tbuckley/cabot-search huggingface dataset:
Nivolumab Therapy for Treatment-Related Vitiligo in a Patient With Relapsed Metastatic Melanoma
Authors: Yasuhiro Nakamura, Yukiko Teramoto, Yuri Asami, Taisuke Matsuya, Jun-ichi Adachi, Ryo Nishikawa, Akifumi Yamamoto
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Hypoglycemia in Diabetes
Authors: Elizabeth R. Seaquist, Lisa S. Chow
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 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
Clinical significance of extranuclear expression of hormone receptors in breast cancer
Authors: R. Kim, M. Kaneko, K. Arihiro, M. Emi, K. Tanabe, S. Murakami, A. Osaki, K. Inai
Journal: Journal of Clinical Oncology (2006)

644 Background: Hormone receptor (HR)-positive breast cancer cells grow through estrogen receptor (ER)-signaling pathways that mediate both genomic and nongenomic actions, which cross-talk with growth factors associated with resistance to tamoxifen. The aim of this study is to explore the clinical significance of extranuclear expression of ER and PR in the cross-talk between HR and growth factor signaling pathways. Methods: We examined the extranuclear expression of ER and PR in 219 primary breast cancers by immunohistochemical staining. Specimens showing such expression were further examined for the expression of pAkt and aromatase. Due to heterogeneity, staining was scored on the basis of intensity and distribution in the tumors. Results: Extranuclear expression of ER or PR was observed in 21 cases (9.5%), which included 4 cases (19.0%) for ER and 20 cases (95.2%) for PR. Among these patients, HER-2, pAkt, and aromatase-positivity were observed in 14 cases (66.6%), 13 cases (61.9%), and 14 cases (66.6%), respectively. On the basis of nuclear HR expression, 11 of these cases were categorized as ER-positive/PR-negative, while 2 were ER-negative/PR-positive. Of those 13 cases, increased pAkt staining was found in 11 cases (84.6%). In particular, among the 11 ER-positive/PR-negative, elevated pAkt and aromatase were found in 10 (90.9%; p&lt;0.01) and 9 cases (81.8%), respectively. Conclusion: PR is more frequently expressed extranuclearly than ER in primary breast cancer, and extranuclear HRs cross-talk with the Akt/HER-2-signaling pathway and activation of aromatase, providing an explanation for the observation that aromatase inhibitors are more beneficial than tamoxifen for ER-positive/PR-negative patients. No significant financial relationships to disclose.
Posttranscriptional Regulation of <i>PARG</i> mRNA by HuR Facilitates DNA Repair and Resistance to PARP Inhibitors
Authors: Saswati N. Chand, Mahsa Zarei, Matthew J. Schiewer, Akshay R. Kamath, Carmella Romeo, Shruti Lal, Joseph A. Cozzitorto, Avinoam Nevler, Laura Scolaro, Eric Londin, Wei Jiang, Nicole Meisner-Kober, Michael J. Pishvaian, Karen E. Knudsen, Charles J. Yeo, John M. Pascal, Jordan M. Winter, Jonathan R. Brody
Journal: Cancer Research (2017)

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9-mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3' untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to inhibit HuR directly promoted DNA damage accumulation, inefficient PAR removal, and persistent PARP-1 residency on chromatin (PARP-1 trapping). Immunoprecipitation assays demonstrated that the PARP-1 protein binds and posttranslationally modifies HuR in PARPi-treated PDAC cells. In a mouse xenograft model of human PDAC, PARPi monotherapy combined with targeted silencing of HuR significantly reduced tumor growth compared with PARPi therapy alone. Our results highlight the HuR-PARG axis as an opportunity to enhance PARPi-based therapies. Cancer Res; 77(18); 5011-25. ©2017 AACR.
Epidemiology of PD-L1 and ALK expression and EGFR mutational status in Argentinian patients with lung cancer.
Authors: Ruben Salanova, Julio C Calderazzo Pereyra, Laura Leguina, Asuncion Bena, Mariana Barberis, Rosana Vargas, Rocio Jimenez del Toro, Kevin Kreimberg, Yanina Powazniak
Journal: Journal of Clinical Oncology (2017)

