PELMI: Realize robust DNA image storage under general errors via parity encoding and local mean iteration.

DNA molecules as storage media are characterized by high encoding density and low energy consumption, making DNA storage a highly promising storage method. However, DNA storage has shortcomings, especially when storing multimedia data, wherein image reconstruction fails when address errors occur, resulting in complete data loss. Therefore, we propose a parity encoding and local mean iteration (PELMI) scheme to achieve robust DNA storage of images. The proposed parity encoding scheme satisfies the common biochemical constraints of DNA sequences and the undesired motif content. It addresses varying pixel weights at different positions for binary data, thus optimizing the utilization of Reed-Solomon error correction. Then, through lost and erroneous sequences, data supplementation and local mean iteration are employed to enhance the robustness. The encoding results show that the undesired motif content is reduced by 23%-50% compared with the representative schemes, which improves the sequence stability. PELMI achieves image reconstruction under general errors (insertion, deletion, substitution) and enhances the DNA sequences quality. Especially under 1% error, compared with other advanced encoding schemes, the peak signal-to-noise ratio and the multiscale structure similarity address metric were increased by 10%-13% and 46.8%-122%, respectively, and the mean squared error decreased by 113%-127%. This demonstrates that the reconstructed images had better clarity, fidelity, and similarity in structure, texture, and detail. In summary, PELMI ensures robustness and stability of image storage in DNA and achieves relatively high-quality image reconstruction under general errors.

A tumor-suppressive function for Notch3 in the parous mammary gland.

Notch3 promotes mammary luminal cell specification and forced Notch3 activation can induce mammary tumor formation. However, recent studies suggest a tumor-suppressive role for Notch3. Here, we report on Notch3 expression and functional analysis in the mouse mammary gland. Notch3 is expressed in the luminal compartment throughout mammary gland development, but switches to basal cells with initiation of post-lactational involution. Deletion of Notch3 caused a decrease of Notch activation in luminal cells and diminished luminal progenitors at puberty, as well as reduced alveolar progenitors during pregnancy. Parous Notch3-/- mammary glands developed hyperplasia with accumulation of CD24hiCD49flo cells, some of which progressed to invasive tumors with luminal features. Notch3 deletion abolished Notch activation in basal cells during involution, accompanied by altered apoptosis and reduced brown adipocytes, leading to expansion of parity-identified mammary epithelial cells (PI-MECs). Interestingly, the postpartum microenvironment is required for the stem cell activity of Notch3-/- PI-MECs. Finally, high expression of NOTCH3 is associated with prolonged survival in patients with luminal breast cancer. These results highlight an unexpected tumor-suppressive function for Notch3 in the parous mammary gland through restriction of PI-MEC expansion.

Unconventional Superconducting Diode Effects via Antisymmetry and Antisymmetry Breaking.

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

Reproductive factors and mammographic density within the International Consortium of Mammographic Density: A cross-sectional study.

BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene mutations have been associated with BC, no single gene alteration has been identified as a universal driver. RRAS2 is a RAS-related GTPase rarely found mutated in cancer. METHODS: Conditional knock-in mice were generated to overexpress wild type human RRAS2 in mammary epithelial cells. A human sample cohort was analyzed by RT-qPCR to measure RRAS2 transcriptional expression and to determine the frequency of both a single-nucleotide polymorphism (SNP rs8570) in the 3'UTR region of RRAS2 and of genomic DNA amplification in tumoral and non-tumoral human BC samples. RESULTS: Here we show that overexpression of wild-type RRAS2 in mice is sufficient to develop TNBC in 100% of females in a pregnancy-dependent manner. In human BC, wild-type RRAS2 is overexpressed in 68% of tumors across grade, location, and molecular type, surpassing the prevalence of any previously implicated alteration. Still, RRAS2 overexpression is notably higher and more frequent in TNBC and young parous patients. The increased prevalence of the alternate C allele at the SNP position in tumor samples, along with frequent RRAS2 gene amplification in both tumors and blood of BC patients, suggests a cause-and-effect relationship between RRAS2 overexpression and breast cancer. CONCLUSIONS: Higher than normal expression of RRAS2 not bearing activating mutations is a key driver in the majority of breast cancers, especially those of the triple-negative type and those linked to pregnancy.

