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Foods (Basel, Switzerland) Jul 2020The beer production chain includes some crucial steps regarding processing, delivery, service, and consumption that can benefit from the implementation of IoT (Internet... (Review)
Review
The beer production chain includes some crucial steps regarding processing, delivery, service, and consumption that can benefit from the implementation of IoT (Internet of Things) based technologies. Large breweries implemented the use of sensors and digitization before smaller ones among which are craft breweries. Internet of Beer (IoB) technologies are becoming accessible to mid and small sized brewing companies. Therefore, the objective of this work is to review mainly low-cost IoB smart technologies that can be implemented from the mash to the final product and its service, to improve the brewing production, control, delivery, and final quality increasing profitability. The reviewed applications were retrieved both from the scientific databases and from the web. The work is structured in three macro areas such as beer processing, product logistics and traceability, and service. The results show a future trend characterized by a very fast increase in the use of IoB (also open source) systems to drive efficiency, productivity, quality, and safety. This will be done by real-time monitoring and a data-driven decision support system (DSS). Crucial aspects needing further investigation are data ownership and data standardization. The access price of IoB devices and software is destined for a significant decrease while their diversification on the market will grow leading to a massive future implementation within all the production levels.
PubMed: 32709156
DOI: 10.3390/foods9070950 -
Nucleic Acids Research Jul 2022Gliomas are one of the most common and lethal brain tumors among adults. One process that contributes to glioma progression and recurrence is the epithelial to...
Gliomas are one of the most common and lethal brain tumors among adults. One process that contributes to glioma progression and recurrence is the epithelial to mesenchymal transition (EMT). EMT is regulated by a set of defined transcription factors which tightly regulate this process, among them is the basic helix-loop-helix family member, TWIST1. Here we show that TWIST1 is methylated on lysine-33 at chromatin by SETD6, a methyltransferase with expression levels correlating with poor survival in glioma patients. RNA-seq analysis in U251 glioma cells suggested that both SETD6 and TWIST1 regulate cell adhesion and migration processes. We further show that TWIST1 methylation attenuates the expression of the long-non-coding RNA, LINC-PINT, thereby promoting EMT in glioma. Mechanistically, TWIST1 methylation represses the transcription of LINC-PINT by increasing the occupancy of EZH2 and the catalysis of the repressive H3K27me3 mark at the LINC-PINT locus. Under un-methylated conditions, TWIST1 dissociates from the LINC-PINT locus, allowing the expression of LINC-PINT which leads to increased cell adhesion and decreased cell migration. Together, our findings unravel a new mechanistic dimension for selective expression of LINC-PINT mediated by TWIST1 methylation.
Topics: Humans; Epithelial-Mesenchymal Transition; Nuclear Proteins; Protein Methyltransferases; Twist-Related Protein 1; Glioma; RNA, Long Noncoding; Cell Line, Tumor
PubMed: 35694846
DOI: 10.1093/nar/gkac485 -
Journal of the American Heart... Mar 2023Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death,... (Randomized Controlled Trial)
Randomized Controlled Trial
Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo; =0.004). Methods and Results We performed post hoc efficacy and safety analyses of patients with or without prior AF (before randomization) and with or without in-study time-varying AF hospitalization to assess relationships of IPE (versus placebo) and outcomes. In-study AF hospitalization event rates were higher in patients with prior AF (12.5% versus 6.3%, IPE versus placebo; =0.007) versus without prior AF (2.2% versus 1.6%, IPE versus placebo; =0.09). Serious bleeding rates trended higher in patients with (7.3% versus 6.0%, IPE versus placebo; =0.59) versus without prior AF (2.3% versus 1.7%, IPE versus placebo; =0.08). With IPE, serious bleeding trended higher regardless of prior AF (interaction value []=0.61) or postrandomization AF hospitalization (=0.66). Patients with prior AF (n=751, 9.2%) versus without prior AF (n=7428, 90.8%) had similar relative risk reductions of the primary composite and key secondary composite end points with IPE versus placebo (=0.37 and =0.55, respectively). Conclusions In REDUCE-IT, in-study AF hospitalization rates were higher in patients with prior AF especially in those randomized to IPE. Although serious bleeding trended higher in those randomized to IPE versus placebo over the course of the study, serious bleeding was not different regardless of prior AF or in-study AF hospitalization. Patients with prior AF or in-study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01492361; Unique Identifier: NCT01492361.
Topics: Humans; Atrial Fibrillation; Risk Factors; Eicosapentaenoic Acid; Stroke; Treatment Outcome
PubMed: 36802845
DOI: 10.1161/JAHA.121.026756 -
Cardiovascular Diabetology Aug 2023Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects....
Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis.
BACKGROUND
Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk.
METHODS
Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated.
RESULTS
Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [p] > 0.05). Semaglutide reduced HbA regardless of baseline eGFR and UACR (p>0.05); reductions in BW were affected by baseline eGFR (p<0.001) but not UACR (p>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup.
CONCLUSIONS
MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage.
TRIAL REGISTRATIONS
NCT01720446; NCT02692716.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Cardiovascular System; Kidney; Renal Insufficiency
PubMed: 37620807
DOI: 10.1186/s12933-023-01949-7 -
Cancer Cell International Sep 2022Sonic Hedgehog (Shh) signaling cascade is one of the complex signaling pathways that control the accurately organized developmental processes in multicellular organisms.... (Review)
Review
Sonic Hedgehog (Shh) signaling cascade is one of the complex signaling pathways that control the accurately organized developmental processes in multicellular organisms. This pathway has fundamental roles in the tumor formation and induction of resistance to conventional therapies. Numerous non-coding RNAs (ncRNAs) have been found to interact with Shh pathway to induce several pathogenic processes, including malignant and non-malignant disorders. Many of the Shh-interacting ncRNAs are oncogenes whose expressions have been increased in diverse malignancies. A number of Shh-targeting miRNAs such as miR-26a, miR-1471, miR-129-5p, miR-361-3p, miR-26b-5p and miR-361-3p have been found to be down-regulated in tumor tissues. In addition to malignant conditions, Shh-interacting ncRNAs can affect tissue regeneration and development of neurodegenerative disorders. XIST, LOC101930370, lncRNA-Hh, circBCBM1, SNHG6, LINC-PINT, TUG1 and LINC01426 are among long non-coding RNAs/circular RNAs that interact with Shh pathway. Moreover, miR-424, miR-26a, miR-1471, miR-125a, miR-210, miR-130a-5p, miR-199b, miR-155, let-7, miR-30c, miR-326, miR-26b-5p, miR-9, miR-132, miR-146a and miR-425-5p are among Shh-interacting miRNAs. The current review summarizes the interactions between ncRNAs and Shh in these contexts.
PubMed: 36100906
DOI: 10.1186/s12935-022-02702-y -
International Immunopharmacology Oct 2021Asthma is a chronic respiratory disease worldwide. This study aimed to explore the functions of the long noncoding RNA LINC-PINT (LINC-PINT) in asthma and to determine...
BACKGROUND
Asthma is a chronic respiratory disease worldwide. This study aimed to explore the functions of the long noncoding RNA LINC-PINT (LINC-PINT) in asthma and to determine its underlying molecular mechanisms.
METHODS
Rat asthma model was established with ovalbumin sensitization and challenge. The serum level of IgE, airway hyperresponsiveness (AHR), airway inflammation, and pathological changes of lung were evaluated. Airway smooth muscle cells (ASMCs) were stimulated with platelet-derived growth factor-BB (PDGF-BB) to mimic the asthma-like condition at cellular level. QRT-PCR was performed to detect the expression of LINC-PINT, microRNA-26a-5p (miR-26a-5p), and PTEN. MTT and transwell assays were performed to measure the viability and migration of ASMCs. The protein expression of airway remodelling marker MMP-1 and MMP-9 was measured by western blot. The interactions among LINC-PINT, miR-26a-5p, and PTEN were determined by dual-luciferase reporter assay.
RESULTS
The expression of LINC-PINT and PTEN was decreased, while miR-26a-5p expression was increased in PDGF-BB-stimulated ASMCs. In vivo, overexpression of LINC-PINT decreased the serum level of IgE, AHR, airway inflammation, and pathological changes of lung in asthma rat model. In vitro, up-regulation of LINC-PINT decreased the viability, migration, and MMP-1 and MMP-9 protein expression in PDGF-BB-stimulated ASMCs. Dual-luciferase reporter assay determined that LINC-PINT targeted miR-26a-5p, and miR-26a-5p targeted PTEN in ASMCs. Feedback approaches confirmed that miR-26a-5p up-regulation or PTEN down-regulation reversed the suppressive effect of LINC-PINT overexpression on the abnormal growth of ASMCs.
CONCLUSIONS
LINC-PINT overexpression retarded the abnormal growth of ASMCs by regulating the miR-26a-5p/PTEN axis, offering a potential therapeutic target for asthma.
Topics: Airway Remodeling; Animals; Asthma; Becaplermin; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cytokines; Lung; Matrix Metalloproteinases; MicroRNAs; Models, Animal; Myocytes, Smooth Muscle; PTEN Phosphohydrolase; RNA, Long Noncoding; Rats; Respiratory System
PubMed: 34315115
DOI: 10.1016/j.intimp.2021.107997 -
Journal of the American Heart... Feb 2024There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)- and triglyceride-lowering therapies.
