tbuckley/cabot-search huggingface dataset:
Optimizing Early Prediction Of Outcome In CML Using The Exact Decline Of BCR-ABL Transcript Levels Within 3 Months Of Imatinib Treatment As a Prognostic Marker
Authors: Benjamin Hanfstein, Valeria Shlyakhto, Michael Lauseker, Rüdiger Hehlmann, Susanne Saussele, Philipp Erben, Christian Dietz, Alice Fabarius, Ulrike Proetel, Susanne Schnittger, Stefan W. Krause, Jörg Schubert, Hermann Einsele, Mathias Hänel, Jolanta Dengler, Christiane Falge, Lothar Kanz, Andreas Neubauer, Michael Kneba, Frank Stegelmann, Michael Pfreundschuh, Cornelius F. Waller, Karsten Spiekermann, Gabriela M. Baerlocher, Markus Pfirrmann, Joerg Hasford, Wolf-Karsten Hofmann, Andreas Hochhaus, Martin C. Müller
Journal: Blood (2013)
Selectively Targeting Checkpoint Kinase By Prexasertib Had Potent Anti-Tumor Activity As Single Agent or Combined with Other Chemotherapeutic Drugs in Diffuse Large B-Cell Lymphoma, Especially Double Hit Lymphoma
Authors: Juan Gu, Dennis C Gaughan, Simran Gill, Cory Mavis, Francisco J. Hernandez-Ilizaliturri
Journal: Blood (2018)
Checkpoint Inhibition in CSF3R Mutated Chronic Neutrophilic Leukemia
Authors: Stefanie Kreutmair, Teresa Poggio, Chuanjiang Yu, Sivahari Prasad Gorantla, Khalid Shoumariyeh, Dietmar Pfeifer, Michael Lubbert, Karsten Spiekermann, Robert Zeiser, Justus Duyster, Anna Lena Illert
Journal: Blood (2018)
The EBMT Lymphoma Working Party-European Mantle Cell Lymphoma Network Consensus Project On The Role Of Autologous and Allogeneic Stem Cell Transplantation In Mantle Cell Lymphoma: Recommendations Applying The Delphi Procedure
Authors: Stephen Paul Robinson, Paolo Corradini, Peter Dreger, Dolores Caballero, Christian H Geisler, Michele Ghielmini, Steven Le Gouill, Eva Kimby, Simon Rule, Umberto Vitolo, Martin Dreyling, O. Hermine
Journal: Blood (2013)
Mutations In UBA3 Confer Resistance To The NEDD8-Activating Enzyme Inhibitor MLN4924 In Human Leukemic Cells
Authors: G. Wei Xu, Julia I. Toth, Sara R. da Silva, Stacey-Lynn Paiva, Julie L. Lukkarila, Rose Hurren, Neil Maclean, Mahadeo A. Sukhai, Rabindra N. Bhattacharjee, Carolyn A. Goard, Bruno C Medeiros, Patrick T. Gunning, Sirano Dhe-Paganon, Matthew D. Petroski, Aaron Schimmer
Journal: Blood (2013)
Understanding patient engagement in breast cancer survivorship care: A national web-based survey.
Authors: Kathryn Elizabeth Post
Journal: Journal of Clinical Oncology (2019)

223 Background: Little is known about patient engagement (PE) into survivorship care (SC). Information is needed to further explore PE into SC, what factors may contribute to it and which patients are more likely to engage in SC and thus be better equipped to self-manage during survivorship. Purpose: The purpose of this study was to explore how demographic/personal factors and survivorship variables are related to and may contribute to PE in early stage breast cancer survivors. Methods: A cross-sectional, web-based self-report national survey was conducted using measures assessing personal/demographic factors, survivorship variables: health-related quality of life (HRQOL), fear of cancer recurrence, cancer health literacy and two measures of PE (patient activation (PA) and knowing participation in change (KPC). There was one open-ended question regarding additional survivorship concerns. Participants were recruited using Dr. Susan Love’s Army of Women Research Foundation and Craigslist. Data were analyzed via bivariate associations and backwards linear regression modeling in SPSS. Results: The final sample included 303 participants (301 females and 2 males), Μ age 50.70. The sample was predominantly White, non-Hispanic and equally dispersed across the United States. PE was significantly correlated with 13 predictors. There were 10 predictors resulting in significant ANOVA relationships with PA and KPC. In the KPC and PA regression models, HRQOL significantly predicted PE (p ≤ .001). In the KPC regression model, social support and level of education significantly predicted PE (p ≤ .001) and receipt of a survivorship care plan contributed unique variance to the model (9.1%). The open-ended question response categories included: physical and mental health concerns, financial toxicity, social support, body image concerns, other concerns or none. Conclusions: This study provides evidence that personal/demographic factors and survivorship variables may contribute to PE in breast cancer survivors. Findings may provide insight as to which survivors may be ready to engage in SC and those that may need more resources and support.
