bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence
Authors: Costa Viviana , De Fine Marcello , Raimondi Lavinia , Bellavia Daniele , Cordaro Aurora , Carina Valeria , Alessandro Riccardo , Pignatti Giovanni , Fini Milena , Giavaresi Gianluca , De Luca Angela
Published: February 2023

Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1β. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1β improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1β was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1β, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint.
Molecular Mechanisms and Therapeutic Implications of Endothelial Dysfunction in Patients with Heart Failure
Authors: Tsigkou Vasiliki , Oikonomou Evangelos , Anastasiou Artemis , Lampsas Stamatios , Zakynthinos George E. , Kalogeras Konstantinos , Katsioupa Maria , Kapsali Maria , Kourampi Islam , Pesiridis Theodoros , Marinos Georgios , Vavuranakis Michael-Andrew , Tousoulis Dimitris , Vavuranakis Manolis , Siasos Gerasimos
Published: February 2023

Heart failure is a complex medical syndrome that is attributed to a number of risk factors; nevertheless, its clinical presentation is quite similar among the different etiologies. Heart failure displays a rapidly increasing prevalence due to the aging of the population and the success of medical treatment and devices. The pathophysiology of heart failure comprises several mechanisms, such as activation of neurohormonal systems, oxidative stress, dysfunctional calcium handling, impaired energy utilization, mitochondrial dysfunction, and inflammation, which are also implicated in the development of endothelial dysfunction. Heart failure with reduced ejection fraction is usually the result of myocardial loss, which progressively ends in myocardial remodeling. On the other hand, heart failure with preserved ejection fraction is common in patients with comorbidities such as diabetes mellitus, obesity, and hypertension, which trigger the creation of a micro-environment of chronic, ongoing inflammation. Interestingly, endothelial dysfunction of both peripheral vessels and coronary epicardial vessels and microcirculation is a common characteristic of both categories of heart failure and has been associated with worse cardiovascular outcomes. Indeed, exercise training and several heart failure drug categories display favorable effects against endothelial dysfunction apart from their established direct myocardial benefit.
Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence
Authors: Pillai Prakash P. , Kannan Muthukumar , Sil Susmita , Singh Seema , Thangaraj Annadurai , Chivero Ernest T. , Dagur Raghubendra Singh , Tripathi Ashutosh , Hu Guoku , Periyasamy Palsamy , Buch Shilpa
Published: February 2023

HIV-1 infection in the era of combined antiretroviral therapy has been associated with premature aging. Among the various features of HIV-1 associated neurocognitive disorders, astrocyte senescence has been surmised as a potential cause contributing to HIV-1-induced brain aging and neurocognitive impairments. Recently, lncRNAs have also been implicated to play essential roles in the onset of cellular senescence. Herein, using human primary astrocytes (HPAs), we investigated the role of lncRNA TUG1 in HIV-1 Tat-mediated onset of astrocyte senescence. We found that HPAs exposed to HIV-1 Tat resulted in significant upregulation of lncRNA TUG1 expression that was accompanied by elevated expression of p16 and p21, respectively. Additionally, HIV-1 Tat-exposed HPAs demonstrated increased expression of senescence-associated (SA) markers—SA-β-galactosidase (SA-β-gal) activity and SA-heterochromatin foci—cell-cycle arrest, and increased production of reactive oxygen species and proinflammatory cytokines. Intriguingly, gene silencing of lncRNA TUG1 in HPAs also reversed HIV-1 Tat-induced upregulation of p21, p16, SA-β gal activity, cellular activation, and proinflammatory cytokines. Furthermore, increased expression of astrocytic p16 and p21, lncRNA TUG1, and proinflammatory cytokines were observed in the prefrontal cortices of HIV-1 transgenic rats, thereby suggesting the occurrence of senescence activation in vivo. Overall, our data indicate that HIV-1 Tat-induced astrocyte senescence involves the lncRNA TUG1 and could serve as a potential therapeutic target for dampening accelerated aging associated with HIV-1/HIV-1 proteins.
FHL2 Genetic Polymorphisms and Pro-Diabetogenic Lipid Profile in the Multiethnic HELIUS Cohort
Authors: Habibe Jayron J. , Boulund Ulrika , Clemente-Olivo Maria P. , de Vries Carlie J. M. , Eringa Etto C. , Nieuwdorp Max , Ferwerda Bart , Zwinderman Koos , van den Born Bert-Jan H. , Galenkamp Henrike , van Raalte Daniel H.
Published: February 2023

