Independent Groups Research Articles

Proteome analysis develops novel plasma proteins classifier in predicting the mortality of COVID-19.

COVID-19 has been a global concern for 3 years, however, consecutive plasma protein changes in the disease course are currently unclear. Setting the mortality within 28 days of admission as the main clinical outcome, plasma samples were collected from patients in discovery and independent validation groups at different time points during the disease course. The whole patients were divided into death and survival groups according to their clinical outcomes. Proteomics and pathway/network analyses were used to find the differentially expressed proteins and pathways. Then, we used machine learning to develop a protein classifier which can predict the clinical outcomes of the patients with COVID-19 and help identify the high-risk patients. Finally, a classifier including C-reactive protein, extracellular matrix protein 1, insulin-like growth factor-binding protein complex acid labile subunit, E3 ubiquitin-protein ligase HECW1 and phosphatidylcholine-sterol acyltransferase was determined. The prediction value of the model was verified with an independent patient cohort. This novel model can realize early prediction of 28-day mortality of patients with COVID-19, with the area under curve 0.88 in discovery group and 0.80 in validation group, superior to 4C mortality and E-CURB65 scores. In total, this work revealed a potential protein classifier which can assist in predicting the outcomes of COVID-19 patients and providing new diagnostic directions.

Predicting perimetric defects from en face maps of retinal nerve fibre layer reflectance.

To develop criteria to predict visual hemifields with deep perimetric defects based on retinal nerve fibre layer (RNFL) reflectance, in a transparent process whose components can be assessed by independent laboratories analysing data from their own small groups. The analysis was carried out in four stages, using three independent groups of patients-30, 33 and 62 participants-with glaucoma and age-similar controls. The first stage used Group 1 to develop a criterion for RNFL reflectance images at 24, 36 or 48 μm below the inner limiting membrane (ILM). The second stage evaluated the criterion using Group 2. The third stage developed a second criterion to improve performance for Groups 1 and 2 combined. The fourth stage evaluated the second criterion with Group 3. Confidence intervals for sensitivity and specificity were then computed by combining results from all three groups. The first criterion identified all hemifields with deep defects and no hemifields from controls, using a within-eye reference for healthy RNFL. For Group 2, specificity remained high but sensitivity was reduced. The second criterion improved sensitivity by using location-specific reference values. For Group 3, sensitivity remained high but reduced specificity was found. Confidence intervals showed substantial overlap for the two criteria. We developed two criteria to identify patients with deep perimetric defects with high specificity and sensitivity. Several improvements are warranted: automated identification of the fovea-disc angle and optic disc locations, evaluation of normal variation in patterns of RNFL thickness, improved segmentation of ILM and major vasculature, reduction of within-eye variability in RNFL reflectance of healthy eyes, assessment of effects of image quality, assessment of effects of comorbidity and effectiveness of other devices.

Effects of the walking independence on lower extremity and trunk muscle activity during straight-leg raising following incomplete cervical cord injury

The purpose of this study was to compare the acceleration and surface electromyography (EMG) of the lower extremity and trunk muscles during straight-leg raising (SLR) in patients with incomplete cervical cord injury according to their levels of walking independence. Twenty-four patients were measured acceleration and EMG during SLR held for 10 s. Data were analyzed separately for the dominant and nondominant sides and compared between the nonindependent (NI) and independent (ID) groups based on their levels of walking independence. Frequency analysis of the EMG showed that the high-frequency (HF) band of the contralateral biceps femoris (BF) in the ID group and bands below the medium-frequency (MF) of the BF and the HF and MF bands of the rectus abdominis in the NI group were significantly higher during dominant and nondominant SLR. During the nondominant SLR, the low-frequency band of the internal oblique and the MF band of the external oblique were significantly higher in the NI group. The ID group mobilized muscle fiber type 2 of the BF, whereas the NI group mobilized type 1 of the BF and types 2 and 1 of the trunk muscles to stabilize the pelvis. This result was more pronounced during the nondominant SLR.

Do Underlying Assets, Duration, Default Risk Level, Sukuk Liquidity, and Profitability Affect Sukuk Yield?

