Statistical methods to detect mother-father genetic interaction effects on risk of infertility: A genome-wide approach.

Infertility is a heterogeneous phenotype, and for many couples, the causes of fertility problems remain unknown. One understudied hypothesis is that allelic interactions between the genotypes of the two parents may influence the risk of infertility. Our aim was, therefore, to investigate how allelic interactions can be modeled using parental genotype data linked to 15,789 pregnancies selected from the Norwegian Mother, Father, and Child Cohort Study. The newborns in 1304 of these pregnancies were conceived using assisted reproductive technologies (ART), and the remainder were conceived naturally. Treating the use of ART as a proxy for infertility, different parameterizations were implemented in a genome-wide screen for interaction effects between maternal and paternal alleles at the same locus. Some of the models were more similar in the way they were parameterized, and some produced similar results when implemented on a genome-wide scale. The results showed near-significant interaction effects in genes relevant to the phenotype under study, such as Dynein axonemal heavy chain 17 (DNAH17) with a recognized role in male infertility. More generally, the interaction models presented here are readily adaptable to the study of other phenotypes in which maternal and paternal allelic interactions are likely to be involved.

High-Performance Li-Ion and Na-Ion Capacitors Based on a Spinel Li4Ti5O12 Anode and Carbonaceous Cathodes.

Lithium-ion hybrid capacitors (LICs) have become promising electrochemical energy storage systems that overcome the limitations of lithium-ion batteries and electrical double-layer capacitors. The asymmetric combination of these devices enhances the overall electrochemical performance by delivering simultaneous energy and power capabilities. Lithium titanate (Li4Ti5O12, LTO), a spinel zero-strain material, has been studied extensively as an anode material for LIC applications because of its high-rate capability, negligible volume change, and enhanced cycling performance. Here, the different synthetic methods and modifications of the intercalation-type LTO to enhance the overall electrochemical performance of LICs are mainly focused. Moreover, the cathodic part (i.e., the activated carbon derived from various sources, including natural products, polymers, and inorganic materials) is also dealt with as it contributes substantially to the overall performance of the LIC. Not only do the anode and cathode, but also the electrolytes have a substantial influence on LIC performance. The electrolytes used in LTO-based LICs as well as in flexible and bendable configurations are also mentioned. Overall, the previous work along with other available reports on LTO-based LICs in a simplified way is analyzed.

Mechanically Exfoliated Graphite for Highly Reversible Na-Storage with Carbon Coated Na3V2(PO4)3 Cathode with Low-Temperature Conditions.

Tremendous efforts are put forward to develop novel high-performance electrodes for Na-ion batteries (SIBs) in order to replace commercial Li-ion batteries (LIBs). Graphite, the most versatile anode for LIBs, fails to accommodate Na+ions owing to the poor thermodynamic stability of the binary graphite intercalation compound. This study aims to exfoliate the layers of graphite through a simple mechanical process at different time intervals (1, 5, 10, 20, 40, and 80 h) and examine the potential candidate for Na-storage in the presence of carbonate-based electrolytes. This study reports that ball milling plays a vital role in the performance of the graphite in Na-storage. The graphite exfoliated for 80 h (EG-80h) rendered an excellent reversible capacity of 209 mAh g-1 with coulombic efficiency of >99% after 100 cycles in EC-based electrolyte. In situ impedance analysis is performed to validate the charge storage mechanism and Na-ion kinetics. The performance of EG-80h in a full-cell assembly is evaluated with a carbon-coated Na3V2(PO4)3 cathode, which exhibited an initial capacity of ≈75 mAh g-1 and energy density of 201 Wh kg-1. In addition, the adaptability of the NVPC/EG-80h cell at different temperatures is examined from -10 to 50 °C, displaying excellent performance in both high and low-temperature conditions.

Controlled Synthesis of SnO2 Nanostructures as Alloy Anode via Restricted Potential Toward Building High-Performance Dual-Ion Batteries with Graphite Cathode.

