bluuebunny/crossref_metadata_2025 huggingface dataset:
From Feeding Challenges to Oral-Motor Dyspraxia: A Comprehensive Description of 10 New Cases with CTNNB1 Syndrome
Authors: Onesimo Roberta , Sforza Elisabetta , Trevisan Valentina , Leoni Chiara , Giorgio Valentina , Rigante Donato , Kuczynska Eliza Maria , Proli Francesco , Agazzi Cristiana , Limongelli Domenico , Digilio Maria Cistina , Dentici Maria Lisa , Macchiaiolo Maria , Novelli Antonio , Bartuli Andrea , Sinibaldi Lorenzo , Tartaglia Marco , Zampino Giuseppe
Published: September 2023

CTNNB1 syndrome is an autosomal-dominant neurodevelopmental disorder featuring developmental delay; intellectual disability; behavioral disturbances; movement disorders; visual defects; and subtle facial features caused by de novo loss-of-function variants in the CTNNB1 gene. Due to paucity of data, this study intends to describe feeding issues and oral-motor dyspraxia in an unselected cohort of 10 patients with a confirmed molecular diagnosis. Pathogenic variants along with key information regarding oral-motor features were collected. Sialorrhea was quantified using the Drooling Quotient 5. Feeding abilities were screened using the Italian version of the Montreal Children’s Hospital Feeding Scale (I-MCH-FS). Mild-to-severe coordination difficulties in single or in a sequence of movements involving the endo-oral and peri-oral muscles were noticed across the entire cohort. Mild-to-profuse drooling was a commonly complained-about issue by 30% of parents. The mean total I-MCH-FS t-score equivalent was 43.1 ± 7.5. These findings contribute to the understanding of the CTNNB1 syndrome highlighting the oral motor phenotype, and correlating specific gene variants with clinical characteristics.
Ground Motion Duration Patterns for Vrancea (Romania) Intermediate-Depth Earthquakes
Authors: Pavel Florin , Nica George
Published: September 2023

This study is focused on evaluating ground motion durations of Vrancea intermediate-depth earthquakes in Romania, in the context of future updates to the Romanian seismic design code P100-1/2013. The ground motion database compiled for this study consists of about 200 ground motions recorded during five moderate and large Vrancea intermediate-depth earthquakes that occurred in the period of 1977–2004 and had moment magnitudes of MW ≥ 6.0. Two empirical models were derived in this study for the significant ground motion duration considering two time intervals (5–75% and 5–95%) for the accumulation of the Arias Intensity IA. An analysis of the data shows that the mean ratio between D5-95 and D5-75 is about 2.8. Moreover, the regression also shows that the largest share of variability is due to the within-event component (site term). Among the regression coefficients, the hypocentral distance and the soil conditions appear to have a larger impact on the ground motion duration compared to the earthquake magnitude. It was also observed that the median ground motion durations predicted using the empirical model proposed in this study were much smaller than the ones from the proposed Eurocode 8 draft for the same magnitude range. Finally, geographic trends related to the distribution of residuals were also evaluated using the data from the three earthquakes with the largest number of available ground motion recordings.
The Open Landslide Project (OLP), a New Inventory of Shallow Landslides for Susceptibility Models: The Autumn 2019 Extreme Rainfall Event in the Langhe-Monferrato Region (Northwestern Italy)
Authors: Licata Michele , Buleo Tebar Victor , Seitone Francesco , Fubelli Giandomenico
Published: September 2023

Landslides triggered by heavy rainfall pose significant threats to human settlements and infrastructure in temperate and equatorial climate regions. This study focuses on the development of the Open Landslide Project (OLP), an open source landslide inventory aimed at facilitating geostatistical analyses and landslide risk management. Using a multidisciplinary approach and open source, multisatellite imagery data, more than 3000 landslides triggered by the extreme rainfall of autumn 2019 in northwestern Italy were systematically mapped. The inventory creation process followed well-defined criteria and underwent rigorous validation to ensure accuracy and reliability. The dataset’s suitability was confirmed through multivariate correlation and Double Pareto probably density function. The OLP inventory effectiveness in assessing landslide risks was proved by the development of a landslide susceptibility model using binary logistic regression. The analysis of rainfall and lithology revealed that regions with lower rainfall levels experienced a higher occurrence of landslides compared to areas with higher peak rainfall. This was attributed to the response of the lithological composition to rainfalls. The findings of this research contribute to the understanding and management of landslide risks in anthropized climate regions. The OLP has proven to be a valuable resource for future geostatistical analysis.
Enrichment of Low-Level Tritium in Groundwater via an Electrolysis Process for Liquid Scintillation Counting Applications
Authors: Mamun Al
Published: September 2023

