tbuckley/cabot-search huggingface dataset:
Optimality is critical when it comes to testing computation-level hypotheses
Authors: Laura S. Geurts, Andrey Chetverikov, Ruben S. van Bergen, Ying J. Zhou, Andrea Bertana, Janneke F. M. Jehee
Journal: Behavioral and Brain Sciences (2018)

Abstract We disagree with Rahnev &amp; Denison (R&amp;D) that optimality should be abandoned altogether. Rather, we argue that adopting a normative approach enables researchers to test hypotheses about the brain's computational goals, avoids just-so explanations, and offers insights into function that are simply inaccessible to the alternatives proposed by R&amp;D.
Abstract 15679: Coronary Revascularization Can Ameliorate Low Coronary Flow Reserve in Patients With Coronary Artery Disease
Authors: Tadao Aikawa, Masanao Naya, Masahiko Obara, Osamu Manabe, Kazuhiro Koyanagawa, Keiichi Magota, Tohru Shiga, Chietsugu Katoh, Hiroyuki Tsutsui, Nagara Tamaki
Journal: Circulation (2017)

Background: Coronary flow reserve (CFR) can provide significant prognostic information for patients with coronary artery disease (CAD). However, the effects of coronary revascularization including ...
Depth of Response and Outcomes in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation
Authors: Gunjan L. Shah, Kenneth Seier, Sean M Devlin, David J. Chung, Michael Scordo, Malin Hultcrantz, Neha Korde, Nikoletta Lendvai, Alexander M. Lesokhin, Sham Mailankody, Eric L. Smith, Ola Landgren, Heather J. Landau, Sergio Giralt
Journal: Blood (2018)
Abstract 19025: A Novel 3D Approach to Screen for Subclinical Atherosclerosis Using Carotid Ultrasound - Results of the BioImage High Risk Plaque Study
Authors: Henrik Sillesen, Rob Entrekin, Pieter Muntendam, Erling Falk, Mario Garcia, Valentin Fuster
Journal: Circulation (2010)

Introduction: Carotid IMT and plaque are predictors for cardiovascular events. Rather than scanning longitudinally, we scanned in cross-sectional mode along the axis of the carotid artery Resultsin...
Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer
Authors: Anthony D. Saleh, Hui Cheng, Scott E. Martin, Han Si, Pinar Ormanoglu, Sophie Carlson, Paul E. Clavijo, Xinping Yang, Rita Das, Shaleeka Cornelius, Jamie Couper, Douglas Chepeha, Ludmila Danilova, Thomas M. Harris, Michael B. Prystowsky, Geoffrey J. Childs, Richard V. Smith, A. Gordon Robertson, Steven J. M. Jones, Andrew D. Cherniack, Sang S. Kim, Antonina Rait, Kathleen F. Pirollo, Esther H. Chang, Zhong Chen, Carter Van Waes
Journal: Clinical Cancer Research (2019)

Abstract Purpose: To identify deregulated and inhibitory miRNAs and generate novel mimics for replacement nanomedicine for head and neck squamous cell carcinomas (HNSCC). Experimental Design: We integrated miRNA and mRNA expression, copy number variation, and DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen. Results: We reveal that the miR-30 family is commonly repressed, and all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation in vitro. We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SERPINE1). Reexpression of the most differentially repressed family member, miR-30a-5p, suppressed this mRNA program, selected signaling proteins and pathways, and inhibited cell proliferation, migration, and invasion in vitro. Furthermore, a novel miR-30a-5p mimic formulated into a targeted nanomedicine significantly inhibited HNSCC xenograft tumor growth and target growth receptors EGFR and MET in vivo. Significantly decreased miR-30a/e family expression was related to DNA promoter hypermethylation and/or copy loss in TCGA data, and clinically with decreased disease-specific survival in a validation dataset. Strikingly, decreased miR-30e-5p distinguished oropharyngeal HNSCC with poor prognosis in TCGA (P = 0.002) and validation (P = 0.007) datasets, identifying a novel candidate biomarker and target for this HNSCC subset. Conclusions: We identify the miR-30 family as an important regulator of signal networks and tumor suppressor in a subset of HNSCC patients, which may benefit from miRNA replacement nanomedicine therapy.
Combination chemotherapy for pancreatic cancer in older adults: Efficacy and safety analysis of patients at a majority-Hispanic NCI-designated cancer center.
Authors: Emily Henkel, Brian Hernandez, Joel Michalek, Devalingam Mahalingam, Sukeshi Patel Arora
Journal: Journal of Clinical Oncology (2019)

