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Abstract Background The advent of full-time virtual schooling presents unique challenges and opportunities for the promotion of physical activity (PA) among children and adolescents. Despite the recognized benefits of PA as an essential component for combating non-communicable diseases and ensuring holistic development, there is a notable gap in understanding how to effectively integrate PA within the digital learning environments of full-time virtual schools. Current efforts to promote student PA are targeted for implementation exclusively in contexts characterized by physical school campuses that are bound to their surrounding local communities. This is problematic given the digital, widely distributed, and contextually unmoored nature of virtual schooling. Our aim in this scoping review is to advance research on whole-of-school physical activity promotion within full-time virtual schools by examining the published literature on whole-of-school PA promotion within full-time virtual schools. Specifically, this review will map the literature, consolidate knowledge claims and practical implications, and identify evidence gaps that merit further investigation. Methods/design This review will be conducted using evidence-informed scoping review methodology and reporting guidelines. Articles will be included if they are peer-reviewed English-language research, commentary, practical, or grey literature and relate to the participation, support, design, development, and/or provision of remote online PA interventions delivered through primary/elementary and/or secondary/middle school/high schools. Searches will be conducted in PsycInfo, ERIC, SportDiscus, and Web of Science. Additional hand-searching, reference scans, and grey literature searches will also be performed. Two trained research assistants will independently complete study screening and selection and data charting with guidance from a senior author. Charted data will be displayed in table form, and depending on the results, data will also be synthesized through qualitative content analysis using the Active Schools guiding framework as an analytical and interpretive lens. Discussion This scoping review will serve as a guidepost for the application and advancement of research on whole-of-school PA promotion through full-time virtual schools. The results will address the increased importance of equitable online learning and PA promotion due to the expanding virtual education landscape, with implications for public health and education policy. Systematic review registration Open Science Framework: https://osf.io/f6wau/ .

Abstract Background Regular participation in physical activity (PA) benefits children’s health and well-being and protects against the development of unhealthy body weight. A key factor in children’s PA participation is their motor competence (MC). The comprehensive school physical activity program (CSPAP) framework offers a way to classify existing PA interventions that have included children’s MC development and understand the potential avenues for supporting children’s MC. However, there have been no systematic reviews or meta-analyses of PA interventions and their effects on the MC of elementary school children (aged 5–12 years) from a CSPAP perspective. Methods This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched seven electronic databases (PubMed/Medline, Embase, ERIC, SPORTDiscus, CINAHL, Web of Science, and PsycINFO) for articles on 29 November 2021. The CSPAP framework was used to categorize the different intervention approaches. This review was registered with PROSPERO (CRD42020179866). Results Twenty-seven studies were included in the review, and twenty-six studies were included in the meta-analysis. A wide range of PA intervention approaches (e.g., single component or multicomponent) within the context of the CSPAP framework appear to be promising pathways in enhancing children’s MC. The results of the aggregate meta-analysis presented that effect sizes for the development of MC from pre-and post- intervention ranged from moderate to large (Hedges’ g = 0.41−0.79). The analysis revealed that the predicted moderators, including study length, delivery agent, and study design, did not result in statistically significant moderate variations in MC outcomes. There was, however, considerable heterogeneity in study design, instruments, and study context, and studies were implemented in over 11 countries across diverse settings. Conclusions This study uniquely contributes to the literature through its primary focus on the effectiveness of PA interventions on elementary children’s MC. This review emphasizes the importance of customizing CSPAP to fit the specific characteristics of each school setting, including its environmental, demographic, and resource attributes. The effectiveness of CSPAP, particularly its physical education (PE) component, is significantly enhanced when these programs are adapted to address the unique needs of each school. This adaptation can be effectively achieved through targeted professional teacher training, ensuring that PE programs are not only contextually relevant but also optimized for maximum impact in diverse educational environments. Researchers and practitioners should pursue how to effectively translate the evidence into practice to better conceptualize CSPAPs designed for children’s MC development.

