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Abstract Passive acoustic monitoring (PAM) has gained increasing popularity to study behaviour, habitat preferences, distribution and community assembly of birds and other animals. Automated species classification algorithms like ‘BirdNET’ are capable of detecting and classifying avian vocalizations within extensive audio data, covering entire species assemblages. PAM reveals substantial potential for biodiversity monitoring that informs evidence‐based conservation. Nevertheless, fully realizing this potential remains challenging, especially due to the issue of false‐positive species detections. Here, we introduce an optimized thresholding framework, which incorporates contextual information extracted from the time‐series of automated species detections (i.e. covariates on quality and quantity of species' detections measured at varying time intervals) to improve the differentiation of true and false positives. We verified a sample of BirdNET detections per species and modelled species‐specific thresholds using conditional inference trees. These thresholds were designed to minimize false‐positive detections while maximizing the preservation of true positives in the dataset. We tested this framework for a large dataset of BirdNET detections (5760 h of audio data, 60 sites) recorded over an entire breeding season. Our results revealed considerable interspecific variability of precision (percentage of true positives) within raw BirdNET data. Our optimized thresholding approach achieved high precision (≥0.9) for 70% of the 61 detected species, while species‐specific thresholds solely relying on the BirdNET confidence scores achieved high precision for only 31% of the species. Conservative universal thresholds (not species‐specific) reached high precision for 48% of the species. Our thresholding approach outperformed previous thresholding approaches and enhanced interspecific comparability for bird community analyses. By incorporating contextual information from the time‐series of species detections, the differentiation of true and false positives was substantially improved. Our approach may enhance a straightforward application of PAM in biodiversity research, landscape planning and evidence‐based conservation.

Abstract We establish a sample‐ and data‐processing pipeline that allows for high‐throughput optical microscope measurement of porous films, provided they are sufficiently optically scattering. Here, self‐limiting electrospray deposition (SLED) is used to manufacture scattering films of different morphologies. This technique compensates for the scattering of the films through background subtraction of the reflection image with the transmission image. This process is implemented through a combination of an ImageJ and MATLAB data pipeline; the Canny edge‐detector is used as the image‐processing algorithm to identify the boundaries of the film. This process is verified against manually measured images; a comparative study between cross‐sectional scanning electron microscopy (where scattering effects are diminished) and optical microscopy also verifies that our optical microscopy technique can be used to consistently, non‐destructively measure film thickness regardless of film morphology. In addition, this technique can be used in combination with dense film measurements to measure film porosity.

Key Clinical Message Pericardial sarcoidosis is an uncommon cause of chest pain to consider, and it requires a heightened level of suspicion and thorough history gathering. If there is suspicion of inflammatory disease, pursuing advanced imaging and biopsies is crucial, as early immunosuppressive treatment can enhance outcomes. Abstract Pericardial involvement in sarcoidosis is a rare condition with limited research. This case study discusses a 52‐year‐old African American woman who presented with subacute chest pain and was diagnosed with pericardial sarcoidosis. Diagnostic evaluation revealed extensive lymphadenopathy and pericardial effusion, and a pericardial biopsy confirmed non‐caseating granulomatous inflammation. Treatment with steroids and methotrexate resulted in clinical improvement. Eight months follow‐up showed near resolution of pericardial disease. This case emphasizes the importance of considering cardiac sarcoidosis in sarcoidosis patients, utilizing advanced imaging for accurate diagnosis, and tailoring treatment to the level of cardiac involvement.

Abstract Qualifying examinations are an important milestone in geoscience graduate programs, but students with marginalized identities are disproportionately lost from graduate programs around the time of these exams. Inequity in qualifying exams can enter at multiple stages throughout the exam design, student mentorship experience, exam administration, and post exam feedback. Therefore, robust assessment is necessary when building an equitable examination. We provide concrete suggestions for graduate programs to evaluate and modify their qualifying examinations. The data‐driven and iterative process encourages graduate programs to outline specific expectations for success, employ best‐practice pedagogy, proactively support students, and use data to measure progress and inform changes in the examination.

Abstract There has been a recent influx of migrants and asylum seekers to the United States. They often arrive with poor social support and an inability to access reliable health care. This can lead to overutilization of emergency departments (ED) while awaiting legal proceedings. With asylum seekers in all 50 states, it is important for emergency physicians (EP) to understand the barriers to care and difficulties asylum seekers face, and to gain tools to improve both migrants’ and community health. Migration and experiences within the United States can worsen pre‐existing health conditions. EPs are uniquely positioned to screen for acute pathology and link people to care. Psychiatric illnesses may present differently in asylum seekers. EPs must understand the sequalae of trauma to address it. EPs must also be aware of legal protections for asylum seekers to care for these patients, and recognize challenges faced by the population to mitigate health disparities.

