tbuckley/cabot-search huggingface dataset:
Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression
Authors: Matthew L. Hemming, Patrick Bhola, Michael A. Loycano, Justin A. Anderson, Madeleine L. Taddei, Leona A. Doyle, Elizaveta Lavrova, Jessica L. Andersen, Kelly S. Klega, Morgan R. Benson, Brian D. Crompton, Chandrajit P. Raut, Suzanne George, Anthony Letai, George D. Demetri, Ewa Sicinska
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Leiomyosarcoma (LMS) is a neoplasm characterized by smooth muscle differentiation, complex copy-number alterations, tumor suppressor loss, and the absence of recurrent driver mutations. Clinical management for advanced disease relies on the use of empiric cytotoxic chemotherapy with limited activity, and novel targeted therapies supported by preclinical research on LMS biology are urgently needed. A lack of fidelity of established LMS cell lines to their mesenchymal neoplasm of origin has limited translational understanding of this disease, and few other preclinical models have been established. Here, we characterize patient-derived xenograft (PDX) models of LMS, assessing fidelity to their tumors of origin and performing preclinical evaluation of candidate therapies. Experimental Design: We implanted 49 LMS surgical samples into immunocompromised mice. Engrafting tumors were characterized by histology, targeted next-generation sequencing, RNA sequencing, and ultra-low passage whole-genome sequencing. Candidate therapies were selected based on prior evidence of pathway activation or high-throughput dynamic BH3 profiling. Results: We show that LMS PDX maintain the histologic appearance, copy-number alterations, and transcriptional program of their parental tumors across multiple xenograft passages. Transcriptionally, LMS PDX cocluster with paired LMS patient-derived samples and differ primarily in host-related immunologic and microenvironment signatures. We identify susceptibility of LMS PDX to transcriptional cyclin-dependent kinase (CDK) inhibition, which disrupts an E2F-driven oncogenic transcriptional program and inhibits tumor growth. Conclusions: Our results establish LMS PDX as valuable preclinical models and identify strategies to discover novel vulnerabilities in this disease. These data support the clinical assessment of transcriptional CDK inhibitors as a therapeutic strategy for patients with LMS.
ASSOCIATIONS OF ATRIAL FIBRILLATION WITH ISCHEMIC STROKE AND DEMENTIA ARE ATTENUATED AFTER ACCOUNTING FOR LEFT ATRIAL RESERVOIR FUNCTION: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: Michael Zhang, Yuekai Ji, Wendy Wang, Romil Parikh, Anne A. Eaton, Riccardo M. Inciardi, Alvaro Alonso, Elsayed Z. Soliman, Thomas H. Mosley, Michelle Johansen, Rebecca F. Gottesman, Amil M. Shah, Scott D. Solomon, Lin Yee Chen
Journal: Journal of the American College of Cardiology (2022)
When I use a word . . . . Diagnosis
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

Medical students are taught how to take a patient’s history as one would teach schoolchildren their times tables, by rote. However, in time children become able to calculate simple products without repeating whole tables as they were originally taught. By the same token, although the medical history is taught by rote to begin with, the skilled doctor, with experience, comes to choose and frame questions in ways that most appropriately encourage patients to tell their stories lucidly and to best effect, facilitating the path from story to narrative and from narrative to diagnosis. In skilled hands the patient’s tale and the methods of elucidating it combine effectively. Observation, physical examination, and relevant investigations complete the task of making a complete diagnosis. All parts of the process are required.
CONTEMPORARY TRENDS OF PERCUTANEOUS CORONARY INTERVENTION AND COMPLICATIONS IN PATIENTS WITH ACUTE ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: INSIGHTS FROM NATIONAL READMISSIONS DATABASE
Authors: Muhammad Umar Khalid, Rohit Maruthi, Devrat Shah, Syed Shah, Riyaz Bashir
Journal: Journal of the American College of Cardiology (2022)
Restoring Sinus Rhythm Reverses Cardiac Remodeling and Reduces Valvular Regurgitation in Patients With Atrial Fibrillation
Authors: Laurie Soulat-Dufour, Sylvie Lang, Karima Addetia, Stephane Ederhy, Saroumadi Adavane-Scheuble, Marion Chauvet-Droit, Marie-Liesse Jean, Pascal Nhan, Rim Ben Said, Iris Kamami, Pauline Issaurat, Elodie Capderou, Camille Arnaud, Franck Boccara, Roberto M. Lang, Ariel Cohen
Journal: Journal of the American College of Cardiology (2022)
Early Symptomatic Improvement After Ustekinumab Therapy in Patients With Ulcerative Colitis: 16-Week Data From the UNIFI Trial
Authors: Silvio Danese, Bruce E. Sands, Maria T. Abreu, Christopher D. O’Brien, Ivana Bravatà, Maciej Nazar, Ye Miao, Yanli Wang, David Rowbotham, Rupert W.L. Leong, Ramesh P. Arasaradnam, Waqqas Afif, Colleen Marano
Journal: Clinical Gastroenterology and Hepatology (2022)

