bluuebunny/crossref_metadata_2025 huggingface dataset:
FAIR Health Informatics: A Health Informatics Framework for Verifiable and Explainable Data Analysis
Authors: Siddiqi Muhammad Hameed , Idris Muhammad , Alruwaili Madallah
Published: June 2023

The recent COVID-19 pandemic has hit humanity very hard in ways rarely observed before. In this digitally connected world, the health informatics and investigation domains (both public and private) lack a robust framework to enable rapid investigation and cures. Since the data in the healthcare domain are highly confidential, any framework in the healthcare domain must work on real data, be verifiable, and support reproducibility for evidence purposes. In this paper, we propose a health informatics framework that supports data acquisition from various sources in real-time, correlates these data from various sources among each other and to the domain-specific terminologies, and supports querying and analyses. Various sources include sensory data from wearable sensors, clinical investigation (for trials and devices) data from private/public agencies, personnel health records, academic publications in the healthcare domain, and semantic information such as clinical ontologies and the Medical Subject Heading ontology. The linking and correlation of various sources include mapping personnel wearable data to health records, clinical oncology terms to clinical trials, and so on. The framework is designed such that the data are Findable, Accessible, Interoperable, and Reusable with proper Identity and Access Mechanisms. This practically means to tracing and linking each step in the data management lifecycle through discovery, ease of access and exchange, and data reuse. We present a practical use case to correlate a variety of aspects of data relating to a certain medical subject heading from the Medical Subject Headings ontology and academic publications with clinical investigation data. The proposed architecture supports streaming data acquisition and servicing and processing changes throughout the lifecycle of the data management. This is necessary in certain events, such as when the status of a certain clinical or other health-related investigation needs to be updated. In such cases, it is required to track and view the outline of those events for the analysis and traceability of the clinical investigation and to define interventions if necessary.
Nursing Interventions in the Perioperative Pathway of the Patient with Breast Cancer: A Scoping Review
Authors: Cardoso Mafalda Martins , Baixinho Cristina Lavareda , Silva Gilberto Tadeu Reis , Ferreira Óscar
Published: June 2023

The decrease in average hospitalisation time and the increase in outpatient surgery in some types of breast cancer represent gains for the reduction of the negative impact of hospitalisation in women with breast cancer but are also a challenge for the organisation of nursing care to prepare women for surgery, reduce anxiety about the interventions, and ensure continuity of care in the postoperative period. The aim of this study is to identify nursing interventions present in the care provided to patients with breast cancer during the perioperative period. A scoping review was the method chosen to answer the research question: What are the specialised nursing interventions in the perioperative pathway of the patient with breast cancer? Inclusion and exclusion criteria were defined for the articles that were identified in the CINAHL and MEDLINE databases; later, additional sources were identified from the list of bibliographic references for each selected study. The final bibliographical sample consisted of seven articles, which allowed the identification of three key moments of nursing interventions in the perioperative period of patients with breast cancer: the preoperative consultation, the reception of the patient in the operating room, and the postoperative consultation. Factors such as psychological, emotional, and spiritual support, communication and patient-centred care, health education and surgical safety, and the definition of a perioperative pathway for these patients contribute significantly to patients’ satisfaction and the improvement of their quality of life. The results of this study make it possible to establish recommendations for practise and for research, increasing the range of nurses’ actions.
Genetic Diversity Analysis of Guangxi Kumquat (Fortunella Swing) Germplasm Using SRAP Markers
Authors: Liu Binghao , Ding Ping , Ye Rongchun , Li Yi , Ou Shanhan , Gentile Alessandra , Ma Xianfeng , Deng Ziniu
Published: June 2023

In order to understand the genetic diversity of germplasm resources of kumquats in Guangxi, 14 kumquat germplasm resources in Guangxi and 12 accessions from other provinces were analyzed by using SRAP markers. In total, 19 primer pairs with high stability, good reproducibility, and high polymorphism were chosen for analysis of all 26 kumquat genotypes. Among the 104 amplified bands, 90 (86.54%) were polymorphic. SRAP markers were analyzed by employing Principal Coordinate Analysis, Population Structure Analysis, and Hierarchical Cluster Analysis (UPGMA). The classification results showed that the 26 kumquat germplasm resources could be divided into 5 groups, including cultivated kumquat, intergeneric hybrid, wild kumquat from other provinces, wild kumquat, and hybrid kumquat from Guangxi. The Guangxi kumquat germplasm had high genetic diversity, and were clearly divided into three groups: cultivated kumquat, wild kumquat, and hybrid kumquat. Additionally, the eight cultivated kumquat varieties in Guangxi were further divided into two subgroups. Wild kumquat in Guangxi or in other provinces belonged to different groups; meanwhile, the Guangxi kumquat hybrid formed an independent group, thus indicating that Guangxi wild kumquat and hybrid kumquat possess certain specificity, or they possibly belong to different species. Among the tested 26 kumquat accessions, 23 unique genotype-specific SRAP markers were detected for 14 kumquat genotypes, which were positively identified. For the remaining 12 accessions without genotype-specific markers, they were distinguished by various combinations of markers. These results may have certain importance for kumquat genetic research and cultivar selection.
Medicinal Use, Flower Trade, Preservation and Mass Propagation Techniques of Cymbidium Orchids—An Overview
Authors: Balilashaki Khosro , Martinez-Montero Marcos Edel , Vahedi Maryam , Cardoso Jean Carlos , Silva Agurto Catherine Lizzeth , Leiva-Mora Michel , Feizi Fatemeh , Musharof Hossain Mohammad
Published: June 2023

