tbuckley/cabot-search huggingface dataset:
Reward and Aversion
Authors: Hailan Hu
Journal: Annual Review of Neuroscience (2016)

To benefit from opportunities and cope with challenges in the environment, animals must adapt their behavior to acquire rewards and to avoid punishments. Maladaptive changes in the neuromodulatory systems and neural circuits for reward and aversion can lead to manifestation of several prominent psychiatric disorders including addiction and depression. Recent progress is pushing the boundaries of knowledge on two major fronts in research on reward and aversion: First, new layers of complexity have been reported on the functions of dopamine (DA) and serotonin (5-HT) neuromodulatory systems in reward and aversion. Second, specific circuit components in the neural pathways that encode reward and aversion have begun to be identified. This review aims to outline historic perspectives and new insights into the functions of DA and 5-HT systems in coding the distinct components of rewards. It also highlights recent advances in neural circuit studies enabled by new technologies, such as cell-type-specific electrophysiology and tracing, and optogenetics-based behavioral manipulation. This knowledge may provide guidance for developing novel treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.
A Woman With Abdominal Pain and Anemia
Authors: Vasileios Mitrousias, Evangelos Alexiou, Anargyros Giaglaras
Journal: JAMA Surgery (2016)

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
Infections in Early Life and Development of Type 1 Diabetes
Authors: Andreas Beyerlein, Ewan Donnachie, Sibille Jergens, Anette-Gabriele Ziegler
Journal: JAMA (2016)

Infections in Early Life and Development of Type 1 DiabetesViral infections, particularly enteroviruses, 1 have been hypothesized to cause type 1 diabetes (T1D). 2 Recent studies suggest that respiratory tract infections are associated with increased T1D risk if they are encountered within the first 6 months. 3 We explored associations between infection types during the first 2 years and between respiratory tract infections in the first 6 months and T1D in a population-based cohort.Methods | The Kassenärztliche Vereinigung Bayern processes claims data for all statutorily insured patients in Bavaria, Germany (approximately 85% of the total Bavarian population).Infants born between 2005 and 2007 were included and observed until March 2015 or last contact with a physician.Diagnoses of infection, T1D, and juvenile idiopathic arthritis (JIA, as a control autoimmune disease) were obtained using International Classification of Diseases, Tenth Revision, codes recorded in 3-month age intervals over 2 years (eg, birth to 2.9 months).Infections were categorized by symptoms (respiratory, gastrointestinal, dermal, and eye) and causes (viral, bacterial, and mycoses).Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals of time to T1D diagnosis by infection event, adjusting for sex and calendar month of birth.Infections were treated as binary time-varying covariates with nonexposure to a specific infection in a quarterly interval as reference category.Kaplan-Meier analysis was used to estimate cumulative risks of T1D and JIA by respiratory tract infections or viral respiratory tract infections in the first 6 months.Differences were assessed by the log-rank test.Statistical analyses were conducted using SAS (SAS Institute), version 9.3, and R (R Foundation), version 3.0.3.Statistical significance was determined at the 5% level (2-sided).
SPECIAL DEPARTMENTS
Authors: Dimitrios H. Roukos, Paraskevi Paraschou, Lluís Cirera
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.16.3061 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10944141 Dimitrios H. RoukosxDimitrios H. RoukosSearch for articles by this author , Paraskevi ParaschouxParaskevi ParaschouSearch for articles by this author Lluís CireraxLluís CireraSearch for articles by this author Show More University Hospital of Ioannina IoanninaGreeceHospital Mútua de Terrassa Terrassa (Barcelona)Spain https://doi.org/10.1200/JCO.2000.18.16.3061 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse16082000In Reply:Drs Roukos and Paraschou emphasize, in reference to our work recently published in the Journal of Clinical Oncology,1 the high survival rates of the control group to 5 years (36%). This survival coincides with the expected survival for a group of patients with stage III disease (American Joint Committee on Cancer, 1983) the results for whom were published in 1985.2 It is not advisable to compare survival when the groups in question do not use the same TNM classification system.Roukos and Paraschou say that it would be of interest to show whether adjuvant chemotherapy was significantly and independently associated with better survival in a Cox regression analysis that included the pN-pT stage. As can be seen in Table 1 of our article,1 primary tumor size was equally distributed in the two comparison groups (P = .35). Therefore, its inclusion in a Cox regression model would not have changed the measure of the treatment effect. On the other hand, as we commented in the article, although nodal status was a significant variable for mortality and for relapse, the imbalance that was observed in nodal status between the two groups in our study (P = .07) did not confound the estimated effect of the treatment. After including the variable nodal status in a multivariate Cox regression model, the estimated effect of the treatment for mortality was 0.59 (range, 0.38 to 0.93) and for relapse was 0.55 (range, 0.36 to 0.84).We are entirely in agreement that the use of adjuvant chemotherapy cannot be definitively recommended for gastric cancer, and this was explicitly stated in our comments. Nevertheless, our results may be of use in defining strategies for future clinical trials. 2. Cirera L, Balil A, Batiste-Alentorn E, et al: Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. J Clin Oncol 17::3810,1999–3815, Link, Google Scholar2. Curtis RE, Kennedy BJ, Myers MH, et al: Evaluation of AJC stomach cancer staging using the SEER Population, Semin Oncol 12::21,1985–31, Google Scholar
Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism
Authors: Lindsay Hollander, Xiaojia Guo, Heino Velazquez, John Chang, Robert Safirstein, Harriet Kluger, Charles Cha, Gary V. Desir
Journal: Cancer Research (2016)

