Multiple Test Research Articles

Resurrecting a classic design: Examining the refutational text effect using a Solomon four-group design

ABSTRACT One point of contention in the refutation text literature is whether testing is a cognitively neutral task. On the one hand, pretesting is useful to determine what misconceptions learners hold and to what extent the intervention addresses these misconceptions. On the other hand, evidence from previous research has highlighted the potential ramifications of pretesting on both the results and interpretations of refutational text effects. In this study, we leveraged a Solomon four-group design to investigate the potential influence of pretesting on conceptual change and confidence when learning from refutational text. One hundred and thirteen individuals, who were recruited online, participated in the study. We present two findings: first, the two refutational text groups experienced a more successful conceptual change than those in expository groups. Second, no significant differences were found in participants’ retrospective confidence judgments or judgmental accuracy across text structures or pretest conditions. Taken together, the results suggest that refutational text is more effective in facilitating conceptual change, and including pretesting in refutational text studies might not cause overestimations of the refutational text effects. The present study took the first step to examine the potential pretesting sensitization in refutational text studies, and future research is encouraged to include multiple topics, delay tests, and various measurements to examine the potential overestimation of refutational text effects.

Assessing the Causal Relationships Between Lipid Species and Stroke by Using Mendelian Randomization.

Circulating lipids and changes in lipid profiles have long been associated with the development of stroke but causal relationships remain unclear.In this study, we aimed to assess the causal relationships between lipid species and multiple stroke phenotypes to inform stroke prevention and treatment strategies. We conducted a two-sample Mendelian randomization analysis using data from genome-wide association studies. The primary method for causal assessment was inverse variance weighting (IVW), complemented by the MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, based on MR-Egger, MR-PRESSO, and Cochran's Q statistics, were also applied to reinforce the results. In total, potential causality was observed for 133 pairs of lipids with stroke types(P < 0.05). After multiple testing correction (PFDR < 0.05), potential causal associations remained for 10 pairs of lipids, including specific sterol esters and phosphatidylcholines, with various stroke subtypes. The findings demonstrate the significant role that genetically determined lipid profiles may play in the pathogenesis of stroke. Further research is needed to establish whether these biomarkers can be used for stroke prevention or treatment.

A Functional Variant rs2122031 in ATG7 Is Associated with the Risk of Radiation Pneumonitis.

Radiation pneumonitis (RP) is characterized by inflammation and is associated with autophagy. However, the relationship between functional genetic variants of autophagy-related genes and radiation pneumonitis remains unknow. In this study we aimed to investigate whether genetic variants of genes involved in autophagy are associated with radiation pneumonitis. Genotyping was conducted on a total of 301 patients for thirteen single nucleotide polymorphisms (SNPs) of 5 genes in the autophagy pathway using MassArray and Sanger sequencing. Two radiation oncologists independently measured the degree of RP by chest X-ray or CT. The multivariate Cox hazard analysis and multiple testing showed that ATG7: rs2122031 GA/GG significantly decreased the risk of RP ≥ grade 3 (HR=0.369, 95% CI: 0.189-0.720, P=0.003, Pc=0.039). Furthermore, qRT-PCR and immunohistochemical analysis demonstrated that the ATG7: rs2122031 AA genotypes were related to decreased expression of ATG7. Loss of autophagy by deletion of ATG7 in fibroblasts or conditional ATG7 knockout mice was proven to increase radiation pneumonitis. Single-cell RNA-seq revealed regulation of autophagy related genes enriched after irradiation stress in conditional ATG7 knockout mice. Our findings indicated that genetic variants of ATG7 were associated with RP and may therefore be used to predict RP before radiotherapy. Loss of ATG7 was also shown to promote RP, which suggested that ATG7 may be an intervention target for RP.

A meta-analysis of genome-wide association studies to identify candidate genes associated with feed efficiency traits in pigs.

