tbuckley/cabot-search huggingface dataset:
Arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells: comparison of vasorelaxant effects of verapamil and phentolamine
Authors: Jing Jin, Xin Shen, Yu Tai, Shanliang Li, Mingyu Liu, Changlin Zhen, Xiuchen Xuan, Xiyue Zhang, Nan Hu, Xinzi Zhang, Deli Dong
Journal: Acta Pharmaceutica Sinica B (2017)

Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K+ (KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.
A Novel Anti-a Proliferation-Inducing Ligand Hapril.01A Monoclonal Antibody Targets Multiple Myeloma Cells in the Bone Marrow Microenvironment
Authors: Yu-Tzu Tai, Chirag Acharya, Gang An, Mike Y Zhong, Michele Cea, Antonia Cagnetta, Hua Jiang, Hans van Eenennaam, Andrea van Elsas, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2014)
M<sup>2+</sup> Doping Induced Simultaneous Phase/Size Control and Remarkable Enhanced Upconversion Luminescence of NaLnF<sub>4</sub> Probes for Optical‐Guided Tiny Tumor Diagnosis
Authors: Youbin Li, Xiaolong Li, Zhenluan Xue, Mingyang Jiang, Songjun Zeng, Jianhua Hao
Journal: Advanced Healthcare Materials (2017)

Doping has played a vital role in constructing desirable hybrid materials with tunable functions and properties via incorporating atoms into host matrix. Herein, a simple strategy for simultaneously modifying the phase, size, and upconversion luminescence (UCL) properties of the NaLnF 4 (Ln = Y, Yb) nanocrystals by high‐temperature coprecipitation through nonequivalent M 2+ doping (M = Mg 2+ , Co 2+ ) has been demonstrated. The phase transformation from cubic to hexagonal is readily achieved by doping M 2+ . Compared with Mg‐free sample, a remarkable enhancement of overall UCL (≈27.5 times) is obtained by doping Mg 2+ . Interestingly, owing to the efficient UCL, red UCL‐guided tiny tumor (down to 3 mm) diagnosis is demonstrated for the first time. The results open up a new way of designing high efficient UCL probe with combination of hexagonal phase and small size for tiny tumor detection.
Favorable Neurocognitive Outcome with Low Tidal Volume Ventilation after Cardiac Arrest
Authors: Jeremy R. Beitler, Tiffany Bita Ghafouri, Sayuri P. Jinadasa, Ariel Mueller, Leeyen Hsu, Ryan J. Anderson, Jisha Joshua, Sanjeev Tyagi, Atul Malhotra, Rebecca E. Sell, Daniel Talmor
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Neurocognitive outcome after out-of-hospital cardiac arrest (OHCA) is often poor, even when initial resuscitation succeeds. Lower tidal volumes (Vts) attenuate extrapulmonary organ injury in other disease states and are neuroprotective in preclinical models of critical illness.Objective: To evaluate the association between Vt and neurocognitive outcome after OHCA.Methods: We performed a propensity-adjusted analysis of a two-center retrospective cohort of patients experiencing OHCA who received mechanical ventilation for at least the first 48 hours of hospitalization. Vt was calculated as the time-weighted average over the first 48 hours, in milliliters per kilogram of predicted body weight (PBW). The primary endpoint was favorable neurocognitive outcome (cerebral performance category of 1 or 2) at discharge.Measurements and Main Results: Of 256 included patients, 38% received time-weighted average Vt greater than 8 ml/kg PBW during the first 48 hours. Lower Vt was independently associated with favorable neurocognitive outcome in propensity-adjusted analysis (odds ratio, 1.61; 95% confidence interval [CI], 1.13–2.28 per 1-ml/kg PBW decrease in Vt; P = 0.008). This finding was robust to several sensitivity analyses. Lower Vt also was associated with more ventilator-free days (β = 1.78; 95% CI, 0.39–3.16 per 1-ml/kg PBW decrease; P = 0.012) and shock-free days (β = 1.31; 95% CI, 0.10–2.51; P = 0.034). Vt was not associated with hypercapnia (P = 1.00). Although the propensity score incorporated several biologically relevant covariates, only height, weight, and admitting hospital were independent predictors of Vt less than or equal to 8 ml/kg PBW.Conclusions: Lower Vt after OHCA is independently associated with favorable neurocognitive outcome, more ventilator-free days, and more shock-free days. These findings suggest a role for low-Vt ventilation after cardiac arrest.
Transient elastography versus hepatic venous pressure gradient for diagnosing portal hypertension: a systematic review and meta-analysis
Authors: Gaeun Kim, Moon Young Kim, Soon Koo Baik
Journal: Clinical and Molecular Hepatology (2017)

