tbuckley/cabot-search huggingface dataset:
The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA‐matched allogeneic stem cell transplantation
Authors: Xavier Poiré, Myriam Labopin, Emmanuelle Polge, Liisa Volin, Jürgen Finke, Arnold Ganser, Didier Blaise, Ibrahim Yakoub‐Agha, Dietrich Beelen, Edouard Forcade, Bruno Lioure, Gérard Socié, Dietger Niederwieser, Hélène Labussière‐Wallet, Johan Maertens, Jan Cornelissen, Charles Craddock, Mohamad Mohty, Jordi Esteve, Arnon Nagler
Journal: American Journal of Hematology (2019)

Monosomy 7 or deletion 7q (-7/7q-) is the most frequent adverse cytogenetic features reported in acute myeloid leukemia (AML), and is a common indication for allogeneic stem cell transplantation (SCT). Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion of chromosome 3 (inv(3)), the presence of which may influence the outcomes after SCT. A total of 1109 patients were allocated to this study. Two-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. Two-year probability of non-relapse mortality (NRM) was 20%. We defined five different cytogenetic subgroups: the "-7/7q- ± CK group- designated group1," the "MK group-designated group 2," the "-5/5q- group- designated group 3," the "abn(17p) group- designated group 4" and the "inv(3) group- designated group 5." The 2-year probability of LFS in first remission was 48% for group 1, 36.4% for group 2, 28.4% for group 3, 19.1% for group 4 and 17.3% for group 5, respectively (P < .001). Multivariate analysis confirmed those significant differences across groups. Note, SCT in -7/7q- AML provides durable responses in one third of the patients. The presence of -7/7q- with or without CK in the absence of MK, abn(17p) or inv(3) is associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of patients with poor prognosis even after SCT.
Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET
Authors: Renaud La Joie, Adrienne V. Visani, Suzanne L. Baker, Jesse A. Brown, Viktoriya Bourakova, Jungho Cha, Kiran Chaudhary, Lauren Edwards, Leonardo Iaccarino, Mustafa Janabi, Orit H. Lesman-Segev, Zachary A. Miller, David C. Perry, James P. O’Neil, Julie Pham, Julio C. Rojas, Howard J. Rosen, William W. Seeley, Richard M. Tsai, Bruce L. Miller, William J. Jagust, Gil D. Rabinovici
Journal: Science Translational Medicine (2020)

Tau imaging with [ 18 F]flortaucipir predicts the severity and topography of subsequent MRI cortical atrophy in patients with Alzheimer’s disease.
Abstract 255: A Novel and Accurate Method for Assessing Recoil During CPR Training
Authors: Ram Dantu, Satyam Sarma, Mark Dokendorf, Ishan ranasinghearachchilage, Samuel Hearn, Ahamed H Idris
Journal: Circulation (2019)

Introduction: In addition to accurate measurement depth and rate of each compression, accurate measurement of full recoil, after each compression, is mandatory for the CPR training. Permitting complete chest recoil during the decompression phase of CPR is essential for refilling the lungs and for adequate myocardial perfusion. Complete chest recoil is important but not evaluated during CPR training. Currently, the recoil is measured based on the residual force when the rescuer releases the hands. Recent clinical research shows the recoil measurements need to consider the release time, release velocity and release height. Hypothesis: With a commercially available smartphone providing real-time feedback (placed on an armband of the subjects), trainees will improve recoil performance using proper release velocity, release time and release height. Methods: Using a previously validated smartphone application utilizing the smartphone’s accelerometer, gyroscope and magnetometer, we measured these 3 variables. Total of ten sessions was recorded. Each individual CPR session was recorded in the application (acceleration streams, detected pumps with annotations, and the generated feedback). Audio and visual feedback was provided about the measured depth, rate, and recoil quality. Each session has 30 CPR pumps. The scripted patterns consisted of alternating (recoil on and off) window lengths of either 5 or 10 pumps, and the patterns varied between sessions. Recoil was considered to be good if releases velocity is &gt;= 400mm/sec and release time is &lt;=120ms and release height is &gt;= 2 inches. Results: Using the output of a bayesNet classifier on the manually-annotated dataset, 84% true positives (success) was achieved for all the three metrics. Conclusions: With guided feedback recoil efficiency improved.
Is systemic inflammation the result of insufficient cortisol production in patients with colorectal cancer?
Authors: Michelle Leana Ramanathan, Campbell SD Roxburgh, Paul G Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2012)

