tbuckley/cabot-search huggingface dataset:
Abstract PO033: FGFR2 isoform switching strongly associates with progestin treatment failure in atypical hyperplasia and well-differentiated endometrial cancer
Authors: Asmerom Sengal, Deborah Smith, Rebecca Rogers, Cameron Snell, Elizabeth Williams, Pamela Pollock
Journal: Clinical Cancer Research (2021)

Abstract Introduction: Women with atypical hyperplasia (AH) or well-differentiated endometrioid endometrial carcinoma (EEC) who wish to retain fertility and/or with severe comorbidities that preclude surgery, are treated with progestin. Previously, we reported FGFR2c was associated with aggressive tumour behaviour and poor survival outcome in EEC. The purpose of this study was to estimate the response rate of Levonorgestrel IUD treatment and determine the association of FGFR2b and FGFR2c expression with outcome in women with AH/borderline histology (BL) and EEC treated with progestin. Method: BaseScope RNA ISH and immunohistochemistry assays were deployed to detect (FGFR2b and FGFR2c mRNA) and (FGFR2 protein and progesterone receptors), respectively in 89 diagnostic biopsies of patients with AH/BL and EEC treated with progestin. Kaplan Meier Curve and Cox regression model analyses were performed to evaluate the predictive value of FGFR2b and FGFR2c in this cohort. Results: The complete resolution rate (CRR) and overall response rate (ORR) at any time point in the whole cohort were 26/82 (32%) and 35/82 (43%), respectively. When stratified by histologic diagnosis CRR was 47.5% and 17% and ORR 63% and 24% for AH/BL and EEC, respectively. The recurrence rate was 28.7%. FGFR2c expression was documented in 12/72 (15%) cases. Both univariable and multivariable Cox regression analyses showed women with FGFR2c expression were 5-fold more likely to progress compared with FGFR2b positive women (HR 5.4, P&amp;lt;0.0001) and (HR, 5, P&amp;lt;0.001), respectively. Conclusion: Progestin treatment is less effective in patients with EEC. Notably, FGFR2c expression appears to be strongly associated with progestin treatment failure. Citation Format: Asmerom Sengal, Deborah Smith, Rebecca Rogers, Cameron Snell, Elizabeth Williams, Pamela Pollock. FGFR2 isoform switching strongly associates with progestin treatment failure in atypical hyperplasia and well-differentiated endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO033.
Late Vascular Healing Response to Stents: New Insights From Optical Coherence Tomography⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Brigitta C. Brott
Journal: Journal of the American College of Cardiology (2009)
Bilateral Mastectomy in Women With Unilateral Breast Cancer
Authors: David W. Lim, Kelly A. Metcalfe, Steven A. Narod
Journal: JAMA Surgery (2021)

Rates of bilateral mastectomy continue to increase in average-risk women with unilateral in situ and invasive breast cancer. Contralateral prophylactic mastectomy rates increased from 5% to 12% of all operations for breast cancer in the US from 2004 to 2012. Among women having mastectomy, rates of contralateral prophylactic mastectomy have increased from less than 2% in 1998 to 30% in 2012.The increased use of breast magnetic resonance imaging and genetic testing has marginally increased the number of candidates for bilateral mastectomy. Most bilateral mastectomies are performed on women who are at no special risk for contralateral cancer. The true risk of contralateral breast cancer is not associated with the decision for contralateral prophylactic mastectomy; rather, the clinical factors associated with the probability of distant recurrence are associated with bilateral mastectomy. Several changes in society and health care delivery appear to act concurrently and synergistically. First, the anxiety engendered by a fear of cancer recurrence is focused on the contralateral cancer because this is most easily conceptualized and provides a ready target that can be acted upon. Second, the modern woman with breast cancer is supported by the surgeon and the social community of breast cancer survivors. Surgeons want to respect patient autonomy, despite guidelines discouraging bilateral mastectomy, and most women have their expenses covered by a third-party payer. Satisfaction with the results is high, but the association with improved psychosocial well-being remains to be fully understood.Reducing the use of medically unnecessary contralateral prophylactic mastectomy in women with nonhereditary, unilateral breast cancer requires a social change that addresses patient-, physician-, cultural-, and systems-level enabling factors. Such a transformation begins with educating clinicians and patients. The concerns of women who want preventive contralateral mastectomy must be explored, and women need to be informed of the anticipated benefits (or lack thereof) and risks. Areas requiring further study are considered.
Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a <scp>PARADIGM‐HF</scp> analysis
Authors: Luis E. Rohde, Muthiah Vaduganathan, Brian L. Claggett, Carisi A. Polanczyk, Pranav Dorbala, Milton Packer, Akshay S. Desai, Michael Zile, Jean Rouleau, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J.V. McMurray, Scott D. Solomon
Journal: European Journal of Heart Failure (2021)
Barriers to Optimal End-of-Life Care for Adolescents and Young Adults With Cancer: Bereaved Caregiver Perspectives
Authors: Jennifer W. Mack, Erin R. Currie, Vincent Martello, Jordan Gittzus, Asisa Isack, Lauren Fisher, Lisa C. Lindley, Stephanie Gilbertson-White, Eric Roeland, Marie Bakitas
Journal: Journal of the National Comprehensive Cancer Network (2021)

