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Objective: Historically, most high mountain lakes in western North America were devoid of fish, but during the past century, many have been stocked with salmonids to diversify angling opportunities. Basic information on harvest and catch and release (C–R) for high mountain lake fisheries is lacking, as is information on factors influencing catch in such settings; our objectives were to fill these knowledge gaps. Methods: Using angling gear, we captured and implanted T‐bar anchor tags into 1163 salmonids of various species (fish of wild origin or hatchery fish stocked as fry; they could not be distinguished) in 103 high mountain lakes scattered across Idaho. Angler‐reported tag returns were used to estimate annual rates of exploitation and C–R, and a model selection approach was used to investigate factors influencing the angler catch of tagged fish. Result: Anglers reported the catch of 125 tagged fish from 52 different lakes. The mean number of days at large for reported fish was 318 days, with a range of 1 to 1465 days. Annual exploitation was 5.8 ± 7.1% (mean ± 90% confidence interval), the annual C–R rate was 8.5 ± 8.5%, and total annual catch (i.e., exploitation plus C–R) was 14.2 ± 11.0%. Of the predictive factors that we investigated, the likelihood of a fish being caught by an angler was negatively associated with hiking distance and positively associated with shoreline development index and fish length. Conclusion: Our results indicate that exploitation of salmonids in Idaho high mountain lakes is low even with liberal (six‐fish daily bag limit) harvest regulations. Consequently, angler harvest is unlikely to be substantively affecting the abundance or size structure of salmonid populations in these lakes. Continued tagging would improve the precision of exploitation and C–R estimates, especially for comparisons among species. Impact StatementBased on angler reporting of tagged fish, the annual exploitation of salmonids in Idaho high mountain lakes was 5.8% and the catch‐and‐release rate was 8.5%. Less hiking distance, a less uniform shoreline, and larger fish size improved the likelihood that tagged fish would be caught by anglers. [ABSTRACT FROM AUTHOR]

Life history trade‐offs are one of the central tenets of evolutionary demography. Trade‐offs, depicting negative covariances between individuals' life history traits, can arise from genetic constraints, or from a finite amount of resources that each individual has to allocate in a zero‐sum game between somatic and reproductive functions. While theory predicts that trade‐offs are ubiquitous, empirical studies have often failed to detect such negative covariances in wild populations. One way to improve the detection of trade‐offs is by accounting for the environmental context, as trade‐off expression may depend on environmental conditions. However, current methodologies usually search for fixed covariances between traits, thereby ignoring their context dependence. Here, we present a hierarchical multivariate ‘covariance reaction norm’ model, adapted from Martin (2023), to help detect context dependence in the expression of life‐history trade‐offs using demographic data. The method allows continuous variation in the phenotypic correlation between traits. We validate the model on simulated data for both intraindividual and intergenerational trade‐offs. We then apply it to empirical datasets of yellow‐bellied marmots (Marmota flaviventer) and Soay sheep (Ovis aries) as a proof‐of‐concept showing that new insights can be gained by applying our methodology, such as detecting trade‐offs only in specific environments. We discuss its potential for application to many of the existing long‐term demographic datasets and how it could improve our understanding of trade‐off expression in particular, and life history theory in general. [ABSTRACT FROM AUTHOR]

Proteins frequently undergo covalent modification at the post‐translational level, which involves the covalent attachment of chemical groups onto amino acids. This can entail the singular or multiple addition of small groups, such as phosphorylation; long‐chain modifications, such as glycosylation; small proteins, such as ubiquitination; as well as the interconversion of chemical groups, such as the formation of pyroglutamic acid. These post‐translational modifications (PTMs) are essential for the normal functioning of cells, as they can alter the physicochemical properties of amino acids and therefore influence enzymatic activity, protein localization, protein–protein interactions and protein stability. Despite their inherent importance, accurately depicting PTMs in experimental studies of protein structures often poses a challenge. This review highlights the role of PTMs in protein structures, as well as the prevalence of PTMs in the Protein Data Bank, directing the reader to accurately built examples suitable for use as a modelling reference. [ABSTRACT FROM AUTHOR]

Background: The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined. Objectives: To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease‐related genes and disease‐related alterations in ICS responsiveness. Methods: Randomized open‐label bronchoscopy study of high‐dose ICS therapy in 30 healthy adult volunteers randomized 2:1 to (i) fluticasone propionate 500 mcg bd daily or (ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics. Results: ICS induced small between‐group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type‐2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell‐mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA‐DQB2, CD96, PTPN7), B‐cell immunity (CD20, immunoglobulin heavy and light chains) and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL‐17‐dependent gene signature was not upregulated by ICS. Conclusions: In healthy airways, 4‐week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type‐2 inflammation. This implies that homeostasis in health involves tonic type‐2 signalling in the airway mucosa, which is exquisitely sensitive to ICS. [ABSTRACT FROM AUTHOR]

Background: While it has been demonstrated that large asymptomatic pulmonary embolism (PE) can occur, many studies have assessed inpatients or patients with known risk factors for venous thromboembolism (such as malignancy). There are few data regarding incidental PE in outpatients with deep vein thrombosis (DVT) or assessing whether these emboli occur centrally or peripherally in the pulmonary arteries. Aims: To determine the rates of incidental central and peripheral PE in outpatients with proximal and distal DVT. Methods: This was a retrospective cross‐sectional study of 120 patients attending our community imaging clinic between January 2015 and March 2020, with ultrasound‐confirmed lower limb DVT, and subsequent computed tomography pulmonary angiogram (CTPA) within 24 h. Exclusion criteria were symptoms indicative of PE. Imaging reports were retrospectively reviewed to record the proximity of DVT and the location of any PE as either central (pulmonary trunk or main pulmonary arteries) or peripheral (lobar, segmental or subsegmental pulmonary arteries). Results: Incidental PE occurred in 71 patients (59.2%), with a rate of 77.5% in proximal and 50.0% in distal DVT. Sixteen patients had central PE (13.3% of all patients with DVT; 22.5% of all patients with PE). Two patients (both with proximal DVT) had PE in the pulmonary trunk. Conclusions: Incidental PE occur frequently in outpatients with lower limb DVT, including the possibility of asymptomatic central emboli. Further studies with larger patient cohorts would be useful to assess the utility of baseline chest imaging in outpatients with DVT. [ABSTRACT FROM AUTHOR]

Owing to the difficulties associated with working with carbohydrates, validating glycan 3D structures prior to deposition into the Protein Data Bank has become a staple of the structure‐solution pipeline. The Privateer software provides integrative methods for the validation, analysis, refinement and graphical representation of 3D atomic structures of glycans, both as ligands and as protein modifiers. While Privateer is free software, it requires users to install any of the structural biology software suites that support it or to build it from source code. Here, the Privateer web app is presented, which is always up to date and available to be used online (https://privateer.york.ac.uk) without installation. This self‐updating tool, which runs locally on the user's machine, will allow structural biologists to simply and quickly analyse carbohydrate ligands and protein glycosylation from a web browser whilst retaining all confidential information on their devices. [ABSTRACT FROM AUTHOR]

