tbuckley/cabot-search huggingface dataset:
Attention gated networks: Learning to leverage salient regions in medical images
Authors: Jo Schlemper, Ozan Oktay, Michiel Schaap, Mattias Heinrich, Bernhard Kainz, Ben Glocker, Daniel Rueckert
Journal: Medical Image Analysis (2019)

We propose a novel attention gate (AG) model for medical image analysis that automatically learns to focus on target structures of varying shapes and sizes. Models trained with AGs implicitly learn to suppress irrelevant regions in an input image while highlighting salient features useful for a specific task. This enables us to eliminate the necessity of using explicit external tissue/organ localisation modules when using convolutional neural networks (CNNs). AGs can be easily integrated into standard CNN models such as VGG or U-Net architectures with minimal computational overhead while increasing the model sensitivity and prediction accuracy. The proposed AG models are evaluated on a variety of tasks, including medical image classification and segmentation. For classification, we demonstrate the use case of AGs in scan plane detection for fetal ultrasound screening. We show that the proposed attention mechanism can provide efficient object localisation while improving the overall prediction performance by reducing false positives. For segmentation, the proposed architecture is evaluated on two large 3D CT abdominal datasets with manual annotations for multiple organs. Experimental results show that AG models consistently improve the prediction performance of the base architectures across different datasets and training sizes while preserving computational efficiency. Moreover, AGs guide the model activations to be focused around salient regions, which provides better insights into how model predictions are made. The source code for the proposed AG models is publicly available.
Association of Early vs Delayed Cholecystectomy for Mild Gallstone Pancreatitis With Perioperative Outcomes
Authors: Emily D. Dubina, Christian de Virgilio, Eric R. Simms, Dennis Y. Kim, Ashkan Moazzez
Journal: JAMA Surgery (2018)

