tbuckley/cabot-search huggingface dataset:
Cluster Headache Is in Part a Disorder of the Circadian System
Authors: Mark J. Burish, Zheng Chen, Seung-Hee Yoo
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update
Authors: Neelima Denduluri, Mariana Chavez-MacGregor, Melinda L. Telli, Andrea Eisen, Stephanie L. Graff, Michael J. Hassett, Jamie N. Holloway, Arti Hurria, Tari A. King, Gary H. Lyman, Ann H. Partridge, Mark R. Somerfield, Maureen E. Trudeau, Antonio C. Wolff, Sharon H. Giordano
Journal: Journal of Clinical Oncology (2018)

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .
A Mass With High Uptake of Fluorodeoxyglucose on Positron Emission Tomography
Authors: Eric L. Staals, Eugenio Rimondi, Emanuela Palmerini
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Mapping the HLA Ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation
Authors: Markus W. Löffler, Daniel J. Kowalewski, Linus Backert, Jörg Bernhardt, Patrick Adam, Heiko Schuster, Florian Dengler, Daniel Backes, Hans-Georg Kopp, Stefan Beckert, Silvia Wagner, Ingmar Königsrainer, Oliver Kohlbacher, Lothar Kanz, Alfred Königsrainer, Hans-Georg Rammensee, Stefan Stevanović, Sebastian P. Haen
Journal: Cancer Research (2018)

Abstract Immune cell infiltrates have proven highly relevant for colorectal carcinoma prognosis, making colorectal cancer a promising candidate for immunotherapy. Because tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here, we comprehensively describe the naturally presented HLA ligandome of colorectal carcinoma and corresponding nonmalignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA class I ligands on colorectal carcinoma and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic colorectal carcinoma–associated pathways, including Wnt, TGFβ, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired colorectal carcinoma and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be overrepresented merely within the colorectal carcinoma ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T-cell repertoire. Overall, these data show that the HLA ligandome reflects cancer-associated pathways implicated in colorectal carcinoma oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived, tumor antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells, might comprise promising candidates for immunotherapeutic applications. Significance: Cancer-associated pathways are reflected in the antigenic landscape of colorectal cancer, suggesting that tumor-specific antigens do not necessarily have to be mutation-derived but may also originate from other alterations in cancer cells. Cancer Res; 78(16); 4627–41. ©2018 AACR.
FDA seeks injunction against two stem cell clinics in first move against unregulated industry
Authors: Owen Dyer
Journal: BMJ (2018)

The US Food and Drug Administration is seeking a permanent injunction to shut down the operations of two companies offering unproven stem cell treatments.

FDA commissioner Scott Gottlieb said that the US Stem Cell Clinic in Florida, the Cell Surgical Network in California, and others like them are exploiting desperate patients. “Cell based regenerative medicine holds significant medical opportunity, but we’ve also seen some bad actors leverage the scientific promise of this field to peddle unapproved treatments that put patients’ health at risk,” he said.

“In some instances, patients have suffered serious and permanent harm after receiving these unapproved products. In the two cases filed today, the clinics and their leadership have continued to disregard the …
A Longitudinal Comparison of Antibodies to Epstein-Barr Virus and Clinical Parameters in Chronic Lymphocytic Leukemia and Chronic Myelocytic Leukemia
Authors: PAUL H. LEVINE, DEBORAH A. MERRILL, NICHOLAS C. BETHLENFALVAY, LYUBICA DABICH, DAVID A. STEVENS, DEWARD E. WAGGONER
Journal: Blood (1971)
Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution
Authors: Meihua Christina Kuang, Jacek Kominek, William G Alexander, Jan-Fang Cheng, Russell L Wrobel, Chris Todd Hittinger
Journal: Molecular Biology and Evolution (2018)

Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.
Whole-Body Distribution and Clinical Association of Telangiectases in Systemic Sclerosis
Authors: Mathieu Jouvray, David Launay, Sylvain Dubucquoi, Vincent Sobanski, Céline Podevin, Marc Lambert, Sandrine Morell-Dubois, Hélène Maillard, Pierre-Yves Hatron, Eric Hachulla, Jonathan Giovannelli
Journal: JAMA Dermatology (2018)

