bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining the Use and Benefits of Low-/Mild-Gain Hearing Aids in Service Members with Normal Hearing Thresholds and Self-Reported Hearing Difficulties
Authors: Davidson Alyssa J. , Ellis Gregory M. , Jenkins Kimberly , Kokx-Ryan Melissa , Brungart Douglas S.
Published: March 2024

Low- (or mild-) gain hearing aids (LGHAs) are increasingly considered for individuals with normal peripheral hearing but significant self-reported hearing difficulties (SHDs). This study assesses the benefits of LGHAs as a management option for individuals with normal hearing thresholds (NHTs) and SHDs, comparing LGHA use and benefit to individuals with non-significant hearing difficulties (NHDs) and those with peripheral hearing loss. Questionnaires addressing hearing aid usage, benefit, hearing difficulties, and tinnitus were administered to 186 individuals who self-identified as hearing aid users in a sample of 6652 service members who were receiving their annual hearing tests. Participants were divided into SHD and NHD groups based on the normative cutoff of the Tinnitus and Hearing Survey-Hearing Subscale (THS-H), and into hearing impairment (HI) and NHT based on their audiometric air-conduction thresholds. Individuals with SHDs and NHTs reported higher LGHA usage and benefit than individuals with NHDs and NHTs. Comparable use and benefit were noted between groups with SHDs regardless of peripheral hearing loss status. The findings support LGHAs as a suitable management option for individuals with NHTs and SHDs, as indicated by hearing aid use and benefit. Quantifying the level of perceived auditory processing deficits (i.e., SHDs), notably with the THS-H, enhances sensitivity in identifying those who may benefit the most from this treatment option.
The Occurrence of Anxiety, Depression, and Distress among Professionals Working in Emergency Care
Authors: Ferkai Luca Anna , Schiszler Bence , Bánfai Bálint , Pandur Attila , Gálos Gergely , Kívés Zsuzsanna , Sipos Dávid , Betlehem József , Stromájer-Rácz Tímea , Deutsch Krisztina
Published: March 2024

Maintaining mental health is essential for professions with higher stress levels and challenging environments, including emergency specializations. In this study, the occurrence of distress, anxiety, and depression among a group of ambulance and hospital emergency care professionals was assessed (n = 202). A cross-sectional, quantitative, descriptive online survey was conducted, including the internationally validated Beck depression inventory (BDI), the perceived stress scale (PSS-14), and the State–Trait Anxiety Inventory (STAI). Statistical analyses involved descriptive statistics, the χ2-test, Mann–Whitney U test, Kruskal–Wallis test, Dunn–Bonferroni test, logistic regression (LR), Cramer coefficient (Cramer’s V), Kolmogorov–Smirnov test, and Spearman’s rank correlation coefficient (rs). Based on the results, female professionals are more likely to have depressive symptoms (OR = 2.6, 95% CI = 1.3–5.1), perceived stress (OR = 1.2, 95% CI = 1.2–4.1), and anxiety (OR = 2.1, 95% CI = 1.0–4.1) than male professionals. Perceived stress levels decreased proportionally with increasing years spent working in healthcare (OR = 7.4, 95% CI = 7.1–8.3). Extended work shifts of 12 or 24 h increase the risk of perceived stress and anxiety in emergency care workers (p = 0.02). Customized stress management interventions are needed to mitigate the amplified mental strain associated with gender, working years, and longer shifts in the emergency care sector to sustain their mental health and well-being.
Vegetation and Dormancy States Identification in Coniferous Plants Based on Hyperspectral Imaging Data
Authors: Dmitriev Pavel A. , Kozlovsky Boris L. , Dmitrieva Anastasiya A.
Published: March 2024

Conifers are a common type of plant used in ornamental horticulture. The prompt diagnosis of the phenological state of coniferous plants using remote sensing is crucial for forecasting the consequences of extreme weather events. This is the first study to identify the “Vegetation” and “Dormancy” states in coniferous plants by analyzing their annual time series of spectral characteristics. The study analyzed Platycladus orientalis, Thuja occidentalis and T. plicata using time series values of 81 vegetation indices and 125 spectral bands. Linear discriminant analysis (LDA) was used to identify “Vegetation” and “Dormancy” states. The model contained three to four independent variables and achieved a high level of correctness (92.3 to 96.1%) and test accuracy (92.1 to 96.0%). The LDA model assigns the highest weight to vegetation indices that are sensitive to photosynthetic pigments, such as the photochemical reflectance index (PRI), normalized PRI (PRI_norm), the ratio of PRI to coloration index 2 (PRI/CI2), and derivative index 2 (D2). The random forest method also diagnoses the “Vegetation” and “Dormancy” states with high accuracy (97.3%). The vegetation indices chlorophyll/carotenoid index (CCI), PRI, PRI_norm and PRI/CI2 contribute the most to the mean decrease accuracy and mean decrease Gini. Diagnosing the phenological state of conifers throughout the annual cycle will allow for the effective planning of management measures in conifer plantations.
Cultural Attunements and Ecological Wellbeing: Embodied Conditions for Mental Health Interventions
Authors: Miller Kara
Published: March 2024

