tbuckley/cabot-search huggingface dataset:
RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp).
Authors: Josep Tabernero, Allen Lee Cohn, Radka Obermannova, Gyorgy Bodoky, Rocio Garcia-Carbonero, Tudor-Eliade Ciuleanu, David Craig Portnoy, Eric Van Cutsem, Axel Grothey, Jana Prausová, Pilar Garcia-Alfonso, Kentaro Yamazaki, Philip R. Clingan, Vittorina Zagonel, Tae Won Kim, Lorinda Simms, Shao-Chun Chang, Federico Nasroulah, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2015)

512 Background: Angiogenesis is an important therapeutic target in CRC; VEGF plays a key role in angiogenesis. RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The RAISE study evaluated the efficacy and safety of adding RAM to standard second-line treatment FOLFIRI. Methods: Eligible pts with mCRC who progressed on or after first-line combination therapy with bev, ox, and fp, had an ECOG PS of 0 or 1, and adequate organ function were randomized 1:1 (stratified by region, KRAS mutation status, and time to progressive disease [PD] after beginning first-line treatment) to receive RAM (8 mg/kg IV) plus FOLFIRI or PBO plus FOLFIRI every 2 weeks until PD, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Planned sample size of 1,050 pts ensured 85% power to demonstrate statistical significance at an overall two-sided alpha of 0.05, assuming a hazard ratio (HR) of 0.8. Results: Between Dec 2010 and Aug 2013, 1,072 eligible pts were randomized (RAM 536; PBO 536). Baseline pt characteristics were similar between treatment arms. The OS HR was 0.84 (95% CI: 0.73, 0.98; log-rank p=0.0219). Median OS was 13.3months (m) for RAM vs 11.7m for PBO. The PFS HR was 0.79 (95% CI: 0.70, 0.90; log-rank p = 0.0005). Median PFS with RAM was 5.7m and 4.5m for PBO. ORR was 13.4% RAM; 12.5% PBO (p = 0.6336). Subgroup results were consistent with the OS and PFS results. Grade ≥3 adverse events (AEs) occurring in &gt;5% of pts in RAM+FOLFIRI were: neutropenia (RAM 38.4% vs PBO 23.3% ), hypertension (11.2% vs 2.8%), diarrhea (10.8% vs 9.7%), and fatigue (11.5% vs 7.8%). Conclusions: RAISE met its primary end-point, demonstrating a statistically significant improvement in OS for RAM and FOLFIRI vs PBO and FOLFIRI in second-line mCRC pts. Benefits were similar across important clinical subgroups and no unexpected AEs were identified. Clinical trial information: NCT01183780.
Randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed (CPx) versus cisplatin and vinorelbine (CVb): TREAT.
Authors: M. Kreuter, J. F. Vansteenkiste, J. R. Fischer, W. E. E. Eberhardt, H. Zabeck, J. Kollmeier, M. H. Serke, N. Frickhofen, M. Reck, W. Engel-Riedel, S. Neumann, M. Thomeer, C. Schumann, P. Deleyn, T. Graeter, G. Stamatis, I. Zuna, F. Griesinger, M. Thomas
Journal: Journal of Clinical Oncology (2011)

