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Abstract Influenza virus pandemics are caused by viruses from animal reservoirs that adapt to efficiently infect and replicate in human hosts. Here, we investigate whether Interferon-Induced Transmembrane Protein 3 (IFITM3), a host antiviral factor with known human deficiencies, plays a role in interspecies virus infection and adaptation. We find that IFITM3-deficient mice and human cells can be infected with low doses of avian influenza viruses that fail to infect WT counterparts, identifying a new role for IFITM3 in controlling the minimum infectious virus dose threshold. Remarkably, influenza viruses passaged through Ifitm3 −/− mice exhibit enhanced host adaptation, a result that is distinct from viruses passaged in mice deficient for interferon signaling, which exhibit attenuation. Our data demonstrate that IFITM3 deficiency uniquely facilitates potentially zoonotic influenza virus infections and subsequent adaptation, implicating IFITM3 deficiencies in the human population as a vulnerability for emergence of new pandemic viruses.

Abstract The rapid release of high-performing computer vision models offers new potential to study the impact of different inductive biases on the emergent brain alignment of learned representations. Here, we perform controlled comparisons among a curated set of 224 diverse models to test the impact of specific model properties on visual brain predictivity – a process requiring over 1.8 billion regressions and 50.3 thousand representational similarity analyses. We find that models with qualitatively different architectures (e.g. CNNs versus Transformers) and task objectives (e.g. purely visual contrastive learning versus vision- language alignment) achieve near equivalent brain predictivity, when other factors are held constant. Instead, variation across visual training diets yields the largest, most consistent effect on brain predictivity. Many models achieve similarly high brain predictivity, despite clear variation in their underlying representations – suggesting that standard methods used to link models to brains may be too flexible. Broadly, these findings challenge common assumptions about the factors underlying emergent brain alignment, and outline how we can leverage controlled model comparison to probe the common computational principles underlying biological and artificial visual systems.

Abstract Much of what we know about terrestrial life during the Carboniferous Period comes from Middle Pennsylvanian (~315–307 Mya) Coal Measures deposited in low-lying wetland environments1–5. We know relatively little about terrestrial ecosystems from the Early Pennsylvanian, which was a critical interval for the diversification of insects, arachnids, tetrapods, and seed plants6–10. Here we report a diverse Early Pennsylvanian trace and body fossil Lagerstätte (~320–318 Mya) from the Wamsutta Formation of eastern North America, distinct from coal-bearing deposits, preserved in clastic substrates within basin margin conglomerates. The exceptionally preserved trace fossils and body fossils document a range of vertebrates, invertebrates and plant taxa (n = 131), with 83 distinct foliage morphotypes. Plant-insect interactions include what may be the earliest evidence of insect oviposition. This site expands our knowledge of early terrestrial ecosystems and organismal interactions and provides ground truth for future phylogenetic reconstructions of key plant, arthropod, and vertebrate groups.

Abstract Meningiomas are associated with inactivation of NF2/Merlin, but approximately one-third of meningiomas with favorable clinical outcomes retain Merlin expression. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that may be used to guide treatment de-escalation or imaging surveillance are lacking. Here, we use single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma xenografts and patients to define biochemical mechanisms and an imaging biomarker that underlie Merlin-intact meningiomas. We find Merlin serine 13 (S13) dephosphorylation drives meningioma Wnt signaling and tumor growth by attenuating inhibitory interactions with β-catenin and activating the Wnt pathway. MRI analyses show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC). These results define mechanisms underlying a potential imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with Merlin-intact meningiomas.

Abstract Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families.

Abstract As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1−/− mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.

In this mini review, we propose the use of the Julia programming language and its software as a strong candidate for reproducible, efficient, and sustainable physiological signal analysis. First, we highlight available software and Julia communities that provide top-of-the-class algorithms for all aspects of physiological signal processing despite the language’s relatively young age. Julia can significantly accelerate both research and software development due to its high-level interactive language and high-performance code generation. It is also particularly suited for open and reproducible science. Openness is supported and welcomed because the overwhelming majority of Julia software programs are open source and developed openly on public platforms, primarily through individual contributions. Such an environment increases the likelihood that an individual not (originally) associated with a software program would still be willing to contribute their code, further promoting code sharing and reuse. On the other hand, Julia’s exceptionally strong package manager and surrounding ecosystem make it easy to create self-contained, reproducible projects that can be instantly installed and run, irrespective of processor architecture or operating system.

No abstract available.

Purpose: To evaluate the impact anterior cruciate ligament reconstruction (ACLR) has on strike evasion rates, strike and landing rates, win percentage, and career longevity in Ultimate Fighting Championship (UFC) fighters. Methods: UFC fighters who underwent ACLR from 1993 to 2022 were matched 2:1 with uninjured controls. The percentage of each injured fighter’s career that occurred before ACLR was deemed the “index percentage.” Injured fighter performance pre-/post-ACLR was compared with control metrics pre-/postindex percentage. Results: Of the 82 patients with documented ACL injuries identified, 48 met the inclusion criteria. Of these, 27 returned for more than 2 fights and were paired with 54 controls. UFC fighters demonstrated return-to-sport rates of 81.25% and 56.25% for at least 1 and 2 fights, respectively. On average, it took 411.85 ± 174.73 (range, 165-879) days for fighters to return. All fighters had significantly lower evasion rates against total significant strikes, distance strikes, and head strikes, postindex (P < .05 for each). ACLR fighters had significantly lower submission attempts and evasion rates against clinch strikes, ground strikes, and total strikes, postindex (P < .05 for each). Controls had a significantly lower evasion rate against leg strikes, postindex. Both groups’ win percentages significantly declined (ACLR, P = .001; control, P = .012). No significant difference in total career fights was observed (P = .873). Conclusions: In this study, we found that most UFC fighters who undergo ACLR return to sport for at least 1 fight; however, just over half return for at least 2 fights. There was not a significant difference in career length between fighters who returned to sport following ACLR for at least 2 fights and their controls. Defensive performance, but not offensive performance, declined significantly following ACLR. All fighters demonstrated significant declines in their win percentage as their career progressed, irrespective of ACLR. Level of Evidence: Level III, retrospective comparative study.

