bluuebunny/crossref_metadata_2025 huggingface dataset:
The Early Impacts of the COVID-19 Pandemic on Mental Health Facilities and Psychiatric Professionals
Authors: Gourret Baumgart Jade , Kane Hélène , El-Hage Wissam , Deloyer Jocelyn , Maes Christine , Lebas Marie-Clotilde , Marazziti Donatella , Thome Johannes , Fond-Harmant Laurence , Denis Frédéric
Published: July 2021

(1) Background: While in many countries, the psychiatric and mental health sectors had been in crisis for years, the onset of a novel coronavirus pandemic impacted their structures, organizations, and professionals worldwide. (2) Methods: To document the early impacts of the COVID-19 health crisis on psychiatry and mental health sectors, a systematic review of the international literature published in 2020 was conducted in PubMed (MEDLINE), Cairn.info, and SantéPsy (Ascodocpsy) databases. (3) Results: After applying inclusion and exclusion criteria, 72 articles from scientific journals were selected, including papers documenting the early impact of the COVID-19 pandemic on the organization of psychiatric care delivery, work processes in psychiatry and mental health units, and personal experiences of mental health professionals. This review identified the contributions aimed at preventing the onset of mental disorders in the early stages of the health crisis. It lists the organizational changes that have been implemented in the first place to ensure continuity of psychiatric care while reducing the risk of SARS-CoV-2 transmission. It questions the evolution of the rights and duties of mental health professionals in the first months of the pandemic. (4) Discussion and conclusions: Although this literature review exclusively documented the early impacts of the COVID-19 health crisis, it is of significant interest, as it pictures the unprecedent situation in which psychiatry and mental health care professionals found themselves in the first stages of the pandemic. This work is a preliminary step of a study to be conducted with mental health professionals on an international scale—the Psy-GIPO2C project—based on more than 15 group interviews, 30 individual interviews, and 2000 questionnaires. The final aim of this study is to formulate concrete recommendations for decision-makers to improve work in psychiatry and mental health.
Whether Public Hospital Reform Affects the Hospital Choices of Patients in Urban Areas: New Evidence from Smart Card Data
Authors: Du Fangye , Wang Jiaoe , Jin Haitao
Published: July 2021

The effects of public hospital reforms on spatial and temporal patterns of health-seeking behavior have received little attention due to small sample sizes and low spatiotemporal resolution of survey data. Without such information, however, health planners might be unable to adjust interventions in a timely manner, and they devise less-effective interventions. Recently, massive electronic trip records have been widely used to infer people’s health-seeking trips. With health-seeking trips inferred from smart card data, this paper mainly answers two questions: (i) how do public hospital reforms affect the hospital choices of patients? (ii) What are the spatial differences of the effects of public hospital reforms? To achieve these goals, tertiary hospital preferences, hospital bypass, and the efficiency of the health-seeking behaviors of patients, before and after Beijing’s public hospital reform in 2017, were compared. The results demonstrate that the effects of this reform on the hospital choices of patients were spatially different. In subdistricts with (or near) hospitals, the reform exerted the opposite impact on tertiary hospital preference compared with core and periphery areas. However, the reform had no significant effect on the tertiary hospital preference and hospital bypass in subdistricts without (or far away from) hospitals. Regarding the efficiency of the health-seeking behaviors of patients, the reform positively affected patient travel time, time of stay at hospitals, and arrival time. This study presents a time-efficient method to evaluate the effects of the recent public hospital reform in Beijing on a fine scale.
Physical Presence during Moral Action in Immersive Virtual Reality
Authors: Terbeck Sylvia , Charlesford Jaysan , Clemans Heather , Pope Emily , Lee Aimee , Turner Joshua , Gummerum Michaela , Bussmann Bettina
Published: July 2021

Research on morality has focused on differences in moral judgment and action. In this study, we investigated self-reported moral reasoning after a hypothetical moral dilemma was presented on paper, and moral reasoning after that very same dilemma was experienced in immersive virtual reality (IVR). We asked open-ended questions and used content analysis to determine moral reasoning in a sample of 107 participants. We found that participants referred significantly more often to abstract principles and consequences for themselves (i.e., it is against the law) after the paper-based moral dilemma compared to the IVR dilemma. In IVR participants significantly more often referred to the consequences for the people involved in the dilemma (i.e., not wanting to hurt that particular person). This supports the separate process theory, suggesting that decision and action might be different moral concepts with different foci regarding moral reasoning. Using simulated moral scenarios thus seems essential as it illustrates possible mechanisms of empathy and altruism being more relevant for moral actions especially given the physical presence of virtual humans in IVR.
An Association between Maternal Occupations and Low Birth Weight Infants in Japan from 1995 to 2015
Authors: Okui Tasuku , Ochiai Masayuki , Nakashima Naoki
Published: July 2021

