tbuckley/cabot-search huggingface dataset:
The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
Authors: Deborah R. Caswell, Philippe Gui, Manasi K. Mayekar, Emily K. Law, Oriol Pich, Chris Bailey, Jesse Boumelha, D. Lucas Kerr, Collin M. Blakely, Tadashi Manabe, Carlos Martinez-Ruiz, Bjorn Bakker, Juan De Dios Palomino Villcas, Natalie I. Vokes, Michelle Dietzen, Mihaela Angelova, Beatrice Gini, Whitney Tamaki, Paul Allegakoen, Wei Wu, Timothy J. Humpton, William Hill, Mona Tomaschko, Wei-Ting Lu, Franziska Haderk, Maise Al Bakir, Ai Nagano, Francisco Gimeno-Valiente, Sophie de Carné Trécesson, Roberto Vendramin, Vittorio Barbè, Miriam Mugabo, Clare E. Weeden, Andrew Rowan, Caroline E. McCoach, Bruna Almeida, Mary Green, Carlos Gomez, Shigeki Nanjo, Dora Barbosa, Chris Moore, Joanna Przewrocka, James R. M. Black, Eva Grönroos, Alejandro Suarez-Bonnet, Simon L. Priestnall, Caroline Zverev, Scott Lighterness, James Cormack, Victor Olivas, Lauren Cech, Trisha Andrews, Brandon Rule, Yuwei Jiao, Xinzhu Zhang, Paul Ashford, Cameron Durfee, Subramanian Venkatesan, Nuri Alpay Temiz, Lisa Tan, Lindsay K. Larson, Prokopios P. Argyris, William L. Brown, Elizabeth A. Yu, Julia K. Rotow, Udayan Guha, Nitin Roper, Johnny Yu, Rachel I. Vogel, Nicholas J. Thomas, Antonio Marra, Pier Selenica, Helena Yu, Samuel F. Bakhoum, Su Kit Chew, Jorge S. Reis-Filho, Mariam Jamal-Hanjani, Karen H. Vousden, Nicholas McGranahan, Eliezer M. Van Allen, Nnennaya Kanu, Reuben S. Harris, Julian Downward, Trever G. Bivona, Charles Swanton
Journal: Nature Genetics (2023)

Abstract In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.
A Universal Cyclodextrin‐Based Nanovaccine Platform Delivers Epitope Peptides for Enhanced Antitumor Immunity
Authors: Jiarong Mao, Zhetong Jin, Xue Rui, Lu Li, Chengchen Hou, Xuejiao Leng, Xiaolin Bi, Zhipeng Chen, Yugen Chen, Jingjing Wang
Journal: Advanced Healthcare Materials (2023)

Adv. Healthcare Mater. 2023, 12, 2301099 https://doi.org/10.1002/adhm.202301099 In the originally published version of this article, two of the authors' e-mail addresses were attributed to the wrong author. The correct e-mail adresses are as follows: Zhipeng Chen: [email protected] Yugen Chen: [email protected] Jingjing Wang: [email protected]
Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies
Authors: Federica Laguzzi, Agneta Åkesson, Matti Marklund, Frank Qian, Bruna Gigante, Traci M. Bartz, Julie K. Bassett, Anna Birukov, Hannia Campos, Yoichiro Hirakawa, Fumiaki Imamura, Susanne Jäger, Maria Lankinen, Rachel A. Murphy, Mackenzie Senn, Toshiko Tanaka, Nathan Tintle, Jyrki K. Virtanen, Kazumasa Yamagishi, Matthew Allison, Ingeborg A. Brouwer, Ulf De Faire, Gudny. Eiriksdottir, Luigi Ferrucci, Nita G. Forouhi, Johanna M. Geleijnse, Allison M Hodge, Hitomi Kimura, Markku Laakso, Ulf Risérus, Anniek C. van Westing, Stefania Bandinelli, Ana Baylin, Graham G. Giles, Vilmundur Gudnason, Hiroyasu Iso, Rozenn N. Lemaitre, Toshiharu Ninomiya, Wendy S. Post, Bruce M. Psaty, Jukka T. Salonen, Matthias B. Schulze, Michael Y. Tsai, Matti Uusitupa, Nicholas J. Wareham, Seung-Won Oh, Alexis C. Wood, William S. Harris, David Siscovick, Dariush Mozaffarian, Karin Leander
Journal: Circulation (2023)

