tbuckley/cabot-search huggingface dataset:
2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play
Authors: Ty J. Gluckman, Nicole M. Bhave, Larry A. Allen, Eugene H. Chung, Erica S. Spatz, Enrico Ammirati, Aaron L. Baggish, Biykem Bozkurt, William K. Cornwell, Kimberly G. Harmon, Jonathan H. Kim, Anuradha Lala, Benjamin D. Levine, Matthew W. Martinez, Oyere Onuma, Dermot Phelan, Valentina O. Puntmann, Saurabh Rajpal, Pam R. Taub, Amanda K. Verma
Journal: Journal of the American College of Cardiology (2022)
Immune phenotypic linkage between colorectal cancer and liver metastasis
Authors: Yedan Liu, Qiming Zhang, Baocai Xing, Nan Luo, Ranran Gao, Kezhuo Yu, Xueda Hu, Zhaode Bu, Jirun Peng, Xianwen Ren, Zemin Zhang
Journal: Cancer Cell (2022)

The tumor microenvironment (TME) is connected to immunotherapy responses, but it remains unclear how cancer cells and host tissues differentially influence the immune composition within TME. Here, we performed single-cell analyses for autologous samples from liver metastasized colorectal cancer to disentangle factors shaping TME. By aligning CD45+ cells across different tissues, we classified exhausted CD8+ T cells (Texs) and activated regulatory T cells as M-type, whose phenotypes were associated with the malignancy, while natural killer and mucosal-associated invariant T cells were defined as N-type, whose phenotypes were associated with the niche. T cell receptor sharing between Texs in primary and metastatic tumors implicated the presence of common peripheral non-exhausted precursors. For myeloid cells, a subset of dendritic cells (DC3s) and SPP1+ macrophages were M-type, and the latter were predominant in liver metastasis, indicating its pro-metastasis role. Our analyses bridge immune phenotypes of primary and metastatic tumors, thereby helping to understand the tumor-specific contexture and identify the pro-metastasis components.
IMPACT OF PREOPERATIVE ATRIAL FIBRILLATION ON ONE YEAR MORTALITY AND QUALITY OF LIFE FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Raymond G. McKay, Sean Robert McMahon, Nicole E. Hoover, Lauren Curtis, William L. Duvall, Bhaskar Arora, Jeff Mather, Hina Amin, Ritika Kompella
Journal: Journal of the American College of Cardiology (2022)
Small-molecule targeted therapies induce dependence on DNA double-strand break repair in residual tumor cells
Authors: Moiez Ali, Min Lu, Hazel Xiaohui Ang, Ryan S. Soderquist, Christine E. Eyler, Haley M. Hutchinson, Carolyn Glass, Christopher F. Bassil, Omar M. Lopez, D. Lucas Kerr, Christina J. Falcon, Helena A. Yu, Aaron N. Hata, Collin M. Blakely, Caroline E. McCoach, Trever G. Bivona, Kris C. Wood
Journal: Science Translational Medicine (2022)

Residual cancer cells that survive drug treatments with targeted therapies act as a reservoir from which eventual resistant disease emerges. Although there is great interest in therapeutically targeting residual cells, efforts are hampered by our limited knowledge of the vulnerabilities existing in this cell state. Here, we report that diverse oncogene-targeted therapies, including inhibitors of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), KRAS, and BRAF, induce DNA double-strand breaks and, consequently, ataxia-telangiectasia mutated (ATM)–dependent DNA repair in oncogene-matched residual tumor cells. This DNA damage response, observed in cell lines, mouse xenograft models, and human patients, is driven by a pathway involving the activation of caspases 3 and 7 and the downstream caspase-activated deoxyribonuclease (CAD). CAD is, in turn, activated through caspase-mediated degradation of its endogenous inhibitor, ICAD. In models of EGFR mutant non–small cell lung cancer (NSCLC), tumor cells that survive treatment with small-molecule EGFR-targeted therapies are thus synthetically dependent on ATM, and combined treatment with an ATM kinase inhibitor eradicates these cells in vivo. This led to more penetrant and durable responses in EGFR mutant NSCLC mouse xenograft models, including those derived from both established cell lines and patient tumors. Last, we found that rare patients with EGFR mutant NSCLC harboring co-occurring, loss-of-function mutations in ATM exhibit extended progression-free survival on first generation EGFR inhibitor therapy relative to patients with EGFR mutant NSCLC lacking deleterious ATM mutations. Together, these findings establish a rationale for the mechanism-based integration of ATM inhibitors alongside existing targeted therapies.
Abstract P2-03-04: Characteristics and clinical differences of breast cancer patients with negative or low HER2 expression
Authors: Ioannis Voutsadakis, Christopher Rosso
Journal: Cancer Research (2022)

