bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Role of Contingent Negative Variation (CNV) in Migraine: A Review of Electrophysiological Studies in Adults and Children
Authors: de Lahoz María E. , Barjola Paloma , Peláez Irene , Ferrera David , Fernandes-Magalhaes Roberto , Mercado Francisco
Published: November 2023

Migraine has been considered a chronic neuronal-based pain disorder characterized by the presence of cortical hyperexcitability. The Contingent Negative Variation (CNV) is the most explored electrophysiological index in migraine. However, the findings show inconsistencies regarding its functional significance. To address this, we conducted a review in both adults and children with migraine without aura to gain a deeper understanding of it and to derive clinical implications. The literature search was conducted in the PubMed, SCOPUS and PsycINFO databases until September 2022m and 34 articles were retrieved and considered relevant for further analysis. The main results in adults showed higher CNV amplitudes (with no habituation) in migraine patients. Electrophysiological abnormalities, particularly focused on the early CNV subcomponent (eCNV), were especially prominent a few days before the onset of a migraine attack, normalizing during and after the attack. We also explored various modulatory factors, including pharmacological treatments—CNV amplitude was lower after the intake of drugs targeting neural hyperexcitability—and other factors such as psychological, hormonal or genetic/familial influences on CNV. Although similar patterns were found in children, the evidence is particularly scarce and less consistent, likely due to the brain’s maturation process during childhood. As the first review exploring the relationship between CNV and migraine, this study supports the role of the CNV as a potential neural marker for migraine pathophysiology and the prediction of pain attacks. The importance of further exploring the relationship between this neurophysiological index and childhood migraine is critical for identifying potential therapeutic targets for managing migraine symptoms during its development.
The Evolvement of OCT and OCT-A in Identifying Multiple Sclerosis Biomarkers
Authors: Donica Vlad Constantin , Alexa Anisia Iuliana , Pavel Irina Andreea , Danielescu Ciprian , Ciapă Manuela Andreea , Donica Alexandra Lori , Bogdănici Camelia Margareta
Published: November 2023

The prevalence of multiple sclerosis (MS) has been increasing among young people in developing countries over the last years. With the continuous development of new technology, the diagnosis and follow-up of these patients has received new parameters that physicians may use in their practice. This paper reviews the main biomarkers identified through Optical Coherence Tomography Angiography (OCT-A) involved in the development and progression of MS and investigates the role it may have in detecting changes to the central nervous system (CNS).
Drosophila as a Rapid Screening Model to Evaluate the Hypoglycemic Effects of Dipeptidyl Peptidase 4 (DPP4) Inhibitors: High Evolutionary Conservation of DPP4
Authors: Lagunas-Rangel Francisco Alejandro , Liao Sifang , Williams Michael J. , Trukhan Vladimir , Fredriksson Robert , Schiöth Helgi B.
Published: November 2023

Dipeptidyl peptidase 4 (DPP4) inhibitors, commonly known as gliptins, have been an integral part of the treatment of type 2 diabetes mellitus (T2DM) for several years. Despite their remarkable efficacy in lowering glucose levels and their compatibility with other hypoglycemic drugs, recent studies have revealed adverse effects, prompting the search for improved drugs within this category, which has required the use of animal models to verify the hypoglycemic effects of these compounds. Currently, in many countries the use of mammals is being significantly restricted, as well as cost prohibitive, and alternative in vivo approaches have been encouraged. In this sense, Drosophila has emerged as a promising alternative for several compelling reasons: it is cost-effective, offers high experimental throughput, is genetically manipulable, and allows the assessment of multigenerational effects, among other advantages. In this study, we present evidence that diprotin A, a DPP4 inhibitor, effectively reduces glucose levels in Drosophila hemolymph. This discovery underscores the potential of Drosophila as an initial screening tool for novel compounds directed against DPP4 enzymatic activity.
Alveolar Type 2 Epithelial Cell Organoids: Focus on Culture Methods
Authors: Jain Krishan Gopal , Xi Nan Miles , Zhao Runzhen , Ahmad Waqas , Ali Gibran , Ji Hong-Long
Published: November 2023

Lung diseases rank third in terms of mortality and represent a significant economic burden globally. Scientists have been conducting research to better understand respiratory diseases and find treatments for them. An ideal in vitro model must mimic the in vivo organ structure, physiology, and pathology. Organoids are self-organizing, three-dimensional (3D) structures originating from adult stem cells, embryonic lung bud progenitors, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). These 3D organoid cultures may provide a platform for exploring tissue development, the regulatory mechanisms related to the repair of lung epithelia, pathophysiological and immunomodulatory responses to different respiratory conditions, and screening compounds for new drugs. To create 3D lung organoids in vitro, both co-culture and feeder-free methods have been used. However, there exists substantial heterogeneity in the organoid culture methods, including the sources of AT2 cells, media composition, and feeder cell origins. This article highlights the currently available methods for growing AT2 organoids and prospective improvements to improve the available culture techniques/conditions. Further, we discuss various applications, particularly those aimed at modeling human distal lung diseases and cell therapy.
GLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer’s Disease Therapy
Authors: Złotek Magdalena , Kurowska Antonina , Herbet Mariola , Piątkowska-Chmiel Iwona
Published: November 2023

