Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury*

Rationale:Despite recent advances in critical care and ventilator management, acute lung injury and acute respiratory distress syndrome continue to cause significant morbidity and mortality. Granulocyte-macrophage colony stimulating factor may be beneficial for patients with acute respiratory distress syndrome. Objectives:To determine whether intravenous infusion of granulocyte-macrophage colony stimulating factor would improve clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome. Design:A randomized, double-blind, placebo-controlled clinical trial of human recombinant granulocyte-macrophage colony stimulating factor vs. placebo. The primary outcome was days alive and breathing without mechanical ventilatory support within the first 28 days after randomization. Secondary outcomes included mortality and organ failure-free days. Setting:Medical and surgical intensive care units at three academic medical centers. Patients:One hundred thirty individuals with acute lung injury of at least 3 days duration were enrolled, out of a planned cohort of 200 subjects. Interventions:Patients were randomized to receive human recombinant granulocyte-macrophage colony stimulating factor (64 subjects, 250 &mgr;g/M2) or placebo (66 subjects) by intravenous infusion daily for 14 days. Patients received mechanical ventilation using a lung-protective protocol. Measurements and Main Results:There was no difference in ventilator-free days between groups (10.7 ± 10.3 days placebo vs. 10.8 ± 10.5 days granulocyte-macrophage colony stimulating factor, p = .82). Differences in 28-day mortality (23% in placebo vs. 17% in patients receiving granulocyte-macrophage colony stimulating factor (p = .31) and organ failure-free days (12.8 ± 11.3 days placebo vs. 15.7 ± 11.9 days granulocyte-macrophage colony stimulating factor, p = .16) were not statistically significant. There were similar numbers of serious adverse events in each group. Conclusions:In a randomized phase II trial, granulocyte-macrophage colony stimulating factor treatment did not increase the number of ventilator-free days in patients with acute lung injury/acute respiratory distress syndrome. A larger trial would be required to determine whether treatment with granulocyte-macrophage colony stimulating factor might alter important clinical outcomes, such as mortality or multiorgan failure. (ClinicalTrials.gov number, NCT00201409 [ClinicalTrials.gov]).
BRCA1 mutations drive oxidative stress and glycolysis in the tumor microenvironment

Mutations in the BRCA1 tumor suppressor gene are commonly found in hereditary breast cancer. Similarly, downregulation of BRCA1 protein expression is observed in the majority of basal-like breast cancers. Here, we set out to study the effects of BRCA1 mutations on oxidative stress in the tumor microenvironment. To mimic the breast tumor microenvironment, we utilized an in vitro co-culture model of human BRCA1-mutated HCC1937 breast cancer cells and hTERT-immortalized human fibroblasts. Notably, HCC1937 cells induce the generation of hydrogen peroxide in the fibroblast compartment during co-culture, which can be inhibited by genetic complementation with the wild-type BRCA1 gene. Importantly, treatment with powerful antioxidants, such as NAC and Tempol, induces apoptosis in HCC1937 cells, suggesting that microenvironmental oxidative stress supports cancer cell survival. In addition, Tempol treatment increases the apoptotic rates of MDA-MB-231 cells, which have wild-type BRCA1, but share a basal-like breast cancer phenotype with HCC1937 cells. MCT4 is the main exporter of L-lactate out of cells and is a marker for oxidative stress and glycolytic metabolism. Co-culture with HCC1937 cells dramatically induces MCT4 protein expression in fibroblasts, and this can be prevented by either BRCA1 overexpression or by pharmacological treatment with NAC. We next evaluated caveolin-1 (Cav-1) expression in stromal fibroblasts. Loss of Cav-1 is a marker of the cancer-associated fibroblast (CAF) phenotype, which is linked to high stromal glycolysis, and is associated with a poor prognosis in numerous types of human cancers, including breast cancers. Remarkably, HCC1937 cells induce a loss of Cav-1 in adjacent stromal cells during co-culture. Conversely, Cav-1 expression in fibroblasts can be rescued by administration of NAC or by overexpression of BRCA1 in HCC1937 cells. Notably, BRCA1-deficient human breast cancer samples (9 out of 10) also showed a glycolytic stromal phenotype, with intense mitochondrial staining specifically in BRCA1-deficient breast cancer cells. In summary, loss of BRCA1 function leads to hydrogen peroxide generation in both epithelial breast cancer cells and neighboring stromal fibroblasts, and promotes the onset of a reactive glycolytic stroma, with increased MCT4 and decreased Cav-1 expression. Importantly, these metabolic changes can be reversed by antioxidants, which potently induce cancer cell death. Thus, antioxidant therapy appears to be synthetically lethal with a BRCA1-deficiency in breast cancer cells and should be considered for future cancer prevention trials. In this regard, immunostaining with Cav-1 and MCT4 could be used as cost-effective biomarkers to monitor the response to antioxidant therapy.
The Classification Method of Matching Parts Quality Based on Empirical Mode Decomposition