Transient elastography (TE) has been proposed as a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for detecting portal hypertension (PH). However, previous studies have yielded conflicting results. We gathered evidence from literature on the clinical usefulness of TE versus HVPG for assessing PH.We conducted a systematic review by searching databases for relevant literature evaluating the clinical usefulness of non-invasive TE for assessing PH in patients with cirrhosis. A literature search in Ovid Medline, EMBASE and the Cochrane Library was performed for all studies published prior to December 30, 2015.Eight studies (1,356 patients) met our inclusion criteria. For the detection of PH (HVPG ≥6 mmHg), the summary sensitivity and specificity were 0.88 (95% confidence interval [CI] 0.86-0.90) and 0.74 (95% CI 0.67-0.81), respectively. Regarding clinically significant PH (HVPG ≥10 mmHg), the summary sensitivity and specificity were 0.85 (95% CI 0.63-0.97) and 0.71 (95% CI 0.50-0.93), respectively. The overall correlation estimate of TE and HVPG was large (0.75, 95% CI: 0.65; 0.82, P<0.0001).TE showed high accuracy and correlation for detecting the severity of PH. Therefore, TE shows promise as a reliable and non-invasive procedure for the evaluation of PH that should be integrated into clinical practice.
Abstract P6-10-07: Long survival of patients with locally advanced breast cancer on combined neoadjuvant chemotherapy and immune potentiation: Modern lessons from an old study
Authors: PR Pohlmann, H van Cruijsen, AGM Stam, SM Lougheed, AJM van den Eertwegh, K Hoekman, R Scheper, J Buter, JJM van der Hoeven, E van der Wall, HM Pinedo, TD de Gruijl
Journal: Cancer Research (2017)

Abstract This abstract was not presented at the symposium.
Identification of an epithelial member of the protease family, supporting the potential diagnostic and therapeutic role of serine proteases in IBS
Authors: Benedicte Y De Winter
Journal: Gut (2017)

The quest for appropriate diagnostic tools and therapies for IBS runs in parallel with the different pathogenic mechanisms investigated. One of these mechanisms is visceral hypersensitivity, resulting from a disturbed neuronal signalling at the peripheral and/or central levels.1 ,2 Rolland-Fourcade et al 3 show, in this issue of Gut , that intestinal epithelial cells (Caco-2 cells) release a trypsin-like activity at the basolateral side of the cells after stimulation with a classical inflammatory stimulus (lipopolysaccharide) or with a stress-related stimulus (epinephrine), and they identified it as trypsin-3. They confirmed the clinical relevance of trypsin-3 by proving its presence in colonic tissue from patients with IBS (all subgroups). Besides, trypsin-3 increased epithelial permeability in the Caco-2 monolayers and increased the excitability of mouse dorsal root ganglia neurons in vitro . Moreover, it induced Ca+2 transients in human submucosal neurons in vitro and caused visceral hyperalgesia in response to colorectal distension in two rat models of visceral hypersensitivity.3 The novelty of this manuscript lies within the identification of a specific protease, namely trypsin-3 and its source, the intestinal epithelium, providing additional evidence for serine proteases and protease-activated receptors (PAR).