389 Background: Pancreatic cancer (PCa) is more frequent in older adults, but older patients are underrepresented in large clinical trials. There is limited data on efficacy and safety of regimens such as FOLFIRINOX or nab-paclitaxel/gemcitabine (nab-gem) in older adults, especially Hispanics. Therefore, we compared the efficacy and safety of first-line PCa regimens in older adults. Methods: Retrospective analysis of stage IV PCa at our Hispanic-majority NCI-designated cancer center from 2000-2017. mPFS and mOS estimated from KM curves and groups were statistically compared with the log-rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Results: Forty-eight pts, mean age 71.7 years, median 69.2 (range 65-90). 31% Hispanic; 50% Male. First-line treatment: FOLFIRINOX (n=9), nab-gem (n=11), gem (n=11), other (n=9), supportive care (n=2). Baseline ECOG 0-1: 100%, 94%, 45%, 100%, 1% (p=0.004). Baseline albumin: 3.4, 3.4, 3.1, 3.5, 2.25 (p=0.06). mOS 7.1 months (95% CI 5.9-10.1). mPFS 5.6 months (95% CI: 5.3-NR). mOS by group: 8.6 mo, 7.1 mo, 3.2 mo, 2.9 mo, not available (p=0.95). Most patients had grade 0-2 toxicities (See table). Grade 3-4: fatigue n=2, neutropenia n=1, neuropathy n=1, mucositis n=1. Conclusions: Combination systemic chemotherapy are tolerated in older adults with PCa; however, in our cohort, survival was lower than historic phase 3 clinical trials with these regimens. Patients receive 2+ drugs had higher ECOG and albumin at baseline. Prospective studies with geriatric assessments are needed to determine patients who benefit from combination chemotherapy. [Table: see text]
Long-Term Outcomes of Omalizumab in Chronic Idiopathic Urticaria (CIU): Evidence from a Large Allergy Practice in the United States (US)
Authors: Jason Lecocq, Abhishek Kavati, Maryia Zhdanava, Benjamin Ortiz, Bradd Schiffman, Hoi Ching Cheung, Patrick Lefebvre, Brian D. Stone
Journal: Journal of Allergy and Clinical Immunology (2019)
Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in patients (pts) with metastatic gastric cancer (mGC) with or without prior gastrectomy: Results from a phase III study (TAGS).
Authors: David H. Ilson, Aliaksandr Prokharau, Hendrik-Tobias Arkenau, Michele Ghidini, Kazumasa Fujitani, Eric Van Cutsem, Peter C. Thuss-Patience, Giordano D. Beretta, Wasat Mansoor, Edvard Zhavrid, Maria Alsina, Ben George, Daniel V.T. Catenacci, Robert E. Winkler, Lukas Makris, Toshihiko Doi, Kohei Shitara
Journal: Journal of Clinical Oncology (2019)

3 Background: The phase 3 study TAGS demonstrated that the novel oral therapy FTD/TPI (TAS-102) represents an effective treatment option with a manageable safety profile for pts with heavily pretreated mGC. In an earlier single-arm Japanese phase 2 trial in mGC, no differences were found in the pharmacokinetics of either FTD or TPI in pts with or without prior gastrectomy. We evaluated the efficacy and safety of FTD/TPI in pts with or without prior gastrectomy within the TAGS study. Methods: In this global phase 3 study of adult pts with mGC who had received ≥ 2 prior regimens of chemotherapy, pts were randomized 2:1 to receive FTD/TPI (35 mg/m 2 BID on days 1–5 and 8–12 of each 28-day cycle) or placebo, plus best supportive care. We performed a preplanned analysis of efficacy and safety endpoints in pt subgroups with or without prior gastrectomy. Results: Of 507 randomized pts, 221 (44%) had a prior gastrectomy (FTD/TPI, 147/337; placebo, 74/170). Baseline pt characteristics were balanced across pt subgroups. FTD/TPI prolonged survival versus placebo regardless of gastrectomy (table). The frequency of neutropenia/leukopenia appeared to be higher among FTD/TPI-treated pts with vs without gastrectomy, but this did not result in more treatment discontinuations (table). Conclusions: In the TAGS study, subgroup analysis demonstrated that FTD/TPI is an effective treatment option with a manageable safety profile for pts with heavily pretreated mGC, regardless of prior gastrectomy. Clinical trial information: NCT02500043. [Table: see text]
Fibroblasts: Dangerous travel companions
Authors: Hans Schreiber
Journal: The Journal of Experimental Medicine (2019)