The purpose of this research is to determine how underlying assets, duration, default risk level, Sukuk liquidity, and profitability affect Sukuk yields between 2016 and 2019. One of the primary motivations for such studies was the failure of asset-based Sukuk with low default risk but not with asset-backed Sukuk. Then, this study focuses on two types of Sukuk, namely asset-based Sukuk and asset-backed Sukuk, and how the yield of each type is determined by the underlying asset. Until then, duration, default risk level, Sukuk liquidity, and profitability are used as control variables in evaluating the impact of underlying assets on Sukuk yields. This study employed an analysis of the difference between the two independent sample groups as well as multiple regression. The analysis was performed on each type of Sukuk. The analysis revealed that the Sukuk yields of the two groups differed, with an asset-based Sukuk generating more than an asset-backed Sukuk. Meanwhile, in asset-based Sukuk, the risk of default raises the yield while duration, liquidity, and profitability remain unchanged. The default risk level and profitability do not affect the yield in the asset-backed Sukuk group, whereas the duration and liquidity of the Sukuk have a positive effect on the yield.

Histone deacetylase inhibitor decreases hyperalgesia in a mouse model of alcohol withdrawal-induced hyperalgesia.

Alcohol withdrawal-induced hyperalgesia (AWH) is characterized as an increased pain sensitivity observed after cessation of chronic alcohol use. Alcohol withdrawal-induced hyperalgesia can contribute to the negative affective state associated with abstinence and can increase susceptibility to relapse. We aimed to characterize pain sensitivity in mice during withdrawal from two different models of alcohol exposure: chronic drinking in the dark (DID) and the Lieber-DeCarli liquid diet. We also investigated whether treatment with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could ameliorate AWH in mice treated with the Lieber-DeCarli diet. Male and female C57BL/6J mice were used for these studies. In the DID model, mice received bottles of 20% ethanol or water during the dark cycle for 4 h per day on four consecutive days per week for 6 weeks. Peripheral mechanical sensitivity was measured weekly the morning of Day 5 using von Frey filaments. In the Lieber-DeCarli model, mice received ethanol (5% v/v) or control liquid diet for 10 days, along with a single binge ethanol gavage (5 g/kg) or control gavage, respectively, on Day 10. Peripheral mechanical sensitivity was measured during the liquid diet administration and at 24 and 72 h into ethanol withdrawal. An independent group of mice that received the Lieber-DeCarli diet were administered SAHA (50 mg/kg, i.p.) during withdrawal. Male mice exhibited mechanical hypersensitivity after consuming ethanol for 5 weeks in the DID procedure. In the Lieber-DeCarli model, ethanol withdrawal led to hyperalgesia in both sexes. Suberoylanilide hydroxamic acid treatment during withdrawal from the ethanol liquid diet alleviated AWH. These results demonstrate AWH in mice after chronic binge drinking in males and after Lieber-DeCarli liquid diet administration in both sexes. Like previous findings in rats, HDAC inhibition reduced AWH in mice, suggesting that epigenetic mechanisms are involved in AWH.

Investigating the level of medication adherence and subjective recovery in patients diagnosed with schizophrenia

Background & Aim: Low compliance with medication in patients with schizophrenia may negatively affect the quality of life and subjective recovery. The objective was to analyze the association between medical adherence and subjective recovery in individuals diagnosed with schizophrenia.
 Methods & Materials: This descriptive and correlational research was conducted between July and August 2023. 120 patients registered with a Schizophrenia Relatives Association in Türkiye were included in the study using simple random sampling. Demographic questionnaire, Medication Adherence Report Scale, and Subjective Recovery Assessment Scale were used in the study. Percentage, mean, t-test in independent groups, one-way ANOVA, and Pearson correlation coefficient were used to data analysis in SPSS 25.
 Results: Medication Adherence and Subjective Recovery mean scores were 22.85±3.57 and 61.82±15.37 respectively. It was revealed that there is a positive and statistically significant relationship between Medication Adherence and Subjective Recovery scores (r=0.269, p<0.01). As well as between age and Medication Adherence Report Scale (r=0.215, p<0.05). The subjective recovery level was significantly lower in smokers compared to non-smokers (p<0.05).
 Conclusion: Subjective recovery levels of psychiatric patients can be increased by monitoring their medication adherence levels. Supportive interventions (giving motivational talks for medication use, following up with patients by phone or home visit, etc.) should be implemented for those who do not adhere to their medication regimen.

