tbuckley/cabot-search huggingface dataset:
Genomic Response to Selection for Predatory Behavior in a Mammalian Model of Adaptive Radiation
Authors: Mateusz Konczal, Paweł Koteja, Patrycja Orlowska-Feuer, Jacek Radwan, Edyta T. Sadowska, Wiesław Babik
Journal: Molecular Biology and Evolution (2016)

If genetic architectures of various quantitative traits are similar, as studies on model organisms suggest, comparable selection pressures should produce similar molecular patterns for various traits. To test this prediction, we used a laboratory model of vertebrate adaptive radiation to investigate the genetic basis of the response to selection for predatory behavior and compare it with evolution of aerobic capacity reported in an earlier work. After 13 generations of selection, the proportion of bank voles (Myodes [=Clethrionomys] glareolus) showing predatory behavior was five times higher in selected lines than in controls. We analyzed the hippocampus and liver transcriptomes and found repeatable changes in allele frequencies and gene expression. Genes with the largest differences between predatory and control lines are associated with hunger, aggression, biological rhythms, and functioning of the nervous system. Evolution of predatory behavior could be meaningfully compared with evolution of high aerobic capacity, because the experiments and analyses were performed in the same methodological framework. The number of genes that changed expression was much smaller in predatory lines, and allele frequencies changed repeatably in predatory but not in aerobic lines. This suggests that more variants of smaller effects underlie variation in aerobic performance, whereas fewer variants of larger effects underlie variation in predatory behavior. Our results thus contradict the view that comparable selection pressures for different quantitative traits produce similar molecular patterns. Therefore, to gain knowledge about molecular-level response to selection for complex traits, we need to investigate not only multiple replicate populations but also multiple quantitative traits.
Health-related quality of life in locally advanced and metastatic breast cancer: methodological and clinical issues in randomised controlled trials
Authors: Irina Ghislain, Efstathios Zikos, Corneel Coens, Chantal Quinten, Vasiliki Balta, Konstantinos Tryfonidis, Martine Piccart, Dimitrios Zardavas, Eva Nagele, Vesna Bjelic-Radisic, Fatima Cardoso, Mirjam A G Sprangers, Galina Velikova, Andrew Bottomley
Journal: The Lancet Oncology (2016)
PD-024 Retrospective analysis of quality of life and early tumour shrinkage during first-line FOLFOX4 ± panitumumab in RAS wild-type metastatic colorectal carcinoma
Authors: S. Siena, J. Tabernero, G. Bodoky, D. Cunningham, F. Rivera, P. Ruff, J.-L. Canon, R. Koukakis, G. Demonty, J.-Y. Douillard
Journal: Annals of Oncology (2016)
Neoadjuvant q4week carboplatin and weekly paclitaxel ± trastuzumab in resectable and locally advanced breast cancer: A Brown University Oncology Group (BrUOG) study
Authors: L. M. Ries, M. A. Fenton, D. S. Dizon, J. S. Gass, T. A. Graves, R. S. Strenger, W. M. Sikov
Journal: Journal of Clinical Oncology (2005)