A critical need for mental health interventions is clear in the modern era. Bodily attunements to place and space can help cultivate belongingness and heal the anxious modern body, as well as facilitate community solidarity to combat the loneliness and isolation that many are experiencing. Human systems and services have the potential to facilitate meaningful experiences for community members and to incite joyful, thoughtful, or motivating multisensory interactions. Humans’ surroundings have paramount effects on inhabitants and should offer opportunity and inspiration. This paper suggests that such inspiration be drawn from ecological knowledge that can garner healing and wellbeing and offers suggestions and recommendations for doing so. Humane designs are integrated with nature and include environmental access and information that encourages civic participation. This work uses theories and models in ecological community psychology and cultural ecology as well as anthropological approaches to human health to offer somatic principles for healthy community planning and development and for integrating such nature-based health principles into existing structures, including the built environment as well as education. Healing through nature is highlighted here as an approach for attuning to post-pandemic landscapes in order to move into the future in the most generative, sustainable, and supportive ways possible.
Developing a Collaborative Approach to Support Access and Acceptability of Mental Health Care for Refugee Youth: An Exploratory Case Study with Young Afghan Refugees
Authors: Versteele Jakob , Rousseau Cécile , Danckaerts Marina , De Haene Lucia
Published: March 2024

Despite an increased prevalence of psychiatric morbidity, minor refugees resettled in Western host societies are less likely to access mental health care services than their native peers. This study aims to explore how a collaborative approach can be implemented to promote access to specialized mental health care. Collaborative mental health care embeds specialized intervention in primary care settings and emphasizes the inclusion of minority cultural perspectives through an interdisciplinary, intersectoral network. In this study, we analyze how such a collaborative approach can support access to specialized mental health care for refugee youth. The study presents findings from a qualitative multiple-case study (n = 10 refugee patients), conducted in the setting of a psychiatric day program for young refugees that develops an intersectional, collaborative practice in supporting minor refugees’ trajectory from referral to admission. Building on in-depth interviews, participant observation and case documents, within-case analysis and cross-case inductive thematic analysis identify the specific working mechanisms of a collaborative approach. The results indicate how this intersectoral approach addresses the interplay between traumatic suffering and both cultural and structural determinants of mental health. To conclude, a discussion identifies future research directions that may further strengthen the role of collaborative practice in promoting mental health care access for refugee youth.
Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2low Adult T-Cell Leukemia/Lymphoma
Authors: Ichikawa Tomonaga , Suekane Akira , Nakahata Shingo , Iha Hidekatsu , Shimoda Kazuya , Murakami Takashi , Morishita Kazuhiro
Published: March 2024

N-myc downstream-regulated gene 2 (NDRG2), which is a tumour suppressor, is frequently lost in many types of tumours, including adult T-cell leukaemia/lymphoma (ATL). The downregulation of NDRG2 expression is involved in tumour progression through the aberrant phosphorylation of several important signalling molecules. We observed that the downregulation of NDRG2 induced the translocation of protein arginine methyltransferase 5 (PRMT5) from the nucleus to the cytoplasm via the increased phosphorylation of PRMT5 at Serine 335. In NDRG2low ATL, cytoplasmic PRMT5 enhanced HSP90A chaperone activity via arginine methylation, leading to tumour progression and the maintenance of oncogenic client proteins. Therefore, we examined whether the inhibition of PRMT5 activity is a drug target in NDRG2low tumours. The knockdown of PRMT5 and binding partner methylsome protein 50 (MEP50) expression significantly demonstrated the suppression of cell proliferation via the degradation of AKT and NEMO in NDRG2low ATL cells, whereas NDRG2-expressing cells did not impair the stability of client proteins. We suggest that the relationship between PRMT5/MEP50 and the downregulation of NDRG2 may exhibit a novel vulnerability and a therapeutic target. Treatment with the PRMT5-specific inhibitors CMP5 and HLCL61 was more sensitive in NDRG2low cancer cells than in NDRG2-expressing cells via the inhibition of HSP90 arginine methylation, along with the degradation of client proteins. Thus, interference with PRMT5 activity has become a feasible and effective strategy for promoting cancer vulnerability in NDRG2low ATL.
UBA6 Inhibition Accelerates Lysosomal TRPML1 Depletion and Exosomal Secretion in Lung Cancer Cells
Authors: Lee Dongun , Lee Peter Chang-Whan , Hong Jeong Hee
Published: March 2024

Ubiquitin-like modifier-activating enzyme 6 (UBA6) is a member of the E1 enzyme family, which initiates the ubiquitin–proteasome system (UPS). The UPS plays critical roles not only in protein degradation but also in various cellular functions, including neuronal signaling, myocardial remodeling, immune cell differentiation, and cancer development. However, the specific role of UBA6 in cellular functions is not fully elucidated in comparison with the roles of the UPS. It has been known that the E1 enzyme is associated with the motility of cancer cells. In this study, we verified the physiological roles of UBA6 in lung cancer cells through gene-silencing siRNA targeting UBA6 (siUBA6). The siUBA6 treatment attenuated the migration of H1975 cells, along with a decrease in lysosomal Ca2+ release. While autophagosomal proteins remained unchanged, lysosomal proteins, including TRPML1 and TPC2, were decreased in siUBA6-transfected cells. Moreover, siUBA6 induced the production of multivesicular bodies (MVBs), accompanied by an increase in MVB markers in siUBA6-transfected H1975 cells. Additionally, the expression of the exosomal marker CD63 and extracellular vesicles was increased by siUBA6 treatment. Our findings suggest that knock-down of UBA6 induces lysosomal TRPML1 depletion and inhibits endosomal trafficking to lysosome, and subsequently, leads to the accumulation of MVBs and enhanced exosomal secretion in lung cancer cells.
Therapeutic Effect of Natural Products and Dietary Supplements on Aflatoxin-Induced Nephropathy
Authors: Ofori-Attah Ebenezer , Hashimoto Mai , Oki Mayu , Kadowaki Daisuke
Published: March 2024

