tbuckley/cabot-search huggingface dataset:
Editor's Note: Dual Targeting of Wild-Type and Mutant p53 by Small-molecule RITA Results in the Inhibition of N-Myc and Key Survival Oncogenes and Kills Neuroblastoma Cells <i>In Vivo</i> and <i>In Vitro</i>
Authors: Mikhail Burmakin, Yao Shi, Elisabeth Hedström, Per Kogner, Galina Selivanova
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about this article (1): in Fig. 3D, the p21 and Noxa Western blots for SKN-DZ were accidentally duplicated as the PUMA and Noxa Western blots for SKN-BE(2). The SKN-DZ blots were correct, and the authors have additional SKN-BE(2) blots available for review upon request. The authors regret this error and stand by the conclusions in the article.
Urgent Intervention for Both de Winter and Wellens
Authors: Wen-Biao Chen, Zhuo-Yu An
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Inhaled corticosteroids reduce senescence in endothelial progenitor cells from patients with COPD
Authors: Koralia Paschalaki, Christos Rossios, Charis Pericleous, Mairi MacLeod, Stephen Rothery, Gavin C Donaldson, Jadwiga A Wedzicha, Vassilis Gorgoulis, Anna M Randi, Peter J Barnes
Journal: Thorax (2022)

Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Using endothelial colony-forming-cells (ECFC), we have demonstrated accelerated senescence in smokers and patients with COPD compared with non-smokers. Subgroup analysis suggests that ECFC from patients with COPD on inhaled corticosteroids (ICS) (n=14; eight on ICS) exhibited significantly reduced senescence (Senescence-associated-beta galactosidase activity, p21 CIP1 ), markers of DNA damage response (DDR) and IFN-γ-inducible-protein-10 compared with patients with COPD not on ICS. In vitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICS on the DDR, senescence and apoptosis caused by oxidative stress, suggesting a protective molecular mechanism of action of corticosteroids on endothelium.
European Association of Urology COVID intermediate prioritisation group is poorly predictive of pathological high-risk among patients with renal tumours
Authors: P. Satish, T. Kuusk, N. Campain, Y. Abu-Ghanem, J. Neves, R. Barod, S. El-Sheikh, F. Mumtaz, P. Patki, M. Tran, M. Tran-Dang, L.A. Grant, T. Klatte, A. Bex
Journal: European Urology (2021)
Results from a Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Intermediate, or High Risk, Relapsed/Refractory Myelofibrosis
Authors: Naveen Pemmaraju, Vikas Gupta, Haris Ali, Abdulraheem Yacoub, Eunice S. Wang, Sangmin Lee, Gary J. Schiller, Megan Sardone, Halyna Wysowskyj, Janice Chen, Christopher Brooks, Enrique Poradosu, Peter McDonald, Nicole Rupprecht, Animesh Pardanani, Ayalew Tefferi, Moshe Talpaz, Minakshi S. Taparia, Srdan Verstovsek, Joseph D. Khoury, Mrinal M Patnaik
Journal: Blood (2019)
Erratum. Characteristics of the Gut Microbiota and Metabolism in Patients With Latent Autoimmune Diabetes in Adults: A Case-Control Study. Diabetes Care 2021;44:2738–2746
Authors: Yuanyuan Fang, Chenhong Zhang, Hongcai Shi, Wei Wei, Jing Shang, Ruizhi Zheng, Lu Yu, Pingping Wang, Junpeng Yang, Xinru Deng, Yun Zhang, Shasha Tang, Xiaoyang Shi, Yalei Liu, Huihui Yang, Qian Yuan, Rui Zhai, Huijuan Yuan
Journal: Diabetes Care (2022)
Combined Varenicline With Nicotine Patch and Extended Duration of Therapy for Smoking Cessation
Authors: Adam Edward Lang
Journal: JAMA (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 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
Final Results of a Phase 1/2a, Dose Escalation Study of Pvx-410 Multi-Peptide Cancer Vaccine in Patients with Smoldering Multiple Myeloma (SMM)
Authors: Ajay K Nooka, Michael Wang, Andrew J. Yee, Sheeba K. Thomas, Elizabeth K. O'Donnell, Jatin J. Shah, Jonathan L. Kaufman, Doris Peterkin, Sagar Lonial, Paul G. Richardson, Noopur Raje
Journal: Blood (2016)
Comparison of robot-assisted partial nephrectomy and percutaneous ablation for ct1 renal masses: Mid term outcome analysis
Authors: U. Carbonara, A.T. Beksac, A. Larcher, G. Basile, F. Crocerossa, A. Celia, F. Montorsi, I. Derweesh, U. Capitanio, J.K. Kaouk, R. Autorino
Journal: European Urology (2021)
Safety evaluation of sequential Mitomycin and Bacillus Calmette-Guérin treatment versus Bacillus Calmette-Guérin monotherapy in patients with high risk non-muscle invasive bladder cancer: MITOBCG study (EUDRACT Number 2017-004540-37) preliminary results
Authors: C. De Nunzio, A. Nacchia, R. Lombardo, O.A. Voglino, V. Baldassarri, L. Costantino, G. Simone, A. Pastore, A. Tubaro
Journal: European Urology (2021)
Re: Luca F. Valle, Eric J. Lehrer, Daniela Markovic, et al. A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER). Eur Urol. In press. https://doi.org/10.1016/j.eururo.2020.11.010
Authors: Sung Eun Kim, Jae Il Shin, Jonathan Evan Shoag
Journal: European Urology (2021)
Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL
Authors: Felix Seyfried, Felix Uli Stirnweiß, Alexandra Niedermayer, Stefanie Enzenmüller, Rebecca Louise Hörl, Vera Münch, Stefan Köhrer, Klaus-Michael Debatin, Lüder Hinrich Meyer
Journal: Leukemia (2022)

