tbuckley/cabot-search huggingface dataset:
Abstract 18606: Pulmonary Arterial Hypertension Significantly Attenuates Baroreflex Total Loop Dynamic Gain While Preserving its Quickness of Arterial Pressure Regulation
Authors: Keita Saku, Masako Sakamoto, Yasuhiro Oga, Takeshi Tohyama, Takuya Nishikawa, Kotaro Abe, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa
Journal: Circulation (2017)

Background: Baroreflex (BR) is a powerful negative feedback system to stabilize arterial pressure (AP). BR consists of two subsystems. The central arc translates baroreceptor-sensed AP into an appr...
<i>SeqSQC</i>: A <i>Bioconductor</i> Package for Evaluating the Sample Quality of Next-Generation Sequencing Data
Authors: Qian Liu, Qiang Hu, Song Yao, Marilyn L. Kwan, Janise M. Roh, Hua Zhao, Christine B. Ambrosone, Lawrence H. Kushi, Song Liu, Qianqian Zhu
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductor package, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor.org/packages/SeqSQC.
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets
Authors: Luca Cassetta, Stamatina Fragkogianni, Andrew H. Sims, Agnieszka Swierczak, Lesley M. Forrester, Hui Zhang, Daniel Y.H. Soong, Tiziana Cotechini, Pavana Anur, Elaine Y. Lin, Antonella Fidanza, Martha Lopez-Yrigoyen, Michael R. Millar, Alexandra Urman, Zhichao Ai, Paul T. Spellman, E. Shelley Hwang, J. Michael Dixon, Lisa Wiechmann, Lisa M. Coussens, Harriet O. Smith, Jeffrey W. Pollard
Journal: Cancer Cell (2019)

The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes.
Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000–2016: a spatial and temporal modelling study
Authors: Jonathan F Mosser, William Gagne-Maynard, Puja C Rao, Aaron Osgood-Zimmerman, Nancy Fullman, Nicholas Graetz, Roy Burstein, Rachel L Updike, Patrick Y Liu, Sarah E Ray, Lucas Earl, Aniruddha Deshpande, Daniel C Casey, Laura Dwyer-Lindgren, Elizabeth A Cromwell, David M Pigott, Freya M Shearer, Heidi Jane Larson, Daniel J Weiss, Samir Bhatt, Peter W Gething, Christopher J L Murray, Stephen S Lim, Robert C Reiner, Simon I Hay
Journal: The Lancet (2019)

BackgroundRoutine childhood vaccination is among the most cost-effective, successful public health interventions available. Amid substantial investments to expand vaccine delivery throughout Africa and strengthen administrative reporting systems, most countries still require robust measures of local routine vaccine coverage and changes in geographical inequalities over time.MethodsThis analysis drew from 183 surveys done between 2000 and 2016, including data from 881 268 children in 49 African countries. We used a Bayesian geostatistical model calibrated to results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, to produce annual estimates with high-spatial resolution (5 × 5 km) of diphtheria-pertussis-tetanus (DPT) vaccine coverage and dropout for children aged 12–23 months in 52 African countries from 2000 to 2016.FindingsEstimated third-dose (DPT3) coverage increased in 72·3% (95% uncertainty interval [UI] 64·6–80·3) of second-level administrative units in Africa from 2000 to 2016, but substantial geographical inequalities in DPT coverage remained across and within African countries. In 2016, DPT3 coverage at the second administrative (ie, district) level varied by more than 25% in 29 of 52 countries, with only two (Morocco and Rwanda) of 52 countries meeting the Global Vaccine Action Plan target of 80% DPT3 coverage or higher in all second-level administrative units with high confidence (posterior probability ≥95%). Large areas of low DPT3 coverage (≤50%) were identified in the Sahel, Somalia, eastern Ethiopia, and in Angola. Low first-dose (DPT1) coverage (≤50%) and high relative dropout (≥30%) together drove low DPT3 coverage across the Sahel, Somalia, eastern Ethiopia, Guinea, and Angola.InterpretationDespite substantial progress in Africa, marked national and subnational inequalities in DPT coverage persist throughout the continent. These results can help identify areas of low coverage and vaccine delivery system vulnerabilities and can ultimately support more precise targeting of resources to improve vaccine coverage and health outcomes for African children.FundingBill & Melinda Gates Foundation.
Hypertension in Young Adults and Subsequent Cardiovascular Disease—Reply
Authors: Yuichiro Yano, Paul Muntner, Donald Lloyd-Jones
Journal: JAMA (2019)

