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Utilizing photocatalytic CO2 reduction presents a promising avenue for combating climate change and curbing greenhouse gas emissions. However, maximizing its potential hinges on the development of materials that not only enhance efficiency but also ensure process stability. Here, we introduce Hiroshima University Silicate‐7 (HUS‐7) with immobilized Ti species as a standout contender. Our study demonstrates the remarkable photocatalytic activity of HUS‐7 in CO2 reduction, yielding substantially higher carbonaceous product yields compared to conventional titanium‐based catalysts TS‐1 and P25. Through thorough characterization, we elucidate that their boosted photocatalytic performance is attributed to the incorporation of isolated Ti species within the silica‐based precursor, serving as potent photoinduced active sites. Moreover, our findings underscore the crucial role of the Ligand‐to‐Metal Charge Transfer (LMCT) process in facilitating the photoactivation of CO2 molecules, shedding new light on key mechanisms underlying photocatalytic CO2 reduction. [ABSTRACT FROM AUTHOR]

Circadian rhythms, governed by the dominant central clock, in addition to various peripheral clocks, regulate almost all biological processes, including sleep–wake cycles, hormone secretion and metabolism. In certain contexts, the regulation and function of the peripheral oscillations can be decoupled from the central clock. However, the specific mechanisms underlying muscle‐intrinsic clock‐dependent modulation of muscle function and metabolism remain unclear. We investigated the outcome of perturbations of the primary and secondary feedback loops of the molecular clock in skeletal muscle by specific gene ablation of Period circadian regulator 2 (Per2) and RAR‐related orphan receptor alpha (Rorα), respectively. In both models, a dampening of core clock gene oscillation was observed, while the phase was preserved. Moreover, both loops seem to be involved in the homeostasis of amine groups. Highly divergent outcomes were seen for overall muscle gene expression, primarily affecting circadian rhythmicity in the PER2 knockouts and non‐oscillating genes in the RORα knockouts, leading to distinct outcomes in terms of metabolome and phenotype. These results highlight the entanglement of the molecular clock and muscle plasticity and allude to specific functions of different clock components, i.e. the primary and secondary feedback loops, in this context. The reciprocal interaction between muscle contractility and circadian clocks might therefore be instrumental to determining a finely tuned adaptation of muscle tissue to perturbations in health and disease. Key points: Specific perturbations of the primary and secondary feedback loop of the molecular clock result in specific outcomes on muscle metabolism and function.Ablation of Per2 (primary loop) or Rorα (secondary loop) blunts the amplitude of core clock genes, in absence of a shift in phase.Perturbation of the primary feedback loop by deletion of PER2 primarily affects muscle gene oscillation.Knockout of RORα and the ensuing modulation of the secondary loop results in the aberrant expression of a large number of non‐clock genes and proteins.The deletion of PER2 and RORα affects muscle metabolism and contractile function in a circadian manner, highlighting the central role of the molecular clock in modulating muscle plasticity. [ABSTRACT FROM AUTHOR]

Treatment of severe acute malnutrition aims at producing quick catch‐up growth in children to decrease their short‐term mortality risk. The extent to which catch‐up growth is influenced by the amount of energy provided is unclear. This study assessed whether energy provided at admission is associated with catch‐up ponderal growth among children with mid‐upper arm circumference (MUAC) < 115 mm at admission. We conducted a secondary data analysis an operational cohort in Mali. The children were treated with a simplified protocol providing 1000 kcal/day of therapeutic food until MUAC ≥ 115 mm was achieved for two consecutive weeks and 500 kcal/day thereafter until discharge with MUAC ≥ 125 mm for two consecutive weeks. Linear mixed‐effects regression models were fitted to assess the relationship between energy provided at admission (kcal/kg/day) with weight gain velocity (g/kg/day) (primary outcome), change in MUAC ‐for‐age z‐score and change in weight‐for‐age z‐score. Unadjusted models and models adjusted for sex, age, seasonality and MUAC at admission were fitted. Both models included the study site as a random effect. A 10 kcal/kg/day increase in energy provided at admission was associated with increments in all outcomes; for weight gain velocity, the mean (95% CI) increment was 0.340 [0.326, 0.354] g/kg/day and 0.466 [0.446, 0.485] g/kg/day in the unadjusted and adjusted analysis, respectively. A positive relationship exists between energy provided at admission and catch‐up ponderal growth in children with MUAC < 115 mm treated using a simplified protocol. Determining the ideal weight gain rate remains essential for assessing the benefits and risks of increased energy intake during treatment. Key messages: Among children diagnosed with severe wasting (MUAC < 115 mm), higher provisions of energy at admission (kcal/kg/day) are associated with a higher rate of weight gain, higher changes in weight‐for‐age and MUAC‐for‐age z‐scores.Children treated for severe wasting (MUAC < 115 mm) receiving Ready‐to‐use therapeutic foods (RUTFs) at a dose higher at admission than the WHO 2023 recommendation of 150–185 kcal/kg/day experience higher rates of weight gain and higher changes in weight‐for‐age and MUAC‐for‐age z‐scores.The optimal rate of weight gain in children treated for severe wasting (MUAC < 115 mm) using RUTF remains unknown. [ABSTRACT FROM AUTHOR]

Plant responses to environmental heterogeneity depend on life‐history traits, which could relate to phenotypical and genetic characteristics. To elucidate this relationship, we examined the variation in population genetics and functional traits of short‐ and long‐lived Artemisia species that are co‐occurring in the steppes of Mongolia. Mongolian steppes represent stressful and water‐limited habitats, demanding phenotypic modifications in the short term and/or genetic adaptation in the long term. However, detailed knowledge is missing about both plant phenotypic and genetic differentiation, and their interrelationships in temperate grasslands. Here, we investigated 21 populations of the widely distributed subshrub Artemisia frigida and the herbaceous biennial Artemisia scoparia. Genetic variation was assessed with newly developed simple sequence repeats (SSRs) markers. Functional trait data were collected from each individual, and data on environmental variables was collected for each population. We detected significantly higher genetic diversity in the biennial species (HE = 0.86) compared with the perennial (HE = 0.79). For both species, the largest share of genetic variation was partitioned within populations (96%). Population genetic structure in the biennial A. scoparia was weak, while the perennial A. frigida showed some spatial genetic structure, which was impacted by geographical factors, soil nutrients, and precipitation amount. Morphology‐related functional traits (i.e., plant height) were predominantly associated with environmental variables rather than with genetic variation, whereas physiology‐related trait (i.e., specific leaf area [SLA]) was partly genetically determined. [ABSTRACT FROM AUTHOR]