Type 2 diabetes mellitus (T2D) is a prevalent disease often accompanied by the occurrence of dyslipidemia. Four and a half LIM domains 2 (FHL2) is a scaffolding protein, whose involvement in metabolic disease has recently been demonstrated. The association of human FHL2 with T2D and dyslipidemia in a multiethnic setting is unknown. Therefore, we used the large multiethnic Amsterdam-based Healthy Life in an Urban Setting (HELIUS) cohort to investigate FHL2 genetic loci and their potential role in T2D and dyslipidemia. Baseline data of 10,056 participants from the HELIUS study were available for analysis. The HELIUS study contained individuals of European Dutch, South Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan descent living in Amsterdam and were randomly sampled from the municipality register. Nineteen FHL2 polymorphisms were genotyped, and associations with lipid panels and T2D status were investigated. We observed that seven FHL2 polymorphisms associated nominally with a pro-diabetogenic lipid profile including triglyceride (TG), high-density and low-density lipoprotein-cholesterol (HDL-C and LDL-C), and total cholesterol (TC) concentrations, but not with blood glucose concentrations or T2D status in the complete HELIUS cohort upon correcting for age, gender, BMI, and ancestry. Upon stratifying for ethnicity, we observed that only two of the nominally significant associations passed multiple testing adjustments, namely, the association of rs4640402 with increased TG and rs880427 with decreased HDL-C concentrations in the Ghanaian population. Our results highlight the effect of ethnicity on pro-diabetogenic selected lipid biomarkers within the HELIUS cohort, as well as the need for more large multiethnic cohort studies.
PLGA-Based Micro/Nanoparticles: An Overview of Their Applications in Respiratory Diseases
Authors: Guo Xiaoping , Zuo Xu , Zhou Zhengjie , Gu Yinuo , Zheng Haoyu , Wang Xinlei , Wang Guoqiang , Xu Caina , Wang Fang
Published: February 2023

Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are critical areas of medical research, as millions of people are affected worldwide. In fact, more than 9 million deaths worldwide were associated with respiratory diseases in 2016, equivalent to 15% of global deaths, and the prevalence is increasing every year as the population ages. Due to inadequate treatment options, the treatments for many respiratory diseases are limited to relieving symptoms rather than curing the disease. Therefore, new therapeutic strategies for respiratory diseases are urgently needed. Poly (lactic-co-glycolic acid) micro/nanoparticles (PLGA M/NPs) have good biocompatibility, biodegradability and unique physical and chemical properties, making them one of the most popular and effective drug delivery polymers. In this review, we summarized the synthesis and modification methods of PLGA M/NPs and their applications in the treatment of respiratory diseases (asthma, COPD, cystic fibrosis (CF), etc.) and also discussed the research progress and current research status of PLGA M/NPs in respiratory diseases. It was concluded that PLGA M/NPs are the promising drug delivery vehicles for the treatment of respiratory diseases due to their advantages of low toxicity, high bioavailability, high drug loading capacity, plasticity and modifiability. And at the end, we presented an outlook on future research directions, aiming to provide some new ideas for future research directions and hopefully to promote their widespread application in clinical treatment.
COL7A1 Editing via RNA Trans-Splicing in RDEB-Derived Skin Equivalents
Authors: Liemberger Bernadette , Bischof Johannes , Ablinger Michael , Hainzl Stefan , Murauer Eva M. , Lackner Nina , Ebner Patricia , Kocher Thomas , Nyström Alexander , Wally Verena , Mayr Elisabeth , Guttmann-Gruber Christina , Hofbauer Josefina Piñón , Bauer Johann W. , Koller Ulrich
Published: February 2023

Mutations in the COL7A1 gene lead to malfunction, reduction or complete absence of type VII collagen (C7) in the skin’s basement membrane zone (BMZ), impairing skin integrity. In epidermolysis bullosa (EB), more than 800 mutations in COL7A1 have been reported, leading to the dystrophic form of EB (DEB), a severe and rare skin blistering disease associated with a high risk of developing an aggressive form of squamous cell carcinoma. Here, we leveraged a previously described 3′-RTMS6m repair molecule to develop a non-viral, non-invasive and efficient RNA therapy to correct mutations within COL7A1 via spliceosome-mediated RNA trans-splicing (SMaRT). RTM-S6m, cloned into a non-viral minicircle-GFP vector, is capable of correcting all mutations occurring between exon 65 and exon 118 of COL7A1 via SMaRT. Transfection of the RTM into recessive dystrophic EB (RDEB) keratinocytes resulted in a trans-splicing efficiency of ~1.5% in keratinocytes and ~0.6% in fibroblasts, as confirmed on mRNA level via next-generation sequencing (NGS). Full-length C7 protein expression was primarily confirmed in vitro via immunofluorescence (IF) staining and Western blot analysis of transfected cells. Additionally, we complexed 3′-RTMS6m with a DDC642 liposomal carrier to deliver the RTM topically onto RDEB skin equivalents and were subsequently able to detect an accumulation of restored C7 within the basement membrane zone (BMZ). In summary, we transiently corrected COL7A1 mutations in vitro in RDEB keratinocytes and skin equivalents derived from RDEB keratinocytes and fibroblasts using a non-viral 3′-RTMS6m repair molecule.
Cell-Type-Specific Gene Regulatory Networks of Pro-Inflammatory and Pro-Resolving Lipid Mediator Biosynthesis in the Immune System
Authors: Hoch Matti , Rauthe Jannik , Cesnulevicius Konstantin , Schultz Myron , Lescheid David , Wolkenhauer Olaf , Chiurchiù Valerio , Gupta Shailendra
Published: February 2023

