bluuebunny/crossref_metadata_2025 huggingface dataset:
Stabilized Electrospun Polyacrylonitrile Fibers for Advancements in Clean Air Technology
Authors: Beckman Ivan P. , Berry Gentry , Ucak-Astarlioglu Mine , Thornell Travis L. , Cho Heejin , Riveros Guillermo
Published: March 2023

Particulate matter air pollution and volatile organic compounds released into the air from the incomplete combustion of fossil fuels and wildfires creates significant damage to human health and the environment. Advances in air filtration and purification technology are needed to mitigate aerosol hazards. This article details an effort to explore the potential benefits of new materials and methods for the production of nonwoven air filtration media through electrospinning and stabilizing polyacrylonitrile fibers. The investigated production methods include electrospinning fibrous matting onto a stainless steel wire mesh and stabilizing the nonwoven media in a chamber furnace. The media is then tested for air filtration penetration and airflow resistance, and the fiber size distribution is measured using scanning electron microscopy. The experimental results show that the electrospun media approaches the performance criteria for airflow resistance and particle capture efficiency of high-efficiency particulate air (HEPA) filter media. Furthermore, performance estimations for electrospun media of increased thickness and for a decreased filtration velocity show potential to exceed the HEPA media resistance and efficiency criteria. Thus, it is suggested that electrospun and stabilized nonwoven fibrous media are candidates as alternatives to traditionally manufactured HEPA media and may potentially benefit modern air filtration technology and reduce hazards associated with particulate matter. Additionally, the authors recommend future exploration into the carbonization and activation of electrospun filter media for the adsorption and mitigation of volatile organic compounds as a secondary benefit, while maintaining high efficiency and low airflow resistance in the removal of particulate matter from aerosol streams.
Werner Eissner (1930–2022): A Pioneer in Computational Atomic Physics
Authors: Bhatia Anand K. , Lynas-Gray Anthony E. , Mendoza Claudio , Nahar Sultana , Nussbaumer Harry , Pradhan Anil K. , Seaton Anthony M. , Wunner Günter , Zeippen Claude J.
Published: March 2023

Werner Eissner (Figure 1), a pioneer in computational atomic physics, was born on 16 October 1930 in the city of Görlitz, Germany, to Bernhard and Frieda (née Eckert) Eissner [...]
A Bi-Level Vaccination Points Location Problem That Aims at Social Distancing and Equity for the Inhabitants
Authors: Salinas Edith , Camacho-Vallejo José-Fernando , Nucamendi-Guillén Samuel
Published: March 2023

Designing efficient vaccination programs that consider the needs of the population is very relevant to prevent reoccurrence of the COVID-19 pandemic. The government needs to provide vaccination points to give out vaccine doses to the population. In this paper, the authors analyze the location of vaccination points whilst addressing the inhabitants’ preferences. Two objectives that prevent crowding of inhabitants are considered. The government aims for the minimum distance between located vaccination points is maximized, and for the number of inhabitants that attend the different vaccination points to be equitable. One of the key aspects of this problem is the assumption that inhabitants freely choose the located vaccination point to go. That decision affects the objectives of the government, since crowding at vaccination points may appear due to the inhabitants’ decisions. This problem is modeled as a bi-objective, bi-level program, in which the upper level is associated to the government and the lower level to the inhabitants. To approximate the Pareto front of this problem, a cross-entropy metaheuristic is proposed. The algorithm incorporates criteria to handle two objective functions in a simultaneous manner, and optimally solve the lower-level problem for each government decision. The proposed algorithm is tested over an adapted set of benchmark instances and pertinent analysis of the results is included. An important managerial insight is that locating far vaccination points does not lead us to a more equitable allocation of inhabitants.
Implementing Binder Gradients in Thick Water-Based NMC811 Cathodes via Multi-Layer Coating
Authors: Neidhart Lukas , Fröhlich Katja , Winter Franz , Jahn Marcus
Published: March 2023

Multi-layer coating of electrodes with different material compositions helps unlock the full potential of high-loaded electrodes. Within this work, LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes with an areal capacity of >8.5 mA h cm−2 and tuned binder concentrations were fabricated by using an industrially relevant roll-to-roll process. Rate capability tests revealed an increase in practical specific discharge capacity independent from the C-rate for cathodes with reduced binder concentration in the top layer. At high current densities (C-rate of 1C) an improved performance of up to 27% was achieved. Additionally, at lower C-rates, binder gradients perpendicular to the current collector have beneficial effects on thick electrodes. However, surface analysis and electrochemical impedance spectroscopy revealed that without an adequate connection between the active material particles through a carbon-binder domain, charge transfer resistance limits cycling performance at high current densities.
Strontium Ranelate Inhibits Osteoclastogenesis through NF-κB-Pathway-Dependent Autophagy
Authors: Wu Dongle , Sun Xuan , Zhao Yiwei , Liu Yuanbo , Gan Ziqi , Zhang Zhen , Chen Xin , Cao Yang
Published: March 2023