Tritium levels in the groundwater of arid regions are very low; in most cases, these low tritium levels cannot be detected using a conventional liquid scintillation counter (LSC). To measure the tritium activity concentration, low-level tritium in groundwater needs to be enriched by a known factor so that the scintillation counter can detect it. An electrolysis process with electrolytic cells was designed and fabricated in our laboratory following the International Atomic Energy Agency (IAEA) instructions. Nine spiked samples with a known quantity of tritium were enriched, and the tritium activity concentration was measured using the scintillation counter. The enriched water exhibits a comparable level of spiked samples, albeit with some degree of uncertainty. A correlation was drawn among the tritium activity, enrichment factor, and the required time for the electrolysis procedure. This study confirmed that an enrichment process of approximately ten- to fortyfold of the initial concentration of the tritium could be achieved using the electrolysis process with the fabricated electrolytic cells. The simple design and fabrication of the electrolysis process by controlling various parameters make it affordable to measure low-level tritium using a conventional LSC. Various statistical analyses confirmed the accuracy and precision of the data obtained by the electrolysis process. This enrichment technique would prove valuable in regions where tritium levels in groundwater are extremely low, making them challenging to detect using conventional liquid scintillation counter.
The Mechanical Characterization of Pyroclastic Deposits for Landslide Early Warning Systems
Authors: Damiano Emilia , de Cristofaro Martina , Brunzo Antonia , Carrieri Goffredo , Iavazzo Luisa , Netti Nadia , Olivares Lucio
Published: September 2023

Broad mountainous areas in the western Campania (southern Italy), where young pyroclastic deposits extensively outcrop, frequently experience rainfall-induced slope movements of different degrees of mobility, causing heavy damage and fatalities. Such landslides cannot be easily mitigated, and the implementation of physically based early warning systems is still not able to predict the post-failure evolution of slope movements and the exposed areas at risk. This paper is devoted to overcoming this limit. To this end, the mechanical characterization of pyroclastic soil, carried out through an extensive laboratory testing program, is presented and compared with those of two other ashy soils of different depositional mechanisms. The results show that the depositional mode influences soil properties; to begin with, it affects the unsaturated shear strength, whose intercept of cohesion is up to 5 kPa higher in ashes of flow deposition than in airfall ash deposits. The saturated undrained soil response allowed for the identification of different levels of susceptibility to the liquefaction of pyroclastic deposits, which is one of the main factors governing the post-failure evolution of landslides. Gathering all the acquired information, including saturated and unsaturated soil shear strength, permeability function, and water retention curves, into a soil database, it was possible to present all data under a unitary framework. Finally, the implementation of the proposed flowchart for a simplified assessment of post-failure evolution to be employed in regional early warning systems can enhance our knowledge of the areas at risk.
Examining the Use of Autonomous Systems for Home Health Support Using a Smart Mirror
Authors: Dowthwaite Liz , Cruz Gisela Reyes , Pena Ana Rita , Pepper Cecily , Jäger Nils , Barnard Pepita , Hughes Ann-Marie , Nair Roshan das , Crepaz-Keay David , Cobb Sue , Lang Alexandra , Benford Steve
Published: September 2023

The home is becoming a key location for healthcare delivery, including the use of technology driven by autonomous systems (AS) to monitor and support healthcare plans. Using the example of a smart mirror, this paper describes the outcomes of focus groups with people with multiple sclerosis (MS; n = 6) and people who have had a stroke (n = 15) to understand their attitudes towards the use of AS for healthcare in the home. Qualitative data were analysed using a thematic analysis. The results indicate that the use of such technology depends on the level of adaptability and responsiveness to users’ specific circumstances, including their relationships with the healthcare system. A smart mirror would need to support manual entry, responsive goal setting, the effective aggregation of data sources and integration with other technology, have a range of input methods, be supportive rather than prescriptive in messaging, and give the user full control of their data. The barriers to its adoption include a perceived lack of portability and practicality, a lack of accessibility and inclusivity, a sense of redundancy, feeling overwhelmed by multiple technological devices, and a lack of trust in data sharing. These results inform the development and deployment of future health technologies based on the lived experiences of people with health conditions who require ongoing care.
The Effects of the Situated Simulation Program on the Cultural Competence of Hemodialysis Nurses: A Quasi-Experimental Study
Authors: Hsu Jui-Chin , Wang Min-Shu , Wang Pao-Yu , Lian Shu-Yu , Lin Mei-Hsiang
Published: September 2023

The rise in the number of hemodialysis (HD) patients underscores the importance of culturally competent HD nurses. This study aimed to examine the effectiveness of a situated simulation program on HD nurses’ cultural competence. This was a quasi-experimental pilot study with a total of 40 participants who met the inclusion criteria from an HD center in northern Taiwan. Participants took part in two separate 3 h education programs. The first program focused on the basic concepts of cultural competence, while the second program involved situated simulations utilizing the Gather–Analyze–Summarize (GAS) method of debriefing. The generalized estimating equations (GEEs) were employed to estimate the intervention effect. The baseline scores were divided into low-score and high-score groups using the median score for subgroup analysis. The subgroup analysis revealed that a significant group-time interaction was identified regarding cultural competence and subscale, verifying the situated simulation’s immediate effect. In this study, an integration of the GAS method of debriefing and situated simulation teaching was implemented. The results showed that this approach empowered HD nurses with the ability to foster positive attitudes and demonstrate professional expertise in an organized manner when facing similar clinical scenarios in the future.
Distribution and Prevalence of Elbow Pain (EP) in Elite Swimmers in Tianjin, China—A Regional Epidemiological Study
Authors: Li Weihan , Hadizadeh Maryam , Yusof Ashril , Naharudin Mohamed Nashrudin
Published: September 2023

