bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Intranodally Administered Dendritic Cell-Based HIV Vaccine in Combination With Pegylated Interferon α-2a on Viral Control Following ART Discontinuation: A Phase 2A Randomized Clinical Trial
Authors: Leal Lorna , Couto Elvira , Sánchez-Palomino Sonsoles , Climent Núria , Fernández Irene , Miralles Laia , Romero Yolanda , González Tania , Maleno Maria José , Paño Blanca , Pich Judit , Nicolau Carlos , Gatell José Maria , Plana Montserrat , García Felipe ,   the DCV3-RISVAC04 Study Group
Published: December 2021

IntroductionFunctional cure has been proposed as an alternative to lifelong antiretroviral therapy and therapeutic vaccines represent one of the most promising approaches.Materials and MethodsWe conducted a double-blind randomized placebo-controlled clinical trial to evaluate the safety, immunogenicity, and effect on viral dynamics of a therapeutic vaccine produced with monocyte-derived dendritic cells (MD-DC) loaded with a high dose of heat-inactivated autologous (HIA) HIV-1 in combination with pegylated interferon alpha 2a (IFNα-2a) in people with chronic HIV-1.ResultsTwenty-nine male individuals on successful ART and with CD4+ ≥450 cells/mm3 were randomized 1:1:1:1 to receive three ultrasound-guided inguinal intranodal immunizations, one every 2 weeks: (1) vaccine ~107 MD-DC pulsed with HIA-HIV-1 (1010 HIV RNA copies) (n = 8); (2) vaccine plus three doses of 180 mcg IFNα-2a at weeks 4–6 (n = 6); (3) placebo = saline (n = 7); and (4) placebo plus three doses of 180 mcg IFNα-2a (n = 8). Thereafter, treatment was interrupted (ATI). Vaccines, IFNα-2a, and the administration procedures were safe and well tolerated. All patients’ viral load rebounded during the 12-week ATI period. According to groups, changes in viral set-point between pre-ART and during ATI were not significant. When comparing all groups, there was a tendency in changes in viral set-point between the vaccine group vs. vaccine + IFNα-2a group (&gt;0.5log10p = 0.05). HIV-1-specific T-cell responses (IFN-ƴ Elispot) were higher at baseline in placebo than in the vaccine group (2,259 ± 535 vs. 900 ± 200 SFC/106 PBMC, p = 0.028). A significant difference in the change of specific T-cell responses was only observed at week 4 between vaccine and placebo groups (694 ± 327 vs. 1,718 ± 282 SFC/106 PBMC, p = 0.04). No effect on T-cell responses or changes in viral reservoir were observed after INFα-2a administration.DiscussionResults from this study show that intranodally administered DC therapeutic vaccine in combination with IFNα-2a was safe and well-tolerated but had a minimal impact on viral dynamics in HIV-1 chronic infected participants.Clinical Trial Registration(www.ClinicalTrials.gov), identifier NCT02767193
Native CGRP Neuropeptide and Its Stable Analogue SAX, But Not CGRP Peptide Fragments, Inhibit Mucosal HIV-1 Transmission
Authors: Mariotton Jammy , Sams Anette , Cohen Emmanuel , Sennepin Alexis , Siracusano Gabriel , Sanvito Francesca , Edvinsson Lars , Delongchamps Nicolas Barry , Zerbib Marc , Lopalco Lucia , Bomsel Morgane , Ganor Yonatan 
Published: December 2021

