bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Calprotectin (S100A8/A9): A Promising Biomarker in Diagnosis and Follow-up in Different Subgroups of Juvenile Idiopathic Arthritis
Authors: La Céline , Lê Phu Quoc , Ferster Alina , Goffin Laurence , Spruyt Delphine , Lauwerys Bernard , Durez Patrick , Boulanger Cecile , Sokolova Tatiana , Rasschaert Joanne , Badot Valérie 
Published: January 2021

Abstract
BackgroundManagement of juvenile idiopathic arthritis (JIA) lacks of diagnostic and prognostic biomarkers. Therefore, this study was designed to assess the use of serum calprotectin (sCal) as a marker of disease activity and its monitoring, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. MethodsEighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 healthy controls. Enzyme-linked immunosorbent assay (ELISA) method was used to quantify sCal with a commercial kit. Mann-Whitney tests were used to compare results, correlations were assessed with Spearman’s rank correlation coefficients and Receiver Operating Characteristic curves were also generated to evaluate serum calprotectin as a prognostic tool.ResultsPatients with an active disease compared to healthy controls and to patients with inactive disease showed an 8-fold and a 2-fold increased level of sCal respectively. sCal was found to be correlated with the CRP and even more strongly with the ESR. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. As for the CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis or systemic forms. However, sCal brought an added value compared to the CRP as a prognosis marker. Indeed, patients with active disease and good responder to treatment (pediACR > 30) at 6 months following the sample test had higher sCal levels, while patients with inactive disease had higher sCal levels in case a flare was observed up to 3 to 9 months following the sample test.ConclusionsThis study confirms the potential uses of serum calprotectin as a biomarker in diagnosis and follow-up in JIA.
Additional Treatment for Digital Ulcers in Patients with Systemic Sclerosis: A Prospective, Open-Label, Multi-Arm Study for the use of Platelet-Rich Plasma-Lipofilling and Ultrasound-Based Treatments
Authors: PIRRELLO ROBERTO , SCHINOCCA CLAUDIA , SCATURRO DALILA , RIZZO CHIARA , TERRANA PIETRO , TUMMINELLI LUIGI , RUSCITTI PIERO , CORDOVA ADRIANA , GIACOMELLI ROBERTO , CICCIA FRANCESCO , MAURO GIULIA LETIZIA , GUGGINO Giuliana 
Published: January 2021

Abstract
Background: Local treatments such as ultraviolet-A (UVA) phototherapy, topical calcitriol, injection of autologous fat grafting, Platelet-Rich Plasma (PRP), hyaluronic acid (HA) and local ultrasound (US) treatment are considered alternative approaches for skin involvement in Systemic sclerosis (SSc).The aim of our study was to evaluate the efficacy of PRP injection and lipofilling or local ultrasound in the treatment of SSc-related digital ulcers (DUs). Methods: We enrolled 28 patients with SSc. At baseline time (T0), all patients were treated with Iloprost intravenous infusions. Then, six patients (group 1) received a first inoculation of PRP, after 15 days a second inoculation of PRP and after 15 days a third of lipofilling. Other six patients (group 2) received the three consecutive injections associated with a maintenance therapy with additional injections of PRP every 30 days for 12 months. Six patients continued only the Iloprost therapy (controls). Ten patients (group 3) underwent medical sessions with ultrasound treatment for 10 days. Clinical evaluation was assessed at baseline, after 3 and 12 months of treatment for all patients.Results: In our study have shown an improvement in cutaneous and microvascular level, in quality of life, in mobility of extremities of upper limbs and a reduction of administration of Iloprost after PRP-Lipofilling and US treatment.Conclusions: Our findings suggest that PRP, coupled with lipofilling, and ultrasound treatment in SSc patients, can be considered additional procedures in the management of DUs.
Sacubitril/valsartan Inhibits Obesity-associated Diastolic Dysfunction through Suppression of Ventricular-vascular Stiffness
Authors: Aroor Annayya R , Mummidi Srinivas , Lopez-Alvarenga Juan Carlos , Das Nitin , Habibi Javad , Jia Guanghong , Lastra Guido , Chandrasekar Bysani , Demarco Vincent G 
Published: January 2021