e20565 Background: Until now, the results of the correlation between PD-L1, ALK expression and EGFR mutations remain controversial. We prospectively evaluated patterns among EGFR mutant, ALK positive and PD-L1 positive lung cancer patients. Methods: PD-L1 and ALK expression was evaluated in 342 adenocarcinomas (AD) of the lung using inmunohistochemestry (anti-PD-L1 22C3, anti-ALK D5F3), and EGFR mutations using real time PCR (therascreen EGFR RGQ PCR Kit version 2). PD-L1 was also evaluated in 36 squamous (SQ) cell carcinomas. Results: 181 of 342 patients with AD were positive for PD-L1. 108 were positive with a TPS value between 1 and 49, and 73 were positive with a TPS value higher than 50 (p = 0.002). 25 of 36 patients with SQ were positive for PD-L1. 17 were positive with a TPS value between 1 and 49, and 8 were positive with a TPS value higher than 50. 133 samples with AD PD-L1 positive and 97 PD-L1 negative were tested for EGFR and ALK, 33 and 14 respectively were positive for EGFR mutations (p = 0.15), with 45% for exon 19 deletions (p = 0.003), 5 and 0 respectively were positive for ALK translocations (p = 0.053). 210 of 342 patients were men and 132 were women, 117 and 64 were positive for PD-L1 expression respectively (p &gt; 0.1). Conclusions: NSCLC with EGFR mutation showed a trend for higher frequency of positive PD-L1 expression and NSCLC harboring ALK rearrangement was significantly associated with PD-L1 expression. These findings might contribute to the understanding of the regulation of PD-L1 expression in lung cancer and its relation to ALK expression and EGFR mutation.
A Potential Role of Doxycycline in Cancer Chemotherapy
Authors: J Sagar, K Sales, S Dijk
Journal: Endoscopy (2006)

Aims: Doxycycline, long-acting tetracycline, is well-known antibiotic used widely. Its works by inhibition of mitochondrial protein-synthesis, thus restricting oxidative-phosphorylation and reducing ATP synthesis. Recently, doxycycline has been shown to prevent metastatic invasion in cancer-cells by inhibiting matrix-metalloproteinase. We aimed to establish whether doxycycline affects vitality of cultured HT29 colorectal cancer-cells.
Characteristics and response outcomes of long-term survivors in studies of first-line panitumumab for metastatic colorectal cancer
Authors: Claus-Henning Köhne, Marc Peeters, Alfredo Carrato, Romain Coriat, Fernando Rivera, Reija Koukakis, Gaston Demonty, Michael Geissler
Journal: Annals of Oncology (2017)
Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition
Authors: Eszter Szekely, Gustavo P. Sudre, Wendy Sharp, Ellen Leibenluft, Philip Shaw
Journal: American Journal of Psychiatry (2017)

Understanding the neural processes tied to the adult outcome of childhood attention deficit hyperactivity disorder (ADHD) could guide novel interventions to improve its clinical course. It has been argued that normalization of prefrontal cortical activity drives remission from ADHD, while anomalies in subcortical processes are "fixed," present even in remission. Using multimodal neuroimaging of inhibitory processes, the authors tested these hypotheses in adults followed since childhood, contrasting remitted against persistent ADHD.
Management of stage IV rectal cancer with operable liver metastases: Hypofractionated radiotherapy, surgery and chemotherapy
Authors: Laura Diaz Gomez, Alvaro Seguro Fernandez, Patricia Ramirez Daffos, Esther Gonzalez, Isabel Villanego, Veronica Diaz, Sara Garduño, Lucia Gutierrez, Salas M. Carmen, Javier Jaen Olasolo
Journal: Annals of Oncology (2017)
The ‘Goldilocks Principle’: designing physical activity at work to be ‘just right’ for promoting health
Authors: Leon Straker, Svend Erik Mathiassen, Andreas Holtermann
Journal: British Journal of Sports Medicine (2017)

Physical activity is generally accepted to promote good health. However, it is well documented that the wrong type of physical activity can be bad for health in both occupational and leisure contexts. For example, too much mechanical force can lead to musculoskeletal injury,1 too frequent activity can lead to fatigue2 and too prolonged standing can lead to varicose veins.3 Similarly, too little force can lead to bone and muscle loss, too infrequent moderate/vigorous physical activity can lead to cardiorespiratory deconditioning and too little standing or walking can lead to impaired cardiometabolic health.4 

Therefore, we argue that the benefits of physical activity, both at work and leisure, can only be seen when the various aspects of physical activity are ‘just right.’ When being ‘just right,’ activity promotes physical capacity and health, when being ‘not right,’ it impairs health. We coin this ‘just right’ paradigm, the ‘Goldilocks Principle.’ In the Goldilocks fairy tale, a child comes across a house in the woods belonging to a family of bears. She tried the porridge, chairs and beds; some were too hot/large/hard, some too cold/small/soft, but some were ‘just right.’ In exercise and sports, the Goldilocks Principle of …
A Proposed Process for Reliably Updating the Common Rule
Authors: Benjamin E. Berkman, David Wendler, Haley K. Sullivan, Christine Grady
Journal: The American Journal of Bioethics (2017)

