bluuebunny/crossref_metadata_2025 huggingface dataset:
miRNA deregulation and relationship with metabolic parameters after Mediterranean dietary intervention in BRCA-mutated women
Authors: De Summa Simona , Traversa Debora , Daniele Antonella , Palumbo Orazio , Carella Massimo , Stallone Raffaella , Tufaro Antonio , Oliverio Andreina , Bruno Eleonora , Digennaro Maria , Danza Katia , Pasanisi Patrizia , Tommasi Stefania
Published: April 2023

Background

Breast cancer onset is determined by a genetics-environment interaction. BRCA1/2 gene alterations are often genetically shared in familial context, but also food intake and hormonal assessment seem to influence the lifetime risk of developing this neoplasia. We previously showed the relationship between a six-months Mediterranean dietary intervention and insulin, glucose and estradiol levels in BRCA1/2 carrier subjects. The aim of the present study was to evidence the eventual influence of this dietary intervention on the relationship between circulating miRNA expression and metabolic parameters in presence of BRCA1/2 loss of function variants.

Methods

Plasma samples of BRCA-women have been collected at the baseline and at the end of the dietary intervention. Moreover, subjects have been randomized in two groups: dietary intervention and placebo. miRNA profiling and subsequent ddPCR validation have been performed in all the subjects at both time points.

Results

ddPCR analysis confirmed that five (miR-185-5p, miR-498, miR-3910, miR-4423 and miR-4445) of seven miRNAs, deregulated in the training cohort, were significantly up-regulated in subjects after dietary intervention compared with the baseline measurement. Interestingly, when we focused on variation of miRNA levels in the two timepoints, it could be observed that miR-4423, miR-4445 and miR-3910 expressions are positively correlated with variation in vitaminD level; whilst miR-185-5p difference in expression is related to HDL cholesterol variation.

Conclusions

We highlighted the synergistic effect of a healthy lifestyle and epigenetic regulation in BC through the modulation of specific miRNAs. Different miRNAs have been reported involved in the tumor onset acting as tumor suppressors by targeting tumor-associated genes that are often downregulated.
Prognostic value and immune-infiltration pattern of FOXD3-AS1 in patients with glioma
Authors: Chen Zhenhua , Zhang Yi , Feng Sujuan , Yuan Jiaqi , Shi Dongliang , Wang Yong , Li Yongdong , Dong Jun
Published: April 2023

Gliomas are difficult-to-treat brain tumors due to their aggressive nature, rapid proliferation, and high invasiveness (Zhang et al., J Cell Biochem, 2019, 120 (9), 15106–15118; Ge et al., Int J Biochem Cell Biol, 2021, 139, 106054). FOXD3-AS1 has been identified as an emerging potential target for tumor prediction and treatment in many studies (Qin et al., Front Oncol, 2021, 11, 688027). However, the utility of FOXD3-AS1 has not been reported in glioma patients (Li et al., Cancer Manag Res, 2021, 13, 9037–9048). The differential profiles of FOXD3-AS1 in TCGA–GBMLGG database were analyzed across clinical subgroups. The analysis of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) revealed that a high level of FOXD3-AS1 was associated with a poor prognosis and survival outcome. Based on the Cox regression analysis, FOXD3-AS1 was found to be a high-risk factor for glioma that affects prognosis outcomes independently. More importantly, because oxidative stress is closely linked to glioma prognosis, we focused on the potential mechanisms of six oxidative stress co-expressed genes with FOXD3-AS1. In addition, the predictive value of FOXD3-AS1 was determined for each clinical subgroup status. The ROC curve results showed that FOXD3-AS1 had a good predictive performance. A stratified clinicopathological subgroup analysis revealed that high expression of FOXD3-AS1 is associated with a poor prognosis. This also indicates a link between FOXD3-AS1 and tumorigenesis and prognosis, which has potential application value. Furthermore, the immune cell infiltration of FOXD3-AS1 and the signal marker correlation suggested that immune cell infiltration differed significantly between immune cell subsets. To the best of our knowledge, this is the first report to investigate FOXD3-AS1 in glioma and how it may modulate GBM and LGG immune microenvironments. Furthermore, FOXD3-AS1 was detected in tumor and paraneoplastic tissues using RT–qPCR. Transwell analysis verified the migration and invasion of the FOXD3-AS1 knockout group in vitro to a certain extent. In conclusion, FOXD3-AS1 can be used as a prognostic indicator for GBM and LGG, and it is closely related to immune infiltration and response to oxidative stress, which may contribute to the advancement of glioma immunotherapy research.
Using the Social Skills Improvement System (SSiS) Rating Scales to assess social skills in youth with Down syndrome
Authors: Channell Marie Moore , Mattie Laura J. , Schworer Emily K. , Fidler Deborah J. , Esbensen Anna J.
Published: April 2023

Introduction and Methods

This study provides preliminary data on the Social Skills Improvement System (SSiS) Rating Scales Parent Form to measure social skills in a sample of 124 children and adolescents with Down syndrome (DS) ages 6–17 years.

