Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Biomarkers for Breast Cancer Prognosis: Coexpression of c-erbB-2 and p53

ObjectiveTo assess the prognostic significance of molecular biomarkers, particularly c-erbB-2 and p53, through study of prospective clinical data and archival breast cancer tissues for women accrued to the Alabama Breast Cancer Project. Summary Background DataDefining molecular abnormalities in breast cancer is an important strategy for early detection, assessment of prognosis, and treatment selection. Evidence is strong that selective biomarkers, including c-erbB-2 and p53, have prognostic significance in breast cancer. Few studies have analyzed the prognostic significance of coexpression of biomarkers. MethodsStudy patients were those accrued to the Alabama Breast Cancer Project (1975–1978) who had archival breast cancer tissues available for analysis. Criteria for entrance into the Alabama Breast Cancer Project were T1–3 breast cancer with M0 status. Age, nodal status, and histologic grade were also documented. Patients were randomized to radical versus modified radical mastectomy, and node-positive patients were also randomized to adjuvant chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) versus melphalan. Archival breast cancer tissues were studied for c-erbB-2, TGF-&agr;, p53, cathepsin D, bcl-2, and estrogen and progesterone receptor expression using immunohistochemistry. Survival curves were developed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, multivariate analysis using a rank regression model. ResultsThree hundred eleven patients were accrued to the Alabama Breast Cancer Project, and paraffin-embedded breast cancer tissues for 90 patients were available for immunohistochemical analysis of molecular biomarkers. Univariate analysis showed nodal status, c-erbB-2 expression, and p53 expression to have prognostic significance. Coexpression of c-erbB-2 and p53 was also found to have prognostic significance by the log-rank test. Multivariate analysis showed T stage, nodal status, c-erbB-2 expression, and p53 expression to have independent prognostic significance. ConclusionsThese data suggest that c-erbB-2 and p53 expression in breast cancer have prognostic significance. After median follow-up of 16 years, coexpression of c-erbB-2 and p53 may have more prognostic significance than traditional prognostic factors such as T stage and nodal status. Prospective study of large numbers of patients with breast cancer is encouraged to validate these findings.
UIMA Ruta: Rapid development of rule-based information extraction applications

Abstract Rule-based information extraction is an important approach for processing the increasingly available amount of unstructured data. The manual creation of rule-based applications is a time-consuming and tedious task, which requires qualified knowledge engineers. The costs of this process can be reduced by providing a suitable rule language and extensive tooling support. This paper presents UIMA Ruta, a tool for rule-based information extraction and text processing applications. The system was designed with focus on rapid development. The rule language and its matching paradigm facilitate the quick specification of comprehensible extraction knowledge. They support a compact representation while still providing a high level of expressiveness. These advantages are supplemented by the development environment UIMA Ruta Workbench. It provides, in addition to extensive editing support, essential assistance for explanation of rule execution, introspection, automatic validation, and rule induction. UIMA Ruta is a useful tool for academia and industry due to its open source license. We compare UIMA Ruta to related rule-based systems especially concerning the compactness of the rule representation, the expressiveness, and the provided tooling support. The competitiveness of the runtime performance is shown in relation to a popular and freely-available system. A selection of case studies implemented with UIMA Ruta illustrates the usefulness of the system in real-world scenarios.
Early inflammatory response during the development of right ventricular heart failure in a rat model

Inflammatory activation plays an important role in the pathogenesis and progression of left ventricular (LV) heart failure. In right ventricular (RV) heart failure, little is known about the role of inflammatory activation. We aimed to study the role of inflammatory activation in RV heart failure by serial monitoring during disease progression.
Pharmacokinetics of florfenicol in the plasma of Japanese quail

