bluuebunny/crossref_metadata_2025 huggingface dataset:
An Assessment of Administration Route on MSC-sEV Therapeutic Efficacy
Authors: Zhang Bin , Lai Ruenn Chai , Sim Wei Kian , Tan Thong Teck , Lim Sai Kiang
Published: May 2024

Mesenchymal stem/stromal cell-derived small extracellular vesicles (MSC-sEVs) are promising therapeutic agents. In this study, we investigated how the administration route of MSC-sEVs affects their therapeutic efficacy in a mouse model of bleomycin (BLM)-induced skin scleroderma (SSc). We evaluated the impact of topical (TOP), subcutaneous (SC), and intraperitoneal (IP) administration of MSC-sEVs on dermal fibrosis, collagen density, and thickness. All three routes of administration significantly reduced BLM-induced fibrosis in the skin, as determined by Masson’s Trichrome staining. However, only TOP administration reduced BLM-induced dermal collagen density, with no effect on dermal thickness observed for all administration routes. Moreover, SC, but not TOP or IP administration, increased anti-inflammatory profibrotic CD163+ M2 macrophages. These findings indicate that the administration route influences the therapeutic efficacy of MSC-sEVs in alleviating dermal fibrosis, with TOP administration being the most effective, and this efficacy is not mediated by M2 macrophages. Since both TOP and SC administration target the skin, the difference in their efficacy likely stems from variations in MSC-sEV delivery in the skin. Fluorescence-labelled TOP, but not SC MSC-sEVs when applied to skin explant cultures, localized in the stratum corneum. Hence, the superior efficacy of TOP over SC MSC-sEVs could be attributed to this localization. A comparison of the proteomes of stratum corneum and MSC-sEVs revealed the presence of >100 common proteins. Most of these proteins, such as filaggrin, were known to be crucial for maintaining skin barrier function against irritants and toxins, thereby mitigating inflammation-induced fibrosis. Therefore, the superior efficacy of TOP MSC-sEVs over SC and IP MSC-sEVs against SSc is mediated by the delivery of proteins to the stratum corneum to reinforce the skin barrier.
Manual Reduction for Subacute Osteoporotic Burst and Severe Compression Thoracolumbar Fractures
Authors: Li Kung-Chia , Hsieh Ching-Hsiang , Liao Ting-Hua , Chen Chih-Hung
Published: May 2024

The objective of this study was to retrospectively assess the impact of manual reduction (MR) on patients with subacute osteoporotic thoracolumbar burst fractures and severe compression fractures (OTLBFSCFs). From January 2016 to May 2020, 101 cases of OTLBFSCFs were reviewed, comprising 73 women and 28 men, with an average age of 77.4 ± 8.5 years. Preoperative radiographs, CT or MRI scans, intraoperative C-arm fluoroscopic images, and postoperative X-ray films were utilized to evaluate spinal radiographic parameters. Initially, all patients underwent 3 min of prone positioning as posture reduction (PR), followed by 1–3 sessions of six-member MR to approximate anatomical reduction of the fracture. The average preoperative anterior body height ratio (ABH%) and lateral Cobb angle (LCA) were 38.8% ± 6.2% and 22.6° ± 4.2°, respectively. Post-PR, the average ABH% and LCA were 50.5% ± 8.0% and 14.7° ± 2.7°, respectively. Following MR, the average ABH% and LCA were 99.6% ± 2.4% and 0.4° ± 2.4°, respectively. PR achieved an ABH% correction of 11.7%, while MR achieved 49.1%. LCA restoration was 7.9° with PR and 14.3° with MR. It was deduced that MR proved to be safe and efficacious for subacute OTLBFSCFs and could potentially alter the approach to subsequent surgeries.
Non-Invasive Spinal Cord Stimulation for Motor Rehabilitation of Patients with Spinal Muscular Atrophy Treated with Orphan Drugs
Authors: Novikov Anton , Maldova Maria , Shamantseva Natalia , Shalmiev Ivan , Shoshina Elena , Epoyan Natalia , Krutikova Natalia , Moshonkina Tatiana
Published: May 2024

Spinal muscular atrophy (SMA) is an orphan disease characterized by the progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in this study. The median duration of drug treatment was over 20 months. The application of tSCS was performed during physical therapy for 20–40 min per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, and forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both type 2 and 3 SMA participants. The magnitude of functional changes was not associated with participant age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation on SMA.
The Role of αvβ3 Integrin in Cancer Therapy Resistance
Authors: Pachane Bianca Cruz , Selistre-de-Araujo Heloisa S.
Published: May 2024