Results

Overall, participants demonstrated relatively mild symptoms, with the sample’s average standard score falling within 1 standard deviation from the mean of the normative sample for the social skills (M = 92, SD = 15) and problem behaviors (M = 104, SD = 12) domains (normative sample M = 100, SD = 15 for both domains). However, a wide range of scores was observed across the sample for the composite and subscale scores. Differential patterns were also observed by subscale. For some subscales (i.e., Cooperation, Assertion, Responsibility, Engagement, Externalizing, Hyperactivity/Inattention, and Autism Spectrum), a disproportionate number of participants scored in the below average (i.e., lower levels of social skills) or above average (i.e., more symptomatic in problem behaviors or autism spectrum) range relative to the normative sample; for other subscales (i.e., Communication, Empathy, Self-Control, Bullying, and Internalizing), participants’ score distribution aligned more closely to that of the normative sample. SSiS composite scores correlated in the expected directions with standardized measures of autism characteristics, executive function, and expressive language.

Discussion

This study provides some of the first evidence validating the use of the SSiS in youth with DS, filling a gap in standardized measures of social functioning in this population.
Cluster analysis for the overall health status of elderly, multimorbid patients with diabetes
Authors: Bing Yan , Yuan Lei , Liu Ji , Wang Zezhong , Chen Lifu , Sun Jinhai , Liu Lijuan
Published: April 2023

Purpose

To evaluate the overall health status and health-related abilities and problems of elderly patients with diabetes and multimorbidity compared with those with diabetes only. Additionally, we aimed to identify different subgroups of elderly, multimorbid patients with diabetes.

Methods

This cross-sectional study included 538 elderly patients with diabetes. The participants completed a series of questionnaires on self-rated health (SRH), diabetes self-management, self-efficacy, health literacy, depression, and diabetes distress. Differences in health-related abilities and problems were compared between elderly patients with diabetes and multimorbidity and those with diabetes only, with adjustments for covariates using propensity score matching. A cluster analysis was also performed to identify the overall health status subgroups of elderly, multimorbid patients with diabetes. Additionally, we conducted a multinomial logistic regression analysis to examine the predictors of health-related abilities and problem-cluster group membership.

Results

Elderly patients with diabetes and multimorbidity experienced more health-related abilities and problems than those with diabetes only, particularly within the domains of depression (p < 0.001), and diabetes distress. The level of health literacy (p < 0.001) and self-management (p = 0.013) in elderly, multimorbid patients with diabetes was also significantly higher than that in elderly patients with diabetes only. Cluster analysis of elderly, multimorbid patients with diabetes revealed three distinct overall health status clusters. Multinomial logistic regression analysis indicated that age (OR = 1.090, p = 0.043), sex (OR = 0.503, p = 0.024), living situation (OR = 2.769, p = 0.011), BMI (OR = 0.838, p = 0.034), regular exercise (OR = 2.912, p = 0.041 in poor vs. good; OR = 3.510, p < 0.001 in intermediate vs. good), and cerebral infarction (OR = 26.280, p < 0.001) independently and significantly predicted cluster membership.

Conclusion

Compared with elderly patients with diabetes only, those with diabetes and multimorbidity experienced more health-related abilities and problems within the domains of depression, and diabetes distress. Additionally, the level of health literacy and self-management in elderly, multimorbid patients with diabetes was significantly higher than that in those with diabetes only. Among the multimorbid diabetes group, old age, male sex, living without a partner, slightly lower BMIs, not exercising regularly, and experiencing cerebral infarctions were all positively correlated with worse overall health status.
Spinal dural and epidural arteriovenous fistula: Recurrence rate after surgical and endovascular treatment
Authors: Vercelli Giovanni Giulio , Minardi Massimiliano , Bergui Mauro , Zenga Francesco , Garbossa Diego , Cofano Fabio
Published: April 2023

Introduction

Spinal dural arteriovenous fistula consist of an heterogenous group of vascular malformation often causing severe neurological deficit due to progressive myelopathy. This type of malformation could be associated with subarachnoid or subdural hemorrhage inside the spinal canal. In the English literature surgical treatment is regarded as the best option if compared to endovascular procedure, being the latter associated with an increased risk of relapse despite its less invasiveness.

Methods

In this study a retrospective analysis of 30 patients with spinal dural and epidural fistula associated with perimedullary venous congestion was undertaken. The radiological and clinical presentation of each patient is analyzed, and the grade of myelopathy is classified through the mJOA score.

Results

A total number of 31 out of 41 collected procedures (22 surgery vs. 19 endovascular) were dural fistulas while the remaining 10 were classified as epidural. A 46% recurrence rate for endovascular treatment against 0% for surgical (p-value 0.004) was described for dural fistulas, while in the epidural fistula group the rate of recurrence was 80% and 20% respectively for endovascular and surgery treatment (p-value 0.6).

Discussion

According to the results, surgical treatment could be considered as first-line treatment for spinal dural arteriovenous fistulas. Endovascular embolization can be proposed in selected cases, as a less invasive technique, for elderly patients or with important comorbidities. In spinal epidural arteriovenous fistulas, in view of the greater invasiveness of the surgical treatment and the non-significant difference in terms of recurrence risk between the two techniques, endovascular treatment could be proposed as a first choice treatment; in the event of a recurrence, a surgical intervention will instead be proposed in a short time.
The Mediating Role of Depression in Association Between Total Sleep Time and Instrumental Activities of Daily Living in China
Authors: Wu Yunyi , Li Sangsang , Han Dan , Zhang Mei , Zhao Jie , Liao Hui , Ma Ying , Yan Chaoyang , Wang Jing
Published: April 2023

Objectives: This study aims to investigate the mediating role of depression and the moderating effect of gender in the relationship between total sleep time (TST) and instrumental activities of daily living (IADL) in middle-aged and elderly people (aged 45 or above).

