tbuckley/cabot-search huggingface dataset:
Abstract 13884: Predictor of Right Ventricular Reverse Remodeling After Treatment in Patients With Pulmonary Hypertension
Authors: Hiroyuki Sano, Hidekazu Tanaka, Yoshiki Motoji, Yuko Fukuda, Hiroki Takada, Fumitaka Soga, Yutaka Hatani, Hiroki Matsuzoe, Keiko Hatazawa, Hiroyuki Shimoura, Junichi Ooka, Keiko Ryo-Koriyama, Kensuke Matsumoto, Noriaki Emoto, Ken-ichi Hirata
Journal: Circulation (2016)

Background: Right ventricular (RV) function is one of the most important determinants of outcome for patients with pulmonary hypertension (PH). Furthermore, mid-term RV reverse remodeling after treatment is also associated with long-term outcome as well as RV remodeling before treatment. However, baseline factors influencing mid-term RV reverse remodeling after treatment remains unclear. Methods: We studied 54 PH patients. RV function was calculated by averaging peak speckle-tracking longitudinal strain from RV free-wall (RV free-wall strain). Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined as a relative decrease in RVESA of at least 15% at 10.2 ± 9.4 months after treatment. Long-term follow-up was tracked for 5 years. Results: Adverse events occurred in 10 patients (19%). Mid-term RV reverse remodeling after treatment was observed in 37 patients (69%). Patients with mid-term RV reverse remodeling had more favorable long-term outcome than those without (log-lank p=0.01). Multivariate logistic regression analysis showed that RV relative wall thickness (RV-RWT), which was calculated from RV free-wall thickness/RV basal linear dimension at end-diastole, was the independent predictor of mid-term RV reverse remodeling (OR 1.403; 95% CI, 1.090-1.807; p=0.009). In addition, patients with RV-RWT≥0.21 experienced favorable long-term outcome than those without (log-rank p=0.03). Sequential Cox models show that a model based on symptom, hemodynamic parameters was improved by addition of RV free-wall strain (χ 2 =13.3; p=0.08), and was further improved by addition of RV-RWT (χ 2 =28.9; p&lt;0.01). Conclusion: RV-RWT could predict mid-term RV reverse remodeling after treatment in PH patients, and was associated with long-term outcomes. Our findings may have clinical implications for better management of PH patients.
Fully retargeted measles viruses for cancer therapy
Authors: Takafumi Nakamura, Kah-Whye Peng, Mary Harvey, Suzanne Greiner, Stephen J. Russell
Journal: Cancer Research (2005)

5294  Attenuated replication-competent Edmonston lineage strains of measles virus (MV-Edm) have proven anti-tumor activity against xenograft models of human multiple myeloma, ovarian cancer, lymphoma and glioma. The virus is selectively oncolytic, causing extensive lethal cell to cell fusion via CD46, which is more highly expressed on tumor cells than normal cells. However, MV-Edm retains the capacity to infect a variety of nontransformed cell types via its native receptors, CD46 and SLAM. CD46 is a ubiquitous regulator of complement activation, which is found on all human nucleated cells. SLAM (signaling lymphocyte activation molecule) is expressed only on activated T and B cells, dendritic cells and macrophages. Therefore, there is a chance that oncolytic MV-Edm may cause immunosupression, or other unwanted damage to normal tissues. One approach to avoid this risk is to engineer the viral attachment protein to ablate its natural tropisms and at the same time, redirect its specificity to interact with alternative tumor specific receptors. The measles Hemagglutinin (H) protein recognizes CD46 or SLAM, and this leads to membrane fusion triggered by the viral Fusion protein (F). We previously engineered the H protein of measles virus to restrict and retarget membrane fusion through various antibody-receptor interactions (Nakamura T. et. al., Nature Biotechnology, 2004). However, ablation of the native receptor interactions makes it difficult to grow the virus on Vero cells. To address this limitation, we have developed pseudoreceptor system “STAR”, which allows rescue and propagation of fully retargeted viruses with modified H proteins that no longer bind to the native measles receptors. The H proteins of the fully retargeted viruses are tagged with a C-terminal peptide tag comprising six histidine residues (H6). The recombinant viruses can then be grown on a Vero-αHis cell line that expresses a membrane-anchored single-chain antibody recognizing the H6 peptide. For validation of the system we rescued three fully retargeted viruses incorporating single chain antibodies against CD38, epidermal growth factor receptor (EGFR), or EGFR mutant vIII, each one tagged with the H6 peptide and displayed at the C-terminus of an ablated H protein. These retargeted viruses propagated efficiently on Vero-αHis cells (but not on parental Vero cells) and efficiently entered target cells through their respective targeted receptors in vitro and in vivo, but not through CD46 and SLAM. When administered intratumorally or intravenously to mice bearing human CD38 or EGFR-positive human tumor xenografts, the targeted viruses demonstrated specific receptor-mediated anti-tumor activity. Fully retargeted MV-Edms may prove to be more selective and safer oncolytic agents than wild-type MV-Edm. Also, our data suggest that receptor choice is not a significant limitation for targeting oncolytic measles viruses and that it should therefore be possible to target a variety of tumors.
Abstract 20762: IL-35, a Newly Proposed Homeostasis-Associated Molecular Pattern, Suppresses Aortic Endothelial Cell Activation and Atherosclerosis by Inhibiting Mitochondrial ROS-Mediated Site-Specific Acetylation of H3K14
Authors: Xiao-feng Yang, Xinyuan Li, Xiaojin Sha, Ying Shao, Yin-Ming Kuo, Andrew J Andrews, David W Pascual, Hong Wang
Journal: Circulation (2017)

