tbuckley/cabot-search huggingface dataset:
Abstract ES13-1: Targeting EZH2 functions
Authors: CG Kleer
Journal: Cancer Research (2022)

Abstract Anaplasia, or loss of mature specialized features, is a characteristic of malignant cells. Thus, it is not surprising that deregulation of proteins that govern cell type identity may lead to cancer. EZH2, a Polycomb group protein which regulates transcriptional memory in normal cells through H3K27 trimethylation, is overexpressed in breast cancer compared to normal breast, and is a tissue-based biomarker of survival in patients with breast cancer. EZH2 enhances breast cancer initiation and progression, making it a desirable therapeutic target with several inhibitors already in clinical trials. While the main mechanism of EZH2 oncogenic function has been ascribed to trimethylation of H3K27, mounting evidence supports that EZH2 also functions through non-canonical H3K27me3-independent mechanisms, especially in triple negative breast carcinomas (TNBC). These include transcriptional activation through direct binding to the NOTCH1 promoter to regulate cancer stem cells, and EZH2 phosphorylation at specific sites to either reduce affinity for histone H3 and/or increase binding to nonhistone proteins to promote metastasis. This body of work highlights the importance of blocking EZH2 H3K27me3-dependent as well as non-canonical functions in TNBC to improve outcomes. In this Educational Session, I will discuss current insights into EZH2 oncogenic mechanisms in TNBC including metaplastic carcinomas, an aggressive and chemoresistant TNBC subtype. We will also discuss how the discovery of novel EZH2 mechanisms may set the stage for the development of previously unconsidered therapeutic opportunities. Citation Format: CG Kleer. Targeting EZH2 functions [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 ES13-1.
OUTCOMES OF DIABETIC PATIENTS COMPARED TO NON-DIABETIC PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION AND SUBSEQUENT TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Roberto Herrera, Ahmed Sayed Ahmed, Parsa Mirmehdi, Mohammed Al-Hijji, Mayra Guerrero, Mandeep Singh, Charanjit S. Rihal, S. Michael Gharacholou, Abdallah El Sabbagh
Journal: Journal of the American College of Cardiology (2022)
ASSOCIATION OF TRANSTHYRETIN VAL122ILE VARIANT WITH INCIDENT HEART FAILURE AND MORTALITY AMONG BLACK AMERICANS
Authors: Vibhu Parcha, Gargya Malla, Marguerite Ryan Irvin, Nicole Armstrong, Suzanne Judd, Leslie Lange, Mathew S. Maurer, Emily Levitan, Parag Goyal, Garima Arora, Pankaj Arora
Journal: Journal of the American College of Cardiology (2022)
USEFULNESS OF NEW METHOD TO QUANTIFY PERICORONARY ADIPOSE TISSUE ON ECG-GATED NON-CONTRAST CHEST CT SCAN
Authors: Daigo Takahashi, Shinichiro Fujimoto, Yui Okada Nozaki, Ayako Kudo, Chihiro Aoshima, Yuki Kamo, Yuko Kawaguchi, Kazuhisa Takamura, Makoto Hiki, Hideyuki Sato, Nobuo Tomizawa
Journal: Journal of the American College of Cardiology (2022)
Global landscape of SARS-CoV-2 genomic surveillance and data sharing
Authors: Zhiyuan Chen, Andrew S. Azman, Xinhua Chen, Junyi Zou, Yuyang Tian, Ruijia Sun, Xiangyanyu Xu, Yani Wu, Wanying Lu, Shijia Ge, Zeyao Zhao, Juan Yang, Daniel T. Leung, Daryl B. Domman, Hongjie Yu
Journal: Nature Genetics (2022)

Abstract Genomic surveillance has shaped our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. We performed a global landscape analysis on SARS-CoV-2 genomic surveillance and genomic data using a collection of country-specific data. Here, we characterize increasing circulation of the Alpha variant in early 2021, subsequently replaced by the Delta variant around May 2021. SARS-CoV-2 genomic surveillance and sequencing availability varied markedly across countries, with 45 countries performing a high level of routine genomic surveillance and 96 countries with a high availability of SARS-CoV-2 sequencing. We also observed a marked heterogeneity of sequencing percentage, sequencing technologies, turnaround time and completeness of released metadata across regions and income groups. A total of 37% of countries with explicit reporting on variants shared less than half of their sequences of variants of concern (VOCs) in public repositories. Our findings indicate an urgent need to increase timely and full sharing of sequences, the standardization of metadata files and support for countries with limited sequencing and bioinformatics capacity.
LONG STORY SHORT. LONG-TERM OUTCOMES IN ALCOHOL SEPTAL ABLATION VS SEPTAL MYECTOMY IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Sanskriti Shrivastava, Hamza Hanif, Raza Naseer, Muhammad Siddique Pir, Najam U. Saqib, Mahboob Alam
Journal: Journal of the American College of Cardiology (2022)
Abstract P1-01-02: Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping
Authors: Rak Saengphongchawan, Sopark Manasnayakorn
Journal: Cancer Research (2022)

