tbuckley/cabot-search huggingface dataset:
Abstract 9394: Establishing Validity of a Midlife Black Women's Wellness Program
Authors: Holly J Jones, Melinda Butsch Kovacic, Tamilyn Bakas
Journal: Circulation (2021)

Introduction: Expert ratings and qualitative feedback are essential for establishing validity of materials developed for interventions. Validation of intervention content should be established prior to initiation of trials. In collaboration with a community research advisory board, the purpose of this study was to analyze expert ratings and qualitative feedback for the Midlife Black Women’s Stress Reduction Wellness (B-SWELL) intervention materials. Methods: The B-SWELL is a culturally tailored 8-week program that leverages stress reduction to lower cardiovascular disease (CVD) risk in midlife Black women by promoting the adoption of the AHA’s Life’s Simple 7 healthy lifestyle behaviors (LS7). Using community participatory methods, the LS7 metrics and B-SWELL binder were culturally tailored and targeted to midlife Black women. A multilevel mixed methods approach was used to establish content and face validity for the B-SWELL binder made up of eight modules. Twelve experts consisting of midlife Black women (n=6), researchers (n=3), and integrative health specialists (n=3) were purposefully recruited to rate each B-SWELL module and the overall binder for content accuracy, topic relevance, stress relevance, cultural appropriateness, feasibility, usefulness, ease of use, and appeal using a 5-point Likert scale (1 strongly disagree to 5 strongly agree). Open ended questions were integrated with ratings to obtain insight into areas needing improvement. Results: Combined mean expert ratings for individual B-SWELL modules were high with means ranging between 4.43 and 4.66. Group ratings differed for individual B-SWELL modules and the B-SWELL binder with midlife Black women having the highest mean ratings (4.71, 4.97), followed by researchers (4.56, 4.73), and integrative health specialists (4.11, 4.40). Narrative data provided details to guide refinement. Conclusions: The B-SWELL intervention materials exhibited strong evidence of content and face validity. Testing feasibility of the B-SWELL intervention in a future study is warranted, ultimately leading to a well-powered randomized control clinical trial to test efficacy of the B-SWELL in lowering CVD risk in midlife Black women through adoption of the LS7 healthy lifestyle behaviors.
78 Novel RNA-seq platform improve patient outcome in clinical oncology and enable implementation of AI in the clinic
Authors: Vy Nguyen, Gitte Pedersen, Morten Pedersen
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Only 1 out of 4 cancer treatments prolongs life while expenditure for cancer treatment is greater than $100 billion/year. RNA-sequencing has allowed researchers to gain insight into the transcriptome of human cancers. However, RNA-sequencing remains widely unused in clinical oncology. We address this issue through the development and CLIA validation of OneRNA—an RNA-sequencing platform for cancer diagnostics and the design of new treatments. The development of OneRNA had to overcome the two main hurdles for implementation of RNA sequencing in the clinic: 1) clinical samples are typically embedded in FFPE which results in highly fragmented RNA making sequencing of these samples difficult. 2) how to interpret aberrant gene expression events and translate these results into clinical action. We demonstrate how OneRNA® would enable the design of sophisticated combinatorial clinical studies. An example is combining immune targeting agents such as checkpoint inhibitors with mRNA vaccines. OneRNA also supports the integration of gene expression algorithms because of its ability to interrogate the entire sample transcriptome. OneRNA® has been CLIA certified using FFPE, FF, blood, and saliva samples. Furthermore, the sample preparation method has demonstrated &gt;95% concordance between FF and FFPE and 5–10X the sensitivity compared to Truseq. Methods This study aims to demonstrate the clinical utility of OneRNA in detecting aberrant gene expression events and connecting these to already approved drugs that targets these events to offer truly individualized treatment options. Results We show that OneRNA has the ability to predict results for not only validated biomarkers used in standard of care such as ER, PR and HER2 in breast cancer, but also provide insight into biomarkers for response to already approved drugs independent of tissue type and with no standard test. Finally, we demonstrate the reproducibility of OneRNA in predicting IHC status in ER, PR and HER2. Conclusions These results demonstrate that OneRNA has applications in both cancer research, drug discovery and development, development of companion diagnostic algorithms and implementation of truly individualized treatment.
