North European Research Articles

Underreporting or Failed Notification? Global Botulism Reporting, 2000-2022.

Botulism is a rare, potentially fatal illness caused by botulinum toxins produced by Clostridium bacteria. There are no coordinated worldwide reporting mechanisms for botulism cases and therefore few reliable case frequency estimates. This study aimed to establish an international benchmark for case frequency to determine estimated global rates of underreporting of botulism cases. To this end, a comprehensive, multilingual search of major global and national databases, including gray data and government sources, was performed. Data from case series were pooled, standardized against United Nations midyear population estimates, and analyzed using Kolmogorov-Smirnov tests to identify normally distributed data series. National incidence rates of normally distributed series were compared with that of the United States, which was considered the gold standard due to its extensive data reported for 2004-2018. A total of 6,932 botulism cases from 59 nations were identified in the literature, with a global case fatality rate of 1.37%. The national mean incidence rate ranged from 0.00 to 8.04 cases per million people, with an international mean incidence rate of 0.62 cases per million people. At the continent level, incidence rates tended toward normal distributions, although few countries outside of North America and Europe exhibited normal distributions. Based on comparisons with the US standard, an estimated 88.71% of botulism cases worldwide were unreported in 2016. Better awareness of botulism among healthcare professionals, coordinated global reporting mechanisms, and research on additional contributing factors to underreporting would enable better understanding of global case frequency, thereby potentially reducing the global incidence of botulism and improving outcomes.

Parallel patterns of genetic diversity and structure in circumboreal species of the Sphagnum capillifolium complex.

Shared geographical patterns of population genetic variation among related species is a powerful means to identify the historical events that drive diversification. The Sphagnum capillifolium complex is a group of closely related peat mosses within the Sphagnum subgenus Acutifolia and contains several circumboreal species whose ranges encompass both glaciated and unglaciated regions across the northern hemisphere. In this paper, we (1) inferred the phylogeny of subg. Acutifolia and (2) investigated patterns of population structure and genetic diversity among five circumboreal species within the S. capillifolium complex. We generated RAD sequencing data from most species of the subg. Acutifolia and samples from across the distribution ranges of circumboreal species within the S. capillifolium complex. We resolved at least 14 phylogenetic clusters within the S. capillifolium complex. Five circumboreal species show some common patterns: One population system comprises plants in eastern North America and Europe, and another comprises plants in the Pacific Northwest or around the Beringian and Arctic regions. Alaska appears to be a hotspot for genetic admixture, genetic diversity, and sometimes endemic subclades. Our results support the hypothesis that populations of five circumboreal species within the S. capillifolium complex survived in multiple refugia during the last glacial maximum. Long-distance dispersal out of refugia, population bottlenecks, and possible adaptations to conditions unique to each refugium could have contributed to current geographic patterns. These results indicate the important role of historical events in shaping the complex population structure of plants with broad distribution ranges.

Consistent efficacy and safety of sublingual immunotherapy tablets across allergens and geographic regions.

The clinical development program of the SQ grass, ragweed, tree, and house dust mite (HDM) sublingual immunotherapy (SLIT)-tablets for allergicrhinitis/conjunctivitis (AR/C) included clinical trials conducted in North America,Europe, and Japan. Data from these trials were analyzed to assess efficacy, immunologic mechanisms, and safety outcomes acrossallergens and geographic regions. Thirteen phase III, double-blind, placebo controlled trials in the subjects with AR/C were conducted in NorthAmerica, Europe (including Russia), and Japan (N = 7763 analyzed). Trials were generally similar with respect to medicalpractice, target population, eligibility criteria, and efficacy and safety monitoring. Data were analyzed for the approved dosesin North America and Europe. Four statistical models were used to enhance comparison of the efficacy end points among the trials. The SLIT-tablets demonstrated consistent efficacy across allergens and regions, regardless of the statistical analysis used. Relative improvement in the primary efficacy end point compared with placebo by using the predefined protocol analysis ranged from 17.9% to 32.8%, 17.5% to 19.3%, 20.6% to 38.3%, and 39.6% with the grass, HDM, ragweed, and tree SLIT-tablets, respectively. The kinetics of specific immunoglobulin E (IgE) and IgG4 responses were similar among the allergensand regions. Local application-site reactions were the most common adverse events for all allergens and in all regions. Mosttreatment-related adverse events for all allergens and in all regions were mild in severity. The rate of systemic allergic reactions was similar across regions (0%-0.54%). Confirmatory phase III trials for SLIT-tablets in the treatment of AR/C showed consistent efficacy, immunologic,and safety outcomes across allergens and geographic regions.

