tbuckley/cabot-search huggingface dataset:
Abstract 201: Neuroprotective Effect of Hypothermic Total Liquid Ventilation in Newborn Piglets Subjected to Neonatal Cardiac Arrest
Authors: Emilie Boissady, Matthias Kohlhauer, Fanny Lidouren, Jérôme Rambaud, Alain Berdeaux, Nicolas Mongardon, Philippe Micheau, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2018)

Introduction: Hypothermic total liquid ventilation (TLV) has been shown to be highly protective in adult models of cardiac arrest. Hypothesis: TLV could also provide benefits through ultrafast cooling during neonatal cardiac arrest and subsequent hypoxic-ischemic encephalopathy in piglets. Methods: Newborn piglets were anesthetized and submitted to 30 min of hypoxia (FiO 2 =10%) followed by 7 min of asphyxia. After resucitation, animals underwent either normothermic follow-up (38°C; Control, n=6) or ultra-fast cooling by TLV (TLV, n=6). TLV was implemented during 30 min for cooling induction and hypothermia was further maintained during 3 h using external techniques before rewarming. A third group of piglets was submitted to a Sham procedure (n=4) with neither hypoxia nor ischemia. All groups underwent mechanical ventilation during 6-8 h before awakening. Survival and neurological dysfunction were assessed during 7 days. Animals were then euthanized and histological brain damages were assessed (fluorojade-C staining). Results: After hypoxia-ischemia, Control and TLV animals presented marked metabolic acidosis and lactate levels elevation as compared to Sham (e.g., pH=6.91±0.05, 6.93±0.02 vs 7.33±0.05 at t=30 min after ischemia in Control, TLV and Sham, respectively; p&lt;0.05). Despite a trend toward reduced mortality, survival was not significantly different between TLV and Control groups at the end of the survival follow-up (survival = 0/6, 3/6 and 3/4 in Control, TLV and Sham groups). Nevertheless, neurological dysfunction was significantly reduced in TLV as compared to Control (median scores = 23% vs 87 at day 2, respectively; Sham value = 0%). Blood levels of the brain injury biomarker protein S100B were also reduced at the time of euthanasia in TLV vs Control. Fluoro-jade C staining showed a significantly lower number of degenerating neurons in TLV vs Control (e.g., medians = 17 vs 39 degenerating neurons per field in caudate nucleus, respectively; Sham value = 1). Conclusion: Hypothermic TLV improves neurological recovery in a swine model of neonatal cardiac arrest and hypoxic-ischemic encephalopathy when started early after resuscitation.
Receptor tyrosine kinase dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated colorectal cancer cell lines
Authors: P.P. Vitiello, C. Cardone, D. Ciardiello, G. Barra, N. Matrone, V. Belli, G. Martini, L. Poliero, C. Borrelli, M. Terminiello, T. Troiani, F. Morgillo, F. Ciardiello, E. Martinelli
Journal: Annals of Oncology (2018)
Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders
Authors: Heath E. O’Brien, Eilis Hannon, Matthew J. Hill, Carolina C. Toste, Matthew J. Robertson, Joanne E. Morgan, Gemma McLaughlin, Cathryn M. Lewis, Leonard C. Schalkwyk, Lynsey S. Hall, Antonio F. Pardiñas, Michael J. Owen, Michael C. O’Donovan, Jonathan Mill, Nicholas J. Bray
Journal: Genome biology (2018)

Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to date, there have been no studies that have mapped genome-wide expression quantitative trait loci (eQTL) specifically in the human prenatal brain.We performed deep RNA sequencing and genome-wide genotyping on a unique collection of 120 human brains from the second trimester of gestation to provide the first eQTL dataset derived exclusively from the human fetal brain. We identify high confidence cis-acting eQTL at the individual transcript as well as whole gene level, including many mapping to a common inversion polymorphism on chromosome 17q21. Fetal brain eQTL are enriched among risk variants for postnatal conditions including attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. We further identify changes in gene expression within the prenatal brain that potentially mediate risk for neuropsychiatric traits, including increased expression of C4A in association with genetic risk for schizophrenia, increased expression of LRRC57 in association with genetic risk for bipolar disorder, and altered expression of multiple genes within the chromosome 17q21 inversion in association with variants influencing the personality trait of neuroticism.We have mapped eQTL operating in the human fetal brain, providing evidence that these confer risk to certain neuropsychiatric disorders, and identifying gene expression changes that potentially mediate susceptibility to these conditions.
Image Gallery: Granulomatous dermatitis due to infection with the chlorophyllic green alga <i>Desmodesmus</i>
Authors: M. Fujimoto, Y. Inaba, T. Takahashi, G. Nakanishi, Y. Muraosa, M. Yahiro, K. Kamei, S-i. Murata
Journal: British Journal of Dermatology (2018)
A personal neoantigen vaccine, NEO-PV-01, with anti-PD1 induces broad de novo anti-tumor immunity in patients with metastatic melanoma, NSCLC, and bladder cancer
Authors: P.A. Ott, R. Govindan, A. Naing, T.W. Friedlander, K. Margolin, J.J. Lin, N. Bhardwaj, M.D. Hellman, L. Srinivasan, J. Greshock, M. Moles, R.B. Gaynor, M.J. Goldstein, S. Hu-Lieskovan
Journal: Annals of Oncology (2018)
Abstract 18821: Plasma MicroRNA Sequencing Reveals Novel MicroRNA Biomarkers of Systolic Heart Failure
Authors: Palak Shah, Joe Vockley, Anatoly Ulyanov, Ramaswamy K Iyer, Sheila Phillips, Thierry Vilboux, Christopher O Connor, John Niederhuber
Journal: Circulation (2016)

Introduction: Plasma microRNAs (miRs) are RNA molecules that regulate messenger RNA transcription. MiRs are remarkably stable in the plasma and select miRs have been demonstrated to be useful bioma...
CARF regulates EMT through Wnt/b-catenin signaling: its clinical relevance & potential as a therapeutic cancer target
Authors: Renu Wadhwa, Rajkumar S. Kalra, Anupama Chaudhary, Yue Yu, Ling Li, Sunil Kaul
Journal: Annals of Oncology (2018)

Background: CARF (Collaborator of ARF)/CDKN2AIP was discovered in our laboratory as a novel ARF-binding protein. It was shown to interact with p53-tumor suppressor and HDM2 proteins, and regulate p53-HDM2-p21 pathway in two directions in a dose-dependent manner. Whereas CARF-overexpression results in growth arrest, its super-high level of expression led to aggressive malignant transformation of cancer cells. Suppression of CARF, on the other hand, triggered apoptosis, suggesting that it is an essential cell survival protein and could serve as a target for cancer therapy. We demonstrated that a moderate upregulation of CARF caused growth arrest and senescence, its excessively enriched levels were shown to facilitate aggressive proliferation and malignant transformation of cancer cells. Methods: We have examined the expression level of CARF in clinical cancer datasets. CARF-enriched cells were used to investigate its role in EMT transition, malignant transformation and cancer metastasis. siRNA and shRNA were used to target CARF in vitro and in vivo. Results: We found amplification of CARF (both at gene and transcript levels) in a variety of invasive and metastatic malignancies. Consistent to the clinical readouts, CARF-enriched cells showed enhanced epithelial-mesenchymal transition (EMT). By molecular assays, we determined that the latter is mediated by activation of Wnt/b-catenin signaling axis. CARF-enriched cells showed enhanced nuclear localization and transcriptional activation of b-catenin as marked by increased level of its several effector proteins. Of note (i) CARF-silencing in cells either by siRNA or miRNA led to growth arrest of cells and (ii) CARF-targeting in vivo caused suppression of tumor progression and lung metastasis. Conclusion: We report clinical and therapeutic relevance of CARF in EMT and cancer invasiveness/metastasis, and propose it as a potent therapeutic target of aggressive cancers.
Abstract 19576: Impaired Fitness is Common in Adults Living With HIV, Despite Viral Suppression, and Correlates With Markers of Immune Dysregulation
Authors: Allison R Webel, Trevor Jenkins, Chris T Longenecker, Abuds Sattar, Shirley M Moore, Richard Josephson
Journal: Circulation (2015)