Ocular manifestation in patients with HIV/AIDS: a hospital-based retrospective study
Authors: Wangting Li, Xiaoli Wang, Lanqin Zhao, Duoru Lin, Zhenzhen Liu, Xiaohang Wu, Jinghui Wang, Xiayin Zhang, Yahan Yang, Ruixin Wang, Ruiyang Li, Wenyong Huang, Haotian Lin
Journal: The Lancet (2019)
Abstract 479: Cardiomyopathy Phenotypes Observed in Human Engineered Heart Tissue Depend on Functional Maturation
Authors: Lorenzo R Sewanan, Shi Shen, Ronald Ng, Xia Li, Stuart G Campbell
Journal: Circulation Research (2019)

Human iPSC-based models of cardiomyopathies have become increasingly prevalent. These models enable the study of genotype-phenotype relationships within a human context and have already led to new insights. A potential limitation of iPSC-derived cardiomyocytes (iPSC-CMs) is their varying degrees of functional maturation with respect to electrophysiology, calcium handling, and contractility. Variable levels of maturity may explain how different groups investigating hypertrophic cardiomyopathy (HCM) mutations in iPSC cardiomyocytes have arrived at conflicting results. Nevertheless, whether or not advanced functional maturation truly impacts disease phenotype in iPSC cardiomyocyte models remains an open question. Using a novel protocol that combines pacing and physiological media in a three-dimensional engineered heart tissue (EHT) derived from decellularized myocardium, we are able to mature human engineered heart tissues within three weeks to recapitulate key functional characteristics of adult heart tissue, such as a robustly positive force-frequency response, a strong post-rest potentiation, potent calcium handling and excitation-contraction handling, and mature isometric twitches that closely match that of intact adult human ventricular myocardium. Using our platform, we investigated the effect of maturation on the functional consequence of a classic variant (E62Q) in the thin filament protein alpha-tropomyosin (TPM1). Initial characterization of TPM1 E62Q in EHTs show a hypercontractile phenotype compared to its isogenic wild-type line, with limited changes in calcium handling. Preliminary data on maturing TPM1 E62Q EHTs show that additional hallmarks of disease may develop with maturation such as arrhythmogenicity, hypertrophy, and fibrosis. In our work, we develop a method for advanced maturation of hiPSC-CMs in EHTs and show the dependence on maturation status of progressive hallmarks of HCM in human EHTs compared to EHTs grown under conditions standard for the field.
Comparing clinician- and patient-rated performance status and association with psychosocial status in advanced genitourinary cancer.
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Errol James Philip, Joann Hsu, Nazli Dizman, Meghan Salgia, Dena Battle, Ulka N. Vaishampayan, Matthew J. Loscalzo, William Dale, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2019)

195 Background: Assessing patient-reported outcomes (PROs) is a critical element of comprehensive cancer care. Performance status (PS) is a widely used clinical measure to assess patients’ general well-being and, in clinical trials, provide insight into patients’ quality of life (QOL). This study compared PS as reported by clinicians and by patients, and explored whether associations between PS, QOL and psychological symptoms differed by patient or provider. Methods: This cross-sectional survey study enrolled patients with metastatic genitourinary cancers at a single institution. Patients completed measures assessing their PS (self-reported version of the Eastern Cooperative Oncology Group, ECOG), QOL (FACT-G) and psychiatric symptoms (PROMIS-Anxiety and Depression). Clinical data, including ECOG PS by physician rating, was extracted from medical records. Multivariate analysis was used to determine the association between PFS, QOL and psychological symptoms. Results: A total of 83 patients were enrolled. Median age was 67 (range, 31-91), 74% were male and 74% were married. Patients were diagnosed with advanced renal cell carcinoma (RCC; 54%), urothelial cancer (UC; 23%), or prostate cancer (PC; 23%) and were predominantly receiving first (39%) or second line (25%) therapy. Physicians were more likely to classify patients as ECOG PS 0 as compared to patients themselves (90% versus 63%, P = 0.01). Worse ECOG PS by patient-report was significantly associated with poorer psychosocial outcomes, including increased anxiety and decreased social well-being (P = 0.001 for each). In contrast, there was no association between physician-reported PS and these outcomes. Conclusions: This is the first study comparing PS as reported by clinicians and patients. Physicians appeared to overestimate ECOG PS when compared to patient self-rating, and this may have a downstream impact on the accuracy of PS for other psychosocial outcomes. This has potential implications for clinical trials in which PS is used for eligibility/stratification. This phenomenon will be examined prospectively in an upcoming SWOG trial in advanced RCC.
