Miracle-dz/UniFAR-FTUs huggingface dataset:
Nephrotoxicity of Cephalosporin-Gentamicin Combinations in Rats

To study the possibility that cephalosporins augment the nephrotoxicity of gentamicin, groups of rats were given four hourly subcutaneous doses of: gentamicin (5 mg/kg), gentamicin plus cephalothin (100 mg/kg), gentamicin plus cefazolin (20 mg/kg), gentamicin plus cefazolin (50 mg/kg), gentamicin plus cephaloridine (50 mg/kg), or saline diluent for 15 days. Periodic measurements were made of urine volume, urine osmolality, urine protein excretion and lysosomal enzymuria, as well as blood urea nitrogen, creatinine clearance, and drug concentrations in renal cortex and medulla. Tissue was examined by light and electron microscopy. Enzymuria and proteinuria increased early in the course of all treatment groups, whereas urine osmolality declined. No distinct patterns of these variables were discernable among the groups. Gentamicin alone, gentamicin plus cephalothin, and gentamicin plus cefazolin (20 mg/kg) caused the same significant fall in glomerular filtrate rate from control values by day 15 (P < 0.05). Gentamicin plus cefazolin (50 mg/kg) and gentamicin plus cephaloridine failed to cause a decline in glomerular filtration rate compared with controls (P > 0.05). Gentamicin concentrations in renal cortex were 5 to 10 times higher than those in medulla in all groups. Cephaloridine and cefazolin (50 mg/kg) also displayed a gradient pattern in renal cortex, whereas cephalothin and cefazolin (20 mg/kg) did not. Cytosegrosomes with myeloid figures were characteristic ultra-structural changes seen in all groups; however, they tended to be smaller with less numerous myeloid bodies in the groups receiving gentamicin plus cephalothin, cefazolin (50 mg/kg), or cephaloridine. Cephalosporins did not augment gentamicin toxicity. High doses of cefazolin and cephaloridine protected kidneys from gentamicin nephrotoxicity. The protection may involve intracellular drug interaction within the renal cortex.
Re-evaluation of 400 Crimean-Congo hemorrhagic fever cases in an endemic area: is ribavirin treatment suitable?

BACKGROUND Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease, seen in various regions around the world, leading to death following a clinical syndrome of hemorrhagic fever. METHODS This trial was conducted in Tokat State Hospital that is located in an endemic area. Four hundred patients referring to hospital between 2007 and 2009 and diagnosed as having CCHF with RT-PCR were enrolled in this trial. Ribavirin was not administered to any patient. Epidemiological, clinical, and laboratory findings of CCHF and factors affecting mortality were evaluated. RESULTS Twenty patients (5%) died and 380 patients recovered (95%). It was found that mean age, white blood cells (WBC), active tromboplastine time (aPTT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values were significantly higher in patients who died, as compared with recovered cases and the difference was significant. Platelet values were significantly lower in patients who died, as compared with recovered cases. CONCLUSIONS Age, male gender, high levels of ALT, AST, WBC aPTT values, platelet levels, and decrease in these values during follow-up are indicative of a poor prognosis. Use of ribavirin is not required in treatment of CCHF.
Chimeric proteins composed of Jun and CREB define domains required for interaction with the human T-cell leukemia virus type 1 Tax protein

The regulation of human T-cell leukemia virus type 1 (HTLV-1) long terminal repeat gene expression is dependent on three cis-acting elements known as 21-bp repeats and the transactivator protein Tax. Mutagenesis has demonstrated that sequences in each of the 21-bp repeats can be divided into three domains designated A, B, and C. Tax stimulates the binding of CREB to the B domain, which is essential for Tax activation of HTLV-1 gene expression. In this study, we demonstrate that Tax will stimulate the binding of CREB to the HTLV-1 21-bp repeats but does not stimulate CREB binding to the consensus cyclic AMP response element (CRE) element found in the somatostatin promoter. However, Tax stimulates CREB binding to a consensus CRE in the context of the 21-bp repeats, indicating the importance of these sequences in stimulating CREB binding. To determine the mechanism by which Tax stimulates CREB binding and determine potential interactions between Tax and CREB, we used the mammalian two-hybrid system in conjunction with in vitro binding and gel retardation assays. Two-hybrid analysis indicated that mutations in either the basic or leucine zipper region of CREB prevented interactions with Tax. Since several studies have demonstrated that Tax will also stimulate the binding of a variety of different basic region-leucine zipper proteins to their cognate binding sites, we assayed whether chimeric proteins composed of portions of CREB and another basic region-leucine zipper protein, Jun, could be used to map domains required for interactions with Tax. These studies were possible because we did not detect in vivo or in vitro interactions between Tax and Jun. The amino acid sequence of the CREB basic region and a portion of its leucine zipper were required for both in vivo and in vitro interactions with Tax and increased binding of CREB to the 21-bp repeats in response to Tax. These studies define the domains in CREB required for both in vivo and in vitro interactions by the HTLV-1 Tax protein.
Superscalar microprocessor design