Abstract AIM: To determine the pharmacokinetics and bioavailability of florfenicol in the plasma of healthy Japanese quail (Coturnix japonica). METHODS: Sixty-five quail were given an I/V and I/M dose of florfenicol at 30 mg/kg bodyweight (BW). A two-period sequential design was used, with a wash-out period of 2 weeks between the different routes of administration. Concentrations of florfenicol in plasma were determined using high-performance liquid chromatography (HPLC). RESULTS: A naíve pooled data analysis approach for the plasma concentration-time profile of florfenicol was found to fit a non-compartmental open model. After I/V administration, the mean residence time (MRT), mean volume of distribution at steady state (Vss), and total body clearance of florfenicol were 12.0 (SD 0.37) h, 8.7 (SD 0.22) L/kg, and 1.3 (SD 0.08) L/h/kg, respectively. After I/M injection, the MRT, mean absorption time (MAT), and bioavailability were 12.3 (SD 0.37) h, 0.2 (SD 0.02) h, and 79.1 (SD 1.79)%, respectively. CONCLUSIONS: The time for the concentration of florfenicol to fall below the probable effective concentration of 1 µg/ml of approximately 10 h is sufficient for the minimum inhibitory concentration needed for many bacterial isolates. Further pharm acodynamic studies in quail are needed to evaluate a suitable dosage regimen.
What factors influence nurses' assessment practices? Development of the Barriers to Nurses' use of Physical Assessment Scale.

AIM To develop and psychometrically test the Barriers to Nurses' use of Physical Assessment Scale. BACKGROUND There is growing evidence of failure to recognize hospitalized patients at risk of clinical deterioration, in part due to inadequate physical assessment by nurses. Yet, little is known about the barriers to nurses' use of physical assessment in the acute hospital setting and no validated scales have been published. DESIGN Instrument development study. METHOD Scale development was based on a comprehensive literature review, focus groups, expert review and psychometric evaluation. The scale was administered to 434 acute care Registered Nurses working at a large Australian teaching hospital between June and July 2013. Psychometric analysis included factor analysis, model fit statistics and reliability testing. RESULTS The final scale was reduced to 38 items representing seven factors, together accounting for 57·7% of the variance: (1) reliance on others and technology; (2) lack of time and interruptions; (3) ward culture; (4) lack of confidence; (5) lack of nursing role models; (6) lack of influence on patient care; and (7) specialty area. Internal reliability ranged from 0·70-0·86. CONCLUSION Findings provide initial evidence for the validity and reliability of the Barriers to Nurses' use of Physical Assessment Scale and point to the importance of understanding the organizational determinants of nurses' assessment practices. The new scale has potential clinical and research applications to support nursing assessment in acute care settings.
Characterization of an infectious molecular clone of human T-cell leukemia virus type I

An infectious molecular clone of human T-cell leukemia virus type I (HTLV-I) was derived from an HTLV-I-transformed rabbit T-cell line, RH/K30, obtained by coculture of rabbit peripheral blood mononuclear cells (PBMC) with the human HTLV-I-transformed cell line MT-2. The RH/K30 cell line contained two integrated proviruses, an intact HTLV-I genome and an apparently defective provirus with an in-frame stop codon in the env gene. A genomic DNA fragment containing the intact HTLV-I provirus was cloned into bacteriophage lambda (K30 phi) and subcloned into a plasmid vector (K30p). HTLV-I p24gag protein was detected in culture supernatants of human and rabbit T-cell and fibroblast lines transfected with these clones, at levels comparable to those of the parental cell line RH/K30. Persistent expression of virus was observed in one of these lines, RL-5/K30p, for more than 24 months. Biologic characterization of this cell line revealed the presence of integrated HTLV-I provirus, spliced and unspliced mRNA transcripts, and typical extracellular type C retrovirus particles. As expected, these virus particles contained HTLV-I RNA and reverse transcriptase activity. The transfected cells also expressed surface major histocompatibility complex class II, whereas no expression of this molecule was detected in the parental RL-5 cell line. Virus was passaged by cocultivation of irradiated RL-5/K30p cells with either rabbit PBMC or human cord blood mononuclear cells, demonstrating in vitro infectivity. The virus produced in these cells was also infectious in vivo, since rabbits injected with RL-5/K30p cells became productively infected, as evidenced by seroconversion, amplification of HTLV-I-specific sequences by PCR from PBMC DNA, and virus isolation from PBMC. Availability of infectious molecular clones will facilitate functional studies of HTLV-I genes and gene products.
Caveolae: molecular insights and therapeutic targets for stroke