This survey study aimed to contribute to the extensive debate on the dimensionality of the Posttraumatic Stress Disorder Checklist for the DSM‐5 (PCL‐5) questionnaire by examining the psychometric properties and construct validity of its Hungarian version and relying on the inspection of a conceptual network of related variables, that is, perceived stress, hostility, and resilience. Confirmatory factor analysis (CFA), exploratory structural equation modelling (ESEM) and path analysis were applied on data collected from 177 paramedics and 66 professionals from the social field (58.4% male; Mage = 43.5 ± 9.96 years). Despite the acceptable fit indices gained with CFA when testing the original four‐factor DSM‐5 model of PCL‐5, strong associations (r = 0.69–0.90) between subscales were found. Thus, ESEM was applied and as a result a new, three‐factor version of the DSM‐5 model of PCL‐5 was proposed due to significant crossloadings that was theoretically also supported. The Reexperiencing and Avoidance subscales were merged and named Difficulty with Assimilation of Experience (DAE). In the path analysis only two of the tested associations were not significant using the new factor structure, in which stress fully mediated the relationship between resilience and DAE, and resilience and Hyperarousal. Overall, the hypothesised pathways between variables fit the collected data well. (weighted least squares mean‐and variance‐adjusted χ2 = 503.750 (df = 270), comparative fit index = 0.948, Tucker–Lewis index = 0.939, root mean square error of approximation (90% confidence interval) = 0.064 (0.055–0.073), weighted root mean square residual = 1.024). Our analysis of the Hungarian version of PCL‐5 contributes to the testing of a DSM‐5‐based questionnaire measuring posttraumatic stress disorder symptomology. [ABSTRACT FROM AUTHOR]

A logarithmic sprayer was suggested about 70 years ago, but it has not yet been seriously used in research and development, and subsequent registration of plant protection products. Logarithmic sprayers have resorted to mere demonstration experiments to show end users and others how plant protection products work. Fitting dose–response curves in field experiments, however, generates much essential information, e.g., extraction of various effective field rate levels (e.g., ED20, ED50, and ED80). One of the reasons for it rarely being used in the registration of plant protection products is that the dose–response curve regression was hitherto difficult to fit; the registration requirement solely focuses on analyses of variance. Another alleged obstacle is that the logarithmic plots have systematically, not randomly distributed field rates. This paper goes through some of the problems of how to non‐randomly analyze field rates by taking autocorrelation into account to make the logarithmic sprayer palatable as registration documentation by assessing efficacy, selectivity, environmental side effects, general toxicity of plant protection products, and cost‐effectiveness. The development in precision agriculture, drone technology, and automation of data capture and subsequent analysis could make the logarithmic sprayer a cost‐effective alternative to numerous ANOVA experiments with very few fixed field rates to aid the precision spraying of pesticides and thus reduce unnecessary environmental side effects. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

New Approach Methodologies (NAMs), broadly understood to include in silico, in chemico, in vitro and ex vivo methods, show great potential in advancing risk assessment albeit their regulatory implementation is lagging. The EFSA Guidance on risk assessment of nanomaterials (EFSA Guidance on Nano‐RA) suggests nano‐specific risk assessment is best achieved through Integrated Approaches to Testing and Assessment (IATAs) with NAMs as the first choice to generate new information. Integrating NAMs in risk assessment promises several advantages such as a better human focus, more detailed insights into molecular mechanisms and a higher efficacy. However, applying NAMs to NMs also poses considerable challenges such as issues related to dispersion stability, dosimetry, agglomeration, dissolution, transformations or assay interferences. Significant efforts are being undertaken by standardisation organisations and research projects to establish various NAMs for NMs. Here a thorough review is provided covering NAMs that will be potentially useful for risk assessment of NMs in the food and feed sector. It follows the structure of the EFSA Guidance on Nano‐RA and expands it, where needed, to support decision‐making in selection of NAMs for NM risk assessment. The review begins with an overview on nano‐specific NAM‐frameworks, followed by a description of individual NAMs including those relevant to NM physicochemical characterisation, exposure and hazard assessment covering toxicodynamics and toxicokinetics. The focus is on NAMs concerning NM degradation/dissolution, genotoxicity, cytotoxicity, oxidative stress, (pro‐)inflammation, and barrier integrity as those are important endpoints for initial screening according to the EFSA framework. As a result, in total 267 individual nano‐relevant NAMs, mostly "not validated" (with a few notable exceptions), were included in this review. Validation notwithstanding, NAMs could already prove relevant and reliable for risk assessment of NMs, especially in integrated approaches. [ABSTRACT FROM AUTHOR]

Plenty of new approach methodologies (NAMs) for risk assessment have been developed but only some are included in OECD Test Guidelines (TGs) for regulatory implementation. Nevertheless, NAMs are increasingly applied, e.g. for nanomaterial (NM) risk assessments. The EFSA Guidance on NM risk assessment suggests that NAM‐derived data concerning degradation/dissolution (in relevant biofluids), intestinal uptake/crossing, genotoxicity, cytotoxicity, oxidative stress, (pro‐)inflammatory potential and barrier integrity, for many of which no OECD TGs exist, have to be evaluated first. Consequently, NM risk assessments involve data from non‐guideline studies, requiring time‐consuming and challenging case‐by‐case evaluations. Establishing an OECD TG is a formal process aiming for international use according to the Mutual Acceptance of Data (MAD). However, not every promising NAM can be prioritised for OECD TGs. A qualification, based on an expert opinion, may enable an efficient use of adequate NAMs for a specific context‐of‐use. Furthermore, it supports the optimisation of promising NAMs for regulatory applications. Existing qualification systems operate in the context of e.g., drug development tools (FDA) and research and development into pharmaceuticals (EMA). The NAMS4NANO consortium was tasked to propose a generic framework for a qualification system for chemical risk assessment in the food and feed sector to speed up the regulatory use of NAMs. Here we describe our proposal including the process and evaluation criteria. A detailed test method description, preferably as standard operating procedures (SOPs), describing the set‐up of the NAM including its application and evaluation phase is crucial. Furthermore, the scientific validity, i.e. its reliability and relevance for the context‐of‐use, needs to be demonstrated, for which we suggest a less rigorous process compared to OECD TGs. We propose to initially establish a qualification system for NM risk assessment, aligned with the EFSA framework. This document is an interim version to stipulate a broader discussion among experts and stakeholders. [ABSTRACT FROM AUTHOR]