The Effect of Family Education Program on Paternity Role and Children's Play Skills

The objective of the study was to evaluate the effects of fathers' participation in the Father Support Education Programme on their perception of their role as fathers and the development of play skills in their children. The study sample comprised 40 fathers whose children, aged 5 and 6, were enrolled in independent pre-schools located in the city centre of Bartın. The experimental design of pre-test and post-test control group was adopted to facilitate the study. All technical terms were defined when first used. The study comprised 20 fathers, who were divided into control and study groups. Fathers in the study group received the Father Support Education Program over a period of 10 weeks, while no education program was provided to the control group. Information was collected using the "Personal Information Form," "Father Role Perception Scale (FRPS)," and "Game Skills Assessment Scale (PSAS)." The research's quantitative data was analysed using the SPSS (Statistical Package for Social Sciences) programme for Windows 22.0. To compare continuous data between two independent groups, the t-test was employed. The analysis established that following the educational programme, fathers in the study group exhibited a significant difference between their pre-test and post-test mean scores for their roles in their children's play skills. It was found that the Father Support Education Programme had a positive impact on fathers' roles and the development of children's play skills.

Development, Validity and Reliability Study of the Play Preferences Scale (PPS) for Children Receiving Preschool Education

The aim of the study is to develop a Likert-type scale to determine the play preferences of children attending pre-school education. The research was designed and carried out according to the survey research model. Data collected from 3 different study groups were used in the scale development process. The study groups consist of parents of children attending pre-school education in Istanbul Province in the 2022-2023 academic year. The 33-item and 8-dimensional structure obtained after EFA was also confirmed with CFA. Dimensions were determined as solitary play, parallel play, together play, collaborative play, building-building play, dramatic play, games with rules and digital play. It is seen that the reliability coefficients of the scale after EFA and CFA vary between 0.757 and 0.900. In order to distinguish between the lower and upper groups and to make comparisons between the groups, an independent group t test was performed, and it was revealed that there was a difference between the 27% lower and 27% upper groups (p <.05). It was determined that the test-retest values of the game type preferences scale were significant. According to these values, it was determined that the scale gave consistent results. When all studies were evaluated, it was concluded that the play preferences scale is a measurement tool that can validly and reliably measure the play preferences of children receiving preschool education.

Regional environmental differences significantly affect the genetic structure and genetic differentiation of Carpinus tientaiensis Cheng, an endemic and extremely endangered species from China.

Differences in topography and environment greatly affect the genetic structure and genetic differentiation of species, and endemic or endangered species with limited geographic ranges seem to be more sensitive to changes in climate and other environmental factors. The complex topography of eastern China is likely to affect genetic differentiation of plants there. Carpinus tientaiensis Cheng is a native and endangered plants from China, and exploring its genetic diversity has profound significance for protection and the collection of germplasm resources. Based on AFLP markers, this study found that C. tientaiensis has low genetic diversity, which mainly came from within populations, while Shangshantou and Tiantai Mountain populations have relatively high genetic diversity. The Nei genetic distance was closely related to geographical distance, and temperature and precipitation notablely affected the genetic variation and genetic differentiation of C. tientaiensis. Based on cpDNA, this study indicated that C. tientaiensis exhibits a moderate level of genetic diversity, and which mainly came from among populations, while Tiantai Mountain population have the highest genetic diversity. It demonstrated that there was genetic differentiation between populations, which can be divided into two independent geographical groups, but there was no significant phylogeographic structure between them. The MaxEnt model showed that climate change significantly affects its distribution, and the suitable distribution areas in Zhejiang were primarily divided into two regions, eastern Zhejiang and southern Zhejiang, and there was niche differentiation in its suitable distribution areas. Therefore, this study speculated that the climate and the terrain of mountains and hills in East China jointly shape the genetic structure of C. tientaiensis, which gived rise to an obvious north-south differentiation trend of these species, and the populations located in the hilly areas of eastern Zhejiang and the mountainous areas of southern Zhejiang formed two genetic branches respectively.

Effectiveness of an Informationized Teaching-management Strategy to Enhance Performance in National Nursing Licensure Examination: A Quasi-experimental Study

Objective: This study was to verify the effectiveness of an information-based teaching-management strategy applied during students’ clinical internship, designed to improve their performance in the National Nursing Licensure Examination (NNLE) Methods: All nursing students of eleven classes from grade 2017 in a vocational school were included (n=547). Considering the convenience of operational interventions, the experimental group consisted of students from Class 8, where the teacher in charge is the first author (n=49). The control group (n=498) comprised individuals selected from the other ten classes, with each class serving as an independent control group. From January 2020 to April 2021, a teaching-management strategy containing two stages was implemented in both groups from the students’ one-year clinical internship until the overall review period. In addition to this, a cloud-based knowledge-review program (e.g., layered teaching, four-step method, and paired assistance) was used in experimental group. The main outcome measures were the scores and pass rate of each examination. Results: Experimental group performed better than control group in both the simulation tests and the NNLE, in which the pass rate was 100%, showing a statically significant difference (P<0.01). Conclusion: Information-based teaching-management strategy is beneficial for long-distance education during students’ clinical internship, and it can effectively help students prepare for the NNLE to get a higher score.