Cymbidium is an economically important genus in the orchid family (Orchidaceae) that has a pronounced medicinal and ornamental value. Medicinally, the plant is employed as a tonic to treat weakness in chronic diseases, dizziness, eye problems, burns, and wounds, etc. Cymbidiums are highly prized for their graceful flowers and sweet fragrance and are among the top ten most popular cut flowers. They are one of the most important commercial orchid groups and account for 3% of cut flowers in floriculture. Some orchid species in this genus are particularly threatened by excessive harvesting, so conservation measures are needed. Several enthusiastic organizations (e.g., The Cymbidiums Society of America, The Cymbidiums Club in Australia, The Golden Gate Cymbidiums Society, Alameda, CA, etc.) are dedicated to propagating, conserving, promoting, appreciating, and disseminating information about these beautiful and charming orchids. Through organogenesis (direct and indirect) and somatic embryogenesis, extensive propagation techniques for Cymbidiums have been developed to create protocols for synthetic seed production leading to large-scale propagation and long-term ex situ and in vitro conservation. This review highlights the medicinal uses, flower trade, conservation, and massive propagation techniques of Cymbidium orchids.
Impacts of U.S. Stock Market Crash on South African Top Sector Indices, Volatility, and Market Linkages: Evidence of Copula-Based BEKK-GARCH Models
Authors: Mudiangombe Benjamin Mudiangombe , Muteba Mwamba John Weirstrass
Published: June 2023

This paper examines the effects of the Standard and Poor’s 500 (SP500) stock index crash during the global financial crisis and the COVID-19 pandemic periods on the South African top sector indices (basic materials, consumer goods, consumer services, financials, healthcare, industrials, technology, and telecommunication). The results of a copula-based BEKK-GARCH approach technique demonstrate the existence of price and volatility spillover during times of stock crashes. We discover that during a stock crisis, strong shocks and higher volatility spillover effects from the United States (U.S.) SP500 index to the top sector indices of the South African Johannesburg Stock Exchange (JSE) markets are more significant. However, there is no integrated economy, as the results did not show any spillover effects from South Africa to U.S. markets. Furthermore, the Gumbel copulas have higher dependence parameters, implying that extreme co-movements occur in the upper tails, suggesting the possibility of a large transmission of shocks from the SP500 to the eight top sector indices of the JSE and showing an asymmetric dependence between these markets. This result is important for investors willing to invest in the South African sector of equity markets to develop hedging strategies to prevent risk spillover from developed markets.
Reviewing the Regulators of COL1A1
Authors: Devos Hanne , Zoidakis Jerome , Roubelakis Maria G. , Latosinska Agnieszka , Vlahou Antonia
Published: June 2023

The collagen family contains 28 proteins, predominantly expressed in the extracellular matrix (ECM) and characterized by a triple-helix structure. Collagens undergo several maturation steps, including post-translational modifications (PTMs) and cross-linking. These proteins are associated with multiple diseases, the most pronounced of which are fibrosis and bone diseases. This review focuses on the most abundant ECM protein highly implicated in disease, type I collagen (collagen I), in particular on its predominant chain collagen type I alpha 1 (COLα1 (I)). An overview of the regulators of COLα1 (I) and COLα1 (I) interactors is presented. Manuscripts were retrieved searching PubMed, using specific keywords related to COLα1 (I). COL1A1 regulators at the epigenetic, transcriptional, post-transcriptional and post-translational levels include DNA Methyl Transferases (DNMTs), Tumour Growth Factor β (TGFβ), Terminal Nucleotidyltransferase 5A (TENT5A) and Bone Morphogenic Protein 1 (BMP1), respectively. COLα1 (I) interacts with a variety of cell receptors including integrinβ, Endo180 and Discoidin Domain Receptors (DDRs). Collectively, even though multiple factors have been identified in association to COLα1 (I) function, the implicated pathways frequently remain unclear, underscoring the need for a more spherical analysis considering all molecular levels simultaneously.
Lipidome Investigation of Carnosine Effect on Nude Mice Skin to Prevent UV-A Damage
Authors: Zoanni Beatrice , Aiello Gilda , Negre-Salvayre Anne , Aldini Giancarlo , Carini Marina , D’Amato Alfonsina
Published: June 2023

