tbuckley/cabot-search huggingface dataset:
Abstract 177: Hemodynamic Status From Photoplethysmography, Signs of Successful Pregnancy
Authors: Chi-Wei Chang, Dan ni Xie, Shu jia Wang, Xao ran Li, Meng jie Li, Chun Huang, An ran Wang, Li Zhou, Xiao feng Zhu, Yan mei Li, Zi-Xin Huang, Gin-Chung Wang
Journal: Circulation Research (2019)

The key physiological condition for successful pregnancy is a critical issue in reproductive science. Many studies have shown that the pregnancy process requires a lot of subtle cardiovascular adaptation, including a decrease in systemic vascular resistance, an increase in maternal heart rate, stroke volume, and cardiac output. Those adaptation will also lead to changes in the arterial pulse spectrum. Since pregnancy requires the mother's competency to change the hemodynamic state, an interesting question is if the pre-pregnancy hemodynamics of the cardiovascular system affect the clinical pregnancy rate of each embryo transfer. Therefore, we initiated an observational study to validate our conjecture. We recruited 116 women of childbearing age(range 22 to 41 years) who planned to carry out in vitro fertilization(IVF). Each subject underwent photoplethysmography(PPG) before embryo implantation. We calculated the first ten harmonic amplitudes (C1~C10) and phases (P1~P10) from the pulse data of PPG using the Fourier transform method, and tracked these women to 42 days after implantation to confirm the successful pregnancy. The results showed that the subjects with successful IVF had higher C4 and C7(P=0.006; P=0.018), compared with those who failed the IVF. We then classified the enrolled patients into quartile groups of C4 and C7 respectively. Log rank test further proved that the cumulative rates of successful pregnancy were significant higher for those with the higher C4 and C7, taking groups with smaller values as reference(Figure 1). In conclusion, maternal hemodynamic state before implantation have an impact on the successful pregnancy rate during IVF.
Fatty Acid Synthase Inhibitor TVB‐2640 Reduces Hepatic de Novo Lipogenesis in Males With Metabolic Abnormalities
Authors: Majid M. Syed‐Abdul, Elizabeth J. Parks, Ayman H. Gaballah, Kimberlee Bingham, Ghassan M. Hammoud, George Kemble, Douglas Buckley, William McCulloch, Camila Manrique-Acevedo
Journal: Hepatology (2019)

Elevated hepatic de novo lipogenesis (DNL) is a key distinguishing characteristic of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. In rodent models of NAFLD, treatment with a surrogate of TVB-2640, a pharmacological fatty acid synthase inhibitor, has been shown to reduce hepatic fat and other biomarkers of DNL. The purpose of this phase I clinical study was to test the effect of the TVB-2640 in obese men with certain metabolic abnormalities that put them at risk for NAFLD.Twelve subjects (mean ± SEM, 42 ± 2 years, body mass index 37.4 ± 1.2 kg/m2 , glucose 103 ± 2 mg/dL, triacylglycerols 196 ± 27 mg/dL, and elevated liver enzymes) underwent 10 days of treatment with TVB-2640 at doses ranging from 50-150 mg/day. Food intake was controlled throughout the study. Hepatic DNL was measured before and after an oral fructose/glucose bolus using isotopic labeling with 1-13 C1 -acetate intravenous infusion, followed by measurement of labeled very low-density lipoprotein palmitate via gas chromatography mass spectometry. Substrate oxidation was measured by indirect calorimetry. Across the range of doses, fasting DNL was reduced by up to 90% (P = 0.003). Increasing plasma concentrations of TVB-2640 were associated with progressive reductions in the percent of fructose-stimulated peak fractional DNL (R2 = -0.749, P = 0.0003) and absolute DNL area under the curve 6 hours following fructose/glucose bolus (R2 = -0.554, P = 0.005). For all subjects combined, alanine aminotransferase was reduced by 15.8 ± 8.4% (P = 0.05). Substrate oxidation was unchanged, and safety monitoring revealed that the drug was well tolerated, without an increase in plasma triglycerides. Alopecia occurred in 2 subjects (reversed after stopping the drug), but otherwise no changes were observed in fasting glucose, insulin, ketones, and renal function.These data support the therapeutic potential of a fatty acid synthase inhibitor, TVB-2640 in particular, in patients with NAFLD and nonalcoholic steatohepatitis.
