tbuckley/cabot-search huggingface dataset:
WST11 Vascular Targeted Photodynamic Therapy Effect Monitoring by Multispectral Optoacoustic Tomography (MSOT) in Mice
Authors: Volker Neuschmelting, Kwanghee Kim, Jaber Malekzadeh-Najafabadi, Sylvia Jebiwott, Jaya Prakash, Avigdor Scherz, Jonathan A Coleman, Moritz F Kircher, Vasilis Ntziachristos
Journal: Theranostics (2017)

Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and understanding the time-dynamics of treatment effects remains challenging. We interrogated whether handheld multispectral optoacoustic tomography (MSOT) could noninvasively monitor the effect of VTP using WST11, a vascular-acting photosensitizer, on tumor tissues over time using a renal cell cancer mouse model. We also investigated whether MSOT illumination can induce VTP, to implement a single-modality theranostic approach. Materials and Methods: Eight BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous illumination at 753 nm following intravenous infusion using WST11 or saline as control. Handheld MSOT images were collected prior to VTP administration and subsequently thereafter over the course of the first hour, at 24 and 48 h. Data collected were unmixed for blood oxygen saturation in tissue (SO2) based on the spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen saturation over time, relative to baseline, were examined by paired t-test for statistical significance (p < 0.05). In-vivo findings were corroborated by histological analyses of the tumor tissue. Results: MSOT is shown to prominently resolve changes in oxygen saturation in tumors within the first 20 min post WST11-VTP treatment. Within the first hour post-treatment, SO2 decreased by more than 60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham-treated group. Moreover, unlike in the control group, SO2 in treated tumors further decreased over the course of 24 to 48 h post-treatment, concomitant with the propagation of profound central tumor necrosis present in histological analysis. We further show that pulsed MSOT illumination can activate WST11 as efficiently as the continuous wave irradiation employed for treatment. Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the SO2 signal and detected blood saturation changes within the first 20 min post-treatment. MSOT may potentially serve as a means for both VTP induction and real-time VTP monitoring in a theranostic approach.
Abstract 18122: Ideal Cardiovascular Health Score & Vascular Function
Authors: Talal Shakas M Alghamdi, Heval Mohamed Kelli, Yi-An Ko, Yi Deng, Muhammad Hammadah, Ayman Samman-Tahhan, Pratik Sandesara, Ibhar Al Mheid, Frank E. Corrigan, Viola Vaccarino, Thomas R. Ziegler, Greg Gibson, Michelle Lampl, Ken Brigham, Greg S. Martin, Arshed A. Quyyumi
Journal: Circulation (2017)

Introduction: Ideal cardiovascular health (CVH) promotion is effective for cardiovascular disease prevention. Whether lifestyle intervention-induced changes in cardiovascular risk factors change va...
Efficacy of subsequent cytotoxic chemotherapy after nivolumab for patients with advanced non-small cell lung cancer
Authors: N. Tamura, H. Horinouchi, K. Sekine, Y. Matsumoto, S. Murakami, Y. Goto, S. Kanda, Y. Fujiwara, N. Yamamoto, Y. Ohe
Journal: Annals of Oncology (2017)
Progress in Rubella and Congenital Rubella Syndrome Control and Elimination — Worldwide, 2000<b>–</b>2016
Authors: Gavin B. Grant, Susan E. Reef, Minal Patel, Jennifer K. Knapp, Alya Dabbagh
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Although rubella virus infection usually causes a mild fever and rash illness in children and adults, infection during pregnancy, especially during the first trimester, can result in miscarriage, fetal death, stillbirth, or infants with a constellation of congenital malformations known as congenital rubella syndrome (CRS) (1). Rubella is a leading vaccine-preventable cause of birth defects. Preventing these adverse pregnancy outcomes is the focus of rubella vaccination programs. In 2011, the World Health Organization (WHO) updated guidance on the preferred strategy for introduction of rubella-containing vaccine (RCV) into national immunization schedules and recommended an initial vaccination campaign, usually targeting children aged 9 months-14 years (1). The Global Vaccine Action Plan 2011-2020 (GVAP), endorsed by the World Health Assembly in 2012, includes goals to eliminate rubella in at least five of the six WHO regions by 2020 (2). This report updates a previous report (3) and summarizes global progress toward rubella and CRS control and elimination from 2000 to 2016. As of December 2016, 152 (78%) of 194 countries had introduced RCV into the national immunization schedule, representing an increase of 53 countries since 2000, including 20 countries that introduced RCV after 2012.
Evaluation of the safety and efficacy of combined the CART and chemotherapy for gastrointestinal cancers with massive ascites
Authors: Y. Nagata, K. Kato, T. Miyamoto, H. Shoji, S. Iwasa, Y. Honma, A. Takashima, T. Hamaguchi, M. Saruta, N. Boku
Journal: Annals of Oncology (2017)
Lung cancer–associated pulmonary hypertension: Role of microenvironmental inflammation based on tumor cell–immune cell cross-talk
Authors: Soni Savai Pullamsetti, Baktybek Kojonazarov, Samantha Storn, Henning Gall, Ylia Salazar, Janine Wolf, Andreas Weigert, Nefertiti El-Nikhely, Hossein Ardeschir Ghofrani, Gabriele A. Krombach, Ludger Fink, Stefan Gattenlöhner, Ulf R. Rapp, Ralph Theo Schermuly, Friedrich Grimminger, Werner Seeger, Rajkumar Savai
Journal: Science Translational Medicine (2017)

