tbuckley/cabot-search huggingface dataset:
I’m Talking to You-Mab—How to Pronounce the New, Unpronounceable Pharmaceuticals
Authors: Daniel S. Frank
Journal: JAMA Internal Medicine (2018)

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
Development and Validation of a Risk Prediction Model for Acute Kidney Injury After the First Course of Cisplatin
Authors: Shveta S. Motwani, Gearoid M. McMahon, Benjamin D. Humphreys, Ann H. Partridge, Sushrut S. Waikar, Gary C. Curhan
Journal: Journal of Clinical Oncology (2018)

Purpose Cisplatin-associated acute kidney injury (C-AKI) is common. We sought to develop and validate a predictive model for C-AKI after the first course of cisplatin. Methods Clinical and demographic data were collected on patients who received cisplatin between 2000 and 2016 at two cancer centers. C-AKI was defined as a 0.3 mg/dL rise in serum creatinine within 14 days of receiving cisplatin. Using multivariable logistic regression models with C-AKI as the primary outcome, we created a scoring model from the development cohort (DC) and tested it in the validation cohort (VC). Results C-AKI occurred in 13.6% of 2,118 patients in the DC and in 11.6% of 2,363 patients in the VC. Factors significantly associated with C-AKI included age 61 to 70 years (odds ratio [OR], 1.64 [95% CI, 1.21 to 2.23]; P = .001) and 71 to 90 years (OR, 2.97 [95% CI, 2.06 to 4.28]; P < .001) compared with ≤ 60 years; cisplatin dose 101 to 150 mg (OR, 1.58 [95% CI, 1.14 to 2.19]; P = .007) and > 150 mg (OR, 3.73 [95% CI, 2.68 to 5.20]; P < .001) compared with ≤ 100 mg; a history of hypertension (OR, 2.10 [95% CI, 1.54 to 2.72]; P < .001) compared with no hypertension; and serum albumin 2.0 to 3.5 g/dL (OR, 2.21 [95% CI, 1.62 to 3.03]; P < .001) compared with > 3.5 g/dL. The baseline estimated glomerular filtration rate was not significantly associated with the risk of C-AKI. The c-statistics of the score-based model in the DC and the VC were 0.72 (95% CI, 0.69 to 0.75) and 0.70 (95% CI, 0.67 to 0.73), respectively. Scores of 0, 3.5, and 8.5 were associated with a probability of C-AKI of 0.03 (95% CI, 0.03 to 0.05), 0.12 (95% CI, 0.11 to 0.14), and 0.51 (95% CI, 0.43 to 0.60), respectively. Conclusion A score-based model created by using the patient's age, cisplatin dose, hypertension, and serum albumin is predictive of C-AKI.
Outcome of Non-Germinal Center/Activated B-Cell Type Diffuse Large B-Cell Lymphoma Determined By Immunohistochemistry in a Single Institution over 7 Years
Authors: Marian Girgis, Joyce Philip, Zora Cvetkovski Injic, Edward M. Peres, Madhu P. Menon, Shatha Y. Farhan, Nalini Janakiraman
Journal: Blood (2017)
Smoking, Sex, and Non–Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)
Authors: Ting-Yuan David Cheng, Amy K Darke, Mary W Redman, Gary R Zirpoli, Warren Davis, Rochelle Payne Ondracek, Wiam Bshara, Angela R Omilian, Robert Kratzke, Mary E Reid, Julian R Molina, Jill M Kolesar, Yuhchyau Chen, Robert M MacRae, James Moon, Philip Mack, David R Gandara, Karen Kelly, Regina M Santella, Kathy S Albain, Christine B Ambrosone
Journal: JNCI Journal of the National Cancer Institute (2017)

To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Patients with primary non–small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)–α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = –15.8, P = .003) and nuclear ER-β (β = –12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = –42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.
Young Male With Incessantly Wide Complex Tachycardia
Authors: Andrés F. Miranda-Arboleda, Rafael Correa, Gloria Saenz, Juan F. Agudelo, Juan D. Ramírez
Journal: Circulation (2018)

