tbuckley/cabot-search huggingface dataset:
Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems
Authors: Lawrence Toll, Michael R. Bruchas, Girolamo Calo', Brian M. Cox, Nurulain T. Zaveri
Journal: Pharmacological Reviews (2016)

The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward. In addition to opioid modulatory actions, NOP receptor activation has important effects on motor function and other physiologic processes. This review discusses how NOP pharmacology intersects, contrasts, and interacts with the mu opioid receptor in terms of tertiary structure and mechanism of receptor activation; location of receptors in the central nervous system; mechanisms of desensitization and downregulation; cellular actions; intracellular signal transduction pathways; and behavioral actions with respect to analgesia, tolerance, dependence, and reward. This is followed by a discussion of the agonists and antagonists that have most contributed to our current knowledge. Because NOP receptors are highly expressed in brain and spinal cord and NOP receptor activation sometimes synergizes with mu receptor-mediated actions and sometimes opposes them, an understanding of NOP receptor pharmacology in the context of these interactions with the opioid receptors will be crucial to the development of novel therapeutics that engage the NOP receptor.
Impact of CMS Competitive Bidding Program on Medicare Beneficiary Safety and Access to Diabetes Testing Supplies: A Retrospective, Longitudinal Analysis
Authors: Gary A. Puckrein, Gail Nunlee-Bland, Farhad Zangeneh, Jaime A. Davidson, Robert A. Vigersky, Liou Xu, Christopher G. Parkin, David G. Marrero
Journal: Diabetes Care (2016)

In 2011, the Centers for Medicare & Medicaid Services (CMS) launched the Competitive Bidding Program (CBP) in nine markets for diabetes supplies. The intent was to lower costs to consumers. Medicare claims data (2009-2012) were used to confirm the CMS report (2012) that there were no disruptions in acquisition caused by CBP and no changes in health outcomes.The study population consisted of insulin users: 43,939 beneficiaries in the nine test markets (TEST) and 485,688 beneficiaries in the nontest markets (NONTEST). TEST and NONTEST were subdivided: those with full self-monitoring of blood glucose (SMBG) supply acquisition (full SMBG) according to prescription and those with partial/no acquisition (partial/no SMBG). Propensity score-matched analysis was performed to reduce selection bias. Outcomes were impact of partial/no SMBG acquisition on mortality, inpatient admissions, and inpatient costs.Survival was negatively associated with partial/no SMBG acquisition in both cohorts (P < 0.0001). Coterminous with CBP (2010-2011), there was a 23.0% (P < 0.0001) increase in partial/no SMBG acquisition in TEST vs. 1.7% (P = 0.0002) in NONTEST. Propensity score-matched analysis showed beneficiary migration from full to partial/no SMBG acquisition in 2011 (1,163 TEST vs. 605 NONTEST) was associated with more deaths within the TEST cohort (102 vs. 60), with higher inpatient hospital admissions and associated costs.SMBG supply acquisition was disrupted in the TEST population, leading to increased migration to partial/no SMBG acquisition with associated increases in mortality, inpatient admissions, and costs. Based on our findings, more effective monitoring protocols are needed to protect beneficiary safety.
Mesangial lupus nephritis with associated nephrotic syndrome.
Authors: N Stankeviciute, W Jao, A Bakir, J P Lash
Journal: Journal of the American Society of Nephrology (1997)

Patients with mesangial proliferative lupus glomerulonephritis (World Health Organization class II) are generally believed to have only mild to moderate proteinuria and normal renal function. However, there have been several reports of patients with mesangial lupus with nephrotic-range proteinuria. In this report, we present two additional cases and review the literature. Of seven reported cases, persistent nephrotic syndrome was observed in four, morphologic transformation occurred in three, and all but one presented with varying degrees of azotemia. These cases reinforce the concept that in systemic lupus erythematosus, laboratory findings may not correlate well with the underlying glomerular lesion, and therefore, the renal biopsy is an essential clinical tool in the approach to lupus nephritis.
Chemotherapy induction followed by preoperative chemoradiation versus preoperative chemoradiation alone in locally advanced rectal cancer (LARC): A randomized controlled phase II study.
Authors: R. Maréchal, B. Vos, M. Polus, T. Delaunoit, M. Peeters, P. Demetter, P. Van Houtte, A. Demols, J. Van de Stadt, J. Van Laethem
Journal: Journal of Clinical Oncology (2010)

