tbuckley/cabot-search huggingface dataset:
Prevalence of Immunophenotypes in Neoplastic Hematology At Laboratorios Fatima De Michoacan
Authors: Gregorio Campos-Cabrera, Salvador Campos-Cabrera, Virgina Campos-Cabrera, Maria Mora-Torres, Miguel-Angel Gomez-Guijosa, Maria-Luisa Pedraza-Colin, Alicia Rivera-Trujillo, Sonia Hernandez-Rodriguez, Luis Pita-Ramirez, Jose-Luis Campos-Villagomez
Journal: Blood (2012)
Glucose-Lowering Therapies and Heart Failure in Type 2 Diabetes Mellitus
Authors: Shilpa Vijayakumar, Muthiah Vaduganathan, Javed Butler
Journal: Circulation (2018)

Diabetes mellitus independently increases the risk of and mortality from heart failure in a manner that is well established but inadequately understood. Glycemic optimization does not eliminate this risk, and measures of glycemic control are insufficient markers of cardiovascular risk. In response to a regulatory guidance from the US Food and Drug Administration, glucose-lowering agents are now routinely evaluated in large cardiovascular outcome trials. These recent trial experiences of novel and established glucose-lowering therapies have shown variable risks and benefits with respect to heart failure. Cardiovascular outcome trials have increasingly included heart failure events as either a component of the primary end point or a secondary adjudicated end point. We comprehensively review each established and novel currently marketed glucose-lowering therapy, their biological targets, mechanisms of action, and relationships with heart failure. We then highlight gaps in available evidence and directions for future research regarding the ascertainment of heart failure-related data in the evaluation of emerging glucose-lowering therapies.
Establishing a prostate cancer referral pathway between urology and medical oncology at Lyndon B. Johnson Hospital.
Authors: Andrew Wiele, Helen Ajufo, Joshua Michael Gulvin, Andrew L. Laccetti, Sarah Brown, Leslie Stapleton, Sarah Rizvi, Anne Park, Hilary Y. Ma, Alyssa G. Rieber
Journal: Journal of Clinical Oncology (2019)

60 Background: Treatment for biochemically recurrent (bcr) and metastatic prostate cancer (pc) is evolving, making multidisciplinary evaluation a critical need. Our center, a community public hospital, lacked clear referral criteria between the Urology (Uro) and Medical Oncology (Onc) clinics, resulting in inconsistent care. We aimed to improve multidisciplinary communication and the rate of patient (pt) referrals by establishing standardized referral criteria for pc pts between Uro and Onc. Methods: Referral criteria were based on the presence or concern for primary refractory, bcr, castrate resistant (cr), or metastatic pc, as established by the PCWG3 and RTOG-ASTRO Phoenix consensuses. Primary refractory pc was defined as a failure of the PSA to fall to undetectable levels after radical prostatectomy (rp). Bcr pc was defined as two consecutive PSA values ≥ 0.2ng/mL after rp, or a rise in PSA 2ng/mL above post-treatment nadir after radiation therapy. Cr pc was defined as radiographic (progressive measurable disease) or chemical (two rising PSA levels 6-12 weeks apart) progression despite castrate levels of testosterone (T), defined as a serum T &lt; 50ng/dL. Metastatic pc was defined as the development of bone lesion(s), organ involvement, or lymphadenopathy above the bifurcation of common iliac vessels. The referral criteria were organized into a chart and visibly displayed, discussed during multidisciplinary meetings, and distributed during educational sessions with Uro Residents and Onc Fellows in January 2019. Referral rate was collected from July 2018 through December 2018, and collection of post-intervention referral rate is planned from January 2019 through June 2019. Results: Pre-intervention, 39% (23/59 pts) of the pts that met referral criteria were referred to Onc. Preliminary data from January through April 2019 demonstrated a referral rate of 60% (9/15 pts). Conclusions: In 4 months, our intervention improved the referral rate by 21%. These criteria continue to be reinforced during multidisciplinary meetings and more educational sessions are planned as new personnel establish in the clinics. Ultimately, more time and pts are required to determine the full impact of this project.
Abstract 435: SUMOylation Site in MCL-1 Regulates its Anti-Apoptotic Activity
Authors: Leonardo J Leon, Alexandra G Moyzis, Asa B Gustafsson
Journal: Circulation Research (2019)

