Miracle-dz/UniFAR-FTUs huggingface dataset:
Children's Oncology Group's 2013 blueprint for research: Hodgkin lymphoma

In childhood Hodgkin lymphoma, estimated 5 years survival rates exceed 90%. Long‐term survival continues to decline from delayed toxicities. Key findings from recent Children's Oncology Group trials include: (1) Radiotherapy selection may be based on early chemotherapy response assessed by both FDG‐PET and CT imaging, (2) A new prognostic factor score stratifies patients into risk categories; and (3) novel retrieval regimens were identified. A phase I/II trial is investigating Brentuximab vedotin (Bv) with gemcitabine in relapsed patients. A phase 3 trial will modify conventional chemotherapy and radiotherapy approaches through the addition of Bv, while incorporating translational biology to identify molecular targets. Pediatr Blood Cancer 2013; 60: 972–978. © 2012 Wiley Periodicals, Inc.
[Analysis of clinicopathology and prognosis in 181 patients with gastrointestinal stromal tumors].

OBJECTIVE To investigate the therapeutic experience of gastrointestinal stromal tumors (GIST) and to analyze the pathological features and prognostic factors of GIST. METHODS The clinicopathological and follow-up data of 181 patients with GIST admitted in Renji Hospital between January 1999 and December 2007 were analyzed retrospectively. All the cases were grouped according to Fletcher's risk scheme. Life table and COX regression model were used to evaluate the prognostic factors. RESULTS Out of 181 tumors, 107(59.1%) were located in stomach, 51 (28.2%) in intestine and 23(12.7%) in colorectum or other sites. Distant metastases,including liver metastases were found in 7 patients intraoperatively. Tumor size ranged from 0.5 to 30 cm with the mean of 7.02 cm. The positive rate of CD117 was 94.5% (171/181) and that of CD34 was 86.2% (156/181). One hundred and seventy-six patients underwent complete resections, including multi-organ resections in 26 patients. The other patients underwent palliative operations. The 1-, 3- and 5-year overall survival rates of 181 patients were 95.2%, 87.9% and 78.5% respectively. Univariate analysis revealed age, tumor size, primary organ of tumor, mitotic count, Fletcher's classification and multi-organ resection were associated with survival rate. No significant difference of sex was existed among groups. COX hazard proportional model revealed that advanced stage and large tumor size indicated worse prognosis. Eight patients with high risk of recurrence and 3 patients with recurrence and metastasis were stable after receiving imatinib therapy. CONCLUSIONS The diagnosis of GIST depends on endoscope and CT. Fletcher's classification is simple and effective to evaluate GIST behavior and prognosis. Surgical resection is still the main therapy for GIST and targeted therapy will play a more important role for prognosis in the future.
Estrogen-Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation1

Despite numerous observations of the effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. Using rats in which irradiation had completely blocked spermatogonial differentiation, we previously showed that testosterone suppression with gonadotropin-releasing hormone-antagonist acyline and the antiandrogen flutamide stimulated spermatogenic recovery and that addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and using concurrent data on regulation of the genes by these hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or testosterone changes. Expression of 20 genes, largely in somatic cells, was up- or downregulated between 2- and 5-fold by E2. The unexpected and striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes suggested that these might represent noncoding mRNAs; indeed, we have identified several as miRNAs and their potential target genes in this system. We propose that genes for which expression levels are altered in one direction by irradiation and in the opposite direction by both testosterone suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.
Oropharyngeal collapse predicts treatment response with oral appliance therapy in obstructive sleep apnea.

STUDY OBJECTIVES To examine whether primary oropharyngeal collapse of the upper airway during sleep predicts treatment success with oral appliance therapy in patients with obstructive sleep apnea. DESIGN Prospective physiologic study. SETTING Multidisciplinary sleep disorders clinic in a university teaching hospital. PATIENTS Twelve treatment-naïve adult patients with obstructive sleep apnea (apnea-hypopnea index > or = 10/h and at least 2 of the following symptoms: snoring, fragmented sleep, witnessed apneas, or daytime sleepiness). INTERVENTION Custom-made mandibular advancement splint (MAS). MEASUREMENTS AND RESULTS A baseline diagnostic polysomnogram confirmed AHI > or = 10 per hour. During the following acclimatization period, a custom-made adjustable MAS was incrementally advanced until maximum comfortable mandibular protrusion was reached. A second polysomnogram with MAS in situ determined efficacy. Following a 1-week washout period, a final sleep study was performed using multisensor catheters (with and without MAS, in random order during the same night) to determine upper-airway closing pressures and the site or sites of upper-airway collapse. MAS resulted in significant improvements, mean +/- SEM, in AHI (22.0 +/- 2.6 vs 9.2 +/- 1.9/h, p < .01) and upper-airway closing pressures during stage 2 non-rapid eye movement sleep (-1.1 +/- 0.3 vs -2.8 +/- 0.5 cm H2O, p < .01). All 4 patients with primary oropharyngeal collapse achieved an AHI < 5 per hour. Only 1 of the 8 patients with primary velopharyngeal collapse achieved an AHI < 5 per hour. Oropharyngeal collapse, compared with velopharyngeal collapse, predicted treatment success with MAS (p < .02). CONCLUSIONS These preliminary data suggest that primary oropharyngeal collapse of the upper airway during sleep is an important predictor of treatment outcome with MAS therapy.
Intracellular aggregation of human stefin B: confocal and electron microscopy study