Typical matching parts of servo valve have high precision requirement and strict fit tolerance, which reduces the matching quality and practical performance. The traditional fit quality control method of the matching parts is based on expert experience and tolerance analysis, which is subjective and indirect. In this paper, a novel method was proposed to determine the matching quality before precision grinding processing. Firstly, the Empirical Mode Decomposition (EMD) was used to decompose the frequency of radial surface tolerance, and the intrinsic mode functions (IMFs) of the tolerance were obtained. Secondly, the correlation coefficients of the IMFs and the matching gap were calculated. Finally, the mode features are classified by using decision tree. The experimental results showed that the method can effectively identify the matching quality, and improve the pass rate of the precision grinding processing.
Antimycobacterial spectrum of sparfloxacin and its activities alone and in association with other drugs against Mycobacterium avium complex growing extracellularly and intracellularly in murine and human macrophages

The MICs and MBCs of the new difluorinated quinolone drug sparfloxacin against type strains belonging to 21 species of mycobacteria were screened. The MICs and MBCs were within the range of 0.1 to 2.0 and 0.1 to 4.0 micrograms/ml, respectively (with an MBC/MIC ratio of 1 to 2), and against 18 of the 21 species tested, the drug showed significant bactericidal activity (at least 99% killing or more of the initial inoculum added) at concentrations well within the reported peak concentrations in serum (Cmax) in humans. MICs of sparfloxacin for 7 of 10 Mycobacterium avium complex strains were below the Cmax, with MBC/MIC ratios within the range of 2 to 4. Enhancement of its activity by ethambutol, rifampin, amikacin, and clarithromycin (which were used at sublethal concentrations) assessed by using BACTEC radiometry revealed that its activity was further enhanced in 2 of 10 strains by rifampin and in 7 of 10 strains by ethambutol. The bactericidal effects of various drugs used alone as well as two-drug combinations used at Cmax levels were also screened against four strains of M. avium complex growing intracellularly in two different macrophage systems, namely, mouse bone marrow-derived macrophages and peripheral blood monocyte-derived human macrophages. Our results showed a satisfactory correlation between the extracellular and intracellular drug activity data.
The embryology and surgical management of gastroschisis

Thirteen cases of gastroschisis are presented and a reduction in the operative mortality to 15 per cent is recorded. The aetiology of the condition is discussed and the opinion expressed that it represents the result of an intrauterine rupture of an incarcerated ‘hernia into the cord’ rather than any specific failure of development of the abdominal wall musculature. Early skin closure and the creation of a ventral hernia remain the surgical treatment of choice, but it is recognized that the use of a prosthetic sac may occasionally be necessary. Infection is now the most important single factor influencing mortality, and the prolonged administration of prophylactic antibiotics is justified on this basis. Skilled management of the protracted ileus is essential. In view of the low incidence of serious coexistent malformations the children who survive the initial operation can be offered the prospect of a life of normal duration and quality.
Process-Oriented Guided Inquiry Learning Strategy Enhances Students’ Higher Level Thinking Skills in a Pharmaceutical Sciences Course

Objective. To determine if the process-oriented guided inquiry learning (POGIL) teaching strategy improves student performance and engages higher-level thinking skills of first-year pharmacy students in an Introduction to Pharmaceutical Sciences course. Design. Overall examination scores and scores on questions categorized as requiring either higher-level or lower-level thinking skills were compared in the same course taught over 3 years using traditional lecture methods vs the POGIL strategy. Student perceptions of the latter teaching strategy were also evaluated. Assessment. Overall mean examination scores increased significantly when POGIL was implemented. Performance on questions requiring higher-level thinking skills was significantly higher, whereas performance on questions requiring lower-level thinking skills was unchanged when the POGIL strategy was used. Student feedback on use of this teaching strategy was positive. Conclusion. The use of the POGIL strategy increased student overall performance on examinations, improved higher-level thinking skills, and provided an interactive class setting.
Comparison of FecalSwab and ESwab Devices for Storage and Transportation of Diarrheagenic Bacteria