Myeloid Cell Leukemia-1 (MCL-1) is an anti-apoptotic BCL-2 protein upregulated in various types of cancer. It is also highly expressed in the myocardium. We previously found that MCL-1 plays a key role in maintaining mitochondrial homeostasis and myocyte survival. Cardiac specific deletion of MCL-1 in myocytes leads to mitochondrial dysfunction, loss of myocytes, and rapid development of heart failure. However, MCL-1’s function in the heart is unclear and the exact mechanism by which MCL-1 protects against apoptotic stimuli is not fully understood. Studies have reported that MCL-1 is subjected to phosphorylation and ubiquitination at several different residues which leads to changes in its stability. MCL-1 has a short half-life and proteasomal-mediated degradation of MCL-1 allows for apoptosis to proceed. Here, we screened the amino acid sequence of MCL-1 to identify novel sites of post-translational modifications involved in regulating MCL-1 function. We discovered the presence of a sumoylation site at lysine 219 that is conserved between species. To examine the function of the site, we generated a mutant of MCL-1 where the lysine residue was mutated to an arginine, MCL-1K219R. First, we investigated whether the sumoylation site was involved in regulating protein stability of MCL-1, but we found no differences in the degradation rates between MCL-1 and MCL-1K219R at baseline and after staurosporine treatment. Interestingly, MCL-1K219R failed to protect against staurosporine-induced apoptosis, while both MCL-1 and MCL-1K219R protected against doxorubicin-mediated cell death. This suggest that the mechanism of doxorubicin-mediated cell death is different from staurosporine. Moreover, MCL-1 has been reported to prevent activation of apoptosis via the mitochondrial pathway by sequestering pro-apoptotic BCL-2 proteins such as PUMA and NOXA. Hence, we examined whether MCL-1 sumoylation is involved in regulating its interaction with pro-apoptotic proteins. A better understanding of how MCL-1 regulates cell survival will not only aid the development of drugs that combat harmful cells, but will also help the production of drugs that effectively protect limited and valuable cells like myocytes.
Abstract 197: Transcription Factor Interactome in Human iPS-derived Cardiac Progenitors is Enriched for Proteins Associated With Congenital Heart Disease
Authors: Barbara Gonzalez Teran, Maureen Pittman, Desmond Richmond-Buccola, Kaitlen Samse, Bonnie Cole, Ruth Huttenhain, Michael McGregor, Nevan Krogan, Katherine Pollard, Deepak Srivastava
Journal: Circulation Research (2019)

Congenital heart disease (CHD) affects ~1% of live births and remains the leading cause of mortality in infants. While large-scale genetic studies have uncovered genes associated with CHD, distinguishing variants that confer risk from the background noise of inconsequential variants remains a challenge. Causative mutations in transcription factors (TF) essential for cardiovascular development, such as NKX2-5, GATA4 and TBX5, have been identified in familial cases of CHD, however they are rare. To expand our understanding of their molecular function and to test whether their interacting proteins may be enriched for variants associated with CHD. We defined the protein-protein interaction (PPI) network of NKX2-5, GATA4 and TBX5 using unbiased mass spectrometry in human iPSC-derived cardiac progenitors (iPS-CPs). This approach yielded a network of 172 proteins. An interdependent gene-regulatory role has been reported at the DNA-binding level for these 3 TF during cardiac development, and we also found interdependent protein interactomes where loss of one TF affected the interactome of the others. Interactomes for each were enriched in proteins involved in similar biological processes, such as chromatin remodeling and gene regulation, or previously unrelated processes such as splicing and mRNA transport. Integration of the iPS-CP-PPI network with the CHD-associated damaging variants found in the Pediatric Cardiac Genomics Consortium whole-exome sequencing cohort revealed statistically significant enrichment in the GATA4 interactome for de novo missense variants. In contrast, neither the TBX5 or NKX2-5 PPIs were enriched for either de novo missense or rare damaging variants. Finally, we developed a framework to rank PPIs with reported damaging variants for functional validation studies. Overall, this work identified novel protein interactors of TFs essential for cardiac development, offering new insights regarding their regulatory roles and the mechanisms through which they may cause CHD.
Efficacy and Safety of 1 Year’s Treatment with Deferasirox (Exjade®): Assessment of Regularly Transfused Patients with Diamond-Blackfan Anemia Enrolled in the EPIC Study.
Authors: John B Porter, Gian Luca Forni, Photis Beris, Ali Taher, Dany Habr, Gabor Domokos, Abdel Hmissi, Maria Domenica Cappellini
Journal: Blood (2008)
Patient-Reported Fatigue, Functional Aspects and Quality of Life in Elderly Patients with High-Risk Myelodysplastic Syndromes. Evidence From a Large Prospective International Study.
Authors: Fabio Efficace, Gianluca Gaidano, Maria Teresa Voso, Giovanni Caocci, Massimo Breccia, Reinhard Stauder, Dominik Selleslag, Grazia Sanpaolo, Uwe Platzbecker, Marianna Criscuolo, Anna Di Tucci, Monica Lunghi, Anna Jonasova, Francesco Buccisano, Alessandra Ricco, Zhang Huiyong, David Bowen, Giuseppe A Palumbo, Pasquale Niscola, Francesco Cottone, Marco Vignetti, Franco Mandelli
Journal: Blood (2012)
Identifying a Murine Xenograft Model Relevant to Light-Chain Specific Approaches to Human Ig Light-Chain Diseases
Authors: Adin Kugelmass, Ping Zhou, Xun Ma, Denis Toskic, Amandeep Godara, Melissa Warner, Lisa Xingguang Lee, Teresa Fogaren, Cindy Varga, Raymond L Comenzo
Journal: Blood (2018)
Abstract 567: Fgf21 as a Biomarker for Metabolic Stress in Heart Failure
Authors: Salah Sommakia, Naredos Almaw, Elizabeth Nguyen, Dinesh Ramadurai, Thirupura Shankar, Sutip Navankasattusas, Robert Campbell, Stavros Drakos, Dipayan Chaudhuri
Journal: Circulation Research (2019)