Background: Alcohol‐based skin preparations were first approved for surgical use in 1998 and have since become standard in most surgical fields. The purpose of this report is to examine incidence of surgical fires because of alcohol‐based skin preparation and to understand how approval and regulation of alcohol‐based skin preparations impacted trends in fires over time. Methods: We identified all reported surgical fires resulting in patient or staff harm from 1991 through 2020 reported to the Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database. We examined incidence of fires because of these preparations, trends after approval and regulation, and common causes. Results: We identified 674 reports of surgical fires resulting in harm to patients and surgical personnel, in which 84 involved an alcohol‐based preparation. The time‐adjusted model shows that from 1996 through 2006, there was a 26.4% increase in fires followed by a 9.7% decrease from 2007 to 2020. The decrease in fires was most rapid for head and neck and upper aerodigestive tract surgeries. Qualitative content analysis revealed improper surgical site preparation as well as close proximity of surgical sites to an oxygen source as the most common causes of fires. Conclusion: Since FDA approval, alcohol‐based preparation solutions have been associated with a significant percentage of surgical fires. Warning label updates from 2006 to 2012 coupled with increased awareness efforts of associated risks of alcohol‐based surgical solutions likely contributed to the decrease in fires. Improper surgical site preparation technique and close proximity of surgical sites to oxygen continue to be risk factors for fires. Level of Evidence: 4 Laryngoscope, 134:607–613, 2024 [ABSTRACT FROM AUTHOR]

Fixation in cementless total knee arthroplasty is provided by osseous integration. Radiography, radiostereometric analysis (RSA), and magnetic resonance imaging (MRI) were used simultaneously to investigate fixation. Relationships between RSA‐measured implant micromotions and MRI‐evaluated osseous integration at the component–bone interface were assessed in 10 patients up to 6 months postoperation. Supine MRI (using multispectral imaging sequences) and RSA exams were performed to evaluate osseous integration and measure longitudinal migration, respectively. Inducible displacement was measured from standing RSA exams. Radiolucent lines were detected on conventional radiographs. Of 10 patients, 6 had fibrous membranes detected on MRI. No fluid or osteolytic interfaces were found, and no components were scored loose. Of 10 patients, 6 had radiolucent lines detected. Average maximum total point motion (MTPM) for longitudinal migration at 6 months was 0.816 mm (range 0.344–1.462 mm). Average MTPM for inducible displacement at 6 months was 1.083 mm (range 0.553–1.780 mm). Fictive points located in fibrous‐classified baseplate quadrants had greater longitudinal migration than fictive points located in baseplate quadrants with normal interfaces at 2 weeks (p = 0.031), 6 weeks (p = 0.046), and 3 months (p = 0.047), and greater inducible displacements at 3 months (p = 0.011) and 6 months (p = 0.045). Greater early micromotion may be associated with the presence of fibrous membranes at the component–bone interface. Clinical significance: This multimodal imaging study contributes knowledge of the fixation of modern cementless TKA, supporting the notion that osseous integration is important for optimal implant fixation. [ABSTRACT FROM AUTHOR]

We examined whether perceptions of the health and economic threats posed by COVID‐19 predict different patterns of intergroup attitudes, using data gathered during the early phase of the pandemic. Using data from 1339 geographically and politically diverse White US residents, we show that subjective economic threat predicted general anti‐outgroup attitudes, while subjective health threat predicted negative attitudes towards both Asian and Latinx ("stereotypically foreign") outgroups but not towards other outgroups. Among 303 geographically and politically diverse Black US residents, the pattern instead suggested that threat (regardless of type) was associated with reduced evaluative differentiation between racial ingroups and outgroups. [ABSTRACT FROM AUTHOR]

Biodiversity conservation and management requires surveillance that captures the full spectrum of taxa. Here, we showcase the potential for a portfolio of visual, extractive, and molecular methods for detecting previously hidden components of tropical fish biodiversity in an economically and culturally valuable marine site that spans a tropical‐temperate ecotone—the Ningaloo Coast World Heritage Area. With scale and practicality in mind, we demonstrate how environmental DNA (eDNA) methods deployed in a stratified sampling design can yield a more comprehensive monitoring program for species presence than current alternatives (e.g., extractive sampling via anesthetic). eDNA from filtered water samples detected up to six times as many cryptobenthic fish species per site than samples collected with anesthetic, indicating it is a potentially powerful tool for assessing biodiversity of tropical fishes. However, there were also species that were only found when using anesthetic and the contribution of cryptobenthic species to overall diversity of the fish assemblage was unexpectedly low, suggesting not all cryptobenthic fish species have been detected with eDNA. There were also distinct differences in cryptobenthic assemblages both among sites and sample depths (2–3 m) when using eDNA from filtered water, suggesting this technique may be able to identify fine scale spatial differences in cryptobenthic fish assemblage. eDNA collected from water detects the most cryptobenthic species and is therefore an efficient tool for rapidly assessing biodiversity, but extractive techniques may still be required for biological and monitoring studies, and when combined with eDNA sampling provides the most comprehensive assessment of cryptobenthic fishes. [ABSTRACT FROM AUTHOR]

Kinematics of total knee replacements (TKR) play an important role in assessing the success of a procedure and would be a valuable addition to clinical practice; however, measuring TKR kinematics is time consuming and labour intensive. Recently, an automatic single‐plane fluoroscopic method utilizing machine learning has been developed to facilitate a quick and simple process for measuring TKR kinematics. This study aimed to validate the new automatic single‐plane technique using biplanar radiostereometric analysis (RSA) as the gold standard. Twenty‐four knees were imaged at various angles of flexion in a dedicated RSA lab and 113 image pairs were obtained. Only the lateral RSA images were used for the automatic single‐plane technique to simulate single‐plane fluoroscopy. Two networks helped automate the kinematics measurement process, one segmented implant components and the other generated an initial pose estimate for the optimization algorithm. Kinematics obtained via the automatic single plane and manual biplane techniques were compared using root‐mean‐square error and Bland–Altman plots. Two observers measured the kinematics using the automated technique and results were compared with assess reproducibility. Root‐mean‐square errors were 0.8 mm for anterior–posterior translation, 0.5 mm for superior–inferior translation, 2.6 mm for medial–lateral translation, 1.0° for flexion–extension, 1.2° for abduction–adduction, and 1.7° for internal–external rotation. Reproducibility, reported as root‐mean‐square errors between operator measurements, was submillimeter for in‐plane translations and below 2° for all rotations. Clinical Significance: The advantages of the automated single plane technique should aid in the kinematic measurement process and help researchers and clinicians perform TKR kinematic analyses. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have demonstrated that stimulating pyruvate dehydrogenase (PDH, gene Pdha1), the rate‐limiting enzyme of glucose oxidation, can reverse obesity‐induced non‐alcoholic fatty liver disease (NAFLD), which can be achieved via treatment with the antianginal ranolazine. Accordingly, our aim was to determine whether ranolazine's ability to mitigate obesity‐induced NAFLD and hyperglycaemia requires increases in hepatic PDH activity. Methods: We generated liver‐specific PDH‐deficient (Pdha1Liver−/−) mice, which were provided a high‐fat diet for 12 weeks to induce obesity. Pdha1Liver−/− mice and their albumin‐Cre (AlbCre) littermates were randomized to treatment with either vehicle control or ranolazine (50 mg/kg) once daily via oral gavage during the final 5 weeks, following which we assessed glucose and pyruvate tolerance. Results: Pdha1Liver−/− mice exhibited no overt phenotypic differences (e.g. adiposity, glucose tolerance) when compared to their AlbCre littermates. Of interest, ranolazine treatment improved glucose tolerance and mildly reduced hepatic triacylglycerol content in obese AlbCre mice but not in obese Pdha1Liver−/− mice. The latter was independent of changes in hepatic mRNA expression of genes involved in regulating lipogenesis. Conclusions: Liver‐specific PDH deficiency is insufficient to promote an NAFLD phenotype. Nonetheless, hepatic PDH activity partially contributes to how the antianginal ranolazine improves glucose tolerance and alleviates hepatic steatosis in obesity. [ABSTRACT FROM AUTHOR]

