tbuckley/cabot-search huggingface dataset:
Proposed New Dynamic Prognostic Index for Diffuse Large B-Cell Lymphoma: International Metabolic Prognostic Index
Authors: N. George Mikhaeel, Martijn W. Heymans, Jakoba J. Eertink, Henrica C.W. de Vet, Ronald Boellaard, Ulrich Dührsen, Luca Ceriani, Christine Schmitz, Sanne E. Wiegers, Andreas Hüttmann, Pieternella J. Lugtenburg, Emanuele Zucca, Gerben J.C. Zwezerijnen, Otto S. Hoekstra, Josée M. Zijlstra, Sally F. Barrington
Journal: Journal of Clinical Oncology (2022)

PURPOSE Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model. METHODS PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma. Transformations of MTV were compared with the primary end points of 3-year progression-free survival (PFS) and overall survival (OS) to derive the best relationship for further analyses. MTV was compared with IPI categories and individual components to derive the best model. Patients were grouped into three groups for survival analysis using Kaplan-Meier analysis; 10% at highest risk, 30% intermediate risk, and 60% lowest risk, corresponding with expected clinical outcome. Validation of the best model was performed using four studies as a test set and the fifth study for validation and repeated five times. RESULTS The best relationship for MTV and survival was a linear spline model with one knot located at the median MTV value of 307.9 cm 3 . MTV was a better predictor than IPI for PFS and OS. The best model combined MTV with age as continuous variables and individual stage as I-IV. The MTV-age-stage model performed better than IPI and was also better at defining a high-risk group (3-year PFS 46.3% v 58.0% and 3-year OS 51.5% v 66.4% for the new model and IPI, respectively). A regression formula was derived to estimate individual patient survival probabilities. CONCLUSION A new prognostic index is proposed using MTV, age, and stage, which outperforms IPI and enables individualized estimates of patient outcome.
Functional dissection of neural circuitry using a genetic reporter for fMRI
Authors: Souparno Ghosh, Nan Li, Miriam Schwalm, Benjamin B. Bartelle, Tianshu Xie, Jade I. Daher, Urvashi D. Singh, Katherine Xie, Nicholas DiNapoli, Nicholas B. Evans, Kwanghun Chung, Alan Jasanoff
Journal: Nature Neuroscience (2022)
A MACHINE LEARNING MODEL FOR THE PREDICTION OF 1-YEAR MORTALITY AFTER HEART TRANSPLANTATION IN ADULTS WITH CONGENITAL HEART DISEASE
Authors: Maria Emfietzoglou, Athanasios Siouras, Jef Van den Eynde, Serafeim Moustakidis, Ilias Doulamis, George Giannakoulas, Dimitrios Vasileios Avgerinos, Alexandros Briasoulis, Polydoros Kampaktsis
Journal: Journal of the American College of Cardiology (2022)
T cell-attracting CCL18 chemokine is a dominant rejection signal during limb transplantation
Authors: Thiago J. Borges, Phammela Abarzua, Rodrigo B. Gassen, Branislav Kollar, Mauricio Lima-Filho, Bruno T. Aoyama, Diana Gluhova, Rachael A. Clark, Sabina A. Islam, Bohdan Pomahac, George F. Murphy, Christine G. Lian, Simon G. Talbot, Leonardo V. Riella
Journal: Cell Reports Medicine (2022)

Limb transplantation is a life-changing procedure for amputees. However, limb recipients have a 6-fold greater rejection rate than solid organ transplant recipients, related in part to greater immunogenicity of the skin. Here, we report a detailed immunological and molecular characterization of individuals who underwent bilateral limb transplantation at our institution. Circulating Th17 cells are increased in limb transplant recipients over time. Molecular characterization of 770 genes in skin biopsies reveals upregulation of T cell effector immune molecules and chemokines, particularly CCL18. Skin antigen-presenting cells primarily express the chemokine CCL18, which binds to the CCR8 receptor. CCL18 treatment recruits more allo-T cells to the skin xenograft in a humanized skin transplantation model, leading to signs of accelerated graft rejection. Blockade of CCR8 remarkedly decreases CCL18-induced allo-T cell infiltration. Our results suggest that targeting the CCL18:CCR8 pathway could be a promising immunosuppressive approach in transplantation.
Abstract PD4-07: Targeting latent residual HER2+ breast cancer brain metastatic cells
Authors: Mauricio Marquez-Palencia, Srinivas Malladi
Journal: Cancer Research (2022)