BackgroundThe vasodilator neuropeptide calcitonin gene-related peptide (CGRP) plays both detrimental and protective roles in different pathologies. CGRP is also an essential component of the neuro-immune dialogue between nociceptors and mucosal immune cells. We previously discovered that CGRP is endowed with anti-viral activity and strongly inhibits human immunodeficiency virus type 1 (HIV-1) infection, by suppressing Langerhans cells (LCs)-mediated HIV-1 trans-infection in-vitro and mucosal HIV-1 transmission ex-vivo. This inhibition is mediated via activation of the CGRP receptor non-canonical NFκB/STAT4 signaling pathway that induces a variety of cooperative mechanisms. These include CGRP-mediated increase in the expression of the LC-specific pathogen recognition C-type lectin langerin and decrease in LC-T-cell conjugates formation. The clinical utility of CGRP and modalities of CGRP receptor activation, for inhibition of mucosal HIV-1 transmission, remain elusive.MethodsWe tested the capacity of CGRP to inhibit HIV-1 infection in-vivo in humanized mice. We further compared the anti-HIV-1 activities of full-length native CGRP, its metabolically stable analogue SAX, and several CGRP peptide fragments containing its binding C-terminal and activating N-terminal regions. These agonists were evaluated for their capacity to inhibit LCs-mediated HIV-1 trans-infection in-vitro and mucosal HIV-1 transmission in human mucosal tissues ex-vivo.ResultsA single CGRP intravaginal topical treatment of humanized mice, followed by HIV-1 vaginal challenge, transiently restricts the increase in HIV-1 plasma viral loads but maintains long-lasting higher CD4+ T-cell counts. Similarly to CGRP, SAX inhibits LCs-mediated HIV-1 trans-infection in-vitro, but with lower potency. This inhibition is mediated via CGRP receptor activation, leading to increased expression of both langerin and STAT4 in LCs. In contrast, several N-terminal and N+C-terminal bivalent CGRP peptide fragments fail to increase langerin and STAT4, and accordingly lack anti-HIV-1 activities. Finally, like CGRP, treatment of human inner foreskin tissue explants with SAX, followed by polarized inoculation with cell-associated HIV-1, completely blocks formation of LC-T-cell conjugates and HIV-1 infection of T-cells.ConclusionOur results show that CGRP receptor activation by full-length CGRP or SAX is required for efficient inhibition of LCs-mediated mucosal HIV-1 transmission. These findings suggest that formulations containing CGRP, SAX and/or their optimized agonists/analogues could be harnessed for HIV-1 prevention.
The Role of Interleukin-6 (IL-6) in the Systemic Inflammatory Response in Xenograft Recipients and in Pig Kidney Xenograft Failure
Authors: Zhang Guoqiang , Iwase Hayato , Li Qi , Yamamoto Takayuki , Jagdale Abhijit , Ezzelarab Mohamed B. , Ayares David , Cooper David K. C. , Hara Hidetaka , Wang Gangcheng 
Published: December 2021

BackgroundIn pig-to-baboon transplantation models, there is increasing evidence of systemic inflammation in xenograft recipients (SIXR) associated with pig xenograft failure. We evaluated the relationship between systemic inflammatory factors and pig kidney xenograft failure.MethodsBaboons received kidney transplants from genetically engineered pigs (n=9), and received an anti-CD40mAb-based (n=4) or conventional (n=5) immunosuppressive regimen. The pig kidney grafts were monitored by measurements of serum creatinine, serum amyloid A (SAA), white blood cell (WBC) and platelet counts, plasma fibrinogen, and pro-inflammatory cytokines (baboon and pig IL-6, TNF-α, IL-1β).ResultsSix baboons were euthanized or died from rejection, and 3 were euthanized for infection. Changes in serum creatinine correlated with those of SAA (r=0.56, p&lt;0.01). Serum baboon IL-6 was increased significantly on day 1 after transplantation and at euthanasia (both p&lt;0.05) and correlated with serum creatinine and SAA (r=0.59, p&lt;0.001, r=0.58, p&lt;0.01; respectively). but no difference was observed between rejection and infection. Levels of serum pig IL-6, TNF-α, IL-1β were also significantly increased on day 1 and at euthanasia, and serum pig IL-6 and IL-1β correlated with serum creatinine and SAA. The level of serum baboon IL-6 correlated with the expression of IL-6 and amyloid A in the baboon liver (r=0.93, p&lt;0.01, r=0.79, p&lt;0.05; respectively).ConclusionEarly upregulation of SAA and serum IL-6 may indicate the development of rejection or infection, and are associated with impaired kidney graft function. Detection and prevention of systemic inflammation may be required to prevent pig kidney xenograft failure after xenotransplantation.
MicroRNA Expression and Intestinal Permeability in Children Living in a Slum Area of Bangladesh
Authors: Rashid Humaira , Siddiqua Towfida J. , Hossain Biplob , Siddique Abdullah , Kabir Mamun , Noor Zannatun , Alam Masud , Ahmed Mamun , Haque Rashidul 
Published: December 2021

