bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis Viruses Control Host Immune Responses by Modifying the Exosomal Biogenesis Pathway and Cargo
Authors: Karamichali Eirini , Foka Pelagia , Papadopoulou Georgia , Loukaki-Gkountara Domniki , Andresaki Konstantina , Koskinas Ioannis , Georgopoulou Urania
Published: September 2022

The development of smart immune evasion mechanisms is crucial for the establishment of acute and chronic viral hepatitis. Hepatitis is a major health problem worldwide arising from different causes, such as pathogens, metabolic disorders, and xenotoxins, with the five hepatitis viruses A, B, C, D, and E (HAV, HBV, HCV, HDV, and HEV) representing the majority of the cases. Most of the hepatitis viruses are considered enveloped. Recently, it was reported that the non-enveloped HAV and HEV are, in reality, quasi-enveloped viruses exploiting exosomal-like biogenesis mechanisms for budding. Regardless, all hepatitis viruses use exosomes to egress, regulate, and eventually escape from the host immune system, revealing another key function of exosomes apart from their recognised role in intercellular communication. This review will discuss how the hepatitis viruses exploit exosome biogenesis and transport capacity to establish successful infection and spread. Then, we will outline the contribution of exosomes in viral persistence and liver disease progression.
IDH Inhibitors and Immunotherapy for Biliary Tract Cancer: A Marriage of Convenience?
Authors: Brandi Giovanni , Rizzo Alessandro
Published: September 2022

Systemic treatments have traditionally reported limited efficacy for biliary tract cancer (BTC), and although targeted therapies and immune checkpoint inhibitors have been found to play an increasingly important role in treatment, several questions remain unanswered, including the identification of biomarkers of response. The tumor microenvironment (TME) has recently attracted the attention of the BTC medical community, and is currently being studied due to its potential role in modulating response and resistance to systemic therapies, including immunotherapy. In this perspective article, we discuss available evidence regarding the interplay between TME, IDH inhibitors, and immunotherapy, providing rationale for the design of future clinical trials.
Resveratrol Affects Sphingolipid Metabolism in A549 Lung Adenocarcinoma Cells
Authors: Momchilova Albena , Pankov Roumen , Staneva Galya , Pankov Stefan , Krastev Plamen , Vassileva Evgenia , Hazarosova Rusina , Krastev Nikolai , Robev Bozhil , Nikolova Biliana , Pinkas Adriana
Published: September 2022

Resveratrol is a naturally occurring polyphenol which has various beneficial effects, such as anti-inflammatory, anti-tumor, anti-aging, antioxidant, and neuroprotective effects, among others. The anti-cancer activity of resveratrol has been related to alterations in sphingolipid metabolism. We analyzed the effect of resveratrol on the enzymes responsible for accumulation of the two sphingolipids with highest functional activity—apoptosis promoting ceramide (CER) and proliferation-stimulating sphingosine-1-phosphate (S1P)—in human lung adenocarcinoma A549 cells. Resveratrol treatment induced an increase in CER and sphingosine (SPH) and a decrease in sphingomyelin (SM) and S1P. Our results showed that the most common mode of CER accumulation, through sphingomyelinase-induced hydrolysis of SM, was not responsible for a CER increase despite the reduction in SM in A549 plasma membranes. However, both the activity and the expression of CER synthase 6 were upregulated in resveratrol-treated cells, implying that CER was accumulated as a result of stimulated de novo synthesis. Furthermore, the enzyme responsible for CER hydrolysis, alkaline ceramidase, was not altered, suggesting that it was not related to changes in the CER level. The enzyme maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was downregulated, and its expression was reduced, resulting in a decrease in S1P levels in resveratrol-treated lung adenocarcinoma cells. In addition, incubation of resveratrol-treated A549 cells with the SK1 inhibitors DMS and fingolimod additionally downregulated SK1 without affecting its expression. The present studies provide information concerning the biochemical processes underlying the influence of resveratrol on sphingolipid metabolism in A549 lung cancer cells and reveal possibilities for combined use of polyphenols with specific anti-proliferative agents that could serve as the basis for the development of complex therapeutic strategies.
Role of RBMS3 Novel Potential Regulator of the EMT Phenomenon in Physiological and Pathological Processes
Authors: Górnicki Tomasz , Lambrinow Jakub , Mrozowska Monika , Podhorska-Okołów Marzena , Dzięgiel Piotr , Grzegrzółka Jędrzej
Published: September 2022

RNA-binding protein 3 (RBMS3) plays a significant role in embryonic development and the pathogenesis of many diseases, especially cancer initiation and progression. The multiple roles of RBMS3 are conditioned by its numerous alternative expression products. It has been proven that the main form of RBMS3 influences the regulation of microRNA expression or stabilization. The absence of RBMS3 activates the Wnt/β-catenin pathway. The expression of c-Myc, another target of the Wnt/β-catenin pathway, is correlated with the RBMS3 expression. Numerous studies have focused solely on the interaction of RBMS3 with the epithelial–mesenchymal transition (EMT) protein machinery. EMT plays a vital role in cancer progression, in which RBMS3 is a new potential regulator. It is also significant that RBMS3 may act as a prognostic factor of overall survival (OS) in different types of cancer. This review presents the current state of knowledge about the role of RBMS3 in physiological and pathological processes, with particular emphasis on carcinogenesis. The molecular mechanisms underlying the role of RBMS3 are not fully understood; hence, a broader explanation and understanding is still needed.
Mitochondrial Dysfunction in Spinal Muscular Atrophy
Authors: Zilio Eleonora , Piano Valentina , Wirth Brunhilde
Published: September 2022

Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by recessive mutations in the SMN1 gene, globally affecting ~8–14 newborns per 100,000. The severity of the disease depends on the residual levels of functional survival of motor neuron protein, SMN. SMN is a ubiquitously expressed RNA binding protein involved in a plethora of cellular processes. In this review, we discuss the effects of SMN loss on mitochondrial functions in the neuronal and muscular systems that are the most affected in patients with spinal muscular atrophy. Our aim is to highlight how mitochondrial defects may contribute to disease progression and how restoring mitochondrial functionality may be a promising approach to develop new therapies. We also collected from previous studies a list of transcripts encoding mitochondrial proteins affected in various SMA models. Moreover, we speculate that in adulthood, when motor neurons require only very low SMN levels, the natural deterioration of mitochondria associated with aging may be a crucial triggering factor for adult spinal muscular atrophy, and this requires particular attention for therapeutic strategies.
Near-Infrared Photothermally Enhanced Photo-Oxygenation for Inhibition of Amyloid-β Aggregation Based on RVG-Conjugated Porphyrinic Metal–Organic Framework and Indocyanine Green Nanoplatform
Authors: Wang Jiuhai , Gu Yutian , Liu Xu , Fan Yadi , Zhang Yu , Yi Changqing , Cheng Changming , Yang Mo
Published: September 2022

Amyloid aggregation is associated with many neurodegenerative diseases such as Alzheimer’s disease (AD). The current technologies using phototherapy for amyloid inhibition are usually photodynamic approaches based on evidence that reactive oxygen species can inhibit Aβ aggregation. Herein, we report a novel combinational photothermally assisted photo-oxygenation treatment based on a nano-platform of the brain-targeting peptide RVG conjugated with the 2D porphyrinic PCN−222 metal–organic framework and indocyanine green (PCN−222@ICG@RVG) with enhanced photo-inhibition in Alzheimer’s Aβ aggregation. A photothermally assisted photo-oxygenation treatment based on PCN@ICG could largely enhance the photo-inhibition effect on Aβ42 aggregation and lead to much lower neurotoxicity upon near-infrared (NIR) irradiation at 808 nm compared with a single modality of photo-treatment in both cell-free and in vitro experiments. Generally, local photothermal heat increases the instability of Aβ aggregates and keeps Aβ in the status of monomers, which facilitates the photo-oxygenation process of generating oxidized Aβ monomers with low aggregation capability. In addition, combined with the brain-targeting peptide RVG, the PCN−222@ICG@RVG nanoprobe shows high permeability of the human blood–brain barrier (BBB) on a human brain-on-a-chip platform. The ex vivo study also demonstrates that NIR-activated PCN−222@ICG@RVG could efficiently dissemble Aβ plaques. Our work suggests that the combination of photothermal treatment with photo-oxygenation can synergistically enhance the inhibition of Aβ aggregation, which may boost NIR-based combinational phototherapy of AD in the future.
Regulatory T Cells in Development and Prediction of Necrotizing Enterocolitis in Preterm Neonates: A Scoping Review
Authors: Zuiderwijk Mara O. , van der Burg Mirjam , Bekker Vincent , Schoenaker Michiel H. D.
Published: September 2022

Necrotizing enterocolitis (NEC) is a leading cause of mortality in premature infants. However, the pathophysiology and influence of regulatory T cells (Tregs) have not been sufficiently elucidated. We performed a scoping review to investigate current knowledge on the influence of Tregs in NEC, and to investigate the predictive value of Treg number in NEC development. Pubmed, Embase, Prospero and Cochrane Library were searched during December 2020. Primary research articles discussing Tregs and NEC development written in English were selected. Two reviewers screened title and abstract for relevance, after which full-text screening was performed. A total of 20 articles were selected—13 of the articles discussed studies performed in animal models, while 8 used human neonate data. One study discussed both animal and human data. It was shown that after NEC diagnosis or induction, Treg levels were decreased while Th17 levels were increased. No studies were found which investigated the predictive value of Treg number in NEC development. A reduced Treg level is found in animals and neonates with NEC. The question remains whether this effect is a factor on the causal pathway of NEC development or a bystander effect. Future research focusing on the pathophysiological timeline of NEC and the involvement of Tregs is required for better understanding of this disease.
Skeletal Muscle Dysfunction in Experimental Pulmonary Hypertension
Authors: Kosmas Kosmas , Michael Zoe , Papathanasiou Aimilia Eirini , Spyropoulos Fotios , Adib Elio , Jasuja Ravi , Christou Helen
Published: September 2022