Ectomycorrhizal fungi and non-ectomycorrhizal fungi are responsive to changes in environmental and nutrient availabilities. Although many species of ectomycorrhizas are known to enhance the uptake of phosphorus and other nutrients for Pinus taeda, it is not understood how to optimize these communities to have tangible effects on plantation silviculture and P use efficiency. The first step of this process is the identification of native fungi present in the system that are associated with P. taeda and influence P uptake efficiency. We used sand-filled mesh bags baited with finely ground apatite to sample ectomycorrhizal and non-ectomycorrhizal fungi associated with the rhizosphere of P-responsive P. taeda under several field conditions. Mesh bags were assessed for biomass accumulation over three years using a single three-month burial period pre-harvest and three six-month burial periods post-planting. Amplicon sequencing assessed ectomycorrhizal and non-ectomycorrhizal communities between phosphorus treatments, sites, mesh bags, and the rhizosphere of actively growing P. taeda in the field. We found biomass accumulation within the mesh bags was inversely related to increasing phosphorus fertilization (carryover) rates from pre-harvest to post-planting. Up to 25% increases in total biomass within the bags were observed for bags baited with P. Taxonomic richness was highest in Alfisol soils treated with phosphorus from the previous rotation and lowest in the Spodosol regardless of phosphorus treatment.

The dynamic fluctuations in autumn temperatures, particularly the marked diurnal variations and the subsequent precipitous drops are key and a pivotal role in viticulture, as they critically influence the acclimation process of grapevines to cold, thereby directly impacting their survival and productivity in cold-climate regions. In this comprehensive study, we investigated the cold hardiness of four grapevine cultivars: ‘Itasca’, ‘Frontenac’, ‘La Crescent’, and ‘Marquette’, focusing on how these cultivars and their individual buds (1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, and 9th) respond to fluctuating weather and low temperatures typical of autumn [-1.1°C (30°F) -9.4°C (15°F) and -17.8°C (0°F)]. Our results illuminated the striking variability in cold hardiness that was manifest not only among the different cultivars but also within individual buds on the same vine, underscoring the critical influence of bud position on a vine for cold hardiness. ‘Frontenac’ showed greater cold hardiness at critical temperatures at which 10%, and 50% of the dormant buds were lethally affected by cold (LT10 and LT50) compared to ‘Itasca’ and ‘La Crescent’, with ‘Marquette’ exhibiting intermediate values. However, in cultivars such as ‘Itasca’ and ‘Marquette’, certain buds demonstrated a pronounced hardiness when faced with colder temperatures, while others exhibited a heightened sensitivity, thereby revealing a nuanced interplay between bud position and a vine’s ability to withstand cold stress. Our study revealed a notable divergence from traditional viticulture understanding; apical buds demonstrated greater cold hardiness than basal buds and opened new paths for research into grapevine physiology. Our results also indicated a significant trend wherein older vines across all studied cultivars displayed enhanced cold hardiness, particularly pronounced at the critical LT50 and the critical temperature at which 90% of the dormant buds were lethally affected by cold (LT90) thresholds, in comparison to younger vines. Moreover, our findings shed light on the impact of autumn’s diurnal temperature variations and the subsequent drop in temperatures on vine cold hardiness, thus highlighted the complex interplay between environmental temperature dynamics and dormant bud hardiness. In conclusion, our study showed that the cold damage observed in grapevines in North Dakota was not a result of extreme temperature fluctuations in the fall. This was confirmed by testing the vines after they had reached various threshold temperatures through differential thermal analysis (DTA) and optical differential nucleation and expansion analysis (ODNEAL) methodologies, particularly before the onset of severe pre-winter cold conditions. These comprehensive findings highlighted the complexity of the vine’s response to climatic conditions and viticultural management, pointing to the need for specific strategies in vineyard management and cultivar selection to optimize bud hardiness and productivity in the face of various environmental challenges, especially in cold climate viticulture.

Major advances in RNA secondary structural motif prediction have been achieved in the last few years; however, few methods harness the predictive power of multiple approaches to deliver in-depth characterizations of local RNA motifs and their potential functionality. Additionally, most available methods do not predict RNA pseudoknots. This work combines complementary bioinformatic systems into one robust discovery pipeline where: • RNA sequences are folded to search for thermodynamically favorable motifs utilizing ScanFold. • Motifs are expanded and refolded into alternate pseudoknot conformations by Knotty/Iterative HFold. • All conformations are evaluated for covariance via the cm-builder pipeline (Infernal and R-scape).