The recent Common Rule revision process took almost a decade and the resulting changes are fairly modest, particularly when compared to the ambitious ideas proposed in the advance notice of proposed rulemaking (ANPRM) and notice of proposed rulemaking (NPRM). Furthermore, the revision process did not even attempt to tackle any of the Common Rule subparts pertaining to vulnerable populations (i.e., pregnant women and fetuses, prisoners, children) where commentators think the rules unduly restrict important research. We believe that this was a missed opportunity to make desirable changes, and that given the usual process the next opportunity to revisit the Common Rule is unacceptably remote. In this article, we argue that the Common Rule should be regularly reassessed, with a mechanism for making substantive (and expeditious) changes. Drawing on lessons learned from the recent revision process, we make recommendations about ways to structure future attempts to maximize the ability to make timely and necessary changes.
FABP1 as a novel potential biomarker for predicting mortality in acetaminophen‐induced acute liver failure
Authors: Heng Fan, Jian‐hua Zhu
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: In a recent issue of Hepatology, Karvellas et al.1 reported a study in which they investigated whether early (day 1) or late (day 3‐5) elevations in levels of serum liver‐type fatty acid binding protein (FABP1) are associated with 21‐day mortality in the absence of liver transplantation. The authors concluded that in patients with acetaminophen (APAP)‐induced acute liver failure (ALF), FABP1 may have good potential to discriminate survivors from nonsurvivors and may improve models currently used in clinical practice. We thank Karvellas et al. for their comprehensive contribution. FABP1, which is expressed in hepatocytes, enterocytes, and to a lesser degree in renal tubular cells, has been associated with liver injury.2 Karvellas et al. wisely noted that serum levels of FABP1 were significantly higher at early (admission) and late (day 3‐5) time points in APAP‐ALF nonsurvivors. After adjusting for significant covariates reflecting severity of illness, serum FABP1 was significantly associated with 21‐day mortality measured at both early and late time points. Karvellas et al. did not have access to a control group with critical illness but not APAP‐ALF as a comparator to elucidate the association between FABP1 and critical illness. We would like to know why the authors did not perform subgroup analysis according to a control group with critical illness. In addition, of the 99 APAP‐ALF survivors, 19 and 10 patients underwent renal replacement therapy (RRT) at early and late time points, respectively, and of the 99 APAP‐ALF nonsurvivors, 24 and 27 patients underwent RRT at early and late time points, respectively. Although no significance between these groups was reported, it is unclear whether RRT influenced the actual values of FABP1. Another limitation of the study by Karvellas et al. is that no comparison of FABP1 and other well‐established prognostic biomarkers was made. As a result, it remains unclear whether FABP1 shows superior prognostic performance than bilirubin or blood coagulation function, which is a strong predictor of APAP‐ALF. In addition to FABP1, there are several other useful biomarkers that can be used to predict the severity of APAP‐ALF, such as total protein, alanine aminotransferase, and bilirubin.3 Therefore, FABP1 should be evaluated along with other important markers; only in this way can accurate information be obtained about the prognostic indication of patients with APAP‐ALF. Finally, we believe the research by Karvellas et al. will promote further research of the relationship of FABP1 and mortality in patients with APAP‐ALF.
GC1118, a novel EGFR-targeted monoclonal antibody, exhibits potent growth and migration inhibitory efficacies in gastric cancer cell lines
Authors: Minkyu Hur, Jae-Chul Lee, Shi-Nai Lee, Yangmi Lim, Eun Hee Lee, Jun Cho Hyung, Lim Kim Jung, hee Lee Dae, Cheul Oh Sang, Jonghwa Won
Journal: Annals of Oncology (2017)
Abstract 14701: Greater Nighttime Blood Pressure Variability is Associated With Left Atrial Enlargement in Atrial Fibrillation Patients With Preserved Ejection Fraction
Authors: Naoki Norioka, Shinichi Iwata, Kenichi Sugioka, Yu Kawai, Shinichi Nonin, Suwako Fujita, Sera Ishikawa, Asahiro Ito, Masahiko Takagi, Minoru Yoshiyama
Journal: Circulation (2016)

Introduction: The presence of left atrial (LA) enlargement is an independent risk factor for ischemic stroke in patients with atrial fibrillation (AF). Increased nighttime blood pressure (BP) varia...
Abstract 17915: Brainstem Neuronal Networks for Breathing Control Involve a Disinhibitory Projection From the Dorsal Medulla
Authors: Shuang Zhang, Yang Wu, Ningren Cui, Chun Jiang
Journal: Circulation (2015)

