Dear Editor,The coronavirus disease 2019 (COVID-19) pandemic will stretch hospital resources all over the world. EDs in high-income countries are not immune, but those in low-income and middle-income countries (LMICs) are likely to be impacted more significantly. Emerging data speak to overwhelming demands for care and widespread disruption of hospital functioning.1In order to support colleagues in resource-limited settings, the Australasian College from Emergency Medicine (ACEM) has developed a...
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Related ArticlesPrimordial Prevention of High Blood Pressure in Childhood: An Opportunity Not to be Missed. Hypertension. 2020 Mar 30;:HYPERTENSIONAHA11914059 Authors: Falkner B, Lurbe E Abstract Hypertension is a condition with increased risk for subsequent adverse events, and treatment of hypertension is prescribed for primary prevention of adverse events. Primordial prevention is a concept that precedes primary prevention and focuses on risk factor...
Related ArticlesA placebo prognostic index (PI) as a moderator of outcomes in the treatment of adolescent depression: Could it inform risk-stratification in treatment with cognitive-behavioral therapy, fluoxetine, or their combination? Psychother Res. 2020 Mar 29;:1-14 Authors: Lorenzo-Luaces L, Rodriguez-Quintana N, Riley TN, Weisz JR Abstract Introduction: Researchers have proposed that predicting who is a likely placebo responder may help guide treatment...
Related ArticlesEditorial: hepatocellular carcinoma in the absence of cirrhosis-a nightmare without solution. Aliment Pharmacol Ther. 2019 11;50(9):1062-1063 Authors: Ioannou GN PMID: 31625189 [PubMed - indexed for MEDLINE]
Related ArticlesProblems of feeding, sleeping and excessive crying in infancy: a general population study. Arch Dis Child. 2019 11;104(11):1034-1041 Authors: Olsen AL, Ammitzbøll J, Olsen EM, Skovgaard AM Abstract OBJECTIVE: To study regulatory problems (RPs) of feeding, sleeping and excessive crying in infancy, and explore the influence of maternal mental health problems and parent-child relationship problems. DESIGN AND SETTING: Data were...
Related ArticlesManaging burnout in medical personnel. J Paediatr Child Health. 2019 06;55(6):728-729 Authors: Lee JC, Kapur N, Chong JW PMID: 31155787 [PubMed - indexed for MEDLINE]
Related ArticlesAre they sleeping and talking? The students in 'how to give a better lecture'. J Paediatr Child Health. 2019 04;55(4):488-489 Authors: Phelps M, Scott KM PMID: 30957326 [PubMed - indexed for MEDLINE]
Related ArticlesTomorrow's gonna suck: Today's stress anticipation predicts tomorrow's post-awakening cortisol increase. Psychoneuroendocrinology. 2019 08;106:38-46 Authors: Kramer AC, Neubauer AB, Stoffel M, Voss A, Ditzen B Abstract The cortisol awakening response (a rapid rise in cortisol concentration shortly after awakening) is hypothesized to prepare the organism to cope with upcoming demands, suggesting a key role for anticipatory stress in its...
Related ArticlesPharmacotherapy for the Treatment of Cannabis Use Disorder: A Systematic Review Book. 2019 02 Authors: Kondo K, Morasco BJ, Nugent S, Ayers C, O’Neil ME, Freeman M, Paynter R, Kansagara D Abstract Social, medical, and legal acceptance of cannabis has grown dramatically over the last 15 years, and cannabis use – for medical and recreational purposes – has also increased. From 2002 to 2012, the prevalence of daily cannabis use in the United States increased...
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J. Intell., Vol. 8, Pages 14: Mitochondrial Functioning and Its Relation to Higher-Order Cognitive Processes Journal of Intelligence doi: 10.3390/jintelligence8020014 Authors: Alexander P. Burgoyne Randall W. Engle One of the most replicated findings in psychology is the positive manifold between cognitive ability measures (Jensen 1998; Spearman 1904) [...]
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Abstract Objective The objective was to assess the 2‐year clinical performance of three drug‐eluting stents in all‐comer patients with severely calcified coronary lesions. Background Severe lesion calcification increases cardiovascular event risk after coronary stenting, but there is a lack of data on the clinical outcome of all‐comers with severely calcified lesions who were treated with more recently introduced drug‐eluting stents. Methods The BIO‐RESORT trial (clinicaltrials.gov:...