The oligosaccharides in N‐glycosylation provide key structural and functional contributions to a glycoprotein. These contributions are dependent on the composition and overall conformation of the glycans. The Privateer software allows structural biologists to evaluate and improve the atomic structures of carbohydrates, including N‐glycans; this software has recently been extended to check glycan composition through the use of glycomics data. Here, a broadening of the scope of the software to analyse and validate the overall conformation of N‐glycans is presented, focusing on a newly compiled set of glycosidic linkage torsional preferences harvested from a curated set of glycoprotein models. [ABSTRACT FROM AUTHOR]

Relapse to drug seeking involves transient synaptic remodelling that occurs in response to drug‐associated cues. This remodelling includes activation of matrix metalloproteinases (MMPs) to initiate catalytic signalling in the extracellular matrix in the nucleus accumbens core (NAcore). We hypothesized that MMP activity would be increased in the NAcore during cue‐induced methamphetamine (meth) seeking in a rat model of meth use and relapse. Male and female rats had indwelling jugular catheters and bilateral intracranial cannula targeting the NAcore surgically implanted. Following recovery, rats underwent meth or saline self‐administration (6 h/day for 15 days) in which active lever responding was paired with a light + tone stimulus complex, followed by home cage abstinence. Testing occurred after 7 or 30 days of abstinence. On test day, rats were microinjected with a fluorescein isothiocyanate (FITC)‐quenched gelatin substrate that fluoresces following cleavage by MMP‐2,9, allowing for the quantification of gelatinase activity during cued‐relapse testing. MMP‐2,9 activity was significantly increased in the NAcore by meth cues presentation after 7 and 30 days of abstinence, indicating that remodelling by MMPs occurs during presentation of meth associated cues. Surprisingly, although cue‐induced seeking increased between Days 7 and 30, MMP‐2,9 activity did not increase. These findings indicate that although MMP activation is elicited during meth cue‐induced seeking, MMP activation did not parallel the meth seeking that occurs during extended drug abstinence. [ABSTRACT FROM AUTHOR]

To understand the drivers of variation in digestive performance and their effects on growth, we examined relationships among food consumption, digestive metabolism, food processing efficiency, and growth rate in juveniles of fast‐growing piscivore versus slow‐growing insectivore ecotypes of rainbow trout reared at satiation rations on the same diet (i.e., commercial food pellets). Relative to slow‐growing insectivores with lower basal metabolism, and despite a much larger maximum food ration, faster‐growing piscivores presented an unexpected pattern of higher digestive efficiency through a reduction in the absolute costs of postprandial metabolism coupled with shorter or similar gut residence time and higher assimilation efficiency. These results suggest that the increase in digestive metabolism following the ingestion of larger meals can be mitigated by displacing the costs of digestion from SDA to SMR. Reducing total digestion costs (SDA + SMR) while maintaining higher assimilation efficiency may be possible through potential adaptations including (1) increased intestinal absorption capacity; (2) economies of scale that shorten gut transit time with increasing ration level; or (3) a permanently larger digestive tract that increases maintenance costs but reduces the need for cyclic upregulation and associated overhead costs. [ABSTRACT FROM AUTHOR]

The behavioural and metabolic attributes that favour post‐emergence dispersal by larval fish may differentiate juvenile phenotypes along downstream ecological gradients in riverine systems, but the extent to which fish with contrasting dispersal capacities differ in underlying metabolic, behavioural and life‐history traits remains unclear. In this study, we used common environment experiments to evaluate the extent of inter‐individual differentiation in growth rate, metabolic performance (active metabolism [maximum metabolic rate, MMR], temperature tolerance [CTmax]) and behaviour (emergence time, exploration, sociability) associated with the downstream dispersal of juvenile trout along a 50 km reach of the Lardeau River (British Columbia) characterised by multiple ecological gradients (i.e. distance from the emergence area, water temperature and prey abundance). Growth rate of fish reared under common environment satiation conditions in the laboratory was significantly lower at the most downstream site, which was consistent with an upstream‐to‐downstream gradient of decreasing prey availability, whereby faster‐growing fry were present in the more productive upstream habitats of the upper Lardeau River. In contrast with growth, temperature tolerance (i.e. CTmax) and traits associated with active movement (i.e. MMR, boldness, exploration, sociability) did not differ among individuals or clearly map onto upstream‐to‐downstream gradients of water temperature and distance travelled during dispersal. These results suggest that spatial differentiation of juvenile phenotypes following post‐emergence dispersal may reflect a sorting process where variation in attributes like growth matches the productivity of the terminal habitat, rather than behavioural or metabolic attributes that might promote dispersal (e.g. proactive behaviours and active metabolism). [ABSTRACT FROM AUTHOR]

Deep learning (DL) models are increasingly used to make accurate hindcasts of management‐relevant variables, but they are less commonly used in forecasting applications. Data assimilation (DA) can be used for forecasts to leverage real‐time observations, where the difference between model predictions and observations today is used to adjust the model to make better predictions tomorrow. In this use case, we developed a process‐guided DL and DA approach to make 7‐day probabilistic forecasts of daily maximum water temperature in the Delaware River Basin in support of water management decisions. Our modeling system produced forecasts of daily maximum water temperature with an average root mean squared error (RMSE) from 1.1 to 1.4°C for 1‐day‐ahead and 1.4 to 1.9°C for 7‐day‐ahead forecasts across all sites. The DA algorithm marginally improved forecast performance when compared with forecasts produced using the process‐guided DL model alone (0%–14% lower RMSE with the DA algorithm). Across all sites and lead times, 65%–82% of observations were within 90% forecast confidence intervals, which allowed managers to anticipate probability of exceedances of ecologically relevant thresholds and aid in decisions about releasing reservoir water downstream. The flexibility of DL models shows promise for forecasting other important environmental variables and aid in decision‐making. [ABSTRACT FROM AUTHOR]

There is a well‐documented link between bilingual language development and the relative amounts of exposure to each language. Less is known about the role of quality indicators of caregiver‐child interactions in bilingual homes, including caregiver input diversity, warmth and sensitivity. This longitudinal study examines the relation between caregiver input (lexical diversity, amount), warmth and sensitivity and bilingual toddlers' subsequent vocabulary outcomes. We video‐recorded caregiver‐child interactions in Spanish‐English Latino homes when toddlers (n = 47) were 18 months of age (M = 18.32 months; SD = 1.02 months). At the 24‐month follow‐up, we measured children's vocabulary as total vocabulary (English, Spanish combined) as well as within language (Spanish, English). Results revealed that Spanish lexical diversity exposure at 18 months from caregivers was positively associated with children's Spanish and total vocabulary scores at 24 months, while English lexical diversity was positively associated with children's English scores; lexical diversity and amount were highly correlated. Additionally, caregivers' warmth was positively associated with children's Spanish, English and total vocabulary scores. Together, these factors accounted for substantial variance (30–40%) in vocabulary outcomes. Notably, caregiver input accounted for more variance in single language outcomes than did caregiver warmth, whereas caregiver warmth uniquely accounted for more variance in total vocabulary scores. Our findings extend prior research findings by suggesting that children's dual language development may depend on their exposure to a diverse set of words, not only amount of language exposure, as well as warm interactions with caregivers. A video abstract of this article can be viewed at https://youtu.be/q1V%5f7fz5wog Highlights: Video‐recorded observations of caregiver‐child interactions revealed warmth and high sensitivity from Latino caregivers.Linguistically‐detailed analyses of caregiver input revealed wide variation in the diversity of Spanish and English directed at 18‐month‐old bilingual toddlers.Bilingual toddlers' vocabulary (single language, total) was positively associated with caregivers' diverse input and warmth, thus extending prior findings on bilinguals' amount of language exposure.Findings suggest that caregivers' lexical diversity explains more variance in bilingual toddlers' single language outcomes, whereas warmth explains more variance in total vocabulary scores. [ABSTRACT FROM AUTHOR]