Abstract 176: The Effects of Age, Menopause, and Body Mass Index on Blood Pressure and Radial Pulse Wave in Women
Authors: Chih-Yu Chen, Chi-Wei Chang, Yi-Ting Chang, Sheng-Hung Wang, Gin-Chung Wang Wang
Journal: Circulation Research (2019)

Age, gender, and body mass index (BMI) play an important roles in cardiovascular risk. However, the independent effects of menopause on the ventricular-arterial system in female individuals have not been fully investigated. Thus, this study aimed to assess the effect of age, menopause and body mass index on different hemodynamic parameters including systolic blood pressure (SBP), diastolic blood pressure (DBP) and harmonics of radial pulse wave. This study enrolled 327 female subjects(230 pre-menopausal and 97 post-menopausal), aged 20-87 and without cardiovascular history. SBP and DBP were evaluated by an automatic blood pressure monitor. A 12-second continuous radial pulse data was recorded using medical grade pulse measuring instrument and standard protocol. Spectrum analysis of radial pressure wave was calculated and transformed into first five harmonic amplitudes(C1~C5). We further performed multivariable linear regression models to assess the independent effects of age, menopause, and body mass index on SBP, DBP, and C1 to C5 respectively. The mean age, BMI, SBP, and DBP in enrolled subjects were 43±13 yeas, 23±4 kg/m 2 , 116±16 mmHg, and 69±11 mmHg. Regression analysis demonstrated that age was positively correlated with SBP(P&lt;0.001), whereas effect of age exerted no significant influence on DBP. BMI had positive associations with SBP and DBP(P&lt;0.001), while menopause had no significant effect on neither SBP nor DBP. Multivariable linear regression showed that menopause had significant effects on C1 (P&lt;0.05) and C3 (P&lt;0.05). C1 is associated with atherosclerosis and is an independent risk predictor for adverse cardiac events. We proposed that an increase in cardiovascular risk during menopause may be due to hormonal changes exacerbating the progression of atherosclerosis and reflected in the radial pulse spectrum. Conclusively, this study demonstrates that age and BMI have an independent effect on SBP, whereas menopause has no significant independent effect on SBP. The effects of menopause on C1 and C3, independent of age and BMI, may partially explain the reasons of dramatically increased cardiovascular risk during menopause and provide clues to the underlying mechanisms of the change in cardiovascular system.
Presence of an Abnormal Serum Free Light Ratio Is an Independent Risk Factor for Progression in Monoclonal Gammopathy of Undetermined Significance (MGUS).
