Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutaneous vasculitis induced by risedronate

Risedronate is an orally administered pyridinyl bisphosphonate that inhibits osteoclastmediated bone resorption and modulates bone metabolism (1). It is licensed for the prevention and treatment of osteoporosis, as well as for treatment of Paget s disease (1). Cutaneous reactions to this medication are exceptional (2, 3). We report here the first case of vasculitis related to risedronate therapy. A 72-year-old woman with postmenopausal osteoporosis started treatment with risedronate (Actonel ; Procter Gamble Pharmaceuticals, Nanterre, France) 35 mg orally/week. Three weeks later, the patient noticed the onset of an eruption on her legs and was referred to the department of dermatology for investigation. Physical examination revealed multiple infiltrated purpuric plaques on both legs. There were no physical signs suggesting clinical evidence of connective tissue or other systemic disease. A skin biopsy showed perivascular infiltrates of neutrophils and eosinophils with nuclear dust. There were extravasated red blood cells and fibrin deposition around some vessels. These findings were consistent with leukocytoclastic vasculitis. Direct immunofluorescence of perilesional skin was negative. All laboratory tests performed [complete blood cell count, C reactive protein, creatinine, liver function panel, hepatitis B and C virus serologies, serum protein electrophoresis, proteinuria, antinuclear antibody, ANCA, cryoglobulins, complement levels (CH50, C3, C4), and rheumatoid factor] were unremarkable. Risedronate was withdrawn and skin lesions resolved within 2 weeks. Three months later and despite our recommendations, the woman took again risedronate. One day after restarting therapy, an acute episode of cutaneous vasculitis was developed, and she was readmitted to the hospital. A new skin biopsy showed leukocytoclastic vasculitis and direct immunofluorescence of perilesional skin was always negative. Repeated laboratory tests remained unremarkable. Risedronate was stopped and 3 weeks after discontinuation, the patient was clear of all lesions. There was no relapse during a follow-up period of more than 2 years. Thus, the diagnosis of risedronate-induced cutaneous vasculitis was established. Vasculitis is inflammation of vessel walls that can occur secondary to many conditions, including drug intake, infection, malignancy, inflammatory disease, and connective tissue disease (4). Several drugs from different pharmacological classes have been associated with cutaneous vasculitis (4). Adverse cutaneous drug reactions to bisphosphonates are very rare (2, 3) and are mostly reported with alendronate (5–8). In our case, the diagnosis of risedronate-induced cutaneous vasculitis was confirmed by the lack of other triggers of cutaneous vasculitis and mainly by the positive systemic re-exposition to the drug which remains the gold standard for the diagnosis. To the best of our knowledge, our case is considered to be the first reported case of cutaneous vasculitis induced by risedronate. Thus, physicians should be aware of potential severe drug reactions when prescribing risedronate.
Basic Measures for Imprecise Point Sets in R d

Most algorithms in computational geometry tend to assume that all input is exact, with no imprecision or error. Most real-world data however, has some imprecision (for example due to measurement error). Thus, there exists a need for algorithms that can produce meaningful output for imprecise input data. In this thesis, I present results on the computation of upper and lower bounds on various basic measures (such as diameter, width, closest pair, volume of smallest enclosing ball and volume of minimum axis aligned bounding box) for imprecise point sets in Rd. I model the imprecision by representing an imprecise point set as a set of regions (balls or polytopes), such that each point may lie anywhere within one of the regions. This work is an extension of previous research by Löffler and van Kreveld on imprecise point sets in R2, to higher dimensions.
Bifid T waves induced by isoprenaline in a patient with Brugada syndrome

A 41 year old man with incomplete right bundle branch block and persistent coved-type ST elevation in the right precordial leads during sinus rhythm had an episode of syncope while driving. He had never had syncope before and there was no family history of sudden cardiac death. Ventricular fibrillation was induced during electrophysiological study (EPS) by double extrastimuli applied to the right ventricle. Disopyramide was effective in preventing ventricular fibrillation during EPS. β Adrenoceptor stimulation manifested bifid T waves and reduced ST segment elevation in right precordial leads. Simultaneously recorded monophasic action potential (MAP) duration at 90% repolarisation did not change in the right ventricular outflow tract, while it shortened in the left ventricular septum. These findings suggest that right precordial bifid T waves might result from relatively early repolarisation of the left ventricles. Moreover the gradient of action potential duration might explain the mechanism of ST segment abnormalities in a patient with Brugada syndrome.
Chemical Composition and Hypotensive Effect of Campomanesia xanthocarpa

