Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of KDT501 on Metabolic Parameters in Insulin-Resistant Prediabetic Humans

Context: KDT501 is an isohumulone drug that has demonstrated beneficial effects on metabolic parameters in mice. Objective: This study was intended to examine potential improvements in metabolism in humans. Design and Setting: Changes in carbohydrate and lipid metabolism, along with inflammatory markers, were evaluated in prediabetic humans in a clinical research center. Participants: Nine obese patients participated. All had prediabetes or normal glucose tolerance plus three features of metabolic syndrome. Intervention: All participants were treated with escalating doses of KDT501 to a maximum dose of 1000 mg every 12 hours for a total of 28 days. Outcome Measures: Changes in carbohydrate metabolism were measured with oral glucose tolerance, homeostatic model of insulin resistance, and euglycemic clamp; changes in plasma lipids and response to a lipid tolerance test; and changes in plasma inflammatory markers. Results: The drug was well tolerated. After KDT501 treatment, plasma triglycerides were reduced at 4 hours during a lipid tolerance test. Furthermore, plasma adiponectin and high-molecular-weight adiponectin increased significantly, and plasma tumor necrosis factor-α decreased significantly. There were no significant changes in oral glucose tolerance test results or insulin sensitivity measures. Conclusions: Despite the small sample size and the short duration of therapy, KDT501 administration reduced measures of systemic inflammation and improved postmeal plasma triglyceride levels, which may be beneficial in participants with insulin resistance or metabolic syndrome.
Dose–response study of recombinant human soluble thrombomodulin (ART‐123) in the prevention of venous thromboembolism after total hip replacement

Summary. Background: Recombinant human soluble thrombomodulin (ART‐123) is composed of the active, extracellular, domain of thrombomodulin. ART‐123 binds to thrombin and this complex converts protein C into the natural anticoagulant activated protein C. This study was performed to identify an effective and safe dose of ART‐123 for prevention of venous thromboembolism after elective, unilateral total hip replacement. Methods and results: An open‐label, sequential, dose‐ranging study was performed in which 312 patients received either 0.3 mg kg−1 or 0.45 mg kg−1 of ART‐123, subcutaneously, 2–4 h after surgery (day 1). Those who received 0.3 mg kg−1 were given a second dose of 0.3 mg kg−1 on day 6, and the first 29 of these patients also used intermittent pneumatic compression devices. Those who received 0.45 mg kg−1 were not given a second dose. Primary efficacy outcome was all deep vein thrombosis on mandatory bilateral venography performed on day 9 ± 2 and symptomatic venous thromboembolism up to day 11. Primary safety outcome was major bleeding up to day 11. Among patients who did not use intermittent pneumatic compression, venous thromboembolism occurred in 3.4% of 116 evaluable patients in the 0.3 mg kg−1 group and 0.9% of 111 patients in the 0.45 mg kg−1 group. Major bleeding occurred in 1.4% of 139 patients in the 0.3 mg kg−1 group and 6.3% of 144 patients in the 0.45 mg kg−1 group. Conclusion: ART‐123 is a highly effective antithrombotic agent that should be directly compared with current methods of prophylaxis in patients who have major orthopedic surgery.
Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study).

BACKGROUND Although quantification of the impact of treatment on survival remains the cornerstone of clinical research, the assessment of a broader range of disease outcomes is growing increasingly important. This manuscript provides an overview of the considerations made regarding quantification of a range of clinical and economic outcomes in the EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study) study, a 6200-patient, randomized, controlled trial of aldosterone blockade in patients with heart failure as a complication of acute myocardial infarction. METHODS AND RESULTS Relevant clinical outcomes include disease progression (mortality, hospitalization), health status (symptoms, functioning, and quality of life), and costs. The primary hypothesis for the quality of life component of EPHESUS is that eplerenone will improve health status as defined by the Kansas City Cardiomyopathy Questionnaire summary score. In addition to the Kansas City Cardiomyopathy Questionnaire, the Short Form-12, the EuroQOL, the Medical Outcomes Study-Depression Scale and an Anxiety measure will be collected throughout the trial. Health care resource utilization including hospitalizations, emergency room visits, outpatient procedures and tests, and medications will also be collected. Analyses will estimate and describe the effect of aldosterone blockade on costs over time. If both the clinical effect and costs are greater for patients receiving aldosterone blockade, then eplerenone's cost-effectiveness will be estimated. CONCLUSION The EPHESUS trial has been designed to quantify a wide range of clinical outcomes. This broad range of data will allow a comprehensive assessment of the potential benefits of aldosterone blockade on patient health status and costs.
Voices From the Trenches

