tbuckley/cabot-search huggingface dataset:
Payments to Physicians, Prescribing Rates, and More Appropriate Conclusions
Authors: Joseph D. Feuerstein
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine 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 Internal Medicine journal
Heterozygosity for transmembrane activator and calcium modulator ligand interactor A144E causes haploinsufficiency and pneumococcal susceptibility in mice
Authors: Haifa H. Jabara, John J. Lee, Erin Janssen, Sumana Ullas, Kyriaki Liadaki, Lilit Garibyan, Halli Benson, Tatyana Sannikova, Richard Bram, Lennart Hammarstrom, Anthony C. Cruz, Richard Siegel, John Manis, Richard Malley, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2016)
How Oral Microbes Exacerbate Colorectal Cancer
Authors: Tracy Hampton
Journal: JAMA (2016)

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
Zika viral dynamics and shedding in rhesus and cynomolgus macaques
Authors: Christa E Osuna, So-Yon Lim, Claire Deleage, Bryan D Griffin, Derek Stein, Lukas T Schroeder, Robert Omange, Katharine Best, Ma Luo, Peter T Hraber, Hanne Andersen-Elyard, Erwing Fabian Cardozo Ojeda, Scott Huang, Dana L Vanlandingham, Stephen Higgs, Alan S Perelson, Jacob D Estes, David Safronetz, Mark G Lewis, James B Whitney
Journal: Nature Medicine (2016)
Phase I clinical trial of the anti-CD33 immunotoxin HuM195/rgel in patients (pts) with advanced myeloid malignancies.
Authors: A. Dean, M. Talpaz, H. Kantarjian, S. Faderl, E. Jabbour, F. Ravandi Kashani, S. M. O'Brien, M. Rosenblum, J. E. Cortes
Journal: Journal of Clinical Oncology (2010)

6549 Background: HuM195 is a humanized version of the mouse M195 anti CD-33 monoclonal antibody. CD33 is heavily expressed on the surface of myeloid leukemia cells. The anti-CD33 immunotoxin HuM195/rGel combines HuM195 with recombinant gelonin, a RNA glycosidase that inhibits protein synthesis. Methods: The primary objective of this study was to determine the safety and toxicity of HuM195/rGel in pts with refractory or relapsed leukemia. Pts age ≥ 18 years with relapsed or refractory AML, RAEB-t, RAEB, CMML or CML-AP/BP and CD 33 expression ≥ 80% by flow cytometry, were eligible. Pts received doses of 2.5 to 10 mg/m2 using a standard 3 + 3 design. Therapy was administered over 2 one-hour infusions per week for 2 weeks followed by a 2 week period of observation. Pts taken off study before 28 days for reasons other than toxicity were replaced for MTD calculations. Results: 28 patients were enrolled: 23 AML, 4 MDS, and 1 CMML. Median age was 68 years, median number of prior therapies was 2, median peripheral blood blasts 24%, median bone marrow blasts 39%, and median percentage of CD 33 was 95%. The highest achieved blood levels of HuM195/rGel were 200-300 ng/mL which cleared with a half-life of ∼20 hrs. 2/23 patients (< 10%) developed antibodies to the rGel portion of the drug as assessed by ELISA. 22 pts were evaluable for dose limiting toxicity (DLT). Two patients developed DLT (allergic reaction) at a dose of 10 mg/m2, thus 7 mg/m2 was declared the maximum tolerated dose. Drug-related adverse events at ≤ 7 mg/m2 include: grade ≤ 2 fever and chills at all dose levels. Six (27%) out of the evaluable patients had a ≥ 50% decrease in PB blasts or BM blasts. In addition, 4 pts had an increase in platelet count to > 100 x109/L and 4 pts demonstrated increased neutrophils to > 1 x109/L. There were no complete or partial responses. Conclusions: HuM195/rGel can be administered safely at doses up to 7 mg/m2 with an improvement in the tumor load in some patients. No significant financial relationships to disclose.
Multisensory integration substantiates distributed and overlapping neural networks
Authors: Achille Pasqualotto
Journal: Behavioral and Brain Sciences (2016)

