Miracle-dz/UniFAR-FTUs huggingface dataset:
EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1α and STAT3

ABSTRACT Programmed cell death (PD)-1/PD-1 ligand-1 (PD-L1)-targeted therapy has emerged as a promising therapeutic strategy for lung cancer. However, whether EML4-ALK regulates PD-L1 expression in lung cancer remains unknown. A total of 532 pulmonary adenocarcinomas (pADCs), including 58 ALK-translocated tumors, were immunohistochemically evaluated for PD-L1 and PD-1. H23 (EGFRWild-typeEML4-ALK−PD-L1Low) and H2228 (EGFRWild-typeEML4-ALK+PD-L1High) cells were transfected with EML4-ALK or ALK short interfering RNAs and used to investigate the alterations in PD-L1 expression. PD-L1 expression was detected in 81% of ALK-translocated pADCs; this value was significantly higher than those of pADCs with EGFR mutation, KRAS mutation or lacking ALK, EGFR or KRAS mutation (p <0.005 for all). Moreover, ALK-translocated pADC with PD-L1 expression showed significantly higher numbers of tumor-infiltrating PD-1+ cells. ALK knockdown or inhibition (crizotinib treatment) in H2228 cells downregulated PD-L1 expression. Transfection of H23 cells with EML4-ALK enhanced PD-L1 expression, which was compromised by crizotinib treatment. This ALK-dependent upregulation of PD-L1 expression was mediated by STAT3 and hypoxia-inducible factor (HIF)-1α under normoxia and hypoxia. Furthermore, EML4-ALK enhanced HIF-1α expression through increasing transcription and decreasing ubiquitination of HIF-1α. In ALK-translocated pADC tissues, significant positive correlations between PD-L1 and nuclear HIF-1α (p < 0.05) or pSTAT3 expression levels (p<0.005) were observed. Among patients with ALK-translocated pADC, strong PD-L1 expression was significantly associated with shorter progression-free (p = 0.001) and overall survival (p = 0.002) after crizotinib treatment. Collectively, our findings demonstrate that ALK-derived pADCs increase PD-L1 expression via HIF-1α and/or STAT3, thus providing a rationale for PD-1/PD-L1 pathway-targeted therapy in ALK-translocated lung cancer.
Beta Stability Over Bull and Bear Market on the Warsaw Stock Exchange

Abstract Beta parameter is one of the commonly used measures of the investment risk of individual stock or portfolio. It plays a crucial role in modern portfolio theory particularly in management of financial investment portfolios. In the field of beta parameter, numerous studies have been conducted, especially beta properties stability in the context of the stock market cycle phases, measuring frequency of rate of return, and the length of a sample period. There are much fewer studies concerned beta parameter in the countries of Central and Eastern Europe which have undergone systemic transformation at the end of the previous century. From a scientific point of view, it is interesting to know how the beta parameter behaves in these countries. The main goal of this article is to examine the beta parameter stability over bull and bear market conditions on the Warsaw Stock Exchange. The paper presents an analysis of beta stability for 134 stocks of the largest companies listed at the WSE during years 2005–2013. To verify statistically the hypothesis of beta parameter stability, we used monthly returns in the Sharpe’s single-index model. In the first part of the article, we present a brief review of the literature and methodology of the study, while in the second part, the obtained results and conclusions are shown.
Development regulates a switch between post- and presynaptic strengthening in response to activity deprivation

In response to decreased activity, neurons make global compensatory increases in excitatory synaptic strength. However, how neuronal maturity affects this process is unclear. We silenced cultured hippocampal neurons with TTX at 7 days in vitro, during rapid synaptogenesis, and at 14 days, when major synaptogenesis is complete. For each age, we have explored the effects of short (1 day) and longer (2 days) periods of silencing. We have confirmed that the changes in synaptic strength depend on 2 main mechanisms, one presynaptic and the other postsynaptic. The presynaptic mechanism involves an increase in the probability of neurotransmitter release, mostly arising through an increase in the number of synaptic vesicles available for release. The postsynaptic mechanism operates through an increase in the number of postsynaptic receptors for the excitatory neurotransmitter glutamate. When neurons are silenced for 1 day, young neurons employ the postsynaptic mechanism, whereas more mature neurons increase their strength through the presynaptic mechanism. The postsynaptic strengthening in young neurons does not depend on gene transcription, whereas the presynaptic mechanism does. If neurons are silenced for 2 days, younger and older neurons employ both pre and postsynaptic mechanisms for synaptic strengthening. We also found evidence for 2 additional mechanisms that increased the effective synaptic coupling between neurons after 2 days of silencing: an increase in the number of synapses, and an increase in the electrotonic length of dendrites. These results expand our basic understanding of neuronal homeostasis, and reveal the developmental regulation of its expression mechanisms.
StrengthsFinder Signature Themes of Talent in Doctor of Pharmacy Students in Five Midwestern Pharmacy Schools

