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Clinical Scenario: Ankle sprains are one of the most common injuries in athletics, and many lead to recurrent sprains, chronic ankle instability, and persistent symptoms. Treatment improvements are needed. Platelet-rich plasma (PRP) involves formulating autologous plasma with higher platelet concentration to be injected in the desired tissue. There is currently high-quality evidence supporting the use of PRP with lateral epicondylitis and knee osteoarthritis to accelerate the healing process and decrease pain. Clinical Question: Does the injection of PRP relieve pain faster and improve function compared with no injection or placebo in patients with a lateral ankle sprain? Summary of Key Findings: A computerized search yielded 191 studies; of these, 3 studies fit the inclusion and exclusion criteria. PRP injection reduces pain and increases function after lateral ankle sprain 5 to 8 weeks after intervention. Clinical Bottom Line: The use of PRP after lateral ankle sprain to decrease pain and increase function is supported with moderate evidence. Strength of Recommendation: Based on the Strength of Recommendation Taxonomy, evidence from the included studies is considered as level B, reflecting limited quality patient-oriented evidence. [ABSTRACT FROM AUTHOR]

Vanadium dioxide (VO2) manifests an abrupt metal–insulator transition (MIT) from monoclinic to rutile phases, with potential use for tunable electronic and optical properties and spiking neuromorphic devices. Understanding pathways to modulate electronic transport in VO2, as well as its response to irradiation (e.g., for space applications), is critical to better enable these applications. In this work, we investigate the selective modulation of electronic transport in VO2 films subject to different 10 keV helium ion (He+) fluences. Under these conditions, the resistivity in the individual monoclinic and rutile phases varied by 50%–200%, while the MIT transformation temperature remains constant within 4 °C independent of irradiation fluence. Importantly, different trends in the resistivity of the monoclinic and rutile phases were observed both as a function of total He fluence as well as in films grown on different substrates (amorphous SiO2/Si vs single crystal Al2O3). Through a combination of measurements including majority carrier sign via Seebeck, low frequency noise, and TEM, our investigation supports the presence of different kinds of point defects (V in; O in), which may arise due to grain boundary defect interactions. Our work suggests the utility of He irradiation for the selective modulation of VO2 transport properties for neuromorphic, in contrast to other established but non-selective methods, like doping. [ABSTRACT FROM AUTHOR]

Purpose: This study examined differences in measures of health-related physical fitness in adolescents before and after extended school closures due to COVID-19. Method: The sample consisted of 298 students (135 males and 163 females) from a laboratory high school. Data were collected through FITNESSGRAM assessments. A repeated-measures multivariate analysis of covariance was calculated to analyze differences in fitness before and after COVID-19 closures, including McNemar–Bowker and McNemar tests. Results: Statistically significant differences were identified for Progressive Aerobic Capacity Endurance Run (−4.2%; 1.8 ml·kg−1·min−1) and curl-up (−12.5%; 7.9 repetitions). In addition, 18.8% fewer students were classified within the Healthy Fitness Zone for Progressive Aerobic Capacity Endurance Run, 4% for curl-up, 10.8% for push-up, and 6.4% for sit and reach. Conclusion: Results of this study demonstrate that there was a significant decline in physical fitness for secondary students during extended school closures and social isolation as a result of COVID-19. [ABSTRACT FROM AUTHOR]

Background Minimal clinically important differences (MCIDs) quantify the clinical relevance of quality of life results at the individual patient and group level. The aim of this study was to estimate the MCID for the Brief Fatigue Inventory (BFI) and the Worst and Usual Fatigue items in patients with brain or CNS cancer undergoing curative radiotherapy. Methods Data from a multi-site prospective registry was used. The MCID was calculated using distribution-based and anchor-based approaches. For the anchor-based approach, the fatigue item from the PROMIS-10 served as the anchor to determine if a patient improved, deteriorated, or had no change from baseline to end of treatment (EOT). We compared the unadjusted means on the BFI for the 3 groups to calculate the MCID. For the distribution-based approaches, we calculated the MCID as 0.5 SD of the scores and as 1.96 times the standard error of measurement. Results Three-hundred and fifty nine patients with brain or CNS tumors undergoing curative radiotherapy filled out the 9-item BFI at baseline and EOT. The MCID for the BFI was 1.33 (ranging from 0.99 to 1.70 across the approaches), 1.51 (ranging from 1.16 to 2.02) and 1.76 (ranging from 1.38 to 2.14) for the usual and worst fatigue items, respectively. Conclusions This study provides the MCID ranges for the BFI and Worst and Usual fatigue items, which will allow clinically meaningful conclusions to be drawn from BFI scores. These results can be used to select optimal treatments for patients with brain or CNS cancer or to interpret BFI scores from clinical trials. [ABSTRACT FROM AUTHOR]

Urban climatic challenges can motivate urban planners and designers to implement urban climate-responsive design strategies. But does this process occur sufficiently, and if not, why? This study explores the implementation of urban climate-responsive design strategies, potential functional and aesthetic conflicts, availability of policy instruments that support implementation, strengths and weaknesses, and missed opportunities for integrating agendas. Semi-structured interviews were conducted with experts familiar with urban climate-responsive design. The results suggest that greening measures are most often implemented, strategies tend to compete with other land-uses, designers face aesthetic conflicts, and strategies are predominantly mainstreamed within existing policy instruments. [ABSTRACT FROM AUTHOR]

The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting in vivo gene engineering with Cas9. Mouse line production has two critical steps – generation of founders with the desired allele and germline transmission (GLT) of that allele from founders to offspring. A systematic evaluation of the variables impacting success rates identified gene essentiality as the primary factor influencing successful production of null alleles. Collectively, our findings provide best practice recommendations for using Cas9 to generate alleles in mouse essential genes, many of which are orthologs of genes linked to human disease. [ABSTRACT FROM AUTHOR]

Any electrical signal propagating in a metallic conductor loses amplitude due to the natural resistance of the metal. Compensating for such losses presently requires repeatedly breaking the conductor and interposing amplifiers that consume and regenerate the signal. This century-old primitive severely constrains the design and performance of modern interconnect-dense chips1. Here we present a fundamentally different primitive based on semi-stable edge of chaos (EOC)2,3, a long-theorized but experimentally elusive regime that underlies active (self-amplifying) transmission in biological axons4,5. By electrically accessing the spin crossover in LaCoO3, we isolate semi-stable EOC, characterized by small-signal negative resistance and amplification of perturbations6,7. In a metallic line atop a medium biased at EOC, a signal input at one end exits the other end amplified, without passing through a separate amplifying component. While superficially resembling superconductivity, active transmission offers controllably amplified time-varying small-signal propagation at normal temperature and pressure, but requires an electrically energized EOC medium. Operando thermal mapping reveals the mechanism of amplification—bias energy of the EOC medium, instead of fully dissipating as heat, is partly used to amplify signals in the metallic line, thereby enabling spatially continuous active transmission, which could transform the design and performance of complex electronic chips.A method using semi-stable edge of chaos in LaCoO3 enables continuous signal amplification in metallic conductors without separate amplifiers, potentially revolutionizing electronic chip design. [ABSTRACT FROM AUTHOR]