Background: Survival outcomes are generally better for human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) than other forms of head and neck cancer. However, less is known about oncologic outcomes, late adverse events, and gastrostomy tube dependence associated with salvage surgery after the failure of definitive chemoradiation in patients with HPV+ OPSCC. Methods: A secondary analysis of the Radiation Therapy Oncology Group 1016 randomized trial, which compared radiotherapy plus cetuximab to radiotherapy plus cisplatin in patients with HPV+ OPSCC, was performed. The oncologic and adverse event outcomes for patients who underwent salvage surgery were examined. Results: Among the 805 patients who were assigned to treatment and were eligible for analysis, 198 developed treatment failure. Salvage surgery was required for 61 patients (7.6%), with 33 patients undergoing salvage surgery after locoregional failure (LRF) and 28 patients undergoing salvage neck dissection within the 20 weeks after treatment. Patients with LRF who underwent salvage surgery experienced improved overall survival in comparison with patients with LRF who did not undergo surgery (45% vs. 17% at 5 years after treatment; hazard ratio, 0.41; 95% confidence interval [CI], 0.23–0.74). Surgical salvage after LRF was associated with similar frequencies of late grade 3/4 dysphagia in comparison with LRF without surgery (24% [95% CI, 13%–41%] vs. 20% [95% CI, 12%–32%]; p =.64) and with similar gastrostomy tube dependence at 2 years (29% [95% CI, 15%–49%] vs. 13% [95% CI, 5%–28%]; p =.12). Conclusions: Salvage surgery in patients with HPV+ OPSCC is associated with favorable survival and adverse event outcomes. Surgical salvage is associated with improved overall survival in patients with locoregionally recurrent, human papillomavirus–associated oropharyngeal cancer. The adverse event outcomes of surgical salvage patients are comparable to those of patients with recurrence who do not undergo surgery. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal immune‐related adverse events are frequently caused by immune checkpoint inhibitors (ICIs) and often require interruption of cancer treatment. Compared with ICI colitis and enteritis, limited information exists about ICI gastritis. This study characterized clinical features and treatment outcomes of ICI gastritis. Methods: Consecutive cancer patients who received ICIs and underwent endoscopy with gastric biopsies while on ICIs from 2011 to 2021 were retrospectively assessed. Specific histopathologic features identified ICI gastritis. Results: Of 6450 ICI‐treated patients, 162 (2.5%) underwent endoscopy with gastric biopsies. ICI gastritis was identified in 54 (33%) biopsied patients; 38 (70%) had concurrent ICI enteritis/colitis and 16 (30%) had isolated ICI gastritis. Dyspepsia (38%) and bloating (25%) were the most frequent symptoms of isolated ICI gastritis. Compared with patients with concomitant enteritis/colitis, patients with isolated gastritis were less likely to have diarrhea (13% vs 68%; p <.001) or abdominal pain (19% vs 47%; p =.07). Patients with isolated ICI gastritis less frequently required glucocorticoids (69% vs 92%; p =.04) and had lower incidence of ICI hold/withdrawal (13% vs 42%; p =.06). There was no association between severity or extent of luminal inflammation and antitumor response (p =.85 and p =.44, respectively). Endoscopically, gastric mucosa appeared normal in 11 (20%) patients with biopsy‐proven ICI gastritis. Conclusion: ICI gastritis may present alone or more commonly with concurrent enteritis/colitis, which may differentiate its clinical course. Gastric biopsies are required to diagnose a substantial minority of endoscopically normal, clinically significant cases. Most patients with isolated gastritis can continue ICI therapy uninterrupted, but a notable proportion require glucocorticoids. Plain language summary: Immune checkpoint inhibitors are effective anticancer treatments, but can cause inflammatory toxicities, including of the stomach (gastritis), intestine, and colon. Limited information is available on gastritis triggered by these agents.Adult patients with cancer who were treated with immune checkpoint inhibitors and had an upper gastrointestinal endoscopy with biopsies of the stomach were examined. More than two‐thirds (70%) of people with checkpoint inhibitor gastritis also had inflammatory changes of the small intestine and/or colon.Compared with patients with isolated checkpoint gastritis, the subgroup with concomitant enteritis/colitis more frequently had abdominal pain, diarrhea, needed steroids, and/or needed to pause or stop antitumor therapy. Immune checkpoint inhibitor (ICI) gastritis frequently presents with concomitant enteritis/colitis, which differentiates its clinical presentation and management from patients with isolated gastric involvement. A substantial minority of ICI gastritis cases are diagnosed histologically despite normal endoscopic appearance, highlighting the importance of gastric biopsies in patients with suspicious symptoms of or risk factors for checkpoint inhibitor gastritis. [ABSTRACT FROM AUTHOR]

Bioengineered tissues or organs produced using matrix proteins or components derived from xenogeneic sources pose risks of allergic responses, immune rejection, or even autoimmunity. Here, we report successful xeno-free isolation, expansion, and cryopreservation of human endothelial cells (EC), fibroblasts (FBs), pericytes (PCs), and keratinocytes (KCs). We further demonstrate the bioprinting of a human skin substitute with a dermal layer containing xeno-free cultured human EC, FBs, and PCs in a xeno-free bioink containing human collagen type I and fibronectin layered in a biocompatible polyglycolic acid mesh and subsequently seeded with xeno-free human KCs to form an epidermal layer. Following implantation of such bilayered skin grafts on the dorsum of immunodeficient mice, KCs form a mature stratified epidermis with rete ridge-like structures. The ECs and PCs form human EC-lined perfused microvessels within 2 weeks after implantation, preventing graft necrosis, and eliciting further perfusion of the graft by angiogenic host microvessels. As proof-ofconcept, we generated 12 individual grafts using a single donor of all four cell types. In summary, we describe the fabrication of a bioprinted vascularized bilayered skin substitute under completely xeno-free culture conditions demonstrating feasibility of a xeno-free approach to complex tissue engineering. [ABSTRACT FROM AUTHOR]

Objectives: In humans and known fossil hominins, lumbar lordosis is produced by vertebral body wedging and other bony and soft tissue features such as the shape of the intervertebral discs. Current techniques for quantifying the wedging of vertebral bodies are limited in utility, especially when analyzing incomplete fossil material. Here, we introduce a 3D method to quantify vertebral body wedging angles that yields the angles between two "best fit" planes in the software GeoMagic Wrap (3D Systems). Materials and Methods: To test that this new method is repeatable with existing methods, we measure the wedging of 320 lumbar vertebrae representing 64 modern human individuals. For each vertebra, wedging angles were calculated from linear measurements taken with calipers and compared with estimates generated from the 3D best fit plane method. We also apply the 3D plane method to fossil hominin lumbar vertebrae, including newly described lumbar vertebrae of Homo naledi, the majority of which do not preserve the four landmarks necessary to calculate wedging angles using the traditional approach. Results: The results of the two methods are highly and significantly correlated (r2 = 0.98, p < 0.0001). The 3D plane method was successfully applied to nearly all of the fossil hominin specimens included in the study. Discussion: The new 3D plane method introduced here is repeatable with the traditional linear measurement method and allows for the estimation of wedging angles in incomplete material. When applied to Homo naledi lumbar vertebrae, similarities to other fossil hominins and modern humans are found. [ABSTRACT FROM AUTHOR]