3637 Background: Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in LARC. To evaluate the feasibility and efficacy of a short-intense course of induction chemotherapy in LARC patients treated with standard preoperative radiochemotherapy (RCT). Methods: Patients with T2-T4/N+ rectal adenocarcinoma were randomized to Arm A (A): concomitant RCT (45 Gy/25 fr/5weeks + 5-FU in continuous infusion, 250 mg/m2/day) or Arm B (B): two courses of mFOLFOX6 (oxaliplatin: 100 mg/m2; folinic acid 400 mg/m2, 5-FU bolus 400 mg/m2 followed by 2,000 mg/m2 continuous infusion, d1 = d15) followed by RCT (idem A). Surgery was planned 6 to 8 weeks after the end of RCT. Primary endpoint was ypT0-1 stage rate and secondary endpoints were tolerance, toxicity, sphincter preservation rate and tumor regression grade rate. Results: 57 patients from 6 Belgian centers were randomized between 04/2007 and 08/2009 (Arm A/B: 29/28) and evaluated for interim analysis. Patients characteristics (age, sex, performance status, clinical TNM stage, tumor location and size) were well balanced at baseline. Completion of full sequence was similar in both groups: 27/29 (96%, A) vs. 25/28 (88%, B) pts (p = ns). About surgery, there was no significant difference in terms of type, R0 resection, number of lymph nodes resected or invaded, longitudinal and circumferential margin. ypT0-1 stage were reported in 10/29 (34%, A) vs. 8/28 pts (29%, B) (p = ns). T and N downstaging occurred in 14/29 (58%, A), 13/28 (65%, B) and 16/29 (55%, A), 12/28 (43%, B) pts, respectively (p = ns). pCR was observed in 8/29 (27%, A) vs. 7/28 (25%, B) pts (p = ns) and the tumor regression grades (Dworak) distribution was similar. Sphincter preservation was obtained in 67% (A) vs 100% (B) (p = 0.058). Overall grade 3/4 toxicity was significantly higher in chemotherapy induction group: 8% (A) vs. 35% (B) (p = 0.017). Conclusions: Oxaliplatin-based chemotherapy induction is feasible for patients with LARC without compromising the preoperative RCT completion although preliminary results do not indicate increased locoregional impact on standard therapy. No significant financial relationships to disclose.
Colon Epithelium. III. In Vitro Studies of Colon Carcinogenesis in Fischer 344 Rats. &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N′&lt;/italic&gt;-nitro-&lt;italic&gt;N&lt;/italic&gt;-nitrosoguanidine-Induced Changes in Colon Epithelium in Explant Culture&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn5"&gt;5&lt;/xref&gt;
Authors: A K Shamsuddin, B F Trump
Journal: JNCI Journal of the National Cancer Institute (1981)

Colon explants from the inbred F344 rat descending colon pretreated in vivo with azoxymethane and maintained in explant culture were exposed to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). One week after the MNNG treatment, the colon crypts showed marked crowding, hypercellularity, and stratification of cells. Nine weeks after the treatment, the explants showed epithelial papillary projections on the surface epithelium and within the crypts, in addition to hypercellularity and stratification. The control untreated explants maintained a single layer of epithelium during the entire culture period. Ultrastructurally, the treated cells showed an unusual concentration of free polysomes and thin and thick filaments, multiple and bizarre nucleoli, nuclear indentations and pseudoinclusions, and intracellular lumina. Sulfomucin was the predominant component in the control untreated explants as well as in the normal descending colons of rats and humans. One week after treatment the crypts of the carcinogen-treated explants showed an increase in sialomucin, and by 9 weeks after treatment, they showed mostly sialomucin. These features, compared and correlated with those of the parallel in vivo animal model as well as with human material, lend additional support to de novo histogenesis of colon carcinoma.
Effect of Cytosine Arabinoside on the Replication of the Moloney Sarcoma Virus in 3T3 Cell Cultures
Authors: S Z Hirschman, P J Fischinger, J J Zaccari, T E O'Connor
Journal: JNCI Journal of the National Cancer Institute (1969)

