Miracle-dz/UniFAR-FTUs huggingface dataset:
Stat3 Is Required for Cytoprotection of the Respiratory Epithelium during Adenoviral Infection1

The role of Stat3 in the maintenance of pulmonary homeostasis following adenoviral-mediated lung injury was assessed in vivo. Stat3 was selectively deleted from bronchiolar and alveolar epithelial cells in Stat3ΔΔ mice. Although lung histology and function were unaltered by deletion of Stat3 in vivo, Stat3ΔΔ mice were highly susceptible to lung injury caused by intratracheal administration of AV1-GFP, an early (E) region 1- and E3-deleted, nonproliferative adenovirus. Severe airspace enlargement, loss of alveolar septae, and sloughing of the bronchiolar epithelium were observed in Stat3ΔΔ mice as early as 1 day after exposure to the virus. Although surfactant protein A, B, and C content and surfactant protein-B mRNA expression in Stat3ΔΔ mice were similar, TUNEL staining and caspase-3 were increased in alveolar type II epithelial cells of Stat3ΔΔ mice after exposure to virus. RNA microarray analysis of type II epithelial cells isolated from Stat3ΔΔ mice demonstrated significant changes in expression of numerous genes, including those genes regulating apoptosis, supporting the concept that the susceptibility of Stat3-deficient mice to adenovirus was related to the role of Stat3 in the regulation of cell survival. AV1-Bcl-xL, an E1- and E3-deleted, nonproliferative adenovirus expressing the antiapoptotic protein Bcl-xL, protected Stat3ΔΔ mice from adenoviral-induced lung injury. Adenoviral infection of the lungs of Stat3-deficient mice was associated with severe injury of the alveolar and bronchiolar epithelium. Thus, Stat3 plays a critical cytoprotective role that is required for epithelial cell survival and maintenance of alveolar structures during the early phases of pulmonary adenoviral infection.
New Ventures in the Genotoxic and Cytotoxic Effects of Macrocyclic Lactones, Abamectin and Ivermectin

Abamectin and Ivermectin are 2 closely related members of the Avermectin family of 16-membered macrocyclic lactones derived from the actinomycete Streptomyces avermectinius which exhibit extraordinary anthelmintic activity. They are used worldwide in veterinary and human medicine as well as in agriculture. In the present review we summarized the results published so far for estimating the genotoxicity and cytotoxicity exerted by both compounds in several cellular systems. Although both compounds do not induce in vitro and in vivo gene mutations in either bacterial or mammalian cells, there is no concrete evidence of a clear clastogenic effect exerted both in vitro and in vivo in mammalian cells. However, reports indicating that both anthelmintic agents are able to induce single DNA-strand breaks in vitro and inhibit cell growth either in vitro or in in vivo bioassays, are scarce. Taking into account the similarity of the genotoxicity and cytotoxicity exerted by both antibiotics, and that only Abamectin has been classified so far as a class II toxicity pesticide by the EPA, the necessity of reconsideration for a further hazard evaluation of Ivermectin by an international regulatory agency(ies) is strongly recommended.
Neuroepithelial oxygen chemoreceptors of the zebrafish gill

In aquatic vertebrates, hypoxia induces physiological changes that arise principally from O2 chemoreceptors of the gill. Neuroepithelial cells (NECs) of the zebrafish gill are morphologically similar to mammalian O2 chemoreceptors (e.g. carotid body), suggesting that they may play a role in initiating the hypoxia response in fish. We describe morphological changes of zebrafish gill NECs following in vivo exposure to chronic hypoxia, and characterize the cellular mechanisms of O2 sensing in isolated NECs using patch‐clamp electrophysiology. Confocal immunofluorescence studies indicated that chronic hypoxia (P O 2 = 35 mmHg, 60 days) induced hypertrophy, proliferation and process extension in NECs immunoreactive for serotonin or synaptic vesicle protein (SV2). Under voltage clamp, NECs responded to hypoxia (P O 2 = 25–140 mmHg) with a dose‐dependent decrease in K+ current. The current–voltage relationship of the O2‐sensitive current (I KO 2 ) reversed near EK and displayed open rectification. Pharmacological characterization indicated that I KO 2 was resistant to 20 mm tetraethylammonium (TEA) and 5 mm 4‐aminopyridine (4‐AP), but was sensitive to 1 mm quinidine. In current‐clamp recordings, hypoxia produced membrane depolarization associated with a conductance decrease; this depolarization was blocked by quinidine, but was insensitive to TEA and 4‐AP. These biophysical and pharmacological characteristics suggest that hypoxia sensing in zebrafish gill NECs is mediated by inhibition of a background K+ conductance, which generates a receptor potential necessary for neurosecretion and activation of sensory pathways in the gill. This appears to be a fundamental mechanism of O2 sensing that arose early in vertebrate evolution, and was adopted later in mammalian O2 chemoreceptors.
Activation of Poly(ADP)-ribose Polymerase (PARP-1) Induces Release of the Pro-inflammatory Mediator HMGB1 from the Nucleus*

