tbuckley/cabot-search huggingface dataset:
Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review and Meta-Analysis
Authors: Aghilès Hamroun, Rémi Lenain, Jean Joel Bigna, Elodie Speyer, Linh Bui, Paul Chamley, Nicolas Pottier, Christelle Cauffiez, Edmone Dewaeles, Xavier Dhalluin, Arnaud Scherpereel, Marc Hazzan, Mehdi Maanaoui, François Glowacki
Journal: Drugs (2019)
IMMUNIZATION AGAINST TUBERCULOSIS.
Journal: JAMA (1903)

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
Pulmonary Embolism Hospitalization, Readmission, and Mortality Rates in US Older Adults, 1999-2015
Authors: Behnood Bikdeli, Yun Wang, David Jimenez, Sahil A. Parikh, Manuel Monreal, Samuel Z. Goldhaber, Harlan M. Krumholz
Journal: JAMA (2019)

This study uses Medicare billing codes to characterize trends in readmission and mortality rates for Medicare fee-for-service beneficiaries with pulmonary embolism (PE) between 1999 and 2015 to assess changes accompanying recent diagnostic and therapeutic changes in management of the disease.
Predictors of leptomeningeal disease following hypofractionated stereotactic radiotherapy for intact and resected brain metastases
Authors: Timothy K Nguyen, Arjun Sahgal, Jay Detsky, Eshetu G Atenafu, Sten Myrehaug, Chia-Lin Tseng, Zain Husain, Chris Heyn, Pejman Maralani, Mark Ruschin, James Perry, Hany Soliman
Journal: Neuro-Oncology (2019)

Abstract Background The objective was to evaluate the risk and predictors of developing leptomeningeal disease (LMD) in patients with brain metastases treated with 5-fraction hypofractionated stereotactic radiotherapy (HSRT). Methods Patients treated with HSRT for intact brain metastases and/or surgical cavities were reviewed from a prospectively maintained database. Radiographic patterns of LMD were classified as focal classical, diffuse classical, focal nodular, and diffuse nodular. Results HSRT was delivered, most commonly 30 Gy in 5 fractions, to 320 intracranial lesions (57% intact and 43% surgical cavities) in 235 patients. The median follow-up was 13.4 months (range, 0.8 to 60 mo). LMD developed in 19% of patients with a 1-year LMD rate of 12%. From the diagnosis of LMD, the median overall survival (OS) was 3.8 months (range, 2–20.8 mo). The most common LMD pattern was diffuse nodular (44%). No difference in OS was observed between LMD patterns (P = 0.203). Multivariable analysis identified surgical cavities at significantly higher risk of LMD compared with intact lesions (odds ratio [OR] = 2.30, 95% CI: 1.24, 4.29, P = 0.008). For cavities, radiosensitive tumors (OR = 2.35, 95% CI: 1.04, 5.35, P = 0.041) predicted for LMD, while, for intact metastases, patients receiving treatment with targeted agents or immunotherapy (TA/I) were at lower risk (OR = 0.178, 95% CI: 0.04, 0.79, P = 0.023). Conclusions Patients who had a brain metastasis resected were at an increased risk of LMD. OS was poor despite treatment of LMD, and no differences in OS based on the pattern of LMD was observed. Treatment with TA/I was observed to be protective against LMD and requires further study.
Coversin, a Novel C5 Complement Inhibitor, Is Safe and Effective in the Treatment of PNH: Results of a Phase II Clinical Trial
Authors: Anita Hill, Wynne Weston-Davies, Miles Nunn, Tadeusz Robak, Jerzy Windyga, Andrzej Hellmann, Austin G. Kulasekararaj, Agniezka Piekarska, Anna Szmigielska-Kaplon, Morag Griffin, Talha Munir
Journal: Blood (2017)
Cooperation of oncolytic virotherapy with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9
Authors: Hans-Georg Wirsching, Sonali Arora, Huajia Zhang, Frank Szulzewsky, Patrick J Cimino, Christophe Quéva, A McGarry Houghton, Joseph C Glorioso, Michael Weller, Eric C Holland
Journal: Neuro-Oncology (2019)
Abstract #LB-84: Secretome analyses from staged pancreatic cancer cell lines
Authors: Rowena Chu, Steven Miller, David Wells, Chris Sakoda, Lianji Jin, Jason Bush
Journal: Cancer Research (2009)

