tbuckley/cabot-search huggingface dataset:
A retrospective single centre study exploring the efficacy of sequential tyrosine kinase inhibitors (TKI) in patients with hepatocellular cancer.
Authors: Catherine Roberts, Phillipa Kaina, David Propper, Nikolaos Diamantis, Rachael Delderfield, Alice Karuri, Marilyn Reyes, Rajinder Nijjar, Sarah Slater
Journal: Journal of Clinical Oncology (2022)

443 A retrospective single centre study exploring the efficacy of sequential tyrosine-kinase inhibitors (TKI) for patients with hepatocellular carcinoma. Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality. In the UK patients with advanced or intermediate disease despite locoregional treatments are offered a tyrosine-kinase inhibitor (TKI). Sorafenib (SOR) remains the approved first-line choice, with lenvatinib (LEN) and regorafenib (REG) used as either alternative first line or second line therapies, respectively. Previous studies have shown increased overall survival when comparing a single drug to placebo; however few have studied outcomes for patients treated with one or more TKIs. Methods: Data was collected from patients who received TKI therapy for HCC between January, 2016 and September, 2020, within the Barts Health NHS Trust, London. The Electronic Medical Record system was used to gather information pertaining to treatment. The non-parametric Pearson correlation coefficient was calculated using IBM SPSS software to explore the duration of TKI therapy and overall survival. Results: 64 patients were included in the cohort, 17% (n=11) female, 83% (n=53) were male. Median age was 68 years (range 38 - 92 years) and median survival from diagnosis was 18 months (range 4 - 106 months). 51 patients received one TKI, 12 patients received two and 1 patient received three sequential TKIs There was no significant correlation between the number of cycles of SOR or LEN received and overall survival ( p = 0.387), but there was a statistically significant correlation in the group of patients who received SOR and then REG (r s = 0.973, p = 0.000). There was also a statistically significant correlation (r s = 0.360, p = 0.004) between the cumulative number of cycles of TKI treatment and overall survival for all patients (i.e. SOR only, LEN only and those who received more than one TKI). Conclusions: Our analysis suggests that across the cohort, a longer duration of TKI treatment (measured in cycles) may be associated with increased overall survival for patients with advanced HCC. Further data is required to explore the impact on quality of life during therapy. [Table: see text]
Abstract 154: CCDC80 Functions as a Protein Kinase GI Substrate and is Secreted by Cardiac Myocytes
Authors: Robert M Blanton, Craig Cooper, Anja Hergruetter, Mark Aronovitz, Timothy D Calamaras
Journal: Circulation Research (2017)

