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Abstract Background The ancient kauri (Agathis australis) dominated forests of Aotearoa New Zealand are under threat from a multitude of ecological disturbances such as forest fragmentation, biodiversity loss, climate change, and the spread of the virulent soil pathogen Phytophthora agathidicida. Taking a wider ecosystem-level approach, our research aimed to explore the impacts of forest disturbance and disease outbreaks on the biosynthetic potential and taxonomic diversity of the kauri soil microbiome. We explored the diversity of secondary metabolite biosynthetic gene clusters (BGCs) in soils from a range of kauri forests that varied according to historical disturbance and dieback expression. To characterise the diversity of microbial BGCs, we targeted the non-ribosomal peptide synthetase (NRPS) and polyketide synthetase (PKS) gene regions for sequencing using long-read PacBio® HiFi sequencing. Furthermore, the soil bacterial and fungal communities of each forest were characterized using 16 S rRNA and ITS gene region sequencing. Results We identified a diverse array of naturally occurring microbial BGCs in the kauri forest soils, which may offer promising targets for the exploration of secondary metabolites with anti-microbial activity against P. agathidicida. We detected differences in the number and diversity of microbial BGCs according to forest disturbance history. Notably, soils associated with the most undisturbed kauri forest had a higher number and diversity of microbial NRPS-type BGCs, which may serve as a potential indicator of natural levels of microbiome resistance to pathogen invasion. Conclusions By linking patterns in microbial biosynthetic diversity to forest disturbance history, this research highlights the need for us to consider the influence of ecological disturbances in potentially predisposing forests to disease by impacting the wider health of forest soil ecosystems. Furthermore, by identifying the range of microbial BGCs present at a naturally high abundance in kauri soils, this research contributes to the future discovery of natural microbial compounds that may potentially enhance the disease resilience of kauri forests. The methodological approaches used in this study highlight the value of moving beyond a taxonomic lens when examining the response of microbial communities to ecosystem disturbance and the need to develop more functional measures of microbial community resilience to invasive plant pathogens.

Objective: TikTok is a rapidly growing social media platform with over 800 million users worldwide. Many patients access fertility-related content across social media platforms, however, this has never been studied related to TikTok. This study aimed to describe patient perspectives and experiences using TikTok for fertility-related content. Materials and methods: We conducted a cross-sectional web-based survey from April 1st 2023 to October 1st 2023 at a large fertility center in Toronto, Canada. Patients were eligible for inclusion if they self-identified that they use TikTok for fertility-related content and had pursued any form of fertility care. Results of the survey were described with descriptive statistics and thematic analysis. Results: A total of 23 patients with a mean age of 36.74±6.67 years participated in the online survey. Fertility-related TikTok content included lived experiences of fertility journeys descriptions of fertility treatments or procedures, live-streaming of fertility treatments or procedures, interactive questions and answers, and educational videos. Creators of fertility-related TikTok content include patients undergoing fertility treatments, physicians, naturopaths, counselors, and patient advocates. The most common reasons for liking TikTok for fertility content included empathy or shared experiences, stress relief, and self-education. Reasons for disliking TikTok for fertility information included misinformation, commercialization or advertisements, and negative emotions of stress, anxiety, or emotional upset. Misconceptions seen on TikTok included misinformation about complications and success rates for assisted reproductive therapy, as well as nutritional advice. Conclusion: Fertility providers should have a growing awareness of information available on TikTok for patients accessing fertility care and assisted reproductive technology.

Abstract The ongoing degradation of natural systems and other environmental changes has put our society at a crossroad with respect to our future relationship with our planet. While the concept of One Health describes how human health is inextricably linked with environmental health, many of these complex interdependencies are still not well‐understood. Here, we describe how the advent of real‐time genomic analyses can benefit One Health and how it can enable timely, in‐depth ecosystem health assessments. We introduce nanopore sequencing as the only disruptive technology that currently allows for real‐time genomic analyses and that is already being used worldwide to improve the accessibility and versatility of genomic sequencing. We showcase real‐time genomic studies on zoonotic disease, food security, environmental microbiome, emerging pathogens, and their antimicrobial resistances, and on environmental health itself – from genomic resource creation for wildlife conservation to the monitoring of biodiversity, invasive species, and wildlife trafficking. We stress why equitable access to real‐time genomics in the context of One Health will be paramount and discuss related practical, legal, and ethical limitations.

