tbuckley/cabot-search huggingface dataset:
Rates of asthma exacerbations and mortality and associated factors in Uganda: a 2-year prospective cohort study
Authors: Bruce J Kirenga, Corina de Jong, Levicatus Mugenyi, Winceslaus Katagira, Abdallah Muhofa, Moses R Kamya, H Marike Boezen, Thys van der Molen
Journal: Thorax (2018)

Data on asthma treatment outcomes in Africa are limited. 449 patients with asthma (age 5-93 years) in Uganda were followed up for 2 years to determine rates of exacerbations and mortality and associated factors. During follow-up the median number of exacerbations per patient was 1 (IQR 0-5) and 17 patients died (3.7%, 27.3 deaths per 1000 person years). Considering only the first year of follow-up, 59.6% of the patients experienced at least one exacerbation, 32.4% experienced three or more exacerbations. A multivariable model showed that the likelihood of experiencing at least one exacerbation in the first year of follow-up was lower with better baseline asthma control (higher asthma control test (ACT) score), with OR 0.87 (95% CI: 0.82 to 0.93, P=0.000), and was higher with more exacerbations in the year prior to enrolment (OR for log number of exacerbations 1.28, 95% CI: 1.04 to 1.57, P=0.018). Better asthma control (OR 0.93, 95% CI: 0.88 to 0.99, P=0.021) and number of baseline exacerbations (OR 1.35,95% CI: 1.11 to 1.66, P=0.005) were also the only factors that were independently associated with experiencing three or more exacerbations during the first year of follow-up. The only factor found to be associated with all-cause mortality was FEV1, with higher recent FEV1 associated with lower all-cause mortality (OR 0.30, 95% CI: 0.14 to 0.65; P=0.002). Rates of asthma exacerbations and mortality are high in Uganda and are associated with poor asthma control. Health systems should be strengthened to care for asthma patients.
Abstract 13871: Target Vascular Remodeling and Right Heart Failure With Selective Hypoxia Inducible Factor-2α Inhibitors
Authors: Zhiyu Dai, Maggie M Zhu, You-Yang Zhao
Journal: Circulation (2017)

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by excessive vasoconstriction and obliterative vascular remodeling, leading to right heart failure and death...
Phenotypic Characteristics of a French Cohort of Patients with X-Linked Retinoschisis
Authors: Raphaëlle Orès, Saddek Mohand-Said, Claire-Marie Dhaenens, Aline Antonio, Christina Zeitz, Edouard Augstburger, Camille Andrieu, José-Alain Sahel, Isabelle Audo
Journal: Ophthalmology (2018)
Re: Srinivasan et al.: Comparison of new visual disturbances after superior versus nasal/temporal laser peripheral iridotomy: a prospective randomized trial ( Ophthalmology . 2018;125:345-351)
Authors: Graham W. Belovay, Vanessa Vera, Devesh K. Varma, Iqbal Ike K. Ahmed
Journal: Ophthalmology (2018)
TCTAP A-091 Results of Endovascular Treatment for TASC Type D Aorto-iliac Chronic Total Occlusion Lesions
Authors: Sun Hack Lee, Han Cheol Lee, Jeong Cheon Choe, Jinhee Ahn, Jin Sup Park, Hye Won Lee, Jun-Hyok Oh, Jung Hyun Choi, Kwang Soo Cha, Taek Jong Hong
Journal: Journal of the American College of Cardiology (2018)
Losartan prevents the imbalance between renal dopaminergic and renin angiotensin systems induced by fructose overload. l-Dopa/dopamine index as new potential biomarker of renal dysfunction
Authors: Natalia Lucía Rukavina Mikusic, Nicolás Martín Kouyoumdzian, Ana Uceda, Julieta Sofía Del Mauro, Marcela Pandolfo, Mariela Mercedes Gironacci, Ana María Puyó, Jorge Eduardo Toblli, Belisario Enrique Fernández, Marcelo Roberto Choi
Journal: Metabolism (2018)
Neutral Theory, Microbial Practice: Challenges in Bacterial Population Genetics
Authors: Eduardo P C Rocha
Journal: Molecular Biology and Evolution (2018)

