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Abstract In recent years, blooms of the neurotoxic dinoflagellate Alexandrium catenella have been documented in Pacific Arctic waters, and the paralytic shellfish toxins (PSTs) that this species produces have been detected throughout the food web. These observations have raised significant concerns about the role that harmful algal blooms (HABs) will play in a rapidly changing Arctic. During a research cruise in summer 2022, a massive bloom of A. catenella was detected in real time as it was advected through the Bering Strait region. The bloom was exceptional in both spatial scale and density, extending > 600 km latitudinally, reaching concentrations > 174,000 cells L−1, and producing high‐potency PST congeners. Throughout the event, coastal stakeholders in the region were engaged and a multi‐faceted community response was mobilized. This unprecedented bloom highlighted the urgent need for response capabilities to ensure safe utilization of critical marine resources in a region that has little experience with HABs.

ABSTRACT The Additively‐Manufactured, System‐Integrated Tip (AMSIT) project is leveraging the flexibility of 3D printing to integrate several technologies in a wind turbine blade tip, while reducing the levelized cost of electricity (LCOE) produced. The design integration is demonstrated for a 200‐kW–scale turbine with 13‐m blades, with the outer 15% of the blade replaced with a 3D‐printed design. Aerodynamic performance is enhanced without increasing swept area through inclusion of a winglet and surface texturing, both challenging for traditional manufacturing. Longevity and durability are improved through integrated lightning and leading edge erosion protection. Increased power, reduced repair frequency, and ease of repair through blade modularity all contribute to reduced LCOE. The analysis is also extended to modern MW‐scale designs to estimate the impact of the technology at scale, demonstrating the potential to reduce LCOE significantly for modern onshore turbines, with even higher potential savings offshore.

ABSTRACT In this work, we develop a new analytical turbine induction model that can incorporate complex inflow conditions including cases where the wind velocity and temperature profiles can vary as functions of height. This induction model is derived from the linearized Navier–Stokes and leads to a second‐order ODE that can be solved using a Green's function formulation. The corresponding Green's function for several configurations are found including the infinite domain, semi‐infinite domain with ground plane, and a power law velocity inflow profile. The results of this approach are then compared with simulations of the turbine induction field using the AMR‐Wind CFD solver with a uniformly loaded actuator disk model. These comparisons show that the Green's function approach captures the centerline blockage, three‐dimensional blockage flow field, and streamwise velocity slow down, with very good agreement for lower thrust conditions and at larger distances away from rotor disk. The effects of shear on the turbine blockage were also compared using a power law inflow profile, and we show that this approach matches the CFD predictions for the cases considered.

ABSTRACT Background Testing for targeting programmed death ligand 1 (PD‐L1) is standard of care for patients with newly diagnosed non‐small cell lung cancer (NSCLC) but is only approved for use with core biopsy specimens. Endobronchial ultrasound guided miniforceps biopsy (EBUS‐MFB) is an approach to obtain core biopsy material but data assessing the ability of EBUS‐MFB to adequately test for PD‐L1 is lacking. We evaluate the feasibility of EBUS‐MFB to acquire adequate tissue for PD‐L1 testing and look to compare the quality of specimens between EBUS‐MFB and endobronchial ultrasound guided transbronchial needle aspiration (EBUS‐TBNA) using a standard method of tissue analysis. Methods Twenty patients with suspected non‐small cell lung cancer undergoing bronchoscopy were recruited for enrollment. For each patient with NSCLC diagnosed on rapid onsite pathology with EBUS‐TBNA, EBUS‐MFB was performed. PD‐L1 immunostaining was completed to assess for adequacy. A comparison of tissue collection was performed using the total surface area measured by digital imaging. Results Among 20 patients, 65% were male with a mean age of 66 years with a total procedure time of 50 min and an average of 14 biopsy passes per procedure. 15 (75%) patients were diagnosed with NSCLC, and PD‐L1 analysis was successfully performed in 12 of the 15 (80%). The mean total tissue area obtained by the MFB technique was 9.757 mm2 compared to 6.941 mm2 with TBNA (p = 0.427). Conclusion In this feasibility study, EBUS‐MFB was successful in performing PD‐L1 testing in 80% of patients with NSCLC.

ABSTRACT Introduction Small cell neuroendocrine carcinoma of the urinary tract (SCNEC‐URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery. Materials and Methods We identified a definitive‐surgery cohort (n = 224) from an institutional database of patients with cT1‐T4NxM0 SCNEC‐URO treated in 1985–2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time‐to‐event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine‐Gray distribution models assessed covariate associations. Results Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) patients had relapse with 77 (83.7%) having distant organs as first metastatic sites, including 10 (10.9%) with exclusive central nervous system (CNS) metastases, mostly (9/10) within 1 year of surgery. Patients with pathologic complete response (pCR) after neoCTx had the lowest 5‐year CIF (16.5% [95% CI 9.3%–25.6%]). Patients with remaining exclusively small cell (SC) histology had the highest CIF (85.7% [95% CI 46.6–96.9]). Patients with eradicated SCNEC but remaining UC components had an intermediate‐risk CIF (32.5% [95% CI 18.6–47.2]). Multivariable analysis adjusting for neoCTx, clinical stage at diagnosis (T3/4, N0/N+ vs. T1/T2, N0), and pathologic stage (pN+ vs. pN0) demonstrated that any SCNEC histology at resection (vs. pCR) was associated with relapse risk (hazard ratio = 3.69 [95% CI 1.91–7.13], p = 0.0001). Conclusions SCNEC‐URO is a systemic disease with high risk of distant relapse including CNS. Our findings highlight unmet needs for neoadjuvant/adjuvant approaches targeting the rare SCNEC subtype and suggest adding CNS surveillance within the first year after definitive surgery to high‐risk patients. Précis (Condensed Abstract) Alongside neoadjuvant chemotherapy and cancer stage, histology at resection strongly impacts relapse risk in small cell neuroendocrine carcinomas of the urinary tract. The incidence of brain metastasis is notably higher than in “traditional” urothelial cancer within the first year after surgery, especially if small cell cancer persists, thus necessitating close neurological monitoring during this period.

ABSTRACT Objective Obesity is related to the recurrence of breast cancer. In‐person groups or individual telephone counseling currently comprise the behavioral weight loss (BWL) programs tested for cancer survivors. Group support via telehealth may be convenient and provide support from fellow survivors, but feasibility, acceptability, and efficacy testing are needed. Methods A single‐arm, 6‐month BWL program was conducted for female breast cancer survivors with an ECOG performance 0 or 1, BMI > 25 kg/m2, and > 6 months from completion of adjuvant chemotherapy and/or radiation treatment. Participants attended 22 video group sessions over 6 months, completing acceptability ratings, weight measurements, Patient Health Questionnaire (PHQ‐9), City of Hope Breast Cancer Quality of Life Scale (QOL), and International Physical Activity Questionnaire. Changes in survey scores and weight (last‐observation carried forward) and differences in outcomes by patients' race were computed with paired t‐tests, ANCOVAs and Chi‐square tests. Results Twenty‐one (5 Black, 15 White, 1 Asian American; Mean (SD) = 60.7 (11.6) years; BMI 33.1 (5.9) kg/m2) survivors enrolled with 90% retention and 81.3% of sessions attended. Acceptability ratings were high (all > 4 on a five‐point scale). Mean (SD) weight loss was 5.9% (5.2%), with 60% losing ≥ 5% of baseline weight; White participants lost 7.5% and Black participants lost 1.9% (p = 0.04). Significant improvements were observed in mood (PHQ‐9; p = 0.01) and physical wellbeing QOL (p = 0.01). Physical activity did not change. Conclusion This telehealth group BWL program was feasible and acceptable for breast cancer survivors, yielding a clinically significant weight loss. Future studies should test this intervention in larger, more diverse samples. Trail Registration ClinicalTrials.gov identifier: NCT04855552, posted April 22, 2021