Differences in low birth weight rate depending on maternal socioeconomic characteristics have not yet been demonstrated using the Vital Statistics in Japan; therefore, this study aimed to investigate these differences according to maternal occupations. “Report of Vital Statistics: Occupational and Industrial Aspects” and the Vital Statistics in Japan were used every five years from 1995 to 2015. Nine types of occupations were compared. The low birth weight rate was calculated according to maternal occupations and year. Also, the standardized low birth weight ratio was obtained by dividing the number of low-birth-weight infants for each maternal occupation by an expected number of low birth weight infants. The standardized low birth weight ratio for manual workers was the highest among all occupations from 2000 to 2015, and it was significantly higher than one throughout the years. The ratio for clerical workers was also significantly higher than one from 1995 to 2010. Whereas, the ratio for farmers was significantly lower than one in most of the years. It was suggested that health guidance and prenatal care are particularly needed for manual workers, and a study investigating the differences in prenatal characteristics among maternal occupations is necessary for finding a reason for disparity.
Premature Aging in Chronic Kidney Disease: The Outcome of Persistent Inflammation beyond the Bounds
Authors: Figuer Andrea , Bodega Guillermo , Tato Patricia , Valera Gemma , Serroukh Nadia , Ceprian Noemi , de Sequera Patricia , Morales Enrique , Carracedo Julia , Ramírez Rafael , Alique Matilde
Published: July 2021

Over the last hundred years, life expectancy in developed countries has increased because of healthier living habits and the treatment of chronic pathologies causing premature aging. Aging is an inexorable, time-dependent, multifactorial process characterized by a series of progressive and irreversible physiological changes associated with loss of functional, psychological, and social capabilities. Numerous factors, such as oxidative stress, inflammation, and cellular senescence, and an irreversible geriatric syndrome known as frailty, contribute to human body deterioration in aging. The speed of aging may differ between individuals depending on the presence or absence of multiple factors (genetic and/or environment) and the subsequent misbalance of homeostasis, together with the increase of frailty, which also plays a key role in developing chronic diseases. In addition, pathological circumstances have been reported to precipitate or accelerate the aging process. This review investigated the mechanisms involved in the developing pathologies, particularly chronic kidney disease, associated with aging.
Analysis of the Association between Female Medical History and Thyroid Cancer in Women: A Cross-Sectional Study Using KoGES HEXA Data
Authors: Jin Young Ju , Lee Suk Woo , Song Chang Myeon , Park Bumjung , Choi Hyo Geun
Published: July 2021

The purpose of this study was to evaluate the association between female medical history and thyroid cancer. Methods: Data from the Korean Genome and Epidemiology Study were collected from 2004 to 2016. Among a total of 1303 participants with thyroid cancer and 106,602 control (non-thyroid cancer) participants, the odds ratios (ORs) with 95% confidence intervals (CIs) of hysterectomy, oophorectomy, use of oral contraceptives, and number of children were evaluated. Results: The adjusted OR of hysterectomy for thyroid cancer was 1.73 (95% CI = 1.48–2.01, p < 0.001) in the minimally adjusted model. The adjusted ORs for thyroid cancer were 1.89 (95% CI = 1.06–3.37, p = 0.031), 0.89 (95% CI = 0.83–0.94, p < 0.001), and 0.85 (95% CI = 0.73–0.99, p = 0.040) for bilateral oophorectomy, number of children, and use of oral contraceptives, respectively, in the fully adjusted model. In the subgroup analysis, the adjusted ORs of bilateral oophorectomy were significant in the younger age (OR = 3.62, 95% CI = 1.45–9.03, p = 0.006), while the number of children was significant in the older age (OR = 0.86, 95% CI = 0.80–0.93, p < 0.001). Conclusions: The ORs of hysterectomy and bilateral oophorectomy were significantly higher in the thyroid cancer group in the younger age group. The adjusted ORs of the number of children were significantly low in the older age group.
How Does Income Inequality Influence Environmental Regulation in the Context of Corruption? A Panel Threshold Analysis Based on Chinese Provincial Data
Authors: Wang Shi , Zhang Wen , Wang Hua , Wang Jue , Jiang Mu-Jun
Published: July 2021

The question of how the income inequality of residents affects the level of environmental regulation in the context of official corruption was the core research issue of this study. We analyzed this problem using the panel threshold regression model from 26 provinces in China from 1995 to 2017. We found that when there is no official corruption, the widening of the residents’ income inequality promotes stricter environmental regulations; when the corruption problem is serious, the expansion of the residents’ income inequality leads to the decline in environmental standards; that is, the impact of residents’ income inequality on environmental regulation has a threshold effect due to corruption. In addition, the threshold effect due to corruption of all residents’ income inequality on environmental regulation is mainly generated by the urban residents’ income inequality and the urban–rural income inequality. This paper contributes to the literature that concentrates on the relationship between income inequality and environmental regulation, and shows that corruption is a key factor that can deeply influence that relationship. The research conclusion shows that increasing anti-corruption efforts can not only maintain national political stability, social fairness, and justice, but also be a powerful measure for environmental pollution governance.
Determination of the Strongest Factor and Component in a Relationship between Lower-Extremity Assessment Protocol and Patient-Oriented Outcomes in Individuals with Anterior Cruciate Ligament Reconstruction: A Pilot Study
Authors: Jeon Hyung Gyu , Kim Byong Hun , Kang Tae Kyu , Jeong Hee Seong , Lee Sae Yong
Published: July 2021

