Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant upregulation of PDK1 in ovarian cancer cells impairs CD8+ T cell function and survival through elevation of PD-L1

ABSTRACT Blockade of the programmed cell death 1(PD-1)/PD-1 ligand-1(PD-L1) pathway has been exploited therapeutically in many cancer types. Upregulation of PD-L1 in tumor cells contributes to malignancy through suppression of the T cell-mediated antitumor response. Pyruvate dehydrogenase kinase 1 (PDK1), a glycolytic gate-keeping enzyme, is also known to promote tumor development. Here, we have uncovered a mechanism of regulation of PD-L1 by PDK1 through activation of c-Jun-NH2-kinase (JNK)-c-Jun in ovarian cancer cells. Elevated PDK1 expression was correlated with that of PD-L1 in the TCGA ovarian cancer dataset and ovarian cancer tissue array. Overexpression of PDK1 in ovarian cancer cells impaired CD8+ T cell function by suppressing IFN-γ secretion through the PD-1/PD-L1 pathway. Conversely, knockdown of PDK1 in ovarian cancer cells relieved suppression of CD8+ T cell function. CD8+ T cell apoptosis induced by binding of PD-1 with PD-L1 was increased after co-culture with ovarian cancer cells overexpressing PDK1, while depletion of PDK1 exerted the opposite effect. In vivo experiments revealed synergistic improved overall survival and enhanced inhibition of tumor growth upon co-treatment with dichloroacetate (DCA), a PDK inhibitor, and PD-L1 antibody, accompanied by increased IFN-γ secretion by monocytes infiltrating tumor islets. Moreover, PDK1 expression and CD8+ T cell infiltration were inversely correlated in the ovarian cancer tissue array. Our collective findings provide a novel explanation of how PDK1 contributes to upregulation of PD-L1 in ovarian cancer and highlight its potential as a target therapeutic molecule that cooperates with the immune checkpoint blockade.
The clinical significance of serum adipocytokines level in patients with lung cancer.

Background Adipocytokines were known to play a relevant role in metabolism, inflammation responses and carcinogenesis of several malignancies. Our aims were to detect the expression of serum adipocytokines, explore their potential diagnostic ability and relationship with clinicopathological characteristics of lung cancer. Methods Adipocytokines, insulin-like growth factor binding protein 1 (IGFBP-1), resistin, tumor necrosis factors (TNFα), TNF RI and TNF RII, vascular endothelial growth factor (VEGF), leptin, interleukin (IL)-6 and IL-10, chemerin, brain-derived neurotrophic factor (BDNF), plasminogen activator inhibitor-1 (PAI-1) were assessed in 49 untreated lung cancer patients and 20 healthy controls. The protein chip was used to detect the serum levels of adipocytokines. Results Lung cancer patients exhibited significantly elevated serum IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 levels compared to controls (P<0.05) and most of these adipocytokines revealed a modest discriminative ability for the diagnosis of lung cancer, while BDNF were lower in patients (P<0.05). TNF RI was associated with distant metastasis of lung cancer, while there was no relation between other adipocytokines and the patient clinicopathological features. Conclusions These results suggest that cytokines IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 may be involved in the development and progression of lung cancer, and TNF RI may be involved in distant metastasis of lung cancer. Additionally, IGFBP-1, TNF RI, VEGF and TNF RII probably represent potentially useful biomarkers for the diagnosis of lung cancer.
Hemoglobinopathy and Systemic Lupus: A Rare Association

The authors report a case of systemic lupus associated with a composite heterozygosis SC with thalassemic component in a 19-year-old patient hospitalized for anemia and polyarthralgia who has a staturoponderal delay, macular erythematous lesions in butterfly wings on the face and ears, photosensitivity, puffy face, alopecia, pubic and axillary hair loss, scalp dermatophytosis, painful swelling of the interphalangeal joints, wrists and knees. The hemoglobin electrophoresis showed a compound heterozygote SC associated with β thalassemia. Antinuclear antibodies were positive with an anti-Sm positive antibody. Conclusion: The diagnosis of both diseases can be difficult when symptoms are concomitant and look alike.
Screening and authentication of molecular markers in malignant glioblastoma based on gene expression profiles

