bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Multiple Homeostasis-Maintaining Systems by Ionophore Nigericin Is a Novel Approach for Senolysis
Authors: Deryabin Pavel I. , Shatrova Alla N. , Borodkina Aleksandra V.
Published: November 2022

Within the present study we proposed a novel approach for senolysis based on the simultaneous disturbance of the several homeostasis-maintaining systems in senescent cells including intracellular ionic balance, energy production and intracellular utilization of damaged products. Of note, we could not induce senolysis by applying ouabain, amiloride, valinomycin or NH4Cl—compounds that modify each of these systems solely. However, we found that ionophore nigericin can disturb plasma membrane potential, intracellular pH, mitochondrial membrane potential and autophagy at once. By affecting all of the tested homeostasis-maintaining systems, nigericin induced senolytic action towards stromal and epithelial senescent cells of different origins. Moreover, the senolytic effect of nigericin was independent of the senescence-inducing stimuli. We uncovered that K+ efflux caused by nigericin initiated pyroptosis in senescent cells. According to our data, the higher sensitivity of senescent cells compared to the control ones towards nigericin-induced death was partially mediated by the lower intracellular K+ content in senescent cells and by their predisposition towards pyroptosis. Finally, we proposed an interval dosing strategy to minimize the negative effects of nigericin on the control cells and to achieve maximal senolytic effect. Hence, our data suggest ionophore nigericin as a new senotherapeutic compound for testing against age-related diseases.
Complexities of Prostate Cancer
Authors: Wasim Sobia , Lee Sang-Yoon , Kim Jaehong
Published: November 2022

Prostate cancer has a long disease history and a wide variety and uncertainty in individual patients’ clinical progress. In recent years, we have seen a revolutionary advance in both prostate cancer patient care and in the research field. The power of deep sequencing has provided cistromic and transcriptomic knowledge of prostate cancer that has not discovered before. Our understanding of prostate cancer biology, from bedside and molecular imaging techniques, has also been greatly advanced. It is important that our current theragnostic schemes, including our diagnostic modalities, therapeutic responses, and the drugs available to target non-AR signaling should be improved. This review article discusses the current progress in the understanding of prostate cancer biology and the recent advances in diagnostic and therapeutic strategies.
Study on the Optimal Treatment Condition Control of Photothermal Therapy under Various Cooling Time Ratios of Lasers
Authors: Kim Donghyuk , Kim Hyunjung
Published: November 2022

Photothermal therapy is a treatment technique that has attracted attention as an alternative to conventional surgical techniques. It is based on the photothermal effect, wherein light energy is converted into thermal energy, and facilitates rapid recovery after treatment. This study employed various laser irradiation conditions and presented conditions with the optimal treatment effects through a numerical analysis based on heat transfer. A skin layer comprising four stages containing squamous cell carcinoma was targeted, and the treatment effect was confirmed by varying the heating conditions of the laser and volume fraction of gold nanoparticles. The therapeutic effect was confirmed through both the apoptosis retention ratio, which quantitatively estimated the degree of maintenance of the apoptosis temperature range within the tumor, and the thermal hazard retention value, which quantitatively calculates the amount of thermal damage to the surrounding normal tissues. Finally, the optimal treatment conditions were determined based on the laser intensity, cooling time ratio, and volume fraction of injected gold nanoparticles through numerical analysis.
Studying the Impact of Persistent Organic Pollutants Exposure on Human Health by Proteomic Analysis: A Systematic Review
Authors: Guillotin Sophie , Delcourt Nicolas
Published: November 2022

Persistent organic pollutants (POPs) are organic chemical substances that are widely distributed in environments around the globe. POPs accumulate in living organisms and are found at high concentrations in the food chain. Humans are thus continuously exposed to these chemical substances, in which they exert hepatic, reproductive, developmental, behavioral, neurologic, endocrine, cardiovascular, and immunologic adverse health effects. However, considerable information is unknown regarding the mechanism by which POPs exert their adverse effects in humans, as well as the molecular and cellular responses involved. Data are notably lacking concerning the consequences of acute and chronic POP exposure on changes in gene expression, protein profile, and metabolic pathways. We conducted a systematic review to provide a synthesis of knowledge of POPs arising from proteomics-based research. The data source used for this review was PubMed. This study was carried out following the PRISMA guidelines. Of the 742 items originally identified, 89 were considered in the review. This review presents a comprehensive overview of the most recent research and available solutions to explore proteomics datasets to identify new features relevant to human health. Future perspectives in proteomics studies are discussed.
Molecular Mechanisms of Cartilage Repair and Their Possible Clinical Uses: A Review of Recent Developments
Authors: Rodríguez-Merchán Emérito Carlos
Published: November 2022