Although the Lower-Extremity Assessment Protocol (LEAP) assesses multidimensional aspects of a patient with anterior cruciate ligament (ACL) injury, there is a need to reduce the dimensionality of LEAP items to effectively assess patients. Therefore, the present study aimed to establish the validity of LEAP and to determine associated factors and components in a relationship between LEAP and the International Knee Documentation Committee (IKDC) questionnaire. Fifteen patients who had ACL reconstruction more than 1 year and less than 5 years earlier were recruited. Patients performed LEAP, including muscular strength, fatigue index, static balance, drop landing, and functional hopping assessment. They also completed the IKDC questionnaire and the Tegner Activity Score. Factor analysis and stepwise regression analysis were performed. The 14 components of LEAP were categorized into four factors (functional task, muscle strength, neuromuscular control, and fatigue), which accounted for 83.8% of the cumulative variance by factor analysis. In the stepwise regression analysis, the functional task (R2 = 0.43, p = 0.008) in factors and single-leg hop (R2 = 0.49, p = 0.004) in components were associated with patient-oriented outcomes, respectively. In conclusion, the functional task and single-leg hop may be used for providing valuable information about knee joints to patients and clinicians.
Fusion of Higher Order Spectra and Texture Extraction Methods for Automated Stroke Severity Classification with MRI Images
Authors: Faust Oliver , En Wei Koh Joel , Jahmunah Vicnesh , Sabut Sukant , Ciaccio Edward J. , Majid Arshad , Ali Ali , Lip Gregory Y. H. , Acharya U. Rajendra
Published: July 2021

This paper presents a scientific foundation for automated stroke severity classification. We have constructed and assessed a system which extracts diagnostically relevant information from Magnetic Resonance Imaging (MRI) images. The design was based on 267 images that show the brain from individual subjects after stroke. They were labeled as either Lacunar Syndrome (LACS), Partial Anterior Circulation Syndrome (PACS), or Total Anterior Circulation Stroke (TACS). The labels indicate different physiological processes which manifest themselves in distinct image texture. The processing system was tasked with extracting texture information that could be used to classify a brain MRI image from a stroke survivor into either LACS, PACS, or TACS. We analyzed 6475 features that were obtained with Gray-Level Run Length Matrix (GLRLM), Higher Order Spectra (HOS), as well as a combination of Discrete Wavelet Transform (DWT) and Gray-Level Co-occurrence Matrix (GLCM) methods. The resulting features were ranked based on the p-value extracted with the Analysis Of Variance (ANOVA) algorithm. The ranked features were used to train and test four types of Support Vector Machine (SVM) classification algorithms according to the rules of 10-fold cross-validation. We found that SVM with Radial Basis Function (RBF) kernel achieves: Accuracy (ACC) = 93.62%, Specificity (SPE) = 95.91%, Sensitivity (SEN) = 92.44%, and Dice-score = 0.95. These results indicate that computer aided stroke severity diagnosis support is possible. Such systems might lead to progress in stroke diagnosis by enabling healthcare professionals to improve diagnosis and management of stroke patients with the same resources.
Life Aspirations, Generativity and Compulsive Buying in University Students
Authors: Otero-López José Manuel , Santiago María José , Castro María Cristina
Published: July 2021

The study of goal-oriented behaviour, because of its undeniable repercussions on physical and mental health, is one of the target topics of contemporary research. However, the content of life aspirations, emphasised from the self-determination theory, has received little attention from the field of compulsive buying although it plays an important role in the regulation of behaviour and well-being. Generativity, the personal construct that captures the intentions and/or the need to contribute (leave a legacy) to others, has never been analysed with respect to compulsive buying although it has been the source of interest of related fields (responsible consumption). Accordingly, this study seeks to shed light on the role of both constructs (life aspirations and generativity) in compulsive buying among university students. The sample consisted of 1093 Spanish university students classified either as non-compulsive buyers or compulsive buyers. Estimated prevalence of compulsive buying was 7.9%. The results of Student’s test confirm that, besides gender (women report greater propensity to the phenomenon), compulsive buyers score higher and show statistically significant differences with respect to non-compulsive buyers in all extrinsic goals (financial success, image, popularity and conformity) and hedonism. Non-compulsive buyers show significantly higher scores for the intrinsic goals of self-acceptance, affiliation and community feeling and also report a higher generative concern. The logistic regression analysis confirms that being female and the life aspirations of image, popularity and hedonism act as risk factors in compulsive buying in university students while generativity and the importance granted to the intrinsic goals of self-acceptance and affiliation are protective factors. Potential lines of action for this worrying phenomenon are discussed in the light of the findings.
Effectiveness of Soft versus Rigid Back-Support Exoskeletons during a Lifting Task
Authors: Schwartz Mathilde , Theurel Jean , Desbrosses Kévin
Published: July 2021