vival found with increasing CD4 + cell levels.Patients were also divided into groups with high (n = 26) and low (n = 27) levels of CD3 + using median expression as a cutoff.Median survival was 20.5 and 18.8 months, respectively, and the 5-year survival estimate was 18.0 months (95% CI, 6.0-35.1 months) and 5.56 months (95% CI, 0.5-2.6 months), respectively.A similar analysis was performed for those with high (n = 22) and low (n = 22) levels of postoperative circulating monocytes.Median survival was 25.3 and 21.6 months, respectively; 5-year estimate of survival, 21.3 months (95% CI, 4.7-45.9months) and 9.5 months (95% CI, 0.9-31.1 months), respectively.Multivariate Cox proportional hazards regression was performed using clinicopathologic and immunohistochemical information.Initially, all variables significant on the univariate analysis were included, and subsequently nonsignificant variables were removed in a stepwise fashion until the final model was generated.American Joint Committee on Cancer stage, CD3 + tumor infiltrate, lymphovascular invasion, and postoperative circulating monocytes remained significant (Table 2).Discussion | Only a subgroup of patients with pancreatic cancer present with malignant neoplasms that are eligible for surgical resection, and these are skewed toward early-stage disease.Within our study population and within the immune cell types studied, preoperative analysis of peripheral lymphocytes was not associated with survival and was not reflective of the intratumoral immune infiltrate.However, higher levels of tumor-infiltrating CD3 + T cells and higher postoperative circulating levels of monocytes were associated with an improved prognosis.These data suggest that, although peripheral blood immunocytes do not reflect the immune environment of the tumor, consideration of the systemic immune response during recovery from resection may be of value.Our data suggest a possible role for the patient's immune response on the outcome of pancreatic tumor resection and that interven-
Phase II Study of Iniparib with Concurrent Chemoradiation in Patients with Newly Diagnosed Glioblastoma
Authors: Jaishri O. Blakeley, Stuart A. Grossman, Andrew S. Chi, Tom Mikkelsen, Myrna R. Rosenfeld, Manmeet S. Ahluwalia, L. Burt Nabors, April Eichler, Ignacio Garcia Ribas, Serena Desideri, Xiaobu Ye
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Iniparib is a purported prodrug causing cell death through intracellular conversion to nitro radical ions. We assessed the efficacy and safety of iniparib with standard radiotherapy and temozolomide in patients with newly diagnosed glioblastoma (GBM). Patients and Methods: Adults meeting eligibility criteria were enrolled in this prospective, single-arm, open-label multi- institution phase II trial with median overall survival (mOS) compared with a historical control as the primary objective. A safety run-in component of radiotherapy + temozolomide + iniparib (n = 5) was followed by an efficacy study (n = 76) with the recommended phase II doses of iniparib (8.0 mg/kg i.v. twice/week with radiotherapy + daily temozolomide followed by 8.6 mg/kg i.v. twice/week with 5/28-day temozolomide). Results: The median age of the 81 evaluable participants was 58 years (63% male). Baseline KPS was ≥ 80% in 87% of participants. The mOS was 22 months [95% confidence interval (CI), 17–24] and the HR was 0.44 (95% CI, 0.35–0.55) per-person-year of follow-up. The 2- and 3-year survival rates were 38% and 25%, respectively. Treatment-related grade 3 adverse events (AEs) occurred in 27% of patients; 9 patients had AEs requiring drug discontinuation including infusion-related reaction, rash, gastritis, increased liver enzymes, and thrombocytopenia. Conclusions: Iniparib is well tolerated with radiotherapy and temozolomide in patients with newly diagnosed GBM at up to 17.2 mg/kg weekly. The primary objective of improved mOS compared with a historical control was met, indicating potential antitumor activity of iniparib in this setting. Dosing optimization (frequency and sequence) is needed prior to additional efficacy studies.
<i>Notes from the Field:</i> Mumps Outbreak — Alaska, May 2017–July 2018
Authors: Amanda Tiffany, Drew Shannon, Willy Mamtchueng, Louisa Castrodale, Joseph McLaughlin
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In response to a mumps outbreak in Anchorage, Alaska, the Alaska Section of Epidemiology (SOE) disseminated educational materials and recommended that all Alaskans ensure that they were up to date on their measles-mumps-rubella (MMR) vaccinations.
Abstract 11187: Doxorubicin Provokes Maladaptive Autophagy and Necrotic Cell Death of Cardiac Myocytes by Disrupting Mitochondrial Respiration Chain Complex IV
Authors: Rimpy Dhingra, Hongying Gang, Victoria Margulets, Lorrie A. Kirshenbaum
Journal: Circulation (2016)

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure, however, the underlying mechanisms remain cryptic. Earlier we established the inducible - death protein, Bcl-2-like Nineteen- Kilodalton- Interacting - Protein 3 (Bnip3) to be crucial for disrupting mitochondrial function and inducing cell death of cardiac myocytes. Whether Bnip3 underlies cardiotoxic effects of doxorubicin toxicity is unknown. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to the cardiotoxic properties of doxorubicin. Perturbations to mitochondria were observed in cardiac myocytes treated with doxorubicin. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Notably, mitochondrial associated Bnip3 in cells treated with doxorubicin formed strong protein interactions with Cytochrome c oxidase subunit1 (COX1) of respiratory chain. This displaced uncoupling protein 3 (UCP3) from COX1 resulting in increased ROS production, decline in maximal and reserved respiration capacity and cell viability. Interestingly, inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed doxorubicin induced necrotic cell death. Importantly genetic inhibition of Bnip3 preserved UCP3-COX complexes, mitochondrial respiratory integrity and abrogated doxorubicin induced necrotic cell death. Moreover, Bnip3-/- mice were resistant to doxorubicin cardiotoxicity displaying normal mitochondrial morphology, cardiac function and survival rates comparable to wild type vehicle treated litter mates. In this report, we demonstrate that doxorubicin provokes maladaptive autophagy resulting in necrotic cell death of ventricular myocytes by a mechanism that involves mitochondria dysfunction induced by the Bcl-2 death protein Bnip3.
Abstract 17141: Assessment of Dyssynchrony as an Indicator of Right Ventricular Free Wall Function by Gated Blood Pool SPECT (GBPS) in Patients undergoing LVAD Implantation
Authors: Aditi Nayak, Christopher B Link, Andrew D Althouse, Robert Kormos, Marc A Simon, Jeffrey Teuteberg, Luigi Lagazzi, Prem Soman
Journal: Circulation (2016)