e14092 Background: Patients with colorectal cancer who have a raised systemic inflammatory response have been shown to have poorer outcomes, independent of their tumour stage. In particular, the combination of C-reactive protein (CRP) and albumin, the modified Glasgow Prognostic Score (mGPS) has been shown to have consistent and superior prognostic value. However, the basis of a systemic inflammatory response in these patients is not clear. One hypothesis is that the presence of a systemic inflammatory response in patients with colorectal cancer may be due to impaired cortisol production, a potent anti-inflammatory agent. Therefore, the aim of the present study was to examine the relationship between preoperative systemic inflammatory response and endogenous cortisol production. Methods: A prospective study was performed to incorporate the assessment of adrenocortical function using synthetic ACTH, a short Synacthen test, as part of the preoperative assessment of patients undergoing potentially curative resection for colorectal cancer. Preoperative systemic inflammatory response was assessed using mGPS. Results: A total of 80 patients underwent short Synacthen testing. The majority of patients were under 75 years old (79%), were male (59%), had colon cancer (75%) and had TNM stage I/II disease (54%). Approximately 50% received adjuvant treatment. Using standard criteria (peak cortisol &lt;450 nmol/L = inadequate) impaired cortisol response was seen in 3 (4%) patients. There were no significant associations between the baseline, 30 minute, or change in cortisol (both relative and absolute) and age (p=0.814, p=0.443, p=0.730, p=0.929), sex (p=0.714, p=0.440, p=0.324, p=0.953), site (p=0.519, p=0.255, p=0.145, p=0.222), TNM stage (p=0.115, p=0.591, p=0.492, p=0.289), mGPS (p=0.280, p=0.202, p=0.800, p=0.818), or white cell count (p=0.787, p=0.316, p=0.462, p=0.567). Conclusions: The results of the present study show that impaired cortisol production, as evidenced by the short Synacthen test, was uncommon in patients with potentially curable colorectal cancer. Moreover, they indicate that the presence of a systemic inflammatory response is not associated with impaired cortisol production.
Assessment of viable cells as a predictor of response in soft tissue sarcomas treated with neoadjuvant therapy.
Authors: Ranyell Spencer Sobreira Batista, Samuel Aguiar, Isabela Werneck Cunha, Ademar Lopes, Fernando A. Soares, Paulo Roberto Stevanato, Celso Lopes Mello
Journal: Journal of Clinical Oncology (2013)

e21507 Background: Soft Tissue Sarcomas (STS) are an uncommon neoplasm with many histological subtypes with different behaviors, response to treatments and developments. The treatment of these tumors is using surgery, radiotherapy or chemotherapy. The pathological response using degree of tumor necrosis has been implicated in survival rates. However comes to assessing the degree of tumor necrosis in the surgical specimens as response parameter could be confuse because the high-grade sarcomas exhibit a high rate of necrosis even without any treatment. Methods: 31 patients with STS of high grade located in extremities treated with neoadjuvant doxorubicin and ifosfamide were observed prospectively since January 2005 to June 2011. For evaluation of surgical specimens post neoadjuvant chemotherapy, a slice of the specimen in with lower gross of necrosis was represented and after mapped evaluating grade of necrosis, fibrosis and percentage of viable cells. Results: Six patients had ≤5% of viable cells, eight had ≤10% and 12 with 30% or less in the sample. Overall survival (OS) was 100%, 100% and 91% with Disease free survival (DFS) were 100%, 85.7% and 82.5%, respectively. No patient had ≥95% necrosis in the surgical specimens considering that a large part of the tissue had fibrosis in patients with few viable cells, which do not correlate with survival. Conclusions: The viable cell count in the sample is feasible, and relates well with survival. We consider this the ideal method for response evaluation in SPM instead of counting necrosis. In combination with the literature data we suggest cutoff points of 5%, 10% and 30%.
The economic assessment of eribulin compared to treatment of physician's choice (TPC) in Australia.
Authors: Trefor Jones, W. Robert Simons
Journal: Journal of Clinical Oncology (2013)