ABSTRACT This tutorial describes single‐step low‐dimensional simultaneous inference with a focus on the availability of adjusted p values and compatible confidence intervals for more than just the usual mean value comparisons. The basic idea is, first, to use the influence of correlation on the quantile of the multivariate t‐distribution: the higher the less conservative. In addition, second, the estimability of the correlation matrix using the multiple marginal models approach (mmm) using multiple models in the class of linear up to generalized linear mixed models. The underlying maxT‐test using mmm is discussed by means of several real data scenarios using selected R packages. Surprisingly, different features are highlighted, among them: (i) analyzing different‐scaled, correlated, multiple endpoints, (ii) analyzing multiple correlated binary endpoints, (iii) modeling dose as qualitative factor and/or quantitative covariate, (iv) joint consideration of several tuning parameters within the poly‐k trend test, (v) joint testing of dose and time, (vi) considering several effect sizes, (vii) joint testing of subgroups and overall population in multiarm randomized clinical trials with correlated primary endpoints, (viii) multiple linear mixed effect models, (ix) generalized estimating equations, and (x) nonlinear regression models. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the association of explicitly severe chronic obstructive pulmonary disease (COPD) with oral conditions considering in‐depth shared risk factors. Methods: A case–control study was conducted with 104 participants, 52 with severe COPD and 52 matched controls without COPD. Dental and periodontal status were clinically assessed and oral health‐related quality of life (OHRQoL) by OHIP‐G14‐questionnaire. Results: Between COPD‐ and control‐group, there were no statistically significant differences regarding age (66.02 ± 7.30), sex (female: 52 [50%]), smoking history (44.69 ± 23.23 pack years) and number of systemic diseases (2.60 ± 1.38). COPD patients demonstrated significantly fewer remaining teeth (12.58 ± 9.67 vs. 18.85 ± 6.24, p < 0.001) besides higher DMFT (decayed, missing and filled teeth) index (21.12 ± 5.83 vs. 19.10 ± 3.91, p = 0.036). They had significantly greater probing pocket depths (PPD: 3.24 mm ± 0.71 mm vs. 2.7 mm ± 0.37 mm, p < 0.001) and bleeding on probing (BOP: 34.52% ± 22.03% vs. 22.85% ± 17.94%, p = 0.003) compared to controls, but showed no significant difference in clinical attachment level or staging of periodontitis. The OHIP‐G14 sum score was significantly higher in COPD patients (7.40 ± 7.28 vs. 3.63 ± 4.85, p = 0.002). Common risk factors such as educational status, physical activity, dentist visit frequency, oral hygiene regimens and dietary habits were less favourable in patients with COPD. Conclusions: COPD was significantly associated with higher tooth loss, PPD, BOP and DMFT besides lower OHRQoL. [ABSTRACT FROM AUTHOR]

Little is known about central nervous system (CNS) responses to emotional stimuli in asthma. Nitric oxide in exhaled breath (FENO) is elevated in asthma due to allergic immune processes, but endogenous nitric oxide is also known to modulate CNS activity. We measured fMRI blood oxygen‐dependent (BOLD) brain activation to negative (blood–injection–injury themes) and neutral films in 31 participants (15 with asthma). Regions‐of‐interest analysis was performed on key areas relevant to central adaptive control, threat processing, or salience networks, with dorsolateral prefrontal cortex (PFC), anterior insula, dorsal anterior cingulate cortex (dACC), amygdala, ventral striatum, ventral tegmentum, and periaqueductal gray, as well as top‐down modulation of emotion, with ventrolateral and ventromedial PFC. Both groups showed less BOLD deactivation from fixation cross‐baseline in the left anterior insula and bilateral ventromedial PFC for negative than neutral films, and for an additional number of areas, including the fusiform gyrus, for film versus recovery phases. Less deactivation during films followed by less recovery from deactivation was found in asthma compared to healthy controls. Changes in PCO2 did not explain these findings. FENO was positively related to BOLD activation in general, but more pronounced in healthy controls and more likely in neutral film processing. Thus, asthma is associated with altered processing of film stimuli across brain regions not limited to central adaptive control, threat processing, or salience networks. Higher levels of NO appear to facilitate CNS activity, but only in healthy controls, possibly due to allergy's masking effects on FENO. Using fMRI and emotion induction by films, this study shows for the first time that individuals with asthma process both affective and neutral stimuli differently at the central nervous system level. Nitric oxide, a vasodilator, measured in exhaled breath, was consistently related to stronger activation across brain areas. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) contains carcinogens similar to those generated by tobacco smoking, which may increase the risks of developing smoking‐related cancers, such as upper aerodigestive track (UADT) cancers, for both smokers and never‐smokers. Therefore, it is imperative to understand the relation between ambient PM2.5 exposure and risk of UADT cancers. A population‐based case–control study involving 565 incident UADT cancer cases and 983 controls was conducted in Los Angeles County from 1999 to 2004. The average residential PM2.5 concentration 1 year before the diagnosis date for cases and the reference date for controls was assessed using a chemical transport model. The association between ambient PM2.5 and the UADT cancers was estimated by unconditional logistic regression, adjusting for confounders at the individual and block‐group level. Stratified analyses were conducted by sex, tobacco smoking status and UADT subsites. We also assessed the interaction between PM2.5 and tobacco smoking on UADT cancers. PM2.5 concentrations were associated with an elevated odds of UADT cancers (adjusted odds ratio = 1.21 per interquartile range [4.5 μg/m3] increase; 95% confidence interval: 1.02, 1.44). The association between PM2.5 and UADT cancers was similar across UADT subsites, sex and tobacco smoking status. The interaction between PM2.5 and tobacco smoking on UADT cancers was approximately additive on the odds scale. The effect estimate for PM2.5 and UADT cancers was similar among never smokers. Our findings support the hypothesis that exposure to PM2.5 increases the risk of UADT cancers. Improvements in air quality may reduce the risk of UADT cancers. [ABSTRACT FROM AUTHOR]