Abstract To sustain their proliferation, cancer cells overcome negative-acting signals that restrain their growth and promote senescence and cell death. Renalase (RNLS) is a secreted flavoprotein that functions as a survival factor after ischemic and toxic injury, signaling through the plasma calcium channel PMCA4b to activate the PI3K/AKT and MAPK pathways. We show that RNLS expression is increased markedly in primary melanomas and CD163+ tumor-associated macrophages (TAM). In clinical specimens, RNLS expression in the tumor correlated inversely with disease-specific survival, suggesting a pathogenic role for RNLS. Attenuation of RNLS by RNAi, blocking antibodies, or an RNLS-derived inhibitory peptide decreased melanoma cell survival, and anti-RNLS therapy blocked tumor growth in vivo in murine xenograft assays. Mechanistic investigations showed that increased apoptosis in tumor cells was temporally related to p38 MAPK-mediated Bax activation and that increased cell growth arrest was associated with elevated expression of the cell-cycle inhibitor p21. Overall, our results established a role for the secreted flavoprotein RNLS in promoting melanoma cell growth and CD163+ TAM in the tumor microenvironment, with potential therapeutic implications for the management of melanoma. Cancer Res; 76(13); 3884–94. ©2016 AACR.
Over-expression of the A<sub>3</sub> adenosine receptor in tumor and PBMC of hepatocellular carcinoma patients: A specific therapeutic target
Authors: P. Fishman, S. Stemmer, D. Castel, A. Ochaion, S. Cohn, F. Barer, A. Zabutti, S. Bar Yehuda
Journal: Journal of Clinical Oncology (2007)

14085 Background: The Gi protein associated A 3 adenosine receptor (A 3 AR) is highly expressed in colon carcinoma tissue and is reflected in peripheral blood mononuclear cells (PBMC) of the patients. Drug candidates with high affinity to the receptor possess anti-cancer effect when administered orally to colon carcinoma bearing animals. The receptor was suggested as a potent therapeutic target and predictive biological marker. Since there is no adequate therapy for Hepatocellular Carcinoma (HCC) we looked at the presence of A 3 AR in tumor and PBMC of HCC patients and tested the efficacy of the A 3 AR agonist, CF102 in an experimental rat HCC model. Methods: mRNA and protein A 3 AR expression level were examined in paraffin embedded slides and PBMC from HCC patients utilizing RT-PCR and Western blot (WB) analysis, respectively. Rat HCC model was established by inoculating N1S1 cells to the animals’ liver. Oral treatment with CF102 was initiated 5 days after tumor inoculation. Signaling proteins in tumor lesions and PBMC from the animals was tested by WB analysis. Results: A 3 AR over-expression was found in tumor and PBMC of HCC patients. Receptor over-expression was attributed to high expression of NF-κB, known to act as a transcription factor of A 3 AR. In the HCC bearing rats, A 3 AR was over-expressed in the tumor tissue and PBMC. Upon treatment with CF102 A 3 AR expression was down-regulated followed by inhibition of tumor size (60%±18.4%, p&lt;0.05). Mechanistically, CF102 de-regulated the NF-κB and Wnt signaling pathways. Conclusions: A 3 AR which is up- regulated in HCC tumors may be suggested as a new target to treat this malignancy and as a biological marker to follow up tumor response to the drug. No significant financial relationships to disclose.
Abstract 198: Noninvasive Approach Assessing Atrial Mechanics and Serum Biomarkers of Collagen Turnover Provides a Surrogate for Fibrosis and Atrial Fibrillation
Authors: Mahek Mirza, Farhan Rizvi, Melissa Albrecht, Anton Strunets, Larisa Emelyanova, Ekhson Holmuhamedov, Paul H. Werner, David C. Kress, Bijoy K. Khandheria, Jasbir Sra, Arshad Jahangir
Journal: Circulation Research (2014)

