Miracle-dz/UniFAR-FTUs huggingface dataset:
The echinocandin antifungals: an overview of the pharmacology, spectrum and clinical efficacy

For over four decades, the principal target of antifungal therapy has been the fungal cell membrane sterol ergosterol. Although this has proven to be a successful and relatively selective antifungal target, collateral toxicity to mammalian cells (amphotericin B) and drug interactions (azoles) have been by-products of agents that target the fungal cell membrane. In the 1970s, the echinocandins were identified during the screening of fungal fermentation products for new antibiotic agents. These agents were subsequently shown to inhibit production of β(1,3)-glucan, a key structural component of the fungal cell wall. Subsequent chemical modification of these natural products has led to the development of safer, semi-synthetic β(1,3)-glucan synthase inhibitors with enhanced microbiological and clinical efficacy against infections caused by Candida and Aspergillus species. In this review, the pharmacology, spectrum and clinical efficacy of the three leading β(1,3)glucan synthase inhibitors (caspofungin, micafungin and anidulafungin), which have completed phase III clinical trials, will be discussed and a perspective for the role of these agents in the management of life-threatening mycoses will be offered.
How to compare and exploit different techniques for unit-test generation

The size and complexity of software is continuously growing, and testing is one of the most important strategies for improving software reliability, quality, and design. Unit testing, in particular, forms the foundation of the testing process and it is effectively supported by automated testing frameworks. Manual unit-test creation is difficult, monotonousand time-consuming. In order to reduce the effort spent on this task, several tools have been developed. Many of them can almost automatically produce unit tests for regression avoidance or failure detection. This paper presents a practical comparison methodology to analyze different unit-testing creation tools and techniques. It validates the effectiveness of tools and spots their weaknesses and strengths. The validity of this methodology is confirmed through a real case experiment, in which both the manual implementation and different automatic test generation tools (based on random testing) are used. In addition, in order to integrate and exploit the benefits of each technique, which result from the comparison process, a testing procedure based on “best practices” is developed.
Sleep Deprivation Does Not Mimic Alcohol Intoxication on Field Sobriety Testing *

Abstract: Previous research shows that sleep deprivation (SD) produces cognitive impairment similar to that caused by alcohol intoxication. Individual studies suggest that SD also causes deficits in motor skills that could be mistaken for intoxication. Consequently, SD often is used as a defense when an impaired driver is charged with driving while intoxicated. Twenty‐nine adult subjects participated in two test sessions each, one after a full night’s rest and the other after wakefulness of at least 24 h. Subjects consumed prescribed amounts of alcohol during each session. Law enforcement officers conducted field sobriety tests identical to those with which a driver would be assessed at roadside. Researchers also measured clinical responses of visual function and vital signs. The presence and number of validated impairment clues increase with increasing blood alcohol concentration but not with SD. Thus, SD does not affect motor skills in a manner that would lead an officer to conclude that the suspect is intoxicated, unless intoxication also is present.
LES CARACTERISTIQUES DES CONTRATS DE DETTE ET LES CLAUSES RESTRICTIVES COMPTABLES : QUELS LIENS ?

Cette etude examine les facteurs determinants le recours aux donnees comptables dans les contrats de dette. Les resultats suggerent que le recours aux clauses comptables est positivement associe au risque de l'emetteur et aux dettes remboursables, et negativement a la maturite du pret et la taille de la firme.
Setting priorities in waiting lists.

Traditionally, surgical waiting lists have served to prioritize care, with the worst cases addressed first, along, in some instances, with those who have shouted the loudest. Patients with less severe symptoms have usually waited for much longer periods. This is now politically unacceptable. Setting priorities in waiting lists would be far simpler and much less relevant were it not for the major discrepancies between demand and supply. These discrepancies, which have for so long been the norm in the NHS, lead to the creation of long waiting times.
Customization in Lingual Orthodontics

