tbuckley/cabot-search huggingface dataset:
Unique Features of Cortical Bone Stem Cells Associated With Repair of the Injured Heart
Authors: Sadia Mohsin, Constantine D. Troupes, Timothy Starosta, Thomas E. Sharp, Elorm J. Agra, Shavonn Smith, Jason M. Duran, Neil Zalavadia, Yan Zhou, Hajime Kubo, Remus M. Berretta, Steven R. Houser
Journal: Circulation Research (2015)

Rationale: Adoptive transfer of multiple stem cell types has only had modest effects on the structure and function of failing human hearts. Despite increasing the use of stem cell therapies, consensus on the optimal stem cell type is not adequately defined. The modest cardiac repair and functional improvement in patients with cardiac disease warrants identification of a novel stem cell population that possesses properties that induce a more substantial improvement in patients with heart failure. Objective: To characterize and compare surface marker expression, proliferation, survival, migration, and differentiation capacity of cortical bone stem cells (CBSCs) relative to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs), which have already been tested in early stage clinical trials. Methods and Results: CBSCs, MSCs, and CDCs were isolated from Gottingen miniswine or transgenic C57/BL6 mice expressing enhanced green fluorescent protein and were expanded in vitro. CBSCs possess a unique surface marker profile, including high expression of CD61 and integrin β4 versus CDCs and MSCs. In addition, CBSCs were morphologically distinct and showed enhanced proliferation capacity versus CDCs and MSCs. CBSCs had significantly better survival after exposure to an apoptotic stimuli when compared with MSCs. ATP and histamine induced a transient increase of intracellular Ca 2+ concentration in CBSCs versus CDCs and MSCs, which either respond to ATP or histamine only further documenting the differences between the 3 cell types. Conclusions: CBSCs are unique from CDCs and MSCs and possess enhanced proliferative, survival, and lineage commitment capacity that could account for the enhanced protective effects after cardiac injury.
Abstract 12362: Long-term Influence of Body Mass Index on Cardiovascular Events After Atrial Fibrillation Ablation
Authors: T J Bunch, Heidi T May, Tami L Bair, Victoria Jacobs, Brian G Crandall, Michael Cutler, J P Weiss, Charles Mallender, Jeffrey S Osborn, Jeffrey L Anderson, John D Day
Journal: Circulation (2015)

Introduction: Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach in symptomatic patients. Obesity is a dominant driver of AF recurrence after ablation. However it is not known what weight status will lower AF risk and also minimize long-term cardiac events. Hypothesis: An increased body mass index (BMI) will negatively impact cardiovascular outcomes after AF ablation. Methods: All patients that underwent an index ablation with a BMI recorded and at least 3 years of follow-up were included (n=1558). The group was separated and compared by index ablation BMI status (≤20, 21-25, 26-30, &gt;30 kg/m 2 ). Long-term outcomes included AF recurrence, stroke/TIA, heart failure (HF) hospitalization, and death. Results: Patients increasing BMI strata were more likely to be male and have hypertension, a smoking history, diabetes, HF and a prior cardioversion. Patients with a BMI≤20 were more likely to have a moderate-high CHADS2 score. At 3 years, recurrence rates of AF increased significantly with increasing BMI status (p=0.02), but stroke rates were similar (p=0.06). Long-term death rates tended to increase inversely with BMI status and HF rates were greatest in the highest and lowest BMI groups (Figure). Conclusion: Lower weight at AF ablation, lowers arrhythmia recurrence risk. However, AF ablation patients that are underweight remain at high risk of other cardiovascular outcomes and the lower arrhythmia outcomes do not result in an observable stroke risk reduction.
High Resolution Autoradiographic Study of the Kinetics of Development of Rous Sarcoma Virus (Schmidt-Ruppin Strain). V. Estimation of the Time of Synthesis of Virus-Associated DNA2
Authors: Susan Michelson-Fiske, Françoise Haguenau, G. F. Rabotti
Journal: JNCI Journal of the National Cancer Institute (1973)

Chick embryo fibroblasts transformed by Rous sarcoma virus were labeled with 3H-thymidine; this percursor was incorporated into the extracellular virus as early as 10 minutes after contact of the cells with the precursor. With electron microscope autoradiography, the DNA was detectable at the level of the budding and mature particles after 10 minutes of pulse labeling and 2 hours of chase. After the virus was purified on sucrose gradients and its nucleic acids were extracted, radioactivity was found in an acid-precipitable material. This material was resistant to NaOH hydrolysis and RNase treatment, but sensitive to DNase digestion.
Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register
Authors: Emmert Roberts, Simon Wessely, Trudie Chalder, Chin-Kuo Chang, Matthew Hotopf
Journal: The Lancet (2016)

