tbuckley/cabot-search huggingface dataset:
The population alteration of CD11b<sup>+</sup>/CD14<sup>-</sup> myeloid-derived suppressor cells in patients with advanced stage, non-small cell lung cancer and the clinical relevance to the responsiveness to epidermal growth factor receptor (EGFR) tyrosi
Authors: Y. Wang, F. Chung, C. Wang, C. Liu, K. Lee, C. Yu, H. Kuo
Journal: Journal of Clinical Oncology (2008)

19082 Background: In animal models and human metastatic renal cell carcinoma, myeloid-derived suppressor cells (MDSC) contribute to tumor-related immune dysfunction. However, there has been little investigation of the cells in human cancer and their clinical relevance. Methods: Patients with advanced stage, non-small cell lung cancer who would receive EGFR-TKI therapy were enrolled in this study. PBMNCs were collected before and after 28 days of therapy. Responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Flow cytometry was used to analyze CD11b+/CD14−/CD15+/CD33+ cells in PBMNCs. The cells were isolated with magnetic microbeads. The expression L-arginase and iNOS in CD11b+/CD14- cells was identified with Western blotting and RT-PCR. Results: Forty-seven patients with advanced stage NSCLC (27 male and 20 female, aged 61.8±13.9 years) were enrolled. The subpopulation of L- arginase- and iNOS-producing CD11b+/CD14- cells in PBMNCs was identified by Western blot analysis, RT-PCR and flow cytometry. The CD11b+/CD14−/CD33+/CD15+ subpopulation in PBMNC was significantly increased (12.10 ± 1.41%, n=47) in NSCLC patients, compared with control subjects (8.11 ± 0.47, n=46, p = 0.001). After 28 days of treatment, the CD11b+/CD14-/CD15+/CD33+ subpopulation was significantly decreased in the patients of partial response subgroup (11.07±1.54%, vs. 5.09±0.74%, p<0.001). The patients with progressive disease revealed a significant increase in the MDSC subpopulation (9.67±2.59 vs. 24.76±3.76%, p=0.002). Beside, the progression- free survival of the patients had a negative correlation with the population of CD11b+/CD14−/CD15+/CD33+ cells in PBMNCs at the time after 28 days of therapy ( r= -0.5482, p<0.0001). Conclusions: We found a subpolulation of L-arginase- and iNOS-producing CD11b+/CD14−/CD33+/CD15+ MDSCs in patients with advanced stage non-small cell lung cancer. The population of the cells changed with disease status. There was a negative correlation between the progression-free survival and the population of MDSC after 28 days of therapy. No significant financial relationships to disclose.
Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus
Authors: Chrysi Koliaki, Michael Roden
Journal: Annual Review of Nutrition (2016)

Mitochondrial function refers to a broad spectrum of features such as resting mitochondrial activity, (sub)maximal oxidative phosphorylation capacity (OXPHOS), and mitochondrial dynamics, turnover, and plasticity. The interaction between mitochondria and insulin sensitivity is bidirectional and varies depending on tissue, experimental model, methodological approach, and features of mitochondrial function tested. In human skeletal muscle, mitochondrial abnormalities may be inherited (e.g., lower mitochondrial content) or acquired (e.g., impaired OXPHOS capacity and plasticity). Abnormalities ultimately lead to lower mitochondrial functionality due to or resulting in insulin resistance and type 2 diabetes mellitus. Similar mechanisms can also operate in adipose tissue and heart muscle. In contrast, mitochondrial oxidative capacity is transiently upregulated in the liver of obese insulin-resistant humans with or without fatty liver, giving rise to oxidative stress and declines in advanced fatty liver disease. These data suggest a highly tissue-specific interaction between insulin sensitivity and oxidative metabolism during the course of metabolic diseases in humans.
From DCPD to NTCP: The long journey towards identifying a functional hepatitis B virus receptor
Authors: Jisu Li, Shuping Tong
Journal: Clinical and Molecular Hepatology (2015)

Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection. Keywords: Hepatitis B virus; Carboxypeptidase D; Glycine decarboxylase; heparan sulfate proteoglycans; Sodium taurocholate cotransporting polypeptide
Antibiotic resistance evaluation and clinical analysis of acute appendicitis; report of 1431 consecutive worldwide patients: A cohort study
Authors: Federico Coccolini, Giuseppe D'Amico, Massimo Sartelli, Fausto Catena, Giulia Montori, Marco Ceresoli, Roberto Manfredi, Salomone Di Saverio, Luca Ansaloni
Journal: International Journal of Surgery (2015)
Role of cytokeratin and vimentin as prognostic markers in oral cancers
Authors: V. Rao, D. Chaukar, M. Vaidya, s. Sawant, A. Dcruz, S. Kane
Journal: Journal of Clinical Oncology (2008)

17030 Background: Oral cancer is the single largest group of malignancies in the Indian subcontinent. Advances in fields of oncology have however not translated into improved survival. Earlier results on CK expression have shown promising results in oral pre-malignant and malignant lesions. Methods: Prospective study. Objectives: Study the expression pattern of cytokeratin 1, 5, 8,18 and Vimentin in squamous cell carcinoma (SCC) of oral cavity along with their cut margins and surrounding normal mucosa and correlate the expression patterns with clinical parameters This study included 48 patients with biopsy proven SCC of oral cavity who underwent surgery with neck dissection between 2003- 2004. Immunohistochemistry was done on formalin fixed, paraffin embedded sections by using monoclonal antibodies specific for CK 1, 5, 8, 18 and vimentin. Results: In the tumor, aberrant expression of CK1 was seen in 30%, CK8 in 54%, CK18 in 44% and vimentin in 85%. CK5 non expression was seen in 29%. In patients with tumor expressing 8, 18 and vimentin, 57% were poorly differentiated, 36% moderately, and 7% well differentiated. 43% showed nodal involvement when all 3 markers were positive and 36% of patients developed recurrence. In cut margins When 8, 18 were not expressed with CK5 expression, 13% developed recurrence as compared to 33% when CK8 and 18 were expressed at the cut margins. CK18 was expressed in 35% of the cut margins specimen 0f which 53% developed recurrence (8 pts). On the contrary, expression of CK 18 was seen in 27% of the specimens who did not develop recurrence. CK 5 expression was seen in all patients with recurrence. In patients who developed recurrence within 6 months, cut margins showed CK 8 or 18 expressions with Vimentin in 88% (7/8) patients. Conclusions: Cytokeratin 8, 18 and vimentin expression patterns exhibit definite relationship with oral cancers. CK18 expression in cut margins is reliable marker to predict recurrence. Vimentin although a good marker had limited value as a prognostic indicator. However it may be of value as a diagnostic tool, as its aberrant expression was most commonly observed in all oral cancers. CK 5 aberrant expression was seen in all patients with recurrence. Thus the aberrant expression of keratin like CK 8 and 18 seems to have a greater prognostic value than the non expression of CK5. No significant financial relationships to disclose.
Tumor Diagnosis: Discovering of Tumor-targeting Peptides using Bi-functional Microarray (Adv. Healthcare Mater. 18/2015)
Authors: Weizhi Wang, Zihua Wang, Xiangli Bu, Ren Li, Mingxing Zhou, Zhiyuan Hu
Journal: Advanced Healthcare Materials (2015)

A silicon based bi-functional microwell array for both in situ peptide sequencing and fluorogenic detection is presented. On page 2802, W. Wang, Z. Hu, and co-workers show how positive hits from high throughput peptide library can be screened out efficiently through the direct reading of the fluorescence and single-bead MS sequencing. Novel peptides with nanomolar affinities and high specificities towards tumor marker are obtained.
The effect of posture on ventilation using structured light plethysmography (SLP) in alpha 1 anti-trypsin deficiency (A1AT)
Authors: Liam O'Reilly, Elizabeth Sapey, Sebastian Desando, James Stockely, Robert Stockley, Brendan Cooper
Journal: European Respiratory Journal (2014)

Introduction 

Structured Light Plethysmography (SLP) can determine changes in ventilatory patterns by utilising relative thorax contribution (RTC), inspiration to expiration ratio (IE50), inspiration time (Ti), inspiration and exhalation flux (Ti/Ttot) & breathing asynchrony by phase angle (PA).

Aims 

To measure the change in breathing patterns by SLP between sitting and supine in patients with A1AT with varying levels of respiratory disease.