Pig production is an agricultural sector of great economic and social relevance to Brazil and global markets. Feed efficiency traits directly influence the sustainability of pig production due to the economic impact of feed costs on the production system and the environmental footprint of the industry. Therefore, breeding for improved feed efficiency has been a target of worldwide pig breeding programs. Genome-wide association studies (GWAS) enable the assessment of the genetic background of complex traits, which contributes to a better understanding of the biological mechanisms regulating their phenotypic expression. In this context, the primary objective of this study was to identify and validate genomic regions and candidate genes associated with feed conversion ratio (FCR) and residual feed intake (RFI) in pigs based on a comprehensive systematic review and meta-analysis of GWAS. The METAL software was used to implement the meta-analysis and the Bonferroni multiple testing correction considering a significance threshold of 0.05. The significant single nucleotide polymorphisms (SNPs) in the meta-analysis were used to identify candidate genes, followed by a functional genomic enrichment analysis. The systematic review identified 13 studies, of which 7 evaluated FCR, 3 evaluated RFI, and 3 studies investigated both traits, with 160 and 96 SNPs identified for FCR and RFI, respectively. After the meta-analysis, 145 markers were significantly associated with FCR and 90 with RFI. The gene annotation process resulted in 105 and 114 genes for FCR and RFI, respectively. The enrichment analysis for FCR resulted in 16 significant gene ontology (GO) terms, while six terms were identified for RFI. The main GO terms were actin cytoskeleton (GO_BP:0030036), membrane (GO_CC:0016020), integral components of the peroxisomal membrane (GO_CC:0005779), and carbohydrate binding (GO_MF:0030246). The main candidate genes identified were MED18, PHACTR4, ABCC2, TRHDE, FRS2, FAR2 and FIS1 for FCR, and ADGRL2, ASGR1, ASGR2, and MAN2B1 for RFI. These findings contribute to a better understanding of the genetic mechanisms associated with feed efficiency traits in pigs, providing a foundation for future improvements in pig breeding programs.

Dual-mode, regenerated DNA motor for simultaneous detection of viral gene fragments and diagnosis of infectious disease.

This study presents a dual-mode and regenerated DNA motor powered by exonuclease III (Exo III) for the simultaneous detection of viral gene fragments. The detection methodology is categorized into two distinct operational modes. The first mode emphasizes the simultaneous detection of two viral gene fragments from a specific virus. The presence of both genes triggers the operation of the DNA motor, generating a singular signal output. This mode operates on an "AND" logical mechanism, which enhances the precision of positive case identification. The second mode facilitates the simultaneous detection of three viral gene fragments from three different viruses within a single assay. The presence of these genes activates their respective motors, yielding distinct signal outputs. This mode supports the multiplex detection of three target genes, thereby aiding in the identification of previously uncharacterized viruses infecting patients and alleviating the logistical and financial burdens associated with multiple testing procedures. The detection limit in the "AND" logical mode is at the aM level, while in the multiplex mode, it reaches the fM level, facilitating the sensitive detection of viral gene fragments. The DNA motor can be regenerated by separating and reconstituting the utilized orbits, enabling its reuse for up to seven cycles in the "AND" logical mode and five cycles in the multiplex mode. Accurate diagnoses were achieved for patients exhibiting upper respiratory symptoms. Therefore, the proposed motor offers a novel and regenerative approach for viral gene fragments detection, demonstrating significant promise for application in the clinical diagnosis of viral infectious diseases.

Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank.

