bluuebunny/crossref_metadata_2025 huggingface dataset:
GB1a Activates SIRT6 to Regulate Lipid Metabolism in Mouse Primary Hepatocytes
Authors: Sun Yongzhi , Zheng Congmin , Li Ting , He Xinqian , Yang Fan , Guo Wenfeng , Song Jianping , Gao Yong , Deng Changsheng , Huang Xinan
Published: May 2023

Lipid accumulation, oxidative stress, and inflammation in hepatocytes are features of nonalcoholic fatty liver disease (NAFLD). Garcinia biflavonoid 1a (GB1a) is a natural product capable of hepatic protection. In this study, the effect of GB1a on anti-inflammatory, antioxidant, and regulation of the accumulation in HepG2 cells and mouse primary hepatocytes (MPHs) was investigated, and its regulatory mechanism was further explored. The result showed that GB1a reduced triglyceride (TG) content and lipid accumulation by regulating the expression of SREBP-1c and PPARα; GB1a reduced reactive oxygen species (ROS) and improved cellular oxidative stress to protect mitochondrial morphology by regulating genes Nrf2, HO-1, NQO1, and Keap1; and GB1a reduced the damage of hepatocytes by inhibiting the expression of inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65. The activities of GB1a were lost in liver SIRT6-specific knockout mouse primary hepatocytes (SIRT6-LKO MPHs). This indicated that activating SIRT6 was critical for GB1a to perform its activity, and GB1a acted as an agonist of SIRT6. It was speculated that GB1a may be a potential drug for NAFLD treatment.
Heat Shock Protein 70 Is Involved in the Efficiency of Preconditioning with Cyclosporine A in Renal Ischemia Reperfusion Injury by Modulating Mitochondrial Functions
Authors: Schleef Maxime , Rozes Margaux , Pillot Bruno , Bidaux Gabriel , Guebre-Egziabher Fitsum , Juillard Laurent , Baetz Delphine , Lemoine Sandrine
Published: May 2023

Cyclosporine A (CsA) preconditioning is known to target mitochondrial permeability transition pore and protect renal function after ischemia reperfusion (IR). The upregulation of heat-shock protein 70 (Hsp70) expression after CsA injection is thought to be associated with renal protection. The aim of this study was to test the effect of Hsp70 expression on kidney and mitochondria functions after IR. Mice underwent a right unilateral nephrectomy and 30 min of left renal artery clamping, performed after CsA injection and/or administration of the Hsp70 inhibitor. Histological score, plasma creatinine, mitochondrial calcium retention capacity, and oxidative phosphorylation were assessed after 24 h of reperfusion. In parallel, we used a model of hypoxia reoxygenation on HK2 cells to modulate Hsp70 expression using an SiRNA or a plasmid. We assessed cell death after 18 h of hypoxia and 4 h of reoxygenation. CsA significantly improved renal function, histological score, and mitochondrial functions compared to the ischemic group but the inhibition of Hsp70 repealed the protection afforded by CsA injection. In vitro, Hsp70 inhibition by SiRNA increased cell death. Conversely, Hsp70 overexpression protected cells from the hypoxic condition, as well as the CsA injection. We did not find a synergic association between Hsp70 expression and CsA use. We demonstrated Hsp70 could modulate mitochondrial functions to protect kidneys from IR. This pathway may be targeted by drugs to provide new therapeutics to improve renal function after IR.
Oncogenic Viruses and the Epigenome: How Viruses Hijack Epigenetic Mechanisms to Drive Cancer
Authors: MacLennan Signe A. , Marra Marco A.
Published: May 2023

Globally, viral infections substantially contribute to cancer development. Oncogenic viruses are taxonomically heterogeneous and drive cancers using diverse strategies, including epigenomic dysregulation. Here, we discuss how oncogenic viruses disrupt epigenetic homeostasis to drive cancer and focus on how virally mediated dysregulation of host and viral epigenomes impacts the hallmarks of cancer. To illustrate the relationship between epigenetics and viral life cycles, we describe how epigenetic changes facilitate the human papillomavirus (HPV) life cycle and how changes to this process can spur malignancy. We also highlight the clinical impact of virally mediated epigenetic changes on cancer diagnosis, prognosis, and treatment.
MITA Promotes Macrophage Proinflammatory Polarization and Its circRNA-Related Regulatory Mechanism in Recurrent Miscarriage
Authors: Liu Bowen , Liu Jun , Qiu Yang , Chen Jiao , Yang Jing
Published: May 2023

MITA (also called STING), a master regulator of DNA-mediated innate immune activation, is a potential therapeutic target for viral infection and virus-related diseases. The circRNA-mediated ceRNA network plays important roles in gene regulation and may contribute to many human diseases. However, the relationship between MITA and recurrent miscarriage (RM) and its circRNA-related regulatory mechanisms remain unclear. In this study, we validated that the decidual M1/M2 ratio was upregulated in RM patients, suggesting the vital roles of decidual macrophages in the pathogenesis of RM. We found that MITA was highly expressed in decidual macrophages of RM patients and validated that MITA could promote apoptosis and macrophage proinflammatory polarization in THP-1-derived macrophage (TDM) cells. Using circRNA sequencing and bioinformatic analysis, we screened out a novel circRNA (circKIAA0391) that is overexpressed in decidual macrophages of RM patients. Mechanistically, we found that circKIAA0391 could promote the apoptosis and proinflammatory polarization of TDM cells by sponging the miR-512-5p/MITA axis. This study provides a theoretical basis for further understanding the impact of MITA on macrophages and its circRNA-related regulatory mechanisms, which may have a crucial immunomodulatory function in the pathophysiology of RM.
Parkinson’s Disease: From Genetics and Epigenetics to Treatment, a miRNA-Based Strategy
Authors: Paccosi Elena , Proietti-De-Santis Luca
Published: May 2023

