tbuckley/cabot-search huggingface dataset:
THE IMPACT OF HEART FAILURE ETIOLOGY AND PROGNOSTIC DISCHARGE TREATMENT ON ONE-YEAR ALL-CAUSE MORTALITY IN A CENTRAL ASIAN AND A WESTERN EUROPEAN ACUTE HEART FAILURE COHORT
Authors: Tamila Abdurashidova, Medet Beishenkulov, Kanzaada Zhorupbekova, Zalina Chazymova, Kurban Kalysov, Aiperi Toktosunova, Kanybek Kaliev, Georgios Tzimas, Nicolas Barras, Stefania Aur, Patrick Yerly, Pierre Monney, Matthias Kirsch, Martin Muller, Roger Hullin
Journal: Journal of the American College of Cardiology (2022)
FULLY AUTOMATED CONTOURING OF CONTRAST ENHANCED ECHOCARDIOGRAMS IN CANCER THERAPY-RELATED CARDIAC DYSFUNCTION IS FEASIBLE AND PRECISE
Authors: Ashley Akerman, Lori Bernard, Tine Deschamps, Bernadette Foster, Will Hawkes, Eila Mirhadi, Hania Piotrowska, Rizwan Sarwar, Louise Tetlow, Gary Woodward, Harald Becher
Journal: Journal of the American College of Cardiology (2022)
Abstract P5-01-10: A panel of murine mammary tumor cell lines to study immune responses to epitopes created by different mutagens including human APOBEC3 enzymes
Authors: Jordan Naumann, Michael Carpenter, Prokopios Argyris, William Brown, Reuben Harris
Journal: Cancer Research (2022)

Abstract Background: Tumor mutation loads are a strong predictor of immunotherapy benefit. This is evidenced by studies on skin, lung, and colon cancer, where well-defined processes elicit high mutation burdens and checkpoint therapies often provoke strong anti-tumor immune responses. In comparison, only a small number of breast cancer patients have responded to checkpoint therapies such as anti-PD-L1 and anti-PD-1 monoclonal antibodies. Approximately one-fourth of primary breast cancer and one-third of metastatic tumors have a significant APOBEC mutation burden defined as C-to-T and C-to-G mutations in TCA or TCT trinucleotide motifs, and many tumors have &amp;gt;10,000 of these APOBEC signature single base substitution mutations. However, to our knowledge, systematic immunotherapy studies focusing on this unique, hypermutated subset of breast cancers have yet to be done. Methods: To address the potential relationship between different checkpoint therapies and APOBEC mutation burden, we created a panel of &amp;gt;30 mammary tumor cell lines derived from fully immune-proficient C57BL/6 animals. At least 6 of these cell lines are immortalized, readily engineered using standard molecular biology procedures, and capable of re-engraftment and tumor formation in immune proficient C57BL/6 animals. Two lines were engineered to inducibly express human APOBEC3A, subjected to 1- to 20-rounds of sublethal mutagenesis, and tested systematically for checkpoint therapy responsiveness. Results: Two cell lines were engineered to inducibly express APOBEC3A or a catalytic mutant (E72A). Clones were characterized for inducible APOBEC3A expression and associated DNA damage responses. After varying rounds of mutagenesis, clones were engrafted into the subcutaneous flank or mammary fat pad of C57BL/6 animals. Immunohistochemical and flow cytometry analysis revealed a robust intratumoral CD8 T cell population including a subset with PD-1 expression. Additionally, engrafted tumor cells expressed high levels PD-L1. Experiments are ongoing and immunotherapy responses will be presented. Conclusions: We have isolated a panel of C57BL/6 mammary tumor-derived cell lines and demonstrated re-engraftment into immunocompetent animals. These cell lines constitute a platform for studying the relationship between different mutagens including APOBEC and immunotherapy responses. Citation Format: Jordan Naumann, Michael Carpenter, Prokopios Argyris, William Brown, Reuben Harris. A panel of murine mammary tumor cell lines to study immune responses to epitopes created by different mutagens including human APOBEC3 enzymes [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 P5-01-10.
Evaluation of a health and social care programme to improve outcomes following critical illness: a multicentre study
Authors: Philip Henderson, Tara Quasim, Martin Shaw, Pamela MacTavish, Helen Devine, Malcolm Daniel, Fiona Nicolson, Peter O’Brien, Ashley Weir, Laura Strachan, Lorraine Senior, Phil Lucie, Lynn Bollan, Jane Duffty, Lucy Hogg, Colette Ross, Malcolm Sim, Radha Sundaram, Theodore J Iwashyna, Joanne McPeake
Journal: Thorax (2022)

