tbuckley/cabot-search huggingface dataset:
Single-cell RNA-seq reveals novel regulators of human embryonic stem cell differentiation to definitive endoderm
Authors: Li-Fang Chu, Ning Leng, Jue Zhang, Zhonggang Hou, Daniel Mamott, David T. Vereide, Jeea Choi, Christina Kendziorski, Ron Stewart, James A. Thomson
Journal: Genome biology (2016)

Human pluripotent stem cells offer the best available model to study the underlying cellular and molecular mechanisms of human embryonic lineage specification. However, it is not fully understood how individual stem cells exit the pluripotent state and transition towards their respective progenitor states. Here, we analyze the transcriptomes of human embryonic stem cell-derived lineage-specific progenitors by single-cell RNA-sequencing (scRNA-seq). We identify a definitive endoderm (DE) transcriptomic signature that leads us to pinpoint a critical time window when DE differentiation is enhanced by hypoxia. The molecular mechanisms governing the emergence of DE are further examined by time course scRNA-seq experiments, employing two new statistical tools to identify stage-specific genes over time (SCPattern) and to reconstruct the differentiation trajectory from the pluripotent state through mesendoderm to DE (Wave-Crest). Importantly, presumptive DE cells can be detected during the transitory phase from Brachyury (T) + mesendoderm toward a CXCR4 + DE state. Novel regulators are identified within this time window and are functionally validated on a screening platform with a T-2A-EGFP knock-in reporter engineered by CRISPR/Cas9. Through loss-of-function and gain-of-function experiments, we demonstrate that KLF8 plays a pivotal role modulating mesendoderm to DE differentiation. We report the analysis of 1776 cells by scRNA-seq covering distinct human embryonic stem cell-derived progenitor states. By reconstructing a differentiation trajectory at single-cell resolution, novel regulators of the mesendoderm transition to DE are elucidated and validated. Our strategy of combining single-cell analysis and genetic approaches can be applied to uncover novel regulators governing cell fate decisions in a variety of systems.
Use of typical in-patient blood pressure measurements to detect bevacizumab-induced elevation in systolic pressure after the first infusion.
Authors: M. R. Levine, K. Wroblewski, D. Dharanipragada, L. Sit, T. Karrison, T. Y. Seiwert, E. E. Cohen, E. E.okes, M. L. Maitland
Journal: Journal of Clinical Oncology (2010)