Introduction: Articular cartilage injuries of the knee are a complex and challenging clinical pathology. Objectives: The purpose of this study was to establish consensus statements via a Delphi process on the nonoperative management of knee cartilage injuries. Methods: A consensus process on knee cartilage injuries utilizing a modified Delphi technique was conducted. Seventy-nine surgeons across 17 countries participated in these consensus statements. Eight questions were generated on the nonoperative management of knee cartilage injuries, with 3 rounds of questionnaires and final voting occurring. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was defined as 100% agreement with a proposed statement. Results: Of the 8 total questions and consensus statements on nonoperative management developed from 3 rounds of voting, 1 achieved unanimous consensus, 2 achieved strong consensus, 2 achieved consensus, and 3 did not achieve consensus. Conclusions: The statements that achieved unanimous or strong consensus related to indications, contraindications, and prognostic factors for nonoperative management of knee cartilage injuries. The statements that did not achieve consensus were primarily related to the use of non–weight-bearing, injections, and biophysical stimulation in the treatment of knee cartilage injuries.

Abstract Feedstock variability represents a challenge in lignocellulosic biorefineries, as it can influence both lignocellulose deconstruction and microbial conversion processes for biofuels and biochemicals production. The impact of feedstock variability on microbial performance remains underexplored, and predictive tools for microbial behaviour are needed to mitigate risks in biorefinery scale‐up. Here, twelve batches of corn stover were deconstructed via deacetylation, mechanical refining, and enzymatic hydrolysis to generate lignin‐rich and sugar streams. These batches and their derived streams were characterised to identify their chemical components, and the streams were used as substrates for producing muconate and butyrate by engineered Pseudomonas putida and wildtype Clostridium tyrobutyricum, respectively. Bacterial performance (growth, product titers, yields, and productivities) differed among the batches, but no strong correlations were identified between feedstock composition and performance. To provide metabolic insights into the origin of these differences, we evaluated the effect of twenty‐three isolated chemical components on these microbes, including three components in relevant bioprocess settings in bioreactors, and we found that growth‐inhibitory concentrations were outside the ranges observed in the streams. Overall, this study generates a foundational dataset on P. putida and C. tyrobutyricum performance to enable future predictive models and underscores their resilience in effectively converting fluctuating lignocellulose‐derived streams into bioproducts.

Proton-exchange-membrane fuel cells (PEMFCs) offer a long-term, carbon-emission free solution to the energy needs of the transportation sector. However, high cost continues to limit PEMFC commercialization. Replacing expensive platinum group metal (PGM) catalysts with PGM-free catalysts could reduce cost, but the low active site density of PGM-free catalysts necessitates the use of thick electrodes that suffer from substantial mass transport losses. In these thick PGM-free electrodes, effective water management and oxygen transport are crucial to achieve high performance. In this work, we investigate the role of anode and cathode gas diffusion layer (GDL) configurations in controlling water management. Asymmetric GDL configurations, in which the anode GDL exhibits higher permeability than the cathode GDL, showed higher performance compared to conventional symmetric configurations. Computational modeling showed that the improved performance is mainly due to improved water management, resulting in lower liquid water saturation and faster oxygen transport in the cathode.

In orthopedic research, many studies have applied vitamin E as a protective antioxidant or used tert-butyl hydroperoxide to induce oxidative injury to chondrocytes. These studies often support the hypothesis that joint pathology causes oxidative stress and increased lipid peroxidation that might be prevented with lipid antioxidants to improve cell survival or function and joint health; however, lipid antioxidant supplementation was ineffective against osteoarthritis in clinical trials and animal data have been equivocal. Moreover, increased circulating vitamin E is associated with increased rates of osteoarthritis. This disconnect between benchtop and clinical results led us to hypothesize that oxidative stress-driven paradigms of chondrocyte redox function do not capture the metabolic and physiologic effects of lipid antioxidants and prooxidants on articular chondrocytes. We used ex vivo and in vivo cartilage models to investigate the effect of lipid antioxidants on healthy, primary, articular chondrocytes and applied immuno-spin trapping techniques to provide a broad indicator of high levels of oxidative stress independent of specific reactive oxygen species. Key findings demonstrate lipid antioxidants were pro-mitochondrial while lipid prooxidants decreased mitochondrial measures. In the absence of injury, radical formation was increased by lipid antioxidants; however, in the presence of injury, radical formation was decreased. In unstressed conditions, this relationship between chondrocyte mitochondria and redox regulation was reproduced in vivo with overexpression of glutathione peroxidase 4. In mice aged 18 months or more, overexpression of glutathione peroxidase 4 significantly decreased the presence of pro-mitochondrial peroxisome proliferation activated receptor gamma and deranged the relationship between mitochondria and the redox environment. This complex interaction suggests strategies targeting articular cartilage may benefit from adopting more nuanced paradigms of articular chondrocyte redox metabolism.

Abstract Plant–herbivore interactions reciprocally influence species’ evolutionary trajectories. These interactions have led to many physical and chemical defenses across the plant kingdom. Some plants have even evolved indirect defense strategies to outsource their protection to ant bodyguards by bribing them with a sugary reward (nectar). Identifying the evolutionary processes underpinning these indirect defenses provide insight into the evolution of plant-animal interactions. Using a cross-kingdom, phylogenetic approach, we examined the convergent evolution of ant-guarding nectaries across ferns and flowering plants. Here, we discover that nectaries originated in ferns and flowering plants concurrently during the Cretaceous, coinciding with the rise of plant associations in ants. While nectaries in flowering plants evolved steadily through time, ferns showed a pronounced lag of nearly 100 My between their origin and subsequent diversification in the Cenozoic. Importantly, we find that as ferns transitioned from the forest floor into the canopy, they secondarily recruited ant bodyguards from existing ant-angiosperm relationships.