Many children in low‐ and middle‐income countries are not attaining their developmental potential. Stunting is associated with poor child development, but it is not known which correlates of stunting are impairing child development. We explored potential socioeconomic, nutritional, clinical, and household correlates of early child development among 12–59‐month‐old children with stunting in a cross‐sectional study in Uganda. Development was assessed using the Malawi Development Assessment Tool (MDAT) across four domains of gross and fine motor, language, and social skills. Linear regression analysis was used to assess correlates of development in the four domains and total MDAT score. Of 750 children included, the median [interquartile range] age was 30 [23−41] months, 55% of the children resided in rural settings with 21% from female‐headed households and 47% of mothers had no schooling. The mean ± standard deviation height‐for‐age z‐score (HAZ) was −3.02 ± 0.74, 40% of the children had a positive malaria test and 65% were anaemic (haemoglobin < 110 g/L). One‐third had children's books at home, majority (96%) used household objects to play with and most of them (70%) used toys as pretence items like those to mimic cooking. After age, sex, and site adjustments, HAZ (0.24, 95% confidence interval [CI]: 0.14−0.33) and head circumference (0.07, 95% CI: 0.02−0.12) were positive correlates of total MDAT score, whereas weight‐for‐height z‐score (WHZ) was not. Current breastfeeding was associated with 0.41 (95% CI: 0.17−0.65) lower total MDAT score. Children from households with a single income earner had 0.22 (95% CI: 0.06−0.37) lower total MDAT score. Furthermore, severe food insecurity, inflammation and positive malaria test were associated with lower scores for motor development. All family care indicator subscales (FCIs) positively correlated with the total MDAT score and this association was independent of household's socioeconomic status. In conclusion, stunting degree, head circumference, number of household income earners and stimulation by improved FCIs correlate with early child development among stunted children. The negative association with prolonged breastfeeding is likely due to reverse causality. Identified correlates may inform initiatives to support children with stunting attain their development potential. Key messages: Our findings reinforce the association between stunting and early child development.The negative association with prolonged breastfeeding is likely due to reverse causality as a result of mothers nursing their smaller, thinner, and more sickly children longer.The strong correlation between all family care indicators with development may express the benefit of improved home stimulation such as provision of reading materials and varied play materials on early child development even among already stunted children in poor settings. [ABSTRACT FROM AUTHOR]

Aim: To investigate the evolution of clinical symptoms of COVID‐19 in children throughout the pandemic. Methods: In this national prospective surveillance study, symptoms in children hospitalised with COVID‐19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS‐CoV‐2 variant: T1 (wild‐type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group. Results: The study included 1323 children. The proportion of children admitted to an intensive care unit remained stable throughout the pandemic. However, the pattern and frequency of clinical manifestations changed over time. Respiratory symptoms were less prevalent during T1 (wild‐type), fever during T2 (Alpha) and rash during T4 (Omicron). In contrast, fever and neurological symptoms were more prevalent during T4 (Omicron). Newly described symptoms during T4 (Omicron) included conjunctivitis, laryngotracheitis and seizures. Fever was more prevalent among neonates and infants whereas respiratory symptoms were more common among infants. Gastrointestinal symptoms were more frequent among toddlers, while both toddlers and school‐aged children presented with neurological symptoms more often than other age groups. Conclusion: Continuous surveillance is required to detect changes in manifestations and there by be prepared for the optimal management of complications in children with COVID‐19. [ABSTRACT FROM AUTHOR]

The Hengill geothermal field, located in southwest Iceland, is host to the Hellisheiði power plant, with its 40+ production wells and 17 reinjection wells. Located in a tectonically active area, the field experiences both natural and induced seismicity linked to the power plant operations. To better manage the risk posed by this seismicity, the development of robust and informative forecasting models is paramount. In this study, we compare the forecasting performance of a model developed for fluid‐induced seismicity (the Seismogenic Index model) and a class of well‐established statistical models (Epidemic‐Type Aftershock Sequence). The pseudo‐prospective experiment is set up with 14 months of initial calibration and daily forecasts for a year. In the timeframe of this experiment, a dense broadband network was in place in Hengill, allowing us to rely on a high quality relocated seismic catalog. The seismicity in the geothermal field is characterized by four main clusters, associated with the two reinjection areas, one production area, and an area with surface geothermal manifestations but where no operations are taking place. We show that the models are generally well suited to forecast induced seismicity, despite some limitations, and that a hybrid ETAS model accounting for fluid forcing has some potential in complex regions with natural and fluid‐induced seismicity. Plain Language Summary: In the southwest of Iceland, the Hengill volcanic region is the seat of a geothermal field exploited with two power plants. The power plants provide district heating and electricity to the capital region. The area continuously experiences small to moderate earthquakes, associated to the volcanic nature of the region and to the power plant operations (injection and withdrawal of fluids from the underground). To better manage the risk posed by these earthquakes, we use statistics‐based computer simulations to forecast the rate of earthquakes during a year‐long experiment. The simulations are trained on 14 months of data. One of the models (the Seismogenic Index) is designed to relate rate of earthquakes to the volumes of fluids injected and withdrawn; while the other relies on statistical characteristics of earthquake sequences. We show that these computer simulations are well suited to forecast earthquake rates in the Hengill geothermal field, even though they have their respective limitations. The combination of the statistical seismicity simulations with a term accounting for the volumes does show promising results in an area with complex earthquake sequences. Key Points: Statistical models are used in a pseudo‐prospective experiment to forecast daily seismicity rates in the Hengill geothermal fieldEpidemic‐Type Aftershock Sequence (ETAS)‐type models are able to adapt quickly to sudden changes in the seismicity rateThe Seismogenic Index‐type model performs at least as well as ETAS‐type models outside periods of high‐intensity seismic activity [ABSTRACT FROM AUTHOR]

Post‐translational modifications are key in the regulation of activity, structure, localization, and stability of most proteins in eukaryotes. Phosphorylation is potentially the most studied post‐translational modification, also due to its reversibility and thereby the regulatory role this modification often plays. While most research attention was focused on kinases in the past, phosphatases remain understudied, most probably because the addition and presence of the modification is more easily studied than its removal and absence. Here, we report the identification of an uncharacterized protein tyrosine phosphatase PPH‐7 in C. elegans, a member of the evolutionary conserved PTPN family of phosphatases. Lack of PPH‐7 function led to reduction of fertility and embryonic lethality at elevated temperatures. Proteomics revealed changes in the regulation of targets of the von Hippel–Lindau (VHL) E3 ligase, suggesting a potential role for PPH‐7 in the regulation of VHL. [ABSTRACT FROM AUTHOR]

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence‐based recommendations for improved patient care. Purpose: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence‐based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence‐based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. Action Statements: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre‐ and co‐seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta‐blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens. [ABSTRACT FROM AUTHOR]

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence‐based recommendations for improved patient care. Purpose: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence‐based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence‐based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. Action Statements: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre‐ and co‐seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta‐blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens. [ABSTRACT FROM AUTHOR]

In recent years, the literature has seen a surge of interest in pass‐through as an economic tool. At the same time, widespread concerns have emerged about the rising market power of firms. How does competition affect pass‐through? A standard intuition is that more competition makes prices more cost‐reflective and hence raises the rate of cost pass‐through. This article shows this conclusion is sensitive to the routine assumption that firms' marginal costs are constant. With modestly convex costs, market power can raise pass‐through (even when it lies below 1). These results have implications for antitrust policy, environmental regulation, and welfare analysis. [ABSTRACT FROM AUTHOR]

