bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous EBV-Reactivation during B Cell Differentiation as a Model for Polymorphic EBV-Driven Lymphoproliferation
Authors: Care Matthew A. , Stephenson Sophie , Owen Roger , Doody Gina M. , Tooze Reuben M.
Published: June 2023

Epstein-Barr virus (EBV)-driven B cell neoplasms arise from the reactivation of latently infected B cells. In a subset of patients, EBV was seen to drive a polymorphous lymphoproliferative disorder (LPD) in which B cell differentiation was retained. In this work, spontaneous EBV reactivation following B cell mitogen stimulation was shown to provide a potential model of polymorphic EBV-driven LPD. Here, we developed an in vitro model of plasma cell (PC) differentiation from peripheral blood memory B cells. To assess the frequency and phenotypes of EBV-associated populations derived during differentiation, we analysed eight differentiations during the PC stage with a targeted single-cell gene expression panel. We identified subpopulations of EBV-gene expressing cells with PC and/or B cell expression features in differentiations from all tested donors. EBV-associated cells varied in frequency, ranging from 3–28% of cells. Most EBV-associated cells expressed PC genes such as XBP1 or MZB1, and in all samples these included a quiescent PC fraction that lacked cell a cycle gene expression. With increasing EBV-associated cells, populations with B cell features became prominent, co-expressing a germinal centre (GC) and activating B cell gene patterns. The presence of highly proliferative EBV-associated cells was linked to retained MS4A1/CD20 expression and IGHM and IGHD co-expression, while IGHM class-switched cells were enriched in quiescent PC fractions. Thus, patterns of gene expression in primary EBV reactivation were shown to include features related to GC B cells, which was also observed in EBV-transformed lymphoblastoid cell lines. This suggests a particular association between spontaneously developing EBV-expansions and IgM+ IgD+ non-switched B cells.
Endoscopic Resection of Early Gastric Cancer and Pre-Malignant Gastric Lesions
Authors: Vasconcelos Ana Clara , Dinis-Ribeiro Mário , Libânio Diogo
Published: June 2023

Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low risk of lymph node metastasis. In general, these lesions consist of two groups of differentiated mucosal adenocarcinomas: non-ulcerated lesions (regardless of their size) and small ulcerated lesions. Endoscopic submucosal dissection is the technique of choice in most cases. This procedure has high rates of complete histological resection while maintaining gastric anatomy and its functions, resulting in fewer adverse events than surgery and having a lesser impact on patient-reported quality of life. Nonetheless, approximately 20% of resected lesions do not fulfill curative criteria and demand further treatment, highlighting the importance of patient selection. Additionally, the preservation of the stomach results in a moderate risk of metachronous lesions, which underlines the need for surveillance. We review the current evidence regarding the endoscopic treatment of early gastric cancer, including the short-and long-term results and management after resection.
Early Detection and Diagnosis of Wind Turbine Abnormal Conditions Using an Interpretable Supervised Variational Autoencoder Model
Authors: Oliveira-Filho Adaiton , Zemouri Ryad , Cambron Philippe , Tahan Antoine
Published: June 2023

The operation and maintenance of wind turbines benefit from reliable information on the wind turbine condition. Data-driven models use data from the supervisory data acquisition system. In particular, great performance is reported for artificial intelligence models. However, the lack of interpretability limits their effective industrial implementation. The present work introduces a new condition-monitoring approach for wind turbines featuring a built-in visualization tool that confers interpretability upon the model outcomes. The proposed approach is based on a supervised implementation of the variational autoencoder model, which allows the projection of the wind turbine system onto a low-dimensional representation space. Three outcomes follow from such representation: a health indicator for the early detection of abnormal conditions, a classifier providing the diagnosis status, and a visualization tool depicting the wind turbine condition as a trajectory in a 2D plot. The approach is implemented with a vast database. Two case studies demonstrate the potential of the proposed approach. The proposed health indicator detects the main bearing overtemperature 11 days before the control system alarm, one week earlier than a competing approach. Study cases illustrate that the built-in visualization tool enhances the interpretability and trust in the model outcomes, thus supporting wind turbine operation and maintenance.
Remnant Magnetisation State Control for Positioning of a Hybrid Tunable Magnet Actuator
Authors: Ronaes Endre , Hunt Andres , HosseinNia Hassan
Published: June 2023