Lingual orthodontics is more difficult and complex than labial orthodontics for several reasons, such as difficulties in bracket positioning, patient comfort, maintenance of oral hygiene, and biomechanics. With the advent of newer materials and technologies, many of these problems have been overcome, and we are able to finish lingual orthodontic cases to the same standards as labial orthodontics. Customization along with the use of 3D treatment planning software in lingual orthodontics has enabled dentists to visualize the end result even before starting the treatment. Individualized brackets and wires can be realized by computer-aided design and computer-aided manufacturing on a target setup made at the outset of treatment so that post-treatment results mirror the pre-treatment setup. New technologies like CAD/CAM, intraoral and cast model scanning, 3D printing and robotics have all led to the emergence of several customized lingual appliance systems that have been instrumental in enhancing the reliability, precision, and feasibility of lingual orthodontics.
Constrangimentos da tarefa e respostas da carga externa e interna no futebol feminino português de elite

ABSTRACT The aim of this study was to characterize the responses of external and internal load in small sided games by manipulating two task constraints: the number of players and the limitation of contact with the ball. In this study, took part 6 elite players of Portuguese female football (age: 25±6,8; years of practice: 3,3±2; height: 169±3,2; weight: 60,6±2,4; body mass: 21,4±0,7;). Separately, the results demonstrated that the influence of both constraints didn’t provoke significant differences in the responses of the load towards the exercise. In interaction, were noticed differences in the percentage of average distance covered in low intensity running as well as the duration of high intensity running. The average heart rate and its percentage values relative to maximum heart rate, proved to be distinct in the 3x3 exercises during free game and in the two touches limited situation. The heart rate study throughout the time allowed identifying the existence of differences not only in average values but also in the variability of records obtained at certain moments of the proposed tasks. In elite levels, the coaches may induce changes in heart rate responses, the distances covered and the duration of displacements association the manipulation of the number of players and the number of contacts with the ball.
Spontaneous emergence of social influence in online systems

Social influence drives both offline and online human behavior. It pervades cultural markets, and manifests itself in the adoption of scientific and technical innovations as well as the spread of social practices. Prior empirical work on the diffusion of innovations in spatial regions or social networks has largely focused on the spread of one particular technology among a subset of all potential adopters. Here we choose an online context that allows us to study social influence processes by tracking the popularity of a complete set of applications installed by the user population of a social networking site, thus capturing the behavior of all individuals who can influence each other in this context. By extending standard fluctuation scaling methods, we analyze the collective behavior induced by 100 million application installations, and show that two distinct regimes of behavior emerge in the system. Once applications cross a particular threshold of popularity, social influence processes induce highly correlated adoption behavior among the users, which propels some of the applications to extraordinary levels of popularity. Below this threshold, the collective effect of social influence appears to vanish almost entirely, in a manner that has not been observed in the offline world. Our results demonstrate that even when external signals are absent, social influence can spontaneously assume an on–off nature in a digital environment. It remains to be seen whether a similar outcome could be observed in the offline world if equivalent experimental conditions could be replicated.
The Association between Sleep Duration and Hypertension in Non-obese Premenopausal Women in Korea

Background Previous studies have revealed that sleep duration is linked to both obesity and hypertension. Here, we evaluated the association between sleep duration and hypertension in obese and non-obese premenopausal women using representative national survey data from the Korean population. Methods A total of 4,748 subjects over 20 years of age from the Korean National Health and Nutrition Examination Survey from 2010 to 2012 were included. To control for risk factors, multivariable logistic regression was used to calculate the adjusted odds ratios and 95% confidence intervals of hypertension across the following sleep duration categories: <6, 6-8, and >8 h/d. Results Among the participants, 367 subjects (7.7%) had hypertension. Their mean sleep duration was 7 hours. In the non-obese subjects, after controlling for potential confounding variables, the odds ratio for hypertension was 1.86 fold greater in those with a sleep duration of <6 hours (odds ratio, 1.79; 95% confidence interval, 1.05 to 3.03) as compared to those who slept for 6.8 hours. However, there was no association between sleep duration and the risk of hypertension in obese subjects. Long sleep duration (over 8 h/d) was not associated with hypertension in either the non-obese or the obese subjects in this study. Conclusion Short sleep duration (less than 6 h/d) may be a significant risk factor for hypertension in non-obese premenopausal women. However, there is no association between sleep duration and the risk of hypertension in obese women.
Thermotolerance protects against endotoxin-mediated microvascular injury.