Abstract Lumpfish (Cyclopterus lumpus) are raised as cleaner fish for controlling sea lice. Intensive rearing is complicated by fin nipping that occurs between juvenile conspecifics. Lumpfish density‐dependent interactions are not well understood; therefore, the effects of rearing density for different fish size classes warranted evaluation. Two size classes (2‐ and 13‐g) of juvenile lumpfish were stocked at four different rearing densities (40, 60, 70, and 90 g/L) with growth, survival, and fish aggression assessed over 8 weeks. Mean weight gain and specific growth rates ranged from 170% to 307% and 1.77% to 2.50%, respectively, depending on density treatments, for the 2‐g fish, and from 286% to 471% and 2.42% to 3.10% for the 13‐g fish. Growth was negatively correlated with density, with faster growth linked to lower densities. No mortality occurred in any treatment and significant fish aggression only occurred among the larger lumpfish in the higher rearing densities. Based on these findings, growth of 2‐g lumpfish can be increased if reared at 40 g/L or slowed at 70 g/L without impacting aggression. For grow out of 13‐g fish to ~70 g with minimal aggression, a 40 g/L rearing density is recommended for faster growth and 60 g/L for slower growth.

Abstract As current treatments for Alzheimer's disease (AD) lack disease‐modifying interventions, novel therapies capable of restraining AD progression and maintaining better brain function have great significance. Anti‐inflammatory extracellular vesicles (EVs) derived from human induced pluripotent stem cell (hiPSC)‐derived neural stem cells (NSCs) hold promise as a disease‐modifying biologic for AD. This study directly addressed this issue by examining the effects of intranasal (IN) administrations of hiPSC‐NSC‐EVs in 3‐month‐old 5xFAD mice. IN administered hiPSC‐NSC‐EVs incorporated into microglia, including plaque‐associated microglia, and encountered astrocyte soma and processes in the brain. Single‐cell RNA sequencing revealed transcriptomic changes indicative of diminished activation of microglia and astrocytes. Multiple genes linked to disease‐associated microglia, NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3)‐inflammasome and interferon‐1 (IFN‐1) signalling displayed reduced expression in microglia. Adding hiPSC‐NSC‐EVs to cultured human microglia challenged with amyloid‐beta oligomers resulted in similar effects. Astrocytes also displayed reduced expression of genes linked to IFN‐1 and interleukin‐6 signalling. Furthermore, the modulatory effects of hiPSC‐NSC‐EVs on microglia in the hippocampus persisted 2 months post‐EV treatment without impacting their phagocytosis function. Such effects were evidenced by reductions in microglial clusters and inflammasome complexes, concentrations of mediators, and end products of NLRP3 inflammasome activation, the expression of genes and/or proteins involved in the activation of p38/mitogen‐activated protein kinase and IFN‐1 signalling, and unaltered phagocytosis function. The extent of astrocyte hypertrophy, amyloid‐beta plaques, and p‐tau were also reduced in the hippocampus. Such modulatory effects of hiPSC‐NSC‐EVs also led to better cognitive and mood function. Thus, early hiPSC‐NSC‐EV intervention in AD can maintain better brain function by reducing adverse neuroinflammatory signalling cascades, amyloid‐beta plaque load, and p‐tau. These results reflect the first demonstration of the efficacy of hiPSC‐NSC‐EVs to restrain neuroinflammatory signalling cascades in an AD model by inducing transcriptomic changes in activated microglia and reactive astrocytes.

ABSTRACT Backround Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing. Methods To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). Results AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%–100%), urothelial carcinoma (74.6%–100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%–99.6%), and pancreaticobiliary cancers (65.2%–98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%–77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (p

Abstract Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague–Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive model developed by Raghavan and Vorp was suitable for rat sciatic nerves, with an average α and β of 0.183 MPa and 1.88 MPa, respectively. We then generated 95% confidence intervals for the stretch at which specific CAP amplitude reductions would occur, which compares well to previous studies. We also developed a finite element model that can predict stretch‐induced signaling deficits, applicable for complex nerve geometries and injuries. This relationship between nerve biomechanics and function can be expanded upon to create a clinical model for peripheral nerve dysfunction due to stretch.

Abstract INTRODUCTION Both micro‐ and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross‐sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia. METHODS Thirty cognitively stable (CS) adults with DS underwent diffusion‐weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts were derived using automatic fiber tracking, and associations with plasma NfL were assessed using Spearman correlation coefficients. RESULTS Higher Plasma NfL was associated with greater altered diffusion measures of select tracts. DISCUSSION Early increases in plasma NfL may reflect early white matter microstructural changes prior to dementia in DS. Highlights The onset of such WM changes in DS has not yet been widely studied. WM microstructural properties correlated with plasma neurofilament light chain (NfL). NfL may reflect early, selective WM changes in adults with DS at high risk of developing AD.

Abstract Two‐dimensional (2D) antiferromagnetic (AFM) semiconductors are promising components of opto‐spintronic devices due to terahertz operation frequencies and minimal interactions with stray fields. However, the lack of net magnetization significantly limits the number of experimental techniques available to study the relationship between magnetic order and semiconducting properties. Here, they demonstrate conditions under which photocurrent spectroscopy can be employed to study many‐body magnetic excitons in the 2D AFM semiconductor NiI2. The use of photocurrent spectroscopy enables the detection of optically dark magnetic excitons down to bilayer thickness, revealing a high degree of linear polarization that is coupled to the underlying helical AFM order of NiI2. In addition to probing the coupling between magnetic order and dark excitons, this work provides strong evidence for the multiferroicity of NiI2 down to bilayer thickness, thus demonstrating the utility of photocurrent spectroscopy for revealing subtle opto‐spintronic phenomena in the atomically thin limit.

Abstract Objectives We evaluated a novel leave‐behind naloxone (LBN) program that allows Emergency Medical Services (EMS) personnel to distribute naloxone after an opioid overdose. Our objective was to explore EMS engagement and experiences with the program, as well as interest in education on addiction and harm reduction. We also assessed the acceptability of LBN programs among people who use drugs (PWUD). Methods We conducted telephone interviews with EMS personnel and residents of substance use recovery housing between February and September 2023. EMS personnel described their direct experiences with the LBN program and perceived facilitating factors and barriers to naloxone distribution. First responder interactions and support for LBN were explored with PWUD. A rapid assessment method was used to analyze the interview data. Results Eighteen of the 23 EMS participants had distributed LBN; most agreed EMS agencies should have an LBN program. Barriers included forgetting, patient acuity, patients declining, and perceived liability. Facilitators included having a clear protocol, accessible kits, and minimal documentation burden. The majority expressed interest in harm reduction education. Eight of the 11 PWUD participants reported recent involvement in an opioid overdose. The majority supported LBN and felt comfortable receiving naloxone training from EMS. Conclusion In this qualitative evaluation, we found broad support for EMS‐based naloxone distribution among EMS personnel and PWUD. We identified several modifiable barriers to the success of such programs, which should be the subject of future investigation. EMS and harm reduction communities should support the expansion of LBN programs across the United States.