Phase 1/2 Study of Oral TP-0184 for the Treatment of Anemia in Adults with Low- or Intermediate-Risk Myelodysplastic Syndromes
Authors: Amit Verma, Andrew M. Brunner, Gregory Pennock, Dragana McMullen, Mark Wade, Huyuan Yang, Yuran Xie, Cliff Whatcott, Jason Foulks, Jason Melear
Journal: Blood (2021)
Synergism between IGF2BP1 and ETV6-RUNX1 in the Pathogenesis of ETV6-RUNX1 Positive B-Acute Lymphoblastic Leukaemia
Authors: Gunjan Sharma, Tiffany Tran, Jaspal Bassi, Amit Kumar Jaiswal, Christine Tso, Ayushi Jain, Jay Singh, Anita Chopra, Archna Singh, Sameer Bakhshi, Dinesh S Rao, Jayanth Kumar Palanichamy
Journal: Blood (2021)
INNV-17. RESPONSE TO AVAPRITINIB IN A PEDIATRIC SPINAL CORD H3K27M-MUTANT GLIOMA PATIENT
Authors: Lisa Mayr, Sibylle Madlener, Rosenmayr Verena, Maria Schmook, Natalia Stepien, Alicia-Christina Baumgartner, Christian Dorfer, Christine Haberler, Leonhard Müllauer, Karin Dieckmann, Andreas Peyrl, Sean Kim, Antony Hsieh, Sasa Dimitrijevic, Johannes Gojo
Journal: Neuro-Oncology (2021)

Abstract H3K27M-mutated diffuse midline glioma (H3K27M-DMG) may arise in the pons, thalamus and spinal cord generally having a dismal prognosis. Notably, H3K27M-DMG are driven by oligodendrocyte precursor-like cells which are partly sustained by PDGFRA signaling. Co-mutations including TP53, ACVR1, PDGFRA, KIT and PI3K pathway alterations are present in a subset of cases, and molecular profiling may allow detection of additional targetable alterations. However, small-molecule inhibitors often have limited efficacy associated with low blood-brain-barrier (BBB) penetration. Here, we report on a patient with spinal, leptomeningeal disseminated H3K27M-DMG treated with avapritinib, an orally administered, BBB-penetrant and highly selective KIT and PDGFR inhibitor, provided through a compassionate-use program. Initial therapy consisted of subtotal resection, focal radiotherapy and temozolomide (TMZ) resulting in disease stabilization. Ten months after diagnosis, leptomeningeal metastases were detected, biopsied and treated with local irradiation and TMZ. The patient subsequently received systemic and intrathecal chemotherapy augmented with dasatinib. Molecular analyses of the biopsy revealed the H3F3A and TP53 mutations present in the primary tumor, as well as de novo PDGFRA and KIT amplifications with gene copy numbers of 25 and 21, respectively. Upon further disease progression, therapy with avapritinib was initiated. Assessment of treatment response according to RANO criteria after four months revealed stable disease of the target lesion in the cerebellum and partial response of all non-target lesions. Avapritinib was generally well tolerated with lower limb edema (Grade 2), small intratumoral bleeding (Grade 1) and unrelated hydrocephalus (Grade 3) as reported adverse events. As precaution, treatment was interrupted and re-initiated after one week as the bleeding was stable. A ventriculoperitoneal shunt was implanted resolving the hydrocephalus. Pharmacokinetic analyses revealed up to 65% avapritinib plasma exposure and clinically relevant levels in cerebrospinal fluid. In summary, we report on first effective therapy of treatment-resistant H3K27M-DMG with avapritinib as clinical proof of concept.