Elbow pain (EP) in overhead sports is a common phenomenon. Swimming is classified as an overhead sport, but a lack of attention regarding EP in swimming has created a gap in the knowledge around elite freestyle swimming in Tianjin, China. The purpose of this study was to identify the distribution and prevalence of EP among elite freestyle swimmers in Tianjin, China. The methodology involved a total of 311 qualified participants who volunteered to undertake all measurements. The main findings showed that 183 of the elite freestyle swimmers in this study had EP (accounting for 58.84% of the total 311 participants), with 147 in slight pain and 36 in critical pain. The characteristics of a heavier body weight, taller height, longer left/right forearm length, and longer weekly average training hours serve as contributing factors to the occurrence of EP issues. Gender, age, weekly average training hours, and left/right forearm length are the primary factors correlating with and influencing the assessment scores. In conclusion, swimmers with longer weekly training hours, older ages, heavier bodyweight, and longer forearm lengths should receive greater attention in relation to EP. Regular assessments at a high frequency serve as a means to identify the risk of EP.
Using Lean Six Sigma in a Private Hospital Setting to Reduce Trauma Orthopedic Patient Waiting Times and Associated Administrative and Consultant Caseload
Authors: Pierce Anthony , Teeling Seán Paul , McNamara Martin , O’Daly Brendan , Daly Ailish
Published: September 2023

In Ireland, the extent of outpatient orthopedic waiting lists results in long waiting times for patients, delays in processing referrals, and variation in the consultant caseload. At the study site, the Define, Measure, Analyze, Improve, and Control (DMAIC) Lean Six Sigma framework was applied to evaluate sources of Non-Value-Added (NVA) activity in the process of registering and triaging patients referred to the trauma orthopedic service from the Emergency Department. A pre- (October–December 2021)/post- (April–August 2022) intervention design was employed, utilizing Gemba, Process Mapping, and the TIMWOODS tool. Embracing a person-centered approach, stakeholder Voice of Customer feedback was sought at each stage of the improvement process. Following data collection and analysis, a co-designed pilot intervention (March 2022) was implemented, consisting of a new triage template, dedicated trauma clinic slots, a consultant triage roster, and a new option to refer directly to physiotherapy services. This resulted in the total wait time of patients for review being reduced by 34%, a 51% reduction in the process steps required for registering, and an increase in orthopedic consultant clinic capacity of 22%. The reduction in NVA activities in the process and the increase in management options for triaging consultants have delivered a more efficient trauma and orthopedic pathway.
Health Providers’ Response to Female Adolescent Survivors of Sexual and Gender-Based Violence and Demand Side Barriers in the Utilization of Support Services in Urban Low-Income Communities of Nigeria
Authors: Ikuteyijo Olutoyin Opeyemi , Kaiser-Grolimund Andrea , Fetters Michael D. , Akinyemi Akanni Ibukun , Merten Sonja
Published: September 2023

Survivors of sexual and gender-based violence (SGBV) are often hindered in their quest to access quality healthcare. This has a significant effect towards the achievement of Sustainable Development Goal SDG Target 3.7. to ensure universal access to sexual and reproductive healthcare services. This study is focused on identifying some of the demand side barriers in accessing health care services, particularly among young girls who are survivors of SGBV within intimate relationships in poor urban areas in Nigeria. The study used an ethnographic approach to solicit information from health providers, adolescents, and young women (AYW) in 10 low-income communities in two major cities in Nigeria, Ibadan and Lagos. Findings showed that there are structural limitations within the primary health care (PHC) system that posed a great challenge for survivors of SGBV to access services. Some of these include non-existing counseling services, a lack of rehabilitation centers, poor referral, and a lack of training for health providers in handling survivors of SGBV. There is also a lack of skills among health service providers that have negative influence on support services to survivors of SGBV. On the demand side, poor knowledge of possible health seeking pathways, a lack of education, and social support are barriers to accessing appropriate services among adolescent and young SGBV survivors. The study concluded that integrated services at the PHC level should include adequate and timely treatment for survivors of SGBV and targeted intervention to upscale skills and knowledge of health care providers.
Sociodemographic and Clinical Profile of Long COVID-19 Patients, and Its Correlation with Medical Leave: A Comprehensive Descriptive and Multicenter Study
Authors: Romero-Rodriguez Esperanza , Perula-de Torres Luis Angel , Monserrat-Villatoro Jaime , Gonzalez-Lama Jesus , Carmona-Casado Ana Belen , Ranchal-Sanchez Antonio
Published: September 2023