Abstract To evaluate the success of a stocking program in Fox Lake, Minnesota, adult (≥76 cm total length) Muskellunge were captured with large nearshore trap nets and individually marked with passive integrated transponder tags during the 2011–2013 and 2015–2017 spawning seasons; then, capture–recapture data were analyzed at two different time scales. Despite substantial sampling effort, daily capture histories within a single season only supported closed‐population abundance estimates for both sexes in half the years; estimates were imprecise, and there was evidence of trap shyness or violation of the short‐term closure assumption in some years. Jolly–Seber models over all years supported relatively precise abundance estimates for both sexes every year, as well as estimates of annual survival, recruitment, and population growth rate. Link–Barker Jolly–Seber models provided estimates of population growth rate λ ≈ 1 indicating that per‐capita annual recruitment rates of only about 0.15–0.20 were adequate to maintain the adult population given the high annual apparent survival rates of 0.80 for adult females and 0.89 for adult males. POPAN Jolly–Seber models revealed that about 80 adult females and 90–126 adult males were vulnerable to capture each year in the 385 ha lake, and about 16–18 fish of each sex recruited to the adult population annually. This study illustrates the importance of open‐population models with multiple years of data to evaluate the abundance and population dynamics of a low‐density, long‐lived species.

ABSTRACT Objective Elexacaftor/tezacaftor/ivacaftor (E/T/I) has provided life‐changing pharmacotherapy for many people with cystic fibrosis (CF), but conflicting literature exists regarding the effect on mental health. While some reports suggest E/T/I may induce adverse psychiatric symptoms, others report improvements in mental health symptoms. To add to this growing body of knowledge, we retrospectively analyzed depression and anxiety symptoms before and after E/T/I initiation in adults with CF at a single large US CF center. Method Patient Health Questionnaire‐9 (PHQ‐9) and Generalized Anxiety Disorder‐7 (GAD‐7) scores recorded in a database were studied. Patients with scores collected before and after E/T/I initiation were included. Regression analyses described associations between score changes and age, race, ethnicity, sex, CFTR variant, and prior depression and/or anxiety diagnoses. Secondary analyses examined possible confounding effects of the COVID‐19 pandemic. Results There was no change in mean GAD‐7 (0.5 ± 5.3, p = 0.41) or PHQ‐9 (−0.02 ± 6.0, p = 0.97) scores following initiation of E/T/I (N = 86). A trend between a prior diagnosis of depression and worsening in PHQ‐9 post‐E/T/I was observed (OR 3.58; p = 0.054). Conclusions Treatment with E/T/I does not lead to changes in depression or anxiety symptoms at the population level in this single center cohort study. A prior diagnosis of depression trended towards an increased odds of worsening PHQ‐9 scores after E/T/I initiation.

Abstract Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical‐grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami‐structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high‐quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post‐stroke patients captures the system's significance in measuring multiple physiological signals in real‐time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non‐invasive alternative for monitoring swallowing and aspiration events.

Abstract Predictive high‐fidelity modeling of wind turbines with computational fluid dynamics, wherein turbine geometry is resolved in an atmospheric boundary layer, is important to understanding complex flow accounting for design strategies and operational phenomena such as blade erosion, pitch‐control, stall/vortex‐induced vibrations, and aftermarket add‐ons. The biggest challenge with high‐fidelity modeling is the realization of numerical algorithms that can capture the relevant physics in detail through effective use of high‐performance computing. For modern supercomputers, that means relying on GPUs for acceleration. In this paper, we present ExaWind, a GPU‐enabled open‐source incompressible‐flow hybrid‐computational fluid dynamics framework, comprising the near‐body unstructured grid solver Nalu‐Wind, and the off‐body block‐structured‐grid solver AMR‐Wind, which are coupled using the Topology Independent Overset Grid Assembler. Turbine simulations employ either a pure Reynolds‐averaged Navier–Stokes turbulence model or hybrid turbulence modeling wherein Reynolds‐averaged Navier–Stokes is used for near‐body flow and large eddy simulation is used for off‐body flow. Being two‐way coupled through overset grids, the two solvers enable simulation of flows across a huge range of length scales, for example, 10 orders of magnitude going from O(μm) boundary layers along the blades to O(10 km) across a wind farm. In this paper, we describe the numerical algorithms for geometry‐resolved turbine simulations in atmospheric boundary layers using ExaWind. We present verification studies using canonical flow problems. Validation studies are presented using megawatt‐scale turbines established in literature. Additionally presented are demonstration simulations of a small wind farm under atmospheric inflow with different stability states.

Abstract Islands have played a key role in our understanding of rapid evolution. A large body of literature has examined morphological changes in response to insularity and isolation, which has yielded useful generalizations about how animals can adapt to live in very small geographic areas. However, understanding the evolution of morphological variation in insular populations often requires detailed data sets on longitudinal patterns of growth and development, and such studies typically necessitate long‐term mark‐recapture on a large sample of individuals. Rattlesnakes provide a unique opportunity to address some of these difficulties because the addition of rattle segments to the rattle string occurs with regular periodicity and their size directly correlates with the body size of the snake at the time of the ecdysis cycle generating the segment. Here, we used a large database of rattle segment sizes recorded from island (Isla Coronado Sur, Baja California, Mexico) and mainland (Camp Pendleton, California, United States) populations of Western Rattlesnakes (Crotalus oreganus and C. o. caliginis) that separated approximately 10,000 years ago to compare body sizes at different ecdysis cycles, which allowed us to assess differences in growth rates and patterns of sexual size dimorphism. Our results show that rattlesnakes on Isla Coronado Sur appear to be born smaller and grow more slowly than their mainland counterparts, resulting in a “dwarfed” island population. However, despite significant differences in body size, both populations exhibited the same degree of sexual dimorphism. Our study demonstrates the potential to use rattle characteristics to recover detailed estimates of fundamental demographic parameters.

Abstract The tissue‐specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM‐containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale‐up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo‐vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post‐MI.

Abstract Sexual trauma (ST) occurs with alarming frequency in the United States in the form of both childhood sexual abuse (CSA) and adulthood sexual assault (ASA). It is well established that the effects of ST are pervasive and that ST can be a risk factor for the development of several psychiatric disorders. However, the potential for distinct psychological consequences or neural correlates between CSA and ASA has received little attention. Furthermore, despite the high prevalence of sexual revictimization, the combinatorial effects of CSA and ASA are understudied in comparison to each form of ST on its own. In the current review, we present results from both clinical psychology and neuroscience research on the impacts of CSA and ASA, describing major psychological, biopsychosocial, and neuroimaging findings for each form of ST. We further highlight limitations in the current state of the research and needed areas of future research to better understand the distinct, overlapping, and cumulative effects of ST in both childhood and adulthood. The present study summarizes the state of the literature on this critical form of trauma and provides recommendations for future clinical research practices to mitigate the deleterious outcomes of ST.