Abstract Background: High expression of HER2 receptor in Immunohistochemistry (IHC) sections or amplification of its gene in in situ hybridization (ISH) assays define a subset of breast cancers that have an aggressive natural history but respond to treatments blocking HER2. In contrast, patients with lower HER2 expression, not meeting the criteria for positivity, are currently treated similarly to completely HER2 negative patients. However, emerging data suggest that patients with low HER2 expression may derive benefit from newer antibody drug conjugates. Thus, this investigation sought to clarify the characteristics of HER2 low expressors and compare them with patients with no HER2 expression. Methods: We undertook a retrospective analysis of all breast cancer patients seen in our cancer center over a six-year period and classified as HER2 negative. Patients were categorized as HER2 negative when they had a score of 0 in IHC and as HER2 low if they had a score of 1+ or 2+ in IHC and no amplification by ISH. Characteristics of the patients and tumors in the two groups were compared. Results: A total of 391 HER2 negative and low patients have been included. Among them, 130 patients (33.2%) were HER2 negative (score 0 by IHC) and 261 patients (66.8%) were HER2 low (score 1+ and 2+ by IHC/ISH non-amplified). There were no differences in age, menopause status, mode of detection of cancer (clinical or screening) and clinical stage at diagnosis between the two groups. Patients in the HER2 low group had less commonly high-grade cancers than HER2 negative patients (25.35 versus 34.6%, x2 p=0.04).In addition, The HER2 low group had higher ER Histoscore (&amp;gt;240) in 88.1% of cases compared with 69.2% in HER2 negative group (x2 p&amp;lt;0.000). Similarly, a higher percentage of HER2 low cases than HER2 negative cases were expressing the progesterone receptor (PR, x2 p&amp;lt;0.000). HER2 low patients were rarely (3.8%) classified as triple negative, while this percentage was 21.5% in HER2 negative patients. Conclusion: HER2 negative staining (IHC score 0) is associated with averse tumor characteristics compared with clinically HER2 negative patients with low HER2 expression (score 1+ and 2+/ISH non-amplified). Citation Format: Ioannis Voutsadakis, Christopher Rosso. Characteristics and clinical differences of breast cancer patients with negative or low HER2 expression [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-03-04.
VESSEL-SPECIFIC ECG LEADS AS A NOVEL STRATEGY FOR MYOCARDIAL ISCHEMIA DETECTION IN PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROME
Authors: Abdullah Ahmad, Ziad Faramand, John Wang, Richard Gregg, Milan Horacek, Christian Martin-Gill, Clifton Callaway, Samir F. Saba, Salah Al-Zaiti
Journal: Journal of the American College of Cardiology (2022)
Real-world Data—A Key Barrier to Building Out the Science of Firearm Safety
Authors: Jayson S. Marwaha, Nicole Lunardi, Joseph V. Sakran
Journal: JAMA Surgery (2022)

