Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical trial risk in type-2 diabetes: importance of patient history.

PURPOSE To determine the risk of clinical trial failure for drugs developed for type-2 diabetes. METHODS Drugs were investigated by reviewing phase I to phase III studies that were conducted between 1998 and February 2013. The clinical trial success rates were calculated and compared to the industry standard. The drugs were classified into GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors and "Other". The exclusion criteria for drugs in this study: Drugs that were started in phase I studies prior to January 1998 for this indication and drugs whose primary indications were not for the control of blood glucose levels. RESULTS Data was extracted from clinicaltrials.gov; there were a total of 131 drug candidates that fit our specified criteria, of which 8 received FDA approval. The cumulative success rate for molecules developed for type-2 diabetes is 10%. Small molecules were more successful than biologics. A strong disparity was observed in phase III, with studies that utilised treatment naïve patients having a 40% success rate, compared to an 83% success rate in patients who have had previous anti-hyperglycemic exposure. CONCLUSIONS 1 in 10 drugs that enter clinical testing in this disease will be approved. The DPP-4 inhibitor class of drugs had the highest success rate of all drug classes with a 63% cumulative success rate; while treatment naïve patients carried the greatest clinical trial risk.
Assessment of buck converter powered by current or voltage sources for LEDs luminary

This paper presents comparative investigation of both voltage and current fed buck converters. This comparison takes into account the controllability, efficiency and size of the converters. The first section of the paper briefly describes a standard voltage fed buck converter. Transformation of voltage fed buck converter into the current fed converter is presented next. Then the operation of current fed buck converter is discussed. On the next stage experimental estimation of current fed buck converter is described. Finally conclusions about current fed buck converter with LEDs are drawn.
Geographic routing in social networks

We live in a "small world," where two arbitrary people are likely connected by a short chain of intermediate friends. With scant information about a target individual, people can successively forward a message along such a chain. Experimental studies have verified this property in real social networks, and theoretical models have been advanced to explain it. However, existing theoretical models have not been shown to capture behavior in real-world social networks. Here, we introduce a richer model relating geography and social-network friendship, in which the probability of befriending a particular person is inversely proportional to the number of closer people. In a large social network, we show that one-third of the friendships are independent of geography and the remainder exhibit the proposed relationship. Further, we prove analytically that short chains can be discovered in every network exhibiting the relationship.
Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Because ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle, resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.
Treatment of whiplash-associated disorders--part II: Medical and surgical interventions.

BACKGROUND Whiplash-associated disorder (WAD) is a term used to describe injury due to an acceleration-deceleration mechanism at the neck. In 1995, the Quebec Task Force published a report that contained evidence-based recommendations regarding the treatment of WAD based on studies completed before 1993 and consensus-based recommendations. OBJECTIVE The objective of the present article--the second installment of a two part review on WAD--is to provide a systematic review of the literature published between January 1993 and July 2003 on medical and surgical interventions for WAD using meta-analytical techniques. METHODS OF THE REVIEW Three medical literature databases were searched for identification of all clinical trials on the treatment of WAD. Randomized controlled trials (RCTs) and epidemiological studies were categorized by treatment modality and analyzed by outcome measures. The methodological quality of the RCTs was assessed. When possible, pooled analyses of the RCTs were completed for meta-analyses of the data. The results of all the studies were compiled and systematically reviewed. RESULTS The studies were categorized as medical or surgical interventions. A total of five RCTs and six non-RCTs were evaluated. The mean methodological quality of the RCTs was 7.3 among studies on medical interventions and 7.5 for studies on surgical intervention. Pooled analyses were completed across all treatment modalities and outcome measures. The outcomes of each study were summarized in tables. CONCLUSIONS While several quality RCTs and epidemiological studies have been published since 1993 on medical and surgical interventions, the cumulative evidence is lacking. Moderate evidence exists in support of radiofrequency neurotomy. Evidence for steroid injections, botulinum treatments, carpal tunnel decompression and cervical discectomy is conflicting or unclear. Future research is required to clarify the utility of radiofrequency neurotomy and pulsed electromagnetic field treatment for WAD.
A Multiplicity Census of Young Stars in Chamaeleon I