Lipid mediators are important regulators in inflammatory responses, and their biosynthetic pathways are targeted by commonly used anti-inflammatory drugs. Switching from pro-inflammatory lipid mediators (PIMs) to specialized pro-resolving (SPMs) is a critical step toward acute inflammation resolution and preventing chronic inflammation. Although the biosynthetic pathways and enzymes for PIMs and SPMs have now been largely identified, the actual transcriptional profiles underlying the immune cell type-specific transcriptional profiles of these mediators are still unknown. Using the Atlas of Inflammation Resolution, we created a large network of gene regulatory interactions linked to the biosynthesis of SPMs and PIMs. By mapping single-cell sequencing data, we identified cell type-specific gene regulatory networks of the lipid mediator biosynthesis. Using machine learning approaches combined with network features, we identified cell clusters of similar transcriptional regulation and demonstrated how specific immune cell activation affects PIM and SPM profiles. We found substantial differences in regulatory networks in related cells, accounting for network-based preprocessing in functional single-cell analyses. Our results not only provide further insight into the gene regulation of lipid mediators in the immune response but also shed light on the contribution of selected cell types in their biosynthesis.
Liposomes: The Brave Old World
Authors: Matos Carla M.
Published: February 2023

Liposomes have been known of for about 60 years, since they were discovered by A [...]
Outdoor Air Pollution and Childhood Respiratory Disease: The Role of Oxidative Stress
Authors: Dondi Arianna , Carbone Claudio , Manieri Elisa , Zama Daniele , Del Bono Chiara , Betti Ludovica , Biagi Carlotta , Lanari Marcello
Published: February 2023

The leading mechanisms through which air pollutants exert their damaging effects are the promotion of oxidative stress, the induction of an inflammatory response, and the deregulation of the immune system by reducing its ability to limit infectious agents’ spreading. This influence starts in the prenatal age and continues during childhood, the most susceptible period of life, due to a lower efficiency of oxidative damage detoxification, a higher metabolic and breathing rate, and enhanced oxygen consumption per unit of body mass. Air pollution is involved in acute disorders like asthma exacerbations and upper and lower respiratory infections, including bronchiolitis, tuberculosis, and pneumoniae. Pollutants can also contribute to the onset of chronic asthma, and they can lead to a deficit in lung function and growth, long-term respiratory damage, and eventually chronic respiratory illness. Air pollution abatement policies, applied in the last decades, are contributing to mitigating air quality issues, but more efforts should be encouraged to improve acute childhood respiratory disease with possible positive long-term effects on lung function. This narrative review aims to summarize the most recent studies on the links between air pollution and childhood respiratory illness.
Autoreactive T-Cells in Psoriasis: Are They Spoiled Tregs and Can Therapies Restore Their Functions?
Authors: Pietraforte Immacolata , Frasca Loredana
Published: February 2023

Psoriasis is a chronic inflammatory skin disease, which affects 2–4% of the population worldwide. T-cell derived factors such as Th17 and Th1 cytokines or cytokines such as IL-23, which favors Th17-expansion/differentiation, dominate in the disease. Therapies targeting these factors have been developed over the years. An autoimmune component is present, as autoreactive T-cells specific for keratins, the antimicrobial peptide LL37 and ADAMTSL5 have been described. Both autoreactive CD4 and CD8 T-cells exist, produce pathogenic cytokines, and correlate with disease activity. Along with the assumption that psoriasis is a T-cell-driven disease, Tregs have been studied extensively over the years, both in the skin and in circulation. This narrative review resumes the main findings about Tregs in psoriasis. We discuss how Tregs increase in psoriasis but are impaired in their regulatory/suppressive function. We debate the possibility that Tregs convert into T-effector cells under inflammatory conditions; for instance, they may turn into Th17-cells. We put particular emphasis on therapies that seem to counteract this conversion. We have enriched this review with an experimental section analyzing T-cells specific for the autoantigen LL37 in a healthy subject, suggesting that a shared specificity may exist between Tregs and autoreactive responder T-cells. This suggests that successful psoriasis treatments may, among other effects, restore Tregs numbers and functions.
Umbilical Cord Blood-Derived Cell Therapy for Perinatal Brain Injury: A Systematic Review & Meta-Analysis of Preclinical Studies
Authors: Nguyen Timothy , Purcell Elisha , Smith Madeleine J. , Penny Tayla R. , Paton Madison C. B. , Zhou Lindsay , Jenkin Graham , Miller Suzanne L. , McDonald Courtney A. , Malhotra Atul
Published: February 2023

