bluuebunny/crossref_metadata_2025_split huggingface dataset:
Criticality of plasma membrane lipids reflects activation state of macrophage cells
Authors: Cammarota Eugenia , Soriani Chiara , Taub Raphaelle , Morgan Fiona , Sakai Jiro , Veatch Sarah L. , Bryant Clare E. , Cicuta Pietro 
Published: June 2019

AbstractSignalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamical point. Macrophage cells are a key component of the innate immune system, responsive to infections, regulating the local state of inflammation. We investigate changes in the plasma membrane’s proximity to the critical point, as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (IFN-γ, Kdo-LipidA, LPS) perturbations induce an increase in the transition temperature of the GMPVs; anti-inflammatory IL4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.
Repurposing protein degradation for optogenetic modulation of protein activities
Authors: Mondal Payel , Krishnamurthy Vishnu V. , Sharum Savanna R. , Haack Neeka , Zhang Kai 
Published: June 2019

AbstractNon-neuronal optogenetic approaches empower precise regulation of protein dynamics in live cells but often require target-specific protein engineering. To address this challenge, we developed a generalizable light modulated protein stabilization system (GLIMPSe) to control intracellular protein level independent of its functionality. We applied GLIMPSe to control two distinct classes of proteins: mitogen-activated protein kinase phosphatase 3 (MKP3), a negative regulator of the extracellular signal-regulated kinase (ERK) pathway, as well as a constitutively active form of MEK (CA MEK), a positive regulator of the same pathway. Kinetics study showed that light-induced protein stabilization could be achieved within 1 minute of blue light stimulation. GLIMPSe enables target-independent optogenetic control of protein activities and therefore minimizes the systematic variation embedded within different photoactivatable proteins. Overall, GLIMPSe promises to achieve light-mediated post-translational stabilization of a wide array of target proteins in live cells.
Intramolecular interactions dominate the autoregulation ofEscherichia colistringent factor RelA
Authors: Turnbull Kathryn Jane , Dzhygyr Ievgen , Lindemose Søren , Hauryliuk Vasili , Roghanian Mohammad 
Published: June 2019

AbstractAmino acid starvation inEscherichia coliactivates the enzymatic activity of the stringent factor RelA, leading to accumulation of the alarmone nucleotide (p)ppGpp. The alarmone acts as an intercellular messenger to regulate transcription, translation and metabolism to mediate bacterial stress adaptation. The enzymatic activity of RelA is subject to multi-layered allosteric control executed both by ligands – such as ‘starved’ ribosomal complexes, deacylated tRNA and pppGpp – and by individual RelA domains. The auto-regulation of RelA is proposed to act eitherin cis(inhibition of the enzymatic activity of the N-terminal region, NTD, by regulatory C-terminal region, CTD) orin trans(CTD-mediated dimerization leading to enzyme inhibition). In this report, we probed the regulatory roles of the individual domains ofE. coliRelA and our results are not indicative of RelA dimerization being the key regulatory mechanism. First, at growth-permitting levels, ectopic expression of RelA CTD does not interfere with activation of native RelA, indicating lack of regulationviainhibitory complex formation in the cell. Second, in our biochemical assays, increasing RelA concentration does not decrease the enzyme activity, as would be expected in the case of efficient auto-inhibitionviadimerization. Third, while high-level CTD expression efficiently inhibits the growth, the effect is independent of native RelA and is mediated by direct inhibition of protein synthesis, likelyviadirect interaction with the ribosomal A-site. Finally, deletion of the RRM domain of the CTD region leads to growth inhibition mediated by accumulation of (p)ppGpp, suggesting de-regulation of the synthetic activity in this mutant.
Using Automated Detection and Classification of Interictal HFOs to Improve the Identification of Epileptogenic Zones in Preparation for Epilepsy Surgery
Authors: Farahmand Sina , Sobayo Tiwalade , Mogul David J. 
Published: June 2019