Authors: S. Vincent Rajkumar, Robert A. Kyle, Terry M. Therneau, L. Joseph Melton, Arthur R. Bradwell, Raynell J. Clark, Dirk R. Larson, Matthew F. Plevak, Jerry A. Katzmann
Journal: Blood (2004)
Effects of anxiety and depression and early detection and management of emotional distress on length of stay in hospital in non-psychiatric inpatients in China: a hospital-based cohort study
Authors: Wan-Jun Guo, Hui-Yao Wang, Wei Deng, Ming-Jin Huang, Zai-Quan Dong, Yang Liu, Shan-Xia Luo, Jian-Ying Yu, Xia Huang, Yue-Zhu Chen, Chun-Tao Shen, Tian-Rui Ren, Wen Wang, Xin Sun, Xiao-Xi Zeng, Lei Chen, Wei-Hong Kuang, Chang-Jian Qiu, Jin-Ping Song, Da-Jiang Li, Yong Zeng, Nan-Sheng Cheng, Wei-Min Li, Wei Zhang, Lan Zhang, Tao Li
Journal: The Lancet (2019)
Abstract 181: Anti-inflammatory Effects of Macitentan on Monocrotaline-induced Pulmonary Hypertension in a Rat Model
Authors: Kyung-hee Kim, Seung-Woon Rha, Yoonjee Park, Jae Kyeong Byun
Journal: Circulation Research (2019)

Background: Inflammation is closely linked to pulmonary arterial hypertension (PAH). Macitentan (MAC) reduces morbidity and mortality among advanced-stage pulmonary arterial hypertension (PAH) patients. However, data regarding anti inflammatory benefits of MAC treatment at an early stage of PAH is lacking. Methods: One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=30), normal saline (MCT, n=30). Fourteen sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 8 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis. Levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1,6) and nuclear factor-kappa B (NF-κB) activity in serum were determined with enzyme-linked immunosorbent assay. Results: RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. On invasive hemodynamic analyses, RV end-systolic (203±79 μL) and end-diastolic volumes (315±83 μL), pulmonary artery systolic pressure (90±6 mmHg), and end-systolic pressurevolume relationship (–264±23) were significantly worse in the MCT vs. in the MAC (98±45 μL, 225±35 μL, 39±12 mmHg, and –147±42, respectively, all p&lt;0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC. MAC significantly ameliorated PAH by acting against pulmonary vascular remodeling, decreasing macrophage infiltration, and reducing pro-inflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity in the lungs of the MCT-treated rats. Conclusions: MAC treatment improves haemodynamic parameters in established pulmonary hypertension. These results suggest that MAC saline ameliorates the progression of pulmonary hypertension induced by monocrotaline in rats, which may be associated with anti-inflammatory effects.
A Susceptibility Locus for Papillary Thyroid Carcinoma on Chromosome 8q24
Authors: Huiling He, Rebecca Nagy, Sandya Liyanarachchi, Hong Jiao, Wei Li, Saul Suster, Juha Kere, Albert de la Chapelle
Journal: Clinical Cancer Research (2009)

Papillary thyroid carcinoma (PTC) displays higher heritability than most other cancers. To search for genes predisposing to PTC, we performed a genome-wide linkage analysis in a large family with PTC and melanoma. Among several peaks the highest was at 8q24, with a maximum nonparametric linkage (NPL) score of 7.03. Linkage analysis was then broadened to comprise 25 additional PTC families that produced a maximum NPL score of 3.2, P = 0.007 at the 8q24 locus. Fine mapping with microsatellite markers was compatible with linkage to the 8q24 locus in 10 of the 26 families. In the large family, a approximately 320 Kb haplotype was shared by individuals with PTC, melanoma, or benign thyroid disease, but not by unaffected individuals. A 12 Kb haplotype of 8 SNP markers within the larger haplotype was shared by 9 of the 10 families in which the 8q24 locus was compatible with linkage. The shared haplotype is located within 2 known overlapping protein-coding genes, thyroglobulin (TG) and Src-like adaptor (SLA). Resequencing of the coding and control regions of TG and SLA did not disclose putative mutations in PTC patients. Embedded in the TG-SLA region are three likely noncoding RNA genes, one of which (AK023948) harbors the 8-SNP haplotype. Resequencing of AK023948 and one of the other RNA genes did not reveal candidate mutations. Gene expression analysis indicated that AK023948 is significantly down-regulated in most PTC tumors. The putative noncoding RNA gene AK023948 is a candidate susceptibility gene for PTC.