Rapid symptomatic relief is an important treatment goal for patients with ulcerative colitis (UC). We aimed to characterize early response with ustekinumab in patients with moderate-to-severe UC during the initial 16 weeks of treatment.We performed a post hoc analysis of data from A Study to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis trial. Patients (N = 961) were randomized (1:1:1) to receive intravenous 130 mg ustekinumab, approximately 6 mg/kg ustekinumab, or placebo at week 0. Symptomatic remission, absolute stool number, Mayo stool frequency and rectal bleeding subscores, partial Mayo score, C-reactive protein, and fecal calprotectin were assessed in the overall population and for patients in the biologic-naïve or prior biologic failure subgroups.A significantly greater percentage of patients in the 130-mg ustekinumab (20.0%; P = .015) or approximately 6-mg/kg ustekinumab (20.2%; P = .012) groups achieved symptomatic remission at week 2 vs placebo (12.9%). Mean [SD] changes from baseline in daily stool number on day 7 were greater in the ustekinumab groups (-1.1 [2.6] in 130 mg [P = .065] and -1.2 [2.5] in ∼6 mg/kg [P = .017]) vs placebo (-0.7 [2.7]). The percentage of patients with Mayo stool frequency subscore of 1 or less and rectal bleeding subscore of 0 increased from baseline through week 16 for both ustekinumab groups. Significant improvements in partial Mayo scores were observed by week 2 in both ustekinumab groups vs placebo (P ≤ .001). Significantly more patients in the ustekinumab groups had normalized C-reactive protein levels from week 2 to week 8 vs placebo (P ≤ .05). Similar results were observed with normalized fecal calprotectin levels between week 2 and week 4 (P ≤ .05).Ustekinumab improved symptoms in patients with UC compared with placebo in as early as 7 days, indicating rapid onset of effect after induction.ClinicalTrials.gov: NCT02407236.
Integration of genetic colocalizations with physiological and pharmacological perturbations identifies cardiometabolic disease genes
Authors: Michael J. Gloudemans, Brunilda Balliu, Daniel Nachun, Matthew G. Durrant, Erik Ingelsson, Martin Wabitsch, Thomas Quertermous, Stephen B. Montgomery, Joshua W. Knowles, Ivan Carcamo-Orive
Journal: Metabolism (2022)
FULMINANT MYOCARDITIS IN A PATIENT WITH COVID-19 AND COMPLETE MYOCARDIAL RECOVERY FOLLOWING TREATMENT WITH INTRAVENOUS IMMUNOGLOBULIN
Authors: Fernanda Tessari, Fernando Reis Menezes, Gabriel Doho, Felipe Fontes Batista de Souza, Gisele Bachur, Arthur Angelo Zogheib Pinatto, Thalita Merluzzi, Tiago Porto Ferreira, Sérgio Kreimer, Rodrigo Chagas de Carvalho, Mariza Silva Ramos Loesch
Journal: Journal of the American College of Cardiology (2022)
POST-TRANSPLANT CARDIOVASCULAR OUTCOMES IN LUNG TRANSPLANT PATIENTS UNDERGOING PRE-TRANSPLANT CARDIAC CATHETERIZATION
Authors: Ji Eun Park, Zulqarnain Khan, Feras Asiri, Hossein Aalaei, Robert Michael Reed, Anuj Gupta, Mukta Chandra Srivastava
Journal: Journal of the American College of Cardiology (2022)
Quantitative Nodal Burden and Mortality Across Solid Cancers
Authors: Anthony T Nguyen, Michael Luu, Vina P Nguyen, Diana J Lu, Stephen L Shiao, Mitchell Kamrava, Katelyn M Atkins, Alain C Mita, Kevin S Scher, Daniel E Spratt, Mark B Faries, Timothy J Daskivich, De-Chen Lin, Michelle M Chen, Jon Mallen-St Clair, Howard M Sandler, Allen S Ho, Zachary S Zumsteg
Journal: JNCI Journal of the National Cancer Institute (2022)

Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors.We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses.Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites.Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors.
Changes in Coverage and Cost-Related Delays in Care for Latino Individuals After Elimination of the Affordable Care Act’s Individual Mandate
Authors: Alexander N. Ortega, Jie Chen, Dylan H. Roby, Karoline Mortensen, Alexandra C. Rivera-González, Arturo Vargas Bustamante
Journal: JAMA Network Open (2022)

This cross-sectional study examines changes in levels of health care coverage and cost-related delays in care for Latino individuals after elimination of the individual coverage mandate from the Affordable Care Act (ACA).
Noncovalent reversible binding-enabled facile fabrication of leak-free PDMS microfluidic devices without plasma treatment for convenient cell loading and retrieval
Authors: Bin Jiang, Alisa White, Wenquan Ou, Sarah Van Belleghem, Samantha Stewart, James G. Shamul, Shaik O. Rahaman, John P. Fisher, Xiaoming He
Journal: Bioactive Materials (2022)

The conventional approach for fabricating polydimethylsiloxane (PDMS) microfluidic devices is a lengthy and inconvenient procedure and may require a clean-room microfabrication facility often not readily available. Furthermore, living cells can't survive the oxygen-plasma and high-temperature-baking treatments required for covalent bonding to assemble multiple PDMS parts into a leak-free device, and it is difficult to disassemble the devices because of the irreversible covalent bonding. As a result, seeding/loading cells into and retrieving cells from the devices are challenging. Here, we discovered that decreasing the curing agent for crosslinking the PDMS prepolymer increases the noncovalent binding energy of the resultant PDMS surfaces without plasma or any other treatment. This enables convenient fabrication of leak-free microfluidic devices by noncovalent binding for various biomedical applications that require high pressure/flow rates and/or long-term cell culture, by simply hand-pressing the PDMS parts without plasma or any other treatment to bind/assemble. With this method, multiple types of cells can be conveniently loaded into specific areas of the PDMS parts before assembly and due to the reversible nature of the noncovalent bonding, the assembled device can be easily disassembled by hand peeling for retrieving cells. Combining with 3D printers that are widely available for making masters to eliminate the need of photolithography, this facile yet rigorous fabrication approach is much faster and more convenient for making PDMS microfluidic devices than the conventional oxygen plasma-baking-based irreversible covalent bonding method.
Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases—Let’s Walk, Not Run
Authors: Shimul A. Shah, Parsia A. Vagefi
Journal: JAMA Surgery (2022)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
Mental Stress–Induced Myocardial Ischemia and Cardiovascular Events in Patients With Coronary Heart Disease
Authors: Yu-Hsuan Lin
Journal: JAMA (2022)

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
SAFETY AND EFFECTIVENESS OF A LOW MOLECULAR WEIGHT HEPARIN IN PULMONARY EMBOLISM ASSOCIATED WITH CHEMOTHERAPY-INDUCED HEART FAILURE AND SEVERE THROMBOCYTOPENIA
Authors: Aldo F. Ponce Barahona, Carlos Jerjes-Sanchez, Jose G. Paredes Vazquez, Arturo A. Martinez Ibarra, Silvia M. Galindo Garza, Jaime A. Guajardo Lozano, Hector Lopez de la Garza, Jorge A. Joya Harrison, Jose A. Salinas Casanova, Erasmo De la Peña Almaguer
Journal: Journal of the American College of Cardiology (2022)
Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome
Authors: Alexander Crits-Christoph, Haley Anne Hallowell, Kalia Koutouvalis, Jotham Suez
Journal: Gut Microbes (2022)

A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.
ANOMALOUS ORIGIN OF RIGHT PULMONARY ARTERY FROM THE AORTA: RARE AND SIGNIFICANT CONGENITAL HEART DISEASE DIAGNOSIS
Authors: Razleen Brar, Rida Shahid, Justin Jin, Sheila Bronish, Ramzi Souki, Munir Ahmad, Hani K. Najm, Rukmini Komarlu
Journal: Journal of the American College of Cardiology (2022)
Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia
Authors: Dipabarna Bhattacharya, Antonella Teramo, Vanessa Rebecca Gasparini, Jani Huuhtanen, Daehong Kim, Jason Theodoropoulos, Gianluca Schiavoni, Gregorio Barilà, Cristina Vicenzetto, Giulia Calabretto, Monica Facco, Toru Kawakami, Hideyuki Nakazawa, Brunangelo Falini, Enrico Tiacci, Fumihiro Ishida, Gianpietro Semenzato, Tiina Kelkka, Renato Zambello, Satu Mustjoki
Journal: Blood Cancer Journal (2022)