Glucagon-like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off-target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill-health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank. All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes. Linear or Logistic regression analyses (adjusted for age, sex, population structure and genotyping chip) were conducted separately in unrelated individuals of self-reported white British (N = 408 774), white European (N = 50 314), South Asian (N = 7667), multiple-ancestry groups (N = 10 437) or African-Caribbean (N = 7641) subsets. All ancestries were subsequently combined in an inverse variance-weighted fixed effects meta-analysis. Bonferroni correction for multiple testing was applied (for number of independent genetic variants). Associations were identified between GLP1R variants and body mass index (BMI), blood pressure and type 2 diabetes in all ancestries. All ancestries except South Asian had significant MIH associations (mood instability: rs111265626-G, odds ratio [OR] 0.851 [confidence interval, CI 0.79-0.92], risk-taking behaviour: rs75408972-T, OR 1.05 [CI 1.03-1.08] or chronic pain: rs9296280-C, OR 0.645 [CI 0.54-0.78]). The trans-ancestry meta-analysis showed mainly consistent effect sizes and directions for metabolic traits, but discordant directions MIH associations. Only signals for chronic pain, stroke and BMI influenced expression of GLP1R. GLP1R variants have consistent cardiometabolic effects across ancestries, but effects on MIH phenotypes are more varied. Any observed behavioural changes with GLP1RA are likely not acting directly through GLP1R.

Evaluating the accuracy of multiple rapid diagnostic tests for HIV detection in serum samples analysed during point-of-care proficiency testing assessments.

HIV rapid diagnostic tests are crucial for timely diagnosis, especially in resource-limited settings. The World Health Organization recommends sensitivity ≥99 % and specificity ≥98 %. This study assessed RDT performance across South Africa's provinces using a proficiency testing program. From April to June 2023, 25,458 blinded serum samples were sent to testing facilities for screening and confirmatory testing. Sensitivity, specificity, predictive values, and concordance (Cohen's Kappa) were evaluated. The response rate was 98.25 %. Sensitivity and specificity were both 98.7 %, with agreement at 98.7 % (kappa 0.97, p < 0.001). Northern Cape showed the lowest sensitivity (91.8 %) and specificity (92.0 %), while Gauteng, KwaZulu-Natal, and Mpumalanga exceeded 99 %. Although national RDT performance met WHO standards, Northern Cape's results reveal the need for improved training, quality assurance, and proficiency testing to strengthen diagnostic accuracy.

The microcirculation : master in normal pregnancy, puppet in preeclampsia.

To investigate the association between functional parameters of the microcirculation and the systemic cardiovascular system in a population of pregnant women at risk for gestational hypertension disorders. For this observational study, women at high cardiovascular risk according to maternal anthropometrics, obstetric and medical history, were recruited at random gestational age depending on time of referral to the outpatient clinic for high risk prenatal care at Ziekenhuis Oost Limburg, Genk Belgium. After birth, data of maternal and neonatal outcome were obtained from the hospital records: only women with normal pregnancy (n = 142) and with preeclampsia (n = 34) were included in this analysis. Nailfold video capillaroscopy measurements were performed in first and/or second and/or third trimester. Video magnification of 200x was used at all fingers except thumbs, and stored images were analyzed offline. Capillary density was counted (n/mm2), mean capillary diameter measured (μm) and capillary bed was calculated as density x diameter. Cardiac output and total peripheral resistance were measured using impedance cardiography, together with sphygmomanometric blood pressure measurement. Linear mixed model for repeated measures was employed to investigate the association between the microvascular and macrovascular parameters. No correction for multiple testing was used. In normal pregnancies, a positive association was observed between capillary bed and total vascular resistance (1.807, p =0.01), and a negative association between capillary density and cardiac output (-0.269, p =0.037). In preeclampsia, a negative association was observed between capillary density and mean arterial pressure (-0.5649, p = 0.010), and between capillary diameter and cardiac output (-0.165, p=0.032). A reduction of capillary density with increase of blood pressure in preeclampsia is similar to observations in chronic hypertension. Here, this is considered the result of capillary closure after constriction of precapillary arterioles. In normal pregnancy however, the increase of the capillary bed with rising vascular resistance can only be explained by a primary role for the microcirculation, preventing capillary overflow via stimulation of arteriolar constriction. These observations enlighten the very first hemodynamic origins of hypertension at the level of the microcirculation in preeclampsia.