A relevant challenge for the treatment of patients with neoplasia is the development of resistance to chemo-, immune-, and radiotherapies. Although the causes of therapy resistance are poorly understood, evidence suggests it relies on compensatory mechanisms that cells develop to replace specific intracellular signaling that should be inactive after pharmacological inhibition. One such mechanism involves integrins, membrane receptors that connect cells to the extracellular matrix and have a crucial role in cell migration. The blockage of one specific type of integrin is frequently compensated by the overexpression of another integrin dimer, generally supporting cell adhesion and migration. In particular, integrin αvβ3 is a key receptor involved in tumor resistance to treatments with tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiotherapy; however, the specific inhibition of the αvβ3 integrin is not enough to avoid tumor relapse. Here, we review the role of integrin αvβ3 in tumor resistance to therapy and the mechanisms that have been proposed thus far. Despite our focus on the αvβ3 integrin, it is important to note that other integrins have also been implicated in drug resistance and that the collaborative action between these receptors should not be neglected.
Renal Arterial and Venous Doppler in Cardiorenal Syndrome: Pathophysiological and Clinical Insights
Authors: Barone Roberta , Di Terlizzi Vito , Goffredo Giovanni , Paparella Domenico , Brunetti Natale Daniele , Iacoviello Massimo
Published: May 2024

In recent decades, there has been considerable effort in investigating the clinical utility of renal Doppler measurements in both cardiovascular and renal disorders. In particular, a measure of renal arterial resistance, the renal resistive index (RRI), has been demonstrated to predict chronic kidney disease progression and acute kidney injury in different clinical settings. Furthermore, it is linked to a poorer prognosis in individuals suffering from chronic heart failure. Examining the renal venous flow through pulsed Doppler can offer additional insights into renal congestion and cardiovascular outcomes for these patients. This review seeks to summarize the existing data concerning the clinical significance of arterial and venous renal Doppler measurements across various cardiovascular and renal disease contexts.
Anti-Inflammatory Therapeutic Mechanisms of Isothiocyanates: Insights from Sulforaphane
Authors: Habtemariam Solomon
Published: May 2024

Isothiocyanates (ITCs) belong to a group of natural products that possess a highly reactive electrophilic −N=C=S functional group. They are stored in plants as precursor molecules, glucosinolates, which are processed by the tyrosinase enzyme upon plant tissue damage to release ITCs, along with other products. Isolated from broccoli, sulforaphane is by far the most studied antioxidant ITC, acting primarily through the induction of a transcription factor, the nuclear factor erythroid 2–related factor 2 (Nrf2), which upregulates downstream antioxidant genes/proteins. Paradoxically, sulforaphane, as a pro-oxidant compound, can also increase the levels of reactive oxygen species, a mechanism which is attributed to its anticancer effect. Beyond highlighting the common pro-oxidant and antioxidant effects of sulforaphane, the present paper was designed to assess the diverse anti-inflammatory mechanisms reported to date using a variety of in vitro and in vivo experimental models. Sulforaphane downregulates the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, cycloxyhenase-2, and inducible nitric oxide synthase. The signalling pathways of nuclear factor κB, activator protein 1, sirtuins 1, silent information regulator sirtuin 1 and 3, and microRNAs are among those affected by sulforaphane. These anti-inflammatory actions are sometimes due to direct action via interaction with the sulfhydryl structural moiety of cysteine residues in enzymes/proteins. The following are among the topics discussed in this paper: paradoxical signalling pathways such as the immunosuppressant or immunostimulant mechanisms; crosstalk between the oxidative and inflammatory pathways; and effects dependent on health and disease states.
Optical Bioassays Based on the Signal Amplification of Redox Cycling
Authors: Feng Yunxiao , Gao Fengli , Yi Xinyao , La Ming
Published: May 2024

Optical bioassays are challenged by the growing requirements of sensitivity and simplicity. Recent developments in the combination of redox cycling with different optical methods for signal amplification have proven to have tremendous potential for improving analytical performances. In this review, we summarized the advances in optical bioassays based on the signal amplification of redox cycling, including colorimetry, fluorescence, surface-enhanced Raman scattering, chemiluminescence, and electrochemiluminescence. Furthermore, this review highlighted the general principles to effectively couple redox cycling with optical bioassays, and particular attention was focused on current challenges and future opportunities.
Sensational Dreams: The Prevalence of Sensory Experiences in Dreaming
Authors: van der Heijden Anna C. , Thevis Jade , Verhaegen Jill , Talamini Lucia M.
Published: May 2024

Dreaming, a widely researched aspect of sleep, often mirrors waking-life experiences. Despite the prevalence of sensory perception during wakefulness, sensory experiences in dreams remain relatively unexplored. Free recall dream reports, where individuals describe their dreams freely, may not fully capture sensory dream experiences. In this study, we developed a dream diary with direct questions about sensory dream experiences. Participants reported sensory experiences in their dreams upon awakening, over multiple days, in a home-based setting (n = 3476 diaries). Our findings show that vision was the most common sensory dream experience, followed by audition and touch. Olfaction and gustation were reported at equally low rates. Multisensory dreams were far more prevalent than unisensory dreams. Additionally, the prevalence of sensory dream experiences varied across emotionally positive and negative dreams. A positive relationship was found between on the one hand sensory richness and, on the other emotional intensity of dreams and clarity of dream recall, for both positive and negative dreams. These results underscore the variety of dream experiences and suggest a link between sensory richness, emotional content and dream recall clarity. Systematic registration of sensory dream experiences offers valuable insights into dream manifestation, aiding the understanding of sleep-related memory consolidation and other aspects of sleep-related information processing.
Enhancing Substance Use Disorder Recovery through Integrated Physical Activity and Behavioral Interventions: A Comprehensive Approach to Treatment and Prevention
Authors: Theodorakis Yannis , Hassandra Mary , Panagiotounis Fotis
Published: May 2024