The importance of visceral hypersensitivity as a key contributor to the generation of symptoms in patients with …
25-hydroxyvitamin D concentrations during fetal life and bone health in children aged 6 years: a population-based prospective cohort study
Authors: Audry H Garcia, Nicole S Erler, Vincent W V Jaddoe, Henning Tiemeier, Edith H van den Hooven, Oscar H Franco, Fernando Rivadeneira, Trudy Voortman
Journal: The Lancet Diabetes & Endocrinology (2017)
Water exchange for screening colonoscopy increases adenoma detection rate: a multicenter, double-blinded, randomized controlled trial
Authors: Sergio Cadoni, Přemysl Falt, Emanuele Rondonotti, Franco Radaelli, Petr Fojtik, Paolo Gallittu, Mauro Liggi, Arnaldo Amato, Silvia Paggi, Vit Smajstrla, Ondřej Urban, Matteo Erriu, Malcolm Koo, Felix Leung
Journal: Endoscopy (2017)

<b>Background and study aims</b> Single-center studies, which were retrospective and/or involved unblinded colonoscopists, have suggested that water exchange, but not water immersion, compared with air insufflation significantly increases the adenoma detection rate (ADR), particularly in the proximal and right colon. Head-to-head comparison of the three techniques with ADR as primary outcome and blinded colonoscopists has not been reported to date. In a randomized controlled trial with blinded colonoscopists, we aimed to evaluate the impact of the three insertion techniques on ADR. <b>Patients and methods</b> A total of 1224 patients aged 50 – 70 years (672 males) and undergoing screening colonoscopy were randomized 1:1:1 to water exchange, water immersion, or air insufflation. Split-dose bowel preparation was adopted to optimize colon cleansing. After the cecum had been reached, a second colonoscopist who was blinded to the insertion technique performed the withdrawal. The primary outcome was overall ADR according to the three insertion techniques (water exchange, water immersion, and air insufflation). Secondary outcomes were other pertinent overall and right colon procedure-related measures. <b>Results</b> Baseline characteristics of the three groups were comparable. Compared with air insufflation, water exchange achieved a significantly higher overall ADR (49.3 %, 95 % confidence interval [CI] 44.3 % – 54.2 % vs. 40.4 % 95 %CI 35.6 % – 45.3 %; <i>P </i> = 0.03); water exchange showed comparable overall ADR vs. water immersion (43.4 %, 95 %CI 38.5 % – 48.3 %; <i>P </i> = 0.28). In the right colon, water exchange achieved a higher ADR than air insufflation (24.0 %, 95 %CI 20.0 % – 28.5 % vs. 16.9 %, 95 %CI 13.4 % – 20.9 %; <i>P </i> = 0.04) and a higher advanced ADR (6.1 %, 95 %CI 4.0 % – 9.0 % vs. 2.5 %, 95 %CI 1.2 % – 4.6 %; <i>P</i> = 0.03). Compared with air insufflation, the mean number of adenomas per procedure was significantly higher with water exchange (<i>P</i> = 0.04). Water exchange achieved the highest cleanliness scores (overall and in the right colon). These variables were comparable between water immersion and air insufflation. <b>Conclusions</b> The design with blinded observers strengthens the validity of the observation that water exchange, but not water immersion, can achieve significantly higher adenoma detection than air insufflation. Based on this evidence, the use of water exchange should be encouraged. Trial registered at ClinicalTrials.gov (NCT02041507).
A distinct entorhinal cortex to hippocampal CA1 direct circuit for olfactory associative learning
Authors: Yiding Li, Jiamin Xu, Yafeng Liu, Jia Zhu, Nan Liu, Wenbo Zeng, Ning Huang, Malte J Rasch, Haifei Jiang, Xiang Gu, Xiang Li, Minhua Luo, Chengyu Li, Junlin Teng, Jianguo Chen, Shaoqun Zeng, Longnian Lin, Xiaohui Zhang
Journal: Nature Neuroscience (2017)
Transcriptional Mediator Subunit MED1/TRAP220 Acts in Stromal Cells to Support Hematopoietic Stem/Progenitor Cells through Coactivation of Osteopontin Transcription.
Authors: Akiko Sumitomo, Norinaga Urahama, Kana Inoue, Ruri Ishino, Kenji Yonezawa, Natsumi Hasegawa, Chisa Iwasaki, Osamu Horie, Naohiko Seki, Mitsuhiro Ito
Journal: Blood (2009)
Intratumor heterogeneity as an opportunity for drug sensitivity prediction and biomarker discovery.
Authors: Qiang Gao, William Niu, Andrew Tse, Jeffrey Lin, Zhou Jian, Simon Shung, Fan Jia
Journal: Journal of Clinical Oncology (2014)