An early event in endotoxin-induced tissue injury is adhesion and migration of leukocytes through the endothelium. This is a three-stage process, initially low-grade selectin-mediated adhesion, seen as a decrease in rolling velocity, followed by integrin-mediated adhesion and transmigration. Thermotolerance has been shown to reduce tissue injury and mortality induced by endotoxin. The aim of this study was to investigate the effect of thermotolerance on leukocyte-endothelial interactions. Intravital video microscopy was used to examine hemodynamic parameters, leukocyte rolling, adhesion, and migration in rat mesenteric postcapillary venules. Sprague-Dawley rats were randomized into control, lipopolysaccharide (LPS), and thermotolerance + LPS groups. Thermotolerance was induced 18 h prior to administration of LPS by elevating core body temperature to 41 + 0.5 degrees C for 15 min. LPS (055:B5 15 mg/kg) was administered via the jugular vein after baseline recording. Leukocyte rolling velocity and the number of adherent and migrated leukocytes were measured by intravital microscopy at baseline 0 min and 10, 30, 60, and 90 min after LPS administration. Heat shock protein 72 (HSP72) expression in tissues was determined by Western immunoblotting. The results indicated that LPS administration significantly decreased leukocyte rolling velocity during endotoxemia and increased leukocyte adhesion (10.3 +/- 1.67, 13.2 +/- 1.40, and 10.0 +/- 1.57/100 microm) and migration (5.7 +/- 1.02 and 8.3 +/- 1.76/field) at 30, 60, and 90 min after LPS injection (P < 0.01 vs baseline and control group). Thermotolerance maintained leukocyte rolling velocity and significantly reduced leukocyte adhesion (5.7 +/- 0.88 and 4.0 +/- 0.68/100 microm) and migration (2.8 +/- 0.32 and 3.0 +/- 0.68/field) at 30 and 60 min after LPS administration (P < 0.01 and 0.05 vs LPS group). Expression of HSP72 was induced in mesentery, gut, and lung by thermotolerance. This study indicates that thermotolerance attenuated LPS-induced microvascular injury by decreasing leukocyte-endothelial adhesion and migration.
Analyse de l'évolution fonctionnelle à long terme de cas d'arthrite de hanche dans l'enfance et de la stratégie de prise en charge chirurgicale initiale

L'arthrite septique de hanche de l'enfant est a risque de sequelles fonctionnelles majeures. Aussi, les recommandations d'usage incluent une arthrotomie pour lavage articulaire en urgence lors de la confirmation diagnostique par ponction articulaire. Ce geste reste neanmoins discutable puisqu'aucune etude n'a evalue son interet sur le plan de l'infection et de l'evolution fonctionnelle. Ainsi, nous avons etudie 40 cas d'arthrites septiques de hanche n'ayant pas comporte d'arthrotomie en urgence, puisque non retenue par le protocole en vigueur dans notre etablissement, avec evaluation fonctionnelle via les scores SF-12 et Oxford-12. Le recul moyen etait de 6,5 ans. Neuf cas ont presente une evolution non satisfaisante (22,5%). Les criteres pronostiques d'evolution defavorable retrouves etaient : âge < 3 mois (p=0,0135), osteomyelite associee (p=0,0397), un taux de CRP initiale superieur a 190 mg/L (p=0,0066). La prematurite, la presence d'une bacterie virulente ainsi qu'un retard dans la prise charge constituaient egalement des criteres defavorables. Cette etude donne donc un premier fondement a la realisation d'une toilette articulaire en urgence, surtout lorsque des criteres de gravite sont presents.
Musculoskeletal Overuse Injuries in the Pediatric Population

