Discovery of novel coumarin-based KRAS-G12C inhibitors from virtual screening and Rational structural optimization.

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

Discovery of indole-2-one derivatives as BRD4 (BD1) selective inhibitors.

Bromodomain protein 4 (BRD4) is a member of the BET family, and its overexpression is closely associated with the development of many tumors. Inhibition of BRD4 shows great therapeutic potential in anti-tumor, and pan-BRD4 inhibitors show adverse effects of dose limiting toxicity and thrombocytopenia in clinical trials. To improve clinical effects and reduce side effects, more efforts have focused on seeking selective inhibitors of BD1 or BD2. Herein, a series of indole-2-one derivatives were designed and synthesized through docking-guided optimization to find BRD4-BD1 selective inhibitors, and their BRD4 inhibitory and antiproliferation activities were evaluated. Among them, compound 21r had potent BRD4 inhibitory activity (the IC50 values of 41 nM and 313 nM in BD1 and BD2 domain), excellent anti-proliferation (the IC50 values of 4.64 ± 0.30 µM, 0.78 ± 0.03 µM, 5.57 ± 1.03 µM against HL-60, MV-4-11 and HT-29 cells), and displayed low toxicity against normal cell GES-1 cells. Further studies revealed that 21r inhibited proliferation by decreasing the expression of proto-oncogene c-Myc, blocking cell cycle in G0/G1 phase, and inducing apoptosis in MV-4-11 cells in a dose-dependent manner. All the results showed that compound 21r was a potent BRD4 inhibitor with BD1 selectivity, which had potential in treatment of leukemia.

Genomic landscape and functional characterization of structural variations in schizophrenia and bipolar disorder.

Multiple types of variations have been postulated to confer risk of schizophrenia and bipolar disorder, but majority of present GWAS solely focused on SNPs or small indels, and the impacts of structural variations (SVs) remain less understood. Nevertheless, accumulating evidence suggest that SVs may explain the association signals in certain GWAS hits. Here, we conducted pairwise linkage disequilibrium (LD) analyses of SNPs and SVs in populations from 1000 Genomes Project. Among the 299 psychiatric GWAS loci, 1213 SVs showed an LD of r2 > 0.1 with GWAS risk SNPs, and 66 of them were in moderate to strong LD (r2 > 0.6) with at least one GWAS risk SNP. Nine SVs were subject to further explorative analyses, including eQTL analysis in DLPFC, luciferase reporter gene assays, CRISPR/Cas9-mediated genome deletion and RT-qPCR. These assays highlighted several functional SVs showing regulatory effects on transcriptional activities, and some risk genes (e.g., BORCS7, GNL3) affected by the SVs were also annotated. Finally, mice overexpressing Borcs7 in the mPFC exhibited schizophrenia-like behaviors, such as abnormal prepulse inhibition and social dysfunction. These data suggest that SNPs association signals at GWAS loci might be driven by SVs, highlighting the necessities of considering such variants in future.

Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada.

BACKGROUND: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). METHODS: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). RESULTS: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. CONCLUSIONS: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Gate-Tunable Quantum Acoustoelectric Transport in Graphene.

Transport probes the motion of quasi-particles in response to external excitations. Apart from the well-known electric and thermoelectric transport, acoustoelectric transport induced by traveling acoustic waves has rarely been explored. Here, by adopting hybrid nanodevices integrated with piezoelectric substrates, we establish a simple design of acoustoelectric transport with gate tunability. We fabricate dual-gated acoustoelectric devices based on hBN-encapsulated graphene on LiNbO3. Longitudinal and transverse acoustoelectric voltages are generated by launching a pulsed surface acoustic wave. The gate dependence of zero-field longitudinal acoustoelectric signal presents strikingly similar profiles to that of Hall resistivity, providing a valid approach for extracting carrier density without magnetic field. In magnetic fields, acoustoelectric quantum oscillations appear due to Landau quantization, which are more robust and pronounced than Shubnikov-de Haas oscillations. Our work demonstrates a feasible acoustoelectric setup with gate tunability, which can be extended to the broad scope of various van der Waals materials.

Infant Infections Following Cesarean Delivery on Maternal Request: A Population-Based Cohort Study.

