Miracle-dz/UniFAR-FTUs huggingface dataset:
The discovery and development of romidepsin for the treatment of T-cell lymphoma

ABSTRACT Introduction: Romidepsin is a potent and selective inhibitor of histone deacetylases (HDCAi). It is also the only bicyclic inhibitor to undergo clinical assessment and is considered a promising drug for the treatment of T-cell lymphomas. The cellular action of romidepsin results in enhanced histone acetylation, as well as the acetylation of other nuclear or cytoplasmic proteins, influencing cell cycle, apoptosis, and angiogenesis. In phase II studies involving patients with relapsed or refractory of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), romidepsin produced overall response rates (ORR) of 34–35% and 25–38%, with complete response (CR) rates of 6% and 15–18%, respectively. Areas covered: This review summarizes the development of romidepsin, the mechanisms behind its antineoplastic action and its pharmacology. It also covers its pharmacokinetic and pharmacodynamic properties, as well as the preclinical and clinical data on its activity in T-cell lymphoma. Expert opinion: Since there are only few effective therapies available for T-cell lymphomas, romidepsin is a valuable option for relapsed/refractory patients with both CTCL and PTCL. It’s also generally well tolerated, and gives potentially durable responses for patients with advanced and symptomatic disease. Combinations of romidepsin with other antineoplastic agents may also further improve drug response and outcomes in T-cell lymphoma.
Gender-dependent associations between socioeconomic status and tooth loss in working age people in the Study of Health in Pomerania (SHIP), Germany.

OBJECTIVES Individual impact and the effect magnitude of socioeconomic key indicators (income, education and occupation) and of gender on oral health are ambiguous. In primary analyses of cross-sectional data among participants of the Study of Health in Pomerania (north-east Germany), women with low school education and low income were at highest risk for missing teeth, whereas being single was a risk indicator for missing teeth in men. Using the 5-year follow-up of this study, we aimed at verifying these findings and at investigating the gender-dependent impact of key socioeconomic indicators on tooth loss. METHODS The longitudinal data originate from 1971 subjects (1062 women) aged 25-59 enrolled from 1997 to 2001 and again from 2002 to 2006. The effects of marital status, household income, school education and occupational prestige for tooth loss were examined by gender using negative binomial regression analyses. RESULTS Low education and low income were moderately [relative risks (RR) between 1.6 and 2.0] associated with tooth loss among both women and men, whereas occupational prestige was not. After multiple imputations of missing data, less-educated women with lower income exhibited the highest risk of tooth loss [RR=3.1; 95% confidence interval (CI)=1.7-5.5 for <10 years of school education and the lowest income tertile] and tooth loss was more likely in single men (RR=1.5; 95% CI=1.0-2.2) than in single women (RR=0.9; 95% CI=0.6-1.3). CONCLUSIONS The primary cross-sectional results were partly confirmed. Socioeconomic factors help to explain differences in tooth loss, although the causal pathways are speculative. To improve dental health, the policies should target not only the individual, e.g. oral health promotion, but also an entire population by better education and higher wage employment.
An LMS Programming Scheme and Floating-Gate Technology Enabled Trimmer-Less and Low Voltage Flame Detection Sensor

In this paper, a Least Mean Square (LMS) programming scheme is used to set the offset voltage of two operational amplifiers that were built using floating-gate transistors, enabling a 0.95 VRMS trimmer-less flame detection sensor. The programming scheme is capable of setting the offset voltage over a wide range of values by means of electron injection. The flame detection sensor consists of two programmable offset operational amplifiers; the first amplifier serves as a 26 μV offset voltage follower, whereas the second amplifier acts as a programmable trimmer-less voltage comparator. Both amplifiers form the proposed sensor, whose principle of functionality is based on the detection of the electrical changes produced by the flame ionization. The experimental results show that it is possible to measure the presence of a flame accurately after programming the amplifiers with a maximum of 35 LMS-algorithm iterations. Current commercial flame detectors are mainly used in absorption refrigerators and large industrial gas heaters, where a high voltage AC source and several mechanical trimmings are used in order to accurately measure the presence of the flame.
Autoimmune Hepatitis in Children and Adolescents: Effect on Quality of Life