ABSTRACT Using a collection (n = 12) of ATCC and known stock isolates, as well as 328 clinical stool specimens, we evaluated the ESwab and the new FecalSwab liquid-based microbiology (LBM) devices for storing and transporting diarrheagenic bacteria. The stock isolates were stored in these swab devices up to 48 h at refrigeration (4°C) or room (∼25°C) temperature and up to 3 months at −20°C or −70°C. With the clinical stool specimens, the performances of the ESwab and FecalSwab were compared to those of routinely used transport systems (Amies gel swabs and dry containers). At a refrigeration temperature, all isolates survived in FecalSwab up to 48 h, while in ESwab, only 10 isolates (83.3%) out of 12 survived. At −70°C, all isolates in FecalSwab were recovered after 3 months of storage, whereas in ESwab, none of the isolates were recovered. At −20°C, neither of the swab devices preserved the viability of stock isolates after 2 weeks of storage, and at room temperature, 7 (58.3%) of the stock isolates were recovered in both transport devices after 48 h. Of the 328 fecal specimens, 44 (13.4%) were positive for one of the common diarrheagenic bacterial species with all transport systems used. Thus, the suitability of the ESwab and FecalSwab devices for culturing fresh stools was at least equal to those of the Amies gel swabs and dry containers. Although the ESwab was shown to be an option for collecting and transporting fecal specimens, the FecalSwab device had clearly better preserving properties under different storage conditions.
Sixth European Working Conditions Survey – Overview Report

Since 1991, Eurofound has been monitoring working conditions in Europe through its European Working Conditions Survey (EWCS). The survey aims to measure working conditions across European countries, analyse the relationships between different aspects of these, identify groups at risk, highlight issues of concern and areas of progress and, ultimately, contribute to developing EU policy aimed at improving job quality.
MnSOD rs4880 and XPD rs13181 polymorphisms predict the survival of breast cancer patients treated with adjuvant tamoxifen

Abstract The enzyme manganese superoxide dismutase (MnSOD) defends against oxidative stress caused by reactive oxygen species (ROS), whereas Xeroderma pigmentosum group D (XPD) protein is involved in DNA repair. Polymorphisms in these genes have previously been associated with the outcome of breast cancer. Material and methods. Two gene polymorphisms, the MnSOD Val16Ala (rs4880A> G) and the XPD Lys751Gln (rs13181A> C), were analyzed in a cohort of 396 Finnish breast cancer patients by using PCR-RFLP-based methods in a prospective case-control study. The overall survival (OS), breast cancer-specific survival (BCSS), and relapse-free survival (RFS), assessed by using Kaplan-Meier survival analysis and multivariate Cox regression analysis, were evaluated according to the adjuvant treatments and the rs4880 and rs13181 genotypes. Results. In the combined analysis of rs4880 and rs13181 genotypes for patients treated with adjuvant tamoxifen (TAM) an increasing number of low-risk genotypes (rs4880 AA, rs4880 AG, or rs13181 AA) was significantly associated with better RFS, BCSS, and OS (n = 64). In addition, there was improved BCSS and RFS among TAM-treated patients carrying the wild-type rs4880 A allele as compared with the other genotypes (n = 64). The wild-type rs13181 AA genotype was similarly associated with better RFS and BCSS in the TAM-treated population (n = 65). Conclusion. This is the first study to show that the MnSOD rs4880 and XPD rs13181 polymorphisms may influence the outcome of breast cancer patients receiving adjuvant TAM monotherapy. Patients carrying the rs4880 A allele or rs13181 AA genotype may have a reduced ability to scavenge ROS and repair the DNA damage generated by TAM treatment.
Clinical comparison of the hybrid dynamic compression plate and the castless plate for pancarpal arthrodesis in 219 dogs.

