tbuckley/cabot-search huggingface dataset:
A Large-Scale Investigation of Hypoxia-Preconditioned Allogeneic Mesenchymal Stem Cells for Myocardial Repair in Nonhuman Primates
Authors: Xinyang Hu, Yinchuan Xu, Zhiwei Zhong, Yan Wu, Jing Zhao, Yingchao Wang, Haifeng Cheng, Minjian Kong, Fengjiang Zhang, Qi Chen, Jianzhong Sun, Qian Li, Jing Jin, Qingju Li, Lihong Chen, Chen Wang, Hongwei Zhan, Youqi Fan, Qian Yang, Lei Yu, Rongrong Wu, Jie Liang, Jinyun Zhu, Ya Wang, Yiping Jin, Yifan Lin, Fan Yang, Liangliang Jia, Wei Zhu, Jinghai Chen, Hong Yu, Jianyi Zhang, Jian’an Wang
Journal: Circulation Research (2016)

The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem-cell-based myocardial therapy are needed.The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP-MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation.MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1×10(7) cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells-treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications.Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted.
Abstract 13204: Re-Induction of Atrial Fibrillation Changes Electrogram and ECG Characteristics in Ablation Patients: Insights Using Novel Signal Analyses
Authors: Angelo Biviano, Edward Ciaccio, William Whang, Hasan Garan
Journal: Circulation (2013)

Introduction: We analyzed electrograms (EGM) in atrial fibrillation (AF) patients at three time points during catheter ablation procedures in order to assess the changes that occur in AF signal cha...
Randomized trial of p53 targeted adjuvant therapy for patients (pts) with organ- confined node-negative urothelial bladder cancer (UBC)
Authors: W. M. Stadler, S. P. Lerner, S. Groshen, J. P. Stein, D. G. Skinner, D. Raghavan, G. D. Steinberg, D. Wood, L. H. Klotz, M. C. Hall, R. Cote
Journal: Journal of Clinical Oncology (2009)

5017 Background: Retrospective studies suggest that p53 mutation and associated immunohistochemical (IHC) detectable expression are prognostic for recurrence in pts with organ confined UBC and may be predictive for benefit from MVAC adjuvant chemotherapy. Methods: Pts with pT1–2N0M0 UBC following radical cystectomy and bilateral pelvic lymph node dissection were eligible. IHC for p53 was centrally performed and pts with ≥10% nuclear reactivity were offered randomization to 3 cycles of adjuvant MVAC vs. observation. P53 negative and p53 positive pts who declined randomization were observed. Primary endpoint was recurrence-free survival (RFS) in the randomized population. Secondary endpoints were RFS in p53 negative versus p53 positive pts and overall survival in each of these groups. Using a one-sided log-rank test with α = 0.05 and β = 0.15, 190 p53 positive patients were planned to be randomized to detect an absolute improvement in RFS at 3 years (yrs) from 50% to 70% (corresponding hazards ratio of 0.51). Results: 521 pts were registered, 499 underwent successful p53 assessment (male: 80%, &lt;65 yrs: 57%, Caucasian: 91%, pathologic stage P1/P2: 37%/63%, lymphovascular invasion: 20% yes/28% unknown), 272 (55%) were p53 positive and 114 were randomized (42%). Further accrual was halted based on data safety monitoring board review of futility analysis on the first 100 randomized pts. P53 positive tumors were higher grade (97% vs 93% grade 3/4, p = 0.04) and less likely to express p21 (59% vs 84%, p &lt; 0.001). Overall 5-yr RFS was 80 ± 2% with no difference based on p53 status. P53 positive patients declining were older but otherwise similar to those accepting randomization. Only 67% of pts randomized to MVAC received all 3 cycles with 12 (21%) receiving none. There was no difference in RFS in the randomized population (overall 5 yr RFS 83 ± 4%, hazard ratio = 0.88, p = 0.78). Conclusions: The prognostic and predictive value of p53 IHC were not confirmed in this prospective study, but the lower than expected event rate and failures to receive assigned therapy severely compromised the study's power. The value of p53 mutations is being assessed. No significant financial relationships to disclose.
Abstract 19132: Urinary 8-hydroxy-2’-deoxyguanosine, a Biomarker of Oxidative Stress, Predicts Cardiac Events in Patients With Cardiac Sarcoidosis
Authors: Takeki Myoren
Journal: Circulation (2014)

Background: Enhanced production of reactive oxygen species plays a crucial role in the pathogenesis of cardiac sarcoidosis (CS). Here, we investigated whether urinary (U) 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, predicts cardiac events in CS patients.

