tbuckley/cabot-search huggingface dataset:
Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases?
Authors: Don D. Sin, S.F. Paul Man
Journal: Circulation (2003)

Background— Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular disease 2- to 3-fold. The factors responsible for this association remain largely unknown. Methods and Results— We analyzed data from participants, ≥50 years of age, of the Third National Health and Nutrition Examination Survey (n=6629) to determine whether C-reactive protein (CRP) and other systemic inflammatory markers are present in participants with chronic airflow obstruction and are associated with cardiac injury. Participants with severe airflow obstruction had circulating leukocyte, platelet, and fibrinogen levels that were 460/μL (95% confidence interval [CI], 30 to 890/μL), 39 510/μL (95% CI, 21 730 to 57 290/μL), and 41.63 mg/dL (95% CI, 19.87 to 63.39 mg/dL) higher, respectively, than in those without airflow obstruction. They were also 2.18 times (95% CI, 1.46 to 3.27) more likely to have an elevated circulating CRP level. Moderate airflow obstruction was associated with smaller but still significant increases in these levels. Moderate and severe airflow obstruction was associated with increased occurrence of ischemic changes on electrocardiograms of participants. In the presence of both highly elevated CRP and moderate or severe airflow obstruction, the Cardiac Infarction Injury Score was 2.68 and 5.88 U higher, respectively, than in those without airflow obstruction and with low CRP, which suggests an additive effect of CRP and COPD on the risk of cardiac injury. Conclusion— Low-grade systemic inflammation was present in participants with moderate to severe airflow obstruction and was associated with increased risk of cardiac injury. This may in part explain the high rates of cardiovascular complications in COPD.
Highly Luminescent Folate‐Functionalized Au<sub>22</sub> Nanoclusters for Bioimaging
Authors: Kyunglim Pyo, Nguyen Hoang Ly, Sook Young Yoon, Yiming Shen, Seon Young Choi, So Yeong Lee, Sang‐Woo Joo, Dongil Lee
Journal: Advanced Healthcare Materials (2017)

Gold nanoclusters are emerging as new materials for biomedical applications because of promises offered by their ultrasmall size and excellent biocompatibility. Here, the synthesis and optical and biological characterizations of a highly luminescent folate-functionalized Au22 cluster (Au22 -FA) are reported. The Au22 -FA clusters are synthesized by functionalizing the surface of Au22 (SG)18 clusters, where SG is glutathione, with benzyl chloroformate and folate. The functionalized clusters are highly water-soluble and exhibit remarkably bright luminescence with a quantum yield of 42%, significantly higher than any other water-soluble gold clusters protected with thiolate ligands. The folate groups conjugated to the gold cluster give rise to additional luminescence enhancement by energy transfer sensitization. The brightness of Au22 -FA is found to be 4.77 mM-1 cm-1 , nearly 8-fold brighter than that of Au22 (SG)18 . Further biological characterizations have revealed that the Au22 -FA clusters are well-suited for bioimaging. The Au22 -FA clusters exhibit excellent photostability and low toxicity; nearly 80% cell viability at 1000 ppm of the cluster. Additionally, the Au22 -FA clusters show target specificity to folate-receptor positive cells. Finally, the time-course in vivo luminescence images of intravenous-injected mice show that the Au22 -FA clusters are renal-clearable, leaving only 8% of them remained in the body after 24 h post-injection.
機械的シグナル伝達タンパク質PIEZO1の突然変異は遺伝性乾燥細胞増加(hereditary xerocytosis)と関連
Authors: Zarychanski Ryan, P Schulz Vincent, L Houston Brett, Maksimova Yelena, S Houston Donald, Smith Brian, Rinehart Jesse, G Gallagher Patrick
Journal: Blood (2012)
Abstract 15874: Effect of Blood Pressure During the Acute Phase on 3-month and 2-year Clinical Outcomes Among Patients With Ischemic Stroke
Authors: Changwei Li, Yonghong Zhang, Tan Xu, Xiaoqing Bu, Hao Peng, Jing Chen, Jiang He
Journal: Circulation (2016)

We studied the effect of systolic blood pressure (SBP, mean and variability) during the acute phase on 3-month and 2-year major clinical outcomes in patients with ischemic stroke. The China Antihyp...
Gene Duplication Leads to Altered Membrane Topology of a Cytochrome P450 Enzyme in Seed Plants
Authors: Hugues Renault, Minttu De Marothy, Gabriella Jonasson, Patricia Lara, David R. Nelson, IngMarie Nilsson, François André, Gunnar von Heijne, Danièle Werck-Reichhart
Journal: Molecular Biology and Evolution (2017)