Introduction: RV function affects prognosis after LVAD, but is difficult to assess by conventional imaging due to complex geometry. Regional RV free wall (RVFW) function may be particularly important after LVAD due to septal shift toward the decompressed LV. We have previously shown feasibility of pre-LVAD GBPS (automated, count-based, without geometric assumptions) assessment of the RV, and the additive value of regional over global dysfunction. Here, we explored the utility of RVFW dyssynchrony assessment using phase analysis as a quantitative predictive parameter of RV regional function. Methods: GBPS was performed using standard procedure on 25 patients awaiting LVAD. Global and regional RV function was assessed. The phase standard deviation (PSD) of the RVFW (non-septal portion of RV) was generated automatically. RV failure was defined as requiring RV assist device or requiring greater than 14 consecutive days of postoperative inotropic support after LVAD implant. Results: Of 25 consecutive patients ...
Time trends in the reporting of conflicts of interest, funding and affiliation with industry in intensive care research: a systematic review
Authors: Michael Darmon, Julie Helms, Audrey De Jong, Peter Buhl Hjortrup, Emmanuel Weiss, Anders Granholm, Riccardo Pinciroli, Charlotte Poussardin, Marie Warrer Petersen, Stéphanie Sigaut, Bruna Brandao Barreto, Morten Hylander Moller, Elie Azoulay
Journal: Intensive Care Medicine (2018)
Abemaciclib Is Active in Preclinical Models of Ewing Sarcoma via Multipronged Regulation of Cell Cycle, DNA Methylation, and Interferon Pathway Signaling
Authors: Michele Dowless, Caitlin D. Lowery, Terry Shackleford, Matthew Renschler, Jennifer Stephens, Robert Flack, Wayne Blosser, Simone Gupta, Julie Stewart, Yue Webster, Jack Dempsey, Alle B. VanWye, Philip Ebert, Philip Iversen, Jonathan B. Olsen, Xueqian Gong, Sean Buchanan, Peter Houghton, Louis Stancato
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Ewing sarcoma (ES) is a rare and highly malignant cancer that occurs in the bone and surrounding tissue of children and adolescents. The EWS/ETS fusion transcription factor that drives ES pathobiology was previously demonstrated to modulate cyclin D1 expression. In this study, we evaluated abemaciclib, a small-molecule CDK4 and CDK6 (CDK4 and 6) inhibitor currently under clinical investigation in pediatric solid tumors, in preclinical models of ES. Experimental Design: Using Western blot, high-content imaging, flow cytometry, ELISA, RNA sequencing, and CpG methylation assays, we characterized the in vitro response of ES cell lines to abemaciclib. We then evaluated abemaciclib in vivo in cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models of ES as either a monotherapy or in combination with chemotherapy. Results: Abemaciclib induced quiescence in ES cell lines via a G1 cell-cycle block, characterized by decreased proliferation and reduction of Ki-67 and FOXM1 expression and retinoblastoma protein (RB) phosphorylation. In addition, abemaciclib reduced DNMT1 expression and promoted an inflammatory immune response as measured by cytokine secretion, antigen presentation, and interferon pathway upregulation. Single-agent abemaciclib reduced ES tumor volume in preclinical mouse models and, when given in combination with doxorubicin or temozolomide plus irinotecan, durable disease control was observed. Conclusions: Collectively, our data demonstrate that the antitumor effects of abemaciclib in preclinical ES models are multifaceted and include cell-cycle inhibition, DNA demethylation, and immunogenic changes.
Abstract 15719: Deletion of Desmoplakin, a Gene Responsible for Arrhythmogenic Cardiomyopathy, Specifically in Cardiac CSPG4pos Cells Leads to Cardiac Arrhythmias and Premature Death
Authors: Jennifer Karmouch, Christina Miyake, Raffaella Lombardi, Xander Wehrens, James T Willerson, Ali J Marian
Journal: Circulation (2016)