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MATERNAL AND FETAL OUTCOME OF THE FIRST PREGNANCY IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Tiziana Claudia Aranzulla, Antonia Luisa Buongiorno, Antonino Imbesi, Barbara Maria Teresa Mabritto, Stefania Luceri, Sergio Bongioanni, Giuseppe Musumeci
Journal: Journal of the American College of Cardiology (2022)
PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer
Authors: Ying Wu, Zhe Wang, Lu Han, Zhihao Guo, Bohua Yan, Lili Guo, Huadong Zhao, Mengying Wei, Niuniu Hou, Jing Ye, Zhe Wang, Changhong Shi, Suling Liu, Ceshi Chen, Suning Chen, Ting Wang, Jun Yi, JianPing Zhou, Libo Yao, Wenxia Zhou, Rui Ling, Jian Zhang
Journal: Molecular Therapy (2022)

Cancer cells respond to various stressful conditions through the dynamic regulation of RNA m6A modification. Doxorubicin is a widely used chemotherapeutic drug that induces DNA damage. It is interesting to know whether cancer cells regulate the DNA damage response and doxorubicin sensitivity through RNA m6A modification. Here, we found that doxorubicin treatment significantly induced RNA m6A methylation in breast cancer cells in both a dose- and a time-dependent manner. However, protein arginine methyltransferase 5 (PRMT5) inhibited RNA m6A modification under doxorubicin treatment by enhancing the nuclear translocation of the RNA demethylase AlkB homolog 5 (ALKBH5), which was previously believed to be exclusively localized in the nucleus. Then, ALKBH5 removed the m6A methylation of BRCA1 for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells. Importantly, we identified the approved drug tadalafil as a novel PRMT5 inhibitor that could decrease RNA m6A methylation and increase doxorubicin sensitivity in breast cancer. The strategy of targeting PRMT5 with tadalafil is a promising approach to promote breast cancer sensitivity to doxorubicin through RNA methylation regulation.
Varying Impact of Gestational Diabetes Mellitus on Incidence of Childhood Cancers: An Age-Stratified Retrospective Cohort Study
Authors: Sophie Marcoux, Gabriel Côté-Corriveau, Jessica Healy-Profitós, Nathalie Auger
Journal: Diabetes Care (2022)

OBJECTIVE We studied the association between gestational diabetes mellitus and early versus late childhood cancer. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study of 1 million children born between 2006 and 2019 in Quebec, Canada. We identified children who were exposed to gestational diabetes mellitus in utero and followed them from birth up to 14 years of age to identify new-onset cancers. We estimated hazard ratios (HRs) for the association between gestational diabetes mellitus and childhood cancer using Cox proportional regression models with adjustment for covariates through inverse propensity score weights. RESULTS A total of 83,626 children (8.2%) were exposed to gestational diabetes mellitus, and 1,702 developed cancer during 7.6 million person-years of follow-up. Children exposed to gestational diabetes mellitus had a higher risk of any cancer (HR 1.19, 95% CI 1.01–1.40), with signals present for blood cancer (HR 1.27, 95% CI 0.92–1.76) and solid tumors (HR 1.14, 95% CI 0.94–1.40). The association between gestational diabetes mellitus and cancer was strongest early in life and decreased with age. Gestational diabetes mellitus was associated with 1.47 times the risk of any cancer (95% CI 1.21–1.79), 1.44 times the risk of solid cancer (95% CI 1.12–1.87), and 1.61 times the risk of blood cancer (95% CI 1.09–2.36) in children age &amp;lt;2 years. Gestational diabetes mellitus was not significantly associated with blood or solid cancers after 2 years of age, and all associations disappeared after 6 years. CONCLUSIONS Hyperglycemia may be carcinogenic in utero and may be a novel risk factor for early childhood cancer.
Incidence and Natural History of Pediatric Large Vessel Occlusion Stroke
Authors: Kartik D. Bhatia, Romain Briest, Robert Goetti, Richard Webster, Christopher Troedson, Russell C. Dale, Prakash Muthusami, Christina Miteff, Ferdinand Miteff, John Worthington, Kylie Tastula, Timothy Ang, Ian Andrews
Journal: JAMA Neurology (2022)

