tbuckley/cabot-search huggingface dataset:
The CLASH model in broader life history context
Authors: Jeffry A Simpson, Vladas Griskevicius
Journal: Behavioral and Brain Sciences (2017)

Abstract In this commentary, we address two questions: (1) Is the drive in many young men to gain status and amass resources, which frequently entails direct competition with members of outgroups, one of the key variables underlying the CLASH model? (2) Why is there so much variation in reactive aggression/violence between people living in the same environment?
Assessment of nivolumab benefit–risk profile of a 240-mg flat dose relative to a 3-mg/kg dosing regimen in patients with advanced tumors
Authors: X. Zhao, S. Suryawanshi, M. Hruska, Y. Feng, X. Wang, J. Shen, H.E. Vezina, M.B. McHenry, I.M. Waxman, A. Achanta, A. Bello, A. Roy, S. Agrawal
Journal: Annals of Oncology (2017)

Nivolumab 3 mg/kg every 2 weeks (Q2W) has shown benefit versus the standard of care in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, flat dosing is expected to shorten preparation time and improve ease of administration. With knowledge of nivolumab safety, efficacy, and pharmacokinetics across a wide dose range in body weight (BW) dosing, assessment of the benefit-risk profile of a 240-mg flat dose relative to the approved 3-mg/kg dose was approached by quantitative clinical pharmacology.A flat dose of 240 mg was selected based on its equivalence to the 3-mg/kg dose at the median BW of ∼80 kg in patients in the nivolumab program. The benefit-risk profile of nivolumab 240 mg was evaluated by comparing exposures at 3 mg/kg Q2W and 240 mg Q2W across BW and tumor types; clinical safety at 3 mg/kg Q2W by BW and exposure quartiles in melanoma, NSCLC, and RCC; and safety and efficacy at 240 mg Q2W relative to 3 mg/kg Q2W in melanoma, NSCLC, and RCC.The median nivolumab exposure and its distribution at 240 mg Q2W were similar to 3 mg/kg Q2W in the simulated population. Safety analyses did not demonstrate a clinically meaningful relationship between BW or nivolumab exposure quartiles and frequency or severity of adverse events. The predicted safety and efficacy were similar across nivolumab exposure ranges achieved with 3 mg/kg Q2W or 240 mg Q2W flat dose.Based on population pharmacokinetic modeling, established flat exposure-response relationships for efficacy and safety, and clinical safety, the benefit-risk profile of nivolumab 240 mg Q2W was comparable to 3 mg/kg Q2W. The quantitative clinical pharmacology approach provided evidence for regulatory decision-making on dose modification, obviating the need for an independent clinical study.
Effects of the combination of RAD001and BKM120 on triple-negative breast cancer stem cells.
Authors: Jin Zhang, Yang Zhou, Yunhui Hu, Jingjing Liu, Sheng Zhang
Journal: Journal of Clinical Oncology (2015)

e13507 Background: Diverse cellular processes are closely identified with the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Abundant evidences show that dysregulation of the pathway enhances cancer stem cells (CSCs) characteristics. Therefore it’s therapeutically targeted in breast cancer. Our studys aim to evaluate the antitumor effects of combination therapy by RAD001 (an mTOR inhibitor) and BKM120 (a pan-Class I PI3K inhibitor) on Triple-negative breast cancers (TNBCs). Methods: In vitro, ESA+CD44+CD24-/lowcells were sorted as CSCs using flow cytometry and the inhibitory effects of the drugs were evaluated by MTT assays. The drug effects on CSC population and characteristics were investigated through mammosphere formation assay and colony formation assay. Cell-cycle progression and apoptosis were analyzed. Western blot was used to observe the related protein expression. In vivo, the BALB/c mice were injected with stem cells and different treatments were administered subsequently. After necropsy, the expression of Ki67, CD31, AKT1, and phospho-AKT (Thr308) was analyzed by immunohistochemistry. Results: Treatment with RAD001 or BKM120 reduced viability of total tumor cells, and similar affects were also found in stem cells. Strong synergistic anti-proliferative effect was noted when BKM120 combined with RAD001. Further, BKM120 suppressed expressions of all four class I PI3K isoforms and reversed the high phosphorylation level of Akt induced by RAD001. Both RAD001 and BKM120 reduced tumor growth mainly by inhibiting cell-cycle progression rather than inducing apoptosis. In vivo, BKM120 plus RAD001 was more effective on reducing tumor volume compared with single-agent group in CSCs derived xenografts while not significantly reducing the mice weight. Conclusions: Our experiments provide further evidence that combination of RAD001 and BKM120 exerts augmented activity against tumor cells, including stem cells. Therapeutic alliance inhibits proliferation, abolishes stem cells, resulting in more prominent tumor volume reduction. Given few effective treatments and poor prognosis of TNBCs, combination of PI3K and mTOR inhibitors could be promising option for TNBCs.
Association of intratumoral regulatory T-cell accumulation in patients with hepatocellular carcinoma (HCC) with poor survival: Effect of autologous dendritic cell immunotherapy on selective reduction of regulatory T cells and survival.
Authors: Spiros P. Hiotis, Qin Wang, Wei Luan, Sima Blank, M. Isabel Fiel, Hena Kadri, Leslie Warren
Journal: Journal of Clinical Oncology (2015)