Methods 

We measured respiratory signals using Thor3Di (PneumaCare, Cambridge, UK) in 27 A1AT patients (16M:11F, Mean (SD): 56.0 (10.4) years; FEV1: 2.10 (1.12)L; FVC: 4.22 (1.30) both sitting and supine for 1-2 minutes and analysed them using Mann-Whitney tests.

Results 

There were only differences in both IE50, Ti & Ti/Ttot between sitting and supine in the patients (see table).

View this table:

Table 1





When these patients supine data were divided into those with reduced FEV1 (<-1.64SR), the reduction in values of RTC & increase in PA was greater in the patients with airflow obstruction (Figure 1.)

![Figure][1] 



Conclusion 

This data shows that breathing when going from seated to supine becomes more abdominally dominant and more asynchronous and that this is related to the degree of airflow obstruction severity. SLP is able to measure this remotely and easily for the patients.

 [1]: pending:yes
Climate change and conflict: more than a fashionable association with health
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

When the refugee crisis hits headlines in Europe and national borders become flashpoints, the public’s first thought probably isn’t climate change. The immediate challenges that refugees pose and their urgent needs dominate the agenda. Upstream issues like the social and political determinants of health, for example, the conflict in Syria, might enter the conversation, but the next step to climate change seems a step too far. However, as this month’s clinical review explains, if you accept that conflict is one of the causes of the refugee crisis, you also accept that climate change is partly responsible. 1 Devin Bowles and colleagues examine the evidence on climate change, conflict and health and find that medical understanding of the threat is inadequate despite the potential scale of the health implications. The worlds of medicine and public health are reluctant to view conflict as a health problem, when the evidence is clear. The public, meanwhile, is more likely to be persuaded to address climate change if it is addressed as a health issue. Improving understanding of the association between climate change and conflict may further support efforts to cope with climate change. Is climate change one of the precipitating factors for the Arab Spring, destablising economies in the Middle East, including Syria? A drought devastated Syria’s economy and climate modelling suggests that climate change partly contributed to its severity. Syria was already home to refugees from the conflict in Iraq, and the drought drove 1.5 million Syrians to move to cities and their outskirts. A fertile breeding ground for internal conflict was created. The authors provide other examples from around the world, and, if you are persuaded by the socio-political effects of climate, it is no surprise that some of the world’s hottest countries are the poorest, most likely to sustain conflicts and maintain the worst health indicators. Indeed, any strategy for health or national security is incomplete if it ignores the impact of climate change. Not everyone accepts the existence or impact of climate change. It might even be an example of ‘fashion-based’ research and journalism. Collecting evidence according to the fashion of the day is a dangerous enterprise as John Hampton reminds us in his sobering experience, from the 1980s, of investigating the use of antiarrhythmic drugs after heart attack and finding them harmful. 2 One of today’s other fashions is the troubling data on weekend mortality, although the implications of these data are unclear. Rahul Potluri attempts to make sense of the latest research. 3
Abstract 40: Integrative Genomics Analysis Reveals Novel Mechanisms For Plasma Lipid Regulation
Authors: Yuqi Zhao, Helen Luk, Ville-Petteri Mäkinen, Qingying Meng, Xia Yang
Journal: Circulation (2014)

