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Abstract The Breast Cancer UK—Breast Cancer Prevention Conference addressed risk from environmental pollutants and health behaviour‐related breast‐cancer risk. Epidemiological studies examining individual chemicals and breast cancer risk have produced inconclusive results including endocrine disrupting chemicals (EDCs) Bisphenol A, per‐ and polyfluorinated alkyl substances as well as aluminium. However, laboratory studies have shown that multiple EDCs, can work together to exhibit effects, even when combined at levels that alone are ineffective. The TEXB‐α/β assay measures total estrogenic load, and studies have provided evidence of a link between multiple‐chemical exposures and breast cancer. However, prospective studies using TEXB‐α/β are needed to establish a causative link. There is also a need to assess real‐life exposure to environmental‐chemical mixtures during pregnancy, and their potential involvement in programming adverse foetal health outcomes in later life. Higher rates of breast cancer have occurred alongside increases in potentially‐modifiable risk factors such as obesity. Increasing body‐mass index is associated with increased risk of developing postmenopausal breast cancer, but with decreased risk of premenopausal breast cancer. In contrast, lower rates of breast cancer in Asian compared to Western populations have been linked to soya/isoflavone consumption. Risk is decreased by breastfeeding, which is in addition to the decrease in risk observed for each birth and a young first‐birth. Risk is lower in those with higher levels of self‐reported physical activity. Current evidence suggests breast‐cancer survivors should also avoid weight gain, be physically active, and eat a healthy diet for overall health. A broad scientific perspective on breast cancer risk requires focus on both environmental exposure to chemicals and health behaviour‐related risk. Research into chemical exposure needs to focus on chemical mixtures and prospective epidemiological studies in order to test the effects on breast cancer risk. Behaviour‐related research needs to focus on implementation as well as deeper understanding of the mechanisms of cancer prevention.

Abstract Fostemsavir is an approved gp120‐directed attachment inhibitor and prodrug for the treatment of human immunodeficiency virus type 1 infection in combination with other antiretrovirals (ARVs) in heavily treatment‐experienced adults with multi‐drug resistance, intolerance, or safety concerns with their current ARV regimen. Initial in vitro studies indicated that temsavir, the active moiety of fostemsavir, and its metabolites, inhibited organic cation transporter (OCT)1, OCT2, and multidrug and toxin extrusion transporters (MATEs) at tested concentration of 100 uM, although risk assessment based on the current Food and Drug Administration in vitro drug–drug interaction (DDI) guidance using the mechanistic static model did not reveal any clinically relevant inhibition on OCTs and MATEs. However, a DDI risk was flagged with EMA static model predictions. Hence, a physiologically based pharmacokinetic (PBPK) model of fostemsavir/temsavir was developed to further assess the DDI risk potential of OCT and MATEs inhibition by temsavir and predict changes in metformin (a sensitive OCT and MATEs substrate) exposure. No clinically relevant impact on metformin concentrations across a wide range of temsavir concentrations was predicted; therefore, no dose adjustment is recommended for metformin when co‐administered with fostemsavir.

Abstract Tuberculosis (TB) may cause significant long‐term cardiorespiratory complications, of which pulmonary vascular disease is most under‐recognized. TB is rarely listed as a cause of pulmonary hypertension (PH) in most PH guidelines, yet PH may develop at various stages in the time course of TB, from active infection through to the post‐TB period. Predisposing risk factors for the development of PH are likely multifactorial, involving active TB disease and post‐TB lung disease (PTLD), host‐related and environment‐related factors. Moreover, post‐TB PH should likely be classified in Group 3 PH, with the pathogenesis similarly complex and multifactorial as other Group 3 PH causes. Identifying risk factors that predispose to post‐TB PH may aid in developing risk stratification criteria for early identification and referral for confirmatory diagnostic tests. Given that universal screening for PH in TB survivors may be impractical and unfeasible, a targeted screening approach for high‐risk individuals would be sensible. In this scoping review of post‐TB PH, resulting from the proceedings of the 2nd International Post‐Tuberculosis Symposium, we aim to describe the epidemiology, risk factors, and pathophysiology of post‐TB PH. We emphasize diagnosing PH with an alternative set of diagnostic guidelines in resource‐constrained settings where right heart catheterization may not be feasible. Research to describe the burden and distribution of post‐TB PH should be prioritized as there is a current gap in knowledge regarding the prevalence and incidence of post‐TB PH among persons with TB.

Key Clinical Message VEXAS syndrome (vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) is a novel autoinflammatory syndrome. We describe a case of VEXAS syndrome with upper airway and oral cavity involvement which are not well described in the literature.

