tbuckley/cabot-search huggingface dataset:
Employment outcomes, anxiety, and depression among caregivers of African American cancer survivors.
Authors: Theresa A. Hastert, Julie J. Ruterbusch, Kendra L. Schwartz, Felicity W. K. Harper, Tara Baird, Jennifer Lynn Beebe-Dimmer, Ann G. Schwartz
Journal: Journal of Clinical Oncology (2019)

175 Background: Cancer patients commonly rely on loved ones to act as informal caregivers during and after treatment. Caregivers may need to take time off work or make other employment changes to handle caregiving demands. Employment changes due to caregiving and their impacts on psychological outcomes are not well understood, especially among caregivers of African American cancer survivors. Methods: Results include information from caregivers of participants in the Detroit Research on Cancer Survivors (ROCS) cohort, a population-based study of African American survivors of breast, colorectal, lung, or prostate cancer from Metropolitan Detroit. ROCS participants nominated a friend or family member who acted as a caregiver to participate in the caregiver study. Caregivers provided information on employment and PROMIS depression and anxiety measures. The relationship between work outcomes and anxiety/depression was assessed using logistic regression models controlling for age, sex, income, and the caregiver’s relationship to the survivor. Results: For the first 350 caregivers enrolled, more than half (56%) were employed (42% full time, 14% part time) at the time of the survivor’s diagnosis. 53% of employed caregivers took time off work, including 40% who took unpaid time off to provide care. 16% took one month or more off work, including 12% who took at least one month of unpaid time. Taking at least one month off was associated with 2.3 (95% CI: 1.0, 5.4) times the odds of depressive symptoms but was not associated with anxiety. Extended unpaid time off was not associated with depression or anxiety. 38% of employed caregivers reported that it was somewhat, very or extremely difficult to balance work and caregiving. Difficulty balancing work and caregiving was associated with 3.1 times the odds of depressive symptoms (95% CI: 1.5, 6.2), and 2.2 times the odds of any anxiety (95% CI: 1.1, 4.3) compared with those who reported little or no difficulty. Conclusions: Difficulty balancing work and caregiving is common among caregivers of African American cancer survivors, and is associated with symptoms of depression and anxiety. Supports for caregivers facing employment challenges may improve their psychosocial wellbeing.
Topoisomerase I-DNA Covalent Complexes in Myeloid Malignancies: A Potential Biomarker for Topoisomerase I Inhibitor Sensitivity
Authors: Mira A. Kohorst, Karen S. Flatten, Kevin L. Peterson, Paula A. Schneider, Cristina Correia, Keith W. Pratz, B. Douglas Smith, Scott H. Kaufmann
Journal: Blood (2018)
Abstract 806: PD-1 in Cardiac Immune Responses After Ischemic Injury or Transverse Aortic Constriction
Authors: Daniel A Zlotoff, Chun Yang Xiao, Robert M Grange, Yoshiko Iwamoto, Gordon Freeman, Anthony Rosenzweig
Journal: Circulation Research (2019)