Introduction: Since transitioning to a chronic health condition, treated HIV infection is now recognized as an independent risk factor for cardiovascular disease. The underlying reasons for this risk association are unclear, but may include poor cardiopulmonary fitness. Objective: To describe cardiopulmonary fitness in people living with HIV (PLHIV) and its association to lifestyle exercise and HIV characteristics. Methods: As part of a larger randomized clinical trial, we conducted a cross sectional analysis of 37 PLHIV at high risk for developing CVD, on HIV medications, with suppressed HIV viremia. All subjects completed a bicycle cardiopulmonary stress test using a ramp protocol, wore an accelerometer on their hip for seven days, and consented to medical chart abstraction. We summarize the exercise habits and baseline cardiopulmonary fitness of our population, and further analyzed associations between continuous variables using Spearman correlation coefficients. Results: Overall, the study population had poor cardiopulmonary fitness (Table 1). Subjects exercised on average twice in the past week, but mostly (85%) light activity. Current CD4+ T cell count was significantly associated with VO2 max, peak heart rate, and % peak heart rate (Table 2). As expected, fitness variables were also associated in a graded fashion with time spent exercising in light, moderate, and moderate-vigorous activity. Conclusions: Current CD4+ T cell count and lifestyle exercise are significantly and consistently associated with cardiopulmonary fitness. Further work is necessary to understand how these relationships change over time and in response to interventions.
Researcher Requests for Inappropriate Analysis and Reporting: A U.S. Survey of Consulting Biostatisticians
Authors: Min Qi Wang, Alice F. Yan, Ralph V. Katz
Journal: Annals of Internal Medicine (2018)

Background: Inappropriate analysis and reporting of biomedical research remain a problem despite advances in statistical methods and efforts to educate researchers. Objective: To determine the frequency and severity of requests biostatisticians receive from researchers for inappropriate analysis and reporting of data during statistical consultations. Design: Online survey. Setting: United States. Participants: A randomly drawn sample of 522 American Statistical Association members self-identifying as consulting biostatisticians. Measurements: The Bioethical Issues in Biostatistical Consulting Questionnaire soliciting reports about the frequency and perceived severity of specific requests for inappropriate analysis and reporting. Results: Of 522 consulting biostatisticians contacted, 390 provided sufficient responses: a completion rate of 74.7%. The 4 most frequently reported inappropriate requests rated as "most severe" by at least 20% of the respondents were, in order of frequency, removing or altering some data records to better support the research hypothesis; interpreting the statistical findings on the basis of expectation, not actual results; not reporting the presence of key missing data that might bias the results; and ignoring violations of assumptions that would change results from positive to negative. These requests were reported most often by younger biostatisticians. Limitations: The survey provides information on the reported frequency of inappropriate requests but not on how such requests were handled or whether the requests reflected researchers' maleficence or inadequate knowledge about statistical and research methods. In addition, other inappropriate requests may have been made that were not prespecified in the survey. Conclusion: This survey suggests that researchers frequently make inappropriate requests of their biostatistical consultants regarding the analysis and reporting of their data. Understanding the reasons for these requests and how they are handled requires further study. Primary Funding Source: U.S. Department of Health and Human Services.
Glioma Cell Secretion: A Driver of Tumor Progression and a Potential Therapeutic Target
Authors: Damian A. Almiron Bonnin, Matthew C. Havrda, Mark A. Israel
Journal: Cancer Research (2018)