Introduction: Caveolae are specialized plasma membrane micro-invaginations of most mammalian cell types. The organization and function of caveolae are carried out by their coat proteins, caveolins and adaptor proteins, cavins. Caveolae/caveolins physically interact with membrane-associated signaling molecules and function in cholesterol incorporation, signaling transduction and macromolecular transport/permeability. Areas covered: Recent investigations have implicated a check-and-balance role of caveolae in the pathophysiology of cerebral ischemia. Caveolin knockout mice displayed exacerbated ischemic injury, whereas caveolin peptide exerted remarkable protection against ischemia/reperfusion injury. This review attempts to provide a comprehensive synopsis of how caveolae/caveolins modulate blood–brain barrier permeability, pro-survival signaling, angiogenesis and neuroinflammation, and how this may contribute to a better understanding of the participation of caveolae in ischemic cascade. The role of caveolin in the preconditioning-induced tolerance against ischemia is also discussed. Expert opinion: Caveolae represent a novel target for cerebral ischemia. It remains open how to manipulate caveolin expression in a practical way to recapitulate the beneficial therapeutic outcomes. Caveolin peptides and associated antagomirs may be efficacious and deserve further investigations for their potential benefits for stroke.
Circulating insulin‐like growth factor‐related biomarkers: Correlates and responses to calcium supplementation in colorectal adenoma patients

Circulating insulin‐like growth factor 1 (IGF‐1) may be directly associated with colorectal cancer risk, and IGF binding protein 3 (IGFBP‐3) is one of the most abundantly expressed binding proteins in various cancers. Calcium intakes, primarily from food, have been directly associated with circulating IGF‐1, but whether supplemental calcium affects IGF‐1 and IGFBP‐3 is unknown. We tested the effects of 1.0 and 2.0 g of supplemental elemental calcium daily on circulating IGF‐1 and IGFBP‐3 concentrations in colorectal adenoma patients in a randomized, double‐blinded, placebo‐controlled clinical trial (n = 193). IGF‐1 and IGFBP‐3 were quantified using enzyme‐linked immunoassay and quantitative Western ligand blot, respectively. We also assessed cross‐sectional associations of these biomarkers with participants’ baseline characteristics. We found no appreciable effect of calcium relative to placebo on circulating IGF‐1, IGFBP‐3, or the IGF‐1:IGFBP‐3 molar ratio. Mean IGF‐1 concentrations were 11.1% higher in those with greater milk intakes (P = 0.05). Mean IGF‐1 and IGFBP‐3 concentrations were, respectively, 18.0% (P = 0.003) and 16.5% (P = 0.01) higher in men and were monotonically lower with increasing age (both P = 0.01). IGFBP‐3 was 17.7% higher among those with higher relative to no alcohol consumption (P = 0.04). While these results support previous findings that IGF‐1 concentrations are higher with greater milk intakes, and IGF‐1 and IGFBP‐3 concentrations differ according to sex and age, they provide no evidence to suggest that supplemental calcium appreciably affects circulating IGF‐1, IGFBP‐3, or the IGF‐1:IGFBP‐3 molar ratio in sporadic colorectal adenoma patients.
Flame-retardant contamination of firefighter personal protective clothing – A potential health risk for firefighters

ABSTRACT There is a high incidence of cardiovascular disease and certain cancers in firefighters that may be related to their occupational exposure to hazardous substances. Exposure may result from contaminated personal protective gear, as well as from direct exposure at fire scenes. This study characterized flame-retardant contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used and unused firefighter protective clothing, including gloves, hoods and a coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270D Specific Ion Method (SIM) for polybrominated diphenyl ethers (PBDEs). Until recently PBDEs were some of the most common flame-retardant chemicals used in the US. Fifteen of the seventeen PBDEs for which analysis was performed were found on at least one clothing swatch. Every clothing sample, including an unused hood and all three layers of an unused glove, held a detectable concentration of at least one PBDE. These findings, along with previous research, suggest that firefighters are exposed to PBDE flame retardants at levels much higher than the general public. PBDEs are found widely dispersed in the environment and still persist in existing domestic materials such as clothing and furnishings. Firefighter exposure to flame retardants therefore merits further study.
Comparison of aminopeptidase activities in four strains of mutans group oral streptococci

