tbuckley/cabot-search huggingface dataset:
Zoledronic Acid Dosing Interval for Metastatic Cancer—Reply
Authors: Andrew L. Himelstein, Charles L. Loprinzi, Charles L. Shapiro
Journal: JAMA (2017)

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
The next generation of immunotherapy: keeping lung cancer in check
Authors: Ashwin Somasundaram, Timothy F. Burns
Journal: Journal of Hematology & Oncology (2017)

Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy. Therefore, PD-1 inhibitors such as nivolumab and pembrolizumab were rapidly approved for both squamous and nonsquamous lung cancer in the pretreated population. The advent of these new therapies have revolutionized the treatment of lung cancer; however, the majority of NSCLC patients still do not respond to PD-1/PD-L1 inhibition leaving an unmet need for a large and growing population. Immunotherapy combinations with chemotherapy, radiation therapy, or novel immunomodulatory agents are currently being examined with the hope of achieving higher response rates and improving overall survival rate. Chemotherapy and radiation therapy has been theorized to increase the release of tumor antigen leading to increased responses with immunotherapy. However, cytotoxic chemotherapy and radiation therapy may also destroy actively proliferating T cells. The correct combination and order of therapy is under investigation. The majority of patients who do respond to immunotherapy have a durable response attributed to the effect of adaptive immune system’s memory. Unfortunately, some patients’ tumors do progress afterward and investigation of checkpoint blockade resistance is still nascent. This review will summarize the latest efficacy and safety data for early and advanced NSCLC in both the treatment-naïve and pretreated settings. The emerging role of immunotherapy for the treatment of small cell lung cancer and malignant mesothelioma will also be discussed.
Whose Autonomy? Which Obligations? Preserving the Right to (Professional) Self-Determination at the Margins of Viability
Authors: Anna-Henrikje Seidlein, Sabine Salloch
Journal: The American Journal of Bioethics (2017)

Prahbu and colleagues (2017) depict a multilayered phenomenon that concerns end-of-life decisions in the two different fields of emergency medicine and transplant medicine. The authors highlight a ...
Sacral Fatigue Fracture in a Military Recruit
Authors: Matthew D. Burgess, Mickaila J. Johnston, Eugene D. Silverman
Journal: Clinical Nuclear Medicine (2017)

A 19-year-old male military recruit presented with 3 weeks of persistent left hip and groin pain after abnormally twisting his hip during a hike. Initial radiographs were interpreted as negative. He subsequently underwent a bone scan which revealed linear left sacral uptake along or paralleling the sacroiliac joint. Differential diagnostic considerations included unilateral sacroiliitis and sacral fracture. SPECT/CT was performed which confirmed left sacral fatigue stress fracture. Transitional lumbosacral anatomy was evident on radiographs with pseudoarticulation of the transitional left S1 transverse process with the sacrum. We postulate this predisposed the recruit to sacral fracture.
Dysfunction of the WT1-MEG3 signaling promotes AML leukemogenesis via p53-dependent and -independent pathways
Authors: Y Lyu, J Lou, Y Yang, J Feng, Y Hao, S Huang, L Yin, J Xu, D Huang, B Ma, D Zou, Y Wang, Y Zhang, B Zhang, P Chen, K Yu, E W-F Lam, X Wang, Q Liu, J Yan, B Jin
Journal: Leukemia (2017)

Long non-coding RNAs (lncRNAs) play a pivotal role in tumorigenesis, exemplified by the recent finding that lncRNA maternally expressed gene 3 (MEG3) inhibits tumor growth in a p53-dependent manner. Acute myeloid leukemia (AML) is the most common malignant myeloid disorder in adults, and TP53 mutations or loss are frequently detected in patients with therapy-related AML or AML with complex karyotype. Here, we reveal that MEG3 is significantly downregulated in AML and suppresses leukemogenesis not only in a p53-dependent, but also a p53-independent manner. In addition, MEG3 is proven to be transcriptionally activated by Wilms' tumor 1 (WT1), dysregulation of which by epigenetic silencing or mutations is causally involved in AML. Therefore MEG3 is identified as a novel target of the WT1 molecule. Ten-eleven translocation-2 (TET2) mutations frequently occur in AML and significantly promote leukemogenesis of this disorder. In our study, TET2, acting as a cofactor of WT1, increases MEG3 expression. Taken together, our work demonstrates that TET2 dysregulated WT1-MEG3 axis significantly promotes AML leukemogenesis, paving a new avenue for diagnosis and treatment of AML patients.
Revealing the Biochemical and Genetic Basis of Color Variation in a Polymorphic Lizard
Authors: Claire A. McLean, Adrian Lutz, Katrina J. Rankin, Devi Stuart-Fox, Adnan Moussalli
Journal: Molecular Biology and Evolution (2017)