Abstract Targeting BCL-2, a key regulator of survival in B-cell malignancies including precursor B-cell acute lymphoblastic leukemia, has become a promising treatment strategy. However, given the redundancy of anti-apoptotic BCL-2 family proteins (BCL-2, BCL-XL, MCL-1), single targeting may not be sufficient. When analyzing the effects of BH3-mimetics selectively targeting BCL-XL and MCL-1 alone or in combination with the BCL-2 inhibitor venetoclax, heterogeneous sensitivity to either of these inhibitors was found in ALL cell lines and in patient-derived xenografts. Interestingly, some venetoclax-resistant leukemias were sensitive to the MCL-1-selective antagonist S63845 and/or BCL-XL-selective A-1331852 suggesting functional mutual substitution. Consequently, co-inhibition of BCL-2 and MCL-1 or BCL-XL resulted in synergistic apoptosis induction. Functional analysis by BH3-profiling and analysis of protein complexes revealed that venetoclax-treated ALL cells are dependent on MCL-1 and BCL-XL, indicating that MCL-1 or BCL-XL provide an Achilles heel in BCL-2-inhibited cells. The effect of combining BCL-2 and MCL-1 inhibition by venetoclax and S63845 was evaluated in vivo and strongly enhanced anti-leukemia activity was found in a pre-clinical patient-derived xenograft model. Our study offers in-depth molecular analysis of mutual substitution of BCL-2 family proteins in acute lymphoblastic leukemia and provides targets for combination treatment in vivo and in ongoing clinical studies.
A flexible split prime editor using truncated reverse transcriptase improves dual-AAV delivery in mouse liver
Authors: Chunwei Zheng, Shun-Qing Liang, Bin Liu, Pengpeng Liu, Suet-Yan Kwan, Scot A. Wolfe, Wen Xue
Journal: Molecular Therapy (2022)