Abstract Approximately fifty percent of breast cancer patients with brain metastasis are positive for human epidermal growth factor receptor 2 (HER2+). Systemically effective cytotoxic drugs, and HER2 targeted therapies are ineffective on brain metastases. Current understanding of HER2 brain metastatic disease is limited as biopsying brain metastatic lesions and detecting micro-metastasis from asymptomatic patients with residual disease remains a challenge. Therefore, to isolate disseminated tumor cells that stay latent in the brain, while retaining their metastasis-initiating capabilities, we performed a phenotypic screen in mouse employing human breast cancer cell lines. Using this approach, we isolated isogenic latent residual cells (Lat) and metachronous brain metastatic outbreaks (M-BM). Phenotypically stable latent cells display stem cell-like characteristics, downregulate immune activating sensors and survive in equilibrium with innate immune surveillance, while M-BM escape and metastasize. Brain-tropic Lat and M-BM cells are resistant to HER2 targeted therapies - lapatinib, neratinib and tucatinib. Transcriptomic analysis identified AXL, a receptor tyrosine kinase from the TAM receptor family, to be highly enriched in brain-tropic Lat and M-BM. Moreover, AXL is over expressed in metachronous brain metastasis samples compared to matched primary tumors from HER2+ breast cancer patients. AXL activation and overexpression has been associated with chemoresitance mechanisms, dormancy maintenance, invasion, tumor angiogenesis, immune regulation, metastasis and poor prognosis in cancer patients. Therefore, we hypothesized AXL promotes residual/latent breast cancer survival and brain metastatic relapse in HER2+ breast cancer. shRNA depletion of AXL in Lat and M-BM resulted in reduced oncosphere formation, an assay used to measure tumor or metastasis initiating capacity. Brain metastatic incidence was significantly attenuated in mice bearing AXL depleted M-BM compared to their controls. Bemcentinib, an AXL inhibitor currently in clinical trials for non-small cell lung cancer, triple negative breast cancer, pancreatic cancer and melanoma, alone or in combination with lapatinib, neratinib or tucatinib, reduced oncosphere formation in HER2 therapy resistant Lat and M-BM cells. Ongoing experiments are designed to assess the impact of bemcentinib on brain metastasis in vivo and to mechanistically define how AXL promotes survival of latent residual and brain metastatic HER2+ breast cancer cells. Citation Format: Mauricio Marquez-Palencia, Srinivas Malladi. Targeting latent residual HER2+ breast cancer brain metastatic cells [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 PD4-07.
COMPARISON OF THE HEMODYNAMICS OF SHOCK IN THE FIRST VERSUS THE SECOND WAVE OF THE COVID PANDEMIC
Authors: Matthew J. Fata, Brent Klinkhammer, Tirth Talati, Osman K. Yousafzai, Taya V. Glotzer, Sameer M. Jamal, David B. Landers, Joseph E. Parrillo, Lucy M. Safi, Jana Tancredi, Zoltan Turi, Steven M. Hollenberg
Journal: Journal of the American College of Cardiology (2022)
Use of Machine Learning to Estimate the Per-Protocol Effect of Low-Dose Aspirin on Pregnancy Outcomes
Authors: Yongqi Zhong, Maria M. Brooks, Edward H. Kennedy, Lisa M. Bodnar, Ashley I. Naimi
Journal: JAMA Network Open (2022)

<h3>Importance</h3> In randomized clinical trials (RCTs), per-protocol effects may be of interest in the presence of nonadherence with the randomized treatment protocol. Using machine learning in per-protocol effect estimation can help avoid model misspecification owing to strong parametric assumptions, as is common with standard methods (eg, logistic regression). <h3>Objectives</h3> To demonstrate the use of ensemble machine learning with augmented inverse probability weighting (AIPW) for per-protocol effect estimation in RCTs and to evaluate the per-protocol effect size of aspirin on pregnancy. <h3>Design, Setting, and Participants</h3> This secondary analysis used data from 1227 women in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a multicenter, block-randomized, double-blind, placebo-controlled clinical trial of the effect of daily low-dose aspirin on pregnancy outcomes in women at high risk of pregnancy loss. Participants were recruited at 4 university medical centers in the US from June 15, 2007, to July 15, 2012. Women were followed up for 6 menstrual cycles for attempted pregnancy and 36 weeks of gestation if pregnancy occurred. Follow-up was completed on August 17, 2012. Data analyses were performed on July 9, 2021. <h3>Exposures</h3> Daily low-dose (81 mg) aspirin taken at least 5 of 7 days per week for at least 80% of follow-up time relative to placebo. <h3>Main Outcomes and Measures</h3> Pregnancy detected using human chorionic gonadotropin (hCG) levels. <h3>Results</h3> Among the 1227 women included in the analysis (mean SD age, 28.74 [4.80] years), 1161 (94.6%) were non-Hispanic White and 858 (69.9%) adhered to the protocol. Five machine learning models were combined into 1 meta-algorithm, which was used to construct an AIPW estimator for the per-protocol effect. Compared with adhering to placebo, adherence to the daily low-dose aspirin protocol for at least 5 of 7 days per week was associated with an increase in the probability of hCG-detected pregnancy of 8.0 (95% CI, 2.5-13.6) more hCG-detected pregnancies per 100 women in the sample, which is substantially larger than the estimated intention-to-treat estimate of 4.3 (95% CI, −1.1 to 9.6) more hCG-detected pregnancies per 100 women in the sample. <h3>Conclusions and Relevance</h3> These findings suggest that a low-dose aspirin protocol is associated with increased hCG-detected pregnancy in women who adhere to treatment for at least 5 days per week. With the presence of nonadherence, per-protocol treatment effect estimates differ from intention-to-treat estimates in the EAGeR trial. The results of this secondary analysis of clinical trial data suggest that machine learning could be used to estimate per-protocol effects by adjusting for confounders related to nonadherence in a more flexible way than traditional regressions. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT00467363
Letter to the editor: Liver outcomes after bariatric surgery in patients with NASH and advanced fibrosis
Authors: Ankur Jindal
Journal: Hepatology (2022)

