Miracle-dz/UniFAR-FTUs huggingface dataset:
MYB–GATA1 fusion promotes basophilic leukaemia: involvement of interleukin‐33 and nerve growth factor receptors

Acute basophilic leukaemia (ABL) is a rare subtype of acute myeloblastic leukaemia. We previously described a recurrent t(X;6)(p11;q23) translocation generating an MYB–GATA1 fusion gene in male infants with ABL. To better understand its role, the chimeric MYB–GATA1 transcription factor was expressed in CD34‐positive haematopoietic progenitors, which were transplanted into immunodeficient mice. Cells expressing MYB–GATA1 showed increased expression of markers of immaturity (CD34), of granulocytic lineage (CD33 and CD117), and of basophilic differentiation (CD203c and FcϵRI). UT‐7 cells also showed basophilic differentiation after MYB–GATA1 transfection. A transcriptomic study identified nine genes deregulated by both MYB–GATA1 and basophilic differentiation. Induction of three of these genes (CCL23, IL1RL1, and NTRK1) was confirmed in MYB–GATA1‐expressing CD34‐positive cells by reverse transcription quantitative polymerase chain reaction. Interleukin (IL)‐33 and nerve growth factor (NGF), the ligands of IL‐1 receptor‐like 1 (IL1RL1) and neurotrophic receptor tyrosine kinase 1 (NTRK1), respectively, enhanced the basophilic differentiation of MYB–GATA1‐expressing UT‐7 cells, thus demonstrating the importance of this pathway in the basophilic differentiation of leukaemic cells and CD34‐positive primary cells. Finally, gene reporter assays confirmed that MYB and MYB–GATA1 directly activated NTRK1 and IL1RL1 transcription, leading to basophilic skewing of the blasts. MYB–GATA1 is more efficient than MYB, because of better stability. Our results highlight the role of IL‐33 and NGF receptors in the basophilic differentiation of normal and leukaemic cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Effects of insulin on wound healing.

BACKGROUND Insulin plus glucose, given for 7 days to hypermetabolic burn patients, has been shown to stimulate limb protein anabolism. We hypothesized that insulin plus glucose given to burn patients would also stimulate wound healing. METHODS Six patients with burns >40% total body surface area were randomized to receive insulin or placebo in a crossover study during the healing of their first and second donor sites. Insulin treatment was titrated at 25 to 49 U/h to achieve a plasma insulin level of 400 to 900 microU/mL for 7 days. Patients receiving insulin received dextrose 50 at 20 to 50 mL/h, titrated to maintain euglycemia. Donor-site biopsies were taken at 7 days and evaluated by three observers blinded to the treatment. RESULTS The mean (+/-SD) donor-site healing time was reduced from 6.5 +/- 1.0 days with placebo to 4.7 +/- 1.2 days during insulin infusion (p < 0.05). Laminin showed intense staining along the basal lamina and blood vessels. Collagen type IV staining also increased after insulin therapy compared with placebo. CONCLUSION Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation.
The p58-positive pre-golgi intermediates consist of distinct subpopulations of particles that show differential binding of COPI and COPII coats and contain vacuolar H(+)-ATPase.

We have studied the structural and functional properties of the pre-Golgi intermediate compartment (IC) in normal rat kidney cells using analytical cell fractionation with p58 as the principal marker. The sedimentation profile (sediterm) of p58, obtained by analytical differential centrifugation, revealed in steady-state cells the presence of two main populations of IC elements whose average sedimentation coefficients, s(H)=1150+/-58S ('heavy') and s(L)=158+/-8S ('light'), differed from the s-values obtained for elements of the rough and smooth endoplasmic reticulum. High resolution analysis of these subpopulations in equilibrium density gradients further revealed that the large difference in their s-values was mainly due to particle size. The 'light' particle population contained the bulk of COPI and COPII coats, and redistribution of p58 to these particles was observed in transport-arrested cells, showing that the two types of elements are also compositionally distinct and have functional counterparts in intact cells. Using a specific antibody against the 16 kDa proteolipid subunit of the vacuolar H(+)-ATPase, an enrichment of the V(o )domain of the ATPase was observed in the p58-positive IC elements. Interestingly, these elements could contain both COPI and COPII coats and their density distribution was markedly affected by GTP(&ggr;)S. Together with morphological observations, these results demonstrate that, in addition to clusters of small tubules and vesicles, the IC also consists of large-sized structures and corroborate the proposal that the IC elements contain an active vacuolar H(+)-ATPase.
Rent-Sharing and Collective Bargaining Coverage: Evidence from Linked Employer–Employee Data