Aflatoxins are harmful natural contaminants found in foods and are known to be hepatotoxic. However, recent studies have linked chronic consumption of aflatoxins to nephrotoxicity in both animals and humans. Here, we conducted a systematic review of active compounds, crude extracts, herbal formulations, and probiotics against aflatoxin-induced renal dysfunction, highlighting their mechanisms of action in both in vitro and in vivo studies. The natural products and dietary supplements discussed in this study alleviated aflatoxin-induced renal oxidative stress, inflammation, tissue damage, and markers of renal function, mostly in animal models. Therefore, the information provided in this review may improve the management of kidney disease associated with aflatoxin exposure and potentially aid in animal feed supplementation. However, future research is warranted to translate the outcomes of this study into clinical use in kidney patients.
Lack of the Histone Deacetylase SIRT1 Leads to Protection against Endoplasmic Reticulum Stress through the Upregulation of Heat Shock Proteins
Authors: Latorre Jessica , de Vera Nuria , Santalucía Tomàs , Balada Rafel , Marazuela-Duque Anna , Vaquero Alejandro , Planas Anna M. , Petegnief Valérie
Published: March 2024

Histone deacetylase SIRT1 represses gene expression through the deacetylation of histones and transcription factors and is involved in the protective cell response to stress and aging. However, upon endoplasmic reticulum (ER) stress, SIRT1 impairs the IRE1α branch of the unfolded protein response (UPR) through the inhibition of the transcriptional activity of XBP-1 and SIRT1 deficiency is beneficial under these conditions. We hypothesized that SIRT1 deficiency may unlock the blockade of transcription factors unrelated to the UPR promoting the synthesis of chaperones and improving the stability of immature proteins or triggering the clearance of unfolded proteins. SIRT1+/+ and SIRT1−/− fibroblasts were exposed to the ER stress inducer tunicamycin and cell survival and expression of heat shock proteins were analyzed 24 h after the treatment. We observed that SIRT1 loss significantly reduced cell sensitivity to ER stress and showed that SIRT1−/− but not SIRT1+/+ cells constitutively expressed high levels of phospho-STAT3 and heat shock proteins. Hsp70 silencing in SIRT1−/− cells abolished the resistance to ER stress. Furthermore, accumulation of ubiquitinated proteins was lower in SIRT1−/− than in SIRT1+/+ cells. Our data showed that SIRT1 deficiency enabled chaperones upregulation and boosted the proteasome activity, two processes that are beneficial for coping with ER stress.
The Relevance, Predictability, and Utility of Annexin A5 for Human Physiopathology
Authors: Jing Jian
Published: March 2024

As an important functional protein molecule in the human body, human annexin A5 (hAnxA5) is widely found in human cells and body fluids. hAnxA5, the smallest type of annexin, performs a variety of biological functions by reversibly and specifically binding phosphatidylserine (PS) in a calcium-dependent manner and plays an important role in many human physiological and pathological processes. The free state hAnxA5 exists in the form of monomers and usually forms a polymer in a specific self-assembly manner when exerting biological activity. This review systematically discusses the current knowledge and understanding of hAnxA5 from three perspectives: physiopathological relevance, diagnostic value, and therapeutic utility. hAnxA5 affects the occurrence and development of many physiopathological processes. Moreover, hAnxA5 can be used independently or in combination as a biomarker of physiopathological phenomena for the diagnosis of certain diseases. Importantly, based on the properties of hAnxA5, many novel drug candidates have been designed and prepared for application in actual medical practice. However, there are also some gaps and shortcomings in hAnxA5 research. This in-depth study will not only expand the understanding of structural and functional relationships but also promote the application of hAnxA5 in the field of biomedicine.
Clinical Insights into MicroRNAs in Depression: Bridging Molecular Discoveries and Therapeutic Potential
Authors: Kaurani Lalit
Published: March 2024