Background: Protein kinase G I alpha (PKGIa) inhibits cardiac hypertrophy, remodeling, and dysfunction. Downstream PKGI substrates remain incompletely understood and represent potential novel therapeutic targets for myocardial disease. We previously identified through a molecular screen that PKGIa binds and phosphorylates the protein coiled-coiled domain containing 80 (Ccdc80; also termed SSG1 and URB) in vascular smooth muscle cells. Previous work also identified that Ccdc80 is secreted from adipocytes. However, the expression and secretion of Ccdc80 from the cardiac myocyte has not been investigated. The current study tested the hypothesis that Ccdc80 is expressed in and secreted from the cardiac myocyte. Results: In cultured rat cardiac myocytes (CM), we detected Ccdc80 by western blot. Western blot for Ccdc80 also detected a band of the predicted Ccdc80 molecular weight present in media from these cells, but not in uncultured media. Ccdc80 could be detected in the human left ventricle (LV), though expression did not differ between hearts of normal controls and patients with hypertrophic cardiomyopathy. In the setting of LV pressure overload induced by transaortic constriction (TAC), we observed an increase in Ccdc80 expression in 1 week TAC LVs, compared with sham LVs (5.0 +/- 0.3 arbitrary densitometric units in sham versus 9.6 +/- 0.9 in TAC; n=4 per group). Conclusion: Taken together, our findings identify that the PKGIa substrate Ccdc80 expresses in cardiac myocytes, becomes secreted from CMs, resides in the human heart, and increases in expression in the mouse LV in response to pressure overload. Given the anti-remodeling role of PKGIa, these findings support future studies to understand the in vivo role of Ccdc80 in the cardiovascular system. Future studies will also explore the significance of Ccdc80 secretion from the CM and its potential regulation by PKG.
Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in Mice
Authors: Yujiro Maeoka, Mohammed Z. Ferdaus, Ryan J. Cornelius, Avika Sharma, Xiao-Tong Su, Lauren N. Miller, Joshua A. Robertson, Susan B. Gurley, Chao-Ling Yang, David H. Ellison, James A. McCormick
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Familial hyperkalemic hypertension (FHHt) results from inappropriate activation of the Na + Cl – cotransporter (NCC). Causative mutations have been identified in the gene encoding Cullin3 (CUL3). Cullin3 with the substrate binding adaptor Kelch-like 3 (KLHL3) forms an E3 ubiquitin ligase that mediates degradation of NCC regulatory kinases. The mechanism by which mutant CUL3 causes FHHt is unclear, but lower abundance of CUL3 and KLHL3 proteins and loss of binding to the CUL3 regulator JAB1 have been implicated. Using several mouse models, we found that mutant CUL3 potently induced KLHL3 degradation. Mice heterozygous for CUL3 and KLHL3 displayed an FHHt-like phenotype. JAB1 disruption mimicked the effects of mutant CUL3 expression. Our data show that reduced functional KLHL3 and CUL3 play a central role in FHHt. Background Mutations in the ubiquitin ligase scaffold protein Cullin 3 ( CUL3 ) gene cause the disease familial hyperkalemic hypertension (FHHt). In the kidney, mutant CUL3 ( CUL3-Δ9 ) increases abundance of With-No-Lysine (K) Kinase 4 (WNK4), inappropriately activating sterile 20/SPS-1–related proline/alanine-rich kinase (SPAK), which then phosphorylates and hyperactivates the Na + Cl – cotransporter (NCC). The precise mechanism by which CUL3-Δ9 causes FHHt is unclear. We tested the hypothesis that reduced abundance of CUL3 and of Kelch-like 3 (KLHL3), the CUL3 substrate adaptor for WNK4, is mechanistically important. Because JAB1, an enzyme that inhibits CUL3 activity by removing the ubiquitin-like protein NEDD8, cannot interact with CUL3-Δ9, we also determined whether Jab1 disruption mimicked the effects of CUL3-Δ9 expression. Methods We used an inducible renal tubule-specific system to generate several mouse models expressing CUL3-Δ9 , mice heterozygous for both CUL3 and KLHL3 ( Cul3+/−/Klhl3+/− ), and mice with short-term Jab1 disruption (to avoid renal injury associated with long-term disruption). Results Renal KLHL3 was higher in Cul3−/− mice, but lower in Cul3−/−/Δ9 mice and in the Cul3+/−/Δ9 FHHt model, suggesting KLHL3 is a target for both WT and mutant CUL3 . Cul3+/−/Klhl3+/− mice displayed increased WNK4-SPAK activation and phospho-NCC abundance and an FHHt-like phenotype with increased plasma [K + ] and salt-sensitive blood pressure. Short-term Jab1 disruption in mice lowered the abundance of CUL3 and KLHL3 and increased the abundance of WNK4 and phospho-NCC. Conclusions Jab1−/− mice and Cul3+/−/Klhl3+/− mice recapitulated the effects of CUL3-Δ9 expression on WNK4-SPAK-NCC. Our data suggest degradation of both KLHL3 and CUL3 plays a central mechanistic role in CUL3-Δ9–mediated FHHt.
Long lesions treated using Sr/Y90 source trains, a sub-analysis of RENO: A European surveillance registry with the NovesteTM Beta-CathTM System Antonio Colombo, Goran Stankovic, Patrick Serruys, Thomas Schiele, Eric Eeckhout, Sigmund Silber, Raoul Bonan, Philip Urban. EMO Centro Cuore Columbus, Milan, Italy, Heart center Rotterdam, Rotterdam, The Netherlands
Journal: Journal of the American College of Cardiology (2001)
Fifth Annual Go Red for Women Issue
Authors: Sana M. Al-Khatib, Joseph A. Hill, Biykem Bozkurt
Journal: Circulation (2021)