Abstract 915: Dysregulation of the Myosin and Myosin Binding Protein-C interaction in Hypertrophic Cardiomyopathy
Authors: Rohit R Singh, James W McNamara, Sakthivel Sadayappan
Journal: Circulation Research (2019)

Rationale: Affecting 1 in 300 individuals, hypertrophic cardiomyopathy (HCM) is a genetic heart disease characterized by left ventricular hypertrophy, myocardial disarray, and sudden cardiac death. Often, HCM is associated with myocardial hypercontractility. The subfragment-2 (S2) of beta-myosin heavy chain contains a cluster of missense and deletion mutations associated with severe HCM. Interestingly, myosin S2 interacts with the C0-C2 region of cardiac myosin binding protein C (cMyBP-C) in a phosphorylation-dependent manner to regulate sarcomere contractility. However, the nature of myosin S2 and cMyBP-C interactions and the mechanism(s) by which mutations in myosin S2 cause HCM remain to be elucidated. Objective: To determine whether mutations in myosin S2 weaken its interaction with cMyBP-C, resulting in enhanced myofilament contractility. Methods and Results: Myosin S2 proteins (126 amino acids) containing three clinically relevant mutations (R870H, E924K, E930del, or wild type), and recombinant C0-C2 region of cMyBP-C were produced and purified by metal affinity chromatography. Solid-phase binding assays and isothermal calorimetry experiments revealed a significantly dampened binding to C0-C2 for these three mutants in myosin S2 (30% lower than wild type, p&lt;0.002), suggesting that mutations in S2 regions reduce their bindings to cMyBP-C. Conversely, upon protein kinase A phosphorylation of C0C2, these S2 mutants displayed an increased affinity to cMyBP-C, an effect opposite that of wild-type S2. Structural analyses of these mutations within myosin S2 are predicted to reduce the alpha-helical content, thereby reducing stability of the critical coiled-coil structure. Conclusions: Mutations in myosin S2 result in reduced binding to cMyBP-C. Functionally, this would result in a greater attachment of cross-bridges, and thus enhance myofilament contractility. Strikingly, these mutations increase their affinity to cMyBP-C upon phosphorylation, demonstrating fundamental changes to the regulation of contractile function.
MYC Functions As a Master Switch for Natural Killer Cell-Mediated Immune Surveillance of Lymphoid Malignancies
Authors: Srividya Swaminathan, Line Dam Heftdal, Daniel F Liefwalker, Renumathy Dhanasekaran, Anja Deutzmann, Crista Horton, Adriane Mosley, Mariola Liebersbach, Holden T. Maecker, Dean Felsher
Journal: Blood (2018)
Barriers and facilitators to the implementation of routine ototoxicity screening for head and neck cancer patients.
Authors: Priya Bapat, Pansy Chow, Katrina Hueniken, Mary Mahler, M. Catherine Brown, Carolyn Falls, Andrew J. Hope, Aaron Richard Hansen, David Paul Goldstein, John Rutka, Doris Howell, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2019)

127 Background: Ototoxicity after cisplatin +/- radiation occurs in 22-58% of patients with head and neck cancers. Routine post-treatment hearing tests are useful in the early detection of hearing loss, allowing for possible early intervention. This study aimed to identify current hearing screening practices for follow-up, barriers to screening, and recommendations for its implementation. Methods: Stakeholders (physicians, nurses, coordinators, audiologists) identified barriers and facilitators to the implementation of a routine hearing screening follow-up program at Princess Margaret Cancer Centre. Themes were identified using an inductive approach and mapped to the Knowledge to Action (KTA) framework, which guides the implementation of new clinical practices. Results: The problem: While all patients received baseline hearing tests, follow-up testing was inconsistently performed in asymptomatic patients. Patients may also lack awareness of subclinical hearing loss. A formalized follow-up hearing test program was identified as the best approach by stakeholders. Barriers: Individual-level barriers included limited knowledge about intervals for hearing testing and lack of time during clinic visits. Institutional-level factors included personnel, financial resources and logistical supports. Patient travel distances and times were barriers, as well as scheduling tests on the same day as other clinic visits. Societal stigma of hearing loss was a possible barrier. Facilitators: These included greater staff and patient education, and designating a local clinic champion. Instructions for follow-up after identifying hearing loss was deemed essential. Adapting to the local context: Automated flagging post-treatment and auto-referrals to the Hearing Clinic through the electronic medical record system could facilitate increased rates of participation. Mail/phone reminders could be useful adjuncts. Conclusions: Participants supported a formal post-treatment hearing test program for patients with head and neck cancers treated with cisplatin +/- radiation. Individual and institutional barriers were identified, but could be mitigated by appropriate facilitators.