The incidence and natural history of large vessel occlusion (LVO) stroke in children is largely unknown. These knowledge gaps limit the uptake of reperfusion therapies and reduce the efficiency of pediatric acute stroke pathways.To determine the incidence and natural history of pediatric LVO stroke.This retrospective population-based cohort study was conducted between January 2010 and December 2019, with a mean (SD) follow-up of 37.0 (28.8) months. Admissions from all pediatric hospitals in the state of New South Wales, Australia, with a final diagnosis of arterial ischemic stroke (AIS) in patients 1 month to younger than 17 years were included. A total of 85 of 251 identified cases were excluded based on selection criteria. Data were analyzed from July 2020 to June 2021.One-third of patients with LVO received mechanical thrombectomy with or without intravenous thrombolysis while the remainder were treated conservatively.The primary outcome was the pediatric modified Rankin Scale (ped-mRS) score 3 months after stroke. Ordinal logistic regression was used to compare non-LVO, LVO without thrombectomy, and LVO with thrombectomy groups.Of 161 included patients, 56 (34.8%) were female, and the mean (SD) age was 6.1 (5.4) years. A total of 166 AIS admissions were studied, and clinical follow-up was available for 164 of 166 admissions. LVO was present in 39 admissions (23.5%). The incidence of LVO stroke was 0.24 per 100 000 patients per year (95% CI, 0.13-0.35). Patients with LVO who did not receive thrombectomy (n = 26) had poor neurological outcomes, with 19 (73.1%) experiencing moderate to severe disability or death (ped-mRS score of 3 to 6) at 3 months (6 of 12 patients receiving thrombectomy [50.0%]; 25 of 38 patients with LVO [65.8%]). Patients with LVO without thrombectomy had significantly worse clinical outcomes than patients with non-LVO at 3 months (odds ratio, 3.64; 95% CI, 1.68-7.87; P = .001). Most patients with LVO presented within time windows suitable for thrombectomy (27 of 39 [69.2%] within 6 hours; 35 of 39 [89.7%] within 24 hours).In this population-based cohort study, the natural history of pediatric patients with LVO stroke treated conservatively was poor, with most experiencing lifelong disability or death. Nearly 90% of pediatric patients with LVO presented within time windows suitable for thrombectomy.
AGE-RELATED EFFECTS OF COVID-19 PANDEMIC ON MECHANICAL REPERFUSION AND 30-DAY MORTALITY FOR STEMI: RESULTS OF THE ISACS-STEMI COVID-19 REGISTRY
Authors: Monica Verdoia, Magdy Algowhary, Berat Uguz, Dinaldo Cavalcanti Oliveira, Vladimir Ganyukov, Busljetiki Oliver, Miha Cercek, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, Alexandre S. Quadros, Gerard Roura I Ferrer, Krzysztof Milewski, Fortunato Scotto d'Uccio, Clemens von Birgelen, Francesco Versaci, Aaron Wong, Giuliana Cortese, Guido Parodi, Mohamed Burgadha, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Matteo Nardin, Giuseppe De Luca
Journal: Journal of the American College of Cardiology (2022)
THE RELATIONSHIP BETWEEN FEMALE SEX AND STROKE RATE IN ELDERLY PATIENTS WITH ATRIAL FIBRILLATION
Authors: Hifza Buhari, Lu Han, Peter Austin, Paul Dorian, Cynthia Jackevicius, Moira Kapral, Sheldon M.S. Singh, Karen Tu, Amy Yu, Dennis T. Ko, Husam Mohamed Abdel-Qadir
Journal: Journal of the American College of Cardiology (2022)
Patterns in the Management of Low-Grade Non–Muscle-Invasive Bladder Cancer—the Human and Economic Costs of Excessive Surveillance
Authors: Grayden S. Cook, Jeffrey M. Howard
Journal: JAMA Network Open (2022)