The global issue of substance abuse demands ongoing initiatives aligned with the United Nations Sustainable Development Goals. With drug use remaining prevalent worldwide, interventions are critical to addressing the associated health challenges and societal implications. Exercise and physical activities have emerged as integral components of substance use disorder (SUD) treatment, offering promising avenues for prevention, intervention, and recovery. Recent research underscores the efficacy of exercise in reducing substance cravings, promoting abstinence, and improving overall well-being. However, integrating exercise into SUD recovery programs presents challenges such as dropout rates and cultural considerations. This paper synthesizes existing literature on exercise integration into SUD recovery, highlighting strategies for enhancing treatment outcomes and addressing barriers to exercise adherence. Drawing on cognitive–behavioral therapy, experiential learning, motivational interviewing, and goal-setting techniques, the holistic approach outlined in this paper aims to empower individuals both mentally and physically, fostering resilience and supporting long-term recovery. In conclusion, new initiatives need to be taken by advocating for inclusive policies, promoting community engagement, and fostering collaborations across sectors. By doing so, stakeholders can optimize the effectiveness of exercise programs and contribute to sustainable rehabilitation efforts for individuals with SUD.
Dual Representation of the Auditory Space
Authors: Clarke Stephanie , Da Costa Sandra , Crottaz-Herbette Sonia
Published: May 2024

Auditory spatial cues contribute to two distinct functions, of which one leads to explicit localization of sound sources and the other provides a location-linked representation of sound objects. Behavioral and imaging studies demonstrated right-hemispheric dominance for explicit sound localization. An early clinical case study documented the dissociation between the explicit sound localizations, which was heavily impaired, and fully preserved use of spatial cues for sound object segregation. The latter involves location-linked encoding of sound objects. We review here evidence pertaining to brain regions involved in location-linked representation of sound objects. Auditory evoked potential (AEP) and functional magnetic resonance imaging (fMRI) studies investigated this aspect by comparing encoding of individual sound objects, which changed their locations or remained stationary. Systematic search identified 1 AEP and 12 fMRI studies. Together with studies of anatomical correlates of impaired of spatial-cue-based sound object segregation after focal brain lesions, the present evidence indicates that the location-linked representation of sound objects involves strongly the left hemisphere and to a lesser degree the right hemisphere. Location-linked encoding of sound objects is present in several early-stage auditory areas and in the specialized temporal voice area. In these regions, emotional valence benefits from location-linked encoding as well.
Gut Microbiota and Gastrointestinal Symptoms in the Global Assessment of Obsessive–Compulsive Disorder: A Narrative Review of Current Evidence and Practical Implications
Authors: Grassi Giacomo , Pampaloni Ilenia
Published: May 2024

A growing body of literature suggests a link between bowel syndromes (e.g., irritable bowel syndrome and inflammatory bowel disease), gut microbiome alterations, and psychiatric disorders. This narrative review aims to explore the potential role of the gut microbiome in the pathogenesis and clinical presentation of obsessive–compulsive disorder (OCD) and to explore whether there is sufficient evidence to warrant considering gastrointestinal symptoms and their implication for the gut microbiome during the assessment and treatment of OCD. For this purpose, a PubMed search of studies focusing on OCD, gut microbiota, irritable bowel syndrome, and inflammatory bowel disease was conducted by two independent reviewers. While the current literature on gut microbiome and gastrointestinal issues in OCD remains limited, emerging evidence suggests gut microbiome alterations and high rates of bowel syndromes in this population. These findings emphasize the importance of incorporating comprehensive gastrointestinal assessments into the “global assessment of OCD”. Such assessment should encompass various factors, including gastrointestinal physical comorbidities and symptoms, nutritional habits, bowel habits, fluid intake, exercise patterns, and potential microbiome dysfunctions and inflammation. Considering the treatment implications, interventions targeting gut health, such as probiotics and dietary modifications, may hold promise in improving symptoms in OCD patients with comorbid gastrointestinal problems. Further research in this area is warranted to better understand the interplay between gut health and OCD and to explore the effectiveness of targeted interventions in improving clinical outcomes.
Advice Network Centrality as a Social Origin of Task Crafting: The Bridging Roles of Basic Psychological Needs
Authors: Shin Inyong
Published: May 2024

