tbuckley/cabot-search huggingface dataset:
Clinical Ophthalmology for the General Practitioner.
Journal: JAMA (1921)

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
Abstract LB-050: Memory sequencing reveals heritable single cell gene expression programs associated with therapy resistance
Authors: Sydney Shaffer, Benjamin Emert, Eduardo Torre, Arjun Raj
Journal: Cancer Research (2019)

Abstract Single cancer cells can have substantial fluctuations in gene expression from non-genetic factors. However, it is unclear how long these fluctuations exist and whether they extend beyond the length of a single-cell division. Current technologies for gene expression measurements in single cells provide just one measurement of each cells’ transcriptome and fail to capture how these gene expression fluctuations change with time. We developed a new method combining Luria and Delbruck's fluctuation analysis with population-based RNA sequencing (MemorySeq) for identifying genes transcriptome-wide whose fluctuations persist for several cell divisions. MemorySeq revealed multiple gene modules that express together in rare cells within otherwise homogeneous clonal populations. Further, we found that these rare cell subpopulations are associated with biologically distinct phenotypes in multiple different cancer cell lines. In melanoma, we identified a rare subpopulation of cells expressing EGFR, NGFR, and AXL, and demonstrated that these cells are resistant to BRAF and MEK inhibitors. In triple-negative breast cancer cells, we identified a different gene expression signature consisting of CA9, and found that this subpopulation is resistant to paclitaxol. We validated these findings in melanoma cell lines by tagging the endogenous locus of MemorySeq gene, NGFR, with a fluorescent protein to directly visualize gene expression fluctuations in individual cells. Broadly, we believe that memory is an essential property of variability that will have phenotypic consequences for cancer cells. Thus, we anticipate that MemorySeq can be extended to uncover the transcriptional states of rare cells driving many phenotypes in cancer including drug resistance, differentiation, invasion, and metastasis. Citation Format: Sydney Shaffer, Benjamin Emert, Eduardo Torre, Arjun Raj. Memory sequencing reveals heritable single cell gene expression programs associated with therapy resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-050.
Abstract 880: Genetic ablation of the cystine transporter xCT in pancreatic ductal adenocarcinoma inhibits mTORC1, growth, survival and tumor formation: Implications for potentiating chemosensitivity <i>via</i> erastin
Authors: Milica Vučetić, Boutaina Daher, Jerome Durivault, Scott K. Parks, Jacques Pouyssegur
Journal: Cancer Research (2019)

Abstract The lethality of pancreatic ductal adenocarcinomas (PDAC) calls for improved therapeutic strategies. Chemoresistance remains a primary challenge in PDAC treatment, and exploiting oxidative stress might offer novel therapeutic clues. In this regard, we explored the cystine/glutamate exchanger (SLC7A11/xCT) that contributes to the maintenance of the intracellular glutathione (GSH). We deleted xCT via CRISPR-Cas9 in two PDAC cell lines (MiaPaCa-2 and Capan-2) and cultivated xCT-KO clones in the presence of N-acetylcysteine (NAC). In both cell lines, xCT-deletion abolished &amp;gt;90% of 14C-cystine uptake and induced a rapid depletion of GSH following NAC removal. Although several cystine/cysteine transporters have been identified in human cells, our finding demonstrates that, in vitro, xCT is the major actor for GSH synthesis. Consequently, both xCT-KO cell lines exhibited amino-acid stress with ATF4 and GCN2 kinase activation, mTORC1 inhibition, and proliferation arrest followed by ferroptotic cell death. Importantly, tumor growth was also abolished in both KO cell lines indicating the key role of xCT in cellular cysteine availability in vivo. Moreover, the rapid depletion of intracellular GSH in xCT-KO cells led to accumulation of lipid peroxides and cell swelling, both being prevented by vitamin E or iron chelation, two hallmarks of cell death by ferroptosis. Finally, in vitro pharmacological inhibition of xCT by erastin (1μM) phenocopied xCT-KO and potentiated the cytotoxic effects of both gemcitabine and cisplatin in these PDAC cell lines. In conclusion, our findings strongly support the concept that xCT inhibition, by its dual induction of nutritional and oxidative cellular stresses, has the great potential of a successful anticancer strategy. Note: This abstract was not presented at the meeting. Citation Format: Milica Vučetić, Boutaina Daher, Jerome Durivault, Scott K. Parks, Jacques Pouyssegur. Genetic ablation of the cystine transporter xCT in pancreatic ductal adenocarcinoma inhibits mTORC1, growth, survival and tumor formation: Implications for potentiating chemosensitivity via erastin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 880.
Patterns of leukemic transformation in patients with <i>TP53</i>-mutant myelodysplastic syndromes.
Authors: Kelly Sharon Chien, Christopher Brent Benton, Caleb A. Class, Tapan M. Kadia, Courtney Denton Dinardo, Marina Konopleva, Michael Andreeff, Koji Sasaki, Kiran Naqvi, Irene Ganan Gomez, Yue Wei, Hui Yang, Sherry A. Pierce, Keyur P. Patel, Rashmi Kanagal-Shamanna, Hagop M. Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo
Journal: Journal of Clinical Oncology (2019)