The lipid profile of skin is fundamental in the maintenance of the protective barrier against the external environment. Signaling and constitutive lipids of this large organ are involved in inflammation, metabolism, aging, and wound healing, such as phospholipids, triglycerides, FFA, and sphingomyelin. Skin exposure to ultraviolet (UV) radiation results in a photoaging process that is an accelerated form of aging. UV-A radiation deeply penetrates the dermis and promotes damage to DNA, lipids, and proteins by increasing the generation of reactive oxygen species (ROS). Carnosine, an endogenous β-alanyl-L-histidine dipeptide, demonstrated antioxidant properties that prevent photoaging and modification of skin protein profiling, making carnosine a compelling ingredient to consider for use in dermatology. The aim of this research was to investigate the modification of skin lipidome after UV-A treatment in presence or not of topic administration of carnosine. Quantitative analyses based on high-resolution mass spectrometry of nude mice skin-extracted lipids resulted in several modifications of barrier composition after UV-A radiation, with or without carnosine treatment. In total, 328 out of 683 molecules showed significant alteration—262 after UV-A radiation and 126 after UV-A and carnosine treatment versus controls. Importantly, the increased oxidized TGs after UV-A radiation, responsible of dermis photoaging, were completely reverted by carnosine application to prevent the UV-A damage. Network analyses also showed that the production of ROS and the calcium and TNF signaling were modulated by UV-A and carnosine. In conclusion, lipidome analyses attested the carnosine activity to prevent the UV-A damage, reducing the lipid oxidation, the inflammation, and the dysregulation of lipid skin barrier.
GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response
Authors: Lösch Lukas , Stemmler Albert , Fischer Adrian , Steinmetz Julia , Schuldt Lisa , Hennig Christoph-Ludwig , Symmank Judit , Jacobs Collin
Published: June 2023

Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including regulating local inflammation and activating further bone-remodeling cells. Previous studies suggested growth differentiation factor 15 (GDF15) as an important pro-inflammatory regulator during the PdLF mechanoresponse. GDF15 exerts its effects through both intracrine signaling and receptor binding, possibly even in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on the cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on the proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we observed altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLF differentiation and their mechanoresponse.
ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries
Authors: Jia Bowen , Li Jing , Song Yiting , Luo Chengliang
Published: June 2023

As an iron-dependent regulated form of cell death, ferroptosis is characterized by iron-dependent lipid peroxidation and has been implicated in the occurrence and development of various diseases, including nervous system diseases and injuries. Ferroptosis has become a potential target for intervention in these diseases or injuries in relevant preclinical models. As a member of the Acyl-CoA synthetase long-chain family (ACSLs) that can convert saturated and unsaturated fatty acids, Acyl—CoA synthetase long-chain familymember4 (ACSL4) is involved in the regulation of arachidonic acid and eicosapentaenoic acid, thus leading to ferroptosis. The underlying molecular mechanisms of ACSL4-mediated ferroptosis will promote additional treatment strategies for these diseases or injury conditions. Our review article provides a current view of ACSL4-mediated ferroptosis, mainly including the structure and function of ACSL4, as well as the role of ACSL4 in ferroptosis. We also summarize the latest research progress of ACSL4-mediated ferroptosis in central nervous system injuries and diseases, further proving that ACSL4-medicated ferroptosis is an important target for intervention in these diseases or injuries.
miR-145 as a Potential Biomarker and Therapeutic Target in Patients with Non-Small Cell Lung Cancer
Authors: Cho William C. , Wong Chi F. , Li Kwan P. , Fong Alvin H. , Fung King Y. , Au Joseph S.
Published: June 2023

Our previous study found that miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and that it could inhibit the cell proliferation in transfected NSCLC cells. In this study, we found that miR-145 was downregulated in NSCLC plasma samples compared to healthy controls. A receiver operating characteristic curve analysis indicated that plasma miR-145 expression was correlated with NSCLC in patient samples. We further revealed that the transfection of miR-145 inhibited the proliferation, migration, and invasion of NSCLC cells. Most importantly, miR-145 significantly delayed the tumor growth in a mouse model of NSCLC. We further identified GOLM1 and RTKN as the direct targets of miR-145. A cohort of paired tumors and adjacent non-malignant lung tissues from NSCLC patients was used to confirm the downregulated expression and diagnostic value of miR-145. The results were highly consistent between our plasma and tissue cohorts, confirming the clinical value of miR-145 in different sample groups. In addition, we also validated the expressions of miR-145, GOLM1, and RTKN using the TCGA database. Our findings suggested that miR-145 is a regulator of NSCLC and it plays an important role in NSCLC progression. This microRNA and its gene targets may serve as potential biomarkers and novel molecular therapeutic targets in NSCLC patients.
Non-Coding RNAs and Adipogenesis
Authors: Ru Wenxiu , Zhang Sihuan , Liu Jianyong , Liu Wujun , Huang Bizhi , Chen Hong
Published: June 2023

Adipogenesis is regarded as an intricate network in which multiple transcription factors and signal pathways are involved. Recently, big efforts have focused on understanding the epigenetic mechanisms and their involvement in the regulation of adipocyte development. Multiple studies investigating the regulatory role of non-coding RNAs (ncRNAs) in adipogenesis have been reported so far, especially lncRNA, miRNA, and circRNA. They regulate gene expression at multiple levels through interactions with proteins, DNA, and RNA. Exploring the mechanism of adipogenesis and developments in the field of non-coding RNA may provide a new insight to identify therapeutic targets for obesity and related diseases. Therefore, this article outlines the process of adipogenesis, and discusses updated roles and mechanisms of ncRNAs in the development of adipocytes.
QbD-Optimized, Phospholipid-Based Elastic Nanovesicles for the Effective Delivery of 6-Gingerol: A Promising Topical Option for Pain-Related Disorders
Authors: Ghazwani Mohammed , Alqarni Mohammed H. , Hani Umme , Alam Aftab
Published: June 2023