Barriers to minority recruitment in a multicenter clinical trial (PRO-TECT [AFT-39]): Research staff insights.
Authors: Marjory Charlot, Sydney Henson, Patty Spears, Deborah Schrag, Angela M. Stover, Ethan M. Basch
Journal: Journal of Clinical Oncology (2019)

145 Background: Rates of minority enrollment in U.S. cancer clinical trials, including supportive care trials, are disproportionately low. Clinical research associates (CRAs) are the linchpin for successful accrual and often help screen and approach patients to discuss research studies. We sought to understand clinic-level factors that influence recruitment of African American patients (AA) in an ongoing U.S. multicenter, cluster- randomized controlled trial (PRO-TECT: Patient-Reported Outcomes to Enhance Cancer Treatment; NCT03249090 AFT-39]). Notably, partway through this trial, a purposeful enrollment strategy was initiated where sites were asked to focus on minority recruitment. Methods: A subset of community oncology practices participating in PRO-TECT was identified with: 1) overall patient populations ≥20% AA; or 2) &lt;20% AA but trial enrollment ≥20% AA. Semi-structured phone interviews were conducted with CRAs at each site to elicit perceived barriers and facilitators in identifying and approaching AA patients for this trial. Results: Among 13 identified community practices out of a potential 50 randomized sites, 3 had populations &lt;20% AA but enrollment &gt;20% AA; 3 had populations ≥20% AA but enrollment &lt;20% AA; and 7 had populations ≥20% AA and enrollment &gt;20% AA. All sites identified participants through review of clinic visit lists with clinicians. Eleven out of 13 sites felt they experienced no barriers to identifying, approaching, or enrolling minority patients. One site CRA felt minority patients are often “too sick to participate”. One CRA felt awkward about the request to purposefully approach minority patients. Conclusions: Site CRAs generally did not perceive barriers to minority recruitment, even when their population demographics were underrepresented in accrual. Results of efforts in this trial to increase minority participation through a purposeful enrollment strategy will be reported elsewhere.
Re: Adam C. Calaway, Lawrence H. Einhorn, Timothy A. Masterson, Richard S. Foster, Clint Cary. Adverse Surgical Outcomes Associated with Robotic Retroperitoneal Lymph Node Dissection Among Patients with Testicular Cancer. Eur Urol 2019;76:607–9
Authors: Gregory J. Nason, Michael A.S. Jewett, Robert J. Hamilton
Journal: European Urology (2019)
Clinical Analysis of Immunodeficiency-Associated Lymphoproliferative Disorders in a Single Institution
Authors: Mizuki Watanabe, Junya Kanda, Yasuyuki Arai, Momoko Nishikori, Masakatsu Hishizawa, Tadakazu Kondo, Kouhei Yamashita, Akifumi Kondo Takaori
Journal: Blood (2018)
Impact of Red Cell Distribution Width on Dysplasia and Clinical Outcome in 66 Patients with Myelodysplastic Syndrome without Increased Blasts
Authors: Yuta Baba, Bungo Saito, Shotaro Shimada, Yohei Sasaki, So Murai, Maasa Abe, Shun Fujiwara, Nana Arai, Yukiko Kawaguchi, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Kouji Yanagisawa, Norimichi Hattori, Hiroshi Harada, Tsuyoshi Nakamaki
Journal: Blood (2018)
THE LOURDES PILGRIMAGE.
