tbuckley/cabot-search huggingface dataset:
Cliff Mann: instrumental in developing new clinical standards for urgent and emergency care
Authors: John Illman
Journal: BMJ (2021)

Photo credit: Richard Smith

Asked by The BMJ who was the person in his life whom he would most like to thank, Clifford Mann named his first comprehensive school form teacher. Young Cliff had thought that he was doing well; Mr Graham told him that he was “coasting.” The former president of the Royal College of Emergency Medicine and national clinical adviser for urgent and emergency care, Mann said, “I’ve never forgotten the implied criticism.”

Patients, colleagues, and the NHS at large should be grateful to Mr Graham. Mann became the opposite of a coaster. NHS chief executive Simon Stevens said, “Cliff was an exceptional clinical leader, patient advocate, and source of wise advice, who stayed grounded in the pressurised realities of day-to-day emergency medicine, while at the same time shaping and helping create a better future.”

His talents were reflected in his national roles, but the many tributes to him suggest that his …
Responsible Inclusion of Pregnant Individuals in Eradicating HCV
Authors: Ravi Jhaveri, Lynn M. Yee, Swati Antala, Margaret Murphy, William A. Grobman, Seema K. Shah
Journal: Hepatology (2021)

HCV infections have increased in recent years due to injection drug use and the opioid epidemic. Simultaneously, HCV cure has become a reality, with the advent of direct‐acting antivirals (DAAs) and expansion of treatment programs. As a result, HCV screening recommendations now include all adults, including pregnant individuals; and many countries have endorsed widespread DAA access as a strategy to achieve HCV eradication. However, almost universally, pregnant individuals have been systematically excluded from HCV clinical research and treatment programs. This omission runs counter to public health strategies focused on elimination of HCV but is consistent with a historical pattern of exclusion of pregnant individuals from research. Our systematic review of publications on HCV treatment with DAAs in pregnancy revealed only one interventional study, which evaluated sofosbuvir/ledipasvir in 8 pregnant individuals. Given the paucity of research on this issue of great public health importance, we aimed to appraise the current landscape of HCV research/treatment and analyze the ethical considerations for responsibly including pregnant individuals. We propose that pregnancy may be an opportune time to offer HCV treatment given improved access, motivation, and other health care monitoring occurring in the antenatal period. Moreover, treatment of pregnant individuals may support the goal of eliminating perinatal HCV transmission and overcome the established challenges with transitioning care after delivery. The exclusion of pregnant individuals without justification denies them and their offspring access to potential health benefits, raising justice concerns considering growing data on DAA safety and global efforts to promote equitable and comprehensive HCV eradication. Finally, we propose a path forward for research and treatment programs during pregnancy to help advance the goal of HCV elimination.
Heterogeneity and plasticity of cancer-associated fibroblasts in the pancreatic tumor microenvironment
Authors: Lenka N.C. Boyd, Katarina D. Andini, Godefridus J. Peters, Geert Kazemier, Elisa Giovannetti
Journal: Seminars in Cancer Biology (2021)