Effectiveness of mesenchymal stem cell therapy in cats with chronic gingivostomatitis

PICO Question In cats with chronic gingivostomatitis, does using intravenous mesenchymal stem cell therapy, compared to not using it, lead to the improvement of clinical signs? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Five interventional studies (clinical trials). Strength of evidence None. Outcomes reported The reviewed studies indicate intravenous mesenchymal stem cell (MSC) therapy is safe to administer and can be effective in remission or alleviating the clinical signs of refractory, chronic gingivostomatitis in cats that have undergone full-mouth tooth extraction. Conclusion The collective evidence supports the intravenous administration of mesenchymal stem cell (MSC) therapy in cats with chronic gingivostomatitis following dental extraction. However, conducted clinical trials are prone to different degrees of bias due to the lack of independent control groups, the small number of subjects, and enrolling subjects with various severity of the disease. Therefore, more robust evidence can be obtained through well-designed randomised controlled trials to confirm the observed positive effects of the treatment in cats with a broader range of characteristics. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Lactation traits and reproductive performances of Sahraoui female camel in two breeding systems at Algerian Sahara.

The main objective of this study is to determine the impact of the camel livestock system on individual and herd performances of milk production, lactation curve, fats, and protein concentrations. For this purpose, 13 she-camels of Sahraoui breed from the south eastern Algeria and belonging and semi-intensive system (N = 6) and intensive system (N = 7) were studied. Recording and sampling of milk were carried out at regular intervals during a full lactation. The lactation curve was estimated using Wood's gamma function and the t-test of independent groups was carried out to compare lactation performances, lactation curve, and reproductive parameters. The overall average daily milk (DMY), fat (DFY), and protein (DPY) yield were 6.77 ± 0.82kg/day, 4.15 ± 0.91%, and 4.49 ± 0.20%, respectively. The mean of total milk yield (TMY) was 2696.39 ± 343.86kg during a mean lactation length (LL) of 398.38 ± 20.65days. The peak of milk production (6.79 ± 0.68kg) was reached at 93.9 ± 55.8days after calving. The open day (DO) and inter-calving interval (ICI) recorded in this study were 348.38 ± 30.33 and 723.38 ± 30.33days, respectively. There is no significant difference (p > 0.05) between intensive and semi-intensive breeding systems for TMY (2795.39 ± 261.88kg vs. 2580.89 ± 414.43kg), DMY (6.96 ± 0.66kg vs. 6.55 ± 1.00kg), and LL (402.14 ± 21.18days vs. 394 ± 21.03days). However, the total amount of fat was significantly higher in intensive system (182.02 ± 33.91kg) and the DPY content was significantly higher in semi-intensive system (4.60 ± 0.13%). The parameters α, β, and γ of lactation, fat, and protein curves between the two systems showed a highly significant difference (p < 0.01) for the parameters (α and β) for the milk production curve, significant (p < 0.05) for the time to reach peak yield, and no significance for the other parameters. The corresponding values of the coefficient of determination (R2) were 0.62, 0.35 for milk yield (p > 0.05), 0.12, 0.13 (p > 0.05) for fat, and 0.03, 0.11 (p < 0.05) for protein, in the intensive and semi-intensive systems, respectively. In addition, DO and ICI were not significantly different between the livestock systems, but were higher in the intensive system than the semi-intensive system (337.17 ± 26.26 vs. 712.17 ± 26.26, respectively). The study concluded that the intensive system had a higher milk performance with a more efficient lactation curve. The incomplete gamma model (Wood) used in this study was inappropriate for estimating milk yield, but acceptable for fat and protein.

Machine learning analysis of RB-TnSeq fitness data predicts functional gene modules in Pseudomonas putida KT2440.