While associations between maternal infections during pregnancy and childhood leukemia in offspring have been extensively studied, the evidence for other types of childhood cancers is limited. Additionally, antibiotic exposure during pregnancy could potentially increase the risk of childhood cancers. Our study investigates associations between maternal infections and antibiotic prescriptions during pregnancy and the risk of childhood cancer in Taiwan. We conducted a population‐based cohort study using the Taiwan Maternal and Child Health Database (TMCHD), linked with national health and cancer registries. The study included 2 267 186 mother‐child pairs, and the median follow‐up time was 7.96 years. Cox proportional hazard models were utilized to estimate effects. Maternal infections during pregnancy were associated with a moderate increase in the risk of childhood hepatoblastoma (adjusted hazard ratio [HR] = 1.34; 95% confidence interval [CI]: 0.90‐1.98) and a weaker increase in the risk of childhood acute lymphoblastic leukemia (ALL) (adjusted HR = 1.15; 95% CI: 0.99‐1.35). Antibiotic prescriptions during pregnancy were also associated with an elevated risk of childhood ALL (adjusted HR = 1.30; 95% CI: 1.04‐1.63), particularly with tetracyclines (adjusted HR = 2.15; 95% CI: 1.34‐3.45). Several specific antibiotics were also associated with an increased risk of hepatoblastoma and medulloblastoma. Children exposed in utero to antibiotic prescription or both infections and antibiotics during pregnancy were at higher risk of developing ALL. Our findings suggest that there are associations between maternal infections, antibiotic use during pregnancy and the risk of several childhood cancers in addition to ALL and highlight the importance of further research in this area. [ABSTRACT FROM AUTHOR]

To identify starting points for therapeutics targeting SARS‐CoV‐2, the Paul Scherrer Institute and Idorsia decided to collaboratively perform an X‐ray crystallographic fragment screen against its main protease. Fragment‐based screening was carried out using crystals with a pronounced open conformation of the substrate‐binding pocket. Of 631 soaked fragments, a total of 29 hits bound either in the active site (24 hits), a remote binding pocket (three hits) or at crystal‐packing interfaces (two hits). Notably, two fragments with a pose that was sterically incompatible with a more occluded crystal form were identified. Two isatin‐based electrophilic fragments bound covalently to the catalytic cysteine residue. The structures also revealed a surprisingly strong influence of the crystal form on the binding pose of three published fragments used as positive controls, with implications for fragment screening by crystallography. [ABSTRACT FROM AUTHOR]

Background: Systematically recorded smoking data are not always available in vital statistics records, and even when available it can underestimate true smoking rates. Objective: To develop a prediction model for maternal tobacco smoking in late pregnancy based on birth certificate information using a combination of self‐ or provider‐reported smoking and biomarkers (smoking metabolites) in neonatal blood spots as the alloyed gold standard. Methods: We designed a case–control study where childhood cancer cases were identified from the California Cancer Registry and controls were from the California birth rolls between 1983 and 2011 who were cancer‐free by the age of six. In this analysis, we included 894 control participants and performed high‐resolution metabolomics analyses in their neonatal dried blood spots, where we extracted cotinine [mass‐to‐charge ratio (m/z) = 177.1023] and hydroxycotinine (m/z = 193.0973). Potential predictors of smoking were selected from California birth certificates. Logistic regression with stepwise backward selection was used to build a prediction model. Model performance was evaluated in a training sample, a bootstrapped sample, and an external validation sample. Results: Out of seven predictor variables entered into the logistic model, five were selected by the stepwise procedure: maternal race/ethnicity, maternal education, child's birth year, parity, and child's birth weight. We calculated an overall discrimination accuracy of 0.72 and an area under the receiver operating characteristic curve (AUC) of 0.81 (95% confidence interval [CI] 0.77, 0.84) in the training set. Similar accuracies were achieved in the internal (AUC 0.81, 95% CI 0.77, 0.84) and external (AUC 0.69, 95% CI 0.64, 0.74) validation sets. Conclusions: This easy‐to‐apply model may benefit future birth registry‐based studies when there is missing maternal smoking information; however, some smoking status misclassification remains a concern when only variables from the birth certificate are used to predict maternal smoking. [ABSTRACT FROM AUTHOR]

In recent years, critical realists have increasingly engaged with the thought of Charles S. Peirce (1839‐1914), the founder of the American pragmatist tradition. But the engagement has been mostly narrow in focus and at times misinformed. This paper examines points of continuity between Peircean thought and critical realism with respect to causation, ontology, and truth. Its purpose is to lay the groundwork for further and more fruitful engagement between the traditions by bringing attention to some things critical realists may not have known, and to correct some inaccurate things they thought they knew, about Peirce's philosophy. [ABSTRACT FROM AUTHOR]

Background: We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population. Methods: Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared. Results: Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30‐day and 90‐day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032). Conclusion: Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30‐day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population [ABSTRACT FROM AUTHOR]

In cell culture process development, we rely largely on an iterative, one‐factor‐at‐a‐time procedure based on experiments that explore a limited process space. Design of experiments (DoE) addresses this issue by allowing us to analyze the effects of process inputs on process responses systematically and efficiently. However, DoE cannot be applied directly to study time‐varying process inputs unless an impractically large number of bioreactors is used. Here, we adopt the methodology of design of dynamic experiments (DoDE) and incorporate dynamic feeding profiles efficiently in late‐stage process development of the manufacture of therapeutic monoclonal antibodies. We found that, for the specific cell line used in this article, (1) not only can we estimate the effect of nutrient feed amount on various product attributes, but we can also estimate the effect, develop a statistical model, and use the model to optimize the slope of time‐trended feed rates; (2) in addition to the slope, higher‐order dynamic characteristics of time‐trended feed rates can be incorporated in the design but do not have any significant effect on the responses we measured. Based on the DoDE data, we developed a statistical model and used the model to optimize several process conditions. Our effort resulted in a tangible improvement in productivity—compared with the baseline process without dynamic feeding, this optimized process in a 200‐L batch achieved a 27% increase in titer and > 92% viability. We anticipate our application of DoDE to be a starting point for more efficient workflows to optimize dynamic process conditions in process development. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Increased levels of sex hormones have been hypothesized to decrease Alzheimer's disease (AD) risk. We assessed the association between sex steroid hormones with AD using a Mendelian randomization (MR) approach. METHODS: An inverse‐variance weighting (IVW) MR analysis was performed using effect estimates from external genome‐wide association study (GWAS) summary statistics. We included independent variants (linkage disequilibrium R2 < 0.001) and a p‐value threshold of 5 × 10−8. RESULTS: An increase in androgens was associated with a decreased AD risk among men: testosterone (odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.32–0.88; p‐value: 0.01; false discovery rate [FDR] p‐value: 0.03); dehydroepiandrosterone sulfate (DHEAS; OR: 0.56; 95% CI: 0.38–0.85; p‐value: 0.01; FDR p‐value: 0.03); and androsterone sulfate (OR: 0.69; 95% CI: 0.46–1.02; p‐value: 0.06; FDR p‐value: 0.10). There was no association between sex steroid hormones and AD among women, although analysis for estradiol had limited statistical power. DISCUSSION: A higher concentration of androgens was associated with a decreased risk of AD among men of European ancestry, suggesting that androgens among men might be neuroprotective and could potentially prevent or delay an AD diagnosis. Highlights: Sex hormones are hypothesized to play a role in developing Alzheimer's disease (AD).The effect of sex hormones on AD was assessed using Mendelian randomization (MR) analysis.Among women, genetically determined effects of sex hormones were limited or null.Among men, a higher concentration of androgens decreased AD risk.This study suggests a causal relationship between androgens and AD among men. [ABSTRACT FROM AUTHOR]