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, characterized by an initial and progressive loss of dopaminergic neurons of the substantia nigra pars compacta via a potentially substantial contribution from protein aggregates, the Lewy bodies, mainly composed of α-Synuclein among other factors. Distinguishing symptoms of PD are bradykinesia, muscular rigidity, unstable posture and gait, hypokinetic movement disorder and resting tremor. Currently, there is no cure for PD, and palliative treatments, such as Levodopa administration, are directed to relieve the motor symptoms but induce severe side effects over time. Therefore, there is an urgency for discovering new drugs in order to design more effective therapeutic approaches. The evidence of epigenetic alterations, such as the dysregulation of different miRNAs that may stimulate many aspects of PD pathogenesis, opened a new scenario in the research for a successful treatment. Along this line, a promising strategy for PD treatment comes from the potential exploitation of modified exosomes, which can be loaded with bioactive molecules, such as therapeutic compounds and RNAs, and can allow their delivery to the appropriate location in the brain, overcoming the blood–brain barrier. In this regard, the transfer of miRNAs within Mesenchymal stem cell (MSC)-derived exosomes has yet to demonstrate successful results both in vitro and in vivo. This review, besides providing a systematic overview of both the genetic and epigenetic basis of the disease, aims to explore the exosomes/miRNAs network and its clinical potential for PD treatment.
Metformin Counteracts the Deleterious Effects of Methylglyoxal on Ovalbumin-Induced Airway Eosinophilic Inflammation and Remodeling
Authors: Medeiros Matheus L. , Oliveira Akila L. , Mello Glaucia C. , Antunes Edson
Published: May 2023

Exposure to methylglyoxal (MGO) increases the levels of receptor for advanced glycation end products (RAGE) and reactive-oxygen species (ROS) in mouse airways, exacerbating the inflammatory responses. Metformin scavenges MGO in plasma of diabetic individuals. We investigated if amelioration by metformin of eosinophilic inflammation reflects its ability to inactivate MGO. Male mice received 0.5% MGO for 12 weeks together or not with 2-week treatment with metformin. Inflammatory and remodeling markers were evaluated in bronchoalveolar lavage fluid (BALF) and/or lung tissues of ovalbumin (OVA)-challenged mice. MGO intake elevated serum MGO levels and MGO immunostaining in airways, which were reduced by metformin. The infiltration of inflammatory cells and eosinophils and levels of IL-4, IL-5 and eotaxin significantly increased in BALF and/or lung sections of MGO-exposed mice, which were reversed by metformin. The increased mucus production and collagen deposition by MGO exposure were also significantly decreased by metformin. In MGO group, the increases of RAGE and ROS levels were fully counteracted by metformin. Superoxide anion (SOD) expression was enhanced by metformin. In conclusion, metformin counteracts OVA-induced airway eosinophilic inflammation and remodeling, and suppresses the RAGE-ROS activation. Metformin may be an option of adjuvant therapy to improve asthma in individuals with high levels of MGO.
Exploiting Security Issues in Human Activity Recognition Systems (HARSs)
Authors: Sakka Sofia , Liagkou Vasiliki , Stylios Chrysostomos
Published: May 2023

Human activity recognition systems (HARSs) are vital in a wide range of real-life applications and are a vibrant academic research area. Although they are adopted in many fields, such as the environment, agriculture, and healthcare and they are considered assistive technology, they seem to neglect the aspects of security and privacy. This problem occurs due to the pervasive nature of sensor-based HARSs. Sensors are devices with low power and computational capabilities, joining a machine learning application that lies in a dynamic and heterogeneous communication environment, and there is no generalized unified approach to evaluate their security/privacy, but rather only individual solutions. In this work, we studied HARSs in particular and tried to extend existing techniques for these systems considering the security/privacy of all participating components. Initially, in this work, we present the architecture of a real-life medical IoT application and the data flow across the participating entities. Then, we briefly review security and privacy issues and present possible vulnerabilities of each system layer. We introduce an architecture over the communication layer that offers mutual authentication, solving many security and privacy issues, particularly the man-in-the-middle attack (MitM). Relying on the proposed solutions, we manage to prevent unauthorized access to critical information by providing a trustworthy application.
An Intelligent Boosting and Decision-Tree-Regression-Based Score Prediction (BDTR-SP) Method in the Reform of Tertiary Education Teaching
Authors: Zhu Ling , Liu Guangyu , Lv Shuang , Chen Dongjie , Chen Zhihong , Li Xiang
Published: May 2023

