tbuckley/cabot-search huggingface dataset:
DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer
Authors: Jiayu Zhang, Yingxi Zhao, Ruijuan Liang, Xue Zhou, Zhonghua Wang, Cheng Yang, Lingyue Gao, Yonghao Zheng, Hui Shao, Yang Su, Wei Cui, Lina Jia, Jingyu Yang, Chunfu Wu, Lihui Wang
Journal: Acta Pharmaceutica Sinica B (2024)

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.
Ultra‐Photostable Bacterial‐Seeking Near‐Infrared CPDs for Simultaneous NIR‐II Bioimaging and Antibacterial Therapy
Authors: Jingyi Duan, Baosheng Li, Yanqun Liu, Tianyang Han, Fengming Ye, Huan Xia, Kaifeng Liu, Jie He, Xueke Wang, Qing Cai, Weiyan Meng, Shoujun Zhu
Journal: Advanced Healthcare Materials (2024)

Bacterial infections can pose significant health risks as they have the potential to cause a range of illnesses. These infections can spread rapidly and lead to complications if not promptly diagnosed and treated. Therefore, it is of great significance to develop a probe to selectively target and image pathogenic bacteria while simultaneously killing them, as there are currently no effective clinical solutions available. This study presents a novel approach using near-infrared carbonized polymer dots (NIR-CPDs) for simultaneous in vivo imaging and treatment of bacterial infections. The core-shell structure of the NIR-CPDs facilitates their incorporation into bacterial cell membranes, leading to an increase in fluorescence brightness and photostability. Significantly, the NIR-CPDs exhibit selective bacterial-targeting properties, specifically identifying Staphylococcus aureus (S. aureus) while sparing Escherichia coli (E. coli). Moreover, under 808 nm laser irradiation, the NIR-CPDs exhibit potent photodynamic effects by generating reactive oxygen species that target and damage bacterial membranes. In vivo experiments on infected mouse models demonstrate not only precise imaging capabilities but also significant therapeutic efficacy, with marked improvements in wound healing. The study provides the dual-functional potential of NIR-CPDs as a highly effective tool for the advancement of medical diagnostics and therapeutics in the fight against bacterial infections.
Accelerating Progress to Reduce the Cancer Burden through Prevention and Control in the US
Authors: Katrina A B Goddard, Eric J Feuer, Asad Umar, Philip E Castle
Journal: JNCI Journal of the National Cancer Institute (2024)

Improvements in cancer prevention and control are poised to be main contributors in reducing the burden of cancer in the US. We quantify top opportunities to accelerate progress using projected life years gained (LYG) and deaths averted as measures. We project that over the next 25 years, realistic gains from tobacco control can contribute 0.4 to 17 million additional LYG per intervention and 8.4 million additional LYG from improving uptake of screening programs over the lifetime of 25 annual cohorts. Additional opportunities include addressing modifiable risk factors (excess weight, alcohol consumption), improving methods to prevent or treat oncogenic infections, and reducing cancer health disparities. Investment is needed in the pipeline of new preventive agents and technologies for early detection to continue progress. There is also a need for additional research to improve the access to and uptake of existing and emerging interventions for cancer prevention and control and to address health disparities. These gains are undeniably within our power to realize for the US population.
Exploring the optimal chain length of modification module in disulfide bond bridged paclitaxel prodrug nanoassemblies for breast tumor treatment
Authors: Danping Wang, Yuetong Huang, Jun Yuan, Shuo Wang, Jingzhe Sheng, Yingjie Zhao, Hao Zhang, Xiyan Wang, Yuanhao Yu, Xianbao Shi, Zhonggui He, Tian Liu, Bingjun Sun, Jin Sun
Journal: Journal of Controlled Release (2024)
Glucagon-Like Peptide-1 Receptor Agonists and Suicidality—Two Important Pieces of Data but an Incomplete Puzzle
Authors: Timothy S. Anderson, Deborah Grady
Journal: JAMA Internal Medicine (2024)