Objective. To describe student pharmacists’ Signature Themes from the Clifton StrengthsFinder across 5 Midwestern pharmacy institutions and to compare themes by gender, institution, and undergraduate population. Methods. Student pharmacists completed the StrengthsFinder 2.0 assessment and received their top 5 Signature Themes. Themes were organized and examined by domains (Executing, Influencing, Relationship Building, Strategic Thinking). The distribution of the themes was compared between student pharmacists and undergraduates and themes and domains were compared by institution and gender. Results. Although results varied by institution, the top 5 themes among the 1244 of 1250 students (99.5%) who completed the assessment were: Achiever, Harmony, Learner, Responsibility, and Empathy. Female student pharmacists had more themes in Executing and Relationship Building, while males had more themes in Influencing and Strategic Thinking. Pharmacy students exhibit more Executing domain talents and fewer Influencing domain talents compared with undergraduates. Conclusion. Signature Themes were consistent among student pharmacists across 5 Midwestern colleges of pharmacy.
Validation of a modified model of TNBS-induced colitis in rats. How to induce a chemical colitis in rats.

BACKGROUND There is no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of TNBS is preferred, because it will result in a local Th1 response that has the characteristics of Crohn`s disease. MATERIALS AND METHODS A total of 30 rats were randomized into two groups, consisting of a saline control group of ten rats and a TNBS groups of 20 rats. After the animals were anesthetized, 0.5 ml of either 0.9% saline (controls) or TNBS 50 mg/kg dissolved in 50% ethanol were instilled into the colon through a rubber catheter. The experiment was repeated weekly for four weeks, then, the rats were killed at day 40, and the distal colon removed. RESULTS At day 40, the bowel wall was basically normal in the control group. In the TNBS group, the bowel lumen became narrow with thickened wall, and the mucosal surface presented adherent membrane with brown black, linear ulcers, proliferous lymphocyte tissue, inflammatory granulomas and submucosal neutrophil infiltration. The median score of the severity of the colonic damage was 0 in the control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the rats was 180+35 g in the TNBS group, while it was 215+25 in the control group. CONCLUSIONS The presented experiment is a cost-effective and safe method to induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the risk of a massive loss of rats. This model is rather suitable for the assessment of the effects of potential therapeutic agents. (www.actabiomedica.it).
Acute Lower Gastrointestinal Bleeding: Characteristics and Clinical Outcome of Patients Treated With an Intensive Protocol

Background In recent years major advances have been made in the management of patients with acute lower gastrointestinal bleeding. The aim of this study was to investigate the characteristics and clinical outcome of patients with acute lower gastrointestinal bleeding (ALGIB) treated with an intensive protocol. Methods We analyzed the medical records of 528 patients with ALGIB. All patients after hemodynamic stabilization underwent colonoscopy during the first 24 h of hospitalization and capsule enteroscopy when needed. Patients with massive ongoing bleeding underwent computed tomography angiography (CTA), and when active bleeding was detected embolization was immediately performed. Results The mean age of the patients was 70.2 ± 14.6 years and 271 (51.3%) of them were men. At least one comorbidity was present in 464 patients (87.9%), cardiovascular disease in 266 (50.4%), while 158 (30%) patients were on antiplatelet drugs and 96 (18.2%) on anticoagulants. The most common causes of bleeding were diverticulosis (19.7%) and ischemic colitis (19.3%). Thirty-six patients (6.9%) had small intestinal bleeding. In 117 patients (22.2%) active bleeding or recent bleeding stigmata were found and in 82 of them (92.1%) endoscopic hemostasis was applied. Embolization was performed in 10 (1.9%) and was successful in seven (70%) cases, while surgical hemostasis was required in only six (1.1%) cases. Forty-four (8.3%) patients had a rebleeding episode, and 13 patients died with an overall mortality of 2.5%. Conclusions Management of ALGIB based on an intensive protocol is safe and effective. The bleeding source can be identified in most cases with a favorable outcome.
Increased expression of metadherin protein predicts worse disease‐free and overall survival in laryngeal squamous cell carcinoma