The reform of tertiary education teaching promotes teachers to adjust timely teaching plans based on students’ learning feedback in order to improve teaching performance. Thefore, learning score prediction is a key issue in process of the reform of tertiary education teaching. With the development of information and management technologies, a lot of teaching data are generated as the scale of online and offline education expands. However, a teacher or educator does not have a comprehensive dataset in practice, which challenges his/her ability to predict the students’ learning performance from the individual’s viewpoint. How to overcome the drawbacks of small samples is an open issue. To this end, it is desirable that an effective artificial intelligent tool is designed to help teachers or educators predict students’ scores well. We propose a boosting and decision-tree-regression-based score prediction (BDTR-SP) model, which relies on an ensemble learning structure with base learners of decision tree regression (DTR) to improve the prediction accuracy. Experiments on small samples are conducted to examine the important features that affect students’ scores. The results show that the proposed model has advantages over its peer in terms of prediction correctness. Moreover, the predicted results are consistent with the actual facts implied in the original dataset. The proposed BDTR-SP method aids teachers and students to predict students’ performance in the on-going courses in order to adjust the teaching and learning strategies, plans and practices in advance, enhancing the teaching and learning quality. Therefore, the integration of information technology and artificial intelligence into teaching and learning practices is able to push forward the reform of tertiary education teaching.
IoT Device Identification Using Unsupervised Machine Learning
Authors: Koball Carson , Rimal Bhaskar P. , Wang Yong , Salmen Tyler , Ford Connor
Published: May 2023

Device identification is a fundamental issue in the Internet of Things (IoT). Many critical services, including access control and intrusion prevention, are built on correctly identifying each unique device in a network. However, device identification faces many challenges in the IoT. For example, a common technique to identify a device in a network is using the device’s MAC address. However, MAC addresses can be easily spoofed. On the other hand, IoT devices also include dynamic characteristics such as traffic patterns which could be used for device identification. Machine-learning-assisted approaches are promising for device identification since they can capture dynamic device behaviors and have automation capabilities. Supervised machine-learning-assisted techniques demonstrate high accuracies for device identification. However, they require a large number of labeled datasets, which can be a challenge. On the other hand, unsupervised machine learning can also reach good accuracies without requiring labeled datasets. This paper presents an unsupervised machine-learning approach for IoT device identification.
Platelet-to-Albumin Ratio: The Prognostic Utility in the Prediction of 2-Month Postoperative Heart Transplant Complications
Authors: Baba Dragos-Florin , Suciu Horatiu , Huma Laurentiu , Avram Calin , Danilesco Alina , Moldovan Diana Andreea , Opincar Andrei Stefan , Sin Anca Ileana
Published: May 2023

Background: The platelet-to-albumin ratio (PAR), leucocyte-to-albumin ratio (LAR), neutrophil percentage-to-albumin ratio (NPAR), and monocyte-to-albumin ratio (MAR) represent easily reproducible markers, which may predict the outcomes in various diseases. Early postoperative complications might appear after heart transplantation, such as infections, diabetes mellitus type 2 (DM2), acute graft rejection, and atrial fibrillation (AFib). Objective: The aim of our study was to investigate the PAR, LAR, NPAR, and MAR values before and after heart transplantation, and the associations of the preoperative levels of these markers with the presence of postoperative complications in first two months after surgery. Methods: Our retrospective research was directed from May 2014 to January 2021, with a total number of 38 patients being included. We used cut-off values for the ratios from previously published studies, as well as our own determination of these levels by using a receiver operating characteristic (ROC) curve. Results: By ROC analysis, the optimal preoperative PAR cut-off value was 38.84 (AUC: 0.771, p = 0.0039), with 83.3% sensitivity, and 75.0% specificity. Applying a Chi square (χ2) test, PAR > 38.84 represented an independent risk factor for complications, regardless of cause, and postoperative infections. Conclusions: Preoperative PAR > 38.84 was a risk factor of developing complications of any cause, and postoperative infections in the first two months after heart transplantation.
Quantitative SPECT/CT Parameters in the Assessment of Transthyretin Cardiac Amyloidosis—A New Dimension of Molecular Imaging
Authors: Gherghe Mirela , Lazar Alexandra Maria , Sterea Maria-Carla , Spiridon Paula Monica , Motas Natalia , Gales Laurentia Nicoleta , Coriu Daniel , Badelita Sorina Nicoleta , Mutuleanu Mario-Demian
Published: May 2023