The persistent condition of COVID-19 is characterized by a wide range of symptoms that have had a significant impact on both the health status and occupational life of the population. In this observational and multicenter study, the relationship between the sociodemographic and clinical profile of Spanish patients diagnosed with long COVID, and the work-related disability resulting from this pathology was analyzed. The analysis included 689 responses. A descriptive analysis of the variables recorded was performed, together with a bivariate analysis to determine associations between work-related disability and variables such as gender, age, health status, disabling symptoms or comorbidities. The results obtained highlight fatigue and lack of concentration (brain fog) as the most incapacitating symptoms among patients diagnosed with long COVID. Multivariate analysis revealed that time since diagnosis (OR: 0.57, CI95%: 0.36–0.89, p: 0.013), concomitant renal insufficiency (OR: 4.04, CI95%: 1.42–11.4, p: 0.008), and symptoms like fatigue (OR: 0.56, CI95%: 0.33–0.99) and tremors (OR: 2.0, CI95%: 1.06–3.69, p: 0.029), were associated with work-related disability. These findings highlight the need to improve the health and work-related management of this condition in the healthcare system. Besides risk factor control, it is suggested to pay special attention to determining the appropriate timing of medical leave work reintegration, along with coordination between primary care and occupational health services to ensure the gradual and tailored return of patients with long COVID to the workforce.
Single-Cell Profiling of Cells in the Lung of a Patient with Chronic Hypersensitivity Pneumonitis Reveals Inflammatory Niche with Abundant CD39+ T Cells with Functional ATPase Phenotype: A Case Study
Authors: de Silva Tharushi Ayanthika , Apte Simon , Voisey Joanne , Spann Kirsten , Tan Maxine , Divithotawela Chandima , Chambers Daniel , O’Sullivan Brendan
Published: September 2023

This study investigated immune cell characteristics in chronic hypersensitivity pneumonitis (HP), focusing on CD39-expressing cells’ impact on inflammation and tissue remodelling. Lung tissue from an HP patient was analysed using single-cell transcriptomics, flow cytometry, and gene expression profiling. The tissue revealed diverse cell types like macrophages, T cells, fibroblasts, and regulatory T cells (Tregs). CD39-expressing Tregs exhibited heightened ATP hydrolysis capacity and regulatory gene expression. CD39hi cells displayed markers of both Tregs and proinflammatory Th17 cells, suggesting transitional properties. Communication networks involving molecules like SPP1, collagen, CSF1, and IL-1β were identified, hinting at interactions between cell types in HP pathogenesis. This research provides insights into the immune response and cell interactions in chronic HP. CD39-expressing cells dual nature as Tregs and Th17 cells suggests a role in modulating lung inflammation, potentially affecting disease progression. These findings lay the groundwork for further research, underscoring CD39-expressing cells as potential therapeutic targets in HP.
Unusual Presentation of SET::NUP214-Associated Concomitant Hematological Neoplasm in a Child—Diagnostic and Treatment Struggle
Authors: Menchits Yaroslav , Salimova Tatiana , Komkov Alexander , Abramov Dmitry , Konyukhova Tatiana , Abasov Ruslan , Raykina Elena , Itov Albert , Gaskova Marina , Borkovskaia Aleksandra , Kazakova Anna , Soldatkina Olga , Kashpor Svetlana , Semchenkova Alexandra , Popov Alexander , Novichkova Galina , Olshanskaya Yulia , Maschan Alexey , Zerkalenkova Elena
Published: September 2023

Simultaneous multilineage hematologic malignancies are uncommon and associated with poorer prognosis than single-lineage leukemia or lymphoma. Here, we describe a concomitant malignant neoplasm in a 4-year-old boy. The child presented with massive lymphoproliferative syndrome, nasal breathing difficulties, and snoring. Morphological, immunocytochemical, and flow cytometry diagnostics showed coexistence of acute myeloid leukemia (AML) and peripheral T-cell lymphoma (PTCL). Molecular examination revealed a rare t(9;9)(q34;q34)/SET::NUP214 translocation as well as common TCR clonal rearrangements in both the bone marrow and lymph nodes. The disease showed primary refractoriness to both lymphoid and myeloid high-dose chemotherapy as well as combined targeted therapy (trametinib + ruxolitinib). Hence, HSCT was performed, and the patient has since been in complete remission for over a year. This observation highlights the importance of molecular techniques for determining the united nature of complex SET::NUP214-positive malignant neoplasms arising from precursor cells with high lineage plasticity.
The Prognostic Significance of Selected HLA Alleles on Prostate Cancer Outcome
Authors: Stokidis Savvas , Baxevanis Constantin N. , Fortis Sotirios P.
Published: September 2023

Recently, we have shown that HLA-A*02:01 and HLA-A*24:02 in de novo metastatic prostate cancer (MPCa) have an important role in disease progression. Since de novo MPCa represents a small group among patients diagnosed with prostate cancer (PCa), it was obvious to try to extend the validity of our results to larger cohorts of PCa patients. Herein, we analyzed patients irrespective of their disease status at diagnosis to include, besides patients with MPCa, those with localized PCa (LPCa). Our goal was to specify the prognostic value of HLA-A*02:01 and HLA-A*24:02 for overall survival (OS) prospectively and for early biochemical recurrence (BCR) and castrate resistance (CR) as additional clinical endpoints in a prospective/retrospective manner, to improve clinical decisions for patients covering all stages of PCa. On univariate analysis, HLA-A alleles were significantly associated as prognostic biomarkers with early BCR (p = 0.028; HR = 1.822), OS (p = 0.013; HR = 1.547) and showed a trend for CR (p = 0.150; HR = 1.239). On multivariate analysis, HLA-A alleles proved to be independent prognosticators for early BCR (p = 0.017; HR = 2.008), CR (p = 0.005; HR = 1.615), and OS (p = 0.002; HR = 2.063). Kaplan–Meier analyses revealed that patients belonging to the HLA-A*02:01+HLA-A*24:02− group progressed much faster to BCR and CR and had also shorter OS compared to HLA-A*24:02+ patients. Patients being HLA-A*02:01−HLA-A*24:02− exhibited varying clinical outcomes, pointing to the presence of additional HLA-A alleles with potential prognostic value. Our data underline the HLA-A alleles as valuable prognostic biomarkers for PCa that may assist with the appropriate treatment and follow-up schedule based on the risk for disease progression to avoid over-diagnosis and over-treatment.
Pharmacological Modulation of Oxidative Stress
Authors: Saha Sarmistha , Saso Luciano
Published: September 2023