Introduction: MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Changes in miRNA expression have been reported in a number of intestinal diseases, in both tissue samples and readily accessible specimens like stools. Pathogenic infections, diet, toxins, and other environmental factors are believed to influence miRNA expression. However, modulation of miRNAs in humans is yet to be thoroughly investigated. In this study, we examined the expression levels of two human miRNAs (miRNA-122 and miRNA-21) in stool samples of a group of Bangladeshi children who had an altered/increased intestinal permeability (IIP).Methods: Stool samples were collected from children with IIP (L:M &gt; 0.09) and normal intestinal permeability (NIP) (L:M ≤ 0.09). Quantitative PCR was performed to quantify the levels of miRNA-122 and miR-21 in stools. Commercial ELISA kits were used to measure gut inflammatory markers Calprotectin and REG1B. Serum samples were tested using Human Bio-Plex Pro Assays to quantify IL-1β, IL-2, IL-5, IL-10, IL-13, IFN-γ, and TNF-α. Total nucleic acid extracted from stool specimens were used to determine gut pathogens using TaqMan Array Card (TAC) system real-time polymerase chain reaction.Results: The expression levels of miRNA-122 (fold change 11.6; p &lt; 0.001, 95% CI: 6.14–11.01) and miR-21 (fold change 10; p &lt; 0.001, 95% CI: 5.05–10.78) in stool were upregulated in children with IIP than in children with normal intestinal permeability (NIP). Significant correlations were observed between stool levels of miR-122 and miR-21 and the inflammatory cytokines IL-1β, IL-2, IFN-γ, and TNF-α (p &lt; 0.05). Children with IIP were frequently infected with rotavirus, Campylobacter jejuni, Bacteroides fragilis, adenovirus, norovirus, astrovirus, and various Escherichia coli strains (ETEC_STh, ETEC_STp, EAEC_aaiC, EAEC_aatA) (p &lt; 0.001). miR-122 significantly correlated with the fecal inflammatory biomarkers REG1B (p = 0.015) and Calprotectin (p = 0.030), however miR-21 did not show any correlation with these fecal biomarkers.
Herbal NF-κB Inhibitors Sensitize Rituximab-Resistant B Lymphoma Cells to Complement-Mediated Cytolysis
Authors: Ge Xiaowen , Du Yiqun , Chen Jianfeng , Zhu Na , Yao Jiamei , Zhang Xin , Wang Na , Sun Yujing , Gao Feng , Hu Weiguo , Hou Yingyong 
Published: December 2021

BackgroundDrug resistance remains a serious challenge to rituximab therapy in B-NHL (B cell non-Hodgkin’s lymphoma). CDC (complement-dependent cytotoxicity) has been proposed as a major antitumor mechanism of rituximab, and direct abrogation of CD59 function partially restores rituximab sensitivity with high efficacy. However, universal blockade of CD59 may have deleterious effects on normal cells. Sp1 regulates constitutive CD59 expression, whereas NF-κB and CREB regulate inducible CD59 expression.MethodsImmunohistochemistry (IHC) assay was used to detect the expression levels of CD59 and other related molecules. Quantitative Real-time PCR (RT-PCR) analysis was used to explore the levels of transcripts in the original and resistant cells. We chose LY8 cells to test the effects of NF-κB and CBP/p300 inhibition on CD59 expression using flow cytometry (FACS). Immunoblotting analysis was employed to detect the effects of curcumin and POH. The in vitro and in vivo experiments were used to evaluate the toxicity and combined inhibitory effect on tumor cells of curcumin and POH.ResultsWe demonstrated that herbal (curcumin and perillyl alcohol) blockade of NF-κB specifically suppresses the expression of inducible CD59 but not CD20, thus sensitizing resistant cells to rituximab-mediated CDC. Moreover, activation of NF-κB and CREB is highly correlated with CD59 expression in B-NHL tissues.ConclusionsOur findings suggest the potential of CD59 expression as a predictor of therapeutic efficacy of NF-κB inhibitors in clinical application as well as the rationality of a NF-κB inhibitor-rituximab regimen in B-NHL therapy.
Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors
Authors: Broberg Olof , Øra Ingrid , Wiebe Thomas , Weismann Constance G. , Liuba Petru 
Published: December 2021