In systemic sclerosis (SSc), to date, no study has precisely described the total number and fine distribution of telangiectases (TAs), their clinical association with the disease, and the biological mechanisms causing their development.To describe the whole-body distribution of TAs and assess the association between the whole-body TA number and the characteristics of patients with SSc.A single-center, cross-sectional study was conducted between July 11, 2016, and March 15, 2017, at the National Referral Centre for Rare Systemic and Autoimmune Diseases in France. A population-based sample of 106 adults who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc were included; 8 patients who had previously received laser treatment for TAs were excluded.The number of TAs on the whole body (total and those >5 mm) and TA distribution in different areas were recorded. The association with clinical and biological data was studied using univariate and multivariate linear regression.A total of 106 patients (83 [78.3%] women) were enrolled, including 12 with precapillary pulmonary hypertension (PH). Mean (SD) age was 60.6 (13.5) years. Telangiectasia distribution was 37.2% on the face, 33.2% on the upper limbs, including 26.4% on the hands, 28.1% on the trunk, including 17.1% for the upper part of the trunk, and 1.5% on the lower limbs. In analysis using the multivariate linear regression model, the whole-body TA number was independently associated with male sex (percentage change, 144.4%; 95% CI, 7.5% to 455.9%; P = .03), PH (162.8%; 95% CI, 5.6% to 553.8%; P = .04), history of pulmonary embolism (336.4%; 95% CI, 39.0% to 1270.1%; P = .01), glomerular filtration rate (-1.6%; 95% CI, -3.2% to -0.1% per 1-mL/min/1.73 m2 increase; P = .04), and soluble endoglin level (28.2%; 95% CI, 1.2% to 62.5% per 1-ng/mL increase; P = .04). Receiver operating characteristic analyses assessing the ability of TAs to identify the presence of PH revealed that the area under the curve was significant for the TA number on the whole body (0.77; 95% CI, 0.57 to 0.88), on the hands and face (0.81; 95% CI, 0.57 to 0.91), and on the hands (95% CI, 0.77; 95% CI, 0.57 to 0.89).In the patients in this study with SSc, TAs were predominantly located on the face, hands, and the upper part of the trunk. Telangiectases appeared to be associated with vasculopathy features of SSc, particularly with PH and soluble endoglin levels.
Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer
Authors: Michael A. Moses, Yeong Sang Kim, Genesis M. Rivera-Marquez, Nobu Oshima, Matthew J. Watson, Kristin E. Beebe, Catherine Wells, Sunmin Lee, Abbey D. Zuehlke, Hao Shao, William E. Bingman, Vineet Kumar, Sanjay V. Malhotra, Nancy L. Weigel, Jason E. Gestwicki, Jane B. Trepel, Leonard M. Neckers
Journal: Cancer Research (2018)

Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling, in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small-molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with Hsp40. Pull-down studies using biotinylated-C86 found Hsp40 present in a multiprotein complex with full-length (FL-) AR, ARv7, and Hsp70 in CRPC cells. Treatment of CRPC cells with C86 or the allosteric Hsp70 inhibitor JG98 resulted in rapid protein destabilization of both FL-AR and ARv, including ARv7, concomitant with reduced FL-AR- and ARv7-mediated transcriptional activity. The glucocorticoid receptor, whose elevated expression in a subset of CRPC also leads to androgen-independent AR target gene transcription, was also destabilized by inhibition of Hsp40 or Hsp70. In vivo, Hsp40 or Hsp70 inhibition demonstrated single-agent and combinatorial activity in a 22Rv1 CRPC xenograft model. These data reveal that, in addition to recognized roles of Hsp40 and Hsp70 in FL-AR LBD remodeling, ARv lacking the LBD remain dependent on molecular chaperones for stability and function. Our findings highlight the feasibility and potential benefit of targeting the Hsp40/Hsp70 chaperone axis to treat prostate cancer that has become resistant to standard antiandrogen therapy.Significance: These findings highlight the feasibility of targeting the Hsp40/Hsp70 chaperone axis to treat CRPC that has become resistant to standard antiandrogen therapy. Cancer Res; 78(14); 4022-35. ©2018 AACR.
Outcomes of Robot-assisted Partial Nephrectomy for Clinical T2 Renal Tumors: A Multicenter Analysis (ROSULA Collaborative Group)
Authors: Riccardo Bertolo, Riccardo Autorino, Giuseppe Simone, Ithaar Derweesh, Juan D. Garisto, Andrea Minervini, Daniel Eun, Sisto Perdona, James Porter, Koon Ho Rha, Alexander Mottrie, Wesley M. White, Luigi Schips, Bo Yang, Kenneth Jacobsohn, Robert G. Uzzo, Ben Challacombe, Matteo Ferro, Jay Sulek, Umberto Capitanio, Uzoma A. Anele, Gabriele Tuderti, Manuela Costantini, Stephen Ryan, Ahmet Bindayi, Andrea Mari, Marco Carini, Aryeh Keehn, Giuseppe Quarto, Michael Liao, Kidon Chang, Alessandro Larcher, Geert De Naeyer, Ottavio De Cobelli, Francesco Berardinelli, Chao Zhang, Peter Langenstroer, Alexander Kutikov, David Chen, Nicolo De Luyk, Chandru P. Sundaram, Francesco Montorsi, Robert J. Stein, Georges Pascal Haber, Lance J. Hampton, Prokar Dasgupta, Michele Gallucci, Jihad Kaouk, Francesco Porpiglia
Journal: European Urology (2018)
Ad5NULL-A20: A Tropism-Modified, αvβ6 Integrin-Selective Oncolytic Adenovirus for Epithelial Ovarian Cancer Therapies
Authors: Hanni Uusi-Kerttula, James A. Davies, Jill M. Thompson, Phonphimon Wongthida, Laura Evgin, Kevin G. Shim, Angela Bradshaw, Alexander T. Baker, Pierre J. Rizkallah, Rachel Jones, Louise Hanna, Emma Hudson, Richard G. Vile, John D. Chester, Alan L. Parker
Journal: Clinical Cancer Research (2018)

Purpose: Virotherapies are maturing in the clinical setting. Adenoviruses (Ad) are excellent vectors for the manipulability and tolerance of transgenes. Poor tumor selectivity, off-target sequestration, and immune inactivation hamper clinical efficacy. We sought to completely redesign Ad5 into a refined, tumor-selective virotherapy targeted to αvβ6 integrin, which is expressed in a range of aggressively transformed epithelial cancers but nondetectable in healthy tissues.Experimental Design: Ad5NULL-A20 harbors mutations in each major capsid protein to preclude uptake via all native pathways. Tumor-tropism via αvβ6 targeting was achieved by genetic insertion of A20 peptide (NAVPNLRGDLQVLAQKVART) within the fiber knob protein. The vector's selectivity in vitro and in vivo was assessed.Results: The tropism-ablating triple mutation completely blocked all native cell entry pathways of Ad5NULL-A20 via coxsackie and adenovirus receptor (CAR), αvβ3/5 integrins, and coagulation factor 10 (FX). Ad5NULL-A20 efficiently and selectively transduced αvβ6+ cell lines and primary clinical ascites-derived EOC ex vivo, including in the presence of preexisting anti-Ad5 immunity. In vivo biodistribution of Ad5NULL-A20 following systemic delivery in non-tumor-bearing mice was significantly reduced in all off-target organs, including a remarkable 107-fold reduced genome accumulation in the liver compared with Ad5. Tumor uptake, transgene expression, and efficacy were confirmed in a peritoneal SKOV3 xenograft model of human EOC, where oncolytic Ad5NULL-A20-treated animals demonstrated significantly improved survival compared with those treated with oncolytic Ad5.Conclusions: Oncolytic Ad5NULL-A20 virotherapies represent an excellent vector for local and systemic targeting of αvβ6-overexpressing cancers and exciting platforms for tumor-selective overexpression of therapeutic anticancer modalities, including immune checkpoint inhibitors. Clin Cancer Res; 24(17); 4215-24. ©2018 AACR.
Trends in Prescription Medication Use Among Children and Adolescents—United States, 1999-2014
Authors: Craig M. Hales, Brian K. Kit, Qiuping Gu, Cynthia L. Ogden
Journal: JAMA (2018)

