bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Endogenous Retrovirus-H-Derived miR-4454 Inhibits the Expression of DNAJB4 and SASH1 in Non-Muscle-Invasive Bladder Cancer
Authors: Park Eun Gyung , Lee Du Hyeong , Kim Woo Ryung , Lee Yun Ju , Bae Woo Hyeon , Kim Jung-min , Shin Hae Jin , Ha Hongseok , Yi Joo Mi , Cho Ssang Goo , Choi Yung Hyun , Leem Sun Hee , Cha Hee Jae , Kim Sang Woo , Kim Heui Soo
Published: July 2023

Although most human endogenous retroviruses (HERVs) have been silenced and lost their ability to translocate because of accumulated mutations during evolution, they still play important roles in human biology. Several studies have demonstrated that HERVs play pathological roles in numerous human diseases, especially cancer. A few studies have revealed that long non-coding RNAs that are transcribed from HERV sequences affect cancer progression. However, there is no study on microRNAs derived from HERVs related to cancer. In this study, we identified 29 microRNAs (miRNAs) derived from HERV sequences in the human genome. In particular, we discovered that miR-4454, which is HERV-H-derived miRNA, was upregulated in non-muscle-invasive bladder cancer (NMIBC) cells. To figure out the effects of upregulated miR-4454 in NMIBC, genes whose expression was downregulated in NMIBC, as well as tumor suppressor genes, were selected as putative target genes of miR-4454. The dual-luciferase assay was used to determine the negative relationship between miR-4454 and its target genes, DNAJB4 and SASH1, and they were confirmed to be promising target genes of miR-4454. Taken together, this study suggests that the upregulation of miR-4454 derived from HERV-H in NMIBC reduces the expression of the tumor suppressor genes, DNAJB4 and SASH1, to promote NMIBC progression.
Genome-Wide Identification, Characterization, and Expression Analysis of the NAC Gene Family in Litchi chinensis
Authors: Liao Guihua , Duan Yu , Wang Congcong , Zhuang Zebin , Wang Haishi
Published: July 2023

NAC proteins play an essential role in the growth and development of litchi, especially during reproductive development. However, a comprehensive analysis of the litchi NAC gene family is currently absent. Based on information from the litchi genome, we found that the 112 NAC genes of litchi show an uneven distribution on the chromosomes. Phylogenetic and conserved structural domain analyses indicated that different types of variability were exhibited in the family of litchi NACs (LcNACs). Gene covariance analysis showed that the LcNACs showed better similarity in the same genus than with Arabidopsis. We further investigated the differential expression patterns of LcNACs in buds and rudimentary leaves of litchi. qRT-PCR results implied that they were involved in the process. Profiling of LcNAC promoter elements in litchi showed that they were extensively involved in light response, phytohormone regulation, abiotic stress response, and plant growth and development processes. This study provides new insights into the identification, structural characterization, tissue-specific expression analysis, and promoter response elements of LcNACs. It reveals the characteristics of the LcNACs and lays the foundation for the subsequent understanding of its biological functions and molecular regulatory mechanisms.
Exploring the Effect of Ethnicity on Chronic Orofacial Pain: A Comparative Study of Jewish and Arab Israeli Patients
Authors: Yanko Robert , Badran Yaara , Leibovitz Shirley , Sharav Yair , Vered Yuval , Keshet Naama , Rettman Andra , Aframian Doron J. , Haviv Yaron
Published: July 2023

The relationship between ethnicity and chronic pain has been studied worldwide. The population of Israel includes two main ethnic groups, 75% Jews and 21% Arabs. The purpose of this study was to compare orofacial chronic pain characteristics and treatment outcomes between Jewish and Arab Israeli citizens. Two hundred patients admitted to the Orofacial Pain Clinic at Hebrew University–Hadassah School of Dental Medicine between 2017 and 2022 were selected randomly for this historical cohort study. Our cohort included 159 (79.5%) Jews and 41 (20.5%) Arabs. Twenty-six pain-related variables were compared of which only two differed significantly between the two groups, awakening due to pain and mean muscle sensitivity; both indicators were higher in the Arab group (p < 0.05). No differences were found in any of the other variables such as diagnosis, pain severity, onset, and treatment outcome. This minimal difference may be explained by the equal accessibility to medical services for all citizens, and the diversity of our staff that includes Jew as well as Arab service providers. These factors minimize or even eliminate racial bias, language, and cultural barriers, and is reflected in the minor differences in orofacial pain characteristics found between the two main ethnic groups in Israel.
Beyond Patient Characteristics: A Narrative Review of Contextual Factors Influencing Involuntary Admissions in Mental Health Care
Authors: Aluh Deborah Oyine , Aigbogun Osaro , Ukoha-Kalu Blessing Onyinye , Silva Manuela , Grigaitė Ugnė , Pedrosa Barbara , Santos-Dias Margarida , Cardoso Graça , Caldas-de-Almeida José Miguel
Published: July 2023