Pulmonary arterial hypertension (PAH) is a serious, progressive, and often fatal disease that is in urgent need of improved therapies that treat it. One of the remaining therapeutic challenges is the increasingly recognized skeletal muscle dysfunction that interferes with exercise tolerance. Here we report that in the adult rat Sugen/hypoxia (SU/Hx) model of severe pulmonary hypertension (PH), there is highly significant, almost 50%, decrease in exercise endurance, and this is associated with a 25% increase in the abundance of type II muscle fiber markers, thick sarcomeric aggregates and an increase in the levels of FoxO1 in the soleus (a predominantly type I fiber muscle), with additional alterations in the transcriptomic profiles of the diaphragm (a mixed fiber muscle) and the extensor digitorum longus (a predominantly Type II fiber muscle). In addition, soleus atrophy may contribute to impaired exercise endurance. Studies in L6 rat myoblasts have showed that myotube differentiation is associated with increased FoxO1 levels and type II fiber markers, while the inhibition of FoxO1 leads to increased type I fiber markers. We conclude that the formation of aggregates and a FoxO1-mediated shift in the skeletal muscle fiber-type specification may underlie skeletal muscle dysfunction in an experimental study of PH.
Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle
Authors: Kravtsova Violetta V. , Fedorova Arina A. , Tishkova Maria V. , Livanova Alexandra A. , Vetrovoy Oleg V. , Markov Alexander G. , Matchkov Vladimir V. , Krivoi Igor I.
Published: September 2022

The damaging effect of ionizing radiation (IR) on skeletal muscle Na,K-ATPase is an open field of research. Considering a therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against the IR-induced disturbances of Na,K-ATPase function in rat diaphragm muscle that co-expresses the α1 and α2 isozymes of this protein. Male Wistar rats (n = 26) were subjected to 6-day injections of vehicle (0.9% NaCl) or ouabain (1 µg/kg/day). On the fourth day of injections, rats were exposed to one-time total-body X-ray irradiation (10 Gy), or a sham irradiation. The isolated muscles were studied 72 h post-irradiation. IR decreased the electrogenic contribution of the α2 Na,K-ATPase without affecting its protein content, thereby causing sarcolemma depolarization. IR increased serum concentrations of ouabain, IL-6, and corticosterone, decreased lipid peroxidation, and changed cellular redox status. Chronic ouabain administration prevented IR-induced depolarization and loss of the α2 Na,K-ATPase electrogenic contribution without changing its protein content. This was accompanied with an elevation of ouabain concentration in circulation and with the lack of IR-induced suppression of lipid peroxidation. Given the crucial role of Na,K-ATPase in skeletal muscle performance, these findings may have therapeutic implications as countermeasures for IR-induced muscle pathology.
Y98 Mutation Leads to the Loss of RsfS Anti-Association Activity in Staphylococcus aureus
Authors: Fatkhullin Bulat , Golubev Alexander , Garaeva Natalia , Validov Shamil , Gabdulkhakov Azat , Yusupov Marat
Published: September 2022

Ribosomal silencing factor S (RsfS) is a conserved protein that plays a role in the mechanisms of ribosome shutdown and cell survival during starvation. Recent studies demonstrated the involvement of RsfS in the biogenesis of the large ribosomal subunit. RsfS binds to the uL14 ribosomal protein on the large ribosomal subunit and prevents its association with the small subunit. Here, we estimated the contribution of RsfS amino acid side chains at the interface between RsfS and uL14 to RsfS anti-association function in Staphylococcus aureus through in vitro experiments: centrifugation in sucrose gradient profiles and an S. aureus cell-free system assay. The detected critical Y98 amino acid on the RsfS surface might become a new potential target for pharmacological drug development and treatment of S. aureus infections.
Quantum-Inspired Evolutionary Algorithm for Optimal Service-Matching Task Assignment
Authors: Vendrell Joan , Kia Solmaz
Published: September 2022

This paper proposes a quantum-inspired evolutionary algorithm (QiEA) to solve an optimal service-matching task-assignment problem. Our proposed algorithm comes with the advantage of generating always feasible population individuals and, thus, eliminating the necessity for a repair step. That is, with respect to other quantum-inspired evolutionary algorithms, our proposed QiEA algorithm presents a new way of collapsing the quantum state that integrates the problem constraints in order to avoid later adjusting operations of the system to make it feasible. This results in lower computations and also faster convergence. We compare our proposed QiEA algorithm with three commonly used benchmark methods: the greedy algorithm, Hungarian method and Simplex, in five different case studies. The results show that the quantum approach presents better scalability and interesting properties that can be used in a wider class of assignment problems where the matching is not perfect.
Influence of Doping-Ion-Type on the Characteristics of Al2O3-Based Nanocomposites and Their Capabilities of Removing Indigo Carmine from Water
Authors: Adam Fatima A.
Published: September 2022