OBJECTIVES: Investigations about cesarean delivery (CD) on maternal request (CDMR) and infant infection risk frequently rely on administrative data with poorly defined indications for CD. We sought to determine the association between CDMR and infant infection using an intent-to-treat approach. METHODS: This was a population-based cohort study of low-risk singleton pregnancies with a term live birth in Ontario, Canada between April 2012 and March 2018. Subjects with prior CD were excluded. Outcomes included upper and lower respiratory tract infections, gastrointestinal infections, otitis media, and a composite of these 4. Relative risk and 95% CI were calculated for component and composite outcomes up to 1 year following planned CDMR versus planned vaginal deliveries (VDs). Subgroup and sensitivity analyses included age at infection (≤28 vs. >28 days), type of care (ambulatory vs. hospitalisation), restricting the cohort to nulliparous pregnancies, and including individuals with previous CD. Last, we re-examined outcome risk on an as-treated basis (actual CD vs. actual VD). RESULTS: Of 422 134 pregnancies, 0.4% (1827) resulted in a planned CDMR. After adjusting for covariates, planned CDMR was not associated with a risk of composite infant infections (adjusted relative risk 1.02; 95% CI 0.92-1.11). Findings for component infection outcomes, subgroup, and sensitivity analyses were similar. However, the as-treated analysis of the role of delivery mode on infant risk for infection demonstrated that actual CD (planned and unplanned) was associated with an increased risk for infant infections compared to actual VD. CONCLUSIONS: Planned CDMR is not associated with increased risk for neonatal or infant infections compared with planned VD. Study design must be carefully considered when investigating the impact of CDMR on infant infection outcomes.

Bipyridine-N,N'-dioxides Catalysts: Design, Synthesis, and Application in Asymmetric Synthesis of 1H-Pyrazolo[3,4-b]pyridine Analogues.

A novel type of highly efficient chiral C2-symmetric bipyridine-N,N'-dioxides ligand application in catalyzing Michael addition/Cyclization of 5-aminopyrazoles with α,ß-unsaturated 2-acyl imidazoles has been developed, affording the corresponding adducts in 85-97% yield with up to 99% enantioselectivity under mild conditions with a lower catalyst loading and broad scope. Remarkably, this protocol exhibits advantages in terms of reactivity and enantioselectivity, giving the fact that as low as 2.2 mol % of L1 and 2.0 mol % of Ni(OTf)2 can promote the title reaction on gram scale to afford the desired product with excellent enantioselectivity.

The impact of isolated obesity compared with obesity and other risk factors on risk of stillbirth: a retrospective cohort study.

BACKGROUND: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. METHODS: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. RESULTS: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. INTERPRETATION: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.

RGA1 regulates grain size, rice quality and seed germination in the small and round grain mutant srg5.

BACKGROUND: Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. RESULTS: In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. CONCLUSIONS: These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Why Female Smokers Have Poorer Long-Term Health Outcomes than Male Smokers: The Role of Cigarette Smoking During Pregnancy.

Objectives: Women's health status is better than men but the opposite is true for female smokers who usually have poorer long-health outcomes than male smokers. The objectives of this study were to thoroughly reviewed and analyzed relevant literature and to propose a hypothesis that may explain this paradox phenomenon. Methods: We conducted a search of literature from three English databases (EMBASE, MEDLINE, and Google Scholar) from inception to 13 November 2023. A combination of key words and/or subject headings in English was applied, including relevant terms for cigarette smoking, sex/gender, pregnancy, and health indicators. We then performed analysis of the searched literature. Results: Based on this review/analysis of literature, we proposed a hypothesis that may explain this paradox phenomenon: female smokers have worse long-term health outcomes than male smokers because some of them smoke during pregnancy, and the adverse effects of cigarette smoking during pregnancy is much stronger than cigarette smoking during non-pregnancy periods. Conclusion: Approval of our pregnancy-amplification theory could provide additional evidence on the adverse effect on women's long-term health outcomes for cigarette smoking during pregnancy.

Tunable anisotropic van der Waals films of 2M-WS2 for plasmon canalization.