AbstractObjectiveFor more than 25 million drug-resistant epilepsy patients, surgical intervention aiming at resecting brain regions where seizures arise is often the only alternative therapy. However, the identification of this epileptogenic zone (EZ) is often imprecise which may affect post-surgical outcomes (PSOs). Interictal high-frequency oscillations (HFOs) have been revealed to be reliable biomarkers in delineating EZ. In this paper, an analytical methodology aiming at automated detection and classification of interictal HFOs is proposed to improve the identification of EZ. Furthermore, the detected high-rate HFO areas were compared with the seizure onset zones (SOZs) and resected areas to investigate their clinical relevance in predicting PSOs.MethodsFIR band-pass filtering as well as a combination of time-series local energy, peak, and duration analysis were utilized to identify high-rate HFO areas in interictal, multi-channel intracranial electroencephalographic (iEEG) recordings. The detected HFOs were then classified into fast-ripple (FR), ripple (R), and fast-ripple concurrent with ripple (FRandR) events.ResultsThe proposed method resulted in sensitivity of 91.08% and false discovery rate of 7.32%. Moreover, it was found that the detected HFO-FRandR areas in concordance with the SOZs would have better delineated the EZ for each patient, while limiting the area of the brain required to be resected.ConclusionTesting on a dataset of 20 patients has supported the feasibility of using this method to provide an automated algorithm to better delineate the EZ.SignificanceThe proposed methodology may significantly improve the precision by which pathological brain tissue can be identified.
Killer Immunoglobulin-like Receptor-Ligand Interactions Predict Clinical Outcomes Following Unrelated Donor Transplants
Authors: Krieger Elizabeth , Sabo Roy , Moezzi Sanauz , Cain Caitlin , Roberts Catherine , Kimball Pamela , Chesney Alden , McCarty John , Keating Armand , Romee Rizwan , Wiedl Christina , Qayyum Rehan , Toor Amir 
Published: June 2019

AbstractKiller immunoglobulin-like receptor (KIR) and KIR-ligand (KIRL) interactions play an important role in natural killer (NK) cell mediated graft versus leukemia effect following hematopoietic cell transplantation (HCT). However, there is considerable heterogeneity in the KIR gene and KIRL content in individuals, making it difficult to estimate the full clinical impact of NK cell reconstitution following HCT. Herein a novel mathematical model designed to quantify these interactions is presented to better assess the influence of NK cell-mediated alloreactivity on transplant outcomes. Ninety-eight HLA matched unrelated donor (URD) HCT recipients were retrospectively studied. The KIR-KIRL interactions were quantified using a system of matrix equations. Unit values were ascribed to each KIR-KIRL interaction and directionality of interactions was denoted by, either a positive (activating) or negative symbol (inhibition); these interactions were then summed. The absolute values of both the missing KIRL as well as inhibitory KIR-KIRL interactions were significantly associated with overall survival and relapse. These score components were initially used to develop a weighted (w-KIR Score) and subsequently a simplified, non-weighted KIR-KIRL interaction scores (IM-KIR Score). Increased w-KIR Score and IM-KIR Score were both predictive of all-cause mortality and relapse; w-KIR score HR of 0.37 (P=0.001) and 0.44 (P=0.044) respectively; IM-KIR score HR of 0.5 (P=0.049) and 0.44 (P=0.002) respectively. IM-KIR score was also associated with NK cell reconstitution post HCT. KIR-KIRL interactions as reflected by the w-KIR and IM-KIR scores influence both relapse risk and survival in recipients of HLA matched URD HCT with hematological malignancies.HighlightsKiller immunoglobulin-like receptor (KIR) – KIR-ligand (KIRL) interactions display a high degree of variability in HLA matched stem cell transplant (SCT) recipients.Individually, the magnitude of inhibitory and missing KIR-KIRL interactions predicts overall survival and relapse risk following SCT.Taken together the known KIR-KIRL interactions also predict clinical outcomes after HLA matched unrelated donor stem cell transplantation.
Opioid prescribing in the emergency department of a tertiary hospital: A retrospective audit of hospital discharge data
Authors: Stanley Beata , Collins Lisa J , Norman Amanda F , Karro Jonathon , Jung Monica , Bonomo Yvonne A 
Published: June 2019

AbstractObjectiveEDs are a common source of prescription opioids on discharge. We explored opioid prescribing practices in an ED at a tertiary hospital in Victoria, Australia.MethodsA retrospective audit over a 6 month period of patients discharged from the ED to the community with the maximum allowable quantities of prescription opioids.ResultsThere was a total of 3301 patient‐episodes discharged with a prescription from the ED. Of these, 766 (23.2%, 95% confidence interval [CI] 21.8–24.6) were prescribed opioids, with over half discharged with the maximum allowable quantities of prescription opioids. Immediate‐release opioids were prescribed in 362 (85.8%, 95% CI 82.5–89.1) patient‐episodes, a combination of immediate‐release and slow‐release preparations were prescribed in 29 (6.9%, 95% CI 4.5–9.3) and 31 (7.3%, 95% CI 4.8–9.8) were prescribed as slow‐release opioids alone. Co‐prescription of other analgesia with opioids occurred in 152 (36.0%, 95% CI 31.4–40.6) patient‐episodes. Possible drug interactions between opioids and other medications were noted in 117 (27.7%, 95% CI 23.4–32.0) patient‐episodes. Discharge summaries were prepared for 360 (85.3%, 95% CI 81.9–88.7) patient‐episodes, but only 171 (40.5%, 95% CI 35.8–45.2) included a plan to address the opioids, be that an opioid‐weaning regimen, analgesia review or referral to a pain specialist on discharge.ConclusionOpioid prescribing was common in this ED, with almost one‐quarter of discharge prescriptions being for a prescription opioid. This audit highlights potential areas for practice improvement including review of the quantity of opioid tablets prescribed as well as an opioid plan on discharge from the ED.
A chromosome‐level genome assembly of the giant grouper (Epinephelus lanceolatus) provides insights into its innate immunity and rapid growth
Authors: Zhou Qian , Gao Haoyang , Zhang Yong , Fan Guangyi , Xu Hao , Zhai Jieming , Xu Wenteng , Chen Zhangfan , Zhang He , Liu Shanshan , Niu Yipeng , Li Wensheng , Li Weiming , Lin Haoran , Chen Songlin 
Published: June 2019