Unprotected Left Main is now no more Domain of Surgeon
Authors: Ranjit Sharma
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Unprotected Left Main Coronary Artery (ULMCA) disease is defined as significant stenosis in the Left Main Coronary Artery (LMCA) and there were no previous Coronary artery bypass surgery (CABG) or patent bypass grafts to the left anterior descending (LAD) or left circumflex (LCX) arteries
Pharyngitis and Tonsillar Exudates in an 18-Year-Old Woman
Authors: Kristin Walter
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Interim FDG 18-PET Δsuvmax Adds Prognostic Value to Deauville 5-Point Scale in the Identification of Patients with Very High-Risk Diffuse Large B Cell Lymphoma
Authors: Sara Duarte, Carolina Afonso, Bárbara Almeida Marques, Carla Barros Lima, Dulcelena Neves, Adriana Roque, Ana Catarina Lai, Tiago Saraiva, Maria José Julião, Mauro Monteiro, Lenka Ruzickova, Jose Pedro Carda, Marilia Gomes, Gracinda Costa, Augusta Cipriano, Ana Espadana
Journal: Blood (2021)
Endothelial Cell Dysfunction Is Involved in the Progression of Myelodysplastic Syndromes
Authors: Tong Xing, Zhong-Shi Lyu, Cai-Wen Duan, Qi Wen, Hong-Yan Zhao, Shu-Qian Tang, Yuan-Yuan Zhang, Meng Lv, Yu Wang, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang, Yuan Kong
Journal: Blood (2021)
Multiomic Mapping of Copy Number and Structural Variation on Chromosome 1 (Chr1) Highlights Multiple Recurrent Disease Drivers
Authors: Patrick Blaney, Eileen M Boyle, Yubao Wang, Hussein Ghamlouch, Jinyoung Choi, Louis Williams, Stoeckle James, Ariel Siegel, Beatrice Razzo, Marc Braunstein, David Kaminetzky, Arnaldo A Arbini, Benedetto Bruno, Jill Corre, Lydia Montes, Daniel Auclair, Faith E. Davies, Aristotelis Tsirigos, Even H Rustad, Francesco Maura, Ola Landgren, Michael A Bauer, Brian Walker, Gareth Morgan
Journal: Blood (2021)
Preliminary Study of Ruxolitinib and Venetoclax for Treatment of Patients with T-Cell Prolymphocytic Leukemia Refractory to, or Ineligible for Alemtuzumab
Authors: Charles Herbaux, Stéphanie Poulain, Damien Roos-Weil, Jacques-Olivier Bay, Yann Guillermin, Francois Lemonnier, Kamel Laribi, Sorin Visanica, Jerome Moreaux, Hugo Gonzalez, Maxime Jullien, Abderrazak El Yamani, Houria Debarri, Sophie Godet, Franck Morschhauser, Olivier Tournilhac, Matthew S. Davids, Loic Ysebaert
Journal: Blood (2021)
Nrf2 Plays a Key Role in Iron-Overload Cardiomyopathy
Authors: Enrica Federti, Francesca Vinchi, Iana Iatcenko, Alessandra Ghigo, Alessandro Mattè, Serge Cedrick, Angela Siciliano, Deborah Chiabrando, Emanuela Tolosano, S. Zebulon Vance, Veronica Riccardi, Immacolata Andolfo, Achille Iolascon, Lucia de Franceschi
Journal: Blood (2021)
Metabolome-wide association study of estimated glomerular filtration rates in Hispanics
Authors: Bridget M. Lin, Ying Zhang, Bing Yu, Eric Boerwinkle, Bharat Thygarajan, Milagros Yunes, Martha L. Daviglus, Qibin Qi, Robert Kaplan, James Lash, Jianwen Cai, Tamar Sofer, Nora Franceschini
Journal: Kidney International (2021)
Sialidase expressed from cancer cells can affect the formation of peritoneal dissemination of ovarian cancer
Authors: Hiroyuki Nomura, Daisuke Aoki, Yutaka Tamada, Atsushi Suzuki, Nao Suzuki, Nobuyuki Susumu, Shiro Nozawa
Journal: Cancer Research (2005)

5600  [Specific Aims] Cell surface carbohydrate expression plays a critical role in the metastatic or invasive characteristics of cancer cells. In previous studies, we determined that sialylated MUC1 expressed on the surface of ovarian cancer cells inhibits the formation of peritoneal dissemination and that sialic acid is critical in inhibiting the binding of tumor cells to peritoneal mesothelial cells. In the present study, we investigated the effects of sialidases, enzymes that remove sialic acid from the non-reducing terminals of carbohydrate structures, on the formation of peritoneal dissemination in vivo and also determined the expression of endogenous sialidases in ovarian cancer cells. [Methods] Initially, we examined whether the intraperitoneal administration of bacterial sialidase or sialidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (DANA), affected the formation of peritoneal dissemination as well as the overall survival in an in vivo murine assay of ovarian cancer peritoneal dissemination. Next, in order to determine the expression of endogenous sialidases, we analyzed the mRNA expression of various sialidases (Neu1, Neu2, Neu3 and Neu4) in 18 different