It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.
CD4+ T-Cell Legumain Deficiency Attenuates Hypertensive Damage via Preservation of TRAF6
Authors: Yuhu He, Pu Zou, Junmi Lu, Yufei Lu, Shuguang Yuan, Xialei Zheng, Jing Liu, Cheng Zeng, Ling Liu, Liang Tang, Zhenfei Fang, Xinqun Hu, Qiming Liu, Shenghua Zhou
Journal: Circulation Research (2023)

BACKGROUND: T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear. METHODS: Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell–specific LGMN-knockout) mice (Lgmn f/f /CD4 Cre ), regulatory T cell (Treg)–specific LGMN-knockout mice (Lgmn f/f /Foxp3 YFP Cre ), and RR-11a (LGMN inhibitor)–treated C57BL/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development. RESULTS: LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II–induced or deoxycorticosterone acetate/salt–induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II–induced or deoxycorticosterone acetate/salt–induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II–induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II–induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor–associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-κB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II–induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects. CONCLUSIONS: LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.
Nanomaterials-combined methacrylated gelatin hydrogels (GelMA) for cardiac tissue constructs
Authors: Erika S. Lisboa, Carine Serafim, Wanessa Santana, Victoria L.S. dos Santos, Ricardo L.C. de Albuquerque-Junior, Marco V. Chaud, Juliana C. Cardoso, Sona Jain, Patrícia Severino, Eliana B. Souto
Journal: Journal of Controlled Release (2023)
Cancer Evolution: A Multifaceted Affair
Authors: Giovanni Ciriello, Luca Magnani, Sarah J. Aitken, Leila Akkari, Sam Behjati, Douglas Hanahan, Dan A. Landau, Nuria Lopez-Bigas, Darío G. Lupiáñez, Jean-Christophe Marine, Ana Martin-Villalba, Gioacchino Natoli, Anna C. Obenauf, Elisa Oricchio, Paola Scaffidi, Andrea Sottoriva, Alexander Swarbrick, Giovanni Tonon, Sakari Vanharanta, Johannes Zuber
Journal: Cancer Discovery (2023)

Cancer cells adapt and survive through the acquisition and selection of molecular modifications. This process defines cancer evolution. Building on a theoretical framework based on heritable genetic changes has provided insights into the mechanisms supporting cancer evolution. However, cancer hallmarks also emerge via heritable nongenetic mechanisms, including epigenetic and chromatin topological changes, and interactions between tumor cells and the tumor microenvironment. Recent findings on tumor evolutionary mechanisms draw a multifaceted picture where heterogeneous forces interact and influence each other while shaping tumor progression. A comprehensive characterization of the cancer evolutionary toolkit is required to improve personalized medicine and biomarker discovery. Tumor evolution is fueled by multiple enabling mechanisms. Importantly, genetic instability, epigenetic reprogramming, and interactions with the tumor microenvironment are neither alternative nor independent evolutionary mechanisms. As demonstrated by findings highlighted in this perspective, experimental and theoretical approaches must account for multiple evolutionary mechanisms and their interactions to ultimately understand, predict, and steer tumor evolution.
A large-scale genomically predicted protein mass database enables rapid and broad-spectrum identification of bacterial and archaeal isolates by mass spectrometry
Authors: Yuji Sekiguchi, Kanae Teramoto, Dieter M. Tourlousse, Akiko Ohashi, Mayu Hamajima, Daisuke Miura, Yoshihiro Yamada, Shinichi Iwamoto, Koichi Tanaka
Journal: Genome biology (2023)

