PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study.

Corrigendum to "PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study" [Biomed. Pharmacother. 159 (2023) 114220]. Biomed Pharmacother. 2023 Apr 27;114803. doi: 10.1016/j.biopha.2023.114803. PMID: 37120412.Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 and PI18CIII/00028 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, PI18CIII/00020 to AFR, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovación (AEI, PID2021-126781OB-I00 to AFR). The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (CB21/13/00044).S

rs7903146 polymorphism at transcription factor 7 like 2 gene is associated with total cholesterol and lipoprotein profile in HIV/hepatitis C virus-coinfected patients

Transcription factor 7 like 2 (TCF7L2) rs7903146 polymorphism has been associated with metabolic disturbance and cardiovascular disease. The aim of this study was to analyze the association between TCF7L2 rs7903146 polymorphism and potential disturbances on the lipid profile in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We performed a cross-sectional study on 263 HIV/HVC-coinfected patients. TCF7L2 polymorphism was genotyped by GoldenGate assay. The analysis was performed by linear and logistic regression under a dominant model of inheritance. The variables analyzed were total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), non-HDL-C, and triglycerides. Patients harboring the rs7903146 TT/TC genotype showed a diminished concentration of TC (p=0.003), LDL-C (p=0.004), HDL-C (p=0.012), and non-HDL-C (p=0.013), a lower percentage of TC≥200 mg/dl (p=0.038), and a higher percentage of HDL≤40 mg/dl (p=0.023). In addition, we observed that rs7903146 was differently related to fasting serum lipid levels according to the HCV-genotype (HCV-GT). With regard to HCV-GT1 patients, the rs7903146 TT/TC genotype was associated with lower levels of HDL-C [adjusted arithmetic mean ratio (aAMR)=0.91; p=0.049] and an elevated percentage of patients with HDL-C≤40 mg/dl [adjusted odds ratio (aOR)=3.26; p=0.003]. For HCV-GT3 patients, the rs7903146 TT/TC genotype was associated with lower serum values of TC (aAMR=0.81; p=0.037), LDL-C (aAMR=0.67; p=0.001), and non-HDL-C (aAMR=0.75; p=0.002) and a reduced percentage of TC≥200 mg/dl (aOR=0.089; p=0.037). In conclusion, the TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of TC, LDL, and HDL in HCV-GT3 patients, and lower levels of HDL-C in HCV-GT1 patients, suggesting a role in cardiovascular disease and a potential use as a biomarker in HIV/HCV-coinfected patients.D.P.T., M.A.JS., and M.G.A. have received research funding from “Instituto de Salud Carlos III” [grants CM12/00043, CM10/00105, and CD12/00442, respectively]. J.B. is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS). This work has been supported by grants from Fondo de Investigación de Sanidad en España (FIS) [Spanish Health Funds for Research] [grants PI08/0738, PI11/00245; PI08/0928, and PI11/01556], and “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE) [grant 361020/10]. This work has been (partially) funded by the RD12/0017/0024 and RD12/0017/0004 projects as part of the Plan Nacional R+D+I and cofinanced by ISCIII––Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).S

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients

Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways ("cytokine-cytokine receptor interaction", "viral protein interaction with cytokine and cytokine receptor", "chemokine signaling pathway", and "hepatitis C"). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.This study was supported by grants from Instituto de Salud Carlos III (ISCII; grant numbers PI20/00474 and PI17/00657 to JB, PI20/00507 and PI17/00903 to JGG, PI18CIII/00020 to AF-R, PI18CIII/00028 to MA, and PI20CIII/00004 and PI17CIII/00003 to SR). AF-R and MA are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MAJS). The study was also funded by the RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002 projects as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Ref. INT16/00100. DS-C is a ‘Sara Borrell’ researcher from ISCIII (grant number CD20CIII/00001) and has also been supported through Fundación SEIMC-GESIDA by a fellowship award from Fundación ONCE ‘Oportunidad al Talento, 2019/20 and 2020/21’ co-financed by Fondo Social Europeo.S

Metabolomic changes after DAAs therapy are related to the improvement of cirrhosis and inflammation in HIV/HCV-coinfected patients