Difficult diagnosis: Disseminated gonorrheal infection manifesting as septic arthritis.

Disseminated gonococcal infection is the causative agent of approximately 0.6%-1.2% of septic arthritis cases in North America and Europe. Typical presentations of this disorder include tenosynovitis, dermatitis, polyarthralgia, or oligoarticular purulent arthritis affecting the distal joints. Diagnosis is contingent on clinical presentation, with urine nucleic acid amplification testing as the preferred diagnostic modality. Synovial fluid cultures, along with imaging, can confirm diagnosis. The recommended treatment is a third-generation cephalosporin, such as intravenous ceftriaxone for 7-14 days and a dose of oral azithromycin.

Intercontinental invasion dynamics of Cercopagis pengoi, an IUCN-listed planktonic invasive species

Predicting the spread of invasive species and understanding the role of niche dynamics in niche transferability are critical challenges in the management of biological invasions, both theoretically and practically. We used complementary species distribution modelling approaches, such as multivariate niche analysis and reciprocal distribution models, to test the niche conservatism hypothesis and to predict the potential distribution of the fishhook waterflea, Cercopagis pengoi. Our analysis indicated a significant similarity between its native and invasive ranges, suggesting that a subset of the Ponto-Caspian propagules may have been the founders of European populations. However, our results contradict the niche conservatism hypothesis, showing that C. pengoi has not fully occupied the available niche within its current invasive ranges. Moreover, we observed a notable niche expansion, reflecting a significant shift in niche following its intercontinental introduction in North America. Given the suitability of new environments for the expansion of C. pengoi and its tendency to evade detection prior to population surges, we recommend a focus on early detection through monitoring of both water columns and bottom sediments. This should be complemented by strict enforcement of ballast water regulations to curtail its spread in North America, Europe, and other suitable non-native regions globally.

Alien invasive pathogens and pests in the changing environment: Focus on North Europe

On 12–13 September 2023, a panel of forest pathologists and entomologists gathered in Visby, Gotland Island, Baltic Sea, Sweden. The participants, a total of 20, represented all five Nordic Countries, three Baltic States, and Ukraine, and also joined by the local stakeholders representing the Swedish Forestry Agency and Gotland Administration. The purpose was to conduct a scientific workshop focusing on invasive tree pests and diseases emerging in each respective country, as well as to participate in an excursion to damaged woodland sites of Gotland. The Nordic Forest Research (SNS) financially supported the event (https://nordicforestresearch.org/n2023-01/). Keywords: Corinectria / Neonectria cankers; Hymenoscyphus fraxineus; Emerald Ash Borer; Diplodia sapinea; Acute Oak Decline; Polygraphus proximus; emerging birch pests; Bronze Birch Borer; Thekopsora areolata; seedborn conifer fungi

Pine needle gasification-based electricity production: Understanding the effect of supply chain.