In this study, elastic nanovesicles, constructed of phospholipids optimized by Quality by Design (QbD), release 6-gingerol (6-G), a natural chemical that may alleviate osteoporosis and musculoskeletal-related pain. A 6-gingerol-loaded transfersome (6-GTF) formulation was developed using a thin film and sonication approach. 6-GTFs were optimized using BBD. Vesicle size, PDI, zeta potential, TEM, in vitro drug release, and antioxidant activity were evaluated for the 6-GTF formulation. The optimized 6-GTF formulation had a 160.42 nm vesicle size, a 0.259 PDI, and a −32.12 mV zeta potential. TEM showed sphericity. The 6-GTF formulation’s in vitro drug release was 69.21%, compared to 47.71% for the pure drug suspension. The Higuchi model best described 6-G release from transfersomes, while the Korsmeyer–Peppas model supported non-Fickian diffusion. 6-GTF had more antioxidant activity than the pure 6-G suspension. The optimized transfersome formulation was converted into a gel to improve skin retention and efficacy. The optimized gel had a spreadability of 13.46 ± 4.42 g·cm/s and an extrudability of 15.19 ± 2.01 g/cm2. The suspension gel had a 1.5 μg/cm2/h ex vivo skin penetration flux, while the 6-GTF gel had 2.71 μg/cm2/h. Rhodamine B-loaded TF gel reached deeper skin layers (25 μm) compared to the control solution in the CLSM study. The gel formulation’s pH, drug concentration, and texture were assessed. This study developed QbD-optimized 6-gingerol-loaded transfersomes. 6-GTF gel improved skin absorption, drug release, and antioxidant activity. These results show that the 6-GTF gel formulation has the ability to treat pain-related illnesses effectively. Hence, this study offers a possible topical treatment for conditions connected to pain.
Exploring the Potential Role of Circulating microRNAs as Biomarkers for Predicting Clinical Response to Neoadjuvant Therapy in Breast Cancer
Authors: Ruiz-Manriquez Luis M. , Villarreal-Garza Cynthia , Benavides-Aguilar Javier A. , Torres-Copado Andrea , Isidoro-Sánchez José , Estrada-Meza Carolina , Arvizu-Espinosa María Goretti , Paul Sujay , Cuevas-Diaz Duran Raquel
Published: June 2023

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide. Neoadjuvant therapy (NAT) is increasingly being used to reduce tumor burden prior to surgical resection. However, current techniques for assessing tumor response have significant limitations. Additionally, drug resistance is commonly observed, raising a need to identify biomarkers that can predict treatment sensitivity and survival outcomes. Circulating microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been shown to play a significant role in cancer progression as tumor inducers or suppressors. The expression of circulating miRNAs has been found to be significantly altered in breast cancer patients. Moreover, recent studies have suggested that circulating miRNAs can serve as non-invasive biomarkers for predicting response to NAT. Therefore, this review provides a brief overview of recent studies that have demonstrated the potential of circulating miRNAs as biomarkers for predicting the clinical response to NAT in BC patients. The findings of this review will strengthen future research on developing miRNA-based biomarkers and their translation into medical practice, which could significantly improve the clinical management of BC patients undergoing NAT.
Primary Undifferentiated/Dedifferentiated Cutaneous Melanomas—A Review on Histological, Immunohistochemical, and Molecular Features with Emphasis on Prognosis and Treatment
Authors: Țăpoi Dana Antonia , Gheorghișan-Gălățeanu Ancuța-Augustina , Dumitru Adrian Vasile , Ciongariu Ana Maria , Furtunescu Andreea Roxana , Marin Andrei , Costache Mariana
Published: June 2023

Diagnosing cutaneous melanoma is usually straightforward based on these malignancies’ histopathological and immunohistochemical features. Nevertheless, melanomas can imitate various other neoplasms, sometimes lacking the expression of conventional melanocytic markers and expressing non-melanocytic ones. Furthermore, divergent differentiation is more often encountered in metastatic melanomas and is still poorly described in primary cutaneous melanomas, and little is known about these patients’ prognosis and therapeutic approach. Therefore, we reviewed the literature on undifferentiated/dedifferentiated cutaneous melanomas, and we discuss the histological, immunohistochemical, and molecular profiles of undifferentiated/dedifferentiated cutaneous melanomas to understand these peculiar lesions better and improve their diagnostic algorithm. In addition to this, we also discuss how different genetic mutations may influence prognosis and become potential therapeutic targets.
DNA Damage Estimation after Chronic and Combined Exposure to Endocrine Disruptors: An In Vivo Real-Life Risk Simulation Approach
Authors: Karzi Vasiliki , Ozcagli Eren , Tzatzarakis Manolis N. , Vakonaki Elena , Fragkiadoulaki Irene , Kalliantasi Aikaterini , Chalkiadaki Christina , Alegakis Athanasios , Stivaktakis Polychronis , Karzi Aikaterini , Makrigiannakis Antonios , Docea Anca Oana , Calina Daniela , Tsatsakis Aristidis
Published: June 2023