Large scale changes in biodiversity and conservation management require long-term goals and planning across multiple sectors in the face of increasing global change. Major trends in land use and management interventions, species additions or losses, and climate are well recognized, but responses are still often short-term and fragmented across agencies and sectors. Scenario-building can be a powerful tool to imagine possible futures, integrating across sectors and disciplines and promoting long-term thinking and planning. As an interdisciplinary team of experts, we developed potential scenarios for a range of future environmental conditions. The scenarios explored: increasing land ownership and stewardship of land by indigenous peoples (Māori); widespread afforestation using native tree species; national-scale eradication of invasive mammalian predators; and increasing frequency of extreme weather events. We explored the implications of these globally-relevant trends at a national scale using Aotearoa New Zealand as our study system. Detailed descriptions of these scenarios were developed by experts using environmental, economic, social science and policy lenses. Across scenarios several common themes were consistently highlighted, including the importance of land use in driving other conservation outcomes. How the value of ecosystem services is recognized and prioritized was also important to a wide range of outcomes. Furthermore, each scenario presented both opportunities and risks to equality, indigenous empowerment and human capital, emphasizing the importance of good policy responses to maximize benefits and minimize unintended harm. These scenarios will be used to stimulate new questions and ideas for biodiversity conservation and management, such as considering the implications of different potential futures for the management of biological invasions. This approach is explicitly designed to be generalisable across different sites or regions and provides a method for considering the implications of potential future changes for a broad range of disciplines or needs.

Background: IMOVE evaluated the contributions of movement and social engagement to quality of life, brain network connectivity, and motor and social-emotional functioning in people with early-stage Alzheimer's disease participating with a caregiver. In response to COVID-19 restrictions, a pilot study was conducted to assess integrity of key elements of the intervention and feasibility of virtual intervention delivery. Methods: Participants in the parent study were randomized to one of 4 study conditions (Movement Group [MG], Movement Alone [MA], Social Group [SG], or Usual Care [UC; control]). To test virtual adaptations of each condition, groups of three participant-caregiver dyads (6 individuals) who had completed the parent trial participated in virtual adaptation classes. We adopted an engineering-inspired, rapid refinement model to optimize virtual interventions on the dimensions of social connectedness, fun, and physical exertion. After completing one iteration, participants gave feedback and adjustments were made to the intervention. This process was repeated until no further adjustments were needed. Results: The MA arm easily transitioned to virtual format. The virtual MG intervention required the most iterations, with participants reporting needs for additional technology support, higher level of physical exertion, and stronger social connection. The virtual SG intervention reported good social connection, but needed additional technology instruction and measures to promote equal participation. Conclusions: Our pilot study results underscore the feasibility of delivering remote social and/or dance interventions for older adults and provide a useful road map for other research teams interested in increasing their reach by adapting in-person group behavioral interventions for remote delivery.

Introduction There is little to no evidence in Canada on the barriers that youth face when accessing contraception. We seek to identify the contraception access, experiences, beliefs, attitudes, knowledge, and needs of youth in Canada, from the perspectives of youth and youth service providers.Methods and analysis This prospective, mixed-methods, integrated knowledge mobilisation study, the Ask Us project, will involve a national sample of youth, healthcare and social service providers, and policy makers recruited via a novel relational mapping and outreach approach led by youth. Phase I will centre the voices of youth and their service providers through in-depth one-on-one interviews. We will explore the factors influencing youth access to contraception, theoretically guided by Levesque’s Access to Care framework. Phase II will focus on the cocreation and evaluation of knowledge translation products (youth stories) with youth, service providers, and policy makers.Ethics and dissemination Ethical approval was received from the University of British Columbia’s Research Ethics Board (H21-01091). Full open-access publication of the work will be sought in an international peer-reviewed journal. Findings will be disseminated to youth and service providers through social media, newsletters, and communities of practice, and to policy makers through invited evidence briefs and face-to-face presentations.