This study investigated the influence of passive back-support exoskeletons (EXOBK) design, trunk sagittal inclination (TSI), and gender on the effectiveness of an exoskeleton to limit erector spinae muscle (ES) activation during a sagittal lifting/lowering task. Twenty-nine volunteers performed an experimental dynamic task with two exoskeletons (two different designs: soft (SUIT) and rigid (SKEL)), and without equipment (FREE). The ES activity was analyzed for eight parts of TSI, each corresponding to 25% of the range of motion (lifting: P1 to P4; lowering: P5 to P8). The impact of EXOBK on ES activity depended on the interaction between exoskeleton design and TSI. With SKEL, ES muscle activity significantly increased for P8 (+36.8%) and tended to decrease for P3 (−7.2%, p = 0.06), compared to FREE. SUIT resulted in lower ES muscle activity for P2 (−9.6%), P3 (−8.7%, p = 0.06), and P7 (−11.1%), in comparison with FREE. Gender did not influence the effect of either back-support exoskeletons on ES muscle activity. These results point to the need for particular attention with regard to (1) exoskeleton design (rigid versus soft) and to (2) the range of trunk motion, when selecting an EXOBK. In practice, the choice of a passive back-support exoskeleton, between rigid and soft design, requires an evaluation of human-exoskeleton interaction in real task conditions. The characterization of trunk kinematics and ranges of motion appears essential to identify the benefits and the negative effects to take into account with each exoskeleton design.
The Role of Participatory Village Maps in Strengthening Public Participation Practice
Authors: Akbar Aulia , Flacke Johannes , Martinez Javier , van Maarseveen Martin F. A. M.
Published: July 2021

This study investigated the role of participatory village maps in strengthening the Musrenbang, an annual multi-stakeholder public consultation forum to discuss development issues and plans in Indonesia. We evaluated the Musrenbang in five villages in Deli Serdang District after conducting participatory mapping workshops to produce village maps to inform the Musrenbang process. Our results show that communication between Musrenbang participants improved because the maps provided a clear definition of the village administrative area, geospatial data as resources for participation, transparency, and a dynamic deliberative process. Collaboration was also evident as the maps enabled participants to exchange knowledge, experience social learning, and have greater influence on the decision-making process. Despite the benefits, some issues impeded the optimal use of the village maps to support the participatory process in the Musrenbang. The maps could not completely overcome the power disparities between Musrenbang participants. Certain actors still dominated the implementation of the Musrenbang, making the deliberative process inaccessible to and less inclusive of some local stakeholders. Several improvements are urgently needed to optimise the use of participatory village maps and enhance Musrenbang implementation.
Staphylococcus aureus Decreases SUMOylation Host Response to Promote Intramacrophage Survival
Authors: Youssouf Nadhuma , Recasens-Zorzo Clara , Molle Virginie , Bossis Guillaume , Soubeyran Philippe , Gannoun-Zaki Laila
Published: July 2021

Staphylococcus aureus is a commensal bacterium that causes severe infections in soft tissue and the bloodstream. During infection, S. aureus manipulates host cell response to facilitate its own replication and dissemination. Here, we show that S. aureus significantly decreases the level of SUMOylation, an essential post-translational modification, in infected macrophages 24 h post-phagocytosis. The reduced level of SUMOylation correlates with a decrease in the SUMO-conjugating enzyme Ubc9. The over-expression of SUMO proteins in macrophages impaired bacterial intracellular proliferation and the inhibition of SUMOylation with ML-792 increased it. Together, these findings demonstrated for the first time the role of host SUMOylation response toward S. aureus infection.
Keratin Profiling by Single-Cell RNA-Sequencing Identifies Human Prostate Stem Cell Lineage Hierarchy and Cancer Stem-Like Cells
Authors: Hu Wen-Yang , Hu Dan-Ping , Xie Lishi , Nonn Larisa , Lu Ranli , Abern Michael , Shioda Toshihiro , Prins Gail S.
Published: July 2021