The recent development of a hybrid tunable magnet actuator proposes to eliminate Joule heating when maintaining a force or position offset. By controlling the remnant magnetic flux in an AlNiCo magnet within the actuator, the actuation force can be linearly varied and maintained. While a method for tuning the magnetisation state of the magnet with minimal magnetic field changes has been demonstrated previously, the method is inefficient due to its slow tuning rate, which hinders its use in controlling the actuator’s position. This paper presents a novel method of magnetisation state tuning with a fast tuning rate and validates its effectiveness for controlling the position of a short-stroke linear actuator. This tuning method is implemented and verified for changing the flux density of an AlNiCo magnet in the range of ±1.2 T, with a root-mean-square error (RMSE) of 7.2 mT. An accurate estimation of the magnetisation state is furthermore achieved during positioning, guided by the design and experimental validation of a lumped parameter model, allowing the position to be controlled with an RMSE of 4.0 µm in a range of −157 to 320 µm.
Flexible Solid-State Lithium-Ion Batteries: Materials and Structures
Authors: Deng Ru , He Tian
Published: June 2023

With the rapid development of research into flexible electronics and wearable electronics in recent years, there has been an increasing demand for flexible power supplies, which in turn has led to a boom in research into flexible solid-state lithium-ion batteries. The ideal flexible solid-state lithium-ion battery needs to have not only a high energy density, but also good mechanical properties. We have taken a systematic and comprehensive overview of our work in two main areas: flexible materials and flexible structures. Specifically, we first discuss materials for electrodes (carbon nanotubes, graphite, carbon fibers, carbon cloth, and conducting polymers) and flexible solid materials for electrolytes. A discussion of the structural design of flexible solid-state lithium-ion batteries, including one-dimensional fibrous, two-dimensional thin-film and three-dimensional flexible lithium-ion batteries, follows this. In addition, the advantages and disadvantages of different materials and structures are summarized, and the main challenges for the future design of flexible solid-state lithium-ion batteries are pointed out, hopefully providing some reference for the research of flexible solid-state lithium-ion batteries.
Modeling Annual Electricity Production and Levelized Cost of Energy from the US East Coast Offshore Wind Energy Lease Areas
Authors: Barthelmie Rebecca J. , Larsen Gunner C. , Pryor Sara C.
Published: June 2023

Offshore wind energy development along the East Coast of the US is proceeding quickly as a result of large areas with an excellent wind resource, low water depths and proximity to large electricity markets. Careful planning of wind turbine deployments in these offshore wind energy lease areas (LA) is required to maximize power output and to minimize wake losses between neighboring wind farms as well as those internal to each wind farm. Here, we used microscale wind modeling with two wake parameterizations to evaluate the potential annual energy production (AEP) and wake losses in the different LA areas, and we developed and applied a levelized cost of energy (LCoE) model to quantify the impact of different wind turbine layouts on LCoE. The modeling illustrated that if the current suite of LA is subject to deployment of 15 MW wind turbines at a spacing of 1.85 km, they will generate 4 to 4.6% of total national electricity demand. The LCoE ranged from $68 to $102/MWh depending on the precise layout selected, which is cost competitive with many other generation sources. The scale of the wind farms that will be deployed greatly exceed those currently operating and mean that wake-induced power losses are considerable but still relatively poorly constrained. AEP and LCoE exhibited significant dependence on the precise wake model applied. For the largest LA, the AEP differed by over 10% depending on the wake model used, leading to a $10/MWh difference in LCoE for the wind turbine layout with 1.85 km spacing.
Laurel Regeneration Management by Smallholders to Generate Agroforestry Systems in the Ecuadorian Amazon Upper Basin: Growth and Yield Models
Authors: Cañadas-López Álvaro , Gamboa-Trujillo Paul , Buitrón-Garrido Santiago , Medina-Torres Byron , Velasco Christian , Vargas-Hernández José de Jesús , Wehenkel Christian
Published: June 2023

Laurel (Cordia alliodora Ruiz & Pav. Oken) is a Neotropical native tree that is easily regenerated in the secondary forest within the Amazon region. Amazonian smallholders use this tree regeneration to obtain a homogeneous forest cover when developing local agroforestry systems, which do not depend on nursery seedling production for tree planting. The objective of the present investigation was to develop growth and yield models for Laurel within the local agroforestry systems. A total of 226 sampling plots were measured between 2010–2011 and 2014–2015. Chapman- Richard, Hosslfeld II, and the generalized algebraic difference approach (GADA) form of the Chapman-Richard’s function was used for modeling height-age and diameter-age relationships. Eight volume models were tested to describe total stem volume. The GADA method was suited to describe the Laurel height and diameter-age growth. The cutting cycle for agroforestry systems with a density of 300 trees ha−1 at the best site index (SI) (22 m) produced 13.9 m3 ha−1 year−1 and a total wood yield of 195.1 m3 ha−1 at age 14. In the worst SI (14 m), the average annual yield was 3.5 m3 ha−1, with a total yield of 83.3 m3 ha−1 at age 24 years. The Spurr potential model was the best fit to describe the volume of the Laurel according to the Akaike information criteria. The Laurel biological (optimal) rotation age suggests that the minimum cutting diameter should be lowered from 30 cm of DBH in the research zone. Management of the natural regeneration of secondary forests by smallholders is a local agroforestry practice that should be given greater attention, especially within protected forest areas.
S2NetM: A Semantic Social Network of Things Middleware for Developing Smart and Collaborative IoT-Based Solutions
Authors: Pliatsios Antonios , Lymperis Dimitrios , Goumopoulos Christos
Published: June 2023