In this study, native cells of Streptococcus mutans VA-29R and Streptococcus rattus FA-1 displayed significantly higher aminopeptidase activity than did cells of Streptococcus cricetus AHT or Streptococcus sobrinus 6715 toward the nitroanilide derivatives of leucine, alanine, methionine, arginine, and lysine. These differences in cellular aminopeptidase activity led us to investigate the subcellular localization of the aminopeptidase in these mutans group streptococci. Following conversion of native cells to protoplasts by treatment with lysozyme, most of the aminopeptidase activity detected in the native-cell preparations remained associated with the intact protoplasts. After lysis of protoplasts and differential centrifugation, most of the total cellular aminopeptidase activity was recovered with the cytoplasmic fraction. Membrane-associated aminopeptidases represented only minor activities in these mutans group streptococci. Although the four strains showed no differences with respect to a predominant cytoplasmic localization for the aminopeptidase activities, the levels of activity in the cytoplasmic fractions from S. cricetus AHT and S. sobrinus 6715 were significantly lower than those measurable in the corresponding fractions from S. mutans VA-29R and S. rattus FA-1. These results support the conclusion that the differences in aminopeptidase activity expressed by these streptococci reflect quantitative differences rather than differences in enzyme subcellular localization.
Unprecedented Silver Resistance in Clinically Isolated Enterobacteriaceae: Major Implications for Burn and Wound Management

ABSTRACT Increased utilization of inorganic silver as an adjunctive to many medical devices has raised concerns of emergent silver resistance in clinical bacteria. Although the molecular basis for silver resistance has been previously characterized, to date, significant phenotypic expression of these genes in clinical settings is yet to be observed. Here, we identified the first strains of clinical bacteria expressing silver resistance at a level that could significantly impact wound care and the use of silver-based dressings. Screening of 859 clinical isolates confirmed 31 harbored at least 1 silver resistance gene. Despite the presence of these genes, MIC testing revealed most of the bacteria displayed little or no increase in resistance to ionic silver (200 to 300 μM Ag+). However, 2 isolates (Klebsiella pneumonia and Enterobacter cloacae) were capable of robust growth at exceedingly high silver concentrations, with MIC values reaching 5,500 μM Ag+. DNA sequencing of these two strains revealed the presence of genes homologous to known genetic determinants of heavy metal resistance. Darkening of the bacteria's pigment was observed after exposure to high silver concentrations. Scanning electron microscopy images showed the presence of silver nanoparticles embedded in the extracellular polymeric substance of both isolates. This finding suggested that the isolates may neutralize ionic silver via reduction to elemental silver. Antimicrobial testing revealed both organisms to be completely resistant to many commercially available silver-impregnated burn and wound dressings. Taken together, these findings provide the first evidence of clinical bacteria capable of expressing silver resistance at levels that could significantly impact wound management.
A flexible strategy for testing subgroups and overall population

Subgroup analyses in addition to the total study population analysis are common in clinical trials. However, it is well recognized that findings from subgroup analyses do not provide confirmatory evidence for subgroup treatment effects without placing a priori criteria for ensuring that their findings are scientifically sound. In this paper we address some of the common pitfalls of subgroup analyses. Subgroups analyses inherently have low power for detecting treatment effects. We investigate the power interplay for a subgroup analysis and that for the total study population and list factors that impact the power of a subgroup analysis. Then we introduce a flexible statistical strategy for testing a pre‐specified sequence of hypotheses for both the overall and a subgroup. The proposed method strongly controls the familywise Type I error rate and enjoys higher power than other traditional methods. This testing strategy allows testing for a subgroup once a pre‐specified degree of consistency in the efficacy findings between the subgroup and the overall study population is met. In addition, it accounts for the dependency between test statistics for the subgroup and the overall study population. We discuss the power performance of this new method and provide significance levels for subgroup analysis. Finally, we illustrate its application through retrospective analysis of data from three published clinical trials. Copyright © 2008 John Wiley & Sons, Ltd.
Decreased Expression of L-Selectin on Peripheral Blood Polymorphonuclear Leukocytes in Neonates with Severe Asphyxia