Background: Childhood cancer survivors (CCS) are at an increased risk for cardiovascular diseases (CVD). It was the primary aim of this study to determine different measures of cardiac, carotid, lipid, and apolipoprotein status in young adult CCS and in healthy controls.Methods: Cardiac and common carotid artery (CCA) structure and function were measured by ultrasonography. Lipids and apolipoproteins were measured in the blood. Peripheral arterial endothelial vasomotor function was assessed by measuring digital reactive hyperemia index (PAT-RHI) using the Endo-PAT 2000.Results: Fifty-three CCS (20–30 years, 35 men) and 53 sex-matched controls were studied. The CCS cohort was divided by the median dose of anthracyclines into a low anthracycline dose (LAD) group (50–197 mg/m2, n = 26) and a high anthracycline dose (HAD) group (200–486 mg/m2, n = 27). Carotid distensibility index (DI) and endothelial function determined by PAT-RHI were both lower in the CCS groups compared with controls (p &lt; 0.05 and p = 0.02). There was no difference in carotid intima media thickness. Atherogenic apolipoprotein-B (Apo-B) and the ratio between Apo-B and Apoliprotein-A1 (Apo-A1) were higher in the HAD group compared with controls (p &lt; 0.01). Apo-B/Apo-A1-ratio was over reference limit in 29.6% of the HAD group, in 15.4% of LAD group, and in 7.5% of controls (p = 0.03). Measured lipid markers (low density lipoprotein and total cholesterol and triglycerides) were higher in both CCS groups compared with controls (p &lt; 0.05). Systolic and diastolic function were measurably decreased in the HAD group, as evidenced by lower EF (p &lt; 0.001) and lower é-wave (p &lt; 0.005) compared with controls. CCA DI correlated with Apo-B/Apo-A1-ratio and Apo-A1. Follow-up time after treatment correlated with decreased left ventricular ejection fraction (p = 0.001).Conclusion: Young asymptomatic CCS exhibit cardiac, vascular, lipid, and apolipoprotein changes that could account for increased risk for CVD later in life. These findings emphasize the importance of cardiometabolic monitoring even in young CCS.
A Comparability of Renal Length and Volume Measurements in MRI and Ultrasound in Children
Authors: Świętoń Dominik , Bernard Weronika , Grzywińska Małgorzata , Czarniak Piotr , Durawa Agata , Kaszubowski Mariusz , Piskunowicz Maciej , Szurowska Edyta 
Published: December 2021

Introduction: Despite the significant increase in use of magnetic resonance imaging (MRI) in children, there is still a lack of normal reference values of renal size in this method and reference values are being interpolated from the ultrasound (US) studies. The study provides comparative analysis of agreement in renal length and volume measurements between MRI and ultrasound.Materials and Methods: Ninety-three children with a mean age of 8.0 ± 6.0 years, who had undergone both renal US and MRI exams, were included in the study. Participants were divided into three subgroups; each kidney was considered separately.Group 1 included 106 kidneys without any anomalies. Group 2 comprised 48 kidneys with a dilated collecting system. Group 3 included 32 kidneys with a duplicated collecting system. Measurements were taken in three dimensions, and renal volume was calculated from the ellipsoid formula.Results: We found no significant difference between US and MRI measurements in Group 1 and Group 2. In Group 3, the difference between measurements in both imaging methods was significant. The mean difference varied from 0.05% in Group 1, 2.95% in Group 2, to 4.99% in Group 3.Conclusion: The US and MRI are comparable methods in renal size measurements. The interpolation of sonographic renal length and volume reference values to the MRI in the pediatric population is justified, as there is a strong agreement between both methods. Both methods can be used interchangeably for following up of the renal size changes in the pediatric population.
Comprehensive Analysis of Chemical Structures That Have Been Tested as CFTR Activating Substances in a Publicly Available Database CandActCFTR
Authors: Nietert Manuel Manfred , Vinhoven Liza , Auer Florian , Hafkemeyer Sylvia , Stanke Frauke 
Published: December 2021