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Vicia villosa agglutinin (lectin)-binding carbohydrate(s) is expressed in atypical MUC1, serotransferrin and immunoglobulin of rat ascites hepatoma AH109A cells with lymphatic metastasis propensity.
Authors: Beatrice E. Bachmeier, Andreas G. Nerlich, Roberta Vené, Cristina M. Iancu, Barbara Mayer, Douglas Noonan, Adriana Albini, Marianne Jochum, Ulrich Pfeffer
Journal: Cancer Research (2005)

222  Several workers including us have demonstrated by immunohistochemistry that expression of Vicia villosa agglutinin-binding carbohydrate(s) (VVA carbohydrate) of cancer cells is related to malignant phenotype of various human cancers. We discovered that VVA carbohydrates are carried by atypical MUC1 expressed on human breast cancer cells and are related to lymph node metastasis and liver metastasis (AACR 94 and 95 annual meetings; Current Drug Targets-Cardiovascular and Heamatological Disorders, in press). In order to advance research, we explored an adequate animal cancer cell line suitable for further research. Here we will describe on rat ascites hepatoma, AH109A. The intraperitoneal(ip) transplantation of about 2X106 cells yields about 10∼20 ml of hemorrhagic ascites and ∼5 X 108 cells with a large nodule in omentum 7 days later. Metastasis was formed preferentially in lymph nodes after inoculation into subcutaneous tissue of eye, penis, abdominal, or legs. Venous inoculation of tumor cells (2x106 cells) hardly formed hematogenous lung metastasis. Ascites and cells of AH109A contained much VVA-reactive proteins as demonstrated by VVA lectin staining. VVA-binding proteins were purified from either ascites or cells. Proteins with VVA carbohydrates separated by affinity chromatography were ∼200, ∼75, ∼68, ∼50, ∼48, ∼30, ∼25 kDa in denaturing and reducing conditions. From studies on amino acid sequencing followed by Western blotting, it was considered that proteins of ∼75 and ∼68 kDa were serotransferrin, proteins of ∼50, ∼48, and 25 kDa were immunoglobulin, and proteins of ∼200 and ∼30 kDa were MUC1. ∼68 kDa serotransferrin was reacted with peanut agglutinin (PNA) as well as VVA and pretreatment of N glycanase did not affect the molecular weight. In addition, VVA reactivity (staining) disappeared completely by pre-incubation with O-glycanase. Therefore, we consider at present that ∼68 kDa serotransferrin possess O- type carbohydrates. The carbohydrates of ∼50 and ∼48 kDa immunoglobulin are N- type, while the carbohydrates of ∼200 and ∼30 kDa MUC1 are O-type. In conclusion, rat ascites hepatoma AH109A cells express atypical proteins with VVA carbohydrates, some of which are similar to those of human breast cancer cells. These atypical proteins may be related to metastatic propensity of lymphatic metastasis of cancer cells.
Metabolic Surgery for Hypertension in Patients With Obesity
Authors: Manan Pareek, Deepak L. Bhatt, Carlos Aurelio Schiavon, Philip R. Schauer
Journal: Circulation Research (2019)

The global prevalence of overweight and obesity has risen substantially over the past 4 decades and is accompanied by an increasing burden of cardiovascular risk factors such as hypertension. Metabolic surgery is the most effective method to treat obesity and may further improve associated conditions. Although most research has been directed toward the glycemic effects of weight loss surgery, there has been a growing interest in exploring its potential blood pressure-reducing properties. Systematic reviews and meta-analyses based primarily on observational data have suggested that metabolic surgery may aid in controlling hypertension. Only one randomized controlled trial specifically addressing this concept has been conducted, though supportive of the findings from observational studies. We review contemporary procedures for weight loss and their effects on cardiometabolic risk, particularly hypertension. In addition, we describe potential pathophysiological mechanisms and the effects of metabolic surgery on cardiovascular events and mortality.
Amelioration of the nigrostriatal pathway facilitated by ultrasound-mediated neurotrophic delivery in early Parkinson's disease
Authors: Maria Eleni Karakatsani, Shutao Wang, Gesthimani Samiotaki, Tara Kugelman, Oluyemi O. Olumolade, Camilo Acosta, Tao Sun, Yang Han, Hermes A.S. Kamimura, Vernice Jackson-Lewis, Serge Przedborski, Elisa Konofagou
Journal: Journal of Controlled Release (2019)
Heparin‐Conjugated Decellularized Bone Particles Promote Enhanced Osteogenic Signaling of PDGF‐BB to Adipose‐Derived Stem Cells in Tissue Engineered Bone Grafts
Authors: Alexandra N. Rindone, Bartlomiej Kachniarz, Chukwuebuka C. Achebe, Ryan C. Riddle, Aine N. O'Sullivan, Amir H. Dorafshar, Warren L. Grayson
Journal: Advanced Healthcare Materials (2019)