Introduction: Arrhythmogenic cardiomyopathy (AC) is an inherited myocardial disease, manifesting with cardiac arrhythmias, sudden cardiac death, and heart failure. AC is commonly caused by mutations in genes encoding desmosome proteins, which are primarily expressed in cardiac myocytes and epithelial cells. Dsp encoding desmoplakin is a major cause of AC and a subgroup of AC, referred to as cardiocutaneous syndrome. In the heart, hitherto, cardiac myocytes are the only cell type known to express desmosome proteins. Thus, AC is considered primarily a disease of myocytes. Hypothesis: Heart, a cellularly heterogeneous organ, contains cells of epithelial origin that express desmosome proteins and contribute to the pathogenesis of AC Methods: Dsp gene was conditionally deleted in the CSPG4pos cells. Cardiac function was assessed by echocardiography, cardiac rhythm by monitoring and electrophysiology studies, and gene expression by molecular biology techniques. Results: DSP is expressed, in addition to cardiac ...
Abstract 18236: Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC): Six Month Safety and Exploratory Efficacy Results
Authors: Tarun Chakravarty, Raj R Makkar, Michelle Kittleson, John Friedman, Daniel S Berman, Richard George, Robert Siegel, Leandro Slipczuk, Andrew Hamer, Rachel R Smith, Shane Smith, Katherine Kacena, Linda Marbán, Timothy D Henry, Eduardo Marbán
Journal: Circulation (2015)

Background: In the CADUCEUS trial, autologous cardiosphere-derived cells (CDCs) decreased infarct size and increased viable tissue in post-MI subjects. In ALLSTAR Phase I, allogeneic CDCs (CAP-1002) were safe and well-tolerated. The DYNAMIC trial is an open-label dose escalating safety trial of multi-vessel intra-coronary CAP 1002 in subjects with dilated cardiomyopathy. Methods &amp; Results: Subjects were matched with CAP-1002 cell lines to which they had no donor specific antibodies by single antigen bead testing. Fourteen subjects (mean age 60.6 yr; range 32-76 years) with NHYA Class III symptoms and echo EF ≤35% (Screening Cardiac CT: mean 26.9%; range 16-34%) due to ischemic (n=7) or non-ischemic cause (n=7) were prospectively enrolled. Four escalating total CAP-1002 doses from 37.5M to 75M were infused via a sequential non-occlusive intracoronary catheter technique, divided among the 3 major coronary arteries (LAD, RCA and circumflex). Post-procedural cardiac enzymes (troponin and CKMB) were measured, with no clinically-significant increases observed in the 24 hr post-infusion. No pre-specified primary safety endpoints occurred; (post infusion reduction of TIMI flow for &gt; 3 minutes, VT/VF, sudden death, major adverse cardiac (MACE) events within 72 hours of infusion, or acute myocarditis within 1 month). Further safety data and exploratory efficacy endpoints include BNP, 6 minute walk and VO2max as well as EF and volumes measured by both echo and cardiac CT at 6 and 12 months. Conclusion: Multi-vessel non-occlusive intracoronary infusion of CAP 1002 in subjects with dilated cardiomyopathy appears to be safe. Six month safety endpoint and adverse event data, as well as exploratory efficacy measures, will be available for presentation November 2015.
Abstract 12222: Patient-Reported Health and its Correlates in Adults With Congenital Heart Disease From 15 Countries
Authors: Philip Moons, Adrienne H Kovacs, Koen Luyckx, Silke Apers
Journal: Circulation (2016)