The Social Internet of Things (SIoT) paradigm combines the benefits of social networks with IoT networks to create more collaborative and efficient systems, offering enhanced scalability, better navigability, flexibility, and dynamic decision making. However, SIoT also presents challenges related to dynamic friendship selection, privacy and security, interoperability, and standardization. To fully unlock the potential of SIoT, it is crucial to establish semantic interoperability between the various entities, applications, and networks that comprise the system. This paper introduces the Semantic Social Network of Things Middleware (S2NetM), which leverages social relationships to enhance semantic interoperability in SIoT systems. The S2NetM employs semantic reasoning and alignment techniques to facilitate the creation of dynamic, context-aware social networks of things that can collaboratively work together and enable new opportunities for IoT-based solutions. The main contributions of this paper are the specification of the S2NetM and the associated ontology, as well as the discussion of a case study demonstrating the effectiveness of the proposed solution.
An Evolutionary Advantage of the Human Glans Penis
Authors: Leach Stephen
Published: June 2023

To account for the bell- or acorn-shaped glans penis, in 1995 Baker and Bellis put forward their ‘semen-displacement hypothesis’. They argued that the existence of the glans penis is indicative of a promiscuous phase in our evolutionary past, in which females would commonly mate with several males in rapid succession. They argued that within this promiscuous scenario the distinctive shape of the glans penis evolved so as to enable the displacement of rival males’ semen. The idea that there was an influential promiscuous phase in our evolutionary past has faced several powerful criticisms that are here briefly reviewed. However, the critics of the semen-displacement hypothesis have not put forward an alternative evolutionary explanation of the glans penis. I try to redress that here, albeit speculatively. I suggest an alternative hypothesis that may more convincingly account for the shape and texture of the human glans penis.
Evaluating Exposure to VOCs and Naphthalene for Firefighters Wearing Different PPE Configurations through Measures in Air, Exhaled Breath, and Urine
Authors: Mayer Alexander C. , Fent Kenneth W. , Wilkinson Andrea F. , Chen I-Chen , Siegel Miriam R. , Toennis Christine , Sammons Deborah , Meadows Juliana , Kesler Richard M. , Kerber Steve , Smith Denise L. , Masoud Farzaneh , Bhandari Deepak , Wang Yuesong , Blount Benjamin C. , Calafat Antonia M. , Horn Gavin P.
Published: June 2023

Firefighters are at an increased risk of cancer due to their occupational exposure to combustion byproducts, especially when those compounds penetrate the firefighter personal protective equipment (PPE) ensemble. This has led to questions about the impact of base layers (i.e., shorts vs. pants) under PPE ensembles. This study asked 23 firefighters to perform firefighting activities while wearing one of three different PPE ensembles with varying degrees of protection. Additionally, half of the firefighters unzipped their jackets after the scenario while the other half kept their jackets zipped for five additional minutes. Several volatile organic compound (VOC) and naphthalene air concentrations outside and inside of hoods, turnout jackets, and turnout pants were evaluated; biological (urinary and exhaled breath) samples were also collected. VOCs and naphthalene penetrated the three sampling areas (hoods, jackets, pants). Significant (p-value < 0.05) increases from pre- to post-fire for some metabolites of VOCs (e.g., benzene, toluene) and naphthalene were found. Firefighters wearing shorts and short sleeves absorbed higher amounts of certain compounds (p-value < 0.05), and the PPE designed with enhanced interface control features appeared to provide more protection from some compounds. These results suggest that firefighters can dermally absorb VOCs and naphthalene that penetrate the PPE ensemble.
Is Social Participation Associated with Successful Aging among Older Canadians? Findings from the Canadian Longitudinal Study on Aging (CLSA)
Authors: Ho Mabel , Pullenayegum Eleanor , Fuller-Thomson Esme
Published: June 2023