Variations in the rates of involuntary admission (IA) reflect the influence of unexplained contextual variables that are typically too heterogeneous to be included in systematic reviews. This paper attempts to gather and analyze factors unrelated to the patients that have been linked to IA. The articles included in this review were selected by iteratively searching four electronic databases (PubMed, PsychINFO, EMBASE, and Web of Science). A total of 54 studies from 19 different countries and regions, including 14 European countries, the United States, Canada, China, Vietnam, and Taiwan, were selected. The factors were categorized as service-related factors, impactful events, seasonal and temporal factors, mental health legislation, staff factors, and public attitudes. The factors rarely act in isolation but rather interact and reinforce each other, causing a greater influence on IA. This paper explains how these factors present opportunities for robust and sustainable interventions to reduce IAs. The paper also identifies future directions for research, such as examining the effects of economic recessions. Enhancing global reporting standards is essential to validate future research and support further in-depth studies. The complexity of the factors influencing IA and the implicit role of society suggest that resolving it will require social change.
Monitoring Water Balance to Predict Hospitalization in Patients with Chronic Heart Failure: A Retrospective Study
Authors: Hirose Kenichi , Otsuka Keita , Shiozawa Shinichiro , Hirose Go , Shino Miwa , Hokari Takeo , Kohno Satoru , Nakayama Kohzo
Published: July 2023

Background: Patients with chronic heart failure often experience repeated acute exacerbations leading to high rates of rehospitalization. Therefore, the management of patients to prevent rehospitalization and retain their physical function is important. Brain natriuretic peptide (BNP) and N-terminal-pro BNP are used to estimate the conditions of patients with chronic heart failure, but some hospitals cannot measure these levels in real time. To overcome this, we used bioelectrical impedance analysis as an alternative. Methods and results: Between April 2017 and December 2019, we measured water balance in the outpatient department of Hirose Hospital in three groups: those who had been hospitalized for chronic heart failure (257 patients), those with chronic heart failure who had not been hospitalized (224 patients), and controls with other chronic diseases (275 patients). We found that water balance was significantly correlated to the history of hospitalization, and age was a confounding bias in this correlation, regardless of whether patients have been hospitalized with chronic heart failure. Moreover, patients who have high extracellular water content/total body water content ratios, even in a stable period, are at risk of becoming unstable and experiencing rehospitalization. Conclusion: Water balance monitoring could be a useful indicator to estimate patient condition in real time and predict improvement in chronic heart failure. This easy-to-use indicator may enable timely management of exacerbation of patient condition and reduce hospitalization events.
Enhanced Differentiation of Wild and Feeding Civet Coffee Using Near-Infrared Spectroscopy with Various Sample Pretreatments and Chemometric Approaches
Authors: Prajna Deyla , Álvarez María , Barea-Sepúlveda Marta , Calle José Luis P. , Suhandy Diding , Setyaningsih Widiastuti , Palma Miguel
Published: July 2023

Civet coffee is the world’s most expensive and rarest coffee bean. Indonesia was the first country to be identified as the origin of civet coffee. First, it is produced spontaneously by collecting civet feces from coffee plantations near the forest. Due to limited stock, farmers began cultivating civets to obtain safe supplies of civet coffee. Based on this, civet coffee can be divided into two types: wild and fed. A combination of spectroscopy and chemometrics can be used to evaluate authenticity with high speed and precision. In this study, seven samples from different regions were analyzed using NIR Spectroscopy with various preparations: unroasted, roasted, unground, and ground. The spectroscopic data were combined with unsupervised exploratory methods (hierarchical cluster analysis (HCA) and principal component analysis (PCA)) and supervised classification methods (support vector machine (SVM) and random forest (RF)). The HCA results showed a trend between roasted and unroasted beans; meanwhile, the PCA showed a trend based on coffee bean regions. Combining the SVM with leave-one-out-cross-validation (LOOCV) successfully differentiated 57.14% in all sample groups (unground, ground, unroasted, unroasted–unground, and roasted–unground), 78.57% in roasted, 92.86% in roasted–ground, and 100% in unroasted–ground. However, using the Boruta filter, the accuracy increased to 89.29% for all samples, to 85.71% for unground and unroasted–unground, and 100% for roasted, unroasted–ground, and roasted–ground. Ultimately, RF successfully differentiated 100% of all grouped samples. In general, roasting and grinding the samples before analysis improved the accuracy of differentiating between wild and feeding civet coffee using NIR Spectroscopy.
The Missing and the Marginalized: A Biocultural Approach to Forensic Anthropology at the US/Mexico Border
Authors: Adams Elise J. , Goliath Jesse R.
Published: July 2023