Adipose-derived stem cells (ASCs) are a promising cell source for regenerating critical-sized craniofacial bone defects, but their clinical use is limited due to the supraphysiological levels of bone morphogenetic protein-2 required to induce bone formation in large grafts. It has been recently reported that platelet-derived growth factor-BB (PDGF) directly enhances the osteogenesis of ASCs when applied at physiological concentrations. In this study, a biomimetic delivery system that tethers PDGF to decellularized bone matrix (DCB) is developed to enhance osteogenic signaling in bone grafts by colocalizing PDGF-extracellular matrix cues. Heparin is conjugated to DCB particles (HC-DCB) to promote sustained binding of PDGF via electrostatic interactions. HC-DCB particles bind to PDGF with >99% efficiency and release significantly less PDGF over 21 days compared to nonconjugated DCB particles (1.1% vs 22.8%). HC-DCB-PDGF signaling in polycaprolactone (PCL)-fibrin grafts promotes >40 µg Ca2+ µg-1 DNA deposition by ASCs during in vitro osteogenic culture compared to grafts without HC-DCB or PDGF. Furthermore, more bone formation is observed in grafts with HC-DCB-PDGF at 12 weeks following implantation of grafts into murine critical-sized calvarial defects. Collectively, these results demonstrate that HC-DCB enhances the osteogenic signaling of PDGF to ASCs and may be applied to promote ASC-mediated bone regeneration in critical-sized defects.
Development of a novel human vestibular schwannoma xenograft model in SCID mice
Authors: John D. Welling, Mark Lorenz, Jon Rock, Kim L. O’Neill, Byron K. Murray, Elena Akhmametyeva, D. B. Welling, Long-Sheng Chang
Journal: Cancer Research (2005)

5923  Vestibular schwannomas arise from Schwann cells comprising the myelin sheath of the vestibular nerve - a cranial nerve controlling balance functions. Vestibular schwannomas are the cause of significant morbidity, particularly when expressed bilaterally with neurofibromatosis type 2, a highly penetrated autosomal dominant disorder. Currently, chemotherapeutic agents effective in the treatment of these tumors are not known. Our objective in this study was to develop a novel murine xenograft model in which the efficacy of potential chemotherapeutic agents against human vestibular schwannoma could be tested. Accordingly, we sought to develop a model, which would support the growth of schwannoma tissue sufficient for such testing. Fresh human schwannoma blocks were implanted subcutaneously in two groups of SCID mice (ho702 and ho713). From each group, two mice (ho702a, ho702b, ho713a and ho713b) underwent follow-up MRI studies using a 4.7T/cm MRI system (Bruker) after two months. Axial and coronal T1 and T2-weighted images were acquired. The weighted images showed that 702a and 702b did not experience a significant increase in tumor volume, while the tumor volume of 713a increased by 146% (from 0.105 cm3 to 0.153 cm3) and that of 173b by 343% (from 0.102 cm3 to 0.350 cm3). The results of this preliminary study indicate the need for further analysis of this xenograft model. While a potential for sustained tumor growth was demonstrated, only half of the mice displayed such. Furthermore, compared to a previous study in which we showed that inoculation of 2-5 x 105 rat schwannoma cells induced tumor growth to greater than 0.5 cm two weeks after injection, tumor volumes of human schwannomas increased at a slower rate and to a lesser extent. Significantly, these rat schwannoma cells demonstrated much higher telomerase activity than the human schwannomas. In future studies, we will observe the affect of telomerase overexpression in human schwannoma cells as a possible means of enhancing tumor growth in the xenograft model. In addition, we plan to image tumors over a more extensive time period for a more comprehensive observation of tumor growth. We believe that further investigation will lead to a valuable model for the study of potential chemotherapeutic agents. We are hopeful that testing of novel agents in this model will lead to clinical trials and ultimately, improved treatment options.
IL-7 receptor influences anti-TNF responsiveness and T cell gut homing in inflammatory bowel disease
Authors: Lyssia Belarif, Richard Danger, Laetitia Kermarrec, Véronique Nerrière-Daguin, Sabrina Pengam, Tony Durand, Caroline Mary, Elise Kerdreux, Vanessa Gauttier, Aneta Kucik, Virginie Thepenier, Jerome C. Martin, Christie Chang, Adeeb Rahman, Nina Salabert-Le Guen, Cécile Braudeau, Ahmed Abidi, Grégoire David, Florent Malard, Celine Takoudju, Bernard Martinet, Nathalie Gérard, Isabelle Neveu, Michel Neunlist, Emmanuel Coron, Thomas T. MacDonald, Pierre Desreumaux, Hoa-Le Mai, Stephanie Le Bas-Bernardet, Jean-François Mosnier, Miriam Merad, Régis Josien, Sophie Brouard, Jean-Paul Soulillou, Gilles Blancho, Arnaud Bourreille, Philippe Naveilhan, Bernard Vanhove, Nicolas Poirier
Journal: Journal of Clinical Investigation (2019)