Alzheimer’s is a prevalent, progressive neurodegenerative disease marked by cognitive decline and memory loss. The disease’s development involves various pathomechanisms, including amyloid-beta accumulation, neurofibrillary tangles, oxidative stress, inflammation, and mitochondrial dysfunction. Recent research suggests that antidiabetic drugs may enhance neuronal survival and cognitive function in diabetes. Given the well-documented correlation between diabetes and Alzheimer’s disease and the potential shared mechanisms, this review aimed to comprehensively assess the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as promising therapeutic approaches for Alzheimer’s disease. This review aims to comprehensively assess the potential therapeutic applications of novel-generation antidiabetic drugs, including GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, in the context of Alzheimer’s disease. In our considered opinion, antidiabetic drugs offer a promising avenue for groundbreaking developments and have the potential to revolutionize the landscape of Alzheimer’s disease treatment.
Biomimetic Systems Involving Macrophages and Their Potential for Targeted Drug Delivery
Authors: Savchenko Ivan V. , Zlotnikov Igor D. , Kudryashova Elena V.
Published: November 2023

The concept of targeted drug delivery can be described in terms of the drug systems’ ability to mimic the biological objects’ property to localize to target cells or tissues. For example, drug delivery systems based on red blood cells or mimicking some of their useful features, such as long circulation in stealth mode, have been known for decades. On the contrary, therapeutic strategies based on macrophages have gained very limited attention until recently. Here, we review two biomimetic strategies associated with macrophages that can be used to develop new therapeutic modalities: first, the mimicry of certain types of macrophages (i.e., the use of macrophages, including tumor-associated or macrophage-derived particles as a carrier for the targeted delivery of therapeutic agents); second, the mimicry of ligands, naturally absorbed by macrophages (i.e., the use of therapeutic agents specifically targeted at macrophages). We discuss the potential applications of biomimetic systems involving macrophages for new advancements in the treatment of infections, inflammatory diseases, and cancer.
Some Mechanical Constraints to the Biomimicry with Peripheral Nerves
Authors: Sergi Pier Nicola
Published: November 2023

Novel high technology devices built to restore impaired peripheral nerves should be biomimetic in both their structure and in the biomolecular environment created around regenerating axons. Nevertheless, the structural biomimicry with peripheral nerves should follow some basic constraints due to their complex mechanical behaviour. However, it is not currently clear how these constraints could be defined. As a consequence, in this work, an explicit, deterministic, and physical-based framework was proposed to describe some mechanical constraints needed to mimic the peripheral nerve behaviour in extension. More specifically, a novel framework was proposed to investigate whether the similarity of the stress/strain curve was enough to replicate the natural nerve behaviour. An original series of computational optimizing procedures was then introduced to further investigate the role of the tangent modulus and of the rate of change of the tangent modulus with strain in better defining the structural biomimicry with peripheral nerves.
Development of Bioactive Scaffolds for Orthopedic Applications by Designing Additively Manufactured Titanium Porous Structures: A Critical Review
Authors: Kiselevskiy Mikhail V. , Anisimova Natalia Yu. , Kapustin Alexei V. , Ryzhkin Alexander A. , Kuznetsova Daria N. , Polyakova Veronika V. , Enikeev Nariman A.
Published: November 2023

We overview recent findings achieved in the field of model-driven development of additively manufactured porous materials for the development of a new generation of bioactive implants for orthopedic applications. Porous structures produced from biocompatible titanium alloys using selective laser melting can present a promising material to design scaffolds with regulated mechanical properties and with the capacity to be loaded with pharmaceutical products. Adjusting pore geometry, one could control elastic modulus and strength/fatigue properties of the engineered structures to be compatible with bone tissues, thus preventing the stress shield effect when replacing a diseased bone fragment. Adsorption of medicals by internal spaces would make it possible to emit the antibiotic and anti-tumor agents into surrounding tissues. The developed internal porosity and surface roughness can provide the desired vascularization and osteointegration. We critically analyze the recent advances in the field featuring model design approaches, virtual testing of the designed structures, capabilities of additive printing of porous structures, biomedical issues of the engineered scaffolds, and so on. Special attention is paid to highlighting the actual problems in the field and the ways of their solutions.
A Review on Motor Imagery with Transcranial Alternating Current Stimulation: Bridging Motor and Cognitive Welfare for Patient Rehabilitation
Authors: Lim Rosary Yuting , Ang Kai Keng , Chew Effie , Guan Cuntai
Published: November 2023

Research has shown the effectiveness of motor imagery in patient motor rehabilitation. Transcranial electrical stimulation has also demonstrated to improve patient motor and non-motor performance. However, mixed findings from motor imagery studies that involved transcranial electrical stimulation suggest that current experimental protocols can be further improved towards a unified design for consistent and effective results. This paper aims to review, with some clinical and neuroscientific findings from literature as support, studies of motor imagery coupled with different types of transcranial electrical stimulation and their experiments onhealthy and patient subjects. This review also includes the cognitive domains of working memory, attention, and fatigue, which are important for designing consistent and effective therapy protocols. Finally, we propose a theoretical all-inclusive framework that synergizes the three cognitive domains with motor imagery and transcranial electrical stimulation for patient rehabilitation, which holds promise of benefiting patients suffering from neuromuscular and cognitive disorders.
The Role of Endoscopy in the Palliation of Pancreatico-Biliary Cancers: Biliary Drainage, Management of Gastrointestinal Obstruction, and Role in Relief of Oncologic Pain
Authors: Rizzo Giacomo Emanuele Maria , Carrozza Lucio , Rancatore Gabriele , Binda Cecilia , Fabbri Carlo , Anderloni Andrea , Tarantino Ilaria
Published: November 2023