Pine needles (pine tree leaves), found abundantly across continents such as North America, Asia, Europe, South America, Africa, and parts of the Southern Hemisphere, are a significant global concern due to their high susceptibility to catching fire, especially in dry and hot climates. The same issue persists in the Uttarakhand state of India, which boasts ample pine forests, yielding a substantial 1.67 × 109kg of pine needles annually. In the present study, the annual potential emissions from forest fires in Uttarakhand were estimated to be 58.37 × 109kg of CO2 equivalent. Therefore, the present research aims to unlock pine needles' potential via gasification for green electricity and biochar production, offering an alternative to coal-based plants while reducing forest fire frequencies. Nevertheless, obstacles hindering pine needle gasification include an unsteady supply chain, limited collection windows (100days), and plant expenses, including transportation and operational costs. The primary focus of the research is to design and assess the performance of a gasification-based supply chain for pine needles in the Almora District of Uttarakhand. Ten plant capacity scenarios were considered, ranging from 25 to 250kW. The study incorporated critical factors, encompassing diverse losses within the supply chain, selecting potential plant sites, minimizing transportation distance, and evaluating the supply chain's economic and environmental performance. The economic analysis revealed that the 250-kW plant scenario exhibited a minimum discounted payback period (DPP) of 3.93years, alongside an internal rate of return (IRR) of 19% and a net present value (NPV) of 653.32 million INR without government subsidies. With subsidies included, the DPP decreased to 1.30years, improving the IRR to 69% with an NPV of 916.17 million INR. The emission analysis indicated that gasification plant capacity scenarios could potentially reduce 44.63 × 106 to 46.16 × 106kg of CO2 equivalent emissions annually compared to grid electricity while meeting nearly 5.5% of the electricity demand of Almora district. The present study aligns with SDG-7 (Affordable and Clean Energy), SDG-13 (Climate Action), SDG-9 (Industry, Innovation, and Infrastructure), SDG-11 (Sustainable Cities and Communities), SDG-3 (Good Health and Well-being), and SDG-15 (Life on Land).

The Basic Process of Lighting as Key Factor in the Transition towards More Sustainable Urban Environments

The design of lighting installations on roads and urban infrastructure has strictly followed the regulatory requirements of each country for a long time. Based on the traffic intensity, the presence of pedestrians and the nature of activities within the area, these regulations have been used to establish the luminance or illuminance levels from or on the pavement, the minimum average uniformity, the maximum glare and the minimum energy efficiency. Accurate values of these static parameters are supposed to ensure safety, security, and efficacy, and have traditionally been considered as the main targets of lighting installations. Therefore, compliance with these regulations indicates whether an installation is legal or not. Although this philosophy is operative, the reality is different due to two main issues. First, the progressive ageing of populations, mainly in North America and Europe, the changing circumstances of traffic flow and modalities and the presence of groves or socioeconomic factors, might have a strong impact on the safety, security and sustainability of cities. Secondly, the current regulations leave out perceived safety and security issues, as well as the well-being of people; that is, how people feel about the city independently of real danger. In this research, the Basic Process of Lighting (BPL) is formulated including, for the first time, the human factors involved when people develop their activities under public lighting. Using this framework, the potential factors influencing human wellbeing and feelings are summarized after being rated by people in a survey distributed among 133 participants. The results highlight a higher perceived impact of social factors compared to physical and visual ones.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Trends of the cannabis market in Poland over the last decade = Tendencje na rynku konopi indyjskich w ostatniej dekadzie w Polsce

Cannabis is the most widely used drug. in recent years, interest in cannabis has grown significantly. over the last decade, the number of cannabis users worldwide has increased by almost 21%, reaching approximately 219 million people in 2021. Can- nabis cultivation covers practically all regions of the world. In recent years, 151 countries have reported cannabis cultivation, both outdoors and indoors. The increased growth of the latter is particularly observed in North America and Europe. Global data shows that in 2021, 5,226 tons of marihuana and 2,014 tons of hashish were confiscated. an increase in seizures of can- nabis products is observed in Europe and Poland. Another trend concerns the increasing content of the psychoactive substance Δ9-tetrahydrocannabinol (Δ9-THC) in cannabis plants. According to UNODC data, over the last 25 years there has been a 4-fold increase in the content of Δ9-THc in cannabis. over the last decade, the average content of Δ9-tetrahydrocannabinol in marihua- na seized in europe has increased approximately twice, and in hashish three times. The aim of this work is to assess potential changes in the content of the main psychoactive ingredients in cannabis in Poland in the last decade (2012–2022), based on expert opinions developed by the Institute of Forensic research in Kraków. The conduct- ed analyses confirmed the trends observed around the world. in the last ten years, the number of cases in which the drug-type cannabis was detected increased from 5.3% to 68.4% of total number of illicit drug cases examined for the presence of narcotic drugs, psychotropic substances and new psychoactive substances. an increasing trend in the content of Δ9-THC in the drug-type cannabis was also noted. over the last decade, the average total content of Δ9-THC increased almost three times and in 2022 reached 12%. This is due to the growth of cannabis cultivation in Europe, carried out using the technique known as sinsemilla, genetic modifications, as well as the appearance on the market of the feminized cannabis seeds.