Background Days alive out of hospital (DAOH) is an objective and patient‐centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. Methods and Results ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double‐blind, double‐dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator‐reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). Conclusions DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Abstract A CoMoS composite is synthesized to combine the benefits of cobalt and molybdenum sulfides as an anodic material for advanced lithium‐ion batteries (LIBs). The synthesis is accomplished using a simple two‐step hydrothermal method and the resulting CoMoS nanocomposites are subsequently encapsulated in a carbonized polydopamine shell. The synthesis procedure exploited the self‐polymerization ability of dopamine to create nitrogen‐doped carbon‐coated cobalt molybdenum sulfide, denoted as CoMoS@NC. Notably, the de‐lithiation capacity of CoMoS and CoMoS@NC is 420 and 709 mAh g⁻1, respectively, even after 100 lithiation/de‐lithiation cycles at a current density of 200 mA g⁻1. Furthermore, excellent capacity retention ability is observed for CoMoS@NC as it withstood 600 consecutive lithiation/de‐lithiation cycles with 94% capacity retention. Moreover, a LIB full‐cell assembly incorporating the CoMoS@NC anode and an NMC‐532 cathode is subjected to comprehensive electrochemical and practical tests to evaluate the performance of the anode. In addition, the density functional theory showcases the increased lithium adsorption for CoMoS@NC, supporting the experimental findings. Hence, the use of dopamine as a nitrogen‐doped carbon shell enhanced the performance of the CoMoS nanocomposites in experimental and theoretical tests, positioning the material as a strong candidate for LIB anode.

Abstract Strong positive Indian Ocean Dipole (pIOD) events like those in 1997 and 2019 caused significant flooding in East Africa. While future projections indicate an increase in pIOD events, limited historical data hinders a comprehensive understanding of these extremes, particularly for unprecedented events. To overcome this we utilize a large ensemble of seasonal reforecast simulations, which show that regional rainfall continues to increase with pIOD magnitude, with no apparent limit. In particular we find that extreme rain days are highly sensitive to the pIOD index and their seasonal frequency increases super‐linearly with higher pIOD magnitudes. It is vital that socio‐economic systems and infrastructure are able to handle not only the increasing frequency of events like 1997 and 2019 but also unprecedented seasons of extreme rainfall driven by as‐yet‐unseen pIOD events. Future studies should prioritize understanding the hydrological implications and population exposure to these unprecedented extremes in East Africa.

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 Background Immuno‐oncology therapy (IO) is associated with a variety of treatment‐related toxicities. However, the impact of toxicity on the treatment discontinuation rate between males and females is unknown. We hypothesized that immune‐related adverse events would lead to more frequent treatment changes in females since autoimmune diseases occur more frequently in females. Aims Our aim was to determine if there was a difference in the rate of immunotherapy treatment change due to toxicity between males and females. Methods and Results The Oncology Research Information Exchange Network Avatar Database collected clinical data from 10 United States cancer centers. Of 1035 patients receiving IO, 447 were analyzed, excluding those who did not have documentation noting if a patient changed treatment (n = 573). Fifteen patients with unknown or gender‐specific cancer were excluded. All cancer types and stages were included. The primary endpoint was documented treatment change due to toxicity. Four hundred and forty‐seven patients (281 males and 166 females) received IO treatment. The most common cancers treated were kidney, skin, and lung for 99, 84, and 54 patients, respectively. Females had a shorter IO course than males (median 3.7 vs. 5.1 months, respectively, p = .02). Fifty‐four patients changed treatment due to toxicity. There was no significant difference between females and males on chi‐square test (11.4% vs. 12.5%, respectively, p = 0.75) and multivariable logistic regression (OR 0.924, 95% CI 0.453–1.885, p = .827). Significantly more patients with chronic obstructive pulmonary disease (COPD) changed therapy due to toxicity (OR 2.491, 95% CI 1.025–6.054, p = .044). Conclusion Females received a shorter course of IO than males. However, there was no significant difference in the treatment discontinuation rate due to toxicity between males and females receiving IO. Toxicity‐related treatment change was associated with COPD.

Abstract Background Excess body weight is a risk factor for the progression of chronic kidney disease (CKD), but weight loss in CKD has been associated with higher mortality. Consequently, blanket weight loss recommendations in this population are controversial. Little data is available on the patterns of weight‐change in CKD. The authors aimed to describe weight‐changes in moderate/severe CKD and explore associations with mortality and renal endpoints in patients with overweight and obesity. Methods Non‐dialysis Canberra Hospital patients with estimated glomerular filtration (eGFR)

Background Consumer wearable devices with health and wellness features are increasingly common and may enhance disease detection and management. Yet studies informing relationships between wearable device use, attitudes toward device data, and comprehensive clinical profiles are lacking. Methods and Results WATCH‐IT (Wearable Activity Tracking for Comprehensive Healthcare‐Integrated Technology) studied adults receiving longitudinal primary or ambulatory cardiovascular care in the Mass General Brigham health care system from January 2010 to July 2021. Participants completed a 20‐question electronic survey about perceptions and use of consumer wearable devices, with responses linked to electronic health records. Multivariable logistic regression was used to identify factors associated with device use. Among 214 992 individuals receiving longitudinal primary or cardiovascular care with an active electronic portal, 11 121 responded (5.2%). Most respondents (55.8%) currently used a wearable device, and most nonusers (95.3%) would use a wearable if provided at no cost. Although most users (70.2%) had not shared device data with their doctor previously, most believed it would be very (20.4%) or moderately (34.4%) important to share device‐related health information with providers. In multivariable models, older age (odds ratio [OR], 0.80 per 10‐year increase [95% CI, 0.77–0.82]), male sex (OR, 0.87 [95% CI, 0.80–0.95]), and heart failure (OR, 0.75 [95% CI, 0.63–0.89]) were associated with lower odds of wearable device use, whereas higher median income (OR, 1.08 per 1‐quartile increase [95% CI, 1.04–1.12]) and care in a cardiovascular medicine clinic (OR, 1.17 [95% CI, 1.05–1.30]) were associated with greater odds of device use. Conclusions Among patients in primary and cardiovascular medicine clinics, consumer wearable device use is common, and most users perceive value in wearable health data.