Therapeutic endoscopy permits many and various treatments for cancer palliation in patients with bilio-pancreatic cancers, enabling different options, supporting patients during their route to oncologic treatments, and trying to improve their quality of life. Therefore, both endoscopic and endoscopic ultrasound (EUS)-guided techniques are performed in this scenario. We performed a literature review focusing on the role of endoscopy in the palliation of those advanced pancreatic and biliary cancers developing malignant biliary obstruction (MBO), gastric outlet obstruction (GOO), and pain unresponsive to medical therapies. Therefore, we explored and focused on the clinical outcomes of endoscopic procedures in this scenario. In fact, the endoscopic treatment is based on achieving biliary drainage in the case of MBO through endoscopic retrograde cholangiopancreatography (ERCP) or EUS-guided biliary drainage (EUS-BD), while GOO is endoscopically treated through the deployment of an enteral stent or the creation of EUS-guided gastro-entero-anastomosis (EUS-GEA). Furthermore, untreatable chronic abdominal pain is a major issue in patients unresponsive to high doses of painkillers, so EUS-guided celiac plexus neurolysis (CPN) or celiac ganglia neurolysis (CGN) helps to reduce dosage and have better pain control. Therefore, therapeutic endoscopy in the palliative setting is an effective and safe approach for managing most of the clinical manifestations of advanced biliopancreatic tumors.
Prognostic Potential of Galectin-9 mRNA Expression in Chronic Lymphocytic Leukemia
Authors: Bojarska-Junak Agnieszka , Kowalska Wioleta , Chocholska Sylwia , Szymańska Agata , Tomczak Waldemar , Zarobkiewicz Michał Konrad , Roliński Jacek
Published: November 2023

Galectin-9 (Gal-9), very poorly characterized in chronic lymphocytic leukemia (CLL), was chosen in our study to examine its potential role as a CLL biomarker. The relation of Gal-9 expression in malignant B-cells and other routinely measured CLL markers, as well as its clinical relevance are poorly understood. Gal-9 mRNA expression was quantified with RT-qPCR in purified CD19+ B-cells of 100 CLL patients and analyzed in the context of existing clinical data. Our results revealed the upregulation of Gal-9 mRNA in CLL cells. High Gal-9 mRNA expression was closely associated with unfavorable prognostic markers. In addition, Gal-9 expression in leukemic cells was significantly elevated in CLL patients who did not respond to the first-line therapy compared to those who did respond. This suggests its potential predictive value. Importantly, Gal-9 was an independent predictor for the time to treatment parameters. Thus, we can suggest an adverse role of Gal-9 expression in CLL. Interestingly, it is possible that Gal-9 expression is induced in B-cells by EBV infection, so we determined the patients’ EBV status. Our suggestion is that EBV coinfection could worsen prognosis in CLL, partly due to Gal-9 expression upregulation caused by EBV.
Differentiation of Hepatocellular Carcinoma from Intrahepatic Cholangiocarcinoma through MRI Radiomics
Authors: Liu Ning , Wu Yaokun , Tao Yunyun , Zheng Jing , Huang Xiaohua , Yang Lin , Zhang Xiaoming
Published: November 2023

The purpose of this study was to investigate the efficacy of magnetic resonance imaging (MRI) radiomics in differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC). The clinical and MRI data of 129 pathologically confirmed HCC patients and 48 ICC patients treated at the Affiliated Hospital of North Sichuan Medical College between April 2016 and December 2021 were retrospectively analyzed. The patients were randomly divided at a ratio of 7:3 into a training group of 124 patients (90 with HCC and 34 with ICC) and a validation group of 53 patients (39 with HCC and 14 with ICC). Radiomic features were extracted from axial fat suppression T2-weighted imaging (FS-T2WI) and axial arterial-phase (AP) and portal-venous-phase (PVP) dynamic-contrast-enhanced MRI (DCE-MRI) sequences, and the corresponding datasets were generated. The least absolute shrinkage and selection operator (LASSO) method was used to select the best radiomic features. Logistic regression was used to establish radiomic models for each sequence (FS-T2WI, AP and PVP models), a clinical model for optimal clinical variables (C model) and a joint radiomics model (JR model) integrating the radiomics features of all the sequences as well as a radiomics–clinical model combining optimal radiomic features and clinical risk factors (RC model). The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUC). The AUCs of the FS-T2WI, AP, PVP, JR, C and RC models for distinguishing HCC from ICC were 0.693, 0.863, 0.818, 0.914, 0.936 and 0.977 in the training group and 0.690, 0.784, 0.727, 0.802, 0.860 and 0.877 in the validation group, respectively. The results of this study suggest that MRI-based radiomics may help noninvasively differentiate HCC from ICC. The model integrating the radiomics features and clinical risk factors showed a further improvement in performance.
Antitumor Activity of Axitinib in Lung Carcinoids: A Preclinical Study
Authors: Dicitore Alessandra , Gaudenzi Germano , Carra Silvia , Cantone Maria Celeste , Oldani Monica , Saronni Davide , Borghi Maria Orietta , Grotteschi Jacopo , Persani Luca , Vitale Giovanni
Published: November 2023