e13622 Background: Hypertension is a mechanism-based toxicity of the antivascular endothelial growth factor (VEGF) agent bevacizumab (Bev). Blood pressure (BP) elevations are a putative biomarker for VEGF inhibition and can be detected 1-8 days after initial treatment with VEGF receptor kinase inhibitors. The earliest time to detect BP changes in patients (pts) receiving Bev is unknown. Methods: BP was measured in hospitalized head and neck cancer pts in 2 clinical trials of Bev added to curative intent therapy. A phase I trial administered Bev on day 2 of each cycle of twice daily radiotherapy with fluorouracil and hydroxyurea (FHX). Complete BP data were available for 21 pts (who received 5 or 10 mg/kg Bev). Another trial randomized 16 pts at 1 institution to receive FHX + 10mg/kg Bev and 7 pts to FHX alone. Over the 6 days inpt treatment in each cycle, BP was measured once every 8 hour shift with a properly sized cuff with a DinaMap PRO400 or similar digital monitor (GE Medical Systems, Milwaukee, WI) by a patient care technician. Retrospectively, mean BP was calculated for each pt for each hospital calendar day. Results: In the phase I trial, the earliest evidence of bev-induced elevation was for the difference between the systolic BP (SBP) on cycle 1 day 3 (mean= 133mmHg; SD 14mmHg) and the baseline BP on cycle 1 day 1 (mean= 126mmHg; SD 11mmHg); mean change = 7mmHg (SD=15mmHg, 95% CI [0, 14], p = 0.04 by paired T-test). A similar effect was seen in cycle 2 but was blunted on subsequent cycles and was not statistically significant for diastolic BP at any cycle. The change in SBP was again detected in pts receiving Bev in the randomized study, mean change = 8mmHg (SD=12mmHg, 95% CI[1, 14], p = 0.03), but was absent in pts receiving FHX alone, mean change = −3.3mmHg (SD=14mmHg, 95% CI [− 16, 9], p = 0.54). There was a statistically significant treatment arm by day interaction for SBP (p = 0.04). Conclusions: With a relatively insensitive BP measurement method these studies detected evidence of a BP-elevating effect of Bev the day after the initial infusion. Studies with larger numbers of pts or more sensitive measurement methods will be needed to confirm the capacity to detect early BP elevations in pts receiving Bev. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Amgen, Astellas Pharma, Biomarin, Inc., Daiichi Sankyo, Genentech, Gilead, Millennium, Pfizer Actelion, Bayer, Bristol-Myers Squibb, EMD Serono, Genentech, Gilead, Lilly, Pfizer, Roche Patent pending for use of sorafenib to treat pulmonary hypertension
Pulmonary Function Parameters Other Than Vital Capacity Should Be Considered in Screening for Interstitial Lung Disease in Patients With Systemic Sclerosis: Comment on the Article by Suliman et al
Authors: Bruno Degano, Thibaud Soumagne, Guillaume Eberst, Nadine Méaux‐Ruault, Helder Gil, Nadine Magy‐Bertrand
Journal: Arthritis & Rheumatology (2016)
Phase 1b/2 Study of Carfilzomib, Pomalidomide, and Dexamethasone (KPd) in Patients (Pts) with Lenalidomide-Exposed and/or -Refractory but Proteasome Inhibitor (PI)-Naive or -Sensitive Multiple Myeloma: A Multiple Myeloma Research Consortium Multi-Center Study
Authors: Cara A. Rosenbaum, Vishal Kukreti, Jeffrey Zonder, Daniel Lebovic, Todd Zimmerman, Jesus G. Berdeja, Kathryn McDonnell, Jessica Waite-Marin, Kent A. Griffith, Andrzej Jakubowiak
Journal: Blood (2014)
Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease
Authors: Dhruv S. Kazi, Andrew E. Moran, Pamela G. Coxson, Joanne Penko, Daniel A. Ollendorf, Steven D. Pearson, Jeffrey A. Tice, David Guzman, Kirsten Bibbins-Domingo
Journal: JAMA (2016)

<h3>Importance</h3> Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD) and have potential for broad ASCVD prevention. Their long-term cost-effectiveness and effect on total health care spending are uncertain. <h3>Objective</h3> To estimate the cost-effectiveness of PCSK9 inhibitors and their potential effect on US health care spending. <h3>Design, Setting, and Participants</h3> The Cardiovascular Disease Policy Model, a simulation model of US adults aged 35 to 94 years, was used to evaluate cost-effectiveness of PCSK9 inhibitors or ezetimibe in heterozygous FH or ASCVD. The model incorporated 2015 annual PCSK9 inhibitor costs of $14 350 (based on mean wholesale acquisition costs of evolocumab and alirocumab); adopted a health-system perspective, lifetime horizon; and included probabilistic sensitivity analyses to explore uncertainty. <h3>Exposures</h3> Statin therapy compared with addition of ezetimibe or PCSK9 inhibitors. <h3>Main Outcomes and Measures</h3> Lifetime major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke), incremental cost per quality-adjusted life-year (QALY), and total effect on US health care spending over 5 years. <h3>Results</h3> Adding PCSK9 inhibitors to statins in heterozygous FH was estimated to prevent 316 300 MACE at a cost of $503 000 per QALY gained compared with adding ezetimibe to statins (80% uncertainty interval [UI], $493 000-$1 737 000). In ASCVD, adding PCSK9 inhibitors to statins was estimated to prevent 4.3 million MACE compared with adding ezetimibe at $414 000 per QALY (80% UI, $277 000-$1 539 000). Reducing annual drug costs to $4536 per patient or less would be needed for PCSK9 inhibitors to be cost-effective at less than $100 000 per QALY. At 2015 prices, PCSK9 inhibitor use in all eligible patients was estimated to reduce cardiovascular care costs by $29 billion over 5 years, but drug costs increased by an estimated $592 billion (a 38% increase over 2015 prescription drug expenditures). In contrast, initiating statins in these high-risk populations in all statin-tolerant individuals who are not currently using statins was estimated to save $12 billion. <h3>Conclusions and Relevance</h3> Assuming 2015 prices, PCSK9 inhibitor use in patients with heterozygous FH or ASCVD did not meet generally acceptable incremental cost-effectiveness thresholds and was estimated to increase US health care costs substantially. Reducing annual drug prices from more than $14 000 to $4536 would be necessary to meet a $100 000 per QALY threshold.
Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts
Authors: A Mupo, M Seiler, V Sathiaseelan, A Pance, Y Yang, A A Agrawal, F Iorio, R Bautista, S Pacharne, K Tzelepis, N Manes, P Wright, E Papaemmanuil, D G Kent, P C Campbell, S Buonamici, N Bolli, G S Vassiliou
Journal: Leukemia (2016)