Dysregulation of plasma lipids, especially cholesterol levels, has been identified as a critical risk factor for various complex human diseases such as cardiovascular diseases and Alzheimer’s disease. Recent genome wide association studies (GWAS) have implicated a number of susceptibility loci for complex traits of lipid metabolism. However, these loci only explain a limited proportion (25-30%) of the genetic heritability and a comprehensive understanding of the underpinning regulatory mechanisms has not been achieved. To better understand the mechanisms and to identify potential novel regulators, in this study, we utilized an integrative genomics approach that leveraged multiple genetic and genomic datasets including 1) GWAS from Global Lipids Genetics Consortium (GLGC) for four lipid traits (high density lipoprotein cholesterol [HDLC], low density lipoprotein cholesterol [LDLC], triglycerides [TG], and total cholesterol [TC]), 2) expression quantitative trait loci(eQTLs) from genetics of gene expression studies of human tissues related to lipid metabolism(such as liver and adipose tissues), 3) knowledge-driven biological pathways, and 4) data-driven regulatory gene networks. The integration of these diverse data sources enabled tissue-specific investigations on whether the genetic variants associated with lipid traits from GWAS were concentrated on specific parts of gene regulatory networks, termed “subnetworks”, and whether novel key regulators of the lipid subnetworks could be identified based on data-driven network structures.We identified 17, 16, 18, and 14 subnetworks for HDLC, LDLC, TC, and TG, respectively. Among these, subnetworks associated with lipid metabolism, protein modification, response to external stimulus, receptor activity, and neurophysiological process were shared among the four lipid traits. Among the trait-specific subnetworks, those involved in glutathione metabolism, and taurine and hypotaurine metabolism were found to be HDLC-specific while cadherin-associated subnetworks were LDLC-specific. Finally, by utilizing the gene-gene relationships revealed by the network architecture, we detected key regulator genes, both known (e.g.APOE, APOA5,and ABCA1) and novel (e.g.NCAM1, and F2), in these lipid-associated subnetworks. Our results shed lights on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation.
Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)
Authors: C. Zhou, Y.L. Wu, G. Chen, J. Feng, X.-Q. Liu, C. Wang, S. Zhang, J. Wang, S. Zhou, S. Ren, S. Lu, L. Zhang, C. Hu, C. Hu, Y. Luo, L. Chen, M. Ye, J. Huang, X. Zhi, Y. Zhang, Q. Xiu, J. Ma, L. Zhang, C. You
Journal: Annals of Oncology (2015)
Genomic Profiling of Pharmacogenetic Variants Establishes a SNP-Based Predictor for Poor Outcome in Asian Children with Acute Lymphoblastic Leukemia (ALL): A Report from Malaysia-Singapore ALL Study Group
Authors: Yi Lu, Marc Hai Liang Wong, Zhenhua Li, Shirley Kow Yin Kham, Ah Moy Tan, Hany Ariffin, Allen Eng Juh Yeoh
Journal: Blood (2014)
Neoadjuvant chemotherapy for invasive bladder cancer: prognostic factors for survival of patients treated with M-VAC with 5-year follow-up.
Authors: P K Schultz, H W Herr, Z F Zhang, D F Bajorin, A Seidman, A Sarkis, W R Fair, D Scherr, G J Bosl, H I Scher
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine survival in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and to analyze prechemotherapy and postchemotherapy factors for prognostic significance. PATIENTS AND METHODS The survival of 111 patients with T2-4N0M0 bladder cancer treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was assessed. Prechemotherapy and postchemotherapy factors were analyzed for correlation with survival. Factors found to be significant on univariate analysis were subjected to multivariate analysis using Cox's proportional hazards model. RESULTS The median follow-up duration was 5.3 years. Initial tumor (T) stage (P = .0001), presence of ureteral obstruction (P = .0074), and presence of a palpable mass (P = .0039) were the only pretreatment factors found to be significant on univariate analysis. Postchemotherapy surgery was performed in 81 patients. In these cases, postchemotherapy clinical stage and pathologic stage were significant factors on univariate analysis. In the multivariate analysis, the initial prechemotherapy T stage and the postchemotherapy pathologic stage (pT stage) were the only two factors to demonstrate independent significance. An association between downstaging postchemotherapy and survival was observed for patients with extravesical disease (T &lt; or = 3B) at the start of treatment. In this subset, the 5-year survival rate was 54% for patients with downstaging versus 12% for those without downstaging. This association was not observed for patients with bladder-confined disease (T &lt; or = 3A) at presentation. CONCLUSION The stage of bladder cancer at presentation and at postchemotherapy pathologic staging are independent prognostic factors for long-term survival in patients treated with neoadjuvant chemotherapy. Downstaging after neoadjuvant chemotherapy was associated with improved survival in patients with muscle-invasive bladder cancers, but only for those with extravesical disease (T &gt; or = 3B) pretreatment. Randomized comparisons will be required to assess the impact of chemotherapy on overall survival.
All Patients With the T(11; 16)(q23; p13.3) That Involves MLL and CBP Have Treatment-Related Hematologic Disorders
Authors: Janet D. Rowley, Shalini Reshmi, Olatoyosi Sobulo, Tarannum Musvee, John Anastasi, Susana Raimondi, Nancy R. Schneider, Julio C. Barredo, Eduardo S. Cantu, Brigitte Schlegelberger, Frederick Behm, Norman A. Doggett, Julian Borrow, Nancy Zeleznik-Le
Journal: Blood (1997)
Polypharmacy in elderly cancer patients.
Authors: T. L. Jorgensen, J. Hallas, J. Herrstedt
Journal: Journal of Clinical Oncology (2010)