An imbalance between the formation of reactive oxygen species (ROS) and the reaction of antioxidant proteins is referred to as oxidative stress [...]
Integrated Cytological, Physiological, and Transcriptome Analyses Provide Insight into the Albino Phenotype of Chinese Plum (Prunus salicina)
Authors: Xie Weiwei , Xu Dantong , Chen Fangce , Wang Zhengpeng , Luo Jiandong , He Yehua , Zheng Qianming , Liu Chaoyang
Published: September 2023

Albino seedlings that arise during seed reproduction can have a significant impact on plant growth and breeding. In this research, we present the first report of albino occurrences in the seed reproduction process of Prunus salicina and describe the cytological, physiological, and transcriptomic changes observed in albino seedlings. The albino seedlings which were observed in several plum cultivars exhibited abnormal chloroplast ultrastructure and perturbed stomatal structure. Compared to normal seedlings, the photosynthetic pigment contents in albino seedlings decreased by more than 90%, accompanied by significant reductions in several chlorophyll fluorescence parameters. Furthermore, substantially changed photosynthetic parameters indicated that the photosynthetic capacity and stomatal function were impaired in albino seedlings. Additionally, the activities of the antioxidant enzyme were drastically altered against the background of higher proline and lower ascorbic acid in leaves of albino seedlings. A total of 4048 differentially expressed genes (DEGs) were identified through transcriptomic sequencing, and the downregulated DEGs in albino seedlings were greatly enriched in the pathways for photosynthetic antenna proteins and flavonoid biosynthesis. GLK1 and Ftsz were identified as candidate genes responsible for the impaired chloroplast development and division in albino seedlings. Additionally, the substantial decline in the expression levels of examined photosystem-related chloroplast genes was validated in albino seedlings. Our findings shed light on the intricate physiological and molecular mechanisms driving albino plum seedling manifestation, which will contribute to improving the reproductive and breeding efforts of plums.
Transcriptome Analysis Reveals the Effect of PdhR in Plesiomonas shigelloides
Authors: Yan Junxiang , Yang Bin , Xue Xinke , Li Jinghao , Li Yuehua , Li Ang , Ding Peng , Cao Boyang
Published: September 2023

The pyruvate dehydrogenase complex regulator (PdhR) was originally identified as a repressor of the pdhR-aceEF-lpd operon, which encodes the pyruvate dehydrogenase complex (PDHc) and PdhR itself. According to previous reports, PdhR plays a regulatory role in the physiological and metabolic pathways of bacteria. At present, the function of PdhR in Plesiomonas shigelloides is still poorly understood. In this study, RNA sequencing (RNA-Seq) of the wild-type strain and the ΔpdhR mutant strains was performed for comparison to identify the PdhR-controlled pathways, revealing that PdhR regulates ~7.38% of the P. shigelloides transcriptome. We found that the deletion of pdhR resulted in the downregulation of practically all polar and lateral flagella genes in P. shigelloides; meanwhile, motility assay and transmission electron microscopy (TEM) confirmed that the ΔpdhR mutant was non-motile and lacked flagella. Moreover, the results of RNA-seq and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) showed that PdhR positively regulated the expression of the T3SS cluster, and the ΔpdhR mutant significantly reduced the ability of P. shigelloides to infect Caco-2 cells compared with the WT. Consistent with previous research, pyruvate-sensing PdhR directly binds to its promoter and inhibits pdhR-aceEF-lpd operon expression. In addition, we identified two additional downstream genes, metR and nuoA, that are directly negatively regulated by PdhR. Furthermore, we also demonstrated that ArcA was identified as being located upstream of pdhR and lpdA and directly negatively regulating their expression. Overall, we revealed the function and regulatory pathway of PdhR, which will allow for a more in-depth investigation into P. shigelloides pathogenicity as well as the complex regulatory network.
Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer’s Disease
Authors: Boboc Ianis Kevyn Stefan , Cojocaru Alexandru , Nedelea Gabriel , Catalin Bogdan , Bogdan Maria , Calina Daniela
Published: September 2023