Methods: The data used in this study is from the China Health and Retirement Longitudinal Study (CHARLS), including a total of 10,460 respondents. Associations between TST, IADL, depression, and gender were analyzed using logistic regression and Karlson, Holm, and Breen (KHB) methods.

Results: Short (OR = 1.42, 95% CI = 1.28–1.58 of ≤6 h) and long TST (OR = 1.16, 95% CI = 1.02–1.32 of 8–9 h; OR = 1.35, 95% CI = 1.19–1.54 of >9 h) were both associated with IADL. The mediation effect analyses observed that depression explained 64.80% of the total effect of short TST (≤6 h) and IADL, but was insignificant in long TST (8–9 h and >9 h). Meanwhile, gender has moderating effects on the mediation effect model.

Conclusion: The study suggests that health interventions that focused on the dimensions of TST and depression are crucial for preventing functional disability while accounting for gender differences.
Aircraft Engine Bleed Valve Prognostics Using Multiclass Gated Recurrent Unit
Authors: Baptista Marcia L. , Prendinger Helmut
Published: April 2023

Prognostics and health management is an engineering discipline that aims to support system operation while ensuring maximum safety and performance. Prognostics is a key step of this framework, focusing on developing effective maintenance policies based on predictive methods. Traditionally, prognostics models forecast the degradation process using regression techniques that approximate a mapping function from input to continuous remaining useful life estimates. These models are typically of high complexity and low interpretability. Classification approaches are an alternative solution to these types of models. We propose a predictive classification model that translates the input into discrete output variables instead of mapping the input to a single remaining useful life estimate. Each discrete output variable corresponds to a range of remaining useful life values. In other words, each output class variable represents the likelihood or risk of failure within a specific time range. We apply this model to a real-world case study involving the unscheduled and scheduled removals of a set of engine bleed valves from a fleet of Boeing 737 aircraft. The model can reach an area under the (micro-average) receiver operating characteristic curve of 72%. Our results suggest that the proposed multiclass gated recurrent unit network can provide valuable information about the different fault stages (corresponding to intervals of residual lives) of the studied valves.
External Validation of the ImAgeS Risk Score for Mortality in Hospitalized Kidney Transplant Recipients with COVID-19: A Retrospective Observational Study
Authors: Domjanović Josipa , Domjanović Škopinić Tea , Gamberažić Kirevski Tea , Matetic Andrija
Published: April 2023

Background: Timely recognition of high-risk individuals with novel Coronavirus disease (COVID-19) is important. Yet, validated risk scores for kidney transplant recipients with COVID-19 are lacking. The present study aimed to externally validate the novel ImAgeS risk score in this population. Methods: A retrospective analysis of 65 kidney transplant recipients with COVID-19 was conducted. A robust external validation of the novel ImAgeS risk score with respect to 30-day all-cause mortality was performed using regression analysis, discrimination and calibration methods. Results: An overall mortality rate during the study follow-up was 18.5% (N = 12). The ImAgeS risk score showed a statistically significant association with 30-day all-cause mortality (HR 1.04 95% CI 1.00–1.08, p =  0.040). This risk score demonstrated a modest, statistically significant discrimination of all-cause mortality (AUC of 0.679 (95% CI 0.519–0.840, p = 0.027). The calibration of the model was acceptable with a Hosmer-Lemeshow value of 3.74, Harrell’s C concordance index of 0.699 and Somers’ D of 0.397. Conclusions: The ImAgeS risk score demonstrated a significant association with 30-day all-cause mortality in kidney transplant recipients with COVID-19. The model showed modest discrimination and satisfactory calibration, confirming the findings from the computational study. Further studies are needed to determine the utility of the ImAgeS score in this high-risk population.
Feasibility of an Intelligent Algorithm Based on an Assist-as-Needed Controller for a Robot-Aided Gait Trainer (Lokomat) in Neurological Disorders: A Longitudinal Pilot Study
Authors: Laszlo Caroline , Munari Daniele , Maggioni Serena , Knechtle Deborah , Wolf Peter , De Bon Dino
Published: April 2023