Abstract Background Breast cancer is the most common cancer in female patients worldwide. Although axillary management in breast cancer has been de-escalated to reduce untoward effects, breast cancer-related lymphedema (BCRL) is still not uncommon. Axillary reverse mapping (ARM) emerges as a novel technique that identifies the lymphatic system draining the upper extremities. Preservation of this system and associated lymph nodes theoretically reduces the chance of BCRL. However, concerns regarding oncologic safety have limited the adoption of the technique. Objective To identify factors associated with metastatic disease in lymph nodes identified by ARM in breast cancer patients. Materials and methods Breast cancer patients treated at King Chulalongkorn Memorial Hospital from October 2018 to January 2021 who underwent axillary lymph node dissection (ALND) underwent concurrent ARM whereby five milliliters of 1% isosulfan blue dye was injected at the medial aspect of the arm as previously described elsewhere. Patient demographics and clinical data such as clinical staging, pathological staging, cancer subtype, and whether neoadjuvant chemotherapy was administered were collected and analyzed. Result Thirty-six patients with a median age of 57 were included in this prospective study. ARM lymph node identification success rate was 83% (30 of 36 patients) with a median of 2 identified ARM lymph nodes (range 0-11 nodes). Metastatic disease in ARM nodes was present in 30% of patients. ARM success rate did not depend on whether preoperative chemotherapy had been given (ARM lymph nodes identified in 7 out of 8 patients without preoperative chemotherapy and 23 out of 28 in patients with preoperative chemotherapy; p=0.36). There was no statistically significant difference in metastatic disease in ARM-identified nodes and clinical stage (stage II=13.3%, stage III=33.3%, and stage IV=50.0%; p=0.18). However, higher pathologic N stage was associated with finding metastasis in ARM-identified lymph nodes (N0=0%, N1=15.8%, N2=33.3%, and N3=80%; p=0.005). Conclusions ARM is a novel technique which can potentially reduce BCRL. However, a significant number of ARM lymph nodes were found to have pathologically-proven metastatic disease, especially in higher pathologic N stages (pN2 and pN3). Therefore, for oncologic safety, consideration should be given to removal of all ARM lymph nodes in breast cancer patients undergoing formal axillary dissection. Keywords: Axillary Reverse Mapping, Axillar dissection, Lymphedema, Breast Cancer Citation Format: Rak Saengphongchawan, Sopark Manasnayakorn. Pathologic nodal status is a predictor for metastatic disease in lymph nodes identified by axillary reverse mapping [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 P1-01-02.
Physical activity as a protective factor for dementia and Alzheimer’s disease: systematic review, meta-analysis and quality assessment of cohort and case–control studies
Authors: Paula Iso-Markku, Urho M Kujala, Keegan Knittle, Juho Polet, Eero Vuoksimaa, Katja Waller
Journal: British Journal of Sports Medicine (2022)