e15151 Background: Individual tumor carrying extensive heterogeneity that can lead to treatment failure and drug resistance is widely accepted. Yet, the relationship between intratumor genetic heterogeneity and drug response has not been systematically investigated. Methods: A set of 26 cell lines derived from one patient with hepatocellular carcinoma (HCC) was established, and systematically integrated by transcriptional profiling, chromosomal copy number variation (CNV) and whole-exome sequencing, along with parental tumor tissues. The drug response profiles of over 70 targeted agents were also examined. Results: CNV data suggested that, among the 26 cell lines, 13 of 23 (~60%) chromosomes had obvious cytogenetical differences with a cell-line specific enrichment. Likewise, the transcriptional profiling and sequencing data further supported the presence of clinically relevant intratumor heterogeneity in those lines. For examples, Sonic Hedgehog (SHH) pathway was active in about 30% of lines, SRC pathway was highly active in 10 (38.5%) lines and completely inactive in 6 (23.1%) lines, and mTOR pathway was active in about 50% of lines. The results indicated a high level of heterogeneity among the lines established from one HCC, which was inherited from the spatially separated original tumor tissues. Notably, based on the compound screening data, the cell panel had same response patterns (sensitive or resistant) to over 80% of tested compounds. For instances, despite the active and inactive status of pathways, all 26 lines were sensitive to KX2-391 (SRC inhibitor) and resistant to Vismodegib (SHH inhibitor). Only very few inhibitors had distinct response profiles among the 26 lines, such as FGFR and MEK inhibitors, where a maximum of 30-folds difference in sensitivity was observed. Conclusions: The 26-cell line panel provides a powerful platform for the genomic heterogeneity screening and validation, favoring the emergence of precision therapeutic regimens. Although the majority of drugs showed similar activity among the cell lines, intratumor heterogeneity affected the action of certain drugs, suggesting that sensitivity could be defined by specific genomic occurrences.
Flow Cytometry Based Detection of MRD in Bone Marrow of Patients with Multiple Myeloma: A Comparison Between Fluorescent-Based Cytometry Versus Cytof
Authors: Arnab Ghosh, Nicole Carreau, Alessandra Moscatello, Adeeb Rahman, Jingjing Qi, Seunghee Kim-Schulze, Shyamala C. Navada, Ajai Chari, Hearn Jay Cho, Sundar Jagannath, Samir Parekh
Journal: Blood (2015)
Depressive symptoms in high-performance athletes and non-athletes: a comparative meta-analysis
Authors: Paul Filip Gorczynski, Melissa Coyle, Kass Gibson
Journal: British Journal of Sports Medicine (2017)