Abstract MALDI-TOF MS-based microbial identification relies on reference spectral libraries, which limits the screening of diverse isolates, including uncultured lineages. We present a new strategy for broad-spectrum identification of bacterial and archaeal isolates by MALDI-TOF MS using a large-scale database of protein masses predicted from nearly 200,000 publicly available genomes. We verify the ability of the database to identify microorganisms at the species level and below, achieving correct identification for &gt; 90% of measured spectra. We further demonstrate its utility by identifying uncultured strains from mouse feces with metagenomics, allowing the identification of new strains by customizing the database with metagenome-assembled genomes.
Extension of the SPIRIT 2013 Statement for Factorial Randomized Trials—A Step Toward Transparency and the Curse of Interaction
Authors: Luca Mastrantoni, Gennaro Daniele, Emilio Bria
Journal: JAMA Network Open (2023)

Brennan C. Kahan, PhD; Sophie S. Hall, PhD; Elaine M. Beller, MAppStat; Megan Birchenall, BSc; Diana Elbourne, PhD; Edmund Juszczak, MSc; Paul Little, MD; John Fletcher, MPH; Robert M. Golub, MD; Beatriz Goulao, PhD; Sally Hopewell, DPhil; Nazrul Islam, PhD; Merrick Zwarenstein, MBBCh, PhD; An-Wen Chan, MD, DPhil; Alan A. Montgomery, PhD
Time to Cancer Treatment and Chemotherapy Relative Dose Intensity for Patients With Breast Cancer Living With HIV
Authors: Daniel S. O’Neil, Yehoda M. Martei, Katherine D. Crew, Brenda S. Castillo, Philippos Costa, Tristan Lim, Alissa Michel, Elizabeth Rubin, Neha Goel, Judith Hurley, Gilberto Lopes, Michael H. Antoni
Journal: JAMA Network Open (2023)

Importance Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer. Objective To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV. Design, Setting, and Participants A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023. Exposure HIV infection detected before or within 90 days of participants’ breast cancer diagnosis. Main Outcomes and Measures The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests. Results The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]). Conclusions and Relevance This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.
Adenotonsillectomy or Watchful Waiting for Pediatric Sleep-Disordered Breathing
Authors: Inbal Hazkani, Kathleen R. Billings, Dana M. Thompson
Journal: JAMA (2023)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Pregnancy Weight Gain After Gastric Bypass or Sleeve Gastrectomy
Authors: Huiling Xu, Natalie Holowko, Ingmar Näslund, Johan Ottosson, Elizabeth V. Arkema, Martin Neovius, Olof Stephansson, Kari Johansson
Journal: JAMA Network Open (2023)

Importance Pregnancy weight gain may affect the association of bariatric surgery with postsurgery pregnancy outcomes. However, the association of pregnancy weight gain with bariatric surgery is unclear. Objective To compare pregnancy weight gain among women with a history of bariatric surgery vs those without and to investigate whether pregnancy weight gain differs by surgical procedure, surgery-to-conception interval, and/or surgery-to-conception weight loss. Design, Setting, and Participants This nationwide, population-based matched cohort study was conducted in Sweden from 2014 to 2021. Singleton pregnancies with a history of bariatric surgery were propensity score matched (1:1) to pregnancies without such a history according to early-pregnancy body mass index (BMI), prepregnancy diabetes, prepregnancy hypertension, maternal age, smoking status, education level, height, country of birth, and delivery year. In addition, post–gastric bypass pregnancies were matched to post–sleeve gastrectomy pregnancies using the same matching strategy. Data analysis was performed from November 2022 to May 2023. Exposure History of bariatric surgery. Main Outcomes and Measures Pregnancy weight gain was standardized by gestational age into early-pregnancy BMI-specific z scores. Results This study included 12 776 pregnancies, of which 6388 had a history of bariatric surgery and 6388 were matched controls. The mean (SD) age was 31.6 (4.9) years for the surgery group and 31.4 (5.2) for the matched controls, with an early-pregnancy mean (SD) BMI of 29.4 (5.2) in both groups. Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls. The differences in pregnancy weight gain z score values between the 2 groups were −0.33 (95% CI, −0.43 to −0.23) for normal weight, −0.33 (95% CI, −0.40 to −0.27) for overweight, −0.21 (95% CI, −0.29 to −0.13) for obese class I, −0.16 (95% CI, −0.29 to −0.03) for obese class II, and −0.08 (95% CI, −0.28 to 0.13) for obese class III. Pregnancy weight gain did not differ by surgical procedure. A shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss was associated with lower pregnancy weight gain. Conclusions and Relevance In this nationwide matched cohort study, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls with similar early-pregnancy characteristics. Pregnancy weight gain was lower in those with a shorter surgery-to-conception interval or lower surgery-to-conception weight loss, but did not differ by surgical procedure.
Bilateral Renal Agenesis—Interpreting the RAFT Trial
Authors: Cynthia Gyamfi-Bannerman, Krishelle Marc-Aurele, Karen Mestan
Journal: JAMA (2023)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Four Methods for Monitoring SARS-CoV-2 and Influenza A Virus Activity in Schools
Authors: Jonathan Temte, Maureen Goss, Shari Barlow, David H. O’Connor, Shelby L. O’Connor, Mitchell D. Ramuta, Amra Uzicanin
Journal: JAMA Network Open (2023)