Campomanesia xanthocarpa is known in Brazil as Guabiroba and is popularly used for various diseases, such as inflammatory, renal, and digestive diseases and dyslipidemia. The aim of the study was to analyze the chemical composition and investigate the effects of aqueous extract of C. xanthocarpa on the blood pressure of normotensive rats, analyzing the possible action mechanism using experimental and in silico procedures. The extract was evaluated for total phenolic compounds and total flavonoid content. The chemical components were determined by HPLC analyses. Systolic and diastolic blood pressure and heart rate were measured with extract and drugs administration. The leaves of C. xanthocarpa presented the relevant content of phenolics and flavonoids, and we suggested the presence of chlorogenic acid, gallic acid, quercetin, and theobromine. The acute administration of aqueous extract of C. xanthocarpa has a dose-dependent hypotensive effect in normotensive rats, suggesting that the action mechanism may be mediated through the renin-angiotensin system by AT1 receptor blockade and sympathetic autonomic response. Docking studies showed models that indicated an interaction between chlorogenic acid and quercetin with the AT1 receptor (AT1R) active site. The findings of these docking studies suggest the potential of C. xanthocarpa constituents for use as preventive agents for blood pressure.
Insulin Sensitizing Pharmacology of Thiazolidinediones Correlates with Mitochondrial Gene Expression rather than Activation of PPARγ

Insulin sensitizing thiazolidinediones (TZDs) are generally considered to work as agonists for the nuclear receptor peroxisome proliferative activated receptor-gamma (PPARγ). However, TZDs also have acute, non-genomic metabolic effects and it is unclear which actions are responsible for the beneficial pharmacology of these compounds. We have taken advantage of an analog, based on the metabolism of pioglitazone, which has much reduced ability to activate PPARγ. This analog (PNU-91325) was compared to rosiglitazone, the most potent PPARγ activator approved for human use, in a variety of studies both in vitro and in vivo. The data demonstrate that PNU-91325 is indeed much less effective than rosiglitazone at activating PPARγ both in vitro and in vivo. In contrast, both compounds bound similarly to a mitochondrial binding site and acutely activated PI-3 kinase-directed phosphorylation of AKT, an action that was not affected by elimination of PPARγ activation. The two compounds were then compared in vivo in both normal C57 mice and diabetic KKAy mice to determine whether their pharmacology correlated with biomarkers of PPARγ activation or with the expression of other gene transcripts. As expected from previous studies, both compounds improved insulin sensitivity in the diabetic mice, and this occurred in spite of the fact that there was little increase in expression of the classic PPARγ target biomarker adipocyte binding protein-2 (aP2) with PNU-91325 under these conditions. An examination of transcriptional profiling of key target tissues from mice treated for one week with both compounds demonstrated that the relative pharmacology of the two thiazolidinediones correlated best with an increased expression of an array of mitochondrial proteins and with expression of PPARγ coactivator 1-alpha (PGC1α), the master regulator of mitochondrial biogenesis. Thus, important pharmacology of the insulin sensitizing TZDs may involve acute actions, perhaps on the mitochondria, that are independent of direct activation of the nuclear receptor PPARγ. These findings suggest a potential alternative route to the discovery of novel insulin sensitizing drugs.
Docking Covalent Inhibitors: A Parameter Free Approach To Pose Prediction and Scoring