7054 Background: TP53 is the most frequently mutated gene in human cancers, including 7-13% of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. Although it is associated with transformation to AML in patients with MDS, the additional genomic events leading to transformation are poorly understood. Methods: We retrospectively evaluated 312 patients with TP53-mutated AML or MDS diagnosed between 2013-2016. Patient characteristics and bone marrow data, including cytogenetic and next generation sequencing information, were assessed at the time of diagnosis and progression to AML. Results: There were 151 TP53-mutated MDS patients and 161 TP53-mutated de novo AML patients with a median follow-up time of 34.1 months. Forty-one patients with TP53-mutated MDS transformed to AML. Sequencing data at transformation was available in 17 patients (41%). At diagnosis, median age was 67 with 2 patients with intermediate-risk, 7 patients with high-risk, and 32 patients with very high-risk MDS by IPSS-R. Complex karyotype was seen in 40 patients, and 12 patients had 1, 25 patients had 2, and 4 patients had 3 TP53 abnormalities. Predictors of transformation to AML include TP53 loss of heterozygosity (p = 0.008), 3 TP53 abnormalities (p = 0.049), complex cytogenetics (p = 0.023), and female gender (p = 0.002). Median time to transformation was 10.4 months. At transformation, an increase in TP53 variant allelic frequency was observed in 7 patients (41%), and new mutations, particularly NRAS, IDH1, TP53, MLL, KDM6A, TET2, and NOTCH1, were acquired by 10 patients (59%). Cytogenetic evaluation revealed identical clones in 5 patients, linear acquisition of cytogenetic abnormalities in 12 patients, and new clones in 8 patients. Patients with TP53-mutated AML from MDS also had worse median overall survival than patients with TP53-mutated de novo AML at 2.5 months vs. 5.7 months respectively (p &lt; 0.001). Conclusions: TP53 mutations confer a worse prognosis, especially in the setting of AML transformed from MDS. This may be due to the acquisition of new mutations and cytogenetic abnormalities. Further exploration of the biological mechanisms leading to transformation in TP53-mutant MDS is warranted.
An Aging Population of Chronic Hepatitis B With Increasing Comorbidities: A Territory‐Wide Study From 2000 to 2017
Authors: Grace Lai‐Hung Wong, Vincent Wai‐Sun Wong, Becky Wing‐Yan Yuen, Yee‐Kit Tse, Hester Wing‐Sum Luk, Terry Cheuk‐Fung Yip, Vicki Wing‐Ki Hui, Lilian Yan Liang, Grace Chung‐Yan Lui, Henry Lik‐Yuen Chan
Journal: Hepatology (2019)

Patients with chronic hepatitis B (CHB) are aging because of improved survival under better health care. This has an important implication on the choice of antiviral treatment (AVT), given that long‐term safety would be a concern in the presence of multiple comorbidities. We aimed to determine the prevalence of key comorbidities and concomitant medications in a territory‐wide CHB cohort in Hong Kong in 2000‐2017. CHB patients who have been under the care at primary, secondary, and tertiary medical centers in the public sector were identified through the Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong. The demographics and prevalence of key comorbidities, including diabetes mellitus, hypertension, chronic kidney disease, osteopenia/osteoporosis based on diagnosis codes, relevant medications, and/or laboratory parameters, were determined according to CHB patients’ first appearance in four time periods: 2000‐2004, 2005‐2009, 2010‐2013, and 2014‐2017. In the final analysis, 135,395 CHB patients were included; the mean age increased with time: 41 ± 15 years in 2000‐2004; 46 ± 17 years in 2005‐2009; 51 ± 16 years in 2010‐2013; and 55 ± 15 years in 2014‐2017. There was a trend of increasing prevalence of several common comorbidities over the four periods: hypertension 25.5%, 23.8%, 27.2%, and 28.6%; diabetes mellitus 10.6%, 12.5%, 16.1%, and 20.1%; cardiovascular disease 12.5%, 16.9%, 20.9%, and 22.2%; and malignancy 7.0%, 13.2%, 17.3%, and 23.6%, respectively (all P &lt; 0.001). Conclusion: CHB patients are getting older with increasing prevalence of common comorbidities. These comorbidities should be taken into account when choosing AVT.
Effect of pedometer-based walking interventions on long-term health outcomes: Prospective 4-year follow-up of two randomised controlled trials using routine primary care data
Authors: Tess Harris, Elizabeth S. Limb, Fay Hosking, Iain Carey, Steve DeWilde, Cheryl Furness, Charlotte Wahlich, Shaleen Ahmad, Sally Kerry, Peter Whincup, Christina Victor, Michael Ussher, Steve Iliffe, Ulf Ekelund, Julia Fox-Rushby, Judith Ibison, Derek G. Cook
Journal: PLoS Medicine (2019)

