tbuckley/cabot-search huggingface dataset:
PF249 NEXT‐GENERATION‐SEQUENCE‐BASED GENE MUTATION DETECTION AND ITS CLINICAL SIGNIFICANCE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
Authors: J. Yu, T. Li, Y. Li, Y. Li, H. Xing, H. Sun, D. Wan, Y. Liu, C. Wang, X. Xie, Z. Jiang
Journal: HemaSphere (2019)

Background: Acute myeloid leukemia (AML) is a biologically heterogeneous disease with many different cytogenetic disorders and gene mutations. The advances of the next‐generation sequence (NGS) made it more practical for the clinical research to explore the cytogenetic analysis and mutation testing for the classification and risk assessment of AML patients. Aims: In this study, we sought to investigate the differences in molecular gene mutations between different type of AML patients and the response from those newly diagnosed AML patients to induction chemotherapy. Methods: We retrospectively evaluated 274 hospitalized non‐M3 AML patients. A next‐generation sequencing assay covering 43 genes was used to investigate recurrently mutated genes. The mutational status of fusion genes was determined by real time PCR. Clinical follow up was based on the patients recent clinic visits. Correlation analysis was done based different groups classified by different categories. Results: The median age at diagnosis was 45 year‐old (range 16–81 years). 231 patients were 59 years or younger with the median age of 41 years. Forty‐three patients were 60 years or older with a median age of 69 years (range 60–81 years). At least one non‐synonymous gene mutation was detected in 233 patients (85%). The median number of gene mutations was two (range 0–8). Comparing to the 59 years or younger patients, there was a significantly higher incidence of gene mutation in 60 years and older patients (p &lt;0.01). The mean number of molecular gene mutations at diagnosis was higher in older patients than younger patients (2.92 vs 1.48, p &lt; 0.05). Older patients had significantly higher frequency of ASXL1 (23.3% vs 13.9%, p &lt;0.05), TP53 (11.6% vs 1.7%, p &lt;0.05), IDH2 (18.6% vs 4.3%, p &lt; 0.05) mutations, higher frequency of CEBPA (21.2% vs 14%, p &lt; 0.05). Among 11 patients with no gene mutation received DA (daunorubicin 80 mg/m2 per day on days 1–3 and cytarabine 100 mg/m2 twice per day on days 1–7) as the induction therapy, 8 patients (73%) achieved CR after 1 course induction treatment. Meanwhile, among 21 patients with one or more gene mutations received DA induction therapy, only 12 patients (57%) achieved CR after 1 course induction treatment. More data need to be collected regarding the significance of each individual gene fusion correlating with induction chemotherapy. Summary/Conclusion: A higher incidence of cytogenetic disorders was found in older AML patients with higher burdens of molecular mutations, comparing to younger patients. Also, significantly higher frequency of ASXL1, TP53, IDH2 and CEBPA had been found with older patients. Patients with fewer gene fusion had a better chance of achieving CR when treated with cytarabine and daunorubicin induction chemotherapy.
Putting the New Alzheimer Disease Amyloid, Tau, Neurodegeneration (AT[N]) Diagnostic System to the Test
Authors: David Wolk, Stephen Salloway, Brad Dickerson
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Regulatory T-cells regulate neonatal heart regeneration by potentiating cardiomyocyte proliferation in a paracrine manner
Authors: Jiatao Li, Kevin Y. Yang, Rachel Chun Yee Tam, Vicken W. Chan, Hui Yao Lan, Shohei Hori, Bin Zhou, Kathy O. Lui
Journal: Theranostics (2019)