Abstract The hypothesis that highly overlapping networks underlie brain functions (neural reuse) is decisively supported by three decades of multisensory research. Multisensory areas process information from more than one sensory modality and therefore represent the best examples of neural reuse. Recent evidence of multisensory processing in primary visual cortices further indicates that neural reuse is a basic feature of the brain.
E2A-PBX1 Remodels Oncogenic Signaling Networks in B-cell Precursor Acute Lymphoid Leukemia
Authors: Jesús Duque-Afonso, Chiou-Hong Lin, Kyuho Han, Michael C. Wei, Jue Feng, Jason H. Kurzer, Corina Schneidawind, Stephen Hon-Kit Wong, Michael C. Bassik, Michael L. Cleary
Journal: Cancer Research (2016)

Abstract There is limited understanding of how signaling pathways are altered by oncogenic fusion transcription factors that drive leukemogenesis. To address this, we interrogated activated signaling pathways in a comparative analysis of mouse and human leukemias expressing the fusion protein E2A-PBX1, which is present in 5%–7% of pediatric and 50% of pre-B-cell receptor (preBCR+) acute lymphocytic leukemia (ALL). In this study, we describe remodeling of signaling networks by E2A-PBX1 in pre-B-ALL, which results in hyperactivation of the key oncogenic effector enzyme PLCγ2. Depletion of PLCγ2 reduced proliferation of mouse and human ALLs, including E2A-PBX1 leukemias, and increased disease-free survival after secondary transplantation. Mechanistically, E2A-PBX1 bound promoter regulatory regions and activated the transcription of its key target genes ZAP70, SYK, and LCK, which encode kinases upstream of PLCγ2. Depletion of the respective upstream kinases decreased cell proliferation and phosphorylated levels of PLCγ2 (pPLCγ2). Pairwise silencing of ZAP70, SYK, or LCK showed additive effects on cell growth inhibition, providing a rationale for combination therapy with inhibitors of these kinases. Accordingly, inhibitors such as the SRC family kinase (SFK) inhibitor dasatinib reduced pPLCγ2 and inhibited proliferation of human and mouse preBCR+/E2A-PBX1+ leukemias in vitro and in vivo. Furthermore, combining small-molecule inhibition of SYK, LCK, and SFK showed synergistic interactions and preclinical efficacy in the same setting. Our results show how the oncogenic fusion protein E2A-PBX1 perturbs signaling pathways upstream of PLCγ2 and renders leukemias amenable to targeted therapeutic inhibition. Cancer Res; 76(23); 6937–49. ©2016 AACR.
Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial
Authors: Edward Litton, Stuart Baker, Wendy N. Erber, Shannon Farmer, Janet Ferrier, Craig French, Joel Gummer, David Hawkins, Alisa Higgins, Axel Hofmann, Bart De Keulenaer, Julie McMorrow, John K. Olynyk, Toby Richards, Simon Towler, Robert Trengove, Steve Webb
Journal: Intensive Care Medicine (2016)
Association of nasopharyngeal microbiota profiles with bronchiolitis severity in infants hospitalised for bronchiolitis
Authors: Kohei Hasegawa, Jonathan M. Mansbach, Nadim J. Ajami, Janice A. Espinola, David M. Henke, Joseph F. Petrosino, Pedro A. Piedra, Chad A. Shaw, Ashley F. Sullivan, Carlos A. Camargo
Journal: European Respiratory Journal (2016)

