tbuckley/cabot-search huggingface dataset:
Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes
Authors: Gottfrid Sjödahl, Johan Abrahamsson, Karin Holmsten, Carina Bernardo, Gunilla Chebil, Pontus Eriksson, Iva Johansson, Petter Kollberg, Claes Lindh, Kristina Lövgren, Nour-al-Dain Marzouka, Hans Olsson, Mattias Höglund, Anders Ullén, Fredrik Liedberg
Journal: European Urology (2021)

For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.
Mannose Metabolism Is a Metabolic Vulnerability Unveiled By Standard and Novel Therapies in Acute Myeloid Leukemia
Authors: Keith Woodley, Laura S Dillingh, George Giotopoulos, Pedro Madrigal, Konstantinos Tzelepis, Celine Philippe, Kevin Rattigan, Ryan Asby, Vilma Dembitz, Aoife S.M. Magee, Gudmundur Helgason, Kevin Rouault-Pierre, George S. Vassiliou, Brian J.P Huntly, Paolo Gallipoli
Journal: Blood (2021)
The Impact of Somatic Mutations upon the Response to Combination Therapy with Ruxolitinib and Interferon in MPN Patients
Authors: Vibe Skov, Anders Lindholm Sørensen, Trine Alma Knudsen, Mads Emil Bjørn, Christina Ellervik, Morten Kranker Larsen, Christina Schjellerup Schjellerup Eickhardt-Dalbøge, Sarah Friis Christensen, Mads Thomassen, Torben A Kruse, Hans C. Hasselbalch
Journal: Blood (2021)
Abstract 8874: Diabetes and Chronic Kidney Disease in Heart Failure With Reduced and Preserved
Authors: Gregory A Nichols, Qing Qiao, Anouk Déruaz-Luyet, Bettina J Kraus
Journal: Circulation (2021)

Introduction: Heart Failure (HF) is a major public health burden, but population-based estimates of incidence rates of clinical outcomes by HF category are scarce. We calculated adjusted incidence rates of type 2 diabetes (T2D) and chronic kidney disease (CKD) in patients with HF with preserved (HFpEF) or reduced ejection fraction (HFrEF). Methods: We identified adult patients with a HF diagnosis from 2005-2017 in the electronic medical record of Kaiser Permanent Northwest and calculated age/sex adjusted incidence or progression rates per 1,000 person-years using generalized estimating equations over 15 years of follow-up (2005-2019). Patients with their first diagnosis of T2D or with two eGFR values &lt;60ml/min/1.73m 2 per the CKD-EPI equation recorded after a HF diagnosis were counted as incident cases. Progression of CKD was calculated among those with CKD at baseline defined as deteriorating to a lower eGFR category (category 3a, 45-59 ml/min/1.73m 2 ; 3b, 30-44; 4, 15-29; 5, &lt;15 or ESKD). Progression to insulin was calculated among those with T2D at baseline not already on insulin. Results: Of the 37,773 patients with a HF diagnosis, 36% had no EF available. 46.4% were categorized as HFpEF, 6.7% HFmrEF and 10.9% HFrEF. Compared with HFrEF patients, those with HFpEF were older (72.1 vs. 68.6 years) and more likely to be female (55% vs. 33%). Patients with HFrEF were more likely than HFpEF to develop CKD or have CKD deterioration (Table). However, due to the much larger size of the HFpEF group, HFpEF generated higher absolute numbers of events. Incidence rates and progression of T2D were smaller for both HFrEF and HFpEF. Conclusions: In a large real-world dataset of HF patients, rates of CKD progression were very high in both HFrEF and HFpEF, affecting approximately half of patients with CKD at baseline. Although progression and new incidence of CKD were relatively lower in HFpEF vs. HFrEF, the greater prevalence of HFpEF was driving the majority of heart failure-associated CKD.