Violence and trauma are nestled in human rights violations worldwide. Since the 1980s, several international and domestic organizations have formed to conduct investigations following instances of political unrest and sociocultural violence. These inhumane events are evidenced by structural violence, an invisible trauma that exacerbates societal discrepancies within a population and can manifest harm to marginalized groups. Structural violence can be observed in both living individuals and through the treatment of human remains. Individuals who are missing or remain unidentified from violent outbreaks are often from marginalized groups. Therefore, a biocultural approach is necessary as it emphasizes the interplay between biology, environment, and culture. Recent work on human rights violations in the Americas has focused on fatalities due to increased migration at the US/Mexico border. Multiple organizations from the United States and other countries have developed strategies to assist in the recovery, identification, and repatriation of migrants. We aim to highlight the biocultural approach in these humanitarian actions, especially the practice of forensic anthropology, with structural violence and humanitarian identification efforts related to the missing and unidentified persons found along the US/Mexico border.
The Effect of Horizontal Specific Temperature on the Flow Systems of the Transdanubian Mountains (Hungary)
Authors: Veress Márton , Péntek Kálmán
Published: July 2023

This study interprets the development of various flow types of the Transdanubian Mountains. For this, pressure was calculated at different depths and along some profiles the horizontal, specific temperature was calculated based on geoisotherms. This is the value of temperature distribution calculated to a given place. It has been established that upwellings develop at sites where the value of horizontal specific temperature is more than 0.8 °C, and partial upwelling can be detected where this value is between 0.6 °C and 0.8 °C. Outflow from the karst is present where this value is below 0.4 °C. Taking into consideration these values, the water temperature of karst springs and the caves of heat effect, the distribution of various flow types are determined. The flow type is also affected by the fault structure of the basin. In the case of horsts subsided to a great degree, since the sediment is thick above such horsts, the water is not able to flow upwards and towards the mountains because the hydrostatic pressure does not prevail any more. Above horsts subsided to a lower degree, the sediment is thin and thus, the water moving upwards is able to flow through.
Completion of the Continuum of Maternity Care in the Emerging Regions of Ethiopia: Analysis of the 2019 Demographic and Health Survey
Authors: Hussen Abdulaziz Mohammed , Ibrahim Ibrahim Mohammed , Tilahun Binyam , Tunçalp Özge , Grobbee Diederick E. , Browne Joyce L.
Published: July 2023

Maternal mortality in Ethiopia was estimated to be 267 per 100,000 live births in 2020. A significant number of maternal deaths occur in the emerging regions of the country: Afar, Somali, Gambela, and Benishangul-Gumuz. Achieving the Sustainable Development Goal (SDG) target requires a dramatic increase in maternal healthcare utilisation during pregnancy, childbirth, and the postpartum period. Yet, there is a paucity of evidence on the continuum of maternity care utilisation in Ethiopia, particularly in the emerging regions. Therefore, this study aimed to assess completion and factors associated with the continuum of maternity care in the emerging regions of Ethiopia. This study used the 2019 Ethiopian Demographic and Health Survey data (n = 1431). Bivariable and multivariable logistic regression analyses were carried out to identify factors associated with the completion of the continuum of maternity care. An adjustment was made to the survey design (weight, stratification, and clustering). 9.5% (95% Confidence Interval (CI): 7.0–13.0) of women completed the continuum of maternity care (four or more antenatal care, institutional delivery, and postnatal care within 24 h). Living in Somali (adjusted Odds Ratio (aOR): 0.23, 95%CI: 0.07–0.78) and Benishangul-Gumuz (aOR 3.41, 95%CI: 1.65–7.04) regions, having a secondary and higher educational level (aOR 2.12, 95%CI: 1.13–4.00), and being in the richest wealth quintile (aOR 4.55, 95%CI: 2.04–10.15) were factors associated with completion of the continuum of maternity care. Although nearly half of the women had one antenatal care, fewer than 10% completed the continuum of maternity care. This indicates that women in these regions are not getting the maximum health benefits from maternal healthcare services, and this might contribute to the high maternal death in the regions. Moreover, the completion of the continuum of maternity care was skewed toward women who are more educated (secondary or higher education) and in the richest quintile.
Current Discoveries and Future Implications of Eating Disorders
Authors: Feng Bing , Harms Jerney , Chen Emily , Gao Peiyu , Xu Pingwen , He Yanlin
Published: July 2023

Eating disorders (EDs) are characterized by severe disturbances in eating behaviors and can sometimes be fatal. Eating disorders are also associated with distressing thoughts and emotions. They can be severe conditions affecting physical, psychological, and social functions. Preoccupation with food, body weight, and shape may also play an important role in the regulation of eating disorders. Common eating disorders have three major types: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). In some cases, EDs can have serious consequences for an individual’s physical and mental health. These disorders often develop during adolescence or early adulthood and affect both males and females, although they are more commonly diagnosed in young adult females. Treatment for EDs typically involves a combination of therapy, nutrition counseling, and medical care. In this narrative review, the authors summarized what is known of EDs and discussed the future directions that may be worth exploring in this emerging area.
Formation of Transient Protein Aggregate-like Centers Is a General Strategy Postponing Degradation of Misfolded Intermediates
Authors: Boronat Susanna , Cabrera Margarita , Vega Montserrat , Alcalá Jorge , Salas-Pino Silvia , Daga Rafael R. , Ayté José , Hidalgo Elena
Published: July 2023