Dual-ion batteries (DIBs) are considered one of the promising energy storage devices in which graphite serves as a bi-functional electrode, i.e., anode and cathode in the aprotic organic solvents. Unlike conventional lithium-ion batteries (LIBs), DIBs reversibly store the cations and anions in the anode and cathodes during redox reactions, respectively. The electrolyte is a source for both cations and anions, so the choice of electrolyte plays a vital role. In the present work, the synthesis of SnO2 nanostructures is reported as a possible alternative for graphite anode, and the Li-storage performance is optimized in half-cell (Li/SnO2 ) assembly with varying amounts of conductive additive (acetylene black) and limited working potential (1 V vs Li). Finally, a DIB using recovered graphite (RG) fabricated from spent LIB as a cathode and SnO2 nanostructures as an anode under balanced loading conditions. Prior to the fabrication, both electrodes are pre-cycled to eliminate irreversibility. An in-situ impedance study has been employed to validate the passivation layer formation during the charge-discharge process. The high-performance SnO2 /RG-based DIB delivered a maximum discharge capacity of 380 mAh g-1 . The electrochemical performance of DIB has been assessed by varying temperature conditions to evaluate their suitability in different climatic conditions.

Impaired glucose tolerance and cardiovascular risk factors in relation to infertility: a Mendelian randomization analysis in the Norwegian Mother, Father, and Child Cohort Study.

STUDY QUESTION: Are impaired glucose tolerance (as measured by fasting glucose, glycated hemoglobin, and fasting insulin) and cardiovascular disease risk (as measured by low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure) causally related to infertility? SUMMARY ANSWER: Genetic instruments suggest that higher fasting insulin may increase infertility in women. WHAT IS KNOWN ALREADY: Observational evidence suggests a shared etiology between impaired glucose tolerance, cardiovascular risk, and fertility problems. STUDY DESIGN, SIZE, DURATION: This study included two-sample Mendelian randomization (MR) analyses, in which we used genome-wide association summary data that were publicly available for the biomarkers of impaired glucose tolerance and cardiovascular disease, and sex-specific genome-wide association studies (GWASs) of infertility conducted in the Norwegian Mother, Father, and Child Cohort Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 68 882 women (average age 30, involved in 81 682 pregnancies) and 47 474 of their male partners (average age 33, 55 744 pregnancies) who had available genotype data and who provided self-reported information on time-to-pregnancy and use of ARTs. Of couples, 12% were infertile (having tried to conceive for ≥12 months or used ARTs to conceive). We applied the inverse variance weighted method with random effects to pool data across variants and a series of sensitivity analyses to explore genetic instrument validity. (We checked the robustness of genetic instruments and the lack of unbalanced horizontal pleiotropy, and we used methods that are robust to population stratification.) Findings were corrected for multiple comparisons by the Bonferroni method (eight exposures: P-value < 0.00625). MAIN RESULTS AND THE ROLE OF CHANCE: In women, increases in genetically determined fasting insulin levels were associated with greater odds of infertility (+1 log(pmol/l): odds ratio 1.60, 95% CI 1.17 to 2.18, P-value = 0.003). The results were robust in the sensitivity analyses exploring the validity of MR assumptions and the role of pleiotropy of other cardiometabolic risk factors. There was also evidence of higher glucose and glycated hemoglobin causing infertility in women, but the findings were imprecise and did not pass our P-value threshold for multiple testing. The results for lipids and blood pressure were close to the null, suggesting that these did not cause infertility. LIMITATIONS, REASONS FOR CAUTION: We did not know if underlying causes of infertility were in the woman, man, or both. Our analyses only involved couples who had conceived. We did not have data on circulating levels of cardiometabolic risk factors, and we opted to conduct an MR analysis using GWAS summary statistics. No sex-specific genetic instruments on cardiometabolic risk factors were available. Our results may be affected by selection and misclassification bias. Finally, the characteristics of our study sample limit the generalizability of our results to populations of non-European ancestry. WIDER IMPLICATIONS OF THE FINDINGS: Treatments for lower fasting insulin levels may reduce the risk of infertility in women. STUDY FUNDING/COMPETING INTEREST(S): The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. This work was supported by the European Research Council [grant numbers 947684, 101071773, 293574, 101021566], the Research Council of Norway [grant numbers 262700, 320656, 274611], the South-Eastern Norway Regional Health Authority [grant numbers 2020022, 2021045], and the British Heart Foundation [grant numbers CH/F/20/90003, AA/18/1/34219]. Open Access funding was provided by the Norwegian Institute of Public Health. The funders had no role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the article for publication. D.A.L. has received research support from National and International government and charitable bodies, Roche Diagnostics and Medtronic for research unrelated to the current work. O.A.A. has been a consultant to HealthLytix. The rest of the authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: N/A.