Lung cancer–associated pulmonary hypertension is associated with microenvironmental inflammation caused by tumor cell–immune cell cross-talk.
Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis
Authors: Benjamin D. Korman, Roberta Goncalves Marangoni, Monique Hinchcliff, Sanjiv J. Shah, Mary Carns, Aileen Hoffmann, Rosalind Ramsey‐Goldman, John Varga
Journal: Arthritis & Rheumatology (2017)

Objective Adipose tissues secrete adipokines, peptides with potent effects modulating fibrosis, inflammation, and vascular homeostasis. Dysregulated adipose tissue biology and adipokine balance have recently been implicated in systemic sclerosis (SSc). This study was undertaken to determine whether altered circulating adipokine levels correlate with SSc disease subsets or clinical manifestations. Methods Multiplex assays were used to measure circulating adipokine levels in 198 patients with SSc and 33 healthy controls. Data were evaluated for correlations between serum adipokine levels and demographic and clinical features, including pulmonary arterial hypertension (PAH). To assess the relevance of adipsin, an adipokine involved in complement pathway activation, in SSc, we analyzed publicly available genetic and transcriptomic data. Results Levels of adiponectin and adipsin differed significantly between controls and patients. Adipsin was significantly elevated in patients with limited cutaneous SSc (odds ratio [OR] 28.3 [95% confidence interval (95% CI) 7.0–113.8]; P &lt; 0.0001), and its levels were associated with serum autoantibody status, pulmonary function and cardiovascular parameters, and PAH (OR 3.3 [95% CI 1.3–8.7]; P = 0.02). Elevated adipsin was more strongly associated with PAH than B‐type natriuretic peptide was. Moreover, in SSc patients, adipsin gene single‐nucleotide polymorphisms were associated with PAH. Transcriptome data set analysis demonstrated elevated adipsin expression in patients with SSc‐related PAH. Conclusion We identify adipsin as a novel adipose tissue–derived marker of SSc‐related PAH. Circulating adipsin levels might serve as predictive biomarkers in SSc. Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation and play an important role in the pathogenesis of SSc‐related PAH.
Abstract 21338: Temporal Trends of In-Hospital Complications Associated With Catheter Ablation of Atrial Fibrillation in United States
Authors: Sopan Lahewala, Byomesh Tripathi, ShilpKumar Arora, Neil Patel, Varun Kumar, Nirali Patel, Prashant Patel, Nikhil Nalluri, Smit Patel, Amer Syed, Nileshkumar Patel, Abhishek Deshmukh
Journal: Circulation (2017)