FGF21, an important metabolic regulator, has recently been suggested as a biomarker for heart failure (HF). FGF21 is involved in the integrated mitochondrial stress response, and has been shown to be upregulated with mitochondrial DNA damage, which occurs more frequently in dilated cardiomyopathy. In this study, we investigated whether FGF21 can be used as a biomarker for metabolic stress in HF. We collected blood and cardiac tissue samples from ischemic and non-ischemic HF patients who have undergone VAD transplantation. We also collected blood and tissue from mice with HF due to 1) combination of transverse aortic constriction and coronary artery ligation (TAC+Lig) or 2) cardiac-specific knockout of the mitochondrial transcription factor A (Tfam). Serum FGF21 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Messenger RNA was extracted from the tissue and FGF21 gene expression was measured using real-time quantitative PCR (qPCR). Immunohistochemical staining was performed on tissue sections (either paraffin embedded or frozen) to observe FGF21 levels. Serum FGF21 was elevated in human HF patients compared to healthy controls, as well as in both mouse models of HF. In human patients, cardiac FGF21 gene expression was upregulated 2.2-fold compared to donors. In the TAC+Lig mouse model we observed a 3.37-fold increase, while the Tfam knockout model which has severe mitochondrial damage exhibited a 218-fold increase in cardiac FGF21 gene expression. Further qPCR assays revealed changes in FGF21 gene expression in the liver and white fat of TFAM-KO, indicating metabolic stress on other organs resulting from HF. In conclusion, serum FGF21 is elevated in multiple models of HF, and appears to have both cardiac and extra cardiac sources. Future work will investigate 1) whether there is a correlation between FGF21 levels and mitochondrial damage, and 2) the signaling pathway resulting in metabolic stress to other organs in HF.
Impact Of The Early Intensification Of Induction Chemotherapy On Complete Remission and Survival Rates For De Novo Adult Acute Myeloid Leukemia
Authors: Seung-Ah Yahng, Jae-Ho Yoon, Sung-Eun Lee, Seung-Hwan Shin, Byung-Sik Cho, Ki-Sung Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Chong-Won Park, Heeje Kim
Journal: Blood (2013)
Prediction of lung cancer risk at follow-up screening with low-dose CT: a training and validation study of a deep learning method
Authors: Peng Huang, Cheng T Lin, Yuliang Li, Martin C Tammemagi, Malcolm V Brock, Sukhinder Atkar-Khattra, Yanxun Xu, Ping Hu, John R Mayo, Heidi Schmidt, Michel Gingras, Sergio Pasian, Lori Stewart, Scott Tsai, Jean M Seely, Daria Manos, Paul Burrowes, Rick Bhatia, Ming-Sound Tsao, Stephen Lam
Journal: The Lancet Digital Health (2019)