Articular cartilage (AC) defects are frequent but hard to manage. Osteoarthritis (OA) is a musculoskeletal illness that afflicts between 250 and 500 million people in the world. Even though traditional OA drugs can partly alleviate pain, these drugs cannot entirely cure OA. Since cartilaginous tissue of the joints has a poor self-repair capacity and very poor proliferative ability, the healing of injured cartilaginous tissue of the joint has not been accomplished so far. Consequently, the discovery of efficacious mediations and regenerative treatments for OA is needed. This manuscript reviews the basic concepts and the recent developments on the molecular mechanisms of cartilage repair and their potential clinical applications. For this purpose, a literature exploration was carried out in PubMed for the years 2020, 2021, and 2022. On 31 October 2022 and using “cartilage repair molecular mechanisms” as keywords, 41 articles were found in 2020, 42 in 2021, and 36 in 2022. Of the total of 119 articles, 80 were excluded as they were not directly related to the title of this manuscript. Of particular note are the advances concerning the mechanisms of action of hyaluronic acid, mesenchymal stem cells (MSCs), nanotechnology, enhancer of zeste 2 polycomb repressive complex 2 subunit (EHZ2), hesperetin, high mobility group box 2 (HMGB2), α2-macroglobulin (α2M), proteoglycan 4 (Prg4)/lubricin, and peptides related to cartilage repair and treatment of OA. Despite the progress made, current science has not yet achieved a definitive solution for healing AC lesions or repairing cartilage in the case of OA. Therefore, further research into the molecular mechanisms of AC damage is needed in the coming decades.
Potential Roles of Selectins in Periodontal Diseases and Associated Systemic Diseases: Could They Be Targets for Immunotherapy?
Authors: Zhong Mei , Huang Jiangyong , Wu Zhe , Chan Kok-Gan , Wang Lijing , Li Jiang , Lee Learn-Han , Law Jodi Woan-Fei
Published: November 2022

Periodontal diseases are predisposing factors to the development of many systemic disorders, which is often initiated via leukocyte infiltration and vascular inflammation. These diseases could significantly affect human health and quality of life. Hence, it is vital to explore effective therapies to prevent disease progression. Periodontitis, which is characterized by gingival bleeding, disruption of the gingival capillary’s integrity, and irreversible destruction of the periodontal supporting bone, appears to be caused by overexpression of selectins in periodontal tissues. Selectins (P-, L-, and E-selectins) are vital members of adhesion molecules regulating inflammatory and immune responses. They are mainly located in platelets, leukocytes, and endothelial cells. Furthermore, selectins are involved in the immunopathogenesis of vascular inflammatory diseases, such as cardiovascular disease, diabetes, cancers, and so on, by mediating leukocyte recruitment, platelet activation, and alteration of endothelial barrier permeability. Therefore, selectins could be new immunotherapeutic targets for periodontal disorders and their associated systemic diseases since they play a crucial role in immune regulation and endothelium dysfunction. However, the research on selectins and their association with periodontal and systemic diseases remains limited. This review aims to discuss the critical roles of selectins in periodontitis and associated systemic disorders and highlights the potential of selectins as therapeutic targets.
Effect of Salinity on Stomatal Conductance, Leaf Hydraulic Conductance, HvPIP2 Aquaporin, and Abscisic Acid Abundance in Barley Leaf Cells
Authors: Sharipova Guzel , Ivanov Ruslan , Veselov Dmitriy , Akhiyarova Guzel , Seldimirova Oksana , Galin Ilshat , Fricke Wieland , Vysotskaya Lidiya , Kudoyarova Guzel
Published: November 2022

The stomatal closure of salt-stressed plants reduces transpiration bringing about the maintenance of plant tissue hydration. The aim of this work was to test for any involvement of aquaporins (AQPs) in stomatal closure under salinity. The changes in the level of aquaporins in the cells were detected with the help of an immunohistochemical technique using antibodies against HvPIP2;2. In parallel, leaf sections were stained for abscisic acid (ABA). The effects of salinity were compared to those of exogenously applied ABA on leaf HvPIP2;2 levels and the stomatal and leaf hydraulic conductance of barley plants. Salinity reduced the abundance of HvPIP2;2 in the cells of the mestome sheath due to it being the more likely hydraulic barrier due to the deposition of lignin, accompanied by a decline in the hydraulic conductivity, transpiration, and ABA accumulation. The effects of exogenous ABA differed from those of salinity. This hormone decreased transpiration but increased the shoot hydraulic conductivity and PIP2;2 abundance. The difference in the action of the exogenous hormone and salinity may be related to the difference in the ABA distribution between leaf cells, with the hormone accumulating mainly in the mesophyll of salt-stressed plants and in the cells of the bundle sheaths of ABA-treated plants. The obtained results suggest the following succession of events: salinity decreases water flow into the shoots due to the decreased abundance of PIP2;2 and hydraulic conductance, while the decline in leaf hydration leads to the production of ABA in the leaves and stomatal closure.
Leucine and Arginine Availability Modulate Mouse Embryonic Stem Cell Proliferation and Metabolism
Authors: Correia Bibiana , Sousa Maria Inês , Branco Ana Filipa , Rodrigues Ana Sofia , Ramalho-Santos João
Published: November 2022