Abstract Background This study examined the efficacy of an interdisciplinary limb preservation service (LPS) in improving surgical outcomes for diabetic foot ulcer (DFU) patients compared to traditional care. Methods Data from January 1, 2017 to September 30, 2020 were retrospectively reviewed. An interdisciplinary LPS clinic began on August 1, 2018, coexisting with a preexisting single specialty service. Primary outcomes were major/minor amputation rates and ratios and hospital length of stay. Surgical endpoints pre‐ and post‐LPS launch were compared. Results Among 976 procedures for 731 unique DFU patients, most were male (80.4%) and Hispanic (89.3%). Patient demographics were consistent before and after LPS initiation. Major amputation rates decreased by 45.5% (15.4%–8.4%, p = 0.001), with outpatient procedures increasing over 5‐fold (3.3% pre‐LPS to 18.7% post‐LPS, p

Abstract Variability of ice microphysical properties like crystal size and density in cirrus clouds is important for climate through its impact on radiative forcing, but challenging to represent in models. For the first time, recent laboratory experiments of particle growth (tied to crystal morphology via deposition density) are combined with a state‐of‐the‐art Lagrangian particle‐based microphysics model in large‐eddy simulations to examine sources of microphysical variability in cirrus. Simulated particle size distributions compare well against balloon‐borne observations. Overall, microphysical variability is dominated by variability in the particles' thermodynamic histories. However, diversity in crystal morphology notably increases spatial variability of mean particle size and density, especially at mid‐levels in the cloud. Little correlation between instantaneous crystal properties and supersaturation occurs even though the modeled particle morphology is directly tied to supersaturation based on laboratory measurements. Thus, the individual thermodynamic paths of each particle, not the instantaneous conditions, control the evolution of particle properties.

Abstract Objectives Adherence to lifestyle modification (diet, exercise, and alcohol cessation) for fatty liver disease (FLD) management remains challenging. The study examined stigma, barriers, and factors associated with motivation to adhere to lifestyle modification in a diverse and vulnerable population with FLD. Methods From 2/19/2020 to 2/28/2022, 249 FLD patients within San Francisco safety‐net hepatology clinics were surveyed along with clinical data taken from medical records. Multivariable modeling assessed factors associated with motivation to adhere to lifestyle modification in a cross‐sectional study. Results Median age was 53 years, 59% female, 59% Hispanic, 25% Asian/Pacific Islander, 9% White, and 2% Black, 79% were non‐English speakers, 64% had ≤ high school education, and 82% reported high school (coef 1.41, 95% CI 0.34–2.48), stigma (coef 0.34, 95% CI 0.07–0.62), and depression (coef −1.52, 95% CI ‐2.79 to −0.26) were associated with motivation. Conclusions Stigma is commonly reported among FLD patients. Interventions to enhance patient education and mental health support are critical to FLD management, especially in vulnerable populations.

Background Long‐term (visit‐to‐visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given the limitations of relying solely on blood pressure level to identify pregnancies at risk, long‐term (visit‐to‐visit) BPV or HRV may provide additional diagnostic/prognostic counsel. To address this, we conducted a systematic review to examine the association between long‐term BPV and HRV in pregnancy and adverse maternal and perinatal outcomes. Methods and Results Databases were searched from inception to May 2023 for studies including pregnant women, with sufficient blood pressure or heart rate measurements to calculate any chosen measure of BPV or HRV. Studies were excluded that reported short‐term, not long‐term, variability. Adjusted odds ratios were extracted. Eight studies (138 949 pregnancies) reporting BPV met our inclusion criteria; no study reported HRV and its association with pregnancy outcomes. BPV appeared to be higher in women with hypertension and preeclampsia specifically, compared with unselected pregnancy cohorts. Greater BPV was associated with significantly more adverse pregnancy outcomes, particularly maternal (gestational hypertension [odds ratio range, 1.40–2.15], severe hypertension [1.40–2.20]), and fetal growth (small‐for‐gestational‐age infants [1.12–1.32] or low birth weight [1.18–1.39]). These associations were independent of mean blood pressure level. In women with hypertension, there were stronger associations with maternal outcomes but no consistent pattern for perinatal outcomes. Conclusions Future work should aim to confirm whether BPV could be useful for risk stratification prospectively in pregnancy, and should determine the optimal management path for those women identified at increased risk of adverse outcomes.