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis, in urgent need of improved treatment strategies. The desmoplastic PDAC tumor microenvironment (TME), marked by a high concentration of cancer-associated-fibroblasts (CAFs), is a dynamic part of PDAC pathophysiology which occasions a variety of effects throughout the course of pancreatic tumorigenesis and disease evolution. A better understanding of the desmoplastic TME and CAF biology in particular, should provide new opportunities for improving therapeutics. That CAFs have a tumor-supportive role in oncogenesis is well known, yet research evidence has shown that CAFs also have tumor-repressive functions. In this review, we seek to clarify the intriguing heterogeneity and plasticity of CAFs and their ambivalent role in PDAC tumorigenesis and progression. Additionally, we provide recommendations to advance the implementation of CAF-directed PDAC care. An improved understanding of CAFs' origins, spatial location, functional diversity, and marker determination, as well as CAF behavior during the course of PDAC progression and metastasis will provide essential knowledge for the future improvement of therapeutic strategies for patients suffering from PDAC.
The role of regulated on activation, normal T cell expressed and secreted (RANTES) in allergic asthma
Authors: N. Li, J. Koelle, A. Kiefer, P. Xepapadaki, M. L. Kowalski, Claus Bachert, T. Jartti, T. Vuorinen, A. Lewandowska-Polak, Nan Zhang, H. Lukkarinen, T. Zimmermann, M. Akdis, N. G. Papadopoulos, S. Finotto
Journal: Allergy (2020)
A perfusable, multifunctional epicardial device improves cardiac function and tissue repair
Authors: Shixing Huang, Dong Lei, Qi Yang, Yang Yang, Chenyu Jiang, Hongpeng Shi, Bei Qian, Qiang Long, Wenyi Chen, Youming Chen, Lan Zhu, Wenjie Yang, Lan Wang, Wangxi Hai, Qiang Zhao, Zhengwei You, Xiaofeng Ye
Journal: Nature Medicine (2021)
P76.32 Real-World Data in Non-Small Cell Lung Cancer with Activating EGFR Mutation Treated with First and Second Generation TKI
Authors: D. Juarez, R. Ruiz, J.M. Gutierrez, L. Mas, Z. Morante, A. Aguilar, C. Flores, T. Paytan
Journal: Journal of Thoracic Oncology (2021)
Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status
Authors: Biagio Ricciuti, Kathryn C. Arbour, Jessica J. Lin, Amir Vajdi, Natalie Vokes, Lingzhi Hong, Jianjun Zhang, Michael Y. Tolstorukov, Yvonne Y. Li, Liam F. Spurr, Andrew D. Cherniack, Gonzalo Recondo, Giuseppe Lamberti, Xinan Wang, Deepti Venkatraman, Joao V. Alessi, Victor R. Vaz, Hira Rizvi, Jacklynn Egger, Andrew J. Plodkowski, Sara Khosrowjerdi, Subba Digumarthy, Hyesun Park, Nuno Vaz, Mizuki Nishino, Lynette M. Sholl, David Barbie, Mehmet Altan, John V. Heymach, Ferdinandos Skoulidis, Justin F. Gainor, Matthew D. Hellmann, Mark M. Awad
Journal: Journal of Thoracic Oncology (2021)
Performance of the DETECT Algorithm for Pulmonary Hypertension Screening in a Systemic Sclerosis Cohort
Authors: Amber Young, Victor M. Moles, Sara Jaafar, Scott Visovatti, Suiyuan Huang, Dharshan Vummidi, Vivek Nagaraja, Vallerie McLaughlin, Dinesh Khanna
Journal: Arthritis & Rheumatology (2021)

Objective Pulmonary arterial hypertension (PAH) is one of the leading causes of mortality in systemic sclerosis (SSc). This study was undertaken to assess predictive accuracies of the DETECT algorithm and the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines in SSc patients who underwent right‐sided heart catheterization (RHC) for pulmonary hypertension (PH) evaluation. Methods Patients with SSc who had diagnostic RHC, had no PH or had PAH, and had available data on variables to allow application of the DETECT and 2015 ESC/ERS guidelines were included for analysis. PH classification was based on hemodynamics using the 2018 revised criteria and extent of lung fibrosis shown on high‐resolution computed tomography. Sensitivity and predictive accuracies of the DETECT algorithm and 2015 ESC/ERS guidelines were calculated, including analysis of subjects with a diffusing capacity for carbon monoxide (DL co ) of ≥60% predicted. Results Sixty‐eight patients with SSc had RHC, of whom 58 had no PH and 10 had PAH. The mean age was 60.0 years, and 58.8% had limited cutaneous SSc. The DETECT algorithm had a sensitivity of 1.00 (95% confidence interval [95% CI] 0.69–1.00) and a negative predictive value (NPV) of 1.00 (95% CI 0.80–1.00), whereas the 2015 ESC/ERS guidelines had a sensitivity of 0.80 (95% CI 0.44–0.97) and an NPV of 0.94 (95% CI 0.81–0.99). In patients with a DL co of ≥60% (n = 27), the DETECT algorithm had a sensitivity of 1.00 (95% CI 0.29–1.00) and an NPV of 1.00 (95% CI 0.59–1.00), whereas the 2015 ESC/ERS guidelines had a sensitivity of 0.67 (95% CI 0.09–0.99) and an NPV of 0.94 (95% CI 0.71–1.00). Conclusion The DETECT algorithm has high sensitivity and NPV for diagnosis of PAH, including among individuals with a DL co of ≥60%.
The Trade-off Between the Bony Carotid Canal and Internal Carotid Artery
Authors: Lizhang Chen, Hua Cao, Muke Zhou
Journal: JAMA Neurology (2021)