In this issue of JEM, Gao et al. (https://doi.org/10.1084/jem.20180765) demystify the exceptional metastatic success of ovarian cancer, the most lethal female malignancy: fibroblasts form heterotypic aggregates with disseminating cancer cells, thereby providing them with reciprocal signaling and matrix for adherence.
Unmanipulated Haploidentical Transplant for Acquired Severe Aplastic Anemia Achieved Comparable Outcomes with Unrelated Donor Transplant in Adult and Children Patients
Authors: Yue Lu, Ruijuan Sun, Yanli Zhao, Xingyu Cao, Min Xiong, Jiangping Zhang, Dao-Pei Lu, Hongxing Liu
Journal: Blood (2017)
Response Rate, Event-Free Survival (EFS), and Overall Survival (OS) in Newly-Diagnosed Acute Myeloid Leukemia (AML): U.S. Food and Drug Administration (FDA) Trial-Level and Patient-Level Analyses
Authors: Kelly J. Norsworthy, Xin Gao, Chia-Wen Ko, Jiaxi Zhou, Yutao Gong, Yuan Li Shen, Rajeshwari Sridhara, Albert B. Deisseroth, Ann T. Farrell, Richard Pazdur, Gideon Blumenthal
Journal: Blood (2018)
Folate-Dependent Normocytic Anemia Caused By a Hypomorphic Mutation in SLC19A1 gene
Authors: Michael Svaton, Karolina Skvarova Kramarzova, Veronika Kanderova, Petr Smisek, Pavel Jesina, Jakub Krijt, Blanka Stiburkova, Andrea Mancikova, Robert Dobrovolny, Violeta Bakardjieva-Mihaylova, Elena Vodickova, Jan Stuchly, Tomas Kalina, Jan Stary, Jan Trka, Eva Fronkova, Viktor Kozich
Journal: Blood (2018)
Abstract 13246: The Impact of Body-Mass Index Trajectories During Early Adulthood on Cardiac Mechanics in Middle Age: The CARDIA Study
Authors: Sadiya S Khan, Sanjiv J Shah, Kiang J Liu, Cora E Lewis, Christina Shay, David C Goff, Jared P Reis, Donald M Lloyd-Jones, Norrina B Allen
Journal: Circulation (2014)

Introduction: Obesity is a risk factor for left ventricular dysfunction and incident heart failure. We hypothesized that baseline body mass index (BMI) and trajectories in weight change through young adulthood are associated with abnormal cardiac mechanics in middle age. Methods: We examined 2,735 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. BMI was calculated at exam years 0, 2, 5, 7, 10, 15, 20, 25. 2D echo was performed with speckle-tracking analysis. Left ventricular ejection fraction (LVEF) and global longitudinal, circumferential, and radial strain (GLS, GCS, GRS, respectively) were measured at y25. Group-based modeling with latent class analysis (PROC TRAJ) was used to identify trajectories in relative changes in BMI (% change in BMI from baseline at each exam). Linear regression examined associations between baseline BMI and trajectory of BMI change and absolute GLS, GCS, and GRS at y25 adjusting for demographics, risk factors, and echo parameters. Results: Mean age at baseline was 25±4 years. Baseline BMI at y0 was significantly associated with mean GLS at y25 (p=0.01), but not GRS or GCS. We identified 4 distinct trajectories of relative BMI change: stable weight (36% of sample), mild increase (40%), moderate increase (18%), and major increase (6%) in weight (Figure). At y25, there was no difference in LVEF across the 4 BMI trajectory groups (P=NS). After adjustment for clinical variables and baseline BMI, absolute GLS was lower in groups with BMI increases (overall P&lt;0.001). GRS and GCS were not significantly different between the groups. Conclusion: In conclusion, baseline BMI and increases in BMI during young adulthood are significantly associated with the presence of subclinical cardiac dysfunction in middle age despite normal EF. This novel characterization of BMI trajectories across young adulthood may assist in improving understanding of the impact of weight gain and obesity on cardiac dysfunction.
Helen Salisbury: Should patients pay for genetic tests?
Authors: Helen Salisbury
Journal: BMJ (2019)

Our technophile health secretary recently announced that patients will be able to pay the NHS to have their genome analysed as long as they consent to their data, appropriately anonymised, being available for research.1 Is this a good idea?