The expression of adherent leukocyte surface molecules, L-selectin (CD62L), and Mac-1 (CD11b/CD18) in peripheral blood polymorphonuclear leukocytes (PMNs) was studied in 48 neonates and 24 healthy adults using fluorescence flow cytometry. L-selectin expression was decreased significantly in neonates, especially those with severe asphyxia (n = 10) compared with adults. Mac-1 expression was significantly increased in neonates compared with adults, but did not differ between 24 normal neonates, 14 neonates with mild asphyxia, and 10 neonates with severe asphyxia. These results suggest that the magnitude of the decrease in L-selectin expression reflects the severity of asphyxia in neonates.
Cortical Thickness of the Second Metatarsal After Correction of Hallux Valgus

Background: Hallux valgus is a functional deformity of the first ray. When incorrectly aligned, the first ray is less effective as a support structure, and the stresses then theoretically transfer to the second metatarsal which could lead to increased cortical density. The aim of this study was to evaluate if surgical correction of hallux valgus lead to changes in the cortical density of the second metatarsal. Materials and Methods: This was a retrospective study involving 13 patients who had surgery for isolated hallux valgus. The average postoperative followup was 16 (range, 11 to 24) months. We analyzed pre- and postoperative radiographs of the feet. We assessed the variations in the medial and lateral cortical thickness, the medullary thickness and the shaft thickness (ST) of the second and fourth metatarsals. Results: A significant reduction of the medial cortical bone thickness of the second metatarsal (MT2) (p < 0.001) and a significant medullary increase of MT2 (p < 0.001) were observed postoperatively. However, no significant difference in the lateral cortical thickness or shaft thickness of the metatarsal was found. A significant reduction of the MCT/ST ratio (p < 0.001) was also observed. Regarding the fourth metatarsal, which was used as a control, no significant change was observed. Conclusion: The isolated cortical variations of the second metatarsal suggests that isolated hallux valgus correction led to a redistribution of the stresses on to the first ray. Level of Evidence: IV, Retrospective Case Series
A Study on the Mechanical Properties and Impact-Induced Initiation Characteristics of Brittle PTFE/Al/W Reactive Materials

Polytetrafluoroethylene/aluminum/tungsten (PTFE/Al/W) reactive materials of three different component mass ratios (73.5/26.5/0, 68.8/24.2/7 and 63.6/22.4/14) were studied in this research. Different from the PTFE/Al/W composites published elsewhere, the materials in our research were fabricated under a much lower sintering temperature and for a much shorter duration to achieve a brittle property, which aims to provide more sufficient energy release upon impact. Quasi-static compression tests, dynamic compression tests at room and elevated temperatures, and drop weight tests were conducted to evaluate the mechanical and impact-induced initiation characteristics of the materials. The materials before and after compression tests were observed by a scanning electron microscope to relate the mesoscale structural characteristics to their macro properties. All the three types of materials fail at very low strains during both quasi-static and dynamic compression. The stress-strain curves for quasi-static tests show obvious deviations while that for the dynamic tests consist of only linear-elastic and failure stages typically. The materials were also found to exhibit thermal softening at elevated temperatures and were strain-rate sensitive during dynamic tests, which were compared using dynamic increase factors (DIFs). Drop-weight test results show that the impact-initiation sensitivity increases with the increase of W content due to the brittle mechanical property. The high-speed video sequences and recovered sample residues of the drop-weight tests show that the reaction is initiated at two opposite positions near the edges of the samples, where the shear force concentrates the most intensively, indicating a shear-induced initiation mechanism.