The present study examines various activities of social participation (i.e., church or religious activities; educational or cultural activities; service club or fraternal organization activities; neighbourhood, community, or professional association activities; volunteer or charity work; and recreational activities) as contributing factors to successful aging. Successful aging in this study includes the following: adequate social support, no limitations with respect to Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs), no mental illness in the preceding year, no serious cognitive decline or pain that prevents activity, as well as high levels of happiness, and self-reports of good physical health, mental health, and successful aging. Methods: The Canadian Longitudinal Study on Aging (CLSA) is a large, national, longitudinal study on aging. A secondary analysis of the baseline (i.e., 2011–2015) and Time 2 (i.e., 2015–2018) data of the CLSA was conducted on a sample of 7623 older adults who were defined as “aging successfully” at baseline and were aged 60+ at Time 2. Binary logistic regression analyses were employed to examine the association between engaging in various social participation activities at baseline and aging successfully at Time 2. Results: In a subsample (n = 7623) of the Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort who were aging successfully at baseline, the prevalence of successful aging at Time 2 was significantly higher among the participants who participated in volunteer or charity work and recreational activities compared to those who were not involved in these activities. After adjusting for 22 potential factors, the results of the binary logistic regression analyses reported that participants who, at baseline, participated in volunteer or charity work and recreational activities had higher age–sex-adjusted odds of achieving successful aging (volunteer or charity work: aOR = 1.17, 95% CI: 1.04, 1.33; recreational activities: aOR = 1.15, 95% CI: 1.00, 1.32). Conclusions: Among six types of social participation activities, people who participated in volunteer or charity work and recreational activities were more likely to achieve successful aging than their counterparts who did not engage in these activities. If these associations are found to be causal, policies and interventions encouraging older adults to participate in volunteer or charity work and recreational activities may support older adults to achieve successful aging in later life.
A Machine Learning Approach for Knee Injury Detection from Magnetic Resonance Imaging
Authors: Mangone Massimiliano , Diko Anxhelo , Giuliani Luca , Agostini Francesco , Paoloni Marco , Bernetti Andrea , Santilli Gabriele , Conti Marco , Savina Alessio , Iudicelli Giovanni , Ottonello Carlo , Santilli Valter
Published: June 2023

The knee is an essential part of our body, and identifying its injuries is crucial since it can significantly affect quality of life. To date, the preferred way of evaluating knee injuries is through magnetic resonance imaging (MRI), which is an effective imaging technique that accurately identifies injuries. The issue with this method is that the high amount of detail that comes with MRIs is challenging to interpret and time consuming for radiologists to analyze. The issue becomes even more concerning when radiologists are required to analyze a significant number of MRIs in a short period. For this purpose, automated tools may become helpful to radiologists assisting them in the evaluation of these images. Machine learning methods, in being able to extract meaningful information from data, such as images or any other type of data, are promising for modeling the complex patterns of knee MRI and relating it to its interpretation. In this study, using a real-life imaging protocol, a machine-learning model based on convolutional neural networks used for detecting medial meniscus tears, bone marrow edema, and general abnormalities on knee MRI exams is presented. Furthermore, the model’s effectiveness in terms of accuracy, sensitivity, and specificity is evaluated. Based on this evaluation protocol, the explored models reach a maximum accuracy of 83.7%, a maximum sensitivity of 82.2%, and a maximum specificity of 87.99% for meniscus tears. For bone marrow edema, a maximum accuracy of 81.3%, a maximum sensitivity of 93.3%, and a maximum specificity of 78.6% is reached. Finally, for general abnormalities, the explored models reach 83.7%, 90.0% and 84.2% of maximum accuracy, sensitivity and specificity, respectively.
Mental Health Needs and Services Utilization among Undergraduate and Graduate Students in Texas during the COVID-19 Pandemic
Authors: Villatoro Alice P. , Errisuriz Vanessa L. , DuPont-Reyes Melissa J.
Published: June 2023

COVID-19 created a global crisis, exacerbating disparities in social determinants of health (SDOH) and mental health (MH). Research on pandemic-related MH and help-seeking is scarce, especially among high-risk populations such as college/university students. We examined self-rated MH and psychological distress, the perceived need for MH services/support, and the use of MH services across the SDOH among college/university students during the start of the pandemic. Data from the COVID-19 Texas College Student Experiences Survey (n = 746) include full- and part-time undergraduate/graduate students. Regressions examined self-rated MH, psychological distress, perceived need, and service use across SDOH, controlling for pre-pandemic MH, age, gender, and race/ethnicity. Economic stability was associated with higher risk of poor MH and need for MH services/support. Aspects of the social/community context protected student MH, especially among foreign-born students. Racial discrimination was associated with both greater psychological distress and use of services. Finally, beliefs related to the sufficiency of available institutional MH resources shaped perceived need for and use of services. Although the worst of the pandemic is behind us, the inequitable distribution of the SDOH among students is unwavering. Demand for MH support is high, requiring higher education institutions to better mobilize MH services to meet the needs of students from diverse social contexts.
Inequalities of Infant Mortality in Ethiopia
Authors: Ebrahim Nasser B. , Atteraya Madhu S.
Published: June 2023