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
Obesity-Dependent Adipokine Chemerin Suppresses Fatty Acid Oxidation to Confer Ferroptosis Resistance
Authors: Sze Kiat Tan, Iqbal Mahmud, Flavia Fontanesi, Michelle Puchowicz, Chase K.A. Neumann, Anthony J. Griswold, Rutulkumar Patel, Marco Dispagna, Hamzah H. Ahmed, Mark L. Gonzalgo, J. Mark Brown, Timothy J. Garrett, Scott M. Welford
Journal: Cancer Discovery (2021)

Clear cell renal cell carcinoma (ccRCC) is characterized by accumulation of neutral lipids and adipogenic transdifferentiation. We assessed adipokine expression in ccRCC and found that tumor tissues and patient plasma exhibit obesity-dependent elevations of the adipokine chemerin. Attenuation of chemerin by several approaches led to significant reduction in lipid deposition and impairment of tumor cell growth in vitro and in vivo. A multi-omics approach revealed that chemerin suppresses fatty acid oxidation, preventing ferroptosis, and maintains fatty acid levels that activate hypoxia-inducible factor 2α expression. The lipid coenzyme Q and mitochondrial complex IV, whose biogeneses are lipid-dependent, were found to be decreased after chemerin inhibition, contributing to lipid reactive oxygen species production. Monoclonal antibody targeting chemerin led to reduced lipid storage and diminished tumor growth, demonstrating translational potential of chemerin inhibition. Collectively, the results suggest that obesity and tumor cells contribute to ccRCC through the expression of chemerin, which is indispensable in ccRCC biology. SIGNIFICANCE: Identification of a hypoxia-inducible factor-dependent adipokine that prevents fatty acid oxidation and causes escape from ferroptosis highlights a critical metabolic dependency unique in the clear cell subtype of kidney cancer. Targeting lipid metabolism via inhibition of a soluble factor is a promising pharmacologic approach to expand therapeutic strategies for patients with ccRCC.See related commentary by Reznik et al., p. 1879.This article is highlighted in the In This Issue feature, p. 1861.
P16.07 Immuno-Modulatory Effects of Ceralasertib in Combination with Durvalumab in NSCLC with Progression on Anti-PD(L)1 Treatment (HUDSON)
Authors: M. Hernandez, B. Besse, M. Awad, P. Forde, M. Thomas, K. Park, G. Goss, N. Rizvi, J. Cosaert, Z. Szucs, P. Mortimer, R. Hobson, H. Ambrose, C. Hayward, M. Dressman, E. Dean, A. Coenen-Stass, C. Barrett, J. Heymach, K. Sachsenmeier
Journal: Journal of Thoracic Oncology (2021)
Long-Term Colorectal Cancer Incidence and Mortality After Colonoscopy Screening According to Individuals’ Risk Profiles
Authors: Kai Wang, Wenjie Ma, Kana Wu, Shuji Ogino, Edward L Giovannucci, Andrew T Chan, Mingyang Song
Journal: JNCI Journal of the National Cancer Institute (2021)

It remains unknown whether the benefit of colonoscopy screening against colorectal cancer (CRC) and the optimal age to start screening differ by CRC risk profile.
Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early
Authors: Sonia N. Wolf, Jana Haddow, Claire Greiller, Graham P. Taylor, Lucy B. M. Cook, Aileen G. Rowan
Journal: Blood Cancer Journal (2021)