Pancreatic ductal adenocarcinoma has the lowest 5-year survival of any cancer; its aggressive nature and late onset of physical symptoms lead to poor prognoses. Pancreatic cancer primarily occurs in the exocrine portion of the organ, with fewer occurrences in the endocrine section. Approximately 95% of cancerous exocrine tumors are derived from ductal cells, while a smaller fraction of tumors are from acinar cells. Recognition of biomarkers is clearly an imperative undertaking for the disease. To tackle this problem, we are attempting to evaluate the secreted protein profile of pancreatic cancer cell lines derived from different stages. Critical to the success of this workflow is the derivation of cells that are sustainable without overt morphological changes in peptide- and protein-free media conditions or dramatic necrosis over a 72 hr profile. We have successfully adapted ten human pancreatic cancer cell lines into low serum environments and pursue collection of conditioned media by a combination of ultracentrifugation, molecular weight cutoff, protein precipitation, gel-based separation, and tryptic digestion followed by MALDI-ToF-MS protein identification. Preliminary data suggested significant cellular autolysis that liberated cytosolic proteins such as beta-actin. Therefore, to minimize cytosolic contamination, cell lines were subsequently cultured from low-serum conditions to synthetic basement membranes in a serum-free media to phenocopy the ductal environment typical for these cells. Consistent with cancer progression models and increased secretory function, earlier-stage pancreatic cancer cell lines showed generally lower protein secretion while later stage cell lines showed generally increased secretion. A catalog of proteins is being compiled in ProteinScape (Bruker Daltonics) and validated biochemically including positive identifications for Glutathione S-Transferase pi (GSTP1), Galectin-3 (GAL3), and Palladin (PALLD)_three proteins that have been correlated with tumor secretions from prostate, breast, and pancreatic cancer, respectively. Taken together, our reproducible workflow demonstrates the utility of assessing the secretome fraction from cultured cancer cells.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-84.
The Law and Ethics of Fetal Burial Requirements for Reproductive Health Care
Authors: Dov Fox, I. Glenn Cohen, Eli Y. Adashi
Journal: JAMA (2019)

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
THE METABOLISM OF ADRENALINE
Authors: Z.M. BACQ
Journal: Pharmacological Reviews (1949)

The statement formulated in 1905 by Elliott (5) that adrenalin disappears in the tissues which it excites is unquestionable. Review of the literature shows 1) that adrenaline may be excreted unchanged in small amounts by the kidneys and stored in the tissues and red blood cells; 2) that its deamination by amineoxidase in the body is unlikely; 3) that an important fraction is sulfoconjugated; 4) that another important fraction is simultaneously oxidized to indole substance; 5) that adrenochrome and its derivatives have important biochemical and physiological properties, entirely different from those of adrenaline, and deserve further study.
Push Hard, Push Fast, Do Not Stop—Optimal Chest Compression Rate and Depth
Authors: David C. Cone
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Novartis delayed notifying about gene therapy data manipulation until after approval, FDA says
Authors: Owen Dyer
Journal: BMJ (2019)

The US Food and Drug Administration has strongly criticised the Novartis subsidiary AveXis for failing to immediately pass on its discovery that data had been manipulated in the early stages of testing Zolgensma (onasemnogene abeparvovec-xioi), a new gene therapy for spinal muscular atrophy, which at $2.1m (£1.7m; €1.9m) a dose is the most expensive drug in the world.

“AveXis became aware of the issue of the data manipulation that created inaccuracies in their biologics licence application before the FDA approved the product, yet did not inform the FDA until after the product was approved,” said Peter Marks, director of the FDA’s biologics division, …
GMC appeals against three suspension decisions it says were too lenient
Authors: Clare Dyer
Journal: BMJ (2019)

The General Medical Council is to mount appeals to the High Court against three decisions by medical practitioners tribunals that the regulator believes were too lenient to the doctors involved.

In all three cases, the GMC argued at the hearing, the doctor should have been struck off the medical register, but the tribunal decided to suspend each instead.

The cases being appealed are those of Robert Walton, a GP academic, Asef Zafar, a GP who wrote reports for accident cases, and Muhammad Saqib Saeed, who was a trainee neurologist.