Objective To assess whether a difference exists in the prevalence of mild or more severe depressive symptoms between high-performance athletes and non-athletes. Design Comparative OR meta-analysis. Data sources We searched PsycINFO, PubMed, MEDLINE, CINAHL, SPORTDiscus and Google Scholar, as well as the reference lists of reviews of mental health issues in high-performance athletes. Eligibility We included studies that compared high-performance athletes and non-athletes, included a validated measure of depressive symptoms and included the prevalence of individuals who indicated at least mild depressive symptoms. Results Five articles reporting data from 1545 high-performance athletes and 1811 non-athletes were examined. A comparative OR meta-analysis found high-performance athletes were no more likely than non-athletes to report mild or more severe depressive symptoms (OR=1.15, 95% CI=0.954 to 1.383, p=0.145). Male high-performance athletes (n=940) were no more likely than male non-athletes (n=605) to report mild or more severe depressive symptoms (OR=1.17, 95% CI=0.839 to 1.616, p=0.362). For females, high-performance athletes (n=948) were no more likely than non-athletes (n=605) to report mild or more severe depressive symptoms (OR=1.11, 95% CI=0.846 to 1.442, p=0.464). Overall, male high-performance athletes (n=874) were 52% less likely to report mild or more severe depressive symptoms than female high-performance athletes (n=705) (OR=0.48, 95% CI=0.369 to 0.621, p&lt;0.001). Summary/conclusions High-performance athletes were just as likely as non-athletes to report depressive symptoms. Researchers need to move beyond self-report measures of depressive symptoms and examine the prevalence of clinically diagnosed depressive disorders in athletes.
Does Heparin Have An Anti-Myeloma Effect? An Analysis On Individual Data From Three Randomized Studies of GIMEMA, Nordic and Turkish Myeloma Study Groups,
Authors: Meral Beksac, Anders Waage, Sara Bringhen, Sigurdur Y Kristinsson, Gulsan Sucak, Peter Gimsing, Lupparelli Giulia, Tulin Firatli Tuglular, Gunnar Juliusson, Antonio Palumbo
Journal: Blood (2011)
Frontline Therapy for Older Patients (pts) with Acute Myeloid Leukemia (AML): Clofarabine Plus Low-Dose Cytarabine Induction Followed by Prolonged Consolidation with Clofarabine Plus Low-Dose Cytarabine Alternating with Decitabine
Authors: Stefan Faderl, Farhad Ravandi, Guillermo Garcia-Manero, Xuelin Huang, Elias Jabbour, Tapan Kadia, Alessandra Ferrajoli, Zeev Estrov, Jennie Feliu, Heather Schroeder, Monica Kwari, Hagop Kantarjian
Journal: Blood (2010)
Atrial Fibrillation in Patients with Chronic Lymphocytic Leukemia (CLL)
Authors: Tait D. Shanafelt, Kari G. Chaffee, Timothy G. Call, Sameer A. Parikh, Susan M. Schwager, Wei Ding, Jose F. Leis, Asher Chanan-Khan, Susan L. Slager, Neil E. Kay
Journal: Blood (2015)
Immunoglobulin Free Light Chain Levels Predict Survival in Primary Myelofibrosis and De Novo Myelodysplastic Syndromes
Authors: Animesh Pardanani, Terra L Lasho, Christy Finke, S. Vincent Rajkumar, Preet Paul Singh, Rhett P Ketterling, Curtis A. Hanson, Jerry A Katzmann, Ayalew Tefferi
Journal: Blood (2011)
Serum microRNA profiling in patients with glioblastoma: a survival analysis
Authors: Hua Zhao, Jie Shen, Tiffany R. Hodges, Renduo Song, Gregory N. Fuller, Amy B. Heimberger
Journal: Molecular Cancer (2017)