Oral bacteria play important roles in human health and disease. Oral samples collected using ethanol-containing mouthwash are widely used for oral microbiome studies. However, ethanol is flammable and not ideal for transportation/storage in large quantities, and some individuals may avoid ethanol due to the burning sensation or due to various personal, medical, religious, and/or cultural factors. Here, we compared ethanol-free and ethanol-containing mouthwashes using multiple microbiome metrics and assessed the stability of the mouthwash samples stored up to 10 days before processing. Forty volunteers provided oral wash samples collected using ethanol-free and ethanol-containing mouthwashes. From each sample, one aliquot was immediately frozen, one was stored at 4°C for 5 days and frozen, while the third aliquot was stored for 5 days at 4°C and 5 days at ambient temperature to mimic shipping delays and then frozen. DNA was extracted, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatic processing was performed using QIIME 2. Microbiome metrics measured in the two mouthwash types were very similar, with intraclass correlation coefficients (ICCs) for alpha and beta diversity metrics greater than 0.85. Relative abundances of some taxa were significantly different, but ICCs of the top four most abundant phyla and genera were high (> 0.75) for the comparability of the mouthwashes. Stability during delayed processing was also high for both mouthwashes based on alpha and beta diversity measures and relative abundances of the top four phyla and genera (ICCs ≥ 0.90). These results demonstrate ethanol-free mouthwash performs similarly to ethanol-containing mouthwash for microbial analyses, and both mouthwashes are stable for at least 10 days without freezing prior to laboratory processing. Ethanol-free mouthwash is suitable for collecting and shipping oral wash samples, and these results have important implications for planning future epidemiologic studies of the oral microbiome.

Although pregnancy and abortion rates have declined in adolescents, unintended pregnancies remain unacceptably high in this age group. The use of highly effective methods of contraception is one of the pillars of unintended pregnancy prevention and requires a shared decision making process within a rights based framework. Adolescents are eligible to use any method of contraception and long-acting reversible contraceptives, which are “forgettable” and highly effective, may be particularly suited for many adolescents. Contraceptive methods may have additional non-contraceptive benefits that address other needs or concerns of the adolescent. Dual method use should be encouraged among adolescents for the prevention of both unintended pregnancies and sexually transmitted infections. Health care providers have an important role to play in ensuring that adolescents have access to high quality and non-judgmental reproductive health care services and contraceptive methods in adolescent-friendly settings that recognize the unique biopsychosocial needs of the adolescent.

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

[This corrects the article DOI: 10.1371/journal.pone.0193730.].

Objectives The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: (1) describe sport related concussion (SRC) epidemiology, (2) classify prevention strategies, (3) define objective, diagnostic tests, (4) identify treatment and (5) integrate science and clinical care into prioritized action plans and policy. Methods Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches and officials) voted to prioritize these action items in the final Summit session. Results (1) establish a national and international hockey data base for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care (POC); and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity and consequences of concussion in the sport of ice hockey.

This study quantified and compared the probability of avian influenza (AI) spread within and between Australian commercial chicken farms via specified spread pathways using scenario tree mathematical modeling. Input values for the models were sourced from scientific literature, expert opinion, and a farm survey conducted during 2015 and 2016 on Australian commercial chicken farms located in New South Wales (NSW) and Queensland. Outputs from the models indicate that the probability of no establishment of infection in a shed is the most likely end-point after exposure and infection of low-pathogenic avian influenza (LPAI) in one chicken for all farm types (non-free range meat chicken, free range meat chicken, cage layer, barn layer, and free range layer farms). If LPAI infection is established in a shed, LPAI is more likely to spread to other sheds and beyond the index farm due to a relatively low probability of detection and reporting during LPAI infection compared to high-pathogenic avian influenza (HPAI) infection. Among farm types, the median probability for HPAI spread between sheds and between farms is higher for layer farms (0.0019, 0.0016, and 0.0031 for cage, barn, and free range layer, respectively) than meat chicken farms (0.00025 and 0.00043 for barn and free range meat chicken, respectively) due to a higher probability of mutation in layer birds, which relates to their longer production cycle. The pathway of LPAI spread between sheds with the highest average median probability was spread via equipment (0.015; 5–95%, 0.0058–0.036) and for HPAI spread between farms, the pathway with the highest average median probability was spread via egg trays (3.70 × 10−5; 5–95%, 1.47 × 10−6–0.00034). As the spread model did not explicitly consider volume and frequency of the spread pathways, these results provide a comparison of spread probabilities per pathway. These findings highlight the importance of performing biosecurity practices to limit spread of the AI virus. The models can be updated as new information on the mechanisms of the AI virus and on the volume and frequency of movements shed-to-shed and of movements between commercial chicken farms becomes available.