The Function of RNA Interference (RNAi) in Crop Enhancement- Mechanism and Applications: A Review

RNA interference (RNAi) is a conserved molecular mechanism that plays a critical role in post-transcriptional gene silencing across diverse organisms. This review delves into the role of RNAi in plant functional genomics and its applications in crop improvement, highlighting its mechanistic insights and practical implications. The overview starts with the fundamental finding of the mechanism of RNAi, following its journey from petunias to its ubiquitous presence in a wide range of species. The discovery of several kinds of regulatory non-coding small RNAs, including as phasiRNAs, miRNAs, and siRNAs, has broadened our knowledge of RNAi-mediated gene regulation beyond what is previously thought. These RNA types have an impact on gene expression through complex post-transcriptional and epigenetic mechanisms. RNA interference (RNAi) has become a potent tool for comprehending gene activities in the context of crop improvement. It has shown to be useful in determining the functions of genes for metabolic pathways, stress tolerance, and more. Furthermore, RNAi-based strategies have potential for sustainable agriculture and integrated pest management, supporting international efforts to ensure food security. The many uses of RNA interference (RNAi) are covered in this article, including improving crop nutrition, changing plant architecture, and increasing shelf life. The challenges and future prospects of RNAi technology are also explored. The worldwide geography of RNA interference research is emphasized, with notable contributions from North America, Europe, and China. In conclusion, RNA interference (RNAi) continues to be a flexible and essential tool in contemporary plant research, providing new pathways for understanding gene activities and enhancing crop characteristics. Its combination with other biotechnological techniques, such as gene editing, might influence how agriculture and sustainable food production develop in the future.

Genome divergence and reproductive incompatibility among populations of Ganaspis near brasiliensis.

During the last decade, the spotted-wing drosophila, Drosophila suzukii, has spread from eastern Asia to the Americas, Europe, and Africa. This fly attacks many species of cultivated and wild fruits with soft, thin skins, where its serrated ovipositor allows it to lay eggs in undamaged fruit. Parasitoids from the native range of D. suzukii may provide sustainable management of this polyphagous pest. Among these parasitoids, host-specificity testing has revealed a lineage of Ganaspis near brasiliensis, referred to in this paper as G1, that appears to be a cryptic species more host-specific to D. suzukii than other parasitoids. Differentiation among cryptic species is critical for introduction and subsequent evaluation of their impact on D. suzukii. Here we present results on divergence in genomic sequences and architecture and reproductive isolation between lineages of Ganaspis near brasiliensis that appear to be cryptic species. We studied five populations, two from China, two from Japan, and one from Canada, identified as the G1 versus G3 lineages based on differences in cytochrome oxidase l sequences. We assembled and annotated the genomes of these populations and analyzed divergences in sequence and genome architecture between them. We also report results from crosses to test reproductive compatibility between the G3 lineage from China and the G1 lineage from Japan. The combined results on sequence divergence, differences in genome architectures, ortholog divergence, reproductive incompatibility, differences in host ranges and microhabitat preferences, and differences in morphology show that these lineages are different species. Thus, the decision to evaluate the lineages separately and only import and introduce the more host-specific lineage to North America and Europe was appropriate.

Systematic review and best practices for drone remote sensing of invasive plants

Abstract Drones have emerged as a cost‐effective solution to detect and map plant invasions, offering researchers and land managers flexibility in flight design, sensors and data collection schedules. A systematic review of trends in drone‐based image collection, data processing and analytical approaches is needed to advance the science of invasive species monitoring and management and improve scalability and replicability. We systematically reviewed studies using drones for plant invasion research to identify knowledge gaps, best practices and a path toward advancing the science of invasive plant monitoring and management. We devised a database of 33 standardized reporting parameters, coded each study to those parameters, calculated descriptive statistics and synthesized how these technologies are being implemented and used. Trends show a general increase in studies since 2009 with a bias toward temperate regions in North America and Europe. Most studies have focused on testing the validity of a machine learning or deep learning image classification technique with fewer studies focused on monitoring or modelling spread. Very few studies used drones for assessing ecosystem dynamics and impacts such as determining environmental drivers or tracking re‐emergence after disturbance. Overall, we noted a lack of standardized reporting on field survey design, flight design, drone systems, image processing and analyses, which hinders replicability and scalability of approaches. Based on these findings, we develop a standard framework for drone applications in invasive species monitoring to foster cross‐study comparability and reproducibility. We suggest several areas for advancing the use of drones in invasive plant studies including (1) utilizing standardized reporting frameworks to facilitate scientific research practices, (2) integrating drone data with satellite imagery to scale up relationships over larger areas, (3) using drones as an alternative to in‐person ground surveys and (4) leveraging drones to assess community trait shifts tied to plant fitness and reproduction.