Abstract CD4+ T-cell large granular lymphocyte leukemia (T-LGLL) is a rare subtype of T-LGLL with unknown etiology. In this study, we molecularly characterized a cohort of patients ( n = 35) by studying their T-cell receptor (TCR) repertoire and the presence of somatic STAT5B mutations. In addition to the previously described gain-of-function mutations (N642H, Y665F, Q706L, S715F), we discovered six novel STAT5B mutations (Q220H, E433K, T628S, P658R, P702A, and V712E). Multiple STAT5B mutations were present in 22% (5/23) of STAT5B mutated CD4+ T-LGLL cases, either coexisting in one clone or in distinct clones. Patients with STAT5B mutations had increased lymphocyte and LGL counts when compared to STAT5B wild-type patients. TCRβ sequencing showed that, in addition to large LGL expansions, non-leukemic T cell repertoires were more clonal in CD4+ T-LGLL compared to healthy. Interestingly, 25% (15/59) of CD4+ T-LGLL clonotypes were found, albeit in much lower frequencies, in the non-leukemic CD4+ T cell repertoires of the CD4+ T-LGLL patients. Additionally, we further confirmed the previously reported clonal dominance of TRBV6-expressing clones in CD4+ T-LGLL. In conclusion, CD4+ T-LGLL patients have a typical TCR and mutation profile suggestive of aberrant antigen response underlying the disease.
Concerns about the external validity of the study ‘prevalence of persistent symptoms after treatment for Lyme borreliosis: A prospective observational cohort study’-authors´ reply
Authors: Cees C. van den Wijngaard, Jeanine Ursinus, Hedwig D. Vrijmoeth, Hans Knoop, Albert Wong, Leo A.B. Joosten, Joppe W. Hovius, Bart Jan Kullberg
Journal: The Lancet Regional Health - Europe (2022)
CRISPR/Cas9 and next generation sequencing in the personalized treatment of Cancer
Authors: Sushmaa Chandralekha Selvakumar, K. Auxzilia Preethi, Kehinde Ross, Deusdedit Tusubira, Mohd Wajid Ali Khan, Panagal Mani, Tentu Nageswara Rao, Durairaj Sekar
Journal: Molecular Cancer (2022)

Abstract Background Cancer is caused by a combination of genetic and epigenetic abnormalities. Current cancer therapies are limited due to the complexity of their mechanism, underlining the need for alternative therapeutic approaches. Interestingly, combining the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9) system with next-generation sequencing (NGS) has the potential to speed up the identification, validation, and targeting of high-value targets. Main text Personalized or precision medicine combines genetic information with phenotypic and environmental characteristics to produce healthcare tailored to the individual and eliminates the constraints of “one-size-fits-all” therapy. Precision medicine is now possible thanks to cancer genome sequencing. Having advantages over limited sample requirements and the recent development of biomarkers have made the use of NGS a major leap in personalized medicine. Tumor and cell-free DNA profiling using NGS, proteome and RNA analyses, and a better understanding of immunological systems, are all helping to improve cancer treatment choices. Finally, direct targeting of tumor genes in cancer cells with CRISPR/Cas9 may be achievable, allowing for eliminating genetic changes that lead to tumor growth and metastatic capability. Conclusion With NGS and CRISPR/Cas9, the goal is no longer to match the treatment for the diagnosed tumor but rather to build a treatment method that fits the tumor exactly. Hence, in this review, we have discussed the potential role of CRISPR/Cas9 and NGS in advancing personalized medicine.
REDUCING BARRIERS TO NEWER GUIDELINE-DIRECTED MEDICAL THERAPY FOR PATIENTS WITH HEART FAILURE THROUGH CENTRALIZED, PHARMACIST-LED ACCESS SERVICES
Authors: Trejeeve Martyn, West Lucianne, Jatinder Gill, Brad Williams, Kathleen D. Faulkenberg, Vardhmaan Jain, Cari Cristiani, Randall C. Starling, Eileen M. Hsich, Jerry D. Estep, Wai Hong Wilson Tang
Journal: Journal of the American College of Cardiology (2022)