Aims: Cardiac transthyretin amyloidosis (ATTR) represents the accumulation of misfolded transthyretin in the heart interstitium. Planar scintigraphy with bone-seeking tracers has long been established as one of the three main steps in the non-invasive diagnosis of ATTR, but lately, single-photon emission computed tomography (SPECT) has gained wide recognition for its abilities to exclude false positive results and offer a possibility for amyloid burden quantitation. We performed a systematic review of the existing literature to provide an overview of the available SPECT-based parameters and their diagnostic performances in the assessment of cardiac ATTR. Methods and Methods: Among the 43 papers initially identified, 27 articles were screened for eligibility and 10 met the inclusion criteria. We summarised the available literature based on radiotracer, SPECT acquisition protocol, analysed parameters and their correlation to planar semi-quantitative indices. Results: Ten articles provided accurate details about SPECT-derived parameters in cardiac ATTR and their diagnostic potential. Five studies performed phantom studies for accurate calibration of the gamma cameras. All papers described good correlation of quantitative parameters to the Perugini grading system. Conclusions: Despite little published literature on quantitative SPECT in the assessment of cardiac ATTR, this method offers good prospects in the appraisal of cardiac amyloid burden and treatment monitoring.
Effectiveness of the Combination of Enalapril and Nifedipine for the Treatment of Hypertension versus Empirical Treatment in Primary Care Patients
Authors: Badillo-Alonso Humberto , Martínez-Alanis Marisol , Sánchez-Huesca Ramiro , Lerma Abel , Lerma Claudia
Published: May 2023

Hypertension in Mexico has a prevalence of 32% and is the second most widespread cause of consultation in primary care. Only 40% of patients in treatment have a blood pressure (BP) below 140/90 mmHg. This clinical trial aimed to compare the effectiveness of the combination of enalapril and nifedipine versus the empirical treatment for hypertension in patients with uncontrolled BP in a primary care center in Mexico City. Participants were randomized to treatment with enalapril and nifedipine (combination group) or to continue with the empirical treatment. Outcome variables were BP control, therapeutic adherence, and adverse effects at 6 months of follow-up. At the end of the follow-up period, BP control (64% versus 77%) and therapeutic adherence (53% versus 93%) showed an improvement from the baseline values in the group that received the combination treatment. BP control (51% versus 47%) and therapeutic adherence (64% versus 59%) in the group who received the empirical treatment did not show improvement from the baseline to follow-up. Combined treatment was 31% more efficacious than conventional empirical treatment (odds ratio = 3.9), which yielded an incremental clinical utility of 18% with high tolerability extent among patients in primary care in Mexico City. These results contribute to the control of arterial hypertension.
Assessment and Improvement of Masticatory Performance in Frail Older People: A Narrative Review
Authors: Schimmel Martin , Anliker Noemi , Sabatini Gabriela Panca , De Paula Marcella Silva , Weber Adrian Roman , Molinero-Mourelle Pedro
Published: May 2023

According to the World Health Organization (WHO), the estimated number of older adults is around 962 million and is projected to increase to 2.1 billion by 2050. The oral frailty concept is associated with gradual oral function loss in relation to aging. There is a need to emphasize the improvement of oral function based on an evaluation of masticatory performance in patients with various oral conditions or systemic diseases and especially in the frail elderly. The present narrative review presents an overview of the current state of the assessment and improvement of masticatory performance in frail older people. To fully encompass oral frailty, oro-facial hypofunction, or oro-facial fitness, dental Patient Reported Outcomes (dPROs) should be included; nevertheless, there are limited evidence-based rehabilitation approaches. The concept of oral frailty, oro-facial hypofunction, or oro-facial fitness should involve dental Patient Reported Outcomes (dPROs), and in this sense, there are only a few evidence-based rehabilitation procedures to improve oro-facial hypofunction besides prosthodontics. It must be considered that reduced neuroplastic capacity in old individuals might preclude a positive outcome of these strategies that might need to be accompanied by functional training and nutritional counseling.
Systemic Anti-Inflammatory Effects of Intravenous Lidocaine in Surgical Patients: A Systematic Review and Meta-Analysis
Authors: Castro Irene , Carvalho Pedro , Vale Nuno , Monjardino Teresa , Mourão Joana
Published: May 2023

There has recently been increasing evidence that the use of perioperative intravenous lidocaine infusion possesses analgesic, opioid-sparing and anti-inflammatory effects in surgical patients. Although opioid-sparing and analgesic properties have been strongly supported, the anti-inflammatory features are not well established in elective surgery. Therefore, the aim of this systematic review is to examine the effect of perioperative intravenous lidocaine infusion on postoperative anti-inflammatory status in patients undergoing elective surgery. A search strategy was created to identify suitable randomised clinical trials (RCTs) in PubMed, Scopus, Web of Science and Clinicaltrials.gov databases until January 2023. RCTs that evaluated the effect of intravenous lidocaine infusion, compared with placebo, on adult patients who underwent elective surgery, in inflammatory markers response were included. Exclusion criteria consisted of paediatric patients, animal studies, non-RCT methodology, intervention without intravenous lidocaine, inadequate control group, duplicated samples, ongoing studies and lack of any relevant clinical outcome measures. The following inflammatory markers—interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1RA, IL-8, IL-10, C-reactive protein (CRP), IL-1, IL-1β, interferon (IFN)-γ, cortisol, IL-4, IL-17, high-mobility group protein B1 (HMGB1) and transforming growth factor (TGF)-β—were evaluated as outcomes in this review. A total of 21 studies, including 1254 patients, were identified. Intravenous lidocaine infusion significantly reduced the change from IL-6 baseline levels at the end of surgery compared to a placebo (standardised mean difference [SMD]: −0.647, 95% confidence interval [CI]: −1.034 to −0.260). Usage of lidocaine was associated with a significant reduction in other postoperative pro-inflammatory markers, such as TNF-α, IL-1RA, IL-8, IL-17, HMGB-1 and CRP. There was no significant difference in other markers, such as IL-10, IL-1β, IL-1, IFN-γ, IL-4, TGF-β and cortisol. This systematic review and meta-analysis provide support for the administration of perioperative intravenous lidocaine infusion as an anti-inflammatory strategy in elective surgery.
The Single Midline Implant in the Edentulous Mandible—Current Status of Clinical Trials
Authors: Passia Nicole , Kern Matthias
Published: May 2023

