tbuckley/cabot-search huggingface dataset:
Myeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures
Authors: Shervin Assassi, Xuan Wang, Guocai Chen, Ellen Goldmuntz, Lynette Keyes-Elstein, Jun Ying, Paul K Wallace, Jacob Turner, W Jim Zheng, Virginia Pascual, John Varga, Monique E Hinchcliff, Chiara Bellocchi, Peter McSweeney, Daniel E Furst, Richard A Nash, Leslie J Crofford, Beverly Welch, Ashley Pinckney, Maureen D Mayes, Keith M Sullivan
Journal: Annals of the Rheumatic Diseases (2019)

In the randomised scleroderma: Cyclophosphamide Or Transplantation (SCOT trial) (NCT00114530), myeloablation, followed by haematopoietic stem cell transplantation (HSCT), led to improved clinical outcomes compared with monthly cyclophosphamide (CYC) treatment in systemic sclerosis (SSc). Herein, the study aimed to determine global molecular changes at the whole blood transcript and serum protein levels ensuing from HSCT in comparison to intravenous monthly CYC in 62 participants enrolled in the SCOT study.
Preclinical and Early Phase 1 Clinical Data of AZD2811 Nanoparticle in AML, an Aurora B Kinase Inhibitor
Authors: Wolfram Brugger, Susan Ashton, Carrie A. Adelman, Nicolas Floc'h, Paula Taylor, Maureen Hattersley, Shenghua Wen, Kimberly Maratea, Philip Overend, Steven Fox, Julie Charlton, Simon T Barry, Donald Strickland, Suzanne Jones, Howard A. Burris, Carol Greenlees, Alexander MacDonald, J. Elizabeth Pease, William Donnellan
Journal: Blood (2017)
Brain connectivity evaluation during selective attention using EEG-based brain-computer interface
Authors: Soheil Borhani, Reza Abiri, Yang Jiang, Taylor Berger, Xiaopeng Zhao
Journal: Brain-Computer Interfaces (2019)

Attentional deficits may be caused by neurological diseases, including Attention-Deficit/Hyperactivity Disorder (ADHD), Alzheimer's disease (AD), Traumatic Brain Injuries (TBI), etc. This work aims to evaluate selective attention under visual stimulations of faces and scenes using electroencephalogram (EEG)-based brain-computer interface.The experiment consisted of two phases: 1) image recognition and 2) attention evaluation. In phase 1, the mean response time was 547 ms vs. 633 ms to faces and scenes, respectively. In phase 2, the mean response time was 667 ms vs. 706 ms to face and scene categories, respectively. We analyzed the event-related time-frequency representation of faces and scenes and the causal relationship between object recognition and the motor response associated with category selection using the brain connectivity based on Granger causality. The developed experimental protocols and connectivity evaluation methods may provide insights for a better understanding of the neural processes for object recognition and category selection.
Association of Vitamin A Intake With Cutaneous Squamous Cell Carcinoma Risk in the United States
Authors: Jongwoo Kim, Min Kyung Park, Wen-Qing Li, Abrar A. Qureshi, Eunyoung Cho
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> Retinoids are bioactive forms of vitamin A that are essential in the maintenance of epithelial maturation and differentiation. Synthetic retinoids are used in chemoprevention of skin cancer among high-risk populations with potential adverse effects. Epidemiologic data on vitamin A intake and risk of cutaneous squamous cell carcinoma (SCC) are limited. <h3>Objective</h3> To examine whether vitamin A intake is associated with a reduction in SCC risk. <h3>Design, Settings, and Participants</h3> This cohort study prospectively examined intake of vitamin A and carotenoids and SCC risk in the Nurses' Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Diet was assessed repeatedly. Incident SCC was confirmed by pathologic reports. Data analysis was performed from June 21, 2017, to December 4, 2018. <h3>Exposures</h3> Intakes of vitamin A, retinol, and carotenoids. <h3>Main Outcomes and Measures</h3> Incident SCC. Cox proportional hazards regression models were used to compute cohort-specific hazard ratios (HRs) and 95% CIs. Pooled HRs of the cohort-specific results were calculated. <h3>Results</h3> A total of 3978 SCC cases in 75 170 women in the Nurses' Health Study (mean [SD] age, 50.4 [7.2] years) and 48 400 men in the Health Professionals Follow-up Study (mean [SD] age, 54.3 [9.9] years) were documented. Higher total vitamin A was associated with a reduction in SCC risk; with quintile 1 as the reference, the pooled multivariate HRs for the increasing quintiles of vitamin A intake were 0.97 (95% CI, 0.87-1.07) for quintile 2, 0.97 (95% CI, 0.80-1.17) for quintile 3, 0.93 (95% CI, 0.84-1.03) for quintile 4, and 0.83 (95% CI, 0.75-0.93) for quintile 5 (<i>P</i> &lt; .001 for trend). Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk; the pooled HRs for the highest quintiles of intake compared with the lowest quintiles were 0.88 (95% CI, 0.79-0.97;<i>P</i> = .001 for trend) for total retinol, 0.86 (95% CI, 0.76-0.96;<i>P</i> = .001 for trend) for beta cryptoxanthin, 0.87 (95% CI, 0.78-0.96;<i>P</i> &lt; .001 for trend) for lycopene, and 0.89 (95% CI, 0.81-0.99;<i>P</i> = .02 for trend) for lutein and zeaxanthin. The results were generally consistent by sex and other SCC risk factors. <h3>Conclusions and Relevance</h3> This study suggests that increased intake of dietary vitamin A is associated with decreased risk of incident SCC. Future studies are needed to determine whether vitamin A supplementation has a role in chemoprevention of SCC.
Synthesis, charatcterization and preclinical studies of tartgeted photo-dynamic therapy agents activated in the tissue transparency window
Authors: Jean Rosalind Starkey, Fanging Meng, Aijun Gong, Britney L. Moss, Aleksandre Rebane, Mikhail Drobizhev, Charles W. Spangler
Journal: Cancer Research (2005)