Rationale At present, clinicians aiming to support patients through the challenges after critical care have limited evidence to base interventions. Objectives Evaluate a multicentre integrated health and social care intervention for critical care survivors. A process evaluation assessed factors influencing the programme implementation. Methods This study evaluated the impact of the Intensive Care Syndrome: Promoting Independence and Return to Employment (InS:PIRE) programme. We compared patients who attended this programme with a usual care cohort from the same time period across nine hospital sites in Scotland. The primary outcome was health-related quality of life (HRQoL) measured via the EuroQol 5-dimension 5-level instrument, at 12 months post hospital discharge. Secondary outcome measures included self-efficacy, depression, anxiety and pain. Results 137 patients who received the InS:PIRE intervention completed outcome measures at 12 months. In the usual care cohort, 115 patients completed the measures. The two cohorts had similar baseline demographics. After adjustment, there was a significant absolute increase in HRQoL in the intervention cohort in relation to the usual care cohort (0.12, 95% CI 0.04 to 0.20, p= 0.01). Patients in the InS:PIRE cohort also reported self-efficacy scores that were 7.7% higher (2.32 points higher, 95% CI 0.32 to 4.31, p =0.02), fewer symptoms of depression (OR 0.38, 95% CI 0.19 to 0.76, p=0.01) and similar symptoms of anxiety (OR 0.58, 95% CI 0.30 to 1.13, p =0.11). There was no significant difference in overall pain experience. Key facilitators for implementation were: integration with inpatient care, organisational engagement, flexibility to service inclusion; key barriers were: funding, staff availability and venue availability. Conclusions This multicentre evaluation of a health and social care programme designed for survivors of critical illness appears to show benefit at 12 months following hospital discharge.
Abstract MS1-3: Targeting DNA damage response and HRD in breast cancer
Authors: TA Yap
Journal: Cancer Research (2022)

Abstract Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. These alterations promote the clonal evolution of cancer cells via the accumulation of driver aberrations, including gene copy-number changes, rearrangements and mutations; however, these same defects also create vulnerabilities that are relatively specific to cancer cells, which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The discovery that BRCA-mutant cancer cells are exquisitely sensitive to inhibition of poly(ADP-ribose) polymerase has ushered in a new era of research on biomarker-driven synthetic lethal treatment strategies for breast and other cancers. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATR, WEE1, ATM, PK-MYT1, DNA-PK, POLQ and USP1. Efforts to optimize these therapies are ongoing across a range of cancers, involving the development of predictive biomarker assays of responsiveness (beyond BRCA mutations), assessment of the mechanisms underlying intrinsic and acquired resistance, and evaluation of rational, tolerable combinations with standard-of-care treatments, novel molecularly targeted agents and immune-checkpoint inhibitors. Citation Format: TA Yap. Targeting DNA damage response and HRD in breast cancer [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 MS1-3.
HSR22-123: Breaking Cost Barriers in Treatment With Biosimilars–Improvement in Affordability of Trastuzumab Against HER2 Positive Breast Cancer Amongst Indian Women
Authors: Annie Alexander, Rakesh S Ramesh, Ravi B Diwakar, Srinath B S, T S Sridhar, Jyothi S Prabhu
Journal: Journal of the National Comprehensive Cancer Network (2022)