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 Journals 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 2024 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
Genomic profiling and immune phenotyping of neuroendocrine bladder cancer
Authors: Jingyu Zang, Akezhouli Shahatiaili, Mei-Chun Cai, Di Jin, Peiye Shen, Lei Qian, Lu Zhang, Tianxiang Zhang, Yuchen Wu, Fan Yang, Zheng Wu, Yanli Hou, Yongrui Bai, Jun Xia, Liang Cheng, Ruiyun Zhang, Guanglei Zhuang, Haige Chen
Journal: Clinical Cancer Research (2024)

Neuroendocrine bladder cancer (NEBC) poses a formidable clinical challenge and attracts keen interests to explore immunotherapy as a viable treatment option. However, a comprehensive immunogenomic landscape has yet to be thoroughly investigated.
A phase II study of atezolizumab, pertuzumab, and high-dose trastuzumab for central nervous system metastases in patients with HER2-positive breast cancer
Authors: Antonio Giordano, Priya U. Kumthekar, Qingchun Jin, Busem Binboga Kurt, Siyang Ren, Tianyu Li, Jose Pablo. Leone, Elizabeth A. Mittendorf, Alyssa M. Pereslete, Laura Sharp, Raechel Davis, Molly DiLullo, Nabihah Tayob, Erica L. Mayer, Eric P. Winer, Sara M. Tolaney, Nancy U. Lin
Journal: Clinical Cancer Research (2024)

Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.
Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations
Authors: Weiling Xu, Yun Soo Hong, Bo Hu, Suzy A.A. Comhair, Allison J. Janocha, Joe G. Zein, Ruoying Chen, Deborah A. Meyers, David T. Mauger, Victor E. Ortega, Eugene R. Bleecker, Mario Castro, Loren C. Denlinger, John V. Fahy, Elliot Israel, Bruce D. Levy, Nizar N. Jarjour, Wendy C. Moore, Sally E. Wenzel, Benjamin Gaston, Chunyu Liu, Dan E. Arking, Serpil C. Erzurum
Journal: Journal of Allergy and Clinical Immunology (2024)
Clinical Review of Non-invasive Ventilation
Authors: Gerard J. Criner, Shameek Gayen, Massa Zantah, Eduardo Dominguez Castillo, Mario Naranjo-Tovar, Bilal Lashari, Seyedmohammad Pourshahid, Andrew Gangemi
Journal: European Respiratory Journal (2024)