The single midline implant in the edentulous mandible is a treatment concept that has often been controversially discussed. Nearly 30 years ago, the first available clinical results revealed high implant survival rates and remarkable improvements in oral comfort, function, patient satisfaction and oral health-related quality of life for edentulous patients compared to the situation with no implant. However, the clinical trials were predominantly conducted with a small number of patients over a short to medium follow-up period. Today, numerous clinical investigations on the single midline implant in the edentulous mandible, which increasingly include longer-term observation periods, are available. It is the aim of this overview to present the current literature and to highlight the clinical problems. This article is a 2023 update of a review published by the authors in the German language in 2021 in the German journal Implantologie. In total, 19 prospective clinical trials with a follow-up period of 0.5–10 years were analyzed. Over this observation period, single implants with modern rough implant surfaces in the edentulous mandible reveal high implant survival rates of between 90.9 and 100% when a conventional delayed loading protocol was applied.
Individual Responses versus Aggregate Group-Level Results: Examining the Strength of Evidence for Growth Mindset Interventions on Academic Performance
Authors: Barnett Mariel K. , Macnamara Brooke N.
Published: May 2023

Mindset theory assumes that students’ beliefs about their intelligence—whether these are fixed or can grow—affects students’ academic performance. Based on this assumption, mindset theorists have developed growth mindset interventions to teach students that their intelligence or another attribute can be developed, with the goal of improving academic outcomes. Though many papers have reported benefits from growth mindset interventions, others have reported no effects or even detrimental effects. Recently, proponents of mindset theory have called for a “heterogeneity revolution” to understand when growth mindset interventions are effective and when—and for whom—they are not. We sought to examine the whole picture of heterogeneity of treatment effects, including benefits, lack of impacts, and potential detriments of growth mindset interventions on academic performance. We used a recently proposed approach that considers persons as effect sizes; this approach can reveal individual-level heterogeneity often lost in aggregate data analyses. Across three papers, we find that this approach reveals substantial individual-level heterogeneity unobservable at the group level, with many students and teachers exhibiting mindset and performance outcomes that run counter to the authors’ claims. Understanding and reporting heterogeneity, including benefits, null effects, and detriments, will lead to better guidance for educators and policymakers considering the role of growth mindset interventions in schools.
Field Investigation into Abrasion of Concrete at a Coastal Stepped Revetment: A U.K. Case Study
Authors: Omoding Nicholas , Cunningham Lee S. , Lane-Serff Gregory F. , Omer Muhammad , Farrington Brian
Published: May 2023

Although concrete abrasion damage is a major maintenance challenge for coastal structures fronted by beaches with hard coarse sediments, there are no readily available field studies that have measured abrasion damage of known concrete mixtures under defined exposure conditions. The objective of this investigation is to evaluate the abrasive exposure conditions of the concrete revetment armour units at Cleveleys on the Fylde coast of the U.K. and examine the feasibility of using terrestrial laser scanning (TLS) to measure concrete abrasion damage in field conditions. It was found that the concrete elements at Cleveleys are exposed to a macro-tidal environment, which experiences significant wave heights that vary from 0.42 to 1.92 m, whilst the peak wave periods range from 3.7 to 6.5 s. The beach sediments have a mean size of 26 mm and are moderately sorted. TLS provides a dense point cloud of abraded surfaces suitable for quantitative assessment of concrete abrasion in the field. Based on the measured abrasion depths and exposure durations, the peak concrete abrasion rates at the site varied from 3.5 to 4.5 mm/year, and severe abrasion was concentrated in the region between mean high-water springs and mean high-water neaps, wherein the highest beach levels were also found during the survey. Finally, the abraded surfaces exhibited a polished texture with no visible craters; thus, the mechanism of concrete material loss was by grinding/polishing due to rolling/sliding sediments.
Acoustic Signals and Behavior of the Invasive Freshwater Crayfish Cherax destructor (Clark, 1936)
Authors: De Vita Clarissa , Mauro Manuela , Vazzana Mirella , Arculeo Marco , Arizza Vincenzo , Ceraulo Maria , Buscaino Giuseppa
Published: May 2023