Introduction: Catheter ablation is widely accepted intervention for atrial fibrillation (AF), but data is limited on contemporary trends in major complications and mortality due to the procedure. Methods: HCUP’s Nationwide inpatient sample (NIS) database was utilized from 2011-14 to identify the AF patients treated with Catheter Ablation using ICD-9- CM codes. χ 2 test was utilized to compare categorical variables, the student’s t-test for continuous variables and hierarchical mixed-effects logistic regression models for multivariate predictors of post-procedural complications. Results: In total 50,969 patients were identified undergoing AF ablation during the study period (37.6% female, 51.4 age ≥ 65). Overall complication rate was 5.5% with relative increase over study period (+56.4%, p &lt; 0.001). In subgroup analysis of complication trends significant relative increase seen in respiratory (+352.7%, p &lt; 0.001), neurological (+43.9%, p = 0.003) and vascular (+38.7%, p = 0.003) complications. While cardiac complications (+9.1%, p = 0.323) and In-hospital mortality (+ 60%, p = 0.173) showed insignificant change. On multivariate analysis of mortality and complication significant increased risk was associated with female gender (OR, 95% CI, p-value) (1.40, 1.17-1.68, p &lt; 0.001), as well as higher comorbidity burden (CCI ≥ 1). While higher hospital volume (≥ 50 procedures) was associated with significantly decreased complication rates. Conclusions: Patients undergoing AF ablation showed an insignificant change in mortality, with increase trends of complication. Which was likely related to higher comorbidity burden over study period.
Abstract 20240: Ventricular Functional Recovery and Neurologic Function After In-Hospital Cardiac Arrest in Pediatric Patients
Authors: Christoph Haller, Lisa Zhao, Rachel Parker, Arezou Saedi, Atsuko Kato, Afrothite Kotsakis, Luc Mertens, Anne-Marie Guerguerian, Osami Honjo
Journal: Circulation (2016)

Introduction: In-hospital cardiac arrest in pediatric patients remains to have high mortality. Despite survival, recovery of ventricular and preservation of neurological function are major concerns...
Coronary Microvascular Dysfunction Identifies Patients at High Risk of Adverse Events Across Cardiometabolic Diseases
Authors: Michael T. Osborne, Navkaranbir S. Bajaj, Viviany R. Taqueti, Ankur Gupta, Paco E. Bravo, Jon Hainer, Courtney F. Bibbo, Sharmila Dorbala, Ron Blankstein, Marcelo F. Di Carli
Journal: Journal of the American College of Cardiology (2017)
P3.01-004 Exceptional Evolution of Benign Metastasizing Leiomyomas of the Lung
Authors: Luigi Ventura, Letizia Gnetti, Vittorio Franciosi, Cesare Braggio, Valeria Balestra, Paolo Carbognani, Michele Rusca, Enrico Maria Silini, Luca Ampollini
Journal: Journal of Thoracic Oncology (2017)
Palliative Care Eligibility, Symptom Burden, and Quality-of-Life Ratings in Nursing Home Residents
Authors: Caroline E. Stephens, Lauren J. Hunt, Nhat Bui, Elizabeth Halifax, Christine S. Ritchie, Sei J. Lee
Journal: JAMA Internal Medicine (2017)

This study identifies which nursing home residents are eligible for palliative care services, describes their characteristics, and delineates resident and family perceptions regarding symptoms and quality of life.
Genotype-based selection of treatment of patients with advanced colorectal cancer (SETICC): a pharmacogenetic-based randomized phase II trial
Authors: A. Abad, E. Martínez-Balibrea, J.M. Viéitez, V. Alonso-Orduña, P. García Alfonso, J.L. Manzano, B. Massutí, M. Benavides, A. Carrato, M. Zanui, J. Gallego, C. Grávalos, V. Conde, M. Provencio, M. Valladares-Ayerbes, R. Salazar, J. Sastre, C. Montagut, F. Rivera, E. Aranda
Journal: Annals of Oncology (2017)

There has been little progress toward personalized therapy for patients with metastatic colorectal cancer (mCRC). TYMS-3' untranslated region (UTR) 6 bp ins/del and ERCC1-118C/T polymorphisms were previously reported to facilitate selecting patients for fluoropyrimidine-based treatment in combination with oxaliplatin as first-line therapy. We assessed the utility of these markers in selecting therapy for patients with mCRC.This randomized, open-label phase II trial compared bevacizumab plus XELOX (control) versus treatment tailored according to TYMS-3'UTR 6 bp ins/del and ERCC1-118C/T polymorphisms. Patients randomized to the experimental treatment received bevacizumab plus FUOX, FUIRI, XELIRI, or XELOX depending on their combination of favorable polymorphisms for FUOX treatment (TYMS-3'UTR ins/del or del/del; ERCC1-118T/T). Progression-free survival (PFS) was the primary end point.Overall, 195 patients were randomized (control n = 65; experimental n = 130). The primary objective was not met: median PFS was 9.4 months in the control group and 10.1 months in the experimental group (P = 0.745). Median overall survival was similar in both groups (16.5 versus 19.1 months, respectively; P = 0.797). Patients in the experimental group had a significantly higher overall response rate (ORR; 65% versus 47% in the control group; P = 0.042) and R0 resection rate (86% versus 44%, respectively; P = 0.018). Neuropathy, hand-foot syndrome, thrombocytopenia, and dysesthesia were significantly less common in the experimental group.This study did not show survival benefits after treatment personalization based on polymorphisms in mCRC. However, the improved ORR and R0 resection rate and fewer disabling toxicities suggest that tailoring therapy by TYMS-3'UTR and ERCC1-118 polymorphisms warrants further investigation in patients with mCRC.NCT01071655.
Response to: ‘Increased stroke incidence in systemic lupus erythematosus patients: risk factors or disease itself?’ by Bruzzese and Zullo
Authors: Elizabeth V Arkema, Marios Rossides, Mia Von Euler, Elisabet Svenungsson, Christopher Sjöwall, Julia F Simard
Journal: Annals of the Rheumatic Diseases (2017)