This study investigated the pathways of exposure to low pathogenic avian influenza (LPAI) virus among Australian commercial chicken farms and estimated the likelihood of this exposure occurring using scenario trees and a stochastic modeling approach following the World Organization for Animal Health methodology for risk assessment. Input values for the models were sourced from scientific literature and an on-farm survey conducted during 2015 and 2016 among Australian commercial chicken farms located in New South Wales and Queensland. Outputs from the models revealed that the probability of a first LPAI virus exposure to a chicken in an Australian commercial chicken farms from one wild bird at any point in time is extremely low. A comparative assessment revealed that across the five farm types (non-free-range meat chicken, free-range meat chicken, cage layer, barn layer, and free range layer farms), free-range layer farms had the highest probability of exposure (7.5 × 10−4; 5% and 95%, 5.7 × 10−4—0.001). The results indicate that the presence of a large number of wild birds on farm is required for exposure to occur across all farm types. The median probability of direct exposure was highest in free-range farm types (5.6 × 10−4 and 1.6 × 10−4 for free-range layer and free-range meat chicken farms, respectively) and indirect exposure was highest in non-free-range farm types (2.7 × 10−4, 2.0 × 10−4, and 1.9 × 10−4 for non-free-range meat chicken, cage layer, and barn layer farms, respectively). The probability of exposure was found to be lowest in summer for all farm types. Sensitivity analysis revealed that the proportion of waterfowl among wild birds on the farm, the presence of waterfowl in the range and feed storage areas, and the prevalence of LPAI in wild birds are the most influential parameters for the probability of Australian commercial chicken farms being exposed to avian influenza (AI) virus. These results highlight the importance of ensuring good biosecurity on farms to minimize the risk of exposure to AI virus and the importance of continuous surveillance of LPAI prevalence including subtypes in wild bird populations.

The objective of this study was to elicit experts' opinions and gather estimates on the perceived probability of introduction and spread of avian influenza (AI) virus in the Australian broiler and layer industry. Using a modified Delphi method and a 4-step elicitation process, 11 experts were asked to give initial individual estimates for the various pathways and practices in the presented scenarios using a questionnaire. Following this, a workshop was conducted to present group averages of estimates and discussion was facilitated to obtain final individual estimates. For each question, estimates for all experts were combined using a discrete distribution, with weights allocated representing the level of expertise. Indirect contact with wild birds either via a contaminated water source or fomites was considered the most likely pathway of introduction of low pathogenic avian influenza (LPAI) on poultry farms. Presence of a water body near the poultry farm was considered a potential pathway for introduction only when the operation type was free range and the water body was within 500m distance from the shed. The probability that LPAI will mutate to highly pathogenic avian influenza (HPAI) was considered to be higher in layer farms. Shared personnel, equipment and aerosol dispersion were the most likely pathways of shed to shed spread of the virus. For LPAI and HPAI spread from farm to farm, shared pick-up trucks for broiler and shared egg trays and egg pallets for layer farms were considered the most likely pathways. Findings from this study provide an insight on most influential practices on the introduction and spread of AI virus among commercial poultry farms in Australia, as elicited from opinions of experts. These findings will be used to support parameterization of a modelling study assessing the risk of AI introduction and spread among commercial poultry farms in Australia.

This paper describes the level of adoption of biosecurity practices performed on Australian commercial chicken meat and layer farms and farmer-perceived importance of these practices. On-farm interviews were conducted on 25 free range layer farms, nine cage layer farms, nine barn layer farms, six free range meat chicken farms and 15 barn meat chicken farms in the Sydney basin bioregion and South East Queensland. There was a high level of treatment of drinking water across all farm types; town water was the most common source. In general, meat chicken farms had a higher level of adoption of biosecurity practices than layer farms. Cage layer farms had the shortest median distance between sheds (7.75m) and between sheds and waterbodies (30m). Equipment sharing between sheds was performed on 43% of free range meat chicken farms compared to 92% of free range layer farms. There was little disinfection of this shared equipment across all farm types. Footbaths and visitor recording books were used by the majority of farms for all farm types except cage layer farms (25%). Wild birds in sheds were most commonly reported in free range meat chicken farms (73%). Dogs and cats were kept across all farm types, from 56% of barn layer farms to 89% of cage layer farms, and they had access to the sheds in the majority (67%) of cage layer farms and on the range in some free range layer farms (44%). Most biosecurity practices were rated on average as 'very important' by farmers. A logistic regression analysis revealed that for most biosecurity practices, performing a practice was significantly associated with higher perceived farmer importance of that biosecurity practice. These findings help identify farm types and certain biosecurity practices with low adoption levels. This information can aid decision-making on efforts used to improve adoption levels.