Background: Heart failure is associated with inflammation, but the precise immune mechanisms that contribute to cardiomyopathy remain elusive. Myocarditis is a rare toxicity of checkpoint inhibitors, which are oncologic therapies that block signaling through the immunoinhibitory molecule PD-1. We investigated whether PD-1 attenuates cardiac immune responses. Methods: Expression of PD-1 and its ligand PD-L1 on cardiac cell populations were assessed by flow cytometry. The functional implications of PD-1 signaling were determined using PD-1 blocking antibodies (Abs) in two surgical models of cardiac injury: ischemia/reperfusion and transverse aortic constriction (TAC). Ischemic injury was measured by troponin release and histology. Systolic function was assayed by echocardiography, diastolic function by invasive pressure-volume loops, and fibrosis by histology. Results: PD-L1 is expressed on most cardiac endothelial cells and a small fraction of cardiomyocytes. While intracardiac T cells do not express PD-1 under baseline conditions, 15% of both CD4 and CD8 T cells express PD-1 after TAC. Blocking PD-1 signaling after ischemic injury did not affect troponin levels (5.8 ng/ml in mice receiving isotype control (IC) Ab vs 7.8 ng/ml in mice receiving anti-PD-1 Ab, p=0.26), size of infarct (1.6% of ventricular cross-sectional area for IC Ab vs 2.0% for anti-PD-1 Ab, p=0.27), or systolic function (fractional shortening 52.6% for IC Ab vs 53.2% for anti-PD-1 Ab, p=0.92). Similarly, abrogation of PD-1 signaling after TAC did not worsen systolic dysfunction (fractional shortening 36.8% for IC Ab vs 32.4% for anti-PD-1 Ab, p=0.38), diastolic function (dP/dT minimum -9445 mmHg/s vs -10950 mmHg/s, p=0.44; Tau 6.8 ms for IC Ab vs 6.0 ms for anti-PD-1 Ab, p=0.45), or the extent of cardiac fibrosis (1.4% of ventricular cross-sectional area for IC vs 1.7% for anti-PD-1 Ab, p=0.41). Conclusion: Collectively, these data do not implicate PD-1 as an important regulator of intracardiac immune responses in the injury models tested. This suggests that additional pathways may contribute to myocarditis occurring in cancer patients treated with anti-PD-1 Ab, the identification of which could provide insight into immune mechanisms active in heart failure.
Long-Term Outcomes of Myeloablative Hematopoietic Cell Transplantation Using Total Body Irradiation Prior to Systemic Therapy
Authors: Cara L. Toretta, Andrzej Niemierko, Erin Coughlin, Steven L. McAfee, Bimalangshu R. Dey, Karen K. Ballen, Eyal C. Attar, Yi-Bin A. Chen, Thomas R. Spitzer, Karen M. Winkfield
Journal: Blood (2012)
Prognostic Importance of Resistant Hypertension in Patients With Type 2 Diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study
Authors: Claudia R.L. Cardoso, Nathalie C. Leite, Giovanna Bacan, Dayane S. Ataíde, Larissa K.C. Gorgonio, Gil F. Salles
Journal: Diabetes Care (2019)

OBJECTIVE To evaluate the prognostic importance of resistant hypertension (RHT) for the development of complications in a cohort of individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 646 patients had the diagnosis of apparent treatment-resistant hypertension (aRHT) based on mean office blood pressure (BP) levels during the 1st year of follow-up. They were reclassified as white-coat/controlled or true/uncontrolled RHT according to 24-h ambulatory BP monitoring (ABPM), using the traditional BP cutoffs and the new 2017 American College of Cardiology (ACC)/American Heart Association (AHA) criteria. Multivariate Cox analyses examined the associations between RHT diagnoses and the occurrence of microvascular and cardiovascular complications and all-cause and cardiovascular mortality. RESULTS During a median follow-up of 10 years, 177 patients had a cardiovascular event (145 major ones); 222 patients died (101 from cardiovascular diseases); 200 had a renal event; 156 had a retinopathy event; and 174 patients had a neuropathy event. In relation to non-RHT individuals, aRHT (present in 44.6% and 50% by the traditional and new criteria, respectively) predicted all cardiovascular and mortality outcomes, with hazard ratios (HRs) between 1.64 and 2.16, but none of the microvascular outcomes. True RHT increased the HRs (from 1.81 to 2.25) and additionally predicted renal outcomes. White-coat/controlled RHT implied an increased risk (HRs 1.33–1.86) that was intermediate between non-RHT and true RHT individuals. Classifications using the traditional and the new ACC/AHA criteria were equivalent. CONCLUSIONS In patients with type 2 diabetes, the presence of aRHT implied an increased risk of cardiovascular and mortality outcomes, and classification based on ABPM predicted renal outcomes and improved cardiovascular/mortality risk stratification.
Comparision of the Clinical and Prognostic Characteristic in Adult and Pediatric AML1/ETO-Positive Acute Myeloid Leukemia
Authors: Guopan Yu, Jiaheng Zhou, Jinchan Zhou, Jiale Qiu, Zhao Yin, Changxin Yin, Dan Xu, Xuejie Jiang, Qifa Liu, Fanyi Meng
Journal: Blood (2018)
Abstract 286: Smyd1 is Required for Cell Survival During Glucose Deprivation
Authors: Amira Sabry, Keiko Cawley, Katie Sciuto, Amanda Horiuchi, David Nix, Chris Stubborn, Yukio Saijoh, Alexey V Zaitsev, Junco S Warren
Journal: Circulation Research (2019)