BackgroundCurrent lung cancer screening guidelines use either mean diameter, volume, or density of the largest lung nodule on the previous CT scan or appearance of a new nodule to ascertain the timing of the next CT scan. We aimed to develop an accurate screening protocol by estimating the 3-year lung cancer risk after two screening CT scans using deep learning of radiologists' CT readings and other universally available clinical information.MethodsA deep learning algorithm (referred to as DeepLR) was developed using data from participants who had received at least two CT screening scans up to 2 years apart in the National Lung Screening Trial (NLST; training cohort). Double-blinded validation was done using data from participants in the Pan-Canadian Early Detection of Lung Cancer (PanCan) study (validation cohort). The primary analysis was to compare accuracy of DeepLR scores to predict lung cancer incidence at 1 year, 2 years, and 3 years with the Lung CT Screening Reporting & Data System (Lung-RADS) and volume doubling time, using time-dependent area under the receiver operating characteristic curve (AUC) analysis.FindingsThe training cohort consisted of 25 097 participants from NLST and the validation cohort comprised 2294 individuals from PanCan. In the validation cohort, DeepLR showed good discrimination, with 1-year, 2-year, and 3-year time-dependent AUC values for cancer diagnosis of 0·968 (SD 0·013), 0·946 (0·013), and 0·899 (0·017), respectively. Among individuals deemed high risk by DeepLR, 94%, 85%, and 71% of incident and interval lung cancers diagnosed within 1 year, 2 years, and 3 years, respectively, after the second screening CT scan were identified. Furthermore, individuals with high DeepLR scores had a significantly higher risk of mortality (hazard ratio 16·07, 95% CI 10·15–25·44; p<0·0001) among people with high scores on Lung-RADS.InterpretationDeepLR recognises patterns in both temporal and spatial changes and synergy among changes in nodule and non-nodule features. DeepLR scores could be used to accurately guide clinical management after the next scheduled repeat screening CT scan.FundingAllegheny Health Network, Johns Hopkins University, Terry Fox Research Institute, and British Columbia Cancer Foundation.
Palliative care impact on symptom burden.
Authors: Kathleen Dunn, Morgan Hannaford, Scott Hartman, Diane Denny, DBA, Timothy Holder MD
Journal: Journal of Clinical Oncology (2019)

217 Background: A national network of five hospitals piloted the use of a patient reported outcomes tool as a means for referring patients to the palliative care program. An externally validated assessment tool that captures patients’ perceived symptom burden from baseline and every 21 days was used as means of identifying patients who might benefit from referral if they met the following criteria: six or &gt; symptoms from 27 increasing in severity by two points or &gt; since their last assessment and determined as having any stage cancer with metastatic disease, stage 3 not in remission, or stage 4 and not already enrolled in palliative care. The data generated from the pre and post referral assessments to the palliative care program was then used to measure the impact of the program on symptom burden for this group versus those patients referred to palliative care but electing not to engage. Methods: The patient population, identified as patients who took the assessment during a selected three-month period, was reviewed to identify two groups: those who were referred through the SIT process and subsequently joined the palliative care program, and those who were referred to palliative care but chose not to attend the appointment. Results were then reviewed for both groups for a six-month period, comparing the scores from the patients’ initial assessment and their subsequent assessment. The data from both groups was compared to identify changes in scores by symptom and overall average symptom scores and the cohorts reviewed for similarities and differences (age, gender, cancer type). Results: Out of the 27 symptoms the cohort electing to utilize palliative care had higher pre-referral scores than the comparison group; and their symptoms improved at a rate greater than those not seeking palliative care. The symptoms in which the greatest impact was experienced included: activity, appetite, drowsiness, sense of family, hope, mood, and sexual interest. Conclusions: Interventions from the Palliative Care program had a positive impact on symptom burden in comparison to the group that was referred for services but did not enter the program.
German Hodgkin Study Group Phase I Trial Of Doxorubicin, Vinblastine, Dacarbazine, and Lenalidomide (AVD-Rev) For Older Hodgkin Lymphoma Patients
Authors: Boris Böll, Annette Plütschow, Michael Fuchs, Dennis A. Eichenauer, Indra Thielen, Bastian von Tresckow, Karolin Behringer, Johannes Atta, Michael Pfreundschuh, Michaela Feuring-Buske, Martin Vogelhuber, Martin Sökler, Andreas Engert, Peter Borchmann
Journal: Blood (2013)
Pragmatic randomized trial of a distress screening program using an effectiveness-implementation hybrid design.
Authors: Erin Elizabeth Hahn, Corrine E. Munoz-Plaza, Dana Pounds, Lindsay Joe Lyons, Janet S. Lee, Ernest Shen, Shannon La Cava, Farah Brasfield, Lara N. Durna, Karen W. Kwan, David B. Beard, Alexander Ferreira, Joanne E. Schottinger, Brian S. Mittman, Michael K. Gould
Journal: Journal of Clinical Oncology (2019)