To the editor, We read with interest the retrospective study by Pais et al. concluding that despite significant long‐term weight loss and reversal of steatohepatitis and metabolic risk factors after bariatric surgery, it may not be sufficient to reverse advanced fibrosis.[1] This is important because persistence of advanced fibrosis/cirrhosis for many years (without specific treatment) is associated with increased risk of clinical decompensation and liver‐related mortality.[2] Independent of weight loss, there are no approved definite therapies for advanced NASH; therefore, novel treatment strategies targeting underlying fibrogenic and inflammatory mechanisms are needed. Some of the issues need further consideration. First, it is a well‐known fact that the magnitude and kinetics of fibrosis regression lag behind improvement in steatosis and/or hepatic inflammation.[3] Fibrosis regression takes time, particularly in those with advanced fibrosis at baseline. In this study, > 70% patients with advanced fibrosis had Stage > 1 fibrosis regression on follow‐up. The median follow‐up in fibrosis nonresponders was only 3.7 years compared to 7.4 years in responders. For estimating the true nonresponders, prolonged follow‐up with serial liver biopsy is warranted. Second, the safety of bariatric surgery in patients with advanced fibrosis or NASH cirrhosis is paramount. A few recent studies suggest that clinical decompensation may appear at low hepatic venous pressure gradient thresholds in some patients with NASH cirrhosis.[4] Rapid weight loss has been reported to induce hepatic inflammation and exacerbate steatohepatitis with progression to liver failure within a relatively short time frame.[5] Although Roux‐en‐Y gastric bypass appears better than sleeve gastrectomy at improving metabolic complications and liver fibrosis regression, it might not be the safest. A prospective randomized study comparing the two bariatric surgeries in patients with NASH cirrhosis is needed. With improvement in Type 2 diabetes, systemic hypertension, obesity, and other metabolic risk factors, the clinical implications of persistent fibrosis several years after bariatric surgery are unknown. Third, the study compared liver fibrosis determined by wedge surgical biopsy at baseline to needle biopsy at follow‐up. Wedge biopsies tend to overestimate the fibrosis stage. Only 30% of patients underwent follow‐up liver biopsy. There was no predetermined protocol for repeat biopsy, resulting in variable lengths of follow‐up. CONFLICT OF INTEREST Nothing to report.
Transplantation for Fanconi anaemia: lessons learned from Brazil
Authors: Carmem Bonfim, Samantha Nichele, Gisele Loth, Vaneuza Araújo Moreira Funke, Samir Kanaan Nabhan, Daniela Vandresen Pillonetto, Alberto Cardoso Martins Lima, Ricardo Pasquini
Journal: The Lancet Haematology (2022)
THE ASSOCIATION OF HIGH-SENSITIVITY C-REACTIVE PROTEIN WITH RATES OF ADVERSE OUTCOMES IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Emily Tam, Lu Han, Peter Austin, Paul Dorian, Cynthia Jackevicius, Sheldon M.S. Singh, Douglas Lee, Dennis T. Ko, Husam Mohamed Abdel-Qadir
Journal: Journal of the American College of Cardiology (2022)
PERIPROCEDURAL PERICARDIAL EFFUSION COMPLICATING TRANSCATHETER LEFT ATRIAL APPENDAGE OCCLUSION: A REPORT FROM THE NCDR LAAO REGISTRY
Authors: Matthew J. Price, Miguel Valderrabano, Sarah Zimmerman, Daniel J. Friedman, Jeptha P. Curtis, Frederick A. Masoudi, James V. Freeman
Journal: Journal of the American College of Cardiology (2022)
UV Exposure and the Risk of Keratinocyte Carcinoma in Skin of Color
Authors: Elysha Kolitz, Fabiana C. P. S. Lopes, Matthew Arffa, Juliana Pineider, Roxanne Bogucka, Adewole S. Adamson
Journal: JAMA Dermatology (2022)