Introduction: Previously we reported that CD4+ regulatory T cell (Treg) cell death pathways regulate vascular inflammation. IL-35 is a new anti-inflammatory cytokine originally identified in Treg. ...
Clinical practice guidelines: Machine learning and natural language processing for automating the rapid identification and annotation of new evidence.
Authors: Craig Whittington, Todd Feinman, Sandra Zelman Lewis, Greg Lieberman, Michael del Aguila
Journal: Journal of Clinical Oncology (2019)

77 Background: In February 2018, ASCO published a guideline on how clinicians should manage immune-related adverse events (irAEs) in cancer patients treated with immune checkpoint inhibitors (ICPis). Recommendations were based on informal consensus due to a lack of "high-quality" evidence. Our objective was to determine whether DOC Search, a cloud-based AI search engine, could be used to rapidly determine if any new evidence matches the inclusion criteria of the guideline. Methods: PubMed, ASCO abstracts, and 85 RSS feeds were queried within DOC Search to identify publications since the guideline search was last conducted. DOC Search automatically includes comprehensive synonym lists for the search terms entered, and annotates co-occurring characteristics, interventions and outcomes. Results: Between 11/1/2017 and 10/31/2018, 1178 published references were identified (85.7% from PubMed, 13.8% from ASCO, and 0.5% from official RSS feeds). Title/abstract screening of a sample of the most recent articles indicated that 44% were relevant, and of these, 8% specifically reported research on the management of irAEs. Through automated term indexing of search results, some of the most frequently reported terms were melanoma, corticosteroids, and colitis (Table). Conclusions: DOC Search employs robust ontology mapping—including UMLS, ASCO’s proprietary toxonomy, and more—which obviated the need for complex search strings. The machine learning and natural language processing technology provided real-time analysis and automated term indexing of search results, improving our understanding of the rapidly changing evidence landscape. This analysis met the objective to use DOC Search for rapid identification and review of new published evidence for an existing guideline.[Table: see text]
Analysis of BRAF mutations in circulating tumor cells selected by size from patients with melanoma and comparision to the primary tumor.
Authors: Janine Wechsler, Naoual Benali-Furet, Fei Ye, Marie-Françoise Avril, Francoise Boitier, Agnes Carlotti, Eric Clauser, Marie- Odile North, Isbou Paraiso, Yvon E Cayre
Journal: Journal of Clinical Oncology (2012)