This study demonstrates a rapid, automated approach for elucidating functional modules within complex genetic networks. While Pseudomonas putida randomly barcoded transposon insertion sequencing data were used as a proof of concept, this approach is applicable to any organism with existing functional genomics data sets and may serve as a useful tool for many valuable applications, such as guiding metabolic engineering efforts in other microbes or understanding functional relationships between virulence-associated genes in pathogenic microbes. Furthermore, this work demonstrates that comparison of data obtained from independent component analysis of transcriptomics and gene fitness datasets can elucidate regulatory-functional relationships between genes, which may have utility in a variety of applications, such as metabolic modeling, strain engineering, or identification of antimicrobial drug targets.

(151) Safety and Feasibility of the COCKTAIL (Combining Shockwave Therapy and Platelet-Rich Plasma for Erectile Dysfunction) Trial: A Single Center, Randomized, Double-Blind, Sham-Controlled Study Update

Abstract Introduction Therapeutic approaches focusing on tissue neovascularization play a crucial role in the development of treatments for erectile dysfunction (ED). Autologous Platelet-Rich Plasma (PRP) and Low-Intensity Shockwave Therapy (SWT) are two restorative therapies that potentially target underlying causes of ED. Pre-clinical evidence suggests their angiogenic and regenerative properties, indicating a potential synergistic pathway to improve vasculogenic ED. Objective The primary objective aims to investigate and compare the treatment efficacy of PRP injection and SWT vs placebo injection/SHAM treatment in men with mild-moderate ED, as measured by IIEF. The secondary objective aims to study incidence of adverse events and safety of PRP injection and SWT treatment in men with mild-moderate ED, as measured by IIEF. Methods The COCKTAIL (Combining Shockwave Therapy and Platelet Rich Plasma) trial is a Phase II, single-center study assessing the safety and efficacy of PRP and SWT in combination for ED (NCT05048667). Thirty-five men with mild to moderate ED were enrolled based on International Index of Erectile Function-EF subdomain (IIEF-EF) questionnaire (12-25). Data from a cohort of men treated with PRP and SWT were analyzed, comparing it to men who received placebo saline injections and sham SWT. Patients received two PRP or placebo injections directly into the corpus cavernosum and penile SWT every week for 5 weeks. Assessment included pain scale evaluations, immediate post-procedure examination, and follow-up for complications. IIEF scores were recorded at baseline, 3-month, and 6-month follow-up visits. All statistics and analyses were conducted with IBM SPSS Statistics 27.0.1. Non-parametric tests were used for analysis. Mann-Whitney U test was used to compare independent groups (Group A vs. Group B) at different time points. Related Samples Wilcoxon -Signed Rank test was used for dependent repeated groups, the serial measurements of IIEF-EF scores at different time points for each patient within a specific group. Findings at p&amp;lt; 0.05 were considered statistically significant. Results The primary endpoint of this study was to investigate the incidence of Serious Adverse Events (SAEs). Encouragingly, no adverse events were reported, suggesting that the procedure appears to be safe for the participants. The median baseline IIEF scores for patients in Group A were 17 (±4), and at the three-month follow-up, the scores increased to 19 (±4), slightly dropping to 18 (±8) at six months. In Group B, the median baseline IIEF scores were 19.50 (±4), which improved to 20 (±7) at the three-month follow-up and further increased to 21 (±10) at six months. No statistical differences were found likely because this is an ongoing study, and we only have complete data for 12 men. We aim to accrue a total of 30 men in each arm and plan to complete the recruitment by January 2024 and complete the study by July 2024. Currently, both the investigators and the patients remain blinded. Conclusions The combination of PRP and SWT appears to be safe, as no adverse events were reported. Although preliminary data do not show differences between the treatment and sham groups currently, we intend to complete the trial to perform a comprehensive statistical calculation for efficacy. Disclosure No.

An Exploratory, Randomized, Double-Blind Clinical Trial of Dipraglurant for Blepharospasm.

Blepharospasm is treated with botulinum toxin, but obtaining satisfactory results is sometimes challenging. The aim is to conduct an exploratory trial of oral dipraglurant for blepharospasm. This study was an exploratory, phase 2a, randomized, double-blind, placebo-controlled trial of 15 participants who were assigned to receive a placebo or dipraglurant (50 or 100 mg) and assessed over 2 days, 1 and 2 hours following dosing. Outcome measures included multiple scales rated by clinicians or participants, digital video, and a wearable sensor. Dipraglurant was well tolerated, with no obvious impact on any of the measurement outcomes. Power analyses suggested fewer subjects would be required for studies using a within-subject versus independent group design, especially for certain measures. Some outcome measures appeared more suitable than others. Although dipraglurant appeared well tolerated, it did not produce a trend for clinical benefit. The results provide valuable information for planning further trials in blepharospasm. © 2024 International Parkinson and Movement Disorder Society.