e14023 Background: The immune status of the tumor microenvironment influences tumor progression in HCC. Regulatory T cells (Tregs) inhibit effector cell responses, and play a pivotal role in effective cancer surveillance. This study examines the role on overall survival of intratumoral Tregs in patients with HCC, and evaluates the impact of autologous dendritic cell (DC) immunotherapy on Treg depletion, tumor progression, and overall survival in an orthotopic murine HCC model. Methods: The expression of Foxp3 and CD4 in 63 paired tumor and non-neoplastic liver resection tissue specimens of HCC patients was evaluated using RT-PCR. Orthotopic murine HCC was established by implanting Hepa1-6 cells in the liver. The effect of DC immunotherapy loaded with Hepa1-6 cell lysate on tumor progression, survival, tumor infiltrating lymphocytes and cytokines was examined. Results: High intratumoral Foxp3 expression in HCC patients treated with resection was associated with poor overall survival. DC immunotherapy in HCC bearing mice resulted in reduced Foxp3+CD4+ regulatory T cell accumulation and TGF-b production within the tumor microenvironment. Moreover, DC immunotherapy reversed murine HCC progression, as assessed by plasma a-fetoprotein levels and in vivo bioluminescence imaging, and increased survival to 90% by day 60, as compared to < 5% in untreated tumor-bearing mice. This anti-tumor response was accompanied by inhibition of STAT3 phosphorylation within tumor tissue Conclusions: High levels of intratumoral Tregs in patients undergoing hepatectomy is with associated poor overall survival. Tumor cell lysate-loaded DC immunotherapy results in tumor regression and increased survival in a clinically relevant orthotopic murine HCC model. The inhibitory effect of DC immunotherapy on the accumulation of Foxp3+CD4+ regulatory T cells within the tumor microenvironment and on the production of TGF-b suggests that effective DC immunotherapy can alter the immunosuppressive tumor microenvironment, thus resulting in tumor regression.
Guideline: Insufficient evidence exists on screening for obstructive sleep apnea in asymptomatic adults
Authors: Shirin Shafazand
Journal: Annals of Internal Medicine (2017)

Source Citation Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for obstructive sleep apnea in adults: US Preventive Services Task Force recommendation statement. JAMA. 2017;317:407-14. 28118461
Two Genetic Variants of von Willebrand's Disease
Authors: Lars Holmberg, Inga Marie Nilsson
Journal: New England Journal of Medicine (1973)

A monospecific precipitating antiserum against an antihemophilic-factor-related protein was developed in rabbits. Using an immunochemical technic, we found our 77 patients with von Willebrand's disease to fall into two separate genetic groups, 57 with a low, and 20 patients with a normal content of the protein, conceivably the von Willebrand factor. The major group corresponds to the classic form of von Willebrand's disease with an autosomal and dominant inheritance, but the second type may be X-chromosomally transmitted. In two patients in the second group, infusion of human antihemophilic factor containing fraction l-0 did not produce the retarded increase in antihemophilic factor characteristic of the first group. The second group thus appears to represent a separate disorder different from von Willebrand's disease and hemophilia A but with features resembling both of them.
Late-Life Depression and the Prodromes of Dementia
Authors: David Carl Steffens
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
How Microneedles Can Change Cutaneous Drug Delivery—Small Needles Make a Big Difference
Authors: Hadar Lev-Tov
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
A systematic review of immune-related adverse event (irAE) reporting in clinical trials of immune checkpoint inhibitors (ICIs).
Authors: Wei-Wu Chen, Albiruni R. A. Razak, Philippe L. Bedard, Lillian L. Siu, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2014)