e21014 Background: The efficacy of anti-BRAF therapies in patients with melanoma has emphasized the need to identify BRAF mutations in the tumour. As circulating tumour cells (CTC) derive from the primary tumour (PT), their analysis may represent a non-invasive tool to follow the molecular-target in blood after tumour removal. Methods: This prospective study included 26 patients: 24 patients had confirmed melanoma, 2 patients had benign lesions (1 naevus and 1 pyogenic granuloma). Blood samples were taken at time of the PT surgical excision; 12 healthy donors were included as controls. The 24 patients, 13 females and 11 males, had invasive melanoma (13 superficial spreading melanoma, 7 nodular melanoma, 1 lentigo malignant melanoma, 1 desmoplastic melanoma, 2 unclassified melanoma.). The mean thickness was 7.8 mm. Cytology, immunophenotyping and analysis of BRAF mutations on exon 15 were performed comparatively in primary tumour and CTC from the same patient. CTC were selected by the ScreenCell method, a single-use innovative system to isolate rare tumour cells through a filter-membrane on the basis of their size. Nucleic acids DNA/RNA were extracted from live CTC after filtration. Results: Isolated CTC and microemboli were found in 21/24 patients and were found comparable to the primary melanoma cells. No CTC was found in 10 healthy donors and 2 patients with benign lesions. The mean number of CTC was 2 CTC per ml, the maximum was 4 CTC and 7 microemboli per ml. Malignancy of CTC was assessed on classic criteria: cell size larger than 15 microns, nucleo-cytoplasmic ratio &gt; 0.5, presence of clusters composed of pleomorphic cells. CTC were positively immunostained either by S-100 or MART1/melanA or HMB45 antibodies; 4 patients were studied for BRAF mutations in both melanoma and CTC. The results (2 negative and 2 positive) were concordant in primary melanoma cells and CTC. The V600E-BRAF mutation was found in the 2 positive cases. Conclusions: The ScreenCell method of CTC selection by size allows to detect BRAF mutations in CTC of patients with melanoma. This simple method could be proposed to follow the molecular-target during the course of evolution and treatment after tumour removal.
Combining gene mutation with gene expression analysis improves outcome prediction in acute promyelocytic leukemia
Authors: Antonio R. Lucena-Araujo, Juan L. Coelho-Silva, Diego A. Pereira-Martins, Douglas R. Silveira, Luisa C. Koury, Raul A. M. Melo, Rosane Bittencourt, Katia Pagnano, Ricardo Pasquini, Elenaide C. Nunes, Evandro M. Fagundes, Ana B. Gloria, Fábio Kerbauy, Maria de Lourdes Chauffaille, Israel Bendit, Vanderson Rocha, Armand Keating, Martin S. Tallman, Raul C. Ribeiro, Richard Dillon, Arnold Ganser, Bob Löwenberg, P. J. M. Valk, Francesco Lo-Coco, Miguel A. Sanz, Nancy Berliner, Eduardo M. Rego
Journal: Blood (2019)
Abstract 18515: Arterial Inflammation in HIV is Associated With Bone Marrow and Splenic Activation
Authors: Megan H MacNabb, Rebecca S Kaplan, Zachary R Lavender, Elaine Nitta, Steven Deeks, Jeffrey Martin, Miguel Hernandez Pampaloni, Peter Ganz, Priscilla Hsue, Ahmed Tawakol
Journal: Circulation (2013)

Introduction: HIV-infected individuals have increased arterial inflammation and higher risk of cardiovascular disease (CVD), likely related to chronic monocyte/macrophage (MΦ) activation. Arterial inflammation as assessed by 18 fluorodeoxyglucose (FDG) PET/CT correlates with MΦ activity and is predictive of CVD risk. Since MΦ that participate in atherosclerosis originate in the bone marrow and transiently reside in the spleen, we sought to evaluate the relationship between arterial inflammation and bone marrow and spleen activity in HIV using FDG-PET/CT. Methods: 20 HIV-infected men and 20 non-infected controls (matched for age, gender and Framingham Risk Score) were studied. Individuals underwent PET-CT imaging and FDG uptake was quantified as standardized uptake values (SUV) in the bone marrow, spleen, wall of the ascending aorta, and control tissues (muscle and subcutaneous fat). For between-subject comparisons, SUV was corrected for blood background (SUVc). Results: The mean age (±SEM) of the participants was 54±2 years. Arterial inflammation was higher among HIV infected individuals vs. controls (SUVc:3.07±0.17 vs. 2.05±0.06, p &lt;0.001, Figure 1a). Similarly, SUVc in both the bone marrow and spleen were higher among in HIV (2.87±0.28 vs 1.73±0.07 p=0.002 and 2.10±0.20 vs 1.56±0.05 p=0.006, respectively). Aortic SUV was strongly related to splenic SUV (r= 0.69, p &lt;0.001, Figure1B) and bone marrow SUV (r=0.62, p&lt;0.001) but was not associated with SUV of muscle (r=0.26, p=0.11) or fat (r=0.24, p=0.20). Conclusions: We demonstrate that arterial inflammation is increased in HIV-infected individuals and is positively associated with bone marrow and splenic activity. In contrast, FDG-uptake in control tissues does not correlate with arterial inflammation. Thus, up regulation of immune cell activity in the bone marrow and splenic reservoir may contribute to arterial inflammation in the setting of HIV infection.
Prospective analysis of mRNA expression signatures as predictive tests in primary breast cancer
Authors: J. Hannemann, H. Halfwerk, A. Velds, C. Loo, E. J. Rutgers, S. Rodenhuis, M. J. van de Vijver
Journal: Journal of Clinical Oncology (2007)