Background: Clostridium autoethanogenum is an acetogenic bacterium that autotrophically converts carbon monoxide (CO) and carbon dioxide (CO2) gases into bioproducts and fuels via the Wood–Ljungdahl pathway (WLP). To facilitate overall carbon capture efficiency, the reaction stoichiometry requires supplementation of hydrogen at an increased ratio of H2:CO to maximize CO2 utilization; however, the molecular details and thus the ability to understand the mechanism of this supplementation are largely unknown. Results: In order to elucidate the microbial physiology and fermentation where at least 75% of the carbon in ethanol comes from CO2, we established controlled chemostats that facilitated a novel and high (11:1) H2:CO uptake ratio. We compared and contrasted proteomic and metabolomics profiles to replicate continuous stirred tank reactors (CSTRs) at the same growth rate from a lower (5:1) H2:CO condition where ~ 50% of the carbon in ethanol is derived from CO2. Our hypothesis was that major changes would be observed in the hydrogenases and/or redox-related proteins and the WLP to compensate for the elevated hydrogen feed gas. Our analyses did reveal protein abundance differences between the two conditions largely related to reduction–oxidation (redox) pathways and cofactor biosynthesis, but the changes were more minor than we would have expected. While the Wood–Ljungdahl pathway proteins remained consistent across the conditions, other post-translational regulatory processes, such as lysine-acetylation, were observed and appeared to be more important for fine-tuning this carbon metabolism pathway. Metabolomic analyses showed that the increase in H2:CO ratio drives the organism to higher carbon dioxide utilization resulting in lower carbon storages and accumulated fatty acid metabolite levels. Conclusions: This research delves into the intricate dynamics of carbon fixation in C. autoethanogenum, examining the influence of highly elevated H2:CO ratios on metabolic processes and product outcomes. The study underscores the significance of optimizing gas feed composition for enhanced industrial efficiency, shedding light on potential mechanisms, such as post-translational modifications (PTMs), to fine-tune enzymatic activities and improve desired product yields. [ABSTRACT FROM AUTHOR]

With the growing role of artificial intelligence (AI) in our lives, attention is increasingly turning to the way that humans and AI work together. A key aspect of human–AI collaboration is how people integrate judgements or recommendations from machine agents, when they differ from their own judgements. We investigated trust in human–machine teaming using a perceptual judgement task based on the judge–advisor system. Participants ( n = 89 ) estimated a perceptual quantity, then received a recommendation from a machine agent. The participants then made a second response which combined their first estimate and the machine's recommendation. The degree to which participants shifted their second response in the direction of the recommendations provided a measure of their trust in the machine agent. We analysed the role of advice distance in people's willingness to change their judgements. When a recommendation falls a long way from their initial judgement, do people come to doubt their own judgement, trusting the recommendation more, or do they doubt the machine agent, trusting the recommendation less? We found that although some participants exhibited these behaviours, the most common response was neither of these tendencies, and a simple model based on averaging accounted best for participants' trust behaviour. We discuss implications for theories of trust, and human–machine teaming. [ABSTRACT FROM AUTHOR]

Background: While adoption of personalized medicine (PM) continues to increase in clinical oncology, there is limited data connecting the level of PM adoption at a given institution to improved clinical outcomes for patients. The purpose of this study was to analyze the correlation between health care providers' scores on a previously described PM integration framework and two outcome measures: the use of targeted therapy and clinical trial enrollment. Methods: This study was conducted using real-world data (RWD) from the Syapse® Learning Health Network (LHN). The PM integration score for six community hospital systems in the LHN was calculated and subsequently correlated with the two outcome measures. Results: Across six institutions, a strong correlation between PM integration score and targeted therapy use was observed in metastatic non-small cell lung cancer (mNSCLC) (R2 = 0.81), an indication with a significant number of approved targeted agents. Conversely, a strong correlation between PM integration score and clinical trial enrollment was observed in metastatic triple-negative breast cancer (TNBC) (R2 = 0.63), an indication with fewer marketed targeted therapies but an active targeted therapy pipeline. Conclusion: The results in these cases suggest that PM integration is a strong indicator of high-quality care practices for both utilization of targeted therapy in more mature PM indications (e.g., mNSCLC) and clinical trial enrollment in more emerging PM indications (e.g., TNBC). [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the quality, reliability, and readability of online patient educational materials on leukocoria. Methods: In this cross-sectional study, the Google search engine was searched for the terms "leukocoria" and "white pupil." The first 50 search outcomes were evaluated for each search term based on predefined inclusion criteria, excluding duplicates, peer-reviewed papers, forum posts, paywalled content, and multimedia links. Sources were categorized as "institutional" or "private." Three independent raters assessed each web-site for quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria. Readability was evaluated using seven formulas: Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG) Index, Automated Readability Index (ARI), Linsear Write (LW), Gunning Fog Index (GFI), and Coleman-Liau Index (CLI). Results: A total of 51 websites were included. Quality, assessed by the DISCERN tool, showed a median score of 4, denoting moderate to high quality, with no significant differences between institutional and private sites or search terms. HONcode scores indicated variable reliability and trustworthiness (median: 10, range: 3 to 16), with institutional sites excelling in financial disclosure and ad differentiation. Additionally, institutional and private sites performed well in reliability and accountability, as measured by the JAMA Benchmark criteria (median: 3; range: 1 to 4). Readability, averaging an 11.3 ± 3.7 grade level, did not differ significantly between site types or search terms, consistently falling short of the recommended sixth-grade level for patient educational materials. Conclusions: The patient educational materials on leukocoria demonstrated moderate to high quality, commendable reliability, and accountability. However, the readability scores were above the recommended level for the layperson. [J Pediatr Ophthalmol Strabismus. 2024;61(5):332–338.] [ABSTRACT FROM AUTHOR]