Perinatal brain injury is a major contributor to long-term adverse neurodevelopment. There is mounting preclinical evidence for use of umbilical cord blood (UCB)-derived cell therapy as potential treatment. To systematically review and analyse effects of UCB-derived cell therapy on brain outcomes in preclinical models of perinatal brain injury. MEDLINE and Embase databases were searched for relevant studies. Brain injury outcomes were extracted for meta-analysis to calculate standard mean difference (SMD) with 95% confidence interval (CI), using an inverse variance, random effects model. Outcomes were separated based on grey matter (GM) and white matter (WM) regions where applicable. Risk of bias was assessed using SYRCLE, and GRADE was used to summarise certainty of evidence. Fifty-five eligible studies were included (7 large, 48 small animal models). UCB-derived cell therapy significantly improved outcomes across multiple domains, including decreased infarct size (SMD 0.53; 95% CI (0.32, 0.74), p < 0.00001), apoptosis (WM, SMD 1.59; 95%CI (0.86, 2.32), p < 0.0001), astrogliosis (GM, SMD 0.56; 95% CI (0.12, 1.01), p = 0.01), microglial activation (WM, SMD 1.03; 95% CI (0.40, 1.66), p = 0.001), neuroinflammation (TNF-α, SMD 0.84; 95%CI (0.44, 1.25), p < 0.0001); as well as improved neuron number (SMD 0.86; 95% CI (0.39, 1.33), p = 0.0003), oligodendrocyte number (GM, SMD 3.35; 95 %CI (1.00, 5.69), p = 0.005) and motor function (cylinder test, SMD 0.49; 95 %CI (0.23, 0.76), p = 0.0003). Risk of bias was determined as serious, and overall certainty of evidence was low. UCB-derived cell therapy is an efficacious treatment in pre-clinical models of perinatal brain injury, however findings are limited by low certainty of evidence.
TiO2-Embedded Biocompatible Hydrogel Production Assisted with Alginate and Polyoxometalate Polyelectrolytes for Photocatalytic Application
Authors: Mansurov Renat , Pavlova Irina , Shabadrov Pavel , Levchenko Anastasiya , Krinochkin Alexey , Kopchuk Dmitry , Nikonov Igor , Prokofyeva Anna , Safronov Alexander , Grzhegorzhevskii Kirill
Published: February 2023

The hybrid hydrogel materials meet important social challenges, including the photocatalytic purification of water and bio-medical applications. Here, we demonstrate two scenarios of polyacrylamide-TiO2 (PAAm@TiO2) composite hydrogel design using calcium alginate (Alg-Ca) or Keplerate-type polyoxometalates (POMs) {Mo132} tuning the polymer network structure. Calcium alginate molding allowed us to produce polyacrylamide-based beads with an interpenetrating network filled with TiO2 nanoparticles Alg-Ca@PAAm@TiO2, demonstrating the photocatalytic activity towards the methyl orange dye bleaching. Contrastingly, in the presence of the POM, the biocompatible PAAm@TiO2@Mo132 composite hydrogel was produced through the photo-polymerization approach (under 365 nm UV light) using vitamin B2 as initiator. For both types of the synthesized hydrogels, the thermodynamic compatibility, swelling and photocatalytic behavior were studied. The influence of the hydrogel composition on its structure and the mesh size of its network were evaluated using the Flory–Rehner equation. The proposed synthetic strategies for the composite hydrogel production can be easily scaled up to the industrial manufacturing of the photocatalytic hydrogel beads suitable for the water treatment purposes or the biocompatible hydrogel patch for medical application.
To Establish an Early Prediction Model for Acute Respiratory Distress Syndrome in Severe Acute Pancreatitis Using Machine Learning Algorithm
Authors: Zhang Wanyue , Chang Yongjian , Ding Yuan , Zhu Yinnan , Zhao Yawen , Shi Ruihua
Published: February 2023

Objective: To develop binary and quaternary classification prediction models in patients with severe acute pancreatitis (SAP) using machine learning methods, so that doctors can evaluate the risk of patients with acute respiratory distress syndrome (ARDS) and severe ARDS at an early stage. Methods: A retrospective study was conducted on SAP patients hospitalized in our hospital from August 2017 to August 2022. Logical Regression (LR), Random Forest (RF), Support Vector Machine (SVM), Decision Tree (DT), and eXtreme Gradient Boosting (XGB) were used to build the binary classification prediction model of ARDS. Shapley Additive explanations (SHAP) values were used to interpret the machine learning model, and the model was optimized according to the interpretability results of SHAP values. Combined with the optimized characteristic variables, four-class classification models, including RF, SVM, DT, XGB, and Artificial Neural Network (ANN), were constructed to predict mild, moderate, and severe ARDS, and the prediction effects of each model were compared. Results: The XGB model showed the best effect (AUC = 0.84) in the prediction of binary classification (ARDS or non-ARDS). According to SHAP values, the prediction model of ARDS severity was constructed with four characteristic variables (PaO2/FiO2, APACHE II, SOFA, AMY). Among them, the overall prediction accuracy of ANN is 86%, which is the best. Conclusions: Machine learning has a good effect in predicting the occurrence and severity of ARDS in SAP patients. It can also provide a valuable tool for doctors to make clinical decisions.
Sonographic Flow-Mediated Dilation Imaging versus Electronic EndoCheck Flow-Mediated Slowing by VICORDER in Pregnant Women—A Comparison of Two Methods to Evaluate Vascular Function in Pregnancy
Authors: Lößner Charlotte , Multhaup Anna , Lehmann Thomas , Schleußner Ekkehard , Groten Tanja
Published: February 2023

