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Journal articleBarnes H, Morisset J, Molyneaux P, et al., 2020,
A systematically derived exposure assessment instrument for Chronic Hypersensitivity Pneumonitis
, Chest, Vol: 157, Pages: 1506-1512, ISSN: 0012-3692BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) is an immune mediated interstitial lung disease, caused by inhalational exposure to environmental antigens, resulting in parenchymal fibrosis. By definition, a diagnosis of CHP assumes a history of antigen exposure, but only half of all patients eventually diagnosed with CHP will have a causative antigen identified. Individual clinician variation in eliciting a history of antigen exposure may affect the frequency and confidence of CHP diagnosis. METHODS: A list of potential causative exposures were derived from a systematic review of the literature. A Delphi method was applied to an international panel of ILD experts, to obtain consensus regarding technique for the elicitation of exposure to antigens relevant to a diagnosis of CHP. The consensus threshold was set at 80% agreement, and median ≤ 2, IQR = 0 on a five-point Likert scale (1: strongly agree, 2: tend to agree, 3: neither agree nor disagree, 4: disagree, 5: strongly disagree). RESULTS: In two rounds, 36/40 experts participated. Experts agreed on 18 exposure items to ask every patient with suspected CHP. Themes included CHP inducing exposures, features that contribute to an exposure's relevance, and quantification of a relevant exposure. Based on the results from the literature review and Delphi process, a CHP exposure assessment instrument was derived. Using cognitive interviews, the instrument was revised by ILD patients for readability and usability. CONCLUSIONS: This Delphi survey provides items that ILD experts agree are important to ask in all patients presenting with suspected CHP and provides basis for a systematically derived CHP exposure assessment instrument. Clinical utility of this exposure assessment instrument may be affected by different local prevalence patterns of exposures. Ongoing research is required to clinically validate these items and consider their impact in more geographically diverse settings.
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Journal articleShackley M, Tate EW, Brown AJH, et al., 2020,
Short chain fatty acids enhance expression and activity of the umami taste receptor in enteroendocrine cells via a Gα <sub>i/o</sub> pathway
<jats:title>Abstract</jats:title> <jats:p> The short chain fatty acids (SCFAs) acetate, butyrate and propionate, are produced by the fermentation of non-digestible carbohydrates by the gut microbiota. SCFAs are of interest because they regulate appetite, adiposity, metabolism, glycemic control and immunity. SCFAs act at two distinct G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. These are expressed in intestinal enteroendocrine cells (EECs), where they mediate SCFA-driven anorectic gut hormone release. EECs also express other GPCRs that act as nutrient sensors, in a manner that is plastic and adaptable to the environment. SCFAs may elicit some of their health-promoting effects by altering levels of GPCRs in EECs, thus, enhancing gut sensitivity to dietary molecules. Here, we identified that exposure of the murine EEC STC-1 cell-line to a concentration of SCFAs found in the colon, specifically enhances mRNA levels of the umami taste receptors TASR1 and TASR3, without altering levels of the SCFA GPCRs, FFAR2 and FFAR3. Interestingly, treatment of EECs with propionate or butyrate, but not acetate, increased levels of umami receptor transcripts. This phenomenon was reversed by inhibiting Gα <jats:sub>i/o</jats:sub> signaling with pertussis toxin, suggesting that SCFAs act through FFAR2/3 to alter gene expression. Surprisingly, neither a FFAR3-nor a FFAR2-selective synthetic ligand could increase TASR1/TASR3 mRNA levels. We assessed the functional impact of increases in TASR1/TASR3 expression using unique pharmacological properties of the umami taste receptor; namely, the potentiation of signaling by inosine monophosphate. We found that the umami taste receptor induced inosine-1-phosphate and calcium signaling in response to L-alanine and L-monosodium glutamate, and that butyrate pretreatment significantly enhanced such signaling. Our study reveals that SCFAs may
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Journal articleHarker JA, Pallett LJ, 2020,
Immunological fortification at our barrier organs: Protecting us as we age
, Immunology, Vol: 160, Pages: 103-105, ISSN: 0019-2805Our barrier surfaces are fundamental in protecting us from the outside world and segregating key biological processes. The immunological fortifications found at these sites therefore possess many distinct qualities, which are discussed in Immunology 's series of reviews on Barrier Immunity. Together these reviews showcase novel biological processes identified through the use of state‐of‐the‐art technologies, and specifically highlight how these change throughout our lives.