Background: Cystic fibrosis (CF) is a genetic disease caused by mutations in CFTR, which encodes a chloride and bicarbonate transporter expressed in exocrine epithelia throughout the body. Recently, some therapeutics became available that directly target dysfunctional CFTR, yet research for more effective substances is ongoing. The database CandActCFTR aims to provide detailed and comprehensive information on candidate therapeutics for the activation of CFTR-mediated ion conductance aiding systems-biology approaches to identify substances that will synergistically activate CFTR-mediated ion conductance based on published data.Results: Until 10/2020, we derived data from 108 publications on 3,109 CFTR-relevant substances via the literature database PubMed and further 666 substances via ChEMBL; only 19 substances were shared between these sources. One hundred and forty-five molecules do not have a corresponding entry in PubChem or ChemSpider, which indicates that there currently is no single comprehensive database on chemical substances in the public domain. Apart from basic data on all compounds, we have visualized the chemical space derived from their chemical descriptors via a principal component analysis annotated for CFTR-relevant biological categories. Our online query tools enable the search for most similar compounds and provide the relevant annotations in a structured way. The integration of the KNIME software environment in the back-end facilitates a fast and user-friendly maintenance of the provided data sets and a quick extension with new functionalities, e.g., new analysis routines. CandActBase automatically integrates information from other online sources, such as synonyms from PubChem and provides links to other resources like ChEMBL or the source publications.Conclusion: CandActCFTR aims to establish a database model of candidate cystic fibrosis therapeutics for the activation of CFTR-mediated ion conductance to merge data from publicly available sources. Using CandActBase, our strategy to represent data from several internet resources in a merged and organized form can also be applied to other use cases. For substances tested as CFTR activating compounds, the search function allows users to check if a specific compound or a closely related substance was already tested in the CF field. The acquired information on tested substances will assist in the identification of the most promising candidates for future therapeutics.
Psychometric Characteristics and Sociodemographic Adaptation of the Corrigan Agitated Behavior Scale in Patients With Severe Mental Disorders
Authors: Garrote-Cámara María Elena , Santolalla-Arnedo Iván , Ruiz de Viñaspre-Hernández Regina , Gea-Caballero Vicente , Sufrate-Sorzano Teresa , del Pozo-Herce Pablo , Garrido-García Rebeca , Rubinat-Arnaldo Esther , Juárez Vela Raúl 
Published: December 2021

Background: Severe mental disorder (SMD) is understood in a first approximation as a disorder of thought, emotion, or behavior of long duration, which entails a variable degree of disability and social dysfunction. One of the most widely used assessment scales for agitated behavior, in its English version, is the Corrigan Agitated Behavior Scale (ABS); several studies have demonstrated solid psychometric properties of the English version, with adequate internal consistency.Objective: The objective of this study was to evaluate the psychometric properties of the Spanish version of the ABS Corrigan scale, in a sample of patients with severe mental disorders. The psychometric analyses of the Spanish version of the ABS Corrigan included tests of the reliability and validity of its internal structure.Results: The structure of the factorial loads of the analyzed elements is consistent with the hypothesized three-dimensional construction referred to in the original ABS. The results suggest that the reliability and validity of the three dimensions are acceptable (First 0.8, Second 0.8, and Third 0.7). The internal consistency of the Spanish version of the complete ABS and of each of the three domains that compose it is high, with values very close to those found in the original version, with approximate figures of 0.9.Conclusion: In our study, the three domains aim to explain 64.1% of the total variance of the scale, which exceeds the 50% found in the original version.
Influence of Parental Psychological Flexibility on Pediatric COVID-19 Vaccine Hesitancy: Mediating Role of Self-Efficacy and Coping Style
Authors: Wang Yongyi , Zhang Xinping 
Published: December 2021

Background: Pediatric COVID-19 vaccine hesitancy hinders the establishment of immune barrier in children. Psychological flexibility may be a key contributing factor to pediatric COVID-19 vaccine hesitancy, and self-efficacy and coping style play an important role in the relationship, but the underlying mechanisms remain unknown.Methods: A cross-sectional study was conducted on parents from June 2021 to July 2021. A total of 382 parents were recruited for an online-investigation. Serial mediation models were used to examine whether self-efficacy and coping style mediated in the psychological flexibility-pediatric COVID-19 vaccine hesitancy linkage.Result: Psychological flexibility was negatively related to pediatric COVID-19 vaccine hesitancy (r = −0.198, P &lt; 0.001). Coping styles rather than self-efficacy played a mediating role independently (95% CI: −0.263 to −0.058). Serial mediation analyses indicated that self-efficacy and coping style co-play a serial mediating role in the association of psychological flexibility and pediatric COVID-19 vaccine hesitancy (95% CI: −0.037 to −0.001).Conclusion: The present study showed that high psychological flexibility, high self-efficacy, and positive coping style were conducive to the lower pediatric COVID-19 vaccine hesitancy.