Glioblastoma (GBM) is a malignant tumor of the central nervous system with high mortality rates. Gene expression profiling may determine the chemosensitivity of GBMs. However, the molecular mechanisms underlying GBM remain to be determined. To screen the novel key genes in its occurrence and development, two glioma databases, GSE122498 and GSE104291, were analyzed in the present study. Bioinformatics analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, the Search Tool for the Retrieval of Interacting Genes, Cytoscape, cBioPortal, and Gene Expression Profiling Interactive Analysis softwares. Patients with recurrent GBM showed worse overall survival rate. Overall, 341 differentially expressed genes (DEGs) were authenticated based on two microarray datasets, which were primarily enriched in ‘cell division’, ‘mitotic nuclear division’, ‘DNA replication’, ‘nucleoplasm’, ‘cytosol, nucleus’, ‘protein binding’, ‘ATP binding’, ‘protein C-terminus binding’, ‘the cell cycle’, ‘DNA replication’, ‘oocyte meiosis’ and ‘valine’. The protein-protein interaction network was composed of 1,799 edges and 237 nodes. Its significant module had 10 hub genes, and CDK1, BUB1B, NDC80, NCAPG, BUB1, CCNB1, TOP2A, DLGAP5, ASPM and MELK were significantly associated with carcinogenesis and the development of GBM. The present study indicated that the DEGs and hub genes, identified based on bioinformatics analyses, had significant diagnostic value for patients with GBM.
Pharmacological investigation of clinically achievable concentrations of resveratrol in colorectal cancer

ii ACKNOWLEDGEMENTS.iii LIST OF CONTENTS.iv INDEX OF FIGURES.ix INDEX OF TABELS.xiii LIST OF ABBREVIATIONS.xiv LIST OF CONFERENCE ABSTRACTS.xvi CHAPTER 1: INTRODUCTION.1 1.1 Cancer and life style.1 1.2 Carcinogenesis.5 1.3 Chemoprevention.7 1.3.1 Classification of chemopreventive agents.8 1.3.2 Preclinical investigation of chemopreventive agents.9 1.3. 3 Clinical trials of chemopreventive agents.10 1.3. 3.1 Important positive trials.11 1.3. 3.2 Important negative trials.14 1.4 Colorectal cancer (CRC). 15 1.4. 1 Preclinical models of colorectal carcinogenesis.18 1.4. 1.1 Apc mice as in vivo model for colon carcinogenesis.19 1.4. 1.2 Apc10.1 cells as in vitro model of colon adenoma development.20 1.5 Resveratrol.21
Pain relief in advanced cancer

Pain and cancer Assessment of pain The concept of pain Pain control: modification of pathological process Non-drug measures Analgesics Pharmacology: opioid responsive pain Non opioid responsive pain Corticosteroids Diamorphine Morphine Alternative strong narcotic agonists Narcotic agonist - Antagonists Co-analgesics General.
Role of ischemia-reperfusion in oxidative stress-mediated injury during kidney transplantation

Renal transplant (RT) is the definitive treatment for end-stage renal disease, which is known as a high prevalence pathology with strong economic repercussion both for patients and health systems. Solid organ transplantation is a classically described clinical setting in which massive amounts of reactive oxygen species (ROS) are produced due to ischaemia-reperfusion, thus becoming an essential pathophysiological element involved in delayed graft function in the context of RT. Nevertheless, no clinical protocol yet exists to counteract the damage mediated by ROS intensively produced throughout the transplant process. The available evidence shows a number of successful experiences in the use of antioxidant supplementation and reinforcement over other oxidative stress-related pathologies. This article addresses the pathophysiological role of oxidative stress in RT and its known consequences in function and structure of the allograft, with the objective of gathering consistent information that demonstrates the central role of oxidative stress in this pathology, and to consider it as a possible therapeutic approach in the future. *Correspondence to: Ramón Rodrigo, Laboratory of Oxidative Stress and Nephrotoxicity, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, P.O. B. 70058, Chile, E-mail: rrodrigo@med.uchile. cl
Development and Clinical Evaluation of Polyherbal Laxative Laxisen