Xenogeneic sources of collagen type I remain a common choice for regenerative medicine applications due to ease of availability. Human and animal sources have some similarities, but small variations in amino acid composition can influence the physical properties of collagen, cellular response, and tissue remodeling. The goal of this work is to compare human collagen type I‐based hydrogels versus animal‐derived collagen type I‐based hydrogels, generated from commercially available products, for their physico‐chemical properties and for tissue engineering and regenerative medicine applications. Specifically, we evaluated whether the native human skin type I collagen could be used in the three most common research applications of this protein: as a substrate for attachment and proliferation of conventional 2D cell culture; as a source of matrix for a 3D cell culture; and as a source of matrix for tissue engineering. Results showed that species and tissue specific variations of collagen sources significantly impact the physical, chemical, and biological properties of collagen hydrogels including gelation kinetics, swelling ratio, collagen fiber morphology, compressive modulus, stability, and metabolic activity of hMSCs. Tumor constructs formulated with human skin collagen showed a differential response to chemotherapy agents compared to rat tail collagen. Human skin collagen performed comparably to rat tail collagen and enabled assembly of perfused human vessels in vivo. Despite differences in collagen manufacturing methods and supplied forms, the results suggest that commercially available human collagen can be used in lieu of xenogeneic sources to create functional scaffolds, but not all sources of human collagen behave similarly. These factors must be considered in the development of 3D tissues for drug screening and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Divergent energy acquisition and processing strategies associated with using different microhabitats may allow phenotypes to specialize and coexist at small spatial scales. To understand how ecological specialization affects differentiation in energy acquisition and processing strategies, we examined relationships among digestive physiology, growth, and energetics by performing captive experiments on juveniles of wild coho salmon (Oncorhynchus kisutch) and steelhead trout (O. mykiss) that exploit adjacent habitats along natural low‐to‐high energy flux gradients (i.e., pools versus riffles) in coastal streams. We predicted that: (i) the specialization of steelhead trout to high‐velocity, high‐energy habitats would result in elevated food intake and growth at the cost of lower growth efficiency relative to coho salmon; (ii) the two species would differentiate along a rate‐maximizing (steelhead trout) versus efficiency‐maximizing (coho salmon) axis of digestive strategies matching their ecological lifestyle; and (iii) the higher postprandial metabolic demand (i.e., specific dynamic action, SDA) associated with elevated food intake would occupy a greater fraction of the steelhead trout aerobic budget. Relative to coho salmon, steelhead trout presented a pattern of faster growth and higher food intake but lower growth efficiency, supporting the existence of a major growth versus growth efficiency trade‐off between species. After accounting for differences in ration size between species, steelhead trout also presented higher SDA than coho salmon, but similar intestinal transit time and lower assimilation efficiency. Both species presented similar aerobic budgets since the elevated SDA of steelhead trout was largely compensated by their higher aerobic scope relative to coho salmon. Our results illustrate the key contribution of digestive physiology to the adaptive differentiation of juvenile growth, energetics, and overall performance of taxa with divergent habitat specializations along a natural productivity gradient. [ABSTRACT FROM AUTHOR]

The dataset described here includes estimates of historical (1980–2020) daily surface water temperature, lake metadata, and daily weather conditions for lakes bigger than 4 ha in the conterminous United States (n = 185,549), and also in situ temperature observations for a subset of lakes (n = 12,227). Estimates were generated using a long short‐term memory deep learning model and compared to existing process‐based and linear regression models. Model training was optimized for prediction on unmonitored lakes through cross‐validation that held out lakes to assess generalizability and estimate error. On the held‐out lakes with in situ observations, median lake‐specific error was 1.24°C, and the overall root mean squared error was 1.61°C. This dataset increases the number of lakes with daily temperature predictions when compared to existing datasets, as well as substantially improves predictive accuracy compared to a prior empirical model and a debiased process‐based approach (2.01°C and 1.79°C median error, respectively). [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: To evaluate the incidence of head and neck cancers (HNC) in high‐risk current and/or former smokers with screening low‐dose computed tomography (LDCT) chest versus chest x‐ray (CXR). Study Design: Second analysis of randomized clinical trial. Methods: We performed a secondary analysis examining the incidence of HNC in the National Lung Screening Trial. This was a randomized trial comparing LDCT versus CXR screening for lung cancer detection in high‐risk individuals (30 pack‐year smokers who currently smoke or quit within the last 15 years, aged 55–74). We compared the incidence of HNC in participants screened with LDCT versus CXR. We performed subgroup analyses in participants with mucosal HNC (oral cavity, oropharynx, larynx, hypopharynx, nasal/sinus cavity, or nasopharynx) or nonmucosal HNC (thyroid or salivary gland) and examined survival in the two screening arms. Results: This trial enrolled 53,452 participants with a median follow‐up of 6.2 years after randomization. The incidence of HNC was 111.8 cases per 100,000 person‐years in the LDCT group versus 87.1 cases per 100,000 person‐years in the CXR group (rate ratio 1.30, 95% confidence interval [CI] 1.05–1.61). There were 11.7 deaths from HNC per 100,000 person‐years in the LDCT group and 12.9 deaths per 100,000 person‐years in the CXR group (hazard ratio 0.80, 95% CI 0.42–1.52). Conclusions: Participants screened with LDCT had a modestly higher incidence of HNC. As uptake and adherence of lung cancer screening guidelines improve, clinicians should recognize that incidental findings from screening may lead to increased detection of HNC. Level of Evidence: 3 Laryngoscope, 132:1609–1614, 2022 [ABSTRACT FROM AUTHOR]

Objective: The only hypoglossal nerve stimulation (HNS) device available for US clinical use is implanted through 3 incisions. A recently proposed 2-incision modification moved the respiratory sensing lead from the fifth to the second intercostal space to eliminate the third lower chest incision. This study compared perioperative data and therapeutic outcomes between the techniques.Study Design: Noninferiority cohort analysis of a retrospective and prospective registry study.Setting: Tertiary care and community surgical centers.Methods: Patients with obstructive sleep apnea underwent HNS implantation via a modified 2-incision technique (I2). A cohort previously implanted via the standard 3-incision technique (I3) were 1:1 propensity score matched for a noninferiority analysis of postoperative outcomes.Results: There were 404 I3 patients and 223 I2 patients across 6 participating centers. Operative time decreased from 128.7 minutes (95% CI, 124.5-132.9) in I3 patients to 86.6 minutes (95% CI, 83.7-97.6) in I2 patients (P < .001). Postoperative sleep study data were available for 76 I2 patients who were matched to I3 patients. The change in apnea-hypopnea index between the cohorts was statistically noninferior (a priori noninferiority margin: 7.5 events/h; mean difference, 1.51 [97.5% CI upper bound, 5.86]). There were no significant differences between the cohorts for baseline characteristics, perioperative adverse event rates, or change in Epworth Sleepiness Score (P > .05).Conclusion: In a multicenter registry, a 2-incision implant technique for a commercially available HNS device had a statistically noninferior therapeutic efficacy profile when compared with the standard 3-incision approach. The 2-incision technique is safe and effective for HNS implantation. [ABSTRACT FROM AUTHOR]

