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Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high-resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non-fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non-IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group-wise analyses of metabolites altered in ILD phenotypes. We utilized limma one-way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p-values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl-hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non-ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: With the coronavirus disease 2019 pandemic exacerbating mental health concerns, the prevalence rates of anxiety and sleep problems have increased alarmingly among youth. Although 90% of patients with anxiety experience sleep problems, current interventions for anxiety often do not target sleep problems in youth. Given this lack, we designed the SMILE app, an intervention that addresses both anxiety and sleep problems simultaneously., Methods: As users' perspectives are essential to ensure app engagement and uptake, the features, designs, and functions of the SMILE app were evaluated using a participatory app design approach. Participants ( N  = 17) were youth aged 15 to 25 who reported co-morbid anxiety and sleep issues above clinical thresholds. After completing an online screening survey assessing demographics, anxiety, and sleep problems, participants shared app feedback through group-based, semi-structured co-design sessions. Qualitative analyses were conducted to identify common themes from participants' feedback., Results: While participants expressed enthusiasm for the SMILE app's features, particularly the Visualization, Journaling, and Psychoeducation features, and their variety, they criticized the design aspects of the app, such as the font and text amount. Most participants stated they would use the SMILE app or recommend it to a friend., Conclusion: By actively involving the target population in the design process, the SMILE app has the potential to notably improve the mental well-being of youth, though further research and development are required to realize this potential fully., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Smartphone-delivered attentional bias modification training (ABMT) intervention has gained popularity as a remote solution for alleviating symptoms of mental health problems. However, the existing literature presents mixed results indicating both significant and insignificant effects of smartphone-delivered interventions., Objective: This systematic review and meta-analysis aims to assess the impact of smartphone-delivered ABMT on attentional bias and symptoms of mental health problems. Specifically, we examined different design approaches and methods of administration, focusing on common mental health issues, such as anxiety and depression, and design elements, including gamification and stimulus types., Methods: Our search spanned from 2014 to 2023 and encompassed 4 major databases: MEDLINE, PsycINFO, PubMed, and Scopus. Study selection, data extraction, and critical appraisal were performed independently by 3 authors using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. When necessary, we pooled the standardized mean difference with a 95% CI. In addition, we conducted sensitivity, subgroup, and meta-regression analyses to explore moderator variables of active and placebo ABMT interventions on reducing symptoms of mental health problems and attentional bias., Results: Our review included 12 papers, involving a total of 24,503 participants, and we were able to conduct a meta-analysis on 20 different study samples from 11 papers. Active ABMT exhibited an effect size (Hedges g) of -0.18 (P=.03) in reducing symptoms of mental health problems, while the overall effect remained significant. Similarly, placebo ABMT showed an effect size of -0.38 (P=.008) in reducing symptoms of mental health problems. In addition, active ABMT (Hedges g -0.17; P=.004) had significant effects on reducing attentional bias, while placebo ABMT did not significantly alter attentional bias (Hedges g -0.04; P=.66)., Conclusions: Our understanding of smartphone-delivered ABMT's potential highlights the value of both active and placebo interventions in mental health care. The insights from the moderator analysis also showed that tailoring smartphone-delivered ABMT interventions to specific threat stimuli and considering exposure duration are crucial for optimizing their efficacy. This research underscores the need for personalized approaches in ABMT to effectively reduce attentional bias and symptoms of mental health problems., Trial Registration: PROSPERO CRD42023460749; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=460749., (©Bilikis Banire, Matt Orr, Hailey Burns, Youna McGowan, Rita Orji, Sandra Meier. Originally published in JMIR Mental Health (https://mental.jmir.org), 02.09.2024.)

Context: Health care providers (HCP) experience high stress and burnout rates. Mindfulness Based Interventions (MBI) with biofeedback may help improve resiliency but require further research., Design and Study Participants: Aims were to evaluate changes in sleep patterns, nocturnal physiology, stress, mood disturbances, and perceived experience with biofeedback during the Mindfulness in Motion (MIM) intervention. Data from 66 HCP were included after removing those below 75 % compliance with wearable sensors and wellness surveys. Participants were enrolled in MIM, including eight weekly one-hour virtually delivered synchronous group meetings and ∼10 min of mindfulness home practice at least 3 times per week using a mobile application. Participants wore wearable sensors to monitor sleep and nocturnal physiology and completed short daily stress and mood disturbances., Results: According to mixed effect models, no sleep nor physiological metrics changed across MIM (p > 0.05). More time was spent in bed after MIM sessions (8.33±1.03 h) compared to night before (8.05±0.93 h; p = 0.040). Heart rate variability was lower nights after MIM (33.00±15.59 ms) compared to nights before (34.50±17.04 ms; p = 0.004) but was not clinically meaningful (effect= 0.033). Significant reductions were noted in perceived stress at weeks 3 through 8 compared to Baseline and lower Total Mood Disturbance at weeks 3, 5, 6, and 8 compared to Baseline (p < 0.001)., Conclusions: Participating in the MIM with mobile applications and wearable sensors reduced perceived stress and mood disturbances but did not induce physiological changes. Additional research is warranted to further evaluate objective physiological outcomes while controlling for confounding variables (e.g., alcohol, medications)., (Copyright © 2024. Published by Elsevier Inc.)