Cellular secretion is an important mediator of cancer progression. Secreted molecules in glioma are key components of complex autocrine and paracrine pathways that mediate multiple oncogenic pathologies. In this review, we describe tumor cell secretion in high-grade glioma and highlight potential novel therapeutic opportunities. Cancer Res; 78(21); 6031-9. ©2018 AACR.
GW29-e1186 Determination of Electrophysiological Effects and Cardiac Safety of Three Chinese Herb Monomers by Using the Isolated Rabbit Ventricular Wedge Model
Authors: Yuan Gao, Ge Song, Wenping Zhao, Tengxian Liu, Ganxin Yan, Youping Wang, Bin Li, Xinfeng Zhu, Zuoying Xing, Mingjun Zhu
Journal: Journal of the American College of Cardiology (2018)
Patritumab with Cetuximab plus Platinum-Containing Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: An Open-Label, Phase Ib Study
Authors: Magnus T. Dillon, Lorna Grove, Kate L. Newbold, Heather Shaw, Nicholas F. Brown, Jeanne Mendell, Shuquan Chen, Robert A. Beckman, Anne Jennings, Marivic Ricamara, Jonathan Greenberg, Martin Forster, Kevin J. Harrington
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose. Patients and Methods: Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m2 loading dose; 250 mg/m2 maintenance dose weekly) + cisplatin (100 mg/m2 every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Fifteen patients completed a median (range) of 8.7 (2.0–20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related n = 4). TEAEs (N = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N = 15) showed mean (SD) AUC0–21d of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N = 15) was 47%. Median (95% confidence interval) PFS and OS (N = 15) were 7.9 (3.7–9.7) and 13.5 (6.6–17.5) months, respectively. Conclusions: Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen.
Classification and Personalized Prognosis in Myeloproliferative Neoplasms
Authors: Jacob Grinfeld, Jyoti Nangalia, E. Joanna Baxter, David C. Wedge, Nicos Angelopoulos, Robert Cantrill, Anna L. Godfrey, Elli Papaemmanuil, Gunes Gundem, Cathy MacLean, Julia Cook, Laura O’Neil, Sarah O’Meara, Jon W. Teague, Adam P. Butler, Charlie E. Massie, Nicholas Williams, Francesca L. Nice, Christen L. Andersen, Hans C. Hasselbalch, Paola Guglielmelli, Mary F. McMullin, Alessandro M. Vannucchi, Claire N. Harrison, Moritz Gerstung, Anthony R. Green, Peter J. Campbell
Journal: New England Journal of Medicine (2018)

Myeloproliferative neoplasms, such as polycythemia vera, essential thrombocythemia, and myelofibrosis, are chronic hematologic cancers with varied progression rates. The genomic characterization of patients with myeloproliferative neoplasms offers the potential for personalized diagnosis, risk stratification, and treatment.
P3.13-26 Outcomes of Patients with Metastatic Lung Cancer Presented in a Multidisciplinary Molecular Tumor Board
Authors: L. Chu, K. Kelly, D. Gandara, P. Lara, A. Borowsky, F. Meyers, J. Mcpherson, R. Erlich, N. Almog, A. Schrock, S. Ali, J. Ross, V. Miller, A. Heilmann, J. Riess
Journal: Journal of Thoracic Oncology (2018)
Reply to the Letter of Dr. Mosca
Authors: T.  H.  Baron
Journal: Endoscopy (2003)

I appreciate the opportunity to expound on the issues raised by Dr. Mosca. The first issue is the use of a retrograde contrast (enema) study to assess the degree of stenosis and to exclude the presence of synchronous lesions, specifically in the patient with an acute (total) colonic obstruction. Although Dr. Mosca raises the concern about explosion, microperforation and bacteremia in patients with acute obstruction, I can personally attest that I have encountered many patients with acute colonic obstruction who have undergone water-soluble retrograde contrast studies without complications [1]. While it is unclear that it is absolutely necessary to perform a retrograde study prior to endoscopic stent placement, an experienced radiologist will not introduce air or excessive pressure in the presence of complete colonic obstruction. I agree with Dr. Mosca that the need to identify synchronous lesions is less important in patients with de novo acute obstruction compared with patients with known metastatic or recurrent malignancy (for example, widespread ovarian cancer).
Abstract 16877: Analysis of the Process and Content of Hot Debriefing After Pediatric In-Hospital Cardiac Arrest in a Multicenter Quality Collaborative
Authors: Todd Sweberg, Anita I Sen, Adam Cheng, Lynda Knight, Jimena del Castillo, Takanari Ikeyama, Tia Raymond, Dana Niles, Vinay Nadkarni, Paul Mullan, Heather Wolfe
Journal: Circulation (2017)

Introduction: Debriefing after pediatric in-hospital cardiac arrest (IHCA) events is recommended by the AHA for quality improvement. The process and content of hot debriefing, occurring shortly aft...
Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a <i>KRT6A</i> mutation
Authors: F. Abdollahimajd, F. Rajabi, M. Shahidi‐Dadras, S. Saket, L. Youssefian, H. Vahidnezhad, J. Uitto
Journal: British Journal of Dermatology (2018)