Strontium ranelate (SR) is a pharmaceutical agent used for the prevention and treatment of osteoporosis and fragility fracture. However, little attention has been paid to the effect of SR on alveolar bone remodeling during orthodontic tooth movement and its underlying mechanism. Here, we investigated the influence of SR on orthodontic tooth movement and tooth resorption in Sprague–Dawley rats and the relationship between the nuclear factor–kappa B (NF-κB) pathway, autophagy, and osteoclastogenesis after the administration of SR in vitro and in vivo. In this study, it was found that SR reduced the expression of autophagy-related proteins at the pressure side of the first molars during orthodontic tooth movement. Similarly, the expression of these autophagy-related proteins and the size and number of autophagosomes were downregulated by SR in vitro. The results also showed that SR reduced the number of osteoclasts and suppressed orthodontic tooth movement and root resorption in rats, which could be partially restored using rapamycin, an autophagy inducer. Autophagy was attenuated after pre-osteoclasts were treated with Bay 11-7082, an NF-κB pathway inhibitor, while SR reduced the expression of the proteins central to the NF-κB pathway. Collectively, this study revealed that SR might suppress osteoclastogenesis through NF-κB-pathway-dependent autophagy, resulting in the inhibition of orthodontic tooth movement and root resorption in rats, which might offer a new insight into the treatment of malocclusion and bone metabolic diseases.
Integrated Thermofluid Lumped Parameter Model for Analyzing Hemodynamics in Human Fatigue State
Authors: Ding Xiaoling , He Ying , Chen Youqiang , Wang Yueping , Long Lili
Published: March 2023

It is well known that driving while fatigued is dangerous and can lead to serious traffic accidents. However, there is a lack of studies on the mechanism of fatigue. This paper sought to infer changes in the cardiovascular system through hand and head skin temperature peripheral factors via an integrated lumped parameter model. A multi-layer inner structure with variable blood perfusion was used to construct a full-body thermal model. The cardiovascular system model provided blood perfusion using lumped parameters. The peripheral resistance and heart rate in the cardiovascular system model were adjusted to match the experimental temperatures of the head and hands obtained from induced fatigue experiments. The simulation results showed that the heart rate and blood pressure decreased, and the peripheral skin resistance of the hands and head increased after fatigue. A decrease in heart rate and an increase in peripheral resistance affect the magnitude of blood flow to the periphery of the body, leading to a decrease in skin temperature during fatigue. The present integrated model elucidates a key effect of human fatigue on the cardiovascular system, which is expected to help improve the accuracy of fatigue monitoring systems.
In Vitro Antibody Quantification with Hyperspectral Imaging in a Large Field of View for Clinical Applications
Authors: De Landro Martina , Cinelli Lorenzo , Marchese Nicola , Spano Giulia , Barberio Manuel , Vincent Cindy , Marescaux Jacques , Mutter Didier , De Mathelin Michel , Gioux Sylvain , Felli Eric , Saccomandi Paola , Diana Michele
Published: March 2023

Hyperspectral imaging (HSI) is a non-invasive, contrast-free optical-based tool that has recently been applied in medical and basic research fields. The opportunity to use HSI to identify exogenous tumor markers in a large field of view (LFOV) could increase precision in oncological diagnosis and surgical treatment. In this study, the anti-high mobility group B1 (HMGB1) labeled with Alexa fluorophore (647 nm) was used as the target molecule. This is the proof-of-concept of HSI’s ability to quantify antibodies via an in vitro setting. A first test was performed to understand whether the relative absorbance provided by the HSI camera was dependent on volume at a 1:1 concentration. A serial dilution of 1:1, 10, 100, 1000, and 10,000 with phosphatase-buffered saline (PBS) was then used to test the sensitivity of the camera at the minimum and maximum volumes. For the analysis, images at 640 nm were extracted from the hypercubes according to peak signals matching the specificities of the antibody manufacturer. The results showed a positive correlation between relative absorbance and volume (r = 0.9709, p = 0.0013). The correlation between concentration and relative absorbance at min (1 µL) and max (20 µL) volume showed r = 0.9925, p < 0.0001, and r = 0.9992, p < 0.0001, respectively. These results demonstrate the HSI potential in quantifying HMGB1, hence deserving further studies in ex vivo and in vivo settings.
miR-4432 Targets FGFBP1 in Human Endothelial Cells
Authors: Avvisato Roberta , Mone Pasquale , Jankauskas Stanislovas S. , Varzideh Fahimeh , Kansakar Urna , Gambardella Jessica , De Luca Antonio , Matarese Alessandro , Santulli Gaetano
Published: March 2023

MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of several target genes. Fibroblast growth factor binding protein 1 (FGFBP1) has been associated with endothelial dysfunction at the level of the blood–brain barrier (BBB). However, the underlying mechanisms are mostly unknown and there are no studies investigating the relationship between miRs and FGFBP1. Thus, the overarching aim of the present study was to identify and validate which miR can specifically target FGFBP1 in human brain microvascular endothelial cells, which represent the best in vitro model of the BBB. We were able to identify and validate miR-4432 as a fundamental modulator of FGFBP1 and we demonstrated that miR-4432 significantly reduces mitochondrial oxidative stress, a well-established pathophysiological hallmark of hypertension.
Lipidomic Analysis of Liver Lipid Droplets after Chronic Alcohol Consumption with and without Betaine Supplementation
Authors: Arumugam Madan Kumar , Perumal Sathish Kumar , Rasineni Karuna , Donohue Terrence M. , Osna Natalia A. , Kharbanda Kusum K.
Published: March 2023

The earliest manifestation of alcohol-associated liver disease is hepatic steatosis, which is characterized by fat accumulation in specialized organelles called lipid droplets (LDs). Our previous studies reported that alcohol consumption elevates the numbers and sizes of LDs in hepatocytes, which is attenuated by simultaneous treatment with the methyl group donor, betaine. Here, we examined changes in the hepatic lipidome with respect to LD size and dynamics in male Wistar rats fed for 6 weeks with control or ethanol-containing liquid diets that were supplemented with or without 10 mg betaine/mL. At the time of sacrifice, three hepatic LD fractions, LD1 (large droplets), LD2 (medium-sized droplets), and LD3 (small droplets) were isolated from each rat. Untargeted lipidomic analyses revealed that each LD fraction of ethanol-fed rats had higher phospholipids, cholesteryl esters, diacylglycerols, ceramides, and hexosylceramides compared with the corresponding fractions of pair-fed controls. Interestingly, the ratio of phosphatidylcholine to phosphatidylethanolamine (the two most abundant phospholipids on the LD surface) was lower in LD1 fraction compared with LD3 fraction, irrespective of treatment; however, this ratio was significantly lower in ethanol LD fractions compared with their respective control fractions. Betaine supplementation significantly attenuated the ethanol-induced lipidomic changes. These were mainly associated with the regulation of LD surface phospholipids, ceramides, and glycerolipid metabolism in different-sized LD fractions. In conclusion, our results show that ethanol-induced changes in the hepatic LD lipidome likely stabilizes larger-sized LDs during steatosis development. Furthermore, betaine supplementation could effectively reduce the size and dynamics of LDs to attenuate alcohol-associated hepatic steatosis.
Effect of Ouabain on Glutamate Transport in the Hippocampus of Rats with LPS-Induced Neuroinflammation
Authors: Garcia Israel José Pereira , Kinoshita Paula Fernanda , Valadares Jéssica Martins de Moura , Carvalho Luciana Estefani Drumond de , Cortes Vanessa Faria , Barbosa Leandro Augusto , Scavone Cristoforo , Santos Hérica de Lima
Published: March 2023

A lipopolysaccharide (LPS)-induced neuroinflammation rat model was used to study the effects of ouabain (OUA) at low concentrations, which can interact with the Na,K-ATPase, causing the modulation of intracellular signalling pathways in the Central Nervous System. Our study aimed to analyse the effects of OUA on glutamate transport in the hippocampus of rats with LPS-induced neuroinflammation. Adult male Wistar rats were divided into four groups: OUA (1.8 µg/kg), saline (CTR), LPS (200 µg/kg), and OUA + LPS (OUA 20 min before LPS). The animals were sacrificed after 2 h, and the hippocampus was collected for analysis. After treatment, we determined the activities of Na,K-ATPase and glutamine synthetase (GS). In addition, expression of the α1, α2, and α3 isoforms of Na,K-ATPase and the glutamate transporters, EAAT1 and EAAT2, were also analysed. Treatment with OUA caused a specific increase in the α2 isoform expression (~20%), whereas LPS decreased its expression (~22%), and treatment with OUA before LPS prevented the effects of LPS. Moreover, LPS caused a decrease of approximately 50% in GS activity compared with that in the CTR group; however, OUA pre-treatment attenuated this effect of LPS. Notably, it was found that treatment with OUA caused an increase in the expression of EAAT1 (~30%) and EAAT2 (~25%), whereas LPS caused a decrease in the expression of EAAT1 (~23%) and EAAT2 (~25%) compared with that in the CTR group. When treated with OUA, the effects of LPS were abrogated. In conclusion, the OUA pre-treatment abolished the effect caused by LPS, suggesting that this finding may be related to the restoration of the interaction between FXYD2 and the studied membrane proteins.
Combination of Hepatitis B Virus Pre-S2 Gene Deletion Mutation and Tumor-Node-Metastasis Stage Predicts Higher Hepatocellular Carcinoma Recurrence after Curative Surgical Resection
Authors: Jeng Long-Bin , Li Tsai-Chung , Chan Wen-Ling , Teng Chiao-Fang
Published: March 2023

