tbuckley/cabot-search huggingface dataset:
Combination of Surgery With Extensive Intraoperative Peritoneal Lavage for Patients With Advanced Gastric Cancer—Reply
Authors: Jing Guo, Da-Zhi Xu
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Protein expression profile of Oxaliplatin-resistant HT29 colon cancer cells
Authors: Eva Martinez-Balibrea, Carmen Plasencia, Anna Martinez-Cardus, Rodrigo Aguilera, Nouri Neamati, Albert Abad
Journal: Cancer Research (2006)

3743  Objectives: In spite of recent advances in clinical oncology with combination chemotherapy, resistance to cytotoxic compounds remains a major obstacle to a successful therapy. Oxaliplatin is a chemotherapeutic agent widely used in the treatment of colorectal cancer. The purpose of this study is to gain further understanding of the molecular mechanisms involved in oxaliplatin resistance in colorectal cancer cells. Methods: We established an oxaliplatin resistant cell line from the HT29 human colon cancer cells. Cytotoxicity was analyzed by MTT and colony formation assays. Proteins were extracted from parental and oxaliplatin resistant (HTOXAR3) cells during exponential growth and were analyzed through comparative proteomics (2D gels and MS). Results: HTOXAR3 showed a 6 fold resistance as compared to HT29 cells. We observed 23 spots in the soluble and 14 spots in the insoluble fraction that were >4 fold over expressed or down-regulated in resistant versus parental cells. Mass spectrometry confirmed down-regulation of HSP60 and Enolase 1 in HTOXAR3 cells and over expression of hnRNP core protein C-like 1 in soluble fraction. HSP70 was overexpressed in insoluble fraction while Pyruvate Kinase was down-regulated. Western Blot analyses are ongoing to confirm these results and would be presented in the meeting. Conclusions: Using the proteomic approach comparing HT29 and its OXA-resistant subline, we have identified a group of proteins that exhibit changes in expression in the resistant subline and that may be involved in the acquisition of OXA-resistant phenotype in HTOXAR3 cells. According to the functional activity many of these proteins fall in the following categories: 1) glycolysis and enzymes involved in metabolic pathways, 2) nucleic acid synthesis, and 3) stress-response and protein-folding. Some of these proteins could serve as putative oxaliplatin resistance markers and further experiments are underway to confirm their clinical significance.
Urban brown rats (Rattus norvegicus) as possible source of multidrug-resistant Enterobacteriaceae and meticillin-resistant Staphylococcus spp., Vienna, Austria, 2016 and 2017
Authors: Amélie Desvars-Larrive, Werner Ruppitsch, Sarah Lepuschitz, Michael P Szostak, Joachim Spergser, Andrea T Feßler, Stefan Schwarz, Stefan Monecke, Ralf Ehricht, Chris Walzer, Igor Loncaric
Journal: Eurosurveillance (2019)

Background Brown rats ( Rattus norvegicus ) are an important wildlife species in cities, where they live in close proximity to humans. However, few studies have investigated their role as reservoir of antimicrobial-resistant bacteria. Aim We intended to determine whether urban rats at two highly frequented sites in Vienna, Austria, carry extended-spectrum β-lactamase-producing Enterobacteriaceae , fluoroquinolone-resistant Enterobacteriaceae and meticillin-resistant (MR) Staphylococcus spp. (MRS). Methods We surveyed the presence of antimicrobial resistance in 62 urban brown rats captured in 2016 and 2017 in Vienna, Austria. Intestinal and nasopharyngeal samples were cultured on selective media. We characterised the isolates and their antimicrobial properties using microbiological and genetic methods including disk diffusion, microarray analysis, sequencing, and detection and characterisation of plasmids. Results Eight multidrug-resistant Escherichia coli and two extensively drug-resistant New Delhi metallo-β-lactamases-1 (NDM-1)-producing Enterobacter xiangfangensis ST114 ( En. cloacae complex) were isolated from nine of 62 rats. Nine Enterobacteriaceae isolates harboured the bla CTX-M gene and one carried a plasmid-encoded ampC gene ( bla CMY-2 ). Forty-four MRS were isolated from 37 rats; they belonged to seven different staphylococcal species: S. fleurettii , S. sciuri , S. aureus , S. pseudintermedius , S. epidermidis , S. haemolyticus (all mecA -positive) and mecC -positive S. xylosus . Conclusion Our findings suggest that brown rats in cities are a potential source of multidrug-resistant bacteria, including carbapenem-resistant En . xiangfangensis ST114. Considering the increasing worldwide urbanisation, rodent control remains an important priority for health in modern cities.