I detail four major open problems in microbial population genetics with direct implications to the study of molecular evolution: the lack of neutral polymorphism, the modeling of promiscuous genetic exchanges, the genetics of ill-defined populations, and the difficulty of untangling selection and demography in the light of these issues. Together with the historical focus on the study of single nucleotide polymorphism and widespread non-random sampling, these problems limit our understanding of the genetic variation in bacterial populations and their adaptive effects. I argue that we need novel theoretical approaches accounting for pervasive selection and strong genetic linkage to better understand microbial evolution.
B Cell‐Mediated Maintenance of Cluster of Differentiation 169–Positive Cells Is Critical for Liver Regeneration
Authors: Kristina Behnke, Yuan Zhuang, Haifeng C. Xu, Balamurugan Sundaram, Maria Reich, Prashant V. Shinde, Jun Huang, Nastaran Fazel Modares, Alexei V. Tumanov, Robin Polz, Jürgen Scheller, Carl F. Ware, Klaus Pfeffer, Verena Keitel, Dieter Häussinger, Aleksandra A. Pandyra, Karl S. Lang, Philipp A. Lang
Journal: Hepatology (2018)

The liver has an extraordinary capacity to regenerate through activation of key molecular pathways. However, central regulators controlling liver regeneration remain insufficiently studied. Here, we show that B cell–deficient animals failed to induce sufficient liver regeneration after partial hepatectomy (PHx). Consistently, adoptive transfer of B cells could rescue defective liver regeneration. B cell–mediated lymphotoxin beta production promoted recovery from PHx. Absence of B cells coincided with loss of splenic cluster of differentiation 169–positive (CD169 + ) macrophages. Moreover, depletion of CD169 + cells resulted in defective liver regeneration and decreased survival, which was associated with reduced hepatocyte proliferation. Mechanistically, CD169 + cells contributed to liver regeneration by inducing hepatic interleukin‐6 (IL‐6) production and signal transducer and activator of transcription 3 activation. Accordingly, treatment of CD169 + cell–depleted animals with IL‐6/IL‐6 receptor rescued liver regeneration and severe pathology following PHx. Conclusion: We identified CD169 + cells to be a central trigger for liver regeneration, by inducing key signaling pathways important for liver regeneration.
Novel Genes, Ancient Genes, and Gene Co-Option Contributed to the Genetic Basis of the Radula, a Molluscan Innovation
Authors: Leon Hilgers, Stefanie Hartmann, Michael Hofreiter, Thomas von Rintelen
Journal: Molecular Biology and Evolution (2018)

The radula is the central foraging organ and apomorphy of the Mollusca. However, in contrast to other innovations, including the mollusk shell, genetic underpinnings of radula formation remain virtually unknown. Here, we present the first radula formative tissue transcriptome using the viviparous freshwater snail Tylomelania sarasinorum and compare it to foot tissue and the shell-building mantle of the same species. We combine differential expression, functional enrichment, and phylostratigraphic analyses to identify both specific and shared genetic underpinnings of the three tissues as well as their dominant functions and evolutionary origins. Gene expression of radula formative tissue is very distinct, but nevertheless more similar to mantle than to foot. Generally, the genetic bases of both radula and shell formation were shaped by novel orchestration of preexisting genes and continuous evolution of novel genes. A significantly increased proportion of radula-specific genes originated since the origin of stem-mollusks, indicating that novel genes were especially important for radula evolution. Genes with radula-specific expression in our study are frequently also expressed during the formation of other lophotrochozoan hard structures, like chaetae (hes1, arx), spicules (gbx), and shells of mollusks (gbx, heph) and brachiopods (heph), suggesting gene co-option for hard structure formation. Finally, a Lophotrochozoa-specific chitin synthase with a myosin motor domain (CS-MD), which is expressed during mollusk and brachiopod shell formation, had radula-specific expression in our study. CS-MD potentially facilitated the construction of complex chitinous structures and points at the potential of molecular novelties to promote the evolution of different morphological innovations.
P560Arterial Flt1 regulates de novo arteriologenesis and arteriolar caliber involving novel endothelial remodeling events
Authors: A Klems, R Wild, R Hinkel, C Kupatt, F Le Noble
Journal: Cardiovascular Research (2018)