Constipation being one of the most common and frequently occurring symptoms of gastrointestinal disorders is high in prevalence rate, causing economic burden and badly effecting quality of life. Multiple research studies have been carried out to clinically evaluate, assess and address the treatment for both acute and chronic constipation in adults. However limited evidences are available for the efficacy of available treatment options for the management of constipation. This study is a prospective, open labeled, uni-center and observational clinical trial and was carried out at out-patient department of clinical medicine at Jinnah Medical Center, Korangi, Karachi, Pakistan to evaluate the clinical efficacy and safety of polyherbal formulation Laxisen in 35 patients with complaints of constipation. The study drug was administered for 1- 2 weeks for acute and 1-6 weeks for chronic constipation patients. After following up patients for specified time period complete remission of constipation was observed and the drug was found significantly effective (p < 0.003). The mean weekly frequency of bowl movements was 9.95 for acute constipation while 9.23 for chronic constipation. Significant increase in frequency of the bowl movements was observed for all patients.
A cross sectional study to determine polycystic ovarian disease among students of a tertiary care teaching hospital

Background: India now has highest number of patients with type 2 diabetes mellitus globally and speedy rise of the incidence of obesity in children is the major reason for increasing insulin resistance, the metabolic syndrome, dyslipidemia and polycystic ovarian syndrome. But proportion for PCOD is unknown in community. Objective of this study was to estimate the prevalence of PCOD among students in Tertiary care teaching hospital.Methods: A cross sectional study was conducted among students of aged 16-24 years in a teaching hospital in Kerala. Sample sizes of 256 students were randomly selected from various batches of medical and paramedical courses. Occurrence of hyper androgenic features and menstrual irregularities were evaluated, and they were physically examined. The diagnosis of PCOS was made based on Rotterdam’s criteria. Epi-info 7 was used for analysis.Results: Seventy-five students (30%) met the criteria to be diagnosed as polycystic ovarian syndrome. Twenty students (10%) had a history of thyroid dysfunction. The other clinical features of hyperandrogenism were like acne (25%), oily skin (13.5%), and increased hair growth (7%), male pattern thinning of hair (9.75%). Conclusions: PCOD can be assumed of as a forerunner syndrome that, if screened for, can help in early identification of risk of highly morbid conditions, in adolescent girls.
Comparative study of tubal patency by sonosalpingogram hysterosalpingography and diagnostic laparoscopy

Background: Sonosalpingography has been suggested as the first-line method to study tubal patency. This study is to bring into focus the value of pelvic sonogram in accessing tubal patency in order to overcome the radiation hazard associated with hysterosalpingogram reduce the cost of examination and encourage it at first-line office. Objective of this study was to compare the diagnostic efficacy of sonosalpingogram, hysterosalpingography and diagnostic laparoscopy for tubal patency as a cause for female infertility.Methods: It is a prospective study in 100 patients attending for evaluation of infertility for a period of 2 years were chosen for this study. All cases with primary and secondary infertility who have attended infertility clinic for tubal causes.Results: 68 cases were found to have bilateral patency as per SSG while 58 cases had bilateral patency as HSG. Similarly 24 cases had bilateral block as per SSG while 28 cases had bilateral block as per HSG. 8 cases had unilateral block as per SSG while 14 cases had unilateral block as per HSG. This difference in observations may probably attribute to tubal spasm in HSG. Bilateral patency was observed in 68 cases as against 64 cases in laparoscopy. Out of these 68 cases 9 cases were false positive as bilaterally patent. However bilateral blocks were shown to be 24 in both methods. Out of 12 cases of unilateral block as per laparoscopy 8 cases were detected by SSG. There was false negative rate of 5%. There was false negative rate of 10% for tubal patency with HSG.Conclusions: For low risk subjects for tubal factors in infertility, sonosalpingogram can be employed as a screening test of choice and for high risk subjects HSG and laparoscopy can be used.
The effects of thrombolysis and endovascular clot retrieval on dysphagia: a scoping review