The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease
Authors: Shirley Yin-Yu Pang, Philip Wing-Lok Ho, Hui-Fang Liu, Chi-Ting Leung, Lingfei Li, Eunice Eun Seo Chang, David Boyer Ramsden, Shu-Leong Ho
Journal: Translational Neurodegeneration (2019)

Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta and intracellular inclusions called Lewy bodies (LB). During the course of disease, misfolded α-synuclein, the major constituent of LB, spreads to different regions of the brain in a prion-like fashion, giving rise to successive non-motor and motor symptoms. Etiology is likely multifactorial, and involves interplay among aging, genetic susceptibility and environmental factors.The prevalence of PD rises exponentially with age, and aging is associated with impairment of cellular pathways which increases susceptibility of dopaminergic neurons to cell death. However, the majority of those over the age of 80 do not have PD, thus other factors in addition to aging are needed to cause disease. Discovery of neurotoxins which can result in parkinsonism led to efforts in identifying environmental factors which may influence PD risk. Nevertheless, the causality of most environmental factors is not conclusively established, and alternative explanations such as reverse causality and recall bias cannot be excluded. The lack of geographic clusters and conjugal cases also go against environmental toxins as a major cause of PD. Rare mutations as well as common variants in genes such as SNCA, LRRK2 and GBA are associated with risk of PD, but Mendelian causes collectively only account for 5% of PD and common polymorphisms are associated with small increase in PD risk. Heritability of PD has been estimated to be around 30%. Thus, aging, genetics and environmental factors each alone is rarely sufficient to cause PD for most patients.PD is a multifactorial disorder involving interplay of aging, genetics and environmental factors. This has implications on the development of appropriate animal models of PD which take all these factors into account. Common converging pathways likely include mitochondrial dysfunction, impaired autophagy, oxidative stress and neuroinflammation, which are associated with the accumulation and spread of misfolded α-synuclein and neurodegeneration. Understanding the mechanisms involved in the initiation and progression of PD may lead to potential therapeutic targets to prevent PD or modify its course.
Novel strategy for oral peptide delivery in incretin-based diabetes treatment
Authors: Yining Xu, Matthias Van Hul, Francesco Suriano, Véronique Préat, Patrice D Cani, Ana Beloqui
Journal: Gut (2019)

To fulfil an unmet therapeutic need for treating type 2 diabetes by developing an innovative oral drug delivery nanosystem increasing the production of glucagon-like peptide-1 (GLP-1) and the absorption of peptides into the circulation.We developed a nanocarrier for the oral delivery of peptides using lipid-based nanocapsules. We encapsulated the GLP-1 analogue exenatide within nanocapsules and investigated in vitro in human L-cells (NCl-H716) and murine L-cells (GLUTag cells) the ability of the nanosystem to trigger GLP-1 secretion. The therapeutic relevance of the nanosystem in vivo was tested in high-fat diet (HFD)-induced diabetic mice following acute (one administration) or chronic treatment (5 weeks) in obese and diabetic mice.We demonstrated that this innovative nanosystem triggers GLP-1 secretion in both human and murine cells as well as in vivo in mice. This strategy increases the endogenous secretion of GLP-1 and the oral bioavailability of the GLP-1 analogue exenatide (4% bioavailability with our nanosystem).The nanosystem synergizes its own biological effect with the encapsulated GLP-1 analogue leading to a marked improvement of glucose tolerance and insulin resistance (acute and chronic). The chronic treatment decreased diet-induced obesity, fat mass, hepatic steatosis, together with lower infiltration and recruitment of immune cell populations and inflammation.We developed a novel nanosystem compatible with human use that synergizes its own biological effect with the effects of increasing the bioavailability of a GLP-1 analogue. The effects of the formulation were comparable to the results observed for the marketed subcutaneous formulation. This nanocarrier-based strategy represents a novel promising approach for oral peptide delivery in incretin-based diabetes treatment.