METHODS AND RESULTS
We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, =0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (=0.14 and =0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30).
CONCLUSIONS
We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies.
REGISTRATION
URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.
Topics: Humans; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Cholesterol, LDL; Hemorrhagic Stroke; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Ezetimibe; Stroke; Triglycerides
PubMed: 38323514
DOI: 10.1161/JAHA.123.030714 -
Scientific Reports May 2022The abnormal function of signaling cascades is currently a candidate in the pathophysiology of bipolar disorder (BD). One of the factors involved in activating these...
The abnormal function of signaling cascades is currently a candidate in the pathophysiology of bipolar disorder (BD). One of the factors involved in activating these signals is oxidative stress. Some long non-coding RNAs (lncRNA) are involved in the oxidative stress. In this study, we compared expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the peripheral blood mononuclear cells (PBMC) from BD patients (n = 50) and healthy individuals (n = 50). Expression levels of lincRNA-p21, lincRNA-ROR, and lincRNA-PINT were significantly reduced in patients with BD compared to controls. In sex-based analyses, down-regulation of these lncRNAs was revealed only in male BD patients compared to male healthy subjects. Also, in BD patients, all three lncRNAs showed a significant pairwise positive correlation in expression level. The area under curve values for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT was 0.66, 0.75, and 0.66, respectively. Thus, the ROC curve analysis showed that lncRNA-ROR might serve as a diagnostic biomarker for distinguishing between BD patients and controls. Altogether, the current study proposes a role for lincRNA-p21, lincRNA-ROR, and lincRNA-PINT in the pathogenesis of bipolar disorder. Moreover, the peripheral expression of these lncRNAs might be useful as potential biomarkers for BD.
Topics: Area Under Curve; Bipolar Disorder; Down-Regulation; Humans; Leukocytes, Mononuclear; Male; RNA, Long Noncoding
PubMed: 35523833
DOI: 10.1038/s41598-022-11674-y -
Research (Washington, D.C.) 2023Evidence available on the independent and combined associations of sleep duration, bedtime, and genetic predisposition with hearing loss was lacking. The present study...
Independent and Combined Associations of Sleep Duration, Bedtime, and Polygenic Risk Score with the Risk of Hearing Loss among Middle-Aged and Old Chinese: The Dongfeng-Tongji Cohort Study.
Evidence available on the independent and combined associations of sleep duration, bedtime, and genetic predisposition with hearing loss was lacking. The present study included 15,827 participants from the Dongfeng-Tongji cohort study. Genetic risk was characterized by polygenic risk score (PRS) based on 37 genetic loci related to hearing loss. We conducted multivariate logistic regression models to assess the odds ratio (OR) for hearing loss with sleep duration and bedtime, as well as the joint association and interaction with PRS. Results showed that hearing loss was independently associated with sleeping ≥9 h/night compared to the recommended 7 to <8 h/night, and with bedtime ≤9:00 p.m. and >9:00 p.m. to 10:00 p.m. compared to those with bedtime >10:00 p.m. to 11:00 p.m., with estimated ORs of 1.25, 1.27, and 1.16, respectively. Meanwhile, the risk of hearing loss increased by 29% for each 5-risk allele increment of PRS. More importantly, joint analyses showed that the risk of hearing loss was 2-fold in sleep duration ≥9 h/night and high PRS, and 2.18-fold in bedtime ≤9:00 p.m. and high PRS. With significant joint effects of sleep duration and bedtime on hearing loss, we found an interaction of sleep duration with PRS in those with early bedtime and an interaction of bedtime with PRS in those with long sleep duration on hearing loss ( <0.05), and such relationships were more evident in high PRS. Similarly, the above relationships were also observed for age-related hearing loss and noise-induced hearing loss, particularly the latter. In addition, age-modified effects of sleep patterns on hearing loss were likewise observed, with stronger estimation among those aged <65 years. Accordingly, longer sleep duration, early bedtime, and high PRS were independently and jointly related to increased risk of hearing loss, suggesting the importance of considering both genetics and sleep pattern for risk assessment of hearing loss.
PubMed: 37383219
DOI: 10.34133/research.0178 -
Critical Care (London, England) Dec 2023Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine...
BACKGROUND
Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles.
METHODS
The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses.
RESULTS
Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires.
CONCLUSIONS
Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.
Topics: Child; Humans; Gene Expression Profiling; Prospective Studies; Sepsis; Shock, Septic; Transcriptome; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 38066613
DOI: 10.1186/s13054-023-04689-y