Little is known about the relationship between the specific airway microbiota composition and severity of bronchiolitis. We aimed to identify nasopharyngeal microbiota profiles and link these profiles to acute severity in infants hospitalised for bronchiolitis. We conducted a multicentre prospective cohort study of 1005 infants (age &lt;1 year) hospitalised for bronchiolitis over three winters, 2011–2014. By applying a 16S rRNA gene sequence and clustering approach to the nasopharyngeal aspirates collected within 24 h of hospitalisation, we determined nasopharyngeal microbiota profiles and their association with bronchiolitis severity. The primary outcome was intensive care use, i.e. admission to an intensive care unit or use of mechanical ventilation. We identified four nasopharyngeal microbiota profiles: three profiles were dominated by one of Haemophilus , Moraxella or Streptococcus, while the fourth profile had the highest bacterial richness. The rate of intensive care use was highest in infants with a Haemophilus -dominant profile and lowest in those with a Moraxella -dominant profile (20.2% versus 12.3%; unadjusted OR 1.81, 95% CI 1.07–3.11, p=0.03). After adjusting for 11 patient-level confounders, the rate remained significantly higher in infants with Haemophilus -dominant profiles (OR 1.98, 95% CI 1.08–3.62, p=0.03). These findings were externally validated in a separate cohort of 307 children hospitalised for bronchiolitis.
The Influence of Monosomal Karyotype On Survival in Patients with Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Survey On Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Angelique V.M. Brands-Nijenhuis, Myriam Labopin, Harry C. Schouten, Liisa Volin, Gérard Socié, Jan J Cornelissen, Michel Attal, Reza Tabrizi, Jordi Esteve, Mohamad Mohty
Journal: Blood (2011)
Docetaxel versus docetaxel plus bevacizumab in progressive castration-resistant prostate cancer following first-line docetaxel.
Authors: A. Heidenreich, D. J. Pfister, D. Thüer, B. Brehmer
Journal: Journal of Clinical Oncology (2010)

e15006 Background: Docetaxel represents the first-line therapy for metastatic castration-resistant prostate cancer (CRPC). There are no standard regimes for patients who relapse following first-line docetaxel. We compare the therapeutic efficacy of docetaxel versus docetaxel plus bevacizumab as second-line treatment for relapsing metastatic CRPC. Methods: 59 relapsing patients following first-line docetaxel underwent docetaxel rechallenge (group 1, 35 mg/sqm for 3 weeks, 1 week drug holiday, 3 repetitions) or combination therapy of docetaxel (group 2, 25 mg/sqm, weekly for 12 weeks) plus bevacizumab (10 mg/kg, 2- weekly). Treatment was continued in case of PSA stabilization or PSA regression until progressive disease or severe side effects. All patients demonstrated PSA regression > 30% following first-line therapy, mean progression-free survival was 6.2 (3–11) months. All patients had osseous metastases, 9/23 (39.1%), 3/23 (13%) and 2/23 (8.6%) had lymph node, hepatic, and pulmonary metastases. PSA doubling time at time of second-line treatment was 5.9 (2-8) months. PSA response, mean progression-free and overall survival were analyzed. Results: Mean patient age was 66.8 (49–67) years, mean PSA was 170.3 (95–1.200) ng/ml. 40/59 (67.8%) demonstrated PSA – decrease > 30%. Additional results are listed in the Table. Overall survival was significantly better in group 2 (p = 0.042). Patients in group 1 and 2 received a mean of 17 cycles (7-24) and 14 (6-28) cycles, respectively. Treatment-associated toxicity of docetaxel did not differ from first-line treatment and WHO grade III toxicity developed in 4/21 (19.1%) patients. 5/28 (17.8%) in group 2 developed clinically relevant arterial hypertension, 1 patient developed significant proteinuria with early discontinuation of therapy. Conclusions: Docetaxel rechallenge and combination of docetaxel plus bevacizumab are effective second-line strategies in relapsing metastatic CRPC. Doc/Bev demonstrates a benefit in progression-free and overall surival. These results need to be validated in larger prospective randomized trials. N Age PSA PSAx > 30% PFS Survival Group 1 27 65.3 yrs 165.2 ng/ml 66% 6.2 m 13.3 m Group 2 32 68.9 yrs 189.4 ng/ml 69% 8.9 m 17.5 m Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Roche, sanofi-aventis
Whole-genome sequencing (WGS) to identify <i>H. pylori</i> and its impact on the gastric microbiome.
Authors: Manish A. Shah, Kyle Cleveland, Chao Zhang, Michelle Bigg, Prashant Thakkar, Brian Turner, Felice Schnoll-Sussman, Doron Betel
Journal: Journal of Clinical Oncology (2014)