Our recent study demonstrated that the histone methyltransferase Smyd1 positively regulates cardiac metabolism through transcriptional control of PGC-1α, a key regulator of mitochondrial energetics. However, it is largely unknown whether Smyd1 plays a role in adaptive responses to metabolic stress in cardiomyocytes. Here, we hypothesized that Smyd1 is required for cell survival during metabolic stress through maintaining energetic balance. To address this hypothesis, neonatal rat ventricular myocytes (NRVMs) were cultured in glucose-free media for 24 hours and real-time quantitative PCR was performed. We found that Smyd1 and its downstream target PGC-1α were upregulated during glucose starvation, concurrent with the significant increase of mRNA levels of PPARα and CPT1b , the key regulators of fatty acid β-oxidation (all p&lt;0.05), indicating enhanced energetics. Control NRVMs were able to withstand 24-hr glucose starvation, maintaining mitochondrial inner membrane potential (MIMP) and the cell membrane integrity. However, siRNA-mediated Smyd1 knockdown (siSmyd1) prior to glucose starvation led to massive cell death, evidenced by the dissipation of MIMP and the uptake of the normally cell-impermeable indicator YO-PRO. To better understand the mechanism of siSmyd-NRVMs vulnerability to glucose starvation, we examined the expression of genes involved in metabolism and apoptosis at the early stage of glucose starvation (3 hr), when autophagy was activated as evidenced by upregulation of LC3 and FoxO1. We found that the upregulation of PGC-1α, PPARα, CPT1b, as well as LC3 and FoxO1, adaptively induced by glucose starvation in control NRVMs, were all abolished by Smyd1 knockdown, concomitant with a significant increase in gene expression of tumor necrosis factor receptor type 1-associated DEATH domain protein (Tradd). Moreover, RNA-seq analysis revealed that Smyd1 -knockdown per se led to upregulation of the genes involved in regulation of apoptosis and cell death (i.e. Tradd, Casp8, Ripk3, Smad1). These data suggest that upregulation of Smyd1 in response to metabolic stress is a critical adaptive mechanism for cell survival, operating via enhancement of fatty acid metabolism, activation of autophagy, and suppression of cell death signaling.
Foundation of wisdom: “I don’t know”
Authors: Kamran Abbasi
Journal: BMJ (2019)

How do you solve a complex problem such as poverty? You might begin by saying, “I don’t know.” It’s hard to admit where your knowledge ends and your ignorance begins unless you, like Socrates, believe an understanding of your ignorance to be the truest wisdom. It’s a philosophy doctors find hard to embrace when talking to patients, but, as Matt Morgan points out (doi:10.1136/bmj.l5918), “I don’t know” can be the trigger for a more nuanced and more honest conversation.

Esther Duflo and colleagues won this week’s Nobel prize for …
Older Age As a Prognostic Factor for Overall Survival for Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation
Authors: David M. Cordas Dos Santos, Rima M. Saliba, Romil Patel, Qaiser Bashir, Chitra Hosing, Partow Kebriaei, Issa F. Khouri, Yago Nieto, Uday Popat, Hans C. Lee, Elisabet E. Manasanch, Krina K. Patel, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Richard E Champlin, Muzaffar H. Qazilbash
Journal: Blood (2018)
Increased Serum Beta-2 Microglobulin during Induction Chemotherapy Associated with Poor Prognosis in Primary Central Nervous System Lymphoma
Authors: Jaewon Hyung, Jung Yong Hong, Dok Hyun Yoon, Shin Kim, Jung Sun Park, Chan-Sik Park, Sang Wook Lee, Jin-Sook Ryu, Jooryung Huh, Cheolwon Suh
Journal: Blood (2018)
Abstract 104: Identification and Characterization of a <i>Titin</i> Enhancer using CRISPR/Cas9 Genome Editing and hiPSC-Derived Cardiomyocytes
Authors: Meraj Neyazi, Manuel Schmid, Arun Sharma, Christopher N Toepfer, Yuri Kim, Lauren K Wasson, Seong Won Kim, Daniel M DeLaughter, Jon A Willcox, Radhika Agarwal, Angela Tai, Joshua M Gorham, Steven DePalma, Jonathan G Seidman, Christine E Seidman
Journal: Circulation Research (2019)

