Tag: statistics

Front Vet Sci. 2024 Dec 6;11:1453196. doi: 10.3389/fvets.2024.1453196. eCollection 2024.

ABSTRACT

Meat rabbits are a small herbivorous livestock and have been popularly raised in China for producing high-quality meat. Therefore, it is economically important to genetically improve both carcass performance and meat quality in meat rabbits. However, we still know less about the underlying candidate genes that may determine phenotypic variation on carcass and meat traits of meat rabbits. The main objective of this study was to identify candidate genes whose mRNA expression levels may be significantly involved in regulating carcass and meat traits of meat rabbits based on the transcriptome-wide association studies (TWAS). Five carcass traits of the carcass weight (CW), dressing out percentage (DP), cut weight of hind legs (LW), weight ratio of cut hind legs to carcass (RLW), and weight of visceral and interscapular fat (WF), as well as two meat traits of the drip loss (DL) and cooking loss (CL) were phenotyped in a F1 crossbred population (N = 119) between Zika rabbits and Sichuan White rabbits. The effects of mRNA expression levels of a total of 10,288 genome-wide genes on these seven traits were statistically estimated using the mixed linear model, in which the polygenic background effects were accounted for. Our results revealed two candidate genes (RDH5 and MTARC2) that were statistically significantly associated with LW trait (the adjusted p values <0.05), whereas no gene reached the statistically significant threshold for all the remaining six traits. Because of the relatively small sample size analyzed, we alternatively selected 20 candidate genes with the lowest p values for every trait and subjected them to functional enrichment analyses, which identified three Gene Ontology (GO) terms that were significantly enriched by the candidate genes of CW and RLW traits. In conclusion, this study used TWAS approach to successfully reveal several candidate genes whose mRNA expression levels may be involved in regulating carcass and meat traits in meat rabbits, which are helpful to explore the underlying molecular mechanism in the future studies.

PMID:39711797 | PMC:PMC11660804 | DOI:10.3389/fvets.2024.1453196

Front Neurol. 2024 Dec 6;15:1503975. doi: 10.3389/fneur.2024.1503975. eCollection 2024.

ABSTRACT

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. With the continuous development of neuromodulation technology, Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a potential non-invasive treatment for ADHD. However, there is a lack of research on the mechanism of rTMS for ADHD. Functional near infrared spectroscopy (fNIRS) is an optical imaging technique that reflects the brain function by measuring changes in blood oxygen concentration in brain tissue. Consequently, this research utilized fNIRS to examine the impact of rTMS on the core symptoms and prefrontal cortex activation in children with ADHD, which provides a reference for the clinical application of rTMS in the treatment of ADHD.

METHODS: Forty children with ADHD were chosen as research subjects and randomly assigned to two groups: a treatment group (20 subjects) and a control group (20 subjects). The control group received non-pharmacological interventions, whereas the treatment group was administered rTMS in conjunction with non-pharmacological interventions. Clinical symptom improvement was evaluated using SNAP-IV scale scores both before and after treatment. Additionally, fNIRS was utilized to monitor alterations in the relative concentrations of oxyhemoglobin (HbO₂) and deoxyhemoglobin (HbR) in the prefrontal cortex during resting state and during the Go/no-go task state, both pre- and post-treatment.

RESULTS: In conclusion, the study comprised 17 participants in the treatment group and 18 in the control group. Initially, the SNAP-scale scores were comparable between the groups, with no significant differences observed (p > 0.05). Post-treatment, a notable reduction in SNAP-scale scores was evident (p < 0.05), with the treatment group exhibiting a more pronounced decrease (p < 0.05). Following the intervention, both groups demonstrated enhanced Resting-state functional connectivity (RSFC) in the prefrontal cortex, as indicated by a significant increase compared to pre-treatment levels (p < 0.05). Specifically, the treatment group showed superior RSFC in the left dorsolateral prefrontal cortex, right dorsolateral prefrontal cortex, left medial prefrontal cortex, and right medial prefrontal cortex compared to the control group (p < 0.05). However, no significant differences were noted in RSFC of the left and right temporal lobes between the two groups (p > 0.05). In the Go/no-go task, the treatment group recorded higher mean HbO₂ concentrations in the aforementioned prefrontal cortical regions compared to the control group (p < 0.05). Conversely, no statistically significant disparities were observed in the left and right temporal lobes of both groups.

CONCLUSION: rTMS shows promise as a treatment for ADHD by modulating prefrontal cortical activation. fNIRS provides a valuable method for assessing these effects, offering insights into the neurobiological mechanisms underlying rTMS therapy.

PMID:39711791 | PMC:PMC11659132 | DOI:10.3389/fneur.2024.1503975

Front Neurol. 2024 Dec 6;15:1479476. doi: 10.3389/fneur.2024.1479476. eCollection 2024.