Amino acids are crucial nutrients involved in several cellular and physiological processes, including fertilization and early embryo development. In particular, Leucine and Arginine have been shown to stimulate implantation, as lack of both in a blastocyst culture system is able to induce a dormant state in embryos. The aim of this work was to evaluate the effects of Leucine and Arginine withdrawal on pluripotent mouse embryonic stem cell status, notably, their growth, self-renewal, as well as glycolytic and oxidative metabolism. Our results show that the absence of both Leucine and Arginine does not affect mouse embryonic stem cell pluripotency, while reducing cell proliferation through cell-cycle arrest. Importantly, these effects are not related to Leukemia Inhibitory Factor (LIF) and are reversible when both amino acids are reconstituted in the culture media. Moreover, a lack of these amino acids is related to a reduction in glycolytic and oxidative metabolism and decreased protein translation in mouse embryonic stem cells (mESCs), while maintaining their pluripotent status.
Rhombohedral/Cubic In2O3 Phase Junction Hybridized with Polymeric Carbon Nitride for Photodegradation of Organic Pollutants
Authors: Cai Xiaorong , Wang Yaning , Tang Shuting , Mo Liuye , Leng Zhe , Zang Yixian , Jing Fei , Zang Shaohong
Published: November 2022

In recent studies, phase junctions constructed as photocatalysts have been found to possess great prospects for organic degradation with visible light. In this study, we designed an elaborate rhombohedral corundum/cubic In2O3 phase junction (named MIO) combined with polymeric carbon nitride (PCN) via an in situ calcination method. The performance of the MIO/PCN composites was measured by photodegradation of Rhodamine B under LED light (λ = 420 nm) irradiation. The excellent performance of MIO/PCN could be attributed to the intimate interface contact between MIO and PCN, which provides a reliable charge transmission channel, thereby improving the separation efficiency of charge carriers. Photocatalytic degradation experiments with different quenchers were also executed. The results suggest that the superoxide anion radicals (O2−) and hydroxyl radicals (·OH) played the main roles in the reaction, as opposed to the other scavengers. Moreover, the stability of the MIO/PCN composites was particularly good in the four cycling photocatalytic reactions. This work illustrates that MOF-modified materials have great potential for solving environmental pollution without creating secondary pollution.
Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System
Authors: D’Oria Rossella , Genchi Valentina Annamaria , Caccioppoli Cristina , Calderoni Isabella , Marrano Nicola , Biondi Giuseppina , Borrelli Anna , Di Gioia Ludovico , Giorgino Francesco , Laviola Luigi
Published: November 2022

Obesity with its associated complications represents a social, economic and health problem of utmost importance worldwide. Specifically, obese patients carry a significantly higher risk of developing cardiovascular disease compared to nonobese individuals. Multiple molecular mechanisms contribute to the impaired biological activity of the distinct adipose tissue depots in obesity, including secretion of proinflammatory mediators and reactive oxygen species, ultimately leading to an unfavorable impact on the cardiovascular system. This review summarizes data relating to the contribution of the main adipose tissue depots, including both remote (i.e., intra-abdominal, hepatic, skeletal, pancreatic, renal, and mesenteric adipose fat), and cardiac (i.e., the epicardial fat) adipose locations, on the cardiovascular system. Finally, we discuss both pharmacological and non-pharmacological strategies aimed at reducing cardiovascular risk through acting on adipose tissues, with particular attention to the epicardial fat.
Isosorbide Fatty Acid Diesters Have Synergistic Anti-Inflammatory Effects in Cytokine-Induced Tissue Culture Models of Atopic Dermatitis
Authors: Swindell William R. , Bojanowski Krzysztof , Chaudhuri Ratan K.
Published: November 2022

Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory (IL1B, ITGA5) and neurogenic pruritus (TRPA1) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.
In Vitro Production of Galactooligosaccharides by a Novel β-Galactosidase of Lactobacillus bulgaricus
Authors: Arsov Alexander , Ivanov Ivan , Tsigoriyna Lidia , Petrov Kaloyan , Petrova Penka
Published: November 2022

