tbuckley/cabot-search huggingface dataset:
LEAP-014: An open-label, randomized, phase 3 study of first-line lenvatinib plus pembrolizumab plus chemotherapy in esophageal squamous cell carcinoma.
Authors: Jong-Mu Sun, Peter C. Enzinger, Antoine Adenis, Manish A. Shah, Ken Kato, Jaafar Bennouna, Toshihiko Doi, Natalyn Nicole Hawk, Li Yu, Sukrut Shah, Pooja Bhagia, Lin Shen
Journal: Journal of Clinical Oncology (2022)

TPS367 Background: Recent data from the KEYNOTE-590 study demonstrated the superiority of pembrolizumab plus chemotherapy compared with chemotherapy as first-line treatment for unresectable locally advanced recurrent or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, or advanced/metastatic Siewert type 1 adenocarcinoma of the gastroesophageal junction. Prior data also suggest promising antitumor activity of lenvatinib plus pembrolizumab in advanced solid tumors. LEAP-014 (NCT04949256) is a randomized, 2-part, open-label, phase 3 study that will evaluate the efficacy and safety of first-line lenvatinib plus pembrolizumab plus chemotherapy versus pembrolizumab plus chemotherapy in patients with metastatic esophageal squamous cell carcinoma (ESCC). Methods: Key eligibility criteria include metastatic ESCC, measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and Eastern Cooperative Oncology Group performance status ≤1. In part 1 (safety run-in), ̃6 patients will be treated for induction with intravenous (IV) pembrolizumab 400 mg every 6 weeks (Q6W) for 2 cycles plus oral lenvatinib 8 mg daily (QD) plus IV 5-fluorouracil (FU; 4000 mg/m 2 on days 1-5) plus IV cisplatin (80 mg/m 2 ) (FP) for 4 cycles and treated for consolidation with pembrolizumab 400 mg Q6W for ≤16 doses plus lenvatinib 20 mg QD; patients will be closely monitored for 21 days after the first dose of study intervention for dose-limiting toxicities. Approximately 850 patients will be randomly assigned 1:1 to induction with pembrolizumab plus lenvatinib plus chemotherapy (FP or mFOLFOX6 [Q2W for 6 cycles {IV oxaliplatin 85 mg/m 2 plus bolus IV 5-FU 400 mg/m 2 plus continuous IV 5-FU 2400 mg/m 2 plus IV leucovorin 400 mg/m 2 or IV levoleucovorin 200 mg/m 2 }]) followed by consolidation with pembrolizumab plus lenvatinib (arm 1) or pembrolizumab plus chemotherapy (FP or mFOLFOX6; arm 2). Randomization will be stratified by PD-L1 combined positive score (CPS; ≥10 vs &lt; 10), region (East Asia vs North America and Western Europe vs rest of world), and chemotherapy backbone (FP vs mFOLFOX6). Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. Tumor imaging assessment will be performed Q6W for ≤1 year and Q9W thereafter. In part 1, the primary end point is safety and tolerability. In part 2, the dual primary end points are overall survival and progression-free survival (per RECIST v1.1 assessed by blinded independent central review [BICR]); secondary end points include objective response rate and duration of response (per RECIST v1.1 assessed by BICR) and safety and tolerability. Clinical trial information: NCT04949256.
HMCES safeguards genome integrity and long-term self-renewal of hematopoietic stem cells during stress responses
Authors: Yinghao Pan, Hongna Zuo, Fei Wen, Fei Huang, Yezhang Zhu, Lanrui Cao, Qian-Qian Sha, Yang Li, Huiying Zhang, Miao Shi, Chengzhen Liang, Jun Huang, Lin Zou, Heng-Yu Fan, Zhenyu Ju, Hu Wang, Li Shen
Journal: Leukemia (2022)
О творческом пути профессора Тамары Николаевны Христич
Authors: . .
Journal: GASTROENTEROLOGY (2013)