Ultraviolet radiation exposure is an important modifiable risk factor for keratinocyte carcinoma (KC) in fair-skinned non-Hispanic White populations; however, the evidence for this relationship in darker-skinned populations is less certain.
HSR22-183: Association Between Cancer Center Accreditation and Compliance With Price Disclosure of Common Oncologic Surgical Procedures
Authors: Yuqi Zhang, Marcelo Cerullo, Andrew Esposito, Vishnukamal Golla
Journal: Journal of the National Comprehensive Cancer Network (2022)

"HSR22-183: Association Between Cancer Center Accreditation and Compliance With Price Disclosure of Common Oncologic Surgical Procedures" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Social Determinants of Health and Response to Disease Associated With Health Outcomes of American Indian and Alaska Native Patients
Authors: Loretta Christensen, Shawnell Damon
Journal: JAMA Network Open (2022)

Leslie A. Musshafen, PhD, MBA, CRA, CPRA; Lamees El-Sadek, MHS; Seth T. Lirette, PhD; Richard L. Summers, MD; Caroline Compretta, PhD; Thomas E. Dobbs III, MD, MPH
Technologies to Assess Drug Response and Heterogeneity in Patient-Derived Cancer Organoids
Authors: Melissa C. Skala, Dustin A. Deming, Jeremy D. Kratz
Journal: Annual Review of Biomedical Engineering (2022)

Patient-derived cancer organoids (PDCOs) are organotypic 3D cultures grown from patient tumor samples. PDCOs provide an exciting opportunity to study drug response and heterogeneity within and between patients. This research can guide new drug development and inform clinical treatment planning. We review technologies to assess PDCO drug response and heterogeneity, discuss best practices for clinically relevant drug screens, and assert the importance of quantifying single-cell and organoid heterogeneity to characterize response. Autofluorescence imaging of PDCO growth and metabolic activity is highlighted as a compelling method to monitor single-cell and single-organoid response robustly and reproducibly. We also speculate on the future of PDCOs in clinical practice and drug discovery.Future development will require standardization of assessment methods for both morphology and function in PDCOs, increased throughput for new drug development, prospective validation with patient outcomes, and robust classification algorithms.
CARDIAC SARCOIDOSIS PATIENTS WHO MEET THE 1993 AND 2006 JAPANESE DIAGNOSTIC CRITERIA ARE MORE LIKELY TO HAVE ADVERSE OUTCOMES
Authors: Shilpa Jasti, Muhammad Afzal, Steven Jack Kalbfleisch, Kenneth A. Ellenbogen, Frank M. Bogun, Alexandru B. Chicos, Henri Roukoz, Peter J. Zimetbaum, Francis Murgatroyd, Mikhail Torosoff, Marc Judson, Pyotr G. Platonov, Adarsh K. Bhan, Lynda E. Rosenfeld, David B. De Lurgio, Ann C. Garlitski, Melody H. Hermel, Vasanth Vedantham, Kyoko Soejima, Timm-Michael L. Dickfeld, Xiaokui Gu, Eric Puroll, Thomas C. Crawford, Jordana Kron
Journal: Journal of the American College of Cardiology (2022)
BASELINE AEROBIC CAPACITY, PSYCHOSOCIAL MOTIVATIONS AND SMARTPHONE USE INFLUENCE EXERCISE BEHAVIOR IN COMMUNITY ELDERLY MEN AND WOMEN
Authors: Angela Su-Mei Koh, Yong Lin Lee, Gina S. Lee, Louis LY Teo, Ru San Tan, Liang Zhong, Fei Gao
Journal: Journal of the American College of Cardiology (2022)
Predicting Probability of Response to Tumor Necrosis Factor Inhibitors for Individual Patients With Ankylosing Spondylitis
Authors: Runsheng Wang, Abhijit Dasgupta, Michael M. Ward
Journal: JAMA Network Open (2022)