Determining the mechanistic and genetic basis of animal coloration is essential to understand the costs and constraints on color production, and the evolution and maintenance of phenotypic variation. However, genes underlying structural color and widespread pigment classes apart from melanin remain largely uncharacterized, in part due to restricted taxonomic focus. We combined liquid chromatography-mass spectrometry and RNA-seq gene expression analyses to characterize the pigments and genes associated with skin color in the polymorphic lizard, Ctenophorus decresii. Throat coloration in male C. decresii may be a combination of orange, yellow, grey, or ultra-violet blue. We confirmed the presence of two biochemically different pigment classes, pteridines (self-synthesized) and carotenoids (acquired through the diet), in all skin colors. Orange skin had the highest levels of pteridine pigments while yellow skin tended to have higher levels of carotenoids, of which the vitamin A precursors β-carotene and β-cryptoxanthin have not been previously confirmed in reptiles. These results were confirmed by gene expression analyses, which detected 489 genes differentially expressed between the skin colors, including genes associated with pteridine production, provitamin A carotenoid metabolism, iridophore-specific synthesis, melanin synthesis, and steroid hormone pathways. For the majority of these 489 genes, however, our study reveals a new association with color production in vertebrates. These data represent a significant contribution to understanding the genetic basis of color variation in vertebrates and a rich resource for further studies.
Abstract 143: Catalase, Oxidative Stress and Ischemic Injury: Role of c-Abl Tyrosine Kinase
Authors: E Bernadette Cabigas, Guoliang Ding, Tao Chen, Talib Saafir, Mary Wagner, Michael E Davis
Journal: Circulation Research (2012)

Thousands of children with congenital heart disease are subjected to corrective surgery which involves stopping the heart and exposing it to ischemia reperfusion (IR) injury. Complications after cardiopulmonary bypass like low cardiac output can lead to inadequate organ perfusion and eventual organ dysfunction if not corrected in a timely manner. Newborn (2-4 days) hearts are more susceptible to ischemic injury than adult (&gt;8 weeks) hearts as evidenced by their diminished ability to scavenge reactive oxygen species (ROS), specifically hydrogen peroxide (H 2 O 2 ). Not only do newborn hearts exhibit decreased scavenging capability (compared to the adult) but they also contain reduced baseline levels of catalase (3.8 + 1.1 U/mg tissue in the LV and 4.3 + 2.3 U/mg tissue in the RV vs. 11.2 + 1.0 U/mg tissue in the adult LV and 11.6 + 0.3 U/mg tissue in the adult RV). We observed significantly increased levels of H 2 O 2 in newborn rabbit myocytes following IR injury (4.3-fold vs 2.2 fold; p&lt;0.05) that was not accompanied by an increase in catalase activity as was seen in the adult myocytes. The tyrosine kinase c-Abl was shown to play a role in regulating phosphyorylation (and activation) of catalase and we hypothesized this pathway may be dysregulated in newborns, leading to differences in catalase activity. We performed immunoprecipitation with c-Abl and catalase as well as Western analysis of whole heart homogenates in both newborn and adult samples (n=3). Results demonstrated an increase in catalase phosphorylation in adult but not newborn hearts after IR. In the newborn, preliminary studies displayed diminished phosphorylation of c-Abl, indicating a potential mechanism. In addition, catalase levels seem to acutely rise following IR, too early for new protein synthesis. Catalase is known to undergo ubiquitination following release from the c-Abl complex and this may play a role in the failure of newborns to increase catalase. Elucidation of this pathway will lead to a greater understanding of the mechanisms controlling catalase activity in the newborn versus the adult heart and will prove beneficial in developing therapeutic interventions to minimize damage following ischemic injury in newborns.
AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy
Authors: Christina Ising, Gilbert Gallardo, Cheryl E.G. Leyns, Connie H. Wong, Hong Jiang, Floy Stewart, Lauren J. Koscal, Joseph Roh, Grace O. Robinson, Javier Remolina Serrano, David M. Holtzman
Journal: The Journal of Experimental Medicine (2017)

Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the Fc domain of HJ8.5 is required for the therapeutic effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5 with variable linker lengths, all specific to human tau. Based on different binding properties, we selected two anti-tau scFvs and tested their efficacy in vivo by adeno-associated virus-mediated gene transfer to the brain of P301S-tg mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated tau in brain tissue of P301S-tg mice, associated with a decrease in detergent-soluble tau species. Interestingly, these mice showed substantial levels of scFvs in the cerebrospinal fluid without significant effects on total extracellular tau levels. Therefore, our study provides a novel strategy for anti-tau immunotherapeutics that potentially limits a detrimental proinflammatory response.
Ticagrelor Versus Clopidogrel on Myocardial Infarct Size in Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Eun Kyoung Kim, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Jin-Ho Choi, Seung-Hyuk Choi, Woo Jung Chun, Yeon Hyeon Choe, Hyeon-Cheol Gwon, Joo-Yong Hahn
Journal: Journal of the American College of Cardiology (2017)
Adenoma detection with blue-water infusion colonoscopy: a randomized trial
Authors: Adriane Lesne, Olivier Rouquette, Sandrine Touzet, Fabien Petit-Laurent, Gwenaelle Tourlonias, Audrey Pasquion, Jérôme Rivory, Guillermo Aguero Garcete, Julien Scanzi, Sylvaine Chalumeau, Christine Chambon-Augoyard, Driffa Moussata, Florence Leger-Nguyen, Stéphane Degeorges, Marion Chauvenet, Thierry Fontanges, Sandrine Baubet, Philippe Brulet, Claire Billioud, Elsa Thimonier, Karine Stroeymeyt-Martin, Benjamin Hamel, Emmanuelle Graillot, Claire Cruiziat, Olivia Scalone, Marc O’Brien, Denis Péré-Vergé, Jean-Christophe Souquet, Jean-Marc Phelip, Laurent Poincloux, Stéphanie Poupon-Bourdy, Angélique Denis, Laurent Magaud, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2017)

Abstract Background and aims Colonoscopy is currently the reference method to detect colorectal neoplasia, yet some adenomas remain undetected. The water infusion technique and dying with indigo carmine has shown interesting results for reducing this miss rate. The aim of this study was to compare the adenoma detection rate (adenoma and adenocarcinoma; ADR) and the mean number of adenomas per patient (MAP) for blue-water infusion colonoscopy (BWIC) versus standard colonoscopy. Methods We performed a multicenter, randomized controlled trial in eight units, including patients with a validated indication for colonoscopy (symptoms, familial or personal history, fecal occult blood test positive). Consenting patients were randomized 1:1 to BWIC or standard colonoscopy. All colonoscopies were performed by experienced colonoscopists. All colonoscopy quality indicators were prospectively recorded. Results Among the 1065 patients included, colonoscopies were performed completely for 983 patients (514 men; mean age 59.1). The ADR was not significantly different between the groups; 40.4 % in the BWIC group versus 37.5 % in the standard colonoscopy group (odds ratio [OR] 1.13; 95 % confidence interval [CI] 0.87 – 1.48; P = 0.35). MAP was significantly greater in the BWIC group (0.79) than in the standard colonoscopy group (0.64; P = 0.005). For advanced adenomas, the results were 50 (10.2 %) and 36 (7.3 %), respectively (P = 0.10). The cecal intubation rate was not different but the time to cecal intubation was significantly longer in BWIC group (9.9 versus 6.2 minutes; P &lt; 0.001). Conclusion Despite the higher MAP with BWIC, the routine use of BWIC does not translate to a higher ADR. Whether increased detection ultimately results in a lower rate of interval carcinoma is not yet known. Clinical trials registration: EudraCT 2012-A00548 – 35; NCT01937429.
Vitamin D downregulates the IL-23 receptor pathway in human mucosal group 3 innate lymphoid cells
Authors: Viktoria Konya, Paulo Czarnewski, Marianne Forkel, Anna Rao, Efthymia Kokkinou, Eduardo J. Villablanca, Sven Almer, Ulrik Lindforss, Danielle Friberg, Charlotte Höög, Peter Bergman, Jenny Mjösberg
Journal: Journal of Allergy and Clinical Immunology (2017)
A prospective, observational cohort study of the seasonal dynamics of airway pathogens in the aetiology of exacerbations in COPD
Authors: Tom M A Wilkinson, Emmanuel Aris, Simon Bourne, Stuart C Clarke, Mathieu Peeters, Thierry G Pascal, Sonia Schoonbroodt, Andrew C Tuck, Viktoriya Kim, Kristoffer Ostridge, Karl J Staples, Nicholas Williams, Anthony Williams, Stephen Wootton, Jeanne-Marie Devaster
Journal: Thorax (2017)