When misfolded intermediates accumulate during heat shock, the protein quality control system promotes cellular adaptation strategies. In Schizosaccharomyces pombe, thermo-sensitive proteins assemble upon stress into protein aggregate-like centers, PACs, to escape from degradation. The role of this protein deposition strategy has been elusive due to the use of different model systems and reporters, and to the addition of artificial inhibitors, which made interpretation of the results difficult. Here, we compare fission and budding yeast model systems, expressing the same misfolding reporters in experiments lacking proteasome or translation inhibitors. We demonstrate that mild heat shock triggers reversible PAC formation, with the collapse of both reporters and chaperones in a process largely mediated by chaperones. This assembly postpones proteasomal degradation of the misfolding reporters, and their Hsp104-dependent disassembly occurs during stress recovery. Severe heat shock induces formation of cytosolic PACs, but also of nuclear structures resembling nucleolar rings, NuRs, presumably to halt nuclear functions. Our study demonstrates that these distantly related yeasts use very similar strategies to adapt and survive to mild and severe heat shock and that aggregate-like formation is a general cellular scheme to postpone protein degradation and facilitate exit from stress.
Conjugated Linoleic Acid-Mediated Connexin-43 Remodeling and Sudden Arrhythmic Death in Myocardial Infarction
Authors: Kelm Natia Qipshidze , Solinger Jane C. , Piell Kellianne M. , Cole Marsha P.
Published: July 2023

Connexin 43 (Cx43) is expressed in the left and right ventricles and is primarily responsible for conducting physiological responses in microvasculature. Studies have demonstrated that NADPH oxidase (NOX) enzymes are essential in cardiac redox biology and are responsible for the generation of reactive oxygen species (ROS). NOX2 is linked to left ventricular remodeling following myocardial infarction (MI). It was hypothesized that conjugated linoleic acid (cLA) treatment increases NOX-2 levels in heart tissue and disrupts connexins between the myocytes in the ventricle. Data herein demonstrate that cLA treatment significantly decreases survival in a murine model of MI. The observance of cLA-induced ventricular tachyarrhythmia’s (VT) led to the subsequent investigation of the underlying mechanism in this MI model. Mice were treated with cLA for 12 h, 24 h, 48 h, or 72 h to determine possible time-dependent changes in NOX and Cx43 signaling pathways in isolated left ventricles (LV) extracted from cardiac tissue. The results suggest that ROS generation, through the stimulation of NOX2 in the LV, triggers a decrease in Cx43 levels, causing dysfunction of the gap junctions following treatment with cLA. This cascade of events may initiate VT and subsequent death during MI. Taken together, individuals at risk of MI should use caution regarding cLA consumption.
The Zebrafish Embryo as a Model Organism for Testing mRNA-Based Therapeutics
Authors: Bondue Tjessa , Berlingerio Sante Princiero , van den Heuvel Lambertus , Levtchenko Elena
Published: July 2023

mRNA-based therapeutics have revolutionized the world of molecular therapy and have proven their potential in the vaccination campaigns for SARS-CoV2 and clinical trials for hereditary disorders. Preclinical studies have mainly focused on in vitro and rodent studies. However, research in rodents is costly and labour intensive, and requires ethical approval for all interventions. Zebrafish embryonic disease models are not always classified as laboratory animals and have been shown to be extremely valuable for high-throughput drug testing. Zebrafish larvae are characterized by their small size, optical transparency and high number of embryos, and are therefore also suited for the study of mRNA-based therapeutics. First, the one-cell stage injection of naked mRNA can be used to assess the effectivity of gene addition in vivo. Second, the intravascular injection in older larvae can be used to assess tissue targeting efficiency of (packaged) mRNA. In this review, we describe how zebrafish can be used as a steppingstone prior to testing mRNA in rodent models. We define the procedures that can be employed for both the one-cell stage and later-stage injections, as well as the appropriate procedures for post-injection follow-up.
Effect of Trace Metal Ions on the Conformational Stability of the Visual Photoreceptor Rhodopsin
Authors: Wang Feifei , Fernandez-Gonzalez Pol , Ramon Eva , Gomez-Gutierrez Patricia , Morillo Margarita , Garriga Pere
Published: July 2023

Trace metals are essential elements that play key roles in a number of biochemical processes governing human visual physiology in health and disease. Several trace metals, such as zinc, have been shown to play important roles in the visual phototransduction process. In spite of this, there has been little research conducted on the direct effect of trace metal elements on the visual photoreceptor rhodopsin. In the current study, we have determined the effect of several metal ions, such as iron, copper, chromium, manganese, and nickel, on the conformational stability of rhodopsin. To this aim, we analyzed, by means of UV-visible and fluorescence spectroscopic methods, the effects of these trace elements on the thermal stability of dark rhodopsin, the stability of its active Metarhodopsin II conformation, and its chromophore regeneration. Our results show that copper prevented rhodopsin regeneration and slowed down the retinal release process after illumination. In turn, Fe3+, but not Fe2+, increased the thermal stability of the dark inactive conformation of rhodopsin, whereas copper ions markedly decreased it. These findings stress the important role of trace metals in retinal physiology at the photoreceptor level and may be useful for the development of novel therapeutic strategies to treat retinal disease.
Transition Networks Unveil Disorder-to-Order Transformations in Aβ Caused by Glycosaminoglycans or Lipids
Authors: Schäffler Moritz , Samantray Suman , Strodel Birgit
Published: July 2023