Evolution of the phenolic metabolism was critical for the transition of plants from water to land. A cytochrome P450, CYP73, with cinnamate 4-hydroxylase (C4H) activity, catalyzes the first plant-specific and rate-limiting step in this pathway. The CYP73 gene is absent from green algae, and first detected in bryophytes. A CYP73 duplication occurred in the ancestor of seed plants and was retained in Taxaceae and most angiosperms. In spite of a clear divergence in primary sequence, both paralogs can fulfill comparable cinnamate hydroxylase roles both in vitro and in vivo. One of them seems dedicated to the biosynthesis of lignin precursors. Its N-terminus forms a single membrane spanning helix and its properties and length are highly constrained. The second is characterized by an elongated and variable N-terminus, reminiscent of ancestral CYP73s. Using as proxies the Brachypodium distachyon proteins, we show that the elongation of the N-terminus does not result in an altered subcellular localization, but in a distinct membrane topology. Insertion in the membrane of endoplasmic reticulum via a double-spanning open hairpin structure allows reorientation to the lumen of the catalytic domain of the protein. In agreement with participation to a different functional unit and supramolecular organization, the protein displays modified heme proximal surface. These data suggest the evolution of divergent C4H enzymes feeding different branches of the phenolic network in seed plants. It shows that specialization required for retention of gene duplicates may result from altered protein topology rather than change in enzyme activity.
Apoptosis induction mediated through PI3-kinase/AKT/mTOR pathway using anti-ROR1 monoclonal antibody in chronic lymphocytic leukemia cells.
Authors: Amir Hossein Daneshmanesh, Mohammad Hojat Farsangi, Ali Moshfegh, Salam Khan, Anders Österborg, Hakan Mellstedt
Journal: Journal of Clinical Oncology (2013)

7087 Background: The PI3K/AKT/mTOR is a central pathway activated in many types of cancer. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase regulating cell growth, proliferation and survival. In CLL cells PI3K pathway is constitutively activated leading to AKT activation with subsequent phosphorylation of other downstream signaling molecules. ROR1 is a type I transmembrane RTK, overexpressed and constitutively phosphorylated in CLL. A unique anti-ROR1 mAb directed against CRD region of ROR1 was capable of inducing direct apoptosis as well as dephosphorylating the ROR1 molecule. Here, we investigated the apoptotic effect of the anti-ROR1 mAb and effects on the PI3K/AKT/mTOR pathway using primary CLL cells. Methods: Apoptosis was detected by the MTT assay and Annexin V/PI methods in a 24 h assay. Antibody untreated and treated cell lysates were prepared and subjected to Western blot analysis for identification of the signaling molecules involved in apoptosis induced by the ROR1 mAb. We analysed total and phosphorylated levels of the following signaling proteins: AKT, p-AKT, PI3K, p-PI3K, mTOR, p-mTOR, ERK, p-ERK, PKC and p-PKC. Phosphoproteins were measured before incubation with the mAb and after 20 min-24 h. Results: ROR1 detection on surface of the CLL cells was 80-85% and apoptotic frequency 45-50%. Western blot analysis showed decreased levels of p-AKT, p85 isoform of p-PI3K and p-mTOR in treated compared to untreated samples. No changes in the phosphorylation levels of ERK and PKC proteins were seen. Conclusions: Incubation of CLL cells with the anti-ROR1 mAb induced apoptosis of CLL cells. Apoptosis was preceded by dephosphorylation of PI3K, AKT and mTOR proteins indicating deactivation of these proteins by the ROR1 mAb. In untreated CLL cells no effect was noted. Furthermore no dephosphorylation of PKC or ERK was seen. We suggest that activation of mTOR might occur via the PI3K/AKT pathway and may be a survival signal in CLL cells associated with the aberrant expression of ROR1. Further studies are warranted to understand better the signaling pathways associated with ROR1 and the downstream signaling effects of ROR1 targeting drugs.
A multi-institution study of the accuracy of BRCAPRO in predicting BRCA1/BRCA2 mutations in women with ovarian cancer.
Authors: Molly S Daniels, Sheri Babb, Robin King, Diana Urbauer, Christopher I. Amos, Amanda C. Brandt, Adam Buchanan, David Gardner Mutch, Karen H. Lu
Journal: Journal of Clinical Oncology (2012)

