• Using systematic data categorisation to quantify the types of data collected in clinical trials: the DataCat project.

      Crowley, Evelyn; Treweek, Shaun; Banister, Katie; Breeman, Suzanne; Constable, Lynda; Cotton, Seonaidh; Duncan, Anne; El Feky, Adel; Gardner, Heidi; Goodman, Kirsteen; et al. (2020-06-16)
    • Methods and indicators for measuring patterns of human exposure to malaria vectors.

      Monroe, April; Moore, Sarah; Okumu, Fredros; Kiware, Samson; Lobo, Neil F; Koenker, Hannah; Sherrard-Smith, Ellie; Gimnig, John; Killeen, Gerry F (2020-06-16)
    • Modeling workflows: Identifying the most predictive features in healthcare operational processes.

      Crowley, Colm; Guitron, Steven; Son, Joseph; Pianykh, Oleg S (2020-06-11)
    • Measuring the effectiveness of an automated text messaging active surveillance system for COVID-19 in the south of Ireland, March to April 2020.

      Barrett, Peter M; Bambury, Niamh; Kelly, Louise; Condon, Rosalind; Crompton, Janice; Sheahan, Anne (2020-06-11)
    • The class II histone deacetylases as therapeutic targets for Parkinson's disease.

      Mazzocchi, Martina; Collins, Louise M; Sullivan, Aideen M; O'Keeffe, Gerard W (2020-06-09)
    • Vancomycin and nisin A are effective against biofilms of multi-drug resistant Staphylococcus aureus isolates from human milk.

      Angelopoulou, Angeliki; Field, Des; Pérez-Ibarreche, Mariana; Warda, Alicja K; Hill, Colin; Ross, R Paul (2020-05-29)
    • Doxycycline and Zinc Loaded Silica-Nanofibrous Polymers as Biomaterials for Bone Regeneration.

      Toledano, Manuel; Toledano-Osorio, Manuel; Osorio, Raquel; Carrasco-Carmona, Álvaro; Gutiérrez-Pérez, José-Luis; Gutiérrez-Corrales, Aida; Serrera-Figallo, María-Angeles; Lynch, Christopher D; Torres-Lagares, Daniel (2020-05-25)
      The main target of bone tissue engineering is to design biomaterials that support bone regeneration and vascularization. Nanostructured membranes of (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt of SiO2-nanoparticles (HOOC-Si-Membrane) were doped with zinc (Zn-HOOC-Si-Membrane) or doxycycline (Dox-HOOC-Si-Membrane). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and covered with the membranes. After six weeks, the bone architecture was evaluated with micro computed tomography. Three histological analyses were utilized to analyse bone regeneration, including von Kossa silver nitrate, toluidine blue and fluorescence. All membrane-treated defects exhibited higher number of osteocytes and bone perimeter than the control group without the membrane. Zn-HOOC-Si-Membranes induced higher new bone and osteoid area than those treated with HOOC-Si-Membranes, and control group, respectively. Zn-HOOC-Si-Membranes and Dox-HOOC-Si-Membranes attained the lowest ratio M1 macrophages/M2 macrophages. Dox-HOOC-Si-Membranes caused the lowest number of osteoclasts, and bone density. At the trabecular new bone, Zn-HOOC-Si-Membranes produced the highest angiogenesis, bone thickness, connectivity, junctions and branches. Zn-HOOC-Si-Membranes enhanced biological activity, attained a balanced remodeling, and achieved the greatest regenerative efficiency after osteogenesis and angiogenesis assessments. The bone-integrated Zn-HOOC-Si-Membranes can be considered as bioactive modulators provoking a M2 macrophages (pro-healing cells) increase, being a potential biomaterial for promoting bone repair.
    • Development of Biosensors for Detection of Diacetyl.