The appeals will be the first to be brought by the GMC since the Court of Appeal ruled in August 2018 that the High Court, which struck the trainee paediatrician Hadiza Bawa-Garba off the medical …
SEVINA-V composed of pegylated liposomal anti-eIF3c shRNA and vinorelbine inhibits oncogenic protein translational initiation,and oncogene addiction inducing type I, II PCD in HRBC.
Authors: John Giannios, Emmanuel Michailakis, Esmeralda Seraj, Nick Alexandropulos
Journal: Cancer Research (2008)

2819  Introduction: eIF3c is required for the initiation of protein translation,and directly interacts with mTOR activating eIF4e,which is overexpressed in advanced hormone refractory breast cancer.mTOR activates the PI3K/AKT signal transduction pathway,which mediates cell proliferation through activation of growth and survival factors.Furthermore,bcl-2 overexpression inhibits apoptosis causing oncogene addiction and chemoresistance.  Methods: We developed xenograft animal models from taxane chemoresistant hormone refractory breast cancer (HRBC) overexpressing eIF3c,4EBP1,and bcl-2.We formulated pegylated liposomal anti-eIF3c shRNA-vinorelbine (SEVINA-V) under pattent.Pegylation circumvented RES elimination.The human HRBC xenograft animal models were treated with SEVINA-V.  Results: Post-treatment,triggering the RNAi pathway through the expression of small hairpin RNA (shRNA) molecules has efficiently silenced the RNA helicase activity of eIF3c disabling cellular cap-dept scanning/initiation.There was subsequent inhibition of PI3K/AKT/mTOR pathway blocking binding of IGFR,PDGFR,EGFR,and HER family receptors in the tumor cell membrane.Inhibition of mTOR prevented downstream activation of mRNA translation,and blocked ribosome biogenesis inhibiting S6K1 and 4E-BPI, which led to inhibition of ribosomal protein,elongation factors,and ODC/cyclin D1,respectively.Thus,4E-BPI-which was induced by taxanes causing chemoresistance-was inhibited.There was upregulation of p53 and cyclin/CDK2-p27 inhibiting CDK1/2,and cyclin D1 activity.Signal transduction initiated by VEGF was inhibited,and translation of c-myc and anti-apoptotic FLIPs was blocked.Ras/Raf/Ral pathway was blocked.Vinorelbine phosphorylated bcl-2,leading to its inactivation,and subsequent circumvention of oncogene addiction.Also,vinorelbine blocked cell cycle at G2/M.Transmission electron microscopy exhibited PCD type I,II and III leading to a bystander killing effect.  Conclusion: With administration of SEVINA-V,we have achieved oncogene transcriptional intervention in HRBC resistant to taxanes via protein translational inhibition of eIF3c downstream of mTOR dependent pathways,which led to apoptosis in synergy with the chemotherapeutic agent vinorelbine,and circumvented oncogene addiction.
Stem cell-based bone and dental regeneration: a view of microenvironmental modulation
Authors: Chenxi Zheng, Ji Chen, Shiyu Liu, Yan Jin
Journal: International Journal of Oral Science (2019)

In modern medicine, bone and dental loss and defects are common and widespread morbidities, for which regenerative therapy has shown great promise. Mesenchymal stem cells, obtained from various sources and playing an essential role in organ development and postnatal repair, have exhibited enormous potential for regenerating bone and dental tissue. Currently, mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering. Nevertheless, the efficacy of MSC-based regeneration is not always fulfilled, especially in diseased microenvironments. Specifically, the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs, both as donors and recipients. Accordingly, approaches targeting a diseased microenvironment have been established, including improving the diseased niche to restore endogenous MSCs, enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies. Moreover, the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy. In this review, we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment, emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.
Response to Comment on “A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands”
Authors: Pouya Faridi, Chen Li, Sri H. Ramarathinam, Patricia T. Illing, Nicole A. Mifsud, Rochelle Ayala, Jiangning Song, Linden J. Gearing, Nathan P. Croft, Anthony W. Purcell
Journal: Science Immunology (2019)

This is our response to the Technical Comment by Rolfs et al. where we point out errors in their reanalysis of our data.
Comprehensive genetic mutation analysis of human gastric adenocarcinomas.
Authors: Jinfei Chen, Zhi Xu, Xinying Huo, Dongying Gu, Meilin Wang, Cuiju Tang, Hua Ye, Zhengdong Zhang, Si-Yi Chen
Journal: Journal of Clinical Oncology (2013)