Permanent areas and changes in forests, grasslands, and wetlands in the North European Plain since the eighteenth century—a case study of the Kościan Plain in Poland

This study investigates the intricate and enduring interplay of historical events, human activities, and natural processes shaping the landscape of North European Plain in western Poland over 230 years. Topographic maps serve as reliable historical data sources to quantify changes in forest, grassland, and wetland areas, scrutinizing their fragmentation and persistence. The primary objectives are to identify the permanent areas of the landscape and propose a universal cartographic visualization method for effectively mapping these changes. Using topographic maps and historical data, this research quantifies land cover changes, especially in forest, grassland, and wetland areas. With the help of retrogressive method we process raster historical data into vector-based information. Over time, wetlands experienced a substantial reduction, particularly in 1960–1982, attributed to both land reclamation and environmental factors. Grassland areas fluctuated, influenced by wetland and drier habitat dynamics. Fragmentation in grassland areas poses biodiversity and ecosystem health concerns, whereas forested areas showed limited fluctuations, with wetland forests nearly disappearing. These findings highlight wetland ecosystems’ sensitivity to human impacts and emphasize the need to balance conservation and sustainable development to preserve ecological integrity. This study advances landscape dynamics understanding, providing insights into historical, demographic, economic, and environmental transformations. It underscores the imperative for sustainable land management and conservation efforts to mitigate human impacts on ecosystems and biodiversity in the North European Plain.

Physiological effects of interacting native and invasive bivalves under thermal stress

AbstractAcross many ecosystems in North America and Europe, native freshwater bivalves (Order Unionida) are threatened by fouling and competition for food by the invasive zebra mussel Dreissena polymorpha. In light of climate change, knowledge on the influence of water temperature on these competitive effects is important, yet poorly understood. This study examines the physiological impact of the interaction between D. polymorpha and the native European unionid Anodonta cygnea over a 28 day—period in response to water temperatures of 12, 19, and 25 °C by comparing their glycogen, glucose, lipid and protein concentrations. The laboratory experiment comprised three treatments: (1) fouling of A. cygnea by D. polymorpha, (2) both species present but not fouling; and (3) a control in which A. cygnea and D. polymorpha were placed separately. Increased water temperatures caused physiological stress in D. polymorpha as evident from reduced glycogen, glucose, lipid and protein concentrations. Dreissena polymorpha benefited from fouling of unionids, as individuals that fouled A. cygnea tended to have increased glycogen, glucose, lipid and protein concentrations. Competitive effects of D. polymorpha over the unionid bivalve species, however, were not intensified by elevated temperatures. Glochidia release, lower infestation intensity, and physiological stress of Dreissena at higher temperatures were likely confounding factors. The results of this study suggest that understanding the physiological consequences of species interactions at changing temperatures can be an important tool to assess future climate change impacts on freshwater bivalves and aquatic community structures.