Neighborhood-level socioeconomic disadvantage is associated with multiple cognitive domains in a community sample of older adults

ABSTRACT Greater neighborhood disadvantage is associated with poorer global cognition. However, less is known about the variation in the magnitude of neighborhood effects across individual cognitive domains and whether the strength of these associations differs by individual-level factors. The current study investigated these questions in a community sample of older adults (N = 166, mean age = 72.5 years, 51% women), who reported current addresses, linked to state-level Area Deprivation Index rankings, and completed remote and validated neuropsychological tests of verbal intelligence (North American Adult Reading Test), verbal fluency (Controlled Oral Word Association Test), attention (Digit Span Forward), and working memory (Digit Span Backward and Sequencing, Letter-Number Sequencing). Linear regressions tested associations between neighborhood disadvantage and each cognitive test, controlling for individual-level factors (age, sex, education). Exploratory analyses tested moderation by each individual-level factor. Independent of individual-level factors, greater neighborhood disadvantage was associated with lower cognitive performance across domains: verbal intelligence (β = 0.30, p < .001), verbal fluency (β = −0.19, p = .014), attention (β = −0.19, p = .024), and two of three tests of working memory (β = −0.17− −0.22, ps = .004−.039). Results were robust to correction for multiple comparisons and tests of spatial autocorrelation. In addition, higher neighborhood disadvantage was associated with lower verbal fluency for older – but not younger-older adults (p = .035) and with poorer working memory in women but not men (p < .001). Education did not moderate associations. Findings suggest that older adults living in more disadvantaged neighborhoods exhibit lower cognitive performance, particularly in the domain of verbal intelligence. Continued investigation of effect modification may be fruitful for uncovering for whom associations are strongest.

Evaluating the association between lipidome and female reproductive diseases through comprehensive Mendelian randomization analyses

This study aimed to assess the causal relationship between lipidome and female reproductive diseases (FRDs) using an advanced series of Mendelian randomization (MR) methods. This study utilized genome-wide association study (GWAS) summary statistics encompassing 179 lipidomes and six prevalent FRDs, namely polycystic ovary syndrome (PCOS), endometriosis, uterine fibroid, female infertility, uterine endometrial cancer, and ovarian cancer. The two-sample MR (TSMR) approach was employed to investigate the causal relationships, with further validation using false discovery rate (FDR) and multivariable MR (MVMR) methods. Subsequently, a range of comprehensive evaluations were performed, including sensitivity analysis, mediation MR analysis, reverse MR analysis, and steiger test. Examining 179 lipidome traits as exposures and 6 FRDs as outcomes, this study identified significant causal effects of 56 lipids on FRDs. Following multiple testing correction and MVMR validation, sphingomyelin (d38:2) was found to have a protective effect against PCOS (β = -0.104, 95% CI: -0.199 ~ -0.010, P = 0.031). Phosphatidylcholine (18:0_22:6) was associated with a decreased risk of developing uterine fibroid (β = -0.111, 95% CI: -0.201~ -0.021, P = 0.016), and sterol ester (27:1/20:3) showed significance in uterine endometrial cancer (β = -0.248, 95% CI: -0.443 ~ -0.053, P = 0.013). Conversely, phosphatidylethanolamine (18:2_0:0) was associated with increased risk of endometriosis (β = 0.183, 95% CI: 0.015 ~ 0.350, P = 0.033), while sterol ester (27:1/18:1) posed a risk influence on uterine fibroid (β = 1.007, 95% CI: 0.925 ~ 1.089, P < 0.001), and phosphatidylcholine (16:0_22:6) on uterine endometrial cancer (β = 0.229, 95% CI: 0.039 ~ 0.420, P = 0.018). Furthermore, it was determined that the causal associations between these lipidome profiles and FRDs were independent of BMI, obesity, diabetes, smoking, alcohol use, physical activity, inflammation, depression, waist-hip ratio, vitamin D, dehydroepiandrosterone sulphate, sex hormone binding globulin, and testosterone levels. Most outcomes passed consistent tests without evidence of heterogeneity, pleiotropy, or reverse causality. The results indicated a close association between specific lipidomes, particularly sphingomyelin, lysophosphatidylethanolamine, cholesterol ester, and phosphatidylcholines, with FRDs. These lipid species may potentially serve as biomarkers and future drug targets for the treatment of FRDs.