Adolescents and young adults (AYAs; aged 15-39 years) with cancer frequently receive intensive measures at the end of life (EoL), but the perspectives of AYAs and their family members on barriers to optimal EoL care are not well understood.We conducted qualitative interviews with 28 bereaved caregivers of AYAs with cancer who died in 2013 through 2016 after receiving treatment at 1 of 3 sites (University of Alabama at Birmingham, University of Iowa, or University of California San Diego). Interviews focused on ways that EoL care could have better met the needs of the AYAs. Content analysis was performed to identify relevant themes.Most participating caregivers were White and female, and nearly half had graduated from college. A total of 46% of AYAs were insured by Medicaid or other public insurance; 61% used hospice, 46% used palliative care, and 43% died at home. Caregivers noted 3 main barriers to optimal EoL care: (1) delayed or absent communication about prognosis, which in turn delayed care focused on comfort and quality of life; (2) inadequate emotional support of AYAs and caregivers, many of whom experienced distress and difficulty accepting the poor prognosis; and (3) a lack of home care models that would allow concurrent life-prolonging and palliative therapies, and consequently suboptimal supported goals of AYAs to live as long and as well as possible. Delayed or absent prognosis communication created lingering regret among some family caregivers, who lost the opportunity to support, comfort, and hold meaningful conversations with their loved ones.Bereaved family caregivers of AYAs with cancer noted a need for timely prognostic communication, emotional support to enhance acceptance of a poor prognosis, and care delivery models that would support both life-prolonging and palliative goals of care. Work to address these challenges offers the potential to improve the quality of EoL care for young people with cancer.
Telehealth Use Among Safety-Net Organizations in California During the COVID-19 Pandemic
Authors: Lori Uscher-Pines, Jessica Sousa, Maggie Jones, Christopher Whaley, Christopher Perrone, Colleen McCullough, Allison J. Ober
Journal: JAMA (2021)

This study describes trends in use of in-person, telephone, and video primary care and behavioral health visits to California Federally Qualified Health Centers from 2019 to August 2020 before and during the coronavirus disease 2019 (COVID-19) pandemic.
Text=book on Mental Diseases.
Journal: JAMA (1897)

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
Prolonged activation of innate immune pathways by a polyvalent STING agonist
Authors: Suxin Li, Min Luo, Zhaohui Wang, Qiang Feng, Jonathan Wilhelm, Xu Wang, Wei Li, Jian Wang, Agnieszka Cholka, Yang-xin Fu, Baran D. Sumer, Hongtao Yu, Jinming Gao
Journal: Nature Biomedical Engineering (2021)