The NHS currently works on the basis of need: if you need a test or treatment it’s free at the point of use. If you want it but don’t need it, or if it’s not likely to be cost effective (often quite contentious decisions), you’ll have to buy it outside the NHS. This proposal introduces something akin to co-payment, a system prevalent in insurance based systems …
Abstract 15837: Long-Term Transplant-Free Survival of Patients With Single Ventricle Congenital Heart Disease: Does Ventricular Morphology Matter?
Authors: Matthew Oster, Jessica Knight, Divya Suthar, Lazaros Kochilas
Journal: Circulation (2017)

Background: The association of ventricular morphology with long-term outcomes in single ventricle congenital heart disease (SVCHD) is unclear. Using data from a large multi-center surgical registry, our objective was to determine the association of ventricular morphology with long-term transplant-free survival of individuals with SVCHD. Methods: We performed a retrospective cohort study of patients who had initial surgery for SVCHD at <1 year of age at 45 centers in the Pediatric Cardiac Care Consortium from 1982-2003 and were linked with records from the National Death Index and United Network for Organ Sharing through 2014. We constructed Kaplan-Meier transplant-free survival curves and mortality/transplant hazard ratios (HR) adjusted for sex, syndrome, center, and surgical era. Results: Of 3903 patients, the dominant ventricular morphology was right ventricle (RV) in 43.4%, left ventricle (LV) in 36.3%, and non-classifiable (NC) in 20.3%. Primary heart transplant or in-hospital death following first su...
Treatment of MDS, AML and CMML Relapse after Allogeneic Blood Stem Cell Transplantation with Azacitidine, Lenalidomide and Donor Lymphocyte Infusions Results from the Second Interim Analysis of the Prospective Azalena-Trial (NCT02472691)
Authors: Thomas Michael Schroeder, Christina Rautenberg, Max Christopeit, Matthias Stelljes, Eva Schmidt, Christoph Groth, Christoph Scheid, Udo Holtick, Stefan A Klein, Dietrich W. Beelen, Kathrin Nachtkamp, Rainer Haas, Ulrich Germing, Nicolaus Kröger, Guido Kobbe
Journal: Blood (2018)
Pembrolizumab treatment of advanced neuroendocrine tumors: Results from the phase II KEYNOTE-158 study.
Authors: Jonathan R. Strosberg, Nobumasa Mizuno, Toshihiko Doi, Enrique Grande, Jean-Pierre Delord, Ronnie Shapira-Frommer, Emily K. Bergsland, Manisha H. Shah, Marwan Fakih, Shunji Takahashi, Sarina Anne Piha-Paul, Bert O'Neil, Sajeve Thomas, Martijn P. Lolkema, Jiang Dian Wang, Nageatte Ibrahim, Scott K. Pruitt, Julien Hadoux
Journal: Journal of Clinical Oncology (2019)

190 Background: Data from the KEYNOTE-028 study (NCT02054806) suggested that pembrolizumab (pembro) has clinical activity in a subset of patients (pts) with heavily pretreated neuroendocrine tumors (NET). The KEYNOTE-158 study (NCT02628067) is a phase II basket study investigating the antitumor activity of pembro in 10 specific cancer types. An analysis of the 107 pts included in the NET cohort is presented. Methods: Key eligibility criteria for this cohort included well- and moderately-differentiated NET of the lung, appendix, small intestine, colon, rectum, or pancreas; progression on or intolerance to ≥ 1 line of standard therapy; ECOG PS 0 or 1; and provision of a tumor sample for biomarker analysis. Pts received pembrolizumab 200 mg Q3W for 2 y or until progression, intolerable toxicity, or physician or patient decision. Tumor imaging was performed every 9 wks for the first 12 mo, and every 12 wks thereafter. PD-L1 positivity, defined as a combined positive score (CPS) ≥ 1, was evaluated retrospectively by IHC. Primary endpoint was ORR assessed per RECIST v1.1 by independent central radiology review. Secondary endpoints included DOR, PFS, OS, and safety. Results: 107 pts were treated. Median age was 59 (range, 29-80) y, 44.9% had ECOG PS 1, and 67.3% received ≥ 2 prior therapies for advanced disease. 15.9% of enrolled pts had PD-L1+ tumors. As of the January 15, 2018 data cutoff, the median follow-up duration was 18.6 (range, 0.2-22.7) mo. ORR was 3.7% (95% CI, 1.0-9.3), with 0 CR and 4 PR (3 pancreatic and 1 gastrointestinal [unknown primary]). 61 pts had SD as best response. The 4 responses were observed in pts with PD-L1 negative tumors. Median DOR had not been reached (range, 4.1-15.9+), with 3 of 4 responses ongoing after ≥ 9 mo follow-up. Median (95% CI) PFS was 4.1 (3.5-5.4) mo, and the 6-mo PFS rate was 38.2%. Median OS (95% CI) had not been reached (18.8-not reached), and the 6-mo OS rate was 84.6%. Treatment-related AEs occurred in 75.7% of pts, and the most common was fatigue (21.5%). 20.6% of pts had treatment-related grade 3-4 AEs. Conclusions: Pembrolizumab monotherapy showed limited antitumor activity and manageable safety in pts with previously treated advanced NET. Clinical trial information: NCT02628067.
Addressing the Psychological Symptoms of Critical Illness
Authors: Erin K. Kross, Kathryn I. Pollak, J. Randall Curtis
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Metabolomics Profiling after Allogeneic Hematopoietic Stem Cell Transplantation Unravels a Specific Signature in Human Acute GVHD
Authors: David Michonneau, Eleonora Latis, Laetitia Dubouchet, Regis Peffault De Latour, Marie Robin, Flore Sicre De Fontbrune, Lars Rogge, Gerard Socie
Journal: Blood (2018)
PTEN-induced partial epithelial-mesenchymal transition drives diabetic kidney disease
Authors: Yajuan Li, Qingsong Hu, Chunlai Li, Ke Liang, Yu Xiang, Heidi Hsiao, Tina K. Nguyen, Peter K. Park, Sergey D. Egranov, Chandrashekar R. Ambati, Nagireddy Putluri, David H. Hawke, Leng Han, Mien-Chie Hung, Farhad R. Danesh, Liuqing Yang, Chunru Lin
Journal: Journal of Clinical Investigation (2019)