Necrotic cells release inflammatory mediators that activate cytokine production from innate immune cells. One mediator of this activation is high mobility group box 1 protein (HMGB1). HMGB1 is normally a chromatin-associated protein and is sequestered at condensed chromatin during apoptosis. How it is released from chromatin during necrotic cell death is not known. Here we show that after DNA-alkylating damage, the activation of poly(ADP)-ribose polymerase (PARP) regulates the translocation of HMGB1 from the nucleus to the cytosol. This displaced HMGB1 is subject to release if the cell then loses plasma membrane integrity as a result of necrosis. Both full-length HMGB1 and a truncated form of HMGB1 lacking the highly conserved glutamate-rich C-terminal tail can induce macrophage activation and tumor necrosis factor-α production. However, displacement of HMGB1 from the nucleus following PARP activation requires the presence of the glutamate-rich C-terminal tail. Although the C-terminal tail is not the sole substrate for PARP modification of HMGB1, it appears to be required to destabilize HMGB1 association with chromatin following PARP-dependent chromatin modifications. These data suggest that PARP-dependent nuclear-to-cytosolic translocation of HMGB1 serves to establish the ability of cells to release this potent inflammatory mediator upon subsequent necrotic death.
The effects of race and body fat distribution on insulin sensitivity.

Central or upper body fat has been implicated as a risk factor for diabetes and cardiovascular disease mortality in a number of crosssectional and prospective studies. These studies have all been in Caucasian men (1,2) and women (3,4). Also, studies have been carried out in Mexican Americans (5-7) and in Japanese Americans (8). Although African-Americans have a high incidence of obesity and of obesityrelated diseases, no studies relating central obesity to disease have been done in this group. This is despite the fact that in the U.S.A. the prevalence of obesity is highest in African-American women. Because of this, we set out to assess diabetic and cardiovascular disease (CVD) risk in four groups of nondiabetic, premenopausal women who differed on the basis of race and body fat distribution. We matched the women for age, menopausal status, degree of obesity, and fat patterning. The objective was to determine whether black upper body obese (UBO) women are similar to their white counterparts with regard to glucose intolerance, hyperinsulinemia, peripheral insulin resistance, altered plasma lipids, elevated blood pressure, and androgenic status. We assessed diabetes risk by levels of plasma glucose and insulin after an oral glucose tolerance test and by in vivo measurement of peripheral insulin sensitivity. CVD risk was assessed by levels of plasma triglyceride, total cholesterol, HDL and LDL cholesterol, and systolic and diastolic blood pressure. In addition, androgenic status was determined by levels of plasma sex-hormone binding globulin (SHBG), total and free testosterone, and DHEA-S04 in blood samples obtained during the early follicular phase of the menstrual cycle.
Chairman and CEO: The Controversy Over Board Leadership Structure