Methods: Thirty consecutive patients were diagnosed as CS according to 2006 Japanese guideline, and they were divided into active CS group (n=20) and non-active CS group (n=10) based on the abnormal accumulation of isotope on heart by 18FDG-PET/CT. U-OHdG, cardiac function and other biomarkers were measured in 30 CS patients before discharge (mean age: 64.8 ± 11.1 years; male: 52%; LVEF: 35 ±13%; NYHA: 1.8 ± 0.6, BNP: 315.0 ± 352.7 pg/ml; U8-OHdG: 16.7 ± 7.0 ng/mg·creatinine). Then, we prospectively followed these patients for a median follow-up period of 48 month, with primary endpoints of cardiac events (death).

Results: U-8OHdG (ng/mg·creatinine) in all CS patients was significantly increased as compared with control subjects (all CS; n=30: 16.7±7.0 vs. normal subjects; n=30: 8.0±2.0, p 19.1 had a significantly higher cardiac event rate than those with U-8-OHdG 19.1 was 1.157 (95% confidence interval, 1.044-1.282) as compared with those with U-8-OHdG<19.1 for cardiac events.

Conclusion: These findings suggested that U8-OHdG is a novel and powerful predictor for cardiac death in CS patients.
Early development of posterior reversible encephalopathy syndrome post lung transplantation
Authors: Letizia Corinna Morlacchi, Valeria Rossetti, Marta DiPasquale, Giulia Salomoni, Maria Pappalettera, Paolo Tarsia
Journal: European Respiratory Journal (2011)

Tacrolimus is a calcineurin inhibitor and has been proven highly effective in preventing graft rejection after transplantation of solid organs. Its major adverse effects are nephrotoxicity and neurotoxicity: the most severe form of the latter is PRES (Posterior Reversible Encephalopathy Syndrome).  We here describe a case of PRES in a 26-year-old woman, 5 days after she received bilateral lung transplantation for cystic fibrosis. She had been administered tacrolimus since the transplantation was performed. While in ICU, she suddenly developed mental status alterations, acute pulmonary deterioration and hypercapnia, with need of mechanical ventilation. A head CT scan and MR were performed, detecting subcortical white matter lesions and patchy, bilaterally symmetric areas of abnormally increased signal on the T1-weighted images within the cerebellum and the occipital-parietal and frontal regions of the brain; a minor alteration was also present in the thalamus. ADC (i.e. Apparent Diffusion Coefficients) mapping showed wide areas of vasogenic and cytotoxic edema.  Tacrolimus was immediately stopped and cyclosporine was introduced: her symptoms promptly improved.  A MRI was repeated two weeks later, documenting a significant improvement both of the cerebellum and the thalamus.  A follow up MRI was performed two months after the transplantation: prior lesions had almost completely resolved.  She still suffers from minor neuro-cognitive deficits (concerning calculus and short-term memory) and visual disturbances.  This case maybe significant in order to better understand the clinical features of PRES, which may present at a very early stage of tacrolimus regimen and is a generally reversible condition.
Survey of Cancer in Children Admitted to a Brazilian Charity Hospital&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Carlos Marigo, M.D., Helena Muller, M.D., J. N. P. Davies, D.Sc., M.D.
Journal: JNCI Journal of the National Cancer Institute (1969)

Childhood malignancies seen over a 15-year period in a Brazil charity hospital in São Paulo City have been retrospectively analyzed. The site and type pattern of these 520 childhood malignancies differ considerably from the United States and European patterns and also from the African patterns. Among the notable differences are the high frequencies of Hodgkin's disease, adrenal cortical tumors, and renal carcinomas. Other less significant differences are discussed.
Memes and the evolution of religion: We need memetics, too
Authors: Susan Blackmore
Journal: Behavioral and Brain Sciences (2016)