Metadherin (MTDH) is involved in tumourigenesis and cancer progression in multiple human malignancies. However, the MTDH protein has rarely been reported in laryngeal squamous cell carcinoma (LSCC). The expression pattern of the MTDH protein in 176 primary archival LSCC and 27 corresponding adjacent noncarcinoma specimens was detected by immunohistochemistry and further correlated with clinicopathological parameters. The results demonstrated that 161 (91.48%) primary LSCC samples stained positive for MTDH; however, staining was barely detectable in all adjacent noncarcinoma samples. Moreover, the expression of the MTDH protein was significantly associated with the primary tumour site (p = 0.021), T classification (p = 0.002), clinical stage (I + II/III + IV; p < 0.001), lymph node metastasis (p < 0.001) and postoperational recurrence (p < 0.001). Kaplan‐Meier analysis revealed that MTDH expression was significantly associated with worse disease‐free survival (DFS) and overall survival (OS) rates in patients with LSCC (both p < 0.001). When lymph node metastasis and MTDH expression were considered together, patients with lymph node metastasis and high MTDH expression had both poorer DFS and OS rates than others (both p < 0.001). Finally, multivariate analysis demonstrated that MTDH expression was an independent prognostic factor for both DFS and OS rates in patients with LSCC. Strong MTDH expression was negatively correlated with a canonical epithelial–mesenchymal transition molecule E‐cadherin (p < 0.001) and positively associated with proangiogenic protein vascular endothelial growth factor (p < 0.001). MTDH overexpression was tightly associated with more aggressive tumour behaviour and a poor prognosis, indicating that MTDH is a valuable molecular biomarker for LSCC progression.
Comparison of radial versus femoral approach for percutaneous coronary interventions in octogenarians

Background: The safety and efficacy of a radial approach for percutaneous coronary intervention (PCI) in octogenarians is not well established. Methods: To evaluate the benefits of a radial approach for preventing vascular complications after PCI, clinical, procedural, and outcome data were prospectively collected and compared for 228 octogenarians undergoing elective PCI either through a radial or a femoral approach. Results: Radial approach was associated with longer cannulation (3.1 ± 2.9 vs. 2.0 ± 2.0 min, P < 0.001) and fluoroscopy times (19.3 ± 16.1 vs. 16.1 ± 11.8 min, P = 0.04), greater utilization of contrast media (224 ± 46 vs. 182 ± 20 ml, P < 0.001) and higher crossover rate (11 vs 4%, P = 0.03) to alternate access site compared with the femoral approach. However, ambulation time (5.2 ± 3.1 vs. 11.6 ± 6.3 hr, P < 0.001), access site bleeding (4 vs. 14%, P = 0.007), hematoma (1 vs. 11%, P = 0.001) or any vascular complication (5 vs 26%, P = 0.001) were significantly reduced with a radial approach. Procedural success rates were equivalent with both approaches. Multivariate regression analysis identified radial approach (OR = 0.23; CI = 0.08, 0.65) as an independent negative predictor of postprocedural vascular complications. Conclusion: Radial approach for PCI in octogenarians is technically challenging for the operator and exposes patients to greater volume of nephrotoxic contrast media. However, it results in early ambulation and significantly reduces vascular complications in this high risk population. These findings support a strategy of preprocedural risk assessment and use of radial approach for PCI in a select group of octogenarians to maximize benefits offered by this technique. © 2006 Wiley‐Liss, Inc.
Citation classics: Top 50 cited articles in ‘respiratory system’