AbstractThe giant grouper (Epinephelus lanceolatus) is the largest coral reef teleost, with a native range that spans temperate and tropical waters in the Pacific and the Indian Oceans. It is cultured artificially and used as a breeding species in aquaculture due to its rapid growth rate. Here we report a giant grouper genome assembled at the chromosome scale from sequences generated using Illumina and high‐throughput chromatin conformation capture (Hi‐C) technology. The assembly comprised 1.086 Gb, with 98.4% of the scaffold sequences anchored into 24 chromosomes. The contig and scaffold N50 values were 119.9 kb and 46.2 Mb, respectively. The assembly is of high integrity, including 96.4% universal single‐copy orthologues based on BUSCO analysis. Through chromosome‐scale evolution analysis, we identified alignments of six giant grouper chromosomes to three stickleback chromosomes and some of the genes located within the breakpoints of reshuffling events may related to development and growth. From the 24,718 protein‐coding genes, we found that several gene families related to innate immunity and glycan biosynthesis were significantly expanded in the giant grouper genome compared to other teleost genomes. In addition, we identified several genes related to the hormone signalling pathway and innate immunity that have experienced positive selection or accelerated evolution, implicating their roles in immune defence and fast growth of the species. The high‐quality genome assembly will provide a valuable genomic resource for further biological and evolutionary studies, and useful genomic tools for breeding of the giant grouper.
Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity
Authors: Soh Wai Tuck , Aglas Lorenz , Mueller Geoffrey A. , Gilles Stefanie , Weiss Richard , Scheiblhofer Sandra , Huber Sara , Scheidt Tamara , Thompson Peter M. , Briza Peter , London Robert E. , Traidl‐Hoffmann Claudia , Cabrele Chiara , Brandstetter Hans , Ferreira Fatima 
Published: June 2019

AbstractBackgroundOver 100 million people worldwide suffer from birch pollen allergy. Bet v 1 has been identified as the major birch pollen allergen. However, the molecular mechanisms of birch allergic sensitization, including the roles of Bet v 1 and other components of the birch pollen extract, remain incompletely understood. Here, we examined how known birch pollen–derived molecules influence the endolysosomal processing of Bet v 1, thereby shaping its allergenicity.MethodsWe analyzed the biochemical and immunological interaction of ligands with Bet v 1. We then investigated the proteolytic processing of Bet v 1 by endosomal extracts in the presence and absence of ligands, followed by a detailed kinetic analysis of Bet v 1 processing by individual endolysosomal proteases as well as the T‐cell epitope presentation in BMDCs.ResultsWe identified E1 phytoprostanes as novel Bet v 1 ligands. Pollen‐derived ligands enhanced the proteolytic resistance of Bet v 1, affecting degradation kinetics and preferential cleavage sites of the endolysosomal proteases cathepsin S and legumain. E1 phytoprostanes exhibited a dual role by stabilizing Bet v 1 and inhibiting cathepsin protease activity.ConclusionBet v 1 can serve as a transporter of pollen‐derived, bioactive compounds. When carried to the endolysosome, such compounds can modulate the proteolytic activity, including its processing by cysteine cathepsins. We unveil a paradigm shift from an allergen‐centered view to a more systemic view that includes the host endolysosomal enzymes.
The role of mobile health technologies in allergy care: An EAACI position paper
Authors: Matricardi Paolo Maria , Dramburg Stephanie , Alvarez‐Perea Alberto , Antolín‐Amérigo Darío , Apfelbacher Christian , Atanaskovic‐Markovic Marina , Berger Uwe , Blaiss Michael S. , Blank Simon , Boni Elisa , Bonini Matteo , Bousquet Jean , Brockow Knut , Buters Jeroen , Cardona Victoria , Caubet Jean‐Christoph , Cavkaytar Özlem , Elliott Tania , Esteban‐Gorgojo Ignacio , Fonseca Joao A. , Gardner James , Gevaert Philippe , Ghiordanescu Ileana , Hellings Peter , Hoffmann‐Sommergruber Karin , Fusun Kalpaklioglu A. , Marmouz Farid , Meijide Calderón Ángela , Mösges Ralph , Nakonechna Alla , Ollert Markus , Oteros José , Pajno Giovanni , Panaitescu Catalina , Perez‐Formigo Daniel , Pfaar Oliver , Pitsios Constantinos , Rudenko Michael , Ryan Dermot , Sánchez‐García Silvia , Shih Jennifer , Tripodi Salvatore , Van der Poel Lauri‐Ann , van Os‐Medendorp Harmieke , Varricchi Gilda , Wittmann Jörn , Worm Margitta , Agache Ioana 
Published: June 2019

AbstractMobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health‐related services, data and information flow, patient self‐management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the “Be He@lthy, Be Mobile” WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the “General Data Protection Regulation” and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician‐ to patient‐centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed.
Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis
Authors: Bieber Thomas 
Published: June 2019

AbstractAtopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)‐driven disease. Interleukin (IL)‐4 and IL‐13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor‐associated signal transduction machinery such as Janus kinases. Recently, IL‐13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL‐4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL‐13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL‐13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD.
Opioid prescribing improvement in orthopaedic specialty unit in a tertiary hospital: a retrospective audit of hospital discharge data pre‐ and post‐intervention for better opioid prescribing practice
Authors: Stanley Beata , Jackson Aidan , Norman Amanda , Collins Lisa , Bonomo Anthony , Bonomo Yvonne 
Published: June 2019

BackgroundThis study aimed to investigate the effects of an intervention focusing on better opioid prescription practice in a tertiary metropolitan hospital orthopaedic unit.MethodsFollowing a previous audit of opioid prescribing in the orthopaedics unit, an intervention comprising the (i) Expert Advisory Group oversight of opioid prescribing, (ii) development of a prescription opioid guideline for various hospital contexts and (iii) a series of education sessions was undertaken to improve opioid prescription practice. A re‐audit was subsequently carried out to determine whether the intervention had had an impact on the previously audited orthopaedic unit.ResultsEach audit period was 6 months. There were 281 orthopaedic patients in the original audit (1 January 2017–30 June 2017) and 289 in the re‐audit (1 March 2018–31 August 2018). In both audits, a high proportion of patients were discharged to the community on opioids, 82.2% (n = 231) pre‐intervention and 79.6% (n = 230) post‐intervention. Statistically significant differences in opioid prescribing were found between audits, including: a reduction in the number of patients discharged on combination opioids from 71.4% to 45.7% (P < 0.001), a reduction in the provision of full pharmaceutical quantities of opioid on discharge from 29.4% to 6.1% (P < 0.001) and an increase in opioid weaning plans included in discharge summaries from 6.9% to 87.4% (P < 0.001).ConclusionRaised awareness across the organization and education for staff more than halved the post‐operative opioid prescription levels. This highlights the capacity for change in hospitals and the ability to work towards safer prescribing of post‐operative opioid therapy.
T‐tube‐free single‐incision laparoscopic common bile duct exploration plus cholecystectomy: a single centre experience
Authors: Yao Chenhui , Tian Yu , Yao Dianbo , Han Jinyan , Wu Shuodong 
Published: June 2019

BackgroundThe present study aimed to explore the indications and feasibility of T‐tube‐free trans‐umbilical single‐incision laparoscopic common bile duct exploration (SILCBDE) plus laparoscopic cholecystectomy (LC) for treating choledocholithiasis.MethodsPatients hospitalized in the Second Affiliated Hospital (Shengjing Hospital) of China Medical University from January 2010 to January 2017 with the diagnosis of common bile duct stones and treated with T‐tube‐free trans‐umbilical single‐incision LC plus common bile duct exploration were retrospectively analysed.ResultsA total of 37 male/female choledocholithiasis patients (mean age 65 years, range 29–86) were treated with T‐tube‐free trans‐umbilical SILCBDE plus LC. No intraoperative complication or conversion to open surgery occurred in any of the cases. The mean operative time was 99.8 min (range 84–125) for endoscopic nasobiliary drainage group (n = 6), 113.8 min (range 70–150) for endoscopic retrogradebiliary drainage group (n = 2), 131.1 min (range 75–161) for pigtail J‐tube group (n = 24), 113.7 min (range 100–150) for primary closure group (n = 5). The mean post‐operative hospital stay length was 5.5 days (range 4–7) for endoscopic nasobiliary drainage group, 12.5 days (range 10–15) for endoscopic retrogradebiliary drainage group, 6.5 days (range 4–10) for J‐tube group, 5.8 days (range 4–9) for primary closure group. Pancreatitis, bile leakage and peritonitis were not presented in any of the group. After 17–101 months follow‐up, three patients presented recurrent common bile duct stones.ConclusionIn selected cases, T‐tube‐free trans‐umbilical SILCBDE plus LC is feasible and safe for experienced surgeons, and can achieve similar therapeutic effects as common LC plus common bile duct exploration procedures.