The neonatal mouse heart is capable of transiently regenerating after injury from postnatal day (P) 0-7 and macrophages are found important in this process. However, whether macrophages alone are sufficient to orchestrate this regeneration; what regulates cardiomyocyte proliferation; why cardiomyocytes do not proliferate after P7; and whether adaptive immune cells such as regulatory T-cells (Treg) influence neonatal heart regeneration have less studied.
Abstract 11300: Low T3 Syndrome is Associated With High Mortality and Impaired Exercise Capacity in Hospitalized Patients With Heart Failure
Authors: Yu Sato, Akiomi Yoshihisa, Yusuke Kimishima, Takatoyo Kiko, Yuki Kanno, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Yasuchika Takeishi
Journal: Circulation (2018)

Introduction: We aimed to clarify whether low T3 syndrome affects the prognosis of patients with heart failure (HF) and underlying clinical and pathophysiological parameters (e.g. cardiac function,...
G protein‐coupled receptors of the hypothalamic–pituitary–gonadal axis: A case for gnrh, LH, FSH, and GPR54 receptor ligands
Authors: Laura H. Heitman, Adriaan P. IJzerman
Journal: Medicinal Research Reviews (2008)

Abstract The hypothalamic–pituitary–gonadal (HPG) axis, important in reproduction and sex hormone‐dependent diseases, is regulated by a number of G protein‐coupled receptors. The recently “deorphanized” GPR54 receptor activated by the peptide metastin is thought to be the key regulator of the axis, mainly by releasing gonadotropin‐releasing hormone (GnRH) from the hypothalamus. The latter decapeptide, through the activation of the GnRH receptor in the anterior pituitary, causes the secretion of luteinizing hormone (LH) and follicle‐stimulating hormone (FSH), which subsequently activate their respective receptors on the gonadotrope cells. In this review we will discuss the small molecule agonists and antagonists that are currently being developed to intervene with the action of these four receptors. For GnRH receptors, 14 different chemical classes of non‐peptidic antagonists have been reported, while for the LH receptor three classes of agonists have been described. Both agonists and antagonists have been introduced for the FSH receptor. Recently, the first non‐peptidic agonist for GPR54 was reported. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 6, 975–1011, 2008
Single-fraction stereotactic versus standard conventional multifraction radiation for predominantly non-spine bone metastases: A randomized phase II trial.
Authors: Quynh Nguyen, Edward Chow, Stephen G. Chun, Zhongxing X. Liao, Rensi Fnu, James William Welsh, Stephen Hahn, Clifton David Fuller, Bryan Moon, Justin E. Bird, Robert L. Satcher, Patrick P. Lin, Melenda Jeter, Michael O'Reilly, Valerae O. Lewis
Journal: Journal of Clinical Oncology (2019)

11578 Background: There lacks a consensus as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases. We assessed the relative efficacy of single high-dose stereotactic radiation therapy (SBRT) versus standard multifraction radiation therapy (MFRT) for alleviation of pain in patients with mostly non-spine bone metastases. Methods: This prospective, randomized, single-institution phase II non-inferiority trial enrolled patients with radiologically confirmed painful bone metastases from September 2014 through June 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for &lt; 4-cm lesions) versus MFRT to 30 Gy in 10 fractions. Results: The primary endpoint was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose [MED]). Failure of pain response was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of ≥50%; re-irradiation; or pathologic fracture. Among evaluable patients who received treatment per protocol, the single-fraction SBRT group had more pain responders (CR+PR) at 2 weeks (62% vs. 36% MFRT, P= 0.01), at 1 month (62% vs 36%, P= 0.01), at 3 months (72% vs. 49% MFRT, P= 0.03), and at 9 months (77% vs. 12% MFRT, P= 0.03). No differences were found in treatment-related toxicity or quality of life scores after SBRT versus MFRT; local control rates at 1 year were higher in patients receiving single-fraction SBRT. Conclusions: Delivering high-dose single-fraction SBRT is an effective, convenient treatment option for patients with painful bone metastases. Among evaluable patients, SBRT led to higher rates of pain response (CR+PR) than did MFRT and thus should be considered for patients expected to have relatively long survival. Clinical trial information: ClinicalTrials.gov ID NCT02163226.
Abstract 80: PI3Kα Regulates Biomechanical Stress-induced Cytoskeletal Remodeling: A Critical Role of Gelsolin
Authors: Vaibhav B Patel, Pavel Zhabyeyev, Brent A McLean, Dong Fan, Ratnadeep Basu, Jessica DesAulniers, Zamaneh Kassiri, Bart Vanhaesebroeck, Christopher A McCulloch, Gavin Y Oudit
Journal: Circulation Research (2016)