We thank Dr Bruzzese and Dr Zullo for their interest in our study on stroke risk in systemic lupus erythematosus (SLE).1 In their letter, they speculate that it might not be SLE, per se, but other factors that could explain the increased risk.2 We would first like to emphasise that the purpose of our study was to determine whether individuals with SLE have a higher risk of stroke compared with the general population, not to determine how much of a role SLE plays in this risk or what the drivers of stroke are above and beyond SLE. Our study was designed so that the risk of stroke could be communicated to patients and clinicians.

Bruzzese and Zullo are interested in better understanding whether SLE plays an independent role in the aetiology of stroke, and suggest that the group of people with SLE with atrial fibrillation, congestive heart disease, hypertension and diabetes are driving …
Abstract 16641: Post Admission Variability in OHCA Survival Outcomes in Pennsylvania
Authors: Steve Balian, David G Buckler, Abhishek Bhardwaj, Benjamin S Abella
Journal: Circulation (2017)

Background:  Interhospital variability in out-of-hospital cardiac arrest (OHCA) survival outcomes have suggested the need for regionalizing care to tertiary centers. To date, no studies have explored variability in post-resuscitation outcomes across hospitals in Pennsylvania (PA).   Objective:  To examine inter-hospital variation in OHCA survival outcomes and assess key hospital characteristics associated with favorable survival in PA.   Methods:  Utilizing PA data from the Cardiac Arrest Registry to Enhance Survival, we analyzed outcomes among adult non-traumatic OHCA events. Analysis included hospitals with ≥ 30 cases during the study period who arrived to the ED with sustained return of spontaneous circulation (ROSC) and survived to hospital admission. Primary outcome was percent of patients with a favorable cerebral performance category score (CPC) of 1 or 2. Demographic and arrest care data were compared between the lowest and highest quartiles for favorable CPC. Multinomial logistic regression was used to assess for correlation of indicators with outcomes.   Results:  Between Jan 2013 and Dec 2015, 1,699 OHCA from 47 hospitals were analyzed. Mean patient age was 62.5 ± 17.5 y. 43% were female, and 35% had a shockable initial rhythm. Hospital arrest volume ranged from 30 to 130 cases in the study period. Hospitals were grouped into quartiles based on percent of patients with a favorable discharge CPC. Significant variability existed when comparing lowest and highest quartiles (18.6% vs 50.3%, p   Conclusions:  These results demonstrate marked variability in favorable neurological outcomes across these 47 hospitals in PA. Frequency of post-arrest interventions such as angiography and TTM were not associated with favorable outcomes, suggesting that other unmeasured variables contribute to post-arrest care quality and outcomes, requiring further investigation.
Public Health Economic Burden Associated with Two Single Measles Case Investigations — Colorado, 2016–2017
Authors: Grace E. Marx, Jennifer Chase, Joseph Jasperse, Kaylan Stinson, Carol E. McDonald, Janine K. Runfola, Jillian Jaskunas, Donna Hite, Meghan Barnes, Michele Askenazi, Bernadette Albanese
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

During July 2016-January 2017, two unrelated measles cases were identified in the Denver, Colorado area after patients traveled to countries with endemic measles transmission. Each case resulted in multiple exposures at health care facilities and public venues, and activated an immediate and complex response by local and state public health agencies, with activities led by the Tri-County Health Department (TCHD), which serves Adams, Arapahoe, and Douglas counties. To track the economic burden associated with investigating and responding to single measles cases, personnel hours and supply costs incurred during each investigation were tracked prospectively. No secondary cases of measles were identified in either investigation. Postexposure prophylaxis (PEP) was administered to 31 contacts involving the first case; no contacts of the second case were eligible for PEP because of a delay in diagnosing measles disease. Public health costs of disease investigation in the first and second case were estimated at $49,769 and $18,423, respectively. Single measles cases prompted coordinated public health action and were costly and resource-intensive for local public health agencies.
Feasibility of real-time molecular profiling for patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation—the NCT Neuro Master Match (N2M2) pilot study
Authors: Elke Pfaff, Tobias Kessler, Gnana Prakash Balasubramanian, Anne Berberich, Daniel Schrimpf, Antje Wick, Jürgen Debus, Andreas Unterberg, Martin Bendszus, Christel Herold-Mende, David Capper, Irini Schenkel, Andreas Eisenmenger, Susan Dettmer, Benedikt Brors, Michael Platten, Stefan M Pfister, Andreas von Deimling, David T W Jones, Wolfgang Wick, Felix Sahm
Journal: Neuro-Oncology (2017)