Abstract Background and Aims Communicating information about the risks and benefits of benzodiazepines so that it is meaningful to the patient has not been previously described. This study aims to determine patient preferences regarding information received before initiating a benzodiazepine. Methods An online survey was distributed through social media and advertisements to Canadians ≥18 years old over a 6‐month period (May–Oct 2022) to collect participant's rating of importance of statements and factors about the risk and benefits of benzodiazepines before initiating treatment using a 10‐point Likert‐type scale. Treatment preferences based on efficacy and risk information were also elicited. The survey was developed and pilot‐tested in collaboration with an advisory committee of individuals with lived and living experience with benzodiazepine use. Results Thirty‐seven participants responded to the survey (mean age 30 years old, 81.1% identified as female). The majority of respondents had a history of anxiety (83.8%) or insomnia (32.4%), and 10 (27.0%) respondents had used a benzodiazepine. Patient counseling related to withdrawal symptoms of benzodiazepines, risk of harm in combination with other sedating agents, risk of physical and psychological dependence, and risk of effects on cognition were rated high in the importance of receiving this information before starting a benzodiazepine relative to efficacy endpoints, such as improvement in sleep parameters. When provided with information about the chance of efficacy and risk of harm, 100% would have selected cognitive behavioral therapy as the best treatment option. The most frequently reported source of medication information where patients have sought information was from the internet (25.0%), followed by doctors (21.9%) and pharmacists (18.8%). Conclusions This study identified patient important factors and statements viewed as important to communicate before initiating a benzodiazepine. The findings of this survey study will help inform decision‐making when considering treatment options for managing anxiety or insomnia.

Abstract Soybean [Glycine max (L.) Merr.] is a globally important crop due to its valuable seed composition, versatile feed, food, and industrial end‐uses, and consistent genetic gain. Successful genetic gain in soybean has led to widespread adaptation and increased value for producers, processors, and consumers. Specific focus on the nutritional quality of soybean seed composition for food and feed has further elucidated genetic knowledge and bolstered breeding progress. Seed components are historical and current targets for soybean breeders seeking to improve nutritional quality of soybean. This article reviews genetic and genomic foundations for improvement of nutritionally important traits, such as protein and amino acids, oil and fatty acids, carbohydrates, and specific food‐grade considerations; discusses the application of advanced breeding technology such as CRISPR/Cas9 in creating seed composition variations; and provides future directions and breeding recommendations regarding soybean seed composition traits.

Abstract Structural batteries are attractive for weight reduction in electric transportation. For their practical applications excellent mechanical properties and electrochemical performance are required simultaneously, which remains a grand challenge. In this study, we present a new scalable and low‐cost design, which uses a quasi‐solid polymer electrolyte (QSPE) to achieve both remarkably improved flexural properties and attractive energy density. The QSPE has a high ionic conductivity of 1.2 mS cm−1 and retains 91% capacity over 500 cycles in graphite/NMC532 cells. Moreover, the resulting structural batteries achieved a modulus of 21.7 GPa and a specific energy of 127 Wh kg−1 based on the total cell weight, which to our knowledge is the highest reported value above 15 GPa. We further demonstrate the application of such structural batteries in a model electric car. The presented design concept enables the industrialization of structural batteries in electric transportation and further applications to improve energy efficiency and multifunctionality.

Abstract Pseudomonas putida has emerged as a promising host for the conversion of biomass‐derived sugars and aromatic intermediates into commercially relevant biofuels and bioproducts. Most of the strain development studies previously published have focused on P. putida KT2440, which has been engineered to produce a variety of non‐native bioproducts. However, P. putida is not capable of metabolizing pentose sugars, which can constitute up to 25% of biomass hydrolysates. Related P. putida isolates that metabolize a larger fraction of biomass‐derived carbon may be attractive as complementary hosts to P. putida KT2440. Here we describe genetic tool development for P. putida M2, a soil isolate that can metabolize pentose sugars. The functionality of five inducible promoter systems and 12 ribosome binding sites was assessed to regulate gene expression. The utility of these expression systems was confirmed by the production of indigoidine from C6 and C5 sugars. Chromosomal integration and expression of non‐native genes was achieved by using chassis‐independent recombinase‐assisted genome engineering (CRAGE) for single‐step gene integration of biosynthetic pathways directly into the genome of P. putida M2. These genetic tools provide a foundation to develop hosts complementary to P. putida KT2440 and expand the ability of this versatile microbial group to convert biomass to bioproducts.