Тамара Николаевна Христич родилась 22 апреля 1943 года в пгт Шуроабад Кулябского района Таджикской ССР в семье военнослужащего, поэтому детство прошло в переездах (Молдавия, Туркмения, Таджикистан, Украина) и школьные годы до 1954 года проходили в разных школах разных республик. В 1954 году семья поселилась в Северной Буковине, г. Черновцы (Украинская ССР).
Nivolumab Treatment Beyond Investigator-Assessed Progression: Extended Follow-up in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 CheckMate 205 Study
Authors: Jonathon B. Cohen, John Kuruvilla, Andreas Engert, Stephen M. Ansell, Anas Younes, Hun Ju Lee, Marek Trněný, Kerry J Savage, Radhakrishnan Ramchandren, Graham P. Collins, Pier Luigi Zinzani, Jan Paul De Boer, Margaret A. Shipp, Armando Santoro, John M. Timmerman, Mariana Sacchi, Oumar Sy, Philippe Armand
Journal: Blood (2018)
A Predictive Model for Aggressive Non-Hodgkin's Lymphoma
Journal: New England Journal of Medicine (1993)

Although many patients with intermediate-grade or high-grade (aggressive) non-Hodgkin's lymphoma are cured by combination chemotherapy, the remainder are not cured and ultimately die of their disease. The Ann Arbor classification, used to determine the stage of this disease, does not consistently distinguish between patients with different long-term prognoses. This project was undertaken to develop a model for predicting outcome in patients with aggressive non-Hodgkin's lymphoma on the basis of the patients' clinical characteristics before treatment.
Magnetic resonance imaging indicates remodeling of the right ventricle early after pulmonary thromboendarterectomy Mario Togni, Anthony N. DeMaria, Stuart W. Jamieson, Peter F. Fedullo, Divya Bolar, Paul J. Friedman. University of California, Division of Cardiology, San Diego, University of California, Department of Radiology, San Diego
Journal: Journal of the American College of Cardiology (2001)
Abstract 469: Targeting Beta Adrenergic Receptor Resensitization Aids in Preservation of Receptor Function
Authors: Elizabeth E Martellli, Yu Sun, John George, Maradumane L Mohan, Randall Starling, Christine Moravec, Sathyamangla V Naga Prasad
Journal: Circulation Research (2017)

Beta adrenergic receptor (βAR) down-regulation and desensitization are hallmarks of heart failure. Traditionally, it has been considered that increased desensitization mechanisms underlie βAR dysfunction in heart failure but it is not known whether resensitization of βARs is altered and is an integral contributor to heart failure. We have previously shown that resensitization is regulated by inhibition of PP2A by I2PP2A via PI3Kγ (Vasudevan et. al., 2011), the underlying mechanisms of I2PP2A binding to PP2A are not well understood. We used PyMOL software to find the binding interaction between PP2A and I2PP2A. Based on in silico predictions, we generated a mutant PP2A that when expressed would compete out I2PP2A and inhibit I2PP2A from binding to endogenous PP2A. Expression of PP2A mutant in β2AR expressing cells showed preservation of β2AR function following stimulation as measured by reduced β2AR phosphorylation, increased cAMP generation and increased phosphatase function. We also generated a small molecule from our in silico predictions that could target the interface of I2PP2A and PP2A binding to find that disruption of the PP2A/I2PP2A interaction underlies receptor function. We will use this small molecule to look at preservation of βAR function and amelioration of cardiac function. To test whether resensitization is altered in heart failure we used plasma membrane and endosomal fractions from non-failing and paired pre- and post-LVAD samples to show PI3K activity, PP2A activity, β2AR phosphorylation and adenylyl cyclase activity as a measure of recovery in βAR function. Our studies showed that endosomal fractions from human heart failure samples had elevated PI3K activity associated with reduced PP2A activity supporting the idea that βAR resensitization is inhibited in human heart failure samples. Since human heart failure samples have inhibited resensitization we tested the underlying mechanisms regulating βAR resensitization. Thus ongoing studies suggest that targeting the resensitization of βAR could provide beneficial cardiac remodeling in conditions of chronic mechanical overload and will be further discussed.
Macular Degeneration
Authors: Harry Eggers
Journal: JAMA (1961)

