Miracle-dz/UniFAR-FTUs huggingface dataset:
Lessons learned from the Sunbelt Melanoma Trial

The Sunbelt Melanoma Trial is an ongoing multicenter prospective randomized trial that involves 79 centers and over 3600 patients from across the United States and Canada. This is one of the first large randomized studies to incorporate molecular staging using reverse transcriptase polymerase chain reaction (RT‐PCR). While the results related to the primary endpoints of the study are not yet available, several analyses have shed light on many aspects of sentinel lymph node (SLN) biopsy and melanoma prognostic factors. In particular, we have developed a practical definition of sentinel nodes based on the degree of radioactivity. We have established the low rate of postoperative complications associated with SLN biopsy as compared to complete lymph node dissection. We have identified factors that predict the presence of SLN metastases. In contrast, we have been unable to identify factors that indicate a low risk of non‐sentinel node metastases in patients with a positive sentinel node, suggesting that completion lymphadenectomy is appropriate for such patients. We have further established the value of identifying interval or in‐transit sentinel nodes, which can be the only site of nodal metastasis. We have evaluated the particular challenges associated with SLN biopsy of head and neck melanomas, have evaluated the patterns of early recurrence, and have identified an interesting correlation between increasing patient age and a number of prognostic factors. Future analyses will evaluate the benefit of early therapeutic lymphadenectomy and early institution of adjuvant interferon alfa‐2b therapy, as well as the validity of molecular staging. J. Surg. Oncol. 2004;86:212–223. © 2004 Wiley‐Liss, Inc.
Seasonal Variation in Myocardial Infarction Is Limited to Patients with ST‐Elevations on Admission

Previous studies have demonstrated seasonal variation in the incidence of acute myocardial infarction (AMI) with an increase in cases during the winter months. However, they did not assess whether ST‐elevation MI (STEMI) and non‐ST‐elevation MI (NSTEMI) exhibit similar changes. The object of this study was to compare the seasonal variation of STEMI and NSTEMI. All patients who presented with AMI and underwent coronary angiography within seven days of admission were identified via the institutional database. STEMI diagnosis required admission ECG demonstrating ST elevation in at least two continguous leads. All AMIs not meeting criteria for STEMI were defined as NSTEMI. Patients were divided into monthly and seasonal groups based on the date of admission with MI. A total of 784 patients were included: 549 patients with STEMI and 235 with NSTEMI. When STEMI patients were analyzed by season, there were 170 patients (31%) in the winter months, a statistically significant difference of excess MI (p<0.005). When NSTEMI patients were analyzed, there were 62 patients (26%) in the winter with no statistically significant difference in the seasonal variation. Our findings suggest that the previously noted seasonal variation in the incidence of AMI is limited to patients presenting with STEMI, and that there are important physiological differences between STEMI and NSTEMI, the nature of which remains to be elucidated.
Study and implementation of asymmetrical half-bridge converter

Compared with conventional hard-switching mode, the soft switching technique causes smaller losses in applications of Switching Power Supply (SPS). The asymmetrical halfbridge converter with synchronous rectification and soft-switching technique uses turn-on and turn-off hours to achieve soft switching mode for reducing losses at high frequency, voltage and current stresses between two power switches. To reduce losses, multiplication of forward voltage and current, and increase efficiency of asymmetrical halfbridge converter, the super fast diodes are replaced with the synchronous rectification technique in secondary side of transformer. In this experiment, the turns ratio of transformer is designed to match duty cycles for devices with asymmetrical and complementary operation. Moreover, operating principle of circuit, analysis of steady-state and transient state, and design consideration are all discussed in this paper. Finally, A 300 W prototype with 400VDC input and 24VDC output operating with PWM IC-L6591 is built and tested, and the efficiency at full load is 92.09% which verifies the feasibility of theoretical analysis.
Early fracture fixation may be "just fine" after head injury: no difference in central nervous system outcomes.