Background: -Angiogenesis is an essential process required to generate, refine and retune a healthy vascular network.However, in certain pathological conditions, such as after a myocardial infarction, blood vessels can be damaged and/or destroyed.Therefore stimulating angiogenesis could be therapeutically advantageous.Plasma membrane calcium ATPases (PMCA) are a family of calcium extrusion pumps which can also mediate intracellular signalling processes.PMCA1, 2 and 4 are expressed in human endothelial cells, and recently PMCA4 has been established as a mediator of angiogenesis through its role in endothelial cell migration and tubule formation.Purpose: -Previous data indicates PMCA4 negatively impacts blood vessel development through modulation of pro-angiogeneic endothelial cell characteristics, therefore we aim to investigate the role of PMCA1 in angiogenesis.Methods: -Transient knockdown of PMCA1 was achieved in HUVECs using siRNA (si-PMCA1) and confirmed with qPCR.HUVEC viability, migration, proliferation and apoptosis was assessed over a period of 6 days-post transfection using the MTT assay, wound healing 'scratch test' assay, Ki-67 immunofluorescence and Caspase-Glo 3/7 assay respectively.Live-cell imaging over a period of 24 hours was performed to further evaluate cytotoxicity, cell death and migration.Fluorescent activated cell sorting using DAPI was performed to evaluate cell cycle distribution.Furthermore, the expression of both zebrafish isoforms of PMCA1 (PMCA1a and PMCA1b) was characterised in whole zebrafish embryos and zebrafish endothelial cells.In the zebrafish, transient knockdown of PMCA1a and PMCA1b, was achieved using splice-site morpholino's.Results: -Transient knockdown of PMCA1 in HUVECs resulted in an 85% reduction in PMCA1 gene expression.Phenotypically, 3 and 6 days post-knockdown, loss of PMCA1 decreased HUVEC viability, but also reduced apoptosis.Additionally, there was no difference in the number of Ki-67 positive nuclei between si-PMCA1 HUVECs and control HUVECs, but si-PMCA1 HUVECs had a reduction in total cell number.FACs-mediated cell cycle analysis revealed si-PMCA1 HUVECs had a larger proportion of cells in S-phase and a smaller proportion of cells in G2/M-phase compared to control HUVECs after serum starvation.Furthermore, loss of PMCA1 impairs migration of HUVECs into the 'wound' 24 hours after the scratch assay was performed.In the zebrafish embryo, both zebrafish isoforms of PMCA1 are detectable in whole embryos and in endothelial cells from 3 days post-fertilisation.Conclusion: -Overall, loss of PMCA1 may be detrimental for HUVEC viability, which could be due to altered cell cycle kinetics.Furthermore, si-PMCA1 targeted HUVECs show impaired migration, although further work is required to establish the pumps direct role in vessel formation.
Pancreatic exocrine insufficiency (PI) secondary to chronic use of long-acting (LA) somatostatin analogues (SA) in patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Authors: Wasif M. Saif, Melissa H Smith, Alicia Romano, Rachna Patel, Valerie Relias
Journal: Journal of Clinical Oncology (2018)

454 Background: SA are used in GEP-NETs and acromegaly. Side effects of SAs include biliary disorders, gastrointestinal disorders, injection-site pain and hyperglycemia. PI is often misdiagnosed as disease progression or failure to SA or diagnosed after a delay in pts receiving SA. We present our experience with PI developing in pts following chronic use of SA. Methods: Retrospective chart and pharmacy review of GEP-NETs pts (6/2009 - 6/2017) was completed. Data including demographics, dose/duration of long and short-acting SA, antidiarrheal, pancreatic enzyme replacement (PER), proton pump inhibitors (PPI), chromogranin A (CgA), urine 5-HIAA and quantitative fecal fat test (QFFT) was collected. Results: 110 GEP-NETs pts (Med. age: 56 yr) were identified. 104 pts received LA Octreotide acetate and 6 Somatuline Depot Injection. Of these, 23 received SA octreotide for worsening diarrhea, 96 had intensification of antidiarrheal and 1 got telotristat ethyl. 79 pts were evaluated by nutritionist and/or gastroenterology. QFFT was performed in 47 pts with worsening diarrhea despite stable or improved CgA/urine 5-HIAA. 19 had evidence of steattorrhea and received PER at a dose of 72,000 lipase units per meal. 13 received PPI concomitantly while 6 started when symptoms did not improve with PER. In addition, low fat diet was recommended. 14 of 19 had improvement in diarrhea within 4-8 weeks. 2 pts were non-compliant and 3 were found to have motility disorders. Deficiency of vitamins and trace elements was found in 11 of 19 pts, who received supplementation. Conclusions: Our experience constitutes first study addressing PI as a rare but serious complication of chronic use of SA. Although SA are used to treat diarrhea, paradoxically they can worsen diarrhea secondary to PI. It is believed that SA may inhibit secretion and release of hormones (amylase, trypsin, lipase, secretin, CCK, motilin, bile acid) leading to PI. Early recognition and diagnosis of this under-diagnosed and under-reported side effect of SA can improve not only diarrhea and weight in these pts but also can reduce cost of using short-acting SA and antidiarrheal.
The anti-fibrotic agent, tipelukast (MN-001) reduces serum triglyceride significantly in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease patients with hypertriglyceridemia after 4 weeks of treatment, an interim analysis of ongoing clinical trial, MN-001-NATG-201
Authors: K. Matsuda, J. Gutierrez, T. Hassanein, Y. Iwaki
Journal: Journal of Hepatology (2018)
Thermoreversible Hyaluronic Acid‐PNIPAAm Hydrogel Systems for 3D Stem Cell Culture
Authors: Barbara L. Ekerdt, Christina M. Fuentes, Yuguo Lei, Maroof M. Adil, Anusuya Ramasubramanian, Rachel A. Segalman, David V. Schaffer
Journal: Advanced Healthcare Materials (2018)