Abstract 11141: Closing the Gap: Evaluating Gender Differences in TAVR Outcomes
Authors: Helena Dickens, Manoj Ambalavanan, Sanket Gokhale, Yolanda Rodríguez-Rivera, Dhairya Jarsania, Gabriel Marrero-Rivera, Mayank M Kansal, Aamir Twing, Erik Simon, Nicole Cho, Elliott Groves, Adhir R Shroff
Journal: Circulation (2021)

Introduction: There are well documented differences in TAVR outcomes among men and women from pre-procedure to 30-days post procedure. However, there is less data comparing the long-term differences in outcomes between genders. This study investigated cardiovascular outcomes between these two groups within 6 months of undergoing a TAVR. Methods: We performed a retrospective study among patients undergoing TAVR between March 2018 and June 2020 at the University of Illinois-Chicago (UIC) in Chicago, Illinois. Primary outcomes included composite MACE (CV death, MI and/or CVA) and all-cause death. Secondary outcomes included change in peak gradient, mean gradient, aortic valve area, and ejection fraction. Outcomes were analyzed at 6 months following the procedure. T and Chi square tests were used to analyze continuous/categorical variables, respectively. Results: There was a total of 115 patients (female: 25, male: 90) in the analysis. The female cohort was older and had a higher BMI. At baseline, the women had a higher peak gradient when compared to the men (64 vs 48mmHg, p=0.03). At 6 months, MACE (female=1.7 vs male=7%, p=0.9) and all cause death (4 vs 4.4%, p=0.9) were statistically similar. There was no significant difference in the change in ejection fraction or aortic valve area between men and women. There was no difference between peak aortic valve gradient or mean aortic valve gradient (p&gt;0.05) between the groups immediately after the procedure or at 6 months following TAVR. Conclusion: Despite having higher baseline aortic valve gradients, women appeared to have similar procedural success and 6-month outcomes following TAVR as compared to men in this analysis. Women presenting with higher baseline gradients suggest that they may be under-diagnosed or misdiagnosed leading to delays in care. Further screening and earlier referral for women is important to maintaining good outcomes.
Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Patients with Lower-Risk Myelodysplastic Syndromes
Authors: Tamanna Haque, Felix López Cadenas, Blanca Xicoy, Ana Alfonso, Uwe Platzbecker, Irit Avivi, Andrew M. Brunner, Jörg Chromik, Daniel Morillo, Manish R. Patel, José F. Falantes, Heather A. Leitch, Ulrich Germing, Meir Preis, David Lavie, Laurie Lenox, Josh Lauring, Anna Kalota, Regina Brown, Jaydeep Mehta, Friederike Pastore, Pankaj Mistry, David Valcarcel
Journal: Blood (2021)
Preclinical Characterization of a Next-Generation Brain Permeable, Paradox Breaker BRAF Inhibitor
Authors: Jürgen Wichmann, Caroline Rynn, Thomas Friess, Jeannine Petrig-Schaffland, Martin Kornacker, Cornelia Handl, Jasmin Emmenegger, Jan Eckmann, Frank Herting, Nicolas Frances, Daniel Hunziker, Daniela Krummenacher, Dominik Rüttinger, Alison Ribeiro, Marina Bacac, Alessandro Brigo, David S. Hewings, Reinhard Dummer, Mitchell P. Levesque, Gabriel Schnetzler, Bruno Martoglio, James R. Bischoff, Piergiorgio Pettazzoni
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Disease progression in BRAF V600E/K positive melanomas to approved BRAF/MEK inhibitor therapies is associated with the development of resistance mediated by RAF dimer inducing mechanisms. Moreover, progressing disease after BRAFi/MEKi frequently involves brain metastasis. Here we present the development of a novel BRAF inhibitor (Compound Ia) designed to address the limitations of available BRAFi/MEKi. Experimental Design: The novel, brain penetrant, paradox breaker BRAFi is comprehensively characterized in vitro, ex vivo, and in several preclinical in vivo models of melanoma mimicking peripheral disease, brain metastatic disease, and acquired resistance to first-generation BRAFi. Results: Compound Ia manifested elevated potency and selectivity, which triggered cytotoxic activity restricted to BRAF-mutated models and did not induce RAF paradoxical activation. In comparison to approved BRAFi at clinical relevant doses, this novel agent showed a substantially improved activity in a number of diverse BRAF V600E models. In addition, as a single agent, it outperformed a currently approved BRAFi/MEKi combination in a model of acquired resistance to clinically available BRAFi. Compound Ia presents high central nervous system (CNS) penetration and triggered evident superiority over approved BRAFi in a macro-metastatic and in a disseminated micro-metastatic brain model. Potent inhibition of MAPK by Compound Ia was also demonstrated in patient-derived tumor samples. Conclusions: The novel BRAFi demonstrates preclinically the potential to outperform available targeted therapies for the treatment of BRAF-mutant tumors, thus supporting its clinical investigation.