Although the association between infection and childhood cancer has been long investigated, there is limited information on rarer cancers. This article aimed to explore the association between postnatal infection and childhood cancers in the Danish population. A matched case‐control study was conducted using Danish nationwide registries from 1978 to 2016. Each childhood cancer case was matched 1:25 with controls by birth date within a week and sex. Postnatal infections were identified from the Danish National Patient Registry, which lists diagnoses seen in hospital, specialist or emergency care services. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (adj.OR) and 95% confidence intervals (CI). Specific types of infections and the number of infection episodes were also considered. The study included 4125 childhood cancer cases and 103 526 matched controls with ages ranging from 0 to 19 years. Medically diagnosed postnatal infections were positively associated with many types of childhood cancer including acute lymphoblastic leukemia (adj.OR = 1.42; 95% CI: 1.23‐1.63), acute myeloid leukemia (adj.OR = 1.80; 95% CI: 1.28‐2.52), non‐Hodgkin lymphoma (adj.OR = 1.53; 95% CI: 1.19‐1.97) and central nervous system tumors (adj.OR = 1.57; 95% CI: 1.39‐1.77). A higher number of infection episodes were also associated with an increased risk of these cancers. Specific infections such as viral, enteric and urinary tract infections were also strongly associated with specific types of cancer. In conclusion, children who later develop cancer appear to have adverse reactions to infections necessitating referral to specialized health care services, perhaps indicating dysregulated immune function. [ABSTRACT FROM AUTHOR]

In children living in endemic areas, the presence of acute-onset PFP along with CSF pleocytosis characterised by over 90% lymphocytes has been found to have a high positive predictive value.[[3], [5]] Definitive diagnosis of neuroborreliosis, however, requires the detection of specific antibodies in CSF. Abbreviations CLIA Chemiluminescence immunoassay CMV Cytomegalovirus CNS Central nervous system CSF Cerebrospinal fluid CXCL13 C-X-C motiv chemokine ligand 13 EBV Epstein-Barr virus ED Emergency department ELISA Enzyme-linked immunosorbent assay Ig Immunoglobulin PCR Polymerase chain reaction PFP Peripheral facial nerve palsy WBC White blood count VZV Varicella-zoster virus INTRODUCTION In areas where pathogenic I Borrelia i spp. are endemic, over half of the children presenting with peripheral facial nerve palsy (PFP) are affected by neuroborreliosis.[[1]] In this setting, I Borrelia i spp. are the most frequent cause of paediatric PFP, surpassing idiopathic PFP (Bell's palsy).[[1]] Diagnosis of neuroborrelioses is based on cerebrospinal fluid (CSF) analysis. A second lumbar puncture will therefore have consequences on the diagnosis and treatment choice. [Extracted from the article]

Exercise effectively promotes and preserves cardiorespiratory, neuromuscular, metabolic, and cognitive functions throughout life. The molecular mechanisms underlying the beneficial adaptations to exercise training are, however, still poorly understood. To improve the mechanistic study of specific exercise training adaptations, standardized, physiological, and well‐characterized training interventions are required. Therefore, we performed a comprehensive interrogation of systemic changes and muscle‐specific cellular and molecular adaptations to voluntary low‐resistance wheel running (Run) and progressive high‐resistance wheel running (RR) in young male mice. Following 10 weeks of training, both groups showed similar improvements in body composition and peak oxygen uptake (V̇O2peak), as well as elevated mitochondrial proteins and capillarization markers in the M. plantaris. Run mice clearly outperformed RR mice in a forced treadmill running capacity test, while RR mice displayed increased grip strength as well as superior mass gains in the M. soleus, associated with distinct proteomic changes specifying the two paradigms. Thus, even though both training modalities induce overlapping adaptations, Run interventions preferably improve submaximal running performance, while progressive RR is a valid model to study training‐induced gains in grip strength and plantar flexor hypertrophy. [ABSTRACT FROM AUTHOR]

Background: Nitrosatable drugs can be synthesized to N‐nitroso compounds in human stomach. In a pregnant woman, N‐nitroso compounds can be translocated to the fetus through the placenta. Maternal exposure of nitrosatable compounds during pregnancy has been associated with childhood brain tumors and leukemia. However, few studies have investigated an association between nitrosatable drug exposure during pregnancy and childhood cancer. We examined if maternal prescriptions of nitrosatable drugs received during pregnancy are associated with childhood cancer. Methods: A matched case‐control study was conducted using Danish nationwide registry data from 1995 to 2016. Each childhood cancer case was matched with twenty‐five controls. Maternal exposure of nitrosatable drugs during pregnancy was identified from the Danish National Prescription Register. A multivariable conditional logistic regression model was used to estimate adjusted odds ratios (adj.OR) with 95% confidence intervals (CI) for each childhood cancer type. Results: Maternal prescriptions of nitrosatable drugs positively associate with central nervous system tumors (adj.OR = 1.25; 95% CI = 1.04–1.51) and neuroblastoma (adj.OR = 1.96; 95% CI = 1.34–2.85) in offspring. We also observed a positive association between perinatal exposure of nitrosatable drugs and acute lymphoblastic leukemia (adj.OR = 1.31; 95% CI = 1.07–1.59), however, it appeared to be due to confounding by indication, i.e., maternal infections. Conclusion: Nitrosatable drug use during pregnancy potentially increased risk of central nervous system tumors and neuroblastoma. While a positive association between maternal prescriptions of nitrosatable drugs and acute lymphoblastic leukemia should be interpreted cautiously because of confounding by indication. [ABSTRACT FROM AUTHOR]