Eliminating Copayments for Skin Cancer Screening—A Public Health Policy With Insufficient Evidence
Authors: Adewole S. Adamson, Michael P. Pignone
Journal: JAMA Dermatology (2019)

The Illinois General Assembly passed House Bill 3113 (HB 3113) on May 30, 2019; it mandates that no copayments or cost sharing of any kind be imposed by health insurers for annual skin cancer screening by any physician. 1House Bill 3113 easily cleared both Houses (114-1 in the House of Representatives and 58-0 in the Senate).The legislature sent the bill to the Illinois Governor on June 28, and he now has 60 days to sign or veto the bill.If he does nothing, the bill automatically becomes law.In their position paper in support of HB 3113, the Illinois State Medical Society argues that HB 3113 will be a public health benefit and "reduce skin cancer" (Illinois State Medical Society Legislative Action Hub).However, on the basis of current evidence (or lack thereof) of the benefits of skin cancer screening, HB 3113 is not sound public health policy and should not become law.Copayments are a form of cost sharing in which patients pay a fixed amount for particular health care services.Copayments are intended to incentivize patients to reduce health care overuse.Ideally, copayments encourage patients to preferentially choose high-value over low-value services; however, copayments are blunt instruments that tend to reduce both high-and low-value care. 2 The increasing prevalence of copayments and other forms of cost sharing is a growing problem as the burden of patient out-ofpocket costs is increasing across the United States, owing in part to a larger proportion of patients choosing or being compelled to choose high-deductible health insurance plans. 3As a result, public health advocates believe that efforts to reduce or eliminate copayments, specifically for high-value services, have the potential to encourage patients to seek high-value care.In this vein, the Affordable Care Act requires insurers to cover, without any cost-sharing requirements, preventive health services with an A or B rating from the United States Preventive Services Task Force (USPSTF), an independent, nongovernmental panel of national experts in disease prevention and evidencebased medicine that develops recommendations for clinical preventive services.Services rated A or B are those that have been found by the USPSTF to have moderate to large confidence of a moderate or greater net benefit.Cancer-specific preventive services with an A or B recommendation include breast, cervical, colorectal, and lung cancer screening.Since the implementation of the Affordable Care Act, evidence suggests evidence-based cancer screening has increased in part through the elimination of copayments. 4 This finding is encouraging, given that evidence-based early detection can save lives and can sometimes reduce the cost associated with detection of late-stage disease.