Tumor necrosis factor inhibitors (TNFis) have revolutionized the management of ankylosing spondylitis (AS); however, the lack of notable clinical responses in approximately one-half of patients suggests important heterogeneity in treatment response. Identifying patients likely to respond or not respond to TNFis could provide opportunities to personalize treatment strategies.To develop models of the probability of short-term response to TNFi treatment in individual patients with active AS.This is a retrospective cohort study using data of the TNFi group (ie, treatment group) from 10 randomized clinical trials (RCTs) of TNFi treatment among patients with active AS, conducted from 2002 to 2016. Participants were adult patients with active AS who failed nonsteroidal anti-inflammatory drugs. Included RCTs were phase 3 and 4 studies that assessed the efficacy of an originator TNFi at week 12 and/or week 24, either compared with placebo or an antirheumatic drug. The cohort was divided into a training and a testing set. Data analysis was conducted from July 1, 2019, to November 30, 2020.All included patients received an originator TNFi for at least 12 weeks.Outcomes included major response and no response based on the change of AS Disease Activity Score at 12 weeks. Machine learning algorithms were applied to estimate the probability of having major response and no response for individual patients.The study included 1899 participants from 10 trials. The training set included 1207 individuals (mean [SD] age, 39 [12] years; 908 [75.2%] men), of whom 407 (33.7%) had major response and 414 (34.3%) had no response. In the reduced logistic regression models, accuracy was 0.74 for major response and 0.75 for no response. The probability of major response increased with higher C-reactive protein (CRP) level, patient global assessment (PGA), and Bath AS Disease Activity Index (BASDAI) question 2 score and decreased with higher body mass index (BMI) and Bath AS Functional Index (BASFI) score. The probability of no response increased with age and BASFI score, and decreased with higher CRP level, BASDAI question 2 score, and PGA. In the testing set (692 participants; mean [SD] age, 38 [11] years; 533 [77.0%] men), models demonstrated moderate to high accuracy.In this cohort study, the probability of initial response to TNFi was predicted from baseline variables, which may facilitate personalized treatment decision-making.
THE ASSOCIATION BETWEEN INTRAPERITONEAL FAT AND LEFT VENTRICULAR PERFORMANCE IN WOMEN RECEIVING CARDIOTOXIC CHEMOTHERAPY FOR STAGE I-IV BREAST, LYMPHOMA, OR SARCOMA
Authors: Leila Mabudian, Nathaniel S. O'Connell, Ralph B. D'Agostino, Emily Heiston, Julia A. Fleshman, Daniel Miller, Kerryn Reding, Kathryn E. Weaver, Amy Ladd, William Ofori Ntim, Heidi D. Klepin, Emily Dressler, Tonya Calhoun, Jennifer H. Jordan, Mary Helen Hackney, Glenn J. Lesser, W. Gregory Hundley
Journal: Journal of the American College of Cardiology (2022)
COMPARING THE LONG-TERM OUTCOMES OF SUCCESSFUL FETAL AORTIC VALVULOPLASTY CASES TO FETAL INTERVENTION ELIGIBLE SUBJECTS WHO HAD NO PRENATAL INTERVENTION - A PRELIMINARY LOOK AT THE INTERNATIONAL FETAL CARDIAC INTERVENTION REGISTRY
Authors: Orsolya Gilicze, Joanna Dangel, Helena Gardiner, Sarah Gelehrter, Sofia Grinenco, Ulrike Herberg, Mats Mellander, Shaine Morris, Anita Moon-Grady
Journal: Journal of the American College of Cardiology (2022)
Diagnostic Evidence GAuge of Single cells (DEGAS): a flexible deep transfer learning framework for prioritizing cells in relation to disease
Authors: Travis S. Johnson, Christina Y. Yu, Zhi Huang, Siwen Xu, Tongxin Wang, Chuanpeng Dong, Wei Shao, Mohammad Abu Zaid, Xiaoqing Huang, Yijie Wang, Christopher Bartlett, Yan Zhang, Brian A. Walker, Yunlong Liu, Kun Huang, Jie Zhang
Journal: Genome Medicine (2022)

We propose DEGAS (Diagnostic Evidence GAuge of Single cells), a novel deep transfer learning framework, to transfer disease information from patients to cells. We call such transferrable information "impressions," which allow individual cells to be associated with disease attributes like diagnosis, prognosis, and response to therapy. Using simulated data and ten diverse single-cell and patient bulk tissue transcriptomic datasets from glioblastoma multiforme (GBM), Alzheimer's disease (AD), and multiple myeloma (MM), we demonstrate the feasibility, flexibility, and broad applications of the DEGAS framework. DEGAS analysis on myeloma single-cell transcriptomics identified PHF19high myeloma cells associated with progression. Availability: https://github.com/tsteelejohnson91/DEGAS .