tbuckley/cabot-search huggingface dataset:
Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in <i>STAT2</i>
Authors: Christopher J. A. Duncan, Benjamin J. Thompson, Rui Chen, Gillian I. Rice, Florian Gothe, Dan F. Young, Simon C. Lovell, Victoria G. Shuttleworth, Vicky Brocklebank, Bronte Corner, Andrew J. Skelton, Vincent Bondet, Jonathan Coxhead, Darragh Duffy, Cecile Fourrage, John H. Livingston, Julija Pavaine, Edmund Cheesman, Stephania Bitetti, Angela Grainger, Meghan Acres, Barbara A. Innes, Aneta Mikulasova, Ruyue Sun, Rafiqul Hussain, Ronnie Wright, Robert Wynn, Mohammed Zarhrate, Leo A. H. Zeef, Katrina Wood, Stephen M. Hughes, Claire L. Harris, Karin R. Engelhardt, Yanick J. Crow, Richard E. Randall, David Kavanagh, Sophie Hambleton, Tracy A. Briggs
Journal: Science Immunology (2019)

STAT2 R148W impairs an essential regulatory function of STAT2, revealing the damage wreaked by excessive IFNα/β activity.
Microsphere oxycodone for pain management in head and neck cancer (HNC) patients receiving radiotherapy.
Authors: Andrew Michael McDonald, Sharon Spencer, Christopher Douglas Willey, James A. Bonner, Thomas A Swain, Lisle Nabell, Susan McCammon, William Carroll, Gerald McGwin, Smita Bhatia, Eddy Shih-Hsin Yang
Journal: Journal of Clinical Oncology (2019)

123 Background: Pain is a common adverse effect of RT in patients with HNC, and extended release analgesic options are limited due to high rates of dysphagia. Wax microsphere bound oxycodone was developed as an abuse-deterrent opioid and maintains a similar pharmacokinetic profile whether administered with or without an intact capsule. We hypothesized that microsphere oxycodone could be used for extended release analgesia in patients undergoing RT for HNC and would not need to be discontinued due to dysphagia or gastrostomy tube dependence. Methods: We performed an open-label prospective clinical trial (NCT03317730) to assess the feasibility of microsphere oxycodone for extended release analgesia during RT for HNC. Participants were &gt; 18y, had histologically confirmed HNC, and were to receive &gt; 50 Gy of RT. Analgesia was prescribed in accordance with the World Health Organization pain ladder. Non-opioid and immediate release opioids were used at the discretion of the treating physicians. Microsphere oxycodone was initiated when total daily opioid dose exceeded 30mg morphine sulfate equivalent and was titrated weekly during RT. The primary feasibility endpoint was frequency of microsphere oxycodone discontinuation within 3 months of RT for reasons other than pain resolution. Secondary endpoints included pain level during RT. Results: Twenty-six eligible patients were enrolled between June and November, 2018. Microsphere oxycodone was initiated in 13 (50%) patients at a median of 5 weeks after beginning RT (range: 0 – 7 weeks). The mean Brief Pain Index Severity composite score at time of microsphere oxycodone initiation was 5.4 (SD ±2.0) and was 4.8 (SD ±1.5) during the final week of RT ( p= 0.21). Six patients utilized a gastrostomy tube to administer microsphere oxycodone for all or part of RT. Microsphere oxycodone was discontinued in 1 (7.6%) patient due to perceived inefficacy, 0 patients due to toxicity, and 0 patients due to difficulty with administration. Conclusions: These results support the feasibility and safety of microsphere oxycodone for extended release analgesia in patients with HNC undergoing RT. Future research should compare microsphere oxycodone and transdermal fentanyl in this population. Clinical trial information: NCT03317730.
International trends in COPD mortality, 1995–2017
Authors: Joannie Lortet-Tieulent, Isabelle Soerjomataram, José Luis López-Campos, Julio Ancochea, Jan Willem Coebergh, Joan B. Soriano
Journal: European Respiratory Journal (2019)