Using a linked employer–employee dataset, this paper analyses the relationship between firm profitability and wages. Particular emphasis is given to the question of whether the sensitivity of wages to firm-specific rents varies with collective bargaining coverage. To address this issue, we distinguish sector- and firm-specific wage agreements and wage determination without any bargaining coverage. Our findings indicate that individual wages are positively related to firm-specific quasi-rents in the non-union sector and under firm-specific contracts. Industry-wide wage contracts, however, are associated with a significantly lower responsiveness of wages to firm-level profitability.
The Impact of Project ECHO on Participant and Patient Outcomes: A Systematic Review

Purpose Project Extension for Community Healthcare Outcomes (ECHO) uses tele-education to bridge knowledge gaps between specialists at academic health centers and primary care providers from remote areas. It has been implemented to address multiple medical conditions. The authors examined evidence of the impact of all Project ECHO programs on participant and patient outcomes. Method The authors searched PubMed, MEDLINE, EMBASE, PsycINFO, and ProQuest from January 2000 to August 2015 and the reference lists of identified reviews. Included studies were limited to those published in English, peer-reviewed articles or indexed abstracts, and those that primarily focused on Project ECHO. Editorials, commentaries, gray literature, and non-peer-reviewed articles were excluded. The authors used Moore’s evaluation framework to organize study outcomes for quality assessment. Results The authors identified 39 studies describing Project ECHO’s involvement in addressing 17 medical conditions. Evaluations of Project ECHO programs generally were limited to outcomes from Levels 1 (number of participants) to 4 (providers’ competence) of Moore’s framework (n = 22 studies, with some containing data from multiple levels). Studies also suggested that Project ECHO changed provider behavior (n = 1), changed patient outcomes (n = 6), and can be cost-effective (n = 2). Conclusions Project ECHO is an effective and potentially cost-saving model that increases participant knowledge and patient access to health care in remote locations, but further research examining its efficacy is needed. Identifying and addressing potential barriers to Project ECHO’s implementation will support the dissemination of this model as an education and practice improvement initiative.
Persistent Kaposi sarcoma in the era of highly active antiretroviral therapy: characterizing the predictors of clinical response

Objectives:To evaluate the role of highly active antiretroviral therapy and chemotherapy on tumor response among persons with AIDS-related Kaposi sarcoma and identify factors associated with response in a clinic setting. Design:Retrospective cohort. Methods:One hundred and fourteen patients from two HIV clinics with a diagnosis of Kaposi sarcoma were identified via a clinical database. Records were reviewed to confirm Kaposi sarcoma diagnosis and abstract clinical and chemotherapy information. Demographics, laboratory values, and highly active antiretroviral therapy use were abstracted electronically. Cox's proportional hazards models identified predictors of Kaposi sarcoma improvement and resolution. Results:Thirty-six months following Kaposi sarcoma diagnosis, the rate of improvement among 64 patients with confirmed Kaposi sarcoma was 77% and that of complete resolution was 51%. In univariate analyses, recent chemotherapy was associated with Kaposi sarcoma improvement, and recent HIV viral load and highly active antiretroviral therapy were associated with both improvement and resolution. No measured baseline characteristics (tumor stage, diagnosis year, CD4 T-cell count, HIV viral load, or prior highly active antiretroviral therapy history) or recent CD4 T-cell counts predicted improvement or resolution. In multivariate analyses, recent chemotherapy (hazard ratio 5.5, 95% confidence interval: 2.7–11.2, P < 0.001) and highly active antiretroviral therapy (hazard ratio 4.1, 95% confidence interval: 1.4–12.6, P = 0.01) were predictors of improvement; only recent highly active antiretroviral therapy was associated with resolution (hazard ratio 6.2, 95% confidence interval: 1.5–26.4, P = 0.01). Response was not associated with type of highly active antiretroviral therapy regimen (non nucleoside reverse transcriptase inhibitor based, protease inhibitor based, or ritonavir-boosted protease inhibitor based). Conclusion:Highly active antiretroviral therapy and chemotherapy are important in clinical Kaposi sarcoma response. Despite widespread availability of these therapies, Kaposi sarcoma continues to be a clinical problem; only half the patients achieved complete resolution of disease. New therapeutic approaches are needed.
Characterization of murine BATF: a negative regulator of activator protein‐1 activity in the thymus