4740  Currently approved photo-dynamic therapy (PDT) agents are limited by their activation wavelengths which fall short of the tissue transparency window (700-1000 nm). With these agents, it is only feasible to treat tumors up 2-3 mm below the skin, or the activating light sources must be introduced into the tissue of interest. Other limitations are poor selectivity for tumor tissue and long residence times leading to extended light sensitivity. We have designed novel modular PDT agents that can be activated in the tissue transparency window, are targeted to the tumor tissue, and possess a module (indodicarbocyanine) for near infrared fluorescence (IR) imaging. Two-photon excited fluorescence has been demonstrated for these compounds at depths of 3 cm in highly scattering tissue phantoms. A protocol for evaluating the ability of PDT to kill tumor cells at specific depths in a tissue phantom was developed and the model was validated using Photofrin® treated MDA-MB-231 cells. Using in vivo near IR fluorescence imaging of SCID mice bearing MDA-MB-231 human breast cancer tumors, we validated the ability of the compounds to be targeted by the octreoate peptide to overexpressed somatostatin 2 (SST2) receptors on the cancer cells. Drug clearance was imaged occurring via the gall bladder and intestinal route, and the in vivo imaging studies indicated that there would likely be a good window of time for therapeutic activation of the compound. Since our compounds are the first ones to have a 2-photon cross section large enough to be considered for therapeutic PDT, appropriate protocols needed to be developed for many of the preclinical studies, and, while we envision any clinical application encompassing the ability to raster the near IR laser beam(s), until such a system is developed, we have adapted a motorized X,Y,Z stage to raster the target cells/tumor bearing mouse. Our initial results using this system will be presented. Supported by a grant from the Montana Board of Research and Commercialization and Technology.
A case of synchronous relapse of breast cancer and uterine mullerian adenosarcoma after adjuvant tamoxifen in a pre-menopausal woman
Authors: F. S. Farhat, N. A. Fakhredin, A. A. Sraj
Journal: Journal of Clinical Oncology (2007)

20533 Background: Uterine müllerian adenosarcoma is a rare tumor of postmenopausal women. An increase in its incidence with the use of tamoxifen therapy for breast carcinoma is reported in several studies. Methods: We report a case of 42 years multigravida, premenopaused woman with breast carcinoma, who presented - after four years of use of adjuvant tamoxifen - a synchronous liver, bone, and lung metastasis of breast cancer with müllerian adenosarcoma. Results: Immunohistochemical stains on uterine tumor for estrogen and progesterone receptors showed positivity for both epithelial and stromal cells, actin, desmin and proliferative index (MIB-1) showed positivity for stromal cells only. The patient underwent a hysterectomy followed by palliative chemotherapy. The patient deceased at 14 months after her relapse because of progressive disease (cerebral, bone, liver and lung metastasis). Conclusion: Our case is the only one reported in the literature with synchronous relapse of the breast adenocarcinoma and a Müllerian adenosarcoma. Also it's of the rare cases occurring in a pre-menopaused woman since all except two cases were postmenopausal. [Table: see text] No significant financial relationships to disclose.
A Three-Sample Test for Introgression
Authors: Matthew W Hahn, Mark S Hibbins
Journal: Molecular Biology and Evolution (2019)