Machine learning can be used to create "biologic clocks" that predict age. However, organs, tissues, and biofluids may age at different rates from the organism as a whole. We sought to understand how cerebrospinal fluid (CSF) changes with age to inform the development of brain aging-related disease mechanisms and identify potential anti-aging therapeutic targets. Several epigenetic clocks exist based on plasma and neuronal tissues; however, plasma may not reflect brain aging specifically and tissue-based clocks require samples that are difficult to obtain from living participants. To address these problems, we developed a machine learning clock that uses CSF proteomics to predict the chronological age of individuals with a 0.79 Pearson correlation and mean estimated error (MAE) of 4.30 years in our validation cohort. Additionally, we analyzed proteins highly weighted by the algorithm to gain insights into changes in CSF and uncover novel insights into brain aging. We also demonstrate a novel method to create a minimal protein clock that uses just 109 protein features from the original clock to achieve a similar accuracy (0.75 correlation, MAE 5.41). Finally, we demonstrate that our clock identifies novel proteins that are highly predictive of age in interactions with other proteins, but do not directly correlate with chronological age themselves. In conclusion, we propose that our CSF protein aging clock can identify novel proteins that influence the rate of aging of the central nervous system (CNS), in a manner that would not be identifiable by examining their individual relationships with age., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Bumblebees are important pollinators for many natural and agricultural systems in temperate regions. Interspecific and intraspecific variation in floral resource preferences have been proposed to influence bumblebee community structure. In particular, sexual dimorphism is a major source of intraspecific niche variation. Although interspecific resource partitioning is well studied, few studies have explored the intraspecific dynamics between workers and males. Here, we report a study on a total of 11 528 workers and 2220 males of 14 bumblebee species recorded over 5 years in the Hengduan Mountains of Southwest China. We first compared the potential for interspecific and intraspecific competition between workers and males using visitation records and resource partitioning indices (overlap index). We then evaluated the influence of nectar traits on flower preference, including nectar volume and the levels of hexose, sucrose and 10 essential amino acids (EAAs). We found that the niche overlap between intraspecific workers and males was higher than that between different species, and temporal overlap alone did not strongly determine diet overlap. Males of most species preferred flowers with high levels of EAAs and hexose, whereas workers of some species preferred flowers with high nectar volume and sucrose levels. This study suggests that there is floral resource partitioning among bumblebee species, and between workers and males, which may play a key role in alleviating interspecific and intraspecific competition. These findings also provide a useful guide for which kinds of plants might be most valuable for bumblebees, especially the understudied males, in this biodiversity hotspot., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Issue Addressed: People with a mental health condition are at risk of developing chronic physical disease due to smoking tobacco, inadequate nutrition, high alcohol consumption, low physical activity and poor sleep (SNAPS). Community managed organisations (CMOs) represent an opportune setting to support mental health consumers to improve their health behaviours through providing preventive care. Reporting of methods used to co-develop implementation strategies to assist CMO staff to deliver preventive care for SNAPS are scarce yet warranted., Objectives: This study aims to: (1) describe a co-development workshop involving CMO staff and researchers to identify preferred implementation support strategies to help staff routinely provide preventive care; (2) describe the strategies that emerged from the workshop; and (3) report staff ratings of the workshop on four co-development principles., Methods: A three-hour co-development workshop was conducted on two occasions with staff of one CMO in New South Wales, Australia. Twenty staff participated in the workshops., Results: Participants generated and ranked a total of seven discrete implementation strategies within five categories (training, point of care prompts, guidelines, continuous quality improvement and consumer activation). Training for staff to have difficult conversations about behaviour change was ranked highest in both workshops. Participants rated the workshops positively across four co-development principles., Conclusions: The co-development workshop enabled implementation strategies to be developed within the context in which they were to be delivered and tested, potentially increasing their feasibility, acceptability, appropriateness and impact. SO WHAT?: Implementation strategies selected from the workshops will inform a pilot implementation support trial to assist CMO staff to provide preventive care to people with mental health conditions., (© 2023 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Background/aims: Primary and review studies show that supported employment interventions showed promise in assisting people with severe mental illness (SMI) in achieving successful employment and health-related outcomes. This umbrella review synthesises evidence from across review studies on supported employment interventions for individuals with SMI, to identify key findings and implementation challenges in relation to five key outcomes: (1) employment, (2) quality of life, (3) social functioning, (4) clinical/service utilisation, and (5) economic outcomes., Methods: A systematic search of eleven databases and registers (CINAHL, Cochrane, EmCare, JBI EBP, ProQuest, PsycINFO, PubMed, Scopus, and Web of Science, and Prospero and Campbell) was conducted to identify meta-analyses and systematic reviews on supported employment interventions for individuals with SMI, peer reviewed and published in English. Quality assessment and data extraction were performed using standardised Joanna Briggs Institute (JBI) tools. A mixed-methods synthesis approach was employed to integrate both quantitative and qualitative evidence., Results: The synthesis of 26 review studies primarily focused on the Individual Placement and Support (IPS) model among various supported employment interventions. Overall, combining supported employment with targeted interventions such as neurocognitive therapy and job-related social skill training showed a positive effect on employment (including job retention) and non-employment outcomes (e.g., health, quality of life, social functioning) relative to standard forms of supported employment for people with SMI. Contextual factors (intervention fidelity, settings, systemic barriers) were important considerations for intervention implementation and effectiveness., Discussion: Significant overlap of primary studies across 26 review studies exposed considerable variations in interpretation and conclusions drawn by authors, raising questions about their reliability. High volume of overlap reporting from the USA on IPS interventions in review studies is likely to have biased perceptions of effectiveness. There is no one-size-fits-all solution for supporting individuals with SMI in obtaining and maintaining employment. Tailoring strategies based on individual needs and circumstances appears crucial to address the complexity of mental health recovery. We propose creating centralised registries or databases to monitor primary studies included in reviews, thus avoiding redundancy., Other: This umbrella study was registered with PROSPERO (No. CRD42023431191)., Competing Interests: One author (MO) is an employee of Flourish Australia’s senior leadership team. Remaining authors (EP, YP, HM, SG, EH) do not have non-financial competing interests to declare. The commercial affiliation between Flinders University and the funder does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Patmisari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Math difficulties (MDs) occur in about 3-7 % of children and have been associated with academic, health, and occupational challenges. To date, findings about the role of working memory in MDs have been conflicting. The Automated Working Memory Assessment Battery (AWMA), which assesses all components of Baddeley and Hitch's model of working memory, was used to investigate which component of the model was most related to math calculation skills in elementary-school children. Participants were 94 (52 male) children (M age = 9 years 1 month; Range = 6 years 0 months to 11 years 8 months). As hypothesized, math calculation scores were correlated with all four working memory components (phonological loop, visuospatial sketchpad, verbal and visuospatial central executive). After accounting for age, phonological processing, and attention, the visuospatial sketchpad was the only memory component that contributed to the prediction of math calculation scores, explaining an additional 10.2 % of unique variance. Short-term visuospatial memory should be assessed in children having difficulty with math and children could benefit from interventions that include attention to the development of both visuospatial memory and math calculation skills. This study did not use a longitudinal design and so we cannot conclude that weak visuospatial memory impedes the development of math calculation skills. Future research should use longitudinal designs and investigate other types of math skills., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Description of the Problem. Gamification is used in pharmacy education as an innovative learning strategy to engage learners with educational content. The March Medication Madness activity used bracketology, a type of gamification not previously described in pharmacy education literature, to increase student engagement and knowledge of key disease states. The Innovation. The activity was developed for use in a capstone course during the final semester of the didactic pharmacy curriculum. Students created medication-related pearls that were placed in a tournament-style bracket. Students then completed brackets to predict the winning pearls and voted biweekly to determine the most clinically significant pearl. Student knowledge was assessed pre- and post-activity along with a post-activity perception assessment. Critical Analysis. Of the 52 student participant responses, most agreed or strongly agreed that the activity increased understanding and stimulated interest in course material, while adding a fun element to the course. There was a statistically significant increase ( P = .002) in the average percentage of multiple-choice questions students answered correctly from the pre-test (57.7% ± 1.5%) to the posttest (63.1% ± 1.9%). Pearls that received the most votes were no more likely to be associated with an increase in knowledge than pearls receiving fewer votes. Next Steps. Implementation of a bracketology activity was perceived by students as fun, engaging, and beneficial in understanding course material. However, increase in knowledge was limited. This shows the importance of structuring gamification in a way that provides educational value and underscores the need to modify the activity to promote student learning., (© Individual authors.)