(1) Background: Infant mortality is viewed as a core health indicator of overall community health. Although globally child survival has improved significantly over the years, Sub-Saharan Africa is still the region with the highest infant mortality in the world. In Ethiopia, infant mortality is still high, albeit substantial progress has been made in the last few decades. However, there is significant inequalities in infant mortalities in Ethiopia. Understanding the main sources of inequalities in infant mortalities would help identify disadvantaged groups, and develop equity-directed policies. Thus, the purpose of the study was to provide a diagnosis of inequalities of infant mortalities in Ethiopia from four dimensions of inequalities (sex, residence type, mother’s education, and household wealth). (2) Methods: Data disaggregated by infant mortalities and infant mortality inequality dimensions (sex, residence type, mother’s education, and household wealth) from the WHO Health Equity Monitor Database were used. Data were based on Ethiopia’s Demographic and Health Surveys (EDHS) of 2000 (n = 14,072), 2005 (n = 14,500), 2011 (n = 17,817), and 2016 (n = 16,650) households. We used the WHO Health Equity Assessment Toolkit (HEAT) software to find estimates of infant mortalities along with inequality measures. (3) Results: Inequalities related to sex, residence type, mother’s education, and household wealth still exist; however, differences in infant mortalities arising from residence type, mother’s education, and household wealth were narrowing with the exception of sex-related inequality where male infants were markedly at a disadvantage. (4) Conclusions: Although inequalities of infant mortalities related to social groups still exist, there is a substantial sex related infant mortality inequality with disproportional deaths of male infants. Efforts directed at reducing infant mortality in Ethiopia should focus on improving the survival of male infants.
The Effects of Exercise during Pregnancy on Gestational Diabetes Mellitus, Preeclampsia, and Spontaneous Abortion among Healthy Women—A Systematic Review and Meta-Analysis
Authors: Paulsen Camilla Paludan , Bandak Elisabeth , Edemann-Callesen Henriette , Juhl Carsten Bogh , Händel Mina Nicole
Published: June 2023

The aim was to compare the effects of different exercise modalities (aerobic, resistance, aerobic and resistance combined, or mind–body exercise) on gestational diabetes mellitus (GDM), preeclampsia, spontaneous abortion, withdrawal from the study, and adverse events in healthy pregnant women. A systematic search was conducted in February 2022 using MEDLINE, EMBASE, Cochrane library, and SPORT Discus to identify eligible randomized trials. The meta-analysis of 18 studies that examined exercise compared to no exercise showed a reduced risk of GDM (RR: 0.66 (95% CI: 0.50 to 0.86)). No subgroup differences were found regarding modality, intensity, or supervision. Exercise did not reduce the risk of preeclampsia (nine studies, RR: 0.65 (95% CI: 0.42 to 1.03)); however, in subgroup analyses, mind–body exercise and low-intensity exercise seemed to be effective in reduction of preeclampsia. There was no effect of exercise on withdrawal or adverse events found. No studies reported on spontaneous abortion, therefore, exercise during pregnancy is beneficial and safe. In the prevention of GDM, any modality and intensity seem equally effective. Subgroup analyses support an association between mind–body exercise and physical activity with low intensity and reduced risk of preeclampsia, but more high-quality randomized studies are needed. PROSPERO: CRD42022307053.
Feasibility and Acceptability of Using Ecological Momentary Assessment to Evaluate Alcohol Use with American Indian Women
Authors: Hanson Jessica D. , Harris Amy , Gilbertson Rebecca J. , Charboneau Megan , O’Leary Marcia
Published: June 2023

Background: Ecological momentary assessments (EMA) are one way to collect timely and accurate alcohol use data, as they involve signaling participants via cell phones to report on daily behaviors in real-time and in a participant’s natural environment. EMA has never been used with American Indian populations to evaluate alcohol consumption. The purpose of this project was to determine the feasibility and acceptability of EMA for American Indian women. Methods: Eligible participants were American Indian women between the ages of 18 and 44 who were not pregnant and had consumed more than one drink within the past month. All participants received a TracFone and weekly automated messages. Self-reported measures of daily quantity and frequency of alcohol consumption, alcohol type, and context were assessed once per week for four weeks. Baseline measurements also included the Drinking Motives Questionnaire-Revised (DMQ-R) and the Interpersonal Support Evaluation List (ISEL). Results: Fifteen participants were enrolled in the study. All but one participant completed all data collection time points, and drinking patterns were consistent across the study period. A total of 420 records were completed across 86 drinking days and 334 non-drinking days. Participants reported drinking an average of 5.7 days over the 30-day period and typically consumed 3.99 drinks per drinking occasion. Sixty-six percent of participants met gender-specific cut-points for heavy episodic drinking, with an average of 2.46 binge drinking occasions across the four week study period. Conclusions: This proof-of-concept project showed that EMA was both feasible and acceptable for collecting alcohol data from American Indian women. Additional studies are necessary to fully implement EMA with American Indian women to better understand the drinking motives, contexts, patterns, and risk factors in this population.
Occupational Health Risk Assessment for Wastewater Treatment and Reuse in Kanpur, India
Authors: Babalola Folake Monsurat , Breitenmoser Lena , Furlong Claire , Campling Paul , Hooijmans Christine Maria
Published: June 2023