ABSTRACT

BACKGROUND: Relapsing multiple sclerosis (RMS) is a chronic, inflammatory disease of the central nervous system. Ublituximab, an anti-CD20 monoclonal antibody (mAb), is indicated for the treatment of RMS. We performed a systematic literature review (SLR) to identify randomized trials reporting the clinical efficacy and tolerability of ublituximab or comparator disease-modifying therapies (DMTs) for treatment of RMS, and assessed their comparative effects using network meta-analysis (NMA).

METHODS: The SLR involved a comprehensive search across various medical databases to identify relevant studies. Included studies were randomized controlled trials (RCTs) of an adult RMS population, focusing on treatment with at least one of ublituximab, alemtuzumab, natalizumab, ocrelizumab, or ofatumumab. For outcomes included in the NMA (annualized relapse rate (ARR), confirmed disability progression (CDP), and treatment discontinuation rate), rate ratios (RR) or hazard ratios (HR), along with their 95% confidence intervals (CIs), were calculated. We performed NMA using a contrast-based random-effects model within a frequentist framework for all outcomes. Ranking probabilities among comparators, and intervention rankings for the NMA, were estimated using surface under the cumulative ranking curve (SUCRA).

RESULTS: We included 15 RCTs in the review. For the ARR outcome, there was no statistically significant difference between ublituximab and the other included mAbs [ofatumumab (RR 1.02 (95% CI 0.64-1.62)), natalizumab (RR 0.99 (0.59-1.65)), alemtuzumab (RR 0.86 (0.51-1.46)), and ocrelizumab (RR 0.75 (0.44-1.28))]. For CDP at 6 months, our results showed no statistically significant difference between ublituximab and the comparator mAbs [ofatumumab (HR 0.97 (0.49-1.92)), natalizumab (HR 1.13 (0.53-2.40)), alemtuzumab (HR 1.25 (0.56-2.81)), and ocrelizumab (HR 1.29 (0.57-2.90))]. For CDP at 3 and 6 months, there was no statistically significant difference between ublituximab and placebo. The all-cause treatment discontinuation rate analysis showed no significant difference between ublituximab and other mAbs, except for alemtuzumab.

CONCLUSIONS: Results of this SLR-informed NMA showed that there is no statistically significant difference between ublituximab and the other mAbs in terms of clinical efficacy. Additionally, the findings show that there is no statistically significant difference in discontinuation rates with the exception of the comparison with alemtuzumab, which may be attributed to its unique dosing schedule.

PMID:39711787 | PMC:PMC11659144 | DOI:10.3389/fneur.2024.1479476

Int J Cardiol Congenit Heart Dis. 2024 Jul 26;17:100533. doi: 10.1016/j.ijcchd.2024.100533. eCollection 2024 Sep.

ABSTRACT

BACKGROUND: The Norwood operation (NO) for infants with univentricular physiology has high interstage mortality. This study evaluated outcomes and risk factors for mortality following NO.

METHODS: Retrospective single-center study of patients undergoing NO from 2010 to 2020. Analysis used appropriate statistics.

RESULTS: Of 269 patients undergoing NO, 213 (79.2 %) survived to discharge. Non-survivors had longer bypass times, delayed sternal closure, required nitric oxide, higher vasoactive scores, required post-operative catheterization, Extracorporeal Life Support (ECLS), and longer ventilation (p < 0.05). Logistic regression showed moderate-severe atrioventricular valve regurgitation on intraoperative TEE (OR 2.6), requiring nitric oxide (OR 2.63), delayed sternal closure (OR 2.94), post-operative catheterization (OR 10.48), and ECLS (OR 14.54) increased mortality odds (p < 0.05). Multivariable analysis confirmed catheterization (aOR 10.48) and ECLS (aOR 14.54) as significant predictors. Of survivors, 26 (12.3 %) developed new morbidity, 9 (4.2 %) had unfavorable outcomes. Functional status improved from 6.0 to 8.04, mainly in feeding and respiratory domains (p < 0.0001).

CONCLUSIONS: Norwood survival was 79.2 %. Requiring post-operative catheterization and ECLS significantly increased mortality risk. Multicenter evaluation of these modifiable risk factors is needed to improve outcomes in this high-risk population.

PMID:39711779 | PMC:PMC11658261 | DOI:10.1016/j.ijcchd.2024.100533

Brain Neurosci Adv. 2024 Dec 20;8:23982128241305890. doi: 10.1177/23982128241305890. eCollection 2024 Jan-Dec.