The study of acoustic signals in aquatic animals contributes to developing new monitoring systems based on passive acoustics and improves our knowledge of their behaviors and ecology. Here, the sounds produced by the invasive species crayfish Cherax destructor and their possible role in intraspecific interactions are analyzed. Synchronized acoustic and video monitoring systems were used in a tank to record acoustic signals and associated behavioral events (tail flips, number of encounters, number of fights) and states (velocity and distance moved, angular velocity, duration of fighting and proximity). The crayfish were monitored in seven layouts combining males (M) and females (F) (F, M, FF, MM, MF, MMF, FFM). Both males and females produced two types of acoustic signals (high- and low-frequency sounds). Grouped animals produced fewer low-frequency sounds than single animals. In a grouped layout, more sounds were recorded when animals were in proximity (distance between two specimen less than 6 cm). In a single layout, sounds were not associated with a specific event or behavioral state. The number of signals emitted in the FF group and single M group were significantly higher than those in other layouts. Our study indicates that low-frequency sounds are produced non-accidentally and provide a baseline for future tests on intraspecific acoustic communication on this species. This study could help implement low-cost passive acoustic monitoring able to identify this species and the possible negative effect of its dispersion in a non-native environment.
Preemptive Therapy in Cryptococcosis Adjusted for Outcomes
Authors: Messina Fernando , Santiso Gabriela , Arechavala Alicia , Romero Mercedes , Depardo Roxana , Marin Emmanuel
Published: May 2023

Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, early diagnosis and appropriate treatment are important. Objectives. The aim of the study was to understand the development of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow assay (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material, and pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia, and 50 had preemptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with preemptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Preemptive therapy avoided progression to meningitis in CrAg LFA-positive patients. Preemptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.
Impact of Iron Mining Activity on the Endophytic Fungal Community of Aspilia grazielae
Authors: Weirich Carlos Eduardo , Marques Maria Rita , de Castro Alinne Pereira , Assumpção Benitez Beatriz , Roque Fabio de Oliveira , Marchetti Clarice Rossato , Rodrigues Amanda Dal’Ongaro , de Lima Dênis Pires , dos Santos Edson dos Anjos
Published: May 2023

Aspilia grazielae (J. U. Santos) is an endemic plant species in Morro do Urucum in the Pantanal wetland (Brazil). A. grazielae is used for the restoration of areas impacted by iron mining activities. This study evaluates the diversity (composition, value and abundance) of endophytic fungal communities, considering parts of the plant and soil condition. The leaves and roots of A. grazielae were collected from native vegetation areas (NVA) and recovery areas (RCA) in Morro do Urucum. Illumina sequencing technology was used to investigate variation in endophytic fungal biodiversity. The operational taxonomic units detected in NVA ranged from 183 to 263 (leaf) and 115 to 285 (root), while RCA samples ranged from 200 to 282 (leaf) and 156 to 348 (root). Ascomycota phylum was the most common species among all plant samples. The most significant classes identified were Lecanoromycetes and Dothideomycetes that differed significantly (p ≤ 0.05) according to their plant hosts and soil stress. The relative abundance of Pestalotiopsis (Sordariomycetes class) and Stereocaulon (Lecanoromycetes class) genera was influenced by the iron mining activities according to the leaf samples analysed. However, the abundance and wealth of endophytic fungal communities in A. grazielae from RCA were evidence that could explain their high resilience to environmental disturbances and the source-sink dynamics of fungal propagules.
Fungal Vaccine Development: State of the Art and Perspectives Using Immunoinformatics
Authors: Inácio Moisés Morais , Moreira André Luís Elias , Cruz-Leite Vanessa Rafaela Milhomem , Mattos Karine , Silva Lana O’Hara Souza , Venturini James , Ruiz Orville Hernandez , Ribeiro-Dias Fátima , Weber Simone Schneider , Soares Célia Maria de Almeida , Borges Clayton Luiz
Published: May 2023

Fungal infections represent a serious global health problem, causing damage to health and the economy on the scale of millions. Although vaccines are the most effective therapeutic approach used to combat infectious agents, at the moment, no fungal vaccine has been approved for use in humans. However, the scientific community has been working hard to overcome this challenge. In this sense, we aim to describe here an update on the development of fungal vaccines and the progress of methodological and experimental immunotherapies against fungal infections. In addition, advances in immunoinformatic tools are described as an important aid by which to overcome the difficulty of achieving success in fungal vaccine development. In silico approaches are great options for the most important and difficult questions regarding the attainment of an efficient fungal vaccine. Here, we suggest how bioinformatic tools could contribute, considering the main challenges, to an effective fungal vaccine.
Alginate-Based 3D A549 Cell Culture Model to Study Paracoccidioides Infection
Authors: dos Santos Kelvin Sousa , Oliveira Lariane Teodoro , de Lima Fontes Marina , Migliato Ketylin Fernanda , Fusco-Almeida Ana Marisa , Mendes Giannini Maria José Soares , Moroz Andrei
Published: May 2023

A three-dimensional (3D) lung aggregate model based on sodium alginate scaffolds was developed to study the interactions between Paracoccidioides brasiliensis (Pb) and lung epithelial cells. The suitability of the 3D aggregate as an infection model was examined using cell viability (cytotoxicity), metabolic activity, and proliferation assays. Several studies exemplify the similarity between 3D cell cultures and living organisms, which can generate complementary data due to the greater complexity observed in these designed models, compared to 2D cell cultures. A 3D cell culture system of human A549 lung cell line plus sodium alginate was used to create the scaffolds that were infected with Pb18. Our results showed low cytotoxicity, evidence of increased cell density (indicative of cell proliferation), and the maintenance of cell viability for seven days. The confocal analysis revealed viable yeast within the 3D scaffold, as demonstrated in the solid BHI Agar medium cultivation. Moreover, when ECM proteins were added to the alginate scaffolds, the number of retrieved fungi was significantly higher. Our results highlight that this 3D model may be promising for in vitro studies of host–pathogen interactions.
Restless Legs Syndrome in Parkinson’s Disease
Authors: Diaconu Ştefania , Irincu Laura , Ungureanu Larisa , Ciopleiaș Bogdan , Țînț Diana , Falup-Pecurariu Cristian
Published: May 2023