Epithelial-mesenchymal transition (EMT) contributes significantly to interstitial matrix deposition in diabetic kidney disease (DKD). However, detection of EMT in kidney tissue is impracticable, and anti-EMT therapies have long been hindered. We reported that phosphatase and tensin homolog (PTEN) promoted transforming growth factor beta 1 (TGF-β), sonic hedgehog (SHH), connective tissue growth factor (CTGF), interleukin 6 (IL-6), and hyperglycemia-induced EMT when PTEN was modified by a MEX3C-catalyzed K27-linked polyubiquitination at lysine 80 (referred to as PTENK27-polyUb). Genetic inhibition of PTENK27-polyUb alleviated Col4a3 knockout–, folic acid–, and streptozotocin-induced (STZ-induced) kidney injury. Serum and urine PTENK27-polyUb concentrations were negatively correlated with glomerular filtration rate (GFR) for diabetic patients. Mechanistically, PTENK27-polyUb facilitated dephosphorylation and protein stabilization of TWIST, SNAI1, and YAP in renal epithelial cells, leading to enhanced EMT. We identified that a small molecule, triptolide, inhibited MEX3C-catalyzed PTENK27-polyUb and EMT of renal epithelial cells. Treatment with triptolide reduced TWIST, SNAI1, and YAP concurrently and improved kidney health in Col4a3 knockout–, folic acid–injured disease models and STZ-induced, BTBR ob/ob diabetic nephropathy models. Hence, we demonstrated the important role of PTENK27-polyUb in DKD and a promising therapeutic strategy that inhibited the progression of DKD.
Association of HLA-dependent islet autoimmunity with systemic antibody responses to intestinal commensal bacteria in children
Authors: Alexandra Paun, Christopher Yau, Shahab Meshkibaf, Michelle C. Daigneault, Leili Marandi, Steven Mortin-Toth, Amit Bar-Or, Emma Allen-Vercoe, Philippe Poussier, Jayne S. Danska
Journal: Science Immunology (2019)

Immune responses to gut bacteria display HLA- dependent associations with progression to type 1 diabetes.
A Critical Role of Host-Derived Semaphorin-4A for Regulating T Cell Immune Responses in Acute Graft Versus Host Disease
Authors: Hideaki Yoshimura, Yukie Tsubokura, Masaaki Hotta, Atsushi Satake, Tomoki Ito, Atsushi Kumanogoh, Shosaku Nomura
Journal: Blood (2018)
Outcomes of Long-term Interval Rescreening With Low-Dose Computed Tomography for Lung Cancer in Different Risk Cohorts
Authors: Reenika Aggarwal, Andrew C.L. Lam, Maureen McGregor, Ravi Menezes, Katrina Hueniken, Hannah Tateishi, Grainne M. O’Kane, Ming Sound Tsao, Frances A. Shepherd, Wei Xu, Micheal McInnis, Heidi Schmidt, Geoffrey Liu, John Kavanagh
Journal: Journal of Thoracic Oncology (2019)