Background Flow diverters are now considered first‐line tools for treating intracranial aneurysms. However, few devices are available for patients with large‐diameter vessels (LDVs). Hence, we evaluated the performance of the largest diameter Surpass Streamline for aneurysms in LDVs. Methods We performed a subanalysis of the SESSIA (Safety and Efficacy of the Surpass Streamline for Intracranial Aneurysms) multicenter cohort study of patients treated with Surpass Streamline between 2018 and 2021. Patients in whom a 5‐mm diameter Surpass Streamline was implanted were divided into 2 groups according to vessel diameter at the landing zones (LDV, ≥5.3 mm versus non‐LDV [N‐LDV],

Background We previously demonstrated that retinal ischemic perivascular lesions (RIPLs), which are indicative of ischemia in the middle retina, may be a biomarker of ischemic cardiovascular disease. In this study, we sought to determine the relationship between RIPLs and atrial fibrillation, a common source of cardiac emboli. Methods and Results In this case‐control study, we identified individuals between the ages of 50 and 90 years who had undergone macular spectral domain optical coherence tomography imaging. Individuals with atrial fibrillation were identified, and age‐ and sex‐matched individuals from the same pool, but without a diagnosis of atrial fibrillation, were selected as controls. Spectral domain optical coherence tomography scans were reviewed by 3 independent and masked observers for presence of RIPLs. The relationship between RIPLs and atrial fibrillation was analyzed using multivariable logistic regression models. There were 106 and 91 subjects with and without atrial fibrillation, respectively. The percentage of subjects with RIPLs was higher in the atrial fibrillation group compared with the control group (57.5% versus 37.4%; P=0.005). After adjusting for age, sex, smoking history, hypertension, diabetes, coronary artery disease, carotid stenosis, stroke, and myocardial infarction, the presence of RIPLs was significantly associated with atrial fibrillation, with an odds ratio of 1.91 (95% CI, 1.01–3.59). Conclusions RIPLs are significantly associated with atrial fibrillation, independent of underlying ischemic heart disease or cardiovascular risk factors. This association may inform the diagnostic cardiovascular workup for individuals with RIPLs incidentally detected on optical coherence tomography scan of the macula.

Abstract As plant species expand their upper limits of distribution under current warming, some retain both traditional climate space and biotic environment while others encounter novel conditions. The latter is the case for Rhododendron campanulatum, a woody shrub that grows both above and below treeline at our study site in the Eastern Himalayas where a very conspicuous, stable treeline was defined by a nearly contiguous canopy of tall Abies spectabilis trees, many of which are over a century old. Prior work showed that treeline had remained static in this region while R. campanulatum expanded its elevational range limit. We tested local adaptation of R. campanulatum by performing reciprocal transplants between the species' current elevational range limit (4023 m above sea level [asl]) and just above treeline (3876 m asl). Contrary to expectation, the coldest temperatures of late winter and early mid‐spring were experienced by plants at the lower elevation: R. campanulatum at species' limit (upper site) were covered by snow for a longer period (40 more days) and escaped the coldest temperatures suffered by conspecifics at treeline (lower site). The harsher spring conditions at treeline likely explain why leaves were smaller at treeline (15.3 cm2) than at species limit (21.3 cm2). Contrary to results from equivalent studies in other regions, survival was reduced more by downslope than by upslope movement, again potentially due to extreme cold temperatures observed at treeline in spring. Upslope transplantation had no effect on mortality, but mortality of species limit saplings transplanted downslope was three times higher than that of residents at both sites. A general expectation is that locals should survive better than foreign transplants, but survival of locals and immigrants at our species limit site was identical. However, those species limit saplings that survived the transplant to treeline grew faster than both locals at treeline and the transplants at species limit. Overall, we found asymmetric adaptation: Compared with treeline saplings, those at species limit (147 m above treeline) were more tolerant of extremes in the growing season but less tolerant of extremes in winter and early mid‐spring, displaying local adaptation in a more complex manner than simply home advantage, and complicating predictions about impacts of future regional climate change.

Abstract Asthma is a chronic inflammatory disorder of the lower airways characterized by modulation of airway smooth muscle (ASM) function. Infiltration of smooth muscle by inflammatory mediators is partially regulated by transmembrane integrins and the major smooth muscle laminin receptor α7β1 integrin plays a critical role in the maintenance of ASM phenotype. The goal of the current study was to investigate the role of α7 integrin in asthma using smooth muscle‐specific α7 integrin transgenic mice (TgSM‐Itgα7) using both acute and chronic OVA sensitization and challenge protocols that mimic mild to severe asthmatic phenotypes. Transgenic over‐expression of the α7 integrin in smooth muscle resulted in a significant decrease in airway resistance relative to controls, reduced the total number of inflammatory cells and substantially inhibited the production of crucial Th2 and Th17 cytokines in airways. This was accompanied by decreased secretion of various inflammatory chemokines such as eotaxin/CCL11, KC/CXCL3, MCP‐1/CCL2, and MIP‐1β/CCL4. Additionally, α7 integrin overexpression significantly decreased ERK1/2 phosphorylation in the lungs of TgSM‐Itgα7 mice and affected proliferative, contractile, and inflammatory downstream effectors of ERK1/2 that drive smooth muscle phenotype in the lung. Taken together, these results support the hypothesis that enhanced expression of α7 integrin in vivo inhibits allergic inflammation and airway resistance. Moreover, we identify ERK1/2 as a potential target by which α7 integrin signals to regulate airway inflammation. We conclude that identification of therapeutics targeting an increase in smooth muscle α7 integrin expression could serve as a potential novel treatment for asthma.