Objectives: The aim of this study was to evaluate the effect of autoimmune hepatitis (AIH) on the quality of life of children and adolescents and to identify which variables effect health-related quality of life (HRQoL). Methods: The Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) was used to evaluate HRQoL. In addition, a questionnaire was applied which included signs, symptoms, and use of medications. Results: A total of 43 patients (mean age, 15.0 ± 3.9 years; 65.1% girls; 90.7% with type 1 AIH) was evaluated. Advanced liver disease was present in 30.2%, and 18.6% had sclerosing cholangitis. Treatment was effective in 93.1% of patients. The lowest HRQoL scores were associated with the school (67.7), emotional (68.2), and psychosocial (75.5) domains. Compared with healthy children, patients presented lower scores on the total, psychosocial, emotional, and school domains (P < 0.05). The presence of symptoms (&bgr; = 0.39, P < 0.01), extrahepatic autoimmune diseases (&bgr; = 0.27, P < 0.05), and a dislike of taking medication (&bgr; = 0.40, P < 0.01) negatively affected the psychosocial PedsQL 4.0 score, and the presence of symptoms (&bgr; = 0.40, P < 0.01) negatively affected the total PedsQL 4.0 score. Conclusions: AIH has a significant and negative effect on HRQoL among children and adolescents. The presence of symptoms, extrahepatic autoimmune diseases, and a dislike of taking medication were associated with the worsening of HRQoL. Providers should work with professionals trained to improve QoL to help improve treatment adherence and disease outcomes.
The Demand for Football in Switzerland: An Empirical Estimation

This paper identifies the factors determining the attendance at football games in Switzerland. Our data covers three seasons of the top division of the Swiss football league, between 2001 and 2004, which includes a major revision of the championship rules in 2003-2004. We were able to gather a high amount of information, allowing us to take into consideration several factors not always accounted for simultaneously in the literature, such as ticket price, capacity constraint, TV coverage, as well as more traditional factors like uncertainty. In order to cope with problems imposed by capacity constraints as well as the panel dimension of the data, we make use of a random effects Tobit model. Among others, our results show that TV coverage does not have a significant impact on the number of spectators, and, except for FC Basel, the price-elasticity is relatively low, which indicates that football clubs could raise their gate revenues by increasing ticket prices. Furthermore, the new championship formula did clearly raise attendances.
A Microfluidic pH Measurement Device with a Flowing Liquid Junction

The pH values of aqueous solutions are conventionally measured with pH-sensitive electrodes such as glass electrodes or ion-sensitive field-effect transistors (ISFETs) used in conjunction with Ag/AgCl reference electrodes and KCl solutions. The speed of pH measurement with these systems can be deficient, however, as the glass electrode responds slowly during measurements of sample solutions with low buffering capacities. Our group has constructed a new pH measurement system using a microfluidic device and ISFET sensors. The device has a channel with two inlets and one outlet, with a junction connected to a Y-shaped channel on the same plane. Two ISFET sensors and an Ag/AgCl pseudo reference electrode are fitted into the channel to construct a differential measurement device. A sample solution and baseline solution supplied into the inlets by gravity-driven pumps form a flowing liquid junction during measurement. The small size and fast response of the ISFET sensors enable measurement of about 2.0 mL of sample solution over a measurement period of 120 s. The 90% response time is within 2 s. The calibrated sensor signal exhibits a wide range (pH 1.68–10.0) of linearity with a correlation factor of 0.9997. The measurement error for all solutions tested, including diluted solutions, was 0.0343 ± 0.0974 pH (average error ± standard deviation (S.D.), n = 42). The new device developed in this research will serve as an innovative technology in the field of potentiometry.
Genetic or Pharmaceutical Blockade of Phosphoinositide 3-Kinase P110δ Prevents Chronic Rejection of Heart Allografts

Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110δ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110δ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110δ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110δ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110δ activity might be a viable strategy for the treatment of heart chronic rejection in humans.
Mortality Risk after Diagnosis of Early-Onset Alzheimer's Disease versus Late-Onset Alzheimer's Disease: A Propensity Score Matching Analysis.

BACKGROUND/OBJECTIVE We aimed to compare the risk of mortality in patients with early-onset Alzheimer's disease (EOAD) versus those with late-onset AD (LOAD) using a large number of study subjects. We applied propensity score matching (PSM) to minimize confounding biases in the comparison between EOAD and LOAD. METHODS We obtained data from elderly Korean subjects with AD (n = 3,611) at baseline from the CREDOS cohort study, which was conducted from November 2005 to July 2013. We conducted PSM to reduce the bias due to confounding variables related to survival in patients with AD. The risks of mortality associated with EOAD and LOAD were evaluated by Cox proportional hazard analyses, controlling for relevant covariates. RESULTS After propensity score matching, 312 subjects with EOAD and 624 subjects with LOAD were selected for further analysis. The Cox proportional hazard analysis showed that patients with EOAD are at a greater risk for mortality compared to those with LOAD (Hazard Ratio: 2.01, 95% CI: 1.01-4.00, p-value: 0.04) when controlling for the direct effect of aging on mortality. The results did not change after adjusting for age at diagnosis, general cognitive function, nutritional factor related to body mass index, and physical disability using activities of daily living. The results support the assumption that EOAD takes a more malignant course than LOAD. CONCLUSIONS Our results provide support for the idea that EOAD takes a clinical course that is distinct from that of LOAD, especially as pertains to the risk of mortality.
Defining and estimating causal direct and indirect effects when setting the mediator to specific values is not feasible