We present the results of a multiplicity survey of 126 stars spanning ~0.1-3 M☉ in the ~2 Myr old Chamaeleon I star-forming region, based on adaptive optics imaging with the ESO Very Large Telescope. Our observations have revealed 30 binaries and six triples, of which 19 and four, respectively, are new discoveries. The overall multiplicity fraction we find for Cha I (~30%) is similar to those reported for other dispersed young associations, but significantly higher than seen in denser clusters and the field, for comparable samples. Both the frequency and the maximum separation of Cha I binaries decline with decreasing mass, while the mass ratios approach unity; conversely, tighter pairs are more likely to be equal mass. We confirm that brown dwarf companions to stars are rare, even at young ages at wide separations. Based on follow-up spectroscopy of two low-mass substellar companion candidates, we conclude that both are likely background stars. The overall multiplicity fraction in Cha I is in rough agreement with numerical simulations of cloud collapse and fragmentation, but its observed mass dependence is less steep than predicted. The paucity of higher order multiples, in particular, provides a stringent constraint on the simulations, and seems to indicate a low level of turbulence in the prestellar cores in Cha I.
Tracking the progress of HIV: the impact of point-of-care tests on antiretroviral therapy

It is now around 30 years since the discovery of HIV, the virus that causes AIDS. More than 70 million people have been infected in that time and around 35 million have died. The majority of those currently living with HIV/AIDS are in low- and middle-income countries, with sub-Saharan Africa bearing a disproportionate burden of the global disease. In high-income countries, the introduction of antiretroviral therapy (ART) has drastically reduced the morbidity and mortality associated with HIV. Patients on ART are now predicted to have near-normal life expectancy and the role of treatment is increasingly recognized in preventing new infections. In low- and middle-income countries, treatment is now more widely available and around half of those who need ART are currently receiving it. Early diagnosis of HIV is essential if ART is to be optimally implemented. Lab-based diagnostics for screening, diagnosis, treatment initiation, and the monitoring of treatment efficacy are critical in managing the disease and reducing the number of new infections each year. The introduction of point-of-care HIV rapid tests has transformed the epidemic, particularly in low- and middle-income countries. For the first time, these point-of-care tests allow for the rapid identification of infected individuals outside the laboratory who can undergo counseling and treatment and, in the case of pregnant women, allow the timely initiation of ART to reduce the risk of vertical transmission. Although survival is markedly improved with ART even in the absence of laboratory monitoring, long-term management of people living with HIV on ART, and their partners, is essential to ensure successful viral suppression. The burden of disease in many resource-poor settings with high HIV prevalence has challenged the ability of local laboratories to effectively monitor those on ART. Diagnostics used to initiate and monitor treatment are now moving out of the laboratory and into the field. These new point-of-care tests for viral load and CD4 are poised to further transform the disease and shift the treatment paradigm in low- and middle-income countries.
Probabilistic Similarity Logic

Many machine learning applications require the ability to learn from and reason about noisy multi-relational data. To address this, several effective representations have been developed that provide both a language for expressing the structural regularities of a domain, and principled support for probabilistic inference. In addition to these two aspects, however, many applications also involve a third aspect-the need to reason about similarities-which has not been directly supported in existing frameworks. This paper introduces probabilistic similarity logic (PSL), a general-purpose framework for joint reasoning about similarity in relational domains that incorporates probabilistic reasoning about similarities and relational structure in a principled way. PSL can integrate any existing domain-specific similarity measures and also supports reasoning about similarities between sets of entities. We provide efficient inference and learning techniques for PSL and demonstrate its effectiveness both in common relational tasks and in settings that require reasoning about similarity.
Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course.