Pachyonychia congenita (PC) is a rare autosomal dominant disorder characterized by nail dystrophy and palmoplantar keratoderma with severe plantar pain affecting quality of life. There is no effective treatment. Heterozygous mutations in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 and KRT17 have been reported as a cause of PC. Herein we present a female patient with an amino acid substitution mutation in KRT6A (c.1381G>A, p.Glu461Lys in exon 7) and classic features of PC associated with oral leucokeratosis and follicular hyperkeratosis. We also demonstrate successful treatment of the patient with rosuvastatin. A 3.6‐mm reduction in plantar callosity thickness was demonstrated by sonography. Our patient also experienced significant pain relief that allowed her to increase physical activity (Children's Dermatology Life Quality Index score dropped nine points following treatment). Collectively, these improvements suggest that rosuvastatin may offer a promising treatment for PC.
Preliminary results of pamiparib (BGB-290), a PARP1/2 inhibitor, in combination with temozolomide (TMZ) in patients (pts) with locally advanced or metastatic solid tumors
Authors: M. Johnson, M. Galsky, M. Barve, S. Goel, H. Park, B. Du, S. Mu, V. Ramakrishnan, K. Wood, V. Wang, N. Lakhani
Journal: Annals of Oncology (2018)
Oral paclitaxel and HM30181A demonstrate clinical activity in metastatic breast cancer (MBC) patients
Authors: M.-S. Dai, T.-Y. Chao, T.-C. Chao, C.-F. Chiu, Y.-S. Lu, H.-S. Shiah, Y.-Y. Wu, G. Gerald Fetterly, N. Hung, D.L. Cutler, R. Kwan, D. Douglas Kramer, W.-K. Chan, T. Hung
Journal: Annals of Oncology (2018)
Experiences of bereaved family caregivers of patients with CTCL
Authors: D. Orlowska, L.E. Selman, T. Beynon, E. Radcliffe, S. Whittaker, F. Child, R. Harding
Journal: British Journal of Dermatology (2018)

Cutaneous T‐cell lymphomas (CTCL) are rare types of skin cancer. Skin may develop tumours or ulcers. Sometimes these may cover quite large areas and feel itchy or uncomfortable. Internal body parts may be affected in more advanced disease. Only a few people are diagnosed each year (8 per million), so most GPs do not meet people with this disease. This study from the U.K. aimed to find out about the experiences of family or close friends of people who had died because of the disease (not all people with this disease die of it). Relatives of 11 patients with CTCL who had died were interviewed, four months or more after the death. The themes from what they said are described. Family members gave vivid descriptions of how the illness changed the appearance of their relative. They spoke of how difficult it was to look after someone with very damaged skin. They described the many different things they had to do to care for their relative both in hospital and at home. Some patients had frequently been in and out of hospital. Some caregivers expected them to come home each time and so had not felt prepared when their relative died. Several caregivers described how upsetting it was to see how illness affected their relative before they died. The authors say that family caregivers should be seen as part of the care team looking after the patient. They recommend that carers’ needs for practical and emotional support and information should be considered during each patient's illness. Support for carers should also be offered following the death of their relative.
Abstract 19795: Clinical Determinants and Relation to Prognosis of Progressive Tubular Damage and Glomerular Decline in Chronic Heart Failure (Bio-SHiFT Study)
Authors: Milos Brankovic, K. Martijn Akkerhuis, Ewout J Hoorn, Nick van Boven, Jan C van den Berge, Alina Constantinescu, Jasper Brugts, Jan van Ramshorst, Tjeerd Germans, Hans Hillege, Eric Boersma, Victor Umans, Isabella Kardys
Journal: Circulation (2017)

Introduction: Tubular damage and glomerular decline predict clinical outcome in chronic heart failure (CHF). Yet, which patients are prone to these renal changes and how their joint assessment rela...
Abstract 17960: Off-Pump Coronary Artery Bypass Grafting Confers a Prognostic Benefit Compared to Percutaneous Coronary Intervention in Patients With Poor Left Ventricular Function: A Single Centre 10-Year Experience
Authors: Ian Cummings, Gianluca Lucchese, Mubassher Husain, Bilal Iqbal, Shahzad Raja
Journal: Circulation (2016)

Hypothesis: The benefits of ‘off-pump’ coronary artery bypass grafting (OPCABG) remain controversial. The ‘gold standard’ for surgical coronary revascularization remains ‘on-pump’ CABG. In selected...