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

Abstract Aims Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are largely managed in primary care, but their intersection in terms of disease burden, healthcare utilization, and treatment is ill‐defined. Methods and results We examined a retrospective cohort including all patients with HF or COPD in the Canadian Primary Care Sentinel Surveillance Network from 2010 to 2018. The population size in 2018 with HF, COPD, and HF with COPD was 15 778, 27 927, and 4768 patients, respectively. While disease incidence declined, age–sex‐standardized prevalence per 100 population increased for HF alone from 2.33 to 3.63, COPD alone from 3.44 to 5.96, and COPD with HF from 12.70 to 15.67. Annual visit rates were high and stable around 8 for COPD alone but declined significantly over time for HF alone (9.3–8.1, P = 0.04) or for patients with both conditions (14.3–11.9, P = 0.006). For HF alone, cardiovascular visits were common (29.4%), while respiratory visits were infrequent (3.5%), with the majority of visits being non‐cardiorespiratory. For COPD alone, respiratory and cardiovascular visits were common (16.4% and 11.3%) and the majority were again non‐cardiorespiratory. For concurrent disease, 39.0% of visits were cardiorespiratory. The commonest non‐cardiorespiratory visit reasons were non‐specific symptoms or signs, endocrine, musculoskeletal, and mental health. In patients with HF with and without COPD, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor use was similar, while mineralocorticoid receptor antagonist use was marginally higher with concurrent COPD. Beta‐blocker use was initially lower with concurrent COPD compared with HF alone (69.3% vs. 74.0%), but this progressively declined by 2018 (74.5% vs. 73.5%). Conclusions The prevalence of HF and COPD continues to rise. Although patients with either or both conditions are high utilizers of primary care, the majority of visits relate to non‐cardiorespiratory comorbidities. Medical therapy for HF was similar and the initially lower beta‐blocker utilization disappeared over time.

Abstract Background Age‐related muscle decline (sarcopenia) associates with numerous health risk factors and poor quality of life. Drugs that counter sarcopenia without harmful side effects are lacking, and repurposing existing pharmaceuticals could expedite realistic clinical options. Recent studies suggest bisphosphonates promote muscle health; however, the efficacy of bisphosphonates as an anti‐sarcopenic therapy is currently unclear. Methods Using Caenorhabditis elegans as a sarcopenia model, we treated animals with 100 nM, 1, 10, 100 and 500 μM zoledronic acid (ZA) and assessed lifespan and healthspan (movement rates) using a microfluidic chip device. The effects of ZA on sarcopenia were examined using GFP‐tagged myofibres or mitochondria at days 0, 4 and 6 post‐adulthood. Mechanisms of ZA‐mediated healthspan extension were determined using combined ZA and targeted RNAi gene knockdown across the life‐course. Results We found 100 nM and 1 μM ZA increased lifespan (P 0.05), whereas 100 and 500 μM ZA were larval lethal. ZA (1 μM) significantly improved myofibrillar structure on days 4 and 6 post‐adulthood (83 and 71% well‐organized myofibres, respectively, vs. 56 and 34% controls, P 0.05). Life/healthspan was extended through knockdown of igdb‐1/FNDC5 (635 ± 10 vs. 523 ± 10% population activity AUC in gene knockdown vs. untreated controls, P 0.05]. Conversely, let‐756/FGF21 and sir‐2.2/SIRT‐4 were dispensable for ZA‐induced healthspan [630 ± 6 vs. 523 ± 10% population activity AUC in knockdown + 1 μM ZA vs. untreated controls, P

Evidence from medicine and other fields has shown that gender diversity results in better decision making and outcomes. The incoming workforce of congenital heart specialists (especially in pediatric cardiology) appears to be more gender balanced, but past studies have shown many inequities. Gender‐associated differences in leadership positions, opportunities presented for academic advancement, and recognition for academic contributions to the field persist. In addition, compensation packages remain disparate if evaluated based on gender with equivalent experience and expertise. This review explores these inequities and has suggested individual and institutional changes that could be made to recruit and retain women, monitor the climate of the institution, and identify and eliminate bias in areas like salary and promotions.

Abstract Introduction Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub‐study within the Wisconsin Registry for Alzheimer's Prevention (WRAP). Methods Ninety‐nine cognitively unimpaired WRAP participants learned their amyloid PET results (mean age ± SD = 72.0 ± 4.8). Measures of reasons for wanting to learn results, study comprehension, result utility, visit satisfaction, research attitudes, and future study enrollment willingness were collected. Between‐group, chi‐squared analysis was conducted to determine differences by result type (elevated vs. not elevated amyloid PET result) in study comprehension, result utility, and visit satisfaction. Linear mixed‐effects modeling was used to evaluate changes in research attitudes and enrollment willingness as a function of time, amyloid result type (elevated/not elevated), and their interaction. Results The reasons most frequently endorsed for wanting to learn amyloid PET result was a “desire to contribute to research on Alzheimer's disease dementia” and “to inform preventative measures [one] might take (e.g., change diet, exercise, or other lifestyle changes).” Overall, participants reported understanding the results and found learning them useful. Satisfaction with the study visits was overwhelmingly high, with over 80% agreeing with visit usefulness and their satisfaction. Few differences were found between participants who learned an elevated and not elevated result. Over the course of the study, participants who learned an elevated amyloid PET result reported higher willingness to enroll in drug trials (beta: 0.12, p = 0.01) and lifestyle interventions (beta: 0.10, p = 0.02) compared to participants who learned a not elevated result. Discussion Formal incorporation of disclosure practices may encourage participant recruitment and retention within AD research. Highlights Participants wanted to learn their amyloid results to contribute to research. Satisfaction with disclosure and post‐disclosure visits was high overall. Returning AD biomarkers can increase willingness to participate in research.

Abstract Introduction Therapeutic interventions for intervertebral disc herniation remain scarce due to the inability of endogenous annulus fibrosus (AF) cells to respond to injury and drive tissue regeneration. Unlike other orthopedic tissues, such as cartilage, delivery of exogenous cells to the site of annular injury remains underdeveloped, largely due to a lack of an ideal cell source and the invasive nature of cell isolation. Human induced pluripotent stem cells (iPSCs) can be differentiated to specific cell fates using biochemical factors and are, therefore, an invaluable tool for cell therapy approaches. While differentiation protocols have been developed for cartilage and fibrous connective tissues (e.g., tendon), the signals that regulate the induction and differentiation of human iPSCs toward the AF fate remain unknown. Methods iPSC‐derived sclerotome cells were treated with various combinations of developmental signals including transforming growth factor beta 3 (TGF‐β3), connective tissue growth factor (CTGF), platelet derived growth factor BB (PDGF‐BB), insulin‐like growth factor 1 (IGF‐1), or the Hedgehog pathway activator, Purmorphamine, and gene expression changes in major AF‐associated ECM genes were assessed. The top performing combination treatments were further validated by using three distinct iPSC lines and by assessing the production of upregulated ECM proteins of interest. To conduct a broader analysis of the transcriptomic shifts elicited by each factor combination, and to compare genetic profiles of treated cells to mature human AF cells, a 96.96 Fluidigm gene expression array was applied, and principal component analysis was employed to identify the transcriptional signatures of each cell population and treatment group in comparison to native AF cells. Results TGF‐β3, in combination with PDGF‐BB, CTGF, or IGF‐1, induced an upregulation of key AF ECM genes in iPSC‐derived sclerotome cells. In particular, treatment with a combination of TGF‐β3 with PDGF‐BB for 14 days significantly increased gene expression of collagen II and aggrecan and increased protein deposition of collagen I and elastin compared to other treatment groups. Assessment of genes uniquely highly expressed by AF cells or SCL cells, respectively, revealed a shift toward the genetic profile of AF cells with the addition of TGF‐β3 and PDGF‐BB for 14 days. Discussion These findings represent an initial approach to guide human induced pluripotent stem cells toward an AF‐like fate for cellular delivery strategies.