The X-factor in ART: does the use of assisted reproductive technologies influence DNA methylation on the X chromosome?

BACKGROUND: Assisted reproductive technologies (ART) may perturb DNA methylation (DNAm) in early embryonic development. Although a handful of epigenome-wide association studies of ART have been published, none have investigated CpGs on the X chromosome. To bridge this knowledge gap, we leveraged one of the largest collections of mother-father-newborn trios of ART and non-ART (natural) conceptions to date to investigate sex-specific DNAm differences on the X chromosome. The discovery cohort consisted of 982 ART and 963 non-ART trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa). To verify our results from the MoBa cohort, we used an external cohort of 149 ART and 58 non-ART neonates from the Australian 'Clinical review of the Health of adults conceived following Assisted Reproductive Technologies' (CHART) study. The Illumina EPIC array was used to measure DNAm in both datasets. In the MoBa cohort, we performed a set of X-chromosome-wide association studies ('XWASs' hereafter) to search for sex-specific DNAm differences between ART and non-ART newborns. We tested several models to investigate the influence of various confounders, including parental DNAm. We also searched for differentially methylated regions (DMRs) and regions of co-methylation flanking the most significant CpGs. Additionally, we ran an analogous model to our main model on the external CHART dataset. RESULTS: In the MoBa cohort, we found more differentially methylated CpGs and DMRs in girls than boys. Most of the associations persisted after controlling for parental DNAm and other confounders. Many of the significant CpGs and DMRs were in gene-promoter regions, and several of the genes linked to these CpGs are expressed in tissues relevant for both ART and sex (testis, placenta, and fallopian tube). We found no support for parental DNAm-dependent features as an explanation for the observed associations in the newborns. The most significant CpG in the boys-only analysis was in UBE2DNL, which is expressed in testes but with unknown function. The most significant CpGs in the girls-only analysis were in EIF2S3 and AMOT. These three loci also displayed differential DNAm in the CHART cohort. CONCLUSIONS: Genes that co-localized with the significant CpGs and DMRs associated with ART are implicated in several key biological processes (e.g., neurodevelopment) and disorders (e.g., intellectual disability and autism). These connections are particularly compelling in light of previous findings indicating that neurodevelopmental outcomes differ in ART-conceived children compared to those naturally conceived.

Associations between epigenetic age acceleration and infertility.

STUDY QUESTION: Is the use of ART, a proxy for infertility, associated with epigenetic age acceleration? SUMMARY ANSWER: The epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers. WHAT IS KNOWN ALREADY: Among mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined. STUDY DESIGN, SIZE, DURATION: The Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents. MAIN RESULTS AND THE ROLE OF CHANCE: We found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E-06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E-05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E-04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations. LIMITATIONS, REASONS FOR CAUTION: We were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents' peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women. WIDER IMPLICATIONS OF THE FINDINGS: A plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S): This study was partly funded by the Research Council of Norway (Women's fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Maternal Anxiety and Infants Birthweight and Length of Gestation. A sibling design.