β-galactosidase is an enzyme with dual activity and important industrial application. As a hydrolase, the enzyme eliminates lactose in milk, while as a trans-galactosidase it produces prebiotic galactooligosaccharides (GOS) with various degrees of polymerization (DP). The aim of the present study is the molecular characterization of β-galactosidase from a Bulgarian isolate, Lactobacillus delbrueckii subsp. bulgaricus 43. The sequencing of the β-gal gene showed that it encodes a new enzyme with 21 amino acid replacements compared to all other β-galactosidases of this species. The molecular model revealed that the new β-galactosidase acts as a tetramer. The amino acids D207, H386, N464, E465, Y510, E532, H535, W562, N593, and W980 form the catalytic center and interact with Mg2+ ions and substrate. The β-gal gene was cloned into a vector allowing heterologous expression of E. coli BL21(DE3) with high efficiency, as the crude enzyme reached 3015 U/mL of the culture or 2011 U/mg of protein. The enzyme’s temperature optimum at 55 °C, a pH optimum of 6.5, and a positive influence of Mg2+, Mn2+, and Ca2+ on its activity were observed. From lactose, β-Gal produced a large amount of GOS with DP3 containing β-(1→3) and β-(1→4) linkages, as the latter bond is particularly atypical for the L. bulgaricus enzymes. DP3-GOS formation was positively affected by high lactose concentrations. The process of lactose conversion was rapid, with a 34% yield of DP3-GOS in 6 h, and complete degradation of 200 g/L of lactose for 12 h. On the other hand, the enzyme was quite stable at 55 °C and retained about 20% of its activity after 24 h of incubation at this temperature. These properties expand our horizons as regards the use of β-galactosidases in industrial processes for the production of lactose-free milk and GOS-enriched foods.
Evaluation of the Wear-Resistant Plate Performance on Different Locations over the Flow Path of a Large-Sized Heavy-Duty Centrifugal Fan
Authors: Aldi Nicola , Casari Nicola , Pinelli Michele , Suman Alessio , Vulpio Alessandro , Mantovani Ottavio , Saccenti Paolo
Published: November 2022

In industrial applications such as chemical plants, cement factories, and glassmakers, large-sized centrifugal fans are commonly used for dust-laden flow processing. In many cases, the contamination is due to solid particles responsible for fouling and erosion issues. Erosion induces the reduction of mechanical resistance and, at the same time, the modification of the geometry and the surface characteristics of the internal flow path. The process works according to the characteristics of the erodent particles, such as dimension and hardness, which have to be coupled with the mechanical properties of the substrate, like hardness and roughness level. In addition to this, the intensity of the erosion depends on the dynamic characteristics of particles, especially velocity and impact angle. For these reasons, erosion-related issues are difficult predict and reduce. In an attempt to preserve the structural integrity of the internal walls, wear-resistant plates are positioned where the impacting contaminants are supposed to be more detrimental. In the present work, a combined experimental and numerical approach is proposed to evaluate the proper setup of wear-resistance plates over the flow path of a large-sized centrifugal fan. The results show how different regions (rotating and stationary walls) are subjected to different impact behavior, determining that the design of the position of the wear-resistant plate is not straightforward. Suggestions related to reducing the erosion intensity are reported, highlighting the possibility of designing the best compromise between erosion, performance, and costs.
Beyond the COVID-19 Pandemic: Can Online Teaching Reduce the Carbon Footprint of the Internationalisation of UK Higher Education?
Authors: Mustafa Asad , Psarikidou Katerina , Pranjol Md Zahidul Islam
Published: November 2022

The COVID-19 pandemic has been a learning curve for Higher Education Institutions (HEIs) in devising and delivering teaching online. This transition has enabled HEIs to continue teaching students, especially international students, who were restricted to travel to their countries of study. In the UK, approximately 20% of the student cohort are international students. The pandemic resulted in a drop in international student recruitment, which generated concerns about a potentially alarming economic crisis in the UK HE sector. However, COVID-19 measures have also been portrayed as a significant contributor to reducing global CO2 emissions. Thus, the question arises: can online teaching reduce the carbon footprint of the internationalisation of education? This paper reviews online teaching as a potential solution to reduce carbon footprint and increase access to HE, whilst maintaining high student performance in HE within the remits of internationalisation.
Determination of Shear Capacity for Load Rating of Concrete Bridges to AS 5100.7-2017
Authors: Wong Koon Wan , Vimonsatit Vanissorn
Published: November 2022

According to Modified Compression Field Theory (MCFT), the ultimate shear capacity of a reinforced concrete section depends on load effects (shear, moment, torsion, and axial force) caused by factored design loads. In many design standards, including Australian AS 5100.7, MCFT has been incorporated for bridge assessment, which requires a load rating to be carried out according to the loading of the nominated rating vehicle as prescribed in the standard. Recently, some approaches have been proposed for bridge load rating that have suggested using an iterative-search procedure to determine the shear capacity by proportionally increasing the load effects until the shear capacity and shear are equal. This paper describes several adverse effects of using the proportional load, which is not consistent with the characteristic of the vehicle loading, to determine the shear capacity for load rating. Numerical examples of two bridge beams, one simply supported and the other continuous, are presented to demonstrate that the characteristic of the load effects caused by a moving vehicle is not representable by proportional load effects. Furthermore, the current practice in the bridge load rating does not load rate the longitudinal steel capacity in resisting the axial force induced by the load effects of the rating vehicle. This paper presents a new approach to the load rating that separately accounts for the load effect for axial failure mode of the longitudinal steel. Finally, it is pointed out that locating the critical section where the rating factor is minimum is tedious but can be automated by integrating load rating into the analysis of load effects.
A Review of Environmental Protection and Sustainable Development in Madagascar
Authors: Harivelo Rakotoarimanana Zy Misa , Harifidy Rakotoarimanana Zy
Published: November 2022