<b>In our international study over 1995–2017, COPD mortality rates declined in most countries. Yet, in females, they remained stable in North America and increased in six countries in Europe. The number of deaths increased or remained stable in most countries.</b>http://bit.ly/2niUQ8d
HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms
Authors: Lanzhu Yue, Vasundhara Sharma, Nathan P. Horvat, Afua A. Akuffo, Matthew S. Beatty, Cem Murdun, Christelle Colin, Julia M. R. Billington, William E. Goodheart, Eva Sahakian, Ling Zhang, John J. Powers, Narmin E. Amin, Que T. Lambert-Showers, Lancia N. Darville, Javier Pinilla-Ibarz, Gary W. Reuther, Kenneth L. Wright, Chiara Conti, Jennifer Y. Lee, Xiaozhang Zheng, Pui Yee Ng, Matthew W. Martin, C. Gary Marshall, John M. Koomen, Ross L. Levine, Amit Verma, H. Leighton Grimes, Eduardo M. Sotomayor, Zonghong Shao, Pearlie K. Epling-Burnette
Journal: Blood (2019)
The Acquirement of Rituximab Resistance Is Associated with a Global Downregulation of CD54 in B-Cell Lymphoma Cells: The Potential Role of Adhesion Molecules in Rituximab Anti-Tumor Activity
Authors: Ping-Chiao Tsai, Naveen Bangia, Scott Olejniczak, Francisco J. Hernandez-Ilizaliturri, Myron Czuczman
Journal: Blood (2008)
New NIH Strategic Research Plan Focuses on Tick-borne Diseases
Authors: Rita Rubin
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 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
Duty of care versus patient confidentiality: High Court hears test case on Huntington’s disease
Authors: Clare Dyer
Journal: BMJ (2019)

The High Court in London is hearing a case that will clarify the duty of doctors to disclose confidential information about a patient’s hereditary disease to relatives.

A woman who learnt accidentally that her father had Huntington’s disease is suing three NHS trusts for not passing on the information. The claimant, referred to as ABC to protect her own daughter’s identity, learnt the truth when her daughter, now aged 9, was 4 months old. She claims that, had she known this earlier, she would have had an abortion.

She told the High Court, “I was utterly traumatised by the way I was …
Efficacy and Safety of Rivaroxaban versus Warfarin in Patients Taking Non-dihydropyridine Calcium Channel Blockers: Results From the ROCKET AF Trial
Authors: Jeffrey B. Washam, Anne S. Hellkamp, Yuliya Lokhnygina, Jonathan P. Piccini, Scott D. Berkowitz, Christopher C. Nessel, Richard C. Becker, Guenter Breithardt, Keith A. Fox, Jonathan L. Halperin, Graeme J. Hankey, Kenneth W. Mahaffey, Daniel E. Singer, Manesh R. Patel
Journal: Circulation (2015)
Identification of New Risk Loci and Regulatory Mechanisms Influencing Genetic Susceptibility to Acute Lymphoblastic Leukaemia
Authors: Jayaram Vijayakrishnan, Maoxiang Qian, James B Studd, Wenjian Yang, Ben Kinnersley, Philip Law, Peter Broderick, Elizabeth A. Raetz, James M. Allan, Ching-Hon Pui, Ajay Vora, William E. Evans, Anthony V. Moorman, Allen Eng Juh Yeoh, Chunliang Li, Claus Bartram, Charles G. Mullighan, Martin Zimmermann, Stephen P. Hunger, Martin Schrappe, Mary V. Relling, Martin Stanulla, Mignon L. Loh, Richard S. Houlston, Jun J. Yang
Journal: Blood (2019)
Factors associated with time to palliative radiotherapy in an academic radiation oncology clinic.
Authors: Ryan T. Hughes, Moeko Nagatsuka, Chase Glenn, Adam G. Johnson, Doris R. Brown
Journal: Journal of Clinical Oncology (2019)