Background: A better understanding of the evolution of cirrhosis after hepatitis C virus (HCV) clearance is essential since the reversal of liver injury may not happen. We aimed to assess the evolution of plasma metabolites after direct-acting antivirals (DAAs) therapy and their association with liver disease scores in HIV/HCV-coinfected patients with advanced HCV-related cirrhosis. Methods: We performed a prospective study in 49 cirrhotic patients who started DAAs therapy. Data and samples were collected at baseline and 36 weeks after SVR. Metabolomics analysis was carried out using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Inflammation-related biomarkers were analyzed using ProcartaPlex Immunoassays. Results: At 36 weeks after SVR, patients experienced significant decrease in taurocholic acid, 2,3-butanediol, and LPC(18:0); while several phosphatidylcholines (LPC(16:1), LPC(18:1), LPC(20:4), and PC(16:0/9:0(CHO))/PC(16:0/9:0(COH)), 2-keto-n-caproic acid/2-keto-isocaproic acid and N-methyl alanine increased, compared to baseline. The plasma decrease in taurocholic acid was associated with a reduction in Child-Turcotte-Pugh (CTP) (AMR=3.39; q-value=0.006) and liver stiffness measurement (LSM) (AMR=1.06; q-value<0.001), the plasma increase in LPC(20:4) was related to a reduction in LSM (AMR=0.98; q-value=0.027), and the rise of plasma 2-keto-n-caproic acid/2-keto-isocaproic acid was associated with a reduction in CTP (AMR=0.35; q-value=0.004). Finally, plasma changes in taurocholic acid were directly associated with inflammation-related biomarkers, while changes in LPC(20:4) were inversely associated. Conclusions: Plasma metabolomic profile changed after HCV clearance with all oral-DAAs in HIV/HCV-coinfected with advanced HCV-related cirrhosis. Changes in plasma levels of LPC (20: 4), 2-keto-n-caproic acid/2-keto-isocaproic acid, and taurocholic acid were related to improvements in cirrhosis scores and inflammatory status of patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 (MPY407/18) and PI18CIII/00028 (MPY385/18) to MAJS, PI14/01094, PI17/00657, and PI20/00474 to JB, PI14/01581, PI17/00903 and PI20/00507 to JGG, and PI14CIII/00011, PI17CIII/00003, and PI20CIII/00004 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11–241). The study was also funded by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002) and Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas (CB21/13/00044 and CB21/13/00039). MAJS is a Miguel Servet researcher supported and funded by ISCIII (grant number: CP17CIII/00007). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT16/00100. CB and DR acknowledge funding from the Ministerio de Ciencia, Innovación y Universidades (RTI2018–095166-B-I00).S

Assessing, quantifying and valuing the ecosystem services of coastal lagoons

The natural conservation of coastal lagoons is important not only for their ecological importance, but also because of the valuable ecosystem services they provide for human welfare and wellbeing. Coastal lagoons are shallow semi-enclosed systems that support important habitats such as wetlands, mangroves, salt-marshes and seagrass meadows, as well as a rich biodiversity. Coastal lagoons are also complex social-ecological systems with ecosystem services that provide livelihoods, wellbeing and welfare to humans. This study assessed, quantified and valued the ecosystem services of 32 coastal lagoons. The main findings of the study are: (i) the definitions of ecosystem services are still not generally accepted; (ii) the quantification of ecosystem services is made in many different ways, using different units; (iii) the evaluation in monetary terms of some ecosystem service is problematic, often relying on non-monetary evaluation methods; (iv) when ecosystem services are valued in monetary terms, this may represent very different human benefits; and, (v) different aspects of climate change, including increasing temperature, sea-level rise and changes in rainfall patterns threaten the valuable ecosystem services of coastal lagoons.DEVOTES project, from the European Union's Seventh Framework Programme for research, technological development and demonstration [308392]; networks and communities of Eurolag; Future Earth Coasts; SCOR; Fundacao para a Ciencia e a Tecnologia (FCT) Investigador Programme [IF/00331/2013]; Fundacao para a Ciencia e a Tecnologia [UID/MAR/04292/2013]; CESAM by FCT/MEC national funds (PIDDAC) [UID/AMB/50017/2013 - POCI-01-0145-FEDER-007638]; FEDER; European Commission, under the 7th Framework Programme through the collaborative research project LAGOONS [283157]; FCT [SFRH/BPD/107823/2015, SFRH/BPD/91494/2012

Community-developed checklists for publishing images and image analysis

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However for scientists wishing to publish the obtained images and image analyses results, there are to date no unified guidelines. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here we present community-developed checklists for preparing light microscopy images and image analysis for publications. These checklists offer authors, readers, and publishers key recommendations for image formatting and annotation, color selection, data availability, and for reporting image analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby heighten the quality of microscopy data is in publications.Comment: 28 pages, 8 Figures, 3 Supplmentary Figures, Manuscript, Essential recommendations for publication of microscopy image dat

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217