Mitral Annular Disjunction in a Large Cohort of Patients With Mitral Valve Prolapse and Significant Regurgitation
Authors: Valentina Mantegazza, Gloria Tamborini, Manuela Muratori, Paola Gripari, Laura Fusini, Gianpiero Italiano, Valentina Volpato, Valentina Sassi, Mauro Pepi
Journal: JACC. Cardiovascular imaging (2019)
Sex Differences in Grant Funding—Reply
Authors: Teresa K. Woodruff, Diego F. M. Oliveira, Yifang Ma
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury
Authors: Yuan Zhuang, Haifeng C Xu, Prashant V Shinde, Jens Warfsmann, Jelena Vasilevska, Balamurugan Sundaram, Kristina Behnke, Jun Huang, Jessica I Hoell, Arndt Borkhardt, Klaus Pfeffer, Mohamed S Taha, Diran Herebian, Ertan Mayatepek, Dirk Brenner, Mohammad Reza Ahmadian, Verena Keitel, Dagmar Wieczorek, Dieter Häussinger, Aleksandra A Pandyra, Karl S Lang, Philipp A Lang
Journal: Gut (2019)

Objective The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease. Design Mice lacking Fmr1 gene expression were used to study the role of FMRP during tumour necrosis factor (TNF)-induced liver damage in disease model systems. Liver damage and mechanistic studies were performed using real-time PCR, Western Blot, staining of tissue sections and clinical chemistry. Results Fmr1 null mice exhibited increased liver damage during virus-mediated hepatitis following infection with the lymphocytic choriomeningitis virus. Exposure to TNF resulted in severe liver damage due to increased hepatocyte cell death. Consistently, we found increased caspase-8 and caspase-3 activation following TNF stimulation. Furthermore, we demonstrate FMRP to be critically important for regulating key molecules in TNF receptor 1 (TNFR1)-dependent apoptosis and necroptosis including CYLD, c-FLIP S and JNK, which contribute to prolonged RIPK1 expression. Accordingly, the RIPK1 inhibitor Necrostatin-1s could reduce liver cell death and alleviate liver damage in Fmr1 null mice following TNF exposure. Consistently, FMRP-deficient mice developed increased pathology during acute cholestasis following bile duct ligation, which coincided with increased hepatic expression of RIPK1, RIPK3 and phosphorylation of MLKL. Conclusions We show that FMRP plays a central role in the inhibition of TNF-mediated cell death during infection and liver disease.
Multivariate analysis of factors affecting overall survival in minority-based population of young colorectal cancer patients: A single-institution experience.
Authors: Shivi Jain, Kireet Agrawal, Shinoj Pattali, Abhijai Singh, Kamal Agrawal, Barbara Cleveland, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2012)

e14186 Background: Overall survival in colorectal cancer is influenced by obesity, age, gender and stage at diagnosis. However, in minority based populations, effect of the above factors on overall survival has not been studied in any detail. Hence, we undertook this retrospective study to evaluate effect of above factors on overall survival in young colorectal cancer patients. Methods: 1,195 subjects with colorectal cancer treated at John H. Stroger Hospital of Cook County between 2000 and 2008 were retrospectively analyzed. 179 subjects with age 50 years and younger were identified. 146 of 179 subjects with available Body Mass Index (BMI) in kg/m 2 were included in the study. Effect of BMI, age, sex, race, LDH and CEA levels, stage, site of tumor, smoking and family history on overall survival was evaluated using standard statistical multivariate analysis. Results: In our population, 22 of 146(15%) were underweight (BMI&lt;20), 56 of 146(38.4%) were normal weight (BMI 20-24.9), 46 of 146(31.5%) were overweight (BMI 25-29.9) and 22 of 146(15%) were obese (BMI &gt;30). Male: female ratio was 1.4:1. 75 of 146(51.7%) were African American, 23 of 146(15.9%) were Caucasians. 50 of 146(34.2%) were stage IV colorectal cancer at diagnosis. On univariate analysis, BMI&lt;20(p=0.031, HR 2.1, 95% CI 1.15-3.82), CEA &gt;4ng/ml (p=0.005, HR 1.93, 95% CI 1.21-3.08) and stage IV colorectal cancer (p&lt;0.001, HR 6.1, 95% CI 2.42-15.53) were significantly associated with decreased overall survival. LDH&lt;200 U/L was significantly associated with improved overall survival (p 0.029, HR 0.6, 95% CI 0.391-0.950). On multivariate analysis, stage IV colorectal cancer was a single significant independent predictor of overall survival (p=0.001, 95% CI 2.47-27.78). CEA&gt;4ng/ml was marginally significant for decreased overall survival (p=0.06, 95% CI 0.978-3.015). On the contrary, no statistically significant difference was found on overall survival with age, BMI&gt;20, gender, race, tumor location, smoking and family history. Conclusions: Advanced stage and CEA &gt;4ng/ml are independent prognostic variables for decreased overall survival in minority based population of young colorectal cancer.