Although many popular docking programs include a facility to account for covalent ligands, large-scale systematic docking validation studies of covalent inhibitors have been sparse. In this paper, we present the development and validation of a novel approach for docking and scoring covalent inhibitors, which consists of conventional noncovalent docking, heuristic formation of the covalent attachment point, and structural refinement of the protein-ligand complex. This approach combines the strengths of the docking program Glide and the protein structure modeling program Prime and does not require any parameter fitting for the study of additional covalent reaction types. We first test this method by predicting the native binding geometry of 38 covalently bound complexes. The average RMSD of the predicted poses is 1.52 Å, and 76% of test set inhibitors have an RMSD of less than 2.0 Å. In addition, the apparent affinity score constructed herein is tested on a virtual screening study and the characterization of the SAR properties of two different series of congeneric compounds with satisfactory success.
p21 loss blocks senescence following Apc loss and provokes tumourigenesis in the renal but not the intestinal epithelium

Senescence has been implicated as an important mechanism of tumour suppression in a number of human malignancies, including colorectal cancer (CRC). However, we still have a relatively poor understanding of how the underlying mutations that occur in cancer cause senescence and its relevance in vivo. The Apc gene is mutated in approximately 80% of CRC as the initiating event, but rarely elsewhere. In this study we have examined the capacity of Apc loss to induce senescence in the intestinal epithelium compared to the renal epithelium. Within the renal epithelium, loss of Apc function led to an induction of senescence, however, bypassing senescence through combined Apc and p21 or Ink4A gene deletion rapidly initiated renal carcinoma. Within the intestinal epithelium, loss of Apc did not induce senescence. Moreover, combined Apc and p21 or Ink4A loss had no impact upon tumourigenesis. Taken together, these results show that Apc loss in vivo invokes a senescence program in a context‐dependent fashion, and implies senescence may play a key barrier to tumourigenesis in the kidney. However, in CRC, escape from senescence is likely to only be a barrier in cancers initiated by other mutations.
Improved performance of polymer/ZnO nanorod hybrid solar cells by slow drying of the photoactive layer

The slow drying of the photoactive layer in polymer/ZnO nanorod hybrid solar cells is studied as a way to improve device performance. The power conversion efficiency can be further improved to 3.05% with an enhanced fill factor of 55% by slowing the spin coating rate of photoactive layer. With the slower spin coating rate, the films of photoactive layer are thicker, and the polymer chains have longer time to self-organize and more effectively infiltrate into ZnO nanorod spacing, resulting in the higher crystallinity of polymer and light harvesting without sacrificing the carrier transportation.
Discrimination of speech sounds based upon temporal envelope versus fine structure cues in 5- to 7-year-old children.

PURPOSE To investigate the capacity of young children and adults with normal hearing to discriminate speech on the basis of either relatively slow (temporal envelope, E) or fast (temporal fine structure, TFS) auditory cues. METHOD Vowel-consonant-vowel nonsense disyllables were processed to preserve either the E or the TFS information in 16 adjacent frequency bands. The band signals were then recombined and resulting stimuli were presented for discrimination to adults or 5-, 6-, and 7-year-old children using an odd-ball paradigm. Discrimination scores (d') and response latencies were measured in each listener. No training was given to listeners. RESULTS Overall, discrimination scores were high (d' >or=1) in all speech-processing conditions, and did not differ across age groups. Overall, and irrespective of age, greater discrimination scores and shorter response latencies were observed for E speech than for TFS speech. CONCLUSIONS These results suggest that normal-hearing children are able to encode and use E and TFS speech cues at adult levels by the age of 5 years. TFS- and E-coded speech stimuli might therefore prove to be a useful tool for the investigation of the developmental time course of speech perception, and for the early diagnosis of peripheral and central auditory processing disorders.
Contextual Integration Testing of Object-Oriented and Aspect-Oriented Programs: A Structural Approach for Java and AspectJ

Aspect-oriented programming (AOP) is a technology that aims to tackle software modularisation problems. Despite the benefits that may be achieved with AOP, its mechanisms represent new potential source of faults that should be handled during the test phase. In this paper a structural integration testing approach for Object-Oriented (OO) and Aspect-Oriented (AO) programs with a configurable integration depth (d) is presented. A model called CoDU (Contextual Def-Use) graph to represent the control flow and data flow between units is proposed. Based on the CoDU, a family of testing criteria is defined: all-i-nodes-Nd (control flow based), all-i-edges-Nd (control flow based), and all-i-uses-Nd (data flow based). We also present the implementation of our approach as an extension to the Java Bytecode Understanding and Testing (JaBUTi) family of testing tools along with an example of usage. The example and an exploratory study involving 8 OO and AO programs present evidence of the effectiveness and feasibility of the proposed approach.
Valuation of Performance‐Dependent Options