The critical neuronal networks for breathing control known to be located in the brainstem are still not fully understood. γ-Aminobutyric acid (GABA) is a neurotransmitter that not only plays an important role in the networks, but also allows investigational interventions to the networks. To gain a fast, local and reversible access to brainstem GABAergic neurons, we developed a strain of transgenic mice that expressed channelrhodopsin in a tandem with eYFP in GABAergic neurons directed by the glutamic acid decarboxylase 2 promotor, the Gad2-ChR mouse. We firstly studied eYFP fluorescence in brainstem tissue sections. Several groups of previously known GABAergic neurons were positively labelled. Breathing response to optostimulation and CO 2 challenge were then studied in the anesthetized mice in vivo . When the optostimulation was applied to the ventral surface of the brainstem, especially the medulla, phrenic nerve activity was remarkably inhibited. Surprisingly, we found that optostimulation to the dorsal surface of the brainstem induced significant augmentation of both breathing activity and CO 2 chemosensitivity in the Gad2-ChR mice. Both breathing frequency and integrated phrenic amplitude were augmented. The effect was reversible and fast reaching peaking activation within 1 min. With respect to ventilation responses, optostimulation was nearly as potent as the response to 6% CO 2 . In the presence of 6% CO 2 , optostimulation was still capable of enhancing breathing activity. The breathing stimulation effect of optical GABA activation was located to the medulla. These observations suggest that respiratory neuronal networks involve a disinhibitory projection from dorsal GABAergic neurons in the medulla to a group of unidentified inhibitory neurons that are actively inhibit central breathing activity.
A randomized controlled trial comparing primary tumor resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (JCOG1017 PRIM-BC).
Authors: Tadahiko Shien, Tomonori Mizutani, Kiyo Tanaka, Takayuki Kinoshita, Fumikata Hara, Tomomi Fujisawa, Norikazu Masuda, Kenji Tamura, Takashi Hojo, Chizuko Kanbayashi, Naoki Niikura, Taro Shibata, Haruhiko Fukuda, Hiroji Iwata
Journal: Journal of Clinical Oncology (2017)

TPS588 Background: The possibility of improving the survival of stage IV breast cancer patients by primary tumor resection (PTR) has been reported by several retrospective studies; however, these studies essentially suffer from biases such as arbitrary patient selection, diverse timing of surgery or various regimens of systemic therapy. Five prospective randomized trials including our trial have evaluated the efficacy of PTR for them. Two have reported final results, but those results were inconsistent. Therefore, this subject still remains a hotly debated topic at major breast conferences. Methods: Our trial is being conducted to confirm the superiority of PTR plus systemic therapy over systemic therapy alone in stage IV pts who are sensitive to primary systemic therapy (PST) in this study. The inclusion criteria are untreated pts with histologically confirmed invasive breast cancer with one or more measurable distant metastatic lesions diagnosed by radiological examination.All pts receive PST according to the ER and HER2 status of the primary breast cancer after the first registration. After three months, the pts who are sensitive to PST are randomized to the PTR plus systemic therapy arm or the systemic therapy alone arm. After randomization and surgery in the former arm, or after randomization in the latter arm, the same systemic therapies are continued until progression of diseases and next appropriate regimens are started after that. The primary endpoint is the overall survival, and the secondary endpoints are proportion of pts without tumor progression at the metastatic sites, yearly local recurrence-free survival, proportion of local ulcer/local bleeding, yearly primary tumor resection-free survival, adverse events (AEs) of chemotherapy, operative morbidity, and serious AEs. Sample size for randomized pts was determined to attain at least 80% of power to detect a 6 months difference with one-sided alpha of 0.05.The pts accrual was started in May 2011. Enrollment of 410 pts for randomization is planned over a 7-year accrual period. 307 pts have been randomized until Jan 2017. This trial was registered at UMIN-CTR[umin.ac.jp/ctr/] as UMIN000005586. Clinical trial information: UMIN000005586.
Impact of the Use of Polymerase Chain Reaction for the Diagnosis and Management of Pneumocystis Jirovecii Pneumoniae in a Retrospective Cohort of Patients with Lymphoid Malignancies
Authors: Felicite De Charry, Damien Dupont, Meja Rabodonirina, Celine Ferlay, Christine Fuhrmann, Emmanuelle Nicolas-Virelizier, Philippe Rey, Catherine Sebban, Amine Belhabri, Pierre Biron, Jean-Yves Blay, Herve Ghesquieres
Journal: Blood (2016)
Imaging of the Liver after Colorectal Carcinoma Resection: A Waste of Time?
Authors: C Canning, Z Martin, S Rajendran, D Beddy, K Bates, D O'Mahony, F Ofori-Kuma, JB O'Mahony, K Mealy
Journal: Endoscopy (2006)

Aims: Guidelines from the American Society of Colon and Rectal Surgeons, 2004 advise that the routine use of hepatic imaging in the follow-up of colorectal cancer should not be performed. As routine CT scanning continues to be the standard of care in this country, we aimed to evaluate whether such aggressive follow-up is justified.
Syngeneic Hematopoietic Stem Cell Transplantation in Acute Leukaemia. A Report of the Acute Leukaemia Working Party of the EBMT.
Authors: Loic Fouillard, Myriam Labopin, Eliane Gluckman, Alois Gratwohl, Francesco Frassoni, Norbert Claude Gorin, Vanderson Rocha
Journal: Blood (2004)