Understanding injection‐induced microseismicity in geothermal systems can provide insight into reservoir connectedness. However, fault and reservoir complexity are difficult to represent in simple analytical models, which makes it difficult to discern clear relationships from incidental associations. Here, we have used data‐driven models to study how fluid injection and microseismicity are related in the Rotokawa (New Zealand) and Hellisheiði (Iceland) geothermal fields. We tested two classes of model: (a) lagged linear regression of seismicity rate as a function of well injection rates; and (b) systematic extraction of injection time series features that are then evaluated for associations with the seismicity. These models allowed us to determine which wells had the greatest correlation with microseismicity and to explain this association in a reservoir context. Finally, exploring different data types and transformations, we were unable to establish a link between rapid changes in injection rate and seismicity spikes, as suggested by some theoretical models. Plain Language Summary: To better understand the small earthquakes triggered in geothermal fields, we used two kinds of data‐driven models: time series feature engineering (a machine learning method) and the non‐negative linear regression method. We applied these techniques to microearthquakes recorded in the Rotokawa geothermal field, New Zealand, and the Húsmúli reinjection area in the Hellisheiði field, Iceland. We searched for associations and patterns hidden within the noisy injection and seismicity data. These patterns are further complicated by the complex injection schedules that involve several wells that switch off and on over time. We found a stronger association between injection and long‐term microseismicity rate as opposed to short‐term fluctuations driven by noise. We showed that particular injection wells are strongly associated with the microseismicity, which we interpret in terms of reservoir connectedness and stress changes in the rock. We found that injection rate and volume are the most useful data for understanding microseismicity, whereas there was no evidence that rapid injection rate changes triggered seismicity at these two locations. Key Points: Relative associations of geothermal wells with seismicity rate are evaluated using regression analysis and time series feature engineeringReservoir operational changes such as injection transfers between wells can affect the association between wells and microseismicityThere is a stronger correlation between injection and long‐term seismicity rate than short‐term seismicity rate at Rotokawa and Hellisheiði site [ABSTRACT FROM AUTHOR]

This large‐scale study used a survey to collect data on K‐12 world language classrooms in Massachusetts public schools, focusing on core instructional practices, curriculum, and assessment. The study resulted in 383 individual teacher completed responses, representing 188 districts, which was analyzed using descriptive statistics. Results indicate encouraging signs in the adoption of core proficiency‐based instructional practices, thematic curriculum design, and the use of performance‐based assessments. Further support for teachers in how to implement these practices is needed, along with attention to school leaders who may have no background in world language education but are tasked with supporting and evaluating world language teachers. Survey data were collected at the beginning of school closures due to COVID‐19, capturing a picture of K‐12 world language education and a point of comparison for future research. The Challenge: How can we make progress in world language education without understanding K‐12 instructional practices, curriculum, and assessment? How can we support teachers without understanding their classroom practices? How can we advocate for the World‐Readiness Standards for Learning Language without understanding what curriculum is being used in the classroom? [ABSTRACT FROM AUTHOR]

Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits the degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells are known to preserve a small pool of dormant ribosomes under nutrient‐limited conditions. However, the regulation of these dormant ribosomes is poorly characterized. Here, we show that upon inhibition of yeast TORC1 by rapamycin or nitrogen starvation, the ribosome preservation factor Stm1 mediates the formation of nontranslating, dormant 80S ribosomes. Furthermore, Stm1‐bound 80S ribosomes are protected from proteasomal degradation. Upon nutrient replenishment, TORC1 directly phosphorylates and inhibits Stm1 to reactivate translation. Finally, we find that SERBP1, a mammalian ortholog of Stm1, is likewise required for the formation of dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. These data suggest that TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner by directly targeting a ribosome preservation factor. Synopsis: Preservation of a pool of dormant ribosomes under nutrient‐limited conditions is important for growth recovery upon nutrient replenishment. Here, TORC1 is found to regulate this process by directly targeting a conserved ribosome preservation factor. TORC1 phosphorylates and inhibits Stm1 to prevent formation of dormant 80S ribosome under nutrient‐sufficient conditions in yeast.TORC1 inhibition by rapamycin or nitrogen starvation causes Stm1 binding to ribosomes.Stm1‐bound dormant, nontranslating 80S ribosomes are protected from proteasomal degradation.mTORC1 phosphorylates and inhibits the mammalian Stm1 ortholog SERBP1.SERBP1 is required for ribosome protection upon mTORC1 inhibition in human cells, suggesting conserved regulation. [ABSTRACT FROM AUTHOR]

Prosumers are individuals who produce goods they consume themselves. The prosumption literature suggests that prosumption can be enhanced through knowledge sharing, creativity and innovation, and developing expertise. In this article, we investigate the relationships between prosumption experiences, prosumption values, and affinity with a prosumption activity. We use a structural equation model approach to evaluate the relationships between these constructs and assume that affinity can mediate the relationship between prosumption experiences and values. We collect empirical data from prosumers who homebrew their own beer and confirm that prosumption experiences and values are positively related, and that affinity mediates the relationship between experiences and values. Implications deriving from these findings are discussed along with directions for future research. [ABSTRACT FROM AUTHOR]

Although the belief that support alleviates the detrimental effect of job demands on employee health is intuitive, past research has produced an equivocal picture, requiring a renewed evaluation of this relationship. In the present study, we examine three sources of support (from the organization, leader, and team) that employees may draw from to reduce the negative effect of a specific job demand, that is, role overload. Unlike most prior research, we focus on these sources of support at the group level of analysis to determine the relative effectiveness of organizational support climate, leadership climate, and team climate as moderators of the role overload–subjective health relationship. Hierarchical linear modeling of data from 2,288 employees nested in 132 workgroups in a state administration of Switzerland revealed that, after controlling for individual perceptions of support, team climate weakened the negative relationship between role overload and health. We did not find support for the buffering effect of organizational support or leadership climates. The article provides a nuanced test of the support‐buffering hypothesis by simultaneously exploring individual and group‐level sources of support and by demonstrating that some sources of support matter more than others in ameliorating the negative outcomes of role overload. [ABSTRACT FROM AUTHOR]

The Challenge: Does leadership matter? In K‐12 world language programs, will a program leader or primary evaluator who is a world language specialist have an impact on teacher practices? The lack of attention to school leadership in our field has left us guessing. Its time to focus research on the importance of program leadership. This large‐scale study used a survey to collect data on K‐12 world language program leadership and instructional practices in Massachusetts public schools, investigating associations between the presence of a program leader or primary evaluator who is a world language specialist and instructional practices, curriculum, and assessment. The study resulted in 383 individual teachers completed responses, representing 188 school districts. Multilevel regressions were fit for groups of questions focusing on different categories of instructional practices by educational level (elementary, middle school, and high school). Results indicate positive associations between a world language specialist in the role of program leader or primary evaluator and a number of teacher practices. Further research is needed to expand understandings of the role and impact of world language leadership at the K‐12 level. Program leadership is an important component of the school system that has largely been omitted in world language educational research. [ABSTRACT FROM AUTHOR]