One of the most controversial issues in corporate governance is whether the CEO of a corporation should also serve as chairman of the board. In theory, an independent board chair improves the ability of the board to oversee management. However, an independent chairman is not unambiguously positive, and can lead to duplication of leadership, impair decision making, and create internal confusion — particularly when an effective dual chairman/CEO is already in place.In this Closer Look, we examine in detail the leadership structure of publicly traded corporations and the circumstances under which they are changed. We ask:• What factors should the board consider in deciding whether to combine or separate board leadership? • How can the board weigh the tradeoffs between stability of leadership, efficient decision making, and decreased oversight? • What structure should be the default setting for a corporation? • Why do activists advocate that corporations strictly separate the roles when there is little research support for this position? The Stanford Closer Look series is a collection of short case studies through which we explore topics, issues, and controversies in corporate governance and executive leadership. In each study, we take a targeted look at a specific issue that is relevant to the current debate on governance and explain why it is so important. Larcker and Tayan are co-authors of the books Corporate Governance Matters and A Real Look at Real World Corporate Governance.
Endothelial Dysfunction: A Marker of Atherosclerotic Risk

Abstract—Endothelial dysfunction is a systemic disorder and a key variable in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk factor burden but rather, may be regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual, including known as well as yet-unknown variables and genetic predisposition. Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of the inherent atherosclerotic risk in an individual. In line with this hypothesis, dysfunction of either the coronary or peripheral vascular endothelium was shown to constitute an independent predictor of cardiovascular events, providing valuable prognostic information additional to that derived from conventional risk factor assessment. Interventions like risk factor modification and treatment with various drugs, including statins and angiotensin-converting enzyme inhibitors, may improve endothelial function and thereby, potentially prognosis. Hence, given its reversibility and granted the availability of a diagnostic tool to identify patients at risk and to control the efficacy of therapy in clinical practice, endothelial dysfunction may be an attractive primary target in the effort to optimize individualized therapeutic strategies to reduce cardiovascular morbidity and mortality.
Could platelet indices be prognostic biomarkers for mild or severe acute pancreatitis ?

The aim of this study was to show the relation of platelet indices with the severity of acute pancreatitis (AP) and if they have any correlation with the severity of AP. Forty-seven patients with AP hospitalized in Department of Gastroenterology, Inonu University Faculty of Medicine were divided into two groups, namely, the severe AP group (n=15) and the mild AP group (n=32). The scores of these patients at days 0, 3 and at the beginning of remission according to the prognostic scoring systems (Ranson, APACHE II, and BISAP criteria), CRP, sedimentation and platelet indices (platelet count, MPV, PDW and PCT) were noted. Mann-Whitney U test was used to compare the groups. Spearman’s Rho test was used to evaluate the correlations between the platelet indices and other prognostic factors. Significant differences were found between the groups as regards platelets (P<0.02), PDW (P<0.001), AST (P<0.001), ALT (P<0.001), Total bilirubin (P<0.007), LDH (P<0.001), CRP (P<0.001), sedimentation (P<0.001), APACHE-II (P<0.001), Ranson (P<0.002) parameters. When considered for the correlation between the platelet indices and other prognostic factors, it was seen that all the platelet indices showed strong positive or negative correlation in mild AP with other prognostic scoring systems, CRP and sedimentation. In contrast, it was seen that platelet indices in severe AP cases did not show strong correlation with other prognostic scoring systems, CRP and sedimentation. We showed that platelet derivatives can be used as a good prognostic biomarker for the course of mild AP. In severe AP cases, however, usability of platelet indices must be supported with further studies.
Judging the Animacy of Words: The Influence of Typicality and Age of Acquisition in a Semantic Decision Task