Abstract In this work, we extend previous results, demonstrating how complexity in an open quantum system can identify decoherence between two fields, even in the presence of an accelerating background. Using the curved-space Caldeira-Leggett two-field model in de Sitter as our toy model, we discover a distinctive feature, namely the appearance of a bump in the growth of complexity of purification, providing an alternative diagnostic for studying decoherence when the adiabatic perturbation is coupled to a heavy field. This paper initiates a new pathway to explore the features of quantum complexity in an accelerating background, thereby expanding our understanding of the evolution of primordial cosmological perturbations in the early universe.

Abstract Exercise has beneficial effects on cognition throughout the lifespan. Here, we demonstrate that specific exercise patterns transform insufficient, subthreshold training into long-term memory in mice. Our findings reveal a potential molecular memory window such that subthreshold training within this window enables long-term memory formation. We performed RNA-seq on dorsal hippocampus and identify genes whose expression correlate with conditions in which exercise enables long-term memory formation. Among these genes we found Acvr1c, a member of the TGF ß family. We find that exercise, in any amount, alleviates epigenetic repression at the Acvr1c promoter during consolidation. Additionally, we find that ACVR1C can bidirectionally regulate synaptic plasticity and long-term memory in mice. Furthermore, Acvr1c expression is impaired in the aging human and mouse brain, as well as in the 5xFAD mouse model, and over-expression of Acvr1c enables learning and facilitates plasticity in mice. These data suggest that promoting ACVR1C may protect against cognitive impairment.

Abstract Background Cardiometabolic disorders pose significant health risks globally. Metabolic syndrome, characterized by a cluster of potentially reversible metabolic abnormalities, is a known risk factor for these disorders. Early detection and intervention for individuals with metabolic abnormalities can help mitigate the risk of developing more serious cardiometabolic conditions. This study aimed to develop an image-derived phenotype (IDP) for metabolic abnormality from unenhanced abdominal computed tomography (CT) scans using deep learning. We used this IDP to classify individuals with metabolic syndrome and predict future occurrence of cardiometabolic disorders. Methods A multi-stage deep learning approach was used to extract the IDP from the liver region of unenhanced abdominal CT scans. In a cohort of over 2,000 individuals the IDP was used to classify individuals with metabolic syndrome. In a subset of over 1,300 individuals, the IDP was used to predict future occurrence of hypertension, type II diabetes, and fatty liver disease. Results For metabolic syndrome (MetS) classification, we compared the performance of the proposed IDP to liver attenuation and visceral adipose tissue area (VAT). The proposed IDP showed the strongest performance (AUC 0.82) compared to attenuation (AUC 0.70) and VAT (AUC 0.80). For disease prediction, we compared the performance of the IDP to baseline MetS diagnosis. The models including the IDP outperformed MetS for type II diabetes (AUCs 0.91 and 0.90) and fatty liver disease (AUCs 0.67 and 0.62) prediction and performed comparably for hypertension prediction (AUCs of 0.77). Conclusions This study demonstrated the superior performance of a deep learning IDP compared to traditional radiomic features to classify individuals with metabolic syndrome. Additionally, the IDP outperformed the clinical definition of metabolic syndrome in predicting future morbidities. Our findings underscore the utility of data-driven imaging phenotypes as valuable tools in the assessment and management of metabolic syndrome and cardiometabolic disorders.

Abstract Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd −/− ) significantly attenuates influenza virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected Gsdmd −/− mice exhibit decreased inflammatory gene signatures shown by lung transcriptomics. Among these, diminished neutrophil gene activation signatures are corroborated by decreased detection of neutrophil elastase and myeloperoxidase in KO mouse lungs. Indeed, directly infected neutrophils are observed in vivo and infection of neutrophils in vitro induces release of DNA and tissue-damaging enzymes that is largely dependent on GSDMD. Neutrophil depletion in infected WT mice recapitulates the reductions in mortality, lung inflammation, and lung dysfunction observed in Gsdmd −/− animals, while depletion does not have additive protective effects in Gsdmd −/− mice. These findings implicate a function for GSDMD in promoting lung neutrophil responses that amplify influenza virus-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic avenue for treating severe influenza.

Purpose: The authors report three separate cases of type 1 retinopathy of prematurity (ROP) treated with intravitreal bevacizumab before, or at 34 weeks postmenstrual age (PMA), with subsequent development of secondary glaucoma. Observations: All three cases involve patients born ≤24 weeks and meeting the American Academy of Pediatrics criteria for ROP screening. Prior to treatment, each patient was noted to have normal anterior chamber structures with no signs of glaucoma. Each patient developed type 1 ROP and was treated with intravitreal bevacizumab, which was administered at or before 34 weeks PMA. Following the administration of intravitreal anti-vascular endothelial growth factor (VEGF), each patient developed a suspected open-angle glaucoma (OAG) within an approximate 4-week time frame. In these cases, the presentation of glaucoma differed from those that have been previously reported in the literature. Conclusion and importance: Based on similar timing of glaucoma development following intravitreal bevacizumab injections, we hypothesize that the administration of anti-VEGF agents to very premature infants (≤24 weeks) at or before 34 weeks PMA, may predispose them to the development of secondary glaucoma through an unknown and possibly novel pathway.

An emerging sector of the nootropic market is tea-based nutraceutical products, but there are limited data assessing the dose-dependent effects of these products.Purpose We conducted a randomized, double-blind, placebo-controlled crossover trial in young adults to examine the dose-dependent (600 mg versus 1200 mg), acute effects of consumption of an Ilex guayusa tea extract (GLE) on mood, cognitive and motor-cognitive performance, as well as its acute cardiovascular effects.Methods Twenty-five adults (mean ± SD, age = 28 ± 7 y; 9 M/16 F) completed familiarization and then three randomly ordered experimental visits where they consumed either 600 mg (GLE600) or 1200 mg (GLE1200) GLE or placebo (PLA). Following supplement consumption, participants completed a mood state survey, assessments of perceived jitteriness, energy, and focus, and neurocognitive and motor-cognitive testing. Blood pressure (BP), heart rate, and QT interval length were determined before and after supplementation.Results GLE600 significantly improved total mood disturbance (mean ± SE difference = -6.9 ± 2.6 au, p = 0.034), fatigue-inertia (−2.84 ± 0.89 au, p = 0.008), perceived energy (+13.00 ± 4.49 au; p = 0.02), motor speed (+4.52 ± 1.42 au, p = 0.008), and psychomotor speed (+7.20 ± 2.16 au, p = 0.005) relative to PLA. GLE1200 also improved psychomotor speed (+5.08 ± 2.16 ms, p = 0.045) and uniquely increased motor-cognitive performance as reflected by a decrease in reaction time (−0.106 ± 0.04 ms, p = 0.026) during a neurocognitive hop test. The effect of GLE on jitteriness was both dose- and sex-dependent. Jitteriness increased with increasing GLE dose in women only (p