Kelly K. Bree, MD; Yong Shan, PhD; Patrick J. Hensley, MD; Niyati Lobo, MD; Chengrui Hu, BS; Douglas S. Tyler, MD; Karim Chamie, MD; Ashish M. Kamat, MD; Stephen B. Williams, MD, MS
Association Between Physical Activity and Risk of Disabling Dementia in Japan
Authors: Hikaru Ihira, Norie Sawada, Manami Inoue, Nobufumi Yasuda, Kazumasa Yamagishi, Hadrien Charvat, Motoki Iwasaki, Shoichiro Tsugane
Journal: JAMA Network Open (2022)

The associations of daily total physical activity and total moderate to vigorous physical activity (MVPA) with dementia are still unclear.
Signal Transducer and Activator of Transcription 5B Deficiency–associated Lung Disease
Authors: Katie A. Krone, Corinne L. Foley, Martha P. Fishman, Sara O. Vargas, Lisa R. Forbes, T. J. Vece, Waleed Al-Herz, Brenna Carey, Sung-Yun Pai, Vivian Hwa, Bruce C. Trapnell
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Signal Transducer and Activator of Transcription 5B Deficiency–associated Lung Disease." American Journal of Respiratory and Critical Care Medicine, 205(10), pp. 1245–1250
UNEXPECTED SUDDEN CARDIAC ARREST DUE TO VENTRICULAR FIBRILLATION IN A 7-YEAR-OLD BOY WITH DUCHENNE MUSCULAR DYSTROPHY WITH ADVANCED MYOCARDIAL FIBROSIS
Authors: Christiane Mhanna, Shannon Nees, Diana Corao-Uribe, Takeshi Tsuda
Journal: Journal of the American College of Cardiology (2022)
USE OF ANGIOVAC DEVICE FOR DEBULKING OF INFERIOR VENA CAVA-RIGHT ATRIAL OBSTRUCTION SECONDARY TO HEPATOCELLULAR CARCINOMA
Authors: Siddharth Agarwal, Satyam Krishan, Muhammad Faraz Anwaar, Mohamad Khattab, Sandeep Mahlesh Patel
Journal: Journal of the American College of Cardiology (2022)
Direct detection of RNA modifications and structure using single-molecule nanopore sequencing
Authors: William Stephenson, Roham Razaghi, Steven Busan, Kevin M. Weeks, Winston Timp, Peter Smibert
Journal: Cell Genomics (2022)

Modifications are present on many classes of RNA, including tRNA, rRNA, and mRNA. These modifications modulate diverse biological processes such as genetic recoding and mRNA export and folding. In addition, modifications can be introduced to RNA molecules using chemical probing strategies that reveal RNA structure and dynamics. Many methods exist to detect RNA modifications by short-read sequencing; however, limitations on read length inherent to short-read-based methods dissociate modifications from their native context, preventing single-molecule modification analysis. Here, we demonstrate direct RNA nanopore sequencing to detect endogenous and exogenous RNA modifications on long RNAs at the single-molecule level. We detect endogenous 2'-O-methyl and base modifications across E. coli and S. cerevisiae ribosomal RNAs as shifts in current signal and dwell times distally through interactions with the helicase motor protein. We further use the 2'-hydroxyl reactive SHAPE reagent acetylimidazole to probe RNA structure at the single-molecule level with readout by direct nanopore sequencing.
A COMPARISON OF METHODS TO EVALUATE THE REAL-WORLD SAFETY AND EFFECTIVENESS OF THE PERCUTANEOUS MICROAXIAL LEFT VENTRICULAR ASSIST DEVICE IN CARDIOGENIC SHOCK
Authors: Zaid Almarzooq, Yang Song, Issa J. Dahabreh, Ajar Kochar, Enrico Ferro, Eric Alexander Secemsky, Robert W. Yeh
Journal: Journal of the American College of Cardiology (2022)
Default Nudges in Medicine—Designing the Right Choice
Authors: Jenny Jia, Jeffrey A. Linder
Journal: JAMA Network Open (2022)