As the unprecedented challenges of the coronavirus disease 2019 (COV-ID-19) pandemic continue to escalate, we are reminded of the quote by Martin Luther King, Jr: "The true measure of a man is not how he behaves in moments of comfort and convenience but how he stands at times of controversy and challenges." 1 The medical and scientific communities have assertively risen to the challenges brought forward by the pandemic in patient care, teaching, and research.Whereas much of the research submitted to Circulation since the beginning of the pandemic has been related to COVID-19, many investigators have continued to prioritize research on cardiovascular diseases (CVD) in women.When the call for the fifth annual Go Red for Women issue of the journal was posted in the summer of 2020, the response was unparalleled.We received close to 100 submissions that were ably and carefully reviewed and processed, culminating in one of the most impactful and powerful Go Red for Women issues the journal has published to date.It is undeniable that CVD remains the number 1 killer of women around the world.According to the 2020 update of the American Heart Association's Heart Disease and Stroke Statistics, of 121.5 million individuals in the United States with CVD, women account for 60 million (44.7%), with a mortality rate of 48.7% in comparison with a mortality rate of 51.3% in men. 2 Sex disparities in cardiovascular care and participation in clinical trials have also persisted. 3-6Therefore, attempts to improve cardiovascular health for women, and female participation in pivotal clinical trials, as well, are critically important to our fight against CVD in women.The present Go Red for Women issue covers a broad array of topics regarding CVD in women presented as 8 Original Research Articles, 4 Research Letters, 2 State of the Art Reviews, 3 On My Mind papers, and 1 Cardiology News story.The Original Research Articles span a wide spectrum of CVD, including results from the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) evaluating the association between sex and outcomes of ablation of atrial fibrillation; results from the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) evaluating the efficacy and safety of edoxaban in women versus men; and insights from TIMI trials on how sex interrelates with permanent drug discontinuation and study retention in clinical trials.Other topics covered in Original Research Articles involve applying advanced imaging techniques to unveil mechanisms underlying myocardial infarction in the absence of obstructive coronary artery disease in women; sex differences in outcomes among survivors of out-of-hospital cardiac arrest; how recurrent coronary heart disease after a myocardial infarction differs among men and women cared for in the United States; cardiac remodeling during pregnancy in the setting of metabolic syndrome; and
New 2021 USPSTF Lung Cancer Screening Criteria—An Opportunity to Mitigate Racial Disparity
Authors: Jonathan A. Nitz, Cherie P. Erkmen
Journal: JAMA Oncology (2022)

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
Type 2 innate immunity drives distinct neonatal immune profile conducive for heart regeneration
Authors: Francis M. Chen, Joyce KY Tse, Leigang Jin, Chui Yiu Bamboo Chook, Fung Ping Leung, Gary Tse, Connie W. Woo, Aimin Xu, Ajay Chawla, Xiao Yu Tian, Ting-Fung Chan, Wing Tak Wong
Journal: Theranostics (2022)