5 Background: Implementation of guideline-recommended distress screening in oncology remains challenging. Evidence suggests that multicomponent care pathways to identify distress severity with algorithm-based referral and management are effective, yet testing of pragmatic implementation in community settings remains limited. We conducted a pragmatic randomized trial of a distress screening program in a large healthcare system to evaluate effectiveness and simultaneously examined implementation outcomes. Methods: We designed a highly pragmatic study per the Pragmatic-Explanatory Continuum Indicator Summary-2 with adaptive workflow design. Randomization was at the medical center level (N=6); eligible patients had a new diagnosis of breast cancer (no exclusions). Eligible patients were offered the distress screening program as part of usual care: PHQ-9 screening, algorithm-based scoring and referral, referral tracking, and audit and feedback of performance data. Control sites had access to the PHQ-9 and scoring algorithm. We compared number screened, distress severity, and referral. We conducted qualitative interviews with stakeholders on implementation barriers and facilitators. Results: We enrolled 1,436 eligible patients; 692 control, 744 intervention. Groups were similar in demographic and tumor characteristics (Table); 80% of patients completed screening at intervention sites vs &lt;1% at control sites. Of those screened at intervention sites, 10% scored in the medium/high range indicating need for referral; 94% received an appropriate referral. We conducted 20 interviews; the program was found to be highly feasible and acceptable. Conclusions: Our pragmatic, adaptive approach resulted in the large majority of patients screened and appropriately referred with a high degree of acceptability and feasibility. Our results can promote more widespread, sustained adoption of effective distress screening programs. Clinical trial information: NCT02941614. [Table: see text]
Transplant Rates and Outcomes of Young Acute Myeloid Leukemia (AML) Patients with Intermediate and Poor Risk Disease Referred to a Coordinated Acute Leukemia and Hematopoietic Stem Cell Transplant (HSCT) Program
Authors: Melhem Solh, Xu Zhang, Asad Bashey, Lawrence E Morris, Zain Bashey, H. Kent Holland, Scott R Solomon
Journal: Blood (2018)
Provider perceptions of the social work role in oncologic pain management.
Authors: Claire Ralli, Michelle Bailiff, Crystal Fields-Burdick, Kali Gajewski, Tara Garza, Nora Larson, Lydia Mills
Journal: Journal of Clinical Oncology (2019)

214 Background: Best practices of cancer care delivery have shifted from medical models to interdisciplinary approaches aimed at holistic care. The social work profession has advanced itself by gaining competence in psycho-oncology, advance care planning, biopsychosocial assessment and intervention, and pain management. While Masters prepared Social Workers (MSW) are widely recognized as experts in most of these areas, it appears that they are underutilized in pain management. This study will examine provider and nursing perceptions about social work expertise and whether those perceptions may limit utilization of social work in multidisciplinary management of cancer pain. Methods: While review of psycho-oncology literature supports the role of social work in pain management, this was not clearly indicated within the medical oncology domain. A survey was created to ascertain the perception of the MSW role in pain management as a supplement to pharmacologic and medically-based care when identifying and treating multidimensional pain. The survey was completed by Physicians, Advanced Practice Providers, and Nurses in outpatient oncology practices in The US Oncology Network. Results: 139 medical professionals responded. As hypothesized, 88% reported they were comfortable with MSWs conducting Advance Care Planning, while 61% reported being comfortable with MSWs educating patients and families about pain management during palliative/end of life care. 95% believed unmet emotional, social, spiritual and existential needs can present as physiological pain, however only 55% indicated they would include Licensed Clinical Social Workers to provide therapeutic interventions as part of pain management. Conclusions: Under half of survey participants reported an understanding of the scope of social work practice, which aligns with the lack of awareness and under-utilization of social work as a vital contributor in oncologic pain management. MSWs have training in evidence-based interventions such as CBT, guided imagery, mindfulness and biofeedback techniques which may diminish the experience of pain. Further research is recommended to identify strategies to promote and integrate social work into multidisciplinary pain management.