E-liquids contain combinations of chemicals, with many enhancing the sensory attractiveness of the product. Studies are needed to understand and characterize e-liquid ingredients, particularly flavorings, to inform future research and regulations of these products. We identified common flavor ingredients in a convenience sample of commercial e-liquids using gas chromatography-mass spectrometry. E-liquid flavors were categorized by flavor descriptors provided on the product packaging. A Flavor Ingredient Wheel was developed to link e-liquid flavor ingredients with flavor categories. An analysis of 109 samples identified 48 flavor ingredients. Consistency between the labeled flavor and ingredients used to produce such flavor was found. Our novel Flavor Ingredient Wheel organizes e-liquids by flavor and ingredients, enabling efficient analysis of the link between ingredients and their flavor profiles and allowing for quick assessment of an e-liquid ingredient's flavor profile. Investigating ingredient profiles and identifying and classifying commonly used chemicals in e-liquids may assist with future studies and improve the ability to regulate these products.

During the eradication program undertaken against Anoplophora glabripennis (Motschulsky) in the Greater Toronto Area, information was collected on the numerous signs of injury found on wounded trees. Herein, we used a portion of this information to assess the characteristics of logs with signs of oviposition (i.e., pits). Specifically, we related the basal diameter, type (log bole vs. log branch), height above ground, and branch hierarchy level of logs with pits to tree size (i.e., height and diameter at breast height) and level of infestation intensity. In general, pits were concentrated on logs from the bole and branches that were 8-14 cm in diameter in the lower 8 m of the bole and in the first 2 levels of the branching hierarchy. Oviposition pit location was strongly influenced by tree size-both height and diameter at breast height, with more pits on the lower bole in small trees and then higher on the bole and into the branches as tree size increased. As tree-level infestation intensity increased, pits were found on both larger and smaller diameter portions of the trees, presumably as preferred oviposition sites became saturated. These findings can improve the efficacy of surveillance activities for A. glabripennis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Guideline Title: An ESPGHAN position paper on the diagnosis, management and prevention of cow's milk allergy RELEASE DATE: Journal of Pediatric Gastroenterology and Nutrition, July 26, 2023 PRIOR VERSION: 2012 DEVELOPER: ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition), NASPGHAN (North American Society of Pediatric Gastroenterology, Hepatology and Nutrition) FUNDING SOURCE: ESPGHAN TARGET POPULATION: Infants and young children with suspected cow's milk allergy., (© 2024 Society of Hospital Medicine.)

Vanadium pentoxide (V +5 ) is a hazardous material that has drawn considerable attention due to its wide use in industrial sectors and increased release into environment from human activities. It poses potential adverse effects on animals and human health, with pronounced impact on lung physiology and functions. In this study, we investigated the metabolic response of human bronchial epithelial BEAS-2B cells to low-level V +5 exposure (0.01, 0.1, and 1 ppm) using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exposure to V +5 caused extensive changes to cellular metabolism in BEAS-2B cells, including TCA cycle, glycolysis, fatty acids, amino acids, amino sugars, nucleotide sugar, sialic acid, vitamin D 3 , and drug metabolism, without causing cell death. Altered mitochondrial structure and function were observed with as low as 0.01 ppm (0.2 μM) V +5 exposure. In addition, decreased level of E-cadherin, the prototypical epithelial marker of epithelial-mesenchymal transition (EMT), was observed following V +5 treatment, supporting potential toxicity of V +5 at low levels. Taken together, the present study shows that V +5 has adverse effects on mitochondria and the metabolome which may result in EMT activation in the absence of cell death. Furthermore, results suggest that high-resolution metabolomics could serve as a powerful tool to investigate metal toxicity at levels which do not cause cell death., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests. Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The hydrological restoration of coastal wetlands is an emerging approach for mitigating and adapting to climate change and enhancing ecosystem services such as improved water quality and biodiversity. This paper synthesises current knowledge on selecting appropriate modelling approaches for hydrological restoration projects. The selection of a modelling approach is based on project-specific factors, such as costs, risks, and uncertainties, and aligns with the overall project objectives. We provide guidance on model selection, emphasising the use of simpler and less expensive modelling approaches when appropriate, and identifying situations when models may not be required for project managers to make informed decisions. This paper recognises and supports the widespread use of hydrological restoration in coastal wetlands by bridging the gap between hydrological science and restoration practices. It underscores the significance of project objectives, budget, and available data and offers decision-making frameworks, such as decision trees, to aid in matching modelling methods with specific project outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alice Twomey reports financial support was provided by Australian Research Council. Catherine Lovelock reports financial support was provided by Australian Research Council. Nathan Waltham reports financial support was provided by James Cook University TropWATER., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Cadmium (Cd) is a naturally occurring, toxic environmental metal found in foods. Humans do not have an efficient mechanism for Cd elimination; thus, Cd burden in humans increases with age. Cell and mouse studies show that Cd burden from low environmental levels of exposure impacts lung cell metabolism, proliferation signaling and cell growth as part of disease-promoting profibrotic responses in the lungs. Prior integrative analysis of metabolomics and transcriptomics identified the zDHHC11 transcript as a central functional hub in response to Cd dose. zDHHC11 encodes a protein S-palmitoyltransferase, but no evidence is available for effects of Cd on protein S-palmitoylation. In the present research, we studied palmitoylation changes in response to Cd and found increased protein S-palmitoylation in human lung fibroblasts that was inhibited by 2-bromopalmitate (2-BP), an irreversible palmitoyltransferase inhibitor. Mass spectrometry-based proteomics showed palmitoylation of proteins involved in divalent metal transport and in fibrotic signaling. Mechanistic studies showed that 2-BP inhibited palmitoylation of divalent metal ion transporter ZIP14 and also inhibited cellular Cd uptake. Transcription analyses showed that Cd stimulated transforming growth factor (TGF)-β1 and β3 expression within 8 h and lung fibrotic markers α-smooth muscle actin, matrix metalloproteinase-2, and collagen 1α1 gene expression and that these effects were blocked by 2-BP. Because 2-BP also blocked palmitoylation of proteins controlled by TGFβ1, these results show that palmitoylation impacts Cd-dependent fibrotic signaling both by enhancing cellular Cd accumulation and by supporting post-translational processing of TGFβ1-dependent proteins., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