In-plane anisotropic van der Waals materials have emerged as a natural platform for anisotropic polaritons. Extreme anisotropic polaritons with in-situ broadband tunability are of great significance for on-chip photonics, yet their application remains challenging. In this work, we experimentally characterize through Fourier transform infrared spectroscopy measurements a van der Waals plasmonic material, 2M-WS2, capable of supporting intrinsic room-temperature in-plane anisotropic plasmons in the far and mid-infrared regimes. In contrast to the recently revealed natural hyperbolic plasmons in other anisotropic materials, 2M-WS2 supports canalized plasmons with flat isofrequency contours in the frequency range of ~ 3000-5000 cm-1. Furthermore, the anisotropic plasmons and the corresponding isofrequency contours can be reversibly tuned via in-situ ion-intercalation. The tunable anisotropic and canalization plasmons may open up further application perspectives in the field of uniaxial plasmonics, such as serving as active components in directional sensing, radiation manipulation, and polarization-dependent optical modulators.

Simultaneous type III congenital esophageal atresia and patent ductus arteriosus in a low-weight patient: A case report.

BACKGROUND: We report a low-birth-weight child (1.8 kg) with neonatal type III congenital esophageal atresia (CEA) combined with symptomatic patent ductus arteriosus (PDA). After comprehensive evaluation, esophageal anastomosis was performed on postnatal day 11 after excluding surgical contraindications, and arterial catheter ligation was performed at the same time. Concurrent surgery for CEA combined with PDA has not been clearly reported in the literature. CASE SUMMARY: We report a 6-day-old female child with type III CEA and PDA. The patient presented with foam at the mouth after birth, cough and shortness of breath after feeding. At another hospital, she was considered to have neonatal pneumonia, neonatal jaundice and congenital heart disease and transferred to our hospital. After iodine oil radiography of the esophagus and echocardiography we confirmed diagnosis of CEA and PDA. The diameter of the PDA was 8 mm, with obvious left to right shunting. We performed right rear extrapleural orificium fistula ligation and esophageal anastomosis, and ligation of PDA via left axilla straight incision after 5 d of hospitalization. The operations were successful, and the incision healed after 12 d, and the patient was discharged. We re-examined the patient 1 mo after surgery. She did not vomit when she ate rice flour. Esophageal angiography showed no stricture of the anastomotic stoma. The patient weighed 3.2 kg. CONCLUSION: For CEA patients with multiple risk factors, comprehensive, timely and accurate diagnosis and evaluation, and early treatment may improve prognosis.

Thyroid allostasis in drug-free affective disorder patients.

AIM: To assess the thyroid allostasis in drug-free patients with affective disorder. METHODS: Patients with major depressive disorder or bipolar disorder as drug-free, defined as those without psychiatric drugs exposure for at least 4 months before admission, from a tertiary hospital were recruited in this cross-sectional study. The primary outcomes were "structure parameters of thyroid homeostasis", which include "thyroid's secretory capacity" (SPINA-GT), "sum step-up activity of deiodinases" (SPINA-GD), the ratio of total to free thyroxine and "thyroid homeostasis central set point" (TSH index and "thyroid feedback quantile-based index" [TFQI]), calculated by TSH and thyroid hormones measured at admission. A healthy population and non-affective psychiatric disorder (schizophrenia) from the same catchment area were recruited as two comparison groups. RESULTS: A total of 1263 cases of major depressive disorder, 1619 cases of bipolar disorder, 1186 cases of schizophrenia, and 162 healthy controls were included in the study. Compared to healthy control, GD and ratio of total to free thyroxine were lower in affective disorders. Bipolar with mania episode had higher GT than bipolar with depressive episode and major depressive disorder (median level at 3.70 vs. 3.04 and 3.03, respectively). Compared with healthy control, schizophrenia had higher TSH index and TFQI, but no increase in these parameters in major depressive disorder and bipolar disorder. CONCLUSION: Affective disorders have a unique profile of thyroid allostasis with impaired step-up deiodinase activity and reduced serum protein binding of thyroid hormones, but no change in thyroid homeostasis central set point. Mania episode may be associated with higher thyroid secretory capacity.

Relationship Between Gestational Weight Gain and Health Service Utilization in Early Childhood: A Retrospective Cohort Study.