Many methods exist for detecting introgression between nonsister species, but the most commonly used require either a single sequence from four or more taxa or multiple sequences from each of three taxa. Here, we present a test for introgression that uses only a single sequence from three taxa. This test, denoted D3, uses similar logic as the standard D-test for introgression, but by using pairwise distances instead of site patterns it is able to detect the same signal of introgression with fewer species. We use simulations to show that D3 has statistical power almost equal to D, demonstrating its use on a data set of wild bananas (Musa). The new test is easy to apply and easy to interpret, and should find wide use among currently available data sets.
Induction cisplatin-irinotecan followed by concurrent cisplatin-irinotecan and radiotherapy in locally advanced esophageal cancer: A single institution’s initial clinical experience
Authors: J. L. Harper, K. Shirai, A. K. Sharma, A. J. Montero, B. J. Hoffman, C. E. Reed, C. A. Sherman
Journal: Journal of Clinical Oncology (2007)

15151 Background: Phase I and Phase II trials of induction Cisplatin (C) and Irinotecan (I) followed by concurrent C+I and radiotherapy (RT) have produced encouraging clinical and pathologic response rates in esophageal cancer. However, to date published data detailing clinical outcome with this regimen is limited. Methods: A retrospective review of 17 patients with locally advanced esophageal cancer was performed to characterize toxicity and outcomes for this regimen in our institutional experience. Patients were treated during the period from August 2003 to July 2006 and staged comprehensively with EUS, CT and PET. Induction therapy with weekly I (65mg/m 2 ) and C (30mg/m 2 ) was administered (wks1,2,4,5). Those without progression received weekly I (65mg/m 2 ) and C (30mg/m 2 ) (wks 8,9,11,12) concurrent with RT. Patients considered surgical candidates based on pre- treatment clinical stage, medical co-morbidities, and pre-operative re-staging were offered an esophagectomy. Results: The patient demographics were as follows: 15 men, 2 women, median age 63 (45–76), white 53%, black 47%, adenocarcinoma 59%, squamous cell carcinoma 41%, 47% stage T3N1, 94% node positive, 6% M1a, and 29% T4 primary tumors. The mean RT dose was 50.4 Gy and median number of elapsed days of RT was 43 days. All patients completed induction C+I. Grade 3–4 hematologic toxicity (CTC v3.0)neutropenia (47%), anemia (6%), thrombocytopenia(18%). One patient died of a TE fistula 22 days after completing therapy. Two patients (12%) progressed during therapy. An esophagectomy was performed on 41% (7/17) of patients; 6 of 7 were R0, 71% (5/7) were downstaged, 14% (1/7) pCR. At median follow-up of 15 months, 8/17 (47%) pt are alive NED, 3/17 are alive with disease, 3/17 dead of disease and 3/17 are dead of other causes. Median DFS is 7 months and median local RFS is 7 months. Median OS has not been reached at 15 months. Conclusions: In this population with very advanced disease, I+C+RT have produced promising OS and local control outcomes with greater toxicity than in previously reported experiences with this regimen. No significant financial relationships to disclose.
Staphylococcus aureus colonization and acquisition of skin and soft tissue infection among Royal Marines recruits: a prospective cohort study
Authors: E. Jauneikaite, T. Ferguson, M. Mosavie, J.L. Fallowfield, T. Davey, N. Thorpe, A. Allsopp, A.M. Shaw, D. Fudge, M.K. O'Shea, D. Wilson, M. Morgan, B. Pichon, A.M. Kearns, S. Sriskandan, L.E. Lamb
Journal: Clinical Microbiology and Infection (2019)
Effect of PDL-1 expression on prognosis in head and neck squamous cell carcinoma.
Authors: Maria Vasilakopoulou, Vamsidhar Velcheti, Theodoros Rampias, Clarence Sasaki, David Rimm, George Fountzilas, Amanda Psyrri
Journal: Journal of Clinical Oncology (2013)