Prime editor (PE) has tremendous promise for gene therapy. However, it remains a challenge to deliver PE (>6.3 kb) in vivo. Although PE can be split into two fragments and delivered using dual adeno-associated viruses (AAVs), choice of split sites within Cas9-which affects editing efficiency-is limited due to the large size of PE. Furthermore, overexpressing reverse transcriptase in mammalian cells might disrupt translation termination via its RNase H domain. Here, we developed a compact PE without the RNase H domain that showed editing comparable with full-length PE. With compact PE, we used a Cas9 split site (Glu 573) that supported robust editing in cells (up to 93% of full-length PE) and in mouse liver. We then demonstrated that split-cPE573 delivered by dual-AAV8 efficiently mediated a 3-bp TGA insertion in the Pcsk9 gene in mouse liver. Compact PE without the RNase H domain abolished its binding to peptidyl release factor 1 (eRF1) and mitigated the stop codon readthrough effect observed with full-length PE. This study identifies a compact PE with a flexible split design to advance utility of prime editing in vivo.
Expression of interferon-γ and its effect on cough hypersensitivity in chronic refractory cough patients
Authors: Jiayang Sun, Chen Zhan, Zheng Deng, Wei Luo, Qiaoli Chen, Mei Jiang, Nanshan Zhong, Kefang Lai
Journal: Thorax (2022)

Chronic refractory cough (CRC) is characterised by cough hypersensitivity. Interferon-γ (IFN-γ) has been reported to induce calcium influx, action potentials of vagal neurons in vitro and cough response in guinea pigs. While the effect of IFN-γ in CRC patients remains unknown. Here, via flow-cytometry and inhalation cough challenge, we found CRC patients had significantly increased levels of sputum IFN-γ + CD4 + T cells, IFN-γ + CD8 + T cells as well as supernatant of IFN-γ. The average number of coughs in CRC patients increased as the concentration of inhaled IFN-γ went up in IFN-γ cough challenge. Two or more coughs and five or more coughs elicited by inhaled IFN-γ in CRC patients occurred in 7 of 10 and 2 of 10, respectively. Preinhaled IFN-γ (100 µg/mL) increased the capsaicin cough sensitivity in CRC patients but not healthy volunteers. Targeting IFN-γ may be a potential effective anti-tussive strategy in CRC patients.
New technologies in robot-assisted kidney transplantation: Improving surgical performances, expanding the indication
Authors: A. Piana, A. Territo, A. Gallioli, M. Fontana, P. Diana, J.M. Gaya, O. Rodríguez Faba, J. Huguet, P. Gavrilov, A. Mercadé, J.D. Subiela, L. Guirado, C. Facundo, A. Bellin, D. Amparore, J. Palou, F. Porpiglia, A. Breda
Journal: European Urology (2021)
274P Metronomic oral vinorelbine (MOV) combined with tremelimumab (T) + durvalumab (D): Efficacy and safety results of the advanced breast cancer (ABC) patients (pts) cohort of the MOVIE study
Authors: T. De La Motte Rouge, J-S. Frenel, E. Borcoman, N. Isambert, G. Emile, P. Augereau, C. Cropet, F. Legrand, A. Gonçalves
Journal: Annals of Oncology (2021)
Engineering interferons and interleukins for cancer immunotherapy
Authors: Patrick G. Holder, Shion A. Lim, Christine S. Huang, Preeti Sharma, Yavuz S. Dagdas, Beyza Bulutoglu, Jonathan T. Sockolosky
Journal: Advanced Drug Delivery Reviews (2022)