The evaluation of endothelial function is gaining interest and importance during pregnancy, since the impaired adaptation in early pregnancy has been associated with an increased risk in preeclampsia and fetal growth restriction. To standardize the risk assessment and to implement the evaluation of vascular function in routine pregnancy care, a suitable, accurate and easy to use method is needed. Flow-mediated dilatation (FMD) of the brachial artery assessed by ultrasound is considered to be the gold standard for measuring the vascular endothelial function. The challenges of the FMD measurement have so far prevented its introduction into clinical routine. The VICORDER® device allows an automated determination of the flow-mediated slowing (FMS). The equivalence of FMD and FMS has not yet been proven in pregnant women. We collected data of 20 pregnant women randomly and consecutively while they presented for a vascular function assessment in our hospital. The gestational age at investigation was between 22 and 32 weeks of gestation, three had preexisting hypertensive pregnancy disease and three were twin pregnancies. The results for FMD or FMS below 11.3% were considered to be abnormal. Comparing FMD to FMS results in our cohort revealed a convergence in 9/9 cases, indicating normal endothelial function (specificity of 100%) and a sensitivity of 72.7%. In conclusion, we verify that the FMS measurement is a convenient, automated and operator-independent test method of endothelial function in pregnant women.
Complementary Therapy Learning in the Setting of Lung Transplantation: A Single-Center Observational Study of Appropriation and Efficacy
Authors: Michel-Cherqui Mireille , Fessler Julien , Szekely Barbara , Glorion Matthieu , Sage Edouard , Fischler Marc , Vallée Alexandre , Le Guen Morgan
Published: February 2023

Transplanted patients could benefit from complementary techniques. This prospective single-center, open study, performed in a tertiary university hospital, evaluates the appropriation and efficacy of a toolbox-kit of complementary techniques. Self-hypnosis, sophrology, relaxation, holistic gymnastics, and transcutaneous electric nerve stimulation (TENS) were taught to adult patients scheduled for double-lung transplantation. Patients were asked to use them before and after transplantation, as needed. The primary outcome was appropriation of each technique within the first three postoperative months. Secondary outcomes included efficacy on pain, anxiety, stress, sleep, and quality-of-life. Among the 80 patients included from May 2017 to September 2020, 59 were evaluated at the 4th postoperative month. Over the 4359 sessions performed, the most frequent technique used before surgery was relaxation. After transplantation, the techniques most frequently used were relaxation and TENS. TENS was the best technique in terms of autonomy, usability, adaptation, and compliance. Self-appropriation of relaxation was the easiest, while self-appropriation of holistic gymnastics was difficult but appreciated by patients. In conclusion: the appropriation by patients of complementary therapies such as mind–body therapies, TENS and holistic gymnastics is feasible in lung transplantation. Even after a short training session, patients regularly practiced these therapies, mainly TENS and relaxation.
Procedures in Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome: Systematic Review and Meta-Analysis
Authors: Rodrigues Tânia , Rodrigues Fialho Sofia , Araújo João Ricardo , Rocha Rita , Moreira-Rosário André
Published: February 2023

Background: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disease with no effective treatment. Altered microbiota composition seems implicated in disease etiology and therefore fecal microbial transplantation (FMT) has emerged as a possible treatment therapy. To clarify the clinical parameters impacting FMT efficacy, we conducted a systematic review with subgroup analysis. Methods: A literature search was performed identifying randomized controlled trials (RCTs) comparing FMT with placebo in IBS adult patients (8-week follow-up) with a reported improvement in global IBS symptoms. Results: Seven RCTs (489 participants) met the eligibility requirements. Although FMT seems not to be effective in global improvement of IBS symptoms, subgroup analysis shows that FMT through gastroscopy or nasojejunal tube are effective IBS treatments (RR 3.03; 95% CI 1.94–4.73; I2 = 10%, p < 0.00001). When considering non-oral ingestion routes, IBS patients with constipation symptoms are more likely to benefit from FMT administration (p = 0.003 for the difference between IBS subtypes regarding constipation). Fresh fecal transplant and bowel preparation seem also to have impact on FMT efficacy (p = 0.03 and p = 0.01, respectively). Conclusion: Our meta-analysis revealed a set of critical steps that could affect the efficacy of FMT as clinical procedure to treat IBS, nevertheless more RCTs are needed.
Point-of-Care Ultrasonography in a Pulmonary Hypertension Clinic: A Randomized Pilot Study
Authors: Avriel Avital , Bar Lavie Shay Anat , Hershko Klement Anat , Taylor Jonathan , Shamia David , Tsaban Gal , Abu-Shakra Mahmoud , Granton John , Fuchs Lior
Published: February 2023

Pulmonary arterial hypertension (PAH) is a rare condition with the potential to progress to right heart failure. Point-of-Care Ultrasonography (POCUS), used and interpreted in real time at the bedside to further the cardiopulmonary assessment, has the potential to improve the longitudinal care of PAH patients in the ambulatory setting. Patients from PAH clinics at two academic medical centers were randomized to either a POCUS assessment cohort or non-POCUS standard care (ClinicalTrials.gov identifier NCT05332847). The POCUS group received blinded heart, lung, and vascular ultrasound assessments. Thirty-six patients were randomized to the study and followed over time. Mean age was 65 in both groups and majority female (76.5% and 88.9% females in POCUS and control, respectively). Median time for POCUS assessment was 11 min (range 8–16). There were significantly more changes in management in the POCUS group than control (73% vs. 27%, p-value < 0.001). Multivariate analysis revealed that management changes were more likely to occur with a POCUS assessment, with an odds ratio (OR) of 12 when POCUS was added to physical exam vs. OR of 4.6 compared to physical examination alone (p < 0.001). POCUS in the PAH clinic is feasible and, when combined with physical examination, increases the number of findings and results in changes in management without significantly prolonging visit encounters. POCUS may help support clinical evaluation and decision making in ambulatory PAH clinics.
Academic Buoyancy: Overcoming Test Anxiety and Setbacks
Authors: Putwain David William , Jansen in de Wal Joost , van Alphen Thijmen
Published: February 2023