4106 Background: Gastric cancer is the one of the major cause of cancer-related death, especially in Asia. Gastric adenocarcinoma, the most common type of gastric cancer, is heterogeneous and its incidence and cause varies widely with geographical regions, gender, ethnicity, and diet. Since unique mutations have been observed in individual human cancer sample, identification and characterization of the molecular alterations underlying individual gastric adenocarcinoma is a critical step for developing more effective, personalized therapies. Until recently, identifying genetic mutations in an individual basis by DNA sequencing remains a daunting task. The recent advance of new next-generation DNA sequencing technologies, such as the semiconductor-based Ion Torrent sequencing platform, makes DNA sequencing cheaper, faster and more reliable. Methods: In this study, we aim to identify genetic mutations in the genes, which are targeted by drugs in the clinical use or under development, in individual human adenocarcinoma sample by using Ion Torrent sequencing. We sequenced 739 loci from 46 cancer-related genes in 242 human gastric adenocarcinoma samples using the Ion Torrent Ampliseq Cancer Panel. Results: The sequencing analysis revealed frequent mutations in MLH1 (8.3%), MET (11.2%), KIT (21.5%), and PIK3CA (40.5%) genes in the human gastric adenocarcinomic samples. Many mutations that are not previously reported in gastric adenocarcinomas were also identified. Moreover, distinctive patterns and the combination of mutations in various sets of genes, including HER2, EGFR, MET, FGFR, PI3K/MTOR, MLH1, MET, KIT, PIK3CA, and P53, were also identified in these gastric adenocarcinoma samples. Conclusions: Thus, this study indicates the necessity of sequencing individual human adenocarcinoma in order to match the use of personalized single targeted drugs or two or more targeted drugs in combination against individual adenocarcinoma-specific mutations.
Phosphorylation of HSF1 by PIM2 Induces PD-L1 Expression and Promotes Tumor Growth in Breast Cancer
Authors: Tingting Yang, Chune Ren, Chao Lu, Pengyun Qiao, Xue Han, Li Wang, Dan Wang, Shijun Lv, Yonghong Sun, Zhenhai Yu
Journal: Cancer Research (2019)

Heat shock transcription factor 1 (HSF1) is the master regulator of the proteotoxic stress response, which plays a key role in breast cancer tumorigenesis. However, the mechanisms underlying regulation of HSF1 protein stability are still unclear. Here, we show that HSF1 protein stability is regulated by PIM2-mediated phosphorylation of HSF1 at Thr120, which disrupts the binding of HSF1 to the E3 ubiquitin ligase FBXW7. In addition, HSF1 Thr120 phosphorylation promoted proteostasis and carboplatin-induced autophagy. Interestingly, HSF1 Thr120 phosphorylation induced HSF1 binding to the PD-L1 promoter and enhanced PD-L1 expression. Furthermore, HSF1 Thr120 phosphorylation promoted breast cancer tumorigenesis in vitro and in vivo. PIM2, pThr120-HSF1, and PD-L1 expression positively correlated with each other in breast cancer tissues. Collectively, these findings identify PIM2-mediated HSF1 phosphorylation at Thr120 as an essential mechanism that regulates breast tumor growth and potential therapeutic target for breast cancer. SIGNIFICANCE: These findings identify heat shock transcription factor 1 as a new substrate for PIM2 kinase and establish its role in breast tumor progression.
TMEM25 modulates neuronal excitability and NMDA receptor subunit NR2B degradation
Authors: Haiqing Zhang, Xin Tian, Xi Lu, Demei Xu, Yi Guo, Zhifang Dong, Yun Li, Yuanlin Ma, Chengzhi Chen, Yong Yang, Min Yang, Yi Yang, Feng Liu, Ruijiao Zhou, Miaoqing He, Fei Xiao, Xuefeng Wang
Journal: Journal of Clinical Investigation (2019)

The expression of the transmembrane protein 25 gene (Tmem25) is strongly influenced by glutamate ionotropic receptor kainate type subunit 4, and its function remains unknown. Here, we showed that TMEM25 was primarily localized to late endosomes in neurons. Electrophysiological experiments suggested that the effects of TMEM25 on neuronal excitability were likely mediated by N-methyl-d-aspartate receptors. TMEM25 affected the expression of the N-methyl-d-aspartate receptor NR2B subunit and interacted with NR2B, and both were colocalized to late endosome compartments. TMEM25 induced acidification changes in lysosome compartments and accelerated the degradation of NR2B. Furthermore, TMEM25 expression was decreased in brain tissues from patients with epilepsy and epileptic mice. TMEM25 overexpression attenuated the behavioral phenotypes of epileptic seizures, whereas TMEM25 downregulation exerted the opposite effect. These results provide some insights into TMEM25 biology in the brain and the functional relationship between TMEM25 and epilepsy.