Observing spatial and temporal variation in aquatic communities provides insight into factors driving community structure. These observations are particularly important as ecosystems are being challenged by new extremes associated with a changing climate. However, since the timing of disturbances is unpredictable, capturing their effects is difficult, unless a study is already gathering data prior to and after these events. During a 2008–2016 study on the spatial and temporal variation of aquatic macroinvertebrate communities in the Gila River of New Mexico, a severe drought from 2011 to 2013, two mega‐wildfires in 2011 and 2012, and the third‐largest monsoon flood on record in 2013 occurred, providing an opportunity to document how these disturbances structure macroinvertebrate communities. Taxonomic richness and biomass of many individual taxa decreased following the wildfires and the extreme flood, yet the total biomass of the macroinvertebrate community decreased only slightly. We also found an association between the response of some taxa to inter‐annual variation in hydrologic conditions and habitat use. This was evidenced by an increase in the relative biomass of taxa associated with pool habitats, such as Nematoda and Ceratopogonidae during drought years, whereas taxa from riffle habitats, such as mayfly (Leptophlebiidae) and stonefly (Perlodidae) nymphs increased in biomass in relatively wet years. Two groups of stonefly nymphs (Nemouridae and Taeniopterygidae) notably increased following the large monsoonal flooding in 2013. Collectively, the observed responses of macroinvertebrates to extreme hydrologic, wildfire and climate disturbances suggest that increasing frequency of disturbance might result in directional changes in the macroinvertebrate communities due to taxa‐specific responses to those events. [ABSTRACT FROM AUTHOR]

Premise: The taxonomic status of Wright's cliff brake fern, Pellaea wrightiana, has been in dispute ever since it was first described by Hooker in 1858. Previously published evidence suggested that this "taxon" may represent a polyploid complex rather than a single discrete species, a hypothesis tested here using a multifaceted analytical approach. Methods: Data derived from cytogenetics, spore analyses, leaf morphometrics, enzyme electrophoresis, and phylogenetic analyses of plastid and nuclear DNA sequences are used to elucidate the origin, relationships, and taxonomic circumscription of P. wrightiana. Results: Plants traditionally assigned to this taxon represent three distinct polyploids. The most widespread, P. wrightiana, is a fertile allotetraploid that arose through hybridization between two divergent diploid species, P. truncata and P. ternifolia. Sterile triploids commonly identified as P. wrightiana, were found to be backcross hybrids between this fertile tetraploid and diploid P. truncata. Relatively common across Arizona and New Mexico, they are here assigned to P. ×wagneri hyb. nov. In addition, occasional sterile tetraploid plants assigned to P. wrightiana are shown here to be hybrids between the fertile allotetraploid and the tetraploid P. ternifolia subsp. arizonica. These tetraploid hybrids originated independently in two regions of parental sympatry (southern Arizona and west Texas) and are here assigned to P. ×gooddingii hyb. nov. Conclusions: Weaving together data from a diversity of taxonomic approaches, we show that plants identified as P. wrightiana represent three morphologically distinguishable polyploids that have arisen through repeated hybridization events involving the divergent sexual taxa P. ternifolia and P. truncata. [ABSTRACT FROM AUTHOR]

Previous research has hypothesized that human sequential processing may be dependent upon hearing experience (the "auditory scaffolding hypothesis"), predicting that sequential rule learning abilities should be hindered by congenital deafness. To test this hypothesis, we compared deaf signer and hearing individuals' ability to acquire rules of different computational complexity in a visual artificial grammar learning task using sequential stimuli. As a group, deaf participants succeeded at all levels of the task; Bayesian analysis indicates that they successfully acquired each of several target grammars at ascending levels of the formal language hierarchy. Overall, these results do not support the auditory scaffolding hypothesis. However, age‐ and education‐matched hearing participants did outperform deaf participants in two out of three tested grammars. We suggest that this difference may be related to verbal recoding strategies in the two groups. Any verbal recoding strategies used by the deaf signers would be less effective because they would have to use the same visual channel required for the experimental task. [ABSTRACT FROM AUTHOR]

In preclinical research, histological analysis of tissue samples is often limited to qualitative or semiquantitative scoring assessments. The reliability of this analysis can be impaired by the subjectivity of these approaches, even when read by experienced pathologists. Furthermore, the laborious nature of manual image assessments often leads to the analysis being restricted to a relatively small number of images that may not accurately represent the whole sample. Thus, there is a clear need for automated image analysis tools that can provide robust and rapid quantification of histologic samples from paraffin‐embedded or cryopreserved tissues. To address this need, we have developed a color image analysis algorithm (DigiPath) to quantify distinct color features in histologic sections. We demonstrate the utility of this tool across multiple types of tissue samples and pathologic features, and compare results from our program to other quantitative approaches such as color thresholding and hand tracing. We believe this tool will enable more thorough and reliable characterization of histological samples to facilitate better rigor and reproducibility in tissue‐based analyses. [ABSTRACT FROM AUTHOR]

Background: Sinusitis is a common outpatient diagnosis made by physicians and is a reason for referral to otolaryngologists. A foundation in basic sinonasal anatomy is critical in understanding sinus pathophysiology and avoiding complications. Our objective in this study was to develop and to validate a self‐directed surgical anatomy video for medical students. Methods: Two multimedia videos were developed highlighting sinonasal anatomy. In Video 1 we included audio narration and radiologic imaging. Video 2 incorporated highlighted images from a sinus surgery video. An assessment was developed to test sinonasal anatomy landmarks, spatial recognition of structures, and their clinical relevance. An expert panel of rhinologists scored face and content validity of the curriculum videos and assessment. Factor analysis was used to separate questions into face and content validity domains, and a one‐sample t test was performed. Results: The panel scored face validity (Videos 1 and 2: 4.4/5) and content validity (Video 1: 4.5/5, 0.83; Video 2: 4.3/5, 0.75) significantly higher than a neutral response. There were no statistical differences for face or content validity between videos. The assessment was rated suitable (29%) or very suitable (57%) for testing basic sinonasal surgical anatomy, and the majority (71%) of respondents agreed (14%) or strongly agreed (57%) that the assessment thoroughly covered the sinus anatomy content with which medical students should be familiar. Conclusion: We have developed two videos and an assessment that highlight and test sinonasal anatomy. Future studies will aim to identify whether the use of a self‐directed video curriculum improves sinonasal anatomy awareness and whether incorporation of surgical endoscopic videos augments training. [ABSTRACT FROM AUTHOR]

Cold seeps represent hot spots of seabed‐derived methane emissions to the water column, where physical and biological barriers regulate transport of methane to the atmosphere. In our study, we used a methane point source in the North Sea to investigate water‐column methane dynamics within the dispersing plumes. The study is based on methane concentration, distribution and activity of methane‐oxidizing bacteria (MOB), and oceanographic observations. Our findings suggest the ejection of benthic MOB into the water column by sediment resuspension and gas‐bubble‐mediated transport. An applied particle‐tracking model demonstrated that the ejection of 4.29 ± 1.9 × 1012 MOB cells s−1 from the seep site would produce the MOB abundance detected in the down‐current water body. The benthic MOB inoculant accelerated methane oxidation rates by a factor of five. Our study highlights the importance of the bentho‐pelagic transport of microorganisms at seep sites and their feedback on the pelagic methane sink. Plain Language Summary: In the marine system, the greenhouse gas methane is primarily produced in sediments. Under specific geologic conditions, methane can accumulate in the sediment and be released as gas bubbles. Such gas seepage also occurs at abandoned oil or gas‐drilling sites. However, direct transport of methane from submarine seeps to the atmosphere is only likely in shallow regions, as ascending bubbles release most of their methane quickly into the surrounding water. Methanotrophic bacteria living in the top sediment layer and the water column metabolize the dissolved methane. These methanotrophs can be transported from the sediment into the water column by gas bubbles or sediment resuspension. To understand the effect of the transported methanotrophs on the methane removal in the water column, we focused on an abandoned oil‐drilling site in the North Sea that has been emitting methane gas bubbles since 1990. We took water samples from different depths near the drilling site and this showed that the transported methanotrophs accelerated methane oxidation rates by a factor of about five. Additionally, we used a numerical model to estimate the number of methanotrophs ejected from the seep site and traced their distribution in the dispersing plume. Key Points: The ejection of benthic methanotrophs from the gas seep site can explain the methanotroph's abundance in the down‐current methane plumeThe seep‐induced inoculation of the water column with methanotrophs decreased the pelagic methane turnover time by a factor of about fiveOur particle‐tracking model showed that tides controlled the areal distribution of methane and methanotrophs released by the seep site [ABSTRACT FROM AUTHOR]