<h3>Background</h3> The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood. Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events. <h3>Methods</h3> In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40–85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Results are presented for subjects in the full cohort, followed for 1 year. Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses. <h3>Findings</h3> The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50). At AECOPD, the most common bacterial species were non-typeable <i>Haemophilus influenzae</i> (NTHi) and <i>Moraxella catarrhalis</i>, and the most common virus was rhinovirus. Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when <i>M. catarrhalis</i> was detected regardless of season (5.09 (95% CI 2.76 to 9.41)). When NTHi was detected, the increased risk of exacerbation was greater in high season (October–March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)). Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%). A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031). <h3>Conclusions</h3> AECOPD aetiology varies with season. Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection. <h3>Trial registration number</h3> Results, NCT01360398.
Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting
Authors: Tullio Palmerini, Letizia Bacchi Reggiani, Diego Della Riva, Mattia Romanello, Fausto Feres, Alexandre Abizaid, Martine Gilard, Marie-Claude Morice, Marco Valgimigli, Myeong-Ki Hong, Byeong-Keuk Kim, Yangsoo Jang, Hyo-Soo Kim, Kyung Woo Park, Antonio Colombo, Alaide Chieffo, Jung-Min Ahn, Seung-Jung Park, Stefanie Schüpke, Adnan Kastrati, Gilles Montalescot, Philippe Gabriel Steg, Abdourahmane Diallo, Eric Vicaut, Gerard Helft, Giuseppe Biondi-Zoccai, Bo Xu, Yaling Han, Philippe Genereux, Deepak L. Bhatt, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2017)
Mitochondrial DNA Microsatellites as New Markers for the Quantitative Determination of Hematopoietic Chimerism after Allogeneic Stem Cell Transplantation.
Authors: Myung-Geun Shin, Hyeoung-Joon Kim, Hye-Ran Kim, Il-Kwon Lee, Je-Jung Lee, Hoon Kook, Tai-Ju Hwang, Duck Cho, Seung-Jung Kee, Jong-Hee Shin, Soon-Pal Suh, Dong-Wook Ryang
Journal: Blood (2005)
Predictive markers for programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis blockade therapy in patients with metastatic melanoma (MM).
Authors: Dae Won Kim, Nitin Chakravarti, VanAnh Trinh, Karen Mae Perdon, Susan E McIntyre, Victor G. Prieto, Wen-Jen Hwu
Journal: Journal of Clinical Oncology (2015)