Drinking-water quality is a rising concern in the United States (US), emphasizing the need to broadly assess exposures and potential health effects at the point-of-use. Drinking-water exposures to per- and poly-fluoroalkyl substances (PFAS) are a national concern, however, there is limited information on PFAS in residential tapwater at the point-of-use, especially from private-wells. We conducted a national reconnaissance to compare human PFAS exposures in unregulated private-well and regulated public-supply tapwater. Tapwater from 716 locations (269 private-wells; 447 public supply) across the US was collected during 2016–2021 including three locations where temporal sampling was conducted. Concentrations of PFAS were assessed by three laboratories and compared with land-use and potential-source metrics to explore drivers of contamination. The number of individual PFAS observed ranged from 1 to 9 (median: 2) with corresponding cumulative concentrations (sum of detected PFAS) ranging from 0.348 to 346 ng/L. Seventeen PFAS were observed at least once with PFBS, PFHxS and PFOA observed most frequently in approximately 15% of the samples. Across the US, PFAS profiles and estimated median cumulative concentrations were similar among private wells and public-supply tapwater. We estimate that at least one PFAS could be detected in about 45% of US drinking-water samples. These detection probabilities varied spatially with limited temporal variation in concentrations/numbers of PFAS detected. Benchmark screening approaches indicated potential human exposure risk was dominated by PFOA and PFOS, when detected. Potential source and land-use information was related to cumulative PFAS concentrations, and the number of PFAS detected; however, corresponding relations with specific PFAS were limited likely due to low detection frequencies and higher detection limits. Information generated supports the need for further assessments of cumulative health risks of PFAS as a class and in combination with other co-occurring contaminants, particularly in unmonitored private-wells where information is limited or not available.

We present the photometric and spectroscopic evolution of SN 2022oqm, a nearby multipeaked hydrogen- and helium-weak calcium-rich transient (CaRT). SN 2022oqm was detected 13.1 kpc from its host galaxy, the face-on spiral galaxy NGC 5875. Extensive spectroscopic coverage reveals an early hot ( T ≥ 40,000 K) continuum and carbon features observed ∼1 day after discovery, SN Ic-like photospheric-phase spectra, and strong forbidden calcium emission starting 38 days after discovery. SN 2022oqm has a relatively high peak luminosity ( M _B = −17 mag) for CaRTs, making it an outlier in the population. We determine that three power sources are necessary to explain the light curve (LC), with each corresponding to a distinct peak. The first peak is powered by an expanding blackbody with a power-law luminosity, suggesting shock cooling by circumstellar material (CSM). Subsequent LC evolution is powered by a double radioactive decay model, consistent with two sources of photons diffusing through optically thick ejecta. From the LC, we derive an ejecta mass and ^56 Ni mass of ∼0.6 M _⊙ and ∼0.09 M _⊙ . Spectroscopic modeling ∼0.6 M _⊙ of ejecta, and with well-mixed Fe-peak elements throughout. We discuss several physical origins for SN 2022oqm and find either a surprisingly massive white dwarf progenitor or a peculiar stripped envelope model could explain SN 2022oqm. A stripped envelope explosion inside a dense, hydrogen- and helium-poor CSM, akin to SNe Icn, but with a large 56Ni mass and small CSM mass could explain SN 2022oqm. Alternatively, helium detonation on an unexpectedly massive white dwarf could also explain SN 2022oqm.

The nearby type II supernova, SN 2023ixf in M101 exhibits signatures of early time interaction with circumstellar material in the first week postexplosion. This material may be the consequence of prior mass loss suffered by the progenitor, which possibly manifested in the form of a detectable presupernova outburst. We present an analysis of long-baseline preexplosion photometric data in the g , w , r , i , z , and y filters from Pan-STARRS as part of the Young Supernova Experiment, spanning ∼5000 days. We find no significant detections in the Pan-STARRS preexplosion light curves. We train a multilayer perceptron neural network to classify presupernova outbursts. We find no evidence of eruptive presupernova activity to a limiting absolute magnitude of −7 mag. The limiting magnitudes from the full set of gwrizy (average absolute magnitude ≈ −8 mag) data are consistent with previous preexplosion studies. We use deep photometry from the literature to constrain the progenitor of SN 2023ixf, finding that these data are consistent with a dusty red supergiant progenitor with luminosity $\mathrm{log}\left(L/{L}_{\odot }\right)$ ≈ 5.12 and temperature ≈ 3950 K, corresponding to a mass of 14–20 M _⊙ .