<h3>To the Editor:—</h3> May I offer a comment on the question appearing on page 171 of the current July 15th issue ofThe Journalregarding the cause of macular degeneration in an apparently normal child? The commentator apparently overlooked the possibility that this might be secondary to infection from<i>Giardia lamblia</i>. If this were the case, improvement or arrest probably would follow from a course of quinacrine hydrochloride, which is specific for this protozoan flagellate. A case of giardiasis with macular lesions in a 9-year-old child was reported recently (<i>Arch Ophthal</i><b>65</b>:775 [June] 1961). At first this was regarded as a form of macular degeneration.
Abstract 121: Development of Enzyme Replacement Therapy in Mammalian Models of Barth Syndrome
Authors: Ana Dinca, Wei-Ming Chien, Michael Chin
Journal: Circulation Research (2017)

Barth Syndrome (BTHS) is caused by a single gene mutation in the mitochondrial transacylase, tafazzin (TAZ), which results in impaired lipid metabolism leading to dysfunction in highly energetic tissues such as the heart and skeletal muscle. TAZ remodels the signature mitochondrial phospholipid, cardiolipin (CL), which is responsible for providing support to the electron transport chain. BTHS patients suffer from growth deficiencies, cardiomyopathy, hypotonia and neutropenia. Currently, treatment for patients with BTHS is supportive, seeking to ameliorate rather than prevent heart problems, skeletal muscle problems and recurring infections. Protein therapy, on the other hand, might treat and even prevent cardiac, skeletal muscle as well as infection-related morbidities. We designed a recombinant TAZ protein containing a cell penetrating peptide in its C-terminus, which enables the recombinant TAZ to penetrate cells and then treated TAZ-deficient cells with it. We tested the permeability of the recombinant protein by direct delivery to H9C2 cardiomyoblasts and found that the protein is successfully taken up by the cells. We have generated a CRISPR-mediated TAZ knock out cardiomyoblast cell line and we found that TAZ knock out cells show a decrease in oxygen consumption as compared to the wild type cells; this is consistent with data from BTHS patient-derived cells. We are using this cell line to assess the enzymatic activity of the delivered protein by conducting mitochondrial respiration measurements. We have also acquired a mouse model of BTHS and are testing the recombinant TAZ in vivo. Preliminary data shows an augmentation in oxygen consumption following treatment with TAZ. These results indicate that the protein is able to reach the mitochondria, where it is enzymatically active and able to enhance respiration. As the protein is able to rescue respiration in cells in which tafazzin was absent, this suggests that our approach should not only be able to prevent onset of symptoms, but also rescue the phenotype in already affected tissues.
Neurofibromatous Dermal Nevus
Journal: JAMA (1963)

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 JOURNAL AND ITS FRIENDS.
Journal: JAMA (1898)

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
Brain Lesions in Scuba Divers
Journal: Annals of Internal Medicine (2001)

Summaries for Patients2 January 2001Brain Lesions in Scuba DiversSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-1-200101020-00005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail What is the problem and what is known about it so far?A known risk of scuba diving is decompression illness, commonly known as “the bends.” The brain can be injured in decompression illness because small gas bubbles that form in the blood as a diver rises to the surface can block circulation to the brain. The symptoms of decompression illness include skin changes, joint pain, confusion, and other transient or lasting neurologic symptoms. Brain imaging tests in divers who have previously had decompression illness show areas that have been injured as a result of getting too little oxygen (ischemic ... Author, Article, and Disclosure InformationAffiliations: The summary below is from the full report titled “Relation between Directly Detected Patent Foramen Ovale and Ischemic Brain Lesions in Sport Divers.” It is in the 2 January 2001 issue of Annals of Internal Medicine (volume 134, pages 21-24). The authors are M Schwerzmann, C Seiler, E Lipp, R Guzman, KO Lövblad, M Kraus, and N Kucher.Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRelation between Directly Detected Patent Foramen Ovale and Ischemic Brain Lesions in Sport Divers Markus Schwerzmann , Christian Seiler , Ernst Lipp , Raphael Guzman , Karl O. Lövblad , Martin Kraus , and Nils Kucher Metrics 2 January 2001Volume 134, Issue 1Page: I-67KeywordsArthralgiaBloodBrainHeartLesionsMagnetic resonance imagingNeuroimagingOxygenSportsUltrasound imaging ePublished: 2 January 2001 Issue Published: 2 January 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans
Authors: Sumedha Gunewardena, Ian Huck, Chad Walesky, Dakota Robarts, Steven Weinman, Udayan Apte
Journal: Hepatology (2022)