Debt To Asset Ratio, Debt To Equity Ratio, Return On Asset, Return On Equity, Net Profit Margin And The Effect On Stock Prices In Indonesia Energy Sector Companies

Abstract: The purpose of this study is to analyze the effect of Debt to Asset Ratio, Debt to Equity Ratio, Return On Asset, Return on Equity, and Net Profit Margin on stock prices, especially in energy sector companies in Indonesia. The data analysis methods used are descriptive statistical tests, classical assumption tests, multiple linear regression analysis tests, T-tests, F-tests, and determination coefficient tests. The sample in this study was 20 energy sector companies listed on the Bursa Efek Indonesia ( BEI ) during the 2017-2021 period and met the sample selection criteria. The sampling technique used was Purposive Sampling. The data used is secondary data obtained from the company's financial statements. The results of the study indicate that Return On Asset has a partial effect on stock prices while Debt to Asset Ratio, Debt to Equity Ratio, Return On Asset, Return on Equity, and Net Profit Margin do not affect stock prices in energy sector companies in Indonesia. Keywords Debt to Asset Ratio, Debt to Equity Ratio, Return on Assets, Return on Equity, Net Profit Margin, and Share Price

Assessment of MpoxPlex, a high-throughput and multiplexed immunoassay: a diagnostic accuracy study.

In May, 2022, the first global outbreak of mpox (formerly known as monkeypox) occurred. In response, public health agencies in the UK have made smallpox vaccines available to individuals at the highest risk of infection. With mpox cases still being detected globally, novel tools are required to aid with diagnosis, serosurveillance, and the evaluation of immune responses following infection and immunisation with current and new vaccine candidates. Here, we describe the development of a multiplexed immunoassay, MpoxPlex, able to measure IgG responses to 12Orthopoxvirus antigens concurrently and distinguish between responses to infection and vaccination. Using the Luminex (DiaSorin, Saluggia, Italy) platform, antibody responses to vaccinia virus (VACV) antigensB5, A27, and A33 and monkeypox virus (MPXV) antigens E8, B6, B2, M1, A27, A35, H3, A29, and A5 were assessed in serum from individuals after MPXV infection (n=24) and after vaccination (n=75) with modified VACV Ankara-Bavarian Nordic. Assay characteristics and cutoffs were calculated by fitting receiver operating characteristic curves to the median fluorescence intensities of these positive samples and negative samples that were run alongside (n=435). Pvalues were calculated using non-parametric Mann-Whitney, Kruskal-Wallis, and Dunn's multiple comparisons tests. Using the results from a combination of eight antigens, we were able to distinguish samples as either post-vaccination or post-infection from negative samples with a sensitivity of 98% and a specificity of 95%.IgG responses to MPXV antigen A27 were able to distinguish post-MPXV infection with a sensitivity of 88% and a specificity of 97%.VACV antigen A27 and MPXV antigens A29 and A5 provided little diagnostic advantage. With additional benefits over current serological assays, we believe this assay will provide substantial insight into the current global outbreak of mpox. MpoxPlex shows use for both serosurveillance and immunological studies of vaccination and infection. Grant-in-aid funding to the Emerging Pathogen Serology Group at Porton Down, UK Health Security Agency.