Most robotic gait assisted devices are designed to provide constant assistance during the training without taking into account each patient’s functional ability. The Lokomat offers an assist-as-needed control via the integrated exercise “Adaptive Gait Support” (AGS), which adapts the robotic support based on the patient’s abilities. The aims of this study were to examine the feasibility and characteristics of the AGS during long-term application. Ten patients suffering from neurological diseases underwent an 8-week Lokomat training with the AGS. They additionally performed conventional walking tests and a robotic force measurement. The difference between robotic support during adaptive and conventional training and the relationship between the robotic assessment and the conventional walking and force tests were examined. The results show that AGS is feasible during long-term application in a heterogeneous population. The support during AGS training in most of the gait phases was significantly lower than during conventional Lokomat training. A relationship between the robotic support level determined by the AGS and conventional walking tests was revealed. Moreover, combining the isometric force data and AGS data could divide patients into clusters, based on their ability to generate high forces and their level of motor control. AGS shows a high potential in assessing patients’ walking ability, as well as in providing challenging training, e.g., by automatically adjusting the robotic support throughout the whole gait cycle and enabling training at lower robotic support.
Endogenous piRNAs Can Interact with the Omicron Variant of the SARS-CoV-2 Genome
Authors: Rakhmetullina Aizhan , Akimniyazova Aigul , Niyazova Togzhan , Pyrkova Anna , Kamenova Saltanat , Kondybayeva Aida , Ryskulova Alma-Gul , Ivashchenko Anatoliy , Zielenkiewicz Piotr
Published: April 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the COVID-19 pandemic, can still infect populations in many countries around the globe. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and its ability to evade immunity necessitate a priority study of its properties in order to quickly create effective means of preventing its spread. The current research aimed to examine the in silico interaction between PIWI-interacting RNAs (piRNAs) and the SARS-CoV-2 genome (gRNA) to identify endogenous piRNAs and propose synthetic piRNAs with strong antiviral activity for drug development. This study used validated bioinformatic approaches regarding the interaction of more than eight million piRNAs with the SARS-CoV-2 genome. The piRNAs’ binding sites (BSs) in the 5′UTR were located with overlapping nucleotide sequences termed clusters of BSs. Several BSs clusters have been found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a, and nucleocapsid. Sixteen synthetic piRNAs that interact with gRNA have been proposed with free binding energy ranging from −170 kJ/mol to −175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2.
Characterization of Micelle Formation by the Single Amino Acid-Based Surfactants Undecanoic L-Isoleucine and Undecanoic L-Norleucine in the Presence of Diamine Counterions with Varying Chain Lengths
Authors: Maynard-Benson Amber , Alekisch Mariya , Wall Alyssa , Billiot Eugene J. , Billiot Fereshteh H. , Morris Kevin F.
Published: April 2023

The binding of linear diamine counterions with different methylene chain lengths to the amino-acid-based surfactants undecanoic L-isoleucine (und-IL) and undecanoic L-norleucine (und-NL) was investigated with NMR spectroscopy. The counterions studied were 1,2-ethylenediamine, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, and 1,6-diaminohexane. These counterions were all linear diamines with varying spacer chain lengths between the two amine functional groups. The sodium counterion was studied as well. Results showed that when the length of the counterion methylene chain was increased, the surfactants’ critical micelle concentrations (CMC) decreased. This decrease was attributed to diamines with longer methylene chains binding to multiple surfactant monomers below the CMC and thus acting as templating agents for the formation of micelles. The entropic hydrophobic effect and differences in diamine counterion charge also contributed to the size of the micelles and the surfactants’ CMCs in the solution. NMR diffusion measurements showed that the micelles formed by both surfactants were largest when 1,4-diaminobutane counterions were present in the solution. This amine also had the largest mole fraction of micelle-bound counterions. Finally, the und-NL micelles were larger than the und-IL micelles when 1,4-diaminobutane counterions were bound to the micelle surface. A model was proposed in which this surfactant formed non-spherical aggregates with both the surfactant molecules’ hydrocarbon chains and n-butyl amino acid side chains pointing toward the micelle core. The und-IL micelles, in contrast, were smaller and likely spherically shaped.
Elucidation of Spin-Correlations, Fermi Surface and Pseudogap in a Copper Oxide Superconductor
Authors: Kamimura Hiroshi , Araidai Masaaki , Ishida Kunio , Matsuno Shunichi , Sakata Hideaki , Sasaoka Kenji , Shiraishi Kenji , Sugino Osamu , Tsai Jaw-Shen , Yamada Kazuyoshi
Published: April 2023

First-principles calculations for underdoped La2−xSrxCuO4 (LSCO) have revealed a Fermi surface consisting of spin-triplet (KS) particles at the antinodal Fermi-pockets and spin-singlet (SS) particles at the nodal Fermi-arcs in the presence of AF local order. By performing a unique method of calculating the electronic-spin state of overdoped LSCO and by measurement of the spin-correlation length by neutron inelastic scattering, the origin of the phase-diagram, including the pseudogap phase in the high temperature superconductor, Sr-doped copper-oxide LSCO, has been elucidated. We have theoretically solved the long-term problem as to why the angle-resolved photoemission spectroscopy (ARPES) has not been able to observe Fermi pockets in the Fermi surface of LSCO. As a result, we show that the pseudogap region is bounded below the characteristic temperature T*(x) and above the superconducting transition temperature Tc(x) in the T vs. x phase diagram, where both the AF order and the KS particles in the Fermi pockets vanish at T*(x), whilst KS particles contribute to d-wave superconductivity below Tc. We also show that the relationship T*(xc) = Tc(xc) holds at xc = 0.30, which is consistent with ARPES experiments. At T*(x), a phase transition occurs from the pseudogap phase to an unusual metallic phase in which only the SS particles exist.
An Intrusion Detection System for Drone Swarming Utilizing Timed Probabilistic Automata
Authors: Subbarayalu Venkatraman , Vensuslaus Maria Anu
Published: April 2023