6012 Background: The recent demonstration that immunotherapeutic approaches may be clinically effective for cancer patients has renewed the interest for this therapeutic strategy. Engagement of programmed death-1 receptor (PD-1), expressed on activated T-cells, by its ligands, results in a negative regulatory effect, with inhibition of downstream cellular signaling events. Our aim was to investigate the expression and prognostic significance of immunoresistance molecule PDL-1 (the negative regulator programmed death-1-ligand 1) on an annotated HNSCC tissue microarray. Methods: A tissue array composed of 400 larynx cancers treated with surgery followed by radiotherapy was constructed. PDL-1 protein expression levels were assessed using automated quantitative protein analysis (AQUA). The objectives of this analysis were to determine the association of PDL-1 with efficacy outcomes ( overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) ). The univariate and multivariate Cox proportional hazards models were used to evaluate the relationship between PDL-1 and event-time distributions. Event-time distributions were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Mean follow-up time for the entire cohort was 39.34 months. Two-hundred thirty eight of 400 cases had sufficient tissue for AQUA analysis. High tumor PDL-1 expression was associated with favorable outcome for OS (P=0.029) and trended towards improved DFS (P=0.06) at 5 years. In multivariable analysis, adjusting for well-characterized prognostic variables, PDL-1 expression status retained its prognostic significance for OS and there was again a trend for PFS (p=0.05). Conclusions: This paradoxical result is in accordance with reported studies in HPV-associated HNSCC where PD-1(+) T cells were associated with favorable clinical outcome. It is possible that PDL-1 detection may reflect a previous immune response against tumors. Further work will determine whether PD-1/PD-L1 blockade induces tumor regression in HNSCC.
<i>Vital Signs:</i> Pharmacy-Based Naloxone Dispensing — United States, 2012–2018
Authors: Gery P. Guy, Tamara M. Haegerich, Mary E. Evans, Jan L. Losby, Randall Young, Christopher M. Jones
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The CDC Guideline for Prescribing Opioids for Chronic Pain recommends considering prescribing naloxone when factors that increase risk for overdose are present (e.g., history of overdose or substance use disorder, opioid dosages ≥50 morphine milligram equivalents per day [high-dose], and concurrent use of benzodiazepines). In light of the high numbers of drug overdose deaths involving opioids, 36% of which in 2017 involved prescription opioids, improving access to naloxone is a public health priority. CDC examined trends and characteristics of naloxone dispensing from retail pharmacies at the national and county levels in the United States.CDC analyzed 2012-2018 retail pharmacy data from IQVIA, a health care, data science, and technology company, to assess U.S. naloxone dispensing by U.S. Census region, urban/rural status, prescriber specialty, and recipient characteristics, including age group, sex, out-of-pocket costs, and method of payment. Factors associated with naloxone dispensing at the county level also were examined.The number of naloxone prescriptions dispensed from retail pharmacies increased substantially from 2012 to 2018, including a 106% increase from 2017 to 2018 alone. Nationally, in 2018, one naloxone prescription was dispensed for every 69 high-dose opioid prescriptions. Substantial regional variation in naloxone dispensing was found, including a twenty-fivefold variation across counties, with lowest rates in the most rural counties. A wide variation was also noted by prescriber specialty. Compared with naloxone prescriptions paid for with Medicaid and commercial insurance, a larger percentage of prescriptions paid for with Medicare required out-of-pocket costs.Despite substantial increases in naloxone dispensing, the rate of naloxone prescriptions dispensed per high-dose opioid prescription remains low, and overall naloxone dispensing varies substantially across the country. Naloxone distribution is an important component of the public health response to the opioid overdose epidemic. Health care providers can prescribe or dispense naloxone when overdose risk factors are present and counsel patients on how to use it. Efforts to improve naloxone access and distribution work most effectively with efforts to improve opioid prescribing, implement other harm-reduction strategies, promote linkage to medications for opioid use disorder treatment, and enhance public health and public safety partnerships.
Identification of cancer care and protocol characteristics associated with recruitment rate in breast cancer clinical trials in Ontario
Authors: J. Lemieux, P. J. Goodwin, K. Pritchard, K. Gelmon, L. Bordeleau, T. Duchesne
Journal: Journal of Clinical Oncology (2007)