Little is known about the predictive role of advice networks in task crafting despite the growing academic and practical interest in its antecedents. Accordingly, as centrality in advice networks is expected to have a positive relationship with task crafting, this study develops a research model encompassing the mediating roles of the fulfillment of basic psychological needs to clarify this relationship. The model was tested using a sample composed of 198 employees from various firms in South Korea. The results showed that employees who occupy central positions in the advice network fulfilled their autonomy and competence needs, consequently engaging in task crafting. This study contributes to the literature on social networks, self-determination, and task crafting by discovering hidden antecedents and pivotal mechanisms in determining task crafting.
Testing the Effect of Cue Consistency on the Past Behavior–Habit–Physical Activity Relationship
Authors: Phipps Daniel J. , Hagger Martin S. , Mejia David , Hamilton Kyra
Published: May 2024

Behavior performed in the presence of consistent cues is a core element for successful habit development, with the repeated presence of consistent cues facilitating the activation of automatic responses in future. Yet, little is known about the effects of different cue types on habit. Using a two-wave prospective PLS-SEM model with a sample of 68 undergraduate students, we assessed the mediating effects of habit on the past-behavior-to-physical-activity relationship, and how the mediating effects of habit were moderated by the consistent presence of different forms of cues. Habit mediated the effects of past behavior on physical activity, with a significantly stronger mediating effect of habit in those reporting undertaking physical activity at the same time of day, doing the same activity, and in the same mood. Consistent place, people, and part of routine did not moderate the effects of habit. The results provide formative evidence for a key assertion of the habit theory that consistent contextual and internal cues are a cornerstone of habitual development and action, but they also indicate the importance of examining different forms of cues and their impact on the formation and enaction of habits as some cues may be more relevant than others.
Unlocking Brilliance: A Smart Approach to Icon Colour Design Inspired by Universal Design Principles
Authors: Zhang Erke , Yang Zhexi , Zhao Wei , Mei Zihan , Xia Yuanyuan , Chen Fei
Published: May 2024

Icons are integral to the signature systems within architectural spaces, serving pivotal roles through human–environment interactions. However, previous icon designs often exhibited a considerable randomness and neglected the needs of visually impaired individuals. To address these issues and to overcome the limitations of the computer-aided design methods, such as most of them focusing only on text design which are not compatible with icons, this study presents an intelligent assistance method named “Universal Colour” for icon colour design based on universal design principles. Such a system enables the rapid generation of icon colour schemes and supports visual and quantitative filtering and comparison during the decision-making process for colour scheme optimization. To assess its usability, fifty-two participants conducted icon colour design experiments using this system, resulting in 87% of the design schemes meeting the universality requirements. The results have demonstrated that Universal Colour has the potential to significantly enhance efficiency and cognitive aspects within the decision-making process for users, regardless of their proficiency in icon design, thereby facilitating the generation of universal icon colour schemes in architectural design.
Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Authors: Nikolouzakis Taxiarchis Konstantinos , Chrysos Emmanuel , Docea Anca Oana , Fragkiadaki Persefoni , Souglakos John , Tsiaoussis John , Tsatsakis Aristidis
Published: May 2024

Cancer of the colon and rectum (CRC) has been identified among the three most prevalent types of cancer and cancer-related deaths for both sexes. Even though significant progress in surgical and chemotherapeutic techniques has markedly improved disease-free and overall survival rates in contrast to those three decades ago, recent years have seen a stagnation in these improvements. This underscores the need for new therapies aiming to augment patient outcomes. A number of emerging strategies, such as immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), have exhibited promising outcomes not only in preclinical but also in clinical settings. Additionally, a thorough appreciation of the underlying biology has expanded the scope of research into potential therapeutic interventions. For instance, the pivotal role of altered telomere length in early CRC carcinogenesis, leading to chromosomal instability and telomere dysfunction, presents a promising avenue for future treatments. Thus, this review explores the advancements in CRC immunotherapy and telomere-targeted therapies, examining potential synergies and how these novel treatment modalities intersect to potentially enhance each other’s efficacy, paving the way for promising future therapeutic advancements.
Optimization, Characterization, and Comparison of Two Luciferase-Expressing Mouse Glioblastoma Models
Authors: Rodgers Louis T. , Schulz Pauly Julia A. , Maloney Bryan J. , Hartz Anika M. S. , Bauer Björn
Published: May 2024

Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and the treatment response are typically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immunohistochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In contrast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying the tumor volume using the HALO® AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for the reliable, high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing insights for preclinical research design.
Epstein–Barr Virus and Clinico-Endoscopic Characteristics of Gastric Remnant Cancers Compared to Proximal Non-Remnant Cancers: A Population-Based Study
Authors: Bringeland Erling A. , Våge Christina , Ubøe Ann A. S. , Sandø Alina D. , Mjønes Patricia , Fossmark Reidar
Published: May 2024