ECG CHALLENGEA 26-year-old male with no past medical issues presented with 24-hour sudden onset palpitations, chest discomfort, and dizziness.He was hemodynamically stable and his heart rate was 189 bpm, with no other remarkable findings on physical examination.A 12-lead ECG (Figure 1) showed regular wide complex tachycardia with right bundle-branch block and extreme superior axis.Stepwise management was provided with vagal maneuvers, escalating doses of adenosine, uptitrated intravenous verapamil, and cardioversion with serial discharges ≤270 J of biphasic energy.However, all interventions were ineffective, and the tachycardia remained incessant.What is the arrhythmia, and what cardiac structure is involved in its origin?Please turn the page to read the diagnosis.
Esophageal IgG4 Levels Are Elevated in Pediatric Eosinophilic Esophagitis and Correlate with Esophageal Histopathology Including Levels of Eosinophils
Authors: Chen E. Rosenberg, Melissa K. Mingler, David W. Morris, Margaret H. Collins, Julie M. Caldwell, Vincent A. Mukkada, Philip E. Putnam, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2018)
Follicular lymphoma: 2018 update on diagnosis and management
Authors: Arnold Freedman
Journal: American Journal of Hematology (2018)

Abstract Disease overview Follicular lymphoma is generally an indolent B cell lymphoproliferative disorder of transformed follicular center B cells. Follicular lymphoma (FL) is characterized by diffuse lymphadenopathy, bone marrow involvement, splenomegaly and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis Diagnosis is based on histology of preferably a biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl‐2 protein. The overwhelming majority of cases have the characteristic t (14;18) translocation involving the IgH/bcl‐2 genes. Risk stratification The Follicular Lymphoma International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age &gt;60 years, hemoglobin &lt;12 g/dL, serum LDH &gt; normal, Ann Arbor stage III/IV, number of involved nodal areas &gt; 4. The presence of 0, 1, 2, and ≥ 3 adverse factors defines low, intermediate, and high‐risk disease. With the use of more modern therapies, outcomes have improved. Risk‐adapted therapy Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias, with no survival advantage for early treatment with either chemotherapy or rituximab alone. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy‐rituximab and single agent rituximab. Experimental therapies as well as stem cell transplantation (SCT) are considered for recurrent disease.
Synthetic Biology: Immunotherapy by Design
Authors: Jamie Brenner, Jang Hwan Cho, Nicole M.L. Wong, Wilson W. Wong
Journal: Annual Review of Biomedical Engineering (2018)

Cellular immunotherapy holds great promise for the treatment of human disease. Clinical evidence suggests that T cell immunotherapies have the potential to combat cancers that evade traditional immunotherapy. Despite promising results, adverse effects leading to fatalities have left scientists seeking tighter control over these therapies, which is reflected in the growing body of synthetic biology literature focused on developing tightly controlled, context-independent parts. In addition, researchers are adapting these tools for other uses, such as for the treatment of autoimmune disease, HIV infection, and fungal interactions. We review this body of work and devote special attention to approaches that may lend themselves to the development of an "ideal" therapy: one that is safe, efficient, and easy to manufacture. We conclude with a look toward the future of immunotherapy: how synthetic biology can shift the paradigm from the treatment of disease to a focus on wellness and human health as a whole.
PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop regulates the biological behavior of glioma cells
Authors: Xiaobai Liu, Jian Zheng, Yixue Xue, Hai Yu, Wei Gong, Ping Wang, Zhen Li, Yunhui Liu
Journal: Theranostics (2018)

Rationale: PIWI-interacting RNAs (piRNAs), a class of newly discovered small RNA molecules that function by binding to the Argonaute protein family (i.e., the PIWIL protein subfamily), and long noncoding RNAs (lncRNA) are implicated in several cancers. However, the detailed roles of ncRNAs in glioma remain unclear. Methods: The expression of PIWIL3, piR-30188, OIP5-AS1, miR-367, CEBPA and TRAF4 were measured in glioma tissues and cells. The role of PIWIL3/OIP5-AS1/miR-367-3p/CEBPA feedback loop was evaluated in cell and animal models. The association of the above molecules was analyzed. Results: Over-expression of PIWIL3, piR-30188 and miR-367-3p or knockdown of OIP5-AS1 resulted in inhibition of glioma cells progression. Binding sites between piR-30188 and OIP5-AS1 as well as between OIP5-AS1 and miR-367-3p were confirmed by RNA immunoprecipitation and luciferase assays. OIP5-AS1 knockdown or miR-367-3p over-expression contributed to a decrease in CEBPA (CCAAT/enhancer binding protein alpha) protein. Furthermore, CEBPA was detected as a target of miR-367-3p and played an oncogenic role in glioma. Treatment with CEBPA and miR-367-3p resulted in the modulation of downstream TRAF4 (TNF receptor-associated factor 4). PIWIL3 was also a target of CEBPA, forming a positive feedback loop in the growth regulation of glioma cells. Significantly, knockdown of OIP5-AS1 combined with over-expression of PIWIL3 and miR-367-3p resulted in tumor regression and extended survival in vivo. Conclusion: These results identified a novel molecular pathway in glioma cells that may provide a potential innovative approach for tumor therapy.
Phase II study of afatinib in recurrent and/or metastatic esophageal squamous cell carcinoma (R/M ESCC) (KCSG HN14-18).
Authors: Min Hee Hong, Yun-Gyoo Lee, Hyo Song Kim, Keon Uk Park, Hoon-Gu Kim, Yoon Ho Ko, Ik-Joo Chung, Young Joo Min, Min Kyoung Kim, HyeRyun Kim, Byoung Chul Cho
Journal: Journal of Clinical Oncology (2017)