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma patients. Glioblastoma without hypermethylated MGMT promoter is largely resistant to treatment with temozolomide. These patients are in particular need of new treatment approaches, which are offered by biomarker-driven clinical trials with targeted drugs based on molecular characterization of individual tumors.In preparation for an upcoming clinical study, a comprehensive molecular profiling approach was undertaken on tissues from 43 glioblastoma patients harboring an unmethylated MGMT promoter at diagnosis. The diagnostic pipeline covered various levels of molecular characteristics, including whole-exome sequencing, low-coverage whole-genome sequencing, RNA sequencing, as well as microarray-based gene expression profiling and DNA methylation arrays.Complex multilayer molecular diagnostics were feasible in this setting with a median turnaround time of 4-5 weeks from surgery to the molecular tumor board. In 35% of cases, potentially relevant therapeutic decisions were derived from the data. Alterations were most frequently found in receptor tyrosine kinases, members of the phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin and mitogen-activated protein kinase pathway as well as cell cycle control and p53 regulation cascades. Individual tumors harbored clonal alterations such as oncogenic fusions of tyrosine kinases which constitute promising targets for targeted therapies. A prioritization algorithm is proposed to allocate patients with multiple targets to the potentially best treatment option.With this feasibility study, a comprehensive molecular profiling approach for patients with newly diagnosed glioblastoma harboring an unmethylated MGMT promoter is presented. Analyses in this pilot cohort serve as a basis for trials based on targetable alterations and on the question of allocation of patients to the best treatment arm.
Cartilage MicroRNA Dysregulation During the Onset and Progression of Mouse Osteoarthritis Is Independent of Aggrecanolysis and Overlaps With Candidates From End-Stage Human Disease
Authors: Louise H. W. Kung, Varshini Ravi, Lynn Rowley, Constanza Angelucci, Amanda J. Fosang, Katrina M. Bell, Christopher B. Little, John F. Bateman
Journal: Arthritis & Rheumatology (2017)

Objective To identify candidate microRNAs (miRNAs) that potentially regulate the initiation and progression of osteoarthritis (OA). Methods OA was induced in 10–12‐week‐old male wild‐type C57BL/6 mice and in mice resistant to aggrecanase cleavage ( Acan p.374ALGS→374NVYS) by destabilization of the medial meniscus (DMM). Pathologic changes of OA were scored histologically. RNA from cartilage and subchondral bone was harvested in parallel by laser microdissection at 1 week and 6 weeks postsurgery. Global miRNA expression profiling was performed using Agilent microarrays and was validated by quantitative polymerase chain reaction analysis. Results Wild‐type DMM mice had characteristic cartilage degeneration, subchondral bone sclerosis, and osteophyte formation. While no miRNA dysregulation was seen in subchondral bone, 139 miRNAs were differentially expressed in cartilage obtained at 1 and/or 6 weeks after OA initiation from wild‐type mice that underwent DMM. To prioritize OA candidates, dysregulated miRNAs with human orthologs were filtered, and paired miRNA/messenger RNA (mRNA) expression analysis was conducted to identify those with corresponding changes in mRNA target transcripts in the DMM mouse cartilage. An important cohort also overlapped with miRNAs identified in human end‐stage OA. Comparisons of miRNA dysregulation in DMM mouse cartilage where aggrecan cleavage was genetically ablated demonstrated that all candidates were independent of aggrecan breakdown, earmarking these as important to the critical stages of OA initiation. Furthermore, functional enrichment analysis and data annotation revealed the responses to mechanical stimuli, apoptotic processes, and core extracellular matrix structural and regulatory factors to be potentially influenced by OA‐dysregulated miRNA/mRNA networks. Conclusion Our comprehensive analyses identified high‐priority miRNA candidates that have potential as biomarkers and therapeutic targets in human OA.