IntroductionExposure to harmful aerosols is of increasing public health concern due to the SARS-CoV-2 pandemic and wildland fires. These events have prompted risk reduction behaviors, notably the use of disposable respiratory protection. This project investigated whether craniofacial morphology impacts the efficiency of disposable masks (N95, KN95, surgical masks, KF94) most often worn by the public to protect against toxic and infectious aerosols. This project was registered with ClinicaltTrials.gov (NCT05388201; registration May 18, 2022).MethodsOne-hundred participants (50 men, 50 women) visited the Environmental Protection Agency’s Human Studies Facility in Chapel Hill, NC between 2022-2023. Craniometrics and 3D scans were used to separate participants into four clusters. Boosting and elastic net regression yielded five measurements (bizygomatic breadth, nose length, bizygomatic nasal arc, neck circumference, ear breadth) that were the best predictors of filtration efficiency based on overall model fit. Fitted filtration efficiency was quantified for each mask at baseline and when tightened using an ear-loop clip.ResultsThe mean unmodified mask performance ranged from 55.3% (15.7%) in the large KF94 to 69.5% (12.3%) in the KN95. Modified performance ranged from 66.3% (9.4%) in the surgical to 80.7% (12.0%) in the KN95. Clusters with larger face width and neck circumference had higher unmodified mask efficiency. Larger nose gap area and nose length decreased modified mask performance.DiscussionWe identify face width, nose size, nose shape, neck circumference, and ear breadth as specific features that modulate disposable mask fit in both unmodified and modified conditions. This information can optimize guidance on respiratory protection afforded by disposable ear-loop masks.

Abstract Resource allocation theory posits that organisms distribute limited resources across functions to maximize their overall fitness. In plants, the allocation of resources among maintenance, reproduction, and growth influences short‐term economics and long‐term evolutionary processes, especially during resource scarcity. The evolution of specialized structures to divide labor between reproduction and growth can create a feedback loop where selection can act on individual organs, further increasing specializaton and resource allocation. Ferns exhibit diverse reproductive strategies, including dimorphism, where leaves can either be sterile (only for photosynthesis) or fertile (for spore dispersal). This dimorphism is similar to processes in seed plants (e.g., the production of fertile flowers and sterile leaves), and presents an opportunity to investigate divergent resource allocation between reproductive and vegetative functions in specialized organs. Here, we conducted anatomical and hydraulic analyses on Onoclea sensibilis L., a widespread dimorphic fern species, to reveal significant structural and hydraulic divergences between fertile and sterile leaves. Fertile fronds invest less in hydraulic architecture, with nearly 1.5 times fewer water‐conducting cells and a nearly 0.5 times less drought‐resistant xylem compared to sterile fronds. This comes at the increased relative investment in structural support, which may help facilitate spore dispersal. These findings suggest that specialization in ferns—in the form of reproductive dimorphism—can enable independent selection pressures on each leaf type, potentially optimizing spore dispersal in fertile fronds and photosynthetic efficiency in sterile fronds. Overall, our study sheds light on the evolutionary implications of functional specialization and highlights the importance of reproductive strategies in shaping plant fitness and evolution.

BackgroundThe management of patients with initially mild acute ischemic stroke (AIS), defined by the National Institutes of Health Stroke Scale (NIHSS) scores 0–5, remains ambiguous despite advances in stroke treatment. The early identification of patients likely to deteriorate is critical in preventing lasting disability.AimsWe investigated the frequency and early predictors of poor functional outcomes in AIS patients with large-vessel occlusion (LVO) and initial mild deficits.MethodsWe performed a retrospective observational study of consecutive AIS patients admitted to a single comprehensive stroke center between 2018 and 2021. The inclusion criteria were a diagnosis of AIS, an arrival NIHSS score of 0–5, imaging-confirmed LVO, and arrival within 24 h of the last-known-well time. The primary outcome was the change in the discharge-modified Rankin Score (ΔmRS) from baseline, categorized as 0–1 (stable outcome) or >1 (poor outcome). Early neurological deterioration was defined as a mean NIHSS score increase of >1 in the first 24-h period. Univariate and multivariable regression analyses were performed. The mean daily NIHSS scores were compared between groups using an analysis of variance (ANOVA).ResultsOf 4,410 stroke admissions, 120 patients met the study inclusion criteria, with 71 (59.2%) patients having a ΔmRS of 0–1 and 49 (40.8%) patients having a ΔmRS of > 1. The mean arrival NIHSS score was similar between groups. However, the mean first-24-h NIHSS score was significantly higher in the poor outcome group vs. the stable outcome group (2.13 vs. 0.95, p < 0.001). A demographic-adjusted multivariable logistic regression revealed that a higher mean first-24-h NIHSS score was the sole early predictor of poor outcome (odds ratio [OR] of 1.65 and a 95% confidence interval [CI] of [1.18, 2.48]). The only association with early neurological deterioration was vertebral artery occlusion, with an OR of 0.35 and a 95% CI of [0.14, 0.81]. The trending mean daily NIHSS scores revealed that patients with poor outcomes deteriorate within 24 h, a significant difference from the stable group (p < 0.001).ConclusionPoor outcomes occurred in a significant proportion of LVO patients with initial mild deficits. The only association was early neurological deterioration. To prevent poor outcomes, rapid identification of any clinical deterioration should prompt consideration of thrombectomy.