human ovarian cancer cell lines (6 serous adenocarcinoma, 5 mucinous adenocarcinoma, and 7 clear cell adenocarcinoma cell lines) by RT-PCR method. In addition, we determined the immunohistochemical expression of Neu3 in ovarian clear cell adenocarcinoma tissue obtained from clinical specimens. [Results] In the in vivo peritoneal dissemination murine model, sialidase administration when compared with control, resulted in greater amounts of peritoneal dissemination and in a shorter survival period. On the other hand, the survival period was prolonged with DANA administration. In all 18 different ovarian cancer cell lines, there was constitutive expression of Neu1 but no expression of Neu2 and Neu4 by RT-PCR. Neu3 expression was positive in 4 serous adenocarcinoma cell lines, 4 mucinous adenocarcinoma cell lines and all 7 clear cell adenocarcinoma cell lines. Neu3 was also deteremined to be immunohistochemically positive in ovarian clear cell adenocarcinoma tissue specimens. [Conclusion] Using an in vivo murine model, this investigation determined that the formation of peritoneal dissemination is accelerated by sialidase administration but is inhibited by DANA administration. In addition, the expression of Neu3, an endogenous sialidase, was found to localize on the plasma membrane in ovarian cancer cells.
Identifying Novel Causes of Cancers to Enhance Cancer Prevention: New Strategies Are Needed
Authors: Paul Brennan, George Davey-Smith
Journal: JNCI Journal of the National Cancer Institute (2021)

The burden of cancer from a clinical, societal, and economic viewpoint continues to increase in all parts of the world, along with much debate regarding how to confront this. Projected increases in cancer indicate a 50% increase in the number of cases over the next 2 decades, with the greatest proportional increase in low- and medium-income settings. In contrast to the historic high cancer burden due to viral and bacterial infections in these regions, future increases are expected to be due to cancers linked to westernization including breast, colorectum, lung, and prostate cancer. Identifying the reasons underlying these increases will be paramount to informing prevention efforts. Evidence from epidemiological and laboratory studies conducted in high-income countries over the last 70 years has led to the conclusion that approximately 40% of the cancer burden is explained by known risk factors-the 2 most important being tobacco and obesity in that order-raising the question of what is driving the rest of the cancer burden. International cancer statistics continue to show that approximately 80% of the cancer burden in high-income countries could be preventable in principle, implying that there are important environmental or lifestyle risk factors for cancer that have not yet been discovered. Emerging genomic evidence from population and experimental studies points to an important role for nonmutagenic promoters in driving cancer incidence rates. New research strategies and infrastructures that combine population-based and laboratory research at a global level are required to break this deadlock.
Modified Risk-Stratified Sequential Treatment in B-Cell Post-Transplant Lymphoproliferative Disorder (PTLD) after Solid Organ Transplantation (SOT): The Prospective Multicenter Phase II PTLD-2 Trial
Authors: Heiner Zimmermann, Christian Koenecke, Martin H. Dreyling, Christiane Pott, Ulrich Dührsen, Dennis Hahn, Norbert Meidenbauer, Ingeborg A Hauser, Mathias J. Rummel, Dominik Wolf, Michael Heuser, Christian Schmidt, Peter Schlattmann, Matthias Ritgen, Reiner Siebert, Ilske Oschlies, Ioannis Anagnostopoulos, Ralf Ulrich Trappe
Journal: Blood (2021)
Influenza Vaccine Uptake in the Year After Concurrent vs Separate Influenza and Zoster Immunization
Authors: Benjamin N. Rome, William B. Feldman, Michael A. Fischer, Rishi J. Desai, Jerry Avorn