Development and Validation of a Deep Learning Model for Earlier Detection of Cognitive Decline From Clinical Notes in Electronic Health Records
Authors: Liqin Wang, John Laurentiev, Jie Yang, Ying-Chih Lo, Rebecca E. Amariglio, Deborah Blacker, Reisa A. Sperling, Gad A. Marshall, Li Zhou
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Detecting cognitive decline earlier among older adults can facilitate enrollment in clinical trials and early interventions. Clinical notes in longitudinal electronic health records (EHRs) provide opportunities to detect cognitive decline earlier than it is noted in structured EHR fields as formal diagnoses. <h3>Objective</h3> To develop and validate a deep learning model to detect evidence of cognitive decline from clinical notes in the EHR. <h3>Design, Setting, and Participants</h3> Notes documented 4 years preceding the initial mild cognitive impairment (MCI) diagnosis were extracted from Mass General Brigham's Enterprise Data Warehouse for patients aged 50 years or older and with initial MCI diagnosis during 2019. The study was conducted from March 1, 2020, to June 30, 2021. Sections of notes for cognitive decline were labeled manually and 2 reference data sets were created. Data set I contained a random sample of 4950 note sections filtered by a list of keywords related to cognitive functions and was used for model training and testing. Data set II contained 2000 randomly selected sections without keyword filtering for assessing whether the model performance was dependent on specific keywords. <h3>Main Outcomes and Measures</h3> A deep learning model and 4 baseline models were developed and their performance was compared using the area under the receiver operating characteristic curve (AUROC) and area under the precision recall curve (AUPRC). <h3>Results</h3> Data set I represented 1969 patients (1046 [53.1%] women; mean [SD] age, 76.0 [13.3] years). Data set II comprised 1161 patients (619 [53.3%] women; mean [SD] age, 76.5 [10.2] years). With some overlap of patients deleted, the unique population was 2166. Cognitive decline was noted in 1453 sections (29.4%) in data set I and 69 sections (3.45%) in data set II. Compared with the 4 baseline models, the deep learning model achieved the best performance in both data sets, with AUROC of 0.971 (95% CI, 0.967-0.976) and AUPRC of 0.933 (95% CI, 0.921-0.944) for data set I and AUROC of 0.997 (95% CI, 0.994-0.999) and AUPRC of 0.929 (95% CI, 0.870-0.969) for data set II. <h3>Conclusions and Relevance</h3> In this diagnostic study, a deep learning model accurately detected cognitive decline from clinical notes preceding MCI diagnosis and had better performance than keyword-based search and other machine learning models. These results suggest that a deep learning model could be used for earlier detection of cognitive decline in the EHRs.