9074 Background: Elderly patients (70+ years) have a high prevalence of comorbidity resulting in a high frequency of polypharmacy (PP) defined as a daily use of five drugs or more. Knowledge of the extent of PP among elderly cancer patients and of its impact on treatment tolerance and effect is sparse. We examined drug use of all incident cancer patients in Funen, Denmark (population 480,000) from 1996 to 2006. Methods: We compared drug use among incident cancer patients with a control group matched by age and gender. Data were obtained by linkage of The Danish Cancer Registry, which holds information on all incident cancer cases in Denmark since 1947 and the Odense Pharmaco-Epidemiologic Database (OPED), including information on all reimbursed prescriptions for the population of Funen since 1990. Drug use was obtained in the last four-month period prior to diagnosis. Conditional logistic regression was used to assess the odds ratio (OR) of PP in cancer patients. Results: All incident cancer cases from 1996-2006 were included (Table). PP was most frequent among lung (48%) and upper gastrointestinal (43%) cancer patients. RR of PP among elderly cancer cases was 1.64 (95% CI 1.57-1.70, P < 0.0001). During the study period, an increase in drug use of, on average, one drug daily for both cases and controls was seen. Five-year survival of elderly cancer cases with PP was 19% compared to 32% of cases without PP. Conclusions: Polypharmacy is more frequent in elderly cancer cases than in controls immediately before the diagnosis of cancer and drug use has increased in both groups from 1996-2006. PP seems to be associated with a lower survival among elderly cancer cases. Cancer cases Controls Cases and controls 1996-2006 30,122 (100%) 120,485 (100%) Age ≥ 70 years 12,832 (42.6%) 51,298 (42.6%) Polypharmacy 7,856 (26.0%) 21,307 (17.7%) Polypharmacy in elderly 5,150 (40.2%) 15,067 (29.4%) Mean drug use (range) of elderly in 1996 3.78 (0-18) 2.79 (0-19) Mean drug use (range) of elderly in 2006 5.12 (0-18) 4.07 (0-25) No significant financial relationships to disclose.
Bayesian Inference Reveals Host-Specific Contributions to the Epidemic Expansion of Influenza A H5N1
Authors: Nídia Sequeira Trovão, Marc A. Suchard, Guy Baele, Marius Gilbert, Philippe Lemey
Journal: Molecular Biology and Evolution (2015)

Since its first isolation in 1996 in Guangdong, China, the highly pathogenic avian influenza virus (HPAIV) H5N1 has circulated in avian hosts for almost two decades and spread to more than 60 countries worldwide. The role of different avian hosts and the domestic-wild bird interface has been critical in shaping the complex HPAIV H5N1 disease ecology, but remains difficult to ascertain. To shed light on the large-scale H5N1 transmission patterns and disentangle the contributions of different avian hosts on the tempo and mode of HPAIV H5N1 dispersal, we apply Bayesian evolutionary inference techniques to comprehensive sets of hemagglutinin and neuraminidase gene sequences sampled between 1996 and 2011 throughout Asia and Russia. Our analyses demonstrate that the large-scale H5N1 transmission dynamics are structured according to different avian flyways, and that the incursion of the Central Asian flyway specifically was driven by Anatidae hosts coinciding with rapid rate of spread and an epidemic wavefront acceleration. This also resulted in long-distance dispersal that is likely to be explained by wild bird migration. We identify a significant degree of asymmetry in the large-scale transmission dynamics between Anatidae and Phasianidae, with the latter largely representing poultry as an evolutionary sink. A joint analysis of host dynamics and continuous spatial diffusion demonstrates that the rate of viral dispersal and host diffusivity is significantly higher for Anatidae compared with Phasianidae. These findings complement risk modeling studies and satellite tracking of wild birds in demonstrating a continental-scale structuring into areas of H5N1 persistence that are connected through migratory waterfowl.