Depression is a major contributor to the overall global burden of disease. The discovery of biomarkers for diagnosis or prediction of treatment responses and as therapeutic agents is a current priority. Previous studies have demonstrated the importance of short RNA molecules in the etiology of depression. The most extensively researched of these are microRNAs, a major component of cellular gene regulation and function. MicroRNAs function in a temporal and tissue-specific manner to regulate and modify the post-transcriptional expression of target mRNAs. They can also be shuttled as cargo of extracellular vesicles between the brain and the blood, thus informing about relevant mechanisms in the CNS through the periphery. In fact, studies have already shown that microRNAs identified peripherally are dysregulated in the pathological phenotypes seen in depression. Our article aims to review the existing evidence on microRNA dysregulation in depression and to summarize and evaluate the growing body of evidence for the use of microRNAs as a target for diagnostics and RNA-based therapies.
Early Impairment of Paracrine and Phenotypic Features in Resident Cardiac Mesenchymal Stromal Cells after Thoracic Radiotherapy
Authors: Picchio Vittorio , Gaetani Roberto , Pagano Francesca , Derevyanchuk Yuriy , Pagliarosi Olivia , Floris Erica , Cozzolino Claudia , Bernava Giacomo , Bordin Antonella , Rocha Filipe , Pereira Ana Rita Simões , Ministro Augusto , Pinto Ana Teresa , De Falco Elena , Serino Gianpaolo , Massai Diana , Tamarat Radia , Pesce Maurizio , Santos Susana Constantino Rosa , Messina Elisa , Chimenti Isotta
Published: March 2024

Radiotherapy-induced cardiac toxicity and consequent diseases still represent potential severe late complications for many cancer survivors who undergo therapeutic thoracic irradiation. We aimed to assess the phenotypic and paracrine features of resident cardiac mesenchymal stromal cells (CMSCs) at early follow-up after the end of thoracic irradiation of the heart as an early sign and/or mechanism of cardiac toxicity anticipating late organ dysfunction. Resident CMSCs were isolated from a rat model of fractionated thoracic irradiation with accurate and clinically relevant heart dosimetry that developed delayed dose-dependent cardiac dysfunction after 1 year. Cells were isolated 6 and 12 weeks after the end of radiotherapy and fully characterized at the transcriptional, paracrine, and functional levels. CMSCs displayed several altered features in a dose- and time-dependent trend, with the most impaired characteristics observed in those exposed in situ to the highest radiation dose with time. In particular, altered features included impaired cell migration and 3D growth and a and significant association of transcriptomic data with GO terms related to altered cytokine and growth factor signaling. Indeed, the altered paracrine profile of CMSCs derived from the group at the highest dose at the 12-week follow-up gave significantly reduced angiogenic support to endothelial cells and polarized macrophages toward a pro-inflammatory profile. Data collected in a clinically relevant rat model of heart irradiation simulating thoracic radiotherapy suggest that early paracrine and transcriptional alterations of the cardiac stroma may represent a dose- and time-dependent biological substrate for the delayed cardiac dysfunction phenotype observed in vivo.
Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy
Authors: Browning Jack L. , Wilson Kelsey A. , Shandra Oleksii , Wei Xiaoran , Mahmutovic Dzenis , Maharathi Biswajit , Robel Stefanie , VandeVord Pamela J. , Olsen Michelle L.
Published: March 2024

Traumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents with several complications, including cognitive and behavioral disturbances and PTE; however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a mouse model of repeated bTBI (rbTBI), this study addresses this gap in the knowledge. After rbTBI, mice were monitored using continuous, uninterrupted video-EEG for up to four months. Following this period, we collected cortex and hippocampus tissues from three groups of mice: those with post-traumatic epilepsy (PTE+), those without epilepsy (PTE−), and the control group (sham). Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE+ and PTE− relative to sham. Focusing on protein pathways unique to PTE+, pathways related to mitochondrial function, post-translational modifications, and transport were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in the epileptic tissue relative to PTE−. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequelae following rbTBI.
The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles
Authors: Beiter Thomas , Zügel Martina , Hudemann Jens , Schild Marius , Fragasso Annunziata , Burgstahler Christof , Krüger Karsten , Mooren Frank C. , Steinacker Jürgen M. , Nieß Andreas M.
Published: March 2024

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.
Brain-Region-Specific Genes Form the Major Pathways Featuring Their Basic Functional Role: Their Implication in Animal Chronic Stress Model
Authors: Babenko Vladimir , Redina Olga , Smagin Dmitry , Kovalenko Irina , Galyamina Anna , Kudryavtseva Natalia
Published: March 2024