Identifying citation classics in the field is one of the key methodologies used to conduct a systematic evaluation of research performance. The objective of this study was to determine the most frequently cited articles published in journals that are placed under the ‘respiratory system’ subject category (Institute for Scientific Information (ISI) Journal Citation Reports) and to compare them with the most frequently cited respiratory‐related articles published in any journal, regardless of subject category. The authors utilized the ISI Journal Citation Reports: Science Edition 2010 database in April 2012 to determine the most frequently cited articles by respiratory system subject category and by respiratory‐related keywords. The top 50 most‐cited articles were identified in each category and evaluated according to various characteristics. The majority of these papers originated from the United States. The median numbers of citations for the top 50 cited articles stratified by respiratory system subject category and respiratory‐related keywords were 841.5 and 2701, respectively. Half of the top 50 cited articles identified by respiratory‐related keywords were published in general medical or basic science journals, whereas only three out of these were published in journals under the respiratory system subject category in ISI Journal Citation Reports. In summary, respiratory‐related articles published in general medical or science journals attracted more citations than those published in the specific respiratory journals.
How CSR and overall service quality lead to affective commitment: mediating role of company reputation

Purpose - The paper focuses on the relationships among corporate social responsibility (CSR), overall service quality (OSQ), company reputation and affective commitment. It investigates whether service quality or CSR is the primer driver of affective commitment. Also the mediating role of company reputation was examined. Design/methodology/approach - Structural equation modeling analysis provided support for the hypotheses from a sample of 522 retail banking consumers in Turkey. Findings - Findings show that both CSR and OSQ influence affective commitment through the mediator role of company reputation. Originality/value - This study tests and confirms that corporate reputation plays a mediator role along the paths from CSR and OSQ to affective commitment. Also this study expands the traditional view of CSR’s and OSQ effect on customers and suggests that CSR and OSQ do not only affect company reputation, but also affective commitment.
TRADE BALANCE AND INFLATION FLUCTUATIONS IN THE EURO AREA

We estimate a medium-scale dynamic stochastic general equilibrium (DSGE) model for the euro area in an open-economy framework. The model includes structural trends on all variables, allowing us to estimate on gross data. First, we provide a theoretical balanced growth path consistent with permanent productivity shocks, inflation target changes, and permanent shocks to the openness of the economies. We then define the cycle as the gap between this sustainable trajectory and the gross data. Hence, we can properly deal with persistent deviations of the trade balance. Finally, we find persistent and strong effects from the asymmetric increase of euro-area imports during the last 10 years on domestic inflation. From 2000Q1 to 2008Q4, we estimate the contribution of the imbalanced development of international trade on euro-area inflation to an average of −0.7%, and on nominal interest rate, to an average of −1.4%.
Contribution of Bradykinin Receptors to the Development of Secondary Brain Damage After Experimental Subarachnoid Hemorrhage

BACKGROUND:Subarachnoid hemorrhage (SAH) is the stroke subtype with the highest mortality and morbidity. Which molecular events mediate brain damage after SAH is not well understood. OBJECTIVE:To investigate the role of proinflammatory bradykinin B1 and B2 receptors for the pathophysiology of SAH. METHODS:B1 and B2 receptor knockout or wild-type mice were subjected to SAH by endovascular puncture. Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure were continuously monitored up to 60 minutes after SAH. Brain water content was quantified 24 hours after SAH; mortality, neurological function, and body weight were assessed daily for 7 days after hemorrhage. RESULTS:Intracranial pressure, regional cerebral blood flow, and mean arterial blood pressure did not differ between groups. Mortality was 60% in wild-type mice and 82% in B1R−/− mice but only 20% in B2R−/− animals (P < .05). B2R−/− mice also exhibited less severe neurological deficits (P < .05), a less pronounced loss of body weight (P < .05), and significantly less brain edema formation (P < .05) compared with wild-type mice. CONCLUSION:Signaling mediated by bradykinin B2 receptors contributes to mortality and secondary brain damage after SAH in mice. Thus, B2 receptors may represent novel targets for the treatment of SAH.
Dual-Band and Dual-Circularly Polarized Shared-Aperture Array Antennas With Single-Layer Substrate