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Background: The dynamics ofpulsatile waveforms travelling the central aorta are governed by pressures and arterial compliance. Arterial stiffness, the inverse of compliance, is an independent risk factor for cardiovascular disease and has been suggested as a superior risk index compared to brachial blood pressure (BP). Arterial stiffness is typically measured via carotid-femoral pulse wave velocity (cfPWV) in the supine position; however, different body positions alter orthostatic column height,...
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Anal squamous cell carcinoma is a rare tumor. Chemo-radiotherapy yields a 50% 3-year relapse-free survival rate in advanced anal cancer, so improved predictive markers and therapeutic options are needed. High-throughput proteomics and whole-exome sequencing were performed in 46 paraffin samples from anal squamous cell carcinoma patients. Hierarchical clustering was used to establish groups de novo. Then, probabilistic graphical models were used to study the differences between groups of patients...
Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting...
State-of-the-art proteomics-grade mass spectrometers can measure peptide precursors and their fragments with ppm mass accuracy at sequencing speeds of tens of peptides per second with attomolar sensitivity. Here we describe a compact and robust quadrupole-orbitrap mass spectrometer equipped with a front-end High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) Interface. The performance of the Orbitrap Exploris 480 mass spectrometer is evaluated in data-dependent acquisition (DDA) and...
In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis...
C9ORF72-associated Motor Neuron Disease patients feature abnormal expression of 5 dipeptide repeat (DPR) polymers. Here we used quantitative proteomics in a mouse neuronal-like cell line (Neuro2a) to demonstrate that the Arg residues in the most toxic DPRS, PR and GR, leads to a promiscuous binding to the proteome compared with a relative sparse binding of the more inert AP and GA. Notable targets included ribosomal proteins, translation initiation factors and translation elongation factors. PR and...
Bacteria secrete siderophores to access iron, a key nutrient poorly bioavailable and the source of strong competition between microorganisms in most biotopes. Many bacteria also use siderophores produced by other microorganisms (exosiderophores) in a piracy strategy. Pseudomonas aeruginosa, an opportunistic pathogen, produces two siderophores, pyoverdine and pyochelin, and is also able to use a panel of exosiderophores. We first investigated expression of the various iron-uptake pathways of P. aeruginosa...
Large-scale identification of N-linked intact glycopeptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in human serum is challenging because of the wide dynamic range of serum protein abundances, the lack of a complete serum N-glycan database and the existence of proteoforms. In this regard, a spectral library search method was presented for the identification of N-linked intact glycopeptides from N-linked glycoproteins in human serum with target-decoy and motif-specific...
The cell cycle is a highly conserved process involving the coordinated separation of a single cell into two daughter cells. To relate transcriptional regulation across the cell cycle with oscillatory changes in protein abundance and activity, we carried out a proteome- and phospho-proteome-wide mass spectrometry profiling. We compared protein dynamics with gene transcription, revealing many transcriptionally regulated G2 mRNAs that only produce a protein shift after mitosis. Integration of CRISPR/Cas9...
We present a technological advancement for the estimation of the affinities of Protein-Protein Interactions (PPIs) in living cells. A novel set of vectors is introduced that enables a quantitative yeast two-hybrid system based on fluorescent fusion proteins. The vectors allow simultaneous quantification of the reaction partners (Bait and Prey) and the reporter at the single-cell level by flow cytometry. We validate the applicability of this system on a small but diverse set of PPIs (eleven protein...
An experimental and computational approach for identification of protein-protein interactions by ex vivo chemical crosslinking and mass spectrometry (CLMS) has been developed that takes advantage of the specific characteristics of cyanurbiotindipropionylsuccinimide (CBDPS), an affinity-tagged isotopically coded mass spectrometry (MS)-cleavable crosslinking reagent. Utilizing this reagent in combination with a crosslinker-specific data-dependent acquisition strategy based on MS2 scans, and a software...
Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale...
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From an economic point of view, Bovidae represent the most important family of the Ruminantia suborder. Thus, the mitochondrial and nuclear genomes of Bos taurus were among the first genomes to be sequenced after the sequencing of the human genomes. Over the millennia, the evolution of the genomes of the 3 main species belonging to the Bovidae family - B. taurus (BTA), Ovis aries (OAR), and Capra hircus (CHI) - has led to few chromosome rearrangements. Certainly, the availability and free access...