Performance‐dependent options are financial derivatives whose payoff depends on the performance of one asset in comparison to a set of benchmark assets. This paper presents a novel approach to the valuation of general performance‐dependent options. To this end, a multidimensional Black–Scholes model is used to describe the temporal development of the asset prices. The martingale approach then yields the fair price of such options as a multidimensional integral whose dimension is the number of stochastic processes used in the model. The integrand is typically discontinuous, which makes accurate solutions difficult to achieve by numerical approaches, though. Using tools from computational geometry, a pricing formula is derived which only involves the evaluation of several smooth multivariate normal distributions. This way, performance‐dependent options can efficiently be priced even for high‐dimensional problems as is shown by numerical results.
Performance measurements of an optical detector designed for monolithic integration with a power VDMOS

This paper demonstrates an accurate measurement procedure to characterize the DC and AC performance of an optical detector designed for monolithic integration with a 600 V vertical power MOS transistor. The spectral quantum efficiency (QE) from 400 nm up to 1 μm wavelengths has been measured. A QE of 26% in the 450 nm - 520 nm wavelength range was achieved. The developed setup and measurement procedures can be used for diced samples, packaged devices, and on-wafer probing (maximum size: 4” wafers); furthermore, it is equipped with temperature control. The integrated optical detectors (IOD) key phenomena have been investigated for a wide range of wavelengths and biasing conditions, both experimentally and numerically. Simulation results as well as experimental results are presented and compared.
Differential contributions of A- and C-nociceptors to primary and secondary inflammatory hypersensitivity in the rat

Abstract Primary hyperalgesia is characterized by increased responsiveness to both heat and mechanical stimulation in the area of injury. By contrast, secondary hyperalgesia is generally associated with increased responses to mechanical but not heat stimuli. We tested the hypothesis that sensitization in secondary hyperalgesia is dependent on the class of peripheral nociceptor (C- or A-nociceptor) rather than the modality of stimulation (mechanical vs heat). A- and C-nociceptors were selectively activated using contact heat ramps applied to the hind paw dorsum in animals with hind paw inflammation (primary hyperalgesia) and knee inflammatory arthritis (secondary hyperalgesia). Sensitization to A- and C-nociceptor activation in primary and secondary hyperalgesia was assessed by reflex withdrawal thresholds and by Fos immunocytochemistry in the dorsal horn of the spinal cord, as an index of neuronal activation. In primary hyperalgesia, only C-nociceptor-evoked withdrawal reflexes were sensitized. This was associated with increased spinal lamina I neuronal activation to both A- and C-nociceptor activation. Fos-like immunoreactivity (FLI) was unchanged in other dorsal horn laminae. In secondary hyperalgesia, only A-nociceptor-evoked withdrawal reflexes were sensitized, and FLI was increased in both superficial and deep dorsal laminae. Neurons in the superficial dorsal horn receive and process nociceptor inputs from the area of primary hyperalgesia, resulting in functional sensitization to C-nociceptive inputs. In inflammatory arthritis, secondary hyperalgesia is evoked by A-nociceptor thermal stimulation, suggesting that secondary hyperalgesia is A-nociceptor, rather than stimulus modality (mechanical vs thermal), dependent. Fos-like immunoreactivity evoked by A-nociceptor stimulation in secondary hyperalgesia suggests that the sensitization is underpinned by spinal neuronal sensitization in laminae I and IV/V.
Study on Pancreatic Insufficiency (Chronic Pancreatitis) and Steatorrhea in Japanese Patients with Low Fat Intake