ABSTRACT

Humans feel visceral disgust when faced with potential contaminants like bodily effluvia. The emotion serves to reject potentially contaminated food and is paired with proto-nausea: alterations in gastric rhythm in response to disgust. Here, we offer a narrative synthesis of the existing literature on the effects of disgust on the stomach as measured through electrogastrography, a non-invasive technique that measures stomach activity with electrodes placed on the abdominal skin surface. After identifying and assessing 368 studies for eligibility and inclusion based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process, we reviewed a final sample of only 10 articles that employed electrogastrography to assess gastric responses to unpleasant stimuli, including disgust elicitors. Reviewed findings illustrate that changes in gastric rhythm are associated with negatively valenced emotions, and most reliably with visceral disgust elicitors. This rhymes with recent evidence for a causal role of gastric state in reductions in visceral disgust avoidance. Because limitations in the reviewed body of work come from the low number of studies and relatively small sample sizes, we strongly encourage studies of proto-nausea in designs with higher statistical power, ideally paired with experimental manipulations of gastric state.

PMID:39711753 | PMC:PMC11662309 | DOI:10.1177/23982128241305890

medRxiv [Preprint]. 2024 Dec 12:2024.12.11.24318870. doi: 10.1101/2024.12.11.24318870.

ABSTRACT

Complex disease genetics is a key area of research for reducing disease and improving human health. Genome-wide association studies (GWAS) help in this research by identifying regions of the genome that contribute to complex disease risk. However, GWAS are computationally intensive and require access to individual-level genetic and health information, which presents concerns about privacy and imposes costs on researchers seeking to study complex diseases. Publicly released pan-biobank GWAS summary statistics provide immediate access to results for a subset of phenotypes, but they do not inform about all phenotypes or hand-crafted phenotype definitions, which are often more relevant to study. Here, we present WebGWAS, a new tool that allows researchers to obtain GWAS summary statistics for a phenotype of interest without needing access to individual-level genetic and phenotypic data. Our public web app can be used to study custom phenotype definitions, including inclusion and exclusion criteria, and to produce approximate GWAS summary statistics for that phenotype. WebGWAS computes approximate GWAS summary statistics very quickly ( < 10 seconds), and it does not store private health information. We also show how the statistical approximation underlying WebGWAS can be used to accelerate the computation of multi-phenotype GWAS among correlated phenotypes. Our tool provides a faster approach to GWAS for researchers interested in complex disease, providing approximate summary statistics in short order, without the need to collect, process, and produce GWAS results. Overall, this method advances complex disease research by facilitating more accessible and cost-effective genetic studies using large observational data.

PMID:39711729 | PMC:PMC11661389 | DOI:10.1101/2024.12.11.24318870

medRxiv [Preprint]. 2024 Dec 11:2024.12.09.24318621. doi: 10.1101/2024.12.09.24318621.

ABSTRACT

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC). Additionally, we explored their linked gene expression patterns in silico . Whole-brain multivariate distance matrix regression revealed a transdiagnostic association between autism severity and iFC of two nodes: the middle frontal gyrus of the frontoparietal network and posterior cingulate cortex of the default mode network. Across children, the greater the iFC between these nodes, the more severe the autism symptoms, even after controlling for ADHD symptoms. Results from segregation analyses were consistent with primary findings, underscoring the significance of internetwork iFC interactions for autism symptom severity across diagnoses. No statistically significant brain-behavior relationships were observed for ADHD symptoms. Genetic enrichment analyses of the iFC maps associated with autism symptoms implicated genes known to: (i) have greater rate of variance in autism and ADHD, and (ii) be involved in neuron projection, suggesting shared genetic mechanisms for this specific brain-clinical phenotype. Overall, these findings underscore the relevance of transdiagnostic dimensional approaches in linking clinically-defined phenomena to shared presentations at the macroscale circuit- and genomic-levels among children with diagnoses of autism and ADHD.

PMID:39711728 | PMC:PMC11661353 | DOI:10.1101/2024.12.09.24318621

medRxiv [Preprint]. 2024 Dec 14:2024.12.13.24319000. doi: 10.1101/2024.12.13.24319000.

ABSTRACT

IMPORTANCE: Persons with substance use disorders (SUD) often suffer from additional comorbidities, including psychiatric conditions and physical health problems. Researchers have explored this overlap in electronic health records (EHR) using phenome wide association studies (PheWAS) to characterize how different indicators are related to all conditions in an individual’s EHR. However, analyses have been largely cross-sectional in nature.

OBJECTIVE: To characterize whether various social and genetic risk factors are associated with time to comorbid diagnoses in electronic health records (EHR) after the first diagnosis of SUD.

DESIGN: Leveraging those with EHR and whole-genome sequencing data in All of Us (N = 287,012), we explored whether social determinants of health are associated with lifetime risk of SUD. Next, within those with a diagnosed SUD (N = 17,460), we examined whether polygenic scores (PGS) were associated with time to comorbid diagnoses performing a phenome-wide survival analysis.