Objective Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This meta-analysis investigates the effect of study length on the association. Design A systematic review and meta-analysis. Pooled effect sizes, dose–response analysis and funnel plots were used to synthesise the results. Data sources CINAHL (last search 19 October 2021), PsycInfo, Scopus, PubMed, Web of Science (21 October 2021) and SPORTDiscus (26 October 2021). Eligibility criteria Studies of adults with a prospective follow-up of at least 1 year, a valid cognitive measure or cohort in mid-life at baseline and an estimate of the association between baseline PA and follow-up all-cause dementia, Alzheimer’s disease or vascular dementia were included (n=58). Results PA was associated with a decreased risk of all-cause dementia (pooled relative risk 0.80, 95% CI 0.77 to 0.84, n=257 983), Alzheimer’s disease (0.86, 95% CI 0.80 to 0.93, n=128 261) and vascular dementia (0.79, 95% CI 0.66 to 0.95, n=33 870), even in longer follow-ups (≥20 years) for all-cause dementia and Alzheimer’s disease. Neither baseline age, follow-up length nor study quality significantly moderated the associations. Dose–response meta-analyses revealed significant linear, spline and quadratic trends within estimates for all-cause dementia incidence, but only a significant spline trend for Alzheimer’s disease. Funnel plots showed possible publication bias for all-cause dementia and Alzheimer’s disease. Conclusion PA was associated with lower incidence of all-cause dementia and Alzheimer’s disease, even in longer follow-ups, supporting PA as a modifiable protective lifestyle factor, even after reducing the effects of reverse causation.
CLO22-087: Safety and Effectiveness of Continuous Denosumab for Unresectable or Advanced Giant Cell Tumor: Monthly and Once Every Three Months Regimen
Authors: Anastasia Tararykova, Alexander Fedenko, Elmar Musaev
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-087: Safety and Effectiveness of Continuous Denosumab for Unresectable or Advanced Giant Cell Tumor: Monthly and Once Every Three Months Regimen" published on 31 Mar 2022 by National Comprehensive Cancer Network.
IMPACT OF VENTRICULAR ARRHYTHMIA ON IN-HOSPITAL OUTCOMES IN PATIENT WITH SARCOIDOSIS
Authors: Kashyap Shah, Israa Taha, Harshith Thyagaturu, Vivek Amit Modi, Matthew Krinock, Maharshi Pandya, Chris Cutitta, Michael J. Durkin
Journal: Journal of the American College of Cardiology (2022)
Natural language processing diagnosed behavioral disturbance vs confusion assessment method for the intensive care unit: prevalence, patient characteristics, overlap, and association with treatment and outcome
Authors: Marcus Young, Natasha Holmes, Kartik Kishore, Nada Marhoon, Sobia Amjad, Ary Serpa-Neto, Rinaldo Bellomo
Journal: Intensive Care Medicine (2022)

To compare the prevalence, characteristics, drug treatment for delirium, and outcomes of patients with Natural Language Processing (NLP) diagnosed behavioral disturbance (NLP-Dx-BD) vs Confusion Assessment Method for intensive care unit (CAM-ICU) positivity. In three combined medical-surgical ICUs, we obtained data on demographics, treatment with antipsychotic medications, and outcomes. We applied NLP to caregiver progress notes to diagnose behavioral disturbance and analyzed simultaneous CAM-ICU. We assessed 2313 patients with a median lowest Richmond Agitation-Sedation Scale (RASS) score of − 2 (− 4.0 to − 1.0) and median highest RASS score of 1 (0 to 1). Overall, 1246 (53.9%) patients were NLP-Dx-BD positive (NLP-Dx-BDpos) and 578 (25%) were CAM-ICU positive (CAM-ICUpos). Among NLP-Dx-BDpos patients, 539 (43.3%) were also CAM-ICUpos. In contrast, among CAM-ICUpos patients, 539 (93.3%) were also NLP-Dx-BDpos. The use of antipsychotic medications was highest in patients in the CAM-ICUpos and NLP-Dx-BDpos group (24.3%) followed by the CAM-ICUneg and NLP-Dx-BDpos group (10.5%). In NLP-Dx-BDneg patients, antipsychotic medication use was lower at 5.1% for CAM-ICUpos and NLP-Dx-BDneg patients and 2.3% for CAM-ICUneg and NLP-Dx-BDneg patients (overall P < 0.001). Regardless of CAM-ICU status, after adjustment and on time-dependent Cox modelling, NLP-Dx-BD was associated with greater antipsychotic medication use. Finally, regardless of CAM-ICU status, NLP-Dx-BDpos patients had longer duration of ICU and hospital stay and greater hospital mortality (all P < 0.001). More patients were NLP-Dx-BD positive than CAM-ICU positive. NLP-Dx-BD and CAM-ICU assessment describe partly overlapping populations. However, NLP-Dx-BD identifies more patients likely to receive antipsychotic medications. In the absence of NLP-Dx-BD, treatment with antipsychotic medications is rare.
Confirmed Drop in Treatment of Patients with Incident End-Stage Kidney Disease During the Novel Coronavirus Disease 2019 Pandemic
Authors: Lucas Jacobs, Arnaud Devresse, Thomas Baudoux, Frédéric Collart
Journal: Journal of the American Society of Nephrology (2022)