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine‐Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person‐years) for dementia over a median follow‐up of 3.3 (interquartile range, 1.7–5.4) years were 2.79 (95% CI, 2.72–2.85) and 2.04 (95% CI, 1.99–2.08) per 100 person‐years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09–1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07–1.15]). Associations were stronger for age

Introduction The safe and effective profile of flow diverters (FD) has allowed neuro‐interventionalists to consider them as a versatile tool for the treatment of aneurysms with different morphologies, locations, and characteristics. Optimal deployment with complete wall apposition affects FD performance. However, few devices are suitable for aneurysms in large caliber vessels. Herein, we aimed to describe the safety and efficacy of a large caliber (5 mm) FD for the treatment of intracranial aneurysms. Methods We performed a retrospective, multi‐center cohort study of adult patients in whom a 5 mm Surpass Streamline FD was implanted between 2018 and 2021 in the United States. Efficacy outcome was complete occlusion at final follow‐up. Safety outcomes were ischemic/hemorrhagic events and mortality up to 30 days following the procedure. Secondary safety was assessed by the rate of adjunctive devices/treatments to overcome technical complications and improve wall apposition. Results A total of 29 patients harboring 29 aneurysms were treated with 39 FDs (36 large‐diameter devices). Mean age was 57.8 ± 15.7 years. Aneurysm morphologies were saccular (n = 15), pseudoaneurysm (n = 7), fusiform (n = 6), and dissecting (n = 1). Locations were internal carotid artery (ICA) petro‐cavernous segment (n = 15), ICA paraophthalmic (n = 5), ICA cervical (n = 4), basilar artery (n = 3), and vertebral artery (n = 2). Aneurysm size mean was 11.4 ± 6.7 mm, and neck size mean 6.5 ± 3.9 mm. Proximal FD landing zone vessel diameter was 4.8 ± 1.3 mm and distal 4.5 ± 1.2 mm. At a mean final follow‐up of 12 ± 6 months, 18 (65%) aneurysms were completely occluded. Ischemic/hemorrhagic events occurred in 2 (7%), and 1 patient died during hospitalization. Balloon‐assisted angioplasty was performed in 19 (66%) cases, adjunctive stenting in 8 (28%), and coiling in 1 (3%). Patients who received an adjunctive device/treatment had an 82% (14/17) complete occlusion compared to 66% (4/6) in those who did not. Conclusions The use of large caliber FDs to treat complex intracranial aneurysms located in large‐diameter dysplastic vessels is technically feasible and safe. The use of adjunctive devices and techniques to achieve optimal wall apposition seems crucial to optimize treatment outcomes. Comparative studies with devices specially designed for this patient population might provide further insights into the best device selection.

Introduction The Surpass Evolve flow diverter (FD) is a 64‐wire cobalt‐chromium device with improved ease of deployment and conformability, compared to its predecessor. Data on procedural outcomes and aneurysm obliteration rate remain limited. The objective of this study was to describe the procedural outcomes, including 6‐month obliteration rates, for patients who underwent Surpass Evolve FD embolization of an unruptured anterior circulation aneurysm. Methods All consecutive patients with an unruptured anterior circulation aneurysm who were treated with the Surpass Evolve FD between Aug 2020 and May 2022 were included. Patients with a ruptured or posterior circulation aneurysm were excluded. Demographic and clinical features, aneurysm morphology, arterial access, and procedural factors and outcome were extracted from our departmental neurointerventional database. Summary statistics included frequencies, and measures of central tendency and dispersion as appropriate. Results Sixty patients (82% female, mean age 57.9 years ± 15.5) underwent elective Surpass Evolve flow diversion for an unruptured anterior circulation aneurysm. In 47 (78%) patients, a native aneurysm was flow‐diverted, and in 13 (22%) patients, FD was performed for a recurrent aneurysm. Distribution of aneurysm location was: supraclinoid ICA (65%), cavernous ICA (12%), cervical ICA (10%) and anterior cerebral artery (13%). Thirty‐nine (65%) patients underwent left‐sided intervention. Mean aneurysm maximal diameter was 8.7 ± 5.7 mm. The majority of patients (49, 82%) underwent radial arterial access. Balloon angioplasty or J‐wire manipulation was used to enhance apposition in 37 (62%) cases. To date, thirty‐five (58%) patients have had a follow up angiogram (mean 0.65 years ± 0.2 from intervention); in 5 patients, there was mild non‐flow‐limiting stenosis. Based on the Raymond‐Roy Occlusion Classification, 25 (71%) had complete occlusion, 1 (2%) had a residual neck, and 9 (26%) had residual aneurysm. Conclusions The Surpass Evolve FD is safe and associated with favorable occlusion rates at six months. In our early experience, complication rates are well within the acceptable limits.