Interpretation of the deep crustal architecture, including the nature and extent of the fundamental basement blocks, is hampered in many regions by limited exposure and because geoscience data tend to reflect the signatures of near-surface units, highlighting the need for tools that image deeper. The northern Mount Isa Province as imaged by long-period magnetotelluric AusLAMP data, has a resistive central core flanked to the east and west by more conductive crust. These structures are elongated in the north–south direction to the extent of current AusLAMP coverage. In the south of the province, sparse broadband magnetotelluric (BBMT) data are available to extend the understanding of the crustal-scale electrical structure of the Mount Isa Province. Two new profiles of BBMT data are used to generate two 3D inversions of impedance and tipper data over a bandwidth of 0.001 to 1.000 s. Data from the 2021 BBMT survey were supplemented with historical MT data in the area, for a total of 285 stations at approximately 10 km station spacing. Two overlapping inversion models, one east–west oriented and one north–south oriented, centred on the township of Boulia were run. A suite of inversion parameters was tested for the two models to establish the reliability of final model features. Consistent with the known electrical structures further north, the inversion models show a major longitudinal resistive block which forms the core of the province, flanked on either side by more conductive crust. Results from the preferred inversion for each model were then compared to deep crustal seismic data, gravity forward modelling and seismic interpretation. The eastern conductive feature is associated with the Numil basement terrane and Gidyea Structure which defines the eastern margin of the Mount Isa Province. The central resistive anomaly extends into the upper mantle and is associated with the Pitta Pitta and Altjawarra East basement terranes, representing the Archean-Paleoproterozoic cratonic core of the Mount Isa Province. The westernmost conductor is associated with the Altjawarra basement terrane and is an extension of the structure imaged in the AusLAMP model. [ABSTRACT FROM AUTHOR]

This document is a guest editorial introducing a special issue of the journal "Social Work in Public Health" focused on the health and well-being of Black men. The editorial highlights the significant health disparities faced by Black men in the United States, including higher rates of chronic illnesses and mental health concerns. It emphasizes the need for targeted and culturally responsive interventions, as well as research and education that prioritize Black men's health. The special issue covers topics such as Black fathers' role in maternal health, chronic disease prevention, mental health stigma, innovative interventions, and the importance of social work education in addressing these issues. The editorial concludes by calling for collective efforts to advance health equity and create a more inclusive society. [Extracted from the article]

Objectives: Research samples that are representative of patient populations are needed to ensure the generalizability of study findings. The primary aim was to assess the efficacy of a study design and recruitment strategy in obtaining a participant sample that was representative of the broader cochlear implant (CI) patient population at the CI center. A secondary aim was to review whether the CI recipient population was representative of the state population. Methods: Demographic variables were compared for a research participant sample (n = 79) and the CI patient population (n = 338). The participant sample was recruited from the CI patient population. The study design included visits that were at the same location and frequency as the recommended clinical follow‐up intervals. The demographics for the combined group (participant sample and patient population) were then compared to the reported demographics for the population in North Carolina. Results: There were no significant differences between the participant sample and patient population for biological sex, age at implantation, racial distribution, socioeconomic position, degree of urbanization, or drive time to the CI center (p ≥ 0.086). The combined CI recipient population was significantly different from the North Carolina population for the distributions of race, ethnicity, and degree of urbanization (p < 0.001). Conclusion: The study design and recruitment strategy allowed for recruitment of a participant sample that was representative of the CI patient population. Disparities in access to cochlear implantation persist, as supported by the significant differences in the combined CI recipient population and the population for our state. Level of Evidence: 3 Laryngoscope, 134:4101–4110, 2024 [ABSTRACT FROM AUTHOR]

Background: Lewy body dementia (LBD) is the second most common neurodegenerative dementia in the US, presenting unique end-of-life challenges. Objective: This study examined healthcare utilization and care continuity in the last year of life in LBD. Methods: Medicare claims for enrollees with LBD, continuously enrolled in the year preceding death, were examined from 2011–2018. We assessed hospital stays, emergency department (ED) visits, intensive care unit (ICU) admissions, life-extending procedures, medications, and care continuity. Results: We identified 45,762 LBD decedents, predominantly female (51.8%), White (85.9%), with average age of 84.1 years (SD 7.5). There was a median of 2 ED visits (IQR 1–5) and 1 inpatient stay (IQR 0–2). Higher age was inversely associated with ICU stays (Odds Ratio [OR] 0.96; 95% Confidence Interval [CI] 0.96–0.97) and life-extending procedures (OR 0.96; 95% CI 0.95–0.96). Black and Hispanic patients experienced higher rates of ED visits, inpatient hospitalizations, ICU admissions, life-extending procedures, and in-hospital deaths relative to White patients. On average, 15 (7.5) medications were prescribed in the last year. Enhanced care continuity correlated with reduced hospital (OR 0.72; 95% CI 0.70–0.74) and ED visits (OR 0.71; 95% CI 0.69–0.87) and fewer life-extending procedures (OR 0.71; 95% CI 0.64–0.79). Conclusions: This study underscored the complex healthcare needs of people with LBD during their final year, which was influenced by age and race. Care continuity may reduce hospital and ED visits and life-extending procedures. [ABSTRACT FROM AUTHOR]

Background: Individuals with spinal cord injuries (SCIs) are at an increased risk of poor oral health compared to the general population. However, little is known about the related barriers and facilitators experienced by these individuals within the hospital setting. Objectives: Understand the oral health knowledge, attitudes and practices of people with SCIs, barriers and facilitators to managing their oral health, and recommendations to improve oral care at acute/rehabilitation hospital settings. Methods: Semi‐structured interviews were conducted with 11 participants, from a major metropolitan hospital in Sydney, Australia. The interviews were thematically analysed. Results: Three themes were constructed. Participants believed that the onus was on them to manage their oral health. Individuals also had limited knowledge of its importance to general health, and placed a lower priority on oral health compared to other aspects of health. All participants identified a combination of factors, such as cost, time, resources and prior negative experiences, that contributed to the neglect of their oral care. Participants also discussed the need of support from the multidisciplinary team and family/carers to facilitate oral care and identified various appropriate oral health education formats. Conclusion: This study highlighted some areas where oral health knowledge among people with SCIs could be improved. It also identified the need for oral health training for the multidisciplinary team, as well as carers, to better integrate oral care during rehabilitation in the hospital. The development of oral health interventions would need to utilise a co‐design approach to best support clients and their carers to facilitate oral care self‐management. [ABSTRACT FROM AUTHOR]

In this paper, we discuss the potential contribution of affective touch to the user experience and robot performance in human-robot interaction, with an in-depth look into upper-limb prosthesis use as a well-suited example. Research on providing haptic feedback in human-robot interaction has worked to relay discriminative information during functional activities of daily living, like grasping a cup of tea. However, this approach neglects to recognize the affective information our bodies give and receive during social activities of daily living, like shaking hands. The discussion covers the emotional dimensions of affective touch and its role in conveying distinct emotions. In this work, we provide a human needs-centered approach to human-robot interaction design and argue for an equal emphasis to be placed on providing affective haptic feedback channels to meet the social tactile needs and interactions of human agents. We suggest incorporating affective touch to enhance user experience when interacting with and through semi-autonomous systems such as prosthetic limbs, particularly in fostering trust. Real-time analysis of trust as a dynamic phenomenon can pave the way towards adaptive shared autonomy strategies and consequently enhance the acceptance of prosthetic limbs. Here we highlight certain feasibility considerations, emphasizing practical designs and multi-sensory approaches for the effective implementation of affective touch interfaces. [ABSTRACT FROM AUTHOR]

