Category: Statistics

Genet Epidemiol. 2023 Aug 13. doi: 10.1002/gepi.22535. Online ahead of print.

ABSTRACT

We propose structural equation models (SEMs) as a general framework to infer causal networks for metabolites and other complex traits. Traditionally SEMs are used only for individual-level data under the assumption that all instrumental variables (IVs) are valid. To overcome these limitations, we propose both one- and two-sample approaches for causal network inference based on SEMs that can: (1) perform causal analysis and discover causal relationships among multiple traits; (2) account for the possible presence of some invalid IVs; (3) allow for data analysis using only genome-wide association studies (GWAS) summary statistics when individual-level data are not available; (4) consider the possibility of bidirectional relationships between traits. Our method employs a simple stepwise selection to identify invalid IVs, thus avoiding false positives while possibly increasing true discoveries based on two-stage least squares (2SLS). We use both real GWAS data and simulated data to demonstrate the superior performance of our method over the standard 2SLS/SEMs. For real data analysis, our proposed approach is applied to a human blood metabolite GWAS summary data set to uncover putative causal relationships among the metabolites; we also identify some metabolites (putative) causal to Alzheimer’s disease (AD), which, along with the inferred causal metabolite network, suggest some possible pathways of metabolites involved in AD.

PMID:37573486 | DOI:10.1002/gepi.22535

NPJ Vaccines. 2023 Aug 12;8(1):119. doi: 10.1038/s41541-023-00724-9.

ABSTRACT

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. Participants were either naïve to SARS-CoV-2 or had been infected before vaccination. SARS-CoV-2-specific memory B-cells expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a significant reduction in expression of the germinal center chemokine receptor CXCR5, and increased class switching. These B cell features correlated with neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). Vaccination-induced effective neutralization of the D614G variant in both infected and naïve participants but boosted neutralizing antibodies against the Beta and Omicron variants only in participants with prior infection. In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell expression of the lung-homing receptor CXCR3, which was sustained in the previously infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the response to vaccination can provide insight into the impact of prior infection on memory B cell homing, CSM, cTfh, and neutralization activity. These data can provide early signals to inform studies of vaccine boosting, durability, and co-morbidities.

PMID:37573434 | DOI:10.1038/s41541-023-00724-9

Sci Rep. 2023 Aug 12;13(1):13156. doi: 10.1038/s41598-023-40453-6.

ABSTRACT

The evolution of secondary sex-specific traits of dioecious species under abiotic stress conditions has received limited research, especially in the case of Amaranthus palmeri, a fast adapting and highly competing plant. Here, we have examined the interactive effects of abiotic stress on mineral accumulation, chlorophyll a and b content, and the operating capacity of Photosystem II (PSII) in both male and female A. palmeri plants grown under three different intensities of white light, and under N, K or P deficiency. Mineral profiling of the leaves and stems (with inflorescence) highlighted intra- and intersexual differences in their accumulation pattern and mineral associations. Chlorophyll a and chlorophyll b were different between the male and the female plants, being slightly lower in the latter, at high light intensity towards maturity, or under K or P deficiency. Further, slight, although statistically significant differences were recorded in the chlorophyll a/b ratio, which was lower at the higher light intensity in the female, over that in the male, plants towards maturity. Chlorophyll fluorescence parameters, i.e., steady state and maximum fluorescence increased under high light intensity, whereas the PSII operating efficiency decreased in the female plants, indicating reduced PSII capacity. Sex-specific differences in A. palmeri showed a differential response to stressful conditions because of differences in their ontogeny and physiology, and possibly due to the cost of reproduction. We suggest that the breeding system of dioecious species has weaknesses that can be used for the ecological management of dioecious weeds without relying on the use of herbicides.

PMID:37573387 | DOI:10.1038/s41598-023-40453-6

Sci Rep. 2023 Aug 12;13(1):13126. doi: 10.1038/s41598-023-40046-3.