1. Beyond Pipelining, CISC, and RISC. 2. An Introduction to Superscalar Concepts. 3. Developing an Execution Model. 4. Instruction Fetching and Decoding. 5. The Role of Exception Recovery. 6. Register Dataflow. 7. Out-of-Order Instruction Execution. 8. Memory Dataflow. 9. Complexity and Controversy. 10. Basic Software Scheduling. 11. Software Scheduling Across Branches. 12. Evaluating Alternatives: A Perspective on Superscalar Microprocessors. References.
Cost Reduction, Informational Efficiency, and Prices of Options

This paper documents four findings in the option market based on two stages of decimalization where switching control and treatment stocks is possible. First, uninformed traders are more cost sensitive than informed traders. Second, the paper proves and verifies that when uninformed traders are more cost sensitive, trading cost reduction causes slower response of price to information. Those findings are contrary to the evidences in the stock market. Third, decimalization narrows bid ask spread, increases volume, and deepens depth, especially for options requiring frequent hedging re-balancing in the stock market. Finally, option prices become more expensive after decimalization.
Building Theory from Case Study Research

This chapter describes core criticisms made by case study researchers of large sample surveys. A need exists for a paradigm shift in research on organizational behavior (including modeling the history of new product performance). The chapter outlines the significant weaknesses of CSR as seen by other researchers. The chapter examines Senge's (1990) core propositions related to the “mental models” of decision participants. Details illustrate the use of specific research methods for case studies to achieve different research objectives and the combination of objectives. Finally, the chapter illustrates basic concept variables in case studies and briefly reviews twelve propositions relevant in many case research studies. This chapter reviews classic and recent contributions to the literature of CSR.
Communicating CSR practices – Role of internationalization of emerging market firms

Abstract Emerging markets suffer from institutional voids, and in such resource deficient economies, corporate social responsibility is given scant attention. However, when firms from emerging markets globalize, international stakeholders become suspicious about firms’ products, services, and business practices. Grounded in the liability of emergingness and legitimacy theory and using a sample of 134 manufacturing firms from one emerging market, India, this study explores how firms’ international diversification intent and market-seeking motives influence emerging markets’ firms communication of socially responsible activities as an attempt to eliminate illegitimacy. Furthermore, the study reveals that business group affiliation enhances the influence of internationalization on firms’ communication of socially responsible activities.
Disruption of mannose activation in Leishmania mexicana: GDP‐mannose pyrophosphorylase is required for virulence, but not for viability

In eukaryotes, the enzyme GDP‐mannose pyrophosphorylase (GDPMP) is essential for the formation of GDP‐mannose, the central activated mannose donor in glycosylation reactions. Deletion of its gene is lethal in fungi, most likely as a consequence of disrupted glycoconjugate biosynthesis. Furthermore, absence of GDPMP enzyme activity and the expected loss of all mannose‐containing glycoconjugates have so far not been observed in any eukaryotic organism. In this study we have cloned and characterized the gene encoding GDPMP from the eukaryotic protozoan parasite Leishmania mexicana. We report the generation of GDPMP gene deletion mutants of this human pathogen that are devoid of detectable GDPMP activity and completely lack mannose‐containing glycoproteins and glycolipids, such as lipophosphoglycan, proteophosphoglycans, glycosylphosphatidylinositol protein membrane anchors, glycoinositolphos pholipids and N‐glycans. The loss of GDPMP renders the parasites unable to infect macrophages or mice, while gene addback restores virulence. Our study demonstrates that GDP‐mannose biosynthesis is not essential for Leishmania viability in culture, but constitutes a virulence pathway in these human pathogens.
Consensus Drug Resistance Mutations for Epidemiological Surveillance: Basic Principles and Potential Controversies

Programmes that monitor local, national and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programmes. The World Health Organization (WHO) has established a global programme for genotypic surveillance of HIV-1 drug resistance and has recommended the adoption of a consensus definition of genotypic drug resistance. Such a definition is necessary to accurately compare transmitted drug resistance rates across geographical regions and time periods. HIV-1 diversity and the large number of mutations associated with antiretroviral drug resistance complicate the development of a consensus definition for genotypic drug resistance. This paper reviews the data that must be considered to determine which of the many HIV-1 drug resistance mutations are likely to be both sensitive and specific indicators of transmitted drug resistance. The process used to create a previously published list of drug resistance mutations for HIV-1 surveillance is reviewed and alternative approaches to this process are discussed.
Immunopathogenetic and therapeutic aspects of autoimmune hepatitis