Shivan J. Mehta, MD, MBA, MSHP; Jessie Torgersen, MD, MHS, MSCE; Dylan S. Small, PhD; Colleen P. Mallozzi, MBA, RN; John D. McGreevey III, MD; Charles A.L. Rareshide, MS; Chalanda N. Evans, MPH; Mika Epps, RN, MSN; David Stabile, RN, MSN; Christopher K. Snider, MPH; Mitesh S. Patel, MD, MBA
OPTIMAL REPERFUSION STRATEGY IN ACUTE HIGH-RISK PULMONARY EMBOLISM REQUIRING EXTRACORPOREAL MEMBRANE OXYGENATION SUPPORT: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Romain Chopard, Peter Nielsen, Fabio Ius, Serghei Cebotari, Fiona Ecarnot, Hugo Pilichowski, Matthieu Schmidt, Benedict Kjaergaard, Iago Sousa, Mehrdad Ghoreishi, Rajeev L. Narayan, Su Nam Lee, Gregory Piazza, Nicolas F. Meneveau
Journal: Journal of the American College of Cardiology (2022)
URINE TROPONIN EXCRETION IN PATIENTS WITH AND WITHOUT RENAL FAILURE
Authors: Yasmeen Abu Fraiha, Roi Weistriech, Vladimir Fridman, Yosef Haviv, Yigal Abramowitz, Merav Cohen, Gal Tsaban, Amjad Abu Salman
Journal: Journal of the American College of Cardiology (2022)
Abstract P3-19-24: Long-term follow-up results of intensity modulated radiotherapy in early-stage breast cancer patients
Authors: Zita Zolcsák, Pierre Loap, Alain Fourquet, Alexandre Arsene Henry, László Landherr, Péter Hamar, Youlia Kirova
Journal: Cancer Research (2022)

Abstract Introduction: Early breast cancer patients with complex anatomy received adjuvant intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) in our Institute. The aim of this study was to evaluate our results in terms of local control, overall survival, progression free survival and adverse events. Materials and methods: This study is a retrospective data analysis, enrolling patients treated with helical tomotherapy irradiation technique. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups. Long-term toxicities were evaluated using Common Terminology Criteria of Adverse Events (CTCAE) version 4.0. Multivariable analysis was performed to determine the predictors of the toxicities. Results: Between 2009 and 2015, 174 patients with 194 treated breasts were irradiated with helical tomotherapy. The median follow-up was 65 months. The 8-year OS was 89,2 % (IC95: 83.5% - 95.4 %), the 8-year PFS was 85,4% (IC95: 80.2%- 91%). The best therapeutic response shown by the 5 year OS data was in the HER2 receptor positive subroup 95% (IC95: 85.9% - 100%). Long-term skin toxicity was the most common long-term side effect, seen in 20.7% of the patients. 5 patients had second primary breast cancer, always located at the contralateral breast. In multivariant analysis, BMI&amp;gt;25 kg/m2 was found to be a predictor of skin toxicity, and pre-existing cardiovascular disease was independently associated with the risk of cardiovascular toxicity. Conclusion: HT can be safely used for adjuvant breast cancer irradiation. In patients with complex anatomy, HT improves clinical target volume coverage and reduces the dose to OARs. Further prospective studies with long follow-up are needed to confirm and validate these results. Citation Format: Zita Zolcsák, Pierre Loap, Alain Fourquet, Alexandre Arsene Henry, László Landherr, Péter Hamar, Youlia Kirova. Long-term follow-up results of intensity modulated radiotherapy in early-stage breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-24.
ASSOCIATION OF ATRIAL FIBRILLATION WITH IN-HOSPITAL OUTCOMES OF WOMEN WITH PERIPARTUM CARDIOMYOPATHY
Authors: Kashyap Shah, Vivek Amit Modi, Israa Taha, Harshith Thyagaturu, Matthew Krinock, Maharshi Pandya, Michael Durkin, Jamshid Shirani
Journal: Journal of the American College of Cardiology (2022)