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Journal articleGreggi S, Falcone F, Scaffa C, et al., 2020,
Evaluation of surgical resection in advanced ovarian, fallopian tube, and primary peritoneal cancer: laparoscopic assessment. A European Network of Gynaecological Oncology Trial (ENGOT) group survey
, International Journal of Gynecological Cancer, Vol: 30, Pages: 819-824, ISSN: 1048-891XOBJECTIVE: Laparoscopy is one of the diagnostic tools available for the complex clinical decision-making process in advanced ovarian, fallopian tube, and peritoneal carcinoma. This article presents the results of a survey conducted within the European Network of Gynaecological Oncology Trial (ENGOT) group aimed at reviewing the current patterns of practice at gynecologic oncology centers with regard to the evaluation of resection in advanced ovarian, fallopian tube, and peritoneal carcinoma. METHODS: A 24-item questionnaire was sent to the chair of the 20 cooperative groups that are currently part of the ENGOT group, and forwarded to the members within each group. RESULTS: A total of 142 questionnaires were returned. Only 39 respondents (27.5%) reported using some form of clinical (not operative) score for the evaluation of resection. The frequency of use of diagnostic laparoscopy to assess disease status and feasibility of resection was as follows: never, 21 centers (15%); only in select cases, 83 centers (58.5%); and routinely, 36 centers (25.4%). When laparoscopy was performed, 64% of users declared they made the decision to proceed with maximal effort cytoreductive surgery based on their personal/staff opinion, and 36% based on a laparoscopic score. To the question of whether laparoscopy should be considered the gold standard in the evaluation of resection, 71 respondents (50%) answered no, 66 respondents (46.5%) answered yes, whereas 5 respondents (3.5%) did not provide an answer. CONCLUSIONS: This study found that laparoscopy was routinely performed to assess feasibility of cytoreduction in only 25.4% of centers in Europe. However, it was commonly used to select patients and in a minority of centers it was never used . When laparoscopy was adopted, the treatment strategy was based on laparoscopic scores only in a minority of centers.
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Journal articleBenfield CT, MacKenzie F, Ritzefeld M, et al., 2020,
Correction: Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain
, Life Science Alliance, Vol: 3, ISSN: 2575-1077 -
Journal articleMathioudakis AG, Custovic A, Deschildre A, et al., 2020,
Research priorities in pediatric asthma: results of a global survey of multiple stakeholder groups by the Pediatric Asthma in Real Life (PeARL) Think Tank
, Journal of Allergy and Clinical Immunology: In Practice, Vol: 8, Pages: 1953-1960.e9, ISSN: 2213-2198BACKGROUND: Pediatric asthma remains a public health challenge with enormous impact worldwide. OBJECTIVE: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. METHODS: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. RESULTS: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. CONCLUSIONS: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider.
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Journal articleIto K, Zhang Y, 2020,
Fighting the common cold: ORMDL3 in the crosshairs?
, American Journal of Respiratory Cell and Molecular Biology, Vol: 62, Pages: 676-677, ISSN: 1044-1549 -
Journal articleAnderson DP, Benns HJ, Tate EW, et al., 2020,
CRISPR-TAPE: protein-centricCRISPRguide design for targeted proteome engineering
, MOLECULAR SYSTEMS BIOLOGY, Vol: 16, ISSN: 1744-4292 -
Journal articleNiespodziana K, Borochova K, Pazderova P, et al., 2020,
Toward personalization of asthma treatment according to trigger factors
, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 145, Pages: 1529-1534, ISSN: 0091-6749Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.
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Journal articleFedoryshchak R, Ocasio C, Strutton B, et al., 2020,
Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
, RSC Chemical Biology, Vol: 1, Pages: 68-78, ISSN: 1747-1613Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogen Z. tritici via inhibition of N-myristoyltransferase (NMT). We characterize Z. tritici NMT biochemically for the first time, profile the in vivo Z. tritici myristoylated proteome and identify and validate the first Z. tritici NMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity in Z. tritici through the application of comparative bioinformatics to deconvolute function from the previously largely unannotated Z. tritici proteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studying Z. tritici.
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