BACKGROUND Recent reports suggest that early fracture fixation worsens central nervous system (CNS) outcomes. We compared discharge Glasgow Coma Scale (GCS) scores, CNS complications, and mortality of severely injured adults with head injuries and pelvic/lower extremity fractures treated with early versus delayed fixation. METHODS Using trauma registry data, records meeting preselected inclusion criteria from the years 1991 to 1995 were examined. We identified 171 patients aged 14 to 65 years (mean age, 32.7 years) with head injuries and fractures who underwent early fixation (< or = 24 hours after admission) (n = 147) versus delayed fixation (> 24 hours after admission) (n = 24). RESULTS Patients were severely injured, with a mean admission GCS score of 9.1, Revised Trauma Score of 6.2, Injury Severity Score of 38, median intensive care unit length of stay of 16.5 days, and hospital length of stay of 23 days. No differences between groups were found by age, admission GCS score, Injury Severity Score, Revised Trauma Score, intensive care unit length of stay, hospital length of stay, shock, vasopressors, major nonorthopedic operative procedures, total intravenous fluids or blood products, or mortality rates. In survivors, no differences in discharge GCS scores or CNS complications were found. CONCLUSION We found no evidence to suggest that early fracture fixation negatively influences CNS outcomes or mortality.
The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions

The extracellular signal-regulated kinase (ERK) cascade is a central pathway that transmits signals from many extracellular agents to regulate cellular processes such as proliferation, differentiation and cell cycle progression. The signaling via the ERK cascade is mediated by sequential phosphorylation and activation of protein kinases in the different tiers of the cascade. Although the main core phosphorylation chain of the cascade includes Raf kinases, MEK1/2, ERK1/2 (ERKs) and RSKs, other alternatively spliced forms and distinct components exist in the different tiers, and participate in ERK signaling under specific conditions. These components enhance the complexity of the ERK cascade and thereby, enable the wide variety of functions that are regulated by it. Another factor that is important for the dissemination of ERKs' signals is the multiplicity of the cascade's substrates, which include transcription factors, protein kinases and phosphatases, cytoskeletal elements, regulators of apoptosis, and a variety of other signaling-related molecules. About 160 substrates have already been discovered for ERKs, and the list of these substrates, as well as the function and mechanism of activation of representative substrates, are described in the current review. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Understanding of these processes may provide a full picture of the distinct, and even opposing cellular processes that are regulated by the ERK cascade.
Ratio of transmitral early filling velocity to early diastolic strain rate predicts outcomes in patients with systolic heart failure

Aims The ratio of transmitral early filling velocity (E) to early diastolic tissue velocity (E′) is a key diastolic function parameter. The early diastolic strain rate (E′sr) has been proposed as a substitute for E′ in the E/E′ ratio for better estimation of left ventricular (LV) filling pressure. This study aims to assess the predictive value of combined E/E′sr ratio and global longitudinal strain (GLS) for prognosis in systolic heart failure (SHF). Methods and results We retrospectively analysed 330 SHF patients with an LV ejection fraction (LVEF) ⩽ 40%. Study end points were defined as all-cause mortality or heart transplantation. The incremental value of GLS and the E/E′sr ratio over LVEF and E/E′ for outcome prediction was assessed using nested Cox models. Ninety-nine (30%) patients reached the end point over a median follow-up of 46 months. Baseline variables associated with outcomes were age, glomerular filtration rate, pulmonary artery systolic pressure, and LV end-systolic volume index. After multivariate adjustment, GLS (hazard ratio: 1.48, P = 0.025) and the E/E′sr ratio (hazard ratio: 1.41, P = 0.002) were both independent predictors. LVEF or E/E′ was not an independent predictor when GLS and E/E′sr were included in the model. Patients with impaired GLS (absolute value <7.5%) and elevated E/E′sr ratios (E/E′sr ≥ 195 cm) showed poor outcomes. Conclusion The E/E′sr ratio is stronger than E/E′ ratio in predicting prognosis of patients with systolic HF. Combined assessments of GLS and E/E′sr by speckle-tracking longitudinal strain facilitate risk stratification of these patients.
DEVELOPMENT, CHARACTERIZATION AND SOLUBILITY STUDY OF SOLID DISPERSIONS OF AZITHROMYCIN DIHYDRATE BY SOLVENT EVAPORATION METHOD