Background. Protein aggregation is a major contributor to the pathogenic mechanisms of human neurodegenerative diseases. Mutations in the CSTB (cystatin B) gene [StB (stefin B)] cause EPM1 (progressive myoclonus epilepsy of type 1), an epilepsy syndrome with features of neurodegeneration and increased oxidative stress. Oligomerization and aggregation of StB in mammalian cells have recently been reported. It has also been observed that StB is overexpressed after seizures and in certain neurodegenerative conditions, which could potentially lead to its aggregation. Human StB proved to be a good model system to study amyloid fibril formation in vitro and, as we show here, to study protein aggregation in cells.
Divergent Host Plant Adaptation and Reproductive Isolation between Ecotypes of Timema cristinae Walking Sticks

Theoretical and empirical studies have demonstrated that divergent natural selection can promote the evolution of reproductive isolation. Three unresolved questions concern the types of reproductive barriers involved, the role of geography, and the factors determining the extent of progress toward complete speciation. Here I synthesize studies of Timema cristinae host plant ecotypes to address these issues. The approach is to compare the magnitude of multiple reproductive barriers among different ecological and geographic scenarios, where pairs of populations within each scenario are the unit of replication. Application of this approach to T. cristinae revealed that divergent host adaptation can promote the evolution of diverse reproductive barriers, including those that are not inherently ecological. Gene flow in parapatry tended to constrain divergence, with the notable exception of the reinforcement of sexual isolation. Thus, geography affected progress toward speciation but did not influence all reproductive barriers in the same way. Studies of any single pair of taxa often capture only certain stages of the speciation process. For example, reproductive isolation between T. cristinae ecotypes is incomplete, and so only the stages before the completion of speciation have been examined. Studies of more divergent taxa within the genus are required to determine the factors that complete speciation.
Defective Fin Regeneration in Medaka Fish (Oryzias latipes) with Hypothyroidism

Abstract Wild-type medaka are known to have remarkable capabilities of fin, or epimorphic, regeneration. However, a hypothyroid mutant, kamaitachi (kmi), frequently suffers from injury in fins, suggesting an important role of thyroid hormone in fin regeneration. This led us to examine the relationship between thyroid hormone and fin regeneration using medaka as a model. For this, we first set up a medaka experimental system in which the rate of regeneration was statistically analyzed after caudal fin amputation under normal and hypothyroid conditions. As expected, the regeneration of amputated caudal fins was delayed in hypothyroid kmi –/– mutants. We then examined wild-type medaka with thiourea-induced hypothyroidism to evaluate the requirement of thyroid hormone during epimorphic fin regeneration. The results demonstrate that the growth rate of regenerates was much reduced in severely hypothyroid medaka throughout the regeneration period. This reduction in regenerative rate was recovered by exogenous administration of L-thyroxine. The present study is thus the first to report the direct involvement of thyroid hormone in teleost fin regeneration, and provides a basic framework for future molecular and genetic analyses.
Vaccination of humans against cutaneous leishmaniasis: cellular and humoral immune responses

Brazilian army conscripts were vaccinated against American cutaneous leishmaniasis by using nonliving polyvalent promastigote Leish vaccine 5 or Leish vaccine 6 (vaccines with five or six Leishmania stocks) with or without Corynebacterium parvum. No statistically significant differences in lymphocyte stimulation indices were found between vaccinated groups with or without C. parvum, but lymphocyte stimulation indices of all vaccinees were significantly higher (P less than 0.001) than those of the placebo group. A correlation of 90% was found between positive skin test results and positive lymphocyte stimulation indices. Eight major antigens with estimated molecular masses of 13.5, 25, 40, 63, 73, 85, 97, and 160 kilodaltons were recognized by Leish vaccine 5 sera. Our finding also demonstrated the predominance of immunoglobulin M antibody in sera of vaccinated subjects and that a component of Leish vaccine 5, gp63, was immunogenic in humans both at the T-cell level and at the antibody level.
The reproductive cycle in male noctule bats, Nyctalus noctula.