BACKGROUND: The overall aim of this study is to examine the effect of prenatal maternal anxiety on birthweight and gestational age, controlling for shared family confounding using a sibling comparison design. METHODS: The data on 77,970 mothers and their 91,165 children from the population-based Mother, Father and Child Cohort Study and data on 12,480 pairs of siblings were used in this study. The mothers filled out questionnaires for each unique pregnancy, at 17th and 30th week in pregnancy. Gestational age and birth weight was extracted from the Medical Birth Registry of Norway (MBRN). Associations between prenatal maternal anxiety (measured across the 17th and 30th weeks) and birth outcomes (birthweight and gestational age) were examined using linear regression with adjustment for shared-family confounding in a sibling comparison design. RESULTS: In the population level analysis the maternal anxiety score during pregnancy was inversely associated with new-born's birthweight (Beta = -63.8 95% CI: -92.6, -35.0) and gestational age (Beta = -1.52, 95% CI: -2.15, -0.89) after adjustment for several covariates. The association of the maternal anxiety score with birthweight was no longer significant, but remained for maternal anxiety at 30th week with gestational age (Beta = -1.11, 95% CI: -1.82, -0.4) after further adjusting for the shared-family confounding in the sibling comparison design. CONCLUSION: No association was found for maternal prenatal anxiety with birth weight after multiple covariates and family environment were controlled. However, there was an association between prenatal maternal anxiety at 30th week only with gestational age, suggesting a timing effect for maternal anxiety in third trimester.

Blood-based epigenetic estimators of chronological age in human adults using DNA methylation data from the Illumina MethylationEPIC array.

BACKGROUND: Epigenetic clocks have been recognized for their precise prediction of chronological age, age-related diseases, and all-cause mortality. Existing epigenetic clocks are based on CpGs from the Illumina HumanMethylation450 BeadChip (450 K) which has now been replaced by the latest platform, Illumina MethylationEPIC BeadChip (EPIC). Thus, it remains unclear to what extent EPIC contributes to increased precision and accuracy in the prediction of chronological age. RESULTS: We developed three blood-based epigenetic clocks for human adults using EPIC-based DNA methylation (DNAm) data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Gene Expression Omnibus (GEO) public repository: 1) an Adult Blood-based EPIC Clock (ABEC) trained on DNAm data from MoBa (n = 1592, age-span: 19 to 59 years), 2) an extended ABEC (eABEC) trained on DNAm data from MoBa and GEO (n = 2227, age-span: 18 to 88 years), and 3) a common ABEC (cABEC) trained on the same training set as eABEC but restricted to CpGs common to 450 K and EPIC. Our clocks showed high precision (Pearson correlation between chronological and epigenetic age (r) > 0.94) in independent cohorts, including GSE111165 (n = 15), GSE115278 (n = 108), GSE132203 (n = 795), and the Epigenetics in Pregnancy (EPIPREG) study of the STORK Groruddalen Cohort (n = 470). This high precision is unlikely due to the use of EPIC, but rather due to the large sample size of the training set. CONCLUSIONS: Our ABECs predicted adults' chronological age precisely in independent cohorts. As EPIC is now the dominant platform for measuring DNAm, these clocks will be useful in further predictions of chronological age, age-related diseases, and mortality.

Highly Perforated V2 O5 Cathode with Restricted Lithiation toward Building "Rocking-Chair" Type Cell with Graphite Anode Recovered from Spent Li-Ion Batteries.