"HSR22-123: Breaking Cost Barriers in Treatment With Biosimilars–Improvement in Affordability of Trastuzumab Against HER2 Positive Breast Cancer Amongst Indian Women" published on 31 Mar 2022 by National Comprehensive Cancer Network.
REAL WORLD EXAMINATION OF PERCUTANEOUS CORONARY INTERVENTION VERSUS CORONARY ARTERY BYPASS GRAFTING FOR LEFT MAIN CORONARY DISEASE IN ONTARIO, CANADA
Authors: Derrick Tam, Jiming Fang, Rodolfo Rocha, Mario F.L. Gaudino, Peter Austin, Stephen E. Fremes, Douglas Lee
Journal: Journal of the American College of Cardiology (2022)
EFFICACY AND SAFETY OF THE NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANT AMONG PATIENTS WITH NONVALVUALR ATRIAL FIBRILLATION AND CANCER: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Mahmoud Barbarawi, Ahmad Al-Abdouh, Owais Barbarawi, Mohammed Mhanna, Mariam Alkasasbeh, Christopher Pickett
Journal: Journal of the American College of Cardiology (2022)
U.S. Public Health Law — Foundations and Emerging Shifts
Authors: Michelle M. Mello, Wendy E. Parmet
Journal: New England Journal of Medicine (2022)

Interview with Prof. Michelle Mello on individual rights and state and federal powers to regulate health matters in the United States. (09:46)Download The Covid pandemic has focused attention on the complex relationship between individual rights and public health protection. This tension has long occupied U.S. courts, but today some long-settled understandings in public health law are being contested and disrupted.
USING ARTIFICIAL INTELLIGENCE TO EVALUATE ADDED VALUE OF CORONARY ARTERY CALCIUM SCORING FROM STANDARD AND LOW-DOSE UNGATED CT IN MYOCARDIAL PERFUSION PET/CT IMAGING MORTALITY RISK ASSESSMENT
Authors: Bryan Bednarski, Konrad Pieszko, Aakash Shanbhag, Ananya Singh, Jacek Kwiecinski, Robert JH Miller, Yuka Otaki, Aditya Killekar, Paul Kavanagh, Serge D. Van Kriekinge, Chih-Chun Wei, Tejas Parekh, Heidi Gransar, Daniel S. Berman, Piotr Slomka
Journal: Journal of the American College of Cardiology (2022)
Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis
Authors: Brian Craven, William Lester, Sara Boyce, Will Thomas, Angela Kanny, Claire Davies, Sue Pavord, Joannes Hermans, Michael Makris, Emily Bart-Smith, Sarah Arnott, Beverley J. Hunt, Pavel Chudakou, Anthony Calvert, Deepak Singh, Marie Scully
Journal: Blood (2022)
Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis
Authors: Kyla A. Britson, Jonathan P. Ling, Kerstin E. Braunstein, Janelle M. Montagne, Jenna M. Kastenschmidt, Andrew Wilson, Chiseko Ikenaga, William Tsao, Iago Pinal-Fernandez, Katelyn A. Russell, Nicole Reed, Tahseen Mozaffar, Kathryn R. Wagner, Lyle W. Ostrow, Andrea M. Corse, Andrew L. Mammen, S. Armando Villalta, H. Benjamin Larman, Philip C. Wong, Thomas E. Lloyd
Journal: Science Translational Medicine (2022)

Sporadic inclusion body myositis (IBM) is the most common acquired muscle disease in adults over age 50, yet it remains unclear whether the disease is primarily driven by T cell–mediated autoimmunity. IBM muscle biopsies display nuclear clearance and cytoplasmic aggregation of TDP-43 in muscle cells, a pathologic finding observed initially in neurodegenerative diseases, where nuclear loss of TDP-43 in neurons causes aberrant RNA splicing. Here, we show that loss of TDP-43–mediated splicing repression, as determined by inclusion of cryptic exons, occurs in skeletal muscle of subjects with IBM. Of 119 muscle biopsies tested, RT-PCR–mediated detection of cryptic exon inclusion was able to diagnose IBM with 84% sensitivity and 99% specificity. To determine the role of T cells in pathogenesis, we generated a xenograft model by transplanting human IBM muscle into the hindlimb of immunodeficient mice. Xenografts from subjects with IBM displayed robust regeneration of human myofibers and recapitulated both inflammatory and degenerative features of the disease. Myofibers in IBM xenografts showed invasion by human, oligoclonal CD8 + T cells and exhibited MHC-I up-regulation, rimmed vacuoles, mitochondrial pathology, p62-positive inclusions, and nuclear clearance and cytoplasmic aggregation of TDP-43, associated with cryptic exon inclusion. Reduction of human T cells within IBM xenografts by treating mice intraperitoneally with anti-CD3 (OKT3) suppressed MHC-I up-regulation. However, rimmed vacuoles and loss of TDP-43 function persisted. These data suggest that T cell depletion does not alter muscle degenerative pathology in IBM.
DIFFERENCES IN CARDIAC PRESENTATIONS BETWEEN THE COVID AND PRE-COVID ERA: SINGLE TERTIARY CENTRE EXPERIENCE FROM MELBOURNE, AUSTRALIA
Authors: Kristoffer Ken Ralota, Hui Lim, Kevin Rajakariar, Natalie Maher, Vinoja Ganeshanathan, Gabriel Wong, Louise Roberts, Daniel Gayed, Danlu Liang, Brendan Backhouse, Jaya Chandrasekhar
Journal: Journal of the American College of Cardiology (2022)
ACUTE MYOCARDITIS AFTER MRNA COVID-19 VACCINATION AND DIAGNOSIS AIDED WITH CARDIAC MAGNETIC RESONANCE FINDINGS CASE SERIES IN YOUNG PATIENTS
Authors: Rupa L. Iyengar, Loba Alam, Swiri Konje, Emamuzo Otobo, Maria Pena, Soheila Talebi
Journal: Journal of the American College of Cardiology (2022)
Case 8-2022: A 54-Year-Old Woman with Episodes of Swelling
Authors: Aleena Banerji, Neelam A. Phadke, Ravi Gottumukkala, Rohit Sharma, Mandakolathur R. Murali
Journal: New England Journal of Medicine (2022)