56 Background: Palliative radiotherapy (PRT) is a common and effective modality for the relief of symptoms due to malignancy. Members of the supportive care team may be hesitant to refer for PRT due to concerns regarding timeliness of treatment and patient/caregiver time burden. The current structure of most radiation oncology clinics is not conducive to the delivery of timely PRT and few metrics aimed at quality improvement have been reported. Methods: We reviewed all courses of PRT delivered at our institution between January 2017 and December 2018. Hematologic/myeloma primary and postoperative cases were excluded. The dates of referral, consultation, PRT planning simulation, PRT start and end were recorded. An inherent delay was noted if PRT was purposefully delayed (workup, imaging). Time to PRT (TTPRT) was defined as the number of days between referral and start of PRT. A remaining life ratio (RLR) representing TTPRT as a proportion of survival from the time of referral, was developed as a practical metric to represent timeliness of PRT with respect to prognosis. Results: 338 courses of PRT were included from 67% outpatient and 33% inpatient referrals. Indications included pain (55%), neurologic deficits/brain metastases (23%), respiratory symptoms (10%), bleeding (6%) and other (7%). Median TTPRT was 13 d (IQR 4-19), comprised of: referral to consult (3 d), consult to simulation (4 d), and simulation to PRT (6 d). Factors associated with TTPRT included ECOG, PRT indication, site (non-spine bone, chest, or brain), outpatient referral and delay. TTPRT was not associated with age, gender, rural residence, distance to hospital, race, median household income, insurance or marital status. Of 229 patients who died, factors associated with increased RLR were outpatient referral (13% v. 5%), abdomen/pelvis treatment site (16% v. 9%) and delay (17% v. 8%). Conclusions: TTPRT is associated with patient, treatment, and systematic factors, some of which are associated with increased RLR, elucidating several opportunities for improvement. Based on these results, our group has established a dedicated Palliative Radiation Oncology Clinic focused on timely, quality PRT, the outcomes of which will be assessed prospectively.
Linking Microenvironmental Signals to Metabolic Switches and Drug Responses in Chronic Lymphocytic Leukemia
Authors: Zhenghao Chen, Gaspard Cretenet, Hanneke ter Burg, Gabriela Andrejeva, Jeffrey C Rathmell, Francesco Forconi, Gerritje J. W. van der Windt, Arnon P. Kater, Eric Eldering
Journal: Blood (2019)
An in vitro evaluation of CYP2D6 enzymatic inhibition activities of a Chinese herbal medicine formulation (Xiang Bei Yangrong Tang) for the management of cancer-related fatigue
Authors: N.Y. Yap, H.K. Ho, H.F. Zheng, C.J. Tan, Y.L. Toh, C.C. Ng, A. Chan
Journal: Annals of Oncology (2019)
Inducible expression of dominant negative DNA polymerase gamma(POLGdn) in human cells: characterizations and applications
Authors: Weiqin Lu, Li Feng, Helene Pelicano, Zhao Chen, Geetha Achanta, Hui Zhang, Peng Huang
Journal: Cancer Research (2006)