Current research motivation on fabricating next-generation lithium-ion batteries by averting the growing demand for battery raw materials brings enormous interest on the V2 O5 cathode again as a result of its abundance, ease synthesis, and tunable Li-intercalation properties. So far, the research activities are mainly focused on V2 O5 to attain a maximum capacity (>300 mAh g-1 ) for more than 1 mol. Li-intercalation which results in poor structural stability. Keeping this issue in mind, here, the full-cell assembly by limiting 1 mol is proposed and constructed. Li-insertion in V2 O5 as a cathode and LiC6 as an anode for the first time. Prior to the full-cell assembly, hydrothermally prepared rod-like V2 O5 reveals the specific capacity of 143 mAh g-1 in half-cell configuration with good cycling stability. The full-cell, V2 O5 /LiC6, offers a specific capacity of ≈236 mAh g-1 with a maximum energy density of ≈197.1 Wh kg-1 . Furthermore, the practical feasibility of the cell has been examined at different temperatures that divulged a maximum energy density of 136 Wh kg-1 at 50 °C. Also, the obtained results encourage V2 O5 as a strong contender for the commercial LiFePO4 /C system andpave the new directions for advanced battery technology.

Nanoengineered Organic Electrodes for Highly Durable and Ultrafast Cycling of Organic Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have become increasingly important as next-generation energy storage systems for application in large-scale energy storage. It is very crucial to develop an eco-friendly and green SIB technique with superior performance for sustainable future use. Replacing the conventional inorganic electrode materials with green and safe organic electrodes will be a promising approach. However, the poor electrochemical kinetics, unstable electrode-electrolyte interface, high solubility of the electrodes in the electrolyte, and large amount of conductive carbon present great challenges for organic SIBs. In this study, the issues of organic electrodes are addressed through atomic-level manipulation of these organic molecules using a series of ultrathin (Å-level) metal oxide coatings (Al2 O3 , ZnO, and TiO2 ). Uniform and precise coatings on the perylene-3,4,9,10-tetracarboxylicacid dianhydride by gas-phase atomic layer deposition technique shows a stable interphase, enhanced electrochemical kinetics (71C, 10 A g-1 ), and excellent stability (89%-500 cycles) compared to conventional organic electrode (70%-200 cycles). Further studies reveal that the chemical stability of the metal oxide coating layer plays a critical role in influencing the redox behavior, and improving kinetics of organic electrodes. This study opens a new avenue for developing high-energy organic SIBs with performance equivalent to inorganic counterparts.

Robust Construction Safety System (RCSS) for Collision Accidents Prevention on Construction Sites.

A proximity warning system to detect the presence of a worker/workers and to warn heavy equipment operators is highly needed to prevent collision accidents at construction sites. In this paper, we developed a robust construction safety system (RCSS), which can activate warning devices and automatically halt heavy equipment, simultaneously, to prevent possible collision accidents. The proximity detection of this proposed system mainly relies on ultra-wideband (UWB) sensing technologies, which enable instantaneous and simultaneous alarms on (a) a worker's personal safety (personal protection unit (PPU)) device and (b) hazard area device (zone alert unit (ZAU)). This system also communicates with electronic control sensors (ECSs) installed on the heavy equipment to stop its maneuvering. Moreover, the RCSS has been interfaced with a global positioning system communication unit (GCU) to acquire real-time information of construction site resources and warning events. This enables effective management of construction site resources using an online user interface. The performance and effectiveness of the RCSS have been validated at laboratory scale as well as at real field (construction site and steel factory). Conclusively, the RCSS can significantly enhance construction site safety by pro-actively preventing collision of a worker/workers with heavy equipment.

Hybrid Blockchain and Internet-of-Things Network for Underground Structure Health Monitoring.

The Internet-of-things (IoT) and blockchain are growing realities of modern society, and both are rapidly transforming civilization, either separately or in combination. However, the leverage of both technologies for structural health monitoring (SHM) to enable transparent information sharing among involved parties and autonomous decision making has not yet been achieved. Therefore, this study combines IoT with blockchain-based smart contracts for SHM of underground structures to define a novel, efficient, scalable, and secure distributed network for enhancing operational safety. In this blockchain-IoT network, the characteristics of locally centralized and globally decentralized distribution have been activated by dividing them into core and edge networks. This division enhances the efficiency and scalability of the system. The proposed system was effective in simulation for autonomous monitoring and control of structures. After proper design, the decentralized blockchain networks may effectively be deployed for transparent and efficient information sharing, smart contracts-based autonomous decision making, and data security in SHM.