Hepatocellular carcinoma (HCC) is one of the most frequent and life-threatening human cancers worldwide. Despite curative resection surgery, the high recurrence rate of HCC leads to poor patient survival. Chronic hepatitis B virus (HBV) infection is a major etiological factor for HCC. HBV pre-S2 gene deletion mutation leads to the expression of an important oncoprotein called a pre-S2 mutant. It represents an independent prognostic biomarker for HCC recurrence. This study aimed to identify other independent prognostic biomarkers from clinicopathological characteristics of 75 HBV-related HCC patients receiving resection surgery and to validate their potential to be combined with pre-S2 gene deletion mutation as a combination biomarker for HCC recurrence. Patients with both the presence of pre-S2 gene deletion mutation and tumor-node-metastasis (TNM) stage IIIA–IIIC had a higher HCC recurrence risk than patients with either one or none of these two factors. Moreover, the combination of pre-S2 gene deletion mutation and TNM stage exhibited better performance than either of these two factors alone in discriminating patients from patients without HCC recurrence. Collectively, this study proposed that the TNM stage held significance as a combination biomarker with pre-S2 gene deletion mutation with a greater performance in predicting HCC recurrence after curative surgical resection.
Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review
Authors: Niculae Cristian-Mihail , Hristea Adriana , Moroti Ruxandra
Published: March 2023

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed of white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells, and platelets. Immune cells, cytokines, chemokines, and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate proinflammatory and procoagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation–endotheliopathy–thrombosis axis, contributing to SARS-CoV-2-associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism with chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalized patients with severe disease that would target the crossroads of inflammatory and coagulation pathways.
Evaluation of Specific Cellular and Humoral Immune Response to Toxoplasma gondii in Patients with Autoimmune Rheumatic Diseases Immunomodulated Due to the Use of TNF Blockers
Authors: Andrade Cristhianne Molinero Ratkevicius , de Lima Marques Aline Caroline , Timóteo Rodolfo Pessato , de Morais Oliveira-Scussel Ana Carolina , De Vito Fernanda Bernadelli , da Silva Marcos Vinícius , Mineo José Roberto , Teodoro Reginaldo Botelho , Rodrigues Denise Bertulucci Rocha , Júnior Virmondes Rodrigues
Published: March 2023

(1) Background: TNF antagonists have been used to treat autoimmune diseases (AD). However, during the chronic phase of toxoplasmosis, TNF-α and TNFR play a significant role in maintaining disease resistance and latency. Several studies have demonstrated the risk of latent infections’ reactivation in patients infected with toxoplasmosis. Our objective was to verify whether patients with autoimmune rheumatic diseases, who use TNF antagonists and/or synthetic drugs and had previous contact with Toxoplasma gondii (IgG+), present any indication of an increased risk of toxoplasmosis reactivation. (2) Methods: Blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were evaluated after stimulation with antigens of Toxoplasma gondii, with anti-CD3/anti-CD28 or without stimulus, at 48 and 96 h. CD69+, CD28+, and PD-1 stains were evaluated, in addition to intracellular expression of IFN-γ, IL-17, and IL-10 by CD4+ and the presence of regulatory CD4+ T cells by labeling CD25+, FOXP3, and LAP. The cytokines IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 were measured in the culture supernatant after 96 h. Serology for IgG and IgG1 was evaluated. (3) Results: There were no differences in the levels of IgG and IgG1 between the groups, but the IgG1 avidity was reduced in the immunobiological group compared to the control group. All groups exhibited a significant correlation between IgG and IgG1 positivity. CD4+ T lymphocytes expressing PD-1 were increased in individuals suffering from autoimmune rheumatic diseases and using disease-modifying antirheumatic drugs. In addition, treatment with TNF blockers did not seem to influence the populations of regulatory T cells and did not interfere with the expression of the cytokines IFN-γ, IL-17, and IL-10 by CD4+ cells or the production of cytokines by PBMCs from patients with AD. (4) Conclusions: This study presents evidence that the use of TNF-α blockers did not promote an immunological imbalance to the extent of impairing the anti-Toxoplasma gondii immune response and predisposing to toxoplasmosis reactivation.
Remotely Programmable Deep Brain Stimulator Combined with an Invasive Blood Pressure Monitoring System for a Non-Tethered Rat Model in Hypertension Research
Authors: Chomanskis Žilvinas , Jonkus Vytautas , Danielius Tadas , Paulauskas Tomas , Orvydaitė Monika , Melaika Kazimieras , Rukšėnas Osvaldas , Hendrixson Vaiva , Ročka Saulius
Published: March 2023

The control circuits of blood pressure have a strong neural regulatory element important in the pathogenesis of essential drug-resistant hypertension. Targeting lower medullary neural control mechanisms of blood pressure by electrical stimulation could be beneficial, and therefore, a novel device is needed. This paper presents a remotely programmable deep brain stimulator with an invasive continuous blood pressure monitoring system in a non-tethered rat model. The device is designed for lower medullary deep brain stimulation research with minimal interference to a daily animal routine. Electrodes were implanted in the caudal ventrolateral medulla. Animal survivability, catheter patency rates, and device data drift were evaluated. Eight out of ten rats survived the surgery and testing period with no or mild temporary neurological compromise. The study revealed that carotid catheters filled with heparinized glycerol ensure better catheter patency rates and blood pressure transduction. There was no significant drift in the device’s pressure sensitivity during the experiment. To our knowledge, this is the first experimental study to show considerable animal survival after lower medullary implantation. Combining the ability to measure and monitor invasive blood pressure with a closed-loop brain pulse generator in a single device could be of potential value in future hemodynamic animal research.
Heterogeneity Influence of Financial Digitalization and Inclusion on Employees’ Psychological States
Authors: Lu Yue , Zhang Zuoqian , Yang Siying
Published: March 2023