Experienced HIV prevention group facilitators have a unique perspective on sexual risk reduction interventions; however, their views are rarely reported in the research literature. To address this gap, the authors solicited input from four men and four women who served as facilitators in a randomized controlled trial of HIV risk reduction interventions. During focus groups or individual interviews, these facilitators commented on issues related to facilitation training and supervision, key facilitator characteristics, and challenges associated with intervention delivery. Facilitators reported that they valued training that was specific to the HIV context, the opportunity to observe workshops and to facilitate a mock workshop before facilitating themselves, and ongoing peer supervision. They recognized several important facilitator characteristics, including being open and nonjudgmental, being flexible, and being culturally competent. Finally, facilitators mentioned that facilitating workshops was made more difficult by the many psychosocial problems many low-income participants experienced, and that facilitating workshops with men was more difficult than with women. Observations such as these, provided by experienced facilitators, can help to improve intervention training and delivery, and may increase the likelihood that interventions will be adopted in community settings.
Error resilient watermarking for MPEG video streams

Due to lack of quality of service guarantees over the Internet, many of the video packets may be lost during the transmission. In case of the watermarked streaming video, packet lost could affect the retrieval of the embedded watermark at the client side. In this paper, we introduce a modified version of the spread spectrum watermarking technique that demonstrates a better performance against video packet loss. The watermarking algorithm and some experimental results will be presented.
The Genesis of Entrepreneurship

The study of entrepreneurship is still in its infancy. Kuhn (1962) points out that fields of knowledge evolve through paradigm competition and the search for better answers to new sets of inquiries, in which the maturing field of entrepreneurship, too, should be engaged. Barriers to evolutionary advances in entrepreneurship include the field's uneven development, its lack of consistency of terminology or method, and its relative isolation from developments in key informing fields. To avoid fragmentation and to enhance the opportunity for the systematic development of the entrepreneurship paradigm, an exploration of its parameters is proposed. Considered are three concepts central to entrepreneurship but heretofore unexamined in an integrated fashion by entrepreneurship researchers. The intent is to explicate their separate and joint conceptual relationships to and means by which they inform or add to the field. A rudimentary process model addressing the factions of change, innovation, and creativity in association with the entrepreneurial event is presented as a fundamental basis for providing continuity and structural consistency to the evolving field of entrepreneurship. Finally, a call is made for careful definitions and explorations of differentiated (but oft-equated) central entrepreneurial terms, processes, and perspectives.
Metformin Does Not Predict for Prostate Cancer Diagnosis, Grade, or Volume of Disease After Transperineal Template-guided Mapping Biopsy

Objectives: Previous studies have evaluated whether metformin is associated with prostate cancer incidence and outcomes with conflicting conclusions. In this study, we evaluate the incidence of prostate cancer in diabetic patients treated with and without metformin compared with nondiabetic patients. Materials and Methods: One thousand thirty-four patients underwent transperineal template-guided mapping biopsy secondary to either an elevated prostate-specific antigen (PSA) or a prior biopsy finding of atypical small acinar proliferation/prostatic intraepithelial neoplasia. The cohort included 881 nondiabetic men, 65 diabetic men treated with metformin, and 88 diabetic men not receiving metformin. In metformin-treated patients, the median duration of usage was 6.0 years. Differences in prostate cancer diagnosis, histologic grade, and tumor volume were compared across the 3 cohorts. Results: There was no statistically significant differences discerned between the 3 cohorts in patient age, prebiopsy PSA, prostate volume, PSA density, PSA doubling time, PSA velocity, or the total number of prior transrectal ultrasound biopsy sessions. Five hundred eighty-four patients were diagnosed with prostate cancer. There was no difference in prostate cancer diagnosis (P=0.153), Gleason score (P=0.960), the number of positive biopsy cores (P=0.764), or risk group stratification (P=0.877) between the 3 cohorts. In multivariate analysis, only older age predicted for prostate cancer diagnosis. In terms of Gleason score ≥7, patient age, PSA velocity, and body mass index predicted for more aggressive histology. Neither diabetes, metformin use or duration was of statistical consequence. Conclusion: Metformin did not impact incidence of prostate cancer diagnosis, Gleason score distribution, or volume of disease.
Evaluation of antiulcerogenic activity of aqueous extract of Brassica oleracea var. capitata (cabbage) on Wistar rat gastric ulceration.