How many species of life are there on Earth? This is a question that we want to know but cannot yet answer. Some scholars speculate that the number of species may reach 2.2 billion when considering cryptic diversity and that each morphology-based insect species may contain an average of 3.1 cryptic species. With nearly two million described species, such high estimates of cryptic diversity would suggest that cryptic species are widespread. The development of molecular species delimitation has led to the discovery of a large number of cryptic species, and cryptic biodiversity has gradually entered our field of vision and attracted more attention. This paper introduces the concept of cryptic species, how they evolve, and methods by which they may be discovered and confirmed, and provides theoretical and methodological guidance for the study of hidden species. A workflow of how to confirm cryptic species is provided. In addition, the importance and reliability of multi-evidence-based integrated taxonomy are reaffirmed as a way to better standardize decision-making processes. Special focus on cryptic diversity and increased funding for taxonomy is needed to ensure that cryptic species in hyperdiverse groups are discoverable and described. An increased focus on cryptic species in the future will naturally arise as more difficult groups are studied, and thereby, we may finally better understand the rules governing the evolution and maintenance of cryptic biodiversity., (© 2024 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Wild bees play crucial roles in pollinating numerous crops and fruits worldwide. However, these essential insect pollinators are threatened with decline due to a variety of stressors. Among stressors, relatively little work has been done on metalloid pollution. Laboratory experiments have shown that arsenic (As) and selenium (Se) can negatively impact on bees, it is unknown if these effects translate in real-world environments. To address this knowledge gap, wild bee communities were sampled from 18 smallholder farmlands in Kaihua County in Quzhou, Southeast China and As and Se concentrations in three bee species were measured (Xylocopa tranquebarorum, Eucera floralia, and Apis cerana). Analyses revealed that the large carpenter bee, X. tranquebarorum, exhibited significantly lower As and Se concentrations than the other two wild bee species. No significant correlations were found between As and Se concentrations in all three wild bee species. Interestingly, the proportion of semi-natural habitat was found to be significantly related to reduced Se concentration in wild bee bodies, though no such effect was observed for As. As pollution negatively impacted bee diversity but not abundance, whereas Se significantly impacted neither bee diversity nor abundance. Furthermore, both As and Se pollution had no significant effect on the abundance of small-bodied wild bees. Given the essential role of wild bees for pollination services, monitoring of As and Se pollution in wild bee bodies and their food resources (pollen and nectar) is recommended across agricultural and other potentially impacted systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Objectives: Terror catastrophizing, defined as an ongoing fear of future terrorist attacks, is associated with a higher incidence of anxiety disorders, among other psychological impacts. However, previous studies examining terror catastrophizing's relationship to other mental health disorders are limited. The current study sought to determine if patients diagnosed with anxiety and depression would experience increased terror catastrophizing. Additionally, this study aimed to investigate whether parental terror catastrophizing increases children's internalizing symptoms. Design & Methods: Individuals were randomly drawn from the Danish Civil Registration System and invited to complete a series of questionnaires to measure terror catastrophizing tendency, lifetime parental trauma, and children's internalizing symptoms. In total, n  = 4,175 invitees completed the survey of which 933 reported on a child between 6 and 18 years. Responses were analyzed using a generalized linear regression model. Results: Participants diagnosed with anxiety alone or comorbid with depression were more likely to experience symptoms of terror catastrophizing than undiagnosed participants ( β  = 0.10, p  < .001; β  = 0.07, p  = .012). Furthermore, the parental tendency to catastrophize terror was associated with higher internalizing symptoms in children ( β  = 0.09, p  = .006), even after taking parental diagnoses, as well as lifetime and childhood trauma into account. Conclusion: The results can inform clinical practices to account for a patient's potential to exhibit increased terror catastrophizing tendencies or be more affected by traumatic events. Additionally, they can offer insights for designing novel preventative interventions for the whole family, due to the relation between parental tendencies for terror catastrophizing and the internalizing symptoms observed in children.

Background: 22q11 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome with broad phenotypic variability, leading to significant morbidity and some mortality. The varied health problems associated with 22q11DS and the evolving phenotype (both medical and developmental/behavioural) across the lifespan can strongly impact the mental health of patients as well as their caregivers. Like caregivers of children with other chronic diseases, caregivers of children with 22q11DS may experience an increased risk of traumatisation and mental health symptoms. Objective: The study's primary objective was to assess the frequency of traumatic experiences and mental health symptoms among mothers of children with 22q11DS. The secondary objective was to compare their traumatic experiences to those of mothers of children with other neurodevelopmental disorders (NDDs). Method: A total of 71 mothers of children diagnosed with 22q11DS completed an online survey about their mental health symptoms and traumatic experiences. Descriptive statistics were used to summarise the prevalence of their mental health symptoms and traumatic experiences. Logistic regression models were run to compare the traumatic experiences of mothers of children with 22q11DS to those of 335 mothers of children with other neurodevelopmental disorders (NDDs). Results: Many mothers of children with 22q11DS experienced clinically significant mental health symptoms, including depression (39%), anxiety (25%), and post-traumatic stress disorder (PTSD) symptoms (30%). The types of traumatic events experienced by mothers of children with 22q11DS differed from those of mothers of children with other NDDs as they were more likely to observe their child undergoing a medical procedure, a life-threatening surgery, or have been with their child in the intensive care unit. Conclusion: 22q11DS caregivers are likely to require mental health support and trauma-informed care, tailored to the specific needs of this population as they experience different kinds of traumatic events compared to caregivers of children with other NDDS.

Introduction: Platelet-rich plasma (PRP) injections may improve symptoms in patients suffering from knee osteoarthritis. However, there is a lack of data on its effectiveness in a "real-life" cohort. This multi-site institutional registry study aimed to assess patients' longitudinal progress after PRP injection for knee osteoarthritis., Materials and Methods: All patients receiving PRP injections for knee osteoarthritis at a large, integrated tertiary academic center (December 18, 2017 to March 1, 2021) were eligible. A prospective data collection instrument was used to collect patient demographics, procedural information, and patient-reported outcome measures. Overall, 97 patients met the inclusion criteria, and 53 were included in the analysis., Results: One in four patients (26%) improved on all three Knee Injury and Osteoarthritis Outcome Score subscales: 17% in two subscales and 20% in one subscale, respectively. Overall, 64% of patients improved in at least one patient-reported outcomes measure. At six months post injection, 49% of patients were satisfied., Conclusion: PRP injection provides positive changes in two out of three patients in different magnitudes and characteristics with careful attention to clinically meaningful differences.