Autoimmune hepatitis is a chronic, progressive liver disease that responds well to immunosuppressive therapy, but has a poor prognosis if untreated. Possible triggering factors include viruses, other autoimmune disorders and drugs. The molecular mechanisms contributing to the pathogenesis include: reactions of autoantibodies against their corresponding autoantigens; aberrant expression of histocompatibility antigen class I and II molecules, cell adhesion molecules and cytokines; increased oxidative stress; and the occurrence of angiogenesis. The prevalence of the disease is highest in Caucasians, Europeans and women. The natural history of autoimmune hepatitis shows a poor prognosis, with frequent progression to cirrhosis and hepatic insufficiency in untreated patients. The occurrence of hepatocellular carcinoma is rare and is found only in long‐standing cirrhosis. Corticosteroids as monotherapy or in combination with azathioprine are the treatments of choice; different therapeutic schedules and particularities of treatment for pregnant women and children have been established. To avoid treatment‐associated adverse effects, alternative therapies have been proposed, including ciclosporin, budesonide, tacrolimus, mycophenolate mofetil, ursodeoxycholic acid, methotrexate, cyclophosphamide, mercaptopurine and free radical scavengers. Liver transplantation is indicated for patients refractory to or intolerant of immunosuppressive therapy.
Ethnic Inequalities in Education in Kenya

This paper uses Kenya’s survey data to explore ethnic inequalities in education in Kenya. It focuses on some ethnic groups that may have resources and opportunities as a result of their geographical location and ethnic proximity to the ruling elite. The factors examined to explain potential educational inequalities among ethnic groups include the Gross Enrolment Ratios, the number of schools, and the number of qualified teachers. The results suggest a close correspondence of differentials between inequalities in education and ethnic affiliation to the ruling elite. Relatively small, clearly defined ethnic groups have accumulated an advantage over the majority in the national population, in terms of the education infrastructure and resources. Based on these results, this paper argues that ethnicity should be placed at the forefront of analyses of educational development in Kenya, as well as in policy efforts to reduce inequalities in education.
A randomized clinical trial of oral versus intramuscular delivery of steroids in acute exudative pharyngitis.

UNLABELLED Previous study has shown that the use of intramuscular (IM) steroid leads to improved symptoms in patients with group A beta-hemolytic streptococcus (GABHS). OBJECTIVE To compare oral with IM steroids as an adjunct to antibiotic therapy in the treatment of acute exudative pharyngitis. The null hypothesis was that there would be no difference in effectiveness of oral versus IM steroids. METHODS The study was a randomized, double-blind outpatient clinical trial. After consent was obtained, each patient was asked to rate his or her pain on a 10-cm numbered visual analog scale (VAS; 0-10). All of the patients received injectable benzathine penicillin or, if allergic to penicillin, a ten-day course of polyenteric-coated erythromycin. Each patient was randomized to receive either injectable steroid plus oral placebo or injectable placebo plus oral steroid. All medications were given in the emergency department. All patients were contacted by telephone at 24 hours (first follow-up) and 48 hours (second follow-up) by one of the study investigators and asked to rate their pain based on another VAS. If their pain was not resolved by 48 hours, they were called again daily for the third to seventh day after the initial visit. The time to total resolution of the sore throat was documented. The main outcome measures were time to complete relief of pain and VAS scores. Pain medication was not controlled; however, use of pain medications and amounts were recorded. RESULTS A total of 78 patients were initially enrolled in the study. Eight patients were excluded from the statistical analysis because of inability to follow up. A total of 70 were entered, with 35 randomized to IM steroid plus oral placebo and 35 to IM placebo plus oral steroid. There was no difference in pain scores for the oral versus IM group at first follow-up (p = 0.13) and second follow-up (p = 0.82), and in number of hours to relief of pain (p = 0.06). Using repeated-measures analysis of variance, no difference in the effects of the two medications over time was detected (p = 0.83). CONCLUSIONS The results of this clinical trial suggest that oral steroid and IM steroid provide similar levels of pain relief in acute exudative pharyngitis.
Estimation of Initial Dissolution Rate of Drug Substance by Thermal Analysis: Application for Carbamazepine Hydrate

We have proposed a theory indicating the correlation between the dissolution rate and the heat of solution of drug substances. The initial dissolution rates of the drug substances containing amorphous were predicted accurately from their heats of solution. In this report, the possibility for the theory to estimate the dissolution rates of hydrate and polymorphs was examined using thermal analysis. The initial dissolution rates of carbamazepine dihydrate and polymorphs (forms I, II, and III) were measured by the rotating disk method. The heats of solution and the heats of fusion of samples were measured by microcalorimetry and Differential Scanning Calorimetry (DSC), respectively. The logarithm of the initial dissolution rate of the sample was correlated linearly with the heat of fusion as well as the heat of solution. The obtained correlation would be applicable for the quality control of the drug substances that contained hydrate and/or polymorphic forms.
JD induced pluripotent stem cell–derived hepatocytes faithfully recapitulate the pathophysiology of familial hypercholesterolemia