Abstract The stimulator of interferon genes (STING) is an endoplasmic reticulum transmembrane protein that is a target of therapeutics for infectious diseases and cancer. However, early-phase clinical trials of small-molecule STING agonists have shown limited antitumour efficacy and dose-limiting toxicity. Here, we show that a polyvalent STING agonist—a pH-sensitive polymer bearing a seven-membered ring with a tertiary amine (PC7A)—activates innate-immunity pathways through the polymer-induced formation of STING–PC7A condensates. In contrast to the natural STING ligand 2′,3′-cyclic-GMP-AMP (cGAMP), PC7A stimulates the prolonged production of pro-inflammatory cytokines by binding to a non-competitive STING surface site that is distinct from the cGAMP binding pocket. PC7A induces antitumour responses that are dependent on STING expression and CD8 + T-cell activity, and the combination of PC7A and cGAMP led to synergistic therapeutic outcomes (including the activation of cGAMP-resistant STING variants) in mice bearing subcutaneous tumours and in resected human tumours and lymph nodes. The activation of the STING pathway through polymer-induced STING condensation may offer new therapeutic opportunities.
Low CtBP2 expression is associated with a stem cell-like signature and adverse clinical outcome in childhood B-cell lymphoblastic leukemia
Authors: Sejong Chun, Hyun-Young Kim, Hee-Jin Kim, Hong Hoe Koo, Keon Hee Yoo, Sun-Hee Kim, Mi Zhou, Seung-Tae Lee, Joseph L. Wiemels
Journal: Leukemia (2021)
Analysis of Polycerate Mutants Reveals the Evolutionary Co-option of <i>HOXD1</i> for Horn Patterning in Bovidae
Authors: Aurélie Allais-Bonnet, Aurélie Hintermann, Marie-Christine Deloche, Raphaël Cornette, Philippe Bardou, Marina Naval-Sanchez, Alain Pinton, Ashleigh Haruda, Cécile Grohs, Jozsef Zakany, Daniele Bigi, Ivica Medugorac, Olivier Putelat, Ockert Greyvenstein, Tracy Hadfield, Slim Ben Jemaa, Gjoko Bunevski, Fiona Menzi, Nathalie Hirter, Julia M Paris, John Hedges, Isabelle Palhiere, Rachel Rupp, Johannes A Lenstra, Louisa Gidney, Joséphine Lesur, Renate Schafberg, Michael Stache, Marie-Dominique Wandhammer, Rose-Marie Arbogast, Claude Guintard, Amandine Blin, Abdelhak Boukadiri, Julie Rivière, Diane Esquerré, Cécile Donnadieu, Coralie Danchin-Burge, Coralie M Reich, David G Riley, Este van Marle-Koster, Noelle Cockett, Benjamin J Hayes, Cord Drögemüller, James Kijas, Eric Pailhoux, Gwenola Tosser-Klopp, Denis Duboule, Aurélien Capitan
Journal: Molecular Biology and Evolution (2021)

Abstract In the course of evolution, pecorans (i.e., higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as “headgear,” which likely share the same origin and genetic basis. However, the nature and function of the genetic determinants underlying their number and position remain elusive. Jacob and other rare populations of sheep and goats are characterized by polyceraty, the presence of more than two horns. Here, we characterize distinct POLYCERATE alleles in each species, both associated with defective HOXD1 function. We show that haploinsufficiency at this locus results in the splitting of horn bud primordia, likely following the abnormal extension of an initial morphogenetic field. These results highlight the key role played by this gene in headgear patterning and illustrate the evolutionary co-option of a gene involved in the early development of bilateria to properly fix the position and number of these distinctive organs of Bovidae.
Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples
Authors: Lívia Bitencourt Pascoal, Patrícia Brito Rodrigues, Lívia Moreira Genaro, Arilson Bernardo dos Santos Pereira Gomes, Daniel Augusto Toledo-Teixeira, Pierina Lorencini Parise, Karina Bispo-Dos-Santos, Camila Lopes Simeoni, Paula Veri Guimarães, Lucas Ildefonso Buscaratti, João Gabriel De Angeli Elston, Henrique Marques-Souza, Daniel Martins-de-Souza, Maria De Lourdes Setsuko Ayrizono, Lício Augusto Velloso, José Luiz Proenca-Modena, Pedro Manoel Mendes Moraes-Vieira, Marcelo Alves Silva Mori, Alessandro Santos Farias, Marco Aurélio Ramirez Vinolo, Raquel Franco Leal
Journal: Gut Microbes (2021)

Microbiota-derived molecules called short-chain fatty acids (SCFAs) play a key role in the maintenance of the intestinal barrier and regulation of immune response during infectious conditions. Recent reports indicate that SARS-CoV-2 infection changes microbiota and SCFAs production. However, the relevance of this effect is unknown. In this study, we used human intestinal biopsies and intestinal epithelial cells to investigate the impact of SCFAs in the infection by SARS-CoV-2. SCFAs did not change the entry or replication of SARS-CoV-2 in intestinal cells. These metabolites had no effect on intestinal cells' permeability and presented only minor effects on the production of anti-viral and inflammatory mediators. Together our findings indicate that the changes in microbiota composition of patients with COVID-19 and, particularly, of SCFAs do not interfere with the SARS-CoV-2 infection in the intestine.
Counteracting COVID-19 Healthcare Inequity: Supporting Antiracist Practices at Bedside
Authors: Crystal E. Brown, Georgina D. Campelia
Journal: The American Journal of Bioethics (2021)