ABSTRACT Purpose The aim of this scoping review was to identify and analyse all available studies exploring the effects of thrombolysis and endovascular clot retrieval on swallowing outcomes from a speech–language pathology perspective. Materials and methods A systematic literature search identified full-text journal articles that reported on swallowing after reperfusion therapies. To be included, studies had to explore the effects of thrombolysis or endovascular clot retrieval on dysphagia, include ‘dysphagia’ or ‘swallowing’ in analysis/discussion, be a peer-reviewed full-text journal article and be in the English language. Relevant studies were assessed for quality and data were extracted regarding study type, reperfusion therapy administered, assessment tools used, speech–language pathology input and dysphagia results. Results Two articles met the inclusion criteria. Both discussed thrombolysis and presented conflicting findings. Thrombolysis was suggested to impact dysphagia presentation in both articles, however, heterogeneity in results did not support clear insight into the nature of the impact. No research was identified exploring the effects of endovascular clot retrieval on swallowing. Conclusion Limited research exists exploring the effects of reperfusion therapies on dysphagia outcomes. As thrombolysis and endovascular clot retrieval increase in clinical use, this review is a call to action for further research to identify potential differences in dysphagia presentation and management for this patient population in order to guide evidence-based rehabilitation.
Community-Acquired Pneumonia in Indonesia

markdownabstract__Abstract__ __Background:__ Knowledge about the etiology and management of community-acquired pneumonia (CAP) in Indonesia is lacking. __Methods:__ Hospital-based and a population-based cohort studies were carried out during 2007-2011 in Semarang, Indonesia. __Results:__ Among 148 consecutive CAP patents admitted to hospital, influenza virus (18%), Klebsiella pneumoniae (14%), and Streptococcus pneumoniae (13%) were the commonest etiologies. Mixed infection occured in 28%. Bacteria presented wild type antibiotic susceptibility profiles. The mortality (rate: 30%) was associated with disease severity (P<0.001), and with failure to establish an etiological diagnosis (P=0.027). Among a cohort of 496 healthy volunteers nasopharyngeal carriage of K. pneumoniae, other Gram-negative bacilli, and S. pneumoniae was 11%, 19%, and 27%, respectively. K. pneumoniae carriage in adults (15%) was higher than in children (7%, P=.004), and strains from adults were more virulent. Carriage of S. pneumoniae among children (43%) was higher compared to adults (11%, P<.001). Capsular typing revealed that current 13-valent conjugate vaccine covers only 45% of these strains. Determinants of K. pneumoniae and other GNB carriage were poor food and water hygiene. To evaluate the quality of management of patients with CAP , we applied a Delphi method to derive six indicators that are feasible and valid for the Indonesian setting. __Conclusions:__ The etiology of CAP and nasopharyngeal colonization in Indonesia differ from that of Western countries requiring adaptation of diagnosis, empiric treatments and prevention. Further multicenter studies are needed to delineate the full etiologic spectrum of CAP and to generate, implement and audit guidelines tailored for CAP management in Indonesia.
Marginal Discrepancy of Cast Copings to Abutments with Three Different Luting Agents

Aim The purpose of this study was to evaluate the MD (marginal discrepancy) on the calcinable copings in abutments for cemented prostheses with three luting agents. Methods Sixty-four analogs of CeraOne-type abutments (NACONIH code, Titanium Fix Implant Sytem SP, Brazil) were divided into four groups (n = 16). The copings were cast and placed on the CeraOne abutment analogs and cemented with eugenol-free zinc oxide (EfZO) (n = 16), with glass ionomer (GI) (n = 16), and with zinc phosphate (ZP) (n = 16), and as a control group, there were CeraOne plastic copings (NACOC code, Titanium Fix Implant Sytem SP, Brazil) (n = 16) which were not cemented with any material. After 24 hours, the MD of the four groups was measured. MD was evaluated using a stereoscopic microscope (Leica EZ4 W, Leica Microsystems, Germany) with an increase of ×100. MD was measured at four predetermined and equidistant sites with respect to the marginal line of the cast adaptation. The measurement was made from the distance between the free edge of the cast cylinder and the margin of preparation of the titanium abutment, with a level of statistical significance of p < 0.05. Results Of the three fixing agents, the ZP was found to have the highest MD (53.59 ± 14.21 μm); however, the lowest MD (41.72 ± 9.10 μm) was found in the GI group. These differences are statistically significant at p < 0.001. Conclusions In summary, according to our results, it was found that ZP cement showed the highest MD after cementation, followed by the glass ionomer, while EfZO showed the lowest MD.
Physician Notified Work-Related Diseases Among Farmers in Norway: Data from 2007 - 2016