Globally, the continuous contamination of natural water resources is a severe issue, and looking for a solution for such a massive problem should be the researcher’s concern. Herein, Al2O3, Al2O3-CuO, Al2O3-NiO, and Al2O3-CoO were prepared via a simple and fast route, utilizing glucose as a capping material. All synthesis conditions were uniform to make the fabricated nanomaterials’ characteristics exclusively influenced by only the ion type. The SEM analysis showed that the particles of the synthesized Al2O3, Al2O3-CuO, Al2O3-NiO, and Al2O3-CoO were all less than 25 nm. The Al2O3-NiO showed the smallest particle size (11 to 14 nm) and the best BET surface area of 125.6 m2 g−1. All sorbents were tested for removing organic pollutants, as exemplified by indigo carmine (IGC) dye. The Al2O3-NiO possessed the highest adsorption capacity among the other sorbents for which it had been selected for further investigations. The IGC sorption reached equilibrium within 2.0 h, and the kinetic study revealed that the IGC removal by Al2O3-NiO nanocomposite fitted the FOM and the LFM. The sorbent showed an experimental adsorption capacity (qt) of 456.3 mg g−1 from a 200 mg L−1 IGC solution and followed the Langmuir model. The thermodynamic findings indicated an endothermic, spontaneous, and physisorption nature. The seawater and groundwater samples contaminated with 5.0 mg L−1 IGC concentrations were fully remediated using the Al2O3-NiO nanocomposite. The reuse study showed 93.3% average efficiency during four successive cycles. Consequently, prepared Al2O3-NiO nanocomposite is recommended for the treatment of contaminated water.
Method of Forming Various Configurations of Telecommunication System Using Moving Target Defense
Authors: Ryapukhin Anatoly V. , Karpukhin Evgeny O. , Zhuikov Ivan O.
Published: September 2022

The purpose of this paper is to improve the effectiveness of the Moving Target Defense (MTD)-based protection method, which reduces the problem of using traditional network protection tools due to the static nature of network services and configurations. Options for solving the problems of choosing an adequate time interval for activating the technology of MTD and its application in networks are given. A new approach is proposed, which consists in creating a set of system configurations and changing it when an attack is detected and determined. The design implementation was tested on a network model using software defined networks (SDN). The advantages of the proposed method are highlighted, among which the most significant are: simple operation scheme, ability to deploy the system without the use of software-defined networks and absence of violations of security policies within the system.
Extreme Hyperferritinemia: Causes and Prognosis
Authors: Fauter Maxime , Mainbourg Sabine , El Jammal Thomas , Guerber Arthur , Zaepfel Sabine , Henry Thomas , Gerfaud-Valentin Mathieu , Sève Pascal , Jamilloux Yvan
Published: September 2022

The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.
Reconstruction of Chronic Proximal Hamstring Tear: A Novel Surgical Technique with Semitendinosus Tendon Allograft Assisted with Autologous Plasma Rich in Growth Factors (PRGF)
Authors: Ríos Luna Antonio , Fahandezh-Saddi Díaz Homid , Villanueva Martínez Manuel , Bueno Horcajadas Ángel , Prado Roberto , Anitua Eduardo , Padilla Sabino
Published: September 2022

The reconstruction of a chronic proximal hamstring tear is a challenging pathology that posits difficulties to surgeons due to the distal retraction of the hamstring tendon stumps and the entrapment of the sciatic nerve within the scar formed around the torn hamstring tendon. We describe a novel surgical technique using a semitendinosus tendon allograft sutured in a “V inversion” manner, thereby avoiding an excess of tension and length of the new reconstructed hamstring tendons. In addition, and in order to speed up the healing process and avoid new sciatic entrapment, we assisted the surgery with liquid plasma rich in growth factors (PRGF) injected intraosseously, intratendinously and within the suture areas, as well as wrapping the sciatic nerve with a PRGF membrane. In conclusion, this novel approach offers mechanical and biological advantages to tackle the large retraction of hamstring stumps and the entrapment of the sciatic nerve within the scar.
The Role of Silicone Oil in the Surgical Management of Endophthalmitis: A Systematic Review
Authors: Sinisi Fabrizio , Della Santina Marco , Loiudice Pasquale , Figus Michele , Casini Giamberto
Published: September 2022

(1) Background: We aimed to systematically review the current literature to evaluate if in patients with postoperative endophthalmitis treated with pars plana vitrectomy, silicone oil tamponade could provide a useful contribution to the control and eradication of infection and if it could influence anatomical recovery and functional outcome. (2) Randomized controlled trials, cross-sectional studies, case series, and case reports published in the English language in peer-reviewed journals were included. No restriction was placed based on the study location. We used medical subject headings (MeSH) and text words. We searched MEDLINE (OVID and PubMed), Google Scholar, ISI Web of Science (Thom-on-Reuters), and the Cochrane Library (Wiley) from January 1995 to the present. To ensure literature saturation, we scanned the reference lists of included studies or relevant reviews identified through the search. Risk of Bias was assessed using the Newcastle-Ottawa scale for longitudinal studies and Cochrane risk-of-bias tool for randomized trials. (3) Results: abstracts of 75 articles were selected for full-text reading; after full-text reading, 44 articles were taken into consideration in the systematic review. 5 out of 7 in vitro experimental studies demonstrated antimicrobial activity against different species of bacteria and fungi. The use of SO as endotamponade associated with PPV led to better visual acuity and a lower rate of retinal detachment and the need for additional surgery. (4) Conclusions: Silicone oil reduces the risk of postoperative retinal detachment, especially in case of undetected retinal breaks, produces compartmentalization of the eye, may lead to early visual recovery, allows laser photocoagulation, prevents severe postoperative hypotony and has antimicrobic activity due to an inhibitory effect for several species of pathogens. Concerns regarding possible toxic effects on the retina and optic disc, compartmentalization and impaired washout of pathogen toxins have been reported. It may also influence intravitreal antibiotic distribution and clearance.
Circulating MicroRNAs Expression Profile in Lung Inflammation: A Preliminary Study
Authors: Mirra Davida , Cione Erika , Spaziano Giuseppe , Esposito Renata , Sorgenti Mario , Granato Elisabetta , Cerqua Ida , Muraca Lucia , Iovino Pasquale , Gallelli Luca , D’Agostino Bruno
Published: September 2022