Unmanned aerial vehicles (UAVs), commonly known as drones, have found extensive applications across diverse sectors, such as agriculture, delivery, surveillance, and military. In recent times, drone swarming has emerged as a novel field of research, which involves multiple drones working in collaboration towards a shared objective. This innovation holds immense potential in transforming the way we undertake tasks, including military operations, environmental monitoring, and search and rescue missions. However, the emergence of drone swarms also brings new security challenges, as they can be susceptible to hacking and intrusion. To address these concerns, we propose utilizing a timed probabilistic automata (TPA)-based intrusion detection system (IDS) to model the normal behavior of drone swarms and identify any deviations that may indicate an intrusion. This IDS system is particularly efficient and adaptable in detecting different types of attacks in drone swarming. Its ability to adapt to evolving attack patterns and identify zero-day attacks makes it an invaluable tool in protecting drone swarms from malicious attacks.
Dynamical Quantum Phase Transitions of the Schwinger Model: Real-Time Dynamics on IBM Quantum
Authors: Pomarico Domenico , Cosmai Leonardo , Facchi Paolo , Lupo Cosmo , Pascazio Saverio , Pepe Francesco V.
Published: April 2023

Simulating the real-time dynamics of gauge theories represents a paradigmatic use case to test the hardware capabilities of a quantum computer, since it can involve non-trivial input states’ preparation, discretized time evolution, long-distance entanglement, and measurement in a noisy environment. We implemented an algorithm to simulate the real-time dynamics of a few-qubit system that approximates the Schwinger model in the framework of lattice gauge theories, with specific attention to the occurrence of a dynamical quantum phase transition. Limitations in the simulation capabilities on IBM Quantum were imposed by noise affecting the application of single-qubit and two-qubit gates, which combine in the decomposition of Trotter evolution. The experimental results collected in quantum algorithm runs on IBM Quantum were compared with noise models to characterize the performance in the absence of error mitigation.
Effect of Chair Yoga Therapy on Functional Fitness and Daily Life Activities among Older Female Adults with Knee Osteoarthritis in Taiwan: A Quasi-Experimental Study
Authors: Yao Ching-Teng , Lee Bih-O , Hong Hong , Su Yi-Ching
Published: April 2023

This study aims to examine the effectiveness of chair yoga therapy on improving functional status and daily life activity scores in older female adults with knee osteoarthritis living in the community. A quasi-experimental design was adopted. In total, 85 female participants with knee osteoarthritis were assigned to the chair yoga therapy intervention group (n = 43) or the comparison (n = 42) group. A 12-week chair yoga exercise program was provided to the intervention group two times per week from January to April 2020. The primary outcomes, which include changes in physical functional ability, body mass index, and biophysiological indicators, were evaluated for all participants in the pre- and post-measures time periods. The analysis shows that the participants had a significantly higher level of functional fitness and daily life activity scores after the chair yoga intervention. This finding indicates that the chair yoga program was effective in improving the functional fitness and daily life activity scores of community-dwelling elderly females with knee osteoarthritis.
Case Report: A Novel Homozygous Variant of the SERPINF1 Gene in Rare Osteogenesis Imperfecta Type VI
Authors: Zhalsanova Irina Zh. , Postrigan Anna Evgenievna , Valiakhmetov Nail Raushanovich , Kolesnikov Nikita Aleksandrovich , Zhigalina Daria Ivanovna , Zarubin Aleksei Andreevich , Petrova Valeria Viktorovna , Minaycheva Larisa Ivanovna , Seitova Gulnara Narimanovna , Skryabin Nikolay Alekseevich , Stepanov Vadim Anatolevich
Published: April 2023

Osteogenesis imperfecta (OI) is a group of connective tissue disorders with different types of inheritance. OI is characterized by bone fragility and deformities, frequent fractures, low bone-mineral density, and impaired bone micro-architectonics. We described here a case of a one-year-old Tuvan patient with multiple fractures. The disease manifestation occurred first at 12 weeks of age as a shoulder joint bruise, and during the year, the patient sustained 27 fractures. Genetic testing revealed a novel homozygous mutation, c.259_260insCGGCC (p.T87fs), in the SERPINF1 gene. This insertion leads to an open-reading frameshift, and the mutation is not represented in the databases. Mutations in SERPINF1 lead to type VI OI, the clinical picture of which is similar to the disease phenotype manifestation of the patient. Thus, the patient’s diagnosis was established by finding a novel pathogenic variant in the SERPINF1 gene.
Aβ Chronic Exposure Promotes an Activation State of Microglia through Endocannabinoid Signalling Imbalance
Authors: Scipioni Lucia , Tortolani Daniel , Ciaramellano Francesca , Fanti Federico , Gazzi Thais , Sergi Manuel , Nazaré Marc , Oddi Sergio , Maccarrone Mauro
Published: April 2023