CONTEXT The cabbage (Brassica oleraceae var. capitata) is an herbaceous and leafy plant which belongs to the Brassicaceae family, native to coastal southern and Western Europe. Used in cooking for its nutritional value also has known anti-inflammatory activity. OBJECTIVE We studied the antiulcerogenic activity of aqueous extract of Brassica oleracea var. capitata (AEB) in order to validate ethnobotanical claims regarding the plant use in the gastric disorders. METHOD Acute gastric ulcers were induced in rats by the oral administration of acetylsalicylic acid. The gastroprotective potential of the AEB (0.250, 0.500 and 1.000 mg.kg-1/body weight) was compared with omeprazole (20 mg.kg-1/body weight). RESULTS The stomach analysis indicated that treatment with AEB inhibited the gastric damage. The gastroprotective activity as evidenced by its significant inhibition in the formation of ulcers induced by chemical agent with a maximum of 99.44% curation (250 mg.kg-1 body weight) in acetylsalicylic acid-induced ulcers. CONCLUSIONS The AEB demonstrated good antiulcerogenic activities which justify the inclusion of this plant in the management of gastric disorders. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.
High Incidence of Respiratory Infections in ‘Nil by Mouth’ Tube-Fed Acute Ischemic Stroke Patients

Background: Respiratory infections are common in acute stroke. Previous studies have found dysphagia is associated with respiratory infections. Of interest is whether patients who are ‘Nil by Mouth’ (NBM) and tube fed have higher risk of developing infections due to aspiration of bacteria-laden saliva or refluxed material than stroke patients who are fed orally. Methods: Prospective cohort of 330 ischemic stroke survivors were followed for 30 days and infections recorded. Results: 115 infections were treated with antibiotics; these included 51 respiratory infections. Incidence of infection in NBM tube-fed stroke patients (n = 74) was 69%, with 30 respiratory infections occurring in 74 patients who received enteral feeding after stroke. Logistic regression analysis showed tube feeding during admission was a significant risk for respiratory infection. We also saw a significant time-to-event effect with 73% (22/30) respiratory infections in tube-fed survivors diagnosed on days 2–4 after stroke, and 76% (39/51) of infections in all tube-fed survivors occurring by day 7 after stroke. Relevance to a theory of critical period of susceptibility to infection in acute stroke is discussed. Conclusions: NBM tube-fed survivors were unlikely to have aspirated anything other than saliva/secretions or reflux, yet experienced significantly higher rates of respiratory infections than survivors fed orally. Stringent oral care and measures to prevent reflux are potentially modifiable aspects of stroke management.
Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins

Plasma protein binding (PPB) influences the free fraction of drug available to bind to its target and is therefore an important consideration in drug discovery. While traditional methods for assessing PPB (e.g. rapid equilibrium dialysis) are suitable for comparing compounds with relatively weak PPB, they are not able to accurately discriminate between highly bound compounds (typically >99.5%). The aim of the present work was to use mathematical modelling to explore the potential utility of receptor binding and cellular functional assays to estimate the affinity of compounds for plasma proteins. Plasma proteins are routinely added to in vitro assays, so a secondary goal was to investigate the effect of plasma proteins on observed ligand–receptor interactions.
Insomnia and global sleep dissatisfaction in Finland