105  Mitochondria, the power houses of the cell, are at the cross-road of many cellular pathways. They play central roles in energy metabolism, maintenance of ion homeostasis and redox balance, and regulation of apoptosis. Mitochondrial DNA (mtDNA) mutations are involved in a variety of pathologies including neurodegenerative diseases, cancer and aging. Here we report the inducible expression of a dominant negative form of the mitochondrial replication enzyme, DNA polymerase (pol γ), in cell culture and the biological consequence. T-ReX293 cells were transfected with a plasmid contains a D1153A substitution in the pol γ gene that encodes a dominant negative form of the enzyme (POLGdn). Severe mitochondrial dysfunction was observed upon the induction of the transgene expression. A decrease in mtDNA content was detected by PCR analysis, and suppressed mtDNA replication activity was revealed by an in vitro replication assay. The mitochondrial encoded protein cytochrome c oxidase II (COII) was substantially reduced at day 6 of the transgene expression, and became undetectable within two weeks. By day 13 of the transgene induction, the cells showed ρ° phenol type, characterized by a lack of electron transport chain activity and deficiency in respiration, auxotrophic for pyruvate and uridine, and a decrease in superoxide radical generation. The cells became dependent on glycolysis and exhibited increased glucose uptake and enhanced lactate production. Mitochondrial mass was increased in cells expressing POLGdn. Interestingly, a concurrent reduction of nucleus-encoded protein APE, cyclophilin D and an elevation of HKII protein were also observed. The data indicate that expression of POLGdn not only caused mitochondrial dysfunction but also affected the nucleus encoded gene expression, leading to profound change in cellular functions. This inducible POLGdn expression system provides a unique experimental model to investigate the roles of mitochondrial dysfunction in causing changes in nuclear gene expression and cellular behaviors, and alterations in apoptosis and cellular response to anticancer drugs.
Beyond Neural Coding? Lessons from Perceptual Control Theory
Authors: Xerxes D. Arsiwalla, Ruben Moreno Bote, Paul Verschure
Journal: Behavioral and Brain Sciences (2019)

Abstract Pointing to similarities between challenges encountered in today's neural coding and twentieth-century behaviorism, we draw attention to lessons learned from resolving the latter. In particular, Perceptual Control Theory posits behavior as a closed-loop control process with immediate and teleological causes. With two examples, we illustrate how these ideas may also address challenges facing current neural coding paradigms.
Current landscape of combined oncology/palliative care training in the United States.
Authors: Ramy Sedhom, Arjun Gupta, Thomas J. Smith, Arif Kamal
Journal: Journal of Clinical Oncology (2019)

68 Background: Recent calls by ASCO and others recommend early integration of oncology and palliative care. The rapid growth of new cancer therapies (e.g. immunotherapy) and their associated side effects and prognostic uncertainty suggest the need for oncologists to have palliative care sub-specialization. Despite the logical integration of oncology and palliative care training, the current landscape of ACGME training programs for these fields is unknown. Methods: We explored the ERAS Fellowship Website (https://www.aamc.org/services/eras/) on June 15, 2019, and collected information on Medical oncology, Medical Oncology/Hematology, and Hospice and Palliative Medicine (HPM) Programs. We identified institutions/ health systems that offered both Medical Oncology and HPM programs. We also identified institutions/ health systems that offered other Fellowships combined with Medical Oncology. We validated information by verifying each training program's website. Results: 152 unique programs offered Medical Oncology fellowship (144 combined with hematology) and 131 unique programs offered HPM fellowship. 7 Medical Oncology programs had tracks that allowed combination with geriatrics or infectious disease. 73 unique institutions/ health systems offered both Medical Oncology and HPM training separately, but no programs offered a combined Medical Oncology/ HPM track. Conclusions: Despite the call to better integrate palliative care in oncology care, we did not find any published descriptions of tracks combining Medical Oncology and HPM training. Successful examples of integrating Medical Oncology with other disciplines such as geriatrics exist. Trainees may still forge their own pathway and do sequential fellowships in Medical Oncology and HPM, but investment by key stakeholders is essential to pilot novel educational programs to address workforce issues in this field. It remains unknown how many programs accommodate combined or sequential training for interested applicants, or how they are funded.
Family Visitation Policies in the ICU and Delirium
Authors: Daniel Garros, Ari R. Joffe
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
Multiplexed Immunofluorescence (IF) Analysis and Gene Expression Profiling of Biopsies from Patients with Relapsed/Refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL) Treated with Lisocabtagene Maraleucel (liso-cel) in Transcend NHL 001 Reveal Patterns of Immune Infiltration Associated with Durable Response
Authors: David J. Reiss, Trevor Do, David Kuo, Vanessa E. Gray, N. Eric Olson, Chung-Wein Lee, Mary H. Young, Shradha Srinivasan, Falon D. Gray, Brian Fox, Suzana Couto, Jason A. Dubovsky, Frank Schmitz, Kathryn Newhall
Journal: Blood (2019)
Efficacy and Safety of Gemcitabine With Trastuzumab and Pertuzumab After Prior Pertuzumab-Based Therapy Among Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer
Authors: Neil M. Iyengar, Lillian M. Smyth, Diana Lake, Ayca Gucalp, Jasmeet C. Singh, Tiffany A. Traina, Patricia DeFusco, Monica N. Fornier, Shari Goldfarb, Komal Jhaveri, Shanu Modi, Tiffany Troso-Sandoval, Sujata Patil, Gary A. Ulaner, Maxine Jochelson, Larry Norton, Clifford A. Hudis, Chau T. Dang
Journal: JAMA Network Open (2019)

