3%) stated that the overall level of questionnaire was high but some of the questions were irrelevant to sexual knowledge. Many questions (90%) gained a CVR less than 0.56, and all of them gained CVIs lower than 0.7. Correlation in test-retest reliability was 0.85. Conclusion: sexual knowledge questionnaire seems to be culturally inappropriate for Iranian women. Although, we need survey data for assessing the evidence-based needs for sexual health and best practice, but the questions addressing various dimensions of sexuality must be culturally sensitive, comprehensive and appropriate. Our findings suggest that ASIT as a well-known measure should be used in Iranian population with caution.
Hospital Center Effect for Laparoscopic Colectomy Among Elderly Stage I-III Colon Cancer Patients

Objective:To investigate hospital-level variation in short-term laparoscopic colectomy outcomes among stage I-III elderly colon cancer patients. Background:Surgical outcomes are associated with patient and surgeon characteristics. If outcomes are also impacted by the hospital where the surgery occurs, there is a hospital center effect (HCE). Methods:Surveillance, Epidemiology, and End Results (SEER)-Medicare data was used to identify stage I-III colon cancer patients treated with laparoscopic colectomies. Multilevel regressions were utilized to study potential HCE for length of stay (LOS), 30-day rehospitalization, and in-hospital mortality, adjusting for patient, surgeon, and hospital-level characteristics. To quantify HCE, we calculated the median instantaneous rate ratio (MIRR) for LOS and median odds ratio (MOR) for in-hospital mortality and 30-day rehospitalization. Sensitivity analyses were conducted for high volume/medical school affiliated hospitals and colorectal surgeons. Results:The multilevel analyses based on 4617 patients from 465 hospitals documented statistically significant HCEs for LOS (MIRR = 1.35; P < 0.001) and in-hospital mortality (MOR = 1.69; P = 0.032), but no HCE for 30-day rehospitalization. Sensitivity analyses confirmed our findings. HCE was significant for LOS in all sensitivity analyses and was significant for in-hospital mortality for high volume/medical school affiliated hospitals. Conclusions:HCE exists for LOS and in-hospital mortality of laparoscopic colectomy, which suggests that the choice of hospital affects outcomes independently of other confounding variables. Reducing the variation in outcomes associated with HCE may improve the quality of cancer care.
Interferon-Stimulated Poly(ADP-Ribose) Polymerases Are Potent Inhibitors of Cellular Translation and Virus Replication

ABSTRACT The innate immune response is the first line of defense against most viral infections. Its activation promotes cell signaling, which reduces virus replication in infected cells and leads to induction of the antiviral state in yet-uninfected cells. This inhibition of virus replication is a result of the activation of a very broad spectrum of specific cellular genes, with each of their products usually making a small but detectable contribution to the overall antiviral state. The lack of a strong, dominant function for each gene product and the ability of many viruses to interfere with the development of the antiviral response strongly complicate identification of the antiviral activity of the activated individual cellular genes. However, we have previously developed and applied a new experimental system which allows us to define a critical function of some members of the poly(ADP-ribose) polymerase (PARP) family in clearance of Venezuelan equine encephalitis virus mutants from infected cells. In this new study, we demonstrate that PARP7, PARP10, and the long isoform of PARP12 (PARP12L) function as important and very potent regulators of cellular translation and virus replication. The translation inhibition and antiviral effect of PARP12L appear to be mediated by more than one protein function and are a result of its direct binding to polysomes, complex formation with cellular RNAs (which is determined by both putative RNA-binding and PARP domains), and catalytic activity. IMPORTANCE The results of this study demonstrate that interferon-stimulated gene products PARP7, PARP10, and PARP12L are potent inhibitors of the replication of Venezuelan equine encephalitis virus and other alphaviruses. The inhibitory functions are determined by more than a single mechanism, and one of them is based on the ability of these proteins to regulate cellular translation. Interference with the cellular translational machinery depends on the integrity of both the amino-terminal domain, containing a number of putative RNA-binding motifs, and the catalytic function of the carboxy-terminal PARP domain. The PARP-induced changes in translation efficiency appear to have a more potent effect on the synthesis of virus-specific proteins than on that of cellular proteins, thus making PARP-specific translational downregulation an important contributor to the overall development of the antiviral response.