Performance of Standard Prognostic Models in Older Adults Receiving Ibrutinib for Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL): A Post Hoc Analysis of Alliance A041202 Phase 3 Trial
Authors: Inhye E. Ahn, Amy S. Ruppert, Adrian Wiestner, James S. Blachly, John C. Byrd, Richard M. Stone, Sumithra J Mandrekar, Jennifer A. Woyach
Journal: Blood (2021)
Selective Cell State in the Clonally Expanded T-Cell Compartment of Vκ*MYC Mice Responding to Treatment with Checkpoint Inhibitors
Authors: Danielle C Croucher, Laura M Richards, Zhihua Li, Ellen nong Wei, Xian Fang Huang, Daniel Waller, Marta Chesi, P. Leif Bergsagel, Michael Sebag, Trevor J. Pugh, Suzanne Trudel
Journal: Blood (2021)
Medicare Spending, Utilization, and Quality in the Oncology Care Model
Authors: Raymond U. Osarogiagbon, Samyukta Mullangi, Deborah Schrag
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Serum Albumin As a Prognostic Factor for Overall Survival at 6-Months in Acute Myeloid Leukemia (AML)
Authors: Ashley D Fox, Chijioke Okereke, Thuy Le, Anand P Jillella, Locke J. Bryan, Tahsin Anwar, Mohammad A. H. Mian, Danielle Bradshaw, Ravindra Kolhe, Natasha M. Savage, Germame Ajebo, Sandeep Padala, Sujith Abbagoni, Vamsi Kota
Journal: Blood (2021)
Integrative Analysis of Primary <i>SF3B1 mt</i> Ring Sideroblasts Provides Fundamental Insights into MDS-RS Pathogenesis and Dyserythropoiesis
Authors: Pedro Luis Moura, Teresa Mortera-Blanco, Isabel Juliana F Hofman, Gabriele Todisco, Warren W Kretzschmar, Indira Barbosa, Ann-Charlotte Björklund, Gunilla Walldin, Monika Jansson, Tetsuichi Yoshizato, Petter S Woll, Sten Eirik Waelgaard Jacobsen, Eva Hellstrom Lindberg
Journal: Blood (2021)
Endothelial Cell Niche Promotes Leukemic Transformation of Human Cord Blood Stem/Progenitor Cells Expressing CBFA2T3-GLIS2 Oncogenic Fusion
Authors: Quy Le, Tiffany A. Hylkema, Sommer Castro, Jenny L. Smith, Amanda R. Leonti, Thao T. Tang, Cynthia Nourigat-Mckay, LaKeisha Perkins, Laura Pardo, Lisa Eidenschink Brodersen, Michael R. Loken, Rhonda E. Ries, Keith R. Loeb, Soheil Meshinchi
Journal: Blood (2021)
Abstract 9141: Cardiac Injury and Mortality Among Covid-19 Patients in a Predominantly Black Community of East Flatbush Brooklyn
Authors: Emmanuel C Adomfeh, Jonathan Francois, Harshith Priyan, Anoop V Puskoor, Clara Wilson, Brandon DaSilva, Jean Adomfeh
Journal: Circulation (2021)

Introduction: Black/African-American (AA) populations have been previously shown to have increased disease burden of COVID-19 and related deaths. However, not many studies have examined cardiovascular comorbidities and associated cardiac injury contributions to morbidity and mortality of COVID-19 in this population. In this study, we investigate the contributions of cardiac injury to mortality of COVID-19 in a predominantly AA population. Study Design: This is a retrospective cohort study of 572 laboratory confirmed COVID-19 patients admitted to SUNY Downstate HSC in East Flatbush, Brooklyn between March 12 and May 12, 2020. Patients with a documented troponin level above 0.15 μg/L were denoted as having cardiac injury. Of this group, 110 patients were in the cardiac injury group and 462 patients were in the no cardiac injury group. Statistical significance was designated at the p=0.05 level. Outcome: The primary outcome is 60-day mortality. Secondary outcomes included length of stay, non-invasive and invasive ventilation requirement, requirement of intensive care unit admission. Results: The median age was 69 years. 303 (52.97%) were males, and 515 (90.03%) were AA. When compared to patient’s non-cardiac injury group, the cardiac injury group tended to be older, and more likely to have comorbidities such as CHF, COPD, and ESRD. Patients with cardiac injury were also more likely to be smokers. In the cardiac injury group, laboratory data showed a higher white blood cell count, blood urea nitrogen, creatinine, and procalcitonin. Patients with cardiac injury had higher proportion of renal failure, were more likely to require intubation, and were more likely to be transferred to ICU. Notably in comparison to the non-cardiac injury group, patients with cardiac injury found to have a statistically significant two-fold increase in 60-day mortality (62.73% vs 32.90%), reduced mean survival time (33.57 vs 52.70) and a hazard ratio of 1.53 after controlling for confounders using the multiple adjusted Cox proportional hazard regression model. Conclusions and Relevance: The study results exhibit a statistically significant association between cardiac injury and mortality among COVID-19 positive individuals from a predominantly AA population.