In “Racism and Bioethics: the myth of color blindness” Braddock (2021) convincingly argues that a “color blind” approach to triage and resource allocation in the setting of the COVID-19 pandemic pe...
NAT2 slow acetylation and GSTM1 null genotype increase bladder cancer risk: Confirmatory results from the spanish bladder cancer study
Authors: Montserrat Garcia-Closas, Núria Malats, Francisco X. Real, Manolis Kogevinas, Debra Silverman, Meredith Yeager, Robert Welch, Stephen Chanock, David W. Hein, Reina García-Closas, Consol Serra, Adonina Tardón, Alfredo Carrato, Claudine Samanic, Mustafa Dosemeci, Nathaniel Rothman
Journal: Cancer Research (2004)

5284  Tobacco use and occupational exposure to carcinogenic aromatic amines have been causally linked to bladder cancer and polycyclic aromatic hydrocarbons (PAH) may play a role as well. Aromatic monoamines are detoxified by NAT2 and PAHs are detoxified by one or more GST gene products. We (Marcus P. et al. Pharmacogenetics,10(2):115-22, 2000; Engel et al. Am J Epidemiol, 156(2):95-109, 2002) and others have previously carried out meta-analyses of relatively small studies suggesting that NAT2 slow acetylation (22 studies, 2,496 cases, OR 1.4, 95% CI 1.2-1.6) and the GSTM1 null genotype (17 studies, 2,149 cases, OR 1.4, 95% CI 1.2-1.7 ) are associated with increased risk of bladder cancer. We evaluated these associations in the Spanish Bladder Cancer Study, a hospital-based case-control study of 1,226 cases and 1,271 controls (87% males) that is one of the largest molecular epidemiology studies of bladder cancer carried out to date. DNA samples were obtained from 96% of cases and 90% of controls and genotyped for NAT2(K268R, G286E, R64Q, Y94, I114T, L161, R197Q),GSTM1 and GSTT1 deletions, GSTM3 (V224I, IVS8-30) and GSTP1I105V using TaqMan assays. Odds ratios (OR) and 95% confidence intervals (95%CI) were adjusted for age, gender, region, smoking status and duration using logistic regression models. NAT2 acetylation phenotype (derived from the 7 NAT2 single nucleotide polymorphisms) and the GSTM1 null genotype were each associated with a significant increase in bladder cancer risk with adjusted ORs (95%CI) of 1.34 (1.12-1.62) and 1.63 (1.37-1.95), respectively. Polymorphisms in other GSTs evaluated were not significantly associated with bladder cancer risk with adjusted ORs (95%CI) of 0.89 (0.72-1.10) for GSTT1 null, 1.06 (0.76-1.48) for GSTM3V224I homozygous variants vs. wild-type, 1.04 (0.76-1.37) for GSTM3IVS8-30 homozygous variants vs. wild-type and 1.24 (0.92-1.67) for GSTP1I105V homozygous variants vs. wild-type. Evaluation of interactions with tobacco smoking as well as gene-gene interactions is underway. This study provides confirmatory evidence that NAT2 slow acetylation and the GSTM1 null genotype are associated with increased risk of bladder cancer. These are among the most consistent findings of common genetic polymorphisms and risk of any tumor site in the literature to date.
Dual targeting of MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia
Authors: Zheng Ge, Chunhua Song, Yali Ding, Bi-Hua Tan, Dhimant Desai, Arati Sharma, Raghavendra Gowda, Feng Yue, Suming Huang, Vladimir Spiegelman, Jonathon L. Payne, Mark E. Reeves, Soumya Iyer, Pavan Kumar Dhanyamraju, Yuka Imamura, Daniel Bogush, Yevgeniya Bamme, Yiping Yang, Mario Soliman, Shriya Kane, Elanora Dovat, Joseph Schramm, Tommy Hu, Mary McGrath, Zissis C. Chroneos, Kimberly J. Payne, Chandrika Gowda, Sinisa Dovat
Journal: Leukemia (2021)