Influence of Financial Management Accountability and The Spirituality of Pastoral Services In the Parishes of The Tomohon Victory Towards The Achievement of Pastoral Work

The Manado Diocese Catholic Church implements a Church financial management system within the framework of transparent, objective and responsible financial management. In this context, it is necessary to involve lay pastoral staff who are considered capable and competent and have a high spirituality of service in order to realize the pastoral works of the Manado Diocese Church. This research aims to examine the phenomenon of the influence of accountability in parish financial management and the spirituality of pastoral servants in the context of achieving pastoral work. This research was conducted in all churches or parishes in the Kevikepan Tomohon area by taking 95 samples from 133 populations. The research method used is a quantitative research method with a survey approach. Through this method, researchers want to test hypotheses and at the same time explain the relationship between variables. The data analysis process uses the application of correlation statistics and multiple regression test to analyze the influence between variables and measure the level of relationship between each variable studied. The research results show that: First, there is a significant and linear influence between Financial Management Accountability and Pastoral Work Achievement, meaning that if Financial Management Accountability is implemented well and appropriately it will increase Pastoral Work Achievement in the Tomohon Kevikepan Parishes. Second, there is a relationship between the Spirituality of Pastoral Servants and the Achievement of Pastoral Work. This means that if the Spirituality of Pastoral Servants is interpreted well and effectively, then this will have the effect of increasing the Achievement of Pastoral Work in Tomohon Kevikepan Parishes. Third, the results of hypothesis testing and multiple correlation and multiple regression analysis prove that there is an influence between Financial Management Accountability and Pastoral Servant Spirituality together on Pastoral Work Achievement. Furthermore, it can be concluded that an accountable financial management model supported by the spirituality of pastoral servants can increase the achievement of pastoral work in parishes.

Pengaruh Minat dan Kemandirian Belajar Terhadap Hasil Belajar Matematika Siswa di Kelas VII MTsS TI

The low student mathematics learning outcomes are caused by several problems, namely the low interest and independence of student learning which is the driving force for conducting this research. Ex Post Facto research using quantitative techniques is this type of research. The research population was 118 class VIII MTsS TI Candung students. The instrument used was a questionnaire on interest and independence in learning. The research results produce a regression equation Y= 11.683 + 0.498 representing interest in learning on learning outcomes. t count = 3.113 &gt; t table = 2.052 is the result of the regression significance test. Interest in learning has a fairly large partial influence on mathematics learning outcomes. Y= 16.171 + 0.525 is the regression equation for learning independence on learning outcomes. After carrying out the regression significance test, it was obtained that t = 2.472 &gt; t table = 2.052. Partially, learning independence has a significant effect on mathematics learning outcomes. The resulting multiple regression equation has a determinant coefficient KD = 38.247% and a correlation coefficient value of 0.618 indicating a moderate relationship. The multiple regression significance test produces calculated F = 13.031 &gt; F table = 3.37. It is known that interest and independence have a big influence on mathematics learning outcomes.

The impact of fatigue on the jumping mechanics and injury risk of basketball players

Fatigue can significantly alter an athlete’s biomechanics and performance, which can increase their risk of injury. Important basketball moves like jump shots (JS) and countermovement jumps (CMJ) primarily use the muscles in the lower back and lower limbs. Basketball players’ jumping mechanics, performance, and risk of injury during CMJ, JS, and ankle sprains were all examined. A total of 415 male collegiate basketball players participated in the league, this season representing varying levels of jumping mechanics. Surface electromyography, a force plate, and a 3D motion analysis system were used to gather data. Field-goal percentage, the center of mass’s (CM) lowest point, joint angles during takeoff and landing, and Electromyography data from the lower leg muscles, erector spinae limbal, and rectus femoris were among the parameters that were recorded. Lower back muscle tiredness was created, and performance was evaluated after the fatigue. Data was analyzed using SPSS, with paired-sample t-tests, logistic, and Multiple Regression tests employed to examine the impact of fatigue on performance and injury risk. These tests assessed how fatigue affects shooting accuracy and joint angles, and increases the chance of injuries in basketball players. Following a period of tiredness, athletes’ field-goal percentages significantly decreased, whereas their CM lowest point increased on jump shots. In both CMJ and JS, fatigue leads to reduced knee flexion angles and increased ankle plantar flexion during landing, changing the contribution ratio of both legs. Due to impaired mechanics, these biomechanical changes suggest an increased probability of ankle sprains and an elevated risk of damage, especially during landing. The risk of lower back, knee, and ankle injuries increased due to major athletic impairments and altered landing mechanics caused by lower back muscular fatigue. To reduce basketball players’ risk of injury, these data highlight how crucial it is to address fatigue in training and recovery plans.