OBJECTIVE To describe and compare a large population of dogs that had pancarpal arthrodesis (PCA) using either a hybrid dynamic compression plate (HDCP) or a CastLess Plate (CLP). STUDY DESIGN Multicenter, retrospective, cohort study. ANIMALS Dogs (n = 240; 261 PCA). METHODS Medical records (2000-2012) from 12 UK orthopedic centers were reviewed for dogs that had PCA to document signalment, diagnosis, arthrodesis method, and complication rates. Follow-up data were used to compare outcome (lameness evaluation and radiographic healing) after use of HDCP and CLP plates. RESULTS PCA was performed with HDCP in 125 cases, CLP in 105, and by other techniques in 31. Carpal hyperextension injury was the most common diagnosis in HDCP and CLP groups. Surgical site infection (18.3%) was the most common postoperative complication. There was no difference in intra- (11% HDCP, 21% CLP) or postoperative (34% HDCP, 41% CLP) complication rates. Use of external coaptation did not affect postoperative complication rates or outcome. External coaptation related complications occurred in 32% HDCP and 18% CLP (P = .02). At median follow-up, most dogs were classified as having no or mild lameness (73% HDCP, 83% CLP) and there was radiographic healing in 40% HDCP and 46% CLP (P = .8) cases. CONCLUSIONS CLP and HDCP may both be used successfully to achieve pancarpal arthrodesis. Adjunctive external coaptation does not appear to have a measurable clinical benefit but is associated with morbidity.
Conserved Network of Proteins Essential for Bacterial Viability

ABSTRACT The yjeE, yeaZ, and ygjD genes are highly conserved in the genomes of eubacteria, and ygjD orthologs are also found throughout the Archaea and eukaryotes. In this study, we have constructed conditional expression strains for each of these genes in the model organism Escherichia coli K12. We show that each gene is essential for the viability of E. coli under laboratory growth conditions. Growth of the conditional strains under nonpermissive conditions results in dramatic changes in cell ultrastructure. Deliberate repression of the expression of yeaZ results in cells with highly condensed nucleoids, while repression of yjeE and ygjD expression results in at least a proportion of very enlarged cells with an unusual peripheral distribution of DNA. Each of the three conditional expression strains can be complemented by multicopy clones harboring the rstA gene, which encodes a two-component-system response regulator, strongly suggesting that these proteins are involved in the same essential cellular pathway. The results of bacterial two-hybrid experiments show that YeaZ can interact with both YjeE and YgjD but that YgjD is the preferred interaction partner. The results of in vitro experiments indicate that YeaZ mediates the proteolysis of YgjD, suggesting that YeaZ and YjeE act as regulators to control the activity of this protein. Our results are consistent with these proteins forming a link between DNA metabolism and cell division.
Features and risk factors of peripheral neuropathy during treatment with bortezomib for advanced multiple myeloma.

BACKGROUND Bortezomib is a first-in-class proteasome inhibitor with remarkable antitumor activity that is approved for the treatment of patients with multiple myeloma. Peripheral neuropathy (PN) is a frequent adverse event reported with bortezomib use. PATIENTS AND METHODS The aim of this retrospective, single-center study was to determine the characteristics of bortezomib-associated PN in 100 patients with advanced myeloma. Peripheral neuropathy was evaluated by investigator's assessment. RESULTS With a median follow-up of 8 months (range, 0.1-32 months) from bortezomib initiation, bortezomib-associated PN was observed in 38 patients (38%; 95% CI, 28%-47%), with grade 3 and 4 PN occurring in 5 patients and 1 patient, respectively. Median time to onset of bortezomib-associated PN was 53 days (range, 11-182 days). Of the 38 patients with bortezomib-associated PN, resolution or improvement occurred in 20 patients (53%) at a median of 3 months (range, 1-8 months). In multivariate analysis, the total number of cycles of bortezomib (< 4 cycles or > 4 cycles; P = .03; odds ratio [OR], 2.6; 95% CI, 1.1-6.1) and a previous history of thalidomide therapy (P = .02; OR, 3.9; 95% CI, 1.2-12.6) were significantly associated with an increased incidence of bortezomib-associated PN. CONCLUSION We conclude that, though relatively frequent, bortezomib-associated PN is reversible in a majority of patients. However, bortezomib-associated PN seems to be dependent on previous therapy with thalidomide, suggesting that bortezomib followed by thalidomide could be an optimal sequence of administration of these drugs in the salvage setting.
Longer time to peak glucose during the oral glucose tolerance test increases cardiovascular risk score and diabetes prevalence