2531 Background: Preoperative chemotherapy is increasingly employed to treat primary breast cancer, allowing an ‘in vivo chemosensitivity test’. Markers which predict a pathological complete response are urgently needed to refine this strategy. This study was conducted to evaluate the use of gene expression profiling to predict response to neoadjuvant anthracycline- or taxane-based chemotherapy. Methods: Patients with operable or locally advanced HER2-negative breast cancer received preoperative chemotherapy: either dose- dense doxorubicin and cyclophosphamide (ddAC) or capecitabine and docetaxel (CD). Core needle biopsies were taken before treatment and gene expression profiling was performed using 35k oligo microarrays. Results: Gene expression profiles were obtained from pretreatment biopsies of 63 tumors. 27% of the patients achieved a (near) pathologic complete remission (pCR), 40% of the patients had a partial remission and 33% of the patients did not respond to chemotherapy. Based on the gene expression profiles, tumors were assigned to the previously identified “molecular subtypes” luminal, basal-like or ERBB2-like (Sorlie et al., PNAS 98: 10869, 2001). 13 out of 25 patients with a basal-like tumor (52%) achieved a complete remission, whereas for the luminal tumors a pCR was only obtained in 2 out of 29 patients. Using four published gene expression classifiers of response to chemotherapy, a reasonable separation between responders and non-responders could be observed for two of these. We also performed exploratory supervised classification analyses on our dataset to identify a novel classifier. This resulted in a classifier for response to therapy irrespective of the chemotherapy regimen used and a second classifier specifically associated with response to ddAC chemotherapy. We will perform validation of these classifiers in samples from patients that are currently being enrolled in the study. Conclusions: Basal-like tumors have a better response to neoadjuvant chemotherapy as compared to other tumor types. The identification of robust gene expression signatures for better response prediction may require larger patient groups and should probably be established separately for each of the molecular subtypes of breast cancer. No significant financial relationships to disclose.
An update on anti-NMDA receptor encephalitis for neurologists and psychiatrists: mechanisms and models
Authors: Josep Dalmau, Thais Armangué, Jesús Planagumà, Marija Radosevic, Francesco Mannara, Frank Leypoldt, Christian Geis, Eric Lancaster, Maarten J Titulaer, Myrna R Rosenfeld, Francesc Graus
Journal: The Lancet Neurology (2019)
Real‐Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles
Authors: Wataru Katagiri, Jeong Heong Lee, Marc‐André Tétrault, Homan Kang, Sinyoung Jeong, Conor L. Evans, Shinya Yokomizo, Sheena Santos, Catherine Jones, Shuang Hu, Georges El Fakhri, Kosuke Tsukada, Hak Soo Choi, Satoshi Kashiwagi
Journal: Advanced Healthcare Materials (2019)

Efficient and timely delivery of vaccine antigens to the secondary lymphoid tissue is crucial to induce protective immune responses by vaccination. However, determining the longitudinal biodistribution of injected vaccines in the body has been a challenge. Here, the near-infrared (NIR) fluorescence imaging is reported that can efficiently enable the trafficking and biodistribution of vaccines in real time. Zwitterionic NIR fluorophores are conjugated on the surface of model vaccines and tracked the fate of bioconjugated vaccines after intradermal administration. Using an NIR fluorescence imaging system, it is possible to obtain time-course imaging of vaccine trafficking through the lymphatics, observing notable uptake in lymph nodes with minimal nonspecific tissue interactions. Flow cytometry analysis confirmed that the uptake in lymph nodes by antigen presenting cells was highly dependent on the hydrodynamic diameter of vaccines. These results demonstrate that the combination of a real-time NIR fluorescence imaging system and zwitterionic fluorophores is a powerful tool to determine the fate of vaccine antigens. Since such non-specific vaccine uptake causes serious adverse reactions, this method is not only useful for optimization of vaccine design, but also for safety evaluation of clinical vaccine candidates.
Early progression after bendamustine-rituximab is associated with high risk of transformation in advanced stage follicular lymphoma
Authors: Ciara L. Freeman, Robert Kridel, Alden A. Moccia, Kerry J. Savage, Diego R. Villa, David W. Scott, Alina S. Gerrie, David Ferguson, Fergus Cafferty, Graham W. Slack, Pedro Farinha, Brian Skinnider, Joseph M. Connors, Laurie H. Sehn
Journal: Blood (2019)
Association Between Specialist Office Visits and Health Expenditures in Accountable Care Organizations
Authors: Vishal Anand Shetty, Laura B. Balzer, Kimberley H. Geissler, David L. Chin
Journal: JAMA Network Open (2019)