4051 Background: Afatinib, an irreversible pan-ErbB kinase inhibitor showed anti-tumor activity against esophageal cancer in phase I trial. In this multicenter, open-label, single arm phase II study, we aimed to evaluate the activity and safety of afatinib in R/M ESCC. Methods: Patients (pts) who had ECOG PS 0-2 and had progressed on platinum-based chemotherapy for R/M ESCC were enrolled. Pts were treated with afatinib 40mg/day until disease progression, unacceptable toxicity, or patient’s refusal. Primary endpoint was objective response rate (ORR) per RECIST 1.1. The estimated sample size was 49, using a two-stage minimax design to evaluate incremental response rate from 5 to 15%. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profile. Additionally, we try to identify biomarker to predict efficacy of afatinib with target capture sequencing and gene expression profile as exploratory endpoints. Results: In a total of 49 enrolled pts (median age 60; range 44 -84), ORR and DCR were 14.3 % and 73.3%, respectively. With a median follow-up of 6.6 months, median PFS and OS was 3.4 months (95% CI 2.2-4.6) and 6.6 months (95% CI 5.2-8.0). Median treatment duration and duration of response were 2.8 months (range, 0.4-15.3) and 7.1 months (range, 2.5-13.9), respectively. Dose reduction and interruption occurred in 19 (38.8%) and 15 (30.6 %) pts. Treatment-related adverse events (TRAE) occurred in 33 pts (67.3%) with most common TRAEs being diarrhea (n=22, 44.9%) and acneiform rash (n=12, 24.5%). G3-4 TRAEs were rare, occurring in 7 pts (14.3 %). Conclusions: Afatinib demonstrated modest efficacy with manageable toxicity in platinum-resistant R/M ESCC patients. Given the modest response rate, identification of predictive biomarkers is essential for further clinical investigation of afatinib in R/M ESCC. Those biomarkers are being analyzed and will be presented in the conference (NCT02353936). Clinical trial information: NCT02353936. [Table: see text]
Superhydrophobic/Superhydrophilic Janus Fabrics Reducing Blood Loss
Authors: Tang Zhu, Junrong Wu, Ning Zhao, Chao Cai, Zhenchao Qian, Fangfang Si, Heng Luo, Jing Guo, Xuan Lai, Longquan Shao, Jian Xu
Journal: Advanced Healthcare Materials (2018)

Abstract Hemostatic fabrics are most commonly used in baseline emergency treatment; however, the unnecessary blood loss due to the excessive blood absorption by traditional superhydrophilic fabrics is overlooked. Herein, for the first time, superhydrophobic/superhydrophilic Janus fabrics (superhydrophobic on one side and superhydrophilic on the other) are proposed: the superhydrophilic part absorbs water in the blood to expedite the clotting while the superhydrophobic part prevents blood from further permeating. Compared with the common counterparts, effective bleeding control with reducing blood loss more than 50% can be achieved while the breathability largely remain by using Janus fabrics. The proposed prototypes can even prolong the survival time in the rat model with serious bleeding. This strategy for reducing blood loss via simply tuning wettability is promising for the practical applications.
High Cost of Investigating Measles Cases
Authors: Rita Rubin
Journal: JAMA (2018)

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
Dualchip human low grade B-cell lymphoma: a specialized low density DNA microarray for the differential diagnostic of small B-cell non-Hodgkin's lymphoma
Authors: Jean-Pierre Gillet, Thierry Molina, Philippe Gaulard, Karen Leroy, Josette Briere, Ivan Theate, Catherine Thieblemont, Andre Bosly, Michel Herin, Jacques Hamels, José Remacle
Journal: Annals of Oncology (2005)
PHD3 Controls Lung Cancer Metastasis and Resistance to EGFR Inhibitors through TGFα
Authors: Higinio Dopeso, Hui-Ke Jiao, Angel M. Cuesta, Anne-Theres Henze, Liane Jurida, Michael Kracht, Amparo Acker-Palmer, Boyan K. Garvalov, Till Acker
Journal: Cancer Research (2018)

Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity to metastasize and to develop therapy resistance. Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are linked to tumor metastasis and drug resistance, but little is known about how oxygen sensing and EMT intersect to control these hallmarks of cancer. Here, we show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis, and therapeutic resistance. PHD3 depletion in tumors, which can be caused by the EMT inducer TGFβ or by promoter methylation, enhanced EMT and spontaneous metastasis via HIF-dependent upregulation of the EGFR ligand TGFα. In turn, TGFα stimulated EGFR, which potentiated SMAD signaling, reinforcing EMT and metastasis. In clinical specimens of lung cancer, reduced PHD3 expression was linked to poor prognosis and to therapeutic resistance against EGFR inhibitors such as erlotinib. Reexpression of PHD3 in lung cancer cells suppressed EMT and metastasis and restored sensitivity to erlotinib. Taken together, our results establish a key function for PHD3 in metastasis and drug resistance and suggest opportunities to improve patient treatment by interfering with the feedforward signaling mechanisms activated by PHD3 silencing.Significance: This study links the oxygen sensor PHD3 to metastasis and drug resistance in cancer, with implications for therapeutic improvement by targeting this system. Cancer Res; 78(7); 1805-19. ©2018 AACR.
Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and Relapse: An Exome Sequencing Study of 50 Patients
Authors: Philipp A. Greif, Luise Hartmann, Sebastian Vosberg, Sophie M. Stief, Raphael Mattes, Ines Hellmann, Klaus H. Metzeler, Tobias Herold, Stefanos A. Bamopoulos, Paul Kerbs, Vindi Jurinovic, Daniela Schumacher, Friederike Pastore, Kathrin Bräundl, Evelyn Zellmeier, Bianka Ksienzyk, Nikola P. Konstandin, Stephanie Schneider, Alexander Graf, Stefan Krebs, Helmut Blum, Martin Neumann, Claudia D. Baldus, Stefan K. Bohlander, Stephan Wolf, Dennis Görlich, Wolfgang E. Berdel, Bernhard J. Wörmann, Wolfgang Hiddemann, Karsten Spiekermann
Journal: Clinical Cancer Research (2018)

Purpose: To study mechanisms of therapy resistance and disease progression, we analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML) based on somatic alterations.Experimental Design: We performed exome sequencing of matched diagnosis, remission, and relapse samples from 50 CN-AML patients treated with intensive chemotherapy. Mutation patterns were correlated with clinical parameters.Results: Evolutionary patterns correlated with clinical outcome. Gain of mutations was associated with late relapse. Alterations of epigenetic regulators were frequently gained at relapse with recurring alterations of KDM6A constituting a mechanism of cytarabine resistance. Low KDM6A expression correlated with adverse clinical outcome, particularly in male patients. At complete remission, persistent mutations representing preleukemic lesions were observed in 48% of patients. The persistence of DNMT3A mutations correlated with shorter time to relapse.Conclusions: Chemotherapy resistance might be acquired through gain of mutations. Insights into the evolution during therapy and disease progression lay the foundation for tailored approaches to treat or prevent relapse of CN-AML. Clin Cancer Res; 24(7); 1716-26. ©2018 AACR.
Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease‐Modifying Antirheumatic Drugs in the Treatment of Moderate‐to‐Severe Rheumatoid Arthritis
Authors: Mark C. Genovese, Maria Greenwald, Christine Codding, Anna Zubrzycka‐Sienkiewicz, Alan J. Kivitz, Annie Wang, Kathyjo Shay, Xuegong Wang, Jay P. Garg, Mario H. Cardiel
Journal: Arthritis & Rheumatology (2017)

To evaluate the efficacy and safety of orally administered once-daily peficitinib in combination with limited conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with moderate-to-severe rheumatoid arthritis (RA).In this randomized, double-blind, phase IIb trial, patients with RA (n = 289) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg or matching placebo once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12.ACR20 response rates at week 12 were 22.0%, 36.8%, 48.3% (P < 0.05), 56.3% (P < 0.01), and 29.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Patients in the peficitinib 100 mg and 150 mg groups achieved a rapid and statistically significant ACR20 response compared with those in the placebo group (P < 0.05), reaching statistical significance by week 2. Overall, the incidence of adverse events (AEs) was similar between patients receiving peficitinib and those receiving placebo. The most common AEs were upper respiratory tract infection (5% [n = 15]), nausea (4% [n = 12]), and urinary tract infection (4% [n = 10]). There was 1 case of herpes zoster in the placebo group, and 1 serious infection (limb abscess) in the peficitinib 25 mg group. There were no incidences of grade 2 or higher neutropenia or lymphopenia.In patients with moderate-to-severe RA, orally administered once-daily peficitinib in combination with limited csDMARDs resulted in a dose-dependent ACR20 response rate over 12 weeks with satisfactory tolerability.