During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress, constitute the main pathological mechanism behind ischemia-reperfusion damage. Swiftly reinstating blood perfusion in the ischemic penumbra zone and suppressing neuronal oxidative injury are key to effective treatment. Presently, antioxidants in clinical use suffer from low bioavailability, a singular mechanism of action, and substantial side effects, severely restricting their therapeutic impact and widespread clinical usage. Recently, nanomedicines, owing to their controllable size and shape and surface modifiability, have demonstrated good application potential in biomedicine, potentially breaking through the bottleneck in developing neuroprotective drugs for ischemic strokes. This manuscript intends to clarify the mechanisms of cerebral ischemia-reperfusion injury and provides a comprehensive review of the design and synthesis of antioxidant nanomedicines, their action mechanisms and applications in reversing neuronal oxidative damage, thus presenting novel approaches for ischemic stroke prevention and treatment.

BackgroundThis study unveils the intricate functional association between cyclic di-3’,5’-adenylic acid (c-di-AMP) signaling, cellular bioenergetics, and the regulation of lipopolysaccharide (LPS) profile in Porphyromonas gingivalis, a Gram-negative obligate anaerobe considered as a keystone pathogen involved in the pathogenesis of chronic periodontitis. Previous research has identified variations in P. gingivalis LPS profile as a major virulence factor, yet the underlying mechanism of its modulation has remained elusive.MethodsWe employed a comprehensive methodological approach, combining two mutants exhibiting varying levels of c-di-AMP compared to the wild type, alongside an optimized analytical methodology that combines conventional mass spectrometry techniques with a novel approach known as FLATn.ResultsWe demonstrate that c-di-AMP acts as a metabolic nexus, connecting bioenergetic status to nuanced shifts in fatty acid and glycosyl profiles within P. gingivalis LPS. Notably, the predicted regulator gene cdaR, serving as a potent regulator of c-di-AMP synthesis, was found essential for producing N-acetylgalactosamine and an unidentified glycolipid class associated with the LPS profile.ConclusionThe multifaceted roles of c-di-AMP in bacterial physiology are underscored, emphasizing its significance in orchestrating adaptive responses to stimuli. Furthermore, our findings illuminate the significance of LPS variations and c-di-AMP signaling in determining the biological activities and immunostimulatory potential of P. gingivalis LPS, promoting a pathoadaptive strategy. The study expands the understanding of c-di-AMP pathways in Gram-negative species, laying a foundation for future investigations into the mechanisms governing variations in LPS structure at the molecular level and their implications for host-pathogen interactions.

Background: Urinary incontinence has been linked to worse postoperative pain, decreased physical function, and reduced quality of life in patients following total joint arthroplasty. The purpose of this study was to analyze whether incontinence is associated with increased postoperative medical and joint complications following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Methods: A retrospective cohort study was conducted using a national insurance database. Thirty-two thousand eight hundred eleven patients with incontinence who underwent primary THA were identified and matched 1:4 with 129,073 patients without incontinence. Ninety-one thousand nine hundred thirty-five patients with incontinence who underwent primary TKA were matched 1:4 with 367,285 patients without incontinence. Medical and joint complication rates at 90 days and 2 years, respectively, were then compared for patient cohorts using multivariable logistic regressions. Results: Patients who underwent primary THA with incontinence had statistically higher rates of dislocation, periprosthetic fracture, aseptic revisions, and overall joint complications compared to controls. Patients who underwent primary TKA with incontinence had higher rates of mechanical failure, aseptic revision, and all-cause revision compared to controls. Conclusions: This study demonstrated an association between patients with incontinence and higher rates of dislocation, periprosthetic fractures, aseptic revisions, and overall joint complications following primary THA compared to controls. Patients with incontinence experience higher rates of mechanical failure, aseptic revision, and all-cause revision following TKA compared to controls. As such, perioperative management of urinary incontinence may help mitigate the risk of postoperative complications.

Abstract There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

ABSTRACTIn this editorial, I share advice and general principles based on recent experiences as a mentor and evaluator for early-career microbiology and immunology faculty seeking promotion and tenure. I outline 10 recommendations covering research, service, teaching, and mentoring. In addition, I encourage nuanced conversations with colleagues to strategically navigate the unique promotion and tenure processes at different institutions. I hope that these practical tips will assist early-career faculty in attaining promotion and tenure, contributing to long-term scientific and career advances.

Enhanced weathering (EW) of silicate rocks spread onto managed lands as agricultural amendments is a promising carbon dioxide removal (CDR) approach. However, there is an obvious need for the development of tools for Measurement, Reporting, and Verification (MRV) before EW can be brought to scale. Shifts in the concentration of mobile elements measured in the solid phase of soils after application of EW feedstocks can potentially be used to track weathering and provide an estimate of the initial carbon dioxide removal of the system. To measure feedstock dissolution accurately it is necessary to control for the amount of feedstock originally present in the sample being analyzed. This can be achieved by measuring the concentration of immobile detrital elements in soil samples after feedstock addition. However, the resolvability of a signal using a soil mass balance approach depends on analytical uncertainty, the ability to accurately sample soils, the amount of feedstock relative to the amount of initial soil in a sample, and on the fraction of feedstock that has dissolved. Here, we assess the viability of soil-based mass-balance approaches across different settings. Specifically, we define a metric for tracer-specific resolvability of feedstock mass addition (φ) and calculate the feedstock application rates (a) and dissolution fractions (b) required to resolve EW. Applying calculations of a, b, and φ to a gridded soil database from the contiguous USA in combination with known compositions of basalt and peridotite feedstocks demonstrates the importance of adequately capturing field heterogeneity in soil elemental concentrations. While EW signals should be resolvable after ~1–3 years of basalt feedstock addition at common application rates for most agricultural settings with adequate sampling protocols, resolving EW in the field is likely to be challenging if uncertainties in tracer concentrations derived from field-scale heterogeneity and analytical error exceed 10%. Building from this framework, we also present a simple tool for practitioners to use to assess the viability of carrying out soil-based EW MRV in a deployment-specific context.