BATF belongs to the AP‐1/ATF superfamily of transcription factors and forms heterodimers with Jun proteins to bind AP‐1 consensus DNA. Unlike Fos/Jun heterodimers which stimulate gene transcription, BATF/Jun heterodimers are transcriptionally inert and inhibit biological processes that are associated with the overstimulation of AP‐1 activity. Here, we describe the murine BATF cDNA and genomic clones and map the BATF locus to chromosome 12 D2‐3. Using in situ hybridization of BATF mRNA, we show that BATF gene expression is highly restricted, with the most prominent signals detected in the thymus. BATF mRNA levels are regulated differentially during discrete stages of T cell development and are up‐regulated following activation of T cells in the periphery. To demonstrate the impact of BATF on AP‐1 activity in vivo, AP‐1 luciferase reporter mice were crossed to transgenic mice overexpressing BATF exclusively inthymic T cells. Results show that elevated levels of BATF protein correlate with reduced transactivation by AP‐1. Since the differential regulation of AP‐1 activity is linked to key transitions in the developing immune system, our observations support a critical role for BATF in determining the overall level of AP‐1 activity, and thus AP‐1 target gene expression, in specific T cell subtypes.
Late Effects in Long-Term Survivors After Treatment for Childhood Acute Leukemia

Background. This is a report of late effects in childhood cancer survivors seen in the follow-up clinic of a single institution. Materials and methods. There were 324 acute leukemia survivors in the database of the Long Term Follow Up Clinic of Children's National Medical Center from January 1, 1997, through June 30, 2005. Results. Of the 324 acute leukemia survivors, 228 were white, 48 black, 20 Hispanic, and 12 other. Their follow-up time was 0 to 25 years (mean 5.3 years). One or more adverse events occurred in 74.1% of the 324 survivors. Defective physical growth was most commonly reported, followed by disturbed neurocognitive function, emotional difficulties, cardiac abnormalities, hypertension, osteoporosis/osteopenia, fractures, and second neoplasms. More black and Hispanic children had acute myeloid leukemia, relapses, cardiac problems, and hypertension than white and other subjects. Conclusion. Childhood cancer survivors require lifelong monitoring, with prompt identification and treatment of adverse late effects.
Seasonal Influenza Vaccination of Healthcare Employees: Results of a 4-Year Campaign

Objective. To document successful substantial increases in healthcare worker influenza vaccination rates and to identify reasons for success and failure. Design. (1) Four-year longitudinal characterization of facility vaccination rates, (2) Web-based facility-level questionnaire for influenza coordinators to identify success factors in year 3, and (3) semistructured telephone interviews of influenza coordinators at facilities with substantial increases or declines in year 4. Setting. National single-payer hospital (healthcare) system with 153 hospitals in 5 levels of complexity. Patients. Facility leadership staff. Methods. (1) Vaccination data collected from management sources (doses from pharmacies, denominator data from payrolls); (2) a Web-based survey aligned with a previously administered instrument (Wisconsin Health Department), piloted in-house, modified to reflect national strategies and improvements; and (3) semistructured telephone interviews with influenza coordinators at facilities that improved or worsened by more than 20% between the 2007–2008 and 2008–2009 influenza seasons. Results. Vaccination acceptance rates improved from 45% of healthcare workers in 2005–2006 to 66.5% in 2008–2009. Facilities with lower complexity had higher vaccination rates. No individual factors were associated with improved performance. Conclusions. Sustained management attention can lead to improvements in healthcare worker influenza vaccination rates. Wavering of attention, though, may lead to rapid loss of effectiveness. Declination statements in this system did not contribute to vaccine acceptance.
The Impact of Socialization on the Role Adjustment of Information Systems Professionals