Single prostate stem cells can generate stem and progenitor cells to form prostaspheres in 3D culture. Using a prostasphere-based label retention assay, we recently identified keratin 13 (KRT13)-enriched prostate stem cells at single-cell resolution, distinguishing them from daughter progenitors. Herein, we characterized the epithelial cell lineage hierarchy in prostaspheres using single-cell RNA-seq analysis. Keratin profiling revealed three clusters of label-retaining prostate stem cells; cluster I represents quiescent stem cells (PSCA, CD36, SPINK1, and KRT13/23/80/78/4 enriched), while clusters II and III represent active stem and bipotent progenitor cells (KRT16/17/6 enriched). Gene set enrichment analysis revealed enrichment of stem and cancer-related pathways in cluster I. In non-label-retaining daughter progenitor cells, three clusters were identified; cluster IV represents basal progenitors (KRT5/14/6/16 enriched), while clusters V and VI represent early and late-stage luminal progenitors, respectively (KRT8/18/10 enriched). Furthermore, MetaCore analysis showed enrichment of the “cytoskeleton remodeling–keratin filaments” pathway in cancer stem-like cells from human prostate cancer specimens. Along with common keratins (KRT13/23/80/78/4) in normal stem cells, unique keratins (KRT10/19/6C/16) were enriched in cancer stem-like cells. Clarification of these keratin profiles in human prostate stem cell lineage hierarchy and cancer stem-like cells can facilitate the identification and therapeutic targeting of prostate cancer stem-like cells.
Sex Differences in the Triad of Acquired Sensorineural Hearing Loss
Authors: Lien Kuang-Hsu , Yang Chao-Hui
Published: July 2021

The triad of noise-generated, drug-induced, and age-related hearing loss is the major cause of acquired sensorineural hearing loss (ASNHL) in modern society. Although these three forms of hearing loss display similar underlying mechanisms, detailed studies have revealed the presence of sex differences in the auditory system both in human and animal models of ASNHL. However, the sexual dimorphism of hearing varies among noise-induced hearing loss (NIHL), ototoxicity, and age-related hearing loss (ARHL). Importantly, estrogen may play an essential role in modulating the pathophysiological mechanisms in the cochlea and several reports have shown that the effects of hormone replacement therapy on hearing loss are complex. This review will summarize the clinical features of sex differences in ASNHL, compare the animal investigations of cochlear sexual dimorphism in response to the three insults, and address how estrogen affects the auditory organ at molecular levels.
Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening
Authors: Dvorácskó Szabolcs , Lázár László , Fülöp Ferenc , Palkó Márta , Zalán Zita , Penke Botond , Fülöp Lívia , Tömböly Csaba , Bogár Ferenc
Published: July 2021

Sigma-1 receptor (S1R) is an intracellular, multi-functional, ligand operated protein that also acts as a chaperone. It is considered as a pluripotent drug target in several pathologies. The publication of agonist and antagonist bound receptor structures has paved the way for receptor-based in silico drug design. However, recent studies on this subject payed no attention to the structural differences of agonist and antagonist binding. In this work, we have developed a new ensemble docking-based virtual screening protocol utilizing both agonist and antagonist bound S1R structures. This protocol was used to screen our in-house compound library. The S1R binding affinities of the 40 highest ranked compounds were measured in competitive radioligand binding assays and the sigma-2 receptor (S2R) affinities of the best S1R binders were also determined. This way three novel high affinity S1R ligands were identified and one of them exhibited a notable S1R/S2R selectivity.
An Evaluation of Human Induced Pluripotent Stem Cells to Test for Cardiac Developmental Toxicity
Authors: Walker Lauren Michelle , Sparks Nicole R. L. , Puig-Sanvicens Veronica , Rodrigues Beatriz , zur Nieden Nicole I.
Published: July 2021

To prevent congenital defects arising from maternal exposure, safety regulations require pre-market developmental toxicity screens for industrial chemicals and pharmaceuticals. Traditional embryotoxicity approaches depend heavily on the use of low-throughput animal models which may not adequately predict human risk. The validated embryonic stem cell test (EST) developed in murine embryonic stem cells addressed the former problem over 15 years ago. Here, we present a proof-of-concept study to address the latter challenge by updating all three endpoints of the classic mouse EST with endpoints derived from human induced pluripotent stem cells (hiPSCs) and human fibroblasts. Exposure of hiPSCs to selected test chemicals inhibited differentiation at lower concentrations than observed in the mouse EST. The hiPSC-EST also discerned adverse developmental outcomes driven by novel environmental toxicants. Evaluation of the early cardiac gene TBX5 yielded similar toxicity patterns as the full-length hiPSC-EST. Together, these findings support the further development of hiPSCs and early molecular endpoints as a biologically relevant embryotoxicity screening approach for individual chemicals and mixtures.
Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3
Authors: D’Onofrio Nunzia , Martino Elisa , Mele Luigi , Colloca Antonino , Maione Martina , Cautela Domenico , Castaldo Domenico , Balestrieri Maria Luisa
Published: July 2021

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.
Osteoarthritis-Related Inflammation Blocks TGF-β’s Protective Effect on Chondrocyte Hypertrophy via (de)Phosphorylation of the SMAD2/3 Linker Region
Authors: Thielen Nathalie , Neefjes Margot , Wiegertjes Renske , van den Akker Guus , Vitters Elly , van Beuningen Henk , Blaney Davidson Esmeralda , Koenders Marije , van Lent Peter , van de Loo Fons , van Caam Arjan , van der Kraan Peter
Published: July 2021