e20029 Background: PD-1/PD-L1 blockade has proven an effective therapeutic strategy in pts with MM. However, no markers are known to clearly predict the clinical benefit of this approach. We evaluated potential clinical and pathological markers in patients (pts) treated with PD-1/PD-L1 blocking mAbs. Methods: We reviewed clinical data of MM pts treated with PD-1/PD-L1 blockade, including 2 anti-PD1 mAbs [pembrolizumab (PEM) and nivolumab (NIVO)] and an anti-PD-L1 mAb (MDX-1105), at MD Anderson Cancer Center. Pretreatment tumor samples were available in all pts. Results: Of the 54 pts in this study, 24 were treated with PEM, 8 with NIVO, and 22 with MDX-1105. Median age was 64.5 yr (range 29-86 yr); 24 pts (44.4%) had previously received ipilimumab (IPI). 22 pts (40.7%) had an objective response (OR); 35 (64.8%) had disease control (DC). At a median follow-up of 21.2 mo, median overall survival (OS) and progression-free survival (PFS) were 41 mo (95% confidence interval (CI) 16.5-65.5) and 8.7 mo (95% CI 3.0-13.0), respectively. Baseline elevated LDH level (P < 0.001) and ECOG PS of 1 (P = 0.01) were associated with poor OS and PFS. Pts with elevated LDH (P = 0.008) also had lower OR. Mutation status (BRAF and NRAS) and prior IPI were not associated with OR or OS. Pathology review, including histological and immunohistochemical evaluation, of tumor samples revealed baseline tumor necrosis inversely correlated with OS (P = 0.01). High PD-1 expression on tumor-infiltrating (TIL) or peritumoral lymphocytes (PTL) was associated with improved DC (P = 0.03 and P = 0.01, respectively). Tumor expression of CTLA-4, PD-L1, or pAKT did not correlate with treatment outcome. Conclusions: Baseline LDH level, ECOG PS and tumor necrosis were significantly associated with OS in MM pts receiving PD-1/PD-L1 blocking mAbs. Pts with normal LDH, ECOG PS of 0, or limited tumor necrosis are most likely to achieve tumor response and prolonged disease survival. PD-1 expression on TIL or PTL was associated with better DC.
Patterns of Genome-Wide Diversity and Population Structure in the Drosophila athabasca Species Complex
Authors: Karen M. Wong Miller, Ryan R. Bracewell, Michael B. Eisen, Doris Bachtrog
Journal: Molecular Biology and Evolution (2017)

The Drosophila athabasca species complex contains three recently diverged, prezygotically isolated semispecies (Western-Northern, Eastern-A, and Eastern-B) that are distributed across North America and share zones of sympatry. Inferences based on a handful of loci suggest that this complex might be an ideal system for studying the genetics of incipient speciation and the evolution of prezygotic isolating mechanisms, but patterns of differentiation have not been characterized systematically. Here, we assembled a draft genome for D. athabasca and analyze whole-genome re-sequencing data for 28 individuals from across the species range to characterize genome-wide patterns of diversity and population differentiation among semispecies. Patterns of differentiation on the X-chromosome vs. autosomes vary, with the X-chromosome showing better phylogenetic resolution and increased levels of between semispecies divergence. Despite low levels of overall differentiation and a lack of phylogenetic resolution of the autosomes for the most closely related semispecies, individuals do exhibit distinct genetic clustering. Demographic analyses provide some support for a model of isolation with migration within D. athabasca, with divergence times <20 kya. The young divergence times of the semispecies of D. athabasca, together with strong levels of sexual isolation, makes them a promising system for studying the evolution of prezygotic isolation and speciation.
A More Sensitive RQ-PCR to Assess Complete Molecular Remission Does Not Allow the Prediction of Relapse After Discontinuation of Imatinib In Chronic Myeloid Leukemia.
Authors: Francois-Xavier Mahon, Stéphanie Dulucq, Francois Guilhot, Laurence Legros, Philippe Rousselot, Coralie Belanger, Gabriel Etienne, Josy Reiffers, Delphine Rea
Journal: Blood (2010)
TCTAP A-085 Vascular Response to Drug-eluting Stent with Biodegradable Versus Durable Polymer
Authors: Yosuke Katayama, Takashi Kubo, Takashi Akasaka, Hiroshi Aoki, Tsuyoshi Nishiguchi, Keisuke Satogami, Takeyoshi Kameyama, Takashi Yamano, Tomoyuki Yamaguchi, Yoshiki Matsuo, Yasushi Ino, Hironori Kitabata, Atsushi Tanaka, Takeshi Hozumi, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2017)
Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments
Authors: Alessia Angelin, Luis Gil-de-Gómez, Satinder Dahiya, Jing Jiao, Lili Guo, Matthew H. Levine, Zhonglin Wang, William J. Quinn, Piotr K. Kopinski, Liqing Wang, Tatiana Akimova, Yujie Liu, Tricia R. Bhatti, Rongxiang Han, Benjamin L. Laskin, Joseph A. Baur, Ian A. Blair, Douglas C. Wallace, Wayne W. Hancock, Ulf H. Beier
Journal: Cell Metabolism (2017)