Abstract This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12‐week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high‐intensity, low‐volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre‐ and post‐training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross‐sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC‐1α (29.7%, p

Background Nerinetide treatment was associated with better clinical outcomes among patients with stroke undergoing endovascular treatment who were not treated with concurrent alteplase in the randomized ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial. In patients receiving alteplase, no such effect was seen due to an inactivation of nerinetide by plasmin – the product of tissue plasminogen activation. We hypothesized that improved outcomes in the no‐alteplase patients were associated with reduced infarct growth, a radiological correlate of improved stroke outcomes. Methods Data are from the no‐alteplase stratum of the ESCAPE‐NA1 trial. Patients who underwent computer tomography perfusion (CTP) as part of routine clinical care were included. Admission CTP source data were processed using RAPID software. Infarct core at baseline was defined as areas of relative cerebral blood flow

Abstract To better understand the regional changes in summertime temperatures across the conterminous United States (CONUS), we adopt a recently developed machine learning framework that can be used to reveal the timing of emergence of forced climate signals from the noise of internal climate variability. Specifically, we train an artificial neural network (ANN) on seasonally averaged temperatures across the CONUS and then task the ANN to output the year associated with an individual map. In order to correctly identify the year, the ANN must therefore learn time‐evolving patterns of climate change amidst the noise of internal climate variability. The ANNs are first trained and tested on data from large ensembles and then evaluated using observations from a station‐based data set. To understand how the ANN is making its predictions, we leverage a collection of ad hoc feature attribution methods from explainable artificial intelligence (XAI). We find that anthropogenic signals in seasonal mean minimum temperature have emerged by the early 2000s for the CONUS, which occurred earliest in the Eastern United States. While our observational timing of emergence estimates are not as sensitive to the spatial resolution of the training data, we find a notable improvement in ANN skill using a higher resolution climate model, especially for its early twentieth century predictions. Composites of XAI maps reveal that this improvement is linked to temperatures around higher topography. We find that increases in spatial resolution of the ANN training data may yield benefits for machine learning applications in climate science.

Biodiesel production from underutilized seed oils offers a sustainable and environmentally friendly alternative to fossil fuels for energy generation. The present study focuses on employing response surface methodology (RSM) based on Box–Behnken experimental design (BBED) to optimize the reaction conditions in biodiesel production from baobab seed oil. The study investigates the impact of various experimental variables on the biodiesel yield. Specifically, the study explores the influence of reaction temperature (40°C–70°C), reaction time (60–120 min), catalyst concentration (0.5–1.5 wt. %), and oil-to-ethanol ratio (1:3–1:9 mol/mol) on the optimal yield. After screening the variables as mentioned above, the optimized reaction conditions were determined to be as follows: a reaction temperature of 55°C, a reaction time of 60 min, a catalyst concentration of 1.5 wt. %, and an oil-to-ethanol ratio of 1:6 mol/mol. These conditions gave a percentage yield of 98.6%. Notably, the biodiesel properties obtained met the recommended standards. Furthermore, the statistical analysis revealed an adjusted R2 value of 0.9465, closely aligned with the predicted R2 value of 0.8703, with a difference of less than 0.2. This indicates a congeniality of the experimental data and the model predictions. Additionally, the analysis of variance (ANOVA) derived from the quadratic model obtained from the RSM indicated that the model could accurately predict the biodiesel conversion with 97.32% accuracy, providing insights into the observed variations.

Herein, controlled-release material for atrazine (ATZ) herbicide was formulated using different ratios of kaoline (Kao) clay-loaded starch (ST)-grafted chitosan (CHT). The materials were characterized by FTIR, SEM and EDX. The ATZ-release kinetics were studied using the zero-order, first-order and Korsmeyer–Peppas models. The percentage release of the active ATZ in the ST-g-CHT/Kao/ATZ, Kao/ATZ and bare ATZ were 9, 57 and 99 within 96 h, respectively. The Korsmeyer–Peppas model better described the release of active ATZ from the ST-g-CHT/Kao/ATZ system (R2 = 0.999), which delineates a non-Fickian diffusion mechanism that the release was controlled by diffusion and dissolution.

Abstract Patients living with advanced dementia (PLADs) face several challenges to attain the goal of avoiding prolonged dying with severe suffering. One is how to determine when PLADs’ current suffering becomes severe enough to cease all life‐sustaining treatments, including withdrawing assistance with oral feeding and hydrating, a controversial order. This article broadens the concept of suffering by including suffering that cannot be observed contemporaneously and the suffering of loved ones. Four paradigm shifts operationalize these concepts. During advance care planning, patients can judge which future clinical conditions would cause severe suffering. To decide when to allow patients to die, treating physicians/providers only need to assess if patients have reached patients' previously judged, qualifying conditions. Questions: Will this protocol prevent PLADs’ prolonged dying with suffering? Deter early‐stage dementia patients from committing preemptive suicide? Sway decision‐making surrogates from withholding life‐sustaining treatments from patients with middle‐stage dementia? Provoke providers’ resistance to relinquish their traditional, unilateral authority to determine patients’ suffering?

Abstract Atlantic Niño is a leading mode of climate variability in the tropical Atlantic Ocean with important regional impacts. Tropical Atlantic sea surface temperatures (SSTs) connected with Atlantic Niño exhibit notable multi‐time scale variations, including a quasi‐linear warming trend and sub‐annual to interdecadal variability associated with different physical processes. Contrasting the tropical Pacific SST associated with the El Niño‐Southern Oscillation (ENSO), which has a weak trend and quasi‐periodic oscillatory variability with a period of 2–7 years, the ATL3 index, the primary index for monitoring the Atlantic Niño, has no dominant time scale, that is likely responsible for its low prediction skills. Following the same spirit as the relative Niño3.4 index, we demonstrate that a relative ATL3 index, which is defined as the difference between the raw ATL3 index and the global SST anomaly, provides distinct advantages for monitoring the sub‐annual‐to‐interdecadal variations for Atlantic Niño in real time.