OBJECT The purpose of this study was to present the authors' clinical experience and long-term angiographic and clinical follow-up results in 350 patients with brain arteriovenous malformations (AVMs) treated using prolonged intranidal Onyx injection with a very slow "staged" reflux technique described by the authors. METHODS Three hundred and fifty consecutive patients with brain AVMs treated using Onyx between 1999 and 2008 and in whom definitive status for endovascular treatment was reached are presented. There were 206 (59%) male and 144 (41%) female patients, with a mean age of 34 years. There were 607 endovascular sessions performed. Onyx was the only agent used for intranidal injections in all patients, but in 42 patients high-concentration N-butyl cyanoacrylate glue was used adjunctively to close high-flow direct arteriovenous intra- or perinidal fistulas, or when a feeding vessel or nidus perforation and/or dissection occurred. RESULTS Angiographically confirmed obliteration was achieved in 179 patients (51%) with only endovascular treatment; 1 patient died due to intracranial hemorrhage after the treatment. Twenty-two patients underwent resection, and 136 patients were sent to radiosurgery after endovascular treatment. In 4 patients embolization therapy was discontinued, and 5 additional patients refused the suggested complementary surgery. In all 178 surviving patients who had angiographically confirmed AVM obliteration by embolization alone, 1-8 years of control angiography (mean 47 months) confirmed stable obliteration, except for 2 patients in whom a very small recruitment was noted in the 1st year on control angiography studies, despite initial apparent total obliteration (recanalization rate 1.1%). In the entire series, 5 patients died; the mortality rate was 1.4%. The permanent morbidity rate was 7.1%. CONCLUSIONS With the prolonged intranidal injection technique described herein, Onyx allows the practitioner to achieve higher rates of anatomical cures compared with the cure rates obtained previously with other embolic agents. More importantly, due to this technique's much more effective intranidal penetration, it allows high-grade AVMs to be made radiosurgically treatable in a group of patients for whom there has been no treatment alternative.
Targeting the dopamine receptor in schizophrenia: investigational drugs in Phase III trials

Introduction: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon after, it was established that blockade of dopamine and, in particular, the D2 receptor was central to this effect. Dopamine continues to represent a critical line of investigation, although much of the work now focuses on its potential in other symptom domains. Areas covered: A search was carried out for investigational drugs using the key words ‘dopamine’, ‘schizophrenia’ and ‘Phase III’ in an American clinical trial registry (clinicaltrials.gov), published articles using the National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. Drugs were excluded that were already FDA approved. Expert opinion: There remains interest, albeit diminished, in developing better antipsychotic compounds. The greatest enthusiasm currently centres on dopamine's role in negative and cognitive symptom domains. With theories conceptualising hypodopaminergic activity as underlying these deficits, considerable effort is focused on drug strategies that will enhance dopamine activity. Finally, a small body of research is investigating dopaminergic compounds vis-à-vis side-effect treatments. In domains beyond psychosis, however, dopamine arguably is not seen as so central, reflected in considerable research following other lines of investigation.
Phase transition kinetics of LiNi0.5Mn1.5O4 electrodes studied by in situ X-ray absorption near-edge structure and X-ray diffraction analysis

In situ time-resolved X-ray absorption near-edge structure (XANES) and X-ray diffraction (XRD) measurements are applied to track the phase transition processes of LixNi0.5Mn1. 5O4, which is one of the most promising positive electrode materials for lithium ion batteries with its high redox potential of 4.7 V vs. Li/Li+ and good rate capability. Thanks to the high time resolution brought by a strong synchrotron X-ray beam, the XANES and XRD measurements separately capture the three phases involved in nearly the same potential region, namely LiNi0.5Mn1. 5O4 (Li1), Li1/2Ni0.5Mn1. 5O4 (Li1/2) and Ni0.5Mn1. 5O4 (Li0), and the phase transition kinetics under fast charging–discharging conditions is elucidated. The detailed kinetic analysis shows that the phase transitions are apparently expressed by the first-order kinetics and that the transition between the Li1 and Li1/2 phases is faster than that between the Li1/2 and Li0 phases, which leads to kinetically asymmetric behavior of the LiNi0.5Mn1. 5O4 electrode. The obtained rate constants can be used to characterize and optimize the rate capability of the electrode.
An outbreak of aflatoxin poisoning in dogs associated with aflatoxin B1–contaminated maize products

An aflatoxicosis outbreak affected 65 dogs from 9 different farms after they were fed diets with cooked corn meal as a common ingredient. Of the dogs, 60 died. Numerous dogs died on additional farms, but those dogs were not included in the study. The farmers acquired the contaminated maize products, in the form of whole corn grain or as corn meal, from the same supplier. The corn product was mixed with meat that was left over from home or commercial rations to form corn polenta, which was fed to the dogs. Necropsy was performed on 3 dogs. Two of the dogs died after a few days of refusing food, showing anorexia, polydipsia, icteric mucous membranes, hematemesis, hematochezia, or melena, and bleeding of the skin, eye, ear, and mouth. The primary necropsy findings included jaundice, hemorrhages in several organs, and yellowish enlarged liver with enhanced lobular pattern. The dog that experienced chronic ascites had a yellowish liver with reduced volume, irregular surface, and increased consistency. The main histological findings included hepatocyte fatty degeneration, biliary duct hyperplasia, cholestasis and, in the chronic case, hepatic fibrosis. High-performance liquid chromatography analysis of the corn meal from 2 affected farms revealed 1,640 ppb and 1,770 ppb of aflatoxin B1, respectively. The current study demonstrates an additional way that dogs can be exposed to, poisoned, and killed by aflatoxin.
Integrating Landscape Disturbance and Indicator Species in Conservation Studies