In pediatric patients, musculoskeletal overuse injuries are common clinical complaints. Recently, the number of youth who are engaged in formal competition has increased. A National Council of Youth Sports survey found that 60 million children aged 6 to 18 yr participate in some form of organized athletics. Surveillance reporting systems, such as the National High School Sports-Related Injury Surveillance System and the High School Reporting Information Online (high school RIO), an Internet-based sports injury surveillance tool, have suggested an increase in the rates of overuse injuries. This article will focus on potential risk factors for overuse injuries, including those that are intrinsic and extrinsic in youth athletes. We also make note of some of the more common overuse injuries seen in the outpatient clinical setting, their diagnoses, and treatment based on current evidence-based literature.
Genotoxicity biomarkers in the assessment of heavy metal effects in mussels: Experimental studies

Heavy metals are stable and persistent environmental contaminants. The range of metal concentrations is generally below acute thresholds in coastal areas, where recognition of chronic sublethal effects is more relevant. Evidence of long‐term adverse effects, such as cancer, due to heavy metals in marine animals comes from a number of field and experimental studies. The mechanism of metal carcinogenicity remains largely unknown, although several lines of experimental evidence suggest that a genotoxic effect may be involved. The aim of our study was to evaluate the sensitivity of genotoxicity tests, alkaline elution and micronucleus test, as biomarkers for the detection of heavy metals in mussels as the sentinel species. Experimental studies were carried out on Mytilus galloprovincialis exposed in aquarium (5 days) to different concentrations of three selected metal salts, CuCl2 (5, 10, 20, 40, 80 µg/l/a), CdCl2 (1.84, 18.4, 184 µg/l/a), and HgCl2 (32 µg/l/a), and to a mixture of equimolar doses of the three metals to study the results of their joint action. Metallothionein quantitation was used as a marker of metal exposure. Lysosomal membrane stability was applied to evaluate the influence of physiological status on genotoxic damage. The ranking of genotoxic potential was in decreasing order: Hg > Cu > Cd. Cu and Hg caused an increase of DNA single‐strand breaks and micronuclei frequency. Cd induced a statistical increase of DNA damage, but gave negative results with the micronucleus test. A relationship between genotoxic effects and metallothionein content was observed. Reduction in lysosomal membrane stability with the increasing concentration of heavy metals was also evident. Environ. Mol. Mutagen. 33:287–292, 1999 © 1999 Wiley‐Liss, Inc.
Predictive Factors in the Quality of Life of Cancer Inpatients

ABSTRACT The purpose of the study was to determine whether sense of coherence (SOC), and demographic variables (age, gender, race, education, length of illness) predict quality of life (QOL) in cancer inpatients. SOC is the extent to which one finds life comprehensible, manageable, and meaningful. Participants were 49 inpatients (66% female) with various forms of cancer, mostly African American (71%), with a mean age of 54.5 years. The mean QOLS of cancer inpatients (84.6) was lower than a healthy population (90.0), however, their mean item scores indicated that they are “mostly satisfied” with most areas of QOL except for active forms of past-time and health. The mean SOC score (133.8) was also lower than other groups; however without appropriate norms, it cannot be concluded that cancer inpatients have a weak SOC. Multiple regressions showed that SOC was a significant predictor of QOL, and that the demographic variables were not predictive of QOL, except when combined with SOC. All findings may be limited by demographics of the sample (race, gender, age, severity of illness), and the inability of cross-sectional investigations to determine causality.
Analysis of the sugar‐binding specificity of mannose‐binding‐type Jacalin‐related lectins by frontal affinity chromatography – an approach to functional classification