Dysfunctional phenotype of microglia, the primary brain immune cells, may aggravate Alzheimer’s disease (AD) pathogenesis by releasing proinflammatory factors, such as nitric oxide (NO). The endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are bioactive lipids increasingly recognised for their essential roles in regulating microglial activity both under normal and AD-driven pathological conditions. To investigate the possible impact of chronic exposure to β-amyloid peptides (Aβ) on the microglial endocannabinoid signalling, we characterised the functional expression of the endocannabinoid system on neonatal microglia isolated from wild-type and Tg2576 mice, an AD-like model, which overexpresses Aβ peptides in the developing brain. We found that Aβ-exposed microglia produced 2-fold more 2-AG than normal microglia. Accordingly, the expression levels of diacylglycerol lipase-α (DAGLα) and monoacylglycerol lipase (MAGL), the main enzymes responsible for synthesising and hydrolysing 2-AG, respectively, were consistently modified in Tg2576 microglia. Furthermore, compared to wild-type cells, transgenic microglia basally showed increased expression of the cannabinoid 2 receptor, typically upregulated in an activated proinflammatory phenotype. Indeed, following inflammatory stimulus, Aβ-exposed microglia displayed an enhanced production of NO, which was abolished by pharmacological inhibition of DAGLα. These findings suggested that exposure to Aβ polarises microglial cells towards a pro-AD phenotype, possibly by enhancing 2-AG signalling.
Identification and Characterization of Development-Related microRNAs in the Red Flour Beetle, Tribolium castaneum
Authors: Li Chengjun , Wu Wei , Tang Jing , Feng Fan , Chen Peng , Li Bin
Published: April 2023

MicroRNAs (miRNAs) play important roles in insect growth and development, but they were poorly studied in insects. In this study, a total of 883 miRNAs were detected from the early embryo (EE), late larva (LL), early pupa (EP), late pupa (LP), and early adult (EA) of Tribolium castaneum by microarray assay. Further analysis identified 179 differentially expressed unique miRNAs (DEmiRNAs) during these developmental stages. Of the DEmiRNAs, 102 DEmiRNAs exhibited stage-specific expression patterns during development, including 53 specifically highly expressed miRNAs and 20 lowly expressed miRNAs in EE, 19 highly expressed miRNAs in LL, 5 weakly expressed miRNAs in EP, and 5 abundantly expressed miRNAs in EA. These miRNAs were predicted to target 747, 265, 472, 234, and 121 genes, respectively. GO enrichment analysis indicates that the targets were enriched by protein phosphorylation, calcium ion binding, sequence-specific DNA binding transcription factor activity, and cytoplasm. An RNA interference-mediated knockdown of the DEmiRNAs tca-miR-6-3p, tca-miR-9a-3p, tca-miR-9d-3p, tca-miR-11-3p, and tca-miR-13a-3p led to defects in metamorphosis and wing development of T. castaneum. This study has completed the identification and characterization of development-related miRNAs in T. castaneum, and will enable us to investigate their roles in the growth and development of insect.
A2AR as a Prognostic Marker and a Potential Immunotherapy Target in Human Glioma
Authors: Rafii Soumaya , Ghouzlani Amina , Naji Oumayma , Ait Ssi Saadia , Kandoussi Sarah , Lakhdar Abdelhakim , Badou Abdallah
Published: April 2023

Gliomas are considered one of the most malignant tumors in the body. The immune system has the ability to control the initiation and development of tumors, including gliomas. Thus, immune cells find themselves controlled by various molecular pathways, inhibiting their activation, such as the immunosuppressive adenosine 2A receptor (A2AR). Our objective was to establish the expression profile and role of A2AR at the transcriptomic level, using real-time RT-PCR in Moroccan glioma patients, in addition to TCGA and CGGA cohorts. The real-time RT-PCR results in Moroccan patients showed that high expression of this gene was associated with poor survival in males. Our study on the CGGA cohort corroborated these results. In addition, there was a positive association of A2AR with T-cell exhaustion genes. A2AR also correlated strongly with genes that are primarily enriched in focal adhesion and extracellular matrix interactions, inducing epithelial mesenchymal transition, angiogenesis, and glioma growth. However, in the TCGA cohort, the A2AR showed results that were different from the two previously examined cohorts. In fact, this gene was instead linked to a good prognosis in patients with the astrocytoma histological type. The correlation and enrichment results reinforced the prognostic role of A2AR in this TCGA cohort, in which its high expression was shown to be related to lymphocyte differentiation and a successful cytolytic response, suggesting a more efficient anti-tumor immune response. Correlations and differential analyses based on A2AR gene expression, to understand the cause of the association of this gene with two different prognoses (CGGA males and TCGA Astrocytoma), showed that the overexpression of A2AR in Chinese male patients could be associated with the overexpression of extracellular adenosine, which binds to A2AR to induce immunosuppression and consequently a poor prognosis. However, in the second group (TCGA astrocytomas), the overexpression of the gene could be associated with an adenosine deficiency, and therefore this receptor does not undergo activation. The absence of A2AR activation in these patients may have protected them from immunosuppression, which could reflect the good prognosis. A2AR can be considered a promising therapeutic target in male CGGA and Moroccan patients with gliomas.
Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review
Authors: Noor Rida , Zahoor Ameer Fawad , Mansha Asim , Khan Samreen Gul , Haq Atta Ul , Ahmad Sajjad , Al-Hussain Sami A. , Irfan Ali , Zaki Magdi E. A.
Published: April 2023