Journal: JAMA (1906)

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
Uninvolved Immunoglobulin Suppression Determined By "Hevylite" ASSAY. Strongly Predicts Evolution of Smoldering Myeloma (SMM) to Symptomatic Multiple Myeloma (MM)
Authors: Paraskevi Papaioannou, Annita Ioanna Gkioka, Kallirroi Tsalimalma, Aspasia Koudouna, Anastasia Kopsaftopoulou, Konstantina Chamoulkou, Ioannis Grafakos, Aikaterini Bitsani, Theodoros Iliakis, Maria Dimou, Nikolitsa Kafassi, Petros Sfikakis, Panayiotis Panayiotidis, Marie-Christine Kyrtsonis
Journal: Blood (2018)
Selective Inhibition of CDK4 and CDK6 Primes Chemoresistant MCL Cells for Killing by Proteasome Inhibitor Bortezomib by Activating Cell Cycle-Coupled Apoptosis
Authors: Maurizio Di Li berto, Xiangao Huang, Amy Chadburn, Peter Martin, Ruben Niesvizky, Scott Ely, John P. Leonard, Selina Chen- Kiang
Journal: Blood (2008)
Normalization of Cerebral Hemodynamics after Hematopoietic Stem Cell Transplant in Children with Sickle Cell Anemia
Authors: Monica L Hulbert, Kristin P Guilliams, Melanie E Fields, Priyesha Bijlani, Dustin K Ragan, Cihat Eldeniz, Slim Fellah, Michael M Binkley, Hongyu An, Yasheng Chen, Shalini Shenoy, Ginny Schulz, Alison Towerman, Robert C McKinstry, Joshua S Shimony, Jin-Moo Lee, Andria L Ford
Journal: Blood (2017)
Dasatinib 100 Mg Once Daily (QD) Maintains Long-Term Efficacy and Minimizes the Occurrence of Pleural Effusion: An Analysis of 24-Month Data in Patients with Resistance, Suboptimal Response, or Intolerance to Imatinib (CA180-034).
Authors: Kimmo Porkka, H. Jean Khoury, Ronald Paquette, Yousif Matloub, David Liu, Ritwik Sinha, Jorge Cortes
Journal: Blood (2008)
Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor
Authors: B. Martín-Antonio, G. Suñe, A. Najjar, L. Perez-Amill, A. Antoñana-Vildosola, M. Castella, S. León, M. Velasco-de Andrés, F. Lozano, E. Lozano, C. Bueno, J. M. Estanyol, C. Muñoz-Pinedo, S. N. Robinson, A. Urbano-Ispizua
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Natural killer (NK) cells are important anti-tumor cells of our innate immune system. Their anti-cancer activity is mediated through interaction of a wide array of activating and inhibitory receptors with their ligands on tumor cells. After activation, NK cells also secrete a variety of pro-inflammatory molecules that contribute to the final immune response by modulating other innate and adaptive immune cells. In this regard, external proteins from NK cell secretome and the mechanisms by which they mediate these responses are poorly defined. <h3>Methods</h3> TRANS-stable-isotope labeling of amino acids in cell culture (TRANS-SILAC) combined with proteomic was undertaken to identify early materials transferred between cord blood-derived NK cells (CB-NK) and multiple myeloma (MM) cells. Further in vitro and in vivo studies with knock-down of histones and CD138, overexpression of histones and addition of exogenous histones were undertaken to confirm TRANS-SILAC results and to determine functional roles of this material transferred. <h3>Results</h3> We describe a novel mechanism by which histones are actively released by NK cells early after contact with MM cells. We show that extracellular histones bind to the heparan sulfate proteoglycan CD138 on the surface of MM cells to promote the creation of immune-tumor cell clusters bringing immune and MM cells into close proximity, and thus facilitating not only NK but also T lymphocyte anti-MM activity. <h3>Conclusion</h3> This study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies.