The aggregation of amyloid-β (Aβ) peptides, particularly of Aβ1−42, has been linked to the pathogenesis of Alzheimer’s disease. In this study, we focus on the conformational change of Aβ1−42 in the presence of glycosaminoglycans (GAGs) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipids using molecular dynamics simulations. We analyze the conformational changes that occur in Aβ by extracting the key structural features that are then used to generate transition networks. Using the same three features per network highlights the transitions from intrinsically disordered states ubiquitous in Aβ1−42 in solution to more compact states arising from stable β-hairpin formation when Aβ1−42 is in the vicinity of a GAG molecule, and even more compact states characterized by a α-helix or β-sheet structures when Aβ1−42 interacts with a POPC lipid cluster. We show that the molecular mechanisms underlying these transitions from disorder to order are different for the Aβ1−42/GAG and Aβ1−42/POPC systems. While in the latter the hydrophobicity provided by the lipid tails facilitates the folding of Aβ1−42, in the case of GAG there are hardly any intermolecular Aβ1−42–GAG interactions. Instead, GAG removes sodium ions from the peptide, allowing stronger electrostatic interactions within the peptide that stabilize a β-hairpin. Our results contribute to the growing knowledge of the role of GAGs and lipids in the conformational preferences of the Aβ peptide, which in turn influences its aggregation into toxic oligomers and amyloid fibrils.
Expression and Role of Toll-like Receptors in Facial Nerve Regeneration after Facial Nerve Injury
Authors: Lee Jae-Min , Yeo Seung Geun , Jung Su Young , Jung Junyang , Kim Sung Soo , Yoo Myung Chul , Rim Hwa Sung , Min Hye Kyu , Kim Sang Hoon , Park Dong Choon
Published: July 2023

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1–13. Among these, TLR2–5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1–5, TLR8, and TLR10–13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration.
Cognitive Normal Older Adults with APOE-2 Allele Show a Distinctive Functional Connectivity Pattern in Response to Cerebral Aβ Deposition
Authors: Wang Sheng-Min , Kang Dong Woo , Um Yoo Hyun , Kim Sunghwan , Kim Regina E. Y. , Kim Donghyeon , Lee Chang Uk , Lim Hyun Kook
Published: July 2023

The ε2 allele of apolipoprotein E (ε2) has neuroprotective effects against beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). However, its impact on the functional connectivity and hub efficiency in cognitively normal older adults (CN) with ε2 is unclear. We investigated the functional connectivity differences in the default mode network (DMN), salience network, and central executive network (CEN) between A-PET-negative (N = 29) and A-PET-positive (N = 15) CNs with ε2/ε2 or ε2/ε3 genotypes. The A-PET-positive CNs exhibited a lower anterior DMN functional connectivity, higher posterior DMN functional connectivity, and increased CEN functional connectivity compared to the A-PET-negative CNs. Cerebral Aβ retention was negatively correlated with anterior DMN functional connectivity and positively correlated with posterior DMN and anterior CEN functional connectivity. A graph theory analysis showed that the A-PET-positive CNs displayed a higher betweenness centrality in the middle frontal gyrus (left) and medial fronto-parietal regions (left). The betweenness centrality in the middle frontal gyrus (left) was positively correlated with Aβ retention. Our findings reveal a reversed anterior–posterior dissociation in the DMN functional connectivity and heightened CEN functional connectivity in A-PET-positive CNs with ε2. Hub efficiencies, measured by betweenness centrality, were increased in the DMN and CEN of the A-PET-positive CNs with ε2. These results suggest unique functional connectivity responses to Aβ pathology in CN individuals with ε2.
Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS
Authors: Carata Elisabetta , Muci Marco , Di Giulio Simona , Mariano Stefania , Panzarini Elisa
Published: July 2023

Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression is attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral and infiltrated T lymphocytes and monocytes/macrophages, as well as the immunoreactive molecules they release, represent the active players for the role of immune dysregulation enhancing neuroinflammation. The crosstalk between the peripheral and CNS immune cells significantly correlates with the survival of ALS patients since the modification of peripheral macrophages can downregulate inflammation at the periphery along the nerves and in the CNS. As putative vehicles for misfolded protein and inflammatory mediators between cells, extracellular vesicles (EVs) have also drawn particular attention in the field of ALS. Both CNS and peripheral immune cells release EVs, which are able to modulate the behavior of neighboring recipient cells; unfortunately, the mechanisms involved in EVs-mediated communication in neuroinflammation remain unclear. This review aims to synthesize the current literature regarding EV-mediated cell-to-cell communication in the brain under ALS, with a particular point of view on the role of peripheral macrophages in responding to inflammation to understand the biological process and exploit it for ALS management.
N,N-Dimethylglycine Sodium Salt Exerts Marked Anti-Inflammatory Effects in Various Dermatitis Models and Activates Human Epidermal Keratinocytes by Increasing Proliferation, Migration, and Growth Factor Release
Authors: Lendvai Alexandra , Béke Gabriella , Hollósi Erika , Becker Maike , Völker Jörn Michael , Schulze zur Wiesche Erik , Bácsi Attila , Bíró Tamás , Mihály Johanna
Published: July 2023

N,N-dimethylglycine (DMG) is a naturally occurring compound being widely used as an oral supplement to improve growth and physical performance. Thus far, its effects on human skin have not been described in the literature. For the first time, we show that N,N-dimethylglycine sodium salt (DMG-Na) promoted the proliferation of cultured human epidermal HaCaT keratinocytes. Even at high doses, DMG-Na did not compromise the cellular viability of these cells. In a scratch wound-closure assay, DMG-Na augmented the rate of wound closure, demonstrating that it promotes keratinocyte migration. Further, DMG-Na treatment of the cells resulted in the upregulation of the synthesis and release of specific growth factors. Intriguingly, DMG-Na also exerted robust anti-inflammatory and antioxidant effects, as assessed in three different models of human keratinocytes, mimicking microbial and allergic contact dermatitis as well as psoriasis and UVB irradiation-induced solar dermatitis. These results identify DMG-Na as a highly promising novel active compound to promote epidermal proliferation, regeneration, and repair, and to exert protective functions. Further preclinical and clinical studies are under investigation to prove the seminal impact of topically applied DMG-Na on relevant conditions of the skin and its appendages.
Monkeypox, Disinformation, and Fact-Checking: A Review of Ten Iberoamerican Countries in the Context of Public Health Emergency
Authors: Morejón-Llamas Noemí , Cristòfol F. J.
Published: July 2023

This paper examines the disinformation and fact-checking activity of ten Ibero-American countries during the outbreak of monkeypox in 2022. Using a mixed-methods approach based on content analysis, the debunkings published by these organizations on their websites between 7 May and 10 September 2022 are studied. The countries with the highest number of debunkings are Spain and Bolivia, with two verification agencies, Maldita and Bolivia Verifica. The outbreak’s onset marked a peak in the spread of hoaxes, particularly following the declaration of the disease as a public health emergency. The identification of disinformants is challenging due to the diverse dissemination channels, although Twitter predominantly serves as the platform of choice. The preferred format for disinformation is image text, and the common theme links monkeypox to a side effect of the SARS-CoV-2 vaccine. Furthermore, the internationalization capacity of scientific hoaxes is demonstrated. Fact-checking agencies conduct adequate and thorough source verification, predominantly relying on official and expert sources. However, they employ limited digital tools that could expedite the verification process. Disinformation regarding monkeypox is closely related to COVID-19 hoaxes, either by resurrecting conspiracy theories or through the dissemination of speeches by well-known anti-vaccine activists who belong to healthcare collectives and were influential during the health pandemic.
Information and Communication Technologies in Primary Education: Teachers’ Perceptions in Greece
Authors: Aivazidi Marina , Michalakelis Christos
Published: July 2023

Innovative learning methods including the increasing use of Information and Communication Technologies (ICT) applications are transforming the contemporary educational process. Teachers’ perceptions of ICT, self-efficacy on computers and demographics are some of the factors that have been found to impact the use of ICT in the educational process. The aim of the present research is to analyze the perceptions of primary school teachers about ICT and how they affect their use in the educational process, through the case of Greece. To do so, primary research was carried out. Data from 285 valid questionnaires were statistically analyzed using descriptive statistics, principal components analysis, correlation and regression analysis. The main results were in accordance with the relevant literature, indicating the impact of teachers’ self-efficacy, perceptions and demographics on ICT use in the educational process. These results provide useful insights for the achievement of a successful implementation of ICT in education.
A Machine-Learning-Based Motor and Cognitive Assessment Tool Using In-Game Data from the GAME2AWE Platform
Authors: Danousis Michail , Goumopoulos Christos
Published: July 2023