Dilated cardiomyopathy (DCM) is a leading cause for heart failure and is associated with a rate of mortality of 20% within 5 years of diagnosis. The most common genetic causes for DCM are mutations of the sarcomere protein titin (encoded by TTN ), which occurs in 10-20% of DCM cases. Dominant DCM mutations truncate titin (TTNtv) and result in haploinsufficiency. Thus, strategies to increase the expression of the wild type TTN allele could attenuate damaging effects of TTNtv. Utilizing bioinformatic tools, we identified a putative enhancer for TTN in its intron 1. We deleted a 658 bp region from intron 1 which encompasses the region of interest in human induced pluripotent stem cells (hiPSCs) using CRISPR/Cas9 genome editing to validate its function. Utilizing RNA sequencing and qPCR of RNA harvested from hiPSC-derived cardiomyocytes (hiPSC-CMs), we demonstrated that a homozygous deletion in this region leads to a drop in TTN expression compared to the wild type (WT) control (0.344-fold change, p &lt; 0.001). To further characterize this region, we subdivided it into three parts which we called E1 (296 bp), E2 (206 bp), and E3 (139 bp). E1 includes a highly conserved region and a region of open chromatin as identified by the Assay for Transposase-Accessible Chromatin Sequencing (ATAC-Seq) performed on hiPSC-CMs. A homozygous E1 deletion resulted in a decreased TTN expression of 0.63-fold compared to the WT control (p &lt; 0.001) when performing RNA sequencing on hiPSC-CMs. Both homozygous E2 and E3 deletions resulted in an increased TTN expression (1.56-fold change, p &lt; 0.001; 1.19 fold change, p &lt; 0.001). Utilizing a published sarcomere tracking platform, SarcTrack, to investigate hiPSC-CM physiology, we saw a decreased contractility of 6.6% in hiPSC-CMs carrying a homozygous E1 deletion compared to 10.1% in the WT control (p &lt; 0.001). Cells carrying homozygous E2 or E3 deletions were hypercontractile (13.8%, p &lt; 0.001; 13.7%, p &lt; 0.001). Given our results, we hypothesize that TTN expression depends on the E1 region. If confirmed, we expect that increasing the activity of this enhancer using small molecules may provide a novel therapeutic target for DCM caused by TTNtv.
Weight change across adulthood in relation to all cause and cause specific mortality: prospective cohort study
Authors: Chen Chen, Yi Ye, Yanbo Zhang, Xiong-Fei Pan, An Pan
Journal: BMJ (2019)

To investigate the association between weight changes across adulthood and mortality.Prospective cohort study.US National Health and Nutrition Examination Survey (NHANES) 1988-94 and 1999-2014.36 051 people aged 40 years or over with measured body weight and height at baseline and recalled weight at young adulthood (25 years old) and middle adulthood (10 years before baseline).All cause and cause specific mortality from baseline until 31 December 2015.During a mean follow-up of 12.3 years, 10 500 deaths occurred. Compared with participants who remained at normal weight, those moving from the non-obese to obese category between young and middle adulthood had a 22% (hazard ratio 1.22, 95% confidence interval 1.11 to 1.33) and 49% (1.49, 1.21 to 1.83) higher risk of all cause mortality and heart disease mortality, respectively. Changing from obese to non-obese body mass index over this period was not significantly associated with mortality risk. An obese to non-obese weight change pattern from middle to late adulthood was associated with increased risk of all cause mortality (1.30, 1.16 to 1.45) and heart disease mortality (1.48, 1.14 to 1.92), whereas moving from the non-obese to obese category over this period was not significantly associated with mortality risk. Maintaining obesity across adulthood was consistently associated with increased risk of all cause mortality; the hazard ratio was 1.72 (1.52 to 1.95) from young to middle adulthood, 1.61 (1.41 to 1.84) from young to late adulthood, and 1.20 (1.09 to 1.32) from middle to late adulthood. Maximum overweight had a very modest or null association with mortality across adulthood. No significant associations were found between various weight change patterns and cancer mortality.Stable obesity across adulthood, weight gain from young to middle adulthood, and weight loss from middle to late adulthood were associated with increased risks of mortality. The findings imply that maintaining normal weight across adulthood, especially preventing weight gain in early adulthood, is important for preventing premature deaths in later life.
Clinical Heterogeneity of AML Is Associated with Mutational Heterogeneity
Authors: Mahesh Swaminathan, Kiyomi Morita, Yan Yuanqing, Feng Wang, Jared K Burks, Curtis Gumbs, Latasha Little, Samantha Tippen, Rebecca Thornton, Marcus Coyle, Jianhua Zhang, Xingzhi Song, Courtney D. DiNardo, Elias J. Jabbour, Tapan M. Kadia, Jorge E. Cortes, Naval G. Daver, Naveen Pemmaraju, Keyur Patel, Guillermo Garcia-Manero, Hagop M. Kantarjian, Carlos E. Bueso-Ramos, Andy Futreal, Koichi Takahashi
Journal: Blood (2018)
Streamlining bortezomib regimen: A quality improvement project for cost-effective and patient-friendly protocol.
Authors: Srinandan Guntupalli, Deepti Bala Kallam, Samip R. Master, Richard P. Mansour
Journal: Journal of Clinical Oncology (2019)