Abstract Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vβ subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26− T-cells) using an ‘oligoclonality index’ (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up ( n = 38) and patients with ATL ( n = 30). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL ( n = 106), 19% of high proviral load (PVL, ≥4 copies of HTLV-1/100 PBMCs) carriers had an OCI-flow in the ATL range, &gt;0.770. Carriers with an OCI-flow &gt;0.770 ( n = 14) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow ≤0.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow ≤0.770 ( p = 0.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease.
Costs and in-Hospital Mortality Rates in Autologous Stem Cell Transplant for Multiple Myeloma: An Analysis of the Nationwide Inpatient Sample (NIS) Database
Authors: Yuzhou Liu, Hedong Han, Xin Wei, Qian Wang, Jia He, Gunjan L. Shah, Sergio A. Giralt, Ola Landgren, Alexander Lesokhin
Journal: Blood (2017)
P14.16 The Early Landscape of Immune Cell Subsets in Metastatic NSCLC Patients Treated with Immune Checkpoint Inhibitors
Authors: J. Zhou, A. Donaubauer, B. Frey, I. Becker, S. Rutzner, R. Sun, H. Ma, R. Fietkau, E. Deutsch, U. Gaipl, M. Hecht
Journal: Journal of Thoracic Oncology (2021)
P57.03 Pathogenic Germline Mutations of Homologous Recombination Deficiency (HRD) Genes in Chinese Lung Cancer Patients
Authors: M. Wang, S. Li, X. Xue, X. Wei, Z. Ye, Y. Su, L. Li, Z. Xu, T. Guo, J. Xie, W. Wang, L. Zhang
Journal: Journal of Thoracic Oncology (2021)
P33.20 Evaluation of Combined Biomarker of Response to Immunotherapy in Patients with Advanced Non-Small Cell Lung Cancer
Authors: H. Ramdani, M. Falk, S. Schatz, L. Heukamp, M. Tiemann, C. Wesseler, E. Schuuring, H. Groen, F. Griesinger
Journal: Journal of Thoracic Oncology (2021)
P78.05 Patterns of irAE During First Line Pembrolizumab for NSCLC: Incidence, Risk Factors, and Impact on Clinical Outcome
Authors: C. Wood, G. Lopez, L. Zhao, M. Li, N. Surya, S. Patel, M. Grogan, E. Bertino, P. Shields, K. He, D. Carbone, G. Otterson, C. Presley, B. Pannecouk, G. Kalemkerian, B. Schneider, S. Gadgeel, N. Ramnath, D. Owen, A. Qin
Journal: Journal of Thoracic Oncology (2021)
Abstract 15340: Reducing Unnecessary Preoperative Cardiology Referral and Cost in Patients Undergoing Bariatric Surgery
Authors: Kaitlyn Ibrahim, Rohit Soans, Lauren Tragesser, Abdullah Haddad, Raj Dalsania, Vikram J Eddy, Liti Zhang, Joseph McComb, Martin G Keane, Isaac R Whitman
Journal: Circulation (2020)

Introduction: Candidates for bariatric surgery are at increased risk for cardiovascular disease, which may increase surgical risk. Currently, there are no society guidelines indicating which patients are appropriate for preoperative cardiovascular evaluation and risk stratification. Hypothesis: We hypothesized that applying a standardized surgical risk calculator with a novel multidisciplinary internal referral algorithm to stratify patients for preoperative cardiovascular evaluation would decrease unnecessary referrals and cost. Methods: All patients undergoing bariatric surgery at our institution between 2014-2018 were identified. After assessing baseline patient characteristics, referral patterns to cardiology, prevalence of cardiac testing ordered, and surgical outcomes were measured. The Revised Cardiac Risk Index (RCRI) score was retrospectively calculated for each patient and grouped as low versus increased risk (RCRI score of 0 versus ≥ 1). Imputing a post hoc referral algorithm requiring an RCRI ≥ 1, age ≥ 65, METS ≤ 4, and/or ever smoking history for cardiology referral, we calculated how referral pattern would be affected and the resultant change in referral costs. Results: A total of 797 patients underwent bariatric surgery during the study period, of which 68% (n=540) were referred to cardiology preoperatively. Those referred had more hypertension, hyperlipidemia, diabetes, smoking history, and were more likely to have BMI &gt;50 kg/m 2 . Of those referred, 81% (n=438), 15% (n=81), 3% (n=17), and 1% (n=4) had RCRI scores of 0, 1, 2, and ≥ 3, respectively. Of those patients with an RCRI score of 0, 53% (n=234) underwent further cardiac testing. Strictly applying our standardized internal referral algorithm, of the 540 patients referred to cardiology, only 45% (n=199) were appropriately referred. Based on Medicare reimbursement for Level 4 outpatient consults, this would have resulted in a savings of approximately $86,000. Conclusions: Among candidates for bariatric surgery, a novel referral algorithm based on RCRI and other cardiovascular risk factors may reduce unnecessary preoperative cardiology referrals, with resultant reduction in resource utilization and overall cost savings.
Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma
Authors: Brian A. Van Tine, Angela C. Hirbe, Peter Oppelt, Ashley E. Frith, Richa Rathore, Joshua D. Mitchell, Fei Wan, Shellie Berry, Michele Landeau, George A. Heberton, John Gorcsan, Peter R. Huntjens, Yoku Soyama, Justin M. Vader, Jose A. Alvarez-Cardona, Kathleen W. Zhang, Daniel J. Lenihan, Ronald J. Krone
Journal: Clinical Cancer Research (2021)