M64HCl, which has drug-like properties, is a water-soluble Focal Adhesion Kinase (FAK) activator that promotes murine mucosal healing after ischemic or NSAID-induced injury. Since M64HCl has a short plasma half-life in vivo (less than two hours), it has been administered as a continuous infusion with osmotic minipumps in previous animal studies. However, the effects of more transient exposure to M64HCl on monolayer wound closure remained unclear. Herein, we compared the effects of shorter M64HCl treatment in vitro to continuous treatment for 24 hours on monolayer wound closure. We then investigated how long FAK activation and downstream ERK1/2 activation persist after two hours of M64HCl treatment in Caco-2 cells. M64HCl concentrations immediately after washing measured by mass spectrometry confirmed that M64HCl had been completely removed from the medium while intracellular concentrations had been reduced by 95%. Three-hour and four-hour M64HCl (100 nM) treatment promoted epithelial sheet migration over 24 hours similar to continuous 24-hour exposure. 100nM M64HCl did not increase cell number. Exposing cells twice with 2-hr exposures of M64HCl during a 24-hour period had a similar effect. Both FAK inhibitor PF-573228 (10 μM) and ERK kinase (MEK) inhibitor PD98059 (20 μM) reduced basal wound closure in the absence of M64HCl, and each completely prevented any stimulation of wound closure by M64HCl. Rho kinase inhibitor Y-27632 (20 μM) stimulated Caco-2 monolayer wound closure but no further increase was seen with M64HCl in the presence of Y-27632. M64HCl (100 nM) treatment for 3 hours stimulated Rho kinase activity. M64HCl decreased F-actin in Caco-2 cells. Furthermore, a two-hour treatment with M64HCl (100 nM) stimulated sustained FAK activation and ERK1/2 activation for up to 16 and hours 24 hours, respectively. These results suggest that transient M64HCl treatment promotes prolonged intestinal epithelial monolayer wound closure by stimulating sustained activation of the FAK/ERK1/2 pathway. Such molecules may be useful to promote gastrointestinal mucosal repair even with a relatively short half-life. [ABSTRACT FROM AUTHOR]

PURPOSE: Real-world data (RWD) holds promise for ascribing a real-world (rw) outcome to a drug intervention; however, ascertaining rw-response to treatment from RWD can be challenging. Friends of Cancer Research formed a collaboration to assess available data attributes related to rw-response across RWD sources to inform methods for capturing, defining, and evaluating rw-response. MATERIALS AND METHODS: This retrospective noninterventional (observational) study included seven electronic health record data companies (data providers) providing summary-level deidentified data from 200 patients diagnosed with metastatic non–small cell lung cancer (mNSCLC) and treated with first-line platinum doublet chemotherapy following a common protocol. Data providers reviewed the availability and frequency of data components to assess rw-response (ie, images, radiology imaging reports, and clinician response assessments). A common protocol was used to assess and report rw-response end points, including rw-response rate (rwRR), rw-duration of response (rwDOR), and the association of rw-response with rw-overall survival (rwOS), rw-time to treatment discontinuation (rwTTD), and rw-time to next treatment (rwTTNT). RESULTS: The availability and timing of clinician assessments was relatively consistent across data sets in contrast to images and image reports. Real-world response was analyzed using clinician response assessments (median proportion of patients evaluable, 77.5%), which had the highest consistency in the timing of assessments. Relative consistency was observed across data sets for rwRR (median 46.5%), as well as the median and directionality of rwOS, rwTTD, and rwTTNT. There was variability in rwDOR across data sets. CONCLUSION: This collaborative effort demonstrated the feasibility of aligning disparate data sources to evaluate rw-response end points using clinician-documented responses in patients with mNSCLC. Heterogeneity exists in the availability of data components to assess response and related rw-end points, and further work is needed to inform drug effectiveness evaluation within RWD sources. Consistency of real-world response taken from EHR data in patients with mNSCLC treated with chemotherapy. [ABSTRACT FROM AUTHOR]

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs. We identified mutations that stabilize the 5' polyA hairpin structure in 3G RNAs, which promote RNA dimerization and Gag binding without sequestering the 5' cap. None of these 3G transcripts were competitively packaged, confirming that cap exposure is a dominant negative determinant of viral genome packaging. For all RNAs examined, conformations that favored 5' cap exposure were both poorly packaged and more efficiently translated than those that favored 5' cap sequestration. We propose that structural plasticity of 5' polyA and other conserved RNA elements place the 5' leader on a thermodynamic tipping point for low-energetic (~3 kcal/mol) control of global transcript structure and function. [ABSTRACT FROM AUTHOR]

Coloniality may grant colony members an energetic advantage in the form of lower individual respiration rates as colony size increases. If this occurs it should be apparent as negative allometric scaling of respiration with colony size, and colonial organisms should have scaling factors < 1. However, colonial members from phylum Rotifera have yet to be examined. To test if colonial rotifers possess allometric scaling relationships between respiration rate and colony size, we measured respiration rates for four solitary and three colonial rotifer species; from these respiration rates we estimated scaling factors. We found mixed evidence for allometric scaling of respiration rate in colonial rotifers. Both rotifers with allometric scaling of respiration rate, Conochilus hippocrepis and Lacinularia flosculosa, have extensive mucilaginous coverings. These coverings may represent an investment of colony members into a shared structure, lowering individual metabolic costs and thus respiratory needs. Additionally, we determined which traits are associated with allometric scaling of respiration. We compiled known scaling factors for animal phyla from a wide phylogenetic spectrum with colonial representatives and conducted a hierarchical mixed regression that included attributes of colonies. Traits associated with allometric scaling in colonial animals included colony shape, the presence of shared extrazooidal structures, and planktonic lifestyle. There are many other colonial rotifers and animal taxa for which allometric scaling factors have yet to be estimated, knowing these may enhance our understanding of the benefits of coloniality in animals. [ABSTRACT FROM AUTHOR]

The topic of proactivity has long captured the attention of career scholars, leading to fertile, yet often disconnected streams of inquiry on personality traits and behaviors that can help workers to advance their own careers, improve their work conditions, or access desired rewards. Based on a review of diverse approaches to conceptualizing and assessing proactive career behavior and related constructs, we identified seven commonly appearing behavioral categories and assembled a representative set of items of each category. An exploratory factor analysis in a sub-sample of adult workers (n = 250) yielded three interrelated factors, labeled (a) planning/reflecting/reskilling (or looking ahead, e.g., engaging in self-reflection and skill development efforts); (b) networking/conferring (or looking to others, e.g., consulting with colleagues and supervisors); and (c) exploring/searching (or looking around, e.g., monitoring career options proactively). A bifactor model fit the data well in another sub-sample (n = 337), suggesting that the three factors were subsumed by a larger construct, which we labeled career sustainability behavior. Results of a structural path analysis indicated that, along with supervisor support, proactive personality, and conceptually-relevant self-efficacy measures, engagement in career sustainability behaviors was predictive of perceived internal and external job marketability. [ABSTRACT FROM AUTHOR]