The addition of intravenous (i.v.) chemotherapy to i.v. immunotherapy for patients with lung cancer results in improved overall survival but is limited by synergistic side effects and an unknown, highly variable final cytotoxic dose within the tumor. The synergy between i.v. chemo- and immunotherapies is hypothesized to occur as a result of cell injury caused by chemotherapy, a mechanism demonstrated to drive antigen presentation within the tumor microenvironment. Intratumoral delivery of chemotherapy may thus be optimized to maximize tumor cell injury. To assess the balance between the damage versus the death of tumor cells, we developed a computational model of intratumoral dynamics within a lung cancer tumor for three different chemotherapy agents following direct injection as a function of location and number of injection sites. We based the model on the morphology of a lung tumor obtained from a thoracic CT scan. We found no meaningful difference in the extent of tumor cell damage between a centrally injected versus peripherally injected agent, but there were significant differences between a single injection versus when the total dose was apportioned between multiple injection sites. Importantly, we also found that the standard chemotherapeutic concentrations used for intravenous administration were effective at causing cell death but were too high to generate significant cell injury. This suggests that to induce maximal tumor cell injury, the optimal concentration should be several orders of magnitude lower than those typically used for intravenous therapy.

Mutations in human CILK1 (ciliogenesis associated kinase 1) are linked to ciliopathies and epilepsy. Homozygous point and nonsense mutations that extinguish kinase activity impair primary cilia function, whereas mutations outside the kinase domain are not well understood. Here, we produced a knock-in mouse equivalent to the human CILK1 A615T variant identified in juvenile myoclonic epilepsy (JME). This residue is in the intrinsically disordered C-terminal region of CILK1 separate from the kinase domain. Mouse embryo fibroblasts (MEFs) with either heterozygous or homozygous A612T mutant alleles exhibited a higher ciliation rate, shorter individual cilia, and upregulation of ciliary Hedgehog signaling. Thus, a single A612T mutant allele was sufficient to impair primary cilia and ciliary signaling in MEFs. Gene expression profiles of wild-type versus mutant MEFs revealed profound changes in cilia-related molecular functions and biological processes. The CILK1 A615T mutant protein was not increased to the same level as the wild-type protein when co-expressed with scaffold protein KATNIP (katanin-interacting protein). Our data show that KATNIP regulation of a JME-associated single-residue variant of CILK1 is compromised, and this impairs the maintenance of primary cilia and Hedgehog signaling.

ABSTRACT The Gram-positive model organism Bacillus subtilis responds to environmental stressors by activating the alternative sigma factor σB. The sensing apparatus upstream of σB activation is thought to consist of cytoplasmic stressosomes—megadalton-sized protein complexes that include five paralogous proteins known as RsbRs. The RsbRs are presumed to be involved in stress sensing and the subsequent response. Perturbations to the RsbR complement in stressosomes by engineering cells that produce only one of the RsbR paralogs (“single-RsbR strains”) lead to altered σB response dynamics with respect to timing and magnitude. Here, we asked whether such changes to σB response dynamics impact the relative fitness of a strain. We competed strain pairs with different RsbR complements under ethanol and sodium chloride stress and found not only differences in relative fitness among wild-type and single-RsbR strains but also different relative fitness values in the two different stressors. We found that the presence of RsbRA, which dominates the wild-type σB response, enhances fitness in ethanol but is detrimental to fitness in NaCl. Meanwhile, RsbRD-only cells were among the most fit in NaCl. Strains producing hybrid RsbR fusion proteins displayed different fitness values that depended on the RsbR proteins from which they were derived. Our results here suggest that σB response dynamics can impact fitness, highlighting the physiological importance of the unusual stressosome-based general stress response system of B. subtilis.IMPORTANCEThe model bacterium Bacillus subtilis uses cytoplasmic multiprotein complexes, termed stressosomes, to activate the alternative sigma factor σB when facing environmental stresses. We have previously shown that genetically manipulating the complement of putative sensor proteins in stressosomes can alter the dynamics of the σB response in terms of its magnitude and timing. However, it is unknown whether these response dynamics impact the fitness of cells challenged by environmental stressors. Here, we examine the fitness of strains with different σB responses by competing strain pairs in exponential-phase co-cultures under environmental stress. We find that strains with different response dynamics show different competitive indices that differ by stressor. These results suggest that the dynamics of the σB response can affect the fitness of cells facing environmental stress, highlighting the relevance of different σB dynamics.

IntroductionRecent research suggests that psychedelics may have potential for the treatment of various substance use disorders. However, most studies to date have been limited by small sample sizes and neglecting to include non-North American and European populations.MethodsWe conducted a global, cross-sectional online survey of adults (n = 5,268, 47.2% women) self-reporting past or current psychedelic use and investigated whether psychedelic use was associated with changes in use of other substances.ResultsNearly three-quarters (70.9%; n = 3,737/5,268) reported ceasing or decreasing use of one or more non-psychedelic substances after naturalistic psychedelic use. Among those with previous use, 60.6% (n = 2,634/4,344) decreased alcohol use, 55.7% (n = 1,223/2,197) decreased antidepressant use, and 54.2% (n = 767/1,415) decreased use of cocaine/crack. Over a quarter of the sample indicated that their decrease in substance use persisted for 26 weeks or more following use of a psychedelic. Factors associated with decreased use included a motivation to either decrease one’s substance use or self-treat a medical condition. Importantly, 19.8% of respondents also reported increased or initiated use of one or more other substances after psychedelic use, with illicit opioids (14.7%; n = 86/584) and cannabis (13.3%; n = 540/4,064) having the highest proportions. Factors associated with increased substance use included having a higher income and residing in Canada or the US.DiscussionAlthough limited by cross-sectional study design, this large observational study will help inform future studies aiming to investigate the relationship between substance use patterns and psychedelic use.