Lung carcinoids (LCs) comprise well-differentiated neuroendocrine tumors classified as typical (TCs) and atypical (ACs) carcinoids. Unfortunately, curative therapies remain elusive for metastatic LCs, which account for 25–30% of cases. This study evaluated the antitumor activity of axitinib (AXI), a second-generation tyrosine kinase inhibitor selectively targeting vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3) in human lung TC (NCI-H727, UMC-11, NCI-H835) and AC (NCI-H720) cell lines. In vitro and in vivo (zebrafish) assays were performed following AXI treatment to gather several read-outs about cell viability, cell cycle, the secretion of proangiogenic factors, apoptosis, tumor-induced angiogenesis and migration. AXI demonstrated relevant antitumor activity in human LC cells, with pronounced effects observed in UMC-11 and NCI-H720, characterized by cell cycle perturbation and apoptosis induction. AXI significantly hindered tumor induced-angiogenesis in Tg(fli1a:EGFP)y1 zebrafish embryos implanted with all LC cell lines and also reduced the invasiveness of NCI-H720 cells, as well as the secretion of several proangiogenic factors. In conclusion, our study provides initial evidence supporting the potential anti-tumor activity of AXI in LC, offering a promising basis for future investigations in mammalian animal models and, eventually, progressing to clinical trials.
The Role of Anticoagulation in Tumor Thrombus Associated with Renal Cell Carcinoma: A Literature Review
Authors: Williams Chelsey M. , Myint Zin W.
Published: November 2023

Tumor thrombus (TT) is a complication of renal cell carcinoma (RCC) for which favorable medical management remains undefined. While radical nephrectomy has been shown to increase overall survival in RCC patients, surgical interventions such as cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) utilized to perform TT resection carry high mortality rates. While it has been documented that RCC with TT is associated with venous thromboembolism (VTE) development, anticoagulation use in these patients remains controversial in clinical practice. Whether anticoagulation is associated with improved survival outcomes remains unclear. Furthermore, if anticoagulation is initiated, there is limited evidence for whether direct oral anticoagulants (DOACs), heparin, or warfarin serve as the most advantageous choice. While the combination of immunotherapy and tyrosine kinase inhibitors (TKIs) has been shown to improve the outcomes of RCC, the clinical benefits of this combination are not well studied prospectively in cases with TT. In this literature review, we explore the challenges of treating RCC-associated TT with special attention to anticoagulation. We provide a comprehensive overview of current surgical and medical approaches and summarize recent studies investigating anticoagulation in RCC patients undergoing surgery, targeted therapy, and/or immunotherapy. Our goal is to provide clinicians with updated clinical insight into anticoagulation for RCC-associated TT patients.
A Systematic Review and Meta-Analysis of the Impact of Cancer and Its Treatment Protocol on the Success of Orthodontic Treatment
Authors: Alam Mohammad Khursheed , Awawdeh Mohammed , Khanagar Sanjeev B. , Aboelmaaty Wael , Abutayyem Huda , Alswairki Haytham Jamil , Alfawzan Ahmed Ali , Hajeer Mohammad Younis
Published: November 2023

Background: There are several significant gaps in current studies of the relationship between anti-cancer medications and orthodontic care that call for more investigation. As a result, the main goals of this systematic review and meta-analysis were to summarise and assess the information that was available regarding the effect of radiotherapy and anti-cancer medications on the overall successful completion of an orthodontic treatment plan. Methods: A standardised data extraction form was devised in accordance with the PRISMA guidelines to conduct a systematic review and meta-analysis, with specific criteria implemented for selecting studies with low to moderate risk of bias. Results: Five studies involving different methodologies were selected at the conclusion of the search strategy. The statistical analysis revealed an estimated odds ratio (OR) of 0.31 and relative risk (RR) of 0.48, indicating a statistically significant association between the use of radiotherapy and anti-neoplastic drugs and a noticeable reduction in the successful completion of orthodontic treatment. The heterogeneity analysis showed significant heterogeneity among the studies. Conclusions: This review emphasises that, although orthodontic therapies can still be beneficial for children receiving chemotherapy, the effectiveness of the therapy may be diminished in older populations. The findings further highlight how crucial it is to take cancer therapies into account when planning and managing orthodontic treatment in order to optimise results and reduce problems.
Rapid On-Site AI-Assisted Grading for Lung Surgery Based on Optical Coherence Tomography
Authors: Liu Hung-Chang , Lin Miao-Hui , Chang Wei-Chin , Zeng Rui-Cheng , Wang Yi-Min , Sun Chia-Wei
Published: November 2023