Background: Biomechanical stress and cytoskeletal remodeling are key determinants in pressure overload-induced heart failure. Class Ia phosphoinositide 3-kinases (PI3Ks) mediate a variety of cellular activities, in response to agonist binding to cell-surface receptors, by generating the phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) phosphoinositide lipid. Gelsolin is a Ca 2+ - and phosphoinositide-regulated actin filament severing and capping protein that is upregulated in failing human hearts and animal models of heart failure. Hypothesis: We hypothesize that PI3Kα regulates cytoskeletal remodeling through PIP 3 -mediated regulation of gelsolin. In addition, loss of gelsolin could attenuate the adverse cytoskeletal remodeling and result in increased resistance to the development of heart failure in response to pressure-overload. Methods and Results: Loss of p110α kinase activity, in two different transgenic models (PI3Kα dominant-negative (PI3KαDN) and cardiomyocyte-specific PI3Kα-null), resulted in dilated cardiomyopathy and markedly worsened cardiac dysfunction in response to transverse aortic constriction-induced pressure overload. Increased levels of mechanosensor proteins along with decreased F/G-actin ratio exhibited an uncoupling between cardiac mechanotransduction and cytoskeletal remodeling in p110α-null mice. Gelsolin activity was markedly increased in the p110α-null hearts in response to pressure-overload, whereas loss of gelsolin in PI3KαDN/gelsolin-null double mutant mice prevented the adverse cytoskeletal remodeling and preserved the cardiac function. In a murine model of chronic heart failure, loss of gelsolin prevented the pressure overload-induced cardiac dysfunction, fibrosis, and impaired cardiomyocyte contractility resulting in increased survival. Loss of gelsolin also mitigated the biomechanical stress-induced adverse cytoskeletal remodeling, via the attenuation of actin severing activity. Conclusions: We have identified a novel role of gelsolin as a mediator of adverse cytoskeletal remodeling leading to heart failure, where PI3Kα is a key regulator of gelsolin activity.
PS1249 EXTRANODAL AND SPLEEN DISEASE DETECTED BY FDG‐PET/CT IS ASSOCIATED WITH EARLY CLINICAL FAILURE IN UNTREATED FOLLICULAR LYMPHOMA
Authors: F. St‐Pierre, S. Broski, B. Laplant, K. Ristow, M. Maurer, W. Macon, T. Habermann, S. Ansell, C. Thompson, I. Micallef, G. Nowakowski, T. Witzig
Journal: HemaSphere (2019)

Background: Predicting early clinical failure in patients with untreated follicular lymphoma (FL) is important but difficult. Lymphoma involvement of extranodal (EN) sites is better detected by FDG‐PET/CT than CT alone, but PET parameters are not part of the usual predictive indices. Aims: We aimed to determine the incidence and patterns of EN and spleen disease, and learn if they were useful in predicting early clinical failure. Methods: PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed for EN and spleen involvement. The location, number, and pattern of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event‐free survival (EFS), overall survival (OS), and early clinical failure at 24 months (EFS24). Results: 49% (301/613) of patients had PET/CT‐detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone or soft tissue involvement all predicted failure to achieve EFS24. These factors, as well as pattern of bone involvement by imaging, were predictors of EFS on univariate analysis; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI‐2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table 1). When the multivariate analysis was performed using PRIMA‐PI factors (marrow and B2 M), the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01–5.18; p = 0.05). Table 1: Extranodal and spleen involvement by PET/CT as predictors of event‐free survival Summary/Conclusion: Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure in FL. These results, when combined with other factors, may better identify high‐risk patients and guide appropriate therapy. image image
Abstract 14965: Risk of Mortality Among Patients With Incident Heart Failure in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Mohammad R Ostovaneh, Bharath Ambale-Venkatesh, Colin O Wu, Harjit Chahal, Hooman Bakhshi, Robyn L McClelland, Kiang Liu, Steven J Shea, Gregory Burke, Wendy Post, Karol E Watson, Aaron R Folsom, David A Bluemke, Joao A Lima
Journal: Circulation (2017)