With age, a decline in motor and cognitive functionality is inevitable, and it greatly affects the quality of life of the elderly and their ability to live independently. Early detection of these types of decline can enable timely interventions and support for maintaining functional independence and improving overall well-being. This paper explores the potential of the GAME2AWE platform in assessing the motor and cognitive condition of seniors based on their in-game performance data. The proposed methodology involves developing machine learning models to explore the predictive power of features that are derived from the data collected during gameplay on the GAME2AWE platform. Through a study involving fifteen elderly participants, we demonstrate that utilizing in-game data can achieve a high classification performance when predicting the motor and cognitive states. Various machine learning techniques were used but Random Forest outperformed the other models, achieving a classification accuracy ranging from 93.6% for cognitive screening to 95.6% for motor assessment. These results highlight the potential of using exergames within a technology-rich environment as an effective means of capturing the health status of seniors. This approach opens up new possibilities for objective and non-invasive health assessment, facilitating early detections and interventions to improve the well-being of seniors.
Association between Plasma Ascorbic Acid Levels and Postoperative Delirium in Older Patients Undergoing Cardiovascular Surgery: A Prospective Observational Study
Authors: Iizuka Yusuke , Yoshinaga Koichi , Takahashi Kyosuke , Oki Sayaka , Chiba Yoshihiko , Sanui Masamitsu , Kimura Naoyuki , Yamaguchi Atsushi
Published: July 2023

Background: The incidence of delirium is high in older patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Intraoperative tissue hypoperfusion and re-reperfusion injury, which generate reactive oxygen species (ROS), are suggested to induce delirium. Ascorbic acid is an excellent antioxidant and may reduce organ damage by inhibiting the production of ROS. This prospective observational study aimed to measure pre- and postoperative plasma ascorbic acid levels and examine their association with delirium. Methods: Patients older than 70 years of age scheduled for elective cardiovascular surgery using CPB were enrolled. From September 2020 to December 2021, we enrolled 100 patients, and the data of 98 patients were analyzed. Results: In total, 31 patients developed delirium, while 67 did not. Preoperative plasma ascorbic acid levels did not differ between the non-delirium and delirium groups (6.0 ± 2.2 vs. 5.5 ± 2.4 µg/mL, p = 0.3). Postoperative plasma ascorbic acid levels were significantly different between the groups (2.8 [2.3–3.5] vs. 2.3 [1.6–3.3] µg/mL, p = 0.037). Conclusions: In patients who undergo cardiovascular surgery with CPB, lower postoperative plasma ascorbic acid levels may be associated with the development of delirium.
Nerve Torsion as a Pattern of Parsonage–Turner Syndrome: Literature Review and Two Representative Cases
Authors: Glorioso Davide , Palestini Rita , Cuccagna Cristina , Lauretti Liverana , Padua Luca
Published: July 2023

(1) Background: Parsonage–Turner Syndrome (PTS) is a rare peripheral nerve disease characterized by different degrees of nerve impairment. The recent development of nerve ultrasound has enabled the use of new data in the diagnosis of the disease. The aim of this study is to conduct a literature review about the ultrasound evaluation of PTS and present two clinical cases that are characteristic of the disease. (2) Methods: A review of the literature from the last 10 years on the topic containing data regarding nerve ultrasound was performed. In addition, two cases of patients on whom nerve ultrasound was performed at the first evaluation and at follow-up after the indicated treatment were described. (3) Results: The results of our review show that although it is defined as plexopathy, PTS is most often a form of multifocal neuropathy. We also report the most frequently used ultrasound classification and possible prognostic correlations and report our experience with the description of two paradigmatic clinical cases. (4) Conclusions: Further studies are needed to understand the true prognostic power of each degree of nerve impairment and the possible implications in clinical practice regarding treatment indications.
The Decline of Physical Activity with Age in School-Aged Children with Cerebral Palsy: A Single-Center Cross-Sectional Observational Study
Authors: Lee Jinuk , Suk Min-Hwa , Yoo Soojin , Kwon Jeong-Yi
Published: July 2023

Maintaining physical activity is important for children with cerebral palsy (CP). This study examined whether age predicted habitual physical activity (HPA) or cardiorespiratory fitness (CRF) in school-aged children with CP and clarified the relationship between HPA and CRF. We utilized cross-sectional data from 39 children with CP (18 girls and 21 boys; mean age 7.44 years; mean body weight 24.76 kg; mean body mass index 15.97 kg/m2; hemiplegic or diplegic CP). The participants wore an accelerometer (ActiGraph) for five days to measure HPA, physical activity energy expenditure (kcal/kg/d), sedentary physical activity (%SPA), light physical activity, moderate-to-vigorous physical activity (%MVPA), and activity counts (counts/min). Participants underwent cardiopulmonary exercise tests on a treadmill using a modified Naughton protocol. Linear regression and correlation analyses were performed. p-value (two-tailed) < 0.05 was considered statistically significant. Age was positively associated with SPA. MVPA negatively correlated with resting heart rate (HR), and activity counts were negatively correlated with resting HR. In conclusion, our study found strong evidence of a negative association between HPA and age in school-aged children with CP. It highlights the importance of creating and improving recreational opportunities that promote physical activity in all children with CP, regardless of whether they are considered therapeutic.
Effects of Peripheral Cooling on Upper Limb Tremor Severity and Functional Capacity in Persons with MS
Authors: Feys Peter , Duportail Marijke , Kos Daphne , Ilsbroukx Stephan , Lamers Ilse , Van Asch Paul , Helsen Werner , Moumdjian Lousin
Published: July 2023