The determination of resection extent traditionally relies on the microscopic invasiveness of frozen sections (FSs) and is crucial for surgery of early lung cancer with preoperatively unknown histology. While previous research has shown the value of optical coherence tomography (OCT) for instant lung cancer diagnosis, tumor grading through OCT remains challenging. Therefore, this study proposes an interactive human–machine interface (HMI) that integrates a mobile OCT system, deep learning algorithms, and attention mechanisms. The system is designed to mark the lesion’s location on the image smartly and perform tumor grading in real time, potentially facilitating clinical decision making. Twelve patients with a preoperatively unknown tumor but a final diagnosis of adenocarcinoma underwent thoracoscopic resection, and the artificial intelligence (AI)-designed system mentioned above was used to measure fresh specimens. Results were compared to FSs benchmarked on permanent pathologic reports. Current results show better differentiating power among minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and normal tissue, with an overall accuracy of 84.9%, compared to 20% for FSs. Additionally, the sensitivity and specificity, the sensitivity and specificity were 89% and 82.7% for MIA and 94% and 80.6% for IA, respectively. The results suggest that this AI system can potentially produce rapid and efficient diagnoses and ultimately improve patient outcomes.
Doxorubicin-Induced Cardiac Senescence Is Alleviated Following Treatment with Combined Polyphenols and Micronutrients through Enhancement in Mitophagy
Authors: Foglio Eleonora , D’Avorio Erica , Vitiello Laura , Masuelli Laura , Bei Roberto , Pacifici Francesca , Della-Morte David , Mirabilii Simone , Ricciardi Maria Rosaria , Tafuri Agostino , Garaci Enrico , Russo Matteo Antonio , Tafani Marco , Limana Federica
Published: November 2023

Oxidative stress and impaired mitophagy are the hallmarks of cardiomyocyte senescence. Specifically, a decrease in mitophagic flux leads to the accumulation of damaged mitochondria and the development of senescence through increased ROS and other mediators. In this study, we describe the preventive role of A5+, a mix of polyphenols and other micronutrients, in doxorubicin (DOXO)-induced senescence of H9C2 cells. Specifically, H9C2 cells exposed to DOXO showed an increase in the protein expression proteins of senescence-associated genes, p21 and p16, and a decrease in the telomere binding factors TRF1 and TRF2, indicative of senescence induction. Nevertheless, A5+ pre-treatment attenuated the senescent-like cell phenotype, as evidenced by inhibition of all senescent markers and a decrease in SA-β-gal staining in DOXO-treated H9C2 cells. Importantly, A5+ restored the LC3 II/LC3 I ratio, Parkin and BNIP3 expression, therefore rescuing mitophagy, and decreased ROS production. Further, A5+ pre-treatment determined a ripolarization of the mitochondrial membrane and improved basal respiration. A5+-mediated protective effects might be related to its ability to activate mitochondrial SIRT3 in synergy with other micronutrients, but in contrast with SIRT4 activation. Accordingly, SIRT4 knockdown in H9C2 cells further increased MnSOD activity, enhanced mitophagy, and reduced ROS generation following A5+ pre-treatment and DOXO exposure compared to WT cells. Indeed, we demonstrated that A5+ protects H9C2 cells from DOXO-induced senescence, establishing a new specific role for A5+ in controlling mitochondrial quality control by restoring SIRT3 activity and mitophagy, which provided a molecular basis for the development of therapeutic strategies against cardiomyocyte senescence.
Age Is Just a Number: Progress and Obstacles in the Discovery of New Candidate Drugs for Sarcopenia
Authors: Kim Hyun-Jun , Jung Da-Woon , Williams Darren Reece
Published: November 2023

Sarcopenia is a disease characterized by the progressive loss of skeletal muscle mass and function that occurs with aging. The progression of sarcopenia is correlated with the onset of physical disability, the inability to live independently, and increased mortality. Due to global increases in lifespan and demographic aging in developed countries, sarcopenia has become a major socioeconomic burden. Clinical therapies for sarcopenia are based on physical therapy and nutritional support, although these may suffer from low adherence and variable outcomes. There are currently no clinically approved drugs for sarcopenia. Consequently, there is a large amount of pre-clinical research focusing on discovering new candidate drugs and novel targets. In this review, recent progress in this research will be discussed, along with the challenges that may preclude successful translational research in the clinic. The types of drugs examined include mitochondria-targeting compounds, anti-diabetes agents, small molecules that target non-coding RNAs, protein therapeutics, natural products, and repositioning candidates. In light of the large number of drugs and targets being reported, it can be envisioned that clinically approved pharmaceuticals to prevent the progression or even mitigate sarcopenia may be within reach.
Recent Advances in the Preparation and Application of DNA-Encoded Metal Nanoclusters
Authors: Yin Fang , Ren Jiangtao , Wang Erkang
Published: November 2023