Introduction Flow diverters (FDs) have demonstrated a safe and effective profile for the treatment of intracranial aneurysms with complex morphologies and variable anatomic locations. However, aneurysmal persistence after flow diversion still presents in up to 25% of treated aneurysms. Herein, we aimed to perform a pooled analysis of two large studies (SCENT [Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Neck Wide Neck Aneurysms] and SESSIA [Safety and Efficacy of the Surpass Streamline for Intracranial Aneurysms]) to evaluate the predictors of occlusion at final follow‐up after treatment with a 72–96 wire device. Methods We pooled all data from the SCENT (prospective) and SESSIA (retrospective) studies that included patients treated with the Surpass Streamline. From the studies, a subset of patients with unruptured saccular aneurysms located in the internal carotid artery (ICA) up to its terminus were included. The authors collected baseline demographics, comorbidities, aneurysm dimensions, and procedural and follow‐up characteristics for each patient. For our analysis, the outcome was complete aneurysm occlusion, as reported by the studies. We performed a multivariable logistic regression to identify the predictors of complete occlusion. Next, we performed a mediation analysis framework to identify the causal relationship of the predictors with the outcome. Finally, we calculated the predicted probability of occlusion for the continuous predictors. Results A total of 348 patients with 348 aneurysms were included, 394 devices were implanted (1.13 per patient). Median age was 61 [22‐85] years, and 83.6% were females. Hypertension was the most common comorbidity (57%) followed by hyperlipidemia (36%). The ICA paraophthalmic segment was the most common location (45%), followed by the petrocavernous (29%) and supraclinoid (25%). Median aneurysm size was 7.5 [1‐29] mm, and neck size was 4.3 [1‐23] mm. At the final follow‐up, the complete occlusion rate was 73% (255/348). After adjusting for confounders and accounting for collinearity, the multivariable analysis identified aneurysm size (OR 0.89; 95% CI 0.85‐0.93;p< .001), procedural technical events (OR 0.31; 95% CI 0.15‐0.65;p = .002), and first device length (OR 0.98; 95% CI 0.96‐1.00;p = .036) as predictors of complete occlusion. Age had a non‐significant direct effect on complete occlusion (p = .091) but a significant indirect effect mediated through aneurysm size (p< .001) and technical events (p< .02). Using our model, the predicted probability of occlusion is≥ 75% in aneurysms measuring < 10 mm when no technical events are encountered. However, when technical events are encountered, the probability decreases to 50–75%. Conclusions Successful aneurysm occlusion after flow diversion is associated with aneurysm size, procedural technical events, and FD length. Age does not directly affect occlusion, but its influence is mediated through the aneurysm size and technical events. Therefore, a priori knowledge of the patient and aneurysm characteristics might guide FD selection to favor the best treatment outcomes.

Introduction Results of systematic reviews and studies evaluating treatment effects of cerebrovascular interventions on the prevalence of post‐stroke cognitive impairment vary likely due to heterogeneity in populations, sample size, variable treatment effect, and time and methods of cognitive examination. Like thrombolytic therapy, endovascular therapy (EVT) in large vessel occlusion (LVO) stroke is strongly associated with successful reperfusion, reduced mortality, and good clinical outcomes. Nevertheless, the effect of successful reperfusion after EVT on cognitive function remains unexplored. Methods Four hundred (400) patients aged 18–75 will be enrolled in the USA and outside USA clinical centers. The primary endpoint will be the association between successful reperfusion, defined as eTICI ≥ 2b50, and cognitive benefit, defined as delta Montreal Cognitive Assessment (MoCA) from 4 days to 180 days post‐EVT or MoCA ≥ 26 at 180 days post‐EVT. Secondary endpoints will include first pass successful revascularization, reduction in hypoperfusion volumes within 24 h, functional evaluations (NIHSS, mRS), MoCA and cognitive battery evaluations, and QOLs at various timepoints, baseline to 180 days post‐EVT. The correlation between cognitive function and stroke characteristics, imaging variables, functional ability, and demographic and socio‐behavioral factors will be explored. Safety endpoints will include all‐cause mortality, symptomatic intracranial hemorrhage within 24 h, and device‐related serious adverse events. Key inclusion criteria are per instructions for use (IFU) and pre‐stroke mRS ≤1. Key exclusion criteria are per IFU, prior hemorrhage or stroke within 3 months, and pre‐existing cognitive impairment and/or dementia. Results More study details including the statistical analysis plan and study status will be discussed. Conclusions COGNITIVE is a very first multi‐center, post‐market, prospective, single‐arm EVT study to evaluate whether successful reperfusion with the Tigertriever device is associated with cognitive benefit in subjects with LVO. The study is a superiority design to evaluate whether Tigertriever treatment significantly reduces cognitive impairment.