3057 Background: ICIs are active in various solid tumors. irAEs are associated with ICI therapy that can affect multiple organ systems. Limited data exist regarding the quality of irAE reporting in ICI clinical trial publications. Methods: A systematic search of citations from MEDLINE, EMBASE and Cochrane databases identified prospective clinical trials involving ICIs in advanced solid tumors from 2003-2013. A 21-point (pt) (title, abstract, introduction 3 pts; methods 6 pts; results 9 pts and discussion 3 pts) quality score (QS) was adapted from the CONSORT harms extension statement. Items included in the 21-pt QS addressed: methods of irAE assessment; duration of irAE evaluation; time of onset, management, and resolution of irAEs; and consistency of safety reporting with authors’ conclusion. Two reviewers independently scored all trials and differences were resolved by consensus. Linear regression was used to identify factors associated with quality reporting. Results: After review of 2628 articles, 50 trial reports were included (50% phase I, 38% phase II, 6% phase III, and 6% not specified) with ICIs as monotherapy (52%) or combination treatments (48%). The median QS was 11.25 pts (range 3.5-17.5 pts). The median grade 3/4 toxicity rate reported was 20.5% (range 0-66%) and 29/50 (58%) of trials concluded that irAEs were tolerable. Of these 29 studies, 5 had grade 3/4 toxicity rates that exceeded 33%. Thirteen (26%) studies did not report any details on the outcome of irAEs and 22% did not provide information on how irAEs were managed. Six trials concluded that the ICI tested had reversible or manageable irAEs without presenting any data on irAE treatment or resolution. Multivariate regression analysis revealed that year of publication (within last 5 years) and journal impact factor >15 were significantly associated with a higher QS (p=0.002 for both). Conclusions: The reporting of irAEs due to ICIs is often incomplete. A standardized reporting method of irAEs that accounts for tolerability, management and reversibility is needed to ensure completeness and transparency of published trial data. This would enable a more precise evaluation of the therapeutic risk benefit ratio of ICIs.
Prognostic Impact of Low-Flow Severe Aortic Stenosis in Small-Body Patients Undergoing TAVR
Authors: Akihisa Kataoka, Yusuke Watanabe, Ken Kozuma, Yugo Nara, Fukuko Nagura, Hideyuki Kawashima, Hirofumi Hioki, Makoto Nakashima, Masanori Yamamoto, Kensuke Takagi, Motoharu Araki, Norio Tada, Shinichi Shirai, Futoshi Yamanaka, Kentaro Hayashida
Journal: JACC. Cardiovascular imaging (2017)
Protein-Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease
Authors: Akihiro Nomura, Hong-Hee Won, Amit V. Khera, Fumihiko Takeuchi, Kaoru Ito, Shane McCarthy, Connor A. Emdin, Derek Klarin, Pradeep Natarajan, Seyedeh M. Zekavat, Namrata Gupta, Gina M. Peloso, Ingrid B. Borecki, Tanya M. Teslovich, Rosanna Asselta, Stefano Duga, Piera A. Merlini, Adolfo Correa, Thorsten Kessler, James G. Wilson, Matthew J. Bown, Alistair S. Hall, Peter S. Braund, David J. Carey, Michael F. Murray, H. Lester Kirchner, Joseph B. Leader, Daniel R. Lavage, J. Neil Manus, Dustin N. Hartze, Nilesh J. Samani, Heribert Schunkert, Jaume Marrugat, Roberto Elosua, Ruth McPherson, Martin Farrall, Hugh Watkins, Jyh-Ming J. Juang, Chao A. Hsiung, Shih-Yi Lin, Jun-Sing Wang, Hayato Tada, Masa-aki Kawashiri, Akihiro Inazu, Masakazu Yamagishi, Tomohiro Katsuya, Eitaro Nakashima, Masahiro Nakatochi, Ken Yamamoto, Mitsuhiro Yokota, Yukihide Momozawa, Jerome I. Rotter, Eric S. Lander, Daniel J. Rader, John Danesh, Diego Ardissino, Stacey Gabriel, Cristen J. Willer, Goncalo R. Abecasis, Danish Saleheen, Michiaki Kubo, Norihiro Kato, Yii-Der Ida Chen, Frederick E. Dewey, Sekar Kathiresan
Journal: Circulation Research (2017)