Effect of Psychological Contract on Employee Turnover Intention: Moderating Role of Select Demographic Variables

Since the inception and the spread of COVID-19 from March 2020 in India, companies have experienced a rapid increase in the rate of unemployment as well as employee turnover intention. However, though employer appears to have additional power due to high unemployment levels, but it’s also been balanced by employees having new and more alternatives over whom they get employed due to extensive adoption of remote working by all the companies. Employees are highly satisfied at the workplace, prone to get retained with the organization, develop faith in the organizational system only if there is fulfillment of their psychological contract; employer’s showing concern for employees. This study aims to examine the relationship between psychological contract and employee turnover intention for the employees working in general insurance companies in India. The study further explores the moderating effect of select demographic variables for the relationship between psychological contract and employee turnover intention. These demographic variables are considered as independent groups and their moderation effect relationship between Psychological Contract and Employee Turnover Intention is tested with the help of SMART PLS software. The findings are insightful and will pave the way for the insurance companies to retain the employees by reducing their employee turnover intention and focusing on fulfillment of psychological contract.

Analysis of similarity among national parks in Korea: A comparison of habitat composition and species presence–absence data (Lepidoptera, aquatic insects, and higher plants)

AbstractA list of species of Lepidoptera, aquatic insects, and higher plant species inhabiting 22 National parks in Korea was compiled. A similarity analysis was performed to compare all National parks, and cladograms were constructed. In the case of higher plants, those inhabiting the Hallasan region were categorized as a separate group, while the plants living in National parks located near the southern and western coasts formed one group, and other terrestrial National parks were divided into two groups as follows: the Taebaek Mountain range/adjacent mountain group and the others group. Species of Lepidoptera, which appear to be related to plants, in the Hallasan, Taebaeksan, Taeanhaean, and Bukhansan mountains were each classified independently, and those in the Hallyeohaesang, Dadohaehaesang, Naejangsan, and Byeonsanbando in the southern and western parts of Korea were classified as a single group. In case of aquatic insects, those in the Hallasan, Taeanhaean, and Bukhansan region were categorized in independent groups, and other terrestrial National parks were placed in one group with high similarity. A similarity analysis was performed through a detailed classification of the habitats in National parks revealed that marine‐coastal National parks particularly showed low similarity with other mountainous National parks. In addition, other terrestrial National parks were further grouped into large and small National parks. Comparing the subject map that divided Korea into climate, vegetation, and topography, some marine‐coastal National park areas were confirmed to be distinguished from other areas. Furthermore, similarity analysis revealed that Gangwon‐do and Baekdu‐Daegan regions in Gyeongsangbuk‐do were categorized into one group with high similarity.

RP1 Dominant p.Ser740* Pathogenic Variant in 20 Knowingly Unrelated Families Affected by Rod-Cone Dystrophy: Potential Founder Effect in Western Sicily.

Background and Objectives. Retinitis pigmentosa (RP) is the most common inherited rod-cone dystrophy (RCD), resulting in nyctalopia, progressive visual field, and visual acuity decay in the late stages. The autosomal dominant form (ADRP) accounts for about 20% of RPs. Among the over 30 genes found to date related to ADRP, RP1 pathogenic variants have been identified in 5-10% of cases. In a cohort of RCD patients from the Palermo province on the island of Sicily, we identified a prevalent nonsense variant in RP1, which was associated with ADRP. The objective of our study was to analyse the clinical and molecular data of this patient cohort and to evaluate the potential presence of a founder effect. Materials and Methods. From 2005 to January 2023, 84 probands originating from Western Sicily (Italy) with a diagnosis of RCD or RP and their relatives underwent deep phenotyping, which was performed in various Italian clinical institutions. Molecular characterisation of patients and familial segregation of pathogenic variants were carried out in different laboratories using Sanger and/or next-generation sequencing (NGS). Results. Among 84 probands with RCD/RP, we found 28 heterozygotes for the RP1 variant c.2219C>G, p.Ser740* ((NM_006269.2)*, which was therefore significantly prevalent in this patient cohort. After a careful interview process, we ascertained that some of these patients shared the same pedigree. Therefore, we were ultimately able to define 20 independent family groups with no traceable consanguinity. Lastly, analysis of clinical data showed, in our patients, that the p.Ser740* nonsense variant was often associated with a late-onset and relatively mild phenotype. Conclusions. The high prevalence of the p.Ser740* variant in ADRP patients from Western Sicily suggests the presence of a founder effect, which has useful implications for the molecular diagnosis of RCD in patients coming from this Italian region. This variant can be primarily searched for in RP-affected subjects displaying compatible modes of transmission and phenotypes, with an advantage in terms of the required costs and time for analysis. Moreover, given its high prevalence, the RP1 p.Ser740* variant could represent a potential candidate for the development of therapeutic strategies based on gene editing or translational read-through therapy for suppression of nonsense variants.