Abstract Background and Aims Hepatocyte nuclear factor 4 alpha (HNF4α) is indispensable for hepatocyte differentiation and critical for maintaining liver health. Here, we demonstrate that loss of HNF4α activity is a crucial step in the pathogenesis of chronic liver diseases (CLDs) that lead to development of HCC. Approach and Results We developed an HNF4α target gene signature, which can accurately determine HNF4α activity, and performed an exhaustive in silico analysis using hierarchical and K‐means clustering, survival, and rank‐order analysis of 30 independent data sets containing over 3500 individual samples. The association of changes in HNF4α activity to CLD progression of various etiologies, including HCV‐ and HBV‐induced liver cirrhosis (LC), NAFLD/NASH, and HCC, was determined. Results revealed a step‐wise reduction in HNF4α activity with each progressive stage of pathogenesis. Cluster analysis of LC gene expression data sets using the HNF4α signature showed that loss of HNF4α activity was associated with progression of Child‐Pugh class, faster decompensation, incidence of HCC, and lower survival with and without HCC. A moderate decrease in HNF4α activity was observed in NAFLD from normal liver, but a further significant decline was observed in patients from NAFLD to NASH. In HCC, loss of HNF4α activity was associated with advanced disease, increased inflammatory changes, portal vein thrombosis, and substantially lower survival. Conclusions In conclusion, these data indicate that loss of HNF4α function is a common event in the pathogenesis of CLDs leading to HCC and is important from both diagnostic and therapeutic standpoints.
Abstract 187: c-Kit Biology Revealed by Two Transgenic Reporter Models.
Authors: Natalie A Gude, Fareheh Firouzi, Kristine Nguyen, Christina Payne, Veronica Sacchi, Roberto Alvarez, Mark A Sussman
Journal: Circulation Research (2017)

Background: The biological significance of c-Kit as a marker of cardiac stem cells, and role(s) of c-Kit+ cells in myocardial development or in response to pathologic injury remain unresolved due to varied findings among investigators and experimental model systems. Alternative experimental models and approaches are needed to achieve a broader perspective of cardiac c-Kit biology that contextualizes discrepant published observations. Objectives: Tracking c-Kit expression using transgenesis overcomes limitations inherent to knock-in reporter models. Two novel, inducible transgenic c-Kit reporter models are presented in this study to further elaborate on myocardial c-Kit biology. Methods: A previously characterized mouse c-Kit promoter segment was engineered to generate a transgenic mouse in which rtTA transactivator is expressed in c-Kit+ cells (c-KitrtTA). c-KitrtTA crossed to Tet-Responsive-Element(TRE)-Histone2B-EGFP or TRE-Cre lines produces the CKH2B and CKCre double transgenic lines, which express doxycycline-inducible H2BEGFP or Cre proteins in c-Kit+ cells. The CKmTmG triple transgenic mouse, arising from CKCre crossed to the ROSAmTmG reporter line, utilizes doxycycline induced recombination to tag c-Kit+ cells irreversibly with membrane bound EGFP. Endogenous c-Kit and transgenic reporter expression was assessed in adult cardiac myocyte and nonmyocyte cells from these mice under resting and cellular stress conditions using immunohistochemistry and flow cytometry. Results: Coincidence of c-Kit and EGFP is observed in approximately 75% of freshly isolated nonmyocyte cells as detected by flow cytometry. A subpopulation of cardiomyocytes express H2BEGFP or mEGFP in the uninjured, doxycycline treated adult heart. H2BEGFP and c-Kit expression increase in myocytes in response to isoproterenol-induced pathologic stress in vivo and in vitro. Conclusion: These c-Kit transgenic reporter models provide sensitive, specific, inducible and persistent tracking of c-Kit promoter activation. Results presented here reveal an unexpected role for c-Kit expression in adult cardiomyocytes. Future studies will use both models to investigate c-Kit expression in all cell types during cardiac formation and repair.
Pure-tone Audiometer: Correction
Journal: BMJ (1944)