Osteoarthritis (OA) is a degenerative joint disease characterized by irreversible cartilage damage, inflammation and altered chondrocyte phenotype. Transforming growth factor-β (TGF-β) signaling via SMAD2/3 is crucial for blocking hypertrophy. The post-translational modifications of these SMAD proteins in the linker domain regulate their function and these can be triggered by inflammation through the activation of kinases or phosphatases. Therefore, we investigated if OA-related inflammation affects TGF-β signaling via SMAD2/3 linker-modifications in chondrocytes. We found that both Interleukin (IL)-1β and OA-synovium conditioned medium negated SMAD2/3 transcriptional activity in chondrocytes. This inhibition of TGF-β signaling was enhanced if SMAD3 could not be phosphorylated on Ser213 in the linker region and the inhibition by IL-1β was less if the SMAD3 linker could not be phosphorylated at Ser204. Our study shows evidence that inflammation inhibits SMAD2/3 signaling in chondrocytes via SMAD linker (de)-phosphorylation. The involvement of linker region modifications may represent a new therapeutic target for OA.
miR-129a-3p Inhibits PEDV Replication by Targeting the EDA-Mediated NF-κB Pathway in IPEC-J2 Cells
Authors: Qi Xiaoyi , Cao Yue , Wu Shenglong , Wu Zhengchang , Bao Wenbin
Published: July 2021

Previous studies have shown that microRNAs (miRNAs) are closely related to many viral infections. However, the molecular mechanism of how miRNAs regulate porcine epidemic diarrhea virus (PEDV) infection remains unclear. In this study, we first constructed a PEDV-infected IPEC-J2 cytopathic model to validate the relationship between miR-129a-3p expression levels and PEDV resistance. Secondly, we explored the effect of miR-129a-3p on PEDV infection by targeting the 3′UTR region of the ligand ectodysplasin (EDA) gene. Finally, transcriptome sequencing was used to analyze the downstream regulatory mechanism of EDA. The results showed that after 48 h of PEDV infection, IPEC-J2 cells showed obvious pathological changes, and miR-129a-3p expression was significantly downregulated (p < 0.01). Overexpression of miR-129a-3p mimics inhibited PEDV replication in IPEC-J2 cells; silencing endogenous miR-129a-3p can promote viral replication. A dual luciferase assay showed that miR-129a-3p could bind to the 3′UTR region of the EDA gene, which significantly reduced the expression level of EDA (p < 0.01). Functional verification showed that upregulation of EDA gene expression significantly promoted PEDV replication in IPEC-J2 cells. Overexpression of miR-129a-3p can activate the caspase activation and recruitment domain 11 (CARD11) mediated NF-κB pathway, thus inhibiting PEDV replication. The above results suggest that miR-129a-3p inhibits PEDV replication in IPEC-J2 cells by activating the NF-κB pathway by binding to the EDA 3′UTR region. Our results have laid the foundation for in-depth study of the mechanism of miR-129a-3p resistance and its application in porcine epidemic diarrhea disease-resistance breeding.
The Role of Caspase-12 in Retinal Bystander Cell Death and Innate Immune Responses against MCMV Retinitis
Authors: Zhang Xinyan , Xu Jinxian , Marshall Brendan , Dong Zheng , Smith Sylvia B. , Zhang Ming
Published: July 2021

(1) Background: caspase-12 is activated during cytomegalovirus retinitis, although its role is presently unclear. (2) Methods: caspase-12−/− (KO) or caspase-12+/+ (WT) mice were immunosup eyes were analyzed by plaque assay, TUNEL assay, immunohistochemical staining, western blotting, and real-time PCR. (3) Results: increased retinitis and a more extensive virus spread were detected in the retina of infected eyes of KO mice compared to WT mice at day 14 p.i. Compared to MCMV injected WT eyes, mRNA levels of interferons α, β and γ were significantly reduced in the neural retina of MCMV-infected KO eyes at day 14 p.i. Although similar numbers of MCMV infected cells, similar virus titers and similar numbers of TUNEL-staining cells were detected in injected eyes of both KO and WT mice at days 7 and 10 p.i., significantly lower amounts of cleaved caspase-3 and p53 protein were detected in infected eyes of KO mice at both time points. (4) Conclusions: caspase-12 contributes to caspase-3-dependent and independent retinal bystander cell death during MCMV retinitis and may also play an important role in innate immunity against virus infection of the retina.
Protein Corona Hinders N-CQDs Oxidative Potential and Favors Their Application as Nanobiocatalytic System
Authors: Czarnecka Joanna , Kwiatkowski Mateusz , Wiśniewski Marek , Roszek Katarzyna
Published: July 2021