Epstein–Barr virus (EBV) is associated with 5–10% of gastric cancers and is recognized as a distinct molecular subtype. EBV positivity is particularly high in gastric remnant cancer (GRC), which may inform the mode of clinical presentation and findings at endoscopy. Most data are from the East, and the question remains how this applies to a Western cohort. We conducted a population-based study in Central Norway, 2001–2016. Patients with GRC (n = 78) and patients with non-GRC proximally located cancer and available tissue for EBV status (n = 116, control group) were identified from the Norwegian Cancer Registry. Relevant data were collected from the individual patient journals. EBV status was assessed using in situ hybridization. The median latency time from the distal gastrectomy to GRC was 37.6 (range 15.7–68.0) years. GRC more often presented with GI bleeding, 31.0% vs. 16.1%, p = 0.017, and at endoscopy more seldom with an ulcer, 19.7% vs. 38.2%, p = 0.012, or a tumour, 40.8% vs. 66.4%, p < 0.001. For GRC, 18.7% were EBV-positive compared to 6.0% among the controls, p = 0.006. EBV status was not associated with patient age, sex, or Lauren histological type. No difference in long-term survival rates between GRC and controls was found or between EBV-positive vs. -negative GRCs. In conclusion, a higher proportion of GRC cases, compared to controls, are EBV positive, indicating different causative factors. The mode of clinical presentation and findings at endoscopy were more subtle in the patients with GRC.
Current Challenges of Methylation-Based Liquid Biopsies in Cancer Diagnostics
Authors: Rendek Tomas , Pos Ondrej , Duranova Terezia , Saade Rami , Budis Jaroslav , Repiska Vanda , Szemes Tomas
Published: May 2024

In current clinical practice, effective cancer testing and screening paradigms are limited to specific types of cancer, exhibiting varying efficiency, acceptance, and adherence. Cell-free DNA (cfDNA) methylation profiling holds promise in providing information about the presence of malignity regardless of its type and location while leveraging blood-based liquid biopsies as a method to obtain analytical samples. However, technical difficulties, costs and challenges resulting from biological variations, tumor heterogeneity, and exogenous factors persist. This method exploits the mechanisms behind cfDNA release but faces issues like fragmentation, low concentrations, and high background noise. This review explores cfDNA methylation’s origins, means of detection, and profiling for cancer diagnostics. The critical evaluation of currently available multi-cancer early detection methods (MCEDs) as well as tests targeting single genes, emphasizing their potential and limits to refine strategies for early cancer detection, are explained. The current methodology limitations, workflows, comparisons of clinically approved liquid biopsy-based methylation tests for cancer, their utilization in companion diagnostics as well as the biological limitations of the epigenetics approach are discussed, aiming to help healthcare providers as well as researchers to orient themselves in this increasingly complex and evolving field of diagnostics.
Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin
Authors: Taroncher Mercedes , Gonzalez-Suarez Alan M. , Gwon Kihak , Romero Samuel , Reyes-Figueroa Angel D. , Rodríguez-Carrasco Yelko , Ruiz María-José , Stybayeva Gulnaz , Revzin Alexander , de Hoyos-Vega Jose M.
Published: May 2024

The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2.
hPSC-Derived Astrocytes at the Forefront of Translational Applications in Neurological Disorders
Authors: Jovanovic Vukasin M. , Mesch Kendall T. , Tristan Carlos A.
Published: May 2024

Astrocytes, the most abundant glial cell type in the brain, play crucial roles in maintaining homeostasis within the central nervous system (CNS). Impairment or abnormalities of typical astrocyte functions in the CNS serve as a causative or contributing factor in numerous neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Currently, disease-modeling and drug-screening approaches, primarily focused on human astrocytes, rely on human pluripotent stem cell (hPSC)-derived astrocytes. However, it is important to acknowledge that these hPSC-derived astrocytes exhibit notable differences across studies and when compared to their in vivo counterparts. These differences may potentially compromise translational outcomes if not carefully accounted for. This review aims to explore state-of-the-art in vitro models of human astrocyte development, focusing on the developmental processes, functional maturity, and technical aspects of various hPSC-derived astrocyte differentiation protocols. Additionally, it summarizes their successful application in modeling neurological disorders. The discussion extends to recent advancements in the large-scale production of human astrocytes and their application in developing high-throughput assays conducive to therapeutic drug discovery.
Visualization Analysis of Small Extracellular Vesicles in the Application of Bone-Related Diseases
Authors: Chen Xinjiani , Yang Ning , Li Bailei , Gao Xinyu , Wang Yayu , Wang Qin , Liu Xiaojun , Zhang Zhen , Zhang Rongqing
Published: May 2024

Small extracellular vesicles were shown to have similar functional roles to their parent cells without the defect of potential tumorigenicity, which made them a great candidate for regenerative medicine. The last twenty years have witnessed the rapid development of research on small extracellular vesicles. In this paper, we employed a scientometric synthesis method to conduct a retrospective analysis of small extracellular vesicles in the field of bone-related diseases. The overall background analysis consisted the visualization of the countries, institutions, journals, and authors involved in research. The current status of the research direction and future trends were presented through the analysis of references and keywords, which showed that engineering strategies, mesenchymal stem cell derived exosomes, and cartilage damage were the most concerning topics, and scaffold, osteoarthritis, platelet-rich plasma, and senescence were the future trends. We also discussed the current problems and challenges in practical applications, including the in-sight mechanisms, the building of relevant animal models, and the problems in clinical trials. By using CiteSpace, VOSviewer, and Bibliometrix, the presented data avoided subjective selectivity and tendency well, which made the conclusion more reliable and comprehensive. We hope that the findings can provide new perspectives for researchers to understand the evolution of this field over time and to search for novel research directions.
Plasma Gelsolin Inhibits Natural Killer Cell Function and Confers Chemoresistance in Epithelial Ovarian Cancer
Authors: Onuma Toshimichi , Asare-Werehene Meshach , Fujita Yuko , Yoshida Yoshio , Tsang Benjamin K.
Published: May 2024