Accountable care organizations (ACOs) aim to control health expenditures while improving quality of care. Primary care has been emphasized as a means to reduce spending, but little is known about the implications of using specialists for achieving this ACO objective.To examine the association between ACO-beneficiary office visits conducted by specialists and the cost and utilization outcomes of those visits.This cross-sectional study obtained data on 620 distinct ACOs from the Centers for Medicare & Medicaid Services Shared Savings Program Accountable Care Organizations Public-Use Files from April 1, 2012, to September 30, 2017. Generalized estimating equation models were used for analysis of ACOs, adjusting for ACO-beneficiary health status, Medicare enrollment groups, ACO size, and proportion of participating specialists.Specialist encounter proportion, the percentage of office visits provided by a specialist, was categorized into 7 discrete groups: less than 35%, 35% to less than 40%, 40% to less than 45% (reference group), 45% to less than 50%, 50% to less than 55%, 55% to less than 60%, and 60% or greater.The primary outcome was total expenditures (given in US dollars) per assigned beneficiary person-year. The secondary outcomes were total numbers of emergency department visits, hospital discharges, skilled nursing facility discharges, and magnetic resonance imaging orders.In total, the data set included 1836 ACO-year (number of participation years per ACO) observations for 620 distinct ACOs. Those ACOs with a specialist encounter proportion of 40% to less than 45% had $1129 (95% CI, $445-$1814) lower per-beneficiary person-year spending than did ACOs in the lowest specialist encounter proportion group and had $752 (95% CI, $115-$1389) lower per-beneficiary person-year spending compared with ACOs in the highest specialist encounter proportion group. Monotonic decreases in emergency department visits, hospital discharges, and skilled nursing facility discharges were observed with increasing specialist encounter proportion. Conversely, monotonic increases in magnetic resonance imaging volume discharges were observed with increasing specialist encounter proportion.These findings suggest that an ACO's ability to reduce spending may require sufficient involvement in care processes from specialists, who seem to complement the intrinsic primary care approach in ACOs.
Combined estimation of disease progression and retention on antiretroviral therapy among treated individuals with HIV in the USA: a modelling study
Authors: Linwei Wang, Emanuel Krebs, Jeong E Min, W Christopher Mathews, Ank Nijhawan, Charurut Somboonwit, Judith A Aberg, Richard D Moore, Kelly A Gebo, Bohdan Nosyk, Howard Edelstein, Richard Rutstein, Amy Baranoski, Sara Allen, Stephen Boswell, Kenneth Mayer, Kelly A. Gebo, Richard D. Moore, Allison Agwu, Robert Beil, Uriel Felsen, Judith A. Aberg, Antonio Urbina, P. Todd Korthuis, Ank Nijhawan, Muhammad Akbar, Aditya Gaur, Charurut Somboonwit, William Valenti, W. Christopher Mathews, Fred Hellinger, John Fleishman, Robert Mills, Jeanne Keruly, Cindy Voss, Charles Collins, Rebeca Diaz-Reyes
Journal: The Lancet HIV (2019)
Assessment of menstrual health status and evolution through mobile apps for fertility awareness
Authors: Laura Symul, Katarzyna Wac, Paula Hillard, Marcel Salathé
Journal: npj Digital Medicine (2019)

For most women of reproductive age, assessing menstrual health and fertility typically involves regular visits to a gynecologist or another clinician. While these evaluations provide critical information on an individual's reproductive health status, they typically rely on memory-based self-reports, and the results are rarely, if ever, assessed at the population level. In recent years, mobile apps for menstrual tracking have become very popular, allowing us to evaluate the reliability and tracking frequency of millions of self-observations, thereby providing an unparalleled view, both in detail and scale, on menstrual health and its evolution for large populations. In particular, the primary aim of this study was to describe the tracking behavior of the app users and their overall observation patterns in an effort to understand if they were consistent with previous small-scale medical studies. The secondary aim was to investigate whether their precision allowed the detection and estimation of ovulation timing, which is critical for reproductive and menstrual health. Retrospective self-observation data were acquired from two mobile apps dedicated to the application of the sympto-thermal fertility awareness method, resulting in a dataset of more than 30 million days of observations from over 2.7 million cycles for two hundred thousand users. The analysis of the data showed that up to 40% of the cycles in which users were seeking pregnancy had recordings every single day. With a modeling approach using Hidden Markov Models to describe the collected data and estimate ovulation timing, it was found that follicular phases average duration and range were larger than previously reported, with only 24% of ovulations occurring at cycle days 14 to 15, while the luteal phase duration and range were in line with previous reports, although short luteal phases (10 days or less) were more frequently observed (in up to 20% of cycles). The digital epidemiology approach presented here can help to lead to a better understanding of menstrual health and its connection to women's health overall, which has historically been severely understudied.