Because circulating microRNAs (miRNAs) have drawn a great deal of attention as promising novel cancer diagnostics and prognostic biomarkers, we sought to identify serum miRNAs significantly associated with outcome in glioblastoma patients. To do this, we performed global miRNA profiling in serum samples from 106 primary glioblastoma patients. The study subjects were randomly divided into two sets: set one (n = 40) and set two (n = 66). Using a Cox regression model, 3 serum miRNAs (miR-106a-5p, miR-182, and miR-145-5p) and 5 serum miRNAs (miR-222-3p, miR-182, miR-20a-5p, miR-106a-5p, and miR-145-5p) were identified significantly associated with 2-year patient overall survival and disease-free survival (P < 0.05) in both sets and the combined set. We then created the miRNA risk scores to assess the total impact of the significant serum miRNAs on survival. The high risk scores were associated with poor patient survival (overall survival: HR = 1.92, 95% CI: 1.19, 10.23, and disease-free survival: HR = 2.03, 95%CI: 1.24, 4.28), and were independent of other clinicopathological factors. Our results suggest that serum miRNAs could serve as prognostic predictors of glioblastoma.
Abstract P3-07-19: Dual inhibition of the MEK5 and PI3K pathways synergistically reduces proliferation and viability in triple negative breast cancer cells
Authors: TD Wright, C Raybuck, K Wendekier, JE Cavanaugh
Journal: Cancer Research (2017)

Abstract Aberrations in the MAPK/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide-3-kinase (PI3K) pathways have been linked to increased proliferation and survival in triple negative breast cancer (TNBC) cells. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. Promising combinations of MEK and PI3K inhibition have been evaluated in phase I clinical trials for various cancer types. However, these clinical trials have had limited efficacy and have yet to encompass the MEK5/ERK5 pathway, which has been shown to promote cell survival. The goal of this study was to examine the crosstalk between the MEK1/2, MEK5, and PI3K pathways and determine the most promising combination of the MEK1/2, ERK5, and PI3K inhibitors, U0126, XMD8-92, and LY294002, respectively, in a diverse panel of triple negative breast cancer cell lines: BT549, MDA-MB-231, and MDA-MB-468. Our results indicate that dual inhibition of the MEK5 and PI3K pathways significantly reduced proliferation (45.53%) in MDA-MB-231 TNBC cells. Also, the combination of MEK5 and PI3K inhibition was shown to be synergistic. In contrast, inhibition of ERK1/2 alone or in combination with PI3K or ERK5 inhibition yielded mixed responses. Additionally, treatment with LY294004 in MDA-MB-231 (ERK 5 KO) was more potent (IC50= 2.5 uM) than treatment in the native MDA-MB-231 cell line (IC50= 13.7 uM). These data suggest that crosstalk between these kinases occurs and dual inhibition of PI3K and ERK5 may be a novel therapeutic approach for treating TNBC. Citation Format: Wright TD, Raybuck C, Wendekier K, Cavanaugh JE. Dual inhibition of the MEK5 and PI3K pathways synergistically reduces proliferation and viability in triple negative breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-07-19.
Clonal Gammopathies Following Reduced Intensity Conditioning Transplantation with Fludarabine, Busulphan and Alemtuzumab for Myeloid Malignancies Predict Improved Overall Survival.
Authors: ZiYi Lim, Antonio Pagliuca, Wendy Ingram, Dragana Milojkovic, Mojtaba Akthari, Aloysius Ho, Stephen Devereux, Rafael Duarte, Ghulam J. Mufti
Journal: Blood (2005)
Long-Term Health Outcomes and Costs Associated with the Use of Rituximab in Combination with fludarabine and Cyclophosphamide (R-FC) in the Treatment of relapsed or Refractory Chronic Lymphocytic Leukaemia (CLL) in Poland.
Authors: Tadeusz Robak, Monika Szkultecka-Dêbek, Rick Aultman, Emma S Carr, P. Kawalec
Journal: Blood (2009)
SCID-Synth-Hu: a Novel Multiple Myeloma Model for In Vivo Expansion of Primary Cells
Authors: Teresa Calimeri, Edmondo Battista, Francesco Conforti, Paola Neri, Maria Teresa Di Martino, Marco Rossi, Umberto Foresta, Eugenio Piro, Fiorenzo Ferrara, Andrea Amorosi, Nizar Bahlis, Kenneth C. Anderson, Nikhil C. Munshi, Pierosandro Tagliaferri, Filippo Causa, Pierfrancesco Tassone
Journal: Blood (2010)