The study of socialization and its practices has only recently been applied to organizations to investigate the manner in which new employees adjust to corporate culture. Past studies have examined the nature of human-resource development from an individual perspective. Research in socialization practices represents an organizational approach toward understanding the manner in which new employees adjust to their roles. This study examines the impact of socialization practices on the nature of this role adjustment with respect to information systems professionals. One hundred and sixty newly hired IS personnel in five different cities were surveyed to examine the relationship between organizational socialization tactics and adjustment variables such as role orientation, role ambiguity, and role clarity. Results suggest that socialization practices affect professional role adjustment. Specifically, institutionalized socialization tactics lead to a custodial role orientation and individualized socialization tactics produce an innovative role orientation. In addition, institutionalized tactics are shown to reduce role ambiguity and role conflict in new employees. Implications for human-resource management of IS personnel and future research in this area are discussed.
Cardiovascular risks associated with low-dose ibuprofen and diclofenac as used OTC

Introduction: The cardiovascular (CV) risks of non-steroidal anti-inflammatory drugs (NSAIDs) are dose- and duration-dependent. As over-the-counter (OTC) NSAIDs are widely used for the treatment of common painful disorders, without medical supervision, their cardiovascular risks need to be assessed. Areas covered: Individual clinical trials and observational studies of the CV risks associated with NSAIDs and meta-analyses thereof were retrieved and analysed. The article focuses on the risk associated with low-dose ibuprofen and diclofenac, two drugs available OTC in many countries. Very few studies reported on dose-related CV risks of NSAIDs. The usual cut-off for low-dose ibuprofen was 1200 mg daily, the upper limit of the approved OTC daily dose. For diclofenac, the usual cut-off was 100 mg, 33% above the approved daily dose for OTC preparations (75 mg/day). Only one study reported on the CV risks of doses at or below this limit. The studies retrieved found a clear dose-dependent risk with both drugs and no clearly increased cardiovascular risk for doses at or below the maximal approved OTC doses. No study looked at actual OTC usage. Expert opinion: At doses below the maximal daily OTC dose and for durations associated with OTC usage, there was no clear association with increased CV risk.
3-D Modeling of High-$T_{c}$ Superconductor for Magnetic Levitation/Suspension Application—Part II: Validation With Experiment

In this paper, the 3-D model proposed in Part I of this study is verified in detail on the basis of a levitation/suspension system composed of a rectangular single-domain Y-Ba-Cu-O and a cylindrical Nd-Fe-B magnet or a permanent magnet guideway (PMG) assembled by the Nd-Fe-B magnets. The magnetic forces along the vertical direction perpendicular or the transverse direction parallel to the surface of the PMG (or magnet) were calculated and compared well with the measured data under vertical and transverse displacements. The computed results of the induced current distribution within the Y-Ba-Cu-O domain, as well as the magnetic field profiles in the Y-Ba-Cu-O and its vicinal region, were also presented and discussed.
Repetitive transcranial magnetic stimulation in patients with drug-resistant major depression: A six-month clinical follow-up study

Objective. In this study we aimed to assess the long-term efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) on depressive symptoms and cognitive performance in patients with drug-resistant major depressive disorder (MDD). Methods. Fifteen drug-resistant depressed outpatients completed an acute trial with augmentative high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) and were compared with 15 drug-resistant MDD patients who underwent sham procedure. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale and Montgomery–Asberg Depression Rating Scale. The Frontal Assessment Battery and the Stroop Color–Word Test Interference (Stroop T) were used to probe executive functions. Outcome measures were obtained at baseline, 4 weeks after the rTMS, as well as 3 months and 6 months after the end of the stimulation protocol. Results. After the active rTMS, patients showed a significant decrease in the scores at the depression rating scales that lasted for 6 months. A transient improvement was also observed at the Stroop T, although it did not persist in time. Conclusions. High-frequency rTMS over the left DLPFC may have long-term antidepressant effect in drug-resistant MDD. TMS is a valuable tool for the add-on treatment of mood disorders and for the design of customized stimulation protocols.
Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies.