759 Background: In resectable breast cancer (BrCa), pathologic complete response (pCR) to anthracycline-based neoadjuvant chemotherapy (NAC) reduces risk of recurrence and death. Adding a taxane increases pCRs, and weekly (wkly) paclitaxel (P) is more active than q3wk P in this setting (M Green, ASCO 2002). In advanced BrCa, adding carboplatin (Cb) to P enhances activity, as does, in HER2+ pts, adding wkly trastuzumab (T) to single agent P or Cb to the combination of P and T. We are studying a novel NAC regimen based on these observations. Methods: Eligible pts are stratified by extent of disease, resectable (Stage IIA-IIIA) vs. unresectable (Stage IIIB-C), and HER2 status (determined by FISH). Biopsy of suspicious lymph nodes (LN) and pre-NAC sentinel LN sampling in clinical/radiographic N0 pts are encouraged. Pts receive Cb AUC 6 q4wks and P 80 mg/m2 wkly X 16 wks, with T (4 mg/kg wk 1, then 2 mg/kg wkly) if HER2+, followed by surgery, with LN sampling unless preop SLN(-). Post-op therapy is at the discretion of the treating physicians. The study is powered to detect a pCR rate of >25% in resectable pts. Results: As of 11/2004, 48 pts were enrolled. 29 had completed NAC and surgery - median age 48 (31–74), median doses of NAC received = 16. Doses were held for ANC<800 (9) and plts<100,000 (6). The P dose was reduced in 2 pts for grade (gr) 2 peripheral neuropathy. Febrile neutropenia has not been reported. Gr 3/4 toxicities include ANC 9/2, plts 3/0, nausea 2/0, anemia 2/0, LFTs 2/0, and diarrhea 1/0. pCRs (in breast and axillary LN) are as follows: (pCRs include 2 pts each with scattered individual tumor cells in the breast or a micrometastasis in a single LN and 4 pts with residual DCIS) Conclusions: Preliminary pCR data demonstrate significant activity for this well-tolerated NAC regimen, despite the absence of an anthracycline, especially in the small cohort of HER2+ pts who also receive trastuzumab. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
Results of a Phase 2 NCI Multicenter Study of Romidepsin in Patients with Relapsed Peripheral T-Cell Lymphoma (PTCL).
Authors: Richard Piekarz, John Wright, Robin Frye, Steven L. Allen, Michael Craig, Larisa Geskin, Laura Hutchins, David Joske, Mark Kirschbaum, John P Leonard, Miles Prince, Craig B. Reeder, Elaine Jaffe, Susan Bates
Journal: Blood (2008)
Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study
Authors: P Moreau, D Joshua, W-J Chng, A Palumbo, H Goldschmidt, R Hájek, T Facon, H Ludwig, L Pour, R Niesvizky, A Oriol, L Rosiñol, A Suvorov, G Gaidano, T Pika, K Weisel, V Goranova-Marinova, H H Gillenwater, N Mohamed, S Aggarwal, S Feng, M A Dimopoulos
Journal: Leukemia (2016)

The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ⩾2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one prior line), 72.0 vs 59.7% (⩾2 prior lines), 71.2 vs 60.3% (prior bortezomib) and 70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines subgroups was qualitatively similar to that in the broader ENDEAVOR population. In RMM, outcomes are improved when receiving treatment with carfilzomib compared with bortezomib, regardless of the number of prior therapy lines or prior exposure to bortezomib or lenalidomide.
The Doppelgänger Effect: Hidden Duplicates in Databases of Transcriptome Profiles
Authors: Levi Waldron, Markus Riester, Marcel Ramos, Giovanni Parmigiani, Michael Birrer
Journal: JNCI Journal of the National Cancer Institute (2016)

Whole-genome analysis of cancer specimens is commonplace, and investigators frequently share or re-use specimens in later studies. Duplicate expression profiles in public databases will impact re-analysis if left undetected, a so-called "doppelgänger" effect. We propose a method that should be routine practice to accurately match duplicate cancer transcriptomes when nucleotide-level sequence data are unavailable, even for samples profiled by different microarray technologies or by both microarray and RNA sequencing. We demonstrate the effectiveness of the method in databases containing dozens of datasets and thousands of ovarian, breast, bladder, and colorectal cancer microarray profiles and of matching microarray and RNA sequencing expression profiles from The Cancer Genome Atlas (TCGA). We identified probable duplicates among more than 50% of studies, originating in different continents, using different technologies, published years apart, and even within the TCGA itself. Finally, we provide the doppelgangR Bioconductor package for screening transcriptome databases for duplicates. Given the potential for unrecognized duplication to falsely inflate prediction accuracy and confidence in differential expression, doppelgänger-checking should be a part of standard procedure for combining multiple genomic datasets.
Phosphatase and tensin homolog ( PTEN ) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome–like immunodeficiency
Authors: Yuki Tsujita, Kanako Mitsui-Sekinaka, Kohsuke Imai, Tzu-Wen Yeh, Noriko Mitsuiki, Takaki Asano, Hidenori Ohnishi, Zenichiro Kato, Yujin Sekinaka, Kiyotaka Zaha, Tamaki Kato, Tsubasa Okano, Takehiro Takashima, Kaoru Kobayashi, Mitsuaki Kimura, Tomoaki Kunitsu, Yoshihiro Maruo, Hirokazu Kanegane, Masatoshi Takagi, Kenichi Yoshida, Yusuke Okuno, Hideki Muramatsu, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seiji Kojima, Seishi Ogawa, Osamu Ohara, Satoshi Okada, Masao Kobayashi, Tomohiro Morio, Shigeaki Nonoyama
Journal: Journal of Allergy and Clinical Immunology (2016)
Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma
Authors: Avery D. Posey, Robert D. Schwab, Alina C. Boesteanu, Catharina Steentoft, Ulla Mandel, Boris Engels, Jennifer D. Stone, Thomas D. Madsen, Karin Schreiber, Kathleen M. Haines, Alexandria P. Cogdill, Taylor J. Chen, Decheng Song, John Scholler, David M. Kranz, Michael D. Feldman, Regina Young, Brian Keith, Hans Schreiber, Henrik Clausen, Laura A. Johnson, Carl H. June
Journal: Immunity (2016)
Genes Associated with Alloimmunization to Blood Group Antigens in Sickle Cell Disease
Authors: Jacqueline N. Milton, Allison E. Ashley-Koch, Melanie E. Garrett, Karen L. Soldano, Eugene P. Orringer, Paola Sebastiani, Daniel A. Dworkis, Karen Quillen, Martin H. Steinberg, Marilyn J. Telen
Journal: Blood (2014)
Phase I/II, open-label study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) as monotherapy or combined with ipilimumab in advanced or metastatic solid tumors.
Authors: Margaret K. Callahan, Johanna C. Bendell, Emily Chan, Michael Morse, Rathi Narayana Pillai, Petri Bono, Dirk Jaeger, T.R. Jeffry Evans, Ian Chau, Emiliano Calvo, Dung T. Le, Patrick Alexander Ott, Matthew Hiram Taylor, Padmanee Sharma, Scott Joseph Antonia, Brian Sharkey, Olaf Christensen, Asim Amin
Journal: Journal of Clinical Oncology (2014)