The oxidative properties of nanomaterials arouse legitimate concerns about oxidative damage in biological systems. On the other hand, the undisputable benefits of nanomaterials promote them for biomedical applications; thus, the strategies to reduce oxidative potential are urgently needed. We aimed at analysis of nitrogen-containing carbon quantum dots (N-CQDs) in terms of their biocompatibility and internalization by different cells. Surprisingly, N-CQD uptake does not contribute to the increased oxidative stress inside cells and lacks cytotoxic influence even at high concentrations, primarily through protein corona formation. We proved experimentally that the protein coating effectively limits the oxidative capacity of N-CQDs. Thus, N-CQDs served as an immobilization support for three different enzymes with the potential to be used as therapeutics. Various kinetic parameters of immobilized enzymes were analyzed. Regardless of the enzyme structure and type of reaction catalyzed, adsorption on the nanocarrier resulted in increased catalytic efficiency. The enzymatic-protein-to-nanomaterial ratio is the pivotal factor determining the course of kinetic parameter changes that can be tailored for enzyme application. We conclude that the above properties of N-CQDs make them an ideal support for enzymatic drugs required for multiple biomedical applications, including personalized medical therapies.
LPEATs Tailor Plant Phospholipid Composition through Adjusting Substrate Preferences to Temperature
Authors: Klińska Sylwia , Demski Kamil , Jasieniecka-Gazarkiewicz Katarzyna , Banaś Antoni
Published: July 2021

Acyl-CoA:lysophosphatidylethanolamine acyltransferases (LPEATs) are known as enzymes utilizing acyl-CoAs and lysophospholipids to produce phosphatidylethanolamine. Recently, it has been discovered that they are also involved in the growth regulation of Arabidopsis thaliana. In our study we investigated expression of each Camelina sativa LPEAT isoform and their behavior in response to temperature changes. In order to conduct a more extensive biochemical evaluation we focused both on LPEAT enzymes present in microsomal fractions from C. sativa plant tissues, and on cloned CsLPEAT isoforms expressed in yeast system. Phylogenetic analyses revealed that CsLPEAT1c and CsLPEAT2c originated from Camelina hispida, whereas other isoforms originated from Camelina neglecta. The expression ratio of all CsLPEAT1 isoforms to all CsLPEAT2 isoforms was higher in seeds than in other tissues. The isoforms also displayed divergent substrate specificities in utilization of LPE; CsLPEAT1 preferred 18:1-LPE, whereas CsLPEAT2 preferred 18:2-LPE. Unlike CsLPEAT1, CsLPEAT2 isoforms were specific towards very-long-chain fatty acids. Above all, we discovered that temperature strongly regulates LPEATs activity and substrate specificity towards different acyl donors, making LPEATs sort of a sensor of external thermal changes. We observed the presented findings not only for LPEAT activity in plant-derived microsomal fractions, but also for yeast-expressed individual CsLPEAT isoforms.
Diagnosis and Therapeutic Management of Liver Fibrosis by MicroRNA
Authors: Tadokoro Tomoko , Morishita Asahiro , Masaki Tsutomu
Published: July 2021

Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called “exosomes” have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.
Brain Glucose Transporters: Role in Pathogenesis and Potential Targets for the Treatment of Alzheimer’s Disease
Authors: Szablewski Leszek
Published: July 2021

The most common cause of dementia, especially in elderly people, is Alzheimer’s disease (AD), with aging as its main risk factor. AD is a multifactorial neurodegenerative disease. There are several factors increasing the risk of AD development. One of the main features of Alzheimer’s disease is impairment of brain energy. Hypometabolism caused by decreased glucose uptake is observed in specific areas of the AD-affected brain. Therefore, glucose hypometabolism and energy deficit are hallmarks of AD. There are several hypotheses that explain the role of glucose hypometabolism in AD, but data available on this subject are poor. Reduced transport of glucose into neurons may be related to decreased expression of glucose transporters in neurons and glia. On the other hand, glucose transporters may play a role as potential targets for the treatment of AD. Compounds such as antidiabetic drugs, agonists of SGLT1, insulin, siRNA and liposomes are suggested as therapeutics. Nevertheless, the suggested targets of therapy need further investigations.
Molecular Mechanism of Microbiota Metabolites in Preterm Birth: Pathological and Therapeutic Insights
Authors: Ansari AbuZar , Bose Shambhunath , You Youngah , Park Sunwha , Kim Youngju
Published: July 2021

Preterm birth (PTB) refers to the birth of infants before 37 weeks of gestation and is a challenging issue worldwide. Evidence reveals that PTB is a multifactorial dysregulation mediated by a complex molecular mechanism. Thus, a better understanding of the complex molecular mechanisms underlying PTB is a prerequisite to explore effective therapeutic approaches. During early pregnancy, various physiological and metabolic changes occur as a result of endocrine and immune metabolism. The microbiota controls the physiological and metabolic mechanism of the host homeostasis, and dysbiosis of maternal microbial homeostasis dysregulates the mechanistic of fetal developmental processes and directly affects the birth outcome. Accumulating evidence indicates that metabolic dysregulation in the maternal or fetal membranes stimulates the inflammatory cytokines, which may positively progress the PTB. Although labour is regarded as an inflammatory process, it is still unclear how microbial dysbiosis could regulate the molecular mechanism of PTB. In this review based on recent research, we focused on both the pathological and therapeutic contribution of microbiota-generated metabolites to PTB and the possible molecular mechanisms.
The Role of PERK in Understanding Development of Neurodegenerative Diseases
Authors: Smedley Garrett Dalton , Walker Keenan E. , Yuan Shauna H.
Published: July 2021