ABSTRACT

Electromagnetic wave-based analogue computing has become an interesting computing paradigm demonstrating the potential for high-throughput, low power, and parallel operations. In this work, we propose a technique for the calculation of derivatives of temporal signals by exploiting transmission line techniques. We consider multiple interconnected waveguides (with some of them being closed-ended stubs) forming junctions. The transmission coefficient of the proposed structure is then tailored by controlling the length and number of stubs at the junction, such that the differentiation operation is applied directly onto the envelope of an incident signal sinusoidally modulated in the time domain. The physics behind the proposed structure is explained in detail and a full theoretical description of this operation is presented, demonstrating how this technique can be used to calculate higher order or even fractional temporal derivatives. We envision that these results may enable the development of further time domain wave-based analogue processors by exploiting waveguide junctions, opening new opportunities for wave-based single operators and systems.

PMID:37573358 | DOI:10.1038/s41598-023-40046-3

Biotechnol Biofuels Bioprod. 2023 Aug 12;16(1):127. doi: 10.1186/s13068-023-02377-1.

ABSTRACT

β-Carotene is one of the economically important carotenoids, having functions as the antioxidant to remove harmful free radicals and as the precursor for vitamin A and other high-valued xanthophyll such as zeaxanthin and astaxanthin. Lycopene cyclase plays an important role in the branching of β-carotene and α-carotene. Aiming to develop the microalgae with enhanced β-carotene productivity, the CrtY gene from bacterium Pantoea agglomerans was integrated into Chlamydomonas reinhardtii. The lycopene-producing E. coli harboring CrtY gene produced 1.59 times of β-carotene than that harboring DsLcyb1 from Dunaliella salina (a microalga with abundant β-carotene), confirming the superior activity of CrtY on β-carotene biosynthesis. According to the pigment analysis by HPLC, in microalgal transformants that were confirmed by molecular analysis, the expression of CrtY significantly increased β-carotene content from 12.48 mg/g to 30.65 mg/g (dry weight), which is about 2.45-fold changes. It is noted that three out of five transformants have statistically significant higher amount of lutein, even though the increment was 20% in maximum. Besides, no growth defect was observed in the transformants. This is the first report of functional expression of prokaryotic gene in eukaryotic microalgae, which will widen the gene pool targeting carotenoids biosynthesis using microalgae as the factory and thereby provide more opportunity for high-valued products engineering in microalgae.

PMID:37573357 | DOI:10.1186/s13068-023-02377-1

BDJ Open. 2023 Aug 12;9(1):37. doi: 10.1038/s41405-023-00165-5.

ABSTRACT

AIM: This study was undertaken to compare direct composite resin restorations (DCRR) and indirect composite resin restorations (ICRR) for treating permanent first molars affected by MIH in terms of clinical performance.

MATERIALS AND METHODS: This was a controlled, randomized, clinical split-mouth study. The studied sample consisted of 40 asymptomatic first permanent hypomineralised mandibular molars in 20 children aged between 7-11 years, these cases were divided randomly into two groups: Group 1 (experimental): 20 first permanent mandibular molars were restored with ICRR, and Group 2 (control): 20 first permanent mandibular molars that were restored with DCRR. The cavity was prepared using a diamond bur on a high-speed handpiece, and the prepared cavity was wiped with cotton moistened with sodium hypochlorite. The composite was applied directly with a total-etch bonding system. In the ICRR group, an impression for the prepared cavity was taken using a silicon-based material, and the restoration was adhesive with self-adhesive resin cement. The child’s satisfaction with each of the two application techniques was assessed through the scale FACES. Restorations were evaluated during follow-up periods (3, 6, and 12 months) according to Modified USHPH criteria.

RESULTS: The clinical success rate was 90% in the ICRR group versus 85% in the DCRR group after 12 months of follow-up without statistically significant differences (P = 0.218). Children were significantly more satisfied (P = 0.0351) with ICRR than DCRR.