Association of parity with the timing and type of menopause: A longitudinal cohort study.

We investigated the time-varying association between parity and timing of natural menopause, surgical menopause, and premenopausal hysterectomy among 23,728 women aged 40-65 years at enrollment in the Alberta's Tomorrow Project cohort study (2000-2022), using flexible parametric survival analysis. Overall, natural menopause was most common by study end (57.2%), followed by premenopausal hysterectomy (11.4%) and surgical menopause (5.3%). Risks of natural menopause before age 50 years were elevated for 0 births (adjusted hazard ratio at age 45: 1.33, 95% CI 1.18-1.49) and 1 birth (age 45: 1.21, 1.07-1.38), but similar for ≥3 births (age 45: 0.95, 0.85-1.06), compared to 2 births (reference). Elevated risks of surgical menopause before age 45 years for 0 births (age 40: 1.37, 1.09-1.69) and 1 birth (age 40: 1.11, 0.85-1.45) attenuated when excluding women with past infertility or recurrent pregnancy loss, and reduced risks were observed over time for ≥3 births (age 50: 0.84, 0.75-0.94). Risks of premenopausal hysterectomy were lower before age 50 years for 0 births (age 45: 0.82, 0.76-0.88) but elevated after age 40 years for ≥3 births (age 50: 1.25, 1.08-1.45). These complex associations necessitate additional research on the sociobiological impacts of childbearing on gynecologic health.

Previous pregnancies might mitigate cortical brain differences associated with surgical menopause.

Surgical menopause causes a sharp drop in estrogen levels in middle-aged women, thus preventing the gradual physiological adaptation that is characteristic of the perimenopause. Previous studies suggest that surgical menopause might increase the risk of dementia later in life. In addition, the transition to motherhood entails long-lasting endocrine and neuronal adaptations. We compared differences in whole-brain cortical volume between women who reached menopause by surgery and a group of women who reached spontaneous non-surgical menopause and determined whether these cortical differences were influenced by previous childbearing. Using surface-based neuroimaging techniques, we investigated cortical volume differences in 201 middle-aged women (134 women who experienced non-surgical menopause, 78 of whom were parous women; and 67 women who experienced surgical menopause, 39 of whom were parous women). We found significant atrophy in the frontal and temporal regions in women who experienced surgical menopause. Nulliparous women with surgical menopause showed significant lower cortical volume in the left temporal gyrus extending to the medial temporal lobe cortex, as well as in the precuneus bilaterally compared to parous women with surgical menopause; whereas our results revealed no significant differences between parous women with surgical menopause and both parous and nulliparous women who reached a non-surgical menopause. Furthermore, in the surgical menopause group, we found a negative correlation between cortical volume and age at first pregnancy in the temporal lobe. Our study suggests that the long-term brain remodeling of parity may mitigate the neural impact of the sudden drop in estrogen levels that characterizes surgical menopause.

Infertility and risk of postmenopausal breast cancer in the women's health initiative.

PURPOSE: Although infertility (i.e., failure to conceive after ≥ 12 months of trying) is strongly correlated with established breast cancer risk factors (e.g., nulliparity, number of pregnancies, and age at first pregnancy), its association with breast cancer incidence is not fully understood. Previous studies were primarily small clinic-based or registry studies with short follow-up and predominantly focused on premenopausal breast cancer. The objective of this study was to assess the relationship between infertility and postmenopausal breast cancer risk among participants in the Women's Health Initiative (analytic sample = 131,784; > 25 years of follow-up). METHODS: At study entry, participants were asked about their pregnancy history, infertility history, and diagnosed reasons for infertility. Incident breast cancers were self-reported with adjudication by trained physicians reviewing medical records. Cox proportional hazards models were used to estimate risk of incident postmenopausal breast cancer for women with infertility (overall and specific infertility diagnoses) compared to parous women with no history of infertility. We examined mediation of these associations by parity, age at first term pregnancy, postmenopausal hormone therapy use at baseline, age at menopause, breastfeeding, and oophorectomy. RESULTS: We observed a modest association between infertility (n = 23,406) and risk of postmenopausal breast cancer (HR = 1.07; 95% CI 1.02-1.13). The association was largely mediated by age at first term pregnancy (natural indirect effect: 46.4% mediated, CI 12.2-84.3%). CONCLUSION: These findings suggest that infertility may be modestly associated with future risk of postmenopausal breast cancer due to age at first pregnancy and highlight the importance of incorporating reproductive history across the life course into breast cancer analyses.

Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Strong Laser Emission Modulation by Coherent Perfect Absorption Inside Complex-Coupled Distributed Feedback Laser Diodes.

The proof-of-concept of the exploitation of Coherent Perfect Absorption (CPA) in electrically-injected distributed-feedback laser sources is reported. Capitalizing on the essence of CPA as "light extinction by light", an integrated laser-modulator scheme emerges. The key ingredient compared to conventional single-frequency laser diodes is a careful periodic in-phase modulation of both real and imaginary parts of the complex grating index profile that enables both single-frequency operation and 40 dB line purity at the Bragg frequency. It is shown that this combination is most apt for the operation of CPA as a modulation mechanism that respects the laser spectral purity. The specific proof-of-concept is based on an ultra-short external cavity formed by a metallic micro-mirror, whose role is to generate the second beam of more conventional CPA interferometric approaches. The implemented complex-coupled grating is compatible with existing industrial technologies and promising for real-life laser source applications. Furthermore, the concept can be directly transferred to other material platforms and other wavelengths ranging from terahertz to ultraviolet.

Identifying conceptual neural responses to symbolic numerals.

The goal of measuring conceptual processing in numerical cognition is distanced by the possibility that neural responses to symbolic numerals are influenced by physical stimulus confounds. Here, we targeted conceptual responses to parity (even versus odd), using electroencephalogram (EEG) frequency-tagging with a symmetry/asymmetry design. Arabic numerals (2-9) were presented at 7.5 Hz in 50 s sequences; odd and even numbers were alternated to target differential, 'asymmetry' responses to parity at 3.75 Hz (7.5 Hz/2). Parity responses were probed with four different stimulus sets, increasing in intra-numeral stimulus variability, and with two control conditions composed of non-conceptual numeral alternations. Significant asymmetry responses were found over the occipitotemporal cortex to all conditions, even for the arbitrary controls. The large physical-differences control condition elicited the largest response in the stimulus set with the lowest variability (one font). Only in the stimulus set with the highest variability (20 drawn, coloured exemplars/numeral) did the response to parity surpass both control conditions. These findings show that physical differences across small sets of Arabic numerals can strongly influence, and even account for, automatic brain responses. However, carefully designed control conditions and highly variable stimulus sets may be used towards identifying truly conceptual neural responses.

Association between parity and pregnancy-associated tumor features in high-grade serous ovarian cancer.

PURPOSE: High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer subtype. Parity is an important risk-reducing factor, but the underlying mechanism behind the protective effect is unclear. Our aim was to study if the expression of hormones and proteins involved in pregnancy were affected by the woman's parity status, and if they may be associated with tumor stage and survival. METHODS: We evaluated expression of progesterone receptor (PR), progesterone receptor membrane component 1 (PGRMC1), relaxin-2, and transforming growth factor beta 1 (TGFß1) in tumor tissue from 92 women with HGSC parous (n = 73) and nulliparous (n = 19). Key findings were then evaluated in an independent expansion cohort of 49 patients. Survival rates by hormone/protein expression were illustrated using the Kaplan-Meier method. The independent prognostic value was tested by Cox regression, using models adjusted for established poor-prognostic factors (age at diagnosis, FIGO stage, type of surgery, and macroscopic residual tumor after surgery). RESULTS: HGSC tumors from parous women were PR positive (≥ 1% PR expression in tumor cells) more often than tumors from nulliparous women (42% vs. 16%; p-value 0.04), and having more children was associated with developing PR positive tumors [i.e., ≥ 3 children versus nulliparity, adjusted for age at diagnosis and stage: OR 4.31 (95% CI 1.12-19.69)]. A similar result was seen in the expansion cohort. Parity status had no impact on expression of PGRMC1, relaxin-2 and TGFß1. No associations were seen with tumor stage or survival. CONCLUSION: Tumors from parous women with HGSC expressed PR more often than tumors from nulliparous women, indicating that pregnancies might possibly have a long-lasting impact on ovarian cancer development.

Pregnancy-induced oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function.

Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress, yet the impact of inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy is unclear. We hypothesized that healthy pregnancy transiently reduces learning and memory and these deficits are associated with pregnancy-induced elevations in inflammation and oxidative stress. Cognitive performance was tested with novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [nonpregnant (nulliparous), pregnant (near term), and 1-2 mo after pregnancy (primiparous); n = 7 or 8/group]. Plasma and CA1 proinflammatory cytokines were measured with a MILLIPLEX magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via Western blot analysis. Our results demonstrate that CA1 oxidative stress-associated markers were elevated in pregnant compared with nulliparous rats (P ≤ 0.017) but there were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (P ≤ 0.007) whereas anxiety-like behavior (P ≤ 0.034) was reduced in primiparous rats. Overall, our data suggest that maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.NEW & NOTEWORTHY Healthy pregnancy is associated with elevated maternal systemic and brain oxidative stress. During postpregnancy, brain oxidative stress remains elevated whereas systemic oxidative stress is resolved. This sustained maternal brain oxidative stress is associated with learning impairments and decreased anxiety-like behavior during the postpregnancy period.

Association between parity and female mortality: the mediative role of depressive symptoms.

STUDY QUESTION: Is parity associated with all-cause and cause-specific mortality among women in a nationally representative cohort of the US population, and does depression mediate this association? SUMMARY ANSWER: Nulliparous women have a higher risk of all-cause and cause-specific mortality, with depression partially mediating the relationship between parity and women's all-cause and cause-specific mortality. WHAT IS KNOWN ALREADY: Parity, a significant state in reproductive life, has enduring implications for women's health. There is also a complex relationship between depression, a prevalent mental and emotional disorder, and female fertility. Previous studies have elucidated the relationships between parity and depression, both of which are associated with mortality. However, findings from studies examining parity and women's mortality have been inconsistent. Moreover, few studies have investigated whether the effect of parity on mortality is mediated by depression. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study using data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort comprised adult women with available parity and survival follow-up data. Parity data were self-reported and sourced from the Reproductive Health Questionnaire. Depression scores were derived from the Patient Health Questionnaire 9, and cause-specific deaths were identified using the International Statistical Classification of Diseases, 10th Revision (ICD-10). Weighted multivariable Cox regression was applied to analyze the association between parity, depression, and mortality. Weighted linear regression was performed to examine the relationship between parity and depression. Mediation analyses were employed to determine whether and to what extent depression mediated the effect of parity on mortality. MAIN RESULTS AND THE ROLE OF CHANCE: Our study ultimately encompassed 16 962 American women. Following multivariable adjustment, compared to nulliparous women, those with one to three live births exhibited a 17% and 33% reduction in all-cause and cancer mortality, respectively (all-cause mortality: HR = 0.83, 95% CI = 0.69-0.99, P = 0.040; cancer mortality: HR = 0.67, 95% CI = 0.45-0.99, P = 0.045). Women with more than four live births demonstrated lower all-cause mortality and mortality from other (not cancer or cardiovascular disease) diseases (all-cause mortality: HR = 0.73, 95% CI = 0.58-0.93, P = 0.011; other diseases mortality: HR = 0.66, 95% CI = 0.47-0.91, P = 0.013). No correlation was detected between parity and the risk of cardiovascular disease mortality among women. Furthermore, depression was found to partially mediate the impact of parity on all-cause mortality and mortality from other diseases in women. LIMITATIONS, REASONS FOR CAUTION: Firstly, a single index of parity was used as an exposure factor, and other reproductive factors such as birth spacing, age at first birth, and mode of delivery were not taken into account. Secondly, despite accounting for important potentially confounders in our analysis, such as BMI, smoking status, and educational level, the influence of unmeasured confounders (e.g., social class, latent reproductive system diseases) on reproductive behavior or mortality cannot be dismissed. Thirdly, women's vulnerability to depression fluctuates across reproductive stages, and the effect of depression on female fertility varies over time. Due to data constraints, we were unable to obtain information on women's mental health status at different reproductive stages. Fourthly, due to the data accessibility limitations of NHANES, we were unable to specifically explore the relationship between parity and different specific types of cancer, a limitation that may obscure potential correlations. Additionally, despite our efforts to control for various confounding factors in subgroup analyses, the smaller sample sizes in some subgroups may limit the statistical power, affecting the ability to detect effects. Finally, studies exploring the association between parity and depression are cross-sectional designs, making it difficult to infer causality. These results should be interpreted with caution, and further research is warranted to corroborate our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our study underscores the elevated risk of all-cause and cause-specific mortality in nulliparous women and reveals that depression partially mediates the negative correlation between parity and women's all-cause mortality and mortality from other diseases. These results should be interpreted with caution, and further investigation is needed to support our findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2023YFC2705700), the Key Research & Developmental Program of Hubei Province (2022BCA042), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Associations of the placental metabolome with immune maturation up to one year of age in the Swedish NICE-cohort.