Plasma gelsolin (pGSN) overexpression in ovarian cancer (OVCA) disarms immune function, contributing to chemoresistance. The aim of this study was to investigate the immunoregulatory effects of pGSN expression on natural killer (NK) cell function in OVCA. OVCA tissues from primary surgeries underwent immunofluorescent staining of pGSN and the activated NK cell marker natural cytotoxicity triggering receptor 1 to analyze the prognostic impact of pGSN expression and activated NK cell infiltration. The immunoregulatory effects of pGSN on NK cells were assessed using apoptosis assay, cytokine secretion, immune checkpoint-receptor expression, and phosphorylation of STAT3. In OVCA tissue analyses, activated NK cell infiltration provided survival advantages to patients. However, high pGSN expression attenuated the survival benefits of activated NK cell infiltration. In the in vitro experiment, pGSN in OVCA cells induced NK cell death through cell-to-cell contact. pGSN increased T-cell immunoglobulin and mucin-domain-containing-3 expression (TIM-3) on activated NK cells. Further, it decreased interferon-γ production in activated TIM-3+ NK cells, attenuating their anti-tumor effects. Thus, increased pGSN expression suppresses the anti-tumor functions of NK cells. The study provides insights into why immunotherapy is rarely effective in patients with OVCA and suggests novel treatment strategies.
Incidence and Characteristics of Cerebellar Atrophy/Volume Loss in Children with Confirmed Diagnosis of Tuberous Sclerosis Complex
Authors: Mertiri Livja , Boltshauser Eugen , Kralik Stephen F. , Desai Nilesh K. , Lequin Maarten H. , Huisman Thierry A. G. M.
Published: May 2024

Objectives: The goal of our study was to determine the incidence of cerebellar atrophy, assess the imaging findings in the posterior fossa and determine the incidence of hippocampal sclerosis in a cohort of pediatric patients with confirmed tuberous sclerosis complex (TSC). Material and methods: MRI studies of 98 TSC pediatric patients (mean age 7.67 years) were evaluated for cerebellar atrophy, cerebral/cerebellar tubers, white matter lesions, subependymal nodules, subependymal giant cell astrocytomas, ventriculomegaly, and hippocampal sclerosis. Clinical charts were revisited for clinical symptoms suggesting cerebellar involvement, for seizures and treatment for seizures, behavioral disorders and autism. Results: Cerebral tubers were present in 97/98 cases. In total, 97/98 had subependymal nodules, 15/98 had SEGA, 8/98 had ventriculomegaly and 4/98 had hippocampal sclerosis. Cerebellar tubers were found in 8/98 patients (8.2%), whereas cerebellar atrophy was described in 38/98 cases (38.8%). In 37/38 patients, cerebellar volume loss was mild and diffuse, and only one case presented with left hemi-atrophy. Briefly, 32/38 presented with seizures and were treated with anti-seizure drugs. In total, 8/38 (21%) presented with behavioral disorders, 10/38 had autism and 2/38 presented with seizures and behavioral disorders and autism. Conclusions: Several studies have demonstrated cerebellar involvement in patients with TSC. Cerebellar tubers differ in shape compared with cerebral tubers and are associated with cerebellar volume loss. Cerebellar atrophy may be focal and diffuse and one of the primary cerebellar manifestations of TSC, especially if a TSC2 mutation is present. Cerebellar degeneration may, however, also be secondary/acquired due to cellular damage resulting from seizure activity, the effects of anti-seizure drugs and anoxic–ischemic injury from severe seizure activity/status epilepticus. Further, prospective studies are required to identify and establish the pathogenic mechanism of cerebellar atrophy in patients with TSC.
Clinical Characteristics of Offspring Born to Parents with Type 2 Diabetes Diagnosed in Youth: Observations from TODAY
Authors: Tryggestad Jeanie B. , Kelsey Megan M. , Drews Kimberly L. , Zhou Shirley , Chang Nancy , Escaname Elia , Gidding Samuel S. , Isganaitis Elvira , McKay Siripoom , Shah Rachana , Van Name Michelle
Published: May 2024