CONCLUSIONS: Both DCRR and ICRR can be considered effective restorations with acceptable clinical performance in the restoration of hypomineralised first permanent molars with an advantage of ICRR in terms of child acceptance of the restoration application technique.

PMID:37573344 | DOI:10.1038/s41405-023-00165-5

Nat Commun. 2023 Aug 12;14(1):4873. doi: 10.1038/s41467-023-40658-3.

ABSTRACT

Multiplexed DNA fluorescence in situ hybridization (FISH) imaging technologies have been developed to map the folding of chromatin fibers at tens of nanometers and up to several kilobases in resolution in single cells. However, computational methods to reliably identify chromatin loops from such imaging datasets are still lacking. Here we present a Single-Nucleus Analysis Pipeline for multiplexed DNA FISH (SnapFISH), to process the multiplexed DNA FISH data and identify chromatin loops. SnapFISH can identify known chromatin loops from mouse embryonic stem cells with high sensitivity and accuracy. In addition, SnapFISH obtains comparable results of chromatin loops across datasets generated from diverse imaging technologies. SnapFISH is freely available at https://github.com/HuMingLab/SnapFISH .

PMID:37573342 | DOI:10.1038/s41467-023-40658-3

BMC Vet Res. 2023 Aug 12;19(1):123. doi: 10.1186/s12917-023-03673-6.

ABSTRACT

BACKGROUND: Subclinical mastitis (SCM) is one of the most economically important diseases affecting the dairy industry. The SCM does not cause visible changes in the udder or physical changes of the milk as compared to clinical mastitis, and a clear overview of the prevalence and risk factors in the different regions of Africa is still lacking. The objective of this study was to investigate the prevalence of SCM and assess the associated risk factors and dominant bacterial pathogens among cattle in Africa.

MATERIALS AND METHODS: We gathered and systematically reviewed literature concerning SCM, published in English from January 2010 through December 2020 in two databases (PubMed and Web of Science), and meta-analysis was conducted using the ‘meta’ and ‘metafor’ packages in the R statistical software.

RESULTS: A total of 258 studies were retrieved and at the end of the screening, 82 full-texts were eligible for inclusion in the meta-analysis. The prevalence of SCM was reported in 11 countries in five regions of Africa, and the random-effects model showed that the weighted pooled prevalence estimate (PPE) was 48.2% (95% CI: 43.6-52.8%). Heterogeneity was high and statistically significant as I² (proportion of observed variation) was 98.1% (95% CI: 98.0-98.3%), τ² (true between-study variance) was 0.0433 (95% CI: 0.0322-0.0611), and the Cochran Q statistic was 4362.8 (p < 0.0001). Subgroup and meta-regression analyses showed that East Africa had significantly (p = 0.0092) the highest PPE of SCM (67.7%, 95% CI: 55.7-78.7) followed by West Africa (50.5%, 95%CI: 31.4-69.5), and the lowest was in North Africa (40.3%, 95%: 32.2-48.6). Other significant moderators for SCM were age (p < 0.0001), breed (p = 0.0002), lactation stage (p = 0.019) and parity (p = 0.0008) of cattle. Staphylococcus species (prevalence 43.7%) were the most predominant pathogens, followed by Streptococcus (18.2%) and Escherichia species (9.5%).

CONCLUSION: The present study showed a high variation of SCM prevalence in various parts of Africa, although there is a need for more data in some regions. The reported prevalence is a clear sign of inappropriate management practices among cattle herds and an indicator of the threat that SCM poses to the dairy industry. The information about the predisposing factors may guide effective management and control strategies to reduce transmission of the disease.

PMID:37573335 | DOI:10.1186/s12917-023-03673-6

BMC Pregnancy Childbirth. 2023 Aug 12;23(1):583. doi: 10.1186/s12884-023-05894-x.

ABSTRACT

BACKGROUND: This study aimed to investigate the factors associated with the antenatal umbilical cord pitch value by ultrasound measurement in late pregnancy. We investigated the factors associated with the umbilical cord pitch value under prenatal ultrasound measurement.