Summary. Spermatogenesis took place in noctule bats during summer; spermatozoa were released from the testis in August and September, and the testes then involuted. Although no more spermatozoa were produced, they continued to be stored in the cauda epididymidis for the duration of winter. The testosterone content of the testes rose with the progress of spermatogenesis from 10 ng/pair in May to 847 ng/pair in August. The concentration of the hormone in the blood plasma paralleled this increase, rising from 4\m=. \7 ng/ml to 134 ng/ml over the same period. Testosterone levels were maintained during autumn, when most mating took place, but decreased during the subsequent winter period of sperm storage. The weights of the accessory glands and their fructose content were maintained over this period. It appears that the maintenance of active accessory glands of reproduction and of fertile spermatozoa in the epididymis has a comparatively low androgen requirement in noctule bats.
Mechanism of hcnA mRNA recognition in the Gac/Rsm signal transduction pathway of Pseudomonas fluorescens

In the plant‐beneficial bacterium Pseudomonas fluorescens CHA0, the expression of antifungal exoproducts is controlled by the GacS/GacA two‐component system. Two RNA binding proteins (RsmA, RsmE) ensure effective translational repression of exoproduct mRNAs. At high cell population densities, GacA induces three small RNAs (RsmX, RsmY, RsmZ) which sequester both RsmA and RsmE, thereby relieving translational repression. Here we systematically analyse the features that allow the RNA binding proteins to interact strongly with the 5′ untranslated leader mRNA of the P. fluorescens hcnA gene (encoding hydrogen cyanide synthase subunit A). We obtained evidence for three major RsmA/RsmE recognition elements in the hcnA leader, based on directed mutagenesis, RsmE footprints and toeprints, and in vivo expression data. Two recognition elements were found in two stem‐loop structures whose existence in the 5′ leader region was confirmed by lead(II) cleavage analysis. The third recognition element, which overlapped the hcnA Shine–Dalgarno sequence, was postulated to adopt either an open conformation, which would favour ribosome binding, or a stem‐loop structure, which may form upon interaction with RsmA/RsmE and would inhibit access of ribosomes. Effective control of hcnA expression by the Gac/Rsm system appears to result from the combination of the three appropriately spaced recognition elements.
Psychosocial Stress and Susceptibility to Upper Respiratory Tract Illness in an Adult Population Sample

Objective To assess the influence of life event stress and hassles, and the moderating effects of psychological coping style, social support, and family environment, on susceptibility to upper respiratory tract infectious illness. Method One hundred seven adults aged 18 to 65 years took part in a 15-week study. Measures of life event stress were obtained for the 12 months preceding the study and for the study period itself, and social support, information seeking and avoidant coping styles, and family environment were assessed. Hassles and perceived stress were measured weekly, whereas dysphoric mood and changes in personal health practices (smoking, alcohol consumption, exercise, and sleep patterns) were assessed at three weekly intervals. Episodes of upper respiratory tract infectious illness were verified by clinical examination. Results During the study period, 29 individuals experienced at least one clinically verified episode of upper respiratory tract illness. There were no differences in cigarette smoking, sleep habits, or exercise between those who did and did not become ill, but alcohol consumption was lower among those who experienced verified episodes. Risk of infectious illness was greater in those who experienced high life event stress both before and during the study period, but the impact of life events was buffered by an avoidant coping style. Strict family organization was associated with illness risk. The three weeks preceding illness onset were characterised by high levels of perceived stress, but also by a decrease in the number of hassles reported. Conclusions Results suggest that under naturalistic conditions, the influence of stressful experience on risk of infectious illness is moderated by psychosocial resources. Variations in personal health practices do not seem to be responsible.
Microstructure and mechanical properties of lead-free solders and solder joints used in microelectronic applications

The replacement of lead (Pb)-bearing solders used in the electronic industry with Pb-free solders will become a reality in the near future. Several promising Pb-free solders have recently been identified, including Sn-0.7Cu, Sn-3.5Ag, Sn-3.8Ag-0.7Cu, and Sn-3.5Ag-4.8Bi (in wt.% with slight variations in composition). These are all Sn-rich solders with melting temperatures between 210°C and 227°C, and are recommended for various soldering applications, including surface mount technology (SMT), plated-through-hole (PTH), ball grid array (BGA), flip-chip bumping, and others. Although a considerable amount of information on Pb-free solders has been published in the last few years, the database on these new materials is still at an infant stage compared with that for Pb-containing solders. This paper addresses several aspects of the current fundamental materials understanding associated with Pb-free solders and various issues regarding their imminent use in electronic interconnect applications, including microstructure-processing-property relations, mechanical properties, interfacial reactions, and the thermal-fatigue life and failure mechanisms of Pb-free solder joints.
The Metabolic Topography of Normal Aging