7002 Background: Adjuvant chemotherapy is beneficial in early stage NSCLC, but toxicity and dose delivery are an issue in many patients. Therapy with CPx showed clear activity and good tolerability in advanced NSCLC (Scagliotti, JCO 26:3543,2008). Aim of this phase II trial was to compare dose delivery and clinical feasibility of CPx and CVb in the adjuvant setting. Methods: R0 resected NSCLC patients, stage pIB-T3N1, were randomized to 4 cycles of C(50 mg/m2 d1+8)/Vb(25 mg/m2 d1,8,15,22) q4 weeks (Winton, NEJM 352:2589,2005) or to 4 cycles of C(75 mg/m2)/Px(500 mg/m2)d1 q3 weeks. Primary objective was clinical feasibility (no grade (G) 4 neutro-/thrombocytopenia >7 days or bleeding, no G3/4 febrile neutropenia, no G3/4 non-hematological toxicity; no premature withdrawal; no death). Secondary objectives were drug delivery and efficacy. Results: 132 pts (74% male, mean age 59 years) were randomized (10/06-12/09, 16 sites, majority before Px-label change to non-squamous). Surgery: lobectomy 83%, pneumonectomy 14%, complex resections 3%. Tumor stages: 38% IB, 10% IIA, 47% IIB, 5% pT3pN1; histology: 43% squamous, 57% non-squamous. Feasibility rate was 95.5% (95%CI 87.5-99.1) for CPx compared to 75.4% (63.1-85.2) for CVb (p=0.001). Prevalence of G3/4 toxicities for CPx vs. CVb were: hematological 10% vs. 74% (p<0.001); non-hematological 33% vs. 31% (p=0.798). Delivery of absolute intended dose was higher for CPx (74.6%, 95%CI 62.5-84.5) than for CVb (20.0%, 11.1-31.8) (p<.0001). Mean doses (mg) for CPx were C: 272 (90% of planned, dose density 23 mg/m2/wk) and Px: 1810 (90%, 150 mg/m2/wk); for CVb were C: 263 (66% of planned dose, 16 mg/m2/wk) and V: 256 (64%, 16 mg/m2/wk). Median number of cycles was 4 for CPx (11.2 wks) and 3 for CVb (9.9 wks). Time to withdrawal from therapy differed significantly between arms favoring CPx (p<0.001). During early follow-up (4 months), relapses and deaths occurred in 1 and 1 patient for CPx and in 3 and 2 for CVb. Conclusions: Adjuvant chemotherapy with CPx is safe and feasible with less toxicity and superior dose delivery compared to CVb, mostly due to Vb delivery failure (d 15, 22). For efficacy, longer follow-up data have to be awaited.
Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice
Authors: Clarissa C Parker, Shyam Gopalakrishnan, Peter Carbonetto, Natalia M Gonzales, Emily Leung, Yeonhee J Park, Emmanuel Aryee, Joe Davis, David A Blizard, Cheryl L Ackert-Bicknell, Arimantas Lionikas, Jonathan K Pritchard, Abraham A Palmer
Journal: Nature Genetics (2016)
Gastric Acidity in Cases of Adenomatous Gastric Polyp<xref ref-type="fn" rid="fn1"><sup>1</sup></xref><xref ref-type="fn" rid="fn2"><sup>2</sup></xref>
Authors: Horace E. Cromer, Jr., M. D., Mandred W. Comfort, M. D., Hugh R. Butt, M. D.
Journal: JNCI Journal of the National Cancer Institute (1949)

Gastric Acidity in Cases of Adenomatous Gastric Polyp Get access Horace E. Cromer, Jr., M. D., Horace E. Cromer, Jr., M. D. Fellow in medicine Mayo Foundation Search for other works by this author on: Oxford Academic PubMed Google Scholar Mandred W. Comfort, M. D., Mandred W. Comfort, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hugh R. Butt, M. D. Hugh R. Butt, M. D. Division of Medicine, Mayo Clinic, Rochester, Minn. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 2, October 1949, Pages 497–503, https://doi.org/10.1093/jnci/10.2.497 Published: 01 October 1949
Reinventing doctors
Authors: C. Chantler
Journal: BMJ (1998)

This is not a happy Christmas for our profession or indeed for many doctors. Doctors work extremely long hours under difficult conditions and many are demoralised by lack of resources and constant criticism. We feel proud of the advances in medical science and find it difficult to understand when patients complain because our efforts are not always effective. Much of the recent poor publicity has originated from the reporting of cases before the General Medical Council. It is ironic that these demonstrations of self regulation should lead to criticism of the system of self regulation by both the public and politicians. Now the government is introducing legislation to ensure the quality of clinical services and to make the profession more accountable.

Last year Professor Roy Porter published a history of medicine entitled The Greatest Benefit to Mankind, which was Samuel Johnson's accolade to the medical profession.1 Porter points out that we are healthier than ever before yet more distrustful of doctors and the “medical system.” As he writes, such ambiguity is not new, but we need to attempt to understand it.