e17552 Background: The Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus E7389 (EMBRACE) established clinical benefits. This study evaluates its translation into comparative economic value. Methods: Because of superior survival benefits and a non-inferior safety profile, we use a cost-effectiveness analysis. Costs include medication and administration costs, cost of toxicity management, and indirect cost. The primary endpoint is the ratio of incremental means of costs and quality adjusted life years (QALY) yielding an incremental cost effectiveness ratio (ICER). Partitioned survival analyses were evaluated using a log-logistic function for overall survival, progression free survival, response duration, and toxicity time. Health state utilities or quality weights are applied to each component and aggregated. Sensitivity analyses assessed the influence of variability in a number of parameters. Results: Overall survival based on the log-logistic extrapolation was 686 days in the eribulin group compared to 550 days in the TPC group for a difference of 136 days. Mean time without progressive disease was 214 days and 160 days, respectively, for a difference of 59 days. Time spent with Grade 3 and 4 toxicity were 3.62 and 2.25 days in the eribulin group versus 2.25 and 0.98 days in the TPC group. Response times were 15.62 and 9.64 days, 5.98 days longer in the eribulin group. After weight components of overall survival with corresponding utilities and converting to years, the QALY were 1.166 in the eribulin group compared to 0.926 in the TPC group for a mean incremental improvement of 0.24 years. Mean treatment costs were $14,302.80 AUD and $1,672.02 AUD for a difference of $12,630.78 AUD. Total incremental cost is $13,794.35 AUD. The ICER with and without discounting is $48,134.29 AUD and $45,770.97 AUD, respectively. Survival time and drug cost were the most influential variables on the ICER. Conclusions: At a threshold of $50,000 AUD per QALY, eribulin is good value at $48,134 AUD per QALY. Clinical trial information: NCT00388726.
Co-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity
Authors: Standwell C. Nkhoma, Simon G. Trevino, Karla M. Gorena, Shalini Nair, Stanley Khoswe, Catherine Jett, Roy Garcia, Benjamin Daniel, Aliou Dia, Dianne J. Terlouw, Stephen A. Ward, Timothy J.C. Anderson, Ian H. Cheeseman
Journal: Cell Host & Microbe (2019)
Abstract #3456: DACH1 is a cell-fate determination factor that governs Forkhead protein function in tumorigenesis
Authors: Jie Zhou, Wei Zhang, Will Dampier, Min Wang, Zuoren Yu, Kongming Wu, Vladimir Popov, Nicole Willmarth, Mathew Casimiro, Michael Lisanti, Aydin Tozeren, Richard Pestell, Chenguang Wang
Journal: Cancer Research (2009)

The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive EGFR mutant, ellipse, encodes a key component of the Retinal Determination Gene Network (RDGN) which governs cell fate. DACH1 regulates gene expression indirectly through DNA sequence-specific binding to Six or Jun proteins. Herein, CASTing identified a DACH1 DNA-binding sequence which resembles the FOX (Forkhead Box containing protein)binding site. Genome-wide In-silico promoter analysis of DACH1 binding sites identified clusters of genes populating cellular pathways associated with cancers such as the cell cycle pathway and the glioma pathway. The Forkhead proteins are a family of evolutionarily conserved transcriptional regulators involved in diverse biological processes such as organismal development, cell differentiation, and proliferation. Altered expression of Forkhead protein has been associated with tumor initiation, progression, and metastasis. FOXM1 promotes tumor growth and FOXC2, associated with aggressive basal-like breast cancer, enhances cell invasion and tumor metastasis. The expression levels of DACH1 and FOXM1 in breast cancer specimen are inversely correlated. Our data showed that DACH1 repressed FOXM1 induction of U2OS cell colony formation. We examined whether DACH1 attenuates transcription of known FOXM1-regulated genes and competes for occupancy of FOXM1 binding sites in the context of local chromatin. DACH1 antagonized expression of FOXM1 target gene including Cdc25B, Aurora B kinase, Survivin, PLK1, CENPA, and CENPB, promoter occupancy in the context of local chromatin, contact-independent growth and FOXC2-dependent invasiveness. Proteomic analysis identified CA150 as the transcriptional co-integrator of DACH1 activity. Our results suggest that reconstitution of DACH1 expression and function could be a potential strategy for prevention and treatment of Forkhead protein-associated metastatic cancer. This study provides fundamental understanding of molecular mechanisms through which DACH1 tumor suppressor negatively regulates the Forkhead protein signaling. Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3456.
Synthesis and applications of theranostic oligonucleotides carrying multiple fluorine atoms
Authors: Valeriy G Metelev, Alexei A Bogdanov
Journal: Theranostics (2020)