The incidence of steatorrhea is said to be lower and its grade milder in Japanese because their fat intake is lower than that of Europeans and Americans. Failure to take this into account creates difficulties when attempting to compare data on pancreatic exocrine insufficiency in different countries. The authors examined the incidence and grade of steatorrhea in Japanese chronic pancreatitis (CP) patients whose daily fat intake was <40 g (25 patients) or ≥40 g (35 patients). In addition, 23 CP patients with steatorrhea and daily fecal fat excretion ≥5 g were given a pancreatic enzyme preparation at a dose 3–8 times higher than the usual dose to investigate its effect on fecal fat excretion. Among CP patients whose fat intake was <40 g, the incidence of fecal fat excretion <5 g was 56% and that of fecal fat excretion ≥10 g (severe steatorrhea) was 8%. In CP patients whose fat intake was ≥40 g, the incidences were 27.9 and 34.9%, respecetively; a significant increase in the number of affected patients was noted when fat intake was ≥40 g. The fat absorption rate was 76.2% among patients whose fat intake was <40 g and 77.8% among patients whose fat intake was ≥40 g, revealing no significant difference between the two groups. The proportion of CP patients whose fat absorption rate ≦80% was 32% at a fat intake <40 g and 39% at a fat intake ≥40 g, revealing no significant difference between the two groups.
Eukaryotic Intron Loss

Recently, attention has been drawn to eukaryotic genomes with very few introns ( [1][1], [2][2] ) and to the biased position of introns within genes ( [3][3] ). We show here that intron-poor eukaryotes for which genome data is available have a 5′ bias in the position of their introns within genes
Neuroimaging of Essential Tremor: What is the Evidence for Cerebellar Involvement?

Background Clinical observations and electrophysiological studies have provided initial evidence for the involvement of the cerebellum in essential tremor (ET), the most frequent hyperkinetic disorder. Recently, this hypothesis has been reinvigorated by post-mortem studies that demonstrated a number of pathological changes in the cerebellum of ET patients compared with age-matched healthy controls. Advanced neuroimaging techniques have also made it possible to detect in vivo which cerebellar abnormalities are present in ET patients and to reveal the core mechanisms implicated in the development of motor and cognitive symptoms in ET. Objective We discuss the neuroimaging research investigating the brain structure and function of ET patients relative to healthy controls. In particular, we review 1) structural neuroimaging experiments assessing the density/volume of cortical/subcortical regions and the integrity of the white-matter fibers connecting them; 2) functional studies exploring brain responses during motor/cognitive tasks and the function of specific neurotransmitters/metabolites within cortical–cerebellar circuits. Methods A search in PubMed was conducted to identify the relevant literature. Discussion Current neuroimaging research provides converging evidence for the role of the cerebellum in the pathophysiology of ET, although some inconsistencies exist, particularly in structural studies. These discrepancies may depend on the high clinical heterogeneity of ET and on differences among the experimental methods used across studies. Further investigations are needed to disentangle the relationships between specific ET phenotypes and the underlying patterns of neural abnormalities.
Sound and Complete Query Answering in Intensional P2P Data Integration

Contemporary use of the term 'intension' derives from the traditional logical doctrine that an idea has both an extension and an intension. In this paper we introduce an intensional FOL (First-order-logic) for P2P systems by fusing the Bealer's intensional algebraic FOL with the S5 possible-world semantics of the Montague, we define the intensional equivalence relation for this logic and the weak deductive inference for it. The notion of ontology has become widespread in semantic Web. The meaning of concepts and views defined over some database ontology can be considered as intensional objects which have particular extension in some possible world: for instance in the actual world. Thus, non invasive mapping between completely independent peer databases in a P2P systems can be naturally specified by the set of couples of intensionally equivalent views, which have the same meaning (intension), over two different peers. Such a kind of mapping has very different semantics from the standard view-based mappings based on the material implication commonly used for Data Integration. We show how a P2P database system may be embedded into this intensional modal FOL, and how we are able to obtain a weak non-omniscient inference, which can be effectively implemented. For a query answering we consider non omniscient query agents and we define object-oriented class for them which implements as method the query rewriting algorithm. Finally, we show that this query answering algorithm is sound and complete w.r. t. the weak deduction of the P2P intensional logic.