17042 Background: Recruitment rate (RR) in clinical trials (CT) has been recognized to be low. Poor accrual may lead to premature closing of CT or decrease of the planned power to detect an effect if present. Methods: Objectives were primarily to identify characteristics of cancer care settings and clinical trials protocols associated with low RR and secondarily (1) to determine the RR and (2) to compare the RR between years. A cross-sectional design was used. Poisson regression was used for multivariate analysis. RR was calculated by CT, hospital and year in Ontario between 1997 and 2002. Number of patients recruited in each CT was obtained from cooperative groups and pharmaceutical companies. Number of patients with breast cancer (BC) was obtained from the Ontario Cancer Registry. Prevalence of women with metastatic BC was calculated from the British Columbia Breast Cancer Outcome Unit database. Characteristics of cancer care and protocols were collected. Results: Response rates were 84% (66/79) for hospitals, 69% (9/13) for cooperative groups and 80% (8/10) for pharmaceutical companies. Recruitment rates varied between 1.3% and 5.5% (median, p=0.0003). Characteristics of cancer care were not associated with RR (number of oncologists, breast oncologists, breast surgeons, investigators, clinical research associates and being a cancer centre or an academic centre). Among protocol characteristics, the following were associated with RR in univariate analysis: phase, randomization, type of intervention, placebo, extent of the trials (local vs. national vs. international), number of sites, population (adjuvant vs. metastatic), menopausal status, premature closing of the trial, time frame for enrolment, extra baseline and follow-up testing. In multivariate analysis, type of control arm and time frame for enrolment were significant. CT using placebo compared to an active control arm were less likely to recruit patients (relative risk 0.57, p=0.0144). CT with a time frame for enrolment greater than 9 weeks were more likely to enrol patients (relative risk 1.43, p=0.0020). Conclusions: RR is very low. No easily modifiable factors have been identified. This project was funded by the Canadian Breast Cancer Foundation, Ontario Chapter. [Table: see text]
Mechanistic profiling of the release kinetics of siRNA from lipidoid-polymer hybrid nanoparticles in vitro and in vivo after pulmonary administration
Authors: Kaushik Thanki, Delphine van Eetvelde, Antonia Geyer, Juan Fraire, Remi Hendrix, Hannelore Van Eygen, Emma Putteman, Haider Sami, Cristiane de Souza Carvalho-Wodarz, Henrik Franzyk, Hanne Mørck Nielsen, Kevin Braeckmans, Claus-Michael Lehr, Manfred Ogris, Camilla Foged
Journal: Journal of Controlled Release (2019)
Paradigm of Sudden Death Prevention in Hypertrophic Cardiomyopathy
Authors: Barry J. Maron, Ethan J. Rowin, Martin S. Maron
Journal: Circulation Research (2019)

Hypertrophic cardiomyopathy (HCM) is a worldwide genetic heart disease and a common cause of sudden death in the young. Penetration of the implantable cardioverter-defibrillator (ICD) into this patient population over the past 20 years has made accurate selection of patients for primary prevention ICDs a priority. Consequently, a new paradigm has emerged in the management of this complex disease with ICD therapy responsible for a substantial decrease in overall HCM-related mortality (to 0.5%/y) and independent of patient age. Selection of candidates for ICDs has matured substantially with the formulation of an enhanced risk stratification algorithm. One or more contemporary risk markers judged major within a given patient's clinical profile, in association with physician judgment and shared decision-making, is sufficient to consider a primary prevention ICD implant. An enhanced American College of Cardiology/American Heart Association risk factor model (including new contrast-magnetic resonance-based markers, such as left ventricular apical aneurysm) used prospectively to make ICD decisions proved to be 95% sensitive for identifying patients who would experience ≥1 appropriate device therapies terminating ventricular tachycardia/fibrillation. The number of HCM patients required to treat with ICDs to save 1 patient with abolition of lethal ventricular tachyarrhythmias was 6:1, similar to randomized defibrillator trials in other cardiomyopathies. In contrast to patients with ischemic heart disease, after ICD shock HCM patients rarely experience transformation to heart failure deterioration or sudden arrhythmic death. The mathematically derived risk score model proposed by the European Society of Cardiology was inferior for identifying high-risk patients susceptible to arrhythmic sudden death with a sensitivity of only 33%, leaving many patients exposed to the possibility of sudden death without ICDs. In conclusion, introduction of the ICD associated with a matured risk stratification algorithm has altered management strategy and clinical course of many HCM patients, making the likelihood of sudden death prevention a reality and fulfilling the aspiration of preservation of life and reduced mortality for this vulnerable patient population.