The age at which members of a semantic category are learned (age of acquisition), the typicality they demonstrate within their corresponding category, and the semantic domain to which they belong (living, non-living) are known to influence the speed and accuracy of lexical/semantic processing. So far, only a few studies have looked at the origin of age of acquisition and its interdependence with typicality and semantic domain within the same experimental design. Twenty adult participants performed an animacy decision task in which nouns were classified according to their semantic domain as being living or non-living. Response times were influenced by the independent main effects of each parameter: typicality, age of acquisition, semantic domain, and frequency. However, there were no interactions. The results are discussed with respect to recent models concerning the origin of age of acquisition effects.
Ultrastructural Hippocampal and White Matter Alterations in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) is considered to be a transitional stage between normal aging and dementia. In Alzheimer’s disease (AD), white matter structural pathology is due to Wallerian degeneration and central angiopathy. However, in MCI patients, the presence and extent of white matter alterations as a possible correlate of impaired memory function and as predictor of subsequent progression to AD is not clarified yet. Diffusion tensor imaging (DTI) reveals the ultrastructural integrity of cerebral white matter tracts. Therefore, it could detect pathological processes that modify tissue integrity in patients with MCI. In our prospective study, conventional and diffusion tensor MR scans were obtained from 14 patients with MCI, 19 patients with AD, and 10 healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu and splenium) and the hippocampus. MCI patients showed higher MD values in the left centrum semiovale (p = 0.013; right: p = 0.026), in the left temporal (p = 0.006), the right temporal (p = 0.014) and the left hippocampal (p = 0.002) region as compared to the control group. FA values of MCI patients and controls did not differ significantly in any region. Compared to controls, AD patients had increased MD values in the left centrum semiovale (p = 0.012), the left parietal (p = 0.001), the right parietal (p = 0.028), the left temporal (p = 0.018), the right temporal (p = 0.011) and the left hippocampal region (p = 0.002). Decreased FA values were measured in the left temporal area (p = 0.017) and in the left hippocampus (p = 0.031) in AD patients compared to controls. FA and MD values did not differ significantly between AD and MCI patients. Elevated MD values indicating brain tissue alterations in MCI patients were found in regions that are typically involved in early changes due to AD, particularly the left hippocampus. The sensitivity of distinguishing MCI patients from controls was 71.4% (with a specificity set at 80%). Therefore, the DTI technique validates the MCI concept, and diffusion tensor MR measurement can be a helpful tool to quantify MCI pathology in vivo.
Patients' Satisfaction With Provided Care/Information and Expectations on Clinical Outcome After Lumbar Disc Herniation Surgery

Study Design. A prospective study of patients undergoing lumbar disc herniation surgery. Objectives. To assess patients' satisfaction with care/preoperative information, if expectations on surgical results and ability to return to work are related to baseline characteristics, and/or can predict self-reported outcome. Self-reported outcome was compared with objective outcome. Summary of Background Data. Patients' expectations on treatment results have been discussed as a predictive factor for postoperative outcome and satisfaction demonstrated to be directly related to patient expectations. Methods. The study includes 148 patients, 46% women, mean age 40 (range 18–66). Before and 2 years after surgery, questionnaires about given information/care, expected/present work ability, and expectations on/obtained improvement of physical functions/symptoms (leg and back pain, sensibility, and muscle function) were filled in. The visual analog scale leg pain, Zung Depression Scale, and Oswestry Disability Index were used as baseline characteristics. At 2-year follow-up, self-reported and objective outcome was assessed. Results. Satisfaction with given information/care were reported by 46% and 82%, respectively. Zung Depression Scale related to expectations on leg pain recovery (P = 0.022), work ability (P = 0.046), and satisfaction with given information (P = 0.031). Patients who expected to return (76%) and not return (24%) to work, returned in 78% and 26%, respectively (P = 0.021). A high agreement between self-reported outcome and objective outcome were found (P < 0.001). Conclusions. Patients undergoing lumbar disc herniation surgery are mostly satisfied with provided care before and after surgery, however, less satisfied with information provided. Further, patients with preoperative positive expectations on work return and realistic expectations on pain and physical recovery have a greater chance to be satisfied with the surgical results.
Patient Life Experience and Activity of Daily Living before and after Total Knee Arthroplasty

Background: As the population ageing, more patients suffer from joint disease. Joint replacement surgery performed in Taiwan is about 10,000 to 20,000 cases yearly. Aims: The purpose of this study is to realize Total Knee Arthroplasty (TKA) patients’ views about life experiences and difficulty in daily life before and after the surgery. Methods: In this study, in-depth interview with interview guideline was used to analyze patients’ experience by using a qualitative research method, and questionnaires were used to collect quantity data. Results: 1) A total of 20 participants were recruited. Average age was 75.15 (SD = 6.468). Eighteen of the participants were female and the other two were male. The majority of participants indicated that their home facilities were convenient or very convenient. 2) Motivations of the participants to undergo TKA were joint pain, limited joint range of motion, and weakness in legs. Participants’ expectations after surgery were no more pain and ease in walking, and able to manage daily life. 3) Depending on the time after surgery, joint pain and walking ability had improved to some extent. The joint range of motion increased, but kneeling remained difficult, and the participants’ mood and exercise capacity were improved. Conclusions: The finding can be as a reference for clinical practitioner to provide preoperative education for total knee arthroplasty patients.
Development and validation of the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ)