Taxanes with trastuzumab and pertuzumab for initial treatment of human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-positive metastatic breast cancer is associated with improved progression-free survival (PFS) and overall survival. While continued use of trastuzumab in therapeutic combinations after disease progression is standard, the efficacy of continuing pertuzumab is unknown.To evaluate the efficacy and safety of pertuzumab in combination with gemcitabine and trastuzumab after prior treatment with pertuzumab for ERBB2-positive metastatic breast cancer.This is a phase 2 single-arm clinical trial of dual anti-ERBB2 therapy after prior treatment with pertuzumab. The study took place at a single academic center from March 2015 to April 2017 among women with ERBB2-positive metastatic breast cancer, prior pertuzumab-based treatment, and 3 or fewer prior chemotherapy regimens. Data were analyzed between January 2019 and March 2019.Treatment consisted of gemcitabine, 1200 mg/m2 (later amended to 1000 mg/m2) on days 1 and 8 every 3 weeks, plus trastuzumab (8-mg/kg loading dose, then 6 mg/kg) and pertuzumab (840-mg loading dose, then 420 mg) once every 3 weeks.The primary end point was 3-month PFS. Based on prior trials, a target rate of 70% or higher was selected as the promising progression-free rate at 3 months. Secondary outcomes included safety, tolerability, and overall survival.A total of 45 patients (median [range] age, 57.1 [31.7-77.2] years) were enrolled; 22 (49%) were treated in the second-line setting, and 23 (51%) were treated in the third-line setting or beyond. Of these, 22 (49%) received prior trastuzumab emtansine (T-DM1). At a median (range) follow-up of 27.6 (8.3-36.0) months, 3-month PFS was 73.3% (95% CI, 61.5%-87.5%). Overall, median PFS was 5.5 months (95% CI, 5.4-8.2 months). Treatment was well tolerated, with no occurrences of febrile neutropenia or symptomatic left ventricular systolic dysfunction.In this phase 2 trial, treatment with gemcitabine, trastuzumab, and pertuzumab after prior pertuzumab-based therapy for ERBB2-positive metastatic breast cancer was associated with a 3-month PFS rate of 73.3% and was well tolerated. Continuation of pertuzumab beyond progression was associated with apparent clinical benefit.ClinicalTrials.gov identifier: NCT02252887.
Real-world assessment of clinical effectiveness and safety of pazopanib in patients with advanced or metastatic renal cell carcinoma (RCC) in Asia, North Africa and Middle East countries: A prospective, observational study (PARACHUTE)
Authors: R. Kanesvaran, B. Biswas, P. Danchaivijitr, C.S. Lim, B. Karabulut, Y.F. Wong, H.S. Coskun, C.-H. Chang, I. Cicin, S. Ingles, K. Slimane, M. Erman
Journal: Annals of Oncology (2019)
Fructose-1,6-Bisphosphatase 2 Inhibits Sarcoma Progression by Restraining Mitochondrial Biogenesis
Authors: Peiwei Huangyang, Fuming Li, Pearl Lee, Itzhak Nissim, Aalim M. Weljie, Anthony Mancuso, Bo Li, Brian Keith, Sam S. Yoon, M. Celeste Simon
Journal: Cell Metabolism (2019)