Abstract In their analysis, Norenzayan et al. completely ignore memetics, which, unlike other theories, treats memes as replicators and looks to memetic as well as genetic advantage. Now that memes are evolving ever faster, genetic advantage is less relevant. So when religious and secular values are at odds, we need a memetic analysis to understand what is going on.
Sclerostin inhibition promotes TNF-dependent inflammatory joint destruction
Authors: Corinna Wehmeyer, Svetlana Frank, Denise Beckmann, Martin Böttcher, Christoph Cromme, Ulrich König, Michelle Fennen, Annelena Held, Peter Paruzel, Christine Hartmann, Athanasios Stratis, Adelheid Korb-Pap, Thomas Kamradt, Ina Kramer, Wim van den Berg, Michaela Kneissel, Thomas Pap, Berno Dankbar
Journal: Science Translational Medicine (2016)

Blocking the Wnt inhibitor sclerostin leads to inflammatory joint destruction through enhanced activation of TNF receptor–mediated signaling, implicating sclerostin as protective in TNFα-dependent chronic inflammation.
Cytologic Evaluation of Breast Fluid in the Detection of Breast Disease 2
Authors: Otto W. Sartorius, Helene S. Smith, Peter Morris, Doris Benedict, Lawrence Friesen
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Cytologic Evaluation of Breast Fluid in the Detection of Breast Disease Get access Otto W. Sartorius, Otto W. Sartorius 3Santa Barbara Diagnostic Breast Clinic, Santa Barbara, Calif. 93105. 4Present address: Peralta Cancer Research Institute, University of California, 3023 Summit St., Oakland, Calif. 94609. Search for other works by this author on: Oxford Academic PubMed Google Scholar Helene S. Smith, Helene S. Smith 5Cell Culture Laboratory, School of Public Health, University of California, Berkeley, Calif. 94720. 4Present address: Peralta Cancer Research Institute, University of California, 3023 Summit St., Oakland, Calif. 94609. Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Morris, Peter Morris 6Department of Pathology, Cottage Hospital, Santa Barbara, Calif. 93105. Search for other works by this author on: Oxford Academic PubMed Google Scholar Doris Benedict, Doris Benedict 3Santa Barbara Diagnostic Breast Clinic, Santa Barbara, Calif. 93105. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence Friesen Lawrence Friesen 3Santa Barbara Diagnostic Breast Clinic, Santa Barbara, Calif. 93105. 7We thank Dr. B. Strickland for her interest in and help with this project. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 4, October 1977, Pages 1073–1080, https://doi.org/10.1093/jnci/59.4.1073 Published: 01 October 1977 Article history Received: 23 November 1976 Accepted: 05 May 1977 Published: 01 October 1977
Coagulation and fibrinolytic activities in 2 siblings with β2-glycoprotein I deficiency
Authors: Rie Takeuchi, Tatsuya Atsumi, Masahiro Ieko, Hiroyuki Takeya, Shinsuke Yasuda, Kenji Ichikawa, Akito Tsutsumi, Koji Suzuki, Takao Koike
Journal: Blood (2000)
Complexity of cardiac ion channel macromolecular complexes
Authors: Peter J. Mohler, Hugues Abriel
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Nav1.5 N-terminal domain binding to α1-syntrophin increases membrane density of human Kir2.1, Kir2.2 and Nav1.5 channels’ by M. Matamoros et al. , pp. 279–290. 

Proper cardiac function depends on a myriad of fine-tuned molecular interactions within myocytes.1 The critical role of these interactions is clearly illustrated by a growing list of human cardiovascular diseases due to defects in the biogenesis and maintenance of large macromolecular complexes.2 This paradigm is particularly relevant in the field of human cardiac arrhythmias where ‘gain-of-function’ or ‘loss-of-function’ mutations leading to seemingly small changes in the protein structure of ion channel proteins may lead to potential fatal events.