Data are lacking from physical activity (PA) trials with long-term follow-up of both objectively measured PA levels and robust health outcomes. Two primary care 12-week pedometer-based walking interventions in adults and older adults (PACE-UP and PACE-Lift) found sustained objectively measured PA increases at 3 and 4 years, respectively. We aimed to evaluate trial intervention effects on long-term health outcomes relevant to walking interventions, using routine primary care data.
Abstract 411: Rapid and sensitive detection of EGFR C797S mutations using a blood-based droplet digital PCR assay
Authors: Victoria Edwards, Leisa Jackson, Jordan Reese, Hestia S. Mellert, Gary Pestano
Journal: Cancer Research (2019)

Abstract The adoption of third-generation tyrosine kinase inhibitors (TKIs) to treat non-small cell lung cancer (NSCLC) for EGFR positive patient cases has led to the emergence of acquired resistance pathways. Approximately 40% of EGFRT790M-positive NSCLC cases display an acquired mutation of amino acid 797 (C797S) that mediates this resistance, which can develop after a median of 10 months following treatment. The effectiveness of treatment for patients with EGFRC797S may depend on whether the mutation is present in cis or trans with EGFRT790M, the type of sensitizing mutation (EGFRdel19 or EGFRL858R), and previous treatment(s). Patients with EGFRdel19 or EGFRL858R in conjunction with EGFRT790M and EGFRC797S remain resistant to all current targeted therapies. Several fourth-generation inhibitors are in development but have yet to be validated in clinical trials. We have developed a blood-based test that can detect two of the most common C797S nucleotide mutations (T&amp;gt;A and G&amp;gt;C) in cis or trans with EGFRT790M using the droplet digital PCR (ddPCR) technology and assays. Analytic sensitivity and specificity were assessed using synthetic DNA designed to mimic the EGFRC797S variants and their locus detected in the assay. Normal healthy donors as well as reference ddPCR positive and negative NSCLC donor samples were assessed for clinical specificity and sensitivity. Finally, the precision of the assay was evaluated with both clinical and analytical samples. Specifically, we evaluated the assay at high, medium, and low mutation frequencies over three consecutive days, including repeat runs on one day, and with multiple operators. This assay is capable of accurately and precisely detecting multiple EGFRC797S variants and their locus from blood specimens in the clinical laboratory. Consistent with other ddPCR blood-based EGFR variant assays we have developed, the limit of detection was 0.02%for C797S variants detected in both cis and trans with the T790M mutation. Once validated, the EGFR C797S assay described here may be of utility in diagnosing patients who have developed resistance to osimertinib. Citation Format: Victoria Edwards, Leisa Jackson, Jordan Reese, Hestia S. Mellert, Gary Pestano. Rapid and sensitive detection of EGFR C797S mutations using a blood-based droplet digital PCR assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 411.
A Phase II Study of Midostaurin and 5-Azacitidine for Elderly Patients with Acute Myeloid Leukemia
Authors: Molly M Gallogly, Ben K. Tomlinson, Pam Bunner, Paolo Caimi, Michael Craig, Marcos de Lima, Stanton L. Gerson, Donna Kane, Hillard M Lazarus, Mark J. Levis, Ehsan Malek, Jane A. Little, Crystal Street, Willem J. van Heeckeren, William Tse, Brenda W. Cooper
Journal: Blood (2017)
CRP predicts tolerance of treatment and overall survival with weekly carboplatin-paclitaxel and concomitant irradiation for locally advanced non-small cell lung cancer
Authors: K. Webber, A. Fontela, N. Bonner, J. Bell, J. Bucci, C.R. Lewis, P.L. De Souza, P.H. Graham, M.J. Links
Journal: Journal of Thoracic Oncology (2009)
Lateral Lymph Nodes as the Achilles Heel of Low Rectal Cancer Surgery After Neoadjuvant Chemoradiation Therapy
Authors: Linda Ferrari, Alessandro Fichera
Journal: JAMA Surgery (2019)

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
Abstract 14600: Thyroid Dysfunction and the Immediate Risk of Heart Failure
Authors: Henrik Hovgaard, Christoffer Polcwiartek, Steen M Hansen, Christian Selmer, Emil Fosbøl, Christian Torp-Pedersen, Christina J Lee
Journal: Circulation (2018)