A 54-year-old woman was evaluated in the emergency department because of abdominal pain, nausea, and vomiting. Computed tomography of the abdomen and pelvis revealed circumferential jejunal-wall thickening. Medical history was notable for episodic swelling of the arms, hands, and feet. Diagnostic tests were performed, and treatment decisions were made.
Abstract ES11-3: Optimizing immunotherapy efficacy in the clinic through biomarkers: Advances in single cell and spatial histology analyse
Authors: M Kok
Journal: Cancer Research (2022)

Abstract Single cell technologies and spatial analyses are emerging as powerful tools to investigate tumor heterogeneity, cell state of key effector or suppressing immune cells and detailed distribution of cells within the tumor microenvironment. Their application will undoubtedly provide further understanding of the effects of cancer immunotherapy on the tumor microenvironment, which is particularly important for the largely non-immunogenic breast carcinomas. However, analyses of clinical samples require well-coordinated, multidisciplinary teams and specific expertise. Moreover, large scale analyses have major technical challenges and is still relatively costly. We will discuss the promise and hurdles of single cell and spatial analyses on the road to find biomarker for breast cancer immunotherapy and avenues for novel immunomodulatory treatments for breast cancer patients. Citation Format: M Kok. Optimizing immunotherapy efficacy in the clinic through biomarkers: Advances in single cell and spatial histology analyse [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 ES11-3.
When Desperate Patients Go to Court for Unproven Treatments — The Battle for Hospital Independence
Authors: Christopher Robertson, Margaret Houtz
Journal: New England Journal of Medicine (2022)

Interview with Prof. Christopher Robertson on the outcomes and implications of cases in which patients sued hospitals for access to ivermectin. (06:18)Download During the Covid-19 pandemic, patients have asked courts to compel hospitals to administer unproven therapies, including ivermectin. These lawsuits have called into question the judiciary's role in medical decision making.
Abstract P4-02-10: Pfkfb3 inhibition significantly decreases endocrine-resistant breast cancer growth and induces necroptotic cell death
Authors: Brandon C Jones, Surojeet Sengupta, Catherine M Sevigny, Lu Jin, Paula R Pohlmann, Ayesha Shajahan-Haq, Robert Clarke
Journal: Cancer Research (2022)