Normal aging is associated with the degeneration of specific neural systems. We used [18F]fluorode-oxyglucose (FDG)/positron emission tomography (PET) and a statistical model of regional covariation to explore the metabolic topography of this process. We calculated global and regional metabolic rates for glucose (GMR and rCMRglc) in two groups of normal subjects studied independently on different tomographs: Group 1—130 normal subjects (62 men and 68 women; range 21–90 years); Group 2—20 normal subjects (10 men and 10 women; range 24–78 years). In each of the two groups, the Scaled Subprofile Model (SSM) was applied to rCMRglc data to identify specific age-related profiles. The validity of these profiles as aging markers was assessed by correlating the associated subject scores with chronological age in both normal populations. SSM analysis disclosed two significant topographic profiles associated with aging. The first topographic profile, extracted in an analysis of group 1 normals, was characterized by relative frontal hypometabolism associated with covariate metabolic increases in the parietooccipital association areas, basal ganglia, mid-brain, and cerebellum. Subject scores for this profile correlated significantly with age in both normal groups (R2 = 0.48 and 0.33, p < 0.0001 for groups 1 and 2, respectively). Because of clinical similarities between normal motoric aging and parkinsonism, we explored the possibility of shared elements in the metabolic topography of both processes. We performed a combined group SSM analysis of the 20 group 2 normals and 22 age-matched Parkinson's disease patients, and identified another aging-related topographic profile. This profile was characterized by relative basal ganglia hypermetabolism associated with covariate decreases in frontal premotor cortex. Subject scores for this profile also correlated significantly with age in both normal groups (group 1: R2 = 0.30, p < 0.00001; group 2: R2 = 0.59, p < 0.01). Healthy aging is associated with reproducible topographic covariation profiles associated with specific neural systems. FDG/PET may provide a useful metabolic marker of the normal agingprocess.
Mesh adaptive direct search approach for D2D resource management

Device-to-device (D2D) communications are being considered a way forward to achieve higher data rate targets for futuristic wireless networks. D2D introduces interference among cellular users and D2D users. A joint resource allocation (JRA) strategy in cellular network with D2D functionality can definitely enhance overall data rate. The strategy under consideration maximizes the overall data rate of cellular network besides meeting threshold of power and interference constraints. The JRA is a class of mixed integer non-linear constraint optimization problems and is NP hard. Because of discrete nature of variables in the problem, optimal solution performs extensive search of integer variables, and problem becomes exponentially complex with the increasing number of user pairs. In this paper, mesh adaptive direct search algorithm is applied to solve the aforementioned problem. The algorithm is suitable for complex problems of combinatorial nature to solve the JRA strategy in D2D. The proposed algorithm converges to optimal solution within acceptable computational iterations. Simulation results of system capacity and interference also demonstrate the suitability of the proposed approach viz-a-viz other algorithms. Copyright © 2016 John Wiley & Sons, Ltd.
The involvement of matrix metalloproteinases in basement membrane injury in a murine model of acute allergic airway inflammation

Background Airway remodelling in asthma such as subepithelial fibrosis is thought to be the repair process that follows the continuing injury as of chronic airway inflammation. However, how acute allergic inflammation causes tissue injury in the epithelial basement membrane in asthmatic airways remains unclear. Matrix metalloproteinases (MMPs) capable of degrading almost all of the extracellular matrix components have been demonstrated to be involved in cell migration through the basement membrane in vivo and in vitro.
Evaluation of Sex Differences in the Pharmacokinetics of Ranitidine in Humans

A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half‐life of ranitidine was 7% shorter and the oral apparent clearance 10.5% higher in women (1.44 L/h/kg) than in men (1.29 L/h/kg), although this difference did not reach statistical significance. No differences were observed in maximum concentration (Cmax) or the time of its occurrence (tmax). Sex, age, and weight did not correlate significantly with oral clearance. These results suggest that there are no sex differences in the pharmacokinetics of ranitidine, or that any differences would not be of clinical relevance. It also should be emphasized that bioequivalence trials also can be used to study other pharmacokinetic or pharmacodynamic characteristics of drugs without damaging the main endpoint of the study.
Virtual patient care: an interprofessional education approach for physician assistant, physical therapy and occupational therapy students

Abstract The purpose of this retrospective qualitative case report is to describe how a case-based, virtual patient interprofessional education (IPE) simulation activity was utilized to achieve physician assistant (PA), physical therapy (PT) and occupational therapy (OT) student IPE learning outcomes. Following completion of a virtual patient case, 30 PA, 46 PT and 24 OT students were required to develop a comprehensive, written treatment plan and respond to reflective questions. A qualitative analysis of the submitted written assignment was used to determine whether IPE learning objectives were met. Student responses revealed three themes that supported the learning objectives of the IPE experience: benefits of collaborative care, role clarification and relevance of the IPE experience for future practice. A case-based, IPE simulation activity for physician assistant and rehabilitation students using a computerized virtual patient software program effectively facilitated achievement of the IPE learning objectives, including development of greater student awareness of other professions and ways in which collaborative patient care can be provided.