High levels of test anxiety can be damaging for academic achievement, wellbeing, and mental health. It is important, therefore, to consider those psychological attributes that may offer protection against the development of test anxiety and its negative consequences, thereby contributing to a potential positive future life trajectory. Academic buoyancy, the ability to respond effectively to academic pressures and setbacks, is one such attribute that offers protection from high test anxiety. We begin by defining test anxiety and a brief review of the literature to consider the harmful nature of test anxiety. This is followed by a definition of academic buoyancy and brief review of the literature to consider the beneficial character of academic buoyancy. Next, we describe the Self-Regulatory Executive Function model of test anxiety and consider the mechanisms and processes by which academic buoyancy exerts beneficial effects on test anxiety. The paper concludes with a consideration of critical issues for the conceptualisation and measurement of academic buoyancy, arising from the synergies, connections, and relations, theorised with test anxiety, and how these may inform future studies.
A Novel Short-Term Ship Motion Prediction Algorithm Based on EMD and Adaptive PSO–LSTM with the Sliding Window Approach
Authors: Geng Xiaoyu , Li Yibing , Sun Qian
Published: February 2023

Under the influence of variable sea conditions, a ship will have an oscillating motion comprising six degrees of freedom, all of which are connected to each other. Among these degrees of freedom, rolling and pitching motions have a severe impact on a ship’s maritime operations. An accurate and effective ship motion attitude prediction method that makes the prediction in a short period of time is required to guarantee the safety and stability of the ship’s maritime operations. Traditional methods are based on time domain analysis, such as the autoregressive moving average (ARMA) models. However, these models have limitations when it comes to predicting the nonlinear and nonstationary characteristics of real ship motion attitude data. Many intelligent algorithms continue to be applied in nonlinear and nonstationary ship attitude prediction, such as extreme learning machines (ELMs) and the long short-term memory (LSTM) neural network, as well as other deep learning methods, showing promising results. By using the sliding window approach, the time-varying dynamic characteristics of the ship’s motion attitude can be preserved better. The simulation results demonstrate that the proposed model performs well in terms of predicting the nonlinear and nonstationary ship motion attitude.
Global Molecular Response of Paracoccidioides brasiliensis to Zinc Deprivation: Analyses at Transcript, Protein and MicroRNA Levels
Authors: Mesquita Lorena Alves , Bailão Alexandre Melo , de Curcio Juliana Santana , da Silva Kassyo Lobato Potenciano , da Rocha Fernandes Gabriel , Silva-Bailão Mirelle Garcia , Novaes Evandro , de Almeida Soares Célia Maria
Published: February 2023

Zinc is one of the main micronutrients for all organisms. One of the defense mechanisms used by the host includes the sequestration of metals used in fungal metabolism, such as iron and zinc. There are several mechanisms that maintain the balance in the intracellular zinc supply. MicroRNAs are effector molecules of responses between the pathogen and host, favoring or preventing infection in many microorganisms. Fungi of the Paracoccidioides genus are thermodimorphic and the etiological agents of paracoccidioidomycosis (PCM). In the current pandemic scenario world mycosis studies continue to be highly important since a significant number of patients with COVID-19 developed systemic mycoses, co-infections that complicated their clinical condition. The objective was to identify transcriptomic and proteomic adaptations in Paracoccidioides brasiliensis during zinc deprivation. Nineteen microRNAs were identified, three of which were differentially regulated. Target genes regulated by those microRNAs are elements of zinc homeostasis such as ZRT1, ZRT3 and COT1 transporters. Transcription factors that have zinc in their structure are also targets of those miRNAs. Transcriptional and proteomic data suggest that P. brasiliensis undergoes metabolic remodeling to survive zinc deprivation and that miRNAs may be part of the regulatory process.
MLN4924 Promotes Self-Renewal of Limbal Stem Cells and Ocular Surface Restoration
Authors: Li Qingjian , Shen Yankun , Wu Shinan , Wei Hong , Zou Jie , Xu Sanhua , Ling Qian , Kang Min , Huang Hui , Chen Xu , Shao Yi
Published: February 2023