Explorando la influencia de oscilaciones climáticas en acuíferos: Revisión de estudios observacionales

Groundwater is critical for society’s adaptation to climate variability and change but simultaneously, is threatened by them. This paper reviews the linkages between climate oscillations and groundwater, focusing on studies reported in the Scopus database that use wavelet analysis. A total of 27 records published since 2009, covering North America, Europe, and Asia, have been analysed. El Niño Southern Oscillation (ENSO), the North Atlantic Oscillation (NAO), Arctic Oscillation, and the Pacific Decadal Oscillation (PDO) show important effects on groundwater levels in North America. In Europe, NAO is the most dominant, while in Asia, distinct climate indices impact groundwater levels at different periodicities. The hydrogeological features of the aquifers condition the magnitude of the response of groundwater to the climate signal and there is conflicting evidence concerning the effects of land-use change and human activities on detecting climate signals in aquifers. Further research must focus on understanding the effect of human activities in the climate signal perception in aquifers, unravelling the physical mechanisms underlying the propagation of climate signals through aquifers, developing predictive models to support water management decisions, and finding alternative methods to assess this influence in regions with limited observational data. The interaction between the atmosphere and groundwater is of critical relevance for the achievement of water security and this review contributes to synthesizing our current understanding of this relationship.

Enviro‐economic and feasibility analysis of industrial hemp value chain: A systematic literature review

AbstractA recent renaissance of industrial hemp has been driven by a plethora of ecologically amicable products and their profitability. To identify its environment and economic fate across the value chain (VC), this study conducts a systematic review of 98 studies published in ScienceDirect, Web of Science, and Scopus‐indexed journals. The thematic content of the articles is categorized using three deductively derived classification categories: lifecycle analysis (n = 40), VC analysis (n = 30), and feasibility analysis (n = 28). Bibliometric analysis indicates that the majority (&gt;90%) of the studies were conducted in selected regions of Europe or North America, with further findings around regionally prioritized industrial hemp products, such as hempcrete in Southwest Europe, solid biofuel in North European states, and textile fiber and bio‐composites in East Europe and North America. Lifecycle analysis studies highlight nitrogenous fertilizer use during industrial hemp cultivation as a major ecological hotspot, which is taking a toll on the climate change index. However, hemp‐based products are generally climate‐friendly solutions when contrasted against their fossil fuel counterparts, with hempcrete in particular a highly touted carbon‐negative (−4.28 to −36.08 kg CO2 eq/m2) product. The review also identifies key issues within the hemp VC and presents innovative solutions alongside the recognition of value‐adding opportunities. Furthermore, feasibility analysis indicates unprofitability in using hemp for bioenergy production and there is a relative cost worthiness of hemp bio‐composites and hempcrete at the upstream level. Positive returns are observed under co‐production schemes. In contemplating the literature findings, we discussed and identified gap in existing literature for future exploration, including more studies to provide insights from the Global South, and the production of industrial hemp under a biophysically constrained landscape.

Abstract PS10-09: Development of an absolute risk prediction model for premenopausal breast cancer in an international consortium

Abstract Risk prediction models that have been developed for overall breast cancer risk are based on a limited number of premenopausal cases in individual cohorts. As some risk factors differ in their associations with pre- versus postmenopausal breast cancer, a distinct risk prediction model is needed for premenopausal breast cancer. We developed a risk prediction model for premenopausal breast cancer using 779,601 participants and 9,665 incident cases from 18 prospective studies within the Premenopausal Breast Cancer Collaborative Group (PBCCG), across North America (N=9), Europe (N=6), Australia (N=1), and Asia (N=2). Data were split, within each cohort, into training (2/3) and testing (1/3) datasets. Individual risk was assessed in five-year intervals, using variables reported at the start of the time interval. Cox proportional hazards regression was used to model risk factors in a backwards-selection method, stratified by cohort: age at menarche, age at first birth, parity, breastfeeding (months), height (cm), BMI (kg/m2), BMI at age 18, recent weight change (kg), alcohol consumption (drinks/week), first-degree family history of breast cancer, and personal history of benign breast disease. To enable the use of information from all cohorts despite differences in missing variables by design, cohorts were grouped by available variables and risk models were fit for each group. In cohorts with incomplete data, model coefficients were adjusted based on the correlation of covariates with the missing variables in the complete case dataset. Coefficients were meta-analyzed with inverse variance weighting to obtain final coefficients. Discrimination was evaluated in the testing dataset by calculation of the c-index. Work is ongoing to calibrate the model based on five-year absolute risk using GLOBOCAN continent- and age-specific incidence rates to represent baseline risk. The final model included age at menarche, parity, height, BMI, BMI at age 18, first-degree family history of breast cancer, and history of benign breast disease. Young adulthood BMI and BMI (at start of the 5-year risk interval) were associated with a decreased risk (Hazard Ratio (HR) (95% confidence interval (CI)) per 5 kg/m2 = 0.87 (0.81-0.93) and 0.90 (0.86-0.95), respectively) as was parity (HR (95% CI) = 0.92 (0.90-0.94)). Height was associated with increased risk (HR (95% CI) per 10 cm = 1.14 (1.07-1.21)), while history of benign breast disease and family history were associated with larger increases in risk (HR (95% CI) = 1.64 (1.30-2.06) and 1.76 (1.63-1.90), respectively). Model discrimination was higher than that reported for women under 50 years in existing breast cancer risk prediction models considering clinical factors (AUC (95% CI) = 0.61 (0.59-0.62)). Calibration of absolute 5-year risk is ongoing. Several factors driving risk prediction of postmenopausal breast cancer have similar influence on risk of premenopausal breast cancer, while family history has a stronger influence on premenopausal breast cancer risk. Our model demonstrates acceptable discrimination and will enable individual 5-year absolute risk prediction for premenopausal breast cancer. Citation Format: Kristen Brantley, Michael Jones, Minouk Schoemaker, Hazel Nichols, Anthony Swerdlow, Robert MacInnis, Roger Milne, Tess Clenenden, Yu Chen, Xiao-Ou Shu, Wei Zheng, Woon-Puay Koh, Jian-Min Yuan, Cari Kitahara, Martha Linet, Dale Sandler, Bernard A Rosner, Peter Kraft, A. Heather Eliassen. Development of an absolute risk prediction model for premenopausal breast cancer in an international consortium [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-09.