The analysis of RNA-Sec data from murine bulk tissue samples taken from five brain regions associated with behavior and stress response was conducted. The focus was on the most contrasting brain region-specific genes (BRSG) sets in terms of their expression rates. These BRSGs are identified as genes with a distinct outlying (high) expression rate in a specific region compared to others used in the study. The analysis suggested that BRSG sets form non-randomly connected compact gene networks, which correspond to the major neuron-mediated functional processes or pathways in each brain region. The number of BRSGs and the connection rate were found to depend on the heterogeneity and coordinated firing rate of neuron types in each brain region. The most connected pathways, along with the highest BRSG number, were observed in the Striatum, referred to as Medium Spiny Neurons (MSNs), which make up 95% of neurons and exhibit synchronous firing upon dopamine influx. However, the Ventral Tegmental Area/Medial Raphe Nucleus (VTA/MRN) regions, although primarily composed of monoaminergic neurons, do not fire synchronously, leading to a smaller BRSG number. The Hippocampus (HPC) region, on the other hand, displays significant neuronal heterogeneity, with glutamatergic neurons being the most numerous and synchronized. Interestingly, the two monoaminergic regions involved in the study displayed a common BRSG subnetwork architecture, emphasizing their proximity in terms of axonal throughput specifics and high-energy metabolism rates. This finding suggests the concerted evolution of monoaminergic neurons, leading to unique adaptations at the genic repertoire scale. With BRSG sets, we were able to highlight the contrasting features of the three groups: control, depressive, and aggressive mice in the animal chronic stress model. Specifically, we observed a decrease in serotonergic turnover in both the depressed and aggressive groups, while dopaminergic emission was high in both groups. There was also a notable absence of dopaminoceptive receptors on the postsynaptic membranes in the striatum in the depressed group. Additionally, we confirmed that neurogenesis BRSGs are specific to HPC, with the aggressive group showing attenuated neurogenesis rates compared to the control/depressive groups. We also confirmed that immune-competent cells like microglia and astrocytes play a crucial role in depressed phenotypes, including mitophagy-related gene Prkcd. Based on this analysis, we propose the use of BRSG sets as a suitable framework for evaluating case–control group-wise assessments of specific brain region gene pathway responses.
Deletion of Sarcolemmal Membrane-Associated Protein Isoform 3 (SLMAP3) in Cardiac Progenitors Delays Embryonic Growth of Myocardium without Affecting Hippo Pathway
Authors: Rehmani Taha , Dias Ana Paula , Kamal Marsel , Salih Maysoon , Tuana Balwant S.
Published: March 2024

The slmap gene is alternatively spliced to generate many isoforms that are abundant in developing myocardium. The largest protein isoform SLMAP3 is ubiquitously expressed and has been linked to cardiomyopathy, Brugada syndrome and Hippo signaling. To examine any role in cardiogenesis, mice homozygous for floxed slmap allele were crossed with Nkx2.5-cre mice to nullify its expression in cardiac progenitors. Targeted deletion of the slmap gene resulted in the specific knockout (KO) of the SLMAP3 (~91 KDa) isoform without any changes in the expression of the SLMAP2 (~43 kDa) or the SLMAP1 (~35 kDa) isoforms which continued to accumulate to similar levels as seen in Wt embryonic hearts. The loss of SLMAP3 from cardiac progenitors resulted in decreased size of the developing embryonic hearts evident at E9.5 to E16.5 with four small chambers and significantly thinner left ventricles. The proliferative capacity assessed with the phosphorylation of histone 3 or with Ki67 in E12.5 hearts was not significantly altered due to SLMAP3 deficiency. The size of embryonic cardiomyocytes, marked with anti-Troponin C, revealed significantly smaller cells, but their hypertrophic response (AKT1 and MTOR1) was not significantly affected by the specific loss of SLMAP3 protein. Further, no changes in phosphorylation of MST1/2 or YAP were detected in SLMAP3-KO embryonic myocardium, ruling out any impact on Hippo signaling. Rat embryonic cardiomyocytes express the three SLMAP isoforms and their knockdown (KD) with sh-RNA, resulted in decreased proliferation and enhanced senescence but without any impact on Hippo signaling. Collectively, these data show that SLMAP is critical for normal cardiac development with potential for the various isoforms to serve compensatory roles. Our data imply novel mechanisms for SLMAP action in cardiac growth independent of Hippo signaling.
Yeast-Derived Nucleotides Enhance Fibroblast Migration and Proliferation and Provide Clinical Benefits in Atopic Dermatitis
Authors: Segarra Sergi , Bošnjak Ivica , Mioč Igor , Čurčija Bojana , Csik Vlatka-Antonija , Krešić Srećko , Romero-Rueda Jessica , Rodríguez Anna , Martínez-Puig Daniel
Published: March 2024

Nucleotides, glycosaminoglycans, and omega-3 essential fatty acids (O3s) could be used for improving skin health, although their modes of action, alone or in combination, are not yet fully understood. To gain some insight into these mechanisms, we performed two in vitro tests and one in vivo pilot trial. The effects on human dermal fibroblast proliferation and migration were evaluated with the following compounds and combinations: 0.156 mg/mL O3s, 0.0017 mg/mL hyaluronic acid (HA), 0.0004 mg/mL dermatan sulfate (DS), 0.0818 mg/mL nucleotides, and [O3s + HA + DS] and [O3s + HA + DS + nucleotides] at the same concentrations. In both in vitro assays, adding nucleotides to [O3s + HA + DS] provided significant improvements. The resulting combination [O3s + HA + DS + nucleotides] was then tested in vivo in dogs with atopic dermatitis by oral administration of a supplement providing a daily amount of 40 mg/kg nucleotides, 0.9 mg/kg HA, 0.18 mg/kg DS, 53.4 mg/kg EPA, and 7.6 mg/kg DHA. After 30 days, the pruritus visual analog scale (pVAS) score was significantly reduced, and no adverse effects were observed. In conclusion, the combination of nucleotides plus glycosaminoglycans and O3s could serve as a useful therapeutic alternative in skin health applications.
Biophysical and Structural Characterization of the Interaction between Human Galectin-3 and the Lipopolysaccharide from Pseudomonas aeruginosa
Authors: Pirone Luciano , Lenza Maria Pia , Di Gaetano Sonia , Capasso Domenica , Filocaso Martina , Russo Rita , Di Carluccio Cristina , Saviano Michele , Silipo Alba , Pedone Emilia
Published: March 2024