Abstract As the quantity of renewable electricity generation from wind farms increases in a region, the costs associated with integrating it into the broader electricity system also grow. This is primarily due to the need for dispatchable generators that vary power output to compensate for wind farm power variations. Such “balancing services” are an economic cost to the system that is typically not passed on to wind farms. We propose including the use of technical merits other than capacity factor and cost of energy for evaluating new wind farm sites and present a new graphical geospatial method, with the intention of identifying sites that minimize the need for additional electricity balancing service and transmission congestion. Specifically, locations with low correlation to existing wind farms, locations with high correlation to load, locations with high characteristic power time‐shift from existing wind farms, and locations that relieve or do not negatively impact electricity transmission congestion are identified. A geospatial Venn diagram‐based method of visualization is presented. These methods will equip regional planners with new tools to encourage wind farm development in areas that benefit the electricity grid beyond the lowest bid price.

Abstract Background Recurrence of early‐stage non‐small cell lung cancer (eNSCLC) is associated with significant mortality and costs. Atezolizumab (ATZ) was recently approved as adjuvant treatment following resection and platinum‐based chemotherapy for adults with stage II‐IIIA NSCLC with PD‐L1 expression ≥1% after demonstrating significant improvement in disease‐free survival (DFS) relative to best supportive care (BSC) in the IMpower010 trial (NCT02486718). This study evaluated the population‐level impact of ATZ as adjuvant treatment for eNSCLC in the United States by estimating the number and costs of recurrences avoided. Methods A Monte Carlo simulation model estimated the cumulative number of recurrences and deaths prevented, along with direct, indirect, and terminal care costs, by treating eNSCLC patients with ATZ compared to BSC. The model included eligible patients treated in any given year and followed over a 5‐year period. Recurrence and mortality rates and costs were based on the IMpower010 data and supplemented by estimates from published literature. Results An estimated 4400 eNSCLC patients in the United States were eligible for adjuvant ATZ in any given year, of whom 2387 would experience recurrence within 5 years with BSC. Following the introduction of ATZ, 1030 (95% confidence interval [CI]: 1023, 1036) recurrences and 369 (95% CI: 362, 376) deaths would be avoided with estimated reductions in cumulative recurrence‐related direct, indirect, and terminal care costs of $785 million, $15 million, and $32 million, respectively, over a 5‐year time horizon. Conclusions Adjuvant ATZ is estimated to prevent a significant number of recurrences and reduce the economic burden of eNSCLC.

Abstract We investigated the test–retest reliability of, and age‐related differences in, markers of skeletal muscle metabolism and microvascular function derived from the near‐infrared spectroscopy with vascular occlusion test (NIRS‐VOT) in younger women (YW) and middle‐aged and older women (MAOW). Seventeen YW (age 23 ± 4 years) and 17 MAOW (age 59 ± 8 years) completed this study. Participants completed identical experimental visits separated by ∼4 weeks during which the NIRS‐VOT was used to quantify the occlusion slope, minimum and maximum tissue saturation, ischaemic index, reperfusion magnitude, the reperfusion and 10‐s reperfusion slopes (slope 2 and slope 210‐s), time to max tissue saturation, and area under the reperfusion curve using the local tissue oxygen saturation signal. Except for slope 210‐s (intraclass correlation coefficient (ICC) = 0.37; coefficient of variation (CV) = 31%), time to max tissue saturation (ICC = 0.21), and ischaemic index (ICC = 0.37) for MAOW, all of the NIRS variables demonstrated good to excellent relative reliability for the YW (ICCs = 0.74–0.86) and the MAOW (ICCs = 0.51–0.87), with CVs of 2–21% and 2–22%, respectively. The occlusion slope was significantly lower, indicating accelerated deoxygenation, while maximum tissue saturation, reperfusion magnitude, and ischaemic index were significantly higher in YW versus MAOW. No other group differences were found. In conclusion, our data support the use of the NIRS‐VOT as a simple, reliable, non‐invasive technique for the assessment of peripheral skeletal muscle metabolism and microvascular function in women, with the reliability being generally greater in YW versus MAOW. Further, our data suggest that ageing is associated with lower skeletal muscle metabolism and microvascular hyperaemic responsiveness in women.

Abstract To date, the restricted capability to fabricate ceramics with independently tailored nano‐ and macroscopic features has hindered their implementation in a wide range of crucial technological areas, including aeronautics, defense, and microelectronics. In this study, a novel approach that combines self‐ and digital assembly to create polymer‐derived ceramics with highly controlled structures spanning from the nano‐ to macroscale is introduced. Polymerization‐induced microphase separation of a resin during digital light processing generates materials with nanoscale morphologies, with the distinct phases consisting of either a preceramic precursor or a sacrificial polymer. By precisely controlling the molecular weight of the sacrificial polymer, the domain size of the resulting material phases can be finely tuned. Pyrolysis of the printed objects yields ceramics with complex macroscale geometries and nanoscale porosity, which display excellent thermal and oxidation resistance, and morphology‐dependent thermal conduction properties. This method offers a valuable technological platform for the simplified fabrication of nanostructured ceramics with complex shapes.

Introduction Recombinant tissue plasminogen activator (rtPA) is the only approved treatment for acute ischemic stroke (AIS) patients, however, only a minuscule percentage of patients receive rtPA [1, 2]. In some cases, the reason for patients' exclusion from rtPA is due to risk factors and comorbidities [1, 2]. Research has been conducted previously on rtPA exclusion in obese AIS patients as well as AIS patients with a history of smoking [3, 4, 5, 6]. However, little is known regarding the comorbidities associated with exclusion from rtPA in obese AIS patients with a history of smoking. ​ Therefore, a discussion surrounding these patients is warranted in order to better identify AIS patients who require special management in order to be eligible for rtPA. We hypothesize that the comorbidities associated with rtPA exclusion in obese AIS patients with a history of smoking will differ from comorbidities associated with rtPA exclusion in obese AIS patients or AIS patients with a history of smoking. Methods Retrospective data on demographic and clinical risk factors of obese AIS patients with a history of smoking was collected from a large stroke center from January 2010 to December 2016. Univariate analysis was used to differentiate between risk factors and demographics associated with exclusion and inclusion from rtPA. Variables in the univariate analysis were further analyzed using logistic regression. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each clinical risk factor were used to predict the increasing odds of an association of a specific clinical baseline risk factor with exclusion or inclusion from rtPA. Results In the adjusted analysis, Obese AIS patients with a history of smoking excluded from rtPA were more likely to present with CAS (OR = 0.069, 95% CI, 0.011‐0.442), diabetes (OR = 0.604, 95% CI, 0.366‐0.997), higher total cholesterol (OR = 0.975, 95% CI, 0.956‐0.995), history of drug and alcohol use (OR = 0.438, 95% CI, 0.232‐0.828). Higher NIHSS score (OR = 1.051, 95% CI, 1.017‐1.086), ambulation improvement (OR = 2.230, 95% CI, 1.423‐3.496), higher triglycerides (OR = 1.004, 95% CI, 1.001‐1.006), and higher HDL (OR = 1.028, 95% CI, 1.000‐1.057) were associated with Obese AIS patients that received rtPA. Conclusion Our findings reveal specific risk factors or comorbidities that contribute to the exclusion of Obese AIS patients with a history of smoking from rtPA. Specifically, a history of diabetes and higher total cholesterol were associated with rtPA exclusion in obese AIS patients with a history of smoking. These associations were not significantly correlated with rtPA exclusion in the populations of obese AIS patients or AIS patients with a history of smoking. These findings suggest the need to develop management strategies to improve the use of rtPA in obese AIS patients with a history of smoking.