A total of fourteen diverse, interspecific hybrid grapevines (Vitis spp.) were evaluated for their adaptability to North Dakota winter conditions using differential thermal analysis (DTA) of low-temperature exotherms (LTE) and bud cross-sectional assessment of survival techniques. This research was conducted in two vineyard locations in eastern North Dakota. This work demonstrates the use of DTA for monitoring and selecting cultivars capable of withstanding sub-zero temperatures. These results were assessed for quantitative genetic traits. High heritability was observed for bud LTE traits and may thus be a useful target for cold hardiness breeding programs; however, it is necessary to ensure that variance is reduced when pooling multiple sample events. After DTA sampling, grapevines were assessed for survival of primary and secondary dormant buds using cross-sectional visual evaluation of death. ‘Valiant’ had the greatest primary bud survival (68%), followed by ‘Frontenac gris’, ‘Crimson Pearl’, and ‘King of the North’. These varieties are among those with potential for production in eastern North Dakota’s environment. The newly evaluated relationships between traits and the heritability of DTA results provide valuable tools to grapevine breeders for the development of cold-tolerant genotypes for future climatic challenges.

We present high-cadence ultraviolet through near-infrared observations of the Type Ia supernova (SN Ia) 2023bee at D = 32 ± 3 Mpc, finding excess flux in the first days after explosion, particularly in our 10 minutes cadence TESS light curve and Swift UV data. Compared to a few other normal SNe Ia with early excess flux, the excess flux in SN 2023bee is redder in the UV and less luminous. We present optical spectra of SN 2023bee, including two spectra during the period where the flux excess is dominant. At this time, the spectra are similar to those of other SNe Ia but with weaker Si ii , C ii, and Ca ii absorption lines, perhaps because the excess flux creates a stronger continuum. We compare the data to several theoretical models on the origin of early excess flux in SNe Ia. Interaction with either the companion star or close-in circumstellar material is expected to produce a faster evolution than observed. Radioactive material in the outer layers of the ejecta, either from double detonation explosion or from a ^56 Ni clump near the surface, cannot fully reproduce the evolution either, likely due to the sensitivity of early UV observable to the treatment of the outer part of ejecta in simulation. We conclude that no current model can adequately explain the full set of observations. We find that a relatively large fraction of nearby, bright SNe Ia with high-cadence observations have some amount of excess flux within a few days of explosion. Considering potential asymmetric emission, the physical cause of this excess flux may be ubiquitous in normal SNe Ia.

Abstract RNA plays vital functional roles in almost every component of biology, and these functional roles are often influenced by its folding into secondary and tertiary structures. An important role of RNA secondary structure is in maintaining proper gene regulation; therefore, making accurate predictions of the structures involved in these processes is important. In this study, we have expanded on our previous work that led to the creation of the RNAStructuromeDB. Unlike this previous study that analyzed the human genome at low resolution, we have now scanned the protein-coding human transcriptome at high (single nt) resolution. This provides more robust structure predictions for over 100,000 isoforms of known protein-coding genes. Notably, we also utilize the motif identification tool, ScanFold, to model structures with high propensity for ordered/evolved stability. All data have been uploaded to the RNAStructuromeDB, allowing for easy searching of transcripts, visualization of data tracks (via the Integrative Genomics Viewer or IGV), and download of ScanFold data—including unique highly-ordered motifs. Herein, we provide an example analysis of MAT2A to demonstrate the utility of ScanFold at finding known and novel secondary structures, highlighting regions of potential functionality, and guiding generation of functional hypotheses through use of the data.