Therapies that inhibit CETP (cholesteryl ester transfer protein) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human DNA sequence variants that truncate the
Legal Ramifications of Ambiguous Clinical Guidelines
Authors: Charles G. Kels, Lori H. Kels
Journal: JAMA (2017)

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
Integrating Models of Neurologic and Psychiatric Disease
Authors: David Silbersweig
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
Cloning and Functional Analysis of the Rhesus Macaque ABCG2 Gene: Forced Expression Confers an SP Phenotype among Hematopoietic Stem Cell Progeny in Vivo.
Authors: Takahiro Ueda, Sebastian Brenner, Harry Malech, Saskia Langemeijer, Martha Kirby, Oswald Phang, Allen Krouse, Robert E. Donahue, Elizabeth M. Kang, John F. Tisdale
Journal: Blood (2004)
Challenges of Toxicity Management in Immuno-Oncology
Authors: Stephanie Andrews
Journal: Journal of the National Comprehensive Cancer Network (2017)

Immunotherapies are conveying unprecedented efficacy in some tumor types, but with this success comes challenges in managing toxicities that are distinct from those of cytotoxic agents. Although most immune-related adverse events can be ameliorated by temporarily withholding the drug and administering steroids, grade 3 to 4 toxicities can be challenging and some adverse effects can be long-lasting. NCCN has developed an immunotherapy teaching and monitoring tool that can help in evaluating and managing these autoimmune-mediated inflammatory conditions, which can affect virtually all organ systems.
Oxygen Transport in Man
Authors: Clement A. Finch, Claude Lenfant
Journal: New England Journal of Medicine (1972)

OXYGEN transport is a corporate process involving several organs, each with its own regulatory system. Individual diseases of the heart, lungs or blood may impair the functional capacity of a single component; yet oxygen transport is sustained by adjustments in the remainder of the transport system. This review is an attempt to examine the working relations involved in oxygen transport and the clinical implications of hypoxia.Components of Oxygen SupplyEssential components of the oxygen supply system that may be evaluated are pulmonary gas exchange, blood flow, hemoglobin concentration and hemoglobin affinity for oxygen. In the normal subject this complex . . .
The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy
Authors: Edmund J. Lewis, Lawrence G. Hunsicker, Raymond P. Bain, Richard D Rohde
Journal: New England Journal of Medicine (1993)

Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy.
Correlation of loss of spinophilin expression with increased proliferation and viability as a prognostic factor in patients with hepatocellular carcinoma.
Authors: Anna Lena Ress, Ariane Aigelsreiter, Silvia Schauer, Florian Eisner, Hellmut Samonigg, Carolin Lackner, Johannes Haybaeck, Thomas Bauernhofer, Martin Pichler
Journal: Journal of Clinical Oncology (2013)

e15064 Background: A loss of the putative tumorsuppressor protein spinophilin has been recently involved in the pathogenesis of lung and other carcinoma types. However, a detailed study of the clinical significance and functional cellular effects of spinophilin in hepatocellular carcinoma (HCC) has never been performed. Methods: In this study, we determined for the first time the expression pattern of spinophilin and some of it´s known interacting/down-stream genes (p53, p14ARF, pRB) and proliferation markers (MIB-1 and Cyclin D) in human hepatocellular carcinoma (HCC). The prognostic relevance of spinophilin expression was determined on a cohort of 104 HCC patients who underwent primary tumor resection, followed by functional gene silencing studies. Results: Reduced spinophilin expression was detected by three independent methods (Western blot, RT-PCR and IHC) in a substantial number of patients (70%, p&lt;0.05). Loss of spinophilin expression in HCC tissue was correlated with increased MIB-1 proliferation marker (p=0.01). In terms of clinical outcome, the disease-free survival (DFS) rate was 14.8% and 39.1% (p=0.010) and the cancer-specific survival (CSS) rate was 23.5% and 43.5% (p=0.006) for patients with low and high spinophilin expression, respectively. Multivariate Cox regression analysis identified low expression of spinophilin as an independent poor prognostic factor with respect to DFS (HR=1.8, CI=1.04-3.40, p=0.043) and CSS (HR=2.0, CI=1.1-3.8, p=0.025). Silencing of spinophilin expression in HepG2 cells was associated with increased cellular growth rate (p&lt;0.05). Conclusions: According to our data, the loss of this putative tumor suppressor protein is an independent negative prognosticator for the clinical outcome of HCC patients. Reduced levels of spinophilin expression are associated with higher proliferation rates of HCC cells.