tbuckley/cabot-search huggingface dataset:
Evolving Treatment Paradigm in the Treatment of Locally Advanced Rectal Cancer
Authors: Clayton A. Smith, Lisa A. Kachnic
Journal: Journal of the National Comprehensive Cancer Network (2018)

Locally advanced rectal cancer (LARC) carries higher risks of local and distant recurrence when treated with surgical resection alone. Multiple treatment strategies have been investigated to reduce recurrence risk and improve survival. Currently, there are 3 primary strategies for managing LARC: (1) preoperative long-course radiotherapy (RT) combined with radiosensitizing chemotherapy, which is better tolerated than postoperative chemoradiotherapy and provides tumor downstaging and improved pathologic complete response (pCR), followed by postoperative chemotherapy; (2) preoperative short-course RT alone as an alternative strategy for reducing the risk of local recurrence, followed by adjuvant postoperative chemotherapy; and (3) total neoadjuvant therapy with induction chemotherapy followed by chemoradiotherapy to improve pCR and reduce the difficulty of delivering chemotherapy in the postoperative setting. In addition to these currently recommended treatment paradigms, promising new strategies are available for treatment reduction. Neoadjuvant chemotherapy alone may allow for omission of RT in select patients with favorable LARC. For patients who have complete clinical responses to neoadjuvant chemotherapy and RT, nonoperative management is being considered for sphincter preservation, with surgery used as salvage. These are active areas of investigation in both institutional and cooperative group trials. The results are anticipated to provide better tailoring of neoadjuvant therapy based on patient tumor and disease response characteristics.
And Still We Believed
Authors: Rebekah Mannix
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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
Protective effects of breastfeeding on respiratory symptoms in infants with 17q21 asthma risk variants
Authors: O. Gorlanova, S. Illi, A. A. Toncheva, J. Usemann, P. Latzin, M. Kabesch, J.‐C. Dalphin, R. Lauener, J. R. Pekkanen, E. Von Mutius, J. Riedler, C. E. Kuehni, M. Röösli, U. Frey
Journal: Allergy (2018)

Dr. von Mutius reports holding grants from the European Commission, the European Research Council, and the German Research Foundation, during the conduct of the study. Dr. von Mutius has also received personal fees from the following organizations for her contribution outside the context of the submitted work: the American Academy of Allergy, Asthma & Immunology, the Ökosoziales Forum Oberösterreich, Mundipharma, HAL Allergie GmbH, from DOC Congress SRL, American Thoracic Society, University of Tampere; GBS RE HEFCE, Novartis Pharma, OM Pharma SA, AbbVie Deutschland GmbH & Co. KG, medUpdate GmbH, and System Analytic Ltd. Dr. Latzin reports personal fees from OM Pharma SA, Roche, Vertex and Gilead, all outside of the submitted work. Dr. Frey reports a personal fee from a GSK scientific board meeting 2016, outside of the submitted work. Dr. Pekkanen reports holding grants from the European Commission and Academy of Finland during the conduct of the study. Dr. Lauener reports holding grants from the Kühne Foundation/Christine Kühne-Center for Allergy Research and Education, the European Union and the Swiss National Research Foundation during the conduct of the study. Dr. Lauener has received fees and/or served on advisory boards from Menarini, Meda, Nestlé, AstraZeneca, the Pfizer Research Prize Foundation, Vifor and the Swiss Government, all outside of the submitted work. Dr. Kabesch reports holding grants from the European Union, German Ministry of Education and Research, German Research Foundation during the conduct of the study. Dr. Kabesch reports a personal fees from Bionorica, ERS, EAACI, ATS, Novartis, Glaxo, Nutricia, and Hipp, all outside of the submitted work. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses
Authors: Israel Cañadas, Rohit Thummalapalli, Jong Wook Kim, Shunsuke Kitajima, Russell William Jenkins, Camilla Laulund Christensen, Marco Campisi, Yanan Kuang, Yanxi Zhang, Evisa Gjini, Gao Zhang, Tian Tian, Debattama Rai. Sen, Diana Miao, Yu Imamura, Tran Thai, Brandon Piel, Hideki Terai, Amir Reza Aref, Timothy Hagan, Shohei Koyama, Masayuki Watanabe, Hideo Baba, Anika Elise Adeni, Christine Anne Lydon, Pablo Tamayo, Zhi Wei, Meenhard Herlyn, Thanh Uyen Barbie, Ravindra Uppaluri, Lynnette Marie Sholl, Ewa Sicinska, Jacob Sands, Scott Rodig, Kwok Kin Wong, Cloud Peter Paweletz, Hideo Watanabe, David Allen Barbie
Journal: Nature Medicine (2018)
[18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM
Authors: Eline E. Verwer, Taylor R. Kavanagh, William J. Mischler, You Feng, Kazue Takahashi, Shuyan Wang, Timothy M. Shoup, Ramesh Neelamegam, Jing Yang, Nicolas J. Guehl, Chongzhao Ran, Walter Massefski, Ye Cui, Souheil El-Chemaly, Peter M. Sadow, William M. Oldham, Marie F. Kijewski, Georges El Fakhri, Marc D. Normandin, Carmen Priolo
Journal: Clinical Cancer Research (2018)