Exposure to chemical substances has always been a matter of concern for the scientific community. During the last few years, researchers have been focusing on studying the effects resulting from combined exposure to different substances. In this study, we aimed to determine the DNA damage caused after chronic and combined exposure to substances characterized as endocrine disruptors using comet and micronuclei assays, specifically glyphosate (pure and commercial form), bisphenol A, parabens (methyl-, propyl- and butylparaben), triclosan and bis (2-ethylhexyl) phthalate. The highest mean tail intensity was observed in the group exposed to a high-dose (10 × ADI) mixture of substances (Group 3), with a mean value of 11.97 (11.26–13.90), while statistically significant differences were noticed between the groups exposed to low-dose (1 × ADI) (Group 2) and high-dose (10 × ADI) (Group 3) mixtures of substances (p = 0.003), and between Group 3 and both groups exposed to high doses (10 × ADI) of the pure and commercial forms of glyphosate (Groups 4 (p = 0.014) and 5 (p = 0.007)). The micronuclei assay results were moderately correlated with the exposure period. Group 5 was the most impacted exposure group at all sampling times, with mean MN counts ranging between 28.75 ± 1.71 and 60.75 ± 1.71, followed by Group 3 (18.25 ± 1.50–45.75 ± 1.71), showing that commercial forms of glyphosate additives as well as mixtures of endocrine disruptors can enhance MN formation. All exposure groups showed statistically significant differences in micronuclei counts with an increasing time trend.
MicroRNA-675-5p Overexpression Is an Independent Prognostic Molecular Biomarker of Short-Term Relapse and Poor Overall Survival in Colorectal Cancer
Authors: Christodoulou Spyridon , Sotiropoulou Christina D. , Vassiliu Panteleimon , Danias Nikolaos , Arkadopoulos Nikolaos , Sideris Diamantis C.
Published: June 2023

Colorectal cancer (CRC) is the main cause of cancer-related deaths globally, highlighting the importance of accurate biomarkers for early detection and accurate prognosis. MicroRNAs (miRNAs) have emerged as effective cancer biomarkers. The aim of this study was to investigate the prognostic potential of miR-675-5p as a molecular prognostic biomarker in CRC. For this reason, a quantitative PCR assay was developed and applied to determine miR-675-5p expression in cDNAs from 218 primary CRC and 90 paired normal colorectal tissue samples. To assess the significance of miR-675-5p expression and its association with patient outcome, extensive biostatistical analysis was performed. miR-675-5p expression was found to be significantly downregulated in CRC tissue samples compared to that in adjacent normal colorectal tissues. Moreover, high miR-675-5p expression was associated with shorter disease-free (DFS) and overall survival (OS) in CRC patients, while it maintained its unfavorable prognostic value independently of other established prognostic factors. Furthermore, TNM stage stratification demonstrated that higher miR-675-5p levels were associated with shorter DFS and OS intervals, particularly in patients with CRC of TNM stage II or III. In conclusion, our findings suggest that miR-675-5p overexpression constitutes a promising molecular biomarker of unfavorable prognosis in CRC, independent of other established prognostic factors, including TNM staging.
Non-Alcoholic Fatty Liver Disease: Translating Disease Mechanisms into Therapeutics Using Animal Models
Authors: Basha Amina , May Sarah C. , Anderson Ryan M. , Samala Niharika , Mirmira Raghavendra G.
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) is a range of pathologies arising from fat accumulation in the liver in the absence of excess alcohol use or other causes of liver disease. Its complications include cirrhosis and liver failure, hepatocellular carcinoma, and eventual death. NAFLD is the most common cause of liver disease globally and is estimated to affect nearly one-third of individuals in the United States. Despite knowledge that the incidence and prevalence of NAFLD are increasing, the pathophysiology of the disease and its progression to cirrhosis remain insufficiently understood. The molecular pathogenesis of NAFLD involves insulin resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. Better insight into these molecular pathways would allow for therapies that target specific stages of NAFLD. Preclinical animal models have aided in defining these mechanisms and have served as platforms for screening and testing of potential therapeutic approaches. In this review, we will discuss the cellular and molecular mechanisms thought to contribute to NAFLD, with a focus on the role of animal models in elucidating these mechanisms and in developing therapies.
Ethyl Caffeate Can Inhibit Aryl Hydrocarbon Receptor (AhR) Signaling and AhR-Mediated Potentiation of Mast Cell Activation
Authors: Nguyen Phuc-Tan , Nakamura Yuki , Tran Nguyen Quoc Vuong , Ishimaru Kayoko , Nguyen Thuy-An , Kobayashi Yoshiaki , Watanabe-Saito Fumie , Okuda Tohru , Nakano Nobuhiro , Nakao Atsuhito
Published: June 2023