TPS3114 Background: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, and ipilimumab, a fully human IgG1 cytotoxic T-lymphocyte antigen-4 receptor (CTLA-4) blocking antibody, have shown antitumor activity and durable responses in patients (pts) with solid tumors including melanoma, renal cell cancer and non-small cell lung cancer. Preclinical and clinical data indicate that combined PD-1 and CTLA-4 blockade may improve antitumor activity. We hypothesize that nivolumab alone or combined with ipilimumab may have activity in additional solid tumor types. We describe a phase I/II signal detection, open-label study to analyze the safety and efficacy of these agents in locally advanced or metastatic triple-negative breast, small-cell lung, gastric or pancreatic cancer—areas of significant unmet medical need. Methods: The primary and secondary objectives of this study are objective response (OR) rate and safety, respectively. Exploratory objectives include progression-free survival, overall survival, immunogenicity, pt-reported global health outcomes, and analysis of pharmacodynamic activity of nivolumab alone or combined with ipilimumab in peripheral blood and tumor tissue. Additionally, evaluation of putative biomarkers such as PD-1 ligand (PD-L1) expression will be performed. The study uses a modified Simon 2-stage design. In stage 1, 36 pts for each tumor type will be assigned 1:1 to treatment with either nivolumab 3 mg/kg IV Q2W (arm N), or nivolumab 1 mg/kg + ipilimumab 3 mg/kg IV Q3W for 4 doses then nivolumab 3 mg/kg IV Q2W (arm N+I), until progression or toxicity. Responses will be assessed using RECIST criteria at wks 6, 12, 18, 24 and then Q12W. Treatment arms will proceed independently into stage 2 if ≥2 pts in a given arm for each tumor type have an OR. In stage 2, an additional 22 pts per tumor type will be assigned to each arm (N or N+I) and receive the stage 1 dosing regimen. Key eligibility criteria include ECOG status ≤1, available fresh or archival tumor tissue, measurable disease by CT or MRI (RECIST 1.1), and adequate bone marrow, liver and renal function. Clinical trial information: NCT01928394.
The BET Inhibitor OTX015 (MK-8628) Shows in Vivo Antitumor Activity in Combination with Additional Targeted Agents in Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Eugenio Gaudio, Luciano Cascione, Maurilio Ponzoni, Chiara Tarantelli, Elena Bernasconi, Maria Eugenia Riveiro, Esteban Cvitkovic, Emanuele Zucca, Francesco Bertoni
Journal: Blood (2015)
Clinical experience with uridine triacetate for 5-FU overexposure: An update.
Authors: Michael K. Bamat, Robert Tremmel, Reid von Borstel, Joan Helton
Journal: Journal of Clinical Oncology (2013)