Total knee arthroplasty (TKA) is the sole disease-modifying intervention for end-stage osteoarthritis. However, the temporal trends and stratification of age and patient demographics of pain and function levels at which surgeons perform TKA have not been characterized. The present investigation aimed to analyze the temporal trends of preoperative pain and functional patient-reported outcomes measures (PROMs) over the past 5 years when stratifying patient demographics. A prospective cohort of all patients who underwent primary elective TKA between January 2016 and December 2020 at a North American integrated tertiary health care system was retrospectively reviewed. The primary outcome was quarterly baseline (preoperative) pain and function PROM values before primary elective TKA. Evaluated PROMs included Knee Osteoarthritis Outcome Score (KOOS)-pain and KOOS-physical function shortform (PS) for the 5-year study period and were stratified by patient demographics (age, sex, race, and body mass index [BMI]). A total of 10,327 patients were analyzed. Preoperative pain levels remained unchanged over the study period for patients in the 45- to 64-year category (P-trend = 0.922). Conversely, there was a significant improvement in preoperative pain levels in the 65+ years group. Sex-stratified trends between males and females did not demonstrate a significant change in pre-TKA baseline pain over the study period (P-trend = 0.347 and P-trend = 0.0744). Both white and black patients demonstrated consistent KOOS-pain levels throughout the study period (P-trend = 0.0855 and P-trend = 0.626). Only white patients demonstrated improving preoperative KOOS-PS (P-trend = 0.0001), while black and "other" patients demonstrated consistent lower preoperative functional levels throughout the study period (P-trend = 0.456 and P-trend = 0.871). All BMI categories demonstrated relatively consistent preoperative KOOS-pain and KOOS-PS except for overweight and obese patients who demonstrated progressive improvement in preoperative KOOS-PS over the study period. Patients and surgeons are electing to perform primary TKA at higher levels of preoperative function. Stratification by race showed black patients did not experience a similar trend of improving function and exhibited a consistently lower functional level versus white patients. This disparity is likely to be multifactorial but may indicate underlying barriers to TKA access., Competing Interests: R.W.S., A.K.E., M.O., A.K.K., P.J.R., and T.J.P. have nothing to disclose. V.E.K. has the following disclosures not related to the present study: Journal of Arthroplasty: editorial or governing board; publishing royalties, financial or material support Stryker: IP royalties; paid consultant; stock or stock options. R.M.M. has the following disclosures not related to the present study: American Association of Hip and Knee Surgeons: board or committee member Stryker: paid consultant; paid presenter or speaker; research support Zimmer: research support. N.S.P. has the following disclosures not related to the present study: American Association of Hip and Knee Surgeons: board or committee member ISCT; board or committee member Journal of Hip Surgery; editorial or governing board Journal of Knee Surgery; editorial or governing board Orthopaedic Research Society; board or committee member Regeneron; paid consultant RegenLab; research support Stryker; paid consultant Zimmer: research support., (Thieme. All rights reserved.)

Abstract: McGrath, R, FitzSimmons, S, Andrew, S, Black, K, Bradley, A, Christensen, BK, Collins, K, Klawitter, L, Kieser, J, Langford, M, Orr, M, and Hackney, KJ. Prevalence and trends of weakness among middle-aged and older adults in the United States. J Strength Cond Res 37(12): 2484-2490, 2023-Muscle weakness, which is often determined with low handgrip strength (HGS), is associated with several adverse health conditions; however, the prevalence and trends of weakness in the United States is not well-understood. We sought to estimate the prevalence and trends of weakness in Americans aged at least 50 years. The total unweighted analytic sample included 22,895 Americans from the 2006-2016 waves of the Health and Retirement Study. Handgrip strength was measured with a handgrip dynamometer. Men with weakness were below at least one of the absolute or normalized (body mass, body mass index) cut points: <35.5 kg, <0.45 kg/kg, <1.05 kg/kg/m 2 . The presence of any weakness in women was also identified as being below one of the absolute or normalized HGS cut points: <20.0 kg, <0.34 kg/kg, or <0.79 kg/kg/m 2 . There was an increasing trend in the prevalence of any weakness over time ( p < 0.001). The prevalence of weakness was 45.1% (95% confidence interval [CI]: 44.0-46.0) in the 2006-2008 waves and 52.6% (CI: 51.5-53.7) in the 2014-2016 waves. Weakness prevalence was higher for older (≥65 years) Americans (64.2%; CI: 62.8-65.5) compared with middle-aged (50-64 years) Americans (42.2%; CI: 40.6-43.8) in the 2014-2016 waves. Moreover, the prevalence of weakness in the 2014-2016 waves was generally higher in women (54.5%; CI: 53.1-55.9) than in men (50.4%; CI: 48.7-52.0). Differences existed in weakness prevalence across races and ethnicities. The findings from our investigation suggest that the prevalence of weakness is overall pronounced and increasing in Americans. Efforts for mitigating and better operationalizing weakness will elevate in importance as our older American population grows., (Copyright © 2023 National Strength and Conditioning Association.)

Clostridium novyi has demonstrated selective efficacy against solid tumors largely due to the microenvironment contained within dense tumor cores. The core of a solid tumor is typically hypoxic, acidic, and necrotic-impeding the penetration of current therapeutics. C. novyi is attracted to the tumor microenvironment and once there, can both lyse and proliferate while simultaneously re-activating the suppressed immune system. C. novyi systemic toxicity is easily mitigated by knocking out the phage DNA plasmid encoded alpha toxin resulting in C. novyi-NT; but, after intravenous injection spores are quickly cleared by phagocytosis before accomplishing significant tumor localization. C. novyi-NT could be designed to accomplish intravenous delivery with the potential to target all solid tumors and their metastases in a single dose. This study characterizes CRISPR/Cas9 modified C. novyi-NT to insert the gene for RGD, a tumor targeting peptide, expressed within the promoter region of a spore coat protein. Expression of the RGD peptide on the outer spore coat of C. novyi-NT indicates an increased capacity for tumor localization of C. novyi upon intravenous introduction based on the natural binding of RGD with the αvβ3 integrin commonly overexpressed on the epithelial tissue surrounding a tumor, and lead to immune stimulation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dailey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The transgenerational effects of parental diagnoses, trauma and coping mechanisms on children's internalizing symptoms are not well understood. In a population-based study of 933 families combining data from a web-based survey and the Danish registers, we used an online survey of parents to examine how parental diagnoses, trauma and coping mechanisms affect the development of internalizing symptoms in children aged 6 to 18 years. To account for attrition, we used inverse probability weights in our regression models. Children of parents diagnosed with depression or anxiety displayed more internalizing symptoms than children of controls. Similarly, children of parents who experienced multiple trauma had significantly more internalizing symptoms. In contrast, we observed significantly fewer internalizing symptoms among children of parents who felt they could cope well. The protective effect of parental coping persisted even after adjusting for parental diagnoses or trauma. Interventions boosting parental coping mechanisms might help to prevent the development of internalizing symptoms in children even among patients who have been diagnosed with depression or anxiety or experienced a high trauma load., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Bronchiolitis is a viral respiratory illness most commonly caused by respiratory syncytial virus (RSV). COVID-19 disrupted typical patterns of viral transmission. Our study aimed to compare low value care for bronchiolitis in a tertiary emergency department (ED) in the United States from March 2017 to March 2022., Methods: This was a descriptive cohort study through a retrospective chart review from 2017 to 2022 analyzing ED visits for bronchiolitis including disposition, disease severity, chest radiographs, albuterol, and high flow nasal cannula usage. A year was a 12-month period from March to February., Results: From 2017 to 2020, there were over 2000 ED visits for bronchiolitis per year (3.1% of all ED visits), which decreased to 450 visits for bronchiolitis (1%) in 2020-2021. Human rhino/enterovirus was the most common virus detected (92%) at that time, and admission rates, albuterol, high flow nasal cannula, and chest radiographs were all higher. The summer of 2021 had the highest visits across the 5-study years with a return to previous rates of resource utilization., Conclusions: Bronchiolitis ED visits due to RSV dramatically reduced during the first year of the COVID-19 pandemic in 2020, with over 80% reduction in bronchiolitis visits from 2018 to 2019. While all ED visits fell in 2020, the proportion of visits due to bronchiolitis also decreased. There was an increase in lower value care during the rhinovirus dominant, low census period. As restrictions lifted in 2021, there was a large resurgence of RSV in the atypical summer months with a return of previous rates of resource utilization., (© 2023 Wiley Periodicals LLC.)