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1K700E/+ animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness. To understand the molecular basis of these observations, we analyzed global RNA splicing in Sf3b1K700E/+ hematopoietic cells. Aberrant splicing was associated with the usage of cryptic 3′ splice and branchpoint sites, as described for human SF3B1 mutants. However, we found a little overlap between aberrantly spliced mRNAs in mouse versus human, suggesting that anemia may be a consequence of globally disrupted splicing. Furthermore, the murine orthologues of genes associated with ring sideroblasts in human MDS, including Abcb7 and Tmem14c, were not aberrantly spliced in Sf3b1K700E/+ mice. Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse. Future studies should focus on understanding the basis of these similarities and differences as a means of deciphering the consequences of spliceosome gene mutations in MDS.
HLA Associated Susceptibility to EBV+ Hodgkin Lymphoma: No Correlation with Infectious Mononucleosis or Number of Circulating EBV+ B Cells.
Authors: Arjan Diepstra, Alison M Leese, Annette Pachnio, Andrew I Bell, Bouke Hepkema, Anke Van Den Berg, Paul AH Moss, Steven P Lee, Alan B Rickinson
Journal: Blood (2012)
Induction Of Anti-Myeloma Cellular and Humoral Immunity By Pre-Targeting Clonogenic Myeloma Cells Prior To Stem Cell Transplant With T Cells Armed With Anti-CD3 x Anti-CD20 Bispecific Antibody Leads To Transfer Of Cellular and Humoral Anti-Myeloma Immunity
Authors: Lawrence G Lum, Archana Thakur, Zaid Al-Kadhimi, Abhinav Deol, Lois Ayash, Elyse N. Tomaszewski, Hiroshi Yano, Dana L Schalk, Sri Vidya Kondadasula, Patricia A. Steele, Jeffrey A. Zonder, Joseph P. Uberti, Voravit Ratanatharathorn, Muneer H. Abidi
Journal: Blood (2013)
<i>Nocturne</i>
Authors: Thomas B. Cole
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 Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Highlights of the Year in JACC 2010
Authors: Anthony N. DeMaria, Jeroen J. Bax, Ori Ben-Yehuda, Gregory K. Feld, Barry H. Greenberg, Jennifer Hall, Mark Hlatky, Wilbur Y.W. Lew, João A.C. Lima, Alan S. Maisel, Sanjiv M. Narayan, Steven Nissen, David J. Sahn, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2011)
Progress in Psychiatry
Authors: Robert Michels, Peter M. Marzuk
Journal: New England Journal of Medicine (1993)