Environmental protection is an important key to achieving sustainable development. Since humans depend on the environment in countless ways, preserving them contributes directly to the sustaining of people and human societies and hence, to social sustainability. The central question in this dissertation asks why the environmental protection policies enacted in Madagascar are not efficient and how they impact the SDG’s achievement at the national level. This paper discusses Madagascar’s achievements of the sustainable development target with special emphasis on environmental issues, which is currently a major concern in the country. This review aimed at suggesting improvements in line with the challenges the country is facing by reviewing the indicators provided by the UN SDGs. It also reaffirmed the nexus of poverty and the environment, which is important for setting the development target. In order to conduct this study, journal articles, review papers, working papers, research reports, and books related to environmental management and sustainable development in Madagascar were reviewed. Madagascar has made a little improvement in accomplishing SDGs 12 and 13 in 2021, but achieving all SDGs goals in 2030 remains a big challenge. The country is a party to numerous international environmental conventions, treaties, and agreements. Many policy changes have been implemented to address both conservation and development issues, but these efforts have had little impact. Forest fires and slash-and-burn were on the rise in Madagascar on October 2022, which poses a major concern for the economic and social development of the island. In order to achieve sustainable development, environmental protection shall constitute an integral part of the development process and cannot be considered in isolation from it. The strategies proposed in this paper might be helpful for the Malagasy government and private sector in decision-making. This paper is also useful for researchers in developing countries. As Madagascar did not reach the Millennium Development Goals 2015 and will not achieve the SDGs in 2030, should we not start learning from our mistakes and thinking about the post-SDGs?
Novel Insights into the Sinoatrial Node in Single-Cell RNA Sequencing: From Developmental Biology to Physiological Function
Authors: Fan Wei , Yang Chao , Hou Xiaojie , Wan Juyi , Liao Bin
Published: November 2022

Normal cardiac automaticity is dependent on the pacemaker cells of the sinoatrial node (SAN). Insufficient cardiac pacemaking leads to the development of sick sinus syndrome (SSS). Since currently available pharmaceutical drugs and implantable pacemakers are only partially effective in managing SSS, there is a critical need for developing targeted mechanism-based therapies to treat SSS. SAN-like pacemaker cells (SANLPCs) are difficult to regenerate in vivo or in vitro because the genes and signaling pathways that regulate SAN development and function have not been fully elucidated. The development of more effective treatments for SSS, including biological pacemakers, requires further understanding of these genes and signaling pathways. Compared with genetic models and bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) technology promises to advance our understanding of cellular phenotype heterogeneity and molecular regulation during SAN development. This review outlines the key transcriptional networks that control the structure, development, and function of the SAN, with particular attention to SAN markers and signaling pathways detected via scRNA-seq. This review offers insights into the process and transcriptional network of SAN morphogenesis at a single-cell level and discusses current challenges and potential future directions for generating SANLPCs for biological pacemakers.
Technical Complications of Coronary Bifurcation Percutaneous Interventions
Authors: Rigatelli Gianluca , Zuin Marco , Vassilev Dobrin , Rodino’ Giulio , Marchese Giuseppe , Pasquetto Giampaolo
Published: November 2022

Coronary bifurcation percutaneous interventions (PCI) comprise a challenging subset of patients with coronary artery disease. Beyond the well-known debate about single versus double stent strategies, which have different outcomes on mid- and long-term follow up, both strategies may be subject, although rarely, to several different technical complications, rarely reported in clinical trials, which need to be defined, classified, and understood by cardiovascular professionals involved in the management of patients with coronary bifurcation disease. The present paper aims to broaden the knowledge of the range of intraprocedural complications and relative treatment during PCI of coronary bifurcations.
COVID-19 Clinical Features and Outcomes in Elderly Patients during Six Pandemic Waves
Authors: Fericean Roxana Manuela , Rosca Ovidiu , Citu Cosmin , Manolescu Diana , Bloanca Vlad , Toma Ana-Olivia , Boeriu Estera , Dumitru Catalin , Ravulapalli Madhavi , Barbos Vlad , Oancea Cristian
Published: November 2022