Digital inclusive finance (DIF) has the power to spawn a new system of Internet finance and realize financial inclusion. However, the role of DIF in improving the health status of individuals is largely unknown. This study aims to demonstrate whether and how the development of DIF impacts the mental health of Chinese employees. This paper performs an empirical study based on the city-level data of the digital inclusive financial index with the China family panel studies. Ordinary least squares (OLS), probit models and mediation techniques are employed with appropriate instruments to alleviate endogeneity concerns. The results show that DIF can help employees improve their mental health. The results were robust to a variety of checks. Moreover, increasing income is the main pathway in which DIF improves individual mental health. Finally, it also reveals the heterogeneous effects of DIF on individual mental health. That is, the use depth of DIF has a significant positive effect on mental health status, but not on other sub-indicators, such as coverage breadth and degree of digital service provision; on those vulnerable groups containing females and employees with low education, its decisive role is larger than their counterparts who are males and have high levels of education. These results highlight the vital role of DIF in improving the mental health status of individuals. Consequently, there is a need to strengthen the construction of financial infrastructure and achieve a deeper integration of the financial system with digital technologies.
An Integrated Model of Destination Attractiveness and Tourists’ Environmentally Responsible Behavior: The Mediating Effect of Place Attachment
Authors: Li Ting , Liao Chenmei , Law Rob , Zhang Mu
Published: March 2023

This study aimed to empirically explore the relationship between destination attractiveness and tourists’ environmentally responsible behavior (TERB), as based on self-regulated attitude theory. In this paper, we have divided destination attractiveness into two aspects: the attractiveness of a facility’s services, and that of the sightseeing experience, so as to build a structural equation model with mediation analysis. For our research, we selected Wolong National Nature Reserve in Sichuan as the site of our case study, and we conducted a survey using a questionnaire. We then analyzed the path using a structural equation model. Our results show: (1) two elements of destination attractiveness have significantly positive effects on TERB; and (2) place attachment exerts a mediating effect among the attractiveness of the facility’s services, that of the sightseeing experience, and TERB. Therefore, enhancing destination attractiveness and tourists’ emotional attachments to locations could help to promote the implementation of TERB and the achievement of sustainable tourism development.
Service Life Prediction of Painted Renderings Using Maintenance Data through Regression Techniques
Authors: Petersen André , Silva Ana , González Marco
Published: March 2023

The increase in rehabilitation actions motivated further research in the scope of service life and/or building maintenance. In defining rational strategies for the buildings’ maintenance, reliable tools that model their performance over time are needed. This research evaluates the impact of maintenance actions on painted renderings. More specifically, the objective of this research is to adapt and extend an existing method, evaluating new periods of service life, with and without maintenance actions, in order to be able to regionalize and expand the existing results. This research was carried out based on an extensive fieldwork survey of painted renderings of facades in vertical buildings in the city of Porto Alegre, RS, Brazil, at different times (before, during and after the execution of maintenance actions). For renderings without maintenance actions, an average service life of 14 years is obtained. After maintenance actions, especially cleaning, the estimated average service life is 16 years. After maintenance, cleaning and partial repair actions, the estimated average service life is 34 years. For painted surfaces without maintenance actions, an average service life of 10 years is estimated. After cleaning actions, the estimated average service life is 11 years. After maintenance (cleaning, partial repair actions on renderings and repainting), the average service life is 15 years, until the last period of service life that precedes the end of the rendering’s life cycle.
Inhibition of IDH3α Enhanced the Efficacy of Chemoimmunotherapy by Regulating Acidic Tumor Microenvironments
Authors: Zhang Lingling , Song Yang , Dai Xiaoyan , Xu Wenwen , Li Mengxia , Zhu Yuxi
Published: March 2023