INTRODUCTION: Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants' metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients, but may also provide immune maturation signals. OBJECTIVES: To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI). METHODS: Untargeted metabolomics was measured using Liquid Chromatography-Mass Spectrometry. Subpopulations of T and B cells were measured using flow cytometry at birth, 48 h, one, four, and 12 months. Random forest analysis was used to link the metabolomics data with the T and B cell sub populations as well as infant and maternal characteristics. RESULTS: Modest associations (Q2 = 0.2-0.3) were found between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin. CONCLUSION: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.

Pregnancy history and estradiol influence spatial memory, hippocampal plasticity, and inflammation in middle-aged rats.

Pregnancy and motherhood can have long-term effects on cognition and brain aging in both humans and rodents. Estrogens are related to cognitive function and neuroplasticity. Estrogens can improve cognition in postmenopausal women, but the evidence is mixed, partly due to differences in age of initiation, type of menopause, dose, formulation and route of administration. Additionally, past pregnancy influences brain aging and cognition as a younger age of first pregnancy in humans is associated with poorer aging outcomes. However, few animal studies have examined specific features of pregnancy history or the possible mechanisms underlying these changes. We examined whether maternal age at first pregnancy and estradiol differentially affected hippocampal neuroplasticity, inflammation, spatial reference cognition, and immediate early gene activation in response to spatial memory retrieval in middle-age. Thirteen-month-old rats (who were nulliparous (never mothered) or previously primiparous (had a litter) at three or seven months) received daily injections of estradiol (or vehicle) for sixteen days and were tested on the Morris Water Maze. An older age of first pregnancy was associated with impaired spatial memory but improved performance on reversal training, and increased number of new neurons in the ventral hippocampus. Estradiol decreased activation of new neurons in the dorsal hippocampus, regardless of parity history. Estradiol also decreased the production of anti-inflammatory cytokines based on age of first pregnancy. This work suggests that estradiol affects neuroplasticity and neuroinflammation in middle age, and that age of first pregnancy can have long lasting effects on hippocampus structure and function.

Genomic compliance with Chargaff's second parity rule may have originated non-adaptively, but stem-loops now function adaptively.

Of Chargaff's four rules on DNA base quantity, his second parity rule (PR-2) is the most contentious. Various biometricians (e.g., Sueoka, Lobry) regarded PR-2 compliance as a non-adaptive feature of modern genomes that could be modeled through interrelations among mutation rates. However, PR-2 compliance with stem-loop potential was considered adaptively relevant by biochemists familiar with analyses of nucleic acid structure (e.g., of Crick) and of meiotic recombination (e.g., of Kleckner). Meanwhile, other biometricians had shown that PR-2 complementarity extended beyond individual bases (1-mers) to oligonucleotides (k-mers), possibly reflecting "advantageous DNA structure" (Nussinov). An "introns early" hypothesis (Reanney, Forsdyke) had suggested a primordial nucleic acid world with recombination-mediated error-correction requiring genome-wide stem-loop potential to have evolved prior to localized intrusions of protein-encoding potential (exons). Thus, a primordial genome was equivalent to one long intron. Indeed, when assessed as the base order-dependent component (correcting for local influences of GC%), modern genes, especially when evolving rapidly under positive Darwinian selection, display high intronic stem-loop potential. This suggests forced migration from neighboring exons by competing protein-encoding potential. PR-2 compliance may have first arisen non-adaptively. Primary prototypic structures were later strengthened by their adaptive contribution to recombination. Thus, contentious views may actually be in harmony.

The Gender Gap in Surgical Literature: Are We Making Progress?