<h3>Importance</h3> Access to appropriate prescription medications, use of inappropriate or ineffective treatments, and adverse drug events are public health concerns among US children and adolescents. <h3>Objective</h3> To evaluate trends in use of prescription medications among US children and adolescents. <h3>Design, Setting, and Participants</h3> US children and adolescents aged 0 to 19 years in the 1999-2014 National Health and Nutrition Examination Survey (NHANES)—serial cross-sectional, nationally representative surveys of the civilian noninstitutionalized population. <h3>Exposures</h3> Sex, age, race and Hispanic origin, household income and education, insurance status, current health status. <h3>Main Outcomes and Measures</h3> Use of any prescription medications or 2 or more prescription medications taken in the past 30 days; use of medications by therapeutic class; trends in medication use across 4-year periods from 1999-2002 to 2011-2014. Data were collected though in-home interview and direct observation of the prescription container. <h3>Results</h3> Data on prescription medication use were available for 38 277 children and adolescents (mean age, 10 years; 49% girls). Overall, use of any prescription medication in the past 30 days decreased from 24.6% (95% CI, 22.6% to 26.6%) in 1999-2002 to 21.9% (95% CI, 20.3% to 23.6%) in 2011-2014 (β = −0.41 percentage points every 2 years [95% CI, −0.79 to −0.03];<i>P</i> = .04), but there was no linear trend in the use of 2 or more prescription medications (8.5% [95% CI, 7.6% to 9.4%] in 2011-2014). In 2011-2014, the most commonly used medication classes were asthma medications (6.1% [95% CI, 5.4% to 6.8%]), antibiotics (4.5% [95% CI, 3.7% to 5.5%]), attention-deficit/hyperactivity disorder (ADHD) medications (3.5% [95% CI, 2.9% to 4.2%]), topical agents (eg, dermatologic agents, nasal steroids) (3.5% [95% CI, 3.0% to 4.1%]), and antihistamines (2.0% [95% CI, 1.7% to 2.5%]). There were significant linear trends in 14 of 39 therapeutic classes or subclasses, or in individual medications, with 8 showing increases, including asthma and ADHD medications and contraceptives, and 6 showing decreases, including antibiotics, antihistamines, and upper respiratory combination medications. <h3>Conclusions and Relevance</h3> In this study of US children and adolescents based on a nationally representative survey, estimates of prescription medication use showed an overall decrease in use of any medication from 1999-2014. The prevalence of asthma medication, ADHD medication, and contraceptive use increased among certain age groups, whereas use of antibiotics, antihistamines, and upper respiratory combination medications decreased.
Capecitabine combined with oxaliplatin (XELOX) as first-line chemotherapy in colorectal cancer with liver metastases
Authors: H. Mahfouf, H. Djeddi, S. Belhadef, K. Bouzid, K. Bentabak
Journal: Journal of Clinical Oncology (2009)

e15146 Background: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated. Methods: Chemotherapy-naive patients confirmed histologic colorectal cancer with liver metastases, adequate born morrow, renal and hepatic function, measurable diseases were considered eligible for the study. Treatment: Six cycles of oxaliplatin 85 mg/m 2 day1 plus capecitabine 1250 mg/m 2 twice daily days 1–14 every 21 days Results: Twenty six patients were evaluated for safety and efficacy (male/female, 12/14). Median age was 53 years (range 32–75 years). A total of 142 cycles have been administered: median per patient 4 (range 3–6 courses). In an intent-to-treat efficacy analysis, One complete and ten partial responses were achieved [overall objective response rate (ORR): 42, 3%; whereas 7 patients had stable disease and eight patients had progressive disease. Seven patients from 11 with objective response underwent major liver resection: 2 bisegmentectomy, 1 left lobectomy, 4 segmentectomy, and receive the same regimen of chemotherapy (Six cycles) as an adjuvant treatment and still alive without recurrence. The overall survival (OS) was 19, 2 months. The median response duration was 7 months. The median time to progression (TTP) was 8 months. The grade 3 toxicities were diarrhea (7%), fatigue (4%), neurotoxicity (2%), neutropenia (2%), and thrombocytopenia 4%). Conclusions: The combination of oxaliplatin and capecitabine is safe and has a promising activity in patients with liver metastatic colorectal carcinoma. No significant financial relationships to disclose.