The treatment and reuse of wastewater for irrigation can lead to occupational health risks for sewage treatment plant (STP) workers and farmers. Sanitation Safety Planning (SSP) is an approach which can be used to measure and mitigate these risks. This paper explores what impact a novel secondary treatment process, consisting of an integrated permeate channel (IPC) membrane combined with a constructed wetland plus, has on the occupational health risks compared with the existing activated sludge wastewater treatment process and reuse system in Kanpur, Uttar Pradesh. A mixed methodology was used, which included key informant interviews, structured observations, and E. coli analysis. This data was used to undertake semi-quantitative risk assessments following the SSP approach. The novel secondary treatment increased the number of health risks which the STP workers were exposed to, but the severity of the risks was lower. This was due to the differences in treatment processes and infrastructures. The number of health risks for the farmers decreased both in number and severity. For their children, the severity of the health impacts decreased. These changes were due to the increase in the microbiological quality of the irrigation water. This study highlights the potential of using a semi-quantitative risk assessment to assess the occupational health impacts of using novel treatment technologies.
Porcine Follicular Fluid-Derived Exosome: The Pivotal Material for Porcine Oocyte Maturation in Lipid Antioxidant Activity
Authors: Kim Euihyun , Ra Kihae , Lee Myung-Shin , Kim Geon A.
Published: June 2023

Several studies have examined exosomes derived from porcine follicular fluid (FF), but few have reported their application in controlled experiments. The main concern in the field of embryology may be that controlled conditions, such as using a defined medium intermittently, cause poor results in mammalian oocyte maturation and embryo development. The first reason is the absence of the FF, which copes with the majority of the processes emerging in oocytes and embryos. Therefore, we added exosomes derived from porcine FF to the maturation medium of porcine oocytes. For morphological assessment, cumulus cell expansion and subsequent embryonic development were evaluated. Moreover, several stainings, such as glutathione (GSH) and reactive oxygen species (ROS), fatty acid, ATP, and mitochondrial activity, as well as evaluations of gene expression and protein analysis, were used for the functional verification of exosomes. When the oocytes were treated with exosomes, the lipid metabolism and cell survival of the oocytes were fully recovered, as well as morphological evaluations compared to the porcine FF-excluded defined medium. Therefore, controlled experiments may produce reliable data if the exosomes are treated with the desired amounts, and we suggest applying FF-derived exosomes to promote experimental data when performing controlled experiments in embryology.
Natural and Pathological Autoantibodies Show Age-Related Changes in a Spontaneous Autoimmune Mouse (NZB) Model
Authors: Gál Szonja , Gajdócsi Erzsébet , Khanfar Esam , Olasz Katalin , Simon Diána , Balogh Péter , Berki Tímea , Németh Péter , Boldizsár Ferenc
Published: June 2023

The natural autoantibody (natAAb) network is thought to play a role in immune regulation. These IgM antibodies react with evolutionary conserved antigens; however, they do not lead to pathological tissue destruction as opposed to pathological autoantibodies (pathAAb). The exact relation between the natAAbs and pathAAbs is still not completely understood; therefore, in the present study, we set out to measure nat- and pathAAb levels against three conserved antigens in a spontaneous autoimmune disease model: the NZB mouse strain which develops autoimmune hemolytic anemia (AIHA) from six months of age. There was an age dependent increase in the natAAb levels in the serum against Hsp60, Hsp70, and the mitochondrial citrate synthase until 6–9 months of age, followed by a gradual decrease. The pathological autoantibodies appeared after six months of age, which corresponded with the appearance of the autoimmune disease. The changes in nat/pathAAb levels were coupled with decreasing B1- and increasing plasma cell and memory B cell percentages. Based on this, we propose that there is a switch from natAAbs towards pathAAbs in aged NZB mice.
Cellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract
Authors: Choi Egan L. , Taheri Negar , Chandra Abhishek , Hayashi Yujiro
Published: June 2023

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.
Single-Cell RNA-Sequencing Reveals the Skeletal Cellular Dynamics in Bone Repair and Osteoporosis
Authors: Wu Sixun , Ohba Shinsuke , Matsushita Yuki
Published: June 2023