Elevated levels of low‐density lipoprotein cholesterol (LDL‐C) in plasma are a major contributor to cardiovascular disease, which is the leading cause of death worldwide. Genome‐wide association studies (GWAS) have identified 95 loci that associate with control of lipid/cholesterol metabolism. Although GWAS results are highly provocative, direct analyses of the contribution of specific allelic variations in regulating LDL‐C has been challenging due to the difficulty in accessing appropriate cells from affected patients. The primary cell type responsible for controlling cholesterol and lipid flux is the hepatocyte. Recently, we have shown that cells with hepatocyte characteristics can be generated from human induced pluripotent stem cells (iPSCs). This finding raises the possibility of using patient‐specific iPSC‐derived hepatocytes to study the functional contribution of GWAS loci in regulating lipid metabolism. To test the validity of this approach, we produced iPSCs from JD a patient with mutations in the low‐density lipoprotein receptor (LDLR) gene that result in familial hypercholesterolemia (FH). We demonstrate that (1) hepatocytes can be efficiently generated from FH iPSCs; (2) in contrast to control cells, FH iPSC‐derived hepatocytes are deficient in LDL‐C uptake; (3) control but not FH iPSC‐derived hepatocytes increase LDL uptake in response to lovastatin; and (4) FH iPSC‐derived hepatocytes display a marked elevation in secretion of lipidated apolipoprotein B‐100. Conclusion: Cumulatively, these findings demonstrate that FH iPSC‐derived hepatocytes recapitulate the complex pathophysiology of FH in culture. These results also establish that patient‐specific iPSC‐derived hepatocytes could be used to definitively determine the functional contribution of allelic variation in regulating lipid and cholesterol metabolism and could potentially provide a platform for the identification of novel treatments of cardiovascular disease. (HEPATOLOGY 2012)
Predicting Students Performance in Educational Data Mining

Predicting student academic performance has been an important research topic in Educational Data Mining (EDM) which uses machine learning and data mining techniques to explore data from educational settings. However measuring academic performance of students is challenging since students academic performance hinges on diverse factors. The interrelationship between variables and factors for predicting performance participate in complicated nonlinear ways. Traditional data mining and machine learning techniques may not be applied directly to these types of data and problems. In this study we develop a classification model to predict student performance using Deep Learning which automatically learns multiple levels of representation. We pre-train hidden layers of features layerwisely using an unsupervised learning algorithm sparse auto-encoder from unlabeled data, and then use supervised training for fine-tuning the parameters. We train model on a relatively large real world students dataset, and the experimental results show the effectiveness of the proposed method which can be applied into academic pre-warning mechanism.
Follow-up findings for women with human papillomavirus-positive and atypical squamous cells of undetermined significance screening test results in a large women's hospital practice.

CONTEXT Reflex human papillomavirus (HPV) testing has been designated in consensus guidelines as "preferred" for women with atypical squamous cells of undetermined significance (ASC-US) liquid-based cytology (LBC) results, and colposcopy is currently recommended for patients with HPV-positive ASC-US results. Data from large clinical practices using newer screening methods and current cytology terminology are limited. OBJECTIVES We analyzed data from patients with ASC-US LBC and positive HPV test results. We also assessed the impact of the presence or absence of an endocervical cell/ transformation zone sample (EC/TZS) on biopsy diagnoses. DESIGN The information system of a large women's hospital serving an older-than-average population was searched over a 21-month period between July 1, 2005, and March 31, 2007, for HPV-positive cases interpreted as ASC-US (Bethesda System 2001) using computer-imaged LBC. Histologic diagnoses, patient ages, and presence or absence of an EC/TZS were analyzed. The average follow-up period was 7.5 months. RESULTS Among 4273 women with HPV-positive ASC-US results, the cumulative cervical intraepithelial neoplasia 2 or 3 (CIN 2/3) and CIN 1 rates for 2192 women with available biopsies were 5.1% and 43.6%, respectively. Cervical intraepithelial neoplasia 2/3 and CIN 1 rates for women with HPV-positive ASC-US results were not significantly different for women with and without an EC/TZS. CONCLUSIONS The risk of CIN 2/3 in the study population was significantly lower than reported in widely cited trial data. Neither presence nor absence of an EC/TZS, nor the age of the patient, had a statistically significant impact on the likelihood of biopsy diagnoses of CIN 2/3 and CIN 1 for patients with HPV-positive ASC-US test results.
Strategies Technology Development Marketing Leaders Used to Commercialize a New Product Innovation

Strategies Technology Development Marketing Leaders Used to Commercialize a New Product Innovation by Roxie Mooney MS, Palm Beach Atlantic University, 2006 BA, Rollins College, 2013 Doctoral Study Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Business Administration Walden University July 2016