A pilot study of the effect of atorvastatin on endothelial function and albuminuria in sickle cell disease
Authors: Kenneth I. Ataga, David Wichlan, Laila Elsherif, Vimal K. Derebail, Adane F. Wogu, Poulami Maitra, Jianwen Cai, Melissa C. Caughey, David M. Pollock, Jennifer S. Pollock, David R. Archer, Alan L. Hinderliter
Journal: American Journal of Hematology (2019)
Long-term macrolide antibiotics for the treatment of bronchiectasis in adults: an individual participant data meta-analysis
Authors: James D Chalmers, Wim Boersma, Mike Lonergan, Lata Jayaram, Megan L Crichton, Noel Karalus, Steven L Taylor, Megan L Martin, Lucy D Burr, Conroy Wong, Josje Altenburg
Journal: The Lancet Respiratory Medicine (2019)
Combination analysis between seliciclib (CYC202; R-roscovitine) and other molecularly targeted anti-cancer agents in non-small cell lung cancer
Authors: Ian N. Fleming, Morag Watson, Simon R. Green
Journal: Cancer Research (2006)

3838  Non-small cell lung cancer (NSCLC) is one of the most prevalent forms of cancer and unfortunately still has a very poor outcome despite chemotherapeutic intervention. Almost all forms of lung cancer are associated with defects in the retinoblastoma pathway and several studies have reported that the absence of cyclin dependent kinase inhibitors (CDKi) such as p16, p21 and p27 in NSCLC tumours are all associated with poor prognosis. Likewise in NSCLC the overexpression of cyclin E, an activator of CDK2, is also associated with poor prognosis. Additional studies have shown that overexpression of Bcl-2 family members such as Mcl-1 has been observed in NSCLC, which appears to make cells resistant to chemotherapy-induced apoptosis. Compounds that inhibit CDKs would be potentially interesting to investigate in NSCLC because activity against cell cycle kinases could compensate for the lack of CDKi. Additionally, activity against CDK7 or 9 causes dephos phorylation of RNA polymerase II and thereby decreased transcription, resulting in a rapid reduction in the level of proteins with short half-lives, such as Mcl-1. The first three CDK inhibitors to enter clinical development were Alvocidib (flavopiridol), seliciclib and BMS387032, all of which have been reported to have activity against CDKs 2, 7 and 9 in vitro. Although no objective responses have been reported with these agents in NSCLC patients, stable disease has been achieved in some patients. In the phase II trial of Alvocidib, the median survival of 7.5 months was comparable to that reported for standard cytotoxic chemotherapies. In this study, we have investigated whether the effects of seliciclib in NSCLC can be enhanced by using it in combination with various anti-cancer agents including: established chemotherapeutic agents such as gemcitabine, cisplatin, and docetaxel; epidermal growth factor (EGFR) inhibitors, which have recently been approved for NSCLC treatment and could synergise with seliciclib to downregulate Mcl-1 by inhibiting ERK activation; histone deacetylase (HDAC) inhibitors, since they influence transcription, but via a different mechanism to seliciclib; and the proteosome inhibitor bortezomib, which previously has been reported to synergise with CDK inhibitors. Synergy was assessed using the Chou and Talalay median effect model and determined for both sequential and concurrent treatments. Several of the combinations tested generated significant synergy. The molecular basis for these synergistic interactions has been explored using a range of approaches including flow cytometry and western blot analysis, and appears to involve an enhancement of the pro-apoptotic effects of seliciclib. Data will be presented from these ongoing studies, describing the most significant synergistic combinations and including detailed analysis at the molecular level.