Much of medicine and medical practice has changed during the past generation. Modern medicine is complicated and often uncertain. For example, babies born at less than 28 weeks' gestation are now routinely ventilated and, though more survive, around a quarter of those who do have disabilities and 10% are severely handicapped.2 Given that about 1% of pregnancies result in premature delivery are we sure that parents are fully informed of …
Diagnostic Features and 2-Hydroxyglutarate (2-HG) Levels Among Acute Myeloid Leukemia (AML) Patients with and without Isocitrate Dehydrogenase (IDH) Mutations
Authors: Andrew M. Brunner, Seth A. Wander, Donna Neuberg, Hossein Sadrzadeh, Karen K. Ballen, Philip C. Amrein, Eyal C. Attar, Yi-Bin Chen, Ashley M. Perry, Meghan Burke, Regina Silver, Sophia Adamia, Katharine Yen, Hua Yang, Kimberly Straley, Sam Agresta, Darrell R. Borger, Anthony J. Iafrate, Richard M. Stone, Amir T. Fathi
Journal: Blood (2014)
P-169 Outcomes of metastatic gastroesophageal cancer patients treated with third line therapy: a 5-year retrospective analysis at a single centre
Authors: C. Lam Justina Yick, C. Ng, E. Ee Samuel Cheng, P. Choo Su, K. Ong Simon Yew, C. Toh Han, H. Koo Wen, H. Tan Iain Bee, K. Tham Chee, D. Tai, H. Teo Patrick Tze
Journal: Annals of Oncology (2016)
Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition
Authors: Ramkumar Menon, Elizabeth A Bonney, Jennifer Condon, Sam Mesiano, Robert N Taylor
Journal: Human Reproduction Update (2016)

The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments. In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes.
Tissue Culture as a Tool for Studying the Development of Autonomy in Neoplastic Plant Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: A C BRAUN
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Tissue Culture as a Tool for Studying the Development of Autonomy in Neoplastic Plant Cells Get access Armin C. Braun Armin C. Braun The Rockefeller Institute for Medical Research, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 4, October 1957, Pages 753–769, https://doi.org/10.1093/jnci/19.4.753 Published: 01 October 1957 Article history Received: 28 May 1957 Published: 01 October 1957
Fossil Tumor Creates Interest in Prehistoric Cancer
Authors: M E Newman
Journal: JNCI Journal of the National Cancer Institute (1991)

Fossil Tumor Creates Interest in Prehistoric Cancer Get access JNCI: Journal of the National Cancer Institute, Volume 83, Issue 18, 18 September 1991, Pages 1289–1290, https://doi.org/10.1093/jnci/83.18.1289 Published: 18 September 1991
Sunscreen Product Performance and Other Determinants of Consumer Preferences
Authors: Shuai Xu, Michael Kwa, Ashwin Agarwal, Alfred Rademaker, Roopal V. Kundu
Journal: JAMA Dermatology (2016)

Sunscreen use is a modifiable behavior that can help reduce the risk for skin cancer, prevent sunburns, mitigate photoaging, and treat photosensitive dermatoses. A better understanding of consumer sunscreen preferences would inform dermatologists in their own recommendations.To determine the characteristics and the most commonly cited positive and negative features of highly rated sunscreens described by consumers.The top 1 percentile of sunscreen products on Amazon.com as of December 2015 was selected according to average consumer review (≥4 stars) and the highest number of consumer reviews. Descriptive data for each product were collected from the product page and manufacturer claims. The top 5 "most helpful" reviews (positive and critical) were analyzed and coded by a consensus qualitative coding scheme, which included positive and negative descriptors in 6 major categories according to consumer comments: affordability, cosmetic elegance, separate ratings, product ingredients, product performance, and skin compatibility.The Kruskal-Wallis test was performed to determine whether characteristics of each product (eg, American Academy of Dermatology [AAD] criteria, sun protection factor [SPF], or vehicle) could be used to predict price per ounce. The number (percentage) of comments categorized by major themes and subthemes was determined. Illustrative consumer comments were also collected.There were 6500 products categorized as sunscreens in the Amazon.com, online catalog. Of the 65 products evaluated, the median price per ounce was $3.32 (range, $0.68-$23.47). Of products, 40% (26 of 65) did not adhere to AAD guidelines (broad spectrum, SPF ≥30, and water resistant) for sunscreens. Vehicles, AAD, and sunscreen type predicted a higher price per ounce. Cosmetic elegance was the most cited positive feature (198 of 325 [61%] comments) followed by product performance (146 of 325 [45%] comments) and skin type compatibility (78 of 325 [24%] comments).In this cohort of highly rated sunscreen products, a significant proportion did not adhere to AAD guidelines, mostly attributable to a lack of water resistance. The most striking variation in this cohort was price, which varied by more than 3000%. Dermatologists should balance the importance of cosmetic elegance, cost, and AAD guidelines for sun protection in making their recommendations to consumers.
Bortezomib Resistance in Mantle Cell Lymphoma Is Associated with Expression of a Plasmacytoid Differentiation Program.
Authors: Patricia Perez Galan, Helena Mora Jensen, Marc A Weniger, Colby M Chapman, Poching Liu, Nalini Raghavachari, Arthur L Shaffer, Louis M. Staudt, Adrian Wiestner
Journal: Blood (2009)
Bones and joints
Authors: E. B. Silberstein
Journal: Clinical Nuclear Medicine (1998)