Introduction: Thyroid dysfunction is associated with various cardiovascular manifestations. Heart failure (HF) has been shown to be the leading cause of mortality in both overt and subclinical hype...
POT1 and TERT promoter molecular screening in Spanish melanoma families
Authors: M. Potrony, J.A. Puig‐Butille, M. Ribera‐Sola, V. Iyer, C.D. Robles‐Espinoza, P. Aguilera, C. Carrera, J. Malvehy, C. Badenas, M.T. Landi, D.J. Adams, S. Puig
Journal: British Journal of Dermatology (2019)

Melanoma is an aggressive type of skin cancer. Each year more than 250,000 new cases are diagnosed worldwide. If diagnosed at early stages, melanoma can be cured with relatively simple surgery. Globally, 20% of melanoma patients will die, but when diagnosed with thick (more advanced / later stage) tumours, the probability of dying increases by up to 60%. The best strategy to improve survival is with early diagnosis. The identification of people at risk is essential. Around 10% of cases occur in a familial context. This means that these individuals have an inherited genetic risk of developing melanoma explained by the presence of alterations (mutations) in specific genes. In a family with known mutation, healthy individuals who carry the mutation can be included in early detection programs that allow the diagnosis of melanomas at early stages. But the gene/genes responsible for this risk is still unknown in more than 70% of families. This study, from Spain, aimed to evaluate the prevalence of mutations in two genes (POT1 and TERT) in Spanish melanoma‐prone families without known mutated genes. The authors sequenced (a way of studying) both genes in cases from 228 families. They found mutations in nearly 2% of the families assessed. They additionally identified two patients in two families who also had thyroid malignances. If this is confirmed in additional studies, the melanoma‐prone families with mutations in this gene will also benefit from early diagnosis of thyroid tumours. No mutations were identified in TERT promoter indicating that this gene does not play an important role in familial melanoma susceptibility in Spain.
Abstract 12858: Relationship of Patent Foramen Ovale Morphology and Shunt Size: Insights from 3D Transoesophageal Echocardiography
Authors: Anna C Kydd, Preety Das, Patrick A Calvert, Leonard M Shapiro, Bushra S Rana
Journal: Circulation (2012)

Background Patent foramen ovale (PFO) is implicated in paradoxical embolism and stroke. The relationship between anatomy, right-to-left shunt and embolic risk is unclear. Certain anatomical feature...
Abstract 2181: A novel CXCR4 antagonist strongly mobilizes hematopoietic stem cells <i>in vivo</i>
Authors: Xiao Fang, Qian Meng, Xiong Fang, Yujia Mao, Yan Xu, Jing An, Ziwei Huang
Journal: Cancer Research (2019)

Abstract Introduction: The transplantation of hematopoietic stem cells (HSCs) has been the standard of care for the treatment of chemotherapy sensitive relapsed acute leukemia. HSCs mainly reside in the bone marrow with only few HSCs circulating in the peripheral blood (PB), due to homing effect mediated by the interaction of chemokine receptor CXCR4 expressed on HSCs with chemotactic ligand SDF-1α rich in the bone marrow. It is clinically desirable to enhance the number of HSCs in the PB for collection during the transplantation procedure. Since SDF-1α/CXCR4 axis and interaction mediates the homing and retention of HSCs in the bone marrow, our laboratory has recently discovered and developed a novel small molecule, HFX51116, that is capable of binding CXCR4 and blocking its interaction with SDF-1α, raising the possibility that this compound can be used for releasing HSCs from the bone marrow to the PB useful for the transplantation of HSCs. Method and Results: In vitro, there was almost no toxicity of HFX51116 at high concentrations in bone marrow stromal cells that were originally extracted from rats. In addition, HFX51116 was stable in rat serum. In vivo, we tested the short-term and long-term mobilization efficacy of HFX51116. For the short-term efficacy study, we determined the dynamic change of efficacy at different times and doses of HFX51116 in HSC mobilization assays. Furthermore, different strains of mice, such as C57/BL6, C3H/HEJ and DBA/2, were sensitive to HFX51116. HFX51116, when used in combination with G-CSF, had higher efficacy than G-CSF alone. For the long-term repopulation study, we employed the CD45.1/CD45.2 competitive assay to demonstrate that the HSCs mobilized by G-CSF and HFX51116 had the repopulation ability when compared with the bone marrow cells. Conclusion: Our studies have demonstrated high HSC mobilization efficacy of HFX51116 in vivo and the promise of this new lead compound for further preclinical and clinical studies. Citation Format: Xiao Fang, Qian Meng, Xiong Fang, Yujia Mao, Yan Xu, Jing An, Ziwei Huang. A novel CXCR4 antagonist strongly mobilizes hematopoietic stem cells in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2181.