These findings are particularly surprising due to the fact that there exist many regulatory and counter-regulatory mechanisms that compensate to preserve cardiac electrical and structural function. For nearly two decades, cardiac ion channels have been shown to exist not simply as a pore-forming subunit, but as constituents of large, diverse, and fluid multiprotein complexes.2 In fact, over the past few years, the emergence of new and highly sophisticated cell and molecular technologies has propelled our understanding into the ‘life’, i.e. cell biology, of these ion channels in highly compartmentalized cardiac cells.1

While all cardiac ion channels appear to be regulated through multiple protein interactions and post-translational modifications, the regulation of the primary cardiac voltage-gated Nav1.5 channel ( SCN5A ) has gained …
Suicide screening should be given to patients who have bariatric surgery, study recommends
Authors: Jacqui Wise
Journal: BMJ (2015)

Patients undergoing bariatric surgery should be screened for suicide risk and given more mental health support, researchers say, after a study published in JAMA Surgery showed that self harm emergencies increased by 50% after surgery.

The study1 followed 8815 adults from Ontario, Canada, for three years before they underwent bariatric surgery and for three years after. The cohort was …
Abstract 15834: Evolution of Differences in Women and Men With Non-ST-Segment Elevation Acute Coronary Syndromes: Insights From Clinical Trials Over 15 Years
Authors: Sharif Halim, Qinghong Yang, Phillip Schulte, Judith Hochman, Chiara Melloni, Kenneth W Mahaffey, David J Moliterno, Robert A Harrington, Harvey D White, Paul W Armstrong, E. Magnus Ohman, Frans Van de Werf, Robert P Giugliano, L. Kristin Newby
Journal: Circulation (2013)
Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas
Authors: C. O. Da Fonseca, Gilberto Schwartsmann
Journal: Journal of Clinical Oncology (2007)

14037 Background: Deregulated p21-Ras function, as a result of mutation, overexpresion or growth factor-induced overactivation, contributes to growth of malignant gliomas. Perillyl alcohol (POH) is a monoterpene with preclinical antitumor activity in several types of tumor in rodent models and is currently under phase I and phase II clinical trials. Its proposed mechanism of action involves inhibition of post- translational isoprenylation of small G proteins, including p21-Ras, thereby blocking signal transduction Methods: The intranasal delivery is a practical and non-invasive approach that allows therapeutic agents, which do not cross the blood brain barrier (BBB) to enter the Central Nervous System (CNS), reducing unwanted systemic side effects. Applying this method we performed a phase I / II study with POH intranasal administration in patients with relapsed malignant gliomas after standard treatment: surgery, radiotherapy and chemotherapy. POH was administrated in concentration 0.3% volume/volume (55mg) 4 times daily. Results: Thirty-seven patients enrolled being 29 with glioblastoma multiform (GBM), 5 with grade III astrocytoma (AA) and 3 with anaplastic oligodendroglioma (AO). The results showed that POH is well tolerated and display at 6 months of treatment partial responses in 1 patient (3,4%) with GBM and 1 patient (33,3%) with AO; stable disease in 13 patients (44,8%) with GBM, 3 patients (60%) with AA and 1 patient (33,3%) with AO; progressive response in 15 patient (51,7%) with GBM, 2 patients (40%) with AA e 1 patient (33,3%) with AO. Conclusions: The POH intranasal delivery in a concentration of 0.3% volume/volume (55 mg) is well tolerated, and may prolong survival in patients with relapsed malignant gliomas patients. No significant financial relationships to disclose.
Assisted Administration Of Subcutaneous 5-Azacytidine to The Patient's Home. Significant Reduction Of Indirect Costs Incurred By Care Recipients and Unpaid Caregivers Together With a Total Adhesion To The Treatment Schedule and Same Safety
Authors: Francesco Iuliano, Eleonora Iuliano, Alessia Perricelli, Angelo Pomillo, Maria Luci, Gianluca Cervo
Journal: Blood (2013)
Prospective multi-center phase II trial of docetaxel and vinorelbine with filgrastim support in subjects with advanced non-small cell lung cancer (NSCLC)
Authors: R. D. Page, F. P. Smith, G. F. Geils, C. L. Beall, M. B. Ross, M. Fridman, B. J. Allen
Journal: Journal of Clinical Oncology (2004)