11070 Background: Although H. pylori is a WHO class I carcinogen for gastric cancer (GC), nearly all infected patients do not develop GC, and H. pylori eradication does not reduce GC risk. We used WGS to examine the hypothesis that changes in the gastric microbiome associated with H. pylori infection may play a role in GC development. Methods: Patients (pts) undergoing upper endoscopy were categorized as follows: (1) active H. pylori infection (H. pylori identified on biopsy or positive CLOtest), (2) prior H. pylori infection (previous H. pylori treatment or ELISA IgG positive), and (3) GC. Endoscopic biopsies from 3 locations in the antrum/body were freshly frozen for WGS (50bp paired-end) on a HiSeq2000 platform at ~10X coverage. We developed a custom computational pipeline algorithm that successively removes human sequences, with remaining un-mapped reads aligned to ~1,400 unique bacteria genomes. Bacterial species were validated by PCR. Results: 15 pts have enrolled: active H. pylori infection (n=6), prior H. pylori infection (n=5), and GC (n=4), with WGS performed in 10 thus far. A total of 16 microbial species are identified (Table). H. pylori was identified in all patients regardless of H. pylori infection state (i.e. active v. prior), as well as in the GC cohort. Conclusions: Multiple bacterial species are identified in gastric mucosa. H. pylori is identified in all pts, including previously treated pts. H. pylori treatment fails to eradicate H. pylori, thus possibly explaining why H. pylori treatment fails to reduce cancer risk. This is the first demonstration of detailed unbiased microbiome detection performed from gastric endoscopic biopsy samples using WGS. Gastric microbiome identified using WGS. Active Active Prior Prior Prior GC Bacterial species 05-An 08-An 07-An 09-An 10-An 11-An Helicobacter_acinonychis 3 15,306 9 1,421 14,817 47 Helicobacter_cetorum 0 873 0 87 753 0 Helicobacter_pylori 19 81,762 43 10,914 245,231 815 Lactobacillus_gasseri 0 0 0 1 89 322 Lactococcus_lactis 0 0 0 2 906 0 Propionibacterium_acnes 208 41 292 46 87 69 Staphylococcus_warneri 13 450 0 2 4 6 Streptococcus_thermophilus 3 0 2 1 461 4 Values are the number of read counts mapped to the respective bacteria species. Top 8 species are shown in subset of pts.
Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan
Authors: Motoko Yamaguchi, Ritsuro Suzuki, Masahiko Oguchi, Naoko Asano, Jun Amaki, Takeshi Akiba, Takeshi Maeda, Satoshi Itasaka, Nobuko Kubota, Yoshihiro Saito, Yukio Kobayashi, Jun Itami, Kyoko Ueda, Kana Miyazaki, Noriko Ii, Naoto Tomita, Nodoka Sekiguchi, Jun Takizawa, Bungo Saito, Tohru Murayama, Toshihiko Ando, Hideho Wada, Rie Hyo, Yasuo Ejima, Masatoshi Hasegawa, Naoyuki Katayama
Journal: Journal of Clinical Oncology (2016)

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients' median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase-containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.
Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation
Authors: David J. Graham, Marsha E. Reichman, Michael Wernecke, Ya-Hui Hsueh, Rima Izem, Mary Ross Southworth, Yuqin Wei, Jiemin Liao, Margie R. Goulding, Katrina Mott, Yoganand Chillarige, Thomas E. MaCurdy, Chris Worrall, Jeffrey A. Kelman
Journal: JAMA Internal Medicine (2016)

Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes.To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention.Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016.Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily.Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated.A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke.Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.