Abstract
Objective: Both cardiac diastolic dysfunction (DD) and arterial stiffness are early manifestations of obesity-associated prediabetes and serve as risk factors for the development of heart failure with preserved ejection fraction (HFpEF). Since the incidence of DD and arterial stiffness are increasing worldwide due to exponential growth in obesity, an effective treatment is urgently needed to blunt their development and progression. Here we investigated whether the combination of an inhibitor of neprilysin (sacubitril), a natriuretic peptide-degrading enzyme, and an angiotensin II type 1 receptor blocker (valsartan), suppresses DD and arterial stiffness in an animal model of prediabetes more effectively than valsartan monotherapy.Methods: Sixteen week-old male Zucker Obese rats (ZO; n=64) were assigned randomly to 4 different groups: Group 1: saline control (ZOC); Group 2: sacubitril/valsartan (sac/val; 68 mg•kg-1•day-1; ZOSV); Group 3: valsartan (31 mg•kg-1•day-1; ZOV) and Group 4: hydralazine, an anti-hypertensive drug (30 mg•kg-1•day-1; ZOH). Six Zucker Lean (ZL) rats that received saline only (Group 5) served as lean controls (ZLC). Drugs were administered daily for 10 weeks by oral gavage.Results: Sac/val improved echocardiographic parameters of impaired left ventricular (LV) stiffness in untreated ZO rats, without altering the amount of food consumed or body weight gained. In addition to improving DD, sac/val also decreased aortic stiffness and reversed impairment of nitric oxide-induced vascular relaxation seen in ZO rats. However, sac/val had no impact on LV hypertrophy. Notably, sac/val was more effective at ameliorating DD compared to val. Although, hydralazine was as effective as sac/val in improving these parameters, it adversely affected LV mass index. Further, proteomics revealed distinct effects of sac/val, including marked suppression of Notch-1 by both valsartan and sac/val suggesting that cardiovascular protection afforded by both share some common mechanisms; however, sac/val increased IL-4 which is increasingly been recognized for its cardiovascular protection, possibly contributing, in part, to more favorable effects of sac/val over val alone in improving obesity associated DD.Conclusions: These studies suggest that sac/val is superior to val in reversing obesity-associated DD. It is an effective drug combination to blunt progression of asymptomatic DD and vascular stiffness to HFpEF development in a preclinical model of obesity-associated prediabetes.
Down Regulation Of The Expression Of Mitochondrial Phosphopantetheinyl-Proteins In Pantothenate Kinase-Associated Neurodegeneration: Pathophysiological Consequences and Therapeutic Perspectives
Authors: Álvarez-Córdoba Mónica , Talaverón-Rey Marta , Villalón-García Irene , Povea-Cabello Suleva , Suárez-Rivero Juan M. , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Salas Joaquín J. , Sanchez-Alcazar Jose A 
Published: January 2021

Abstract
BackgroundNeurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.MethodsIn this manuscript, we examined the effect of PANK2 mutations on the expression levels of proteins with phosphopantetheine cofactors in fibroblast derived from PKAN patients. These proteins include cytosolic acyl carrier protein (ACP), which is integrated within the multifunctional polypeptide chain of the fatty acid synthase involved in cytosolic fatty acid biosynthesis type I (FASI); mitochondrial ACP (mtACP) associated with mitocondrial fatty acid biosynthesis type II (FASII); mitochondrial alpha-aminoadipic semialdehyde synthase (AASS); and 10-formyltetrahydrofolate dehydrogenases (cytosolic, ALD1L1, and mitochondrial, ALD1L2). ResultsIn PKAN fibroblasts the expression levels of cytosolic FAS and ALD1L1 were not affected while the expression levels of mtACP, AASS and ALD1L2 were markedly reduced, suggesting that 4′-phosphopantetheinylation of mitochondrial but no cytosolic proteins were markedly affected in PKAN patients. Furthermore, the correction of PANK2 expression levels by treatment with pantothenate in selected mutations with residual enzyme content was able to correct the expression levels of mitochondrial phosphopantetheinyl-proteins and restore the affected pathways. The positive effects of pantothenate in particular mutations were also corroborated in induced neurons obtained by direct reprograming of mutant PANK2 fibroblasts. ConclusionsOur results suggest that the expression levels of mitochondrial phosphopantetheinyl-proteins are severely reduced in PKAN cells and that in selected mutations pantothenate increases the expression levels of both PANK2 and mitochondrial phosphopantetheinyl-proteins associated with remarkable improvement of cell pathophysiology.
Genomic Insight Into 21 Hypervariable Molecular Markers in The Population of Lower Himalayan Geographical Province Himachal Pradesh, India
Authors: Sharma Arun , Srivast Ankit , Sahajpal Vivek , Kumawat R , Dixit Shivani , Chaubey Gyaneshwer , Shrivastava Pankaj 
Published: January 2021