Background: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation. Methods: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation. Results: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs’ specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway. Conclusions: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response.
Systematic Review and Meta-Analysis of Statin Use and Mortality, Intensive Care Unit Admission and Requirement for Mechanical Ventilation in COVID-19 Patients
Authors: Lao Ut-Sam , Law Chak-Fun , Baptista-Hon Daniel T. , Tomlinson Brian
Published: September 2022

There is mounting evidence that statin use is beneficial for COVID-19 outcomes. We performed a systematic review and meta-analysis to evaluate the association between statin use and mortality, intensive care unit (ICU) admission and mechanical ventilation in COVID-19 patients, on studies which provided covariate adjusted effect estimates, or performed propensity score matching. We searched PubMed, Embase, Web of Science and Scopus for studies and extracted odds or hazard ratios for specified outcome measures. Data synthesis was performed using a random-effects inverse variance method. Risk of bias, heterogeneity and publication bias were analyzed using standard methods. Our results show that statin use was associated with significant reductions in mortality (OR = 0.72, 95% CI: 0.67–0.77; HR = 0.74, 95% CI: 0.69, 0.79), ICU admission (OR = 0.94, 95% CI: 0.89–0.99; HR = 0.76, 95% CI: 0.60–0.96) and mechanical ventilation (OR = 0.84, 95% CI: 0.78–0.92; HR = 0.67, 95% CI: 0.47–0.97). Nevertheless, current retrospective studies are based on the antecedent use of statins prior to infection and/or continued use of statin after hospital admission. The results may not apply to the de novo commencement of statin treatment after developing COVID-19 infection. Prospective studies are lacking and necessary.
Optic Nerve Changes Detected with Ocular Ultrasonography during Different Surgical Procedures: A Narrative Review
Authors: De Bernardo Maddalena , Vitiello Livio , De Luca Martina , La Marca Aniello , Rosa Nicola
Published: September 2022

Ultrasonographic appraisal of the optic nerve sheath diameter has become popular in recent years as a useful diagnostic tool to detect intracranial pressure variations. Intracranial hypertension is a life-threatening disease with possible poor clinical outcomes and can be caused by a variety of neurological and non-neurological conditions. Considering the latter, increases in intracranial pressure have also been described during several surgical procedures. Ocular ultrasonography might be utilized to identify intracranial pressure increases by evaluating optic nerve sheath diameter variations. The aim of this review is to provide a wide overview on the use of the optic nerve ultrasound evaluation to detect intracranial pressure changes during surgical procedures, also discussing the pitfalls of the B-scan technique, the most widely used for such a purpose. PubMed medical database, Web of Science and Scopus were used to carry out this review. The present review showed that ocular ultrasonography could be considered a valuable diagnostic tool in the surgical setting to indirectly assess intracranial pressure. However, the use of the B-scan ultrasound should always be coupled with the standardized A-scan technique for a more accurate, precise and trustworthy ultrasound assessment.
Neuropathic-like Pain Symptoms and Their Association with Muscle Strength in Patients with Chronic Musculoskeletal Pain
Authors: Kim Hee Jung , Ban Min Gi , Yoon Kyung Bong , Jeon Woohyuk , Kim Shin Hyung
Published: September 2022

The relationship between sarcopenia and pain remains unclear; thus, this study evaluated whether muscle strength is independently associated with neuropathic-like pain symptoms in patients with chronic musculoskeletal pain. A cut-off score of painDETECT ≥13 was used to indicate a possible neuropathic component. Handgrip strength was measured, and muscle mass was estimated. A total of 2599 patients, including 439 patients who reported neuropathic-like pain symptoms (16.9%), were included for analysis. Handgrip strength was significantly lower in patients experiencing neuropathic-like pain symptoms (23.23 ± 10.57 vs. 24.82 ± 10.43 kg, p < 0.001), and this result was chiefly found in female patients. However, there was no difference in estimated muscle mass. Shorter duration of pain, opioid usage, pain in lower limbs, sleep disturbance, and lower handgrip strength were significantly associated with neuropathic-like pain symptoms. In patients with handgrip strength below the reference values by sex, experiencing radiating pain and at least moderate sensory symptoms by light touch and thermal stimulation were more frequently reported. In conclusion, lower handgrip strength appeared to be an independent factor associated with symptoms suggestive of neuropathic pain in this population. Interventional studies are required to determine whether improvement in muscle strength can reduce the neuropathic pain component in chronic musculoskeletal pain.
The Small Posterior Cranial Fossa Syndrome and Chiari Malformation Type 0
Authors: Bogdanov Enver I. , Faizutdinova Aisylu T. , Heiss John D.
Published: September 2022