Background and study aims: Patient satisfaction is a key indicator of the quality of gastrointestinal (GI) endoscopy. The aim of this study was to develop and validate a specific patient satisfaction questionnaire for patients undergoing GI endoscopy – the Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ). Patients and methods: We developed and validated the GESQ within the context of a national multi-institution nurse endoscopy trial, based in secondary care, in three stages: (1) item generation with a panel of patients and professionals following a detailed literature review to identify the most relevant items from existing scales; (2) development and piloting of a draft questionnaire on a sample of patients referred for GI endoscopy; and (3) testing of the questionnaire within a large multicenter pragmatic randomized trial. We undertook psychometric analysis of the questionnaire to identify the underlying dimensions and assessed the questionnaire for reliability and validity. Results: The final version of the GESQ contains 21 items. Principal components analysis revealed four subscales with high internal consistency: skills and hospital (seven items; Cronbach’s alpha 0.83), pain and discomfort during and after endoscopy (four items; Cronbach’s alpha 0.84), information before endoscopy (five items; Cronbach’s alpha 0.80), and information after endoscopy (five items; Cronbach’s alpha 0.76). Conclusions: The four identified subscales are clinically relevant and correspond to domains of patient satisfaction identified in previous studies. Our development and validation of the GESQ confirmed that it is a valid, reliable, interpretable, and acceptable tool to measure satisfaction in patients who have undergone a GI endoscopy.
Poor Prognosis Significance of Pretreatment Thrombocytosis in Patients with Colorectal Cancer: a Meta-Analysis.

BACKGROUND Recently, several studies have reported that elevated platelet counts may be associated with the poor prognosis of colorectal cancer. However, conclusions remain controversial. This meta-analysis was therefore designed to analyze and evaluate the prognostic role of preoperative or pretreatment thrombocytosis in patients with colorectal cancer. MATERIALS AND METHODS We searched PubMed, EMBASE, the Cochrane Library and Web of Science to March 29th, 2015. The citation lists of included studies were also hand-searched to identify further relevant trials. To investigate the association between thrombocytosis and prognosis of colorectal cancer, the 1-year, 3-year and 5-year survival of each studies were obtained. The odds ratio (OR) with its 95% confidence interval (CI) was used to evaluate the relation of overall survival (OS) between thrombocytosis and normal platelet counts (PLT). Likewise, disease free survival (DFS) was obtained and evaluated. The analysis was performed and assessed using Review Manager 5.2. RESULTS A total of 14 studies (N=5,566 participants, 11 including 4,468 for OS, 6 including 1,533 for DFS) were included in this meta-analysis, of which seven (N=3810) defined thrombocytosis as a platelet count ≥ 400? 109L, and 375 (9.8%) patients exhibited pretreatment thrombocytosis. Thrombocytosis have a close relationship with the poor OS of colorectal cancer compared with normal PLT, with the pooled ORs of 1-year, 3-year and 5-year survival being 0.41 [95% CI 0.34-0.51; P<0.001], 0.28 [95% CI 0.21-0.38; P<0.001] and 0.26 [95% CI 0.20-0.34; P<0.001], respectively. For DFS, the same results were showed as the pooled ORs of 1-year, 3-year and 5-year survival respectively being 0.34 [95% CI 0.24-0.50; P<0.001], 0.31 [95% CI 0.23-0.43; P<0.001] and 0.25 [95% CI 0.18-0.34; P<0.001]. CONCLUSIONS This meta-analysis indicated that thrombocytosis may predict poor prognosis for patients with colorectal cancer, and platelet counts may be a cost-effective and noninvasive marker.