This chapter describes the use of beta- or electron-emitting radiopharmaceuticals for treating several painful musculoskeletal conditions. These radiopharmaceuticals emit negatively charged particles (beta particles or electrons) with a maximum range of approximately 1–11 mm (Tables 1.1 and 1.2), which can cause sub-lethal or lethal damage to cells by interacting with their DNA [1]. Radionuclide therapy, by eliminating the targeted cells responsible for tissue damage and the resultant pain, provides marked clinical benefit to the patient.KeywordsRadionuclide TherapyFerric HydroxideSynovial LiningOsseous MetastasisRadiation SynovectomyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
The Ikaros family of zinc-finger proteins
Authors: Yingzhi Fan, Duo Lu
Journal: Acta Pharmaceutica Sinica B (2016)

Ikaros represents a zinc-finger protein family important for lymphocyte development and certain other physiological processes. The number of family members is large, with alternative splicing producing various additional isoforms from each of the five homologous genes in the family. The functional forms of Ikaros proteins could be even more diverse due to protein-protein interactions readily established between family members. Emerging evidence suggests that targeting Ikaros proteins is feasible and effective in therapeutic applications, although the exact roles of Ikaros proteins remain elusive within the intricate regulatory networks in which they are involved. In this review we collect existing knowledge as to the functions, regulatory pathways, and molecular mechanisms of this family of proteins in an attempt to gain a better understanding through the comparison of activities and interactions among family members.
Stepping closer to treating Alzheimer’s disease patients with BACE1 inhibitor drugs
Authors: Riqiang Yan
Journal: Translational Neurodegeneration (2016)

Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disease which impairs cognitive function and gradually causes patients to be unable to lead normal daily lives. While the etiology of AD remains an enigma, excessive accumulation of β-amyloid peptide (Aβ) is widely believed to induce pathological changes and cause dementia in brains of AD patients. BACE1 was discovered to initiate the cleavage of amyloid precursor protein (APP) at the β-secretase site. Only after this cleavage does γ-secretase further cleave the BACE1-cleaved C-terminal APP fragment to release Aβ. Hence, blocking BACE1 proteolytic activity will suppress Aβ generation. Due to the linkage of Aβ to the potential cause of AD, extensive discovery and development efforts have been directed towards potent BACE1 inhibitors for AD therapy. With the recent breakthrough in developing brain-penetrable BACE1 inhibitors, targeting amyloid deposition-mediated pathology for AD therapy has now become more practical. This review will summarize various strategies that have successfully led to the discovery of BACE1 drugs, such as MK8931, AZD-3293, JNJ-54861911, E2609 and CNP520. These drugs are currently in clinical trials and their updated states will be discussed. With the promise of reducing Aβ generation and deposition with no alarming safety concerns, the amyloid cascade hypothesis in AD therapy may finally become validated.
Key Elements for Judging the Quality of a Risk Assessment
Authors: Penelope A. Fenner-Crisp, Vicki L. Dellarco
Journal: Environmental Health Perspectives (2016)