Upper limb intention tremor in persons with multiple sclerosis (pwMS) affects the ability to perform activities of daily life and is difficult to treat. The study investigated the effect of peripheral upper limb cooling on tremor severity and functional performance in MS patients with intention tremor. In experiment 1, 17 patients underwent two 15 min cooling conditions for the forearm (cold pack and cryomanchet) and one control condition. In experiment 2, 22 patients underwent whole arm cooling for 15 min using multiple cold packs. In both experiments, patients were tested at four time points (pre- and post-0, -25 and -50 min cooling) on unilateral tasks of the Test Evaluant les Membres supérieurs des Personnes Agées (TEMPA), Fahn’s tremor rating scale (FTRS), Nine Hole Peg Test (NHPT). In experiment 1, the mean FTRS ranged from 13.2 to 14.1 across conditions. A two-way ANOVA showed mainly time effects, showing that cooling the forearm significantly reduced the FTRS, the performance on the NHPT, and three out of four items of the TEMPA, mostly independent of the cooling modality. In experiment 2, the mean FTRS was 13.1. A repeated measures ANOVA showed that cooling the whole arm reduced the FTRS and time needed to execute two out of four items of the TEMPA. These effects occurred immediately after cooling lasting at least 25 min. Cooling the whole upper limb led to a clinically noticeable effect on tremor severity and improved functional performance, which was pronounced during the first half-hour after cooling.
Moving toward Precision Medicine in Acute Coronary Syndromes: A Multimodal Assessment of Non-Culprit Lesions
Authors: Bellino Michele , Silverio Angelo , Esposito Luca , Cancro Francesco Paolo , Ferruzzi Germano Junior , Di Maio Marco , Rispoli Antonella , Vassallo Maria Giovanna , Di Muro Francesca Maria , Galasso Gennaro , De Luca Giuseppe
Published: July 2023

Patients with acute coronary syndrome and multivessel disease experience several recurrent adverse events that lead to poor outcomes. Given the complexity of treating these patients, and the extremely high risk of long-term adverse events, the assessment of non-culprit lesions becomes crucial. Recently, two trials have shown a possible clinical benefit into treat non-culprit lesions using a fraction flow reserve (FFR)-guided approach, compared to culprit-lesion-only PCI. However, the most recent FLOW Evaluation to Guide Revascularization in Multivessel ST-elevation Myocardial Infarction (FLOWER-MI) trial did not show a benefit of the use of FFR-guided PCI compared to an angiography-guided approach. Otherwise, intracoronary imaging using optical coherence tomography (OCT), intravascular ultrasound (IVUS), or near-infrared spectroscopy (NIRS) could provide both quantitative and qualitative assessments of non-culprit lesions. Different studies have shown how the characterization of coronary lesions with intracoronary imaging could lead to clinical benefits in these peculiar group of patients. Moreover, non-invasive evaluations of NCLs have begun to take ground in this context, but more insights through adequately powered and designed studies are needed. The aim of this review is to outline the available techniques, both invasive and non-invasive, for the assessment of multivessel disease in patients with STEMI, and to provide a systematic guidance on the assessment and approach to these patients.
The Magnitude of Contralateral Suppression of Otoacoustic Emissions Is Ear- and Age-Dependent
Authors: Thai-Van Hung , Veuillet Evelyne , Le Normand Marie-Thérèse , Damien Maxime , Joly Charles-Alexandre , Reynard Pierre
Published: July 2023

The maturation of the uncrossed medial olivocochlear (UMOC) efferent remains poorly documented to date. The UMOC efferent system allows listeners to not only detect but also to process, recognize, and discriminate auditory stimuli. Its fibers can be explored non-invasively by recording the effect of contralateral acoustic stimulation (CAS), resulting in a decrease in the amplitude of transient evoked otoacoustic emissions (TEOAE). The objective of the present cross-sectional study was to investigate how the effectiveness of this system varies with age in healthy subjects aged 8 years to adulthood. For this purpose, 120 right-handed native French-speaking subjects (57 females and 63 males) were divided into five age groups of 24 subjects each: 8y–10y, 10y–11y6m, 11y6m–13y, 13y–17y, and ≥18y. TEOAE amplitudes with and without CAS were recorded. The equivalent attenuation (EA) was calculated, corresponding to the change in TEOAE amplitude equivalent to the effect generated by CAS. General linear models were performed to control for the effect of ear, sex, and age on EA. No sex effect was found. A stronger EA was consistently found regardless of age group in the right ear compared to the left. In contrast to the right ear, for which, on average, EA remained constant across age groups, an increasingly weaker TEOAE suppression effect with age was found in the left ear, reinforcing the asymmetrical functioning of the UMOC efferent system in favor of the right ear in adulthood. Further studies are needed to investigate the lateralization of the UMOC efferent system and its changes over time in cases of atypical or reversed cortical asymmetries, especially in subjects with specific learning disorders.