Cytosine arabinoside inhibited DNA synthesis, measured by incorporation of thymidine into DNA, in 3T3 cell cultures, but did not affect RNA synthesis, as measured by the incorporation of uridine into RNA. When added to 3T3 cell cultures, cytosine arabinoside inhibited the growth of Moloney murine sarcoma virus (MSV). MSV-infected 3T3 cell cultures treated with either 10−3 M, 10−4 M, or 10−5 M cytosine arabinoside during the first 16 hours of virus growth yielded no detectable virus at 48 hours of incubation. However, some virus was recoverable after 7 days' incubation of the infected 3T3 cell cultures. The inhibition of DNA synthesis in 3T3 cell cultures by cytosine arabinoside was reversed by deoxycytidine; 10−3 M deoxycytidine canceled the effects of 10−5 M cytosine arabinoside both on growth of 3T3 cells and the replication of MSV. The first 48 hours of the growth curve of MSV in 3T3 cell cultures could be closely duplicated by the addition of cytosine arabinoside for 16 hours at various periods during the first 48 hours of viral growth, and measurement of the titer of MSV at 48 hours. It is concluded that MSV depends on DNA synthesis for successful replication in 3T3 cell cultures.
Double-Blind, Placebo-Controlled, Multicenter, Randomized, Phase Ii Study of Nimotuzumab in Combination with Mitomycin, 5-Fluorouracil and Radiation in Immunocompetent Patients with Anal Carcinoma
Authors: U. Pérez González, F.F. Llorente Llano, M. Ramos Suzarte, J.E. Rodríguez Reigosa, B.F. Mestre Fernández, M. Osorio Rodríguez, E.A. Gracia Medina, M.R. Orellana Alvarado, I. Leonard Feliú, Y.T. Ojeda Abizaid, J. Alert Silva, A.M. Ulloa Balmaseda, N.Y. González Barallobre, E. Galá Barrios, N. Curbelo Sevillano, R.B. Jiménez García, B.B. Brunet Flores, M. Cedeño Arias, R. Blanco Santana
Journal: Annals of Oncology (2014)
Depression, depressive symptoms, and depressed mood among a community sample of adolescents
Authors: J H Kashani, G A Carlson, N C Beck, E W Hoeper, C M Corcoran, J A McAllister, C Fallahi, T K Rosenberg, J C Reid
Journal: American Journal of Psychiatry (1987)

Using a structured interview, the authors found that the prevalence of major depression and dysthymic disorder was 4.7% and 3.3%, respectively, in a community sample of 150 adolescents. All of the adolescents who met the criteria for major depression and dysthymic disorder had other psychiatric disorders as well; anxiety was the most frequent accompanying DSM-III diagnosis.
The Nutrition of Animal Tissues Cultivated &lt;italic&gt;In Vitro&lt;/italic&gt;. I. A Survey of Natural Materials as Supplements to Synthetic Medium 199
Authors: J F MORGAN, M E CAMPBELL, H J MORTON
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article The Nutrition of Animal Tissues Cultivated In Vitro. I. A Survey of Natural Materials as Supplements to Synthetic Medium 199 Get access Joseph F. Morgan, Joseph F. Morgan Laboratory of Hygiene, Department of National Health and Welfare, Ottawa, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Elizabeth Campbell, M. Elizabeth Campbell Laboratory of Hygiene, Department of National Health and Welfare, Ottawa, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen J. Morton Helen J. Morton Laboratory of Hygiene, Department of National Health and Welfare, Ottawa, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 2, October 1955, Pages 557–567, https://doi.org/10.1093/jnci/16.2.557 Published: 01 October 1955 Article history Received: 08 April 1955 Published: 01 October 1955
Relationship Between Residential Proximity To Environmental Protection Agency (EPA) Designated Toxic Release Sites and The Risk Of Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Catherine Bulka, Loretta J. Nastoupil, Jean Koff, Leon Bernal, Kevin Ward, Rana Bayakly, Jeffrey Switchenko, Lance Waller, Christopher R. Flowers
Journal: Blood (2013)
Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013
Authors: Tari A. King, Jaclyn P. Lyman, Mithat Gonen, Amy Voci, Marina De Brot, Camilla Boafo, Amy Pratt Sing, E. Shelley Hwang, Michael D. Alvarado, Minetta C. Liu, Judy C. Boughey, Kandace P. McGuire, Catherine H. Van Poznak, Lisa K. Jacobs, Ingrid M. Meszoely, Helen Krontiras, Gildy V. Babiera, Larry Norton, Monica Morrow, Clifford A. Hudis
Journal: Journal of Clinical Oncology (2016)

The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013.
The impact of paracentesis flow rate in patients with liver cirrhosis on the development of paracentesis induced circulatory dysfunction
Authors: Maha Mohammad Elsabaawy, Shimaa Rashad Abdelhamid, Ayman Alsebaey, Eman Abdelsamee, Manar Abdelaal Obada, Tary Abdelhamid Salman, Eman Rewisha
Journal: Clinical and Molecular Hepatology (2015)