This paper presents a new approach to implement planar shared-aperture dual-band dual-circular polarization (CP) array antennas. The antennas can be fabricated on a single-layer substrate and extended to a larger array easily. In this approach, each array element is obtained by connecting two patches working at different frequencies directly. To form arrays with higher gain, two kinds of feed networks are described, which can be applied in systems where narrowband and wideband are needed, respectively. One is using the conventional feed network and the other is using the sequential rotation technique to further improve the CP axial ratio (AR) performance. Two prototype arrays with $4 \times 4$ elements are fabricated and tested in $X/Ku$ bands. Experimental results show that good CP characteristics are obtained, which agree well with the simulation results. For the first narrow-band prototype array, the 3-dB AR bandwidth is around 1.5% for both bands. For the second array using the sequential rotation technique, the bandwidth of return loss and AR are wider. In the lower band centered at 12.1 GHz, the ${-}10\hbox{-}\text{dB}$ return loss bandwidth is 8.3% and the 3-dB AR bandwidth is 14.2% [right-hand CP (RHCP)]; in the higher band centered at 17.4 GHz, the corresponding data are 18.9% and 14.9% [left-hand CP (LHCP)], respectively.
Chromosomes and speciation in Mus musculus domesticus

Thirty years after its identification, the model of chromosomal speciation in Mus musculus domesticus is reevaluated using the methods of population biology, molecular cytogenetics and functional genomics. Three main points are considered: (1) the structural predisposition of M. m. domesticus chromosomes to Robertsonian fusion; (2) the impediment of structural heterozygosity to gene flow between populations of mice with karyotypes rearranged by Robertsonian fusion and between them and populations with the standard all-acrocentric 40-chromosome karyotype; (3) the selective advantage of chromosomal novelty, essential for the attainment of homozygosis and the rapid fixation of the new karyotype in the population.
The Crisis and Fair Values: Echoes of Early Twentieth Century Debates?

The recent global financial crisis has led to extensive criticism of the role of accounting and its use of fair value measurement in causing and spreading the crisis. This paper argues that the debate surrounding fair value vs. historic cost, and relevance versus reliability, is nothing new; it was at the center of early accounting discussions in the AAA (especially by A.C. Littleton and W.A. Paton), the AICPA (especially G.O. May), and the SEC. Although prominent accounting scholars and practitioners in postdepression 1929 focused on the use of historic cost, the paper discusses the decision of the IASB/FASB to move reliability to a secondary characteristic in its recent conceptual framework. This action ignores lessons learned from a century of research, teaching, and practice of accounting.
A Novel Heterodyne Polarimeter for the Multiple-Parameter Measurements of Twisted Nematic Liquid Crystal Cell Using a Genetic Algorithm Approach

A new method for measuring the multiple parameters of a twisted nematic liquid crystal (TNLC) by applying a genetic algorithm is presented. This paper adopts an electrooptic modulator to modulate the linear polarized light which passed through a TNLC cell in a heterodyne polarimetric setup. The intensity ratio and the phase of the detected heterodyne signal are used for the inverse calculation in the LC cell parameters by applying a genetic algorithm approach. As a result, the multiparameter measurements in the entrance director angle of TNLC, twist angle, and cell thickness are achieved. The advantage of the heterodyne polarimeter introduces high sensitivity on intensity and phase detections, and the multiple parameters could be easily extracted through the genetic algorithm. Also, the ambiguity in the angle extraction could be uniquely solved in this paper. The experimental results show that the average deviation of 0.01deg and 0.013 mum in the measurement of twist angle and cell thickness, respectively, have been obtained. The average deviation of 0.23deg in the measurement of director angle has also been achieved
Risk excess of soft‐tissue sarcoma and thyroid cancer in a community exposed to airborne organochlorinated compound mixtures with a high hexachlorobenzene content

Unusually high levels of hexachlorobenzene (HCB) were detected in the air and in sera of volunteers of a village located in the vicinity of an organochlorinated‐compounds factory (Flix, Catalonia, Spain). A significant increase for specific causes of death was obtained only for neoplasms of unknown origin. However, an excess of incident cases was observed for thyroid neoplasms, soft‐tissue sarcoma and brain neoplasms in men. These descriptive findings are in agreement with previously reported associations between soft‐tissue sarcoma and human exposure to organochlorinated compounds, as well as with animal experiments relating HCB and thyroid cancer, and add new information on the possible relation between organochlorinated compounds, and particularly HCB, and cancer.