It remains unknown what causes inflammatory bowel disease (IBD), including signaling networks perpetuating chronic gastrointestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC), in humans. According to an analysis of up to 500 patients with IBD and 100 controls, we report that key transcripts of the IL-7 receptor (IL-7R) pathway are accumulated in inflamed colon tissues of severe CD and UC patients not responding to either immunosuppressive/corticosteroid, anti-TNF, or anti-α4β7 therapies. High expression of both IL7R and IL-7R signaling signature in the colon before treatment is strongly associated with nonresponsiveness to anti-TNF therapy. While in mice IL-7 is known to play a role in systemic inflammation, we found that in humans IL-7 also controlled α4β7 integrin expression and imprinted gut-homing specificity on T cells. IL-7R blockade reduced human T cell homing to the gut and colonic inflammation in vivo in humanized mouse models, and altered effector T cells in colon explants from UC patients grown ex vivo. Our findings show that failure of current treatments for CD and UC is strongly associated with an overexpressed IL-7R signaling pathway and point to IL-7R as a relevant therapeutic target and potential biomarker to fill an unmet need in clinical IBD detection and treatment.
Durum wheat genome highlights past domestication signatures and future improvement targets
Authors: Marco Maccaferri, Neil S. Harris, Sven O. Twardziok, Raj K. Pasam, Heidrun Gundlach, Manuel Spannagl, Danara Ormanbekova, Thomas Lux, Verena M. Prade, Sara G. Milner, Axel Himmelbach, Martin Mascher, Paolo Bagnaresi, Primetta Faccioli, Paolo Cozzi, Massimiliano Lauria, Barbara Lazzari, Alessandra Stella, Andrea Manconi, Matteo Gnocchi, Marco Moscatelli, Raz Avni, Jasline Deek, Sezgi Biyiklioglu, Elisabetta Frascaroli, Simona Corneti, Silvio Salvi, Gabriella Sonnante, Francesca Desiderio, Caterina Marè, Cristina Crosatti, Erica Mica, Hakan Özkan, Benjamin Kilian, Pasquale De Vita, Daniela Marone, Reem Joukhadar, Elisabetta Mazzucotelli, Domenica Nigro, Agata Gadaleta, Shiaoman Chao, Justin D. Faris, Arthur T. O. Melo, Mike Pumphrey, Nicola Pecchioni, Luciano Milanesi, Krystalee Wiebe, Jennifer Ens, Ron P. MacLachlan, John M. Clarke, Andrew G. Sharpe, Chu Shin Koh, Kevin Y. H. Liang, Gregory J. Taylor, Ron Knox, Hikmet Budak, Anna M. Mastrangelo, Steven S. Xu, Nils Stein, Iago Hale, Assaf Distelfeld, Matthew J. Hayden, Roberto Tuberosa, Sean Walkowiak, Klaus F. X. Mayer, Aldo Ceriotti, Curtis J. Pozniak, Luigi Cattivelli
Journal: Nature Genetics (2019)