OBJECTIVE: Gestational weight gain (GWG) outside recommended ranges can negatively impact both the woman and child. The long-term effects of below-recommended or above-recommended GWG on the child are unclear. METHODS: This retrospective cohort study used a population-based birth registry of 258,005 live births to evaluate the relationship between maternal GWG and paediatric health service use. RESULTS: The results suggest below recommended GWG in underweight women in particular is associated with an increased rate of hospitalizations and specialist visits for the child in the first 24 months. CONCLUSION: Findings indicate that GWG may impact paediatric outcomes in ways that depend on pre-pregnancy body mass index, as derived from maternal height and weight measures.

Asymmetric Synthesis of Tertiary α-Hydroxylation-Cyclopentanones via Synergetic Catalysis of Chiral-at-Metal Rhodium(III) Complexes/Pyrrolidine.

Catalytic and asymmetric domino Michael/aldol reaction of 1,2-dicarbonyl compounds with α,ß-unsaturated ketones under the synergetic catalysis of chiral-at-metal rhodium complexes and pyrrolidine to deliver tertiary α-hydroxylation-cyclopentanones (45-89% yields with 81-99% ee and up to >20:1 dr) bearing three contiguous stereogenic centers had been established. Moreover, the scalability and practical utility of this protocol were well demonstrated by employing a gram-scale reaction and some representative transformations.

Catalytic asymmetric conjugate addition of coumarins to unsaturated ketones catalyzed by a chiral-at-metal Rh(III) complex.

The first catalytic asymmetric vinylogous Michael addition of coumarins to unsaturated ketones catalyzed by chiral rhodium catalysts has been established. This strategy allowed the synthesis of a variety of highly enantioenriched compounds containing coumarin skeletons in 41-99% yields and 84-99% ee. The developed reaction enriches the chemistry of catalytic asymmetric vinylogous Michael additions of 3-cyano-4-methylcoumarins. Furthermore, the protocol showed obvious advantages in reaction enantioselectivity. When the chiral rhodium catalyst was reduced to 0.06 mol%, a Gram-level reaction was still achieved to provide the desired products with 99% ee.

Interpregnancy weight change and risks of stillbirth and infant mortality: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Interpregnancy weight change may impact two important adverse perinatal outcomes: stillbirth and infant mortality. This systematic review aims to synthesise the existing evidence on the association between interpregnancy weight change and stillbirth and infant mortality. METHODS AND ANALYSIS: This systematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines and has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). A comprehensive literature search of four online databases (Embase, Cochrane Libraries, Web of Science and Medline) will be conducted from inception to October 2023. Observational (longitudinal, cohort, case-control) and randomised controlled trials will be included. Interpregnancy weight/body mass index change between two consecutive pregnancies will be the exposure. The primary outcomes will be the incidence of stillbirth and infant mortality in subsequent pregnancy. The Cochrane Risk of Bias tool will be used to assess the risk of bias in the randomised controlled studies and the Risk of Bias in Non-Randomised Studies of Interventions tool will be used for observational studies. If there are sufficient data, a meta-analysis will be conducted to estimate the pooled effect size. Otherwise, qualitative descriptions of individual studies will be summarised. The heterogeneity will be statistically assessed using a χ2 test and I2 statistic. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as all results will be based on published papers. No primary data collection will be needed. Study findings will be presented at scientific conferences or published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: A registration for this review has been submitted to PROSPERO under CRD42020222977.

Controllable Carrier Doping in Two-Dimensional Materials Using Electron-Beam Irradiation and Scalable Oxide Dielectrics.

Two-dimensional (2D) materials, characterized by their atomically thin nature and exceptional properties, hold significant promise for future nano-electronic applications. The precise control of carrier density in these 2D materials is essential for enhancing performance and enabling complex device functionalities. In this study, we present an electron-beam (e-beam) doping approach to achieve controllable carrier doping effects in graphene and MoS2 field-effect transistors (FETs) by leveraging charge-trapping oxide dielectrics. By adding an atomic layer deposition (ALD)-grown Al2O3 dielectric layer on top of the SiO2/Si substrate, we demonstrate that controllable and reversible carrier doping effects can be effectively induced in graphene and MoS2 FETs through e-beam doping. This new device configuration establishes an oxide interface that enhances charge-trapping capabilities, enabling the effective induction of electron and hole doping beyond the SiO2 breakdown limit using high-energy e-beam irradiation. Importantly, these high doping effects exhibit non-volatility and robust stability in both vacuum and air environments for graphene FET devices. This methodology enhances carrier modulation capabilities in 2D materials and holds great potential for advancing the development of scalable 2D nano-devices.