Azithromycin Dihydrate (Poorly water soluble drug), when prepared as solid dispersion showed improved solubility and dissolution. So the main purpose of this investigation was to increase the solubility and dissolution rate of Azithromycin Dihydrate by the preparation of its solid dispersion with urea using solvent evaporation method. Physical mixtures and solid dispersions of Azithromycin Dihydrate were prepared by using urea as water-soluble carrier in various proportions (1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7 by weight), by employing solvent evaporation method. The drug release profile was studied and it was found that the dissolution rate and the dissolution parameters of the drug from the physical mixture as well as solid dispersion were higher than those of the intact drug. FT- IR spectra revealed no chemical incompatibility between drug and urea. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC) and Powder X-Ray Diffraction (PXRD).
Ultraviolet light induced injury: Immunological and inflammatory effects

This article reviews many of the complex events that occur after cutaneous ultraviolet (UV) exposure. The inflammatory changes of acute exposure of the skin include erythema (sunburn), the production of inflammatory mediators, alteration of vascular responses and an inflammatory cell infiltrate. Damage to proteins and DNA accumulates within skin cells and characteristic morphological changes occur in keratinocytes and other skin cells. When a cell becomes damaged irreparably by UV exposure, cell death follows via apoptotic mechanisms. Alterations in cutaneous and systemic immunity occur as a result of the UV‐induced inflammation and damage, including changes in the production of cytokines by keratinocytes and other skin‐associated cells, alteration of adhesion molecule expression and the loss of APC function within the skin. These changes lead to the generation of suppressor T cells, the induction of antigen‐specific immunosuppression and a lowering of cell‐mediated immunity. These events impair the immune system's capacity to reject highly antigenic skin cancers. This review gives an overview of the acute inflammatory and immunological events associated with cutaneous UV exposure, which are important to consider before dealing with the complex interactions that occur with chronic UV exposure, leading to photocarcinogenesis.
A curve tracing algorithm using level set based affine transforms

Existing curve tracing algorithms drive an evolving curve to the mean or median of the data. However, if the data set contains heavy noise, these algorithms may not produce correct results. In this paper, we introduce a level set based affine transform method to enhance the capability of a class of fuzzy curve tracing algorithms. The essential idea of our approach is to drive the initial curve towards the object data using level sets as well as affine transforms. Experimental results show that the proposed method can enhance fuzzy curve tracing algorithms for dealing with the data corrupted by noise.
Albuminuria and its correlates in type 2 diabetic patients.

INTRODUCTION The aim of this study was to determine the prevalence of albuminuria and its correlates and investigate disease management for patients with type 2 diabetes mellitus in Ahvaz. MATERIALS AND METHODS This was a cross-sectional study on the 350 patients with type 2 diabetes mellitus attending the Diabetes Clinic at Golestan Hospital, from October 2010 to September 2011. Demographic characteristics were recorded and height, weight, and blood pressure were measured. Blood urea nitrogen and serum levels of creatinine, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and glycosylated hemoglobin A were measured in fasting blood samples. Spot urine and 24-hour urine collection were tested for albumin and kidney ultrasonography was done. RESULTS A total of 72 of 350 patients (20.6%) had microalbuminuria and 18 (5.1%) had macroalbuminuria. Elevated serum creatinine was seen in 6.9% and azotemia in 6.0%. In multivariable analysis, blood urea nitrogen level, glycosylated hemoglobin A, and duration of diabetes mellitus were associated with urinary albumin excretion (P = .04). A small proportion of the participants achieved optimal treatment goals for modifiable risk factors. CONCLUSIONS Abnormal urinary albumin excretion is seen in one-quarter of type 2 diabetic patients and a small but important number of them have azotemia. Albuminuria was found to be associated with long-term duration of diabetes mellitus, poor glucose control (revealed by high glycosylated hemoglobin A levels), and high blood urea nitrogen. Poor glycemic control may have a significant role in the progression of diabetic nephropathy in these patients.
Molecular and immunological characterization of Babesia gibsoni and Babesia microti heat shock protein‐70