Background: Restless legs syndrome (RLS) might worsen sleep quality and quality of life in people with Parkinson’s disease (PwPD). Objective: The main aim of the present study is to explore the associations between RLS and sleep, quality of life and other non-motor symptoms (NMS) in a sample of PwPD. Methods: We compared the clinical features of 131 PwPD with and without RLS, in a cross-sectional study. We used several validated scales for assessment: the International Restless Legs Syndrome Study Group rating scale (IRLS), Parkinson’s Disease Sleep Scale version 2 (PDSS-2), Parkinson’s Disease Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQ) and International Parkinson and Movement Disorder Society Non-Motor Rating Scale (MDS-NMS). Results: Thirty-five patients (26.71%) out of the total PwPD met the RLS diagnostic criteria, without significant differences between male (57.14%) and female (42.87%) (p = 0.431). Higher total scores of PDSS-2 were recorded among PwPD + RLS (p < 0.001), suggesting worse sleep quality. Significant correlations were observed between the diagnosis of RLS and some types of pain (especially nocturnal pain), physical fatigue and probable sleep-disordered breathing, according to the MDS-NMSS assessment. Conclusions: RLS has a high frequency in PwPD and it requires proper management, considering its consequences on sleep and quality of life.
Effectiveness of Initial Troponin I and Brain Natriuretic Peptide Levels as Biomarkers for Predicting Delayed Neuropsychiatric Sequelae in Patients with CO Poisoning: A Retrospective Multicenter Observational Study
Authors: Jung Myung Hyun , Lee Juncheol , Oh Jaehoon , Ko Byuk Sung , Lim Tae Ho , Kang Hyunggoo , Cho Yongil , Yoo Kyung Hun , Lee Sang Hwan , Sohn Chang Hwan , Kim Won Young
Published: May 2023

Background: Delayed neuropsychiatric sequelae (DNS) are a severe complication of carbon monoxide (CO) poisoning, and predicting DNS is difficult. This study aimed to investigate whether cardiac markers can be used as biomarkers to predict DNS occurrence following acute CO poisoning. Methods: This was a retrospective observational study that included patients with acute CO poisoning who visited two emergency medical centers in Korea from January 2008 to December 2020. The primary outcome was whether the occurrence of DNS was associated with laboratory results. Results: Of the 1327 patients with CO poisoning, 967 patients were included. Troponin I and BNP were significantly higher in the DNS group. As a result of multivariate logistic regression analysis, it was found that troponin I, mentality, creatine kinase, brain natriuretic peptide, and lactate levels independently influenced DNS occurrence in CO poisoning patients. The adjusted odds ratios for DNS occurrence were 2.12 (95% CI 1.31–3.47, p = 0.002) for troponin I and 2.80 (95% CI 1.81–3.47, p < 0.001) for BNP. Conclusion: Troponin I and BNP might be useful biomarkers for predicting the occurrence of DNS in patients with acute CO poisoning. This finding can help to identify high-risk patients who require close monitoring and early intervention to prevent DNS.
Clinical Effect of the C-Reactive Protein to Serum Albumin Ratio in Patients with Metastatic Gastric or Gastroesophageal Junction Cancer Treated with Trifluridine/Tipiracil
Authors: Hashimoto Itaru , Kano Kazuki , Onuma Shizune , Suematsu Hideaki , Nagasawa Shinsuke , Kanematsu Kyohei , Furusawa Kyoko , Hamaguchi Tomomi , Watanabe Mamoru , Hayashi Kei , Furuta Mitsuhiro , Inokuchi Yasuhiro , Machida Nozomu , Aoyama Toru , Yamada Takanobu , Rino Yasushi , Ogata Takashi , Oshima Takashi
Published: May 2023

Trifluridine/tipiracil (FTD/TPI) is an oral anticancer agent used as a third- or later-line treatment for patients with metastatic gastric cancer/gastroesophageal junction cancer (mGC/GEJC). The C-reactive protein-to-serum albumin ratio (CAR) is an inflammation-based prognostic marker in gastric cancer. This retrospective study evaluated CAR’s clinical significance as a prognostic factor in 64 patients with mGC/GEJC administered FTD/TPI as a third- or later-line therapy. Patients were categorized into high- and low-CAR groups based on pre-treatment blood data. This study evaluated associations between CAR and overall survival (OS), progression-free survival (PFS), clinicopathological features, treatment efficacy, and adverse events. The high-CAR group had significantly worse Eastern Cooperative Oncology Group performance status, a higher prevalence of patients administered with a single course of FTD/TPI, and a higher rate of patients not administered chemotherapy after FTD/TPI therapy than the low-CAR group. Median OS and PFS were significantly poorer in the high-CAR group than in the low-CAR group (113 vs. 399 days; p < 0.001 and 39 vs. 112 days; p < 0.001, respectively). In multivariate analysis, high CAR was an independent prognostic factor for OS and PFS. The overall response rate was not significantly different between the high- and low-CAR groups. Regarding adverse events, the high-CAR group had a significantly lower incidence of neutropenia and a higher incidence of fatigue than the low-CAR group. Therefore, CAR may be a potentially useful prognostic factor for patients with mGC/GEJC treated with FTD/TPI as third- or later-line chemotherapy.
Toward a Systematic Assessment of Sex Differences in Cystic Fibrosis
Authors: Gärtner Christiane , Fallmann Jörg , Stadler Peter F. , Kaiser Thorsten , Berkemer Sarah J.
Published: May 2023