Vascular dysfunction is associated with ageing and chronic diseases, but its role in lung repair and fibrosis is unclear. Here, the authors show that the endothelial transcription factor ERG is a mediator of vascular repair whose function declines in aged lungs resulting in sustained fibrosis

Abstract Influenza virus is a persistent threat to human health; indeed, the deadliest modern pandemic was in 1918 when an H1N1 virus killed an estimated 50 million people globally. The intent of this work is to better understand influenza from an RNA-centric perspective to provide local, structural motifs with likely significance to the influenza infectious cycle for therapeutic targeting. To accomplish this, we analyzed over four hundred thousand RNA sequences spanning three major clades: influenza A, B and C. We scanned influenza segments for local secondary structure, identified/modeled motifs of likely functionality, and coupled the results to an analysis of evolutionary conservation. We discovered 185 significant regions of predicted ordered stability, yet evidence of sequence covariation was limited to 7 motifs, where 3—found in influenza C—had higher than expected amounts of sequence covariation.

A major limiting factor in target discovery for both basic research and therapeutic intervention is the identification of structural and/or functional RNA elements in genomes and transcriptomes. This was the impetus for the original ScanFold algorithm, which provides maps of local RNA structural stability, evidence of sequence-ordered (potentially evolved) structure, and unique model structures comprised of recurring base pairs with the greatest structural bias. A key step in quantifying this propensity for ordered structure is the prediction of secondary structural stability for randomized sequences which, in the original implementation of ScanFold, is explicitly evaluated. This slow process has limited the rapid identification of ordered structures in large genomes/transcriptomes, which we seek to overcome in this current work introducing ScanFold 2.0. In this revised version of ScanFold, we no longer explicitly evaluate randomized sequence folding energy, but rather estimate it using a machine learning approach. For high randomization numbers, this can increase prediction speeds over 100-fold compared to ScanFold 1.0, allowing for the analysis of large sequences, as well as the use of additional folding algorithms that may be computationally expensive. In the testing of ScanFold 2.0, we re-evaluate the Zika, HIV, and SARS-CoV-2 genomes and compare both the consistency of results and the time of each run to ScanFold 1.0. We also re-evaluate the SARS-CoV-2 genome to assess the quality of ScanFold 2.0 predictions vs several biochemical structure probing datasets and compare the results to those of the original ScanFold program.

Abstract Cross‐ecosystem subsidies move substantial amounts of nutrients between ecosystems. Emergent aquatic insects are a particularly important prey source for riparian songbirds but may also move aquatic contaminants, such as mercury (Hg), to riparian food webs. While many studies focus on species that eat primarily emergent aquatic insects, we instead study riparian songbirds with flexible foraging strategies, exploiting both aquatic and terrestrial prey sources. The goal in this study is to trace reliance on aquatic prey sources and correlate it to Hg concentrations in common riparian arachnids (Families Tetragnathidae, Opiliones, and Salticidae) and songbirds (Common Yellowthroat Geothlypis trichas, Spotted Towhee Pipilo maculatus, Swainson's Thrush Catharus ustulatus, Song Sparrow Melospiza melodia, and Yellow Warbler Setophaga petechia). We used stable isotopes of δ13C and δ15N and Bayesian mixing models in MixSIAR to determine the reliance of riparian predators on aquatic prey sources. Using mixed effects models, we found that arachnid families varied in their reliance on aquatic prey sources. While songbird species varied in their reliance on aquatic prey sources, songbirds sampled earlier in the season consistently relied more on aquatic prey sources than those sampled later in the season. For both arachnids and songbirds, we found a positive correlation between the amount of the aquatic prey source in their diet and their Hg concentrations. While the seasonal pulse of aquatic prey to terrestrial ecosystems is an important source of nutrients to riparian species, our results show that aquatic prey sources are linked with higher Hg exposure. For songbirds, reliance on aquatic prey sources early in the breeding season (and subsequent higher Hg exposure) coincides with timing of egg laying and development, both of which may be impacted by Hg exposure.

This study examined the social networks of 26 postsecondary students with mobility and sensory disabilities regarding their perceptions of career preparation and career choice confidence. Social networks have been shown to contribute to postsecondary students' academic success and establishing a successful career for those with and without disabilities. This study examined the social capital resulting from social networks consisting of parents, family, friends, acquaintances (e.g., teachers, counselors, advisors), and interest groups or hobbies. Participants rated their perceptions of career preparation and career choice confidence twice during the study: once in the early weeks of a summer employment internship and after a career-focused presentation and internship completion. Measures of career preparation included self-rated abilities in (a) finding a job, (b) interviewing successfully, (c) keeping a job, and (d) resolving career accommodation challenges. Results showed that social capital contributed significantly to perceptions of career preparation. Career choice confidence remained stable suggesting satisfaction with their choice. A path analysis examined both career variables in conjunction with demographic factors, finding that social capital increased with age. Analyses suggested a number of other relationships between social capital, career perceptions, and demographic variables indicating complexities that warrant additional research.