Noninvasive ventilation (NIV) is the mainstay to treat patients who need augmentation of ventilation for acute and chronic forms of respiratory failure. The last several decades has witnessed an extension of the indications for NIV to a variety of acute and chronic lung diseases. Evolving advancements in technology and personalised approaches to patient care make it feasible to prioritise patient centered care models that deliver home-based management using telemonitoring and telemedicine systems support. These trends may improve patient outcomes, reduce healthcare costs, and improve the quality of life for patients who suffer from chronic diseases that precipitate respiratory failure.
Anal intraepithelial neoplasia screening during colonoscopy: a technical proposal
Authors: Willian Ferreira Igi, Daiane Marrai Costa Nascimento, Magda Priscila Cardoso Afonso, Fernando Lander Mota, Lucas Santana Nova da Costa, Eloisa Barbosa Brum, Fernanda Freitas Franca Rocha
Journal: Endoscopy (2024)
Prophylactic abdominal drainage after distal pancreatectomy: really unnecessary? – Author's reply
Authors: Eduard A van Bodegraven, Alberto Balduzzi, Tess M E van Ramshorst, Giuseppe Malleo, Frederique L Vissers, Jony van Hilst, Giovanni Marchegiani, Matteo de Pastena, Roberto Salvia, Casper H J van Eijck, Marc G Besselink
Journal: The Lancet. Gastroenterology & hepatology (2024)
Temporal variations in the short-term effects of ambient air pollution on cardiovascular and respiratory mortality: a pooled analysis of 380 urban areas over a 22-year period
Authors: Maximilian Schwarz, Annette Peters, Massimo Stafoggia, Francesca de'Donato, Francesco Sera, Michelle L Bell, Yuming Guo, Yasushi Honda, Veronika Huber, Jouni J K Jaakkola, Aleš Urban, Ana Maria Vicedo-Cabrera, Pierre Masselot, Eric Lavigne, Souzana Achilleos, Jan Kyselý, Evangelia Samoli, Masahiro Hashizume, Chris Fook Sheng Ng, Susana das Neves Pereira da Silva, Joana Madureira, Rebecca M Garland, Aurelio Tobias, Ben Armstrong, Joel Schwartz, Antonio Gasparrini, Alexandra Schneider, Susanne Breitner
Journal: The Lancet Planetary Health (2024)
Planetary health learning objectives: foundational knowledge for global health education in an era of climate change
Authors: Kathryn H Jacobsen, Caryl E Waggett, Pamela Berenbaum, Brett R Bayles, Gail L Carlson, René English, Carlos A Faerron Guzmán, Meredith L Gartin, Liz Grant, Thomas L Henshaw, Lora L Iannotti, Philip J Landrigan, Nina Lansbury, Hao Li, Maureen Y Lichtveld, Ketrell L McWhorter, Jessica E Rettig, Cecilia J Sorensen, Eric J Wetzel, Dawn Michele Whitehead, Peter J Winch, Keith Martin
Journal: The Lancet Planetary Health (2024)
Risks of infectious disease hospitalisations in the aftermath of tropical cyclones: a multi-country time-series study
Authors: Wenzhong Huang, Thomas Vogt, Jinah Park, Zhengyu Yang, Elizabeth A Ritchie, Rongbin Xu, Yiwen Zhang, Simon Hales, Wenhua Yu, Samuel Hundessa, Christian Otto, Pei Yu, Yanming Liu, Ke Ju, Eric Lavigne, Tingting Ye, Bo Wen, Yao Wu, Wissanupong Kliengchuay, Kraichat Tantrakarnapa, Yue Leon Guo, Ho Kim, Dung Phung, Shanshan Li, Yuming Guo
Journal: The Lancet Planetary Health (2024)
Effectiveness of Wolbachia-mediated sterility coupled with sterile insect technique to suppress adult Aedes aegypti populations in Singapore: a synthetic control study
Authors: Somya Bansal, Jue Tao Lim, Chee-Seng Chong, Borame Dickens, Youming Ng, Lu Deng, Caleb Lee, Li Yun Tan, Evdoxia G Kakani, Yanni Yoong, David Du Yu, Grace Chain, Pei Ma, Shuzhen Sim, Lee Ching Ng, Cheong Huat Tan
Journal: The Lancet Planetary Health (2024)
Expert judgement reveals current and emerging UK climate-mortality burden
Authors: Dann Mitchell, Y T Eunice Lo, Emily Ball, Joanne L Godwin, Oliver Andrews, Rosa Barciela, Lea Berrang Ford, Claudia Di Napoli, Kristie L Ebi, Neven S Fučkar, Antonio Gasparrini, Brian Golding, Celia L Gregson, Gareth J Griffith, Sara Khalid, Caitlin Robinson, Daniela N Schmidt, Charles H Simpson, Robert Stephen John Sparks, Josephine G Walker
Journal: The Lancet Planetary Health (2024)
Planetary health diet and cardiovascular disease: results from three large prospective cohort studies in the USA
Authors: Caleigh M Sawicki, Gautam Ramesh, Linh Bui, Nilendra K Nair, Frank B Hu, Eric B Rimm, Meir J Stampfer, Walter C Willett, Shilpa N Bhupathiraju
Journal: The Lancet Planetary Health (2024)
Race- and Ethnicity-Related Disparities in Predialysis Nephrology Care, Kidney Disease Education, and Home Dialysis Utilization
Authors: Ashutosh M. Shukla, Grant Scheiffele, Wenxi Huang, Rebecca Campbell-Montalvo, Jiang Bian, Yi Guo, Serena Jingchuan Guo
Journal: Journal of the American Society of Nephrology (2024)