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Abstract Disseminated phaeohyphomycosis is a rare and unusual infection that can be caused by dematiaceous fungi. Cyphellophora is an uncommon aetiological agent of cutaneous and systemic fungal infections. This study describes a case of disseminated phaeohyphomycosis caused by C. ludoviensis in Iran. The molecular identification of the isolates was established by DNA sequencing of the internal transcribed spacer (ITS) region of rDNA. The patient was successfully treated with an 8‐month course...
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Purpose:Small-cell neuroendocrine prostate cancer (SCNPC) exhibits an aggressive clinical course and incidence rates seem to be increasing following resistance to potent androgen receptor (AR) antagonists. Currently, treatment options are limited and few model systems are available to identify new approaches for treatment. We sought to evaluate commonalities between SCNPC and other aggressive neuroendocrine carcinomas to identify therapeutic targets. Experimental Design:We generated whole transcriptome...
The present ReACT trial provides data from a small randomized controlled vaccination trial that in addition to other recent immunotherapy trials in glioblastoma allows sketching a rational, advanced trial design for the development of (immune) therapies in glioblastoma elaborating on but not restricting to biological monitoring and endpoints. See related article by Reardon et al., p. 1586
Purpose:This study aims to provide comprehensive insights into longitudinal immune landscape in acute myeloid leukemia (AML) development and treatment, which may contribute to predict prognosis and guide clinical decisions. Experimental Design:Periphery blood samples from 79 patients with AML (at diagnosis or/and after chemotherapy or at relapse) and 24 healthy controls were prospectively collected. We performed phenotypic and functional analysis of various lymphocytes through multiparametric flow...
KRAS G12C inhibitors have shown promise in KRAS G12C–mutant lung cancer but intrinsic and acquired resistance are common. Cotreatment with inhibitors of the protein phosphatase SHP2 can abrogate the adaptive response of cancer cells to KRAS inhibitors resulting in greater suppression of MAPK signaling and enhanced tumor growth inhibition. See related article by Ryan et al., p. 1633
Purpose:Despite its enormous successes, the overall response rate of cancer immunotherapy remains suboptimal, especially in breast cancer. There is an increased interest in combining immune checkpoint inhibitor with targeted agents to enhance antitumor effect. Anti-angiogenic drugs have been shown to synergize with immune checkpoint blockades, but the optimal setting for combining these two modalities and the underlying mechanisms of synergistic responses are not fully understood. Experimental...
The progression of multiple myeloma, a hematologic malignancy characterized by unregulated plasma cell growth, is associated with increasing innate and adaptive immune system dysfunction, notably in the T-cell repertoire. Although treatment advances in multiple myeloma have led to deeper and more durable clinical responses, the disease remains incurable for most patients. Therapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and activating the host immune system...
Purpose:This two-part phase Ib trial determined the maximum tolerated dose (MTD) of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with advanced gastrointestinal tumors, and evaluated the safety, pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and bevacizumab triplet combination in previously treated metastatic colorectal cancer (mCRC). Patients and Methods:Dose escalation (3+3 design) in advanced gastrointestinal tumors was followed by expansion...
Purpose:Emergence of mismatch repair (MMR) deficiency is a frequent mechanism of acquired resistance to the alkylating chemotherapeutic temozolomide (TMZ) in gliomas. Poly(ADP-ribose) polymerase inhibitors (PARPi) have been shown to potentiate TMZ cytotoxicity in several cancer types, including gliomas. We tested whether PARP inhibition could re-sensitize MSH6-null MMR-deficient gliomas to TMZ, and assessed the role of the base excision repair (BER) DNA damage repair pathway in PARPi-mediated effects....
Purpose:To characterize the population pharmacokinetics of cyclophosphamide, active 4-hydroxy-cyclophosphamide (4OH-CTX), and inactive carboxyethylphosphoramide mustard (CEPM), and their associations with hematologic toxicities in infants and young children with brain tumors. To use this information to provide cyclophosphamide dosing recommendations in this population. Patients and Methods:Patients received four cycles of a 1-hour infusion of 1.5 g/m2 cyclophosphamide. Serial samples were collected...
Purpose:Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA THAP9-AS1 in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of THAP9-AS1 in PDAC. Experimental Design:The overexpression of THAP9-AS1 in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the THAP9-AS1...
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