Cytokines are a class of potent immunoregulatory proteins that are secreted in response to various stimuli and act locally to regulate many aspects of human physiology and disease. Cytokines play important roles in cancer initiation, progression, and elimination, and thus, there is a long clinical history associated with the use of recombinant cytokines to treat cancer. However, the use of cytokines as therapeutics has been limited by cytokine pleiotropy, complex biology, poor drug-like properties, and severe dose-limiting toxicities. Nevertheless, cytokines are crucial mediators of innate and adaptive antitumor immunity and have the potential to enhance immunotherapeutic approaches to treat cancer. Development of immune checkpoint inhibitors and combination immunotherapies has reinvigorated interest in cytokines as therapeutics, and a variety of engineering approaches are emerging to improve the safety and effectiveness of cytokine immunotherapy. In this review we highlight recent advances in cytokine biology and engineering for cancer immunotherapy.
666P Pembrolizumab (pembro) monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC): Results after a minimum of 41 months of follow-up from KEYNOTE-427 cohort A
Authors: D.F. McDermott, J-L. Lee, G.A. Bjarnason, J. Larkin, R. Gafanov, M.D. Kochenderfer, N.V. Jensen, F. Donskov, J. Malik, A. Poprach, S.S. Tykodi, T. Alonso-Gordoa, D.C. Cho, P.F. Geertsen, M.A. Climent Duran, C. Di Simone, H. Liu, J. Burgents, K. Rodriguez-Lopez, M.B. Atkins
Journal: Annals of Oncology (2021)
Our Baby
Journal: JAMA (1913)

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
Comprehensive Molecular Characterization Reveals Genomic and Transcriptomic Subtypes of Metastatic Urothelial Carcinoma
Authors: J. Alberto Nakauma-González, Maud Rijnders, Job van Riet, Michiel S. van der Heijden, Jens Voortman, Edwin Cuppen, Niven Mehra, Sandra van Wilpe, Sjoukje F. Oosting, L. Lucia Rijstenberg, Hans M. Westgeest, Ellen C. Zwarthoff, Ronald de Wit, Astrid A.M. van der Veldt, Harmen J.G. van de Werken, Martijn P.J. Lolkema, Joost L. Boormans
Journal: European Urology (2022)

Recent molecular characterization of primary urothelial carcinoma (UC) may guide future clinical decision-making. For metastatic UC (mUC), a comprehensive molecular characterization is still lacking. We analyzed whole-genome DNA and RNA sequencing data for fresh-frozen metastatic tumor biopsies from 116 mUC patients who were scheduled for palliative systemic treatment within the context of a clinical trial (NCT01855477 and NCT02925234). Hierarchical clustering for mutational signatures revealed two major genomic subtypes: GenS1 (67%), which was APOBEC-driven; and GenS2 (24%), which had a high fraction of de novo mutational signatures related to reactive oxygen species and is putatively clock-like. Significantly mutated genes (SMGs) did not differ between the genomic subtypes. Transcriptomic analysis revealed five mUC subtypes: luminal-a and luminal-b (40%), stroma-rich (24%), basal/squamous (23%), and a nonspecified subtype (12%). These subtypes differed regarding expression of key genes, SMGs, oncogenic pathway activity, and immune cell infiltration. We integrated the genomic and transcriptomic data to propose potential therapeutic options by transcriptomic subtype and for individual patients. This in-depth analysis of a large cohort of patients with mUC may serve as a reference for subtype-oriented and patient-specific research on the etiology of mUC and for novel drug development. PATIENT SUMMARY: We carried out an in-depth analysis of the molecular and genetic features of metastatic cancer involving the cells that line the urinary tract. We showed that this is a heterogeneous disease with different molecular subtypes and we identified possible targets for therapy for each subtype.
MYC, mitochondrial metabolism and O-GlcNAcylation converge to modulate the activity and subcellular localization of DNA and RNA demethylases
Authors: An-Ping Lin, Zhijun Qiu, Purushoth Ethiraj, Binu Sasi, Carine Jaafar, Dinesh Rakheja, Ricardo C. T. Aguiar
Journal: Leukemia (2022)
Error in the Abstract
Authors: Alexander Acuña, Tarun Jella, Atul Kamath
Journal: JAMA Surgery (2021)