Children of Hispanic/Latino ancestry have increased incidence of high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) with poor prognosis. This leukemia is characterized by a single-copy deletion of the IKZF1 (IKAROS) tumor suppressor and increased activation of the PI3K/AKT/mTOR pathway. This identifies mTOR as an attractive therapeutic target in HR B-ALL. Here, we report that IKAROS represses MTOR transcription and IKAROS' ability to repress MTOR in leukemia is impaired by oncogenic CK2 kinase. Treatment with the CK2 inhibitor, CX-4945, enhances IKAROS activity as a repressor of MTOR, resulting in reduced expression of MTOR in HR B-ALL. Thus, we designed a novel therapeutic approach that implements dual targeting of mTOR: direct inhibition of the mTOR protein (with rapamycin), in combination with IKAROS-mediated transcriptional repression of the MTOR gene (using the CK2 inhibitor, CX-4945). Combination treatment with rapamycin and CX-4945 shows synergistic therapeutic effects in vitro and in patient-derived xenografts from Hispanic/Latino children with HR B-ALL. These data suggest that such therapy has the potential to reduce the health disparity in HR B-ALL among Hispanic/Latino children. The dual targeting of oncogene transcription, combined with inhibition of the corresponding oncoprotein provides a paradigm for a novel precision medicine approach for treating hematological malignancies.
Predicting COVID-19 Outcomes in Emergency Department Patients
Authors: Jennifer Abbasi
Journal: JAMA (2021)

CRISPR-Based COVID-19 Smartphone Test in DevelopmentA simplified point-of-care assay that turns a smartphone into a fluorescence microscope could expand coronavirus disease 2019 (COVID-19) testing capability, researchers reported in a study in Cell.The assay, which uses clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology, emits a fluorescent signal in the presence of the novel coronavirus's RNA.A smartphone camera can detect this signal directly, without amplification of the viral genome used in most genetic tests.This means the test can quantify the amount of virus in the sample-the quicker the signal is picked up, the higher the viral load.In the study, the assay was able to detect RNA extracted from patients' nasal swabs within 5 minutes.Samples with less virus could be detected within 30 minutes."Monitoring viral loads quantitatively would allow estimation of infection stage and help predict infectivity, recovery, and return from quarantine in real time," the authors wrote."We plan on applying for [Emergency
Upper Airway Microbiota Relates to Season and Asthma Exacerbations
Authors: Kathryn McCauley, Kaitlin Flynn, Vincent DiMassa, Douglas Fadrosh, Kole Lynch, Petra LeBeau, Agustin Calatroni, Brett Jepson, Michelle Gill, James Gern, Dan Jackson, Matthew Altman, Susan Lynch
Journal: Journal of Allergy and Clinical Immunology (2021)
Gold nanorods and nanohydroxyapatite hybrid hydrogel for preventing bone tumor recurrence via postoperative photothermal therapy and bone regeneration promotion
Authors: Jinfeng Liao, Kun Shi, Yanpeng Jia, Yanting Wu, Zhiyong Qian
Journal: Bioactive Materials (2021)

Osteosarcoma is a malignant bone tumor, which often occurs in adolescents. However, surgical resection usually fails to completely remove the tumor clinically, which has been the main cause of postoperative recurrence and metastasis, resulting in the high death rate of patients. At the same time, osteosarcoma invades a large area of the bone defect, which cannot be self-repaired and seriously affects the life quality of the patients. Herein, a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods (GNRs) and nanohydroxyapatite (nHA), which possessed excellent photothermal effect, was constructed to eradicate residual tumor after surgery and bone regeneration. In vitro, K7M2wt cells (a mouse bone tumor cell line) can be efficiently eradicated by photothermal therapy of the hybrid hydrogel. Meanwhile, the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells. The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma. Therefore, the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration, which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.
BACH2 enforces the transcriptional and epigenetic programs of stem-like CD8+ T cells
Authors: Chen Yao, Guohua Lou, Hong-Wei Sun, Ziang Zhu, Yi Sun, Zeyu Chen, Daniel Chauss, E. Ashley Moseman, Jun Cheng, Marc A. D’Antonio, Wangke Shi, Junwei Shi, Kohei Kometani, Tomohiro Kurosaki, E. John Wherry, Behdad Afzali, Luca Gattinoni, Yuwen Zhu, Dorian B. McGavern, John J. O’Shea, Pamela L. Schwartzberg, Tuoqi Wu
Journal: Nature Immunology (2021)