The passage of human civilization into the new geological era of the Anthropocene raises the question of species extinction. How can we confront the possibility of collective death in a way that does not descend into uncontained anxiety or melancholy? Michel Serres's works in the Foundations and Humanism series offer critical insights into the way in which human violence and death operate as mechanisms for binding together human collectives. Serres draws attention to the role of "social technologies" based around sacrificial practices, the scapegoating mechanism, and the use of corpses as markers of social relations (or "statues"). He argues that these mythic logics and practices persist in modern societies and technoscience. They may also be at work in a modified way in the proposed technical solutions to climate change around space travel and planetary colonization. Drawing on the tradition of Folk Horror film-making and literature, it is argued that reversing the direction of travel, back into the Earth, provides better instruction about how to live and die in the Anthropocene. Reflection on the puteal sites where this may be accomplished will serve as the mechanism. [ABSTRACT FROM AUTHOR]

Access to high‐quality early music education programs may mitigate the effects of poverty on the hypothalamic–pituitary–adrenal (HPA) axis, but fundamental questions remain about the role of early educators in conveying these benefits. In the current study, we measured the basal or resting cortisol levels of 76 children (Mage = 4.17 years; 42% female) over the course of the school day while they attended a Head Start preschool that included early music education classes. The results of a series of hierarchical linear models (HLMs) indicated that child‐directed music and movement activities during these classes were associated with lower levels of cortisol (relative to teacher‐directed activities; B = −0.019, p =.013), as were higher quality teacher–child interactions (B = −0.018, p =.013); both associations were moderated by child age. We discuss the implications of these results for future educational neuroscience research that seeks to inform early education programs for young children placed at risk by poverty. We measured levels of the stress hormone cortisol over the course of the school day for 76 children attending a Head Start preschool. We were interested in the role of early educators in conveying the stress reducing benefits of music during early music education classes. Results suggested that child‐directed music and movement activities during these classes were associated with lower levels of cortisol, as were higher quality teacher‐child interactions. Child age influenced these associations. [ABSTRACT FROM AUTHOR]

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2–4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches. [ABSTRACT FROM AUTHOR]

Purpose: Generic lorazepam oral solution is supplied in a 30 mL multi-dose bottle requiring protection from light and refrigeration, with a beyond use date of 90 days once the bottle is opened. The repackaging of 1 mL doses of lorazepam oral solution into oral syringes allows for facilitated dispensing, yet no available data supports repackaging and storing lorazepam oral solution in syringes. The validation and application of a stability-indicating high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method for the quantification of lorazepam allowed for the determination of the stability of lorazepam oral solution when stored in oral syringes. Methods: A stability-indicating HPLC-UV method was developed for the quantification of lorazepam in oral solution. The method was validated using guidance from USP < 1225 >. For the stability investigation, 2 mg/mL lorazepam oral solution was aliquoted into clear plastic oral syringes in 1 mLmilliliter doses from 2 multi-dose stock bottles and randomly allocated for storage in room temperature or refrigerated environment. Baseline lorazepam concentrations were measured on the day the study was initiated and designated as 100% initial concentration samples. Subsequent samples were analyzed in triplicate at time points of 24, 48, and 96 hours and 7, 10, 14, 21, 30, and 60 days. Results: The calibration curves on three non-consecutive days met the linearity criteria of R 2 > 0.99. Inter- day and intra-day precision and accuracy (percent relative standard deviation and percent error) were ≤2% over three days. During the stability investigation, percent initial concentration of lorazepam from room and refrigerated syringes remained above 90% for the duration of the study. Conclusion: The stability-indicating HPLC-UV method was successfully applied to the investigation of lorazepam oral solution stability when stored in syringes at room and refrigerated temperatures. The emergent need for use of lorazepam concentrate for inpatients and the restrictions of how the medication is supplied necessitated a need for the evaluation of repackaging into unit dose syringes for immediate availability from automated dispensing cabinets. Lorazepam oral solution stored in clear plastic syringes maintained greater than 90% initial concentration at both room and refrigerated temperatures for 60 days. [ABSTRACT FROM AUTHOR]

Purpose: To estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early‐onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs. Methods: A new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log‐binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting. Results: The cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person‐years; suicidality with self‐harm: 23.0 vs. 11.1 per 1000 person‐years; overdose‐ and suicide‐related events: 30.0 vs. 15.5 person‐years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86–1.88]); suicidality with self‐harm (adjusted RR, 1.30 [95% CI, 0.89–1.90]); or overdose‐ and suicide‐related events (adjusted RR, 1.30 [95% CI, 0.93–1.80]) was not significant with gabapentinoids. Conclusions: Incidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome. [ABSTRACT FROM AUTHOR]

The newly constructed Bois d'Arc Lake Reservoir in Fannin County, Texas, USA, inevitably flooded a large ground surface area (67.34 km2) when the reservoir began impounding water in April 2021. Inside this (now) flooded area, land-based archaeological data recovery investigations discovered and documented several archaeological sites, now registered in the state of Texas; though, only two neighboring sites, namely, 41FN178 and 41FN244, are examined here. The first phase of archaeological testing at these sites included shovel testing, test unit excavations, and geoarchaeological trenching that yielded archaeological artifacts suggesting that Middle Caddo Indian peoples (AD 1200–1400) might have occupied this landscape. As the sites were recognized before the reservoir's impoundment phase, this merited a non-invasive, non-destructive, high-resolution near-surface geophysical study to map strategic areas within sites 41FN178 and 41FN244 that might yield potential shallow targets of archaeological context. The adopted geophysical survey comprised 3D direct current electrical resistivity imaging (ERI) and land horizontal magnetic gradiometry (HMG), each mapping a total surface area of 2133 and 15,640 m2, respectively. The combination of 3D ERI and land HMG surveys was instrumental in rapidly mapping the horizontal and vertical extent of shallowly buried anomalies within a large area prior to the completion of the dam and the beginning of water impoundment. Based on the geophysical insights, the outline of several Caddo houses with functional internal and external features (e.g., burnt cooking surfaces, storage pits, refuse pits, fired soil, ditches, a dump site, and a compound fence) are thought to exist within the uppermost 2 m of the Quaternary stratigraphy at both sites. At site 41FN244, 3D ERI found numerous resistive anomalies surrounding a conductive anomaly, collectively interpreted as a group of post-holes surrounding the remains of a Caddo house's inner clay floor. It also found a cluster of several resistive anomalies interpreted as midden or middens. The HMG survey carried across areas from which archaeological test units also yielded positive findings, at sites 41FN178 and 41FN244, identified numerous scattered monopolar and dipolar anomalies interpreted as post-molds of Caddo houses, compound enclosures or fences, and adjacent middens. Archaeological excavations guided by the geophysical results yielded significant cultural material and post-mold features at site 244, which validate the geophysical interpretation in a preliminary context. Additionally, several dispersed magnetic anomalies are thought to be shallowly buried hearths, burn cooking surfaces, storage pits, and ditches. The mapped magnetic anomalies agree with the location and distribution of previously found archaeological artifacts and the extent of resistive and conductive resistivity anomalies. Follow-up archaeological excavations of these geophysical anomalies have preliminarily confirmed interpretations. [ABSTRACT FROM AUTHOR]