Effect of polygenic scores of telomere length alleles on telomere length in newborns and parents.

In adults, polygenic scores (PGSs) of telomere length (TL) alleles explain about 4.5% of the variance in TL, as measured by quantitative polymerase chain reaction (qPCR). Yet, these PGSs strongly infer a causal role of telomeres in aging-related diseases. To better understand the determinants of TL through the lifespan, it is essential to examine to what extent these PGSs explain TL in newborns. This study investigates the effect of PGSs on TL in both newborns and their parents, with TL measured by Southern blotting and expressed in base-pairs (bp). Additionally, the study explores the impact of PGSs related to transmitted or non-transmitted alleles on TL in newborns. For parents and newborns, the PGS effects on TL were 172 bp (p = 2.03 × 10-15) and 161 bp (p = 3.06 × 10-8), explaining 6.6% and 5.2% of the TL variance, respectively. The strongest PGS effect was shown for maternally transmitted alleles in newborn girls, amounting to 214 bp (p = 3.77 × 10-6) and explaining 7.8% of the TL variance. The PGS effect of non-transmitted alleles was 56 bp (p = 0.0593) and explained 0.6% of the TL variance. Our findings highlight the importance of TL genetics in understanding early-life determinants of TL. They point to the potential utility of PGSs composed of TL alleles in identifying susceptibility to aging-related diseases from birth and reveal the presence of sexual dimorphism in the effect of TL alleles on TL in newborns. Finally, we attribute the higher TL variance explained by PGSs in our study to TL measurement by Southern blotting.

Synthesis and Characterization of the New Li1+xAl1+xSi1-xO4 (x = 0-0.25) Solid Electrolyte for Lithium-Ion Batteries.

A systematic study was performed to investigate the effect of the sintering temperature, sintering duration, and aluminum doping on the crystalline structure and ionic conductivity of the Li1+xAl1+xSi1-xO4 (LASO; x = 0-0.25) solid electrolyte. There was a strong indication that an increase in the sintering temperature and sintering time increased the ionic conductivity of the electrolyte. In particular, the doping concentration and composition ratio (Li1+xAl1+xSi1-xO4; x = 0-0.25) were found to be crucial factors for achieving high ionic conductivity. The sintering time of 18 h and lithium concentration influenced the lattice parameters of the LASO electrolyte, resulting in a significant improvement in ionic conductivity from 2.11 × 10-6 (for pristine LASO) to 1.07 × 10-5 S cm-1. An increase in the lithium concentration affected the stoichiometry, and it facilitated a smoother Li-ion transfer process since lithium served as an ion-conducting bridge between LASO grains.

Tracing the adaptive evolution of SARS-CoV-2 during vaccine roll-out in Norway.

Vaccination against SARS-CoV-2 has greatly mitigated the impact of the COVID-19 pandemic. However, concerns have been raised about the degree to which vaccination might drive the emergence and selection of immune escape mutations that will hamper the efficacy of the vaccines. In this study, we investigate whether vaccination impacted the micro-scale adaptive evolution of SARS-CoV-2 in the Oslo region of Norway, during the first nine months of 2021, a period in which the population went from near-zero to almost 90 per cent vaccine coverage in the population over 50 years old. Weekly aggregated data stratified by age on vaccine uptake and number of SARS-CoV-2 cases in the area were obtained from the National Immunization Registry and the Norwegian Surveillance System for Communicable Diseases, respectively. A total of 6,438 virus sequences (7.5 per cent of the registered cases) along with metadata were available. We used a causal-driven approach to investigate the relationship between vaccination progress and changes in the frequency of 362 mutations present in at least ten samples, conditioned on the emergence of new lineages, time, and population vaccination coverage. After validating our approach, we identified 21 positive and 12 negative connections between vaccination progress and mutation prevalence, and most of them were outside the Spike protein. We observed a tendency for the mutations that we identified as positively connected with vaccination to decrease as the vaccinated population increased. After modelling the fitness of different competing mutations in a population, we found that our observations could be explained by a clonal interference phenomenon in which high fitness mutations would be outcompeted by the emergence or introduction of other high-fitness mutations.