Diabetes exposure during pregnancy affects health outcomes in offspring; however, little is known about in utero exposure to preexisting parental youth-onset type 2 diabetes. Offspring born to participants during the Treatment Options for Type 2 Diabetes in Adolescent and Youth (TODAY) study were administered a questionnaire at the end of the study. Of 457 participants, 37% of women and 18% of men reported 228 offspring, 80% from female participants. TODAY mothers had lower household income (<$25,000) compared to TODAY fathers (69.4% vs. 37.9%, p = 0.0002). At 4.5 years of age (range 0–18 years), 16.7% of offspring were overweight according to the parental report of their primary care provider, with no sex difference. Offspring of TODAY mothers reported more daily medication use compared to TODAY fathers (50/183, 27.7% vs. 6/46, 12.2%, [p = 0.04]), a marker of overall health. TODAY mothers also reported higher rates of recidivism (13/94) than TODAY fathers (0/23). An Individualized Education Plan was reported in 20/94 (21.3%) offspring of TODAY mothers compared to 2/23 (8.7%) of TODAY fathers. This descriptive study, limited by parental self-reports, indicated offspring of participants in TODAY experience significant socioeconomic disadvantages, which, when combined with in utero diabetes exposure, may increase their risk of health and educational disparities.
Current Challenges in Pediatric Asthma
Authors: Miculinić Andrija , Mrkić Kobal Iva , Kušan Tin , Turkalj Mirjana , Plavec Davor
Published: May 2024

Asthma is a chronic lung disease characterized by reversible bronchoconstriction and inflammation of the bronchi. Its increasing prevalence in childhood as well as different triggers make asthma a challenging disease in several ways: defining its phenotype/endotype, the diagnostic approach (especially in younger children), therapeutic options, and systematic follow-up. Considering these problems, this review approaches the current status and limitations of guidelines used for asthma management in children. It also emphasizes the key points which could lead to a better understanding and the direction to take in future studies.
Microstructure, Hardness, Wear Resistance, and Corrosion Resistance of As-Cast and Laser-Deposited FeCoNiCrAl0.8Cu0.5Si0.5 High Entropy Alloy
Authors: Ji Xiaohu , Zhou Lihua , Li Heng
Published: May 2024

FeCoNiCrAl0.8Cu0.5Si0.5 high-entropy alloys were fabricated using vacuum induction melting and laser deposition processes, followed by a comparison of the structural and mechanical properties of two distinct sample types. The as-cast FeCoNiCrAl0.8Cu0.5Si0.5 alloy is comprised of BCC1, BCC2, and Cr3Si phases, while the laser-deposited alloy primarily features BCC1 and BCC2 phases. Microstructural analysis revealed that the as-cast alloy exhibits a dendritic morphology with secondary dendritic arms and densely packed grains, and the laser-deposited alloy displays a dendritic structure without the formation of granular interdendritic regions. For mechanical properties, the as-cast FeCoNiCrAl0.8Cu0.5Si0.5 alloy demonstrated higher hardness than the as-deposited alloy, with values of 586 HV0.2 and 557 HV0.2, respectively. The wear rate for the as-cast alloy was observed at 3.5 × 10−7 mm3/Nm, with abrasive wear being the primary wear mechanism. Conversely, the as-deposited alloy had a wear rate of 9.0 × 10−7 mm3/Nm, characterized by adhesive wear. The cast alloy exhibited an icorr of 4.062 μA·cm−2, with pitting as the form of corrosion. The laser-deposited alloy showed an icorr of 3.621 μA·cm−2, with both pitting and intergranular corrosion observed. The laser-deposited alloy demonstrated improved corrosion resistance. The investigation of their microstructure and mechanical properties demonstrates the application potential of FeCoNiCrAl0.8Cu0.5Si0.5 alloys in scenarios requiring high hardness and enhanced wear resistance.
A Blockchain-Based Electronic Health Record (EHR) System for Edge Computing Enhancing Security and Cost Efficiency
Authors: Mandarino Valerio , Pappalardo Giuseppe , Tramontana Emiliano
Published: May 2024

Blockchain technology offers unique features, such as transparency, the immutability of data, and the capacity to establish trust without a central authority. Such characteristics can be leveraged to support the collaboration among several different software systems operating within the healthcare ecosystem, while ensuring data integrity and make electronic health records (EHRs) more easily accessible. To provide a solution based on blockchain technology, this paper has evaluated the main issues that arise when large amounts of data are expected, i.e., mainly cost and performance. A balanced approach that maximizes the benefits and mitigates the constraints of the blockchain has been designed. The proposed decentralized application (dApp) architecture employs a hybrid storage strategy that involves storing medical records locally, on users’ devices, while utilizing blockchain to manage an index of these data. The dApp clients facilitate interactions among participants, leveraging a smart contract to enable patients to set authorization policies, thereby ensuring that only designated healthcare providers and authorized entities have access to specific medical records. The blockchain data-immutability property is used to validate data stored externally. This solution significantly reduces the costs related to the utilization of the blockchain, while retaining its advantages, and improves performance, since the majority of data are available off-chain.
Ultrahigh Responsivity In2O3 UVA Photodetector through Modulation of Trimethylindium Flow Rate
Authors: Li Yifei , Chen Tiwei , Ma Yongjian , Hu Yu , Zhang Li , Zhang Xiaodong , Yang Jinghang , Wang Lu , Zhang Huanyu , Yan Changling , Zeng Zhongming , Zhang Baoshun
Published: May 2024