Biofilms are self-organized communities of microorganisms that are encased in an extracellular polymeric matrix and often found attached to surfaces. Biofilms are widely present on Earth, often found in diverse and sometimes extreme environments. These microbial communities have been described as recalcitrant or protective when facing adversity and environmental exposures. On the International Space Station, biofilms were found in human-inhabited environments on a multitude of hardware surfaces. Moreover, studies have identified phenotypic and genetic changes in the microorganisms under microgravity conditions including changes in microbe surface colonization and pathogenicity traits. Lack of consistent research in microgravity-grown biofilms can lead to deficient understanding of altered microbial behavior in space. This could subsequently create problems in engineered systems or negatively impact human health on crewed spaceflights. It is especially relevant to long-term and remote space missions that will lack resupply and service. Conversely, biofilms are also known to benefit plant growth and are essential for human health (i.e., gut microbiome). Eventually, biofilms may be used to supply metabolic pathways that produce organic and inorganic components useful to sustaining life on celestial bodies beyond Earth. This article will explore what is currently known about biofilms in space and will identify gaps in the aerospace industry's knowledge that should be filled in order to mitigate or to leverage biofilms to the advantage of spaceflight.

The regulation and direction of CD4+ T cells into phenotypic and functional lineages is coordinated by a complex set of mechanisms. Here the authors show a role for Aiolos as a regulator of the CD4+ cytotoxic and T follicular helper lineages.

Background: The purpose of this study was to determine whether cold therapy after the first exercise test influences the physical working capacity at the fatigue threshold (PWCFT) during the second exercise test. We hypothesized that cold therapy would delay the onset of PWCFT for the second exercise test relative to the control visit (i.e., no cold therapy). Methods: Eight healthy college-aged men volunteered for the present study. For each of the two visits, subjects performed incremental, single-leg, knee-extensor ergometer, followed by either resting for 30 min (control visit) or having a cold pack applied for 15 min and then resting for 15 min (experimental visit). Then, the same exercise test was performed. The order of visits (control vs. experimental) was randomized for each subject. The exercise indices and PWCFT were determined for each of the two visits and statistically analyzed using two-way repeated measures analysis of variance. Results: The results indicate no significant (p > 0.05) mean differences for maximal power output, heart rate at end-exercise, and PWCFT between the control and cold therapy visits. Moreover, there were no significant (p > 0.05) mean differences between the first and second exercise workbout within each visit. Conclusions: The findings of this study suggest that cold therapy did not influence neuromuscular fatigue.

Neural responsiveness to food images was measured in healthy participants using fMRI, establishing food-selective regions using both data- and hypothesis-driven methods. Further analyses illuminate the organization of food within the visual system.

Isolating the neural mechanisms of consciousness is complicated by task report and other irrelevant signals. Here, the authors removed report and eye movement confounds to uncover large scale cortical-subcortical networks specific for human visual consciousness.

Abstract Regulatory T cells (Tregs) are essential to maintain self-tolerance and immune homeostasis but, as components of the tumor microenvironment (TME), are also a major barrier to effective cancer immunosurveillance and immunotherapy. FH535 and its derivative Y3 are two N-aryl-benzene-sulfonamides (NABs) that inhibit HCC cell proliferation and tumor progression. However, the impact of NABs on the immune cells in the TME is not yet known. Analyses of explanted livers from patients with hepatocellular carcinoma (HCC) showed that high levels of tumor-infiltrating Tregs were associated with poor tumor differentiation. These results lead us to investigate the immunomodulatory effects of NABs in regulatory and effector T cells. Exposure of primary human Tregs to NABs induced a rapid but temporary increase of cell expansion, a gradual disruption of suppressor activity, and concomitant bioenergetics and autophagic flux dysregulations. In contrast to Tregs, no gross effects were observed in effector T cells. Addition of Rapamycin prevented the functional decay of Tregs and restored their metabolic profile, suggesting that NAB effects require the integrity of the mTOR pathway. This study revealed the immunomodulatory properties of NABs with a preferential impact on Treg activity and provided novel insights into the anti-tumor potential of sulfonamides.

Long-term adherence to antiretroviral medication continues to present as a challenge along the continuum of the HIV care cascade. HIV interventions and support programs are significantly threatened in resource-limited settings by challenges in maintaining long-term follow-up for ART adherence. We sought to complete a systematic review to comprehensively examine ART adherence and retention in care interventions in Sub-Saharan Africa and to report on the implementation of interventions in real-world settings to inform future health investments in HIV care. Interventions were grouped according to their impact on individual, community, and health-systems levels. While a vast majority of studies evaluated a combination of interventions, those studies that incorporated the community as a resource were most successful. In addition, providing education and behavior reminders proved effective and should be accompanied by community and peer efforts for best results. Multi-level interventions, such as combining individual and community-level interventions showed promising results for long term ART adherence.

Abstract Clinical guidelines recommend several risk factors to identify women in early pregnancy at high risk of developing pregnancy-associated hypertension. However, these variables result in low predictive accuracy. Here, we developed a prediction model for pregnancy-associated hypertension using graph-based semi-supervised learning. This is a secondary analysis of a prospective study of healthy pregnant women. To develop the prediction model, we compared the prediction performances across five machine learning methods (semi-supervised learning with both labeled and unlabeled data, semi-supervised learning with labeled data only, logistic regression, support vector machine, and random forest) using three different variable sets: [a] variables from clinical guidelines, [b] selected important variables from the feature selection, and [c] all routine variables. Additionally, the proposed prediction model was compared with placental growth factor, a predictive biomarker for pregnancy-associated hypertension. The study population consisted of 1404 women, including 1347 women with complete follow-up (labeled data) and 57 women with incomplete follow-up (unlabeled data). Among the 1347 with complete follow-up, 2.4% (33/1347) developed pregnancy-associated HTN. Graph-based semi-supervised learning using top 11 variables achieved the best average prediction performance (mean area under the curve (AUC) of 0.89 in training set and 0.81 in test set), with higher sensitivity (72.7% vs 45.5% in test set) and similar specificity (80.0% vs 80.5% in test set) compared to risk factors from clinical guidelines. In addition, our proposed model with graph-based SSL had a higher performance than that of placental growth factor for total study population (AUC, 0.71 vs. 0.80, p