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Fewer than half of US adults receive the influenza vaccine each year; many cite concerns about side effects, which occur infrequently. By contrast, the recombinant zoster vaccine causes systemic side effects in a large proportion of patients. <h3>Objective</h3> To determine whether concurrent administration of the influenza and zoster vaccines was associated with a reduced likelihood of influenza vaccination in the subsequent year. <h3>Design, Setting, and Participants</h3> This cohort study included patients aged 50 years or older who received the influenza vaccine between August 1, 2018, and March 31, 2019, and received the zoster vaccine on the same day or separately (within the prior 180 days). Data were gathered from a national claims database of patients with commercial insurance and Medicare Advantage plans. Logistic regression analysis was used to adjust for baseline demographic characteristics, comorbidities, influenza vaccine month and location (pharmacy vs medical office), and health care use (including influenza vaccination in the prior year). <h3>Exposures</h3> Concurrent vs separate influenza and zoster vaccine administration. <h3>Main Outcomes and Measures</h3> Receipt of the influenza vaccine in the subsequent year (August 1, 2019, to March 31, 2020). <h3>Results</h3> Among 89 237 individuals included in this study, the median age was 72 years (IQR, 67-77 years), 58.3% were women, 70.1% were White, and 85.7% had at least 1 comorbidity. Influenza vaccine uptake in 2019-2020 was lower among 27 161 individuals who received concurrent influenza and zoster vaccines compared with the 62 076 individuals who received the vaccines on separate days (87.3% vs 91.3%; adjusted odds ratio, 0.74; 95% CI, 0.71-0.78;<i>P</i> &lt; .001). Results were similar across subgroups. <h3>Conclusions and Relevance</h3> Results of this cohort study suggest that concurrent administration of influenza and zoster vaccines was associated with a reduction in receipt of the influenza vaccine the following year. One possible explanation is that some patients could have misattributed systemic side effects caused by the zoster vaccine to the influenza vaccine. It may be preferable to administer these 2 vaccines separately or enhance patient counseling about expected vaccine side effects.
CTIM-04. BIOMARKER IMMUNE CORRELATES IN NEWLY DIAGNOSED GLIOBLASTOMA (GBM) TREATED WITH ATEZOLIZUMAB IN COMBINATION WITH TEMOZOLOMIDE (TMZ) AND RADIATION
Authors: Shiao-Pei Weathers, Mark Knafl, Edwin Parra, Sharia Hernandez, Luisa Solis, Beatriz Sanchez Espiridion, Ignacio Wistuba, Andrew Futreal, Dipen Maru, Carlos Kamiya-Matsuoka, Rebecca Harrison, Victory Joseph, Cindy Yun, Walter Darbonne, Monica Loghin, Marta Penas-Prado, Nazanin Majd, W K Alfred Yung, Barbara O'Brien, Woodman Scott, John DeGroot
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Checkpoint inhibitor therapy has demonstrated overall limited efficacy in the treatment of GBM. Mechanisms of resistance to checkpoint blockade need to be better elucidated. Analysis of the tumor microenvironment is critical to identify correlates of response to immune checkpoint blockade. 60 newly diagnosed GBM patients unselected for MGMT status underwent treatment with concurrent atezolizumab with radiation therapy and TMZ followed by adjuvant atezolizumab and TMZ (NCT03174197). Clinical data has been reported previously. METHODS Tissue image immunoprofiling was conducted using 2 multiplex immunofluorescence (mIF) panels against; CD3, CD8, PD-1, PD-L1, Granzyme B, FOXP3, CD45RO, CD68, and GFAP antibodies. PDL-1 (Clone SP263) malignant cells expression was assessed by immunohistochemistry. Correlations between mIF biomarkers co-expressions, IHC PD-L1, and clinical outcome including OS, radiographic response, and PFS were evaluated. RESULTS Of 60 patients enrolled, image immunoprofiling was performed successfully on pre-treatment tissue in 48 patients. 20 of 60 patients underwent re-resection for suspected recurrent disease of which 10 patients had immunoprofiling performed successfully on pre and post treatment samples. An analysis of CD3CD8+ cytotoxic T lymphocytes was consistent with prior work, showing no or relatively low levels at baseline, and no association with clinical outcome. PDL-1 expression by IHC, at thresholds of &amp;gt;1% or &amp;gt;5%, was not associated with clinical outcome. Tumors with a higher number of GFAP-expressing cancer cells had a significantly lower tumor response (p&amp;lt; 0.05) and median OS (430 vs. 799 days, p&amp;lt; 0.01). CONCLUSIONS For newly diagnosed GBM patients treated with standard of care radiation and temozolomide in combination with atezolizumab, T-cell levels and PDL-1 expression were not predictive of outcome. GFAP may represent a novel predictive biomarker of overall survival. Ongoing studies to evaluate the gut microbiome and tumor genomic (WES, CNA) and transcriptomic (RNAseq) features of these and matched tumors are underway.