<h2>Summary</h2><h3>Background</h3> Mortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register. <h3>Methods</h3> We calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome. <h3>Findings</h3> We identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex-standardised mortality ratios (SMRs) for all-cause mortality (SMR 1·14, 95% CI 0·65–1·85; p=0·67) or cancer-specific mortality (1·39, 0·60–2·73; p=0·45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6·85, 95% CI 2·22–15·98; p=0·002). <h3>Interpretation</h3> We did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome. <h3>Funding</h3> National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.
Sensitivity and specificity of a whole-blood RNA transcript-based diagnostic test for the diagnosis of prostate cancer (CaP) compared with prostate-specific antigen (PSA) alone
Authors: R. W. Ross, D. Bankaitis-Davis, L. Siconolfi, L. Katz, K. Storm, J. Magidson, K. Wassmann, W. K. Oh
Journal: Journal of Clinical Oncology (2009)

5052 Background: Screening for CaP with PSA testing is limited by a high number of false postives, particularly in the setting of benign prostatic hypertrophy (BPH). The goal of this study was to develop whole blood RNA transcript-based diagnostic tests that improve the diagnosis of CaP over PSA alone. Methods: From August 2006 to October 2008, three prospective cohorts of men consented to the collection of whole blood in PAXgene Blood RNA tubes for gene expression analysis: men with newly diagnosed, localized, untreated CaP, otherwise healthy men without CaP, and otherwise healthy men with BPH. 168 inflammation and CaP-related genes (Source MDx Precision Profiles) were assayed using optimized Q-PCR technology. Logistic regression methods were used to develop models to optimize prostate cancer diagnosis. Results: 182 men underwent expression analysis (n = 76, 76 and 30 for CaP, normal, and BPH cohorts, respectively). The CaP and normal cohorts were age matched (median age 60 yrs); the BPH cohort median age was 70. Considering only the CaP and normal cohorts, PSA alone (using a cut-off of 4 ng/ml) had a specificity of 94.7%, but sensitivity of only 71.1% for diagnosis of CaP, or 90.8% and 77.6%, respectively, when using age-adjusted PSA criteria. A model consisting of the expression analysis of 6 genes and PSA had a higher specificity (96.1%) and a much improved sensitivity (97.4%) for CaP diagnosis. When the BPH cohort was added, the improvement of the 6-gene model remained (sensitivity and specificity of 97.4% and 92.0% vs 77.6% and 88.1% using the age-adjusted PSA criteria). Further model development using the CaP and BPH cohorts yielded a 5-gene model which, integrated with PSA and age, correctly predicted 96.1% of the CaP pts and 93.3% of BPH pts. Conclusions: These results suggest that specific whole blood RNA transcript levels can assess abnormal gene expression associated with CaP. Such a molecular CaP biomarker would be a powerful tool to reduce unnecessary biopsies in patients without CaP and detect CaP in patients with PSA values below the current cutoff. Validation of these results is ongoing and will be available at the time of the meeting. [Table: see text]
Phase II study of vemurafenib in patients with locally advanced, unresectable stage IIIc or metastatic melanoma and activating exon 15 <i>BRAF</i> mutations other than V600E.
Authors: Sigrun Hallmeyer, Omid Hamid, Thuy Anh Sorof, Yong Mun, Shiyao Liu, Sarang Abhyankar, Geoffrey Thomas Gibney, Igor Puzanov
Journal: Journal of Clinical Oncology (2014)