Abstract
A natural geographical barrier between Tibetan plateau and south Asian countries, the Himalayan Mountain range, serves as a natural barrier between these regions for genetic flow. This has lead to vast genomic divergence among the population residing in Indian Himalayan region..This study was designed with an aim to decipher the genomic diversity and molecular characterization of 21 hypervariable molecular markers in the population of geographical province of Himachal Pradesh in the lower Himalayan region. Randomly selected 401 unrelated individuals native of the lower Himalayan geographical region were included for this study. 21 hypervariable molecular markers included in the PowerPlex® 21 system were amplified and genotyped. A total of 246 alleles and 12.3 (SE 0.927) private alleles per locus were observed. Population differentiation analysis revealed that the studied population showed a genetic affinity with the population of North India, North-west India, Central India, and Uttar Pradesh rather than the population of East India, South India, East Asia, and West Asia. Heterozygosity at the studied loci was found in the range of 0.686 to 0.920. The unite discrimination power (PD) and exclusion power (PE) was found to be 1 and 0.999999998073765 respectively. The unite value of matching probability and typical paternity index was found to be 9.33x10-26 and 5.05x108 respectively for the studied population. All the tested loci were found in Hardy Weinberg Equilibrium (HWE) expectations. Overall the studied population exhibited a great extent of genomic diversity and had a greater genetic affinity with Indo-European speakers rather than Dravidian and Tibeto-Burman speakers.
Typhoon Eye Effect Vs. Ripple Effect: the Role of Family Size on the Mental Health Under the COVID-19 Pandemic in Pakistan
Authors: Zhang Stephen X , Lateef Tooba , Chen Jiyao , Tahir Muhammad , Lateef Teba Abdul , Chen Bryan , Li Jizhen 
Published: January 2021

Abstract
Background: The recent outbreak of COVID-19 impacts the mental health of people worldwide. The mental conditions and the associated predictors of adults in Pakistan, the fifth most populous country in the world, during the COVID-19 remains understudied. We aim to investigate distress, anxiety, and overall mental health and their associated predictors among Pakistani adults in this pandemic. We specifically examine the mental health issues based on the distance to the epicenter, a predictor that has revealed opposing evidence in other countries based on the theories of typhoon eye effect and ripple effect. The samples consist of 601 adults who were surveyed online about 2.5 months into the outbreak across Pakistan with varying distance to the epicenter of COVID-19 of Karachi in Pakistan. Results: The results showed that 9.2% and 19.0% of the participants surpassed the cut-off of distress and anxiety disorders, respectively. Overall, the distance to the epicenter positively predicted the mental health of adults in Pakistan, and family size negatively moderated this effect. The distance to the epicenter negatively predicted distress and anxiety disorders for adults in large families, which are quite common in Pakistan. Conclusion: The evidence of the study interestingly finds the prediction of the mental health of people by their distance to the epicenter depends on the family. The evidence of this study can help to provide the initial indicator for mental health care providers to screen vulnerable groups in Pakistan, a populous country that continues struggling to cope with the COVID-19 pandemic.
Generation of Dyskeratosis Congenita-like Hematopoietic Stem Cells through the Stable Inhibition of DKC1
Authors: Carrascoso-Rubio Carlos , Zittersteijn Hidde A. , Pintado-Berninches Laura , Fernández-Varas Beatriz , Lozano M. Luz , Manguan-Garcia Cristina , Sastre Leandro , Bueren Juan A. , Perona Rosario , Guenechea Guillermo 
Published: January 2021

Abstract
Dyskeratosis congenita (DC) is a rare telomere biology disorder, which results in different clinical manifestations, including severe bone marrow failure. To date, the only curative treatment for bone marrow failure in DC patients is allogeneic hematopoietic stem cell transplantation. However due to the toxicity associated to this treatment, improved therapies are recommended for DC patients. Here we aimed at generating DC-like human hematopoietic stem cells in which the efficacy of innovative therapies could be investigated. Because X-linked DC is the most frequent form of the disease and is associated with an impaired expression of DKC1, we have generated DC-like hematopoietic stem cells based on the stable knock-down of DKC1 in human CD34 + cells with lentiviral vectors encoding for DKC1 short hairpin RNAs. At a molecular level, DKC1 -interfered CD34 + cells showed a decreased expression of TERC, as well as a diminished telomerase activity and increased DNA damage, cell senescence and apoptosis. Moreover, DKC1 -interfered human CD34 + cells showed defective clonogenic ability and were incapable of repopulating the hematopoiesis of immunodeficient NSG mice. The development of DC-like hematopoietic stem cells will facilitate the understanding of the molecular and cellular basis of this inherited bone marrow failure syndrome, and will serve as a platform to evaluate the efficacy of new hematopoietic therapies for DC.
Residential exposure to air pollution and access to neighborhood greenspace in relation to hair cortisol concentrations during the second and third trimester of pregnancy
Authors: Verheyen Veerle Josefa , Remy Sylvie , Lambrechts Nathalie , Govarts Eva , Colles Ann , Poelmans Lien , Verachtert Els , Lefebvre Wouter , Monsieurs Pieter , Vanpoucke Charlotte , Nielsen Flemming , Eeden Lena Van den , Jacquemyn Yves , Schoeters Greet 
Published: January 2021