1520 Background: 10-15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation, with significant management implications for both patients and relatives. Genetic testing decisions are guided in part by the estimated likelihood of identifying a mutation. The BRCAPRO model uses personal and family history of breast and ovarian cancer to calculate the likelihood of a BRCA1/2 mutation. This study’s purpose was to assess the ability of BRCAPRO to accurately determine this likelihood. Methods: BRCAPRO scores were calculated using CancerGene v5.1 for 589 ovarian cancer patients referred for genetic counseling at three institutions. The study population was divided into quintiles by BRCAPRO score, with cutpoints chosen such that each quintile represented 20% of the sample. Chi-square goodness-of-fit test was used to compare observed BRCA1/2 mutations to the number predicted. ANOVA models were used to assess factors impacting BRCAPRO accuracy. Results: 180/589 (31%) ovarian cancer patients tested positive for a BRCA1/2 mutation. At BRCAPRO scores under 40%, more mutations were observed than expected (93 observed vs. 34.1 expected, p&lt;0.001). If patients with BRCAPRO scores &lt;10% had not been offered genetic testing, almost one-third of mutations (51/180, 28%) would have been missed. Multivariate analysis demonstrated that BRCAPRO underestimated risk for high grade serous ovarian cancers but overestimated risk for other histologies (p&lt;0.0001), underestimation increased as age at diagnosis decreased (p=0.02), and model performance varied by institution (p=0.02). Conclusions: Ovarian cancer patients classified as low risk by BRCAPRO are more likely to test positive than predicted, therefore the BRCAPRO prediction could falsely reassure patients considering genetic testing. BRCAPRO performance could be improved by incorporating factors such as ovarian cancer histology. Alternatively, given the high prevalence of BRCA1/2 mutations in high grade serous ovarian cancer and the apparent limitations of using family history to predict mutation probability, BRCA1/2 genetic testing could be offered to high grade serous ovarian cancer patients regardless of family history.
Observational study of ferric carboxymaltose in France (OncoFer; interim analysis).
Authors: Alain Toledano, Elisabeth Luporsi, Florian Scotté, Jean F. Morere, Philippe Huot-Marchand, Lorraine B. Zakin, Lamine Mahi, Roland Bugat
Journal: Journal of Clinical Oncology (2013)

e20654 Background: Iron deficiency with anemia is a frequent complication in cancer.Ferric carboxymaltose (FCM) is approved for the correction of iron deficiency in France since the beginning of 2011. This observational multicenter study has recruited 2 cohorts of patients to describe FCM use in daily practice for patients with hematological malignancies or solid tumors. Methods: Cohort 1 (retrospective): 450 patients treated in 2010 with any intravenous (IV) iron or red blood cell transfusion (BT); Cohort 2 (prospective): 450 patients treated with FCM after July 1, 2011. Patient characteristics are collected for 3 months pre and post intervention. Recruitment of the 810 patients has been completed. Results: Outcomes of the first 100 patients are described below. The majority of patients receiving FCM had metastatic solid tumors and received just under 1000 mg iron. Hematological malignancies were only included in BT cohort. Results are detailed below. Number of patients at baseline with serum ferritin (SF) level and TSAT are 10 and 7 respectively in cohort 1 and 28 and 26 respectively in cohort 2, therefore the reason for initiating FCM appeared to be based predominately on Hb level. Functional iron deficiency was present in 85% where TSAT and ferritin were measured. No related serious adverse events were reported for the IV iron preparations. Conclusions: FCM was well tolerated and seemed effective in treating iron deficiency anemia. Administration was usually delivered at home with fewer infusions required for FCM compared to iron sucrose. These interim results need to be confirmed in the final analysis. [Table: see text]
The antimicrobial peptide human beta-defensin 2 promotes itch through Toll-like receptor 4 signaling in mice
Authors: Jing Feng, Jialie Luo, Madison R. Mack, Pu Yang, Feng Zhang, Guan Wang, Xuan Gong, Tao Cai, Zhinan Mei, Brian S. Kim, Shijin Yin, Hongzhen Hu
Journal: Journal of Allergy and Clinical Immunology (2017)
Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia
Authors: Alice Giustacchini, Supat Thongjuea, Nikolaos Barkas, Petter S Woll, Benjamin J Povinelli, Christopher A G Booth, Paul Sopp, Ruggiero Norfo, Alba Rodriguez-Meira, Neil Ashley, Lauren Jamieson, Paresh Vyas, Kristina Anderson, Åsa Segerstolpe, Hong Qian, Ulla Olsson-Strömberg, Satu Mustjoki, Rickard Sandberg, Sten Eirik W Jacobsen, Adam J Mead
Journal: Nature Medicine (2017)
Civil Defense Agency
Authors: Thomas F. Maher
Journal: New England Journal of Medicine (1954)