DNA as an intriguing organic ligand has been widely employed for synthesizing metal nanoclusters and engineering their properties. This review aims to present recent progress on DNA-encoded metal (Ag, Cu, Au, Ag/Pt, Cu/Ag, etc.) nanoclusters (DNA-MNCs), focusing on their applications in the fields of analysis, logic operation, and therapy based on properties including fluorescence, electrochemiluminescence (ECL), and antibacterial and catalytic activity, and summarizes the attractive features of the latest research. The key points are briefly described as follows. (1) Analytical systems have been constructed based on fluorescence regulation, and nuclease-assisted and enzyme-free amplification strategies have been extensively adopted with fluorescent DNA-MNCs for amplified analysis. (2) DNA-MNCs may play more than one role (emitter, quencher, or catalyst) in ECL-based analytical systems. (3) Apart from antibacterial activity, DNA-MNCs also possess apparent catalytic capability, such as enzyme-like activity (i.e., nanozymes), which has been applied in colorimetric systems. (4) Reversibly regulating the catalytic activity of DNA-MNCs has been attained with DNA systems. It is believed that through in-depth investigation of the relationship between atomic structure and property, more novel DNA-MNCs will be explored and applied in the future.
Teachers’ and Parents’ Assessment of Challenges in Children Exhibiting Sensory Seeking Behavior and Possible Effects of the Use of Ball Vests: A Pre–Post Study
Authors: Nielsen Ann Natasja , la Cour Karen , Brandt Åse
Published: November 2023

Children with dysfunction in sensory processing (DSP) may experience challenges, which might affect their participation in activities and potentially also their further development. This study examined the challenges of children with DSP who exhibit sensory seeking behavior, the differences in these challenges between boys and girls, and the possible effects of their use of ball vests. The challenges of 70 pupils (aged 6–12 years) exhibiting sensory seeking behavior were assessed by their parents (n = 66) and teachers (n = 60) by surveys containing items from the ‘Strengths and Difficulties Questionnaire’ (SDQ) and the ‘Five to Fifteen’ (FTF) questionnaire. Differences in the SDQ/FTF scores between boys and girls were explored using chi-square analysis. The potential effects of the ball vest were assessed using a study-specific follow-up survey. Linear mixed model regression analysis was used to examine associations between the extent of use of the vest and the assessed effects. The pupils were assessed for challenges that interfered with their learning (62%), forming friendships (51.7%), and the classroom environment (56.9%). After three weeks, the parents found that some pupils had improved regarding attention (39%), body perception (34%), and hyperactivity and impulsivity (33%). The teachers reported that 30% of the pupils had improved their coping skills in learning.
Comment on Shaniv et al. Neonatal Drug Formularies—A Global Scope. Children 2023, 10, 848
Authors: Giger Elisabeth V. , Tilen Romy
Published: November 2023

We read the article by Shaniv D. et al. entitled “Neonatal Drug Formularies—A Global Scope” [...]
Effects of Top Ceramic Layers with an Ultrathin Dense Layer on the Thermal–Physical Properties of Thermal Barrier Coatings
Authors: Ai Li , Wang Xueying , Yang Ming , Lei Yuntao , Zhu Yongping
Published: November 2023

Thermal barrier coatings have been used to protect superalloys under extremely harsh conditions. The durability of TBCs with a NiCoCrAlY bond layer prepared via the air plasma spray process and an ultrathin dense layer prepared via magnetron sputtering was investigated under different corrosion conditions. This paper discusses the corrosion resistance improvement mechanism of TBCs with a dense layer produced by magnetron sputtering under corrosion conditions with environmental contaminants such as calcium–magnesium–aluminum–silicon oxide systems (CMAS) at 1300 °C and NaCl-Na2SO4-V2O5 (NV) at 900 °C. The corrosion results show that CMAS will react with the stabilizers of zirconium oxide, which will change the rate of the phase transition, as determined via X-ray diffraction tests. A thermal ablation test verified that TBCs with a dense layer have a better corrosion resistance and better thermal insulation properties. All results show that preparing TBCs with a dense layer via the magnetron sputtering method will be an efficient method to improve TBCs’ properties at high temperatures in the future.
Effects of Base Metal Preheating on the Microstructure, Mechanical Properties, and Corrosion Resistance of UNS S32750 SDSS Pulsed Nd:YAG Laser Welding
Authors: da Cruz Junior Eli J. , Varasquim Francisco M. F. A. , Crespo Gillian S. , Ventrella Vicente. A. , Zambon Andrea , Calliari Irene
Published: November 2023

Super duplex stainless steel has a microstructure consisting of equal proportions of austenite and ferrite. However, welding with Nd:YAG pulsed laser results in an imbalanced microstructure that compromises the steel’s properties. This paper studied the effects of preheating the base metal on pulsed Nd:YAG laser welding. Four conditions were evaluated (no preheating and heating at 100 °C, 200 °C, and 300 °C). The analysis included studying the microstructure, microhardness, and corrosion resistance. Preheating the base metals was found to be an effective method for increasing the volume fractions of austenite. The preheated samples showed an improvement in corrosion resistance compared to the untreated sample. The microhardness varied, with the ferrite amount being higher in the untreated sample.
Discharge Characteristics and Mechanisms of Electrolytic Discharge Processing by Jet Mask
Authors: Chen Chaoda , Wu Shaofang , Wu Hao , Shan Liang , Li Kangxing , Wu Siyang
Published: November 2023