As the population ages, a high prevalence of multimorbidity will affect the way physicians need to think about drug interactions. With microglia’s important involvement in the pathology and progression of Alzheimer’s disease (AD), understanding whether systemically administered drugs intended for other affections could impact microglia function, already impacted by the presence of beta-amyloid, is important. The aim of this study was to evaluate morphological changes of microglia, using in vivo 2-photon laser scanning microscopy, in a murine model of AD under systemic administration of sodium or calcium ion channel blockers in order to establish potential effects that these drugs might have on microglia under neuro-inflammatory conditions. A total of 30 mice (age 14–16 weeks, weight 20–25 g) were used, with 25 APP randomly divided into three groups. The remaining animals were CX3CR1GFP/GFP male mice (n = 5) used as WT controls. After baseline behavior testing, all animals received daily intraperitoneal injections for 30 days according to the assigned group [WT (n = 5), Control (n = 5), Carbamazepine (n = 10), and Verapamil (n = 10)]. The results showed that the Verapamil treatment improved short-term memory and enhanced exploratory behavior in APP mice. The Carbamazepine treatment also improved short-term memory but did not elicit significant changes in anxiety-related behavior. Both Verapamil and Carbamazepine reduced the surveillance speed of microglia processes and changed microglia morphology in the cortex compared to the Control group. Due to their complex molecular machinery, microglia are potentially affected by drugs that do not target them specifically, and, as such, investigating these interactions could prove beneficial in our management of neurodegenerative pathologies.
MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis and Secretion in Silica-Induced Pulmonary Fibrosis
Authors: Jiang Qiyue , Zhao Jing , Jia Qiyue , Wang Hongwei , Xue Wenming , Ning Fuao , Wang Jiaxin , Wang Yan , Zhu Zhonghui , Tian Lin
Published: September 2023

Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p’s expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis.
Fluorescent Molecules That Help Reveal Previously Unidentified Neural Connections in Adult, Neonatal and Peripubertal Mammals
Authors: Vasziné Szabó Enikő , Köves Katalin , Csáki Ágnes
Published: September 2023

One hundred and twenty-five years ago there was a lively discussion between Hungarian and Spanish neuroscientists on the nature of neural connections. The question was whether the neurofibrils run from one neuron to the next and connect neurons as a continuous network or the fibrils form an internal skeleton in the neurons and do not leave the cell; however, there is close contact between the neurons. About 50 years later, the invention of the electron microscope solved the problem. Close contacts between individual neurons were identified and named as synapses. In the following years, the need arose to explore distant connections between neuronal structures. Tracing techniques entered neuroscience. There are three major groups of tracers: (A) non-transsynaptic tracers used to find direct connections between two neuronal structures; (B) tracers passing gap junctions; (C) transsynaptic tracers passing synapses that are suitable to explore multineuronal circuits. According to the direction of the transport mechanism, the tracer may be ante- or retrograde. In this review, we focus on the ever-increasing number of fluorescent tracers that we have also used in our studies. The advantage of the use of these molecules is that the fluorescence of the tracer can be seen in histological sections without any other processes. Genes encoding fluorescent molecules can be inserted in various neuropeptide or neurotransmitter expressing transcriptomes. This makes it possible to study the anatomy, development or functional relations of these neuronal networks in transgenic animals.
A Study on the Effect of Energy on the Development of Silkworm Embryos Using an Estrogen-Related Receptor
Authors: Shen Guanwang , Liu Die , Xu Haoran , Wu Jinxin , Hou Luyu , Yang Chunyan , Xia Qingyou , Lin Ping
Published: September 2023

Energy metabolism is a fundamental process in all organisms. During silkworm (Bombyx mori) embryonic development, there is a high demand for energy due to continuous cell proliferation and differentiation. Estrogen-related receptors (ERRs) are transcriptional regulatory factors that play crucial roles in mammalian energy storage and expenditure. Although most insects have one ERR gene, it also participates in the regulation of energy metabolism, including carbohydrate metabolism in Drosophila, Aphid, and Silkworm. However, no study has reported the direct impact of energy metabolism on embryonic development in silkworms. In this study, we used transgenic technology to increase silkworm (B. mori; Bm) BmERR expression during embryonic development and explored the impact of energy on embryonic development. We found no significant change in the quality of silkworm eggs compared to that of wild-type silkworms. However, there was an increase in the consumption of vitellin, a major nutrient in embryos. This resulted in a decrease in glucose content and a significant increase in ATP content. These findings provide evidence that the acceleration of energy metabolism promotes embryonic development and enhances the motility of hatched silkworms. In addition, these results provide a novel perspective on the relationship between energy metabolism and embryonic development in other insects.
Integrated Secondary Metabolomic and Antioxidant Ability Analysis Reveals the Accumulation Patterns of Metabolites in Momordica charantia L. of Different Cultivars
Authors: Zhang Yongxue , Lu Panling , Jin Haijun , Cui Jiawei , Miao Chen , He Lizhong , Yu Jizhu , Ding Xiaotao , Zhang Hongmei
Published: September 2023