Abstract Persistent abnormalities in microcirculatory function are associated with poor clinical outcomes in patients with circulatory shock. We sought to identify patients with acutely reversible microcirculatory dysfunction using a low-dose topical nitroglycerin solution and handheld videomicroscopy during circulatory shock after cardiac surgery. Forty subjects were enrolled for the study, including 20 preoperative control and 20 post-operative patients with shock. To test whether microcirculatory dysfunction is acutely reversible during shock, the sublingual microcirculation was imaged with incident dark field microscopy before and after the application of 0.1 mL of a 1% nitroglycerin solution (1 mg/mL). Compared to the control group, patients with shock had a higher microcirculation heterogeneity index (MHI 0.33 vs. 0.12, p 1.8 SD from shock baseline. Hemodynamics and vasoactive doses did not change during the 30-min study period. Our findings suggest a topical nitroglycerin challenge with handheld videomicroscopy can safely assess for localized recruitment of the microcirculatory blood flow in patients with circulatory shock and may be a useful test to identify nitroglycerin responsiveness.

Background: Vascular mild cognitive impairment (VMCI) is a common impairment caused by vascular factors. VMCI often occurs after stroke, and it is the main clinical manifestation of long-term disability. Many patients are treated with acupuncture in combination with other therapies. However, evidence regarding the effectiveness of this treatment regimen is lacking. Aims: This meta-analysis aimed to evaluate the efficacy of acupuncture therapy for treating VMCI. Methods: This systematic review was conducted in accordance with the preferred reporting and meta-analysis guidelines. The CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed and Embase databases were searched from inception to August 20, 2022. After two researchers independently screened the literature, they extracted the data and evaluated the risk of bias in the included studies. Revman 5.3 software was used for the meta-analysis. Summary of review: Thirty-two randomized controlled trials (RCTs) were included. The overall effective rate of acupuncture for treating VMCI was 3.06, 95% CI [2.39, 3.91], (P

Background: When COVID-19 cases began rising in early 2020, many universities transitioned online. Purpose/Hypothesis: This mixed-methods study examined how students, staff, and faculty members in a college of engineering experienced the early stages of the pandemic. We hypothesized that our prior work to build community and capacity around teaching and learning among faculty would support an empowered transition to online learning. Design/Method: We collected 70 participant accounts from April 10 to May 28, 2020 (students = 45, staff = 2, and faculty = 24). We collected these data using the SenseMaker® online survey platform. They comprised short stories written by the participants and quantitative data resulting from participant responses to a series of questions about their experiences. We used inferential statistics to determine pivotal variables that correlated to the emotional tone of a story and differentiated faculty and student experiences. Using these pivotal variables for interpretation, we examined participant stories to identify underlying trends in faculty and student experiences. Results: The majority of faculty members rated their stories positively (62%) while the majority of students rated their stories negatively (53%). Compared to students, faculty members reported greater opportunities, fewer struggles, higher levels of willingness to experiment, better treatment by people in positions of power, and more experiences of putting the needs of others before their own. Qualitatively, we identified two themes – ability and empowerment (or lack thereof) – to characterize the key differences between faculty and student experiences. Ability and empowerment are key facets of capacity. Conclusions: These findings confirm our hypothesis that prior work to build community and capacity around teaching and learning among faculty in our college supported an empowered transition to online learning. A next step in the development of our programming is finding ways to ensure our efforts lead to increased capacity for students, too.

Background Audience segmentation is an analysis technique that can identify meaningful subgroups within a population to inform the tailoring of dissemination strategies. We have conducted an empirical clustering audience segmentation study of licensed psychologists using survey data about the sources of knowledge they report most often consulting to guide their clinical decision-making. We identify meaningful subgroups within the population and inform the tailoring of dissemination strategies for evidence-based practice (EBP) materials. Method Data come from a 2018–2019 web-based survey of licensed psychologists who were members of the American Psychological Association (APA; N = 518, response rate = 29.8%). Ten dichotomous variables assessed sources that psychologists regularly consult to inform clinical decision-making (e.g., colleagues, academic literature, and practice guidelines). We used latent class analysis to identify segments of psychologists who turn to similar sources and named each segment based on the segment's most salient characteristics. Results Four audience segments were identified: the No-guidelines (45% of psychologists), Research-driven (16%), Thirsty-for-knowledge (9%), and No-reviews (30%). The four segments differed not only in their preferred sources of knowledge, but also in the types of evidence-based posttraumatic stress disorder (PTSD) treatments they provide, their awareness and usage intention of the APA PTSD clinical practice guideline, and attitudes toward clinical practice guidelines. Conclusion The results demonstrate that licensed psychologists are heterogeneous in terms of their knowledge-seeking behaviors and preferences for knowledge sources. The distinctive characteristics of these segments could guide the tailoring of dissemination materials and strategies to subsequently enhance the implementation of EBP among psychologists.

Abstract Objectives The DSM‐5 Level 1 Cross‐Cutting Symptom Measure (DSM‐XC) was developed by the American Psychiatric Association as a transdiagnostic mental health symptom survey. Despite its promise as a screening tool, few studies have assessed its latent dimensionality or provided guidance on interpreting responses. We examined the factor structure of the DSM‐XC in a convenience sample of participants with varying degrees of psychopathology. Methods Participants (n = 3533) were enrolled in an online study on the mental health impact of COVID‐19 (NCT04339790). We used a factor analytic framework with exploratory and confirmatory analyses to evaluate candidate factor solutions. Convergent validity analysis with concurrent study measures was also performed. Results Six‐factor and bifactor candidate solutions both had good fit and full measurement invariance across age, sex, and enrollment date. The six‐factor solution resulted in constructs labeled as: mood, worry, activation, somatic, thought, and substance use. A general psychopathology factor and two residual factors (mood and anxiety constructs) explained the variance of the bifactor solution. Conclusions Our analysis supports that the DSM‐XC is a multidimensional instrument spanning many mental health symptoms. We provide scoring solutions for two factor structures that capture broader constructs of psychopathology. Use of a convenience sample may limit generalizability of findings.