We read with great interest the study by Wetmore et al.1 showing a drop in the number of patients starting hemodialysis (HD), peritoneal dialysis (PD), or being transplanted preemptively in the context of the coronavirus disease 2019 pandemic. Similar results emerged from the Belgian Registry (Brussels-Capital and Wallonia regions) that aims to annually collect data regarding incident patients with ESKD in the 26 centers participating to the "Groupement des Néphrologues Francophones de Belgique." In 2018, 971 patients started their treatment for ESKD (dialysis initiation or preemptive transplantation), 970 in 2019 but only 892 in 2020,showing an 8% drop. Monthly comparisons showed that this decrease started in March 2020, when the coronavirus disease 2019 pandemic peaked in Belgium. The same trend was observed for each age group, regardless of primary kidney disease. In addition, contrasting with the Wetmore et al. data,1 incident number and percentage of patients starting peritoneal dialysis, home HD, or receiving a preemptive kidney transplantation also decreased in 2020 compared with 2019 (a 33%, 50%, and 36% drop, respectively, compared with 2019) suggesting that home techniques were not favored in the context of the pandemic. In conclusion, the year 2020 was marked by an 8% incidence drop of patients who started a treatment for ESKD, with a particularly marked decline in home dialysis programs (PD and HD) and preemptive kidney transplantation. Disclosures T. Baudoux serves as a consultant for Astra-Zeneca. F. Collart has received honoraria from Astrazeneca and Vifor, and is a member of advisory boards for Vifor. A. Devresse is a member of advisory boards for Alnylam Pharmaceuticals. Funding This study received support from the Belgian federal government.
Stakeholder Research Priorities to Promote Implementation of Shared Decision-Making for Lung Cancer Screening: An American Thoracic Society and Veterans Affairs Health Services Research and Development Statement
Authors: Renda Soylemez Wiener, Anna M. Barker, Lisa Carter-Harris, Tanner J. Caverly, David A. Crocker, Angela Denietolis, Charlotte Doherty, Angela Fagerlin, Mary Gallagher-Seaman, Michael K. Gould, Paul K. J. Han, Abigail N. Herbst, Mayuko Ito Fukunaga, Megan B. McCullough, Danielle A. Miano, Samantha L. Quaife, Christopher G. Slatore, Gemmae M. Fix
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Shared decision-making (SDM) for lung cancer screening (LCS) is recommended in guidelines and required by Medicare, yet it is seldom achieved in practice. The best approach for implementing SDM for LCS remains unknown, and the 2021 U.S. Preventive Services Task Force calls for implementation research to increase uptake of SDM for LCS. Objectives: To develop a stakeholder-prioritized research agenda and recommended outcomes to advance implementation of SDM for LCS. Methods: The American Thoracic Society and VA Health Services Research and Development Service convened a multistakeholder committee with expertise in SDM, LCS, patient-centered care, and implementation science. During a virtual State of the Art conference, we reviewed evidence and identified research questions to address barriers to implementing SDM for LCS, as well as outcome constructs, which were refined by writing group members. Our committee (n = 34) then ranked research questions and SDM effectiveness outcomes by perceived importance in an online survey. Results: We present our committee’s consensus on three topics important to implementing SDM for LCS: 1) foundational principles for the best practice of SDM for LCS; 2) stakeholder rankings of 22 implementation research questions; and 3) recommended outcomes, including Proctor’s implementation outcomes and stakeholder rankings of SDM effectiveness outcomes for hybrid implementation–effectiveness studies. Our committee ranked questions that apply innovative implementation approaches to relieve primary care providers of the sole responsibility of SDM for LCS as highest priority. We rated effectiveness constructs that capture the patient experience of SDM as most important. Conclusions: This statement offers a stakeholder-prioritized research agenda and outcomes to advance implementation of SDM for LCS.
Prime-seq, efficient and powerful bulk RNA sequencing
Authors: Aleksandar Janjic, Lucas E. Wange, Johannes W. Bagnoli, Johanna Geuder, Phong Nguyen, Daniel Richter, Beate Vieth, Binje Vick, Irmela Jeremias, Christoph Ziegenhain, Ines Hellmann, Wolfgang Enard
Journal: Genome biology (2022)

Cost-efficient library generation by early barcoding has been central in propelling single-cell RNA sequencing. Here, we optimize and validate prime-seq, an early barcoding bulk RNA-seq method. We show that it performs equivalently to TruSeq, a standard bulk RNA-seq method, but is fourfold more cost-efficient due to almost 50-fold cheaper library costs. We also validate a direct RNA isolation step, show that intronic reads are derived from RNA, and compare cost-efficiencies of available protocols. We conclude that prime-seq is currently one of the best options to set up an early barcoding bulk RNA-seq protocol from which many labs would profit.
Cumulative burden of psychiatric disorders and self-harm across 26 adult cancers
Authors: Wai Hoong Chang, Alvina G. Lai
Journal: Nature Medicine (2022)