No one tome could ever adequately portray the extent of the widespread havoc caused by 3 of the greatest storms ever to strike New England. The Worcester tornado of June 9, 1953, and the hurricanes of August 31 and September 11, 1954, will be long remembered. Since more than 51 tornadoes and several hurricanes have been counted in New England since 1775, recent experience is of significance for future guidance and planning.Table 1 indicates in a general way the frequency and extent of major disasters in New England in recent years.The tornado and the hurricanes required many of the hospitals . . .
AGA White Paper: Training and Implementation of Endoscopic Image Enhancement Technologies
Authors: Neil Gupta, Joel V. Brill, Marcia Canto, Daniel DeMarco, Brian M. Fennerty, Loren Laine, David Lieberman, Charles Lightdale, Elizabeth Montgomery, Robert Odze, Douglas Rex, Prateek Sharma, Jeffrey L. Tokar, Michael L. Kochman
Journal: Clinical Gastroenterology and Hepatology (2017)
von Hippel-Lindau Disease
Authors: William G. Kaelin
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

von Hippel-Lindau disease, which is characterized by an increased risk of hemangioblastomas, clear cell renal carcinomas, and pheochromocytomas, is caused by inactivating mutations of the VHL tumor suppressor gene. The VHL gene product, pVHL, has multiple functions, but the best documented, and the one most clearly linked to tumor development, relates to its role as the substrate recognition module of a ubiquitin ligase complex that targets hypoxia-inducible factor (HIF) for destruction. pVHL function is often compromised in sporadic kidney cancers, and inhibitors of the HIF-responsive growth factor (vascular endothelial growth factor) are active against this disease. pVHL, by inhibiting atypical protein kinase C and hence JunB, also affects neuronal survival, as do the products of the other genes linked to familial pheochromocytoma or paraganglioma (NF1, RET, SDHB, SDHC, and SDHD). It is hypothesized that tumor-associated alleles of these genes allow primitive sympathoadrenal precursors to escape developmental culling, and that such cells are at increased risk of forming tumors.
Abstract P088: The Rate of Inorganic Phosphate Release in Contracting Rat Trabeculae Is Independent of Calcium After Stretch
Authors: Catherine Mansfield, Timothy West, Mike Ferenczi
Journal: Circulation Research (2011)

We aim to reveal the molecular mechanism underlying the force response to stretch in the heart by examining the dependence of the rate of inorganic phosphate (P i ) release in response to stretch on the degree of calcium activation. Permeabilized trabeculae of rat heart are activated by photolytic release of ATP, at 20°C, in the presence of saturating (32µM), or half-saturating (1µM), calcium concentrations, at an initial sarcomere length of 1.9 or 2.1 µm. For trabeculae with an initial sarcomere length of 1.9 µm, the trabeculae are stretched to 2.1 µm during the isometric plateau, held at a constant length and returned to their original length. The rate of P i release is determined by the fluorescence change associated with phosphate binding to a fluorescently-labelled phosphate binding protein diffused into the preparation. At an initial sarcomere length of 1.9µm, the isometric force at full activation was 51 kN.m −2 compared to 26kN.m −2 at half-maximal activation. During the isometric phase, P i release is at a steady rate of 8.2 and 4.8 s −1 (assuming a myosin head concentration of 120µM) at 32 and 1µM calcium, respectively. During stretch, the rate of P i release decreases markedly at both activation levels, to1.0 and 1.4s −1 respectively. Activation from an initial sarcomere length of 2.1µm produced an isometric force of 65.5 kN.m −2 with a steady P i release rate of 8.1 s −1 at maximal activation, and an isometric force of 49.2 kN.m −2 with a steady P i release rate of 4.8 s −1 at half-maximal activation. The rates of P i release during stretch and after the end of the stretch at low activation are equal to that at high activation indicating stretch-induced activation which occurs for stretches applied prior to activation, and during activation. The results demonstrate that stretch has a dramatic effect causing an immediate reduction in the rate of P i release. Stretch contributes to activation of the trabecula's actomyosin ATPase in a calcium-independent manner, although the effect is more marked at low activation levels. Thus a direct effect of stretch on thin filament activation contributes to the Frank-Starling law.
CT for the Transapical Off-Pump Mitral Valve Repair With Neochord Implantation Procedure
Authors: Andrea Colli, Fabio Zucchetta, Chad Kliger, Roberto Bellu, Marco Francone, Pietro Sedati, Vladimir Jelnin, Carlos E. Ruiz, Erica Manzan, Laura Besola, Eleonora Bizzotto, Gino Gerosa
Journal: JACC. Cardiovascular imaging (2017)
Sodium valproate enhances Imatinib induced apoptosis and growth arrest in Bcr-Abl cell lines
Authors: A. Morotti, D. Cilloni, F. Messa, M. Pautasso, G. Rege-Cambrin, C. Pilatrino, A. Guerrasio, E. Gottardi, D Alberti, G Saglio
Journal: Blood (2003)
Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue
Authors: Batzaya Byambaa, Nasim Annabi, Kan Yue, Grissel Trujillo‐de Santiago, Mario Moisés Alvarez, Weitao Jia, Mehdi Kazemzadeh‐Narbat, Su Ryon Shin, Ali Tamayol, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2017)