Mood DisordersMood disorders include the depressive and manic states and are often intertwined with irritability, anger, emotional upheaval, and anxiety. The disorders may be associated with substance abuse, alcoholism, eating disorders, medical illness, anxiety, and personality disorders25. In the classification of mood disorders, the distinction between bipolar and unipolar disorders is one of the most important157. Patients with bipolar disorders have had at least one manic episode, and most have also had major depressive episodes. These patients appear to be distinct genetically, prognostically, epidemiologically, and therapeutically from patients who have only depressive episodes. Patients with a bipolar . . .
Postponing or Preventing Death? Trends in Infant Survival-Reply
Authors: James W. Buehler
Journal: JAMA (1986)

<h3>In Reply.—</h3> Dujardin et al are correct in noting the limitations of vital records in studying underlying causes of death (determined in Georgia by nosologists, who review all diagnoses listed on death certificates), and their letter raises several issues regarding the question of postponement vs prevention of infant deaths. It is certainly plausible that some infants with chronic illness developing in the perinatal period may succumb late in infancy to infections, sudden infant death syndrome, or other diseases. We attempted to address this question in part by examining underlying causes of death in conjunction with other conditions listed on death certificates; however, multiple diagnoses were available on Georgia's computer records for only the most recent years of our study period. More importantly, we wish to emphasize that the rate of<i>infant</i>death for<i>all</i>causes combined declined for all birth-weight groups. Thus, misclassification of causes of death could not explain
Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission
Authors: Nicolas Mounier, Corinne Haioun, Bernard F. Cole, Christian Gisselbrecht, Catherine Sebban, Pierre Morel, Gerald Marit, Reda Bouabdallah, Christophe Ravoet, Gilles Salles, Felix Reyes, Eric Lepage
Journal: Blood (2000)
Inside or Outside of the Heart?
Authors: Dai-Yin Lu, Jen Wei, Ming-Chon Hsiung
Journal: JAMA Surgery (2016)

A 61-year-old man with progressive shortness of breath for 1 week and myocardial infarction 1 month earlier had progressive dyspnea at rest, tachycardia, and tachypnea. Transthoracic echocardiography showed a hypoechoic mass and CT showed a large crescentic hypodense lesion. What is your diagnosis?
Is there a role for adjuvant cetuximab after radiotherapy (RT) plus cetuximab in patients (pts) with locally advanced squamous cell carcinoma of the oropharynx? A phase II randomized trial.
Authors: R. Mesia, A. Rueda, R. Vera, A. Lozano, J. A. Medina, D. Aguiar Bujanda, F. Arias de la Vega, G. Triana, M. Guix, R. Lopez
Journal: Journal of Clinical Oncology (2010)

5534 Background: Cetuximab combined with RT is a treatment option for locally advanced head and neck cancer, especially for oropharyngeal tumors. The objectives of this prospective, randomized, multicenter, phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in pts with locally advanced oropharyngeal cancer. Methods: Main eligibility criteria: >18 yrs old, stage III-IVM0 squamous tumors. Group A received concomitant boost RT (69.9Gy in 28 days) + cetuximab (400 mg/m2 1 wk before RT and 250 mg/m2/wk during RT). Group B received an additional 12 consecutive wks of cetuximab maintenance therapy. The primary endpoint was locoregional control (LRC) at 1 yr, secondary endpoints included LRC-2yrs, event-free survival, overall survival, safety and a molecular analysis (reported at meeting). Results: Demographics of the 91 enrolled pts (45 [A]; 46 [B]) were (A/B): median age (range), 60(42-75)/61(45-80); males, 80%/91%; Stage IV, 73%/72%, KPS>80, 67%/72%. Safety and compliance were previously reported (ASCO/08): cetuximab was well tolerated during and after RT. In group B, compliance in the maintenance phase was high, but 4 pts did not receive cetuximab as maintenance therapy (2 consent withdrawals and 2 AEs). 3 pts in group A and 2 in group B died within 12 wks after the last RT treatment; none was related to study treatment but occurred in the context of disease complications or underlying disease. Complete responses at 12 wks (A/B): 55.6%/69.6%; posterior cervical neck dissection: 13.3%/8.7%. Median follow-up of 26.5 mths. Efficacy parameters at 1 yr (A/B): LRC: 56.8%/60.5%, event-free survival 55.6%/60.9% and overall survival 75.6%/87%. Total deaths (cut-off July/09): 21(46.6%)/20(43.5%); 14(31.1%)/12(26.1%) due to disease progression. There were 8 (3 vs. 5) secondary tumors, mainly lung cancer. Conclusions: Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma, is feasible and may improve clinical outcomes measured at 1 year. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Serono Merck Serono, Merck Merck Serono
Changing the Terminology of Cancer
Authors: Noah A. Capurso
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Multicenter, open-label trial of PXD 101 in patients with relapsed/refractory peripheral T-cell lymphoma.
Authors: J. M. Zain, O. O'Connor, P. L. Zinzani, A. Norman, P. de Nully Brown
Journal: Journal of Clinical Oncology (2010)