See the commentary-article "What we know about paracentesis induced circulatory dysfunction?" on page 349.
Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells
Authors: Hang Xi, Yuling Zhang, Yanjie Xu, William Y. Yang, Xiaohua Jiang, Xiaojin Sha, Xiaoshu Cheng, Jingfeng Wang, Xuebin Qin, Jun Yu, Yong Ji, Xiaofeng Yang, Hong Wang
Journal: Circulation Research (2016)

Rationale: Endothelial injury is an initial mechanism mediating cardiovascular disease. Objective: Here, we investigated the effect of hyperhomocysteinemia on programed cell death in endothelial cells (EC). Methods and Results: We established a novel flow-cytometric gating method to define pyrotosis (Annexin V − /Propidium iodide + ). In cultured human EC, we found that: (1) homocysteine and lipopolysaccharide individually and synergistically induced inflammatory pyroptotic and noninflammatory apoptotic cell death; (2) homocysteine/lipopolysaccharide induced caspase-1 activation before caspase-8, caspase-9, and caspase-3 activations; (3) caspase-1/caspase-3 inhibitors rescued homocysteine/lipopolysaccharide-induced pyroptosis/apoptosis, but caspase-8/caspase-9 inhibitors had differential rescue effect; (4) homocysteine/lipopolysaccharide-induced nucleotide-binding oligomerization domain, and leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) protein caused NLRP3-containing inflammasome assembly, caspase-1 activation, and interleukin (IL)-1β cleavage/activation; (5) homocysteine/lipopolysaccharide elevated intracellular reactive oxygen species, (6) intracellular oxidative gradient determined cell death destiny as intermediate intracellular reactive oxygen species levels are associated with pyroptosis, whereas high reactive oxygen species corresponded to apoptosis; (7) homocysteine/lipopolysaccharide induced mitochondrial membrane potential collapse and cytochrome- c release, and increased B-cell lymphoma 2–associated X protein/B-cell lymphoma 2 ratio which were attenuated by antioxidants and caspase-1 inhibitor; and (8) antioxidants extracellular superoxide dismutase and catalase prevented homocysteine/lipopolysaccharide -induced caspase-1 activation, mitochondrial dysfunction, and pyroptosis/apoptosis. In cystathionine β-synthase–deficient ( Cbs −/− ) mice, severe hyperhomocysteinemia-induced caspase-1 activation in isolated lung EC and caspase-1 expression in aortic endothelium, and elevated aortic caspase-1, caspase-9 protein/activity and B-cell lymphoma 2–associated X protein/B-cell lymphoma 2 ratio in Cbs −/− aorta and human umbilical vein endothelial cells. Finally, homocysteine-induced DNA fragmentation was reversed in caspase-1 −/− EC. Hyperhomocysteinemia-induced aortic endothelial dysfunction was rescued in caspase-1 −/− and NLRP3 −/− mice. Conclusions: Hyperhomocysteinemia preferentially induces EC pyroptosis via caspase-1–dependent inflammasome activation leading to endothelial dysfunction. We termed caspase-1 responsive pyroptosis and apoptosis as pyrop-apoptosis.
Elucidation of the Molecular Mechanisms of Malignant Bone Tumors: Refining Diagnosis and Identifying Novel Targets for Treatment
Authors: Jorge Casas-Ganem, John H. Healey
Journal: Journal of the National Comprehensive Cancer Network (2005)

Primary bone tumors are rare, accounting for less than 0.2% of all cancers diagnosed yearly in the United States. Study of the molecular mechanisms of these diseases has given insight into their pathobiology. It has also identified molecular alterations that, if present, may be used in conjunction with histologic evaluation to further refine diagnosis, allowing cases to be stratified into prognostic groups more or less likely to show response to current cytotoxic protocols. Recent findings have lead to the identification of molecular pathways that may serve as targets of novel therapies, especially in the case of Ewing sarcoma. Telomere maintenance mechanisms are also emerging as potential targets for anticancer therapy. As the molecular mechanisms underlying malignant bone tumors are better understood, new anticancer agents targeting specific pathways are likely to emerge. This may make it possible to tailor treatment for each individual patient, using a combination of cytotoxic and targeted therapies based on the histologic and molecular profile of the patient's tumor.
Abstract 14844: Regional Variations on Cardiovascular Outcomes in Stable Chronic Heart Failure Outpatients at Risk of or With Atherothrombosis - Insights From REACH Registry
Authors: Eri Toda Kato, Philippe Gabriel Steg, Shinya Goto, Jiangping Guo, KyungAh Im, Efrain Gaxiola, E. Magnus Ohman, Kim Eagle, Deepak L Bhatt
Journal: Circulation (2015)