Given the significant involvement of galectins in the development of numerous diseases, the aim of the following work is to further study the interaction between galectin-3 (Gal3) and the LPS from Pseudomonas aeruginosa. This manuscript focused on the study of the interaction of the carbohydrate recognition domain of Gal3 with the LPS from Pseudomonas aeruginosa by means of different complementary methodologies, such as circular dichroism; spectrofluorimetry; dynamic and static light scattering and evaluation of the impact of Gal3 on the redox potential membranes of Escherichia coli and P. aeruginosa cells, as well as ITC and NMR studies. This thorough investigation reinforces the hypothesis of an interaction between Gal3 and LPS, unraveling the structural details and providing valuable insights into the formation of these intricate molecular complexes. Taken together, these achievements could potentially prompt the design of therapeutic drugs useful for the development of agonists and/or antagonists for LPS receptors such as galectins as adjunctive therapy for P. aeruginosa.
Barium Titanate Synthesis in Water Vapor: From Mechanism to Ceramics Properties
Authors: Kholodkova Anastasia A. , Ivakin Yurii D. , Danchevskaya Marina N. , Muravieva Galina P. , Egorov Alexander V. , Smirnov Aleksey D. , Khrustalev Arseniy N. , Arbanas Levko A. , Bazarova Viktoria E. , Smirnov Andrey V.
Published: March 2024

A facile and environmentally benign method for single-phase barium titanate synthesis in a water vapor medium was studied to reveal the mechanism of phase transformation of the initial simple oxide mixture and estimate the capability of the product to be used as a raw material for low-frequency dielectric ceramics. The composition and structure of the reactants’ mixture, treated in vapor at 130–150 °C as well as at 230 °C for various time periods, were investigated by means of XRD, SEM, TEM, EDX, and FTIR methods. The kinetics of the occurring phase transformation can be described using the Johnson–Mehl–Avrami–Erofeev equation. The reaction between the initial oxides was considered as a topochemical process with an apparent activation energy of 75–80 kJ mol−1. A crucial role in this process belonged to the water vapor medium, which facilitated the generation of the reaction zone and the spreading inward of the solid particles. The synthesized tetragonal barium titanate powder (mean particle size of 135 nm) was sintered using a conventional technique at 1250 °C to obtain ceramics with grains of about 2 μm. Capacitance measurements identified a permittivity and dielectric loss factor of the ceramics that reached 3879 and 6.7 × 10−3, respectively, at 1 kHz and room temperature.
Interaction of Carbon Nanotubes, Capped Carbon Nanotubes, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 Fullerenes with Virulence Factors of Gram-Negative and Gram-Positive Bacteria: Potential Applications for 3D-Printed Scaffolds
Authors: Alavi Mehran , Ashengroph Morahem , Mozafari M. R.
Published: March 2024

The antimicrobial application of carbon nanomaterials, such as carbon nanotubes (CNTs), capped CNTs, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 fullerenes, is increasing, owing to their low cytotoxicity properties compared to other nanomaterials such as metallic nanoparticles. Enhanced mechanical properties and antibacterial activity can be caused by the incorporation of CNTs in 3-dimensional (3D) printed nanocomposites (NCs). The interruption of the bacterial membrane resulting from the cylindrical shape and high aspect ratio properties has been found to be the most prominent antibacterial mechanism of CNTs. However, the unraveling interaction of CNTs, capped CNTs, CNT2–5, C60, C70, HO-C60, [C60]2, and [C60]3 fullerenes with virulence factors of the main bacterial pathogenesis has not yet been understood. Therefore, in the present study, interactions of these carbon-based nanomaterials with the eight virulence factors, including protein kinase A and (ESX)-secreted protein B of Mycobacterium tuberculosis, pseudomonas elastase and exotoxin A of Pseudomonas aeruginosa, alpha-hemolysin and penicillin-binding protein 2a of Staphylococcus aureus, and shiga toxin 2a and heat-labile enterotoxin of Escherichia coli, were evaluated with the molecular docking method of AutoDock Vina. This study disclosed that the binding affinity was highest for CNT2–5 and [C60]3 toward alpha-hemolysin, with binding energies of −32.7 and −26.6 kcal/mol, respectively. The stability of the CNT2–5–alpha-hemolysin complex at different times was obtained according to the normal mode analysis of ElNémo and iMOD servers.
A High-Flux Compact X-ray Free-Electron Laser for Next-Generation Chip Metrology Needs
Authors: Rosenzweig James B. , Andonian Gerard , Agustsson Ronald , Anisimov Petr M. , Araujo Aurora , Bosco Fabio , Carillo Martina , Chiadroni Enrica , Giannessi Luca , Huang Zhirong , Fukasawa Atsushi , Kim Dongsung , Kutsaev Sergey , Lawler Gerard , Li Zenghai , Majernik Nathan , Manwani Pratik , Maxson Jared , Miao Janwei , Migliorati Mauro , Mostacci Andrea , Musumeci Pietro , Murokh Alex , Nanni Emilio , O’Tool Sean , Palumbo Luigi , Robles River , Sakai Yusuke , Simakov Evgenya I. , Singleton Madison , Spataro Bruno , Tang Jingyi , Tantawi Sami , Williams Oliver , Xu Haoran , Yadav Monika
Published: March 2024