Patients showing typical Chiari malformation type 1 (CM1) signs and symptoms frequently undergo cranial and cervical MRI. In some patients, MRI documents >5 mm of cerebellar tonsillar herniation (TH) and the diagnosis of CM1. Patients with 3–5 mm TH have “borderline” CM1. Patients with less than 3 mm of TH and an associated cervical syrinx are diagnosed with Chiari “zero” malformation (CM0). However, patients reporting CM1 symptoms are usually not diagnosed with CM if MRI shows less than 3–5 mm of TH and no syrinx. Recent MRI morphometric analysis of the posterior fossa and upper cervical spine detected anatomical abnormalities in and around the foramen magnum (FM) that explain these patients’ symptoms. The abnormalities include a reduced size of the posterior fossa, FM, and upper cervical spinal canal and extension of the cerebellar tonsils around the medulla rather than inferior to the foramen magnum, as in CM1. These morphometric findings lead some neurologists and neurosurgeons to diagnose CM0 in patients with typical CM1 signs and symptoms, with or without cervical syringes. This article reviews recent findings and controversies about CM0 diagnosis and updates current thinking about the clinical and radiological relationship between CM0, borderline CM1, and CM1.
3D Printing of Bioinert Oxide Ceramics for Medical Applications
Authors: Buj-Corral Irene , Tejo-Otero Aitor
Published: September 2022

Three-dimensionally printed metals and polymers have been widely used and studied in medical applications, yet ceramics also require attention. Ceramics are versatile materials thanks to their excellent properties including high mechanical properties and hardness, good thermal and chemical behavior, and appropriate, electrical, and magnetic properties, as well as good biocompatibility. Manufacturing complex ceramic structures employing conventional methods, such as ceramic injection molding, die pressing or machining is extremely challenging. Thus, 3D printing breaks in as an appropriate solution for complex shapes. Amongst the different ceramics, bioinert ceramics appear to be promising because of their physical properties, which, for example, are similar to those of a replaced tissue, with minimal toxic response. In this way, this review focuses on the different medical applications that can be achieved by 3D printing of bioinert ceramics, as well as on the latest advances in the 3D printing of bioinert ceramics. Moreover, an in-depth comparison of the different AM technologies used in ceramics is presented to help choose the appropriate methods depending on the part geometry.
Machine Learning Algorithms for Prediction of Survival by Stress Echocardiography in Chronic Coronary Syndromes
Authors: Cortigiani Lauro , Azzolina Danila , Ciampi Quirino , Lorenzoni Giulia , Gaibazzi Nicola , Rigo Fausto , Gherardi Sonia , Bovenzi Francesco , Gregori Dario , Picano Eugenio
Published: September 2022

Stress echocardiography (SE) is based on regional wall motion abnormalities and coronary flow velocity reserve (CFVR). Their independent prognostic capabilities could be better studied with a machine learning (ML) approach. The study aims to assess the SE outcome data by conducting an analysis with an ML approach. We included 6881 prospectively recruited and retrospectively analyzed patients with suspected (n = 4279) or known (n = 2602) coronary artery disease submitted to clinically driven dipyridamole SE. The outcome measure was all-cause death. A random forest survival model was implemented to model the survival function according to the patient’s characteristics; 1002 patients recruited by a single, independent center formed the external validation cohort. During a median follow-up of 3.4 years (IQR 1.6–7.5), 814 (12%) patients died. The mortality risk was higher for patients aged >60 years, with a resting ejection fraction < 60%, resting WMSI, positive stress-rest WMSI scores, and CFVR < 3.The C-index performance was 0.79 in the internal and 0.81 in the external validation data set. Survival functions for individual patients were easily obtained with an open access web app. An ML approach can be fruitfully applied to outcome data obtained with SE. Survival showed a constantly increasing relationship with a CFVR < 3.0 and stress-rest wall motion score index > Since processing is largely automated, this approach can be easily scaled to larger and more comprehensive data sets to further refine stratification, guide therapy and be ultimately adopted as an open-source online decision tool.
Effectiveness of Dupilumab in the Treatment of Patients with Uncontrolled Severe CRSwNP: A “Real-Life” Observational Study in Naïve and Post-Surgical Patients
Authors: Ottaviano Giancarlo , Saccardo Tommaso , Roccuzzo Giuseppe , Bernardi Riccardo , Chicco Alessandra Di , Pendolino Alfonso Luca , Scarpa Bruno , Mairani Edoardo , Nicolai Piero
Published: September 2022