PURPOSE To determine the effect of age on the outcome of autologous bone marrow transplantation (ABMT) and/or peripheral-blood progenitor-cell (PBPC) transplantation. PATIENTS AND METHODS A retrospective analysis was performed on 500 consecutive patients who ranged in age from 1 to 65 years (median, 40) with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), multiple myeloma (MM), or acute nonlymphoblastic leukemia (AML) who underwent autologous hematopoietic-cell transplant procedures at Stanford University Medical Center. RESULTS The actuarial 5-year event-free survival (EFS) rate was 44%, the relapse rate 47%, and the regimen-related mortality (RRM) rate 8.6%. Disease status at time of transplantation, categorized as either minimal or advanced disease, was the strongest predictive factor for EFS (relative risk (RR) for advanced-disease group, 1.8; P < . 0003) and relapse rate (RR for advanced-disease group, 1.9; P < .0004). Patients with minimal or advanced disease had an EFS rate of 48% and 30% and relapse rates of 43% and 72%, respectively. The EFS rate of patients less than 50 years verus > or = 50 years of age was 46% versus 34% (P = .03). Cox regression analysis showed that age was predictive for EFS (RR for patients 50 to 65 years, 1.4; P = .03). The actuarial RRM rate for these age groups was 7.4% versus 12.7% (P = .07), respectively. Multivariate analysis demonstrated that age (odds ratio [OR] for patients 50 to 65 years, 1.9; P < .05) and period of transplantation (OR for most recent years [1991 to 1995], 0.6; P = .06) were the most predictive factors for RRM. CONCLUSION Although age greater than 50 years is associated with an inferior outcome following autologous hematopoietic-cell transplantation, it does not appear to be warranted to limit this potentially curative procedure based solely on age. The upper age limit of high-dose therapy with autologous progenitor-cell and/ or bone marrow support remains to be defined.
Locomotion problems of broiler chickens and its relationship with the gait score

The objective of this study was to evaluate the correlation between the ability to walk (gait score), incidence of femoral degeneration, tibial dyschondroplasia, valgus and varus deformity and leg symmetry of broiler chickens. Male chickens of the Cobb strain from a commercial poultry farm were utilized in this experiment. Fifty 35 and 42-day-old birds were evaluated according to the gait score and valgus or varus incidence. To assess the bilateral symmetry and the lesion score for femoral degeneration and tibial dyschondroplasia, broilers were weighed and euthanized for the removal of the femur and tibia of both legs. The lesion scores for femoral degeneration and tibial dyschondroplasia, varus or valgus deformity, bone symmetry and gait scores of the chickens were then correlated. It was found that weight, age and the incidence of femoral degeneration and tibial dyschondroplasia are not always correlated with the gait score and that only valgus deformity is more correlated.
Physical exercise and/or enriched foods for functional improvement in frail, independently living elderly: a randomized controlled trial.

OBJECTIVE To examine the effects of an exercise program and an enriched food regimen on physical functioning of frail elderly persons. DESIGN A 17-week randomized, placebo-controlled trial. SETTING Community. PARTICIPANTS One hundred fifty-seven independently living frail elderly (mean age, 78.7 +/- 5.6yr). INTERVENTION Thirty-nine subjects participated in a twice weekly group exercise designed to improve daily functioning; 39 subjects daily ate foods enriched with vitamins and minerals (at 25%-100% of the recommended daily allowances); 42 subjects exercised and ate enriched foods; and 37 subjects served as controls. Nonexercising groups followed a social program; nonsupplement groups received the same food products without the micronutrients. MAIN OUTCOME MEASURES Functional performance based on 6 performance tests, physical fitness based on 7 fitness tests, and disabilities based on the self-reported ability to perform 16 daily activities. RESULTS Performance sum scores were significantly enhanced in trained (+8%) compared with nontrained subjects (-8%) (difference in change: 1.9 points, p < .001, adjusted for baseline scores). Fitness sum scores were significantly enhanced as well (+3% in trained vs -2% in nontrained) (difference in change: 0.9 points, p = .05, adjusted for baseline scores). No exercise effects on the disability score were observed. Consumption of enriched products did not affect performance, fitness, or disability scores. CONCLUSION Our comprehensive exercise program, designed for widespread applicability, enhanced physical performance and fitness in a population of frail elderly. Daily consumption of micronutrient enriched foods showed no functional benefits within 17 weeks.