Many elderly patients with severe SARS-CoV-2 infections and COVID-19 infections are admitted to intensive care units. Age was previously identified as an independent risk factor for death and contributed to the greater severity of COVID-19. The elderly may have diminished lung functions, poor reactions to artificial ventilation, and compromised immune systems. However, it is yet uncertain how each pandemic wave and the predominant SARS-CoV-2 strains contribute to varying results and how patient groups such as the elderly are impacted. Comparing six COVID-19 pandemic waves, the objective of this study was to examine the variation in case severity, symptomatology, ICU hospitalizations, and mortality among SARS-CoV-2-infected elderly individuals. The study followed a retrospective design, including 60 eligible patients older than 70 years in each of the six pandemic wave groups, after matching them by the number of comorbidities and gender. SARS-CoV-2 infection during the first, third, and fourth pandemic waves had a significantly higher risk of mortality for hospitalized patients. Confusion and dyspnea at admission were significant risk factors for ICU admission in elderly patients (β = 1.92, respectively β = 3.65). The laboratory parameters identified decreased lymphocytes (β = 2.11), elevated IL-6 (β = 1.96), and procalcitonin (β = 2.46) as the most significant risk factors. The third and fourth COVID-19 waves had considerably more severe infections (31.7% and 26.7%) than the sixth wave (13.3%). Median ICU stay and percentage of patients receiving oxygen support also differed across pandemic waves. However, mortality rates between the six pandemic waves were similar. The average length of hospitalization varied dramatically among the six pandemic waves. Although senior patients are more likely to have worse COVID-19 outcomes after hospitalization, this risk is mitigated by the greater prevalence of comorbidities and frailty among the elderly. The six pandemic waves that were specifically evaluated did not reveal considerably disproportionate variations in terms of patient mortality; however, during the fourth pandemic wave, there were likely more hospitalized patients with severe COVID-19 in Romania. It is probable that certain circulating SARS-CoV-2 strains were more infectious, resulting in an increase in infections and a strain on healthcare systems, which might explain the variations found in our research.
The Feasibility of Robot-Assisted Chin Osteotomy on Skull Models: Comparison with Surgical Guides Technique
Authors: Wu Jinyang , Hui Wenyu , Huang Jianhua , Luan Nan , Lin Yanping , Zhang Yong , Zhang Shilei
Published: November 2022

Surgical robotic technology is characterized by its high accuracy, good stability, and repeatability. The accuracy of mandibular osteotomy is important in tumor resection, function reconstruction, and abnormality correction. This study is designed to compare the operative accuracy between robot-assisted osteotomy and surgical guide technique in the skull model trials which simulated the genioplasty. In an experimental group, robot-assisted chin osteotomy was automatically performed in 12 models of 12 patients according to the preoperative virtual surgical planning (VSP). In a control group, with the assistance of a surgical guide, a surgeon performed the chin osteotomy in another 12 models of the same patients. All the mandibular osteotomies were successfully completed, and then the distance error and direction error of the osteotomy plane were measured and analyzed. The overall distance errors of the osteotomy plane were 1.57 ± 0.26 mm in the experimental group and 1.55 ± 0.23 mm in the control group, and the direction errors were 7.99 ± 1.10° in the experimental group and 8.61 ± 1.05° in the control group. The Bland–Altman analysis results revealed that the distance error of 91.7% (11/12) and the direction error of 100% (12/12) of the osteotomy plane were within the 95% limits of agreement, suggesting the consistency of differences in the osteotomy planes between the two groups. Robot-assisted chin osteotomy is a feasible auxiliary technology and achieves the accuracy level of surgical guide-assisted manual operation.
Balancing in Unicompartmental Knee Arthroplasty: Balancing in Flexion or in Extension?
Authors: D’Ambrosi Riccardo , Vaishya Raju , Verde Francesco
Published: November 2022

Unicompartmental knee arthroplasty (UKA) is an established procedure for the treatment of predominant single compartmental femorotibial osteoarthritis (OA) or osteonecrosis [...]
The Effect of Aerobic Exercise and Low-Impact Pilates Workout on the Adaptive Immune System
Authors: Balogh László , Szabó Krisztina , Pucsok József Márton , Jámbor Ilona , Gyetvai Ágnes , Mile Marianna , Barna Lilla , Szodoray Peter , Tarr Tünde , Csiki Zoltán , Papp Gábor
Published: November 2022

Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, especially on the level of adaptive immune system. Our study aimed to investigate and compare the changes in a broad spectrum of lymphocyte subtypes after 14 weeks of aerobic-type total-body-shaping workouts (TBSW) and Pilates workouts (PW) among healthy individuals. We determined the percentages of peripheral natural killer cells and different T and B lymphocyte subtypes with flow cytometry. At the end of the exercise program, significant changes in naïve and memory lymphocyte ratios were observed in TBSW group. Percentages of naïve cytotoxic T (Tc) cells elevated, frequencies of memory Tc and T-helper cell subsets decreased, and distribution of naïve and memory B cells rearranged. Proportions of activated T cells also showed significant changes. Nonetheless, percentages of anti-inflammatory interleukin (IL)-10-producing regulatory type 1 cells and immunosuppressive CD4+CD127lo/−CD25bright T regulative cells decreased not only after TBSW but also after PW. Although weekly performed aerobic workouts may have a more pronounced impact on the adaptive immune system than low-impact exercises, both still affect immune regulation in healthy individuals.
Pumpless Extracorporeal Hemadsorption Technique (pEHAT): A Proof-of-Concept Animal Study
Authors: Fiedler Mascha O. , Muellenbach Ralf M. , Rolfes Caroline , Lotz Christopher , Nickel Felix , Müller-Stich Beat P. , Supady Alexander , Lepper Philipp M. , Weigand Markus A. , Meybohm Patrick , Kalenka Armin , Reyher Christian
Published: November 2022