Ethyl caffeate (EC) is a natural phenolic compound that is present in several medicinal plants used to treat inflammatory disorders. However, its anti-inflammatory mechanisms are not fully understood. Here, we report that EC inhibits aryl hydrocarbon receptor (AhR) signaling and that this is associated with its anti-allergic activity. EC inhibited AhR activation, induced by the AhR ligands FICZ and DHNA in AhR signaling-reporter cells and mouse bone marrow-derived mast cells (BMMCs), as assessed by AhR target gene expressions such as CYP1A1. EC also inhibited the FICZ-induced downregulation of AhR expression and DHNA-induced IL-6 production in BMMCs. Furthermore, the pretreatment of mice with orally administered EC inhibited DHNA-induced CYP1A1 expression in the intestine. Notably, both EC and CH-223191, a well-established AhR antagonist, inhibited IgE-mediated degranulation in BMMCs grown in a cell culture medium containing significant amounts of AhR ligands. Furthermore, oral administration of EC or CH-223191 to mice inhibited the PCA reaction associated with the suppression of constitutive CYP1A1 expression within the skin. Collectively, EC inhibited AhR signaling and AhR-mediated potentiation of mast cell activation due to the intrinsic AhR activity in both the culture medium and normal mouse skin. Given the AhR control of inflammation, these findings suggest a novel mechanism for the anti-inflammatory activity of EC.
A Video Question Answering Model Based on Knowledge Distillation
Authors: Shao Zhuang , Wan Jiahui , Zong Linlin
Published: June 2023

Video question answering (QA) is a cross-modal task that requires understanding the video content to answer questions. Current techniques address this challenge by employing stacked modules, such as attention mechanisms and graph convolutional networks. These methods reason about the semantics of video features and their interaction with text-based questions, yielding excellent results. However, these approaches often learn and fuse features representing different aspects of the video separately, neglecting the intra-interaction and overlooking the latent complex correlations between the extracted features. Additionally, the stacking of modules introduces a large number of parameters, making model training more challenging. To address these issues, we propose a novel multimodal knowledge distillation method that leverages the strengths of knowledge distillation for model compression and feature enhancement. Specifically, the fused features in the larger teacher model are distilled into knowledge, which guides the learning of appearance and motion features in the smaller student model. By incorporating cross-modal information in the early stages, the appearance and motion features can discover their related and complementary potential relationships, thus improving the overall model performance. Despite its simplicity, our extensive experiments on the widely used video QA datasets, MSVD-QA and MSRVTT-QA, demonstrate clear performance improvements over prior methods. These results validate the effectiveness of the proposed knowledge distillation approach.
Diminishing Endograft Apposition during Follow-Up Is an Important Indicator of Late Type 1a Endoleak after Endovascular Aneurysm Repair
Authors: Zuidema Roy , Geraedts Anna C. M. , van Veldhuizen Willemina A. , Mulay Sana , de Vries Jean-Paul P. M. , Schuurmann Richte C. L. , Balm Ron ,   the ODYSSEUS-T1EL Study Group
Published: June 2023

Late type 1a endoleaks (T1aELs) after endovascular aneurysm repair (EVAR) are hazardous complications which should be avoided. This study investigated the evolution of the shortest apposition length (SAL) post-EVAR and hypothesised that a declining apposition during follow-up may be an indicator of T1aEL development. Patients with a late T1aEL were selected from a consecutive multicentre database. For each T1aEL patient, the preoperative computed tomography angiography (CTA), first postoperative CTA, and pre-endoleak CTA were analysed. T1aEL patients were matched 1:1 to uncomplicated controls, based on endograft type and follow-up duration. Anatomical characteristics and endograft dimensions, including the post-EVAR SAL, were measured. Included were 28 patients with a late T1aEL and 28 matched controls. The SAL decreased from 11.2 mm (5.6–20.6 mm) to 3.9 mm (0.0–11.4 mm) in the T1aEL group (p = 0.006), whereas an increase in SAL was seen in the control group from 21.3 mm (14.1–25.8 mm) to 25.4 mm (19.0–36.2 mm; p = 0.015). On the pre-endoleak CTA, 18 patients (64%) in the T1aEL group had a SAL < 10 mm, and one (4%) patient in the control group had a SAL < 10 mm on the matched CTAs. Moreover, three mechanisms of decreasing sealing zone were identified, which might be used to determine optimal imaging or reintervention strategies. Diminishing SAL < 10 mm is an indicator for T1aEL during follow-up, it is imperative to include apposition analysis during follow-up.
Prognostic Value of sST2 in Heart Failure
Authors: Sciatti Edoardo , Merlo Anna , Scangiuzzi Claudio , Limonta Raul , Gori Mauro , D’Elia Emilia , Aimo Alberto , Vergaro Giuseppe , Emdin Michele , Senni Michele
Published: June 2023

In recent years, there has been growing interest in the risk stratification for heart failure, and the use of multiple biomarkers to identify different pathophysiological processes associated with this condition. One such biomarker is soluble suppression of tumorigenicity-2 (sST2), which has shown some potential for integration into clinical practice. sST2 is produced by both cardiac fibroblasts and cardiomyocytes in response to myocardial stress. Other sources of sST2 are endothelial cells of the aorta and coronary arteries and immune cells such as T cells. Indeed, ST2 is also associated with inflammatory and immune processes. We aimed at reviewing the prognostic value of sST2 in both chronic and acute heart failure. In this setting, we also provide a flowchart about its potential use in clinical practice.
Congenital Central Hypoventilation Syndrome in Israel—Novel Findings from a New National Center
Authors: Sivan Yakov , Bezalel Yael , Adato Avital , Levy Navit , Efrati Ori
Published: June 2023