Introduction: Atrial fibrosis alters myocardial electrophysiological properties, increasing susceptibility to postoperative atrial fibrillation (PoAF); however, its estimation is problematic. We hypothesized that a noninvasive approach using history of AF (HxAF), LA mechanics and serum biomarkers of collagen turnover provides a surrogate for the extent of interstitial atrial fibrosis to identify patients at risk for PoAF. Methods: In patients undergoing cardiac surgery from April-Dec 2013, concentrations of biomarkers reflecting collagen synthesis/degradation and extracellular matrix remodeling were determined in serum from preoperative blood using an enzyme-linked immunosorbent assay, and echocardiographic evaluation was performed using M-mode, 2D, Doppler and 3D speckle tracking. Results: Of 66 patients (68 ±11 y, 67% men), 15 had HxAF and 11 of 51 with no HxAF (22%) developed new onset PoAF. In patients with HxAF, biomarkers for collagen turnover were elevated (Fig A) and correlated with a reduction in LA ejection fraction and global and regional relaxation of the LA wall (p=0.01, Fig B). In patients with no HxAF, procollagen type III (PIIINP) was significantly different in those who developed PoAF (p=0.01) and correlated with reduction in contractility in the posterior LA roof (p=&lt;0.001) with a prolonged time to peak end-diastolic volume (p=0.03). LA size or ventricular structure and function were not different between groups. Conclusion: Surrogate serum and imaging biomarkers correlate with the substrate abnormality that promotes AF. These results need to be validated in larger cohorts to assess the power of these parameters in predicting new onset PoAF.
Knowledge about cancer screening among medical students and residents
Authors: C. Villarreal-Garza, A. R. Villa, M. Perfecto-Arroyo, L. García-Aceituno, M. Rojas-Flores, E. León-Rodríguez
Journal: Journal of Clinical Oncology (2009)

1541 Background: Cancer is the second cause of death worldwide. In certain types of cancer, screening may detect the disease in its early stages, increasing survival. Therefore, it becomes extremely important that physicians are aware of its precise indications. We sought to explore the level of knowledge about cancer screening among Mexican medical students and residents. Methods: A questionnaire-based survey about screening in breast, cervical, colon, and prostate cancer was completed by medical students attending either public or private medical schools, and internal medicine residents from five training centers in Mexico City. The survey included 16 questions regarding tumor markers, beginning of screening, method of early detection, and frequency of screening. Knowledge scores were expressed as percentages. Statistical analysis was performed using two-tailed Fisher's exact test and Kruskal-Wallis test. Results: The survey was answered by 451 individuals, 49.22% male and 50.78% female, with a mean age of 24.3 ± 2.55 years (range 20–33). Medical students comprised 64.52% and residents 35.48%. Mean knowledge score was 63.97 ± 14.97 (range 18.75–100), increasing directly with level of training: medical students obtained a mean score of 60.46 ± 14.09 compared to residents with score of 70.35 ± 14.44 (p = 0.0001). Statistical differences were noted between third (50.00), fourth (62.62) and fifth year (60.19) (p = 0.0001) medical students; while there was no difference between sixth and seventh year students, neither between distinct years of residency. No difference was encountered between private and public schools. Comparing screening knowledge regarding tumor subgroups, residents scored higher than students in relation to tumor markers 65.24 versus 22.82, breast cancer 77.33 versus 69.19, and prostate cancer 75.00 versus 68.53 (p = 0.0001 for the three comparisons); whereas there was no difference in the education concerning cervical and colon cancer screening, 69.44 versus 70.83 (p = 0.518) and 50.61 versus 45.20 (p = 0.114), respectively. Conclusions: Knowledge of screening guidelines is suboptimal among medical students and residents, especially regarding cervical and colon cancer. Further educational efforts should be targeted to educational and training programs in this country. No significant financial relationships to disclose.
A novel liposomal recombinant lipoimmunogen enhances anti-tumor immunity
Authors: Kuan-Yin Shen, Hsin-Yu Liu, Hui-Ju Li, Chiao-Chieh Wu, Gunn-Guang Liou, Yuan-Chih Chang, Chih-Hsiang Leng, Shih-Jen Liu
Journal: Journal of Controlled Release (2016)
“Informed choice” in a time of too much medicine—no panacea for ethical difficulties
Authors: Minna Johansson, Karsten Juhl Jørgensen, Linn Getz, Ray Moynihan
Journal: BMJ (2016)