      Hernandez-Valdes, Jhonatan A; Solopova, Ana; Kuipers, Oscar P (2020-05-25)
      Some secondary metabolites of fermentative bacteria are desired compounds for the food industry. Examples of these compounds are diacetyl and acetaldehyde, which are produced by species of the lactic acid bacteria (LAB) family. Diacetyl is an aromatic compound, giving the buttery flavor associated with dairy products, and acetaldehyde is the compound responsible for the yogurt flavor and aroma. The quantification of these compounds in food matrices is a laborious task that involves sample preparation and specific analytical methods. The ability of bacteria to naturally sense metabolites has successfully been exploited to develop biosensors that facilitate the identification and quantification of certain metabolites (Mahr and Frunzke, 2016). The presence of a specific metabolite is sensed by the biosensors, and it is subsequently translated into the expression of one or more reporter genes. In this study we aimed to develop fluorescence-based biosensors to detect diacetyl and acetaldehyde. Since the metabolic pathways for production and degradation of these compounds are present in Lactococcus lactis, the sensing mechanisms in this bacterium are expected. Thus, we identified diacetyl and acetaldehyde responsive promoters by performing transcriptome analyses in L. lactis. The characterization of the biosensors showed their response to the presence of these compounds, and a further analysis of the diacetyl-biosensors (its dynamics and orthogonality) was performed. Moreover, we attempted to produce natural diacetyl from producer strains, namely L. lactis subsp. lactis biovar diacetylactis, to benchmark the performance of our biosensors. The diacetyl-biosensors responded linearly to the amounts of diacetyl obtained in the bacterial supernatants, i.e., the increases in GFP expression were proportional to the amounts of diacetyl present in the supernatants of L. lactis subsp. lactis biovar diacetylactis MR3-T7 strain. The biosensors developed in this study may eventually be used to engineer strains or pathways for increased diacetyl and acetaldehyde production, and may facilitate the detection of these metabolites in complex food matrices.
    • Large-scale genome-wide analysis links lactic acid bacteria from food with the gut microbiome.

      Pasolli, Edoardo; De Filippis, Francesca; Mauriello, Italia E; Cumbo, Fabio; Walsh, Aaron M; Leech, John; Cotter, Paul D; Segata, Nicola; Ercolini, Danilo (2020-05-25)
    • Social Dialogue and Psychosocial Risk Management: Added Value of Manager and Employee Representative Agreement in Risk Perception and Awareness.

      Houtman, Irene; van Zwieten, Marianne; Leka, Stavroula; Jain, Aditya; de Vroome, Ernest (2020-05-22)
    • Glial A Adenosine Receptors Modulate Abnormal Tachykininergic Responses and Prevent Enteric Inflammation Associated with High Fat Diet-Induced Obesity.

      D'Antongiovanni, Vanessa; Benvenuti, Laura; Fornai, Matteo; Pellegrini, Carolina; van den Wijngaard, Renè; Cerantola, Silvia; Giron, Maria Cecilia; Caputi, Valentina; Colucci, Rocchina; Haskó, Gyorgy; et al. (2020-05-18)
      The role played by adenosine A2B receptors (A2BRs) in the regulation of enteric glial cell (EGC) functions remains unclear. This study was aimed at investigating the involvement of A2BRs in the control of EGC functions in a model of obesity. C57BL/6 mice were fed with standard diet (SD) or high fat diet (HFD) for eight weeks. Colonic tachykininergic contractions were recorded in the presence of BAY60-6583 (A2BRs agonist), MRS1754 (A2BRs antagonist), and the gliotoxin fluorocitrate. Immunofluorescence distribution of HuC/D, S100β, and A2BRs was assessed in whole mount preparations of colonic myenteric plexus. To mimic HFD, EGCs were incubated in vitro with palmitate (PA) and lipopolysaccharide (LPS), in the absence or in the presence of A2BR ligands. Toll-like receptor 4 (TLR4) expression was assessed by Western blot analysis. Interleukin-1β (IL-1β), substance P (SP), and glial cell derived neurotrophic factor (GDNF) release were determined by enzyme-linked immunosorbent assay (ELISA) assays. MRS1754 enhanced electrically evoked tachykininergic contractions of colonic preparations from HFD mice. BAY60-6583 decreased the evoked tachykininergic contractions, with higher efficacy in HFD mice. Such effects were blunted upon incubation with fluorocitrate. In in vitro experiments on EGCs, PA and LPS increased TLR4 expression as well as IL-1β, GDNF, and SP release. Incubation with BAY60-6583 reduced TLR4 expression as well as IL-1β, GDNF, and SP release. Such effects were blunted by MRS1754. The present results suggest that A2BRs, expressed on EGCs, participate in the modulation of enteric inflammation and altered tachykininergic responses associated with obesity, thus representing a potential therapeutic target.
    • COST Action 'ImpARAS': what have we learnt to improve food allergy risk assessment. A summary of a 4 year networking consortium.

      Verhoeckx, Kitty; Lindholm Bøgh, Katrine; Constable, Anne; Epstein, Michelle M; Hoffmann Sommergruber, Karin; Holzhauser, Thomas; Houben, Geert; Kuehn, Annette; Roggen, Erwin; O'Mahony, Liam; et al. (2020-05-18)
    • Lidar reveals activity anomaly of malaria vectors during pan-African eclipse.