INTRODUCTION: The percentage of women in surgical leadership roles is not commensurate with percent of women in field of surgery. Citation indexes are used as proxy for scholarly impact and may serve as an indicator of women's progress in academic surgery. We aimed to evaluate gender disparities in authorship of surgery manuscripts in high-impact journals. METHODS: In this bibliometric analysis of original research articles from four high-impact surgical journals from 2008 to 2010 (period A) and 2018-2020 (period B), the gender of primary and senior authors was assigned by Genderize.io. Number of citations per article was identified via Web of Science. Number of citations by gender of authors was compared across time periods. RESULTS: Of the 3575 articles (Period A = 1915; Period B = 1660), 962 (26.9%) had women as primary authors and 590 (17.2%) as senior authors. Over time, significant increases in women primary and senior authorship were noted from 22.8% to 31.7% (P < 0.001) and 13.9% (254/11,915) to 21% (336/1660), respectively (P < 0.001). Articles written with women primary authors had fewer median (interquartile range) citations than those by men as primary author in period A (39 [17-69.5] versus 42 [20.0-84.0]; P = 0.005). Gender parity was noted in period B (9 [4-19] versus 9 [4-20] citations; P = 0.307). In period A, articles written by women as both primary and senior authors had approximately 25% fewer median citations compared with those by men (34 [17-62] versus 44 [21-86]); P < 0.011), and this reached parity in period B (9 [4-20] versus 9 [4-21]); P < 0.658). CONCLUSIONS: Overall, gender authorship and citations parity are improving in high-impact surgery journals.

Gender Parity Among Vascular Surgeons: Progress and Attrition.

INTRODUCTION: Improving representation of women in medicine and surgery has been tempered by higher rates of attrition from residencies and from academic medicine among women compared to men. The attrition of women from the practicing vascular surgery workforce has not been studied. METHODS: We utilized the Center for Medicare and Medicaid Services' Doctors and Clinicians database to study vascular surgery employment patterns from 2015 to 2022. We examined gender balance within the workforce and attrition rates among male and female vascular surgeons. We utilized a logistic regression to calculate the odds of attrition by gender. RESULTS: The percentage of female vascular surgeons grew from 11% to 16% between 2015 and 2022, with each graduating class since 2005 having between 20% and 38% women. Yet, female surgeons were 2.05 (95% confidence interval: 1.36-3.08) times more likely to leave practice than their male counterparts when controlling for graduation year and practice in academic medicine. CONCLUSIONS: The proportion of women in vascular surgery is increasing as more women graduate into the specialty. Despite increasing representation, women are more likely than men to leave the workforce.

The impact of age and parity on the experience of relief and regret in women who have undergone hysterectomy for benign disease: A cross sectional survey.

OBJECTIVE: To investigate the impact of age and parity on the experience on relief and regret following elective hysterectomy for benign disease, and to explore the factors that impact relief and regret. DESIGN: Retrospective cross-sectional survey of a cohort. SETTING: Single-centre tertiary hospital in Melbourne, Australia. POPULATION: Patients who underwent elective hysterectomy for benign indications from 01 January 2008 - 31 July 2015 (inclusive) with age <51 years at time of admission. METHODS: Eligible participants completed a retrospective survey regarding their experience of relief and regret following hysterectomy. MAIN OUTCOME MEASURES: Regret was defined as a positive response to "Do you regret the decision to have a hysterectomy?". Relief was defined as responding "agree/strongly agree" to "I feel relieved I had a hysterectomy". RESULTS: 268 of 1285 (21%) eligible participants completed the study questionnaire. Of these, 29 were aged <36 years at the time of hysterectomy. Seven percent (n=18/262) reported regretting having a hysterectomy and 88% (n=230/262) reported experiencing relief. We did not observe associations between age at hysterectomy and regret (aOR 0.93; 95% CI 0.85, 1.03), age at hysterectomy and relief (aOR 1.01; 95% CI 0.93, 1.09), nulliparity and regret (aOR 0.32; 95% CI 0.06, 1.59) or nulliparity and relief (aOR 2.37; 95% CI 0.75, 7.51). Desire for future pregnancy at the time of hysterectomy was more frequently reported in those who experienced regret vs no regret (46.7% vs 12.1%, OR: 6.33; 95% CI: 2.12, 18.90; p=0.001). CONCLUSIONS: Age and parity are not associated with relief nor regret following elective hysterectomy for benign disease.