Fabricating 3D large‐scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion‐based direct‐writing bioprinting strategy is utilized to fabricate microstructured bone‐like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co‐culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMA LOW ) was printed. We also develop cell‐laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs.
Prognostic factors for brain metastasis in non-small cell lung cancer (NSCLC): A single Institution’s experience for over 10 years.
Authors: Narjust Duma, Larysa Jessica Sanchez, Claudia Miranda, Chad Glisch, Khaled Abu-Ihweij, Shijia Zhang, Carlos Osorio, Matthew Listo, Harry D. Harper, Martin Gutierrez
Journal: Journal of Clinical Oncology (2015)

e19062 Background: NSCLC patients (pts) develop brain metastasis (BM) early, usually within 2 years of diagnosis. BM are an important cause of morbidity and mortality, and the study of prognostic factors is vital in creating measures to prevent BM. The aim of this study was to evaluate the prognostic value of certain clinical characteristics in the development of BM in NSCLC. Methods: We retrospectively analyzed all pts diagnosed with NSCLC at our institution between 2000 and 2013. Demographics, tumor characteristics and metastatic patterns were studied. Median follow up was 45 months. Cox regression was used for multivariate analysis. Results: A total of 1062 pts were studied. Of these, 172 (16%) had BM at the time of analysis, with 61 (35%) pts having BM at diagnosis. Median (M) age was 68 years; M time from diagnosis to BM was 259 days. There were more females than males (64% vs. 36%, p < 0.0001). About NSCLC, pts with BM were more likely to have upper lobe tumors than all other tumor locations combined (63% vs. 37%, p < 0.0001). 32% of the lung tumors were 5-7cm in diameter and adenocarcinoma represented 68% of all the histologic subtypes. In regards to other distant metastases: 34% of the pts had bone metastasis, 23% adrenal and 17% hepatic. BM were most commonly located in the frontal (41%), parietal (17%) and occipital (14%) lobes. There was a significant survival difference between Stage IV pts with/without BM; pts with BM survived 6.1 months compared with 11.9 months in those without BM (p < 0.0001). In univariate analysis, female sex, histologic grade, upper lobe tumors and high LDH were associated with BM. Age < 65 years (HR: 0.60, 95%CI: 0.37-0.95, p < 0.03), T3-4 tumors (HR: 3.4, 95%CI: 2.04-5.64, p < 0.0001), adrenal metastasis (HR: 5.2 95%CI: 2.5-10.7, p < 0.0001) and liver metastasis (HR: 8.6, 95%CI: 4.3-17.2, p < 0.0001) were independent risk factors for BM. Conclusions: We observed that pts with T3-4 tumors, adrenal and liver metastases had the highest risk of developing BM. With this information, criteria for the selection of pts as suitable candidates for intra-cranial radiation, periodic brain imaging, and close follow-up may aid in further prevention of BM, early identification, and timely management.
Future research directions for the insurance hypothesis regarding food insecurity and obesity
Authors: Michelle I Cardel, Greg Pavela, Emily Dhurandhar, David B Allison
Journal: Behavioral and Brain Sciences (2017)

Abstract The focus of this commentary is Nettle et al.'s insurance hypothesis linking food insecurity to a high body mass index (BMI). We discuss how the relationship between race/ethnicity and obesity in the United States is consistent with this hypothesis, then present potential ways forward to elucidate the validity of this hypothesis in humans through rigorous controlled trials.