This cross-sectional study describes 4 parallel approaches used simultaneously to monitor influenza A virus and SARS-CoV-2 activity within a Wisconsin school district during the Fall 2022 semester and briefly following winter break.
Objective Sleep Duration and All-Cause Mortality Among People With Obstructive Sleep Apnea
Authors: Yiqi Lin, Yongxi Wu, Qianwen Lin, Yun Kwok Wing, Lili Xu, Junbo Ge, Qinwei Wu, Zhen Li, Qingjie Wu, Beiwei Lin, Shichao Wei
Journal: JAMA Network Open (2023)

Importance The association between sleep duration and all-cause mortality remains unclear among people with obstructive sleep apnea (OSA). Objective To explore whether there is an association between sleep duration and all-cause mortality among people with OSA. Design, Setting, and Participants This cohort study investigated participants with OSA from the Sleep Heart Health Study (SHHS) in which participants were enrolled between 1995 and 1998 with questionnaires and polysomnography (PSG) assessment and followed up for a median of 11.8 years. SHHS was a multicenter community-based study; 2574 participants with OSA defined by apnea-hypopnea index (AHI) greater than or equal to 15 from SHHS were found; all of them had all-cause mortality data and were included in the study. Data were analyzed from November 2022 to October 2023. Exposures Participants were divided into 4 groups with objective sleep duration of (1) at least 7 hours, (2) 6 to less than 7 hours, (3) 5 to less than 6 hours, and (4) less than 5 hours, which was determined by total sleep time on PSG at baseline. Main Outcomes and Measures All-cause mortality was defined as deaths from any cause and its risk was compared among 4 OSA groups using Cox regression models. Results A total of 2574 participants with OSA were included (1628 [63.2%] men and 946 [36.8%] women; mean [SD] age, 65.4 [10.7] years; 211 [8.2%] Black, 2230 [86.6%] White, 133 [5.2%] other race). Overall, 688 all-cause deaths were observed in participants. Compared with the group sleeping at least 7 hours, the groups sleeping 6 to less than 7 hours (hazard ratio [HR], 1.53 [95% CI, 1.13-2.07]), 5 to less than 6 hours (HR, 1.40 [95% CI, 1.03-1.90]), and less than 5 hours (HR, 1.64 [95% CI, 1.20-2.24]) had significantly higher risks of all-cause mortality independent of AHI. Sensitivity analyses were performed among participants with available data of positive airway pressure treatment during follow-up and the finding was mostly consistent, albeit the HR for the group of 5 to less than 6 hours was not statistically significant. Conclusions and Relevance In this cohort study of 2574 participants with OSA, those with shorter objective sleep duration had higher risk of all-cause mortality independent of AHI compared with those sleeping at least 7 hours. Further studies would be needed to investigate health benefits of extending sleep length among people with OSA with short sleep duration.