Successful conservation plans are conditioned by our ability to detect anthropogenic change in space and time and various statistical analyses have been developed to handle this critical issue. The main objective of this paper is to illustrate a new approach for spatial analysis in conservation biology. Here, we propose a two-step protocol. First, we introduce a new disturbance metric which provides a continuous measure of disturbance for any focal communities on the basis of the surrounding landscape matrix. Second, we use this new gradient to estimate species and community disturbance thresholds by implementing a recently developed method called Threshold Indicator Taxa ANalysis (TITAN). TITAN detects changes in species distributions along environmental gradients using indicators species analysis and assesses synchrony among species change points as evidence for community thresholds. We demonstrate our method with soil arthropod assemblages along a disturbance gradient in Terceira Island (Azores, Portugal). We show that our new disturbance metric realistically reflects disturbance patterns, especially in buffer zones (ecotones) between land use categories. By estimating species disturbance thresholds with TITAN along the disturbance gradient in Terceira, we show that species significantly associated with low disturbance differ from those associated with high disturbance in their biogeographical origin (endemics, non-endemic natives and exotics) and taxonomy (order). Finally, we suggest that mapping the disturbance community thresholds may reveal areas of primary interest for conservation, since these may host indigenous species sensitive to high disturbance levels. This new framework may be useful when: (1) both local and regional processes are to be reflected on single disturbance measures; (2) these are better quantified in a continuous gradient; (3) mapping disturbance of large regions using fine scales is necessary; (4) indicator species for disturbance are searched for and; (5) community thresholds are useful to understand the global dynamics of habitats.
Effect of three single-nucleotide polymorphisms in CAPN1 gene on beef tenderness (Brief Report) Einfluss von drei Einzelnucleotidpolymorphismen im CAPN1 Gen auf die Zartheit von Rindfleisch (Brief Report)

Abstract. Meat tenderness is an important trait in beef cattle production, as consumers consider tenderness the most important attribute of beef palatability. There is ample evidence that post mortem proteolysis of myofibrillar proteins is responsible for the decline in shear force during storage. The bovine micromolar calcium-activated neutral protease (CAPN1) gene encodes the large subunit of μ-calpain, which is thought to be one of the most important enzymes involved in post mortem tenderization (KOOHMARAIE 1996). Three single-nucleotide polymorphisms (SNPs) on the CAPN1 gene (316, 530 and 4 751 markers) have been associated with tenderness in different cattle breeds (PAGE et al. 2002, PAGE et al. 2004, WHITE et al. 2005). A more recent study confirmed that markers 316 and 4 751 had an effect on beef tenderness (VAN EENENNAAM et al. 2007). The objective of this research was to determine the existence of polymorphisms and to assess the effect of the reported SNP in the bovine CAPN1 gene on tenderness from a sample of Angus and Brangus steers fattened on pasture.
Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects.

OBJECTIVE Various immunological effects have been reported during application of mistletoe preparations. Because these data are heterogeneous, we performed a placebo controlled study to investigate (1) effects on peripheral granulocyte and eosinophil counts, (2) related cytokine levels and (3) whether effects are related to mistletoe lectin (ML). METHODS 43 volunteers were randomized to receive the mistletoe plant extract Iscador Quercus spezial (IQ), purified ML, IQ which was depleted from ML, or placebo subcutaneously twice per week for 8 weeks. Weekly, differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells (PBMC) were analyzed. RESULTS Leukocyte-, granulocyte-, and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group. Furthermore, a significant increase of antigen-induced production of GM-CSF, IL-5 and IFNgamma by PBMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo. Severe side effects did not occur in any of the subjects. CONCLUSIONS Treatment with IQ or ML stimulates the production of GM-CSF, IL-5 and IFNgamma by PBMC, and this is accompanied by an increase of eosinophil- and granulocyte-counts. These observations may, therefore, open rational therapeutic indications for mistletoe extracts.