Abstract
Background: Exposure to air pollution during pregnancy has been associated with adverse pregnancy outcomes in studies worldwide, other studies have described beneficial effects of residential greenspace on pregnancy outcomes. The biological mechanisms that underlie these associations are incompletely understood. A biological stress response, which implies release of cortisol, may underlie associations of air pollution exposure and access to neighborhood greenspaces with health. Methods: We explored residential exposure to air pollution and residential access to neighborhood greenspaces in relation to hair cortisol concentrations of participants in a prospective pregnancy cohort study in Flanders, Belgium. Hair samples were collected at the end of the second pregnancy trimester (n = 133) and shortly after delivery (n = 81). Cortisol concentrations were measured in 3-cm scalp-near hair sections, to reflect second and third pregnancy trimester cortisol secretion. We estimated long-term (3 months before sampling) residential exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC), assessed residential distance to major roads and residential access to neighborhood greenspaces (NHGS). Associations between residential exposures and hair cortisol concentrations were studied using linear regression models while adjusting for season of sampling.Results: Three-month mean residential NO2 and BC concentrations were positively associated with third pregnancy trimester hair cortisol concentrations (p = 0.008 and p = 0.017). Access to a large NHGS (10 hectares or more within 800 meters from residence) was negatively associated with third trimester hair cortisol concentrations (p = 0.019). Access to a large NHGS significantly moderated the association between residential proximity to major roads and second trimester hair cortisol concentrations (p = 0.021). Residential distance to major roads was negatively associated with second trimester hair cortisol concentrations of participants without access to a large NHGS (p = 0.003). The association was not significant for participants with access to a large NHGS. The moderation tended towards significance in the third pregnancy trimester (p < 0.10).Conclusions: Our findings suggest a positive association between long-term residential exposure to air pollution and biological stress during pregnancy, residential access to neighborhood greenspaces may moderate the association. Further research is needed to confirm our results.Trial registration: The IPANEMA study is registered under number NCT02592005 at clinicaltrials.gov.
Decreasing the leakage of continuous femoral nerve catheter fixation using 2-octyl cyanoacrylate glue (Demabond®): A randomized controlled trial
Authors: Chalacheewa Theerawat , Arnuntasupakul Vanlapa , Sangkum Lisa , Buachai Rungrawan , Chanvitayapongs Jiravud 
Published: January 2021

Abstract
Background: Continuous peripheral nerve catheters (CPNCs) have been used for postoperative pain relief. A common problem encountered with CPNCs is pericatheter leakage, which can lead to dressing adhesive failure. Frequent dressing changes increase the risk of catheter dislodgement and infections. Adhesive glue is effective in securing the peripheral nerve catheter and decreasing leakage around the catheter insertion site. This study aimed to evaluate the incidence of pericatheter leakage with fixation using 2-octyl cyanoacrylate glue (Dermabond®) as compared to sterile strips.Methods: Thirty patients undergoing unilateral total knee arthroplasty (TKA) with continuous femoral nerve catheter for postoperative analgesia were randomized into the catheter fixation with 2-octyl cyanoacrylate glue (Dermabond®) group or the sterile strip group. The primary outcome was the incidence of pericatheter leakage. Secondary outcomes included the frequent of catheter displacement, the difficulty of catheter removal, pain score and patient satisfaction.Results: The incidence of pericatheter leakage at 24 and 48 hours was 0% versus 93% and 0% versus 100% in the Dermabond® and sterile strip groups, respectively (P < 0.001). The incidence of displacement at 24 and 48 hours was 6.7% versus 93.3% and 6.7% versus 100% in the Dermabond® and sterile strip, respectively (P < 0.001). There was no difference in numeric rating scale, difficulty of catheter removal, or satisfaction scores between groups.Conclusion: Catheter fixation with 2-octyl cyanoacrylate glue (Dermabond®) decreased the incidence of pericatheter leakage, as well as catheter displacement, over 48 hours as compared to sterile strip fixation.
Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species
Authors: Gigout Anne , Harazin Donata , Topping Louise M. , Lindemann Sven , Brenneis Christian , Nissim Ahuva 
Published: January 2021

Abstract
Background: Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Cartilage degradation is mostly driven by chondrocytes which produce inflammatory mediators, proteases and oxidants. Nevertheless, the early pathogenesis events are still unclear. We employed antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA. Methods: The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed at 3, 5, 7, 14 and 28 days or anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) and were sacrificed after 1, 3, 5, 7 and 14 days. Joints were stained with toluidine blue and Saffron du Gatinais for histological scoring, anti-oxPTM-CII and anti- collagen type X antibodies (anti-CX). Results: We observed oxPTM-CII staining as early as 1 or 3 days after ACLT+pMx or DMM surgeries respectively, before overt cartilage lesions were visible. It was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes and co-localized with CX staining. Both staining were weak or absent for the lateral compartment or the contralateral knees except at later timepoints. Conclusion: The results demonstrate that oxidants production and chondrocytes hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead or radiographic changes.