Objectives: The importance of patient-reported health assessment as a critical measure of cardiovascular health has been emphasized. In adults with congenital heart disease (ConHD), geographic differences in patient-reported health are assumed, but international studies using a uniform methodology are non-existent. We sought (1) to explore patient-reported health in an international sample of adults with ConHD, and (2) to investigate the association between patient characteristics and patient-reported health. Methods: In a cross-sectional study, 4,028 patients (median age=32 y; 53% women; 26% mild, 48% moderate, 26% complex defects) from 15 countries worldwide were included. Patient-reported health was assessed using the SF-12, yielding a Physical Component Summary (PCS) and a Mental Component Summary (MCS). Patient characteristics included sex, age, marital status, educational level, employment status, ConHD complexity, and patient-reported New York Heart Association (NYHA) class. Multivariable linear regression analysis was performed. Results: Mean PCS was 77.2 ±20.9 and mean MCS was 72.1 ±19.0, on a scale 0-100. Fig 1 shows the PCS and MCS per country (flags) and per disease complexity (lines). Malta and Sweden have the highest scores; and France, Taiwan and India have the lowest scores. Lower PCS (worse physical health) was significantly associated with female sex; older age; lack of employment; being divorced or widowed; less education; greater disease complexity; and worse NYHA class (adj. R 2 =0.512). Lower MCS (worse mental health) was significantly related to female sex; lack of employment; being divorced or widowed; having complex ConHD; and worse NYHA class (adj. R 2 =0.234). Conclusions: International variation in patient-reported health is confirmed. The detection of both medical and sociodemographic correlates of perceived health status allow clinicians to identify patients at risk for poor health and to target resources accordingly.
Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX
Authors: Amikar Sehdev, Olumide Gbolahan, Brad A. Hancock, Melissa Stanley, Safi Shahda, Jun Wan, Howard H. Wu, Milan Radovich, Bert H. O’Neil
Journal: Clinical Cancer Research (2018)

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX.Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using Kaplan-Meier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage.Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 (N = 7), BRCA2 (N = 5), PALB2 (N = 3), MSH2 (N = 1), and FANCF (N = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29-1.14; log-rank P = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04-2.06; P = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15-0.94; P = 0.04) showed presence of DDR gene mutations was associated with improved OS.In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX.
Abstract 12458: Mineralocorticoid Receptor Antagonist Use in Patients With Heart Failure and Co-Morbid Diabetes or Chronic Kidney Disease
Authors: Lauren B Cooper, Steven J Lippmann, Melissa A Greiner, Jacob P Kelly, Abhinav Sharma, Gregg C Fonarow, Clyde W Yancy, Paul A Heidenreich, Adrian F Hernandez
Journal: Circulation (2016)

Introduction: The risk of hyperkalemia or acute renal insufficiency (ARI) may limit the use of mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) patients, especially in those with diabetes mellitus (DM) or chronic kidney disease (CKD). Hypothesis: Despite risks, MRAs may be beneficial in these patients. Methods: Using the GWTG-HF registry linked to Medicare claims, we analyzed patients hospitalized from 2005-2013 with a history of DM or CKD and not on a MRA at admission. Patients were stratified by MRA use at discharge. We used proportional hazards models, weighted by inverse treatment probability, for associations between MRA use and 30-day, 1- and 3-year mortality, all-cause readmissions, and readmission for HF, hyperkalemia, or ARI. We performed interaction analyses for differential effects on 3-year outcomes for reduced and preserved ejection fraction (HFrEF and HFpEF). Results: Of 16,848 patients, 12.3% received a MRA at discharge. Higher creatinine was associated with lower odds of MRA use (OR 0.66, 95% CI 0.61, 0.71) but higher potassium was not (OR 1.00, 95% CI 0.90, 1.11). There was no difference in risk of mortality between groups (Table). MRA use was associated with increased short- and long-term risk of hyperkalemia and ARI, but decreased risk of 1- and 3- year all-cause rehospitalization. In the interaction analysis, HFpEF patients on MRA had increased rehospitalization for hyperkalemia (HR 1.44, 95% CI 1.17, 1.78) and ARI (HR 1.29, 95% CI 1.15, 1.44), but HFrEF patients did not (hyperkalemia HR 1.04, 95% CI 0.86, 1.25; ARI HR 0.94, 95% CI 0.82, 1.07). There were no significant interactions by EF group for mortality, or all-cause or HF readmission. Conclusions: Among patients with HF and DM or CKD, MRA use was associated with less all-cause hospitalizations despite increased risk of hyperkalemia and ARI. The increased risk of adverse events was confined to patients with HFpEF. MRAs may be safe in a highly selected group of HF patients with DM or CKD.