The microtubule (MT) instability observed in Alzheimer's disease (AD) is commonly attributed to hyperphosphorylation of the MT-associated protein, tau. In vivo PET imaging offers an opportunity to gain critical information about MT changes with the onset and development of AD and related dementia. We developed the first brain-penetrant MT PET ligand, [ 11 C]MPC-6827, and evaluated its in vivo imaging utility in vervet monkeys. Consistent with our previous in vitro cell uptake and in vivo rodent imaging experiments, [ 11 C]MPC-6827 uptake increased with MT destabilization. Radioactive uptake was inversely related to (cerebrospinal fluid) CSF Aβ 42 levels and directly related to age in a nonhuman primate (NHP) model of AD. Additionally, in vitro autoradiography studies also corroborated PET imaging results. Here, we report the preliminary results of PET imaging with [ 11 C]MPC-6827 in four female vervet monkeys with high or low CSF Aβ 42 levels, which have been shown to correlate with the Aβ plaque burden, similar to humans.

Background: Most individuals with 22q11.2 deletion syndrome (22q11DS) have multi-system and lifelong needs requiring substantial support. Their primary caregivers are usually family members who dedicate lifelong time and effort to their role. The pressures of their roles can negatively impact caregivers' psychosocial well-being, suggesting a need for additional support for this community who currently have no specialised interventions available., Method: This online study surveyed 103 caregivers of family members with 22q11DS to determine the barriers to accessing support that they faced, the kind of support they would value and whether an online intervention could meet their needs., Results: The caregivers indicated that a brief online intervention focused on teaching practical skills and connecting them with a peer network of support would be most valuable., Conclusions: Future studies are planned that will build on these results by designing and testing online interventions tailored to this community., (© 2023 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Risk of bias assessment is a critical step of any meta-analysis or systematic review. Given the low sample count of many microbiome studies, especially observational or cohort studies involving human subjects, many microbiome studies have low power. This increases the importance of performing meta-analysis and systematic review for microbiome research in order to enhance the relevance and applicability of microbiome results. This work proposes a method based on the ROBINS-I tool to systematically consider sources of bias in microbiome research seeking to perform meta-analysis or systematic review for microbiome studies., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2023.)

Vanadium is available as a dietary supplement and also is known to be toxic if inhaled, yet little information is available concerning the effects of vanadium on mammalian metabolism when concentrations found in food and water. Vanadium pentoxide (V +5 ) is representative of the most common dietary and environmental exposures, and prior research shows that low-dose V +5 exposure causes oxidative stress measured by glutathione oxidation and protein S-glutathionylation. We examined the metabolic impact of V +5 at relevant dietary and environmental doses (0.01, 0.1, and 1 ppm for 24 h) in human lung fibroblasts (HLFs) and male C57BL/6J mice (0.02, 0.2, and 2 ppm in drinking water for 7 mo). Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that V +5 induced significant metabolic perturbations in both HLF cells and mouse lungs. We noted 30% of the significantly altered pathways in HLF cells, including pyrimidines and aminosugars, fatty acids, mitochondrial and redox pathways, showed similar dose-dependent patterns in mouse lung tissues. Alterations in lipid metabolism included leukotrienes and prostaglandins involved in inflammatory signaling, which have been associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF) and other disease processes. Elevated hydroxyproline levels and excessive collagen deposition were also present in lungs from V +5 -treated mice. Taken together, these results show that oxidative stress from environmental V +5 , ingested at low levels, could alter metabolism to contribute to common human lung diseases. NEW & NOTEWORTHY We used relevant dietary and environmental doses of Vanadium pentoxide (V +5 ) to examine its metabolic impact in vitro and in vivo. Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), we found significant metabolic perturbations, with similar dose-dependent patterns observed in human lung fibroblasts and male mouse lungs. Alterations in lipid metabolism included inflammatory signaling, elevated hydroxyproline levels, and excessive collagen deposition were present in V +5 -treated lungs. Our findings suggest that low levels of V +5 could trigger pulmonary fibrotic signaling.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Smoking is a modifiable risk factor for complications following total knee arthroplasty (TKA). It is unclear if the declining prevalence of tobacco use in the U.S. population is reflected in patients undergoing elective TKA. This study aims to investigate (1) the incidence of 30-day complications following TKA in smokers and (2) trends in preoperative smoking status among TKA patients. In this study, patients undergoing primary elective TKA in the United States from 2011 to 2019 were identified in the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database. Our cohort included 406,553 cases, 8.13% of which had smoked cigarettes within 1 year of undergoing TKA. Smokers were propensity score-matched to a group of nonsmokers, with each n  = 32,533. The incidences of 30-day complications, readmission, and non-home discharge were compared between groups. The rate of preoperative smoking among elective primary TKA patients remained stagnant from 2011 to 2019. Smokers had higher rates of superficial surgical site infections (SSIs; 1.1 vs. 0.5%, p  < 0.001), deep SSI (0.3 vs. 0.2%, p  = 0.012), wound disruption (0.4 vs. 0.2%, p  < 0.001), pneumonia (0.5 vs. 0.3%, p  < 0.001), and 30-day readmission (3.6 vs. 2.7%, p  < 0.001) compared with nonsmokers. No significant trends in 30-day complications were noted between 2011 and 2019. This study supports the success of national efforts to reduce the prevalence of smoking and reports a modest effect within the TKA population. However, almost 1 in 10 patients undergoing elective TKA continues to smoke and maintains a higher risk of postoperative complications., Competing Interests: None declared., (Thieme. All rights reserved.)

There is little significant work at the intersection of mathematical and computational epidemiology and detailed psychological processes, representations, and mechanisms. This is true despite general agreement in the scientific community and the general public that human behavior in its seemingly infinite variation and heterogeneity, susceptibility to bias, context, and habit is an integral if not fundamental component of what drives the dynamics of infectious disease. The COVID-19 pandemic serves as a close and poignant reminder. We offer a 10-year prospectus of kinds that centers around an unprecedented scientific approach: the integration of detailed psychological models into rigorous mathematical and computational epidemiological frameworks in a way that pushes the boundaries of both psychological science and population models of behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Orr, Mortveit, Lebiere and Pirolli.)