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007–2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau–Demjanov rearrangement, Aza–Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard.
Genetic Analysis of Multiple Primary Malignant Tumors in Women with Breast and Ovarian Cancer
Authors: Savkova Alina , Gulyaeva Lyudmila , Gerasimov Aleksey , Krasil’nikov Sergey
Published: April 2023

Familial cancer syndromes, which are commonly caused by germline mutations in oncogenes and tumor suppressor genes, are generally considered to be the cause of primary multiple malignant neoplasias (PMMNs). Using targeted genomic sequencing, we screened for eight germline mutations: BRCA1 185delAG, BRCA1 T300G, BRCA1 2080delA, BRCA1 4153delA, BRCA1 5382insC, BRCA2 6174delT, CHEK2 1100delC, and BLM C1642T, which provoke the majority of cases of hereditary breast and ovary cancer syndrome (HBOC), in genomic (blood) DNA from 60 women with PMMNs, including breast (BC) and/or ovarian cancer(s) (OC). Pathogenic allelic forms were discovered in nine samples: in seven instances, it was BRCA1 5382insC, and in the following two, BRCA1 4153delA and BRCA1 T300G. The age of onset in these patients (46.8 years) was younger than in the general Russian population (61.0) for BC but was not for OC: 58.3 and 59.4, correspondingly. There were invasive breast carcinomas of no special type and invasive serous ovarian carcinomas in all cases. Two or more tumors of HBOC-spectrum were only in five out of nine families of mutation carriers. Nevertheless, every mutation carrier has relatives who have developed malignant tumors.
Alternative Splicing: From Abiotic Stress Tolerance to Evolutionary Genomics
Authors: Gao Bei , Chen Moxian , Oliver Melvin J.
Published: April 2023

The post-transcriptional regulation of gene expression, in particular alternative splicing (AS) events, substantially contributes to the complexity of eukaryotic transcriptomes and proteomes [...]
The Signaling Pathway of the ADP Receptor P2Y12 in the Immune System: Recent Discoveries and New Challenges
Authors: Entsie Philomena , Kang Ying , Amoafo Emmanuel Boadi , Schöneberg Torsten , Liverani Elisabetta
Published: April 2023

P2Y12 is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y12 has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y12 is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y12 could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y12 in the cells of the immune system and the effect of P2Y12 activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.
Once-Daily Subcutaneous Irisin Administration Mitigates Depression- and Anxiety-like Behavior in Young Mice
Authors: Pignataro Patrizia , Dicarlo Manuela , Suriano Clelia , Sanesi Lorenzo , Zerlotin Roberta , Storlino Giuseppina , Oranger Angela , Zecca Chiara , Dell’Abate Maria Teresa , Mori Giorgio , Grano Maria , Colucci Silvia , Colaianni Graziana
Published: April 2023

Major depression is one of the most common psychiatric disorders worldwide, usually associated with anxiety. The multi-etiological nature of depression has increased the search for new antidepressant molecules, including irisin, for which, in a previous study, we tested its effect in young mice when administered intraperitoneally in a long-term intermittent manner. Here, we evaluated the effect of subcutaneous short-term irisin administration (100 µg/Kg/day/5 days) in male and female mice subjected to behavioral paradigms: Tail Suspension Test (TST), Forced Swim Test (FST), Elevated Plus Maze (EPM), and Y Maze (YM). Moreover, a qRT-PCR assay was performed to analyze the impact of irisin treatment on Pgc-1α/FNDC5 expression in the brain. A significant reduction in immobility time in TST and FST was observed in irisin-treated mice. Furthermore, irisin treatment significantly increased the number of entries and time spent in open arms, demonstrating its anxiolytic effect. Memory-enhancing effects were not reported in YM. Interestingly, no gender differences were observed in all behavioral tests. Overall, these results suggest that short-term subcutaneous irisin administration can exert an antidepressant and anxiolytic role, probably due to the activation of the Pgc-1α/FNDC5 system in the brain. Further investigation could lead to the identification of irisin as a new agent for the treatment of psychiatric disorders.
OsLUX Confers Rice Cold Tolerance as a Positive Regulatory Factor
Authors: Huang Peng , Ding Zhengquan , Duan Min , Xiong Yi , Li Xinxin , Yuan Xi , Huang Ji
Published: April 2023

During the early seedling stage, rice (Oryza sativa L.) must overcome low-temperature stress. While a few cold-tolerance genes have been characterized, further excavation of cold-resistance genes is still needed. In this study, we identified a cold-induced transcription factor—LUX ARRHYTHMO (LUX)—in rice. OsLUX was found to be specifically expressed in leaf blades and upregulated by both cold stress and circadian rhythm. The full-length OsLUX showed autoactivation activity, and the OsLUX protein localized throughout the entire onion cell. Overexpressing OsLUX resulted in increased cold tolerance and reduced ion leakage under cold-stress conditions during the seedling stage. In contrast, the knockout of OsLUX decreased seedling cold tolerance and showed higher ion leakage compared to the wild type. Furthermore, overexpressing OsLUX upregulated the expression levels of oxidative stress-responsive genes, which improved reactive oxygen species (ROS) scavenging ability and enhanced tolerance to chilling stress. Promoter analysis showed that the OsLUX promoter contains two dehydration-responsive element binding (DREB) motifs at positions −510/−505 (GTCGGa) and −162/−170 (cCACCGccc), which indicated that OsDREB1s and OsDREB2s probably regulate OsLUX expression by binding to the motif to respond to cold stress. Thus, OsLUX may act as a downstream gene of the DREB pathway. These results demonstrate that OsLUX serves as a positive regulatory factor of cold stress and that overexpressing OsLUX could be used in rice breeding programs to enhance abiotic stress tolerance.
Superalloy—Steel Joint in Microstructural and Mechanical Characterisation for Manufacturing Rotor Components
Authors: Szczucka-Lasota Bożena , Szymczak Tadeusz , Węgrzyn Tomasz , Tarasiuk Wojciech
Published: April 2023