e18565 Background: The study is a multicenter phase II single arm efficacy and safety study of PXD 101 (belinostat, B) monotherapy in patients (pts) with relapsed/refractory peripheral T-cell lymphoma (PTCL) who failed at least one prior systemic therapy. Aims are to determine objective response rate and time-related response parameters. B is a hydroxamate, class I and II histone deacetylase inhibitor (HDACi). Pre-clinically B has a broad antineoplastic spectrum at sub-micromolar concentrations. Phase I and II trials are ongoing in multiple indications. B was safe and well tolerated. Common events nausea, fatigue, and vomiting. A phase II study of B monotherapy in relapsed/refractory PTCL demonstrated 19 evaluable pts an ORR of 32% and median response duration of 268+ days. Methods: Eligible pts have received at least one prior systemic chemotherapy and have histologically confirmed diagnosis (dx) of PTCL of one of the subtypes: anaplastic large cell L (ALK-positive or negative), ALK-negative, angioimmunoblastic T-cell L, enteropathy-associated T-cell L, extranodal NK/T-cell L, nasal type, hepatosplenic T-cell L, peripheral T-cell L, not otherwise specified (NOS) or subcutaneous panniculitis-like T-cell L. The dx should be confirmed by a positive set of T-cell markers and negativity of B-cell markers. A pathology panel reviews all dx specimens. B will be administered as a 30-minute IV infusion of 1,000 mg/m2 on days 1-5 of every 3-week cycle until disease progression or unmanageable treatment-related toxicities. As of Jan. 4, 2010, 19 pts have been included in the trial. The primary study endpoint is objective response rate (ORR). Sample size was based on a 2-stage optimal design with a hypothesized ORR of p1=20% for B and a minimal or "uninteresting" ORR of p0=9%. At least 14 confirmed objective responses in 100 evaluable pts are required to confirm a 20% target response rate with an alpha of 0.05 assuming a power of 90%. Pharmacokinetic data will be collected to explore exposure-response relationships. Results: This is an ongoing phase II clinical trial study. Conclusions: Results are awaited at the end of this trial. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration TopoTarget A/S
Re: Adi J. Klil-Drori, Hui Yin, Vicky Tagalakis, Armen Aprikian, Laurent Azoulay. Androgen Deprivation Therapy for Prostate Cancer and Risk of Venous Thromboembolism. Eur Urol 2016;70:56–61
Authors: Mieke Van Hemelrijck, Hans Garmo, Jan Adolfsson, Pär Stattin
Journal: European Urology (2016)
Vaccination : opinion des parents et des professionnels de santé en Irlande
Authors: S Cotter, F Ryan, H Hegarty, T. J McCabe, E Keane
Journal: Eurosurveillance (2003)

Une etude sur les comportements et pratiques en matiere de vaccination a ete conduite aupres de parents et profes-sionnels de sante en Irlande de mai a aout 2001. Les parents ont exprime leur peur des effets secondaires des vaccins, leur mefiance vis a vis des services sanitaires et se sentaient mal informes. D’apres les groupes de discussions, les pro-fessionnels de sante consideraient qu’ils manquaient de temps et ne disposaient pas de documents facilement com-prehensibles pour informer correctement les parents.