In recent years, chemoimmunotherapy has become effective in some advanced cancers, but its effect is still limited. Transcriptional upregulation of isocitrate dehydrogenase 3α (IDH3α) can promote tumor initiation and progression. However, it is not clear whether the aberrant expression of IDH3α is related to the efficacy of chemoimmunotherapy in cancers. Here, we found that IDH3α was elevated in uterine cervical cancer (UCC) and lung adenocarcinoma (LUAD) samples by using public databases. High expression of IDH3α could promote the epithelial–mesenchymal transition (EMT), alter the intracellular redox status, promote glycolysis, and induce an acidic microenvironments in cancer cells. Furthermore, we found that inhibition of IDH3α combined with chemoimmunotherapy (cisplatin and programmed cell death ligand 1 (PD-L1) antibodies) activated the cGAS–STING pathway, promoted CD8+ T cell infiltration, and decreased tumor growth in mouse models of cervical cancer. In conclusion, our data indicate that silencing IDH3α sensitizes tumors to chemoimmunotherapy by modulating the acidic microenvironment and activating the cGAS–STING pathway.
Vulvar Paget’s Disease: A Systematic Review of the MITO Rare Cancer Group
Authors: Caruso Giuseppe , Barcellini Amelia , Mazzeo Roberta , Gallo Roberta , Vitale Maria Giuseppa , Passarelli Anna , Mangili Giorgia , Pignata Sandro , Palaia Innocenza
Published: March 2023

Vulvar Paget’s disease (VPD) is a rare form of cutaneous adenocarcinoma of the vulva, which accounts for about 1–2% of all vulvar neoplasms and mainly affects post-menopausal women. The clinical presentation is usually non-specific and mimics chronic erythematous skin lesions; therefore, the diagnosis is often difficult and delayed. Although VPD is typically diagnosed at a locally advanced stage and has a high recurrence rate, the prognosis is overall favorable with a 5-year survival of nearly 90%. Due to the limited and poor-quality evidence, there is no global consensus on optimal management. Therefore, we performed a systematic review of the literature through the main electronic databases to deepen the current knowledge of this rare disease and discuss the available treatment strategies. Wide surgical excision is recommended as the standard-of-care treatment and should be tailored to the tumor position/extension and the patient’s performance status. The goal is to completely remove the tumor and achieve clear margins, thus reducing the rate of local recurrences. Non-surgical treatments, such as radiotherapy, chemotherapy, and topical approaches, can be considered, especially in the case of unresectable and recurrent disease. In the absence of clear recommendations, the decision-making process should be individualized, also considering the new emerging molecular targets, such as HER2 and PD-L1, which might pave the way for future targeted therapies. The current review aims to raise awareness of this rare disease and encourage international collaboration to collect larger-scale, high-quality evidence and standardize treatment.
Surgical Approach in Metastatic Renal Cell Carcinoma: A Literature Review
Authors: Matuszczak Milena , Kiljańczyk Adam , Salagierski Maciej
Published: March 2023

The treatment of metastatic renal cell carcinoma has undergone considerable advances in the last two decades. Cytoreductive nephrectomy and metastasectomy retains a role in patients with a limited metastatic burden. The choice of optimal treatment regimen remains a matter of debate. The article summarises the current role of surgery in metastatic kidney cancer.
Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore
Authors: Chua Brandon , Lim Li Min , Ng Joseph Soon Yau , Ma Yan , Wee Hwee Lin , Caro J. Jaime
Published: March 2023

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30–69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.
Sex Differences in the Systemic and Local Immune Response of Pancreatic Cancer Patients
Authors: Ahmed Azaz , Köhler Sophia , Klotz Rosa , Giese Nathalia , Hackert Thilo , Springfeld Christoph , Jäger Dirk , Halama Niels
Published: March 2023

Background: Mounting evidence suggests that sex plays a critical role in various aspects of cancer such as immune responses. However, a male bias exists in human and non-human studies including immunotherapy trials. The role of sex on immune responses in pancreatic ductal adenocarcinoma (PDA) is unclear. Methods: Here, tumor tissues (tumor and stroma separately) and corresponding blood samples from patients with PDA (n = 52) were systematically analyzed by immunohistochemistry and multiplex cytokine measurements and compared by sex. Results: Females showed a stronger systemic immune response with higher levels of CXCL9, IL1B, IL6, IL10 and IL13. Additionally, more peripheral white blood cells were detected in females. In the microenvironment, males showed higher tumoral levels of CXCL12. No differences were detected in the stroma. Females showed a tendency towards an anti-tumoral immune cell profile. CXCL12 blockade indicated a differential microenvironmental effect by sex in an independent immunotherapy trial cohort of patients with PDA (one female, five males). The overall survival did not differ by sex in our cohort. Conclusion: Systemic and local immune responses differ between sexes in PDA. Accordingly, sex-dependent differences need to be considered in human studies and for specific immunological interventions before clinical translation.
Applied Catalysis in Chemical Industry: Synthesis, Catalyst Design, and Evaluation
Authors: Zybert Magdalena
Published: March 2023

Catalysis is a very important process with practical significance for sustainable development, energy production, environmental protection, food production, and water purification, among others, and catalytic processes produce almost 90% of the products in the chemical industry [...]
Quantitative Phosphoproteomics Reveals the Requirement of DYRK1-Mediated Phosphorylation of Ion Transport- and Cell Junction-Related Proteins for Notochord Lumenogenesis in Ascidian
Authors: Wang Zhuqing , Ouyang Xiuke , Tan Zicheng , Yang Likun , Dong Bo
Published: March 2023