Introduction: Patients with heart failure (HF) are at high risk of mortality later in life. The risk factors associated with mortality in these patients are not well established. Hypothesis: The cl...
Circular RNAs negatively regulate cancer stem cells by physically binding FMRP against CCAR1 complex in hepatocellular carcinoma
Authors: Yan-Jing Zhu, Bo Zheng, Gui-Juan Luo, Xu-Kai Ma, Xin-Yuan Lu, Xi-Meng Lin, Shuai Yang, Qing Zhao, Tong Wu, Zhi-Xuan Li, Xiao-Long Liu, Rui Wu, Jing-Feng Liu, Yang Ge, Li Yang, Hong-Yang Wang, Lei Chen
Journal: Theranostics (2019)

Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers.It has been reported playing roles in multiple malignant behaviors including proliferation, migration, metastasis and chemoresistance.However, the underlying correlation between circRNAs and cancer stem cells (CSCs) has not been reported yet.Methods: circZKSCAN1 level was detected in HCC tissue microarrays to clarify its prognostic values.Gain and loss function experiments were applied to investigate the role of circZKSCAN1 in HCC stemness.Bioinformatic analysis was used to predict the possible downstream RNA binding protein and further RNA immunoprecipitation sequencing was carried out to identify the RBP-regulated genes. Results:The absence of circZKSCAN1 endowed several malignant properties including cancer stemness and tightly correlated with worse overall and recurrence-free survival rate in HCC.Bioinformatics analysis and RNA immunoprecipitation-sequencing (RIP-seq) results revealed that circZKSCAN1 exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and β-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restrain the transcriptional activity of Wnt signaling.In addition, RNA-splicing protein Quaking 5 was found downregulated in HCC tissues and responsible for the reduction of circZKSCAN1. Conclusion:Collectively, this study revealed the mechanisms underlying the regulatory role of circZKSCAN1 in HCC CSCs and identified the newly discovered Qki5-circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important therapeutic target for HCC treatment.
FRI0117 THE COMPARATIVE RISK OF OSTEOPOROTIC FRACTURES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING TNF INHIBITORS VERSUS OTHER BIOLOGICS: A NATION-WIDE COHORT STUDY IN KOREA
Authors: Anna Shin, Yaa-Hui Dong, Seunghwan Shin, You-Jung Ha, Yun Jong Lee, Eun Bong Lee, Yeong Wook Song, Eun Ha Kang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Rheumatoid arthritis (RA) is associated with an increased risk of osteoporosis and osteoporotic fracture, but little is known about comparative risk of osteoporotic fractures between biologic agents. <h3>Objectives:</h3> To investigate the comparative risk of osteoporotic fractures among RA patients who initiated TNF inhibitors, abatacept, and tocilizumab. <h3>Methods:</h3> We identified patients aged ≥ 40 years with at least two ICD-10 diagnosis codes for RA who initiated TNF inhibitor, abatacept, or tocilizumab from the 2005-2015 Korean National Health Insurance Service datasets. The primary outcome was a composite osteoporotic fracture endpoint of spine, hip, forearm or humerus fractures requiring hospitalization. Secondary outcomes were spinal and non-spinal fractures. Follow-up period started from the day after the first dispensing date of the study drug to the earliest date among the following events: discontinuation of the study drugs, outcome occurrence, disenrollment, end of study dataset, or death. Propensity score (PS) matching with a variable ratio of 10:1 was conducted for TNF inhibitor versus abatacept initiators and for TNF inhibitor versus tocilizumab initiators to adjust for baseline confounding. We estimated hazard ratio (HR) and 95% confidence interval (CI) of osteoporotic fracture risks comparing TNF inhibitors to abatacept or tocilizumab by Cox proportional hazard models stratified by a matching ratio. <h3>Results:</h3> We included 2,339 TNF inhibitor initiators and 594 abatacept initiators, and 2,486 TNF inhibitor initiators and 647 tocilizumab initiators in each PS-matched cohort. The incidence rates per 100 person-years for the primary outcome were 1.57 and 1.65 for TNF inhibitor and abatacept initiators, and 1.69 and 2.05 for TNF inhibitor and tocilizumab initiators, respectively. The HR (95% CI) for the primary outcome was 1.10 (1.54-2.23) comparing TNF inhibitors versus abatacept and it was 1.00 (0.53-1.92) comparing TNF inhibitor versus tocilizumab initiators. We also did not find any significant difference for secondary outcomes (Table1). <h3>Conclusion:</h3> We did not find a significant difference in the risk of osteoporotic fractures between TNF inhibitor and abatacept initiators, or between TNF inhibitor and tocilizumab initiators in this Korean population-based cohort study. <h3> Disclosure of Interests:</h3> None declared
Sodium Polystyrene Sulfonate for Hyperkalemia
Authors: Monica Parks, Deborah Grady
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
The cognitive effects of modafinil in breast cancer survivors: A randomized clinical trial
Authors: S. Kohli, S. G. Fisher, Y. Tra, K. Wesnes, G. R. Morrow
Journal: Journal of Clinical Oncology (2007)