Background. Congenital central hypoventilation syndrome (CCHS) is a rare autosomal-dominant disorder of the autonomic nervous system that results from mutations in the PHOX2B gene. A national CCHS center was founded in Israel in 2018. Unique new findings were observed. Methods. All 27 CCHS patients in Israel were contacted and followed. Novel findings were observed. Results. The prevalence of new CCHS cases was almost twice higher compared to other countries. The most common mutations in our cohort were polyalanine repeat mutations (PARM) 20/25, 20/26, 20/27 (combined = 85% of cases). Two patients showed unique recessive inheritance while their heterozygotes family members were asymptomatic. A right-sided cardio-neuromodulation was performed on an eight-year-old boy for recurrent asystoles by ablating the parasympathetic ganglionated plexi using radiofrequency (RF) energy. Over 36 months’ follow-up with an implantable loop-recorder, no bradycardias/pauses events were observed. A cardiac pacemaker was avoided. Conclusions. A significant benefit and new information arise from a nationwide expert CCHS center for both clinical and basic purposes. The incidence of CCHS in some populations may be increased. Asymptomatic NPARM mutations may be much more common in the general population, leading to an autosomal recessive presentation of CCHS. RF cardio-neuromodulation offers a novel approach to children avoiding the need for permanent pacemaker implantation.
Characteristics of Multiple Acute Concomitant Cerebral Infarcts Involving Different Arterial Territories
Authors: Simaan Naaem , Fahoum Leen , Filioglo Andrei , Aladdin Shorooq , Beiruti Karine Wiegler , Honig Asaf , Leker Ronen
Published: June 2023

(1) Background: Multiple acute concomitant cerebral infarcts (MACCI) are relatively uncommon. Data regarding the characteristics and outcomes of patients with MACCI are lacking. We, therefore, aimed to characterize the clinical features of MACCI. (2) Methods: Patients with MACCI were identified from a prospective registry of stroke patients admitted to a tertiary teaching center. Patients with an acute single embolic stroke (ASES) involving only one vascular bed served as controls. (3) Results: MACCI was diagnosed in 103 patients who were compared to 150 patients with ASES. MACCI patients were significantly older (p = 0.010), more often had a history of diabetes (p = 0.011) and had lower rates of ischemic heart disease (p = 0.022). On admission, MACCI patients had significantly higher rates of focal signs (p < 0.001), an altered mental state (p < 0.001) and seizures (p = 0.036). The favorable functional outcome was significantly less common in patients with MACCI (p = 0.006). In the multivariable analysis, MACCI was associated with lower chances of achieving favorable outcomes (odds ratio: 0.190, 95% CI: 0.070–0.502). (4) Conclusions: There are important differences in clinical presentation, comorbidities and outcomes between MACCI and ASES. MACCI is less often associated with favorable outcomes and could represent a more severe form of a stroke compared with a single embolic stroke.
Venous Thromboembolism (VTE) in Post-Prostatectomy Patients: Systematic Review and Meta-Analysis
Authors: Wani Mudassir , Al-Mitwalli Abdullah , Mukherjee Subhabrata , Nabi Ghulam , Somani Bhaskar , Abbaraju Jayasimha , Madaan Sanjeev
Published: June 2023

Radical prostatectomy (RP) is one of the recommended treatments to achieve oncological outcomes in localized prostate cancer. However, a radical prostatectomy is a major abdominopelvic surgery. Venous thromboembolism (VTE) is a well-known complication associated with surgical procedures, including RP. There is a lack of consensus regarding VTE prophylaxis in urological procedures. The aim of this systematic review and meta-analysis was to investigate different aspects of VTE in post-radical prostatectomy patients. A comprehensive literature search was performed, and relevant data were extracted. The primary aim was to perform a systematic review and meta-analysis (wherever possible) of VTE occurrence in post-RP patients in relation to surgical approach, pelvic lymph node dissection, and type of prophylaxis (mechanical or combined prophylaxis). The secondary aim was to investigate the incidence and other risk factors of VTE in post-RP patients. A total of 16 studies were included for quantitative analysis. Statistical methods for analysis included the DerSimonian–Laird random effects. We were able to conclude that the overall incidence of VTE in post-radical prostatectomy is 1% (95% CI) and minimally invasive procedures (MIS), including laparoscopic, as well as robotic procedures for radical prostatectomy and RP without pelvic lymph node dissection (PLND), are associated with less risk of developing VTE. Additional pharmacological prophylaxis to mechanical methods may not be necessary in all cases and should be considered in high-risk patients only.
Editorial on: Musculoskeletal Rehabilitation: Current Challenges and New Perspectives
Authors: Perna Andrea , Proietti Luca
Published: June 2023

Musculoskeletal disorders are among the leading causes of disability and chronic pain worldwide, and their impact is expected to increase in the coming years [...]
Digital Breast Tomosynthesis: Towards Dose Reduction through Image Quality Improvement
Authors: Mota Ana M. , Mendes João , Matela Nuno
Published: June 2023