To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS).
Association of Sarcopenia and Body Composition With Postoperative 90-Day Morbidity After Liver Resection for Malignant Tumors
Authors: Yong-Kang Diao, Lei Liang, Tian Yang
Journal: JAMA Surgery (2021)

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
HSP90 inhibitor NVP-BEP800 affects stability of SRC kinases and growth of T-cell and B-cell acute lymphoblastic leukemias
Authors: Rony Mshaik, John Simonet, Aleksandra Georgievski, Layla Jamal, Shaliha Bechoua, Paola Ballerini, Pierre-Simon Bellaye, Zandile Mlamla, Jean-Paul Pais de Barros, Audrey Geissler, Pierre-Jean Francin, François Girodon, Carmen Garrido, Ronan Quéré
Journal: Blood Cancer Journal (2021)

Abstract T-cell and B-cell acute lymphoblastic leukemias (T-ALL, B-ALL) are aggressive hematological malignancies characterized by an accumulation of immature T- or B-cells. Although patient outcomes have improved, novel targeted therapies are needed to reduce the intensity of chemotherapy and improve the prognosis of high-risk patients. Using cell lines, primary cells and patient-derived xenograft (PDX) models, we demonstrate that ALL cells viability is sensitive to NVP-BEP800, an ATP-competitive inhibitor of Heat shock protein 90 (HSP90). Furthermore, we reveal that lymphocyte-specific SRC family kinases (SFK) are important clients of the HSP90 chaperone in ALL. When PDX mice are treated with NVP-BEP800, we found that there is a decrease in ALL progression. Together, these results demonstrate that the chaperoning of SFK by HSP90 is involved in the growth of ALL. These novel findings provide an alternative approach to target SRC kinases and could be used for the development of new treatment strategies for ALL.
Preventing the onset of post traumatic stress disorder
Authors: Jonathan I. Bisson, Laurence Astill Wright, Kimberley A. Jones, Catrin Lewis, Andrea J. Phelps, Marit Sijbrandij, Tracey Varker, Neil P. Roberts
Journal: Clinical Psychology Review (2021)

Post-traumatic stress disorder (PTSD) is a common mental health condition that requires exposure to a traumatic event. This provides unique opportunities for prevention that are not available for other disorders. The aim of this review was to undertake a systematic review and evaluation of randomized controlled trials (RCTs) of interventions designed to prevent PTSD in adults. Searches involving Cochrane, Embase, Medline, PsycINFO, PILOTS and Pubmed databases were undertaken to identify RCTs of pre-incident preparedness and post-incident interventions until May 2019. Six pre-incident and 69 post-incident trials were identified that could be included in meta-analyses. The overall quality of the evidence was low. There was emerging evidence that some interventions may be helpful but an absence of evidence for any intervention that can be strongly recommended for universal, selected or indicated prevention before or within the first three months of a traumatic event. The strongest results were found for cognitive-behavioural therapy with a trauma focus (CBT-T) in individuals with a diagnosis of acute stress disorder which supports calls to detect and treat individuals with significant symptoms rather than providing blanket preventative interventions. Further research is required to optimally configure existing interventions with some evidence of effect and to develop novel interventions to address this major public health issue.