The structure of energy rotor components includes different structural materials in the sections, which are subjected to varying levels of thermal loading. The first component section has to include a precipitation-hardened nickel-based alloy, while the second one may be manufactured from other materials. Due to the installation cost, the use of expensive nickel-based materials is not recommended for applications in sections with a lower degree of thermal loading. Therefore, this aspect is still actually from an engineering point of view and is discussed in the paper by means of manufacturing and experimental approaches. The paper follows the welding problems related to a hybrid joint made of superalloy (Alloy 59) and hard rusting steel (S355J2W+N steel). The problem is solved using the MIG process at various parameters. With respect to the joint quality, microstructural features and mechanical parameters of the examined zone are presented. In the case of microstructure analysis, the dendritic and cellular natures of austenite were dominant elements of the joint. Mechanical tests have expressed a 50% reduction in elongation of the steel and alloy steel weld and lowering mechanical parameters. Mechanical parameters of the joint were on the level of their values observed for the steel, while the hardening coefficient followed the hardening curve of the alloy. Decohesion of the steel and mixed weld has reflected the constant proportion of values of axial and shear stress components up to the total separation. It is noted the tensile curves of the alloy and alloy steel joint follow a very similar shape, reporting the same response on the monotonic tension. The materials can be analysed by applying constitutive equations at very similar values of their coefficients. The obtained results enabled elaborating and examining the MIG welding process for thick-walled structures (not smaller than 8 mm) in detail giving all parameters required for technology. Finally, the technology for producing a hybrid joint using difficult-to-weld materials with different physical and mechanical properties, such as nickel alloys and low-alloy steels, is proposed. Results have shown it possible to develop a technology for producing of hybrid joints (supper alloy + hard rusting steel) with assumed physical and mechanical properties for rotors applied in the power boiler. This solution was proposed instead of previously used elements of rotors from expensive materials. It was assumed that the newly proposed and utilised method of welding will allow for obtaining good properties in terms of energy devices.
The Role of Gene Expression in Stress Urinary Incontinence: An Integrative Review of Evidence
Authors: Miličić Iva , Mikuš Mislav , Vrbanić Adam , Kalafatić Držislav
Published: April 2023

Stress urinary incontinence (SUI) is defined as unintentional urine leakage occurring as a consequence of increased intraabdominal pressure due to absent or weak musculus detrusor contractility. It affects postmenopausal women more often than premenopausal and is associated with quality of life (QoL) deterioration. The complex SUI etiology is generally perceived as multifactorial; however, the overall impact of environmental and genetic influences is deficiently understood. In this research report, we have disclosed the upregulation of 15 genes and the downregulation of 2 genes in the genetic etiology of SUI according to the accessible scientific literature. The analytical methods used for the analysis of gene expression in the studies investigated were immunohistochemistry, immunofluorescence staining, PCR, and Western blot. In order to facilitate the interpretation of the results, we have used GeneMania, a potent software which describes genetic expression, co-expression, co-localization, and protein domain similarity. The importance of this review on the genetic pathophysiology of SUI lies in determining susceptibility for targeted genetic therapy, detecting clinical biomarkers, and other possible therapeutic advances. The prevention of SUI with the timely recognition of genetic factors may be important for avoiding invasive operative urogynecological methods.
Prenatal Diagnosis of Fetal Obstructed Hemivagina and Ipsilateral Renal Agenesis (OHVIRA) Syndrome
Authors: Kim Soo Jung , Shim So-Yeon , Cho Hyun-Hae , Park Mi-Hye , Lee Kyung A.
Published: April 2023

Background: Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome, also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome characterized by the triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Most cases of OHVIRA have been reported in adolescents or adults. Gartner duct cysts, including those manifesting as vaginal wall cysts, are also rare. Fetal OHVIRA syndrome and Gartner duct cysts are difficult to diagnose. Case Presentation: Here, the authors report a case of combined OHVIRA and Gartner duct cyst diagnosed prenatally by ultrasonography, along with a brief review of the relevant published reports. A 30-year-old nulliparous female was referred to our institution at 32 weeks’ gestation for fetal right kidney agenesis. Detailed ultrasonographic examinations using 2D, 3D, and Doppler ultrasounds revealed hydrocolpometra, and uterus didelphys, with a normal anus and right kidney agenesis. Conclusions: When encountering female fetuses with ipsilateral renal agenesis or vaginal cysts, clinicians should be aware of OHVIRA syndrome and Gartner duct cysts and perform systematic ultrasonographic examinations for other genitourinary anomalies.