ABSTRACT Introduction: This study provided a profile of work-related diseases in the farming sector notified by physicians to the Norwegian Labor Inspection Authority’s (NLIA) Registry for Work-Related Diseases (RAS) over a 10-year period. Methods: Data for the occupational code “farmers” were extracted from RAS for the period 2007–2016. We performed a descriptive analysis to obtain frequency, percentage, and incidence distribution of the data. We also explored the relationship of the notified diagnosis with gender, age, occupational exposures and the type of reporting physicians. Results: Four hundred and sixty-nine cases of work-related diseases among farmers were notified in the period 2007–2016. Eighty-seven percent of the reported cases were males. The incidence of work-related diseases for the entire study period was computed to be 114/100 000 workers. The incidence and number of cases notified were highest among males and for the age group 55–74 years. Noise was the most frequently reported occupational exposure accounted for 291 cases. Hearing loss constituted for 62% of the notified cases, followed by respiratory diseases that accounted for 20% of the cases. Forty-eight cases of skin diseases, while only a few cases of musculoskeletal (n = 7) and mental disorders (n = 1) were notified. There was a strong association (λ = 0.51) between occupational exposure and notified diagnosis, and a moderate association (λ = 0.32) between type of reporting physician and the notified diagnosis. Conclusion: This profile of the physician notified work-related diseases among farmers in Norway yielded a suppressed estimate of the actual incidence of cases. The biased distribution of nature and number of work-related diseases amongst farmers is primarily attributed to the significant undercount of cases. Physician underreporting of cases to the NLIA coupled with lack of Occupational Health Services coverage of workers in the farming sector contributes to this undercount of cases.
Dry Eye Indexes Estimated by Keratograph 5M of Systemic Lupus Erythematosus Patients without Secondary Sjögren's Syndrome Correlate with Lupus Activity

Purpose To investigate the incidence, severity, and influencing factors of dry eye in systemic lupus erythematosus (SLE) patients without secondary Sjögren's syndrome (sSS). Methods A total of 78 patients who were diagnosed with systemic lupus erythematosus and met inclusion criteria were selected as the study subjects in this cross-sectional study. Tear meniscus height (TMH) and noninvasive Keratograph tear breakup time (NIKBUT) including NIKBUT-first and NIKBUT-average of the subjects were measured using a noninvasive ocular analyzer, the Keratograph 5M (Oculus, Wetzlar, Germany). Symptoms related to dry eye were assessed using the Ocular Surface Disease Index (OSDI). The severity of SLE was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Results of the levels of 4 serum antibodies were collected from the patients' medical records. Correlations between SLEDAI and various ocular surface parameters were analyzed, and multiple-factor binary logistic regression analysis was conducted. Results In the study subjects, mean TMH was 0.22 mm, mean NIKBUT-first was 9.12 s, and mean OSDI was 13.14. The subjects (19 eyes) whose NIKBUT-average was < 10 s and OSDI was ≥ 13 accounted for 24.36% of all the included patients. SLEDAI showed a statistically significant correlation with TMH (r = −0.233, p=0.040), NIKBUT-first (r = −0.254, p=0.025), NIKBUT-average (r = −0.343, p=0.002), and OSDI (r = 0.256, p=0.024). According to multiple-factor binary logistic regression analysis, SLEDAI could be considered as a risk factor of the incidence of dry eye in SLE patients without sSS. Conclusions One-fourth of the SLE patients without sSS suffered from dry eye, and the severity of dry eye correlated with the activity of SLE.