As a novel microfabrication method, electrochemical discharge machining has remarkable effects on the forming and processing of brittle and hard materials and non-conductive materials, but little research has been done on the electrochemical discharge mode in the jet state. To fulfil the potential of this technology, innovative research on the discharge characteristics and mechanism of electrochemical discharge machining in the jet mask is proposed. A high-speed camera observation experiment was set up to record the process of the jet flow column discharge formation and penetration. Changes in the electric field of the electrolytic jet channel were analysed by simulation software, and the morphology of the machined micro-pits was observed using a microscope. A mathematical derivation of the dielectric electric field in the gas–liquid two-phase jet column reveals the mechanism of discharge channel formation in the jet state. The experiments show that when the processing voltage is 400 V, a stable continuous spark appears, realizing the unique characteristics of a large-gap long-distance discharge and a flat small circle-shaped discharge mark produced at the bottom of the crater. The actual field strength within the bubble of this model obtained by mathematical derivation is approximately 61.5 kV/cm greater than the critical field strength for air bubble breakdown in the standard state, where bubble breakdown occurs in the discharge.
Effects of High Temperature and Different Salt Solutions on Basalt Fiber-Reinforced Composites’ Bonded Joint Durability Impact
Authors: Peng Han , Lin Yinghao , Chen Zeshao , Ma Shengtao , Shangguan Linjian , Cheng Ruixue , Fan Yisa
Published: November 2023

Fiber-reinforced composites are widely used in industrial development due to their excellent performance, and the study of basalt fiber-reinforced resin (BFRP) as a new type of economical and environmentally friendly material is highly valued, since harsh environments can affect the durability of bonded joints. In this paper, the Araldite® 2015 adhesive for BFRP–BFRP single lap joints (SLJs) was selected as the subject of study and the joints were analyzed in aging experiments in three environments: deionized water (DW), 3.5% NaCl solution, and 5% NaCl solution at 80 °C for 0 days (no aging), 10 days, 20 days, and 30 days. Using Fick’s second law to describe water absorption in joints and materials, the comparison shows that the water absorption in the joints occurs primarily in the adhesive. Differential scanning calorimetry (DSC) was used to characterize the decrease in the glass transition temperature (Tg) of the adhesive at each failure point, and the thermogravimetric analysis (TGA) tests showed that moisture and heat led to the degradation of the polymer material in the joint. The failure strength of the joints in quasi-static tensile tests was positively correlated with the moisture content of the solution, and the changes in the absorption peaks of the functional groups of the adhesive after aging were observed. The comprehensive macro-micro failed section analysis showed that the water molecules damage the chemical properties of the adhesive, meaning that the adhesive and BFRP binding ability is decreased. The proportion of failure section tear decreased with the extension of the aging time, and a high temperature induced water evaporation and an adhesive post-curing reaction. The change in the failure mode is a result of the combined effect of the post-curing effect and hydrolysis reaction, which is validated by the results of the Fourier infrared spectroscopy (FTIR). This study contributes to an in-depth understanding of the effect of moisture and heat on the residual properties of bonded joints.
EEG-Based Classification of Spoken Words Using Machine Learning Approaches
Authors: Alonso-Vázquez Denise , Mendoza-Montoya Omar , Caraza Ricardo , Martinez Hector R. , Antelis Javier M.
Published: November 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the nerve cells in the brain and spinal cord. This condition leads to the loss of motor skills and, in many cases, the inability to speak. Decoding spoken words from electroencephalography (EEG) signals emerges as an essential tool to enhance the quality of life for these patients. This study compares two classification techniques: (1) the extraction of spectral power features across various frequency bands combined with support vector machines (PSD + SVM) and (2) EEGNet, a convolutional neural network specifically designed for EEG-based brain–computer interfaces. An EEG dataset was acquired from 32 electrodes in 28 healthy participants pronouncing five words in Spanish. Average accuracy rates of 91.04 ± 5.82% for Attention vs. Pronunciation, 73.91 ± 10.04% for Short words vs. Long words, 81.23 ± 10.47% for Word vs. Word, and 54.87 ± 14.51% in the multiclass scenario (All words) were achieved. EEGNet outperformed the PSD + SVM method in three of the four classification scenarios. These findings demonstrate the potential of EEGNet for decoding words from EEG signals, laying the groundwork for future research in ALS patients using non-invasive methods.
Adaptogen Technology for Skin Resilience Benefits
Authors: Cavagnino Andrea , Breton Lionel , Ruaux Charline , Grossgold Celeste , Levoy Suzy , Abdayem Rawad , Roumiguiere Romain , Cheilian Stephanie , Bouchara Anne , Baraibar Martin A. , Gueniche Audrey
Published: November 2023