Currently, breast cancer is the most commonly diagnosed type of cancer worldwide. Digital Breast Tomosynthesis (DBT) has been widely accepted as a stand-alone modality to replace Digital Mammography, particularly in denser breasts. However, the image quality improvement provided by DBT is accompanied by an increase in the radiation dose for the patient. Here, a method based on 2D Total Variation (2D TV) minimization to improve image quality without the need to increase the dose was proposed. Two phantoms were used to acquire data at different dose ranges (0.88–2.19 mGy for Gammex 156 and 0.65–1.71 mGy for our phantom). A 2D TV minimization filter was applied to the data, and the image quality was assessed through contrast-to-noise ratio (CNR) and the detectability index of lesions before and after filtering. The results showed a decrease in 2D TV values after filtering, with variations of up to 31%, increasing image quality. The increase in CNR values after filtering showed that it is possible to use lower doses (−26%, on average) without compromising on image quality. The detectability index had substantial increases (up to 14%), especially in smaller lesions. So, not only did the proposed approach allow for the enhancement of image quality without increasing the dose, but it also improved the chances of detecting small lesions that could be overlooked.
Metacognitive Cues, Working Memory, and Math Anxiety: The Regulated Attention in Mathematical Problem Solving (RAMPS) Framework
Authors: Scheibe Daniel A. , Was Christopher A. , Dunlosky John , Thompson Clarissa A.
Published: June 2023

Mathematical problem solving is a process involving metacognitive (e.g., judging progress), cognitive (e.g., working memory), and affective (e.g., math anxiety) factors. Recent research encourages researchers who study math cognition to consider the role that the interaction between metacognition and math anxiety plays in mathematical problem solving. Problem solvers can make many metacognitive judgments during a math problem, ranging from global judgments such as, “Do I care to solve this problem?” to minor cue-based judgments such as, “Is my current strategy successful in making progress toward the correct solution?” Metacognitive monitoring can hinder accurate mathematical problem solving when the monitoring is task-irrelevant; however, task-relevant metacognitive experiences can lead to helpful control decisions in mathematical problem solving such as checking work, considering plausibility of an answer, and considering alternate strategies. Worry and negative thoughts (i.e., math anxiety) can both interfere with the accuracy of metacognitive experiences as cues in mathematical problem solving and lead to avoidance of metacognitive control decisions that could otherwise improve performance. The current paper briefly reviews and incorporates prior literature with current qualitative reports (n = 673) to establish a novel framework of regulated attention in mathematical problem solving (RAMPS).
Design of a Highly Compatible Underwater Wireless Power Transfer Station for Seafloor Observation Equipment
Authors: Cai Tianhao , Lyu Feng , Wang Tianzhi , Huang Fushi
Published: June 2023

Conventional cabled seafloor observatories (CSOs) power in-situ instruments via wet-mated or dry-mated direct electrical contact (DEC) connectors to achieve long-term and real-time observation. However, the DEC connectors have high risks of water leakage and short circuits in power feeding, especially under high water pressure. This paper proposes a highly compatible underwater station based on inductive wireless power transfer (IPT) technology to address the above reliability issue. A novel energy transmitter with runway-structure coils is applied to the proposed underwater station to cover a sufficient power feeding area so that various in-situ equipment can be powered with desirable misalignment tolerance. The magnetic field distribution is analyzed by both derivation and finite element analysis (FEA) methods, and the principal parameters of the transmitter are further optimized and compared with both the mixed-integer sequential quadratic programming (MISQP) algorithm and the evolutionary algorithm (EA) for better performance. The same results show a reliable optimization process. The WPT circuit characteristics are also investigated to power different loads and improve the power transmission efficiency. The output power decreases, and the transmission efficiency rises and then decreases as the load increases. In addition, receivers with higher mutual inductance have better transmission performance. A prototype of the underwater station has been tested both in air and in water, and the experimental results have proven it can power multiple seafloor observation instruments stably and achieve compatibility requirements. The maximum output power of the station prototype for testing is 100 W, and the maximum overall transmission efficiency is 61%.
Experimental Study on the Effects of Waves and Current on Ice Melting
Authors: He Tianyi , Hu Huijie , Tang Ding , Chen Xu , Meng Jing , Cao Yong , Lv Xianqing
Published: June 2023

Ice melting plays a crucial role in ocean circulation and global climate. Laboratory experiments were used to study the dynamic mechanisms of the influence of waves and currents on ice melting. The results showed that under near stable air temperature and water temperature conditions, the ice melting rate was significantly greater with waves than that without waves, as well as the higher the wave height, the greater the melting rate. This is related to the increase in the contact area between ice and water by waves. Further research was carried out to observe the flow field at different locations on the ice bottom, ice sides, and behind the ice by particle image velocimetry (PIV) and dyeing experiments. At different flow velocities, the changes in the side melting rate and bottom melting rate were not the same. Meltwater is attached to the bottom in the form of plume at low background flow velocity, which leads to the slowness of the heat exchange between the ice with a higher ambient temperature. Therefore, the melting of the ice bottom and the ice side were slower at low flow velocity. At high background flow velocity, there is strong shear instability and vortex at the ice bottom and behind the ice. The dissipation and mixing effects caused by vortices accelerate the melting of the ice bottom and the ice back. The thermodynamic factors, such as air temperature and water temperature, had significant impacts in the experiments. Further research needs to improve the accuracy of temperature control of experimental equipment. Computational fluid dynamics and sensitive tests of numerical simulation may also be carried out on ice melting.