The dual-specificity tyrosine phosphorylation-regulated kinase (DYRK1) phosphorylates diverse substrates involved in various cellular processes. Here, we found that blocking the kinase activity of DYRK1 inhibited notochord development and lumenogenesis in ascidian Ciona savignyi. By performing phosphoproteomics in conjunction with notochord-specific proteomics, we identified 1065 notochord-specific phosphoproteins that were present during lumen inflation, of which 428 differentially phosphorylated proteins (DPPs) were identified after inhibition of DYRK1 kinase activity. These DPPs were significantly enriched in metal ion transmembrane transporter activity, protein transport and localization, and tight junction. We next analyzed the downregulated phosphoproteins and focused on those belonging to the solute carrier (SLC), Ras-related protein (RAB), and tight junction protein (TJP) families. In vivo phospho-deficient study showed that alanine mutations on the phosphosites of these proteins resulted in defects of lumenogenesis during Ciona notochord development, demonstrating the crucial roles of phosphorylation of transmembrane transport-, vesicle trafficking-, and tight junction-related proteins in lumen formation. Overall, our study provides a valuable data resource for investigating notochord lumenogenesis and uncovers the molecular mechanisms of DYRK1-mediated notochord development and lumen inflation.
Hematologic Risk Factors for the Development of Retinopathy of Prematurity—A Retrospective Study
Authors: Zonda Gabriela Ildiko , Mogos Raluca , Melinte-Popescu Alina-Sînziana , Adam Ana-Maria , Harabor Valeriu , Nemescu Dragos , Socolov Demetra , Harabor Anamaria , Melinte-Popescu Marian , Hincu Maura Adelina , Vasilache Ingrid-Andrada , Carauleanu Alexandru , Adam Gigi , Paduraru Luminita
Published: March 2023

(1) Background: Retinopathy of prematurity (ROP) can cause severe visual impairment or even blindness. We aimed to assess the hematological risk factors that are associated with different stages of ROP in a cohort of preterm newborns, and to compare the clinical characteristics and therapeutic interventions between groups. (2) Methods: This retrospective study included 149 preterm newborns from a tertiary maternity hospital in Romania between January 2018 and December 2018, who were segregated into: Group 1 (with ROP, n = 59 patients), and Group 2 (without ROP, n = 90 patients). The patients that were affected by ROP were subsequently divided into the following subgroups: Subgroup 1 (Stage 1, n = 21), Subgroup 2 (Stage 2, n = 35), and Subgroup 3 (Stage 3, n = 25). The associations were analyzed using multivariate logistic regression and sensitivity analysis. (3) Results: Platelet mass indexes (PMI) that were determined in the first, seventh, and tenth days of life were significantly associated with Stage 1 ROP. PMI determined in the first day of life was also significantly associated with Stage 2 ROP. The sensitivity and specificity of these parameters were modest, ranging from 44 to 57%, and 59 to 63%. (4) Conclusions: PMI has a modest ability to predict the development of ROP.
Teaching Games for Understanding in Game Performance and Psychosocial Variables: Systematic Review and Meta-Analysis of Randomized Control Trial
Authors: Ortiz Marcos , Meroño Lourdes , Morales-Belando María T. , Vaquero-Cristóbal Raquel , González-Gálvez Noelia
Published: March 2023

Different authors have reported on the influence of the Teaching Games for Understanding (TGfU) intervention on game performance and psychosocial variables. This review aimed: (a) to explore the TGfU experimental studies; (b) to compare the effects of the TGfU vs. technical approach pedagogy on game performance; and (c) to determine the effect of the TGfU approach on game performance and psychosocial variables (motivational climate, task orientation, perceived competence and enjoyment). This systematic review with meta-analysis adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four databases (PubMed, WOS, EBSCO and Google scholar metasearch) were searched. Study quality was measured with the Physiotherapy Evidence Database (PEDro) score. Thirteen studies were included. A pooled analysis of all interventions demonstrated a large significant improvement in decision making for TGfU when compared to technical approach pedagogy (SMD = 5.93, I2 = 98%; CI (95%) = 2.15–9.71; p = 0.004) and no differences between groups for skill execution (SMD = 1.70; I2 = 8%; CI (95%) = −5.34–8.73; p = 0.60). The effect of a TGfU intervention on game performance is strong (decision making, execution skills and tactical skills). Moderate evidence is reported by psychosocial variables (motivational climate, task orientation, perception of motivation and achievement in physical education). In addition, it is unclear its effect on perceived competence, enjoyment, knowledge of the game and intention to be physically active. TGfU intervention could be an appropriate approach for males and females in the context of education or sport. There is a need for a greater number of studies.
Pesticidal Toxicity of Phosphine and Its Interaction with Other Pest Control Treatments
Authors: Alzahrani Saad M. , Ebert Paul R.
Published: March 2023