Objective: To study the role of MLN4924 in corneal stem cell maintenance and corneal injury repair. Methods: In cell experiments, the Sprague–Dawley (SD) rat corneal epithelial cells were co-cultured with mitomycin C-inactivated mouse feeder cells in a supplemental hormonal epithelial medium (SHEM) with or without MLN4924. Cells were photographed using an optical microscope. Furthermore, we performed crystal violet, polymerase chain reaction (PCR), and immunofluorescence staining on limbal stem cells (LSCs). In animal experiments, we scraped the corneal epithelium with a central corneal diameter of 4 mm in SD rats. The area of the corneal epithelial defect was calculated by fluorescein sodium staining. Results: LSCs in the MLN4924 group had significantly proliferated. The MLN4924 treatment evidently enhanced the clone formation rate and clone area of LSCs. The expression levels of Ki67, p63, ABCG2, Bmi1, and C/EBPδ increased in LSCs after MLN4924 treatment, whereas the expression of K12 decreased. At 12 and 24 h after scraping, the corneal epithelium recovery rate in the eyes of the MLN4924-treated rats was accelerated. Conclusions: MLN4924 can maintain stemness, reduce differentiation, promote the proliferative capacity of rat LSCs, and accelerate corneal epithelial wound healing in SD rats.
Clinical Consequences of Incidental Durotomy during Full-Endoscopic Lumbar Decompression Surgery in Relation to Intraoperative Epidural Pressure Measurements
Authors: Vargas Roth A. A. , Moscatelli Marco , Vaz de Lima Marcos , Ramírez León Jorge Felipe , Lorio Morgan P. , Fiorelli Rossano Kepler Alvim , Telfeian Albert E. , Fiallos John , Braxton Ernest , Song Michael , Lewandrowski Kai-Uwe
Published: February 2023

Background: Seizures, neurological deficits, bradycardia, and, in the worst cases, cardiac arrest may occur following incidental durotomy during routine lumbar endoscopy. Therefore, we set out to measure the intraoperative epidural pressure during lumbar endoscopic decompression surgery. Methods: We conducted a retrospective observational cohort study to obtain intraoperative epidural measurements with an epidural catheter-pressure transducer assembly through the spinal endoscope on 15 patients who underwent lumbar endoscopic decompression of symptomatic lumbar herniated discs and spinal stenosis. The endoscopic interlaminar technique was employed. Results: There were six (40.0%) female and nine (60.0%) male patients aged 49.0667 ± 11.31034, ranging from 36 to 72 years, with an average follow-up of 35.15 ± 12.48 months. Three of the fifteen patients had seizures with durotomy and one of these three had intracranial air on their postoperative brain CT. Another patient developed spinal headaches and diplopia on postoperative day one when her deteriorating neurological function was investigated with a brain computed tomography (CT) scan, showing an intraventricular hemorrhage consistent with a Fisher Grade IV subarachnoid hemorrhage. A CT angiogram did not show any abnormalities. Pressure recordings in the epidural space in nine patients ranged from 20 to 29 mm Hg with a mean of 24.33 mm Hg. Conclusion: Most incidental durotomies encountered during lumbar interlaminar endoscopy can be managed without formal repair and supportive care measures. The intradural spread of irrigation fluid and intraoperatively used drugs and air entrapment through an unrecognized durotomy should be suspected if patients deteriorate in the recovery room. Ascending paralysis may cause nausea, vomiting, upper and lower motor neuron symptoms, cranial nerve palsies, hypotension, bradycardia, and respiratory and cardiac arrest. The recovery team should be prepared to manage these complications.
Serum and Urinary Biomarkers in COVID-19 Patients with or without Baseline Chronic Kidney Disease
Authors: Filev Rumen , Lyubomirova Mila , Hristova Julieta , Bogov Boris , Kalinov Krassimir , Svinarov Dobrin , Rostaing Lionel
Published: February 2023

In a prospective, observational, non-interventional, single-center study, we assessed various plasma and urinary biomarkers of kidney injury (neutrophil gelatinase-associated Lipocain [NGAL], kidney-injury molecule-1 [KIM-1], and interleukin-18 [IL-18]); inflammation (IL-6, C-reactive protein [CRP]); plus angiotensin converting enzyme 2 (ACE2) in 120 COVID-19 patients (of whom 70 had chronic kidney disease (CKD) at emergency-department (ED) admission). Our aim was to correlate the biomarkers with the outcomes (death, acute kidney injury [AKI]). All patients had received a chest-CT scan at admission to calculate the severity score (0–5). Biomarkers were also assessed in healthy volunteers and non-COVID-19-CKD patients. These biomarkers statistically differed across subgroups, i.e., they were significantly increased in COVID-19 patients, except for urinary (u)KIM1 and uIL-18. Amongst the biomarkers, only IL-6 was independently associated with mortality, along with AKI and not using remdesivir. Regarding the prediction of AKI, only IL-6 and uKIM1 were significantly elevated in patients presenting with AKI. However, AKI could not be predicted. Having high baseline IL-6 levels was associated with subsequent ventilation requirement and death. The mortality rate was almost 90% when the chest CT-scan severity score was 3 or 4 vs. 6.8% when the severity score was 0–2 (p < 0.0001).
Forecasting Methods of Key Ratios and Their Impact in Company’s Value
Authors: Liapis Angelos , Artsidakis Stylianos , Galanos Christos
Published: February 2023

This paper aims to develop a comprehensive procedure for calculating the fair value of a company by predicting its future values using historical data of key ratios and applying dynamic algorithms to improve the selection of forecasting methods. The most important business valuation methodologies are based on discounting a firm’s future variables, and there are many ways to predict them through financial and quantitative methodologies. This paper provides the most important and commonly used time series forecasting methodologies that can be used for variables, such as financial ratios, and proposes three different algorithms to help and improve the selection of the best-fit method for each of the model’s variables. Another, more indirect way of predicting values is using operational research methodologies, such as Monte Carlo simulation, where the output of the sensitivity analysis gives the most likely firm value, taking into account the distribution of each variable. This paper includes a complete example of using the above procedures in a real Greek company to calculate its fair value. It offers alternative approaches to the problem that exists around the process of predicting variables, with the help of technology. We hope this will be a useful tool for future use.
Factors Influencing the Success of Online Education during COVID-19: A Case Analysis of Odisha
Authors: Mohapatra Barada Prasanna , Nanda Sudhansu Sekhar , Hiremath Chetan V. , Halagatti Mahantesh , Das Suresh Chandra , Das Anindita
Published: February 2023