Recently, considerable work has been directed at the development of an ultracompact X-ray free-electron laser (UCXFEL) based on emerging techniques in high-field cryogenic acceleration, with attendant dramatic improvements in electron beam brightness and state-of-the-art concepts in beam dynamics, magnetic undulators, and X-ray optics. A full conceptual design of a 1 nm (1.24 keV) UCXFEL with a length and cost over an order of magnitude below current X-ray free-electron lasers (XFELs) has resulted from this effort. This instrument has been developed with an emphasis on permitting exploratory scientific research in a wide variety of fields in a university setting. Concurrently, compact FELs are being vigorously developed for use as instruments to enable next-generation chip manufacturing through use as a high-flux, few nm lithography source. This new role suggests consideration of XFELs to urgently address emerging demands in the semiconductor device sector, as identified by recent national need studies, for new radiation sources aimed at chip manufacturing. Indeed, it has been shown that one may use coherent X-rays to perform 10–20 nm class resolution surveys of macroscopic, cm scale structures such as chips, using ptychographic laminography techniques. As the XFEL is a very promising candidate for realizing such methods, we present here an analysis of the issues and likely solutions associated with extending the UCXFEL to harder X-rays (above 7 keV), much higher fluxes, and increased levels of coherence, as well as methods of applying such a source for ptychographic laminography to microelectronic device measurements. We discuss the development path to move the concept to rapid realization of a transformative XFEL-based application, outlining both FEL and metrology system challenges.
Experimental Research into an Innovative Green Propellant Based on Paraffin–Stearic Acid and Coal for Hybrid Rocket Engines
Authors: Cican Grigore , Paraschiv Alexandru , Buturache Adrian Nicolae , Hapenciuc Andrei Iaroslav , Mitrache Alexandru , Frigioescu Tiberius-Florian
Published: March 2024

This study focuses on an innovative green propellant based on paraffin, stearic acid, and coal, used in hybrid rocket engines. Additionally, lab-scale firing tests were conducted using a hybrid rocket motor with gaseous oxygen as the oxidizer, utilizing paraffin-based fuels containing stearic acid and coal. The mechanical performance results revealed that the addition of stearic acid and coal improved the mechanical properties of paraffin-based fuel, including tensile, compression, and flexural strength, under both ambient and sub-zero temperatures (−21 °C). Macrostructural and microstructural examinations, conducted through optical and scanning electron microscopy (SEM), highlighted its resilience, despite minimal imperfections such as impurities and micro-voids. These characteristics could be attributed to factors such as raw material composition and the manufacturing process. Following the mechanical tests, the second stage involved conducting a firing test on a hybrid rocket motor using the new propellant and gaseous oxygen. A numerical simulation was carried out using ProPEP software to identify the optimal oxidant-to-fuel ratio for the maximum specific impulse. Following simulations, it was observed that the specific impulse for the paraffin and for the new propellant differs very little at each oxidant-to-fuel (O/F) ratio. It is noticeable that the maximum specific impulse is achieved for both propellants around the O/F value of 2.2. It was observed that no hazardous substances were present, unlike in traditional solid propellants based on ammonium perchlorate or aluminum. Consequently, there are no traces of chlorine, ammonia, or aluminum-based compounds after combustion. The resulting components for the simulated motor include H2, H2O, O2, CO2, CO, and other combinations in insignificant percentages. It is worth noting that the CO concentration decreases with an increase in the O/F ratio for both propellants, and the differences between concentrations are negligible. Additionally, the CO2 concentration peaks at an O/F ratio of around 4.7. The test proceeded under normal conditions, without compromising the integrity of the test stand and the motor. These findings position the developed propellant as a promising candidate for applications in low-temperature hybrid rocket technology and pave the way for future advancements.
Radiation Exposure and Contrast Agent Use during Endovascular Aortic Repair Using Mobile Versus Fixed Angiography Systems
Authors: Arnautovic Amir , Garabet Waseem , Ziegler Reinhold Thomas , Mulorz Joscha , Braß Sönke Maximilian , Oberhuber Alexander , Schelzig Hubert , Wagenhäuser Markus Udo , Dueppers Philip
Published: March 2024