Background: Extracorporeal hemadsorption eliminates proinflammatory mediators in critically ill patients with hyperinflammation. The use of a pumpless extracorporeal hemadsorption technique allows its early usage prior to organ failure and the need for an additional medical device. In our animal model, we investigated the feasibility of pumpless extracorporeal hemadsorption over a wide range of mean arterial pressures (MAP). Methods: An arteriovenous shunt between the femoral artery and femoral vein was established in eight pigs. The hemadsorption devices were inserted into the shunt circulation; four pigs received CytoSorb® and four Oxiris® hemadsorbers. Extracorporeal blood flow was measured in a range between mean arterial pressures of 45–85 mmHg. Mean arterial pressures were preset using intravenous infusions of noradrenaline, urapidil, or increased sedatives. Results: Extracorporeal blood flows remained well above the minimum flows recommended by the manufacturers throughout all MAP steps for both devices. Linear regression resulted in CytoSorb® blood flow [mL/min] = 4.226 × MAP [mmHg] − 3.496 (R-square 0.8133) and Oxiris® blood flow [mL/min] = 3.267 × MAP [mmHg] + 57.63 (R-square 0.8708), respectively. Conclusion: Arteriovenous pumpless extracorporeal hemadsorption resulted in sufficient blood flows through both the CytoSorb® and Oxiris® devices over a wide range of mean arterial blood pressures and is likely an intriguing therapeutic option in the early phase of septic shock or hyperinflammatory syndromes.
The GluA1-Related BDNF Pathway Is Involved in PTSD-Induced Cognitive Flexibility Deficit in Attentional Set-Shifting Tasks of Rats
Authors: Sun Jiaming , Jia Keli , Sun Mingtao , Zhang Xianqiang , Chen Jinhong , Zhu Guohui , Li Changjiang , Lian Bo , Du Zhongde , Sun Hongwei , Sun Lin
Published: November 2022

Background: Post-Traumatic Stress Disorder (PTSD) is a severe psychological disorder characterized by intrusive thoughts, heightened arousal, avoidance, and flashbacks. Cognitive flexibility dysfunction has been linked with the emergence of PTSD, including response inhibition deficits and impaired attentional switching, which results in difficulties for PTSD patients when disengaging attention from trauma-related stimuli. However, the molecular mechanisms of cognitive flexibility deficits remain unclear. Methods: The animals were exposed to a single prolonged stress and electric foot shock (SPS&S) procedure to induce PTSD-like features. Once the model was established, the changes in cognitive flexibility were assessed using an attentional set-shifting task (ASST) in order to investigate the effects of traumatic stress on cognitive flexibility. Additionally, the molecular alterations of certain proteins (AMPA Receptor 1 (GluA1), brain-derived neurotrophic factor (BDNF), and Postsynaptic density protein 95 (PSD95) in the medial prefrontal cortex (mPFC) were measured using Western blot and immunofluorescence. Results: The SPS&S model exhibited PTSD-like behaviors and induced reversal learning and set-shifting ability deficit in the ASST. These behavioral changes are accompanied by decreased GluA1, BDNF, and PSD95 protein expression in the mPFC. Further analysis showed a correlative relationship between the behavioral and molecular alterations. Conclusions: The SPS&S model induced cognitive flexibility deficits, and the potential underlying mechanism could be mediated by GluA1-related BDNF signaling in the mPFC.
Artificial Intelligence in Dermatology Image Analysis: Current Developments and Future Trends
Authors: Li Zhouxiao , Koban Konstantin Christoph , Schenck Thilo Ludwig , Giunta Riccardo Enzo , Li Qingfeng , Sun Yangbai
Published: November 2022

Background: Thanks to the rapid development of computer-based systems and deep-learning-based algorithms, artificial intelligence (AI) has long been integrated into the healthcare field. AI is also particularly helpful in image recognition, surgical assistance and basic research. Due to the unique nature of dermatology, AI-aided dermatological diagnosis based on image recognition has become a modern focus and future trend. Key scientific concepts of review: The use of 3D imaging systems allows clinicians to screen and label skin pigmented lesions and distributed disorders, which can provide an objective assessment and image documentation of lesion sites. Dermatoscopes combined with intelligent software help the dermatologist to easily correlate each close-up image with the corresponding marked lesion in the 3D body map. In addition, AI in the field of prosthetics can assist in the rehabilitation of patients and help to restore limb function after amputation in patients with skin tumors. The aim of the study: For the benefit of patients, dermatologists have an obligation to explore the opportunities, risks and limitations of AI applications. This study focuses on the application of emerging AI in dermatology to aid clinical diagnosis and treatment, analyzes the current state of the field and summarizes its future trends and prospects so as to help dermatologists realize the impact of new technological innovations on traditional practices so that they can embrace and use AI-based medical approaches more quickly.
Perinatal Cerebral Ischemic Lesion and SARS-CoV-2 Infection during Pregnancy: A Case Report and a Review of the Literature
Authors: Brogna Claudia , Brogna Barbara , De Biase Margherita , Sini Francesca , Mirra Federica , Moro Marianna , Romeo Domenico M.
Published: November 2022