Abstract Human pluripotent stem cells (hPSCs) offer considerable potential for biomedical applications including drug screening and cell replacement therapies. Clinical translation of hPSCs requires large quantities of high quality cells, so scalable methods for cell culture are needed. However, current methods are limited by scalability, the use of animal‐derived components, and/or low expansion rates. A thermoresponsive 3D hydrogel for scalable hPSC expansion and differentiation into several defined lineages is recently reported. This system would benefit from increased control over material properties to further tune hPSC behavior, and here a scalable 3D biomaterial with the capacity to tune both the chemical and the mechanical properties is demonstrated to promote hPSC expansion under defined conditions. This 3D biomaterial, comprised of hyaluronic acid and poly( N ‐isopropolyacrylamide), has thermoresponsive properties that readily enable mixing with cells at low temperatures, physical encapsulation within the hydrogel upon elevation at 37 °C, and cell recovery upon cooling and reliquefaction. After optimization, the resulting biomaterial supports hPSC expansion over long cell culture periods while maintaining cell pluripotency. The capacity to modulate the mechanical and chemical properties of the hydrogel provides a new avenue to expand hPSCs for future therapeutic application.
E1A CR2 deletion mutant adenoviral vectors in ovarian cancer: combination with apoptosis inducers and monitoring with [18F] FLT-PET imaging
Authors: Sarah K. Baird, Michelle Lockley, Julius Leyton, Eric O. Aboagye, Nicholas R. Lemoine, Iain A. McNeish
Journal: Cancer Research (2006)

2992   Introduction. Selectively replicating adenoviral mutants hold great promise as gene therapy vectors. dl922-947 contains a 24 bp deletion in E1A CR2, normally responsible for inactivating pRb. Our data indicate that dl922-947 is capable of replicating in and lysing ovarian cancer cells selectively. However, the mechanism of virus-induced cell death is poorly explained. We have explored the roles of classical and caspase-independent apoptosis in the cytotoxicity of adenoviral E1A CR2 mutants and have attempted to augment anti-tumour effects by co-expression of Smac/DIABLO and by co-treatment with cisplatin. We have also explored the ability of [18F] FLT-PET imaging to monitor the activity of dl922-947 in vivo. Methods. In addition to dl922-947, we have created Ad ΔCR2 and Ad ΔCR2 tSmac. Both contain the same E1A CR2 deletion as dl922-947, whilst Ad ΔCR2 tSmac also contains a Smac expression cassette 3′ to the E1 region. Ovarian carcinoma cells were infected in vitro and monitored for markers of classical and non-classical apoptosis and overall survival. Subcutaneous IGROV1 ovarian carcinoma xenografts were grown in nude female mice and injected with dl922-947 and imaged in a quad HIDAC PET scanner for 60 minutes following injection of 80-100μCi [18F]FLT. Results. E1A CR2 deletion mutant adenoviral vectors induce cleavage of PARP and caspase-3, disappearance of XIAP, cIAP-1, survivin, caspase-9 and caspase-8, loss of mitochondrial membrane potential and the appearance of a sub-G1 population of DNA in ovarian cancer cells, all consistent with classical apoptosis, and enhanced by addition of a Smac gene. The changes were also largely reversible with 50μM zVAD-fmk, a pan-caspase inhibitor. However, annexin V staining did not show increased cell surface phosphatidylserine exposure and acridine orange staining suggested lysosomal leakage, whilst zVAD-fmk treatment only partially reversed virus-induced cytotoxicity. Co-treatment with cisplatin enhanced the cytotoxicity of both Smac-expressing and non-expressing viruses, especially when virus was administered 24 hours after cisplatin. Preliminary [18F] FLT-PET imaging data indicate that a reduction in both fractional FLT retention and SUV60 may be detectable as early as 48 hours after dl922-947 injection, with significant reductions by day 7 compared to control virus-treated animals. These data mirror mean tumour volumes, which were 76% lower on day 7 in dl922-947-treated animals than in control mice. Conclusions. Cell death induced by E1A CR2-deleted adenoviral vectors has features of both classical and non-classical apoptosis, but can be augmented by exposure to apoptosis inducers, such as Smac and cisplatin. [18F] FLT-PET imaging may give an early non-invasive indicator of viral activity in ovarian cancer.
Combined Photo‐Therapies: Nanocarrier‐Mediated Photochemotherapy and Photoradiotherapy (Adv. Healthcare Mater. 8/2018)
Authors: Antonia G. Denkova, Robine M. de Kruijff, Pablo Serra‐Crespo
Journal: Advanced Healthcare Materials (2018)