Can CT Image Reconstruction Parameters Impact the Predictive Value of Radiomics Features in Grading Pancreatic Neuroendocrine Neoplasms?

The WHO grading of pancreatic neuroendocrine neoplasms (PanNENs) is essential in patient management and an independent prognostic factor for patient survival. Radiomics features from CE-CT images hold promise for the outcome and tumor grade prediction. However, variations in reconstruction parameters can impact the predictive value of radiomics. 127 patients with histopathologically confirmed PanNENs underwent CT scans with filtered back projection (B20f) and iterative (I26f) reconstruction kernels. 3190 radiomic features were extracted from tumors and pancreatic volumes. Wilcoxon paired tests assessed the impact of reconstruction kernels and ComBat harmonization efficiency. SVM models were employed to predict tumor grade using the entire set of radiomics features or only those identified as harmonizable. The models' performance was assessed on an independent dataset of 36 patients. Significant differences, after correction for multiple testing, were observed in 69% of features in the pancreatic volume and 51% in the tumor volume with B20f and I26f kernels. SVM models demonstrated accuracy ranging from 0.67 (95%CI: 0.50-0.81) to 0.83 (95%CI: 0.69-0.94) in distinguishing grade 1 cases from higher grades. Reconstruction kernels alter radiomics features and iterative kernel models trended towards higher performance. ComBat harmonization mitigates kernel impacts but addressing this effect is crucial in studies involving data from different kernels.

Sex and APOE genotype modulate neuropsychological profile and depression in temporal lobe epilepsy

IntroductionTemporal lobe epilepsy is the most common form of focal epilepsy, often associated with cognitive impairments, particularly in memory functions, and depression. Sex and APOE ε4 genotype play a crucial role in modulating cognitive outcomes and depression in various neurological conditions like Alzheimer's disease. However, the combined effects of APOE genotype and sex on cognitive performance and depression in temporal lobe epilepsy have not been previously investigated.ObjectiveThis study aims to (i) identify impaired cognitive performance and clinically relevant depression; (ii) explore the interaction between sex and APOE ε4 genotype on cognitive performance and depression in individuals with temporal lobe epilepsy.MethodsWe used a comprehensive battery of neuropsychological tests to assess domains such as learning and memory, attention, executive functions, language, and visuo-spatial constructional skills and the Hamilton Depression Rating Scale. We also performed APOE genotyping to assess its role in the study. The final sample was composed by fifty-four patients (53.7% female). Cognitive performance and depression were analyzed using normative cut-off scores. To examine the main effects and interactions of sex and APOE ε4 carrier status on neuropsychological test scores and the Hamilton Depression Rating Scale, we also conducted a two-way Analysis of Variance (ANOVA).ResultsFemale APOE ε4 carriers compared to normative cut-offs, exhibited poor performance on multiple test scores, including the MMSE, The Rey Auditory Verbal Learning Test (immediate and delayed recall), The Corsi Block-Tapping Task, The Verbal Fluency Test, The Raven's Standard Progressive Matrices and The Pentagon-copying Test. Males showed impairment only in visuo-spatial short-term memory. ANOVA analysis revealed significant main effects of APOE ε4 status and sex on the MMSE, The Rey Auditory Verbal Learning Test, The Verbal Fluency, The Raven's Standard Progressive Matrices and The Pentagon-copying Test scores. Specifically, female APOE ε4 carriers performed consistently worse than other groups on many tasks. For depression, only an effect of sex emerged. Females scored higher besides APOE genotype.ConclusionsThese findings underscore the importance of considering both sex and APOE genotype when assessing cognitive performance in patients with temporal lobe epilepsy. The significant cognitive deficits we observed among females carrying the APOE ε4 allele highlight previously unexplored genetic and sex-related influences on cognition. This has potential implications for personalized therapeutic strategies, emphasizing the need for targeted assessment and intervention.