Plastic cutting boards are a potentially significant source of microplastics in human food. Thus, we investigated the impact of chopping styles and board materials on microplastics released during chopping. As chopping progressed, the effects of chopping styles on microplastic release became evident. The mass and number of microplastics released from polypropylene chopping boards were greater than polyethylene by 5-60% and 14-71%, respectively. Chopping on polyethylene boards was associated with a greater release of microplastics with a vegetable (i.e., carrots) than chopping without carrots. Microplastics showed a broad, bottom-skewed normal distribution, dominated by <100 μm spherical-shaped microplastics. Based on our assumptions, we estimated a per-person annual exposure of 7.4-50.7 g of microplastics from a polyethylene chopping board and 49.5 g of microplastics from a polypropylene chopping board. We further estimated that a person could be exposed to 14.5 to 71.9 million polyethylene microplastics annually, compared to 79.4 million polypropylene microplastics from chopping boards. The preliminary toxicity study of the polyethylene microplastics did not show adverse effects on the viability of mouse fibroblast cells for 72 h. This study identifies plastic chopping boards as a substantial source of microplastics in human food, which requires careful attention.

Despite the urgent need for conservation consideration, strategic action plans for the preservation of the Asian honeybee, Apis cerana Fabricius, 1793, remain lacking. Both the convergent and divergent adaptations of this widespread insect have led to confusing phenotypical traits and inconsistent infraspecific taxonomy. Unclear subspecies boundaries pose a significant challenge to honeybee conservation efforts, as it is difficult to effectively prioritize conservation targets without a clear understanding of subspecies identities. Here, we investigated genome variations in 362 worker bees representing almost all populations of mainland A. cerana to understand how evolution has shaped its population structure. Whole-genome single nucleotide polymorphisms (SNPs) based on nuclear sequences revealed eight putative subspecies, with all seven peripheral subspecies exhibiting mutually exclusive monophyly and distinct genetic divergence from the widespread central subspecies. Our results demonstrated that most classic morphological traits, including body size, were related to the climatic variables of the local habitats and did not reflect the true evolutionary history of the organism. Thus, such morphological traits were not suitable for subspecific delineation. Conversely, wing vein characters showed relative independence to the environment and supported the subspecies boundaries inferred from nuclear genomes. Mitochondrial phylogeny further indicated that the present subspecies structure was a result of multiple waves of population divergence from a common ancestor. Based on our findings, we propose that criteria for subspecies delineation should be based on evolutionary independence, trait distinction, and geographic isolation. We formally defined and described eight subspecies of mainland A. cerana . Elucidation of the evolutionary history and subspecies boundaries enables a customized conservation strategy for both widespread and endemic honeybee conservation units, guiding colony introduction and breeding.

Background: Highly pathogenic avian H5 influenza viruses have spread and diversified genetically and antigenically into multiple clades and subclades. Most isolates of currently circulating H5 viruses are in clade 2.3.2.1 or 2.3.4.4., Methods: Panels of murine monoclonal antibodies (mAbs) were generated to the influenza hemagglutinin (HA) of H5 viruses from the clade 2.3.2.1 H5N1 vaccine virus A/duck/Bangladesh/19097/2013 and the clade 2.3.4.4 H5N8 vaccine virus A/gyrfalcon/Washington/41088-6/2014. Antibodies were selected and characterized for binding, neutralization, epitope recognition, cross-reactivity with other H5 viruses, and the ability to provide protection in passive transfer experiments., Results: All mAbs bound homologous HA in an ELISA format; mAbs 5C2 and 6H6 were broadly binding for other H5 HAs. Potently neutralizing mAbs were identified in each panel, and all neutralizing mAbs provided protection in passive transfer experiments in mice challenged with a homologous clade influenza virus. Cross-reacting mAb 5C2 neutralized a wide variety of clade 2.3.2.1 viruses, as well as H5 viruses from other clades, and also provided protection against heterologous H5 clade influenza virus challenge. Epitope analysis indicated that the majority of mAbs recognized epitopes in the globular head of the HA. The mAb 5C2 appeared to recognize an epitope below the globular head but above the stalk region of HA., Conclusions: The results suggested that these H5 mAbs would be useful for virus and vaccine characterization. The results confirmed the functional cross-reactivity of mAb 5C2, which appears to bind a novel epitope, and suggest the therapeutic potential for H5 infections in humans with further development., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Despite its rarity, the risk of mortality following primary elective total knee arthroplasty (TKA) is a critical component of surgical decision-making and patient counseling. The purpose of our study was to (1) determine the overall 30-day mortality rate for unilateral primary elective TKA patients, (2) determine the 30-day mortality rates when stratified by age, comorbidities, and preoperative diagnosis, and (3) identify the distribution of (i) patient demographics, (ii) baseline comorbidities, and (iii) preoperative diagnoses between mortality and mortality-free cohorts. A total of 326,157 patients underwent primary elective TKA (2011-2018) were identified through retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were divided into 30-day mortality ( n  = 320) and mortality-free ( n  = 325,837) cohorts. Patient demographics, preoperative comorbidities, and preoperative diagnoses were compared. Age group, American Society of Anesthesiology (ASA) score, and modified Charlson Comorbidity Index (CCI) scores were normalized per 1000 and stratified by preoperative diagnosis. The overall mortality rate was 0.098%. Older age ( p  < 0.001) and male gender ( p  < 0.001) were associated with increased mortality. There was no association between mortality and race ( p  = 0.346) or body mass index (BMI) class ( p  = 0.722). All reported comorbidities except smoking status were significantly greater in the mortality cohort ( p  < 0.05). For ASA scores of I, II, III, and IV, the number of deaths per 1,000 were 0.16, 0.47, 1.4, and 4.4, respectively. For CCI scores of 0, 1, 2, 3, 4, and 6, mortality rates per 1,000 were 0.76, 2.1, 7.0, 11, 29, and 7.6, respectively. Mortality rates for a preoperative diagnosis of osteoarthritis (OA) versus non-OA were, respectively, 0.096% and 0.19% ( p  < 0.001). Increased age, male gender, increased comorbidity burden, and non-OA preoperative diagnoses are associated with higher rates of 30-day postoperative mortality. There were no significant associations between BMI or race and 30-day mortality. These findings aid in identifying of higher-risk patients, who can then receive appropriate counseling or preoperative interventions to reduce the risk of perioperative mortality., Competing Interests: None declared., (Thieme. All rights reserved.)

Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology., Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II., Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022., Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo., Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension., Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo., Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19., Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests.

Antagonistic interaction refers to opposing beneficial and adverse signaling by a single agent. Understanding opposing signaling is important because pathologic outcomes can result from adverse causative agents or the failure of beneficial mechanisms. To test for opposing responses at a systems level, we used a transcriptome-metabolome-wide association study (TMWAS) with the rationale that metabolite changes provide a phenotypic readout of gene expression, and gene expression provides a phenotypic readout of signaling metabolites. We incorporated measures of mitochondrial oxidative stress (mtOx) and oxygen consumption rate (mtOCR) with TMWAS of cells with varied manganese (Mn) concentration and found that adverse neuroinflammatory signaling and fatty acid metabolism were connected to mtOx, while beneficial ion transport and neurotransmitter metabolism were connected to mtOCR. Each community contained opposing transcriptome-metabolome interactions, which were linked to biologic functions. The results show that antagonistic interaction is a generalized cell systems response to mitochondrial ROS signaling.