      Brydegaard, Mikkel; Jansson, Samuel; Malmqvist, Elin; Mlacha, Yeromin P; Gebru, Alem; Okumu, Fredros; Killeen, Gerry F; Kirkeby, Carsten (2020-05-13)
    • Personality Structure and Attachment in Bipolar Disorder.

      Wagner-Skacel, Jolana; Bengesser, Susanne; Dalkner, Nina; Mörkl, Sabrina; Painold, Annamaria; Hamm, Carlo; Pilz, René; Rieger, Alexandra; Kapfhammer, Hans-Peter; Hiebler-Ragger, Michaela; et al. (2020-05-11)
      We observed positive correlations between personality difficulties, insecure attachment, and symptom load in patients with BD. A low level of structural integration and an insecure attachment style in patients with BD were accompanied by a significantly higher symptom load (r = 0.66, p ≤ 0.01). Interestingly, there were no significant differences in the structural integration (T(1.44) = -0.93, p = 0.357) and in the attachment style attachment related avoidance: (T(1,44) = 1.50, p = 0.140); attachment related anxiety (T(1,44) = -0.781, p = 0.439) of study participants with BD when compared to the normative value of the general population.
    • The Relationship between ECOG-PS, mGPS, BMI/WL Grade and Body Composition and Physical Function in Patients with Advanced Cancer.

      Dolan, Ross D; Daly, Louise E; Simmons, Claribel Pl; Ryan, Aoife M; Sim, Wei Mj; Fallon, Marie; Power, Derek G; Wilcock, Andrew; Maddocks, Matthew; Bennett, Michael I; et al. (2020-05-08)
      Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/ Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p < 0.001), low skeletal muscle density (p < 0.05), and timed up and go test failure (p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p < 0.05) and hand grip strength test failure (p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p < 0.05), low visceral obesity (p < 0.01), and low skeletal muscle density (p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer.
    • CRISPR-based gene editing enables gene repair in IPEX patient cells.

      Goodwin, M; Lee, E; Lakshmanan, U; Shipp, S; Froessl, L; Barzaghi, F; Passerini, L; Narula, M; Sheikali, A; Lee, C M; et al. (2020-05-06)
      The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.
    • Pitfalls in Single Clone CRISPR-Cas9 Mutagenesis to Fine-map Regulatory Intervals.

      Tian, Ruoyu; Pan, Yidan; Etheridge, Thomas H A; Deshmukh, Harshavardhan; Gulick, Dalia; Gibson, Greg; Bao, Gang; Lee, Ciaran M (2020-05-04)
    • Inhibition of UBE2L6 attenuates ISGylation and impedes ATRA-induced differentiation of leukemic cells.

      Orfali, Nina; Shan-Krauer, Deborah; O'Donovan, Tracey R; Mongan, Nigel P; Gudas, Lorraine J; Cahill, Mary R; Tschan, Mario P; McKenna, Sharon L (2020-05-01)
    • Association of distinct type 1 bone morphogenetic protein receptors with different molecular pathways and survival outcomes in neuroblastoma.

      Alshangiti, Amnah M; Wyatt, Sean L; McCarthy, Erin; Collins, Louise M; Hegarty, Shane V; Sullivan, Aideen M; O'Keeffe, Gerard W (2020-04-23)
      Neuroblastoma (NB) is a paediatric cancer that arises in the sympathetic nervous system. Patients with stage 4 tumours have poor outcomes and 20% of high-risk cases have MYCN amplification. The bone morphogenetic proteins (BMPs) play roles in sympathetic neuritogenesis, by signalling through bone morphogenetic protein receptor (BMPR)2 and either BMPR1A or BMPR1B. Alterations in BMPR2 expression have been reported in NB; it is unknown if the expression of BMPR1A or BMPR1B is altered. We report lower BMPR2 and BMPR1B, and higher BMPR1A, expression in stage 4 and in MYCN-amplified NB. Kaplan-Meier plots showed that high BMPR2 or BMPR1B expression was linked to better survival, while high BMPR1A was linked to worse survival. Gene ontology enrichment and pathway analyses revealed that BMPR2 and BMPR1B co-expressed genes were enriched in those associated with NB differentiation. BMPR1A co-expressed genes were enriched in those associated with cell proliferation. Moreover, the correlation between BMPR2 and BMPR1A was strengthened, while the correlation between BMPR2 and BMPR1B was lost, in MYCN-amplified NB. This suggested that differentiation should decrease BMPR1A and increase BMPR1B expression. In agreement, nerve growth factor treatment of cultured sympathetic neurons decreased Bmpr1a expression and increased Bmpr1b expression. Overexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis. The present study shows that expression of distinct BMPRs is associated with different survival outcomes in NB.