The Jacalin‐related lectin (JRL) family comprises galactose‐binding‐type (gJRLs) and mannose‐binding‐type (mJRLs) lectins. Although the documented occurrence of gJRLs is confined to the family Moraceae, mJRLs are widespread in the plant kingdom. A detailed comparison of sugar‐binding specificity was made by frontal affinity chromatography to corroborate the structure–function relationships of the extended mJRL subfamily. Eight mJRLs covering a broad taxonomic range were used: Artocarpin from Artocarpus integrifolia (jackfruit, Moraceae), BanLec from Musa acuminata (banana, Musaceae), Calsepa from Calystegia sepium (hedge bindweed, Convolvulaceae), CCA from Castanea crenata (Japanese chestnut, Fagaceae), Conarva from Convolvulus arvensis (bindweed, Convolvulaceae), CRLL from Cycas revoluta (King Sago palm tree, Cycadaceae), Heltuba from Helianthus tuberosus (Jerusalem artichoke, Asteraceae) and MornigaM from Morus nigra (black mulberry, Moraceae). The result using 103 pyridylaminated glycans clearly divided the mJRLs into two major groups, each of which was further divided into two subgroups based on the preference for high‐mannose‐type N‐glycans. This criterion also applied to the binding preference for complex‐type N‐glycans. Notably, the result of cluster analysis of the amino acid sequences clearly corresponded to the above specificity classification. Thus, marked correlation between the sugar‐binding specificity of mJRLs and their phylogeny should shed light on the functional significance of JRLs.
Evidence for the involvement of interleukin 6 in experimental cancer cachexia.

In this report we describe an experimental model of cachexia that fulfills the criteria of an early effect with a small tumor mass not related to the growth rate of the tumor, and progressive wasting of muscle and fat without a detectable loss of appetite. C-26.IVX is a cell line derived from murine colon-26 adenocarcinoma which retains the transplantability of the original tumor and induces true cachexia in syngeneic hosts. Evidence is presented to support a role for interleukin (IL-6) as a cachectic factor in the development of cancer cachexia in this model system. Thus, increasing levels of IL-6 in C-26.IVX-bearing mice correlate with the development of cachexia. If the primary tumors were resected, mice gained weight and the levels of IL-6 in the serum were reduced significantly. Moreover, monoclonal antibody to murine IL-6 (but not anti-tumor necrosis factor antibody) was able to significantly suppress the development of key parameters of cachexia in tumor bearing mice.
Classification of Somatization and Functional Somatic Symptoms in Primary Care

Objective: A substantial proportion of patients found in primary care complain of physical symptoms not attributable to any known conventionally defined disorder, that is, medically unexplained or functional somatic symptoms. The objective of this paper is to outline the problems with the current classification and propose a classification more suitable for primary health care. Method: We refer to and discuss relevant literature including papers on our own research on the topic in the light of our experiences from major projects on somatizing patients in primary health care. Results: Functional somatic symptoms may impose severe suffering on the patient and are costly for society because of high health-care utilization, lost working years and social expenses. At present, studies on functional somatic symptoms and disorders and their treatment are hampered by lack of a valid and reliable diagnostic classification. The diagnostic categories of somatoform disorders are overlapping. Thus, the present situation is that patients with identical symptoms and clinical pictures may receive different diagnostic labels depending on the focus of interests of the assessing physician. A particular problem in primary care is that the somatoform diagnostic categories only include persistent cases and do not offer the opportunity for classification of the patients with short-symptom duration found in this setting. We present a framework for a new descriptive classification of functional somatic symptoms and unfounded illness worrying, and outline a new classification that covers the whole spectrum of severity seen in clinical practice. Conclusion: A precondition for an appropriate management of patients with functional somatic symptoms is a valid taxonomy common for all medical specialties facilitating cooperative care. Classification systems as outlined in this paper may be a candidate for such a system, but it should be subject to further evaluation in research.
Regulatory cross‐talk between lysine acetylation and ubiquitination: role in the control of protein stability

It is now becoming apparent that cross‐talk between two protein lysine modifications, acetylation and ubiquitination, is a critical regulatory mechanism controlling vital cellular functions. The most apparent effect is the inhibition of proteasome‐mediated protein degradation by lysine acetylation. Analysis of the underlying mechanisms, however, shows that, besides a direct competition between the two lysine modifications, more complex and indirect processes also connect these two signalling pathways. These findings point to protein lysine acetylation as a potential regulator of various cellular functions involving protein ubiquitination. BioEssays 27:408–415, 2005. © 2005 Wiley periodicals, Inc.