SETTING: Participating health care organizations across the United States.

PARTICIPANTS: Participants in the All of Us Research Program with available EHR and genomic data.

EXPOSURES: Social determinants of health and polygenic scores (PGS) for psychiatric and substance use disorders.

MAIN OUTCOMES AND MEASURES: Phecodes for diagnoses derived from International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from EHR.

RESULTS: Multiple social and demographic risk factors were associated with lifetime SUD diagnosis. Most strikingly, those reporting an annual income <$10K had 4.5 times the odds of having an SUD diagnosis compared to those reporting $100-$150K annually (OR = 4.48, 95% CI = 4.01, 5.01). PGSs for alcohol use disorders, schizophrenia, and post-traumatic stress disorder were associated with time to their respective diagnoses (HR _AUD = 1.10, 95% CI = 1.06, 1.14; HR _SCZ = 1.13, 95% CI = 1.06, 1.20; HR _PTSD = 1.15, 95% CI = 1.08, 1.22). A PGS for ever-smoking was associated with time to subsequent smoking related comorbidities and additional SUD diagnoses HR _SMOK = 1.6 to 1.16).

CONCLUSIONS AND RELEVANCE: Social determinants, especially those related to income have profound associations with lifetime SUD risk. Additionally, PGS may include information related to outcomes above and beyond lifetime risk, including timing and severity.

PMID:39711727 | PMC:PMC11661425 | DOI:10.1101/2024.12.13.24319000

J Pediatr Endocrinol Metab. 2024 Dec 24. doi: 10.1515/jpem-2024-0314. Online ahead of print.

ABSTRACT

OBJECTIVES: Exocrine pancreatic insufficiency has been demonstrated in type 1 diabetes (T1D); lower concentrations of pancreatic enzymes have been associated with metabolic risk (MR). Influence of puberty and MR factors on serum concentrations of amylase and lipase remain unexplored in Indian youth with T1D. 1) To characterize and predict determinants of serum amylase and lipase concentrations in adolescents/youth with T1D. 2) To assess relationship between amylase, lipase, and prevalence of MR.

METHODS: Cross sectional, observational study on 291 (155 girls) adolescents/youth (10-24 years) with T1D. History, examination, body composition, biochemistry (glycated hemoglobin [HbA1c], thyroid stimulating hormone [TSH], lipids).

RESULTS: Mean age, diabetes duration and HbA1c were 15.3, 7.0 years and 10.0 ± 2.1, respectively. Relative risk of lower amylase/higher lipase concentrations (<median) in participants with poor glycemic control (HbA1c>9.5 %) was 1.42 and 1.34, respectively, though these did not reach statistical significance. In pubertal participants, amylase was lower and lipase higher; association was not found with MR. Higher TSH and lower serum calcium were significantly associated with higher lipase (p<0.001).

CONCLUSIONS: We have characterized amylase and lipase concentrations across puberty; poor glycemic control tended to be associated with lower amylase and higher lipase, though these findings did not reach statistical significance. Amylase and lipase concentrations should be monitored in Indian adolescents with T1D, particularly in those with poor metabolic control, puberty, uncontrolled hypothyroidism, or reduced calcium intake, while further longitudinal and larger studies are needed to generalize these findings.

PMID:39710861 | DOI:10.1515/jpem-2024-0314

Biol Trace Elem Res. 2024 Dec 22. doi: 10.1007/s12011-024-04495-9. Online ahead of print.

ABSTRACT

Previous studies have proved trace mineral disorders to be related to changes in oxidative stress, inflammatory state, and immune response in asthmatics. However, there is a scarcity of studies that examine the correlation between copper intake with mortality in asthmatic people. The aim of this research was to investigate the effect of copper intake on the asthmatic population’s mortality. This investigation included 3175 individuals from the NHANES. Multiple statistical models were used in this investigation to discuss the correlation between copper intake and the asthmatic population’s mortality. These models included Cox proportional hazards models, trend tests, restricted cubic splines (RCS), threshold effect model, and CoxBoost model. Three Cox hazard models showed an inverse relationship between copper intake and the risk of death in asthmatics. Statistical tests, such as trend tests, RCS models, and threshold effect models, proved an inverse and linear link between dietary copper and the risk of death. Through Kaplan-Meier analysis, asthmatic adults who had higher copper intake had a higher survival rate compared to asthmatics with lower copper intake. The CoxBoost model indicated that the intake of copper, selenium, and zinc had a protective effect on mortality, whereas iron was associated with an increased risk of death. The research proved an inverse and linear correlation between dietary copper intake and the risk of death among asthmatic people. Improving copper intake may have a positive impact on the long-term survival of individuals with asthma.

PMID:39710816 | DOI:10.1007/s12011-024-04495-9