Design and Interpretation Considerations in Registry-Based Studies
Authors: Katie M. O’Brien, Alexander P. Keil
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Pathogenic T cell cytokines in multiple sclerosis
Authors: Catriona A. Wagner, Pamela J. Roqué, Joan M. Goverman
Journal: The Journal of Experimental Medicine (2019)

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system that is believed to have an autoimmune etiology. As MS is the most common nontraumatic disease that causes disability in young adults, extensive research has been devoted to identifying therapeutic targets. In this review, we discuss the current understanding derived from studies of patients with MS and animal models of how specific cytokines produced by autoreactive CD4 T cells contribute to the pathogenesis of MS. Defining the roles of these cytokines will lead to a better understanding of the potential of cytokine-based therapies for patients with MS.
Clinical Outcomes in Cyclin-dependent Kinase 12 Mutant Advanced Prostate Cancer
Authors: Melissa A. Reimers, Steven M. Yip, Li Zhang, Marcin Cieslik, Mallika Dhawan, Bruce Montgomery, Alexander W. Wyatt, Kim N. Chi, Eric J. Small, Arul M. Chinnaiyan, Ajjai S. Alva, Felix Y. Feng, Jonathan Chou
Journal: European Urology (2019)
Germline mutations of PALB2 gene in a sequential series of Chinese patients with breast cancer.
Authors: Jiaojiao Zhou, Kun Zhang, Xuan Zhu, Mei Deng, Meng Luo, Chunjing Xu, Jie-Kai Yu, Yiding Chen
Journal: Journal of Clinical Oncology (2017)

1530 Background: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene, which plays a critical role in genome maintenance via interacting with BRCA1/2 and RAD51 when DNA break. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. Therefore, we assessed the mutational frequency, spectrum and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank, to verify the utility of PALB2 genetic testing in Chinese population. Methods: We examined Chinese breast cancer cases (n = 2279) who agreed to participate in research DNA banking, recruited from 1990 through 2016. To identify the mutations, complete coding sequence and intron–exon boundaries of PALB2 were screened with Next Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. Results: Among the 2279 breast cancer patients, 307 patients were familial breast cancer cases and the rest 1972 patients were sporadic breast cancer cases. PALB2 mutation carriers accounted for 7.8% (n = 24) and 4.8% (n = 95) in familial and sporadic breast cancer cohort separately. In total, 31 missense, 4 nonsense, 3 frameshift, 3 splicing and 1 codon mutations of PALB2 were identified in this study. Among the pathologic variants, PALB2 c.1744C &gt; T, c.2748+1G &gt; A, c.2749-1G &gt; C, c.3114-1G &gt; A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, a total of 6 potential damaging missense variants were novelly found in this study, among which the PALB2 c.3035C &gt; T was detected in both sporadic and familial breast cancer. Conclusions: Our data presents the germline mutation status of PALB2 in Chinese patients with breast cancer, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, this information may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.
Expression Of Immune Checkpoints PD-L1, PD-L2, PD-1 and CTLA4 Predict For Prognosis and Resistance To Hypomethylating Agents (HMAs) In Myelodysplastic Syndromes (MDS)
Authors: Hui Yang, Carlos E. Bueso-Ramos, Courtney D. DiNardo, Marcos R Estecio, Masoud Davanlou, Qi-Rong Geng, Zhihong Fang, Martin Nguyen, Sherry Pierce, Yue Wei, Simrit Parmar, Jorge E. Cortes, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2013)
Concurrent opioid and benzodiazepine use after breast cancer diagnosis.