Laura Dominici, MD; Jiani Hu, MS; Yue Zheng, MSc; Hee Jeong Kim, MD, PhD; Tari A. King, MD; Kathryn J. Ruddy, MD, MPH; Rulla M. Tamimi, ScD; Jeffrey Peppercorn, MD; Lidia Schapira, MD; Virginia F. Borges, MD; Steven E. Come, MD; Ellen Warner, MD; Julia S. Wong, MD; Ann H. Partridge, MD, MPH; Shoshana M. Rosenberg, ScD, MPH
A systematic review of patients’ values, preferences and expectations for the diagnosis and treatment of male Lower Urinary Tract Symptoms (LUTS)
Authors: S. Malde, R. Umbach, J.R. Wheeler, L. Lytvyn, J-N. Cornu, M. Gacci, C. Gratzke, T.R.W. Herrmann, C. Mamoulakis, M. Rieken, M.J. Speakman, S. Gravas, M.J. Drake, G.H. Guyatt, K.A.O. Tikkinen
Journal: European Urology (2021)
Population-Based Penetrance of Deleterious Clinical Variants
Authors: Iain S. Forrest, Kumardeep Chaudhary, Ha My T. Vy, Ben O. Petrazzini, Shantanu Bafna, Daniel M. Jordan, Ghislain Rocheleau, Ruth J. F. Loos, Girish N. Nadkarni, Judy H. Cho, Ron Do
Journal: JAMA (2022)

Population-based assessment of disease risk associated with gene variants informs clinical decisions and risk stratification approaches.To evaluate the population-based disease risk of clinical variants in known disease predisposition genes.This cohort study included 72 434 individuals with 37 780 clinical variants who were enrolled in the BioMe Biobank from 2007 onwards with follow-up until December 2020 and the UK Biobank from 2006 to 2010 with follow-up until June 2020. Participants had linked exome and electronic health record data, were older than 20 years, and were of diverse ancestral backgrounds.Variants previously reported as pathogenic or predicted to cause a loss of protein function by bioinformatic algorithms (pathogenic/loss-of-function variants).The primary outcome was the disease risk associated with clinical variants. The risk difference (RD) between the prevalence of disease in individuals with a variant allele (penetrance) vs in individuals with a normal allele was measured.Among 72 434 study participants, 43 395 were from the UK Biobank (mean [SD] age, 57 [8.0] years; 24 065 [55%] women; 2948 [7%] non-European) and 29 039 were from the BioMe Biobank (mean [SD] age, 56 [16] years; 17 355 [60%] women; 19 663 [68%] non-European). Of 5360 pathogenic/loss-of-function variants, 4795 (89%) were associated with an RD less than or equal to 0.05. Mean penetrance was 6.9% (95% CI, 6.0%-7.8%) for pathogenic variants and 0.85% (95% CI, 0.76%-0.95%) for benign variants reported in ClinVar (difference, 6.0 [95% CI, 5.6-6.4] percentage points), with a median of 0% for both groups due to large numbers of nonpenetrant variants. Penetrance of pathogenic/loss-of-function variants for late-onset diseases was modified by age: mean penetrance was 10.3% (95% CI, 9.0%-11.6%) in individuals 70 years or older and 8.5% (95% CI, 7.9%-9.1%) in individuals 20 years or older (difference, 1.8 [95% CI, 0.40-3.3] percentage points). Penetrance of pathogenic/loss-of-function variants was heterogeneous even in known disease predisposition genes, including BRCA1 (mean [range], 38% [0%-100%]), BRCA2 (mean [range], 38% [0%-100%]), and PALB2 (mean [range], 26% [0%-100%]).In 2 large biobank cohorts, the estimated penetrance of pathogenic/loss-of-function variants was variable but generally low. Further research of population-based penetrance is needed to refine variant interpretation and clinical evaluation of individuals with these variant alleles.
An Educational Model
Journal: JAMA (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 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