Objective Given the rapid shift to in-home teleneuropsychology models, more research is needed to investigate the equivalence of non-facilitator models of teleneuropsychology delivery for people with younger onset dementia (YOD). This study aimed to determine whether equivalent performances were observed on neuropsychological measures administered in-person and via teleneuropsychology in a sample of people being investigated for YOD. Method Using a randomized counterbalanced cross-over design, 43 participants (M age = 60.26, SD age = 7.19) with a possible or probable YOD diagnosis completed 14 neuropsychological tests in-person and via teleneuropsychology, with a 2-week interval. Repeated measures t -tests, intraclass correlation coefficients (ICC), and Bland Altman analyses were used to investigate equivalence across the administration conditions. Results No statistical differences were found between in-person and teleneuropsychology conditions, except for the Hospital Anxiety and Depression Scale Anxiety subtest. Small to negligible effect sizes were observed (ranging from.01 to.20). ICC estimates ranged from.71 to.97 across the neuropsychological measures. Bland Altman analyses revealed that the Wechsler Adult Intelligence Scale—Fourth Edition Block Design subtest had slightly better overall performance in the in-person condition and participants reported higher levels of anxiety symptoms during the teleneuropsychology condition; however, average anxiety symptoms remained within the clinically normal range. Participants reported a high level of acceptability for teleneuropsychology assessments. Conclusions These results suggest that performances are comparable between in-person and teleneuropsychology assessment modalities. Our findings support teleneuropsychology as a feasible alternative to in-person neuropsychological services for people under investigation of YOD, who face significant barriers in accessing timely diagnoses and treatment options. [ABSTRACT FROM AUTHOR]

Thousands struggle with acute and chronic intestinal injury due to various causes. Epithelial intestinal healing is dependent on phenotypic transitions to a mobile phenotype. Focal adhesion kinase (FAK) is a ubiquitous protein that is essential for cell mobility. This phenotype change is mediated by FAK activation and proves to be a promising target for pharmaceutical intervention. While FAK is crucial for intestinal healing, new evidence connects FAK with innate immunity and the importance it plays in macrophage/monocyte chemotaxis, as well as other intracellular signaling cascades. These cascades play a part in macrophage/monocyte polarization, maturation, and inflammation that is associated with intestinal injury. Colony stimulating factors (CSFs) such as macrophage colony stimulating factor (M-CSF/CSF-1) and granulocyte macrophage colony stimulating factor (GM-CSF/CSF-2) play a critical role in maintaining homeostasis within intestinal mucosa by crosstalk capabilities between macrophages and epithelial cells. The communication between these cells is imperative in orchestrating healing upon injury. Diving deeper into these connections may allow us a greater insight into the role that our immune system plays in healing, as well as a better comprehension of inflammatory diseases of the gut. [ABSTRACT FROM AUTHOR]

Respiratory infections caused by the human fungal pathogen Aspergillus fumigatus are a major cause of mortality for immunocompromised patients. Exposure to these pathogens occurs through inhalation, although the role of the respiratory epithelium in disease pathogenesis has not been fully defined. Employing a primary human airway epithelial model, we demonstrate that fungal melanins potently block the post-translational secretion of the chemokines CXCL1 and CXCL8 independent of transcription or the requirement of melanin to be phagocytosed, leading to a significant reduction in neutrophil recruitment to the apical airway both in vitro and in vivo. Aspergillus-derived melanin, a major constituent of the fungal cell wall, dampened airway epithelial chemokine secretion in response to fungi, bacteria, and exogenous cytokines. Furthermore, melanin muted pathogen-mediated calcium fluxing and hindered actin filamentation. Taken together, our results reveal a critical role for melanin interaction with airway epithelium in shaping the host response to fungal and bacterial pathogens. Here, Reedy et al. use a human airway culture model to show that fungal melanin blocks the secretion of pro-inflammatory chemokines resulting in diminished immune responses to Aspergillus fumigatus and Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals' genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor. Reproducibility is key to all fields of research, and in the case of animal research, this can be hampered by inconsistent reporting of animal genetics. Here the authors propose a reporting framework and guidelines designed to discuss the validation and standardise the reporting of genetic backgrounds and genetic alterations in animal models. [ABSTRACT FROM AUTHOR]

Black sexual minority men who have sex with men (MSM) in the United States are at disparate risk for contracting HIV infection, but pre-exposure prophylaxis (PrEP) use is suboptimal. Social network methods were used to recruit a community sample of racial minority MSM and transgender women (TGW) in two Midwestern US cities. 250 PrEP-eligible (HIV-negative) participants completed measures assessing current and intended PrEP use; demographic characteristics; PrEP knowledge, attitudes, norms, stigma, and self-efficacy; and structural barriers to PrEP. Multivariate analyses established predictors of current and intended PrEP use. Only 12% of participants reported currently using PrEP, which was associated with greater PrEP knowledge and not having a main partner, with trends for greater PrEP use by younger participants and those with partners living with HIV. Among participants not currently on PrEP, strength of PrEP use intentions was associated with higher PrEP knowledge, PrEP descriptive social norms, and PrEP use self-efficacy. This study is among few to directly compare Black who have adopted PrEP with those who have not. Its findings underscore the potential benefits of employing social network approaches for strengthening PrEP use peer norms, increasing PrEP knowledge and self-efficacy, and optimizing PrEP uptake among racial minority MSM and TGW. [ABSTRACT FROM AUTHOR]

The first article discusses a recent decision by the Louisiana Supreme Court regarding the duty of architects to ensure the safety of subcontractor employees. The court held that architects do not have a duty to safeguard against injury to subcontractor employees unless there is a contractual provision establishing such a duty. The second article discusses a case in the Seventh Circuit Court of Appeals involving insurance coverage for severe defects in a construction project. The court determined that the defects did not constitute "property damage" under the insurance policies. The third article discusses a unanimous decision by the US Supreme Court clarifying that when a case is referred to arbitration by a federal court, the underlying case should be stayed rather than dismissed. This decision provides clarity and finality to a recurring issue in construction-related disputes. [Extracted from the article]