The bone is an important organ that performs various functions, and the bone marrow inside the skeleton is composed of a complex intermix of hematopoietic, vascular, and skeletal cells. Current single-cell RNA sequencing (scRNA-seq) technology has revealed heterogeneity and sketchy differential hierarchy of skeletal cells. Skeletal stem and progenitor cells (SSPCs) are located upstream of the hierarchy and differentiate into chondrocytes, osteoblasts, osteocytes, and bone marrow adipocytes. In the bone marrow, multiple types of bone marrow stromal cells (BMSCs), which have the potential of SSPCs, are spatiotemporally located in distinct areas, and SSPCs’ potential shift of BMSCs may occur with the advancement of age. These BMSCs contribute to bone regeneration and bone diseases, such as osteoporosis. In vivo lineage-tracing technologies show that various types of skeletal lineage cells concomitantly gather and contribute to bone regeneration. In contrast, these cells differentiate into adipocytes with aging, leading to senile osteoporosis. scRNA-seq analysis has revealed that alteration in the cell-type composition is a major cause of tissue aging. In this review, we discuss the cellular dynamics of skeletal cell populations in bone homeostasis, regeneration, and osteoporosis.
Caffeic Acid Phenethyl Ester and Caffeamide Derivatives Suppress Oral Squamous Cell Carcinoma Cells
Authors: Shih Yin-Hwa , Chen Chieh-Chieh , Kuo Yueh-Hsiung , Fuh Lih-Jyh , Lan Wan-Chen , Wang Tong-Hong , Chiu Kuo-Chou , Nguyen Thanh-Hien Vu , Hsia Shih-Min , Shieh Tzong-Ming
Published: June 2023

Caffeic acid phenethyl ester (CAPE) contains antibiotic and anticancer activities. Therefore, we aimed to investigate the anticancer properties and mechanisms of CAPE and caffeamide derivatives in the oral squamous cell carcinoma cell (OSCC) lines SAS and OECM-1. The anti-OSCC effects of CAPE and the caffeamide derivatives (26G, 36C, 36H, 36K, and 36M) were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. Cell cycle and total reactive oxygen species (ROS) production were analyzed using flow cytometry. The relative protein expression of malignant phenotypes was determined via Western blot analysis. The results showed that 26G and 36M were more cytotoxic than the other compounds in SAS cells. After 26G or 36M treatment for 48 h, cell cycle S phase or G2/M phase arrest was induced, and cellular ROS increased at 24 h, and then decreased at 48 h in both cell lines. The expression levels of cell cycle regulatory and anti-ROS proteins were downregulated. In addition, 26G or 36M treatment inhibited malignant phenotypes through mTOR-ULK1-P62-LC3 autophagic signaling activated by ROS generation. These results showed that 26G and 36M induce cancer cell death by activating autophagy signaling, which is correlated with altered cellular oxidative stress.
Impact of IDH Mutations, the 1p/19q Co-Deletion and the G-CIMP Status on Alternative Splicing in Diffuse Gliomas
Authors: Zhang Lu , Fritah Sabrina , Nazarov Petr V. , Kaoma Tony , Van Dyck Eric
Published: June 2023

By generating protein diversity, alternative splicing provides an important oncogenic pathway. Isocitrate dehydrogenase (IDH) 1 and 2 mutations and 1p/19q co-deletion have become crucial for the novel molecular classification of diffuse gliomas, which also incorporates DNA methylation profiling. In this study, we have carried out a bioinformatics analysis to examine the impact of the IDH mutation, as well as the 1p/19q co-deletion and the glioma CpG island methylator phenotype (G-CIMP) status on alternative splicing in a cohort of 662 diffuse gliomas from The Cancer Genome Atlas (TCGA). We identify the biological processes and molecular functions affected by alternative splicing in the various glioma subgroups and provide evidence supporting the important contribution of alternative splicing in modulating epigenetic regulation in diffuse gliomas. Targeting the genes and pathways affected by alternative splicing might provide novel therapeutic opportunities against gliomas.
Metabolic Mechanisms and Potential Therapeutic Targets for Prevention of Ovarian Aging: Data from Up-to-Date Experimental Studies
Authors: Valtetsiotis Konstantinos , Valsamakis Georgios , Charmandari Evangelia , Vlahos Nikolaos F.
Published: June 2023

Female infertility and reproduction is an ongoing and rising healthcare issue, resulting in delaying the decision to start a family. Therefore, in this review, we examine potential novel metabolic mechanisms involved in ovarian aging according to recent data and how these mechanisms may be addressed through new potential medical treatments. We examine novel medical treatments currently available based mostly on experimental stem cell procedures as well as caloric restriction (CR), hyperbaric oxygen treatment and mitochondrial transfer. Understanding the connection between metabolic and reproductive pathways has the potential to offer a significant scientific breakthrough in preventing ovarian aging and prolonging female fertility. Overall, the field of ovarian aging is an emerging field that may expand the female fertility window and perhaps even reduce the need for artificial reproductive techniques.
mTOR Inhibition Is Effective against Growth, Survival and Migration, but Not against Microglia Activation in Preclinical Glioma Models
Authors: Lisi Lucia , Pizzoferrato Michela , Ciotti Gabriella Maria Pia , Martire Maria , Navarra Pierluigi
Published: June 2023