The purpose of this study is to assess the prevalence of insomnia symptoms and diagnoses in the general population of Finland. A total of 982 participants, aged 18 years or older and representative of the general population of Finland, were interviewed by telephone using the Sleep‐EVAL system. The participation rate was 78%. The questionnaire included the assessment of sleep habits, insomnia symptomatology according to Diagnostic and Statistical Manual of Mental Disorders‐IV (DSM‐IV) and International Classification of Sleep Disorders (ICSD), associated and sleep/mental disorders and daytime consequences. The overall prevalence of insomnia symptoms occurring at least three nights per week was 37.6%. Difficulty initiating sleep were mentioned by 11.9% of the sample, difficulty maintaining sleep by 31.6%, early morning awakenings by 11.0% and non‐restorative sleep by 7.9% of the sample. Global dissatisfaction with sleep was found in 11.9% of the sample. Daytime consequences (fatigue, mood changes, cognitive difficulties or daytime sleepiness) were reported by 39.9% of participants with insomnia symptoms and 87.6% of those with sleep dissatisfaction. A deterioration of sleep in summer or winter was associated with more complaints of sleep dissatisfaction. Prevalence of any DSM‐IV insomnia diagnosis was 11.7%. More specifically, DSM‐IV diagnosis of primary insomnia had a prevalence of 1.6% and DSM‐IV diagnosis of insomnia related to another mental disorder was at 2.1%. Insomnia was a symptom of another sleep disorder in about 16% of cases and of a mental disorder in about 17% of cases. As reported in other Nordic studies, sleep quality was worse in summer. Insomnia symptomatology was common and was reported by more than a third of Finnish participants. Compared with other European countries studied with the same methodology (France, the UK, Germany, and Italy), the prevalence of DSM‐IV insomnia diagnosis was 1.5 to two times higher in Finland.
Circulating oncoproteins HER2/neu, EGFR and CAIX (MN) as novel cancer biomarkers

Pharmaceutical companies have developed targeted therapies such as trastuzumab and lapatinib for human epidermal growth factor receptor (HER)2/neu-positive tumors, while others have developed antiepidermal growth factor receptor (EGFR) therapies, such as tarceva and erbitux for EGFR-positive tumors. A drug called rencarex is targeted to an oncoprotein designated carbonic anhydrase IX (CAIX), which is being evaluated in renal cell carcinoma patients. Based on these targeted therapeutic approaches, this review describes clinical research studies performed with enzyme-linked immunosorbent assays specific for the circulating oncoproteins, HER2/neu, EGFR and CAIX. These circulating biomarkers have the potential to be used in conjunction with the specific targeted therapies for patient selection, monitoring and management. With the variety of new therapeutic options, the major challenge ahead will be to select the appropriate therapy or combinations of therapies for each patient. Specific biomarker tests, either alone or in panels, will be needed at the appropriate time in the course of disease to ensure that patients receive the right drug at the right time. These tests will also be valuable in monitoring the efficacy of the targeted therapies. A circulating biomarker such as serum HER2/neu may be able to specifically identify patients with progressing HER2/neu-positive disease and provide the information needed by physicians to choose from the variety of HER2/neu-targeted therapies that will soon be available to cancer patients.
Experiences of responsibility and professionalism in an educational accountability context

ii Preface . iv Table of Contents . v List of Tables . vii List of Figures . viii Acknowledgements . ix Chapter One -­ Introduction . 1 Background . 1 Statement of the Problem and Purpose of the Study . 1 Forms of Accountability . 2 Structures that Support Teachers’ Engagement in Educational Change . 5 The Present Study . 7 Chapter Two -­ Literature Review . 9 Exploring Accountability . 9 Managerial Accountability . 10 Professional Accountability/Responsibility . 21 Blending Accountabilities . 33 Summary and Research Directions . 38 Chapter Three -­ Methodology . 40 Context . 41 Research Design . 46 Participants . 47
Cytokines and immunodeficiency diseases: critical roles of the γc‐dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways

Summary: In this review, we discuss the role of cytokines and their signaling pathways in immunodeficiency. We focus primarily on severe combined immunodeficiency (SCID) diseases as the most severe forms of primary immunodeficiencies, reviewing the different genetic causes of these diseases. We focus in particular on the range of forms of SCID that result from defects in cytokine‐signaling pathways. The most common form of SCID, X‐linked SCID, results from mutations in the common cytokine receptor γ‐chain, which is shared by the receptors for interleukin (IL)‐2, IL‐4, IL‐7, IL‐9, IL‐15, and IL‐21, underscoring that X‐linked SCID is indeed a disease of defective cytokine signaling. We also review the signaling pathways used by these cytokines and the phenotypes in humans and mice with defects in the cytokines or signaling pathways. We also briefly discuss other cytokines, such as interferon‐γ and IL‐12, where mutations in the ligand or receptor or signaling components also cause clinical disease in humans.
Fluctuating Foville's syndrome caused by a pontine angioma in a patient with a polycystic kidney.

Vascular events are sometimes observed in patients undergoing hemodialysis due to chronic renal failure. If a patient complains of repeated disturbances of eye movement with fluctuation before and after hemodialysis, it suggests the presence of an ischemic stroke due to dehydration. Otherwise it is likely a myasthenic syndrome such as myasthenia gravis. Although intracranial hemorrhage seldom causes a repeated disturbance with fluctuation, an atypical pathogenesis, including angioma-related hemorrhage, sometimes induces a fluctuating disturbance of eye movement. A 61-year-old man with a fluctuating disturbance in his eye movements came to our hospital. He had been diag-
Analyzing string format-based classifiers for botnet detection: GP and SVM

The domain name system (DNS) is an essential component of Internet. As it is expected to be used by all legitimate users and applications, generally there are less inspections, restrictions and filters on it. Botnets rely on this open component to accomplish their malicious operation. Therefore, to defeat the single point of failure and evade static blacklists and firewalls, they employ DNS-based methods to frequently generate new automatic domain names. Stateful-SBB, which is a form of genetic programming (GP), was previously designed and developed by the authors to detect these automatically generated domain names based on minimum a priori information which was shown efficient. In this paper, we compare Stateful-SBB against the String Subsequence Kernel (SSK) and SSK with Lambda Pruning (SSK-LP), which are based on support vector machines (SVM) and also use string format inputs. Analyzing the domain names that each of the classifiers chooses as a part of their solutions in the classification process, we notice that 50% to 63% of the Stateful-SBBs' frequently selected points on the Pareto-front are also used by SSK and SSK-LP, respectively. By analyzing these common domain names, we identify some of the characteristics of the botnet domain names. Moreover, we introduce a pruned version of the Stateful-SBB that resulted in reducing the solution complexity by 83% with the same high accuracy.
Two Transcription Factors Are Negative Regulators of Gibberellin Response in the HvSPY-Signaling Pathway in Barley Aleurone[w]

SPINDLY (SPY) protein from barley (Hordeum vulgare L. cv Himalaya; HvSPY) negatively regulated GA responses in aleurone, and genetic analyses of Arabidopsis thaliana predict that SPY functions in a derepressible GA-signaling pathway. Many, if not all, GA-dependent responses require SPY protein, and to improve our understanding of how the SPY signaling pathway operates, a yeast two-hybrid screen was used to identify both upstream and downstream components that might regulate the activity of the HvSPY protein. A number of proteins from diverse classes were identified using HvSPY as bait and barley cDNA libraries as prey. Two of the HvSPY-interacting (HSI) proteins were transcription factors belonging to the myb and NAC gene families, HSImyb and HSINAC. Interaction occurred via the tetratricopeptide repeat domain of HvSPY and specificity was shown both in vivo and in vitro. Messenger RNAs for these proteins were expressed differentially in many parts of the barley plant but at very low levels. Both HSImyb and HSINAC inhibited the GA3 up-regulation of α-amylase expression in aleurone, both were activators of transcription in yeast, and the green fluorescent protein-HSI fusion proteins were localized in the nucleus. These results are consistent with the model that HSI transcription factors act downstream of HvSPY as negative regulators and that they in turn could activate other negative regulators, forming the HvSPY negative regulator-signaling pathway for GA response.