SNORD3C, a blood biomarker associated to suicide attempts in patients with anorexia nervosa.

Anorexia nervosa (AN) is a psychiatric disorder with a high heritability (h2∼70%). Despite extensive meta-analysis of genome-wide association studies, the molecular mechanisms underlying genetics of AN and its complications, particularly suicidal behavior, remain unclear. We performed mRNA sequencing on peripheral blood mononuclear cells from 15 patients with AN (5 with a lifetime history of suicide attempts and 10 without). After correcting for multiple testing, we identified dysregulation of several genes, and confirmed our findings in an independent cohort of 34 patients with AN. Our analysis revealed significant dysregulation of several genes, including SNORD3C, which is implicated in vitamin D metabolism. These genes were enriched in RNA metabolism and innate immune pathways. The presence of these dysregulated genes was associated with suicidal behavior in patients with AN. Our findings suggest that SNORD3C and other differentially expressed genes may serve as potential biomarkers for suicidal risk in AN. This study enhances our understanding of the biological pathways involved in the pathogenesis of suicidal behavior in AN, paving the way for future research and potential clinical applications.

Migraine Genetic Susceptibility Does Not Strongly Influence Migraine Characteristics and Outcomes in a Treated, Real-World, Community Cohort.

Background/Objectives: Migraine is a common neurological disorder with highly variable characteristics. While genome-wide association studies have identified genetic risk factors that implicate underlying pathways, the influence of genetic susceptibility on disease characteristics or treatment response is incompletely understood. We examined the relationships between a previously developed standardized integrative migraine polygenic genetic risk score (PRS) and migraine characteristics in a real-world, treated patient cohort. Methods: This retrospective cohort study used covariate-adjusted regression to comprehensively evaluate associations between the PRS and clinical characteristics in 1653 treated migraine cases with European ancestry at baseline and, in 800 cases, after one year. Cases were deeply phenotyped by neurologists during extensive interviews, using structured clinical documentation tools to record ~200 discrete data elements. Results: In treated patients, higher standardized PRS showed associations with two common migraine symptoms: photophobia (odds ratio [confidence interval]: 1.33 [1.13-1.56], p = 0.001) and stabbing pain (1.21 [1.08-1.36], p = 0.001]; both retained significance at Q = 0.05. Associations with phonophobia, nausea, emesis, and unilateral headache had similar effect sizes but did not survive correction for multiple tests. In this population, the PRS was not associated with other symptoms of migraine attacks, objective measures of migraine disability, frequency, severity, average duration, time-to-peak intensity of migraine attacks, chronification, emergency department visits, triptan responsiveness, or changes at follow-up. Conclusions: In treated patients, genetic risk was associated with common migraine symptoms but not with the severity of migraine characteristics or treatment outcomes. This suggests that in treated patients, other genetic and non-genetic factors influence migraine symptom severity and disease course more strongly than genetic susceptibility.

PENGARUH MINAT WIRAUSAHA DAN SELF EFFICACY TERHADAP KINERJA UMKM DI BENGKAYANG

Performance is an important thing that must be considered in the growth of Small and Micro Enterprises (MSMEs). This study aims to identify and analyze the effect of entrepreneurial interest and self-efficacy on the performance of MSMEs in Bengkayang City. This research is quantitative research with a survey approach. Questionnaires were used in collecting data on 58 MSME players in Bengkayang City who were included in the culinary, service, basic food and clothing businesses. The variables studied included entrepreneurial interest, self efficacy and MSME performance. The data analysis technique uses multiple regression tests using SPSS as an analytical tool to determine the effect of entrepreneurial interest and self efficacy on MSME performance. The results showed that entrepreneurial interest had no effect on performance while self efficacy had a positive effect on performance. The results also showed that entrepreneurial interest and self efficacy together had an effect on the performance of MSMEs in Bengkayang City. The higher the entrepreneurial interest and self efficacy, the higher the performance of MSMEs.