Serological immunoscreening was used to identify a gene encoding heat shock protein‐70 from Babesia gibsoni (BgHSP‐70) that showed high homology with HSP‐70s from other apicomplexan parasites. This gene corresponded to a full‐length cDNA containing an open reading frame of 1968 bp predicted to result in a 70‐kDa mature protein consisting of 656 amino acids. Analysis of the expression levels of BgHSP‐70 indicated elevated transcription from cultured parasites incubated at 40°C for 1 h, but not at 30°C. Interestingly, antiserum raised against recombinant BgHSP‐70 protein reacted specifically not only with a 70‐kDa protein of B. gibsoni but also with a corresponding native protein of B. microti (BmHSP‐70), indicating the high degree of conservation of this protein. The BmHSP‐70 gene was then isolated and characterized and the immunoprotective properties of recombinant BgHSP‐70 (rBgHSP‐70) and rBmHSP‐70 were compared in vitro and in vivo. Both proteins had potent mitogenic effects on murine and canine mononuclear cells as evidenced by high proliferative responses and IFN‐γ production after stimulation. Immunization regimes in BALB/c and C57BL/6 mice using rBgHSP‐70 and rBmHSP‐70 elicited high antibody levels, with concurrent significant reductions in peripheral parasitaemias. Taken together, these results emphasize the potential of HSP‐70s as a molecular adjuvant vaccine.
Rabbit renal epithelial angiotensin II receptors.

The characteristics of angiotensin II (ANG II) receptors were compared in basolateral (BLM) and brush-border membranes (BBM) of rabbit kidney cortex. BLM showed high-affinity binding of 125I-labeled [Sar1]ANG II [dissociation constant (Kd) = 0.31 +/- 0.04 nM and maximum binding capacity (Bmax) = 136 +/- 17 fmol/mg protein]. Losartan inhibited 125I-[Sar1]ANG II in a heterogeneous manner, with 73 +/- 4% of the sites showing high affinity [inhibition constant (Ki) = 2.63 +/- 0.82 nM] and 27 +/- 4% of sites having low affinity (Ki = 125 +/- 18 nM). Masking studies confirmed the presence of two different binding sites. The sites with high affinity for losartan resemble the AT1A receptor, previously described and cloned. The sites with low affinity resemble the pharmacological AT1B subtype, previously identified as the minority subtype in mesangial cells. In BBM, two sites could be distinguished on the basis of 125I-[Sar1,Ile8]ANG II affinity, with Kd values of 1.43 +/- 0.26 and 782 +/- 90 nM for ANG II. The low-affinity site, however, comprised the main population of binding sites. ANG II binding to BBM was not sensitive to losartan. PD-123319 and CGP-42112A competed for binding with a one-half inhibitory concentration (IC50) of approximately 100 and 19.0 +/- 1.0 microM, respectively. 125I-labeled AT2-selective antagonist PD-122979 bound specifically and with high magnitude to both BLM and BBM. A very high rate of ANG II degradation was observed, despite the presence of protease inhibitors, suggesting the possibility of the presence of receptors for ANG II fragments in BLM and BBM. (ABSTRACT TRUNCATED AT 250 WORDS)
Drug Users' Participation in a Free Hepatitis B Vaccination Program: Demographic, Behavioral, and Social-Cognitive Determinants

The present study was conducted as an evaluation of a two-year pilot program started in 1998 in the Netherlands to provide free hepatitis B vaccination targeted at drug users (DUs). In order to identify which demographic and social-cognitive factors predict vaccination uptake, written questionnaires were distributed in three pilot regions (Amsterdam, Tiel, and Maastricht) amongst all DUs that were invited to participate in the program during a 2-month period. Vaccination behavior 2 years later was anonymously and prospectively linked to the questionnaire data, which allowed us to investigate which factors predict vaccination behavior. Of the 207 DUs eligible for vaccination (i.e., who were not immune and/or had no current infection with the virus), 93 DUs had obtained vaccination in the 2 years following the questionnaire. More than half of them (N = 50) had completed the full program (3 injections). As possible predictors of vaccination uptake, the questionnaire included constructs of the Theory of Planned Behavior as well as of the Health Belief Model. Our results show that attitude toward obtaining hepatitis B vaccination was positively associated with intention toward obtaining hepatitis B vaccination. However, perceived behavioral control was found to be the only construct related to actual vaccination uptake. None of the demographic variables were related to vaccination uptake. Our findings suggest that future interventions aimed at increasing uptake of vaccination against hepatitis B in DUs should address DUs (perceived) control concerning this behavior. The study's limitations are noted.
High sensitivity C-reactive protein in airline pilots with metabolic syndrome.