94 Background: Bortezomib is a novel first-in-class proteasome inhibitor and received it’s FDA approval with twice weekly dosing on day 1, 4, 8 and 11 of a 21-day cycle with weekly complete blood count (CBC). However, subsequent studies have shown that weekly dosing has equal drug efficacy. Our clinical practice at Feist-Weiller cancer center is to administer weekly subcutaneous bortezomib injection after reviewing the CBC. Objective: To analyze hematological toxicities with weekly bortezomib and assess the need for CBC prior to administration of bortezomib. Methods: A retrospective analysis of CBC results was done for every patient receiving bortezomib as part of bortezomib and dexamethasone +/- lenalidomide regimens in a 2-year period (2017-2018). The data extraction was done using Epic Clarity database using an SQL script which identified each treatment duration in minutes between check in and check out, Absolute neutrophil count (ANC) and platelet count on each treatment day. Results: A total of 38 patients received 626 treatment doses of bortezomib. The average patient stay between check-in and check-out was 227 mins. There was very low incidence of grade 3 thrombocytopenia (0.64%) and grade 3 neutropenia (0.32%). There is no evidence of grade 4 cytopenia’s or any dose changes from cytopenia’s. This data suggests that weekly lab monitoring may not be necessary prior to drug administration. Conclusions: Using this data, we have streamlined our approach for monitoring patients receiving weekly bortezomib. During weekly bortezomib administration, we propose to obtain a CBC on day 1 of every 4 weeks. If either platelet count is less than 75,000 /μl and ANC is less than 1000/μl on day 1, we will monitor labs weekly until count recovery. We believe that this new protocol may result in 75% reduction in the average patient stay for the treatment. It will reduce the need for phlebotomy and lab services. We believe that this change will improve patient satisfaction and an another step forward to efficient and safe patient care at our institute.
Abstract 700: Recellularization of Acellular Xenogenic Scaffold With Autologous Human Mesenchymal Stem Cells Rescues the Xenoreactive Immune Response
Authors: Sabin J Bozso, Jimmy Kang, Benjamin Adam, Michael C Moon, Darren H Freed, Jayan Nagendran, Jeevan Nagendran
Journal: Circulation Research (2019)

Background: Pre-clinical evidence suggests that structural valve deterioration (SVD) of bioprosthetic xenogenic tissue heart valves (XTHV) is a result of chronic immune rejection. Recellularization of XTHVs with human autologous cells represents one potential strategy to prevent this xenoreactive immune response and mitigate SVD. Methods: Bone marrow, human pericardium and heparinized whole blood was collected from adult patients undergoing elective cardiac surgery. Decellularized bovine pericardium underwent recellularization with hMSCs, which were isolated and cultured from the bone marrow, via co-incubation to allow for cell seeding. To examine the cell mediated immune response, we performed immunofluorescent staining for CD68+ macrophages and CD3+ T-cells and performed a proliferation assay to quantify T-cell proliferation. To investigate the humoral immune response, we performed an enzyme linked immunosorbent assay for pro-inflammatory cytokines TNF-α and INF-γ. Serum and PBMCs were collected for subsequent biochemical and flow cytometric analysis. Results: We show that decellularized bovine pericardium, exposed to human serum, had significantly decreased T-cell activation, represented by TNF-αand INF-γexpression, as well as a significant decrease in T-cell proliferation, when compared to wild-type bovine pericardium (p&lt;0.01). Moreover, when decellularized bovine pericardium was recellularized with autologous hMSCs and exposed to human serum, there was an additional decrease in TNF-α, INF-γexpression along with a further significant decrease in T-cell proliferation, when compared to both wild-type and decellularized bovine pericardium (p&lt;0.01). Importantly, recellularized XTHVs exposed to human serum had an equivalent expression of TNF-α, INF-γ and T-cell proliferation when compared to native human pericardium exposed to autologous human serum. Conclusions: Taken together, our data suggest that autologous human MSC recellularization of decellularized bovine pericardium abrogates the xenoreactive immune response. As such, autologous hMSC recellularization of an acellular xenogenic scaffolds may be an effective approach to decrease the progression of bioprosthetic SVD.
Synergistic Effect of Imatinib and Ruxolitinib in a Patient with JAK2V617F positive Myelofibrosis and Concomitant BCR-ABL1 positive Chronic Myeloid Leukemia
Authors: Srinivas K. Tantravahi, Soo Jin Kim, Jeffrey A Gilreath, Anthony D. Pomicter, Tsewang Tashi, Michael W. Deininger, Josef T. Prchal
Journal: Blood (2018)