9075^ Background: Approximately 50% of metastatic melanoma are activating BRAF mutation-positive, most commonly in codon V600. Vemurafenib (VEM), an inhibitor of oncogenic BRAF kinase, has been shown to improve progression-free survival (PFS) and overall survival (OS) in pts with advanced V600E-mutated melanoma (Chapman et al, 2011; NEJM). An open-label phase II trial (NCT01586195) is being conducted to determine the activity and safety of VEM in previously treated or untreated stage IIIC or IV melanoma pts with measurable disease and an activating, non-V600E BRAF mutation at exon 15 detected by centralized DNA sequencing. Methods: Eligible pts received oral VEM (960 mg bid) until disease progression, unmanageable toxicity, pt request for discontinuation, or other protocol-specified criteria. Tumor responses were evaluated per RECIST v1.1. The primary endpoint was investigator-assessed objective response rate. Time to response, duration of response, PFS and OS, 6- and 12-month survival rates, and safety were additional endpoints. Results: As of October 2013, 10 US sites had enrolled 29 pts: 12 with V600K (cohort 1) and 17 with non-V600K mutations (cohort 2 [7 V600R, 3 L597S, 7 others]). Median (range) age was 61 (33-88) years, 86% were male, 45% were stage M1c and 17% unresectable stage IIIC, 28% had brain metastases, and 10% had ECOG PS 2 (the remainder were ECOG PS 0-1). 7% of pts were treatment naive. In pts who had prior therapy for advanced disease, the median (range) number of therapies was 2 (1-6). At this interim analysis, 12/29 pts (41%) had an unconfirmed response (5 V600K, 3 V600R, 4 other). Confirmed responses were observed in 3 pts (all PRs; V600K, V600R, and D594G); there were no CRs. Overall toxicity profile is consistent with the reported experience in melanoma, with the following AEs reported most frequently: fatigue (52%), rash (48%), and arthralgia (38%). 11 pts had ≥1 grade 3-5 AEs, irrespective of causality. We plan to present an updated data cut at ASCO. Conclusions: Preliminary results show objective responses in this population of advanced melanoma pts with rarer non-V600E BRAF mutations; however, additional follow-up is required. Clinical trial information: NCT01586195.
Hearing Loss in Patients Who Received Cranial Radiation Therapy for Childhood Cancer
Authors: Johnnie K. Bass, Chia-Ho Hua, Jie Huang, Arzu Onar-Thomas, Kirsten K. Ness, Skye Jones, Stephanie White, Shaum P. Bhagat, Kay W. Chang, Thomas E. Merchant
Journal: Journal of Clinical Oncology (2016)

Purpose Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified. Patients and Methods Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation. Results At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL. Conclusion SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended.
Embodying patient-centered communication: An eHealth prototype and evaluation.
Authors: Niina Haas, DerShung Yang, Ana Maria Lopez
Journal: Journal of Clinical Oncology (2013)

152 Background: An eHealth prototype was developed to embody the principals of Patient-Centered Communication espoused by National Cancer Insitute (NCI). The prototype provides patients with features that support access to their “care” (medical records, symptom reporting and monitoring tools, calendar, treatment schedule), “team” (bio, roles, contact info for care team), “education” (reputable articles, videos, tools), and “community” (local classes, events, support groups, forums). This prototype was evaluated in terms of its usefulness and usability. Methods: The prototype was evaluated through two usability evaluation sessions. 13 cancer patients, 4 caregivers, and 12 cancer health care providers were recruited. During a 30-45 minute session, each subject viewed the prototype and completed a survey about the prototype’s usability and usefulness. The survey included 29 items with Likert scales ranging from 0 (Strongly Disagree) to 4 (Strongly Agree). Descriptive statistics were generated. Results: The results were categorized according to group (patient, caregiver, and provider) and section of prototype (overall, care, team, community, education). The patients rated the prototype higher in terms usefulness and usability across all user groups/sections except for the education section, which was rated highest by providers (Table). Conclusions: The positive feedback on several aspects of the prototype from different user groups indicates that our prototype met our objectives of being useful, easy-to-use, and adding value to the cancer patient’s care journey. Interestingly, there is a difference in the perceived value of the prototype’s different sections among each user group. The patients placed higher value on the “Care” features (medical records, symptom reporting and monitoring tools, and treatment schedule) and “Team” features (bio, roles, contact info for care team) than providers, and caregivers. Whereas providers most valued education content as opposed to patients and caregivers who ranked the team content as most important. [Table: see text]
Gonadal function after surgery and chemotherapy in men with stage II and III nonseminomatous testicular tumors.
Authors: J M Nijman, H Schraffordt Koops, J Kremer, D T Sleijfer
Journal: Journal of Clinical Oncology (1987)