Phosphine is the most widely used fumigant for stored grains due to a lack of better alternatives, all of which have serious shortcomings that restrict their use. The extensive use of phosphine has led to the development of resistance among insect pests of grain, which threatens its status as a reliable fumigant. Understanding the mode of action of phosphine as well as its resistance mechanisms provides insight that may lead to improved phosphine efficacy and pest control strategies. The mechanisms of action in phosphine vary from disrupting metabolism and oxidative stress to neurotoxicity. Phosphine resistance is genetically inherited and is mediated by the mitochondrial dihydrolipoamide dehydrogenase complex. In this regard, laboratory studies have revealed treatments that synergistically enhance phosphine toxicity that may be used to suppress resistance development and enhance efficacy. Here, we discuss the reported phosphine modes of action, mechanisms of resistance and interactions with other treatments.
A Direct Tensile Strength Testing Method for Concrete from Existing Structures
Authors: Nilimaa Jonny , Nilforoush Rasoul
Published: March 2023

Tensile strength is a crucial property for the function, safety and durability of all concrete structures. The general procedure to assess the tensile properties of concrete from existing structures is to perform indirect tests and predict the tensile strength based on established empirical relationships. In this study, the direct tensile strength of concrete was investigated using cylindrical specimens. The aim of the study was to propose, test and evaluate a general method for direct tensile tests of concrete from existing structures. A total of 16 specimens were tested under deformation-controlled tensile-loading until failure. The concrete samples were prepared with 10 or 15 mm grooves at mid-height to obtain cracking in the groove region, where the crack-opening sensors were installed. The load and corresponding deformation were recorded continuously during the test to obtain the load–crack-width relationship of the concrete. The tests showed that the method can be used to assess the tensile properties of concrete from existing structures. The study provides important insights regarding the assessment of direct tensile strength of concrete and the results can be used to improve the structural health monitoring of existing structures and thereby ensure their safety and durability.
Stress-Strained State of the Thrust Bearing Disc of Hydrogenerator-Motor
Authors: Tretiak Oleksii , Kritskiy Dmitriy , Kobzar Igor , Arefieva Mariia , Selevko Volodymyr , Brega Dmytro , Maiorova Kateryna , Tretiak Iryna
Published: March 2023

In this article, the main causes of vibration in the thrust bearing of hydrogenerator motors rated 320 MW are considered. The main types of internal and surface defects that appear on the working surface of the thrust bearing disc during long-term operation are considered. A method of three-dimensional modeling of such defects is presented, and an assessment of the stress-strain state of the heel disc is proposed, taking into account the main forces acting on the working surface using the finite element method. An analysis of the possible further operation of discs with similar defects, in accordance with the technical requirements, is carried out, and we consider ways to eliminate them.
Effect of Lanthanum Oxide on the Microstructure and Properties of Ti-6Al-4V Alloy during CMT-Additive Manufacturing
Authors: Liu Huanyu , Wang Shuang , Liang Jian , Hu Hong , Li Qingtao , Chen Hongrui
Published: March 2023

Lanthanum oxide powder was added to improve the microstructure and properties of a Ti-6Al-4V alloy part during cold metal transfer (CMT) based on wire arc additive manufacturing (WAAM). The macrostructure, microstructure and properties of the part were studied by using an optical microscope (OM), scanning electron microscope (SEM), electron backscatter(ed) diffraction (EBSD), microhardness evaluation and a tensile test. The results showed that the β grain size and martensite (α) size were reduced by adding lanthanum oxide powder. The texture intensity of the part also decreased due to the change in microstructure. Accordingly, the microhardness and tensile properties of the part obtained by adding lanthanum oxide were improved. In addition, based on the interdependence theory model, adding La2O3 particles in the molten pool as heterogeneous nucleation points could reduce the distance of XSD, so fine equiaxed β grains can be formed in the deposition layer.
Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients
Authors: Ahn Ae Ri , Karamikheirabad Maryam , Park Min Su , Zhang Junyue , Kim Hyun Sun , Jeong Ji Su , Kim Kyoung Min , Park Ho Sung , Jang Kyu Yun
Published: March 2023

Background: PAK4 and PHF8 are involved in cancer progression and are under evaluation as targets for cancer therapy. However, despite extensive studies in human cancers, there are limited reports on the roles of PAK4 and PHF8 in gallbladder cancers. Methods: Immunohistochemical expression of PAK4 and PHF8 and their prognostic significance were evaluated in 148 human gallbladder carcinomas. Results: PAK4 expression was significantly associated with PHF8 expression in gallbladder carcinomas. Positive expression of nuclear PAK4, cytoplasmic PAK4, nuclear PHF8, and cytoplasmic PHF8 were significantly associated with shorter overall survival and relapse-free survival in univariate analysis. Multivariate analysis showed that nuclear PAK4 expression and nuclear PHF8 expression were independent predictors of overall survival and relapse-free survival in gallbladder carcinomas. Furthermore, coexpression of nuclear PAK4 and nuclear PHF8 predicted shorter overall survival (p < 0.001) and relapse-free survival (p < 0.001) of gallbladder carcinoma in multivariate analysis. Conclusions: This study suggests that the individual and coexpression patterns of PAK4 and PHF8 as the prognostic indicators for gallbladder carcinoma patients.