e20592 Background: 5-Fluorouracil (5-FU) is broadly used to treat solid tumors. It is typically administered by IV infusion, at or near its maximum tolerated dose, over several days. The use of infusion pumps increases the possibility of life-threatening or lethal toxicity due to errors in pump programming, infusion reservoir errors and dosage miscalculations. Partial or total dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients (up to 3% of the population) to impaired 5-FU elimination, can also result in serious or lethal toxicity, Uridine triacetate is an orally bioavailable direct biochemical antagonist of 5-FU toxicity that has been used successfully to treat patients in emergency overdose situations as well as patients with known or suspected overexposure to 5-FU due to DPD deficiency or other causes. Approximately 100 patients at excess risk of 5-FU toxicity due to 5-FU overdose, accidental Xeloda (capecitabine) ingestion, or possible DPD deficiency (rapid onset of severe toxicities) have been treated with uridine triacetate using a common treatment regimen and protocol. More than 80 of these cases have occurred since uridine triacetate data were presented at ASCO in 2009. Methods: Uridine triacetate was provided under emergency IND provisions or an expanded access protocol when requested by qualified clinical sites following 5-FU overexposures, most due to infusion pump errors. Patients received uridine triacetate (10g q6h for 20 doses) as soon as possible after recognition of the overdose or possible clearance defect. Clinical outcomes, including safety and resumption of chemotherapy, were monitored. Results: To date, 98 patients overexposed to 5-FU have been treated with uridine triacetate. 96 of these 98 patients recovered fully. Reductions in or absence of GI, hematologic, and other toxicities associated with 5-FU poisoning were observed. Adverse events attributable to urdine triacetate were infrequent and mild in severity. Conclusions: Uridine triacetate appears to be a safe and effective life-saving antidote for 5-FU overexposure in emergency situations.
Studies of Various Tests for Malignant Neoplastic Diseases. III. The Hoff-Schwartz Intradermal Test&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Louise Wiegenstein, M. D., Raymond F. Hain, M. D.
Journal: JNCI Journal of the National Cancer Institute (1951)

Journal Article Studies of Various Tests for Malignant Neoplastic Diseases. III. The Hoff-Schwartz Intradermal Test Get access Louise Wiegenstein, M. D., Louise Wiegenstein, M. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Raymond F. Hain, M. D. Raymond F. Hain, M. D. Department of Pathology, University of Washington School of Medicine, Seattle, Wash. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 11, Issue 4, February 1951, Pages 733–737, https://doi.org/10.1093/jnci/11.4.733 Published: 01 February 1951 Article history Received: 14 September 1950 Published: 01 February 1951
Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery
Authors: Geoff Appelboom, Alexandre Detappe, Melissa LoPresti, Sijumon Kunjachan, Stefan Mitrasinovic, Serge Goldman, Steve D. Chang, Olivier Tillement
Journal: Neuro-Oncology (2016)

Drug delivery in the CNS is limited by endothelial tight junctions forming the impermeable blood-brain barrier. The development of new treatment paradigms has previously been hampered by the restrictiveness of the blood-brain barrier to systemically administered therapeutics. With recent advances in stereotactic localization and noninvasive imaging, we have honed the ability to modulate, ablate, and rewire millimetric brain structures to precisely permeate the impregnable barrier. The wide range of focused radiations offers endless possibilities to disrupt endothelial permeability with different patterns and intensity following 3-dimensional coordinates offering a new world of possibilities to access the CNS, as well as to target therapies. We propose a review of the current state of knowledge in targeted drug delivery using noninvasive image-guided approaches. To this end, we focus on strategies currently used in clinics or in clinical trials such as targeted radiotherapy and magnetic resonance guided focused ultrasound, but also on more experimental approaches such as magnetically heated nanoparticles, electric fields, and lasers, techniques which demonstrated remarkable results both in vitro and in vivo. We envision that biodistribution and efficacy of systemically administered drugs will be enhanced with further developments of these promising strategies. Besides therapeutic applications, stereotactic platforms can be highly valuable in clinical applications for interventional strategies that can improve the targetability and efficacy of drugs and macromolecules. It is our hope that by showcasing and reviewing the current state of this field, we can lay the groundwork to guide future research in this realm.
CD19-Redirected Cytotoxic T Cells Prevent Engraftment of Primary Human Leukemia Cells In Vivo.
Authors: Silke Landmeier, Bianca Altvater, Sibylle Pscherer, Jutta Meltzer, Josef Vormoor, Juan F Vera, Martin Pule, Marc Hotfilder, Heribert Juergens, Claudia Rossig
Journal: Blood (2009)
Conflict among psychiatric residents in response to pregnancy
Authors: E L Auchincloss
Journal: American Journal of Psychiatry (1982)