Aims: Neonatal immunity is functionally immature and skewed towards a TH2-driven, anti-inflammatory profile. This neonatal immunotolerance is partly driven by the type 2 cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Studies on neonatal cardiac regeneration reveal the beneficial role of an anti-inflammatory response in restoring cardiac function after injury. However, the role of an imbalanced immune repertoire observed in neonates on tissue regeneration is poorly understood; specifically, whether IL-4 and IL-13 actively modulate neonatal immunity during cardiac injury. Methods and results: Neonatal mice lacking IL-4 and IL-13 (DKOs) examined at 2 days after birth exhibited reduced anti-inflammatory immune populations with basal cardiac immune populations like adult mice. Examination of neonates lacking IL-4 and IL-13 at 2 days post cardiac ischemic injury, induced on the second day after birth, showed impaired cardiac function compared to their control counterparts. Treatment with either IL-4 or IL-13 cytokine during injury restored both cardiac function and immune population profiles in knockout mice. Examination of IL-4/IL-13 downstream pathways revealed the role of STAT6 in mediating the regenerative response in neonatal hearts. As IL-4/IL-13 drives polarization of alternatively activated macrophages, we also examined the role of IL-4/IL-13 signaling within the myeloid compartment during neonatal cardiac regeneration. Injury of IL-4Rα myeloid specific knockout neonates 2 days after birth revealed that loss of IL-4/IL-13 signaling in macrophages alone was sufficient to impair cardiac regeneration. Conclusions: Our results confirm that the TH2 cytokines: IL-4 and IL-13, which skews neonatal immunity to a TH2 profile, are necessary for maintaining and mediating an anti-inflammatory response in the neonatal heart, in part through the activation of alternatively activated macrophages, thereby permitting a niche conducive for regeneration.
Precision Targeting of Mutant PI3Kα in Cancer by Selective Degradation
Authors: Bart Vanhaesebroeck, John E. Burke, Ralitsa R. Madsen
Journal: Cancer Discovery (2022)

Abstract Summary: PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently genetically activated kinases in solid tumors. In this issue of Cancer Discovery, Song and colleagues report that the related PI3Kα inhibitors taselisib and inavolisib trigger receptor tyrosine kinase (RTK)–dependent degradation of the mutant p110α protein in breast cancer cells that are positive for HER2 RTK, limiting feedback-mediated drug resistance and potentially widening the therapeutic index of PI3Kα inhibition. See related article by Song et al., p. 204.
Update: Outbreak of Severe Acute Respiratory Syndrome—Worldwide, 2003
Journal: JAMA (2003)

CDC and the World Health Qrganization (WHO) are continuing to investigate the multicountry outbreak of unexplained atypical pneumonia referred to as severe acute respiratory syndrome (SARS). Pending development of confirmatory laboratory testing capacity, CDC's interim suspected SARS case definition is based on clinical criteria and epidemiologic linkage to other SARS cases or areas with community transmission of SARS. This case definition will be updated periodically as new information becomes available. Epidemiologic and laboratory investigations of SARS are ongoing. As of April 2, 2003, a total of 2,223 suspected and/or probable SARS cases have been reported to WHO from 16 countries, including the United States. The reported SARS cases include 78 deaths (case-fatality proportion: 3.5%). This report summarizes SARS cases among U.S. residents and surveillance and prevention activities in the United States.
Prostacyclin synthase gene transfer inhibits neointimal formation in rat balloon injured arteries: The possible involvement of cyclooxygenase-2(COX-2) Michiharu Yamada, Yasushi Numaguchi, Mitsunori Harada, Hideo Matsui, Kenji Okumura. Nagoya University School of Medicine, Nagoya, Japan
Journal: Journal of the American College of Cardiology (2001)
Study of the behavior of autonomic nervous system in patients with vasovagal syncope: Is there any difference between young and elderly patients? George E. Kochiadakis, Nikos E. Igoumenidis, Maria E. Marketou, Emmanuel M. Kanoupakis, Emmanuel N. Simantirakis, Stavros I. Chrysostomakis, Michael I. Hamilos, Panos E. Vardas. Cardiology Dept., Heraklion University Hospital, Heraklion, Greece
Journal: Journal of the American College of Cardiology (2001)
Die Chemie der Nahrungs- und Genussmittel:
Journal: JAMA (1927)

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
ANTIVACCINATION DELUSION.
Journal: JAMA (1899)

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
Text-Book of Physiology, Normal and Pathological, for Students and Practitioners of Medicine.
Journal: JAMA (1905)

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
THE WORM'S TURN
Journal: JAMA (1967)

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