Identification of necroptosis-associated miRNA signature for predicting prognosis and immune landscape in stomach adenocarcinoma

PurposeThis study aims to identify the potential necroptosis related genes (NRGs)-associated miRNAs signature and explore the impact on the prognosis of stomach adenocarcinoma (STAD). MethodsEmploying rigorous methodologies, we utilized univariate Cox, Lasso and multivariate Cox regression analyses to develop a prognostic signature. Kaplan-Meier (K-M) and ROC curves were applied to assess the prognostic value of signature in a training group and an independent test group. Furthermore, we conducted Gene Set Enrichment Analysis (GSEA) for enrichment of tumor-related pathways. The risk score was calculated for each patient based on the expression of miRNAs which were enrolled in the signature. Patients were stratified into high- and low-risk groups. The immune cell infiltration and immunotherapy were compared between the two groups. Finally, the diagnostic potential of the miRNA was explored by RT-qPCR. ResultsWe constructed a prognostic model based on 6 NRGs-associated miRNAs. K-M plots underscored superior survival outcomes in the low-risk group. GSEA results revealed the enrichment of several tumor-related pathways in the high-risk group. Notably, CD8+ T cells, Tregs and activated memory CD4+ T cells exhibited negative correlations with the risk score. Additionally, a few immune checkpoint genes, such as CTLA4, PD1 and PD-L1, were significantly upregulated in the low-risk group. Furthermore, the serum expression levels of all these 6 miRNAs were significantly elevated in STAD patients. ConclusionsOur study identified a robust risk score derived from a signature of 6 NRGs-associated miRNAs, demonstrating high efficacy for prognosis of STAD. These results not only contributed to our understanding of STAD pathogenesis, but also held promise for potential clinical applications, particularly in the realm of personalized immunotherapy for STAD patients.

Pharmacological Manipulation of Corticotropin-Releasing Factor Receptors in the Anterior and Posterior Subregions of the Insular Cortex Differently Affects Anxiety-Like Behaviors in the Elevated Plus Maze in Rats.

Neuroimaging data in humans and neurobiological studies in rodents have suggested an involvement of the insular cortex (IC) in anxiety manifestations. However, the local neurochemical mechanisms involved are still poorly understood. Corticotropin-releasing factor (CRF) neurotransmission has been described as a prominent neurochemical mechanism involved in the expression of anxiety-like behaviors, but the brain sites related are poorly understood. Additionally, several findings indicate that control of physiological and behavioral responses by the IC occurs in a site-specific manner along its rostrocaudal axis. Thus, this study is aimed at evaluating the effect of CRF receptor agonism and antagonism within the anterior and posterior subregions of the IC in controlling anxiety-related behaviors in the elevated plus maze (EPM). For this, independent groups (six groups) of animals received bilateral microinjections of vehicle, the selective CRF1 receptor antagonist CP376395, or CRF into either the anterior or posterior subregions of the IC. Ten minutes later, the behavior in the EPM was evaluated for five minutes. Treatment of the anterior IC with CP376395, but not with CRF, increased the time and number of entries into the open arms of the EPM. CRF, but not the CRF1 receptor antagonist, microinjected into the posterior IC also increased exploration of the EPM open arms. Taken together, these data indicate that CRFergic neurotransmission in the anterior IC is involved in the expression of anxiety-related behaviors in the EPM. This neurochemical mechanism does not seem to be activated within the posterior IC during exposure to the EPM, but the effects caused by CRF microinjection indicate that activation of CRF receptors in this IC subregion might evoke anxiolytic-like effects.