Abstract Measuring forest biodiversity using terrestrial surveys is expensive and can only capture common species abundance in large heterogeneous landscapes. In contrast, combining airborne imagery with computer vision can generate individual tree data at the scales of hundreds of thousands of trees. To train computer vision models, ground‐based species labels are combined with airborne reflectance data. Due to the difficulty of finding rare species in a large landscape, many classification models only include the most abundant species, leading to biased predictions at broad scales. For example, if only common species are used to train the model, this assumes that these samples are representative across the entire landscape. Extending classification models to include rare species requires targeted data collection and algorithmic improvements to overcome large data imbalances between dominant and rare taxa. We use a targeted sampling workflow to the Ordway Swisher Biological Station within the US National Ecological Observatory Network (NEON), where traditional forestry plots had identified six canopy tree species with more than 10 individuals at the site. Combining iterative model development with rare species sampling, we extend a training dataset to include 14 species. Using a multi‐temporal hierarchical model, we demonstrate the ability to include species predicted at

Key Clinical Message We report an unusual case presentation of a patient with necrotic tissue changes of the right second and third fingers, found to have myeloid sarcoma with Staphylococcus‐positive tenosynovitis and underlying acute myeloid leukemia, to highlight the importance of comprehensive evaluation in patients with atypical wounds.

Abstract CAG repeat‐expansion spinocerebellar ataxias (CAG‐SCAs) are genetically defined multisystemic degenerative diseases, resulting in motor symptoms including dysarthria with a substantial impact on daily living. Whilst speech therapy is widely recommended in ataxia, very limited evidence exists for its use. We evaluated the efficacy of a home‐delivered, ataxia‐tailored biofeedback‐driven speech therapy in CAG‐SCA in 16 individuals with SCA1, 2, 3, or 6. Treatment was delivered intensively over 20 days. Efficacy was evaluated by blinded ratings of intelligibility (primary) and acoustic measures (secondary) leveraging an intra‐individual control design. Intelligibility improved post‐treatment (Z = −3.18, p = 0.004) whilst remaining stable prior to treatment (Z = 0.53, p = 1.00).

Abstract Small, isolated populations present a challenge for conservation. The dueling effects of selection and drift in a limited pool of genetic diversity make the responses of small populations to environmental perturbations erratic and difficult to predict. This is particularly true at the edge of a species range, where populations often persist at the limits of their environmental tolerances. Populations of cisco, Coregonus artedi, in inland lakes have experienced numerous extirpations along the southern edge of their range in recent decades, which are thought to result from environmental degradation and loss of cold, well‐oxygenated habitat as lakes warm. Yet, cisco extirpations do not show a clear latitudinal pattern, suggesting that local environmental factors and potentially local adaptation may influence resilience. Here, we used genomic tools to investigate the nature of this pattern of resilience. We used restriction site‐associated DNA capture (Rapture) sequencing to survey genomic diversity and differentiation in southern inland lake cisco populations and compared the frequency of deleterious mutations that potentially influence fitness across lakes. We also examined haplotype diversity in a region of the major histocompatibility complex involved in stress and immune system response. We correlated these metrics to spatial and environmental factors including latitude, lake size, and measures of oxythermal habitat and found significant relationships between genetic metrics and broad and local factors. High levels of genetic differentiation among populations were punctuated by a phylogeographic break and residual patterns of isolation‐by‐distance. Although the prevalence of deleterious mutations and inbreeding coefficients was significantly correlated with latitude, neutral and non‐neutral genetic diversity were most strongly correlated with lake surface area. Notably, differences among lakes in the availability of estimated oxythermal habitat left no clear population genomic signature. Our results shed light on the complex dynamics influencing these isolated populations and provide valuable information for their conservation.

Abstract Igneous sheet intrusions are a fundamental component of volcano plumbing systems. Identifying how sheet intrusion emplacement and geometry controls later magmatic processes is critical to understanding the distribution of volcanic eruptions and magma‐related ore deposits. Using the Younger Giant Dyke Complex (YGDC), a Mesoproterozoic suite of large (

Fostemsavir, a prodrug of human immunodeficiency virus attachment inhibitor temsavir (TMR), is in phase III development in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type I (HIV‐1) infection in heavily treatment‐experienced adults with multidrug‐resistant HIV‐1 infection for whom it is otherwise not possible to construct a suppressive antiviral regimen due to resistance, intolerance, or safety considerations. The proarrhythmic potential of fostemsavir was studied in a thorough QT study and exposure–response modeling was performed at therapeutic and supratherapeutic concentrations of TMR. Fostemsavir 1,200 mg b.i.d. did not result in a clinically meaningful change from placebo in baseline‐adjusted Fridericia‐corrected QTc (ddQTcF); however, at a supratherapeutic dose of 2,400 mg b.i.d., the upper bound of the two‐sided 90% confidence interval (CI) of ddQTcF was 13.2 msec, exceeding the clinically important 10 msec threshold. A linear model of ddQTcF as a function of TMR plasma concentrations described these observations. Based on simulations with this model, TMR concentrations up to 7,500 ng/mL are expected to have an upper 90% CI bound for QTcF ≤ 10 msec. This concentration is 4.2‐fold higher than the geometric mean TMR peak plasma concentration (Cmax) of 1,770 ng/mL in heavily treatment‐experienced HIV‐1 infected patients administered fostemsavir 600 mg b.i.d. in the phase III BRIGHTE study (NCT02362503).