Providing information to enable informed choices about healthcare sounds immediately appealing to most of us. But <b>Minna Johansson and colleagues</b> argue that preventive medicine and expanding disease definitions have changed the ethical premises of informed choice and our good intentions may inadvertently advance overmedicalisation
Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN)
Authors: Albert J Yoo, Olvert A Berkhemer, Puck S S Fransen, Lucie A van den Berg, Debbie Beumer, Hester F Lingsma, Wouter J Schonewille, Marieke E S Sprengers, René van den Berg, Marianne A A van Walderveen, Ludo F M Beenen, Marieke J H Wermer, Geert J Lycklama à Nijeholt, Jelis Boiten, Sjoerd F M Jenniskens, Joseph C J Bot, Anna M M Boers, Henk A Marquering, Yvo B W E M Roos, Robert J van Oostenbrugge, Diederik W J Dippel, Aad van der Lugt, Wim H van Zwam, Charles B L M Majoie
Journal: The Lancet Neurology (2016)
Evaluation of safety, tolerability and pharmacokinetics (PK) of patupilone in patients (pts) with advanced solid tumors and varying degrees of hepatic function: An open-label phase I study
Authors: T. R. Reid, C. H. Takimoto, C. F. Verschraegen, J. Sarantopoulos, W. Cheung, E. Allen-Freda, J. Li, Y. Xu, J. Ko, A. Johri
Journal: Journal of Clinical Oncology (2008)

2557 Background: Patupilone is a novel epothilone with activity in a wide range of solid tumors. Early phase I studies suggest its systemic levels may be elevated in pts with impaired hepatic function. This study investigates patupilone’s PK profile and optimal doses for varying degrees of hepatic dysfunction. Methods: The study is a multicenter, open-label, 3+3 design for pts with advanced solid tumors and varying degrees of hepatic function: Normal (N), Mildly impaired (M) (T. bilirubin <1.5xULN and SGOT >ULN), and Moderately impaired (Mod) (T. bilirubin >1.5 to 3xULN and any SGOT). Patupilone is given as 10 mg/m2 to pts in N group or as 5 mg/m2 to M group in a single 20-min IV infusion every 3 weeks. PK samples are drawn during cycles 1 and 2. Results: To date 18 pts have enrolled (10 N, 8 M, 0 Mod). Median age is 60 yrs (range 35–79). Median cycles received are 2 (range 1- 14). A DLT (unexplained death) for the M arm lead to this arm’s expansion. The most common reported adverse events (AEs) regardless of relationship were diarrhea 71%, fatigue 41%, nausea 35% and abdominal pain 29%. Most frequent G3/4 AEs reported were diarrhea, GI hemorrhage, and hypokalemia, each 23%, and fatigue, hyponatremia, spinal cord compression and vomiting, each 11%. Of the 16 evaluable pts, 9 (56%) had stable disease: pancreas (3), colon (2) and glioma (1). Preliminary PK data suggest clearance, apparent Vss and elimination t1/2 are similar in both the N and M arm. The mean AUC of the Mild arm at 5mg/m2 (1086 + 410 ng.h/mL, n=3) was approximately half of the Normal (1962 + 469 ng.h/mL, n=9). Conclusions: The pharmacokinetic parameters (clearance, apparent Vss and elimination t1/2) of patupilone were similar between patients with mild hepatic dysfunction at 5 mg/m2 and patients with normal hepatic function at 10 mg/m2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Effect of Chemotherapy With Cyclophosphamide on the Buoyant Density Separation and Volume Distributions of Lymphocytes in Chronic Lymphocytic Leukemia and Lymphosarcoma 2
Authors: Robert M. Zucker, Benedict Cassen
Journal: JNCI Journal of the National Cancer Institute (1974)