The COVID-19 pandemic caused by the coronavirus has dramatically changed the lives of students all around the world, with the virus’s effects profoundly impacting students’ physical and emotional well-being. Due to a series of shutdowns and lockdowns, social distancing, and further closure of schools, colleges, and institutions to ameliorate the pandemic crisis, the teaching and learning process shifted to an online form. As a result, students all over the world have been forced to deal with the problem as a last resort to accepting online education. This study looked at the efficiency of online education in the current situation and the student’s reactions. To enhance the online method of education for students, we examined the success characteristics of online education in the Indian state of Odisha. The study’s samples were collected from the faculty members of various graduate and post-graduate educational institutions in Odisha, who were recruited by questionnaire to get an expert opinion.
1-(4-Bromo-2,3,5,6-tetrafluoropheyl)-3-(3-phenylbenzyl)-4-methylimidazolium Bromide
Authors: Acharige Udari A. I. , Parsot Priya D. , Saunders Graham C.
Published: February 2023

In this paper, we report on the crystal structure of salt 1-(4-bromo-2,3,5,6-tetrafluorophenyl)-3-(3-phenylbenzyl)-4-methylimidazolium bromide, 3, synthesized by the sequential nucleophilic attack of 4-methylimidazole on bromopentafluorobenzene and then 3-phenylbenzyl bromide. The salt was characterized by 1H, 13C, and 19F NMR spectroscopy and mass spectrometry.
Thermally Mendable Self-Healing Epoxy Coating for Corrosion Protection in Marine Environments
Authors: Amendola Eugenio , Palmieri Barbara , Dello Iacono Stefania , Martone Alfonso
Published: February 2023

Polymeric coatings represent a well-established protection system that provides a barrier between a metallic substrate and the environment. The development of a smart organic coating for the protection of metallic structures in marine and offshore applications is a challenge. In the present study, we investigated the use of self-healing epoxy as an organic coating suitable for metallic substrates. The self-healing epoxy was obtained by mixing Diels–Alder (D–A) adducts with a commercial diglycidyl ether of bisphenol-A (DGEBA) monomer. The resin recovery feature was assessed through morphological observation, spectroscopic analysis, and mechanical and nanoindentation tests. Barrier properties and anti-corrosion performance were evaluated through electrochemical impedance spectroscopy (EIS). The film on a metallic substrate was scratched and subsequently repaired using proper thermal treatment. The morphological and structural analysis confirmed that the coating restored its pristine properties. In the EIS analysis, the repaired coating exhibited diffusive properties similar to the pristine material, with a diffusivity coefficient of 1.6 × 10−6 cm2/s (undamaged system 3.1 × 10−6 cm2/s), confirming the restoration of the polymeric structure. These results reveal that a good morphological and mechanical recovery was achieved, suggesting very promising applications in the field of corrosion-resistant protective coatings and adhesives.
Effect of Different Expansive Agents on the Deformation Properties of Core Concrete in a Steel Tube with a Harsh Temperature History
Authors: Lu Anqun , Xu Wen , Wang Qianqian , Wang Rui , Ye Zhiyuan
Published: February 2023

The shrinkage of core concrete during construction is the key reason for the separation of steel pipes and core concrete. Utilizing expansive agents during cement hydration is one of the main techniques to prevent voids between steel pipes and core concrete and increase the structural stability of concrete-filled steel tubes. The expansion and hydration properties of CaO, MgO, and CaO + MgO composite expansive agents in C60 concrete under variable temperature conditions were investigated. The effects of the calcium–magnesium ratio and magnesium oxide activity on deformation are the main parameters to consider when designing composite expansive agents. The results showed that the expansion effect of CaO expansive agents was predominant in the heating stage (from 20.0 °C to 72.0 °C at 3 °C/h), while there was no expansion in the cooling stage (from 72.0 °C to 30.0 °C at 3 °C/d, and then to 20.0 °C at 0.7 °C/h); the expansion deformation in the cooling stage was mainly caused by the MgO expansive agent. With the increase in the active reaction time of MgO, the hydration of MgO in the heating stage of concrete decreased, and the expansion of MgO in the cooling stage increased. During the cooling stage, 120 s MgO and 220 s MgO resulted in continuous expansion, and the expansion curve did not converge, while 65 s MgO reacted with water to form brucite in large amounts, leading to its lower expansion deformation during the later cooling process. In summary, the CaO and 220 s MgO composite expansive agent in the appropriate dosage is suitable for compensating for the shrinkage of concrete in the case of a fast high-temperature rise and slow cooling rate. This work will guide the application of different types of CaO-MgO composite expansive agents in concrete-filled steel tube structures under harsh environmental conditions.