Depth and breadth of knowledge and the governance of technology alliances.

This paper focuses on technology alliances between R&D intensive biotechnology firms and larger pharmaceutical companies. It aims to investigate whether the biotech partners can leverage the depth and the breadth of their knowledge resources to retain their equity ownership when forming an alliance, and whether prior alliance experience adds to their overall leverage. Using a sample of 390 alliances formed between US biotechnology and pharmaceutical companies, we find that biotech firms with deeper technological resources are more likely to retain their equity ownership, and that this relationship is stronger when the biotech firm has more alliance experience

Validity of serum Adenosine deaminase in diagnosis of tuberculosis

Introduction: Tuberculosis is one of the most important infectious causes of death worldwide. Ziehl-Neelsen staining of sputum has high specificity in tuberculosis endemic countries, but modest sensitivity which varies among laboratories. This study was set up to investigate the diagnostic value of serum Adenosine deaminase in diagnosis of tuberculosis. Methods: In a cross sectional and prospective study Serums of 200 patients of positive sputum smear, negative sputum smear, extra-pulmonary tuberculosis and bacterial community acquired pneumonia collected from March 2011 to May 2012 were evaluated. The data were analyzed using SPSS software and P-value of <0.05 was considered significant. Results: A total of 200 subjects were included in the study designed in four groups. In cut-off value of ≥24 U/l for ADA in smear positive patients defined the sensitivity, specificity and positive predictive value 12%, 98% and 86% respectively. In smear negative patients defined the 6%, 98% and 75%, and in extra-pulmonary tuberculosis patients defined the sensitivity 14%, 98% and 88% respectively. Conclusion: This study indicated that measurement of serum ADA level do not have enough sensitivity to assist in the diagnoses of tuberculosis patients from other respiratory diseases and not evaluated perform well enough to replace sputum smear microscopy. Thus, this tests have little role in the diagnosis of pulmonary tuberculosis.Key words: Adenosine deaminase, sensitivity, specificity, Tuberculosi

Differential Methylation Patterns in Lean and Obese Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma

BACKGROUND: Nonalcoholic fatty liver disease affects about 24% of the world\u27s population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. METHODS: In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice. Differentially methylated regions were determined using reduced representation bisulfite sequencing. RESULTS: A larger number of differentially methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice compared to the non-obese mice. No overlap existed in the DMRs with the largest methylation differences between the two models. In lean NASH-HCC, methylation differences were seen in genes involved with cancer progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in hypomethylated DMRs in the obese NASH-HCC. CONCLUSIONS: These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism

Cancer Trends and Risk Factors in Cyprus

Cyprus, a European Union member state, is a small island in the Mediterranean with a population approaching 900,000 people. Cancer is the second leading cause of death; more therapeutic options for any patient with the disease are available in a central oncology centre in the capital of the island (Nicosia) and fewer therapeutic options (e.g. chemotherapy and hormone therapy only) in a few other public hospitals. Palliative care is offered in several hospices and hospitals, although the field needs improvement. With regards to screening, a national breast cancer screening programme has been in place countrywide since 2007 and is offered free of charge to women between the ages of 50 and 69 years, while colorectal and prostate cancer screening is performed on an individual basis (a pilot programme for colorectal cancer screening was recently initiated). Genetic testing is available for breast and colon cancer. To improve understanding of the causes of cancer in the country, a cancer research centre was established in 2010 (Mediterranean Centre for Cancer Research). Recent epidemiologic work has revealed increasing cancer trends in Cyprus; prostate cancer is the most common in men and breast cancer is the most common in women. Interestingly, thyroid cancer incidence in women has been rising from 1998 to 2008. Cancer of the colon and rectum is also on the rise affecting both sexes. Overall, cancer incidence in Cyprus is lower than other EuroMed countries with similar lifestyle and geography

Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. While obesity and diabetes are the hallmarks of NAFLD, it also develops in lean individuals in the absence of metabolic syndrome, with a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD represents the spectrum of liver disease, starting with excess liver fat accumulation (NAFL) that can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). To date, the pathogenesis of lean NASH-HCC is poorly understood and a mouse model is lacking. We aimed to develop a mouse model of lean NASH-HCC using a choline deficient and high trans-fat/sucrose/cholesterol diet to enable better understanding of its molecular pathogenesis. Methods: C57BL/6N mice were fed this diet starting at 4 weeks of age for 52 weeks and were compared to mice fed an isocaloric low fat control diet for the same duration. C57BL/6N mice were chosen instead of the C57BL/6J mice due to the high susceptibility of C57BL/6J mice to diet-induced obesity. The plasma and tumor fatty acid profile of these mice was also investigated. Results: Nearly 61% of the mice developed lean NASH-HCC. These mice showed reduction of plasma polyunsaturated fatty acids (PUFAs) (linolenic acids (α and γ, ω-3 and ω-6, respectively), eicosapentanoic acid (ω-3), docosahexanoic acid (ω-3), and linoleic acid (ω-6)) and increasing levels over time in mice with pre-malignant lesions. Conclusions: We developed a novel high penetrance diet-induced lean NASH-HCC mouse model. Plasma PUFA levels were reduced with tumor progression in parallel with reduced expression of genes controlling desaturase expression suggesting their potential use as biomarkers for lean NASH-HCC progression as well as chemopreventive molecules

Differential progression of unhealthy dietinduced hepatocellular carcinoma in obese and non-obese mice

Background Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25–30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood. Methods In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/ fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice. Results Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice. Conclusions Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis

Differential Progression of Unhealthy Diet-Induced Hepatocellular Carcinoma in Obese and Non-Obese Mice

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood. METHODS: In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice. RESULTS: Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice. CONCLUSIONS: Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis

Thirty-Day Unplanned Readmission and Its Effect on 90-Day Mortality in Hepatocellular Carcinoma Patients Undergoing Partial Hepatectomy

Background: Despite advances of surgical techniques, hepatectomy continues to be potentially dangerous and is associated with postoperative mortality, morbidity and readmission. The objective of this study was to determine the effect of 30-day unplanned readmission on ‘conditional’ 90-day mortality among hepatocellular carcinoma (HCC) patients who underwent partial hepatectomy. Methods: National Cancer Database (NCDB) was queried from 2004 to 2012 for patients with hepatocellular carcinoma (HCC) who underwent partial hepatectomy. Thirty-day unplanned readmission rate, and associated risk factors, was determined for 7,696 patients. The association between 30-day unplanned readmission and conditional 90-day mortality was further addressed. Results: The 30-day unplanned readmission rate for patients with HCC who underwent partial hepatectomy was 5.2%. Risk factors associated with 30-day unplanned readmission were sex, race/ethnicity, Charlson-Deyo score, and annual hospital hepatectomy volume. An overall adjusted odds of having conditional 90-day mortality was 2.325 times higher (95% CI 1.643 - 3.219) among patients with a history of 30-day unplanned readmission than those without. This association was dependent on age, sex, race/ethnicity, insurance status, alpha-fetoprotein (AFP), liver fibrosis, Charlson-Deyo comorbidity score and annual hospital hepatectomy volume. Conclusion: Efforts in patient care should be taken to reduce 30-day unplanned readmission after partial hepatectomy for patients with HCC to reduce conditional 90-day mortality

Disparities in Awareness of and Willingness to Participate in Cancer Clinical Trials Between African American and White Cancer Survivors

BACKGROUND: Cancer clinical trials (CCTs) are essential for cancer care, yet the evidence is scarce when it comes to racial disparities in CCT participation among cancer survivors in the Midwest. This study aimed to 1) assess disparities in the awareness of and willingness to participate in CCTs between African American and White cancer survivors; and 2) compare perceptions about CCTs between the two racial groups. METHODS: The study was based on cross-sectional data from the survey Minority Patient Participation in Cancer Clinical Trials that collected information from 147 Black and White cancer survivors from Nebraska between 2015 and 2016. Chi-square tests and logistic regressions were used to assess differences between Black and White cancer survivors regarding their awareness, willingness, and perceptions associated with CCT participation. RESULTS: After adjusting for the effects of socio-demographic, health status, and psychosocial variables, Black cancer survivors were much less likely than White cancer survivors to be aware of CCTs (AOR 0.26; CI 0.08-0.81), to express willingness to participate in CCTs (AOR 0.03; CI 0.01, 0.32) and to actually participate in CCTs (AOR 0.13; CI 0.04-0.38). Black cancer survivors reported a lower level of trust in physicians and were less likely than White cancer survivors to believe that CCTs make a significant contribution to science. CONCLUSIONS: Relative to White cancer survivors, Black cancer survivors had much lower awareness of and willingness to participate in CCTs. Part of these differences might be related to the differential perception of CCTs, psychosocial factors, and trust in physicians between the two groups