Work-Integrated Learning (WIL) is a form of experiential learning that connects students with workplaces in their chosen field of study. WIL is a vital component of South Africa's teacher education, requiring pre-service teachers to complete a school practicum as part of their qualification. This research explores the question: What are effective WIL models for pre-service teachers in diverse South African contexts? The study reviews the practical and philosophical models of WIL and the concurrent model, examining their implementation in various universities as case studies. The study also identifies challenges, opportunities, and the need for support in South African WIL. The study adopts a social learning theory framework. The study informs how WIL effectively supports pre-service teachers and schools in diverse South African classroom. The study also discusses how WIL can promote education for sustainable development (ESD) and the achievement of the Sustainable Development Goals (SDGs).

Humans contain two nearly identical copies of Survival Motor Neuron genes, SMN1 and SMN2. Deletion or mutation of SMN1 causes spinal muscular atrophy (SMA), one of the leading genetic diseases associated with infant mortality. SMN2 is unable to compensate for the loss of SMN1 due to predominant exon 7 skipping, leading to the production of a truncated protein. Antisense oligonucleotide and small molecule-based strategies aimed at the restoration of SMN2 exon 7 inclusion are approved therapies of SMA. Many cis-elements and transacting factors have been implicated in regulation of SMN exon 7 splicing. Also, several structural elements, including those formed by a long-distance interaction, have been implicated in the modulation of SMN exon 7 splicing. Several of these structures have been confirmed by enzymatic and chemical structure-probing methods. Additional structures formed by inter-intronic interactions have been predicted by computational algorithms. SMN genes generate a vast repertoire of circular RNAs through inter-intronic secondary structures formed by inverted Alu repeats present in large number in SMN genes. Here, we review the structural context of the exonic and intronic cis-elements that promote or prevent exon 7 recognition. We discuss how structural rearrangements triggered by single nucleotide substitutions could bring drastic changes in SMN2 exon 7 splicing. We also propose potential mechanisms by which inter-intronic structures might impact the splicing outcomes.

Naturalistic Developmental Behavioral Interventions have been described as culturally responsive and family-friendly interventions, with research demonstrating improvements in children's development when receiving these services. Given the child-directed nature of Naturalistic Developmental Behavioral Interventions and the intervention's congruence with families' daily routines, many studies have examined the impact of Naturalistic Developmental Behavioral Interventions on family and family member quality of life. Therefore, we conducted a systematic review and meta-analysis to explore the relationship between Naturalistic Developmental Behavioral Interventions and family quality of life. Results suggest that the receipt of Naturalistic Developmental Behavioral Intervention services neither improved nor worsened family and family member quality of life. For those involved in the provision of Naturalistic Developmental Behavioral Intervention services, there is an immediate need to convey to families that children's improvements will likely not translate into improvements in family quality of life (osf.io/3ua5f).

Pharmacists promote vaccinations and challenge misconceptions about vaccine hesitancy, yet pharmacists’ knowledge of vaccine confidence has not been assessed. The objective of this study was to compare pharmacists’ knowledge of coronavirus disease 2019 (COVID-19) vaccine confidence before and after a live continuing education (CE) session. This pretest–posttest study evaluated the differences before and after a live CE session on COVID-19 vaccine confidence provided to pharmacists at a nationwide health technology company. Participants’ total pretest and posttest scores were compared using paired t-tests, while pretest and posttest scores for each item were compared using chi-squared tests. A Bonferroni correction was applied, resulting in an alpha level of 0.005. A total of 279 pharmacists participated in this study. After the CE session, mean knowledge scores increased (5.2 ± 1.5 to 7.4 ± 1.35, p < 0.0001). After the CE session, there was no significant increase in pharmacists’ knowledge about the approach that is not recommended when discussing vaccination beliefs with a patient (71.3% to 77.4%, p = 0.099), determinants of vaccine uptake (83.9% to 87.8%, p = 0.182), and social determinants of health that can influence vaccination rates (93.6% to 96.4%, p = 0.121). There was a significant change in pre- and posttest knowledge for the remaining seven items.