A proactive‐reactive continuum integrating multiple (i.e., 3+) dimensions of animal behaviour has been reported as a major axis of behavioural differentiation, but its stability along a biological hierarchy from individuals to populations remains speculative. Piscivore and insectivore rainbow trout (Oncorhynchus mykiss) represent closely related ecotypes with strong ecological divergence driven by selection for a large‐bodied piscivorous lifestyle with fast juvenile growth vs. selection for smaller adult body size and lower growth associated with an insectivorous diet. To evaluate whether differences in behaviour between ecotypes are consistent with a proactive‐reactive axis and consistent along a biological hierarchy, the authors examined variation in emergence time from a shelter, exploration, activity and predator inspection among individuals, populations and ecotypes of juvenile piscivore and insectivore rainbow trout O. mykiss. As expected, the faster‐growing piscivore ecotype was more proactive (i.e., shorter emergence time, exploration and predator inspection) than the more reactive insectivore ecotype. This behavioural contrast was partly maintained across populations, although activity differences were most pronounced among populations, rather than emergence time. Insectivore fry showed substantial variation in behavioural expression among individuals within populations; by contrast, piscivores showed highly similar proactive behaviours with significantly lower inter‐individual variation in behavioural expression, suggesting intense selection on behaviour supporting their faster growth. This work suggests that piscivore and insectivore O. mykiss broadly differ in behaviour along a proactive vs. reactive continuum, and highlights the greater multidimensionality of behavioural expression within the insectivore ecotype. Contrasting behaviours between ecotypes may result from differential selection for slow vs. fast juvenile growth and associated metabolism, and may contribute to adult trophic specialization. [ABSTRACT FROM AUTHOR]

Background: Dysfunction and inflammation of hearts subjected to cold ischemic preservation may differ between left and right ventricles, suggesting distinct strategies for amelioration. Methods and Results: Explanted murine hearts subjected to cold ischemia for 0, 4, or 8 h in preservation solution were assessed for function during 60 min of warm perfusion and then analyzed for cell death and inflammation by immunohistochemistry and western blotting and total RNA sequencing. Increased cold ischemic times led to greater left ventricle (LV) dysfunction compared to right ventricle (RV). The LV experienced greater cell death assessed by TUNEL+ cells and cleaved caspase‐3 expression (n = 4). While IL‐6 protein levels were upregulated in both LV and RV, IL‐1β, TNFα, IL‐10, and MyD88 were disproportionately increased in the LV. Inflammasome components (NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3), adaptor molecule apoptosis‐associated speck‐like protein containing a CARD (ASC), cleaved caspase‐1) and products (cleaved IL‐1β and gasdermin D) were also more upregulated in the LV. Pathway analysis of RNA sequencing showed increased signaling related to tumor necrosis factor, interferon, and innate immunity with ex‐vivo ischemia, but no significant differences were found between the LV and RV. Human donor hearts showed comparable inflammatory responses to cold ischemia with greater LV increases of TNFα, IL‐10, and inflammasomes (n = 3). Conclusions: Mouse hearts subjected to cold ischemia showed time‐dependent contractile dysfunction and increased cell death, inflammatory cytokine expression and inflammasome expression that are greater in the LV than RV. However, IL‐6 protein elevations and altered transcriptional profiles were similar in both ventricles. Similar changes are observed in human hearts. [ABSTRACT FROM AUTHOR]

Marine reserves are a key tool for the conservation of marine biodiversity, yet only ~2.5% of the world's oceans are protected. The integration of marine reserves into connected networks representing all habitats has been encouraged by international agreements, yet the benefits of this design has not been tested empirically. Australia has one of the largest systems of marine reserves, providing a rare opportunity to assess how connectivity influences conservation success. An Australia‐wide dataset was collected using baited remote underwater video systems deployed across a depth range from 0 to 100 m to assess the effectiveness of marine reserves for protecting teleosts subject to commercial and recreational fishing. A meta‐analytical comparison of 73 fished species within 91 marine reserves found that, on average, marine reserves had 28% greater abundance and 53% greater biomass of fished species compared to adjacent areas open to fishing. However, benefits of protection were not observed across all reserves (heterogeneity), so full subsets generalized additive modelling was used to consider factors that influence marine reserve effectiveness, including distance‐based and ecological metrics of connectivity among reserves. Our results suggest that increased connectivity and depth improve the aforementioned marine reserve benefits and that these factors should be considered to optimize such benefits over time. We provide important guidance on factors to consider when implementing marine reserves for the purpose of increasing the abundance and size of fished species, given the expected increase in coverage globally. We show that marine reserves that are highly protected (no‐take) and designed to optimize connectivity, size and depth range can provide an effective conservation strategy for fished species in temperate and tropical waters within an overarching marine biodiversity conservation framework. [ABSTRACT FROM AUTHOR]

Habitat simulation approaches (e.g., PHABSIM) have been used to model instream flows in thousands of streams and rivers and remain the most widely implemented detailed instream flow methodology. However, recent studies suggest that conventional habitat simulation models incorporate assumptions that may systematically underestimate instream flow needs, particularly for drift‐feeding fish. These include: (i) systematic biases in velocity habitat suitability curves (HSCs) caused by territoriality where dominant individuals displace subordinate fish to lower velocity micro‐habitats at high densities, thereby inflating the fitness value of low velocities; (ii) habitat simulation models do not account for flow effects on prey flux to drift‐feeding fishes, which may decrease more rapidly with reduced flow than does available habitat; (iii) use of focal velocities to construct traditional HSCs, which systematically underestimates velocity preference within the broader foraging arena of a drift‐feeding fish, and (iv) inadvertent use of low‐velocity HSCs associated with daytime refuging behavior from predators that may underestimate the higher velocities necessary for crepuscular foraging. Collectively, these factors suggest that current and historic flow prescriptions using traditional habitat simulation methods may underestimate optimal rearing flows for salmonids and other drift‐feeding species by anywhere from 10 to 50%. This implies that traditional instream flow management may be failing to provide the intended level of protection for drift‐feeding fishes in multiple streams at landscape scales. We provide guidelines for identifying contexts where model predictions are likely to be biased and approaches for correcting them. [ABSTRACT FROM AUTHOR]