Many reports have been published that contain recommendations for improving the quality, transparency, and usefulness of decision making for risk assessments prepared by agencies of the U.S. federal government. A substantial measure of consensus has emerged regarding the characteristics that high-quality assessments should possess.The goal was to summarize the key characteristics of a high-quality assessment as identified in the consensus-building process and to integrate them into a guide for use by decision makers, risk assessors, peer reviewers and other interested stakeholders to determine if an assessment meets the criteria for high quality.Most of the features cited in the guide are applicable to any type of assessment, whether it encompasses one, two, or all four phases of the risk-assessment paradigm; whether it is qualitative or quantitative; and whether it is screening level or highly sophisticated and complex. Other features are tailored to specific elements of an assessment. Just as agencies at all levels of government are responsible for determining the effectiveness of their programs, so too should they determine the effectiveness of their assessments used in support of their regulatory decisions. Furthermore, if a nongovernmental entity wishes to have its assessments considered in the governmental regulatory decision-making process, then these assessments should be judged in the same rigorous manner and be held to similar standards.The key characteristics of a high-quality assessment can be summarized and integrated into a guide for judging whether an assessment possesses the desired features of high quality, transparency, and usefulness.Fenner-Crisp PA, Dellarco VL. 2016. Key elements for judging the quality of a risk assessment. Environ Health Perspect 124:1127-1135; http://dx.doi.org/10.1289/ehp.1510483.
A phase (Ph) Ib study of irinotecan (IRI), levofolinate (LV), and 5-fluorouracil (5-FU) (FOLFIRI) plus ramucirumab (RAM; IMC-1121B) drug product in Japanese (JP) patients (pts) with metastatic colorectal carcinoma (mCRC) progressive during or following first-line therapy with bevacizumab (BEV), oxaliplatin (OXALI), and a fluoropyrimidine (FP) (CP12-1029/NCT01286818).
Authors: Takayuki Yoshino, Kentaro Yamazaki, Motoki Yoshida, Mark Daniel Rutstein, Naoto Yoshizuka, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2013)

591 Background: Vascular endothelial growth factor (VEGF) and the VEGF receptor-2 (VEGFR-2) regulate angiogenesis and are overexpressed in CRC. RAM is a fully human IgG1 monoclonal antibody VEGF-receptor 2 antagonist. We assessed the safety of RAM + FOLFIRI among JP mCRC pts. Methods: Eligible pts had measurable or nonmeasurable disease, ECOG PS 0-1 with disease progression during or within 6 mos following 1st-line therapy with BEV, OXALI, and a FP. Pts received 8 mg/kg RAM IV every 2 wks + FOLFIRI (IRI: 180 mg/m 2 , LV: 200 mg/m 2 , 5-FU: 400 mg/m 2 bolus followed by 2400 mg/m 2 continuous infusion over 46-48 hrs). Dose-limiting toxicities (DLTs) were assessed Cycle 1 Day 1 to Cycle 3 Day 1. We assessed the safety of RAM + FOLFIRI among JP mCRC pts to support the participation of Japan in a global Ph 3 mCRC study. Results: 6 pts were treated; all pts completed study as of 3/19/2012. Median age was 62 yrs (range 48-71). 4 pts had colon cancer and 2 pts had rectal cancer . 1 of 6 pts experienced a DLT (Grade [G] 2 proteinuria and G4 neutropenia resulting in dose delay &gt;2 wks). All 6 pts (100%) experienced at least one G3 adverse event (AE): neutropenia (5 pts; 83%), proteinuria (2 pts; 33%), anemia, thrombocytopenia, hypertension (1 pt each, 17%). 3 pts (50%) experienced G4 neutropenia. 2 pts discontinued (D/C) RAM due to G2 and G3 proteinuria, respectively; 1 pt D/C FOLFIRI due to G3 neutropenia. There were no serious AEs or deaths. Best overall response: 1 PR (17%), 4 SD (67%), 1 PD (17%). Median PFS: 7.3m (range: 1.25-10.91m; 95% CI: 1.2 – 10.9). As of 9/24/2012, 57 JP pts have been enrolled into ongoing P3 study I4T-MC-JVBB. Conclusions: RAM + FOLFIRI were reasonably tolerated and demonstrated anti-tumor activity in JP mCRC pts previously treated with BEV, OXALI, and a FP. The incidence of proteinuria in this small cohort of JP pts appears higher than that observed in other studies evaluating RAM to date. These safety data supported the enrollment of JP pts into an ongoing global P3 mCRC study. Clinical trial information: NCT01286818.