Bitter gourd (Momordica charantia L.) contains rich bioactive ingredients and secondary metabolites; hence, it has been used as medicine and food product. This study systematically quantified the nutrient contents, the total content of phenolic acids (TPC), flavonoids (TFC), and triterpenoids (TTC) in seven different cultivars of bitter gourd. This study also estimated the organic acid content and antioxidative capacity of different cultivars of bitter gourd. Although the TPC, TFC, TTC, organic acid content, and antioxidative activity differed significantly among different cultivars of bitter gourd, significant correlations were also observed in the obtained data. In the metabolomics analysis, 370 secondary metabolites were identified in seven cultivars of bitter gourd; flavonoids and phenolic acids were significantly more. Differentially accumulated metabolites identified in this study were mainly associated with secondary metabolic pathways, including pathways of flavonoid, flavonol, isoflavonoid, flavone, folate, and phenylpropanoid biosyntheses. A number of metabolites (n = 27) were significantly correlated (positive or negative) with antioxidative capacity (r ≥ 0.7 and p < 0.05). The outcomes suggest that bitter gourd contains a plethora of bioactive compounds; hence, bitter gourd may potentially be applied in developing novel molecules of medicinal importance.
Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?
Authors: Spasiano Andrea , Palazzetti Daniela , Dimartino Lucrezia , Bruno Francesca , Baccaro Rocco , Pesce Francesco , Grandaliano Giuseppe
Published: September 2023

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by a genetic dysregulation of the alternative complement pathway, characterized by thrombocytopenia, hemolytic anemia, and acute kidney injury, and included in the group of thrombotic microangiopathies. With the introduction of humanized monoclonal antibodies that inhibit C5 activation, the natural history of aHUS completely changed, with a better prognosis, a quick recovery of renal function, and a significant reduction of end-stage renal disease incidence. Nowadays, there is an increasing interest in the molecular and genetic bases of this severe disease. The aim of this narrative review is to provide readers with a practical guide about different possible involved genes, elucidating the specific role of each transcribed protein in the pathogenesis of aHUS. Moreover, we analyzed the main current evidence about the relationship among genetic mutations, outcomes, and the risk of recurrence of this manifold disease.
Impact of Hypoxia–Hyperoxia Exposures on Cardiometabolic Risk Factors and TMAO Levels in Patients with Metabolic Syndrome
Authors: Bestavashvili Afina , Glazachev Oleg , Ibragimova Shabnam , Suvorov Alexander , Bestavasvili Alexandros , Ibraimov Shevket , Zhang Xinliang , Zhang Yong , Pavlov Chavdar , Syrkina Elena , Syrkin Abram , Kopylov Philipp
Published: September 2023

Along with the known risk factors of cardiovascular diseases (CVDs) constituting metabolic syndrome (MS), the gut microbiome and some of its metabolites, in particular trimethylamine-N-oxide (TMAO), are actively discussed. A prolonged stay under natural hypoxic conditions significantly and multi-directionally changes the ratio of gut microbiome strains and their metabolites in feces and blood, which is the basis for using hypoxia preconditioning for targeted effects on potential risk factors of CVD. A prospective randomized study included 65 patients (32 females) with MS and optimal medical therapy. Thirty-three patients underwent a course of 15 intermittent hypoxic–hyperoxic exposures (IHHE group). The other 32 patients underwent sham procedures (placebo group). Before and after the IHHE course, patients underwent liver elastometry, biochemical blood tests, and blood and fecal sampling for TMAO analysis (tandem mass spectrometry). No significant dynamics of TMAO were detected in both the IHHE and sham groups. In the subgroup of IHHE patients with baseline TMAO values above the reference (TMAO ≥ 5 μmol/l), there was a significant reduction in TMAO plasma levels. But the degree of reduction in total cholesterol (TCh), low-density lipoprotein (LDL), and regression of liver steatosis index was more pronounced in patients with initially normal TMAO values. Despite significant interindividual variations, in the subgroup of IHHE patients with MS and high baseline TMAO values, there were more significant reductions in cardiometabolic and hepatic indicators of MS than in controls. More research is needed to objectify the prognostic role of TMAO and the possibilities of its correction using hypoxia adaptation techniques.
Relationships between Mortar Spread and the Fresh Properties of SCC Containing Local Metakaolin
Authors: Barkat Abderrazak , Kenai Said , Menadi Belkasem , Kadri El-Hadj , Khatib Jamal
Published: September 2023

Self-compacting concrete (SCC) production is a complex operation that requires finding a good combination and suitable dosages for its constituents. Several formulation methods have been developed to meet the workability requirements of SCC. Mortar spread is used to estimate SCC’s rheological properties, but the use of supplementary cementitious materials, such as metakaolin, could affect the accuracy of the estimation. In this paper, the relationships between the fresh properties of local-metakaolin (MK)-based SCC and the spreading of its mortar portion were investigated. The results showed the existence of good correlations between the spreading of mortar portion of SCC and its fresh state properties. The partial substitution of cement with MK did not affect these correlations. The mortar flow should be chosen according to the required rheological properties of the SCC. This can be achieved by using an appropriate viscosity-enhancing agent (VEA).
Numerical Investigation of the Effect of Longitudinal Fiberglass Dowels on Tunnel Face Support in Layered Soils
Authors: Esmaeili Morteza , Hosseini Manoujan Jafar , Chalabii Jafar , Astaraki Farshad , Movahedi Rad Majid
Published: September 2023