Background: For (thoracic) endovascular aortic repair ((T)EVAR) procedures, both mobile (standard operating room (SOR)) and fixed C-arm (hybrid operating room (HOR)) systems are available. This study evaluated differences in key procedural parameters, and procedural success for (T)EVAR in the SOR versus the HOR. Methods: All patients who underwent standard elective (T)EVAR at the Clinic for Vascular and Endovascular Surgery at the University Hospital Duesseldorf, Germany, between 1 January 2012 and 1 January 2019 were included. Data were retrieved from archived medical records. Endpoints were analyzed for SOR versus HOR during (T)EVAR. Results: A total of 93 patients, including 50 EVAR (SOR (n = 20); HOR (n = 30)) and 43 TEVAR (SOR (n = 22); HOR (n= 21)) were included. The dose area product (DAP) for EVAR and TEVAR was lower in the SOR than in the HOR (EVAR, SOR: 1635 ± 1088 cGy·cm2; EVAR, HOR: 7819 ± 8928 cGy·cm2; TEVAR, SOR: 8963 ± 34,458 cGy·cm2; TEVAR, HOR: 14,591 ± 11,584 cGy·cm2 (p < 0.05)). Procedural fluoroscopy time was shorter in the SOR than in the HOR for EVAR and TEVAR (EVAR, SOR: 7 ± 4 min; EVAR, HOR: 18.8 ± 11.3 min; TEVAR, SOR: 6.6 ± 9.6 min; TEVAR, HOR: 13.9 ± 11.8 min (p < 0.05)). Higher volumes of contrast agent were applied during EVAR and TEVAR in the SOR than in the HOR (EVAR, SOR: 57.5 ± 20 mL; EVAR: HOR: 33.3 ± 5 mL (p < 0.05); TEVAR; SOR: 71.5 ± 53.4 mL, TEVAR, HOR: 48.2 ± 27.5 mL (p ≥ 0.05). Conclusion: The use of a fixed C-arm angiography system in the HOR results in higher radiation exposure and longer fluoroscopy times but lower contrast agent volumes when compared with mobile C-arm systems in the SOR. Because stochastic radiation sequelae are more likely to be tolerated in an older patient population and, in addition, there is a higher incidence of CKD in this patient population, allocation of patients to the HOR for standard (T)EVAR seems particularly advisable based on our results.
Enhancing ST-Elevation Myocardial Infarction Diagnosis and Management: The Integral Role of Echocardiography in Patients Rushed to the Cardiac Catheterization Laboratory
Authors: Marrazzo Gemma , Palermi Stefano , Pastore Fabio , Ragni Massimo , Mauriello Alfredo , Zambrano Aniello , Quaranta Gaetano , Manto Andrea , D’Andrea Antonello
Published: March 2024

Coronary artery disease (CAD) remains a significant global health concern, necessitating timely and precise diagnosis, especially for acute coronary syndromes (ACSs). Traditional diagnostic methods like electrocardiograms (ECGs) are critical, yet the advent of echocardiography has revolutionized cardiac care by providing comprehensive insights into heart function. This article examines the integration of echocardiography in the cardiac catheterization laboratory, emphasizing its role in augmenting traditional diagnostics, enhancing patient outcomes, and preparing for targeted interventions. Specifically, we argue for the routine use of focused echocardiographic evaluations in patients presenting with ST-Elevation Myocardial Infarction (STEMI) to the cath lab, illustrating how this practice can significantly refine diagnostic accuracy, identify concurrent life-threatening conditions, and inform the management of STEMI and its complications.
Evolution in the Management of Patella Fractures
Authors: Baid Mahak , Narula Sid , Manara Jonathan R. , Blakeney William
Published: March 2024

Patella fractures usually occur as a result of direct trauma to the anterior knee joint, indirect injury as a result of eccentric muscle contraction, or rapid knee flexion against a contracted quadriceps muscle. The patella functions as part of the extensor mechanism of the knee, where large forces are transmitted, and its subcutaneous nature has made treatment of patella fractures a challenge. In this review article, we evaluate how the management of these fractures has evolved over time and the advantages associated with the various treatment techniques. There are few comparative studies looking at the different treatment types for fractures of the patella, with the goal of achieving a functional extensor mechanism with low rates of post-traumatic arthritis and metal-work irritation.
Significant Reduction in Bone Density as Measured by Hounsfield Units in Patients with Ankylosing Spondylitis or Diffuse Idiopathic Skeletal Hyperostosis
Authors: Swart Alexander , Hamouda Abdelrahman , Pennington Zach , Lakomkin Nikita , Mikula Anthony L. , Martini Michael L. , Shafi Mahnoor , Subramaniam Thirusivapragasam , Sebastian Arjun S. , Freedman Brett A. , Nassr Ahmad N. , Fogelson Jeremy L. , Elder Benjamin D.
Published: March 2024

Background: Multisegmental pathologic autofusion occurs in patients with ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH). It may lead to reduced vertebral bone density due to stress shielding. Methods: This study aimed to determine the effects of autofusion on bone density by measuring Hounsfield units (HU) in the mobile and immobile spinal segments of patients with AS and DISH treated at a tertiary care center. The mean HU was calculated for five distinct regions—cranial adjacent mobile segment, cranial fused segment, mid-construct fused segment, caudal fused segment, and caudal adjacent mobile segment. Means for each region were compared using paired-sample t-tests. Multivariable regression was used to determine independent predictors of mid-fused segment HUs. Results: One hundred patients were included (mean age 76 ± 11 years, 74% male). The mean HU for the mid-construct fused segment (100, 95% CI [86, 113]) was significantly lower than both cranial and caudal fused segments (174 and 108, respectively; both p < 0.001), and cranial and caudal adjacent mobile segments (195 and 115, respectively; both p < 0.001). Multivariable regression showed the mid-construct HUs were predicted by history of smoking (−30 HU, p = 0.009). Conclusions: HUs were significantly reduced in the middle of long-segment autofusion, which was consistent with stress shielding. Such shielding may contribute to the diminution of vertebral bone integrity in AS/DISH patients and potentially increased fracture risk.