The use of various oligonucleotide (ON) syntheses and post-synthetic strategies for targeted chemical modification enables improving their efficacy as potent modulators of gene expression levels in eukaryotic cells. However, the search still continues for new approaches designed for increasing internalization, lysosomal escape, and tissue specific delivery of ON. In this review we emphasized all aspects related to the synthesis and properties of ON derivatives carrying multifluorinated (MF) groups. These MF groups have unique physico-chemical properties because of their simultaneous hydrophobicity and lipophobicity. Such unusual combination of properties results in the overall modification of ON mode of interaction with the cells and making multi-fluorination highly relevant to the goal of improving potency of ON as components of new therapies. The accumulated evidence so far is pointing to high potential of ON probes, RNAi components and ON imaging beacons carrying single or multiple MF groups for improving the stability, specificity of interaction with biological targets and delivery of ONs
Brain microenvironment-induced reduction in microRNAs to promote metastatic tumor growth, drug resistance, and survival.
Authors: James Driscoll, Arasakumar Subramani, Samer Alsidawi, Sajjeev Jagannathan
Journal: Journal of Clinical Oncology (2013)

e22030 Background: Brain metastases remain a serious obstacle that negatively impacts cancer patient survival. Most deaths due to cancer result from the progressive growth of metastatic, drug-resistant lesions. Moreover, the incidence of brain metastases is rising as a result of an aging population, superior imaging modalities, earlier cancer detection and more effective treatment of systemic disease. Methods: To investigate the role of the brain microenvironment in metastasis, tumor cells were co-cultured with astrocytes - the most abundant normal cell type in the metastatic brain tumor niche. This led to increased tumor cell viability, proliferation and chemoresistance. Microarray-based profiling was then performed to address the effect of the brain microenvironment on miRNA expression levels in tumor cells. Results: Profiling revealed that astrocyte co-culture reduced miRNAs-768-3p, 886-5p and 200c in tumor cells. Inhibition of miRNA-768-3p increased KRas expression, and a specific binding site was identified in the KRas 3’UTR and validated using a luciferase construct. miRNA-768-3p levels were reduced in patient-derived brain metastases relative to normal adult brain. Additionally, miRNA-768-3p was also lower in brain metastases compared to the primary tumors in matched paired samples. Our data demonstrates that the brain microenvironment modulates miRNA-768-3p in metastatic lesions to enhance KRas-mediated tumor survival and promote metastasis. Conclusions: The brain microenvironment regulates the expression of individual miRNAs in tumor cells to promote growth, survival and drug resistance. The brain microenvironment down-regulates the level of certain miRNAs to promote oncogenic signaling and tumor growth while our studies indicate that chemically-engineered miRNA mimics can restore the loss-of-function to reduce the viability of cancer cells. miRNA replacement therapy is a promising and novel therapeutic concept that could save thousands of patients from ineffective treatment, improve patient quality-of-life, overall survival and reduce the devastating impact of brain metastases on the healthcare system.
Pilot Study on Frailty and Functionality on Routine Clinical Assessment in Allogeneichematopoietic Cell Transplantation to Predict Outcomes
Authors: Maria Queralt Salas, Eshetu G Atenafu, Ora Bascom, Leeann Wilson, Arjun Law, Wilson Lam, David Loach, Zeyad Al-Shaibani, Fotios V. Michelis, Dennis Dong Hwan Kim, Jeffrey H. Lipton, Auro Viswabandya, Jonas Mattsson, Alibhai M.H. Shabbir, Rajat Kumar
Journal: Blood (2019)
Abstract 13034: Nightmares and Insomnia Are Independently Associated With Depression and Anxiety in Patients Hospitalized With Cardiovascular Diseases
Authors: Haruaki Horie, Takashi Kohno, Yasuyuki Shiraishi, Yoshinori Katsumata, Kentaro Hayashida, Shinsuke Yuasa, Shun Kohsaka, Seiji Takatsuki, Keiichi Fukuda
Journal: Circulation (2018)