Insulin-like growth factor 1 (IGF-1) is a critical fetal anabolic hormone. IGF-1 infusion to the normally growing sheep fetus increases the weight of some organs but does not consistently increase body weight. However, IGF-1 infusion profoundly decreases fetal plasma insulin concentrations, which may limit fetal growth potential. In this study, normally growing late-gestation fetal sheep received an intravenous infusion of either: IGF-1 (IGF), IGF-1 with insulin and dextrose to maintain fetal euinsulinemia and euglycemia (IGF+INS), or vehicle control (CON) for 1 week. The fetus underwent a metabolic study immediately prior to infusion start and after 1 week of the infusion to measure uterine and umbilical uptake rates of nutrients and oxygen. IGF+INS fetuses were 23% heavier than CON (P = 0.0081) and had heavier heart, liver, and adrenal glands than IGF and CON (P < 0.01). By design, final fetal insulin concentrations in IGF were 62% and 65% lower than IGF+INS and CON, respectively. Final glucose concentrations were similar in all groups. IGF+INS had lower final oxygen content than IGF and CON (P < 0.0001) and lower final amino acid concentrations than CON (P = 0.0002). Final umbilical oxygen uptake was higher in IGF+INS compared to IGF and CON (P < 0.05). Final umbilical uptake of several essential amino acids was higher in IGF+INS compared to CON (P < 0.05). In summary, maintaining euinsulinemia and euglycemia during fetal IGF-1 infusion is necessary to maximally support body growth. We speculate that IGF-1 and insulin stimulate placental nutrient transport to support fetal growth. [ABSTRACT FROM AUTHOR]

Aims: The COVID‐19 pandemic caused significant disruption to routine activity in primary care. Medication reviews are an important primary care activity ensuring safety and appropriateness of prescribing. A disruption could have significant negative implications for patient care. Using routinely collected data, our aim was first to describe codes used to record medication review activity and then to report the impact of COVID‐19 on the rates of medication reviews. Methods: With the approval of NHS England, we conducted a cohort study of 20 million adult patient records in general practice, in‐situ using the OpenSAFELY platform. For each month, between April 2019 and March 2022, we report the percentage of patients with a medication review coded monthly and in the previous 12 months with breakdowns by regional, clinical and demographic subgroups and those prescribed high‐risk medications. Results: In April 2019, 32.3% of patients had a medication review coded in the previous 12 months. During the first COVID‐19 lockdown, monthly activity decreased (−21.1% April 2020), but the 12‐month rate was not substantially impacted (−10.5% March 2021). The rate of structured medication review in the last 12 months reached 2.9% by March 2022, with higher percentages in high‐risk groups (care home residents 34.1%, age 90+ years 13.1%, high‐risk medications 10.2%). The most used medication review code was Medication review done 314530002 (59.5%). Conclusions: There was a substantial reduction in the monthly rate of medication reviews during the pandemic but rates recovered by the end of the study period. Structured medication reviews were prioritized for high‐risk patients. [ABSTRACT FROM AUTHOR]

Understanding the factors influencing species range limits is increasingly crucial in anticipating migrations due to human‐caused climate change. In the boreal biome, ongoing climate change and the associated increases in the rate, size, and severity of disturbances may alter the distributions of boreal tree species. Notably, Interior Alaska lacks native pine, a biogeographical anomaly that carries implications for ecosystem structure and function. The current range of lodgepole pine (Pinus contorta var. latifolia) in the adjacent Yukon Territory may expand into Interior Alaska, particularly with human assistance. Evaluating the potential for pine expansion in Alaska requires testing constraints on range limits such as dispersal limitations, environmental tolerance limits, and positive or negative biotic interactions. In this study, we used field experiments with pine seeds and transplanted seedlings, complemented by model simulations, to assess the abiotic and biotic factors influencing lodgepole pine seedling establishment and growth after fire in Interior Alaska. We found that pine could successfully recruit, survive, grow, and reproduce across our broadly distributed network of experimental sites. Our results show that both mammalian herbivory and competition from native tree species are unlikely to constrain pine growth and that environmental conditions commonly found in Interior Alaska fall well within the tolerance limits for pine. If dispersal constraints are released, lodgepole pine could have a geographically expansive range in Alaska, and once established, its growth is sufficient to support pine‐dominated stands. Given the impacts of lodgepole pine on ecosystem processes such as increases in timber production, carbon sequestration, landscape flammability, and reduced forage quality, natural or human‐assisted migration of this species is likely to substantially alter responses of Alaskan forest ecosystems to climate change. [ABSTRACT FROM AUTHOR]

International guidance on bioanalytical method validation recommends the practice of partial validation when introducing a new matrix from the same species into a previously fully validated assay. Planning the partial validation protocol should include an evaluation of analyte chemistry, consideration of sample container materials, and a comparison of properties between the relevant biological matrices. Transition of a serum/plasma‐validated bioanalytical method to analysis from a low‐protein matrix, such as urine, cerebral spinal fluid, or oral fluid can result in inconsistent analyte recovery. The low recovery can potentially be mistaken for signal suppression or lack of drug stability and may be more pronounced in low‐concentration or low‐volume samples. In addition, adsorption and absorption interactions with containers may be exacerbated in low‐protein matrices. Several possibilities exist for mitigating the impact of non‐specific binding and low‐protein matrices, including surfactants, bovine serum albumin, and β‐cyclodextrin. Finally, higher matrix protein can facilitate analyte stability. Given all this, matrix protein content should not be overlooked when anticipating a partial bioanalytical method validation. [ABSTRACT FROM AUTHOR]

We examined associations between adolescent self-reported hunger, health risk behaviors, and adverse experiences during the 2018–2019 school year. Youth Risk Behavior Survey data were pooled from 10 states. Prevalence ratios were calculated, and we assessed effect measure modification by sex. The prevalence of self-reported hunger was 13%. Self-reported hunger was associated with a higher prevalence of every health risk behavior/adverse experience analyzed, even after adjusting for sex, grade, and race/ethnicity. Sex did not modify associations. Findings underscore needs for longitudinal research with more robust measures of adolescent food insecurity to clarify the temporality of relationships. [ABSTRACT FROM AUTHOR]