9004 Background: Patients receiving treatment for cancer can experience a diminution of their cognitive abilities which can persist for many years after. The present study examined the potential of modafinil as a cognitive enhancer on memory and attention in a randomized clinical trial in breast cancer patients following completion of treatment. Methods: Breast cancer patients who reported a score of = 2 on the Brief Fatigue Inventory (BFI) an average of 22.8 months following completion of chemotherapy were enrolled. In Phase 1, patients received 200mg modafinil open-label once daily for 4 weeks. In Phase 2, patients with a positive response following Phase 1 were randomized either to an additional 4 weeks of modafinil or to placebo. Tests of memory and attention selected from the Cognitive Drug Research (CDR) computerized cognitive assessment were performed at baseline (before modafinil) and after completing Phase 1 and 2. The difference between scores at baseline and scores at Phase 1 and Phase 2, were subjected to a Wilcoxon's signed rank test. Results: Of the 82 women enrolled, 68 completed all 3 CDR assessments in the study (range=33–83 years, median age=54 years). At the end of Phase 1 (week 4), modafinil had a significant effect on the Speed of Memory Index (p=0.0047) and the Digit Vigilance Test (p=0.0014) but showed no significant effect on Quality of Working Memory (p=0.3528) nor on Power of Attention (p=0.8953). At the end of phase 2 (week 8), the group that continued modafinil demonstrated improved Mean Continuity of Attention (p=0.0002) compared with the placebo group and also demonstrated significantly greater improvements in Quality of Episodic Secondary Memory relative to placebo (p&lt;0.005). This improvement was observed at week 4, and was maintained throughout the study. Finally, continued modafinil demonstrated significantly greater improvement in Speed of Memory relative to placebo (p=0.009). Conclusions: Modafinil provides significant improvements in attention and speed of memory for breast cancer patients following their treatment of cancer. Although further study is needed, these findings suggest that modafinil may enhance quality of life in this patient population. Supported by a grant from Cephalon, Inc and NCI Grants U10-CA37420 and R25- CA102618. No significant financial relationships to disclose.