(1) Background: Skin undergoes constant changes, providing capabilities to repair and renovate its constituents once damaged and a fundamental shield to contrast environmental stress. Nevertheless, environmental stressors may overcome the skin’s protective potential inducing premature aging and accelerating the appearance of anaesthetic age-related skin aspects. Ultraviolet radiation (UVR) and pollutants (particulate matters, PAHs) contribute to skin aging and functional decline inducing harmful oxidative modifications of macromolecules and stress-related skin disorders. Innovative approaches to preserve skin are needed. (2) Methods: Skin keratinocytes were treated (or not) with a combination of ingredients (Lactobacillus plantarum extract, Withania somnifera root extract and Terminalia ferdinandiana fruit extract; “MIX”) in the presence or absence of stress (oxidative stress or pollution). The effects of the MIX adaptogen technology on (a) cellular resilience, (b) the regulation of cellular functions and (c) regeneration of skin were disclosed through expression proteomics and bioinformatics analyses first, and then through focused evaluations of protein carbonylation as a hallmark of oxidative stress’ deleterious impact and mitochondrial activity. (3) Results: The deleterious impact of stressors was evidenced, as well as the beneficial effects of the MIX through (a) mitochondrial activity preservation, (b) the “vigilance” of the NRF2 pathway activation, (c) NADPH production and protein homeostasis improvements, (d) preserving skin regeneration function and I the contrasting stress-induced oxidation (carbonylation) of mitochondrial and nuclear proteins. (4) Conclusions: The effects of the MIX on increasing cell adaptability and resilience under stress suggested a beneficial contribution in precision cosmetics and healthy human skin by acting as an adaptogen, an innovative approach that may be employed to improve resistance to harmful stress with a potential favourable impact on skin homeostasis.
Hardware Implementations of Elliptic Curve Cryptography Using Shift-Sub Based Modular Multiplication Algorithms
Authors: Li Yamin
Published: November 2023

Elliptic curve cryptography (ECC) over prime fields relies on scalar point multiplication realized by point addition and point doubling. Point addition and point doubling operations consist of many modular multiplications of large operands (256 bits for example), especially in projective and Jacobian coordinates which eliminate the modular inversion required in affine coordinates for every point addition or point doubling operation. Accelerating modular multiplication is therefore important for high-performance ECC. This paper presents the hardware implementations of modular multiplication algorithms, including (1) interleaved modular multiplication (IMM), (2) Montgomery modular multiplication (MMM), (3) shift-sub modular multiplication (SSMM), (4) SSMM with advance preparation (SSMMPRE), and (5) SSMM with CSAs and sign detection (SSMMCSA) algorithms, and evaluates their execution time (the number of clock cycles and clock frequency) and required hardware resources (ALMs and registers). Experimental results show that SSMM is 1.80 times faster than IMM, and SSMMCSA is 3.27 times faster than IMM. We also present the ECC hardware implementations based on the Secp256k1 protocol in affine, projective, and Jacobian coordinates using the IMM, SSMM, SSMMPRE, and SSMMCSA algorithms, and investigate their cost and performance. Our ECC implementations can be applied to the design of hardware security module systems.
Unraveling the Effect of Compositional Ratios on the Kesterite Thin-Film Solar Cells Using Machine Learning Techniques
Authors: Karade Vijay , Sutar Santosh , Jang Jun , Gour Kuldeep , Shin Seung , Suryawanshi Mahesh , Kamat Rajanish , Dongale Tukaram , Kim Jin , Yun Jae
Published: November 2023

In the Kesterite family, the Cu2ZnSn(S,Se)4 (CZTSSe) thin-film solar cells (TFSCs) have demonstrated the highest device efficiency with non-stoichiometric cation composition ratios. These composition ratios have a strong influence on the structural, optical, and electrical properties of the CZTSSe absorber layer. So, in this work, a machine learning (ML) approach is employed to evaluate effect composition ratio on the device parameters of CZTSSe TFSCs. In particular, the bi-metallic ratios like Cu/Sn, Zn/Sn, Cu/Zn, and overall Cu/(Zn+Sn) cation composition ratio are investigated. To achieve this, different machine learning algorithms, such as decision trees (DTs) and classification and regression trees (CARTs), are used. In addition, the output performance parameters of CZTSSe TFSCs are predicted by both continuous and categorical approaches. Artificial neural networks (ANN) and XGBoost (XGB) algorithms are employed for the continuous approach. On the other hand, support vector machine and k-nearest neighbor’s algorithms are also used for the categorical approach. Through the analysis, it is observed that the DT and CART algorithms provided a critical composition range well suited for the fabrication of highly efficient CZTSSe TFSCs, while the XGB and ANN showed better prediction accuracy among the tested algorithms. The present work offers valuable guidance towards the integration of the ML approach with experimental studies in the field of TFSCs.
Normalized Difference Vegetation Index as a Proxy of Urban Bird Species Presence and Distribution at Different Spatial Scales
Authors: Kontsiotis Vasileios J. , Chatzigiovanakis Stavros , Valsamidis Evangelos , Xofis Panteleimon , Liordos Vasilios
Published: November 2023

Birds are important features of the urban landscape, offering valuable ecosystem services, such as physiological and psychological stress reduction, aesthetic pleasure, and education. Knowing the populations of bird species in cities is important for their successful conservation. The normalized difference vegetation index (NDVI) is a remotely sensed metric used as a green cover proxy. We estimated the abundance of 15 bird species in the urban green spaces of Kavala, Greece, and calculated the NDVI at 19 survey stations with three different spatial scales: 50 m, 200 m, and 500 m circular buffers. NDVI was shown to significantly affect the abundance of 13 species. The 50 m buffer best predicted the abundance of 4 species, the 200 m buffer predicted 7 species, and the 500 m buffer predicted 4 species. Abundance decreased with NDVI for 9 species (urban dwellers) and increased for 6 species (urban utilizers). These findings suggest that NDVI is a reliable predictor of the abundance of bird species in urban areas. More importantly, bird abundance and NDVI associations can be better described if determined at various spatial scales. These findings could be used for the prediction and monitoring of urban bird species populations and incorporated into urban conservation management plans.