Neurodegenerative diseases are an ever-increasing problem for the rapidly aging population. Despite this, our understanding of how these neurodegenerative diseases develop and progress, is in most cases, rudimentary. Protein kinase RNA (PKR)-like ER kinase (PERK) comprises one of three unfolded protein response pathways in which cells attempt to manage cellular stress. However, because of its role in the cellular stress response and the far-reaching implications of this pathway, error within the PERK pathway has been shown to lead to a variety of pathologies. Genetic and clinical studies show a correlation between failure of the PERK pathway in neural cells and the development of neurodegeneration, but the wide array of methodology of these studies is presenting conflicting narratives about the role of PERK in these affected systems. Because of the connection between PERK and pathology, PERK has become a high value target of study for understanding neurodegenerative diseases and potentially how to treat them. Here, we present a review of the literature indexed in PubMed of the PERK pathway and some of the complexities involved in investigating the protein’s role in the development of neurodegenerative diseases as well as how it may act as a target for therapeutics.
Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling
Authors: Salama Yousef , Jaradat Nidal , Hattori Koichi , Heissig Beate
Published: July 2021

Patients diagnosed with melanoma have a poor prognosis due to regional invasion and metastases. The receptor tyrosine kinase epidermal growth factor receptor (EGFR) is found in a subtype of melanoma with a poor prognosis and contributes to drug resistance. Aloysia citrodora essential oil (ALOC-EO) possesses an antitumor effect. Understanding signaling pathways that contribute to the antitumor of ALOC-EO is important to identify novel tumor types that can be targeted by ALOC-EO. Here, we investigated the effects of ALOC-EO on melanoma growth and tumor cell migration. ALOC-EO blocked melanoma growth in vitro and impaired primary tumor cell growth in vivo. Mechanistically, ALOC-EO blocked heparin-binding-epidermal growth factor (HB-EGF)-induced EGFR signaling and suppressed ERK1/2 phosphorylation. Myelosuppressive drugs upregulated HB-EGF and EGFR expression in melanoma cells. Cotreatment of myelosuppressive drugs with ALOC-EO improved the antitumor activity and inhibited the expression of matrix metalloproteinase-7 and -9 and a disintegrin and metalloproteinase domain-containing protein9. In summary, our study demonstrates that ALOC-EO blocks EGFR and ERK1/2 signaling, with preclinical efficacy as a monotherapy or in combination with myelosuppressive drugs in melanoma.
Isoconazole and Clemizole Hydrochloride Partially Reverse the Xeroderma Pigmentosum C Phenotype
Authors: Kobaisi Farah , Sulpice Eric , Barette Caroline , Fayyad Nour , Fauvarque Marie-Odile , Badran Bassam , Fayyad-Kazan Mohammad , Fayyad-Kazan Hussein , Gidrol Xavier , Rachidi Walid
Published: July 2021

Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyper-photosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6-4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals.
Ship Classification Based on Improved Convolutional Neural Network Architecture for Intelligent Transport Systems
Authors: Leonidas Lilian Asimwe , Jie Yang
Published: July 2021

In recent years, deep learning has been used in various applications including the classification of ship targets in inland waterways for enhancing intelligent transport systems. Various researchers introduced different classification algorithms, but they still face the problems of low accuracy and misclassification of other target objects. Hence, there is still a need to do more research on solving the above problems to prevent collisions in inland waterways. In this paper, we introduce a new convolutional neural network classification algorithm capable of classifying five classes of ships, including cargo, military, carrier, cruise and tanker ships, in inland waterways. The game of deep learning ship dataset, which is a public dataset originating from Kaggle, has been used for all experiments. Initially, the five pretrained models (which are AlexNet, VGG, Inception V3 ResNet and GoogleNet) were used on the dataset in order to select the best model based on its performance. Resnet-152 achieved the best model with an accuracy of 90.56%, and AlexNet achieved a lower accuracy of 63.42%. Furthermore, Resnet-152 was improved by adding a classification block which contained two fully connected layers, followed by ReLu for learning new characteristics of our training dataset and a dropout layer to resolve the problem of a diminishing gradient. For generalization, our proposed method was also tested on the MARVEL dataset, which consists of more than 10,000 images and 26 categories of ships. Furthermore, the proposed algorithm was compared with existing algorithms and obtained high performance compared with the others, with an accuracy of 95.8%, precision of 95.83%, recall of 95.80%, specificity of 95.07% and F1 score of 95.81%.