Investigating neuromodulatory effect of transauricular vagus nerve stimulation on resting-state electroencephalography.

Purpose: The purpose of this study was to investigate the neuromodulatory effects of transauricular vagus nerve stimulation (taVNS) and determine optimal taVNS duration to induce the meaningful neuromodulatroty effects using resting-state electroencephalography (EEG). Method: Fifteen participants participated in this study and taVNS was applied to the cymba conchae for a duration of 40 min. Resting-state EEG was measured before and during taVNS application. EEG power spectral density (PSD) and brain network indices (clustering coefficient and path length) were calculated across five frequency bands (delta, theta, alpha, beta and gamma), respectively, to assess the neuromodulatory effect of taVNS. Moreover, we divided the whole brain region into the five regions of interest (frontal, central, left temporal, right temporal, and occipital) to confirm the neuromodulation effect on each specific brain region. Result: Our results demonstrated a significant increase in EEG frequency powers across all five frequency bands during taVNS. Furthermore, significant changes in network indices were observed in the theta and gamma bands compared to the pre-taVNS measurements. These effects were particularly pronounced after approximately 10 min of stimulation, with a more dominant impact observed after approximately 20-30 min of taVNS application. Conclusion: The findings of this study indicate that taVNS can effectively modulate the brain activity, thereby exerting significant effects on brain characteristics. Moreover, taVNS duration of approximately 20-30 min was considered appropriate for inducing a stable and efficient neuromodulatory effects. Consequently, these findings have the potential to contribute to research aimed at enhancing cognitive and motor functions through the modulation of EEG using taVNS. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00361-8.

Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study.

In women, shorter telomeres have been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, whereas other studies have reported the opposite. In men, studies mostly report associations between shorter telomeres and sperm quality. To our knowledge, no studies have thus far investigated the associations between TL and fecundability or the use of ART. This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1,054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated the associations between leukocyte TL and fecundability, infertility, and the use of ART. We also repeated the analyses using instrumental variables for TL, including genetic risk scores for TL and genetically predicted TL. Approximately 11% of couples had experienced infertility and 4% had used ART. TL was not associated with fecundability among women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92-1.04) or men (FR, 0.99; CI, 0.93-1.06), nor with infertility among women (odds ratio [OR], 1.03; CI, 0.85-1.24) or men (OR, 1.05; CI, 0.87-1.28). We observed an increased likelihood of using ART with increasing TL among men (OR, 1.22; CI, 1.03-1.46), but not among women (OR, 1.10; CI, 0.92-1.31). No significant associations were observed using the instrumental variables. Our results indicate that TL is a poor biomarker of fecundability, infertility and use of ART in MoBa. Additional studies are required to replicate the association observed between TL and ART in men.

Placental efflux transporters and antiseizure or antidepressant medication use impact birth weight in MoBa cohort.

Low birth weight raises neonatal risks and lifelong health issues and is linked to maternal medication use during pregnancy. We examined data from the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, including 69,828 offspring with genotype data and 81,189 with maternal genotype data. We identified genetic risk variants in placental efflux transporters, calculated genetic scores based on alleles related to transporter activity, and assessed their interaction with prenatal use of antiseizure or antidepressant medication on offspring birth weight. Our study uncovered possible genetic variants in both offspring (rs3740066) and mothers (rs10248420; rs2235015) in placental efflux transporters (MRP2-ABCC2 and MDR1-ABCB1) that modulated the association between prenatal exposure to antiseizure medication and low birth weight in the offspring. Antidepressant exposure was associated with low birth weight, but there were no gene-drug interactions. The interplay between MRP2-ABCC2 and MDR1-ABCB1 variants and antiseizure medication may impact neonatal birth weight.