Background Many patients with cirrhosis have concurrent nonvalvular atrial fibrillation (NVAF). Data are lacking regarding recent oral anticoagulant (OAC) usage trends among US patients with cirrhosis and NVAF. Methods and Results Using MarketScan claims data (2012–2019), we identified patients with cirrhosis and NVAF eligible for OACs (CHA2DS2‐VASc score ≥2 [men] or ≥3 [women]). We calculated the yearly proportion of patients prescribed a direct OAC (DOAC), warfarin, or no OAC. We stratified by high‐risk features (decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease, or end‐stage renal disease). Among 32 487 patients (mean age=71.6 years, 38.5% women, 15.1% with decompensated cirrhosis, mean CHA2DS2‐VASc=4.2), 44.6% used OACs within 180 days of NVAF diagnosis, including DOACs (20.2%) or warfarin (24.4%). Compared with OAC nonusers, OAC users were less likely to have decompensated cirrhosis (18.6% versus 10.7%), thrombocytopenia (19.5% versus 12.5%), or chronic kidney disease/end‐stage renal disease (15.5% versus 14.0%). Between 2012 and 2019, warfarin use decreased by 21.0% (32.0% to 11.0%), whereas DOAC use increased by 30.6% (7.4% to 38.0%), and among all DOACs between 2012 and 2019, apixaban was the most commonly prescribed (46.1%). Warfarin use decreased and DOAC use increased in all subgroups, including in compensated and decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease/end‐stage renal disease, and across CHA2DS2‐VASc categories. Among OAC users (2012–2019), DOAC use increased by 58.9% (18.7% to 77.6%). Among DOAC users, the greatest proportional increase was with apixaban (61.2%; P55% of patients remain untreated, underscoring the need for clearer treatment guidance.

Abstract Noninvasive assessment of pulmonary hemodynamics is often performed by echocardiographic estimation of the pulmonary artery systolic pressure (ePASP), despite limitations in the advanced lung disease population. Other noninvasive hemodynamic variables, such as echocardiographic pulmonary vascular resistance (ePVR), have not been studied in this population. We performed a retrospective analysis of 147 advanced lung disease patients who received both echocardiography and right heart catheterization for lung transplant evaluation. The ePVR was estimated by four previously described equations. Noninvasive and invasive hemodynamic parameters were compared in terms of correlation, agreement, and accuracy. The ePVR models strongly correlated with invasively determined PVR and had good accuracy with biases of

Objective Seropositive rheumatoid arthritis (RA) is a chronic autoimmune disease that is rarely “cured.” Human mesenchymal stem cells (hMSCs) are known to reduce inflammation and restore immune homeostasis. However, methods for predicting therapeutic hMSC potency have not been established. The goal of these studies was to use and refine an ex vivo functional assay that determines potency of hMSCs and can then be validated in clinical trials as a potency measure of hMSCs used therapeutically to treat RA. Methods Allogeneic hMSCs were cytokine‐stimulated, and a conditioned medium (CM) was harvested. The CM was tested for the potential to attenuate RA CD4+ T cell proliferation using suppression assays. Indoleamine 2, 3‐dioxygenase (IDO) mRNA, and protein were quantified in hMSCs as a measure to compare hMSCs across (prior) studies. Results To mimic a proinflammatory environment that resembles that in RA, interleukin‐1(IL1β), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) (alone or in combination) were used to precondition hMSCs. Treating hMSCs with a combination of these cytokines generated a CM “secretome” that suppressed T cell proliferation between 70 and 83%. Forty‐eight hours of cytokine preconditioning hMSCs was required to maximize this effect. T cell suppression positively correlated with increases in hMSC cellular IDO mRNA and protein. Conclusion By standardizing assays to measure hMSC effects, their potency on T cell suppression can be quantified. These studies demonstrate that hMSCs can be compared functionally to identify optimal preparation(s) for therapeutic use in RA and that the potency of hMSC‐dependent T cell suppression may differ between hMSC donors. Clinical studies are warranted to validate the hypothesis that ex vivo potency in suppressing T cells will positively correlate with a reduction in RA disease activity and increase in immunological quiescence.

Abstract Remote sensing imagery can provide critical information on the magnitude and extent of damage caused by forest pests and pathogens. However, monitoring short‐term changes in deciduous forest condition caused by defoliating insects is challenging and requires approaches that directly account for seasonal vegetation dynamics. We implemented a previously published harmonic modeling approach for forest condition monitoring in Google Earth Engine and systematically assessed the relative ability of condition change products generated using various model parameterizations for predicting pest abundances and defoliation during the 2016–2018 gypsy moth (Lymantria dispar) outbreak in southern New England. Our comparisons revealed that most models made reasonable predictions of changes in canopy condition and egg and larval abundances of L. dispar, indicating a strong correlation between our harmonic‐based estimates of condition change and defoliator activity. The greatest differences in predictive ability were in the spectral domain, with assessments based on Tasseled Cap Greenness, Simple Ratio, and the Enhanced Vegetation Index ranking among the top models, and the commonly used Normalized Difference Vegetation Index consistently exhibiting poorer performance. We also observed notable differences in the magnitude of scores for different baseline periods. Additionally, we found that Landsat‐based condition scores better explained larval abundance than egg mass counts, which have historically been used as a proxy for later‐season larval abundance, indicating that our remote sensing approach may be more accurate and cost‐effective for generating consistent retrospective assessments of L. dispar population abundance in addition to estimates of canopy damage. These findings provide important linkages between spectral changes detected using a harmonic modeling approach and biophysical aspects of defoliator activity, with potential to extend monitoring and prediction to regional or even continental scales.