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents 25–30% of all CRS cases, and in the most severe forms it is associated with a poor quality of life and a high rate of nasal polyps’ recurrence after surgery. Dupilumab has been suggested as a treatment option for severe CRSwNP. Methods: Patients with severe CRSwNP receiving dupilumab from January 2021 were followed up at 1, 3, 6, 9 and 12 months from the first administration and were considered for this study. At baseline and at each follow-up, patients underwent nasal endoscopy and completed the Sinonasal Outcome Test (SNOT)-22, a Visual Analogue Scale (VAS) for smell/nasal obstruction, the Nasal Congestion Score and the Asthma Control Test. Peak nasal inspiratory flow (PNIF), a smell test, nasal cytology and blood eosinophilia were also evaluated. Results: Forty-seven patients were included in the study. Of these, 33 patients had a history of previous surgery (ESS) and had recurrent nasal polyps, while 14 patients were naïve to nasal surgery. Both subjective and objective parameters improved after biological treatment and were correlated with each other (p < 0.05), except for the SNOT-22 and the nasal polyp’s score. No correlations were found between nasal and blood eosinophilia. No differences were observed when comparing the post-surgical and the naïve groups. Conclusions: Dupilumab improves nasal obstruction and the sense of smell and reduces the level of local inflammation in severe CRSwNP patients in a similar way in both naïve and post-surgical patients.
Risk Factors for Acute Postoperative Delirium in Cardiac Surgery Patients >65 Years Old
Authors: Spiropoulou Eleni , Samanidis George , Kanakis Meletios , Nenekidis Ioannis
Published: September 2022

Background: Acute postoperative delirium is the most common neuropsychiatric disorder in cardiac surgery patients in the intensive care unit (ICU). The purpose of this study was to evaluate the possible risk factors of postoperative delirium (POD) for cardiac surgery patients in the ICU. Materials and Methods: The study population was composed of 86 cardiac surgery patients managed postoperatively in the cardiac surgery ICU. Presence of POD in patients was evaluated by the CAM-ICU scale. Results: According to the CAM-ICU scale, 22 (25.6%) patients presented POD; history of smoking, alcohol use, COPD, and preoperative permanent atrial fibrillation were associated with POD (for all, p < 0.05). The type of cardiac surgery operations, type of analgesia, and red blood cell transfusion in the ICU were not associated with POD (p > 0.05), while cardiac arrhythmia in the ICU, hypoxemia in the ICU after extubation (pO2 < 60 mmHg), and heart rate after extubation were predisposing factors for POD (for all, p < 0.05). Multivariable logistic regression analysis (adjusted to risk factors) showed that hypoxemia after extubation (OR = 20.6; 95%CI: 2.82–150), heart rate after extubation (OR = 0.95; 95% CI: 0.92–0.98), and alcohol use (OR = 74.3; 95%CI: 6.41–861) were predictive factors for acute postoperative delirium (for all, p < 0.05). Conclusion: Alcohol use and respiratory dysfunction before and after heart operation were associated with acute postoperative delirium in cardiac surgery ICU patients.
Application of Reactive Oxygen Species in Dental Treatment
Authors: Komine Chiaki , Uchibori Satoshi , Tsudukibashi Osamu , Tsujimoto Yasuhisa
Published: September 2022

Reactive oxygen species (ROS) and free radicals, which have been implicated in inflammation, pain, carcinogenesis, and aging, are actually used in dental treatments such as tooth bleaching and composite resin polymerization. Recently, numerous studies have investigated the application of ROS in the medical and dental fields. In previous studies, ROS were generated intentionally through pathways such as photolysis, photocatalytic methods, and photodynamic therapy, which are used in the medical field to target cancer. In the field of dentistry, generated ROS are applied mainly for periodontal treatment and sterilization of the root canal, and its effectiveness as an antibacterial photodynamic therapy has been widely reported.. Given this background, the present article aimed to review the basic effects of ROS in dental medicine, especially endodontic therapy, and to discuss future applications of ROS.
The Spatio-Temporal Pattern and Spatial Effect of Installation of Lifts in Old Residential Buildings: Evidence from Hangzhou in China
Authors: Dai Xinjun , Li Zeling , Ma Lindong , Jin Jing
Published: September 2022

In recent years, in order to improve the quality of living, China has carried out a series of urban renewal projects, such as adding elevators to old communities. Taking Hangzhou as an example, this paper studies the decision to install elevators in old residential buildings. This study used cold spots and hot spots, local autocorrelation and fishnetting analysis to show the spatial and temporal patterns of lift retrofitting in old communities. Finally, the spatial lag model is used to test whether there is a spatial spillover effect in the behavior of residents installing elevators. The research shows that: (1) Hot spots areas for retrofitting lifts are clustered in the central urban areas of Hangzhou, such as the intersection of Shangcheng District, Xiacheng District, Jianggan District, Gongshu District and Xihu District (scenic area); (2) The trend of retrofitting areas spreading from the center to the periphery; (3) In different communities, the number of elevators added in neighboring communities has a positive effect on the decision of adding elevators in other local communities. Therefore, the neighborhood effect cannot be ignored in the topic of community renovation, in which residents spontaneously participate.
The Influence of External Environment Factors on Farmers’ Willingness to Withdraw from Rural Homesteads: Evidence from Wuhan and Suizhou City in Central China
Authors: Chen Ying , Ni Xiaolu , Liang Yajia
Published: September 2022