After a chemical fire, an investigation assessed health effects by using syndromic surveillance to monitor emergency department (ED) visits, a general health survey to assess the general public, and a first responders health survey to assess first responders. A total of four separate multivariable logistic regression models were developed to examine associations between reported exposure to smoke, dust, debris, or odor with any reported symptom in the general public. Syndromic surveillance identified areas with increased ED visits. Among general health survey respondents, 45.1% (911 out of 2,020) reported at least one symptom. Respondents reporting exposure to smoke, dust, debris, or odor had 4.5 (95% confidence interval (CI) [3.7, 5.5]), 4.6 (95% CI [3.6, 5.8]), 2.0 (95% CI [1.7, 2.5]), or 5.8 (95% CI [4.7, 7.3]) times the odds of reporting any symptom compared with respondents not reporting exposure to smoke, dust, debris, or odor, respectively. First responders commonly reported contact with material and being within 1 mi of the fire ≥5 hr; 10 out of 31 of first responders reported at least one symptom. There was high symptom burden reported after the fire. Results from our investigation might assist the directing of public health resources to effectively address immediate community needs and prepare for future incidents.

Background: Pain and function, as reflected by patient-reported outcome measures (PROMs), can influence improvement after total knee arthroplasty (TKA) and can reflect the extent of patient access to orthopaedic surgical care. We aimed to (1) categorize patients according to pain and function PROM phenotypes, (2) identify patient characteristics associated with poor preoperative pain and function, and (3) assess relationships between baseline characteristics and PROM phenotypes., Methods: A prospective cohort of 14,079 TKAs was enrolled. Demographics, comorbidities, surgical details, and preoperative PROMs were collected. Outcomes included preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) Pain (P) and Physical Function (PS) subscores, stratified by demographics. Patients were then categorized into 4 PROM phenotypes defined on the basis of the cohort medians: above or equal to the median for both pain and function scores (P+PS+), below the median for both pain and function (P-PS-), above or equal to the median for pain but below the median for function (P+PS-), and below the median for pain but above or equal to the median for function (P-PS+). Descriptive statistics and multivariable regression analyses were calculated., Results: The largest PROM phenotype was P-PS- (39.4%), followed by P+PS+ (38.9%). The cohort with discordantly poor function but high pain scores (less pain) was the smallest cohort (9.9%). Preoperative KOOS-Pain and KOOS-PS scores at or below the 25th percentile were independently associated with younger age, female sex, higher body mass index (BMI), non-White race, current smoking, lower education, non-commercial insurance, and higher Charlson Comorbidity Index (CCI). Multivariate logistic regression showed that patients in the P+PS+ category were older (odds ratio [OR] = 1.56), were more likely to be male (OR = 2.00), had a lower BMI (OR = 0.67), had more education (OR = 1.63), had a lower CCI, and were less likely to be Black (OR = 0.80) or Other (OR = 0.62) race, be a current smoker (OR = 0.62), and have commercial insurance (OR = 0.74), compared with the P-PS- phenotype., Conclusions: Younger age, obesity, non-White race, female sex, current or recent smoking, non-commercial insurance, and higher CCI were associated with worse pre-TKA PROMs and poor pain-function phenotype combinations. Such a pattern may indicate barriers to TKA access among these patient populations leading to advanced levels of impairment at the time of treatment., Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H358 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Sandra Martell, President of the Northern Illinois Public Health Consortium, has received Local Health Protection Grants covering environmental health services, surveillance, and communicable disease from the Illinois Department of Public Health and has Levy funding through the Winnebago County Health Department. Sarah Patrick is supported by the Illinois State Health Department. No other potential conflicts of interest were disclosed.

Vanadium is a toxic metal listed by the IARC as possibly carcinogenic to humans. Manufactured nanosize vanadium pentoxide (V 2 O 5 ) materials are used in a wide range of industrial sectors and recently have been developed as nanomedicine for cancer therapeutics, yet limited information is available to evaluate relevant nanotoxicity. In this study we used high-resolution metabolomics to assess effects of two V 2 O 5 nanomaterials, nanoparticles and nanofibers, at exposure levels (0.01, 0.1, and 1 ppm) that did not cause cell death (i.e., non-cytotoxic) in a human airway epithelial cell line, BEAS-2B. As prepared, V 2 O 5 nanofiber exhibited a fibrous morphology, with a width approximately 63 ± 12 nm and length in average 420 ± 70 nm; whereas, V 2 O 5 nanoparticles showed a typical particle morphology with a size 36 ± 2 nm. Both V 2 O 5 nanoparticles and nanofibers had dose-response effects on aminosugar, amino acid, fatty acid, carnitine, niacin and nucleotide metabolism. Differential effects of the particles and fibers included dibasic acid, glycosphingolipid and glycerophospholipid pathway associations with V 2 O 5 nanoparticles, and cholesterol and sialic acid metabolism associations with V 2 O 5 nanofibers. Examination by transmission electron microscopy provided evidence for mitochondrial stress and increased lysosome fusion by both nanomaterials, and these data were supported by effects on mitochondrial membrane potential and lysosomal activity. The results showed that non-cytotoxic exposures to V 2 O 5 nanomaterials impact major metabolic pathways previously associated with human lung diseases and suggest that toxico-metabolomics may be useful to evaluate health risks from V 2 O 5 nanomaterials., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We present a computational cognitive model that incorporates and formalizes aspects of theories of individual-level behavior change and present simulations of COVID-19 behavioral response that modulates transmission rates. This formalization includes addressing the psychological constructs of attitudes, self-efficacy, and motivational intensity. The model yields signature phenomena that appear in the oscillating dynamics of mask wearing and the effective reproduction number, as well as the overall increase of rates of mask-wearing in response to awareness of an ongoing pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pirolli, Lebiere and Orr.)

As a global industry, sport makes potentially significant contributions to climate change through both carbon emissions and influence over sustainability practices. Yet, evidence regarding impacts is uneven and spread across many disciplines. This paper investigates the impacts of sport emissions on climate and identifies knowledge gaps. We undertook a systematic and iterative meta-analysis of relevant literature (1992-2022) on organized and individual sports. Using a defined search protocol, 116 sources were identified that map to four sport-related themes: (1) carbon emissions and their measurement; (2) emissions control and decarbonization; (3) carbon sinks and offsets; and (4) behavior change. We find that mega sport events, elite sport, soccer, skiing, and golf have received most attention, whereas grass-roots and women's sport, activity in Africa and South America, cricket, tennis, and volleyball are understudied. Other knowledge gaps include carbon accounting tools and indicators for smaller sports clubs and active participants; cobenefits and tradeoffs between mitigation-adaptation efforts in sport, such as around logistics, venues, sports equipment, and facilities; geopolitical influence; and scope for climate change litigation against hosts and/or sponsors of carbon-intensive events. Among these, researchers should target cobenefits given their scope to deliver wins for both climate mitigation and risk management of sport., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)