Key Points Disparities in predialysis nephrology care and KRT-directed education significantly influenced home dialysis underuse among marginalized populations. The influence of predialysis care disparities on home dialysis underuse lasted for a long time even after starting the dialysis. More studies are needed to uncover the layers through which structural racism influences home dialysis underuse among marginalized populations. Background Predialysis nephrology care and KRT-directed education (KDE) are essential for incident home dialysis use. However, there are substantial disparities in these care parameters among patients with advanced CKD. The effect of these disparities on home dialysis underuse has not been examined. Methods We analyzed the 2021 United States Renal Database System to identify all adult patients with kidney failure with over 6 months of predialysis Medicare coverage initiating their first-ever dialysis between 2010 and 2019. We used a mediation analysis to dissect the attributable influence of disparities in predialysis nephrology care and KDE on incident home dialysis use. In addition, we conducted sensitivity analyses using graded levels of mediators and sustained effect on home dialysis outcomes. Results We identified 464,310 Medicare recipients: 428,301 using in-center hemodialysis and 35,416 using home dialysis as their first-ever dialysis modality during the study period. Compared with non-Hispanic White patients ( n =294,914), adjusted odds ratio (95% confidence intervals) for receiving predialysis nephrology care, KDE service, and incident home dialysis were 0.62 (0.61 to 0.64), 0.58 (0.52 to 0.63), and 0.76 (0.73 to 0.79), respectively, among Hispanic individuals ( n =49,734) and 0.74 (0.73 to 0.76), 0.84 (0.79 to 0.89), and 0.63 (0.61 to 0.65), respectively, among Black individuals ( n =98,992). Mediation analyses showed that compared with non-Hispanic White individuals, lack of nephrology care explained 30% and 14% of incident home dialysis underuse among Hispanic and Black individuals, respectively ( P &lt; 0.001). Sensitivity analyses using a longer duration of nephrology care and KDE services and the sustained effect on home dialysis underuse through the first year after kidney failure showed congruent and consolidating findings. Conclusions Disparities in predialysis nephrology care were significantly associated with lower home dialysis use among Hispanic and Black individuals.
Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Kidney Outcomes across Baseline Cardiovascular-Kidney-Metabolic Conditions
Authors: Tariq Jamal Siddiqi, David Cherney, Hasan Fareed Siddiqui, Tazeen H. Jafar, James L. Januzzi, Muhammad Shahzeb Khan, Adeera Levin, Nikolaus Marx, Janani Rangaswami, Jeffrey Testani, Muhammad Shariq Usman, Christoph Wanner, Faiez Zannad, Javed Butler
Journal: Journal of the American Society of Nephrology (2024)