The external environment has an important impact on farmers’ willingness to withdraw from rural homesteads. Based on the data from 392 farmers in Wuhan and Suizhou City from July to November 2021, we explored the significant role that the external environment played in farmers’ willingness to withdraw from rural homesteads. The empirical results, according to the binary Logit model, showed that the number of homesteads, location, and economy positively affect farmers’ intention to withdraw from their rural homesteads, and the effect in turn decreases. Famers in a village with no tourism resources are more likely to be willing to withdraw from their homesteads. Based on the empirical findings, this paper finally proposed that local governments should adopt a targeted policy to encourage farmers to orderly withdraw from their rural homesteads.
The Effect of Perceived Risk on Public Participation Intention in Smart City Development: Evidence from China
Authors: Cui Qinghong , Wei Ruirui , Huang Rong , Hu Xiancun , Wang Guangbin
Published: September 2022

Smart city development aims at sustainable development and high quality of urban life, which requires the participation of stakeholders. As a crucial stakeholder involved, the public’s key role has been widely concerned. However, a lack of public participation in smart city development still exists due to perceived risk. In order to solve the insufficient public participation in smart city development, this study will identify the perceived risk and explore its influential impact. After defining the concept of perceived risk, this paper constructs a theoretical model concerning the effect of perceived risk on public participation intention based on the theory of reasoned action. On the basis of 193 empirical data from China, the structural equation model is applied to test the influential impact of perceived risk on the public participation intention in smart city development. The results show that the perceived risk has a significantly negative effect on public participation intention, attitude, and subjective norms, while behavioral attitude and subjective norms have positive effects on public participation intention. According to empirical research results, the risk prevention paths and methods of public participation in smart city development are proposed so as to provide useful implications for further public participation practice in smart city development.
The Predictive Value of Systemic Inflammatory Markers, the Prognostic Nutritional Index, and Measured Vessels’ Diameters in Arteriovenous Fistula Maturation Failure
Authors: Kaller Réka , Arbănași Emil Marian , Mureșan Adrian Vasile , Voidăzan Septimiu , Arbănași Eliza Mihaela , Horváth Emőke , Suciu Bogdan Andrei , Hosu Ioan , Halmaciu Ioana , Brinzaniuc Klara , Russu Eliza
Published: September 2022

Background: An arteriovenous fistula (AVF) is the first-line vascular access pathway for patients diagnosed with end-stage renal disease (ESRD). In planning vascular access, it is necessary to check the diameters of the venous and arterial components for satisfactory long-term results. Furthermore, the mechanism underlying the maturation failure and short-term patency in cases of AVFs is not fully known. This study aims to verify the predictive role of inflammatory biomarkers (the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), and C-reactive protein (CRP)), Ca-P product, the prognostic nutritional index (PNI), and the diameters of the venous and arterial components in the failure of AVF maturation. Methods: The present study was designed as an observational, analytical, and retrospective cohort study with a longitudinal follow-up, and included all patients with a diagnosis of ESRD that were admitted to the Vascular Surgery Clinic of the Targu Mures Emergency County Hospital, Romania, between January 2019 and December 2021. Results: The maturation of AVF at 6 weeks was clearly lower in cases of patients in the high-NLR (31.88% vs. 91.36%; p < 0.0001), high-PLR (46.94% vs. 85.55%; p < 0.0001), high-SII (44.28% vs. 88.89%; p < 0.0001), high-CRP (46.30% vs. 88.73%; p < 0.0001), high-Ca-P product (40.43% vs. 88.46%; p < 0.0001), and low-PNI (34.78% vs. 91.14%; p < 0.0001) groups, as well as in patients with a lower radial artery (RA) diameter (40% vs. 94.87%; p = 0.0009), cephalic vein (CV) diameter (44.82% vs. 97.14%; p = 0.0001) for a radio-cephalic AVF (RC-AVF), and brachial artery (BA) diameter (30.43% vs. 89.47%; p < 0.0001) in addition to CV diameter (40% vs. 94.59%; p < 0.0001) for a brachio-cephalic AVF (BC-AVF), respectively. There was also a significant increase in early thrombosis and short-time mortality in the same patients. A multivariate analysis showed that a baseline value for the NLR, PLR, SII, CRP, Ca-P product, and PNI was an independent predictor of adverse outcomes for all of the recruited patients. Furthermore, for all patients, a high baseline value for vessel diameter was a protective factor against any negative events during the study period, except for RA diameter in mortality (p = 0.16). Conclusion: Our findings concluded that higher NLR, PLR, SII, CRP, Ca-P product, and PNI values determined preoperatively were strongly predictive of AVF maturation failure, early thrombosis, and short-time mortality. Moreover, a lower baseline value for vessel diameter was strongly predictive of AVF maturation failure and early thrombosis.