Abstract PO3-17-10: Real-World evidence for Pembrolizumab-based neoadjuvant chemotherapy in early-stage triple negative breast cancer: a single institution experience

Abstract Introduction The improved pathologic complete response (pCR) and event-free survival observed in Keynote-522 trial (NCT03036488) led to the adoption of (neo)adjuvant pembrolizumab (pembro)-based chemotherapy (CT) for high-risk early-stage triple-negative breast cancer (eTNBC) in various jurisdictions. However, Real-World Evidence (RWE) for (neo)adjuvant pembro in this setting would further support its ongoing funding and utilization. The aim of this study was to provide RWE for (neo)adjuvant pembro in eTNBC in the United Arab Emirates (UAE), where patients often present with more-advanced disease stages and poorer prognostic profiles compared with North America and Europe. Method This is a retrospective cohort study involving all patients treated with pembro-based neoadjuvant chemotherapy (NACT) for eTNBC at a major cancer center (Tawam Hospital) in the UAE between October 2021 and June 2023. Patient characteristics, clinicopathologic features, immune related adverse events (irAE) and disease outcomes were reported by descriptive statistics. An exploratory analysis was also conducted to examine the associations between pCR and HER-2 status (HER2 negative vs HER2 low) as well pCR and treatment interruption (&amp;lt; vs = &amp;gt; 2 weeks). ResultA total of 41 patients, with a median age of 44 years, were included in this study. All had an ECOG status of 0-1. The clinical and pathological characteristics are provided in Table 1. Pathogenic germline BRCA (gBRCA) mutations were detected in 8 (21%) of the 38 patients who underwent testing, including 6 with gBRCA1 and 2 with gBRCA2), with additional TP53 and SMARC4 detected in one patient each. Approximately 66% of the patients (n = 27) completed surgery post neoadjuvant pembro+CT, of whom 18 (67%) had breast conserving surgery and 9 (33%) had mastectomy. Of the patients who underwent surgery, 60% (n = 16/27) achieved pCR including 68% (13/19) of the IHC 0+ and 37.5% (3/8) of the HER2 1+ or 2+ ISH negative (p-value = 0.429, Chi Square test). Of the total population, 16 (40%) did not complete NACT; 1 lost to follow-up, 9 were still on ongoing therapy, 2 discontinued therapy due to toxicity, and 4 developed progressions including 1 locoregional relapse, and 3 metastatic diseases. Of the 32 patients who completed at least 3 months of pembro-NACT, 14 (34%) reported any grade irAE: skin toxicity (N = 3, 21%), hypothyroidism (N = 8, 57%), Hyperthyroidism (N = 1, 7%), Hepatitis (N = 4, 28.5%), adrenal insufficiency (N = 1, 7%), and pneumonitis (N = 1, 7%). With a median follow up of 4.5 months, pembro was postponed in 4 patients and permanently discontinued in 1 secondary to severe pneumonitis requiring ICU admission. All irARs were graded at I and II, except for 1 grade III dermatitis, and 1 grade III pneumonitis. Interruption of IO was required for irAE in 5 (36%) patients, and steroids were administered in 4 (29%). pCR was observed in 6 (40%) patients out of 15 who experienced treatment interruption due to IrAE or CT and 10 out of 13 (77%) in those who did not experience treatment interruption (p = 0.04895, Chi-square test). Conclusion The pCR rates for Pembro-based NACT in this RWE study, involving patients with an overall higher risk disease, appeared to be consistent with those observed in keynote-522. Interestingly, pCR rates did not seem to differ between HER2 negative and HER2 low groups. However, pCR rates appeared to be lower in patients who experienced treatment interruptions. Approximately half of the patients developed irAE but the majority of the adverse events were of lower grade and did not require treatment interruptions. Overall, the RWE observed in this study supports the ongoing funding and utilization of Pembro-based NACT in eTNBC. Updated data, including the pCR rate and toxicity, will be presented at the meeting once most of the patients have completed surgery. Table 1: Clinical and Pathological Characteristics of patients (Nf41) XX- XX Citation Format: Aydah Al-Awadhi, Mouza AlShebli, Lina Wahba, Tallal Younis. Real-World evidence for Pembrolizumab-based neoadjuvant chemotherapy in early-stage triple negative breast cancer: a single institution experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-10.