Initially introduced in therapy as immunosuppressants, the selective inhibitors of mTORC1 have been approved for the treatment of solid tumors. Novel non-selective inhibitors of mTOR are currently under preclinical and clinical developments in oncology, attempting to overcome some limitations associated with selective inhibitors, such as the development of tumor resistance. Looking at the possible clinical exploitation in the treatment of glioblastoma multiforme, in this study we used the human glioblastoma cell lines U87MG, T98G and microglia (CHME-5) to compare the effects of a non-selective mTOR inhibitor, sapanisertib, with those of rapamycin in a large array of experimental paradigms, including (i) the expression of factors involved in the mTOR signaling cascade, (ii) cell viability and mortality, (iii) cell migration and autophagy, and (iv) the profile of activation in tumor-associated microglia. We could distinguish between effects of the two compounds that were overlapping or similar, although with differences in potency and or/time-course, and effects that were diverging or even opposite. Among the latter, especially relevant is the difference in the profile of microglia activation, with rapamycin being an overall inhibitor of microglia activation, whereas sapanisertib was found to induce an M2-profile, which is usually associated with poor clinical outcomes.
Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice
Authors: Wang Yawei , Lin Hongbing , Huang Wenxin , Liu Zixian , Chen Zhen , Zhao Xuetao , Ding Tong , Qin Wenguang , Shen Yuqin
Published: June 2023

Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of acsl4, slc7a11, gpx4 and tfr1 were measured using qPCR and the protein expression of ACSL4, SLC7A11, GPX4 and TfR1 were investigated by Western blot and immunocytochemistry (IHC). Curcumin reduced the level of MDA and increased the level of GSH. Additionally, curcumin was proven to significantly increase the expression levels of SLC7A11 and GPX4 and inhibit the expression of ACSL4 and TfR1. In conclusion, curcumin plays a protective role by inhibiting ferroptosis in ligature-induced periodontal-diseased mice.
Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2
Authors: Prüschenk Sally , Majer Michael , Schlossmann Jens
Published: June 2023

The inositol triphosphate-associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins that regulate intracellular Ca2+. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca2+ channel IP3R-I and the PKGIβ and inhibits IP3R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homolog of IRAG1 and was recently also determined as a PKGI substrate. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile elucidated in a variety of human and murine tissues, e.g., of IRAG1 in various smooth muscles, heart, platelets, and other blood cells, of IRAG2 in the pancreas, heart, platelets, and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g., smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these two regulatory proteins to envision their molecular and (patho-)physiological tasks and to unravel their functional interplay as possible (patho-)physiological counterparts.
Mastocytosis and Skin Cancer: The Current State of Knowledge
Authors: Kaszuba Agnieszka , Sławińska Martyna , Żółkiewicz Jakub , Sobjanek Michał , Nowicki Roman J. , Lange Magdalena
Published: June 2023

Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have demonstrated that patients suffering from mastocytosis face an increased risk of melanoma and non-melanoma skin cancer. The cause of this has not yet been clearly identified. In the literature, the potential influence of several factors has been suggested, including genetic background, the role of cytokines produced by mast cells, iatrogenic and hormonal factors. The article summarizes the current state of knowledge regarding the epidemiology, pathogenesis, diagnosis, and management of skin neoplasia in mastocytosis patients.
Folate and Cobalamin Deficiencies during Pregnancy Disrupt the Glucocorticoid Response in Hypothalamus through N-Homocysteinilation of the Glucocorticoid Receptor
Authors: Michel Arnaud , Kokten Tunay , Saber-Cherif Lynda , Umoret Rémy , Alberto Jean-Marc , Helle Déborah , Julien Amélia , Daval Jean-Luc , Guéant Jean-Louis , Bossenmeyer-Pourié Carine , Pourié Grégory
Published: June 2023

Vitamin B9 (folate)/B12 (cobalamin) deficiency is known to induce brain structural and/or functional retardations. In many countries, folate supplementation, targeting the most severe outcomes such as neural tube defects, is discontinued after the first trimester. However, adverse effects may occur after birth because of some mild misregulations. Various hormonal receptors were shown to be deregulated in brain tissue under these conditions. The glucocorticoid receptor (GR) is particularly sensitive to epigenetic regulation and post-translational modifications. In a mother–offspring rat model of vitamin B9/B12 deficiency, we investigated whether a prolonged folate supplementation could restore the GR signaling in the hypothalamus. Our data showed that a deficiency of folate and vitamin B12 during the in-utero and early postnatal periods was associated with reduced GR expression in the hypothalamus. We also described for the first time a novel post-translational modification of GR that impaired ligand binding and GR activation, leading to decrease expression of one of the GR targets in the hypothalamus, AgRP. Moreover, this brain-impaired GR signaling pathway was associated with behavioral perturbations during offspring growth. Importantly, perinatal and postnatal supplementation with folic acid helped restore GR mRNA levels and activity in hypothalamus cells and improved behavioral deficits.