Key Points Sodium-glucose cotransporter-2 (SGLT2) inhibitors slowed the rate of eGFR slope decline in patients with heart failure, CKD, and type 2 diabetes mellitus and in all combinations of multimorbid conditions among these diseases. SGLT2 inhibitors decreased kidney composite outcomes among all disease states and different combinations of multimorbidity, except in patients with heart failure with preserved ejection fraction and heart failure without type 2 diabetes mellitus. SGLT2 inhibitors were found to decrease the risk of kidney failure in patients with type 2 diabetes mellitus and also in those with CKD. Background The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on kidney outcomes in patients with varying combinations of heart failure, CKD, and type 2 diabetes mellitus have not been quantified. Methods PubMed and Scopus were queried up to December 2023 for primary and secondary analyses of placebo-controlled trials of SGLT2is in patients with heart failure, CKD, or type 2 diabetes mellitus. Outcomes of interest were composite kidney end point (combination of eGFR &lt;15 ml/min per 1.73 m 2 , sustained doubling of serum creatinine, varying percent change in eGFR, and need for KRT), rate of eGFR slope decline, and albuminuria progression. Hazard ratios (HRs) and mean differences with their 95% confidence intervals (CIs) were extracted onto an Excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration). Results Eleven trials ( n =80,928 patients) were included. Compared with the placebo, SGLT2is reduced the risk of the composite kidney end point by 41% (HR, 0.59; 95% CI, 0.42 to 0.83) in heart failure with reduced ejection fraction, 36% (HR, 0.64; 95% CI, 0.55 to 0.73) in CKD, and 38% (HR, 0.62; 95% CI, 0.56 to 0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities and in patients without baseline heart failure, CKD, or type 2 diabetes mellitus. SGLT2is slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (HR, 0.64; 95% CI, 0.56 to 0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data. Conclusions SGLT2i improved kidney outcomes in cohorts with heart failure, CKD, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.
Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke
Authors: Opeolu Adeoye, Joseph Broderick, Colin P. Derdeyn, James C. Grotta, William Barsan, Oladi Bentho, Scott Berry, Mauricio Concha, Iris Davis, Stacie Demel, Jordan Elm, Nina Gentile, Todd Graves, Melissa Hoffman, Josephine Huang, James Ingles, Scott Janis, Adam S. Jasne, Pooja Khatri, Steven R. Levine, Aniel Majjhoo, Peter Panagos, Arthur Pancioli, Stephanie Pizzella, Tamra Ranasinghe, Noor Sabagha, Sanjeev Sivakumar, Christopher Streib, Achala Vagal, Alastair Wilson, Max Wintermark, Albert J. Yoo, Andrew D. Barreto
Journal: New England Journal of Medicine (2024)

Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.
Doxorubicin–Trabectedin with Trabectedin Maintenance in Leiomyosarcoma
Authors: Patricia Pautier, Antoine Italiano, Sophie Piperno-Neumann, Christine Chevreau, Nicolas Penel, Nelly Firmin, Pascaline Boudou-Rouquette, François Bertucci, Valérie Lebrun-Ly, Isabelle Ray-Coquard, Elsa Kalbacher, Emmanuelle Bompas, Olivier Collard, Nicolas Isambert, Cécile Guillemet, Maria Rios, Axel Le Cesne, Corinne Balleyguier, Baptiste Archambaud, Florence Duffaud
Journal: New England Journal of Medicine (2024)

The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma.
A Monoclonal Antibody to PACAP for Migraine Prevention
Authors: Messoud Ashina, Ravinder Phul, Melanie Khodaie, Elin Löf, Ioana Florea
Journal: New England Journal of Medicine (2024)

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) is a new avenue for treating migraine. The efficacy and safety of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention are unclear.
A New Orthonairovirus Associated with Human Febrile Illness
Authors: Xiao-Ai Zhang, Yi-Dan Ma, Yun-Fa Zhang, Zhen-Yu Hu, Jing-Tao Zhang, Shuo Han, Gang Wang, Shuang Li, Xi Wang, Fang Tang, Wen-Jun Liang, Hong-Xia Yuan, Jia-Qi Zhao, Lan-Fen Jiang, Lei Zhang, Guang-Qian Si, Cong Peng, Rui Wang, Hong-Han Ge, Nan Li, Bao-Gui Jiang, Chang Li, Hao Li, Wei Liu
Journal: New England Journal of Medicine (2024)

In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV).
BCMA-Targeted T-Cell–Engager Therapy for Autoimmune Disease
Authors: Melanie Hagen, Laura Bucci, Sebastian Böltz, Danae-Mona Nöthling, Tobias Rothe, Kirill Anoshkin, Maria G. Raimondo, Carlo Tur, Andreas Wirsching, Jochen Wacker, Christina Düsing, Jörg H.W. Distler, Torsten Kuwert, Aline Bozec, Andreas Ramming, Georg Schett, Ricardo Grieshaber-Bouyer
Journal: New England Journal of Medicine (2024)