Oxygen vacancies (Vo) can significantly degrade the electrical properties of indium oxide (In2O3) thin films, thus limiting their application in the field of ultraviolet detection. In this work, the Vo is effectively suppressed by adjusting the Trimethylindium (TMIn) flow rate (fTMIn). In addition, with the reduction of the fTMIn, the background carrier concentration and the roughness of the film decrease gradually. And a smooth In2O3 thin film with roughness of 0.44 nm is obtained when the fTMIn is 5 sccm. The MSM photodetectors (PDs) are constructed based on In2O3 thin films with different fTMIn to investigate the opto-electric characteristics of the films. The dark current of the PDs is significantly reduced by five orders from 100 mA to 0.28 μA with the reduction of the fTMIn from 50 sccm to 5 sccm. In addition, the photo response capacity of PDs is dramatically enhanced. The photo-to-dark current ratio (PDCR) increases from 0 to 2589. Finally, the PD with the fTMIn of 5 sccm possesses a record-high responsivity of 2.53 × 103 AW−1, a high detectivity of 5.43 × 107 Jones and a high EQE of 9383 × 100%. Our work provides an important reference for the fabrication of high-sensitivity UV PDs.
The Estimation of the Stress State of the Iron Alloy Strip Material by the Barkhausen Noise Method
Authors: Krawczyk Janusz , Sułek Bartosz , Kokosza Adam , Lijewski Marcin , Kuźniar Nikolaos , Majewski Marcin , Goły Marcin
Published: May 2024

This paper presents the effect of the complex strain state resulting from the asymmetric rolling of TRB products on the changes and distribution of the stress state in the material. The evaluation of the stress state in the material was based on measurements of the magnetoelastic parameter (MP) using the Barkhausen magnetic noise method. The key characteristics of the material under study that enabled the use of changes in the MP parameter to assess the stress state were ferromagnetism and a lack of texture. The first of these enabled the detection of the magnetic signals produced when a magnetic field is applied to the material, causing magnetic domains to align and sudden changes in magnetization. On the other hand, the absence of texture in the material precluded the occurrence of magnetocrystalline anisotropy, which could disturb the results of measurements of the magnetoelastic parameter in the material. In order to determine these features in the material under study, its chemical composition was determined, and a phase analysis was carried out using the X-ray diffraction method. The results of these tests showed the possibility of determining the stress state of the material by means of changes in the values of the MP parameter. On this basis, it was shown that in the TRB strips studied, there is a complex state of stress, the values of which and the nature of the changes depending on the direction of the measurements carried out, as well as on the amount of rolling reduction in the studied area of the strip.
Space Group Choice for an Octahedral Zn Complex with Nalidixic Acid and (R,R)-Diaminocyclohexane as Ligands: Get the Stereochemistry Right
Authors: Lutz Martin , Müller Tom W.
Published: May 2024

With this report, the space group of [Zn(Nal)(DACH)2]Cl is corrected (Nal: nalidixic acid mono-anion; DACH: diaminocyclohexane) from its wrong description in the literature. In the correct, non-centrosymmetric space group P1, the crystal structure is well ordered and the stereochemistry is correct. Crystallographic tools to recognize the correct symmetry are described. This work encourages experienced and inexperienced scientists to remain critical about the output of automatic, black-box crystallographic software.
The Application of Surface Electromyography Technology in Evaluating Paraspinal Muscle Function
Authors: Suo Moran , Zhou Lina , Wang Jinzuo , Huang Huagui , Zhang Jing , Sun Tianze , Liu Xin , Chen Xin , Song Chunli , Li Zhonghai
Published: May 2024

Surface electromyography (sEMG) has emerged as a valuable tool for assessing muscle activity in various clinical and research settings. This review focuses on the application of sEMG specifically in the context of paraspinal muscles. The paraspinal muscles play a critical role in providing stability and facilitating movement of the spine. Dysfunctions or alterations in paraspinal muscle activity can lead to various musculoskeletal disorders and spinal pathologies. Therefore, understanding and quantifying paraspinal muscle activity is crucial for accurate diagnosis, treatment planning, and monitoring therapeutic interventions. This review discusses the clinical applications of sEMG in paraspinal muscles, including the assessment of low back pain, spinal disorders, and rehabilitation interventions. It explores how sEMG can aid in diagnosing the potential causes of low back pain and monitoring the effectiveness of physical therapy, spinal manipulative therapy, and exercise protocols. It also discusses emerging technologies and advancements in sEMG techniques that aim to enhance the accuracy and reliability of paraspinal muscle assessment. In summary, the application of sEMG in paraspinal muscles provides valuable insights into muscle function, dysfunction, and therapeutic interventions. By examining the literature on sEMG in paraspinal muscles, this review offers a comprehensive understanding of the current state of research, identifies knowledge gaps, and suggests future directions for optimizing the use of sEMG in assessing paraspinal muscle activity.