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by inactivating mutations of the TSC1 or TSC2 gene, characterized by neurocognitive impairment and benign tumors of the brain, skin, heart, and kidneys. Lymphangioleiomyomatosis (LAM) is a diffuse proliferation of α-smooth muscle actin-positive cells associated with cystic destruction of the lung. LAM occurs almost exclusively in women, as a TSC manifestation or a sporadic disorder (TSC1/TSC2 somatic mutations). Biomarkers of whole-body tumor burden/activity and response to rapalogs or other therapies remain needed in TSC/LAM.These preclinical studies aimed to assess feasibility of [18F]fluorocholine (FCH) and [18F]fluoroacetate (FACE) as TSC/LAM metabolic imaging biomarkers.We previously reported that TSC2-deficient cells enhance phosphatidylcholine synthesis via the Kennedy pathway. Here, we show that TSC2-deficient cells exhibit rapid uptake of [18F]FCH in vivo and can be visualized by PET imaging in preclinical models of TSC/LAM, including subcutaneous tumors and pulmonary nodules. Treatment with rapamycin (72 hours) suppressed [18F]FCH standardized uptake value (SUV) by >50% in tumors. Interestingly, [18F]FCH-PET imaging of TSC2-deficient xenografts in ovariectomized mice also showed a significant decrease in tumor SUV. Finally, we found rapamycin-insensitive uptake of FACE by TSC2-deficient cells in vitro and in vivo, reflecting its mitochondrial accumulation via inhibition of aconitase, a TCA cycle enzyme.Preclinical models of TSC2 deficiency represent informative platforms to identify tracers of potential clinical interest. Our findings provide mechanistic evidence for testing the potential of [18F]FCH and [18F]FACE as metabolic imaging biomarkers for TSC and LAM proliferative lesions, and novel insights into the metabolic reprogramming of TSC tumors.
AB0192 Discovery of potential skin biopsy biomarkers for systemic sclerosis by high-throughput proteomic approaches
Authors: P. Chairta, P. Nicolaou, K. Sokratous, G. Spyrou, A. Oulas, C. Galant, F. Houssiau, B. Lauwerys, K. Christodoulou
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic Sclerosis (SSc) is an autoimmune connective tissue rheumatic disease characterised by three main hallmarks; vasculopathy, immune system abnormalities and fibrosis. It is considered a multisystemic and heterogeneous disease as many organs of the body may be affected and symptoms vary among patients. Up to date, SSc is untreated and its etiology and pathogenesis remain unclear. Early prognosis and diagnosis of the disease are challenging. <h3>Objectives</h3> The aim of this study was to analyse the proteomic profile of SSc patients in order to gain insights into the mechanisms implicated in disease pathogenesis and also discover new biomarkers that would facilitate early prognosis, more accurate diagnosis and therapeutic targeting of SSc. <h3>Methods</h3> Human biopsies were obtained from ten affected and three non-affected skin areas of SSc patients and have been classified based on histological criteria. Biopsies were cryo-pulverised and proteins were extracted, purified, reduced, alkylated and digested by trypsin. Purified peptides were analysed on a Waters Synapt G2Si HDMS instrument operated in ion mobility mode using a UDMS<sup>E</sup> approach. Data were processed by the Progenesis QIp and functional annotation analysis was carried out using multiple bioinformatics resources. <h3>Results</h3> Proteomic analysis led to the identification and quantification of approximately 1500 non-redundant proteins per sample. About 400 of these proteins, including interferons and interleukins, are differentially expressed between affected and non-affected samples. Functional annotation analysis of these proteins showed that they are involved in multiple pathways including, antigen processing and presentation, complement, ubiquitin mediated proteolysis and Notch signalling, which are known to be associated with autoimmune diseases and fibrosis. <h3>Conclusions</h3> Using a Mass Spectrometry-based proteomic approach for the analysis of SSc human skin biopsies, we identified a number of proteins that might be involved in the development and pathogenesis of SSc. Interestingly, some of these proteins are differentially expressed in specific histological groups and thus could be considered as potential biomarkers for specific SSc stages. <h3>Acknowledgements</h3> This work has received support from the EU/EFPIA/Innovative Medicines Initiative Joint Undertaking PRECISESADS grant n° 115565, the Cyprus Institute of Neurology and Genetics and Université catholique de Louvain. <h3>Disclosure of Interest</h3> None declared
Babylon app will be properly regulated to ensure safety, government insists
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The Department of Health and Social Care has sought to assuage concerns over the regulation of Babylon Health’s GP at Hand app, after the Glasgow GP and BMJ columnist Margaret McCartney raised the issue with MPs.