Gestational weight loss and fetal growth in uncomplicated pregnancies among women with obesity: a population-based retrospective cohort study.

OBJECTIVE: The impact of gestational weight loss (GWL) on fetal growth among women with obesity remains unclear. This study aimed to examine the association between weight loss during pregnancy among women with body mass index (BMI) ≥ 30 kg/m2 and the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) neonates. METHODS: We conducted a retrospective, population-based cohort study of women with pre-pregnancy obesity that resulted in a singleton live birth in 2012-2017, using birth registry data in Ontario, Canada. Women with pregnancy complications or health conditions which could cause weight loss were excluded. GWL is defined as negative gestational weight change (≤0 kg). The association between GWL and fetal growth was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class (I:30-34.9 kg/m2, II:35-39.9 kg/m2, and III + : ≥40 kg/m2). RESULTS: Of the 52,153 eligible women who entered pregnancy with a BMI ≥ 30 kg/m2, 5.3% had GWL. Compared to adequate gestational weight gain, GWL was associated with an increased risk of SGA neonates (aRR:1.45, 95% CI: 1.30-1.60) and a decreased risk of LGA neonates (aRR: 0.81, 95% CI:0.73-0.93). Non-linear L-shaped associations were observed between gestational weight change and SGA neonates, with an increased risk of SGA observed with increased GWL. On the contrary, non-linear S-shaped associations were observed between gestational weight change and LGA neonates, with a decreased risk of LGA observed with increased GWL. Similar findings were observed from the stratified analysis by obesity class. CONCLUSION: These findings highlight that GWL in women with obesity may increase the risk of SGA neonates but reduce the risk of LGA neonates. Recommendations of GWL for women with obesity should be interpreted with caution.

Screening for postpartum depression and risk of suicidality with obstetrical patients: a cross-sectional survey.

BACKGROUND: Pregnancy is a vulnerable time where the physical and social stress of the COVID-19 pandemic affects psychological health, including postpartum depression (PPD). This study is designed to estimate the prevalence and correlates of PPD and risk of suicidality among individuals who gave birth during the COVID-19 pandemic. METHODS: We surveyed individuals who gave birth at The Ottawa Hospital and were ≥ 20 days postpartum, between March 17 and June 16, 2020. A PPD screen consisted of a score ≥ 13 using the Edinburgh Postnatal Depression Scale. A score of 1, 2, or 3 on item 10 ("The thought of harming myself has occurred to me") indicates risk of suicidality. If a participant scores greater than ≥ 13 or ≥ 1 on item 10 they were flagged for PPD, the Principal Investigator (DEC) was notified within 24 h of survey completion for a chart review and to assure follow-up. Modified Poisson multivariable regression models were used to identify factors associated with PPD and risk of suicidality using adjusted risk ratios (aRR) and 95% confidence intervals (CI). RESULTS: Of the 216 respondents, 64 (30%) screened positive for PPD and 17 (8%) screened positive for risk of suicidality. The maternal median age of the total sample was 33 years (IQR: 30-36) and the infant median age at the time of the survey was 76 days (IQR: 66-90). Most participants reported some form of positive coping strategies during the pandemic (97%) (e.g. connecting with friends and family, exercising, getting professional help) and 139 (64%) reported negative coping patterns (e.g. over/under eating, sleep problems). In total, 47 (22%) had pre-pregnancy anxiety and/or depression. Negative coping (aRR:2.90, 95% CI: 1.56-5.37) and pre-existing anxiety/depression (aRR:2.03, 95% CI:1.32-3.11) were associated with PPD. Pre-existing anxiety/depression (aRR:3.16, 95% CI:1.28-7.81) was associated with risk of suicidality. CONCLUSIONS: Almost a third of participants in this study screened positive for PPD and 8% for risk of suicidality. Mental health screening and techniques to foster positive coping skills/strategies are important areas to optimize postpartum mental health.