Lack of Diversity in Research on Females with Ehlers-Danlos Syndromes: Recruitment Protocol for a Quantitative Online Survey.

Ehlers-Danlos syndromes (EDS) are a group of connective tissue disorders caused by fragile lax collagen. Current EDS research lacks racial and ethnic diversity. The lack of diversity may be associated with the complexities of conducting a large international study on an underdiagnosed condition and a lack of EDS health care providers who diagnose and conduct research outside of the United States and Europe. Social media may be the key to recruiting a large diverse EDS sample. However, studies that have used social media to recruit have not been able to recruit diverse samples. This study aims to discuss challenges, strategies, outcomes, and lessons learned from using social media to recruit a large sample of females with EDS. Recruitment on social media for a cross-sectional survey examining dyspareunia (painful sexual intercourse) in females was examined. Inclusion criteria were (1) older than 18 years of age, (2) assigned female at birth, and (3) diagnosed with EDS. Recruitment took place on Facebook and Twitter (now X), from June 1 to June 25, 2019. A total of 1178 females with EDS were recruited from Facebook (n=1174) and X (n=4). On Facebook, participants were recruited via support groups. A total of 166 EDS support groups were identified, 104 permitted the principal investigator to join, 90 approved posting, and the survey was posted in 54 groups. Among them, 30 of the support groups posted in were globally focused and not tied to any specific country or region, 21 were for people in the United States, and 3 were for people outside of the United States. Recruitment materials were posted on X with the hashtag #EDS. A total of 1599 people accessed the survey and 1178 people were eligible and consented. The average age of participants was 38.6 (SD 11.7) years. Participants were predominantly White (n=1063, 93%) and non-Hispanic (n=1046, 92%). Participants were recruited from 29 countries, with 900 (79%) from the United States and 124 (11%) from Great Britain. Our recruitment method was successful at recruiting a large sample. The sample was predominantly White and from North America and Europe. More research needs to be conducted on how to recruit a diverse sample. Areas to investigate may include connecting with more support groups from outside the United States and Europe, researching which platforms are popular in different countries, and translating study materials into different languages. A larger obstacle to recruiting diverse samples may be the lack of health care providers that diagnose EDS outside the United States and Europe, making the pool of potential participants small. There needs to be more health care providers that diagnose and treat EDS in countries that are predominantly made up of people of color as well as research that specifically focuses on these populations. RR1-10.2196/53646.