Authors: Devon Check, Aaron N. Winn, Nicole Fergestrom, Joan Marie Neuner, Andrew Roberts
Journal: Journal of Clinical Oncology (2019)

28 Background: Benzodiazepines contribute to one-third of opioid overdose deaths in the U.S. Guidelines caution against co-prescribing these two drug classes. Although patients with cancer commonly experience pain and anxiety, no studies have assessed trends in concurrent opioid/benzodiazepine use after cancer diagnosis. Our study examined trends in, and predictors of concurrent opioid/benzodiazepine use in older women diagnosed with breast cancer. Methods: We conducted a retrospective cohort analysis using 2012-2016 SEER-Medicare data for women diagnosed with stage 0-III breast cancer who had no concurrent opioid/benzodiazepine use in the 3 months prior to diagnosis. Using modified Poisson regression, we estimated the adjusted probability of concurrent use (≥1 day of overlapping opioid/benzodiazepine supply) in the 12 months post-diagnosis for patients diagnosed in each calendar quarter from Q2:2013 to Q4:2015. We also estimated the overall relative risk (RR) of concurrent use associated with patient demographic and clinical characteristics. Results: Among the 19, 267 women in our cohort, the quarterly adjusted probabilities of concurrent use were stable over time, ranging from 12% to 15%. Risk of concurrent use decreased with age but increased with cancer stage. Prior opioid use and prior benzodiazepine use increased the risk of concurrent use in the 12 months post-diagnosis (RR prior vs. no prior opioids = 2.57, 95% CI = 2.27-2.92; RR prior vs. no prior benzodiazepines = 15.05, 95% CI = 13.19-17.19). Women who underwent mastectomy (vs. no or minimal surgery) were 71% more likely to have concurrent use (RR = 1.71, 95% CI = 1.40-2.10). Similarly, women who received chemotherapy (vs. no chemotherapy) were 28% more likely to have concurrent use (RR = 1.28, 95% CI = 1.07-1.54). Finally, Black women (vs. White women) were 38% less likely to have concurrent use (RR = 0.62, 95% CI = 0.50-0.76). Conclusions: Up to 1 in 8 older women diagnosed with breast cancer exhibited concurrent opioid/benzodiazepine use in the 12 months after diagnosis. Clinicians must be mindful of exposing patients to this high-risk combination during cancer and survivorship care, particularly among patients with more intensive cancer treatment or prior use of either drug.
Abstract 925: Insulin Inhibits β-adrenergic Receptor Resensitization Through PI3KγInsulin Inhibits β-adrenergic Receptor Resensitization Through PI3Kγ
Authors: Anita Sahu, Maradumane Mohan, Sathyamangla V. Naga Prasad
Journal: Circulation Research (2019)

Insulin regulates cardiac metabolism, myocyte survival, and cardiac growth. In addition, insulin is also known to modulate beta adrenergic receptors (βARs) function in the heart regulating cardiac function. βAR function in response to its agonist epinephrine/norepinephrine is regulated by G-protein coupled receptor kinase (GRKs) driven desensitization and protein phosphatase 2A (PP2A) mediated resensitization. Although insulin is known to modulate βAR function through GRKs, less is known about role in insulin in regulating resensitization mechanisms. Phosphoinositide 3-kinase γ (PI3Kγ) is a key regulator of resensitization at it inhibits PP2A activity and therefore, we tested whether insulin could mediate βAR dysfunction through inhibition of resensitization. Insulin stimulation of HEK 293 cells stably expressing β 2 ARs resulted in significant β 2 AR phosphorylation. This β 2 AR phosphorylation was completely abolished with use of pharmacologic inhibitors of PI3K wortmannin or LY 294002 and knock-down of PI3Kγ showing an essential role for PI3Kγ in regulation of βAR function by insulin. Activation of insulin receptor induces downstream signaling via recruitment of the adaptor insulin receptor substrates (IRS). Interestingly, our data suggests that cross talk between the IRs and B 2 ARs are dependent on interaction between PI3Kγ, GRK2 and IRS as identified by co-immunoprecipitation studies and use of surface plasmon resonance using purified proteins. Since cardiomyocytes and fibroblasts represent major cell-types in the heart, primary adult cardiomyocytes and cardiac fibroblasts (CFs) were isolated from WT and PI3Kγ KO hearts for insulin stimulation. While β 2 AR phosphorylation was completely abolished in primary CFs from PI3Kγ KO compared to WT CFs, cardiomyocytes did not show any differences in β 2 AR phosphorylation in response to insulin. These data suggest that PI3Kγ may differentially regulate pathways in cardiomyocytes and CFs in the heart indicating the existence of cell-specific signaling mechanisms that may underlie response to insulin and thereby the cardio-metabolic process.