Introduction Clinical risk factors and co‐morbidities in obese male and female ischemic stroke patients with a history of smoking may contribute to differing stroke outcomes. The objective of this study is to determine gender differences in risk factors in obese ischemic stroke patients with a history of smoking. Methods A retrospective study was conducted on 6‐year data from 5469 patients with an ischemic stroke event from a regional stroke center. A logistic regression model was used to predict clinical risk factors associated with male or female patients. Multicollinearity was assessed using variance inflation factors (VIFs), with values >5 suggestive of multicollinearity Results In the adjusted analysis, (OR = 1.806, 95% CI, 1.028–3.174, P =0.040*), a history of drugs and alcohol (OR = 2.873, 95% CI, 1.349–6.166, P =0.006), Serum Creatinine (OR = 4.724, 95% CI, 2.171–10.281, P

Abstract The onset of osteoporosis leads to a gradual decrease in bone density due to an imbalance between bone formation and resorption. To achieve optimal drug efficacy with minimal side effects, targeted drug delivery to the bone is necessary. Previous studies have utilized peptides that bind to hydroxyapatite, a mineral component of bone, for bone‐targeted drug delivery. In this study, a hydroxyapatite binding (HAB) tag is fused to 30Kc19α‐Runt‐related transcription factor 2 (RUNX2) for bone‐targeting. This recombinant protein can penetrate the nucleus of human mesenchymal stem cells (hMSCs) and act as a master transcription factor for osteogenesis. The HAB tag increases the binding affinity of 30Kc19α‐RUNX2 to mineral deposition in mature osteoblasts and bone tissue, without affecting its osteogenic induction capability. In the osteoporosis mouse model, intravenous injection of HAB‐30Kc19α‐RUNX2 results in preferential accumulation in the femur and promotes bone formation while reducing toxicity in the spleen. These findings suggest that HAB‐30Kc19α‐RUNX2 may be a promising candidate for bone‐targeted therapy in osteoporosis.

Abstract This study was designed to evaluate the nutritional property of plantain‐based dough meal, antioxidant activity and dyslipidemia‐ameliorating potential in high‐fat‐induced rats. The flour blends, that is, plantain 70%, soy cake 30% (PSC); plantain 65%, soy cake 30%, rice bran 5% (PSR); plantain 65%, soy cake 30%, oat‐bran 5% (PSO); plantain 60%, soy cake 30%, rice bran 5%, oat‐bran 5% (PSRO); and controls (100% plantain flour and Cerolina) were evaluated for proximate, amino acids, antioxidants, phenolic profile, and antihyperlipidemia. Protein, fiber, and energy composition varied from 2.2 to 4.97 g/100 g, 16.44 to 19.59 g/100 g, and 369.7 to 385.5 kcal/100 g, respectively. The essential amino acid index and predicted biological values of the foods ranged from 68.31% to 76.31% and 62.19% to 71.48%, respectively. Phenolic profiles (mg/g) were gallic acid (25.33–31.26), caffeic acid (2.75–4.61), ferulic acid (5.16–12.73), luteolin (16.31–23.60), kaempferol (21.51–30.64), quercetin (24.28–37.13), chlorogenic acid (42.25–59.78), myricetin (28.41–38.41), 3,5‐dicaffeoylquinic acid (27.17–41.59), and 4, 5‐dicaffeoylquinic acid (39.96–51.28). The antioxidant activity (2,2‑azino‑bis (3‑ethylbenzthiazoline‑6‑sulfonate)*, 2,2‐ diphenyl‐1‐picryhydrazyl*, ferric‐reducing antioxidant activity, metal (Fe2+) chelation and hydroxyl (OH*) free radicals of PSRO was higher than other experimental food samples. In vivo study shows that the atherogenic index, coronary risk index and log (triglyceride concentration/high‐density lipoprotein concentration) of rats fed on experimental foods were lower than recommended values. The study established that PSRO had higher antioxidant and anti‐hyperlipidemia properties; hence, it may be suitable as a functional food.

Abstract PF‐05251749 is a dual inhibitor of casein kinase 1 δ/ε under clinical development to treat disruption of circadian rhythm in Alzheimer's and Parkinson's diseases. In vitro, PF‐05251749 (0.3–100 μM) induced CYP3A in cryopreserved human hepatocytes, demonstrating non‐saturable, dose–dependent CYP3A mRNA increases, with induction slopes in the range 0.036–0.39 μM−1. In a multiple‐dose study (B8001002) in healthy participants, CYP3A activity was explored by measuring changes in 4β‐hydroxycholesterol/cholesterol ratio. Following repeated oral administration of PF‐05251749, up to 400 mg q.d., no significant changes were observed in 4β‐hydroxycholesterol/cholesterol ratio; this ratio increased significantly (~1.5‐fold) following administration of PF‐05251749 at 750 mg q.d., suggesting potential CYP3A induction at this dose. Physiologically based pharmacokinetic (PBPK) models were developed to characterize the observed clinical pharmacokinetics (PK) of PF‐05251749 at 400 and 750 mg q.d.; the PBPK induction model was calibrated using the in vitro linear fit induction slope, with rifampin as reference compound (Indmax = 8, EC50 = 0.32 μM). Clinical trial simulation following co‐administration of PF‐05251749, 400 mg q.d. with oral midazolam 2 mg, predicted no significant drug interaction risk. PBPK model predicted weak drug interaction following co‐administration of PF‐05251749, 750 mg q.d. with midazolam 2 mg. In conclusion, good agreement was obtained between CYP3A drug interaction risk predicted using linear‐slope PBPK model and exploratory biomarker trends. This agreement between two orthogonal approaches enabled assessment of drug interaction risks of PF‐05251749 in early clinical development, in the absence of a clinical drug–drug interaction study.

Abstract Asia has an enormous number of older people and is the primary contributor to the rise in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The therapy of many neurodegenerative diseases has not yet progressed to the point where it is possible to alter the course of the disease. Mid‐life hypertension is an important predictor of later‐life cognitive impairment and brain neurodegenerative conditions. These findings highlight the pivotal role of preventing and managing hypertension as a risk factor for neurodegenerative disease. Autonomic dysfunction, neuropsychiatric and sleep disturbances can arise in neurodegenerative diseases, resulting in blood pressure variability (BPV). The BPV itself can worsen the progression of the disease. In older people with neurodegenerative disease and hypertension, it is critical to consider 24‐h blood pressure monitoring and personalized blood pressure therapy.

Abstract The conservation of migratory birds poses a fundamental challenge, their conservation requires coordinated action across the hemisphere, but those actions must be designed and implemented locally. To address this challenge, we describe a multilevel framework for linking broad‐scale, full annual cycle prioritizations to local conservation actions for migratory birds. We developed hemisphere‐scale spatial prioritizations for the full annual cycle of migratory birds that breed in six different ecosystems in North America. The full annual cycle prioritizations provide a hemispheric context within which regional priorities can be identified. Finer resolution, regional prioritizations can then inform local conservation actions more effectively. We describe the importance of local conservation practitioner contributions at each level of the process and provide two examples of regional spatial prioritizations that were developed to guide local action. The first example focused on coastal North and South Carolina, USA, and used information on marsh birds, shorebirds, ecological integrity, and co‐benefits for people to identify Cape Romain, South Carolina as a high‐priority site for conservation action. The second example in Colombia used information on migrant and resident birds to identify the Cauca Valley as a high‐priority site. The multilevel conceptual framework we describe is one pathway for identifying sites for implementation of local conservation actions that are guided by conservation priorities for migratory birds across their full annual cycle.