Abstract Cancer is a life-altering event causing considerable psychological distress. However, information on the total burden of psychiatric disorders across all common adult cancers and therapy exposures has remained scarce. Here, we estimated the risk of self-harm after incident psychiatric disorder diagnosis in patients with cancer and the risk of unnatural deaths after self-harm in 459,542 individuals. Depression was the most common psychiatric disorder in patients with cancer. Patients who received chemotherapy, radiotherapy and surgery had the highest cumulative burden of psychiatric disorders. Patients treated with alkylating agent chemotherapeutics had the highest burden of psychiatric disorders, whereas those treated with kinase inhibitors had the lowest burden. All mental illnesses were associated with an increased risk of subsequent self-harm, where the highest risk was observed within 12 months of the mental illness diagnosis. Patients who harmed themselves were 6.8 times more likely to die of unnatural causes of death compared with controls within 12 months of self-harm (hazard ratio (HR), 6.8; 95% confidence interval (CI), 4.3–10.7). The risk of unnatural death after 12 months was markedly lower (HR, 2.0; 95% CI, 1.5–2.7). We provide an extensive knowledge base to help inform collaborative cancer-psychiatric care initiatives by prioritizing patients who are most at risk.
An Updated Approach and Understanding of Breast Implant–Associated Anaplastic Large Cell Lymphoma
Authors: Neha Mehta-Shah, Paola Ghione
Journal: Journal of the National Comprehensive Cancer Network (2022)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare subtype of T-cell non-Hodgkin lymphoma that is usually localized to the fluid and capsule surrounding a breast implant. There have only been <1,000 cases and 36 deaths reported to date and the average patient presents 7 to 10 years following initial breast implant placement. Most patients present with delayed seromas, a breast mass, capsular abnormalities, lymphadenopathy, or cutaneous masses. Unlike other forms of non-Hodgkin lymphoma, most cases are cured with surgery alone. The challenge of BIA-ALCL surrounds its rarity-in regard to both its diagnosis as well as the limited available data to guide therapy for more advanced cases. Careful pathology evaluation to analyze both the fluid surrounding the capsule and the capsule itself is critical. Studies to identify which patients are at greater risk of development of this rare entity are ongoing.
IS ALCOHOL CONSUMPTION ASSOCIATED WITH A LOWER RISK OF CARDIOVASCULAR EVENTS IN PATIENTS TREATED WITH STATINS? AN OBSERVATIONAL REAL-WORLD EXPERIENCE
Authors: Jeffrey L. Anderson, Viet T. Le, Tami L. Bair, J. Brent Muhlestein, Kirk U. Knowlton, Benjamin Davies Horne
Journal: Journal of the American College of Cardiology (2022)
Identification and validation of ecto-5' nucleotidase as an immunotherapeutic target in multiple myeloma
Authors: Arghya Ray, Yan Song, Ting Du, Leutz Buon, Yu-Tzu Tai, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood Cancer Journal (2022)

Abstract Interaction of plasmacytoid dendritic cells (pDCs) with multiple myeloma (MM) cells, T- or NK-effector cells in the bone marrow (BM) microenvironment induces tumor cell growth, as well as inhibits innate and adaptive immune responses. Defining pDC-MM interaction-triggered immunosuppressive mechanism(s) will enable design of interventional therapies to augment anti-MM immunity. In the present study, we show that pDC-MM interactions induce metabolic enzyme Ecto-5' Nucleotidase/CD73 in both pDCs and MM cells. Gene expression database from MM patients showed that CD73 levels inversely correlate with overall survival. Using our pDC-MM coculture models, we found that blockade of CD73 with anti-CD73 Abs: decreases adenosine levels; activates MM patient pDCs; triggers cytotoxic T lymphocytes (CTL) activity against autologous patient MM cells. Combination of anti-CD73 Abs and an immune-stimulating agent TLR-7 agonist enhances autologous MM-specific CD8 + CTL activity. Taken together, our preclinical data suggest that the therapeutic targeting of CD73, alone or in combination with TLR-7 agonist, represents a promising novel strategy to restore host anti-MM immunity.
CONCURRENT WALDENSTROM MACROGLOBULINEMIA AND HEREDITARY ATTR AMYLOIDOSIS IN AN ELDERLY MALE: TUMOR IS THE RUMOR, TISSUE IS THE ISSUE
Authors: Xiaoxiao Qian, Hooman Bakhshi, Raghav Gattani, Araba Ofosu-Somuah, Dennis T. Kim, Jamie Kennedy
Journal: Journal of the American College of Cardiology (2022)
LEFT VENTRICULAR PSEUDOANEURYSM AS A COMPLICATION OF MITRAL VALVE REPLACEMENT SURGERY
Authors: Fernanda Soares, Camila Almeida, Tarso Augusto Accorsi, Flavio Tarasoutchi, Layara Fernanda Lipari, Thiago Pereira, Fernanda Tessari, Bernardo Siqueira, Renan Oliveira, Matheus Luan Cunha
Journal: Journal of the American College of Cardiology (2022)