Tunnel face extrusion rigidity is an important factor for solving stress–strain problems in loose ground conditions. In previous studies, the effect of horizontal and vertical soil layering on tunnel excavation face stability in the presence of longitudinal fiberglass dowels has not been studied. Therefore, in this study, the effect of fiberglass dowels on the stability of the tunnel face in layered soil has been investigated. In this matter, the best dowel arrangement for minimizing the excavation face extrusion in the case of two-layer soil (horizontal or vertical) has been focused on. For this purpose, firstly, a 3D numerical model was validated based on field data provided previously, and then a 3D numerical tunnel was developed in FLAC3D, adopting the Mohr–Coulomb failure criterion. In continuation, the effect of tunnel diameter, initial pressure ranging from 0.5 to 1.5 MPa, and different placement angles of fiberglass dowels ranging from 0 to 9 degrees, with respect to the tunnel longitudinal axes on the tunnel face extrusion, have been investigated. In the case of horizontal layering, the results showed that the maximum extrusion rate is significantly increased where the elasticity modulus of the soil is reduced. In addition, comparing the maximum extrusion in vertical and horizontal layering, it was found that its value in the horizontal mode is much higher than in the vertical. Additionally, the extrusion of the tunnel face has changed significantly due to an alteration in the initial stress. Finally, it was discovered that tunnel face extrusion is not significantly affected by altering the angle of the fiberglass dowels.
Recent Advances in Lanthanide Metal–Organic Framework Thin Films Based on Eu, Tb, Gd: Preparation and Application as Luminescent Sensors and Light-Emitting Devices
Authors: Brunckova Helena , Mudra Erika , Shepa Ivan
Published: September 2023

Lanthanide Metal–Organic Frameworks (LnMOFs), in recent years, have developed into an interesting subclass of MOFs. While the number of published papers, in particular, were dedicated to their synthesis and functional properties, along with the application mechanisms of MOFs, only a few of them have been focused on LnMOFs thin films independently. LnMOFs have become interesting thanks to their outstanding properties, for example, excellent structural flexibility, tunable pore size, surface area, functionality, and good chemical stability. Significant progress over the past two decades in the preparation of MOF films has been achieved, especially towards the development of green, or at least greener, synthesis approaches. We begin with insight into various types of MOFs and summarize recent achievements in the production of LnMOF films, along with various film preparation approaches. Afterward, we briefly discuss the applications of luminescence features of lanthanide ions in films and their potential as white-light source materials. We also covered films based on Eu, Tb, and Gd with particular accents on different design approaches. Moreover, specifically, luminescent features applied for sensing temperature, a variety of ions, gases, and biomolecules are highlighted. The review ends with a comprehensive conclusion about the state-of-art-potential of LnMOFs together with an outlook on the future of LnMOF films in future technologies.
Mono-Alkyl-Substituted Phosphinoboranes (HRP–BH2–NMe3) as Precursors for Poly(alkylphosphinoborane)s: Improved Synthesis and Comparative Study
Authors: Lehnfeld Felix , Oswald Tim , Beckhaus Rüdiger , Scheer Manfred
Published: September 2023

A new synthetic pathway to various mono-alkyl-substituted phosphinoboranes HRP–BH2–NMe3 has been developed. The new synthetic route starting from alkyl halides and NaPH2 followed by metalation and salt metathesis is performed in a one-pot procedure and leads to higher yields and purity of the resulting phosphinoboranes, as compared to previously reported routes. Additionally, the scope of accessible compounds could be expanded from short-chained linear alkyl substituents to longer-chained linear alkyl substituents as well as secondary or functionalized alkyl substituents. The reported examples include primary alkyl-substituted phosphinoboranes RHP-BH2-NMe3 (R = n-butyl, n-pentyl, n-hexyl; 1a–c), the secondary alkyl-substituted derivatives iPrPH-BH2-NMe3 (2), and the functionalized alkyl-substituted 4-bromo-butyl-phosphinoborane (BrC4H8)PH-BH2-NMe3 (3). Compounds 1a, 1c, and 2 were additionally used for preliminary polymerization reactions via a thermal and a transition metal-catalyzed pathway, revealing the formation of high-molecular-weight polymers under certain conditions. Detailed investigations on the influence of temperature, concentration, substituents and reaction time on the respective polymerization reactions were performed.
Diameter-Selective Host-Guest Interactions between Functionalized Fullerenes and Single-Walled Carbon Nanotubes
Authors: Zhang Rui , Gao Wanru , Sun Chang , Liu Yiwen , Lu Xiaojun , Lu Xing
Published: September 2023

Carbon nano peapods, with their electronic properties and spintronics, have attracted great attention regarding their potential applications when combined with fullerenes or their derivatives encapsulated inside. Herein, we have designed and synthesized a series of fullerene derivatives with different functional groups, which are then encapsulated into single-walled carbon nanotubes (SWCNTs). Accurate morphological characterization with high-resolution TEM reveals a clear correlation between the filling ratio of the peapods and the steric bulk of the functionalized groups. Further spectroscopic characterizations reveal diameter-selective interactions between the fullerene derivatives and SWCNTs, which, in turn, influence the electronic structures of the nanotubes. Our results have shed new light on the controlled synthesis and property-tuning of nano peapods.