Background: There is a growing recognition of geographic variation for clinical trial outcomes in patients with chronic HF. This study sought to investigate regional variation among patients with a history of HF in a registry population with or at risk for atherothrombosis. Methods: 4 year CV outcomes of chronic HF patients (n=8,962) in Reduction of Atherothrombosis for Continued Health (REACH) Registry, an international, prospective cohort of stable outpatients with established ischemic events (CAD, CVD, and/or PAD) or multiple risk factors for atherothrombosis, were analyzed by geographic regions (North America (NA), Western Europe (WE), Eastern Europe (EE), Latin America (LA), Middle East (ME), and Asia Pacific (AP)). Results: Among 68,236 patients enrolled, 18.1% (n=1,311) of EE patients, 15.0% (n=4,158) of NA patients, 13.9% (n=118) of ME patients, 13.1% (n=2,161) of WE patients, 7.8% (n=150) of LA patients, and 7.6% (n=1,064) of AP patients had a history of HF at baseline. The prevalence of traditional cardiovascular risk factors and the use of medical therapies varied significantly among regions. At 4 year, the rate of CV death, MI, stroke, or hospitalization for HF ranged from 27.1% in AP to 53.4% in ME (p&lt;0.001). Similarly, a significant regional disparity was observed in recurrent HF hospitalization and CV death, however, with a different pattern for CV death (p&lt;0.001 for both, fig.). These differences among regions persisted after adjustment for regional differences in key prognostic variables. Conclusions: This large long term international database demonstrated regional heterogeneity in CV event rates, including hospitalization for heart failure, in patients with or at risk for atherothrombosis and a reported history of heart failure. These findings may have implications for estimating event rates and planning clinical trials of patients with heart failure.
Phase 2 trial of talabostat and docetaxel in patients with stage IIIb/IV NSCLC
Authors: C. Cunningham, D. Richards, R. Salgia, R. Leonard, R. Raju, J. Arseneau, S. Packer, L. Gregoire, E. Haltom, M. J. Uprichard
Journal: Journal of Clinical Oncology (2005)

7120 Background: Talabostat (T) is an oral inhibitor of dipeptidyl peptidases such as fibroblast activation protein found on the stroma of tumors. Administration of T stimulates cytokine and chemokine production in humans and animals. In a mouse xenograft model, T significantly enhanced the activity of docetaxel in the A549 model of NSCLC. Methods: Open-label, single-arm, Phase 2 study in up to 41 evaluable patients with Stage IIIB/IV NSCLC using the Simon 2-stage design. Two responses (PR or CR) by WHO criteria required in the first 21 evaluable patients (defined as completion of 2 cycles with a response assessment by the investigator) to expand enrollment to 41. Up to six 3-week cycles of docetaxel (D) 75mg/m2 (Day1) with appropriate pre-medication and T-200μg administered orally BID Days 2–15. Dose-escalation of T to 300μg BID allowed in subsequent cycles depending on tolerability. Single-agent T may be continued past 6 cycles at the discretion of the investigator. Prior failure of a platinum-based therapy required with no more than 2 prior regimens allowed. ECOG PS 0–1. Primary endpoint is disease response; secondary endpoints include survival, progression-free survival, and incidence of clinically-significant events of neutropenia or anemia. Results: In the first 21 evaluable patients (10 men, 11 women), the median age is 58 (range 34–80); 14 patients had 1 prior treatment and 7 had 2. Partial responses have been seen in 2 patients. The median PFS is 19 weeks. 8 patients have continued on single-agent T beyond 6 cycles, 4 of whom had SD for at least an additional 6 weeks. The most frequently reported adverse events are edema NOS/peripheral (71%), fatigue (57%), neutropenia and leukopenia (each 43%), cough, hypotension, LDH increase, and arthralgia (each 29%). Grade 3/4 events included neutropenia, leukopenia (each 25%), and febrile neutropenia, edema, and dyspnea (all 10%). 6 patients have died during the study; 5 due to PD and one to an unspecified cardiovascular event. Conclusions: In the initial cohort of 21 patients, 2 PRs were reported. The median PFS is 19 weeks. The most common AEs are edema, fatigue, and neutropenia/leukopenia. Enrollment continues. Updated study results for all 41 evaluable patients will be presented at the annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Point Therapeutics Point Therapeutics Point Therapeutics Point Therapeutics