BACKGROUND Airline pilots belong to a relatively high-income, healthy population, with sedentary behavior during their flight activity, who often eat unsuitable meals. We assessed the prevalence of metabolic syndrome (MS) and the levels of high sensitivity C-reactive protein (hs-CRP) in a population of airline pilot in order to study a possible relationship between the hs-CRP and MS. METHODS MS was established according to the National Cholesterol Education Program, Adult Treatment Panel III. hs-CRP was classified into three categories: Low < 1 mg x L(-1); intermediate: 1-3 mg x L(-1); and high: > 3 mg x L(-1). RESULTS The prevalence of MS was 14.8%. The hs-CRP level in the population studied was 1.68 +/- 1.79 mg x L(-1). hs-CRP significantly increased with age. The pilots with MS presented significantly higher hs-CRP levels (median = 1.9 with an interquartile range (IQR) = 2.5 mg x L(-1)) than the pilots without MS (median = 0.9 and IQR = 1.275 mg x L(-1)). MS significantly increased in the groups with high hs-CRP in comparison with pilots with intermediate hs-CRP levels and with those with low hs-CRP levels. A similar association was found between the levels of hs-CRP and the prevalence of MS in the three age groups. The levels of hs-CRP increased in pilots as they presented greater numbers of MS diagnostic criteria. DISCUSSION hs-CRP rises significantly in pilots of increasing age, in pilots with MS as compared to those without the syndrome, and in pilots as they present greater numbers of MS diagnostic criteria. The prevalence of MS increased among the groups with higher levels of hs-CRP.
Neurotransmitter release mechanisms and microtubules

The morphological mechanisms involved in translocation of the synaptic vesicle to the presynaptic membrane, release of transmitter from the vesicle and recycling of the vesicle membrane are still far from understood. However, there is strong evidence that vesicles move along the surfaces of a specific set of highly labile presynaptic microtubules that direct the vesicles to the active zones. These microtubules are focused in a precise geometrical array, which is in register with and in contact with presynaptic dense projections of the central nervous system synapse or presynaptic dense bars of the motor endplate. These dense complexes constitute the presynaptic grid or active zones. The regular arrays of dense projections or bars are in turn coincident with rings or chains of synaptic vesicles mobilized at release sites on the presynaptic membrane (having arrived at these precise points by microtubule translocation). Thus it is suggested that the presynaptic microtubules not only translocate synaptic vesicles, but because of their ordered arrays determine, in ontogeny, the ordered structure of the presynaptic grid.
MAPKinase Gene Expression, as Determined by Microarray Analysis, Distinguishes Uncomplicated from Complicated Reconstitution after Major Surgical Trauma

Abstract: Microarray expression analysis was performed in patients with major surgical trauma to identify signaling pathways which may be indicative for complicated versus uneventful reconstitution post trauma. In addition to a generalized upregulation of nonspecific stress response genes in all patients, a remarkable number of differences in gene expression patterns were found in individual patients. Some of the differing genes were associated with uncomplicated convalescence such as upregulation of both the ERK5 pathway (MAPK7 [mitogen‐activated protein kinase‐7]) and transcription factors which stimulate hematopoiesis and tissue reconstitution (MEF2, BMP‐2, TNFRSF11A [RANK], and RUNX‐1). Chemokine genes active in stem cell recruitment from the bone marrow as well as dendritic cell and natural killer (NK) cell maturation (SCYA14 [HCC‐1]), and activators of the lymphoid compartment (TNFRSF7 [CD27], CD3zeta and perforin [PRF1]) were increased. In contrast, all these transcripts were downregulated in complicated reconstitution and later development of septic shock. Moreover, p38 kinase (MAPK14), S100 molecules, and members of the lipoxygenase pathway were associated with a more eventful outcome. Microarray expression studies are a promising tool for screening and then selecting differentially regulated genes in favorable as compared to complicated reconstitution post trauma.