Perinatal stroke is related to possible differences in predisposing factors and outcomes between acutely and retrospectively diagnosed cases. In most cases, there are different risk factors and infections that could play an important role. Thus far, different clinical manifestations have been reported in children presenting with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from asymptomatic status to severe disease sustained by an immune-mediated inflammatory response. SARS-CoV-2 has been associated with severe neurological diseases including seizures and encephalitis in both adults and children. However, there are still few reports regarding the possible relation between SARS-CoV-2 infection of mothers during pregnancy and the neurologic outcome of the newborns. We described the case of a newborn diagnosed with a perinatal stroke, born at 35 weeks of gestation from a mother presenting with SARS- CoV-2 infection during the last months of pregnancy. We also added a brief review of the literature with similar cases. Close monitoring and early intervention in young children born to infected mothers would be highly recommended for the potential neurodevelopmental risk.
Minimally Invasive Glaucoma Surgery: Safety of Individual Devices
Authors: Rowson Antonia C. , Hogarty Daniel T. , Maher Dominic , Liu Lei
Published: November 2022

Primary open-angle glaucoma progression in those already on maximal medical therapy has traditionally been treated with trabeculectomy, a surgical procedure that carries a high degree of morbidity. In the last few decades, significant advances have been made in the field of minimally invasive glaucoma surgery (MIGS) devices, which aim to defer or prevent trabeculectomy via less arduous surgical techniques in certain types of glaucoma. Although reviews have been published examining the efficacy of various MIGS techniques, no article synthesises the comparative safety of all available devices. We performed a literature review examining the safety of MIGS devices. Fifteen devices were included, variously attempting to increase aqueous outflow through the trabecular meshwork or the suprachoroidal space, shunting into the subconjunctival space, or reducing aqueous production through ciliary body ablation. Notably, the earliest product attempting to increase outflow to the suprachoroidal space, Alcon’s CyPass Micro-Stent, was withdrawn from the market due to concerns regarding increased corneal endothelial cell loss at five years post-implantation. All other devices were described as well-tolerated, with the most common adverse effects including hyphaema, intraocular pressure spikes, and device migration or obstruction. MIGS devices are purported to be uniformly safe, and many studies report no statistically significant increased complications beyond those associated with cataract surgery alone. It is important to note, however, the generally poor quality of current studies, with a dearth of randomised, or even prospective, data, and a large proportion of studies funded by device producers.
The Learning Curve for Hand-Assisted Laparoscopic Total Gastrectomy in Gastric Cancer Patients
Authors: Seika Philippa , Biebl Matthias , Raakow Jonas , Kröll Dino , Çetinkaya-Hosgör Candan , Thuss-Patience Peter , Maurer Max , Dobrindt Eva , Pratschke Johann , Denecke Christian
Published: November 2022

(1) Background: Hand-assisted laparoscopic total gastrectomy (LTG) for patients with gastric cancer (GC) has been established as the standard surgical treatment at our center. This study aims to quantify the learning curve for surgeons performing minimally invasive total gastrectomy at a high-volume single center. (2) Methods: One hundred and eighteen consecutive patients who underwent minimally invasive total gastrectomy between January 2014 and December 2020 at a single high-volume center were included and reviewed retrospectively. Risk-adjusted cumulative sum analysis (RA-CUSUM) was used to monitor the surgical outcomes for patients with different risks of postoperative mortality using varying-coefficient logistic regression models. Patients were ordered by the sequential number of the procedure performed and divided into two groups according to the degree of surgeon proficiency as determined by RA-CUSUM analysis (group A: 45; group B: 73 patients). Age, gender, body mass index (BMI), tumor location, pathology, and comorbidities were compared while primary endpoints comprised surgical parameters, postoperative course, and survival outcomes. (3) Results: Forty-four cases were required for the completion of the learning curve. During this time, the mean operating time decreased. Hand-assisted laparoscopic total gastrectomy performed after a learning curve was associated with a shorter median operating time (OT) (360 min vs. 289 min, <0.001), and a reduced length of stay (A = 18.0 vs. B = 14.0 days) (p = 0.154), while there was a trend toward less major complications (Clavien–Dindo (CD) 3–5 within 90 days (12 (26.67%) vs. 10 (13.70%) p = 0.079). Our results showed no difference in anastomotic leakage between the two groups (group A vs. group B, 3 (6.67%) vs. 4 (5.48%) p = 0.99). Similarly, 30-day (0 (0%) vs. 1 (1.7%), p = 0.365) and 90-day mortality (1 (2.08%) vs. 2 (3.39%), p = 0.684) were comparable. Following multivariate analysis, the level of surgical proficiency was not a significant prognostic factor for overall survival. (4) Conclusions: A minimum of 44 cases are required for experienced laparoscopic surgeons to achieve technical competence for performing LTG. While operation time decreased after completion of the learning curve, quality criteria such as achievement of R0 resection, anastomotic leakage, and perioperative mortality remained unaltered. Of note, the level of surgical training showed no significant impact on the 2 year OS or DFS.