Abstract Estrogen receptor-positive breast cancers constitute the majority of newly diagnosed breast cancers in patients. While commonly treated with various approved endocrine therapy strategies, these cancers can unfortunately also develop resistance to such therapies, indicating a need to explore other avenues of treatment in endocrine-resistant breast cancer. Rapidly dividing cancer cells are known to have an increased energy demand and altered reprogramming of glucose metabolism, leading to a subsequent heavy reliance on glycolysis. A critical rate-limiting step in the glycolysis pathway, the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate, is greatly influenced by an allosteric activator produced by the enzyme PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3), thus making PFKFB3 an essential regulator of glycolytic flux. Furthermore, PFKFB3 has been shown to be overexpressed in many human cancers, including breast cancer, as well as be upregulated by estrogen. Through the following work, we show that endocrine-resistant BC cell growth is strongly reduced by PFKFB3 targeting using different commercial PFKFB3 inhibitors, which can be further exacerbated by combination treatment with well-established endocrine therapies like fulvestrant in some cell lines. Moreover, we relatedly show that PFKFB3 inhibition reduced tumor size in mouse xenografts of endocrine-resistant BC cells. Endocrine-resistant cells also presented higher basal glucose uptake and greater reduction of glucose uptake in response to PFKFB3 inhibition than endocrine-sensitive cells, indicating that endocrine-resistant breast cancer cells may have a more significant reliance on glycolysis and PFKFB3 activity for their metabolic needs than sensitive cells. Additionally, PFKFB3 inhibition produced an increase in phosphorylation of the necroptotic markers RIPK1 (receptor-interacting kinase 1), and MLKL (Mixed Lineage Kinase Domain Like Pseudokinase), and pre-treatment with the necroptosis inhibitor necrostatin-1 was able to partially rescue cell death caused by PFKFB3 targeting, suggesting that necroptosis is a primary method of cell death induced by PFKFB3 inhibition. In summation, this study showcases the glycolytic enzyme PFKFB3 as an encouraging therapeutic target in endocrine-resistant breast cancer, and warrants further review as a monotherapy or in combination with current endocrine therapies. Citation Format: Brandon C Jones, Surojeet Sengupta, Catherine M Sevigny, Lu Jin, Paula R Pohlmann, Ayesha Shajahan-Haq, Robert Clarke. Pfkfb3 inhibition significantly decreases endocrine-resistant breast cancer growth and induces necroptotic cell death [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 P4-02-10.
New Metabolic Alterations and a Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma
Authors: Lei Liu, Jia Wu, Minxin Shi, Fengying Wang, Haimin Lu, Jibing Liu, Weiqin Chen, Guanzhen Yu, Dan Liu, Jing Yang, Qin Luo, Yan Ni, Xing Jin, Xiaoxia Jin, Wen-Lian Chen
Journal: Genomics Proteomics & Bioinformatics (2022)

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.
QIM22-194: Using the Merlin Assay to Reduce Sentinel Lymph Node Biopsy Rates and Its Complications: A Retrospective Cohort Study
Authors: Tina J. Hieken, Mariana B. Sadurní, Enrica Quattrocchi, Ajdin Kobic, Sindhuja Sominidi-Damodaran, Lisette Meerstein, Jvalini T. Dwarkasing, Alina G. Bridges, Alexander Meves
Journal: Journal of the National Comprehensive Cancer Network (2022)
ATRIAL FIBRILLATION PREDICTS POOR OUTCOMES AND HIGHER COST OF CARE IN PATIENTS ADMITTED FOR INPATIENT CHEMOTHERAPY-INSIGHT FROM THE NATIONAL INPATIENT SAMPLE
Authors: Satyam Krishan, Sreeram Yalamanchili, Ramtej Atluri, Omar Khdeir, Muhammad Khan, Bilal Munir, Abhishek Deshmukh, Zain Ul Abideen Asad
Journal: Journal of the American College of Cardiology (2022)
Viable SARS-CoV-2 shedding under remdesivir and dexamethasone treatment
Authors: Jin Gu Yoon, Jin Sae Yoo, Jungmin Lee, Hak-Jun Hyun, Hye Seong, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Young Rong Kim, Jung Yeon Heo, Joon-Yong Bae, Chunguang Cui, Sohyun Lee, Man-Seong Park, Joon Young Song
Journal: Journal of Infection (2022)
Childhood Body Size and Premenstrual Disorders—Is There an Association?
Authors: Chighaf Bakour
Journal: JAMA Network Open (2022)

Donghao Lu, MD, PhD; Jurate Aleknaviciute, PhD; Astrid M. Kamperman, PhD; Rulla M. Tamimi, ScD; Jonas F. Ludvigsson, MD, PhD; Unnur A. Valdimarsdóttir, PhD; Elizabeth R. Bertone-Johnson, ScD