Recent advancements in nanotechnology create opportunities to combine different treatment modalities such as photothermal and photodynamic therapy with chemo-or radiotherapy in just one nanocarrier. These new multi—functional nanocarriers have a much better tumor killing efficiency than photo-induced therapies alone and are expected to reduce side effects usually associated with conventional chemo- and radiotherapy. This is reviewed in article number 1701211 by Antonia G. Denkova and co-workers.
Transition Intervention for Adolescents With Congenital Heart Disease
Authors: Andrew S. Mackie, Gwen R. Rempel, Adrienne H. Kovacs, Miriam Kaufman, Kathryn N. Rankin, Ahlexxi Jelen, Maryna Yaskina, Renee Sananes, Erwin Oechslin, Dimi Dragieva, Sonila Mustafa, Elina Williams, Michelle Schuh, Cedric Manlhiot, Samantha J. Anthony, Joyce Magill-Evans, David Nicholas, Brian W. McCrindle
Journal: Journal of the American College of Cardiology (2018)
Involvement of neural crest and paraxial mesoderm in oral mucosal development and healing
Authors: Juliane Isaac, Ali Nassif, Audrey Asselin, Ihsène Taïhi, Hélène Fohrer-Ting, Christophe Klein, Bruno Gogly, Ariane Berdal, Benoît Robert, Benjamin P. Fournier
Journal: Biomaterials (2018)
Association of genetic variations within the PD-L2 immune checkpoint gene with outcome in stage II and III colon cancer.
Authors: Martin D. Berger, Inti Zlobec, Dongyun Yang, Shu Cao, Yu Sunakawa, Satoshi Matsusaka, Viktor H. Koelzer, Daniel Inderbitzin, Yan Ning, Satoshi Okazaki, Yuji Miyamoto, Mitsukuni Suenaga, Marta Schirripa, Shivani Soni, Alberto Puccini, Ryuma Tokunaga, Madiha Naseem, Wu Zhang, Alessandro Lugli, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2018)

626 Background: Immune checkpoints can either inhibit or stimulate T-cell responses and therefore play a key role in maintaining an equilibrium between self tolerance and autoimmunity. Targeting immune checkpoint molecules can result in increased antitumor immunity by stimulation of the immune system. We hypothesize, that variations in genes encoding for both inhibitory or stimulatory immune checkpoint proteins may predict outcome in stage II and III colon cancer patients. Methods: The impact of 6 functional single nucleotide polymorphisms (SNPs) within the PD1, PD-L1, PD-L2, TIM3, OX40 and CD27 genes on time to recurrence was evaluated in 201 patients with stage II and III colon cancer. Genomic DNA was extracted from formalin-fixed paraffin embedded tissue and the SNPs were analyzed by PCR-based direct sequencing. Results: Baseline characteristics were as follows: female/male ratio = 42.8% / 57.2%; median age = 70y (19-91); median follow-up = 43months. The PD-L2 rs16923189 SNP showed significant association with recurrence rate. Patients with a G/G genotype had a higher 3-years recurrence rate compared to those harboring any A allele (41% vs 19%) in both univariate (HR 2.68, 95% Confidence interval (CI) 1.28-5.61, p = 0.006) and multivariate analyses (HR 3.13, 95% CI 1.42-6.28, p = 0.003). The high recurrence rate was most evident among patients with stage III and left-sided tumors carrying the G/G genotype (53% vs 24% and 65% vs 18%) in both univariate (HR 2.87, 95% CI 1.24-6.66, p = 0.009 and HR 5.28, 95% CI 2.24-12.44, p &lt; 0.0001) and multivariate analyses (HR 4.32, 95% CI 1.76-9.91, p = 0.001 and HR 5.20, 95% CI 2.02-12.75, p = 0.001). Conclusions: Our results provide the first evidence, that polymorphisms within the PD-L2 gene might serve as prognostic markers in patients with stage II and III colon cancer. Interestingly, the prognostic effect is most significant among patients with stage III and left-sided colon cancers. Targeting PD-L2 might be a promising approach to further optimize treatment options and to improve outcome of colon cancer patients in the adjuvant setting.