Abstract Over recent decades, there has been a dramatic increase in the manufacture of engineered nanomaterials, which has inevitably led to their environmental release. Zinc oxide (ZnO) is among the more abundant nanomaterial manufactured due to its advantageous properties, used for piezoelectric, semiconducting, and antibacterial purposes. Plastic waste is ubiquitous and may break down or delaminate into smaller microplastics, leaving open the question of whether these small polymers may alter the fate of ZnO through adsorption within aquatic media (tap‐water and seawater). Here, scanning electron microscopy analysis confirms the effective Zn nano/microstructures adsorption onto polystyrene surfaces after only 24‐h incubation in the aquatic media. After pre‐aging the nanomaterials for 7‐days in different environmental media, nanoprobe X‐ray absorption near‐edge spectroscopy analysis reveals significant ZnO transformation toward Zn‐sulfide and Zn‐phosphate. The interaction between a commercial ZnO‐based sunscreen with polystyrene and a cleanser consumer containing microbeads with ZnO nanomaterials is also studied, revealing the adsorption of transformed Zn‐species in the microplastics surfaces, highlighting the environmental relevancy of this work. Understanding the structural and functional impacts of the microplastics/ZnO complexes, and how they evolve, will provide insights into their chemical nature, stability, transformations, and fate, which is key to predicting their bioreactivity in the environment.

Abstract Sorghum is an essential crop for resilient and adaptive responses to climate change. The root systems of crop plants significantly contribute to the tolerance of abiotic stresses. There is little information on sorghum genotypes' root systems and plasticity to external P supply. In this paper, we investigated the variations in root systems, as well as the responses, trait relationships, and plasticity of two sorghum genotypes (Naga Red and Naga White), popularly grown in Ghana, to five external P concentrations ([P]ext): 0, 100, 200, 300, and 400 mg P kg−1 soil. Sorghum plants were grown in greenhouse pots and harvested for root trait measurements at the five‐leaf and growing point differentiation (GPD) developmental stages. The plants were responsive to [P]ext and formed rhizosheaths. The two genotypes showed similar characteristics for most of the traits measured but differed significantly in total and lateral root lengths in favor of the red genotype. For example, at the five‐leaf growth stage, the lateral root length of the red and white genotypes was 22.8 and 16.2 cm, respectively, but 124 and 88.9 cm, at the GPD stage. The responses and plasticity of the root system traits, including rhizosheath, to [P]ext were more prominent, positive, and linear at the five‐leaf stage than at the GPD growth stage. At the five‐leaf growth stage, total root length increased by about 2.5‐fold with increasing [P]ext compared to the unamended soil. At the GPD stage, however, total root length decreased by about 1.83‐fold as [P]ext increased compared to the unamended soil. Specific rhizosheath weight correlated with RHD, albeit weakly, and together explained up to 59% of the variation in tissue P. Root hair density was more responsive to P supply than root hair length and showed a similar total and lateral root length pattern. Most desirable responses to P occurred at a rate of 200–300 mg P kg−1 soil. It is concluded that sorghum would form rhizosheath, and [P]ext could be critical for the early vigorous growth of sorghum's responsive root and shoot traits. Beyond the early days of development, additional P application might be necessary to sustain the responses and plasticity observed during the early growth period, but this requires further investigation, potentially under field conditions.

Abstract In recent decades, severe cold winters and springs have frequently occurred over mid‐latitude North America, despite the anthropogenic global warming trend. In this study, we reveal a possible mechanism by investigating the teleconnection between tropical oceans and North America. Through observational analysis and numerical experiments, we reveal that an anomalous tropical Atlantic warming can trigger a cold spring over central‐western mid‐latitude North America. The tropical Atlantic warming intensifies regional deep atmospheric convection and generates a stationary Rossby wave train propagating poleward, forming an anomalous low pressure center over the mid‐latitude North Atlantic. This low‐level circulation adjustment further intensifies the cold advection and increases the cloud cover over central‐western North America, cooling the surface through cloud radiative feedback. The mechanisms revealed in this study may contribute to the improvement of predictability of cold springs over North America, and have broad implications for agriculture production, power supply, and public health.

Abstract There is an urgent need for improved and timely health and nutrition data. We developed and tested a smartphone application that caregivers from a pastoral population used to measure, record and submit high‐frequency and longitudinal health and nutrition information on themselves and their children. The data were assessed by comparing caregiver‐submitted measurements of mid–upper arm circumference (MUAC) to several benchmark data sets, including data collected by community health volunteers from the participating caregivers during the project period and data generated by interpreting photographs of MUAC measurements submitted by all participants. We found that the caregivers participated frequently and consistently over the 12‐month period of the project; most of them made several measurements and submissions in at least 48 of the 52 weeks of the project. The evaluation of data quality was sensitive to which data set was used as the benchmark, but the results indicate that the errors in the caregivers' submissions were similar to that of enumerators in other studies. We then compare the costs of this alternative approach to data collection through more conventional methods, concluding that conventional methods can be more cost‐effective for large socioeconomic surveys that value the breadth of the survey over the frequency of data, while the alternative we tested is favoured for those with objectives that are better met by high‐frequency observations of a smaller number of well‐defined outcomes.

Abstract BACKGROUND In the asymptomatic “preclinical” phase of Alzheimer's disease (AD), abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed to participants in research settings, and biomarker testing and results disclosure will be implemented in clinical settings in the future. Biomarker disclosure has potential psychosocial benefits and harms, impacting affected individuals and their support person(s). Limited data are available about with whom research participants share their results, information that will be necessary to develop disclosure protocols and post‐disclosure resources. Additionally, existing research has been conducted in largely White cohorts, limiting applicability to future clinical populations. METHODS We enrolled a diverse cohort of 329 adults (184 non‐Hispanic White and 145 Black/African American individuals) who previously participated in AD research. After reviewing a vignette describing a hypothetical biomarker research study, participants indicated their anticipated willingness to share biomarker results with loved ones, and what reactions they anticipated from others. Using mixed‐methods analysis, we identified responses related to willingness to share results. RESULTS A majority (78.7%) were willing to share their results with support persons. Many (59.6%) felt it would not be difficult to share, and most (90.6%) believed their loved ones would be supportive. The most common reasons for sharing were to prepare for possible future AD (41.0% of respondents), while the most common reason for not sharing was to avoid worrying loved ones (4.8% of respondents). A total of 7.3% of respondents related reasons regarding being unsure about sharing. DISCUSSION Participants’ interest in sharing results supports integrating support persons into AD biomarker research, and may help maximize potential benefits for participants. Communicating with this "dyad" of research participant and support person(s) may improve involvement in research, and help prepare for implementation of clinical biomarker testing by clarifying communication preferences and the influence of support persons on psychosocial outcomes.