7138 Background. Although platinum based chemotherapy (CT) regimens are the standard of therapy in first line NSCLC, a subset of patients are ineligible to receive such agents. Docetaxel and vinorelbine are each active agents in NSCLC and when combined may provide enhanced activity. The purpose of this study was to evaluate the safety and efficacy of this combination therapy when administered on a Q2W schedule with Filgrastim support. Methods. This multi-center, community based study was conducted in 10 sites that enrolled 61 CT naïve patients with Stage IIIb/IV NSCLC. Treatment consisted of vinorelbine 45mg/m2and docetaxel 60mg/m2 D1 and Filgrastim 5 mcg/kg D2 -D14 repeated Q2W for 8 cycles. Patients were evaluated for response at the end of cycles 2, 5 and 8. Confirmed response was defined as complete or partial response (CR, PR) based upon two or more evaluations, while best response was defined as the best of the three evaluations. We report response rate and Kaplan-Meier estimate (95%CL) of time to disease progression and one-year survival. Results. Of 61 enrolled patients 42% (95% confidence interval [CI], 30% to 54%) achieved either CR or PR as best response; and 13% (95% CI, 9% to 17%) of patients had a confirmed response. Median time to disease progression was 160 days. With a median follow-up time of 14.2 months, the estimated median survival time is 14.1 months (95% CI lower bound, 8.5), and the 1-year survival rate is 57% (95% CI, 44% to 70%). Five patients (8%) experienced febrile neutropenia (ANC < 500/mm3 plus body temperature >= 38.2°C). Overall calculated dose intensity (delivered/planned dose x 100) was 95% for vinorelbine and 93% for docetaxel. Conclusion. The combination of docetaxel and vinorelbine can be delivered with high dose intensity with Filgrastim support. Additionally in this multi-center non-controlled study completed in a community setting, an interesting 1-year and overall median survival is observed and supports further evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc. Amgen, Inc. Amgen, Inc.
Safety and efficacy of pegfilgrastim in pediatric oncology patients: The M.D. Anderson Cancer Center experience
Authors: S. E. Koontz, L. R. Mohassel, N. Jaffe, M. Pearson, C. Herzog, I. Ramirez, R. B. Raney
Journal: Journal of Clinical Oncology (2004)

8272 Background: The growth factor filgrastim (G-CSF) reduces the severity and duration of neutropenia in cancer patients. Due to its short half-life, it has to be injected daily, usually for 7–10 days, which is a special challenge in treating children. Pegfilgrastim, a pegylated form of G-CSF, has a long half-life and thus only has to be injected once per chemotherapy cycle. Data on the use of pegfilgrastim in children is limited. Therefore we evaluated the safety and efficacy of pegfilgrastim in children. Methods: To date, we have retrospectively reviewed the charts of 21 pediatric patients (12 males, ages 4–20, median 13 yrs) with various cancers (19 solid tumors and 2 lymphomas) who received pegfilgrastim. All patients had life expectancy > 6 weeks and baseline lab values acceptable to receive chemotherapy. A total of 101 doses (median/patient 5, range 2–9) of pegfilgrastim were administered (98% 24–72 hours post-chemotherapy). Patients ≥ 45 kg received 6 mg each (44 doses), and patients < 45 kg received an average dose of 110 mcg/kg (57 doses). We evaluated the efficacy [measured by total white blood cell (WBC) recovery] and safety [measured by adverse drug reactions (ADRs)] of pegfilgrastim in these patients. Results: Of the 101 pegfilgrastim doses, 82 were followed by grade 3 or 4 neutropenia [absolute neutrophil count (ANC) < 1 x 109/L], 13 were not, and six could not be evaluated because of infrequent clinic visits. For the doses involving neutropenia, the average time to achieving an ANC ≥ 1 x 109/L was 10 days. For the 95 evaluable doses, the average time to peak WBC count was 12.5 days, and 25 admissions for febrile neutropenia (grade 3 or 4) occurred prior to WBC recovery. Identifiable ADRs included: 4 episodes of bone/muscular pain, 1 episode of chills, and 28 episodes of leukocytosis (8 cases of WBC > 2 times upper limit of normal for age). No reports of organ dysfunction were noted. Conclusions: Pegfilgrastim appears to be a safe and effective alternative to G-CSF in children with cancer, and we continue to use this agent at our center. No significant financial relationships to disclose.