(1) Background: Cystic fibrosis (CF) is a disease with well-documented clinical differences between female and male patients. However, this gender gap is very poorly studied at the molecular level. (2) Methods: Expression differences in whole blood transcriptomics between female and male CF patients are analyzed in order to determine the pathways related to sex-biased genes and assess their potential influence on sex-specific effects in CF patients. (3) Results: We identify sex-biased genes in female and male CF patients and provide explanations for some sex-specific differences at the molecular level. (4) Conclusion: Genes in key pathways associated with CF are differentially expressed between sexes, and thus may account for the gender gap in morbidity and mortality in CF.
The Challenges and Therapeutic Prospects in Eye Disease
Authors: Tsai Chieh-Chih
Published: May 2023

A number of key insights into eye disease have been revealed in the past decade, which has resulted in the development of novel, effective, targeted therapies such as teprotumumab for the treatment of thyroid eye disease (also known as Graves’ orbitopathy) [...]
National and International Financial Market Regulation and Supervision Systems: Challenges and Solutions
Authors: Shavshukov Viacheslav M. , Zhuravleva Natalia A.
Published: May 2023

The purpose of this original study is to critically analyse the emergence and development of the national models of financial regulation, international standards and codes, and regional and national financial regulation and supervision (for the cases of the UK, USA, Sweden, the EU, and Finland). The research raises both academic and regulatory concerns. The relevance and purpose of this research arise from a need for an academic analysis of the economic nature and classification of financial market regulation systems. They represent a theoretical justification for changes in the policies and supervisory practices of national and international regulatory authorities in response to innovations in financial technologies and instruments, digital products, and risks. Secondly, it will stimulate more systematic work on regulatory databases, registration, and reporting procedures in various economies in different financial markets. The author identifies five main systems of national financial regulatory markets: the multi-tiered, multi-agency US system, the twin peaks model (UK), and the mega-regulatory model (Sweden). There is a thorough review of the international standards and institutions that work for the stability of financial systems. The analysis of the regional and national systems of financial regulation and supervision is based on the examples of the EU and Finnish institutions. National macro- and micro-economic regulation and supervision have been examined, with a focus on the US Federal Reserve and the US Treasury. An important result of the study is the systematisation of the directions of the development of national and international regulatory institutions (since the 1980s). First, the minimum capital and credit risk requirements for banks (the 1980s) were complemented in the 21st century by buffer reserves, liquidity, and leverage standards. Second, regulation focuses on ensuring the sustainability of the national economy. The regulatory focus is on ensuring the sustainability of national and global financial systems. Third, there is an increase in the number of supervised institutions. Fourth, there is a division of the functions between central banks (macro-economic regulation) and one or two mega-regulators (micro-economic regulation and supervision). Fifth, there is a division of labour between the international financial institutions (BIS, IMF, and WB) and national regulators. Sixth, the focus is on protecting consumers and investors and countering money laundering and the financing of terrorism. Seventh, there is an understanding based on a common approach by central banks to new financial technologies and cybersecurity.
Research Progress and Hotspot Analysis of Urban Heat Island Effects Based on Cite Space Analysis
Authors: Liu Yan , Wang Zhijie
Published: May 2023

The urban heat island (UHI) effect has become a hot topic in the global urban ecological environment. Research on the UHI effect is of great significance for alleviating urban environmental problems. Therefore, it has attracted the extensive attention of a large number of researchers in the field of urban environmental issues, such as urban ecologists, urban climatologists, urban planners, geographers, relevant policy makers, etc. However, systematic reviews are lacking on UHI research in the context of rapid urbanization and global change in recent years. In this study, we used Cite Space software to analyze the development process and current situation of UHI research from multiple perspectives during 2008–2021, aiming to reveal research hotspots and predict future trends. We found that UHI has gradually become a multidisciplinary field, and has existed in a flourishing period since 2008 with the rapid development of a number of publications. A large amount of research has been carried out by relevant institutions and scholars in 85 countries from 2008 to 2021. The hotspot research frontier focuses on the influencing factors, mitigation measures, and quantitative analysis of the UHI effect. Based on these trends and the status of the field, we proposed further research directions to promote interdisciplinary integration, optimize quantitative monitoring methods, strengthen the impact of three-dimensional urban landscape and vegetation landscape patterns, and expand the study of the urban agglomeration scale. Our results provide a valuable reference and potential frontier for future research in the field of the UHI effect.