The domestication of wild emmer wheat led to the selection of modern durum wheat, grown mainly for pasta production. We describe the 10.45 gigabase (Gb) assembly of the genome of durum wheat cultivar Svevo. The assembly enabled genome-wide genetic diversity analyses revealing the changes imposed by thousands of years of empirical selection and breeding. Regions exhibiting strong signatures of genetic divergence associated with domestication and breeding were widespread in the genome with several major diversity losses in the pericentromeric regions. A locus on chromosome 5B carries a gene encoding a metal transporter (TdHMA3-B1) with a non-functional variant causing high accumulation of cadmium in grain. The high-cadmium allele, widespread among durum cultivars but undetected in wild emmer accessions, increased in frequency from domesticated emmer to modern durum wheat. The rapid cloning of TdHMA3-B1 rescues a wild beneficial allele and demonstrates the practical use of the Svevo genome for wheat improvement. Genome assembly of durum wheat cultivar Svevo enables genome-wide genetic diversity analyses highlighting modifications imposed by thousands of years of empirical selection and breeding.
Synovial C-reactive protein features high negative predictive value but is not useful as a single diagnostic parameter in suspected periprosthetic joint infection (PJI)
Authors: A. Plate, A. Anagnostopoulos, J. Glanzmann, L. Stadler, L. Weigelt, R. Sutter, M. Kästli, A.S. Zinkernagel, P.O. Zingg, Y. Achermann
Journal: Journal of Infection (2019)
Comparing the Staging/Restaging Performance of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Choline PET/CT in Prostate Cancer
Authors: Chun-Yi Lin, Ming-Tsung Lee, Cheng-Li Lin, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2019)

PET/CT using prostate-specific membrane antigen (PSMA) and choline radiotracers is widely used for diagnosis of prostate cancer. However, the roles of and differences in diagnostic performance between these 2 radiotracers for prostate cancer are unclear. The aim of this study was to compare the staging and restaging performance of Ga-labeled PSMA and F-choline PET/CT imaging in prostate cancer.A comprehensive search was performed in PubMed for studies reporting the staging performance of Ga-PSMA and F-choline PET/CT in prostate cancer from the inception of the database to October 1, 2018, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Thirty-five studies were included in this systematic review and meta-analysis. Pooled estimates of patient- and lesion-based sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) for Ga-PSMA and F-choline PET/CT were calculated alongside 95% confidence intervals. Summary receiver operating characteristic curves were plotted, and the area under the summary receiver operating characteristic curve (AUC) was determined alongside the Q* index.The patient-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of Ga-PSMA PET/CT for staging in prostate cancer (13 studies) were 0.92, 0.94, 7.91, 0.14, 79.04, and 0.96, respectively, whereas those of F-choline PET/CT (16 studies) were 0.93, 0.83, 4.98, 0.10, 68.27, and 0.95. The lesion-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of Ga-PSMA PET/CT for staging in prostate cancer (9 studies) were 0.83, 0.95, 23.30, 0.17, 153.58, and 0.94, respectively, and those of F-choline PET/CT (4 studies) were 0.81, 0.92, 8.59, 0.20, 44.82, and 0.98. In both patient- and lesion-based imaging, there was no statistically significant difference in the abilities of detecting or excluding prostate cancer between Ga-PSMA PET/CT and F-choline PET/CT.For staging and restaging performance in patients with prostate cancer, there was no significant difference between Ga-PSMA PET/CT and F-choline PET/CT. Ga-PSMA PET/CT and F-choline PET/CT have demonstrated high diagnostic performance for accurate staging and restaging in patients with prostate cancer, and thus both should be considered for staging in this disease.
Blocking ATM-dependent NF-κB pathway overcomes niche protection and improves chemotherapy response in acute lymphoblastic leukemia
Authors: Ya-Li Chen, Chao Tang, Meng-Yi Zhang, Wen-Li Huang, Yan Xu, Hui-Yin Sun, Fan Yang, Li-Li Song, He Wang, Li-Li Mu, Ming-Hao Li, Wei-Wei Zheng, Yan Miao, Li-Xia Ding, Ben-Shang Li, Shu-Hong Shen, Sheng-Li Liu, Hui Li, Zhong-Qun Zhu, Hui-Wen Chen, Zhong-Hua Tang, Jing Chen, Deng-Li Hong, Hong-Zhuan Chen, Cai-Wen Duan, Bin-Bing S. Zhou
Journal: Leukemia (2019)