Lymphocytes of patients with chronic lymphocytic leukemia (CLL) were separated by bovine serum albumin density gradients and classified by electronic cell volume. Many density populations having differing volume distributions existed in the circulating blood. The density of the lymphocytes was related to cell size and morphologic features. In general, the larger cells with predominantly diffuse chromatin were less dense than the smaller cells with predominantly condensed chromatin. The lymphocyte size distributions revealed that most lymphocytes in CLL patients were smaller than those of hematologically normal individuals, whereas most cells from lymphosarcoma were larger than normal. Combined electronic cell volume analysis and density gradient separation were necessary to observe the populations of small lymphocytes. These small lymphocyte populations were the most sensitive to Cytoxan destruction. Prednisone was nonselective in the destruction of leukemic Iymphocytes.
Lithium in the treatment of depression
Authors: J Mendels
Journal: American Journal of Psychiatry (1976)

The author reviews the studies of lithium as an antidepressant, evaluates the evidence that there might be specific subgroup of patients for whom it is effective, and reports a study he and his associates conducted that found lithium to be effective for 13 of 21 depressed patients. He concludes that there is convincing, although not conclusive, evidence for an antidepressant effect of lithium and that only by identifying the subgroup of patients for whom it is effective can the continuing uncertainty surrounding lithium's role in affective disorder be resolved. He also calls for a reevaluation of the relationship between mania and depression.
Novel Small Molecule Inhibitors Of The Gas6/TAM Signaling Pathway Mediate Synergistic Inhibition Of Platelet Aggregation In Combination With ADP/P2Y Antagonists
Authors: Gilbert Acevedo, Brian R. Branchford, Luke Law, Christine Brzezinski, Susan Sather, Gary Brodsky, Deborah DeRyckere, Weihe Zhang, H. Shelton Earp, Stephen V Frye, Douglas K. Graham, Jorge Di Paola
Journal: Blood (2013)
Small-Molecule Inhibitors of Pendrin Potentiate the Diuretic Action of Furosemide
Authors: Onur Cil, Peter M. Haggie, Puay-wah Phuan, Joseph-Anthony Tan, Alan S. Verkman
Journal: Journal of the American Society of Nephrology (2016)

Pendrin is a Cl-/HCO3- exchanger expressed in type B and non-A, non-B intercalated cells in the distal nephron, where it facilitates Cl- absorption and is involved in Na+ absorption and acid-base balance. Pendrin-knockout mice show no fluid-electrolyte abnormalities under baseline conditions, although mice with double knockout of pendrin and the Na+/Cl- cotransporter (NCC) manifest profound salt wasting. Thus, pendrin may attenuate diuretic-induced salt loss, but this function remains unconfirmed. To clarify the physiologic role of pendrin under conditions not confounded by gene knockout, and to test the potential utility of pendrin inhibitors for diuretic therapy, we tested in mice a small-molecule pendrin inhibitor identified from a high-throughput screen. In vitro, a pyrazole-thiophenesulfonamide, PDSinh-C01, inhibited Cl-/anion exchange mediated by mouse pendrin with a 50% inhibitory concentration of 1-3 µM, without affecting other major kidney tubule transporters. Administration of PDSinh-C01 to mice at predicted therapeutic doses, determined from serum and urine pharmacokinetics, did not affect urine output, osmolality, salt excretion, or acid-base balance. However, in mice treated acutely with furosemide, administration of PDSinh-C01 produced a 30% increase in urine output, with increased Na+ and Cl- excretion. In mice treated long term with furosemide, in which renal pendrin is upregulated, PDSinh-C01 produced a 60% increase in urine output. Our findings clarify the role of pendrin in kidney function and suggest pendrin inhibition as a novel approach to potentiate the action of loop diuretics. Such combination therapy might enhance diuresis and salt excretion for treatment of hypertension and edema, perhaps including diuretic-resistant edema.