Self diagnosis apps or symptom checkers, such as the one available to patients who join the GP at Hand service, are becoming increasingly popular.

McCartney outlined her concerns about Babylon’s health app to Sarah Wollaston, former GP and the chair of the health select committee, who wrote to the former health secretary, Jeremy Hunt, about the issues raised.

She was worried that the app missed symptoms, that it generated a high rate of false positives, and that regulators (the Care Quality Commission, the Medicines and Healthcare Products Regulatory Agency, and the Advertising Standards Authority) considered the app to be outside their regulatory remit.

In Hunt’s …
Longitudinal In Vivo Monitoring of the CNS Demonstrates the Efficacy of Gene Therapy in a Sheep Model of CLN5 Batten Disease
Authors: Nadia L. Mitchell, Katharina N. Russell, Martin P. Wellby, Hollie E. Wicky, Lucia Schoderboeck, Graham K. Barrell, Tracy R. Melzer, Steven J. Gray, Stephanie M. Hughes, David N. Palmer
Journal: Molecular Therapy (2018)
A Transforming Growth Factor‐β and H19 Signaling Axis in Tumor‐Initiating Hepatocytes That Regulates Hepatic Carcinogenesis
Authors: Jinqiang Zhang, Chang Han, Nathan Ungerleider, Weina Chen, Kyoungsub Song, Ying Wang, Hyunjoo Kwon, Wenbo Ma, Tong Wu
Journal: Hepatology (2018)

Functions of transforming growth factor-β (TGF-β) in the liver vary depending on specific cell types and their temporal response to TGF-β during different stages of hepatocarcinogenesis (HCG). Through analysis of tumor tissues from hepatocellular carcinoma (HCC) patients, we were able to cluster hepatic epithelial cell-derived TGF-β gene signatures in association with distinct clinical prognoses. To delineate the role of hepatic epithelial TGF-β signaling in HCC development, we used an experimental system in which tumor-initiating hepatocytes (TICs) were isolated from TGF-β receptor II floxed mice (Tgfbr2fl/fl ) and transplanted into syngeneic C57BL/6J mice by splenic injection. Recipient mice were then administered Cre-expressing adenovirus (Ad-Cre) to inactivate Tgfbr2 in transplanted TICs. After latency, Tgfbr2-inactivated TICs formed larger and more tumor nodules in recipient livers compared to TICs without Tgfbr2 inactivation. In vitro analyses revealed that treatment of cultured TICs with TGF-β inhibited expression of progenitor cell factors (including SRY (sex determining region Y)-box 2 [Sox2]). RNA sequencing (RNA-seq) analysis identified H19 as one of the most up-regulated long noncoding RNA (lncRNA) in association with Tgfbr2 inactivation in TICs. Tgfbr2 inactivation by Ad-Cre led to a 5-fold increase of H19 expression in TICs. Accordingly, TGF-β treatment reduced H19 expression. We observed that forced overexpression of Sox2 in TICs increased transcription of H19, whereas knockdown of Sox2 decreased it. Furthermore, depletion of H19 reduced the progenitor property of TICs in vitro and decreased their tumorigenic potential in vivo. Finally, we observed a low level of H19 mRNA expression in human HCC tissues from patients with the epithelial TGF-β gene signature in association with favorable prognosis. Conclusion: Our findings describe a TGF-β and H19 signaling axis by Sox2 in TICs that importantly regulates HCG.
Evidence for Two Components of Delayed Rectifier K+ Current in Human Ventricular Myocytes
Authors: Gui-RongLi, JianlinFeng, LixiaYue, MichelCarrier, StanleyNattel
Journal: Circulation Research (1996)