Limestone (calcite, CaCO3) is an abundant and cost-effective source of calcium oxide (CaO) for cement and lime production. However, the thermochemical decomposition of limestone (∼800 °C, 1 bar) to produce lime (CaO) results in substantial carbon dioxide (CO2(g)) emissions and energy use, i.e., ∼1 tonne [t] of CO2 and ∼1.4 MWh per t of CaO produced. Here, we describe a new pathway to use CaCO3 as a Ca source to make hydrated lime (portlandite, Ca(OH)2) at ambient conditions (p, T)-while nearly eliminating process CO2(g) emissions (as low as 1.5 mol. % of the CO2 in the precursor CaCO3, equivalent to 9 kg of CO2(g) per t of Ca(OH)2)-within an aqueous flow-electrolysis/pH-swing process that coproduces hydrogen (H2(g)) and oxygen (O2(g)). Because Ca(OH)2 is a zero-carbon precursor for cement and lime production, this approach represents a significant advancement in the production of zero-carbon cement. The Zero CArbon Lime (ZeroCAL) process includes dissolution, separation/recovery, and electrolysis stages according to the following steps: (Step 1) chelator (e.g., ethylenediaminetetraacetic acid, EDTA)-promoted dissolution of CaCO3 and complexation of Ca2+ under basic (>pH 9) conditions, (Step 2a) Ca enrichment and separation using nanofiltration (NF), which allows separation of the Ca-EDTA complex from the accompanying bicarbonate (HCO3 -) species, (Step 2b) acidity-promoted decomplexation of Ca from EDTA, which allows near-complete chelator recovery and the formation of a Ca-enriched stream, and (Step 3) rapid precipitation of Ca(OH)2 from the Ca-enriched stream using electrolytically produced alkalinity. These reactions can be conducted in a seawater matrix yielding coproducts including hydrochloric acid (HCl) and sodium bicarbonate (NaHCO3), resulting from electrolysis and limestone dissolution, respectively. Careful analysis of the reaction stoichiometries and energy balances indicates that approximately 1.35 t of CaCO3, 1.09 t of water, 0.79 t of sodium chloride (NaCl), and ∼2 MWh of electrical energy are required to produce 1 t of Ca(OH)2, with significant opportunity for process intensification. This approach has major implications for decarbonizing cement production within a paradigm that emphasizes the use of existing cement plants and electrification of industrial operations, while also creating approaches for alkalinity production that enable cost-effective and scalable CO2 mineralization via Ca(OH)2 carbonation.

PurposeTo assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).Patients and methodsThis was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.ResultsA total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).ConclusionTreatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Glycosylation is a predominant strategy plants use to fine-tune the properties of small molecule metabolites to affect their bioactivity, transport, and storage. It is also important in biotechnology and medicine as many glycosides are utilized in human health. Small molecule glycosylation is largely carried out by family 1 glycosyltransferases. Here, we report a structural and biochemical investigation of UGT95A1, a family 1 GT enzyme from Pilosella officinarum that exhibits a strong, unusual regiospecificity for the 3'-O position of flavonoid acceptor substrate luteolin. We obtained an apo crystal structure to help drive the analyses of a series of binding site mutants, revealing that while most residues are tolerant to mutations, key residues M145 and D464 are important for overall glycosylation activity. Interestingly, E347 is crucial for maintaining the strong preference for 3'-O glycosylation, while R462 can be mutated to increase regioselectivity. The structural determinants of regioselectivity were further confirmed in homologous enzymes. Our study also suggests that the enzyme contains large, highly dynamic, disordered regions. We showed that while most disordered regions of the protein have little to no implication in catalysis, the disordered regions conserved among investigated homologs are important to both the overall efficiency and regiospecificity of the enzyme. This report represents a comprehensive in-depth analysis of a family 1 GT enzyme with a unique substrate regiospecificity and may provide a basis for enzyme functional prediction and engineering.