Natural direct and indirect effects decompose the effect of a treatment into the part that is mediated by a covariate (the mediator) and the part that is not. Their definitions rely on the concept of outcomes under treatment with the mediator ‘set’ to its value without treatment. Typically, the mechanism through which the mediator is set to this value is left unspecified, and in many applications, it may be challenging to fix the mediator to particular values for each unit or patient. Moreover, how one sets the mediator may affect the distribution of the outcome. This article introduces ‘organic’ direct and indirect effects, which can be defined and estimated without relying on setting the mediator to specific values. Organic direct and indirect effects can be applied, for example, to estimate how much of the effect of some treatments for HIV/AIDS on mother‐to‐child transmission of HIV infection is mediated by the effect of the treatment on the HIV viral load in the blood of the mother. Copyright © 2016 John Wiley & Sons, Ltd.
Microstructure and Properties of Liquefied Wood-Based Activated Carbon Fibers Prepared from Precursors and Carbon Fibers

Liquefied wood-based activated carbon fibers (LWACF) were prepared from liquefied wood-based precursors (LWP) and liquefied wood-based carbon fibers. Microstructure and properties of LWACF were studied using analysis of X-ray diffraction, nitrogen adsorption-desorption isotherms, X-ray photoelectron spectroscopy, and a microtensile tester. It was found that LWACF prepared from LWP (LWACF1) could form a larger crystal size and denser graphite-like structure than those prepared from LWCF (LWACF2). However, for LWACF2, micropores were more numerous and average micropore width was larger, leading to the conclusion that LWACF2 had smaller diameter and lower mechanical properties than LWACF1 and that the burn-off value of LWACF2 was larger than that of LWACF1. Furthermore, excess amounts of element carbon (C) and C bonded to oxygen-containing functions were found on the surface of LWACF2. In conclusion, postcarbonization could damage the graphite-like structure, resulting in expanded micropores and impaired mechanical properties. Postcarbonization brought about an increase in the amount of element C and in the relative content of C bonded to oxygen-containing functions.
Outbreak investigation report of dengue fever during June-November 2014: A case study of district Swat, Pakistan.

OBJECTIVE To determine the frequency distribution of dengue fever during the 2014 outbreak in a district in northern Pakistan. METHODS This cross-sectional study was conducted between June and November, 2014, at Saidu Sharif Teaching Hospital, Swat, Pakistan, where patients were screened for dengue virus non-structural protein using Dengue Duo strips from Standard Diagnostics (SD). Data was obtained from patient's record, filled forms and through questionnaire. RESULTS Of the total 812 patients, 290(35.71%) tested positive for dengue virus non-structural protein, of whom 175(60.34%) were males and 115(39.66%) were females. Overall, 146(50.34%), cases were recorded in the 16-30 age group, while 7(2.41%) were reported in those aged >60 years. The highest numbers of cases were recorded from Faizabad 84(28.96%), whereas the lowest numbers of cases 42(14.48%) were reported from Sethi Amankot. CONCLUSIONS Dengue virus affected male individuals more compared to female. The affected areas had poor drainage and water storage system.
Detailed study of survival of patients with renal cell carcinoma in India.

PURPOSE Renal cell carcinoma (RCC) accounts for approximately 90% of all renal malignancies. The rates of kidney cancers are high in developed countries and low in eastern countries and Africa. The objective was to conduct a survival study among Indian population following nephrectomy for RCC as there was a paucity of Indian studies in medical literature. MATERIALS AND METHODS We conducted a follow-up study of eighty RCC patients who had nephrectomy between January 2003 and December 2010. These patients had pathological diagnosis after nephrectomy. The follow-up was done up to December 2015. The survival statistics were compiled according to Kaplan-Meier survival curves. RESULTS The overall survival of eighty patients was 77%. The patients with tumor size ≤7 cm and the patients with tumor size> 7 cm showed significant statistical difference at 5-year survival (P < 0.0001). The patients with low nuclear grade (1 and 2) and the patients with high nuclear grade (3 and 4) showed significant statistical difference at 5-year survival (P < 0.0001). The patients with tumor node metastasis stage below T3 and the patients with clinical stage above or equal to T3 showed significant statistical difference at 5-year survival (P = 0.003). CONCLUSION This study has demonstrated the importance of factors such as tumor size, nuclear grade, and stage in the assessment of prognosis of RCC patients. More studies in India with more patients are needed to demonstrate the importance of these prognostic factors.
Fetuin-A levels in hyperthyroidism

OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1. Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels.
Running Memory for Clinical Handoffs: A Look at Active and Passive Processing

Objective: The goal of the present study was to examine the effects of domain-relevant expertise on running memory and the ability to process handoffs of information. In addition, the role of active or passive processing was examined. Background: Currently, there is little research that addresses how individuals with different levels of expertise process information in running memory when the information is needed to perform a real-world task. Method: Three groups of participants differing in their level of clinical expertise (novice, intermediate, and expert) performed an abstract running memory span task and two tasks resembling real-world activities, a clinical handoff task and an air traffic control (ATC) handoff task. For all tasks, list length and the amount of information to be recalled were manipulated. Results: Regarding processing strategy, all participants used passive processing for the running memory span and ATC tasks. The novices also used passive processing for the clinical task. The experts, however, appeared to use more active processing, and the intermediates fell in between. Conclusion: Overall, the results indicated that individuals with clinical expertise and a developed mental model rely more on active processing of incoming information for the clinical task while individuals with little or no knowledge rely on passive processing. Application: The results have implications about how training should be developed to aid less experienced personnel identify what information should be included in a handoff and what should not.
Gluing together Proof Environments: Canonical extensions of LF Type Theories featuring Locks

We present two extensions of the LF Constructive Type Theory featuring monadic locks. A lock is a monadic type construct that captures the effect of an external call to an oracle. Such calls are the basic tool for gluing together diverse Type Theories and proof development environments. The oracle can either be invoked in order to check that a constraint holds or to provide a suitable witness. The systems are presented in the canonical style developed by the CMU School. The first system, CLLF_P , is the canonical version of the system LLF_P , presented earlier by the authors. The second system, CLLF_P? , features the possibility of invoking the oracle to obtain a witness satisfying a given constraint. We discuss encodings of Fitch-Prawitz Set theory, call-by-value λ-calculi, and systems of Light Linear Logic. Finally, we show how to use Fitch-Prawitz Set Theory to define a type system that types precisely the strongly normalizing terms.
Recent developments concerning the application of the Mannich reaction for drug design

ABSTRACT Introduction: The versatile multicomponent Mannich reaction occupies a salient position in organic chemistry and drug design. Sound knowledge of its scope and variations and of the biological activities of Mannich bases is crucial for the development and improvement of drugs for various diseases. Areas covered: The following article provides an overview of the latest developments in the field of drugs based on the Mannich reaction. Web-based literature searching tools such as PubMed and SciFinder were applied to obtain useful articles. In addition, pertinent literature that was recently published by the authors is discussed in this manuscript. The chemical structures of bioactive Mannich bases are also given. Expert opinion: The Mannich reaction represents a feasible and cost-effective procedure with great potential for drug development. Several newly discovered Mannich bases exhibit sound activities against various human diseases as well as favorable pharmacokinetics. Thus, scientific research about Mannich bases is prospering and appears very attractive both for chemists and for clinicians.
Crack Detection in Concrete Tunnels Using a Gabor Filter Invariant to Rotation

In this article, a system for the detection of cracks in concrete tunnel surfaces, based on image sensors, is presented. Both data acquisition and processing are covered. Linear cameras and proper lighting are used for data acquisition. The required resolution of the camera sensors and the number of cameras is discussed in terms of the crack size and the tunnel type. Data processing is done by applying a new method called Gabor filter invariant to rotation, allowing the detection of cracks in any direction. The parameter values of this filter are set by using a modified genetic algorithm based on the Differential Evolution optimization method. The detection of the pixels belonging to cracks is obtained to a balanced accuracy of 95.27%, thus improving the results of previous approaches.
On the boundary of the zero set of super-Brownian motion and its local time

If $X(t,x)$ is the density of one-dimensional super-Brownian motion, we prove that $\text{dim}(\partial\{x:X(t,x)>0\})=2-2\lambda_0\in(0,1)$ a.s. on $\{X_t\neq 0\}$, where $-\lambda_0\in(-1,-1/2)$ is the lead eigenvalue of a killed Ornstein-Uhlenbeck process. This confirms a conjecture of Mueller, Mytnik and Perkins who proved the above with positive probability. To establish this result we derive some new basic properties of a recently introduced boundary local time and analyze the behaviour of $X(t,\cdot)$ near the upper edge of its support. Numerical estimates of $\lambda_0$ suggest that the above Hausdorff dimension is approximately $. 224$.