METHODS: This study included 528 pregnant women who underwent routine antenatal ultrasound examinations in Ningbo Women and Children’s Hospital from December 2020 to August 2021. Their umbilical cord pitch values and diameter, Wharton’s jelly thickness, amniotic fluid indexes, umbilical artery blood flow parameters, and other relevant data, such as ages and gestational ages, were measured. Information about delivery methods, placenta, umbilical cord, and neonatal weight were recorded during follow-up. Statistical analysis was performed on the above data, and the factors associated with the pitch values were analyzed by linear regression.

RESULTS: This study revealed that cord torsion (p < 0.001, 95% confidence interval [CI]=-34.81 to -19.01), cord entanglement (p < 0.001, 95% CI = 10.71 to 20.11), thickening of Wharton’s jelly (p = 0.001, 95% CI = 5.39 to 20.24), and cord edema (p = 0.015, 95%CI = 2.09 to 19.44), gestational age (p = 0.024, 95%CI = 0.14 to 1.89), age of pregnant woman (p = 0.009, 95%CI= -1.15 to -0.16), and neonatal weight (p = 0.011, 95%CI = 0.002 to 0.012) were significantly correlated with the pitch values.

CONCLUSION: The umbilical cord pitch value significantly correlated with cord entanglement, cord torsion, cord edema, Wharton’s jelly thickening, gestational age, age of the pregnant woman, and neonatal weight. Notably, the pitch value by prenatal ultrasound measurement is predictive of cord morphological abnormalities such as cord entanglement, cord torsion, cord edema, and Wharton’s jelly thickening.

PMID:37573329 | DOI:10.1186/s12884-023-05894-x

Mol Autism. 2023 Aug 12;14(1):30. doi: 10.1186/s13229-023-00562-5.

ABSTRACT

BACKGROUND: Prenatal exposure to maternal metabolic conditions associated with inflammation and steroid dysregulation has previously been linked to increased autism risk. Steroid-related maternal serum biomarkers have also provided insight into the in utero steroid environment for offspring who develop autism.

OBJECTIVE: This study examines the link between autism among offspring and early second trimester maternal steroid-related serum biomarkers from pregnancies enriched for prenatal metabolic syndrome (PNMS) exposure.

STUDY DESIGN: Early second trimester maternal steroid-related serum biomarkers (i.e., estradiol, free testosterone, total testosterone, and sex hormone binding globulin) were compared between pregnancies corresponding to offspring with (N = 68) and without (N = 68) autism. Multiple logistic regression analyses were stratified by sex and gestational duration. One-way ANCOVA with post hoc tests was performed for groups defined by autism status and PNMS exposure.

RESULTS: Increased estradiol was significantly associated with autism only in males (AOR = 1.13 per 100 pg/ml, 95% CI 1.01-1.27, p = 0.036) and only term pregnancies (AOR = 1.17 per 100 pg/ml, 95% CI 1.04-1.32, p = 0.010). Autism status was significantly associated with decreased sex hormone binding globulin (AOR = 0.65 per 50 nmol/L, 95% CI 0.55-0.78, p < 0.001) overall and when stratified by sex and term pregnancy status. The inverse association between sex hormone binding globulin and autism was independent of PNMS exposure.

LIMITATIONS: The relative racial and ethnic homogeneity of Utah’s population limits the generalizability of study results. Although significant differences by autism status were identified in concentrations of sex hormone binding globulin overall and of estradiol in participant subgroups, differences by PNMS exposure failed to reach statistical significance, which may reflect insufficient statistical power.

CONCLUSION: Both elevated maternal serum estradiol in males only and low maternal serum sex hormone binding globulin in both sexes are associated with increased autism risk. Further investigation is merited to identify how steroid, metabolic, and inflammatory processes can interact to influence neurodevelopment in early second trimester.

PMID:37573326 | DOI:10.1186/s13229-023-00562-5