The gonadal functions were studied in 54 patients with disseminated nonseminomatous testicular tumors who had been subjected to combination chemotherapy (cisplatin, vinblastine, and bleomycin [PVB]) and surgery (hemiorchiectomy, retroperitoneal lymph node dissection or removal of retroperitoneal residual tumor after chemotherapy) and in 17 patients with a stage I tumor subjected to hemiorchiectomy exclusively. In the patients treated with chemotherapy, the plasma testosterone levels remained at the lower limit of normal and the luteinizing hormone (LH) levels remained elevated for 2 years after completion of treatment. The follicle-stimulating hormone (FSH) levels also remained significantly elevated, but showed a tendency to decrease after 2 years. Semen analysis was performed in 25 patients; of the other patients, 18 had no antegrade ejaculation, eight had undergone a vasectomy and three patients did not cooperate. Before treatment, 72% of the patients showed azoo- or oligozoospermia; 2 years after discontinuation of the chemotherapy, 48% had azoo- or oligozoospermia while 28% had more than 60 X 10(6) spermatozoa/mL. However, interestingly the proportion of patients with azoospermia had increased from 4% to 28%. In the course of this study, eight pregnancies occurred; one ended in an early spontaneous abortion; the other seven pregnancies ran an uncomplicated course. Seven healthy children were born. In 17 patients with a stage I tumor treated by hemiorchiectomy only, the testosterone, LH and FSH levels were also observed for 2 years; until 2 years after treatment, the testosterone levels remained lower and the FSH levels remained higher than normal. Insufficiency of the Leydig's cells in the unaffected gonad appeared to be responsible for the altered hormone concentrations in the blood.
Inflammatory breast cancer.
Authors: C J Williams
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.6.986 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3295134 Inflammatory breast cancer. C J WilliamsxC J WilliamsSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.6.986 PDF "Inflammatory breast cancer.." Journal of Clinical Oncology, 5(6), pp. 986–987© 1987 by American Society of Clinical Oncology
The Regulation Of Central Nervous System Acute Lymphoblastic Leukemia By Natural Killer Cells
Authors: Liron Frishman-Levy, Avishai Shemesh, Shahar Frenkel, Allan Bar-Sinai, Zhenya Ni, Dan S. Kaufman, Lueder Hinrich Meyer, Gunnar Cario, Jacob Hochman, Angel Progador, Shai Izraeli
Journal: Blood (2013)
Renal tubular dysgenesis
Authors: J Bernstein, L Barajas
Journal: Journal of the American Society of Nephrology (1994)

Renal tubular dysgenesis is an autosomal recessive condition characterized by short, abnormally developed cortical tubules that lack proximal differentiation. Despite the lack of normal proximal tubules, the major site of water resorption in the kidney, the principal clinical manifestations are caused by fetal and neonatal oliguria. The kidneys in three cases of neonatal renal tubular dysgenesis were found to contain large amounts of immunohistochemically reactive renin in preglomerular arterioles, glomerular hilums, and glomerular mesangial areas, far exceeding the intensity of staining and the numbers of sites stained in control kidneys. The increased accumulation of renin may reflect strong local vasoconstriction, which is responsible for reduced glomerular perfusion. This accumulation suggests faulty feedback control of renin secretion, the basis of which is still to be identified.
Charles Harold Edwards Alexander Clarkson Forrester John Arnott MacDougall Leila Mary Wainman
Authors: Colin Watson
Journal: BMJ (1997)

# Charles Harold Edwards {#article-title-2}

For most of his professional life Harold Edwards practised neurology without the latest technology, basing this on history taking, observation, and meticulous clinical observation, at which he was a master. Not surprisingly his ward rounds were packed with eager students. As the first director of clinical studies at St Mary's Hospital Medical School he introduced progressive assessment and initiated the elective period; the latter had to be self funded but if there was any financial difficulty he helped arrange scholarships. Harold had spent some of his early training in general practice, and realising the importance of this experience he increased the number of practices associated with the medical school so that each student could experience it. Despite selection by A level results he believed that each student should also have a personal interview to assess his or her suitability to study medicine. He knew virtually each student by name.

In Who's Who he mentioned “words” as a hobby: his speeches were examples of detailed …
Asthma and Psychiatric Disorders: is there a link? A perspective study
Authors: A Cappai, F Pinna, F Manunza, S Floris, E Zaccheddu, C Carruba Toscano, A Mancuso, S Palmieri, L Gambula, W Orru, F Argiolas, B Carpiniello, P Manconi, S Del Giacco
Journal: Allergy (2010)