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome‐wide association study approach. Methods Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self‐reported unintentional weight loss > 5% in the past year or low BMI (BMI

Summary The development of P. putida as an industrial host requires a sophisticated molecular toolbox for strain improvement, including vectors for gene expression and repression. To augment existing expression plasmids for metabolic engineering, we developed a series of dual‐inducible duet‐expression vectors for P. putida KT2440. A number of inducible promoters (Plac, Ptac, PtetR/tetA and Pbad) were used in different combinations to differentially regulate the expression of individual genes. Protein expression was evaluated by measuring the fluorescence of reporter proteins (GFP and RFP). Our experiments demonstrated the use of compatible plasmids, a useful approach to coexpress multiple genes in P. putida KT2440. These duet vectors were modified to generate a fully inducible CRISPR interference system using two catalytically inactive Cas9 variants from S. pasteurianus (dCas9) and S. pyogenes (spdCas9). The utility of developed CRISPRi system(s) was demonstrated by repressing the expression of nine conditionally essential genes, resulting in growth impairment and prolonged lag phase for P. putida KT2440 growth on glucose. Furthermore, the system was shown to be tightly regulated, tunable and to provide a simple way to identify essential genes with an observable phenotype.

Abstract Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer‐specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre‐2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second‐line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small.

Abstract The dry phase of intermittent rivers promotes the accumulation of leaf litter on various terrestrial and aquatic habitats. This environmental heterogeneity causes a chemical diversification of leaf litter by a range of physical and biological degradation processes acting across the various habitats. After flow resumption, the chemically diversified leaves are mixed and subject to continued decomposition downstream. We hypothesized that the chemical diversification of leaf litter during the dry phase would affect leaf litter decomposition under re‐established lotic conditions. Our laboratory treatments mimicking dry‐phase habitats caused a strong chemical diversification of leaf litter, which—upon combination in mixed litter bags—accelerated its decomposition in a perennial river reach. We suggest that intermittent rivers may act as hotspots of organic matter diversification, with potential implications for organic matter processing at the river‐network scale.

Abstract Background Although some emergency department risk stratification tools consider non‐specific ECG findings as an aid in disposition decisions, their clinical value in patients with an initially low high‐sensitivity cardiac troponin I (hsTnI) is unclear. Objective Our purpose was to determine if non‐specific ECG (ns‐ECG) findings are associated with 30‐day major adverse cardiac events (MACE) in ED patients presenting with suspected acute coronary syndromes (ACS) who have a low initial hsTnI. Methods Using the prospective Siemens Atellica hsTnI Food and Drug Administration submission observational database, we conducted a retrospective cohort study of the association between ns‐ECG findings (defined as left bundle branch block [LBBB], ST depression [STD], or T‐wave inversions [TWI]) and 30‐day MACE (death, myocardial infarction, heart failure hospitalization, or coronary revascularization). Eligible patients presented with suspected ACS to one of 29 US EDs from April 2015 to April 2016, had stable vital signs, a blood sample for hsTnI (Siemen's Atellica, Siemens Healthineers, Inc, Malvern, PA) obtained at 1, 3, and 6 hours after ED presentation, and were followed for 30 days. The relationship between 30‐day outcome, initial hsTnI, and ns‐ECG was evaluated using chi‐square testing. Results Of 2676 enrolled, 1313 patients met the inclusion criteria and are included in the analysis. Median (interquartile range) age was 62 years (54, 72), 54% were male, with 56% white, and 39% African American. Median (interquartile range) times from symptom onset to presentation and presentation to specimen collection were 92 (0, 216) and 146 (117, 177) minutes, respectively. The most common presenting symptoms were chest pain (84%), followed by dyspnea (9%). ECG findings were categorized as T‐wave inversion or non‐specific T wave changes (42%), ST depression ns‐ECG ST changes (16%), or LBBB (2%). Thirty‐day MACE occurred in 72 (5.5%) patients, with coronary revascularization (35 patients, 2.7%) and heart failure (25 patients, 1.9%) being the most frequent outcomes. In patients with an initial hsTnI below the limit of quantitation (LOQ) of 2.5 ng/L (n = 449), there was no association between ns‐ECG changes and 30‐day MACE (P = 0.42). If the hsTnI was ≥LOQ (2.5 ng/L), there were increased rates of 30‐day MACE and ns‐ECG findings (P = 0.01). Conclusion In ED suspected ACS patients without unstable vital signs, and an initial hsTnI less than the LOQ (2.5 ng/L), ns‐ECG findings are not associated with 30‐day major adverse cardiac events. The use of ns‐ECG findings in ACS disposition should be considered in the context of hsTnI levels.