Most environmental data come from a minority of well‐monitored sites. An ongoing challenge in the environmental sciences is transferring knowledge from monitored sites to unmonitored sites. Here, we demonstrate a novel transfer‐learning framework that accurately predicts depth‐specific temperature in unmonitored lakes (targets) by borrowing models from well‐monitored lakes (sources). This method, meta‐transfer learning (MTL), builds a meta‐learning model to predict transfer performance from candidate source models to targets using lake attributes and candidates' past performance. We constructed source models at 145 well‐monitored lakes using calibrated process‐based (PB) modeling and a recently developed approach called process‐guided deep learning (PGDL). We applied MTL to either PB or PGDL source models (PB‐MTL or PGDL‐MTL, respectively) to predict temperatures in 305 target lakes treated as unmonitored in the Upper Midwestern United States. We show significantly improved performance relative to the uncalibrated PB General Lake Model, where the median root mean squared error (RMSE) for the target lakes is 2.52°C. PB‐MTL yielded a median RMSE of 2.43°C; PGDL‐MTL yielded 2.16°C; and a PGDL‐MTL ensemble of nine sources per target yielded 1.88°C. For sparsely monitored target lakes, PGDL‐MTL often outperformed PGDL models trained on the target lakes themselves. Differences in maximum depth between the source and target were consistently the most important predictors. Our approach readily scales to thousands of lakes in the Midwestern United States, demonstrating that MTL with meaningful predictor variables and high‐quality source models is a promising approach for many kinds of unmonitored systems and environmental variables. Key Points: Meta‐transfer learning (MTL) learns from models trained on data‐rich systems to inform predictions in systems where no observations existWe use MTL with process‐based and process‐guided deep learning models to accurately predict lake temperatures in the Midwest United StatesThe most important predictor of transfer model success is the difference in maximum depth between the data‐rich and unmonitored lake [ABSTRACT FROM AUTHOR]

Intergroup dialogue contributes to community development by providing structured and facilitated opportunities for narrative engagement and perspective taking that can foster social change. Both art and art therapy can be infused within intergroup dialogue to harness imagination and creativity in order to heighten reflection and promote emotional connections. An art therapy‐informed model enhanced self‐awareness, storytelling, and interpersonal interactions by helping participants discuss direct encounters of difference as well as specific events and people. [ABSTRACT FROM AUTHOR]

Adverse clinical outcomes related to SARS‐CoV‐2 infection among liver transplant (LTx) recipients remain undefined. We performed a meta‐analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID‐19. A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines. Twelve studies comprising 517 hospitalized LTx recipients with COVID‐19 were analyzed. Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%). Approximately 77% (95% CI, 61%‐93%) of LTx recipients had a history of liver cirrhosis. The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%). In‐hospital mortality was 20% (95% CI, 13%‐28%) and rose to 41% (95% CI, 19%‐63%) (P < 0.00) with ICU admission. Additional subgroup analysis demonstrated a higher mortality risk in the elderly (>60‐65 years) (OR 4.26; 95% CI, 2.14‐8.49). There was no correlation in respect to sex or time since transplant. In summary, LTx recipients with COVID‐19 had a high prevalence of dyspnea and gastrointestinal symptoms. In‐hospital mortality was comparable to non‐transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%‐40%). Importantly, the observed high case fatality in the elderly could be due to age‐associated comorbidities. [ABSTRACT FROM AUTHOR]

Background: In the current study, the authors assessed the risks and outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with resolved grade 3 to 4 ICI hepatitis because current guidelines recommend permanent ICI discontinuation in these patients. Methods: The authors performed a retrospective cohort study from 2010 through 2019 of patients with melanoma who were treated with ≥1 ICIs and who recovered from grade 3 to 4 ICI hepatitis. The primary outcome was hepatitis recurrence and the secondary outcome was the development of any immune‐related adverse event (irAE) requiring the discontinuation of ICI rechallenge. Best overall response and time to all‐cause death were compared between the patients who did and those who did not undergo ICI rechallenge. Grading was performed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Results: Of the 102 patients with melanoma who developed high‐grade ICI hepatitis, 31 underwent ICI rechallenge. Although 15 of 31 patients (48%) developed an irAE of any grade, only 6 patients (19%) required ICI discontinuation due to irAE severity (4 of 29 patients [14%] rechallenged with anti–PD‐1 or anti‐PD‐L1 and 2 of 2 patients [100%] rechallenged with ipilimumab). Recurrent hepatitis accounted for 4 of these 6 cases. Rechallenged patients who did not require ICI discontinuation were found to be significantly less likely to receive ipilimumab rather than anti–PD‐1 or anti‐PD‐L1 monotherapy (0% vs 33%; relative risk (RR), 0.1 [95% CI, 0.1‐0.3; P =.032]) and significantly less likely to be rechallenged with their original ICI (8% vs 50%; RR, 0.2 [95% CI, 0.1‐0.7; P =.038]). There was no difference noted with regard to best overall response or time to death between rechallenged and non‐rechallenged patients. Conclusions: ICI therapy can be resumed in patients with melanoma who have recovered from grade 3 to 4 ICI hepatitis with a modest risk of serious irAEs. It remains unclear whether ICI retreatment improves clinical outcomes. After resolution of high‐grade immune‐mediated hepatitis, the majority of patients who are rechallenged with immune checkpoint inhibitors can remain on treatment without developing serious immune‐related adverse events. It remains unclear whether immune checkpoint inhibitor retreatment improves clinical outcomes. [ABSTRACT FROM AUTHOR]

Habitat suitability curves (HSCs) are the biological component of habitat simulation tools used to evaluate instream flow management trade‐offs (e.g., the physical habitat simulation model). However, traditional HSCs based on empirical observations of habitat use relative to availability have been criticized for generating biased estimates of flow requirements and for being poorly transferable across locations. For fish like salmonids that feed on drifting invertebrates, bioenergetics‐based foraging models that relate habitat conditions to net energy gain offer an alternative approach that addresses some of these shortcomings. To make this technique more accessible for practitioners, we present free and user‐friendly software for generating bioenergetics‐based HSCs. The software also allows sensitivity analyses of HSCs to factors like fish size or prey abundance as well as direct integration of hydraulic data. While some caveats remain, bioenergetic HSCs should offer a more rigorous and credible means for quantifying habitat suitability for instream flow modeling. [ABSTRACT FROM AUTHOR]

Adaptive trade‐offs are fundamental mechanisms underlying phenotypic diversity, but the presence of generalizable patterns in multivariate adaptation and their mapping onto environmental gradients remain unclear.To understand how life history affects multivariate trait associations, we examined relationships among growth, metabolism, anatomy and behaviour in rainbow trout juveniles from piscivore versus insectivore ecotypes along an experimental gradient of food availability. We hypothesized that (a) selection for larger size in piscivorous adults would select for higher juvenile growth at the cost of lower active metabolism; (b) elevated growth of piscivores would be supported by a greater productivity of their natal stream and more proactive foraging behaviours and (c) general patterns of multivariate trait associations would match the predictions of the Pace‐Of‐Life Syndrome.Relative to insectivores, piscivorous fry showed a pattern of higher growth (+63%), maximum food intake (+33%), growth efficiency (+41%) and standard metabolic rate (SMR; +47%), but lower active metabolic capacity (maximum metabolic rate [MMR; −17%], aerobic scope [AS; −48%]), suggesting that faster piscivore growth is supported by greater food intake and digestive capacity but is traded‐off against lower scope for active metabolism. A similar trade‐off appeared among organ systems, with piscivorous fry exhibiting an 83% greater investment in average mass of organs associated with food consumption and processing (i.e. stomach and intestine), but an apparently smaller relative investment in organs involved in cardiovascular or cognitive activities (heart and brain, respectively). Higher invertebrate drift in their natal rearing habitat, quicker behavioural transition to a novel food source and lower anxiety after a frightening event in piscivorous fry suggest that faster growth requires both proactive foraging behaviours and higher prey availability in the environment. Finally, the sampling of replicate insectivore populations confirmed their lower juvenile growth (−73% on average) and reduced environmental productivity of their natal streams (−45% lower drift abundance) relative to the piscivore ecotype.Our results suggest that selection for large adult body size influences selection on high juvenile growth, high basal metabolism and proactive behaviours, and that the intense phenotypic divergence between piscivorous and insectivorous rainbow trout may be constrained by environmental productivity. [ABSTRACT FROM AUTHOR]