An angry conflict erupted between male and female psychiatric residents when 3 of 12 residents at a major training center become pregnant in the second year of training. The author explores the fantasies and feelings that fueled this conflict from the points of view of intrapsychic and group dynamics. Problems within the institution are seen as providing the context for the residents' conflicts aroused by the event of pregnancy.
Massachusetts Medical Society
Authors: Claude E. Welch
Journal: New England Journal of Medicine (1974)

PSRO's — PROS AND CONSHistory will be made in June, 1974, when the House of Delegates of the American Medical Association must decide whether to support the concept of PSRO (Professional Standards Review Organization) and work for appropriate changes in PL92–603, or to adopt a position of non-co-operation. For this reason it seems desirable to list the arguments, for and against the provisions of the law, in the hope that decisions may be made on a basis of reason rather than emotion.At the outset, however, it must be admitted that any analysis is difficult, considering the fact that . . .
Vaccine preventable diseases: a regional surveillance can help improve data comparability between countries
Authors: J C Desenclos
Journal: Eurosurveillance (2001)

The way that surveillance of a given disease is undertaken in European countries varies greatly. Each study that has been undertaken on this subject so far has come to this conclusion, the variation between countries being related to many factors among which the organisation of the health care delivery plays a major role. This rule applies to vaccine preventable diseases and vaccine coverage surveillance as this Eurosurveillance issue shows. However, as the surveys undertaken for measles and pertussis indicate, there is a lot of common information gathered by each EU member state for both diseases. Therefore the definition of a minimal data set of pertinent variables common to most countries may be defined and is a way to initiate common EU data base. Whether this will be enough to effectively monitor timeliness and to compare the incidence in countries with different immunisation strategies and coverage needs to be further evaluated.
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines
Authors: Jessica Lauriol, Janel R. Cabrera, Ashbeel Roy, Kimberly Keith, Sara M. Hough, Federico Damilano, Bonnie Wang, Gabriel C. Segarra, Meaghan E. Flessa, Lauren E. Miller, Saumya Das, Roderick Bronson, Kyu-Ho Lee, Maria I. Kontaridis
Journal: Journal of Clinical Investigation (2016)

Hypertrophic cardiomyopathy is a common cause of mortality in congenital heart disease (CHD). Many gene abnormalities are associated with cardiac hypertrophy, but their function in cardiac development is not well understood. Loss-of-function mutations in PTPN11, which encodes the protein tyrosine phosphatase (PTP) SHP2, are implicated in CHD and cause Noonan syndrome with multiple lentigines (NSML), a condition that often presents with cardiac hypertrophic defects. Here, we found that NSML-associated hypertrophy stems from aberrant signaling mechanisms originating in developing endocardium. Trabeculation and valvular hyperplasia were diminished in hearts of embryonic mice expressing a human NSML-associated variant of SHP2, and these defects were recapitulated in mice expressing NSML-associated SHP2 specifically in endothelial, but not myocardial or neural crest, cells. In contrast, mice with myocardial- but not endothelial-specific NSML SHP2 expression developed ventricular septal defects, suggesting that NSML-associated mutations have both cell-autonomous and nonautonomous functions in cardiac development. However, only endothelial-specific expression of NSML-associated SHP2 induced adult-onset cardiac hypertrophy. Further, embryos expressing the NSML-associated SHP2 mutation exhibited aberrant AKT activity and decreased downstream forkhead box P1 (FOXP1)/FGF and NOTCH1/EPHB2 signaling, indicating that SHP2 is required for regulating reciprocal crosstalk between developing endocardium and myocardium. Together, our data provide functional and disease-based evidence that aberrant SHP2 signaling during cardiac development leads to CHD and adult-onset heart hypertrophy.