A Polygenic DNA Damage Repair Pharmacogenomics (DDR_PGx8) Score Predicts GO Response in AML
Authors: Vivek M. Shastri, Lata Chauhan, Todd A. Alonzo, Yi-Cheng Wang, Richard Aplenc, Betsy A Hirsch, Alan S. Gamis, Soheil Meshinchi, Jatinder K. Lamba
Journal: Blood (2021)
The Framing of machine learning risk prediction models illustrated by evaluation of sepsis in general wards
Authors: Simon Meyer Lauritsen, Bo Thiesson, Marianne Johansson Jørgensen, Anders Hammerich Riis, Ulrick Skipper Espelund, Jesper Bo Weile, Jeppe Lange
Journal: npj Digital Medicine (2021)

Problem framing is critical to developing risk prediction models because all subsequent development work and evaluation takes place within the context of how a problem has been framed and explicit documentation of framing choices makes it easier to compare evaluation metrics between published studies. In this work, we introduce the basic concepts of framing, including prediction windows, observation windows, window shifts and event-triggers for a prediction that strongly affects the risk of clinician fatigue caused by false positives. Building on this, we apply four different framing structures to the same generic dataset, using a sepsis risk prediction model as an example, and evaluate how framing affects model performance and learning. Our results show that an apparently good model with strong evaluation results in both discrimination and calibration is not necessarily clinically usable. Therefore, it is important to assess the results of objective evaluations within the context of more subjective evaluations of how a model is framed.
Integrated Transcriptomics and Proteomics Identifies Therapeutic Targets in Pediatric Acute Myeloid Leukemia
Authors: Benjamin J. Huang, Jenny L. Smith, Timothy I. Shaw, Scott N Furlan, Rhonda E. Ries, Amanda R. Leonti, Erin Lynn Crowgey, Lisa Wei, Jason E Farrar, Tim Triche, Xiaotu Ma, Quy Le, Soheil Meshinchi
Journal: Blood (2021)
A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background
Authors: Sara Falcone, Thomas Nicol, Andrew Blease, Michael J. Randles, Elizabeth Angus, Anton Page, Frederick W.K. Tam, Charles D. Pusey, Rachel Lennon, Paul K. Potter
Journal: Kidney International (2021)

Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminaemia, edema and hyperlipidaemia. Genetic studies of nephrotic syndrome have led to the identification of proteins playing a crucial role in slit diaphragm signaling, regulation of actin cytoskeleton dynamics and cell-matrix interactions. The laminin α5 chain is essential for embryonic development and, in association with laminin β2 and laminin γ1, is a major component of the glomerular basement membrane, a critical component of the glomerular filtration barrier. Mutations in LAMA5 were recently identified in children with nephrotic syndrome. Here, we have identified a novel missense mutation (E884G) in the uncharacterized L4a domain of LAMA5 where homozygous mice develop nephrotic syndrome with severe proteinuria with histological and ultrastructural changes in the glomerulus mimicking the progression seen in most patients. The levels of LAMA5 are reduced in vivo and the assembly of the laminin 521 heterotrimer significantly reduced in vitro. Proteomic analysis of the glomerular extracellular fraction revealed changes in the matrix composition. Importantly, the genetic background of the mice had a significant effect on aspects of disease progression from proteinuria to changes in podocyte morphology. Thus, our novel model will provide insights into pathologic mechanisms of nephrotic syndrome and pathways that influence the response to a dysfunctional glomerular basement membrane that may be important in a range of kidney diseases.