A prerequisite for the survival and reproduction of organisms is to successfully navigate thermal environmental conditions that unfold over time and space. While effective movement behaviour has been highlighted as a key mechanism by which organisms and populations may persist amidst the backdrop of directional environmental warming, it remains unclear how behavioural plasticity may mediate such effects, particularly across time‐scales that span multiple generations.Here, we examine the capacity for transgenerational plasticity to alter the movement behaviour of the motile green algae Chlamydomonas reinhardtii in response to changes in thermal conditions.We first acclimated C. reinhardtii populations to thermal environments near (25°C), below (12.5°C) or above (37.5°C) the temperature range that maximizes population growth rate. Subsequently, we assayed the micro‐spatial scale movement behaviour of these populations in thermally homogeneous environments across a period of 2 weeks in each respective environment, with the goal of evaluating the influence of thermal history on movement behaviour in a novel thermal environment.Our results indicate that thermal history can mediate the movement patterns of C. reinhardtii individuals for up to 10 generations and that the trajectory by which phenotypes converge on their acclimated values can be highly nonlinear. Subsequently, we demonstrated—using a dispersal assay in spatially variable environments—that thermal acclimation history can additionally alter movement patterns at ecologically relevant scales.Collectively these findings indicate the possibility for transgenerational plasticity to modify behaviour across extended time‐scales and converge on acclimated states via nonlinear trajectories. Understanding the efficacy of behaviour for navigating novel thermal environments, such as environments anticipated amidst environmental warming, may thus require considering past as well as present environmental conditions. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Charles S. Peirce's realism has been neglected by pragmatists and critical realists alike in the current debate over metatheoretical realism in sociology. This paper introduces Peirce's view of what is at stake in the question of realism, specifically regarding causation. Leveraging current interest in Peirce's conception of abduction, I show how realism about causation is implicit therein. I present a genealogy of the concept of real causation Peirce embraces. I explicate Peirce's view of the scientific significance of realism about causation, and why he finds it compelling. Finally, I argue that Peirce would intervene in the current debate by saying that those committed to abductive theorizing and causal explanation are implicitly realist. [ABSTRACT FROM AUTHOR]

Viral respiratory diseases, such as avian influenza, Newcastle disease, infectious bronchitis and infectious laryngotracheitis, have considerable negative economic implications for poultry. Ensuring the virus‐free status of premises by environmental sampling after cleaning and disinfection is essential for lifting a quarantine and/or safely restocking the premises following an outbreak. The objectives of this study were to identify optimal sample collection devices and to determine the locations in poultry housing which are best for poultry respiratory virus sample collection. Chickens exposed to infectious bronchitis virus, which was used as a representative virus for enveloped poultry respiratory viruses, were housed in floor‐pens in either a curtain‐sided wood framed house or a cement block house. Foam swabs, cellulose sponges, polyester swabs, dry cotton gauze and pre‐moistened cotton gauze were evaluated for comparative efficiency in recovering viral RNA. Cotton gauze pre‐moistened with the viral transport media had the highest sensitivity among the devices (wood‐framed house: 78% positive, geometric mean titre [GMT] of 2.6 log10 50% egg infectious doses [EID50] equivalents/ml; cement block houses: 55% positive, GMT of 1.7 log10 EID50 equivalents/ml). Targeting virus deposition sites is also crucial for efficient virus elimination procedures and subsequent testing; therefore, 10 locations within the houses were compared for virus detection. In both housing types, the highest viral RNA loads were recovered from the tops of drinker lines within the pen. Places the chickens could contact directly (e.g., feeder rim) or were contacted by caretaker feet (hallway floor) also yielded higher levels of viral RNA more consistently. These results will facilitate the establishment of efficient environmental sampling procedures for respiratory viruses of poultry. [ABSTRACT FROM AUTHOR]

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID‐19. Few studies have investigated regulators of iron metabolism in the context of COVID‐19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community‐acquired pneumonia (CAP) caused by SARS‐CoV‐2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross‐sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C‐reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS‐CoV‐2 with 143.8 (100.7–180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1–125.4) and 53.5 (25.2–125.8) ng/mL, respectively. The median ferritin level was more than 2‐fold higher in patients with SARS‐CoV‐2 compared with the other etiologies (p < 0.001). Patients with SARS‐CoV‐2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS‐CoV‐2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS‐CoV‐2 infection. [ABSTRACT FROM AUTHOR]

Aim: The effect of different protein sources on the appetite‐related hormones in children is largely unknown. We investigated the effect of milk protein versus blends of milk and rapeseed protein on plasma leptin and adiponectin in children. Methods: We included 88 Danish 7‐ to 8‐year‐old children randomised to receive 35 g protein/day for 4 weeks in 2018 as either milk protein or blends of milk and rapeseed protein (ratio 54:46 or 30:70). Outcomes included absolute and fat mass‐adjusted adiponectin and leptin measured at baseline, Weeks 1 and 4. Results: There was no difference in changes in absolute and fat mass‐adjusted adiponectin and leptin after 1 or 4 weeks between the three groups (p ≥ 0.100). Leptin increased within all groups (p ≤ 0.046). Combining the three groups, leptin and fat mass‐adjusted leptin increased by 23% (95% CI 11;35) and 17% (6.4;29) during the intervention respectively (both p ≤ 0.001). Adiponectin variables did not change during the intervention period. Conclusion: There were no differences between milk protein and blends of milk and rapeseed protein on absolute and fat mass‐adjusted leptin and adiponectin in healthy children with a habitual intake of milk. However, leptin increased within all three groups. Future studies should further investigate effect on appetite‐related hormones of rapeseed protein alone. [ABSTRACT FROM AUTHOR]

Magic Spot Nucleotides (MSN) regulate the stringent response, a highly conserved bacterial stress adaptation mechanism, enabling survival under adverse external challenges. In times of antibiotic crisis, a detailed understanding of stringent response is essential, as potentially new targets for pharmacological intervention could be identified. In this study, we delineate the MSN interactome in Escherichia coli and Salmonella typhimurium applying a family of trifunctional photoaffinity capture compounds. We introduce MSN probes covering a diverse phosphorylation pattern, such as pppGpp, ppGpp, and pGpp. Our chemical proteomics approach provides datasets of putative MSN receptors both from cytosolic and membrane fractions that unveil new MSN targets. We find that the activity of the non‐Nudix hydrolase ApaH is potently inhibited by pppGpp, which itself is converted to pGpp by ApaH. The capture compounds described herein will be useful to identify MSN interactomes across bacterial species. [ABSTRACT FROM AUTHOR]