Abstract Previous voltage-clamp studies have suggested that the delayed rectifier current (IK) is small or absent in the human ventricle and, when present, consists only of the rapid component (IKr); however, molecular studies suggest the presence of functionally important IK in the human heart, specific IKr blockers are known to delay ventricular repolarization and cause the long QT syndrome in humans, and we have shown that the expression of IK is strongly influenced by cell isolation techniques. The present experiments were designed to assess the expression of IK in myocytes obtained by arterial perfusion of right ventricular tissue from explanted human hearts. Of 35 cells from three hearts, 33 (94%) showed time-dependent currents typical of IK. The envelope-of-tails test was not satisfied under control conditions but became satisfied in the presence of the benzenesulfonamide E-4031 (5 μmol/L). E-4031 suppressed a portion of IK in 32 of 33 cells, with properties of the drug-sensitive and -resistant com...
How to Combat the Opioid Epidemic, 1 Nudge at a Time
Authors: David D. Q. Zhang, Fahima Dossa, Nancy N. Baxter
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Off-label Use of Medications—Reply
Authors: Joshua D. Wallach, Joseph S. Ross
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Opioid prescriptions outnumber patients in some parts of the US
Authors: Bob Roehr
Journal: BMJ (2018)

Prescribing rates for opioids are up to sevenfold higher in rural areas compared with urban ones in the United States, according to a new analysis of prescribing patterns by congressional district.

Heading the list was Alabama’s 4th district, where doctors wrote 166.69 opioid prescriptions per 100 persons. The largely rural area sprawls across the northern region of the state and is 88% white, compared with 73% white for the state as a whole.

At the bottom of the list were two congressional districts in Brooklyn, New York, where the prescribing rate …
Prescribing patterns for FOLFIRINOX in the real world.
Authors: Chad Michael Guenther, Nizar Bhulani, Adam Korenke, Jenny Jing Li, Leticia Khosama, Samira K. Syed, Syed Mohammad Ali Kazmi, Naga Koteswari Cheedella, Sirisha Karri, Jay Lohrey, Aravind Sanjeevaiah, Udit N. Verma, John Vernon Cox, Yull Edwin Arriaga, Muhammad Shaalan Beg
Journal: Journal of Clinical Oncology (2018)

463 Background: FOLFIRINOX therapy is associated with improved outcome in patients with gastrointestinal cancers. The regimen can be associated with significant toxicity and empiric dose modifications are often used. We analyzed 1) real-world prescribing patterns of FOLFIRINOX and 2) toxicity of therapy. Methods: Patients undergoing FOLFIRINOX chemotherapy at an academic, NCI-Designated Comprehensive Cancer Center were identified and electronic medical records reviewed. Patients who received at least one dose of FOLFIRINOX were included. Chemotherapy dose, growth factor use and toxicity data was abstracted for the first 8 weeks. ‘Standard FOLFIRNOX’ was defined as the regimen utilized by Conroy et al (NEJM 2011). Any empiric reduction/withholding of drug dose for cycle 1 was classified as ‘modified FOLFIRINOX’. Bivariate analysis was performed on the data. Results: There were 111 patients seen between 5/2011-3/2017 and 94% had pancreatic cancer. Age range was 29-87 years and 52% were female. 59% received ‘modified FOLFIRINOX’ and 20% received empiric growth factors. Line of therapy for standard vs modified respectively was 71.1% vs 45.5% for 1st, 17.8% vs 36.4% for 2nd, and 11.1% vs 18.2% for beyond 2nd (p = 0.03). Patients with ‘modified FOLFIRINOX’ were more likely to have metastatic disease (p = 0.01), have received second line or beyond, and higher ECOG score (p = 0.03). Patients with ‘modified FOLFIRINOX’ had a trend toward fewer treatment-related ED visits or hospitalization vs ‘standard FOLFIRINOX’ (27.2% vs 42.2% p = 0.10) and fewer treatment delays (25.8% vs 42.2% p = 0.07). Conclusions: In the real world setting, a majority of patients on FOLFIRINOX receive empiric dose modifications. Although modified dose did not translate to a significant difference in ED visits, hospitalizations or treatment delays, there was a trend toward fewer events.
Procalcitonin to Guide Antibiotic Decisions
Authors: David A. Talan
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Testing and treating within an hour of suspecting sepsis in children reduces deaths, shows study
Authors: Susan Mayor
Journal: BMJ (2018)

Use of a protocol that was based on testing for infection and treatment with antibiotics and fluids within one hour of recognising possible sepsis in children was associated with a significant reduction in the risk of death, a cohort study in New York state has shown.1

“No child should die from a treatable infection,” said study author Christopher Seymour, from the University of Pittsburgh School of Medicine. He added, “This is the best evidence to date that prompt identification and treatment of suspected sepsis leads to better outcomes in children.”

After …