America for the Referee Board of the Council of Pharmacy and Chemistry of the American Medical Association.They found that large doses (0.75 to 1.5 g., or 12 to 20 gr., daily) occasionally pro- duced hyperacidity and increased intestinal putrefaction.There were no such effects with small doses.It can, therefore, be safely used in ordinary amounts by patients with peptic ulcer.An anti- pyretic action is not described, but iu large dose-e.g., 10 gr.(20 tablets)-it might well have one, judging by its composition.
X versus XELOX versus PF in definitive concurrent chemoradiotherapy (DCRT) for local-advanced squamous esophageal cancer (ESCC): 2021 update from a multicenter, open-label, randomized III trial, CRTCOESC trial.
Authors: Ruinuo Jia, Tanyou Shan, Lixin Wan, Anping Zheng, Shuang Hui, Zhiqiao Xu, Feng Wang, Guobao Zheng, Ping Lu, Guifang Zhang, Yingjuan Zheng, Yanhui Cui, Xiaoyong Luo, Weiguo Zhang, Wanying Li, Ruonan Li, Fuyou Zhou, Shegan Gao
Journal: Journal of Clinical Oncology (2022)

274 Background: PF (5-fluorouracil plus cisplatin) is the standard regimen for local advanced ESCC with DCRT. CRTCOESC aims to evaluate the effect and safety of X (capecitabine) regimen versus XELOX (capecitabine plus oxaliplatin) and PF in Chinese local advanced ESCC with DCRT by randomized, open-label, multicenter designed. Methods: Patients with ESCC (T2-4N0-2M0) were randomized to 3 groups as X (capecitabine 625mg/m 2 , bid d1-5, 6 weeks), XELOX (oxaliplatin: 65mg/m 2 , d1, 8, 22, 29; capecitabine: 625mg/m 2 , bid d1-5; 6 weeks), or PF (cisplatin: 75mg/m 2 d1, 29, 5-Fu: 750mg/m 2 CIV24h d1-4, d29-32), Intensity Modulated Radiation Therapy (IMRT) was delivered by 50Gy/2Gy currently. In addition, quadratic randomize were done within all groups to decide whether 2 cycles chemotherapy adding or not after DCRT. 2-year OS and Grade 3-5 AEs were the primary endpoints, 2-year PFS and short-term efficacy (STE) as rates of CR and ORR (CR+PR) (confirmed by gastroscopy biopsy at 16 weeks) were the secondary endpoints. Results: 249 pts successfully were accrued from 13 centers during 2014.10-2020.04. All pts were finished DCRT and evaluated STE at 16 weeks. 229 pts were followed up for 2- years. There were no differences between 3 groups on patients’ baseline characters including age, gender, ECGO score, clinical stage, pathology grade and smoking. In X, XELOX and PF groups, the 2-year OS were 73.8% (59/80), 74.3% (55/47) and 73.3% (55/75) ( P = 0.991), the median OS were 41.43 (3.29), 53.3 (7.686) and 44.6 (4.946) (months, P = 0.896); the incidences of AEs (grade 3-5) were 24.1% (20/83), 31.8% (28/88) and 43.6% (34/78) ( P = 0.03); the 2-year PFS were 63.7% (51/80), 60.8% (45/74) and 61.3% (46/75) ( P = 0.922), the median PFS were 38.467 (2.965), 39.5 (7.619) and 35.8 (4.435) (months, P = 0.87); the CR rate were 36.1% (30/83), 36.4% (32/88), and 35.9% (28/78) ( P = 0.998), and the ORR were 73.5%, 79.5%, and 75.6% ( P = 0.64), respectively. There were no differences on OS, PFS and rates of CR and ORR between 3 groups but the incidence of AEs in X group was the lowest significantly. Subgroup analysis results shown adding 2 cycles chemotherapy after CRT had both OS and PFS advantages but lacked statistically significance. Conclusions: Compared with PF, DCRT with X or XELOX shown lower incidence of AEs and similar OS, PFS and STE. X regimen carried out the lowest AEs incidence. Adding 2 cycles chemotherapy after DCRT seemly had advantages on OS and PFS. Clinical trial information: NCT02025036.