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995-2009; Adventist Health Study 2, 2002-2008; Black Women's Health Study, 1995-2009; Cancer Prevention Study II, 1982-2008; Multiethnic Cohort Study, 1993-2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993-2009; Southern Community Cohort Study, 2002-2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30-104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25-27.4, 27.5-29.9, 30-34.9, 35-39.9, 40-49.9, and 50-60 kg/m(2) were 1.02 (0.92-1.12), 1.06 (0.95-1.18), 1.32 (1.18-1.47), 1.54 (1.29-1.83), 1.93 (1.46-2.56), and 1.93 (0.80-4.69), respectively among men and 1.06 (0.99-1.15), 1.15 (1.06-1.25), 1.24 (1.15-1.34), 1.58 (1.43-1.74), 1.80 (1.60-2.02), and 2.31 (1.74-3.07) respectively among women (reference category 22.5-24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans.

Pathway analysis of genome-wide association studies (GWAS) offer a unique opportunity to collectively evaluate genetic variants with effects that are too small to be detected individually. We applied a pathway analysis to a bladder cancer GWAS containing data from 3,532 cases and 5,120 controls of European background (n = 5 studies). Thirteen hundred and ninety-nine pathways were drawn from five publicly available resources (Biocarta, Kegg, NCI-PID, HumanCyc, and Reactome), and we constructed 22 additional candidate pathways previously hypothesized to be related to bladder cancer. In total, 1421 pathways, 5647 genes and ∼90,000 SNPs were included in our study. Logistic regression model adjusting for age, sex, study, DNA source, and smoking status was used to assess the marginal trend effect of SNPs on bladder cancer risk. Two complementary pathway-based methods (gene-set enrichment analysis [GSEA], and adapted rank-truncated product [ARTP]) were used to assess the enrichment of association signals within each pathway. Eighteen pathways were detected by either GSEA or ARTP at P≤0.01. To minimize false positives, we used the I(2) statistic to identify SNPs displaying heterogeneous effects across the five studies. After removing these SNPs, seven pathways ('Aromatic amine metabolism' [P(GSEA) = 0.0100, P(ARTP) = 0.0020], 'NAD biosynthesis' [P(GSEA) = 0.0018, P(ARTP) = 0.0086], 'NAD salvage' [P(ARTP) = 0.0068], 'Clathrin derived vesicle budding' [P(ARTP) = 0.0018], 'Lysosome vesicle biogenesis' [P(GSEA) = 0.0023, P(ARTP)

A recent ovarian cancer genome-wide association study (GWAS) identified a locus on 9p22 associated with reduced ovarian cancer risk. The single nucleotide polymorphism (SNP) markers localize to the BNC2 gene, which has been associated with ovarian development.We analyzed the association of 9p22 SNPs with transvaginal ultrasound (TVU) screening results and CA-125 blood levels from participants without ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO); 1,106 women with adequate ultrasound screening results and available genotyping information were included in the study.We observed a significantly increased risk of abnormal suspicious TVU results for seven SNPs on 9p22, with odds ratios between 1.68 (95% CI: 1.04-2.72) for rs4961501 and 2.10 (95% CI: 1.31-3.38) for rs12379183. Associations were restricted to abnormal suspicious findings at the first TVU screen. We did not observe an association between 9p22 SNPs and CA-125 levels.Our findings suggest that 9p22 SNPs, which were found to be associated with decreased risk of ovarian cancer in a recent GWAS, are associated with sonographically detectable ovarian abnormalities. Our results corroborate the relevance of the 9p22 locus for ovarian biology. Further studies are required to understand the complex relationship between screening abnormalities and ovarian carcinogenesis and to evaluate whether this locus can influence the risk stratification of ovarian cancer screening.

Abstract Cytoplasmic proliferating cell nuclear antigen (PCNA) is highly expressed in acute myeloid leukemia (AML) cells, supporting oxidative metabolism and leukemia stem cell (LSC) growth. We report on AOH1996 (AOH), an oral compound targeting cancer-associated PCNA, which shows significant antileukemic activity. AOH inhibited growth in AML cell lines and primary CD34 + CD38 − blasts (LSC-enriched) in vitro while sparing normal hematopoietic stem cells (HSCs). In vivo, AOH-treated mice demonstrated prolonged survival compared to controls (50 vs. 35 days; p