Fetuses affected by intrauterine growth restriction have an increased risk of developing heart disease and failure in adulthood. Compared with controls, late gestation intrauterine growth‐restricted (IUGR) fetal sheep have fewer binucleated cardiomyocytes, reflecting a more immature heart, which may reduce mitochondrial capacity to oxidize substrates. We hypothesized that the late gestation IUGR fetal heart has a lower capacity for mitochondrial oxidative phosphorylation. Left (LV) and right (RV) ventricles from IUGR and control (CON) fetal sheep at 90% gestation were harvested. Mitochondrial respiration (states 1–3, LeakOmy, and maximal respiration) in response to carbohydrates and lipids, citrate synthase (CS) activity, protein expression levels of mitochondrial oxidative phosphorylation complexes (CI–CV), and mRNA expression levels of mitochondrial biosynthesis regulators were measured. The carbohydrate and lipid state 3 respiration rates were lower in IUGR than CON, and CS activity was lower in IUGR LV than CON LV. However, relative CII and CV protein levels were higher in IUGR than CON; CV expression level was higher in IUGR than CON. Genes involved in lipid metabolism had lower expression in IUGR than CON. In addition, the LV and RV demonstrated distinct differences in oxygen flux and gene expression levels, which were independent from CON and IUGR status. Low mitochondrial respiration and CS activity in the IUGR heart compared with CON are consistent with delayed cardiomyocyte maturation, and CII and CV protein expression levels may be upregulated to support ATP production. These insights will provide a better understanding of fetal heart development in an adverse in utero environment. Key points: Growth‐restricted fetuses have a higher risk of developing and dying from cardiovascular diseases in adulthood.Mitochondria are the main supplier of energy for the heart. As the heart matures, the substrate preference of the mitochondria switches from carbohydrates to lipids.We used a sheep model of intrauterine growth restriction to study the capacity of the mitochondria in the heart to produce energy using either carbohydrate or lipid substrates by measuring how much oxygen was consumed.Our data show that the mitochondria respiration levels in the growth‐restricted fetal heart were lower than in the normally growing fetuses, and the expression levels of genes involved in lipid metabolism were also lower. Differences between the right and left ventricles that are independent of the fetal growth restriction condition were identified.These results indicate an impaired metabolic maturation of the growth‐restricted fetal heart associated with a decreased capacity to oxidize lipids postnatally. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate misinformation surrounding infertility and the COVID-19 vaccine on X (formerly known as Twitter) by analyzing the prevalence and content of this misinformation across a sample of posts on X. Methods: This study is a retrospective review of posts on X (formerly known as tweets) from the COVID-19-TweetIDs dataset from July 2021 and November 2021. Included posts were from crucial time points in the COVID-19 vaccine discourse and contained at least one word related to COVID-19 vaccination and fertility. Posts were analyzed and categorized based on factuality, common words, and hashtags. Descriptive statistics on total followers, account verification status, and engagement were obtained. Differences between posts on X classified as factual and misinformation were examined using analysis of variance or χ 2 tests. Sentiment analysis determined if post content was generally positive, neutral, or negative. Results: A total of 17,418 relevant posts on X were reviewed: 11,436 from timeframe 1 (July 2021) and 5982 from timeframe 2 (December 2021). Misinformation posts rose from 29.9% in July 2021 to 45.1% in November 2021. In both timeframes, accounts sharing factual information had more followers (p < 0.001), and verified users were more likely to share accurate posts (p ≤ 0.001). Factual and misinformation posts had similar engagement. Sentiment analysis identified that real posts were more positive and misinformation posts were more negative (p < 0.001). Conclusions and Relevance: Misinformation about the COVID-19 vaccine and fertility is highly prevalent on X and threatens vaccine uptake in patients desiring future fertility. Accounts sharing factual information were likely to have more followers and be verified; therefore, verifying more physicians sharing accurate information is critical. [ABSTRACT FROM AUTHOR]

New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. Here we show that SARS-CoV-2 lineages have distinct evolutionary spaces (a probabilistic definition of the sequence states that can be occupied by expanding virus subpopulations). This space can be accurately inferred from the patterns of amino acid variability at the whole-protein level. Robust networks of co-variable sites identify the highest-likelihood mutations in new VOC sublineages and predict remarkably well the emergence of subvariants with resistance mutations to COVID-19 therapeutics. Our studies reveal the contribution of low frequency variant patterns at heterologous sites across the protein to accurate prediction of the changes at each position of interest. Author summary: We describe a systematic approach to identify "clues" that can predict the mutational profiles of SARS-CoV-2 subvariants at early stages after emergence of their parental lineages. We found that the likelihood for mutations at each position of spike is lineage-specific, and is estimated well by the mutational patterns at all positions of the protein. As examples, we apply the model to forecast emergence of resistance to the antibody therapeutics Bebtelovimab and Cilgavimab, which appeared in sublineages of VOCs BA.5 and BA.4, respectively. Emergence of these subvariants required changes in treatment protocols of COVID-19 patients. In both cases, the escape mutations were predicted well by the mutational profiles at all positions of spike at early time points after emergence of the parental VOCs. Accurate estimations of the imminent changes in SARS-CoV-2 lineages can contribute to design and selection of therapeutics that maintain their efficacy against future forms of this virus. [ABSTRACT FROM AUTHOR]

Stephanorhynchus White, 1846 is a eugnomine weevil genus endemic to New Zealand, with 18 nominal taxa described within the genus. Examination of the type specimens of these taxa with greater understanding of related genera has led to the distinction of four well-defined genera from the species ascribed to the genus. These are the monotypic genus Pittosporobiusgen. nov., with type species P. crassus (Broun, 1880) comb. nov.; Moanusgen. nov., with type species M. lawsoni (Sharp, 1876) comb. nov., and including M. brevipennis (Pascoe, 1876) comb. nov. (= Stephanorhynchus griseipictus Broun, 1886 syn. nov.), M. nigrosparsus (Broun, 1893) comb. nov. (= Stephanorhynchus pygmaeus Broun, 1903 - syn. nov.) and M. tumulus Mazur and Brown sp. nov. (type locality Mt Dick, Otago Lakes, South Island, New Zealand); Glabrorhynchusgen. nov., with type species G. costifer (Broun, 1893) comb. nov., and including G. insolitus (Broun, 1893) comb. nov., G. purus (Pascoe, 1876) comb. nov., and G. halli (Broun, 1914) comb. nov. A reduced concept of Stephanorhynchus White, 1846 contains now four species: S. curvipes White, 1846, S. tuberosus Broun, 1881, S. attelaboides (Fabricius, 1775), S. aper Sharp, 1886. All species within the complex have been redescribed, with details provided of their external morphology and terminal structure and supported by drawings and colour photographs. Keys to genera and species are also provided as well as distribution maps and information about host plants and biology. The systematic position of these genera within the Eugnomini and their similarity with the genus Callistomorphus Perroud, 1865 from New Caledonia are discussed.Article registered number New taxa Glabrorhynchus gen. nov. Moanus gen. nov. Moanus tumulus sp. nov.Pittosporobius gen. nov. [ABSTRACT FROM AUTHOR]

Background EuroQoL EQ-5D-5L is a commonly used measure of health-related quality of life in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D-5L is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. Methods A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. Results EQ-5D-5L mean index and VAS score changes between patients who had cognitive failure and those who had preserved cognition showed no statistically significant differences at any timepoint. In contrast, VAS changes at 4 months (1.61 vs -5.13, P  = .05) and 6 months (8.17 vs −0.14, P  = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were improved in the cohort of patients with preserved neurocognitive function at 2 months (1.68 vs 2.08, P  = .05) and 4 months (1.35 vs 1.83, P  = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. Conclusion EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a quality of life metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. Trial Registration NCT# 02360215. [ABSTRACT FROM AUTHOR]