Introduction: Sleep and psychological disturbances contribute to the development of various cardiovascular (CV) diseases. However, there is insufficient literature regarding the prevalence of treat...
Open label phase I/II study of <i>Wilms' tumor gene 1 (WT1)</i> mRNA-transfected autologous dendritic cell vaccination in patients with solid tumors.
Authors: Yannick Willemen, Manon Thirza Huizing, Evelien Smits, Sébastien Anguille, Griet Nijs, Barbara Stein, Viggo Van Tendeloo, Marc Peeters, Zwi N. Berneman
Journal: Journal of Clinical Oncology (2012)

e13051 Background: Active specific immunotherapy, aimed at stimulating tumor-specific immunity, is widely under investigation to determine its place in cancer treatment. Methods: We are conducting an open label phase I/II clinical trial to evaluate the feasibility, toxicity and immunogenicity of intradermal vaccination with keyhole limpet hemocyanin (KLH)-exposed WT1 mRNA-transfected autologous monocyte-derived dendritic cells (DC). Recruitment has finished, but vaccination and follow-up continue. Vaccination consists of biweekly intradermal injection of 10 million DC in the medial region of the arm close to the axilla. Clinical evaluation with PET, CAT or MRI is done before start of the vaccination and repeated every 8 weeks. After 4 vaccinations patients undergo a delayed-type hypersensitivity (DTH) skin test to evaluate immunological responses. Results: 18 patients (8 breast cancer and 3 astrocytoma patients, 1 melanoma, 1 mesothelioma, 1 ovarian, 1 colon, 1 esophageal, 1 renal cell and 1 peritoneal cancer patient) were included in this trial from May, 2010 until January, 2012 to whom we administered a total of 175 vaccines. The median number of vaccines produced per patient was 15 (range 5-34). Median follow-up from start of the vaccination is 26 weeks (range 2-83). All evaluable patients exhibited local symptoms such as itching and/or redness at the sites of injection after the second vaccination and onward (n=17) and displayed positive DTH skin reactions (induration ≥2 mm) to the vaccine and its components (n=15). Systemic side effects were limited to 2 patients who each experienced a single episode of flu-like symptoms within 24 hours after vaccination. Thus far, 3 patients died of disease progression, while 7 others had progressive disease and 6 had stable disease at the most recent evaluation compared to before vaccination according to RECIST 1.1. Of the latter group 4 patients received another form of therapy at some point during vaccination. Conclusions: Based on these results our WT1 mRNA-transfected DC vaccination appears to be feasible and safe for patients with solid tumors. Furthermore, our vaccine is capable of inducing immune responses in these patients.
MicroRNA-647 targets SRF-MYH9 axis to suppress invasion and metastasis of gastric cancer: Erratum
Authors: Gengtai Ye, Kunzhai Huang, Jiang Yu, Liying Zhao, Xianjun Zhu, Qingbin Yang, Wende Li, Yuming Jiang, Baoxiong Zhuang, Hao Liu, Zhiyong Shen, Da Wang, Li Yan, Lei Zhang, Haipeng Zhou, Yanfeng Hu, Haijun Deng, Hao Liu, Guoxin Li, Xiaolong Qi
Journal: Theranostics (2018)

[This corrects the article DOI: 10.7150/thno.20512.].
Staphylococcus aureus toxin suppresses antigen-specific T cell responses
Authors: Brandon Lee, Reuben Olaniyi, Jakub M. Kwiecinski, Juliane Bubeck Wardenburg
Journal: Journal of Clinical Investigation (2019)

Staphylococcus aureus remains a leading cause of human infection. These infections frequently recur when the skin is a primary site of infection, especially in infants and children. In contrast, invasive staphylococcal disease is less commonly associated with reinfection, suggesting that tissue-specific mechanisms govern the development of immunity. Knowledge of how S. aureus manipulates protective immunity has been hampered by a lack of antigen-specific models to interrogate the T cell response. Using a chicken egg OVA-expressing S. aureus strain to analyze OVA-specific T cell responses, we demonstrated that primary skin infection was associated with impaired development of T cell memory. Conversely, invasive infection induced antigen-specific memory and protected against reinfection. This defect in adaptive immunity following skin infection was associated with a loss of DCs, attributable to S. aureus α-toxin (Hla) expression. Gene- and immunization-based approaches to protect against Hla during skin infection restored the T cell response. Within the human population, exposure to α-toxin through skin infection may modulate the establishment of T cell-mediated immunity, adversely affecting long-term protection. These studies prompt consideration that vaccination targeting S. aureus may be most effective if delivered prior to initial contact with the organism.