Introduction The pattern of glucose levels during an oral glucose tolerance test (OGTT) may be useful for predicting diabetes or cardiovascular disease (CVD). Our aim was to determine whether the time to peak glucose during the OGTT is associated with CVD risk scores and diabetes. Methods Individuals with impaired fasting glucose (IFG) were enrolled in this observational study. Participants were grouped by the measured time to peak glucose (30, 60, 90 and 120 min) during the 75g OGTT. The primary outcome was 10-year CVD risk scores (using the Framingham risk score calculator). Secondary outcomes evaluated effect of time to peak glucose on prevalence of diabetes and indicators of glucose homeostasis. Results A total of 125 patients with IFG underwent OGTTs. Framingham 10-year risk score for the 90-min group was 1.7 times higher than for the 60-min group (6.98±6.56% vs. 4.05±4.60%, P = 0.023). Based on multivariate linear regression, time to peak glucose at 90 min was associated with a higher Framingham risk score than 60-min group (β coefficient: 2.043, 95% confidence interval: 0.067–6.008, P = 0.045). The percentages of patients with HbA1c ≥6.5%, isolated post-challenge hyperglycemia (IPH) and diabetes (combined IPH and HbA1c ≥6.5%) were significantly increased with longer times to peak glucose. Prevalence of diabetes was higher in the 90-min group than in the 60-min group (31.5% vs. 5.7%, P = 0.001). Conclusions In subjects with IFG, those with a longer time to peak glucose had a higher Framingham 10-year risk score and were associated with a greater likelihood of IPH and diabetes.
The relationship between public expenditure and economic growth in Romania: Does it obey Wagner’s or Keynes’s Law?

After joining the European Union, Romania began a harmonization process with European requirements and best practices in both the economic and political system. This new approach influenced policy making processes with implications in fiscal and budgetary areas in order to ensure durable economic growth. The purpose of this paper is to examine the relationship between public expenditure and economic growth from the perspectives of Keynes and Wagner′s law on Romania. Five representations of both Wagner’s and Keynes’s Law are tested, using annual time series data covering the period 1991-2014 after the fall of the Iron Curtain. To estimate the long-run relationship between government expenditure and economic growth, ARDL (Auto- Regression Distributed Lag) approach and Bounds Test based on Unrestricted Error Correction Model (UECM) estimation are used. Empirical results indicate that there exists a unidirectional long-run relationship from government expenditures to economic growth in Romania, which means the economic growth could affect the government expenditure. In contrast, Keynes’s Law does not hold for over the period. Based on this result the government can determine the causality between economic growth and public expenditure and better formulate strategies for different faces of the economic conjuncture.
Towards cyber-physical approach for prototyping indoor lighting automation systems

During daily operations of a building, a significant amount of energy is spent on indoor illumination. The choice of different lighting sources and control strategies can notably affect the energy consumption. To achieve the most economical lighting design, a number of factors from both physical and cyber perspectives must be considered. More importantly, these factors must be taken into account during early design phrases of building architecture and automation systems. This paper proposes an infrastructure towards the cyber-physical approach for prototyping indoor illumination. In particular, the distributed lighting automation system is modeled using the IEC 61499 standard. The lighting energy performance of a building is evaluated according to the EN 15193 standard. By integrating the evaluation methodology of energy efficiency in the development of lighting automation systems, adequate indications regarding the correlation between physical and cyber designs can be revealed. The proposed design approach has been demonstrated on a case study house, where impacts of different lighting control strategies on the house's energy efficiency can be quantitatively compared.
Internal Carotid Artery Dissection and Ischemic Cerebral Infarction in the Setting of Essential Thrombocythemia

Cervical artery dissection (CAD) is an important etiology of stroke in young adults. Its etiology is incompletely understood. Here, we report a young woman who presented with acute ischemic stroke in the setting of internal carotid artery (ICA) dissection and essential thrombocythemia (ET). We present a review of previous cases with comorbidity of CAD and ET and discuss the pathophysiological implications of this co-occurrence. In particular, we speculate that ET may increase the susceptibility of cervical vessels to spontaneous dissection, for example, by disturbing the microcirculation within the vessel wall.