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Electron superlattices allow the engineering of correlated and topological quantum phenomena. The recent emergence of moiré superlattices in two-dimensional heterostructures has led to exciting discoveries related to quantum phenomena. However, the requirement for the moiré pattern poses stringent limitations, and its potential cannot be switched on and off. Here, we demonstrate remote engineering and on/off switching of correlated states in bilayer graphene. Employing a remote Coulomb superlattice realized by localized electrons in twisted bilayer WS2, we impose a Coulomb superlattice in the bilayer graphene with period and strength determined by the twisted bilayer WS2. When the remote superlattice is turned off, the two-dimensional electron gas in the bilayer graphene is described by a Fermi liquid. When it is turned on, correlated insulating states at both integer and fractional filling factors emerge. This approach enables in situ control of correlated quantum phenomena in two-dimensional materials hosting a two-dimensional electron gas.

Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring to systematically investigate ECM composition (matreotype) during aging in C. elegans revealing three distinct collagen dynamics. Longevity interventions slow age-related collagen stiffening and prolong the expression of collagens that are turned over. These prolonged collagen dynamics are mediated by a mechanical feedback loop of hemidesmosome-containing structures that span from the exoskeletal ECM through the hypodermis, basement membrane ECM, to the muscles, coupling mechanical forces to adjust ECM gene expression and longevity via the transcriptional co-activator YAP-1 across tissues. Our results provide in-vivo evidence that coordinated ECM remodeling through mechanotransduction is required and sufficient to promote longevity, offering potential avenues for interventions targeting ECM dynamics.

Name that Neutrino is a citizen science project where volunteers aid in classification of events for the IceCube Neutrino Observatory, an immense particle detector at the geographic South Pole. From March 2023 to September 2023, volunteers did classifications of videos produced from simulated data of both neutrino signal and background interactions. Name that Neutrino obtained more than 128,000 classifications by over 1800 registered volunteers that were compared to results obtained by a deep neural network machine-learning algorithm. Possible improvements for both Name that Neutrino and the deep neural network are discussed.

The IceCube Neutrino Observatory instruments about 1ĝ€¯km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.

BackgroundCystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelination and remyelination.MethodsWildtype controls and Cst7-/- mice were intracranially (i.c.) infected with a sublethal dose of the neurotropic JHM strain of mouse hepatitis virus (JHMV), with disease progression and survival monitored daily. Viral plaque assays and qPCR were used to assess viral levels in CNS. Immune cell infiltration into the CNS and immune cell activation were determined by flow cytometry and 10X genomics chromium 3' single cell RNA sequencing (scRNA-seq). Spinal cord demyelination was determined by luxol fast blue (LFB) and Hematoxylin/Eosin (H&E) staining and axonal damage assessed by immunohistochemical staining for SMI-32. Remyelination was evaluated by electron microscopy (EM) and calculation of g-ratios.ResultsJHMV-infected Cst7-/- mice were able to control viral replication within the CNS, indicating that cystatin F is not essential for an effective Th1 anti-viral immune response. Infiltration of T cells into the spinal cords of JHMV-infected Cst7-/- mice was increased compared to infected controls, and this correlated with increased axonal damage and demyelination associated with impaired remyelination. Single-cell RNA-seq of CD45 + cells enriched from spinal cords of infected Cst7-/- and control mice revealed enhanced expression of transcripts encoding T cell chemoattractants, Cxcl9 and Cxcl10, combined with elevated expression of interferon-g (Ifng) and perforin (Prf1) transcripts in CD8 + T cells from Cst7-/- mice compared to controls.ConclusionsCystatin F is not required for immune-mediated control of JHMV replication within the CNS. However, JHMV-infected Cst7-/- mice exhibited more severe clinical disease associated with increased demyelination and impaired remyelination. The increase in disease severity was associated with elevated expression of T cell chemoattractant chemokines, concurrent with increased neuroinflammation. These findings support the idea that cystatin F influences expression of proinflammatory gene expression impacting neuroinflammation, T cell activation and/or glia cell responses ultimately impacting neuroinflammation and neurologic disease.

Situation models are known to help structure our experiences in our memory. But what are the ingredients of a situation model and to what degree do abstract event features contribute to updating of situation models? We manipulated abstract event feature dimensions and narrative specific factors in an experiment in which participants actively constructed a narrative from a random order of event descriptions. We investigated the influence of abstract factors (“degree of feature-change”, “event position”) on response speeding during a subsequent oddball task. Participants were faster for oddballs with a different degree of feature change, which interacted with whether the oddball was from within the same story or from another story. When looking at other-story-oddballs only, we found an interaction between position within the event structure and degree of feature change. Our results suggest that people use abstractions of event features which are important for the instantiation of a situation model.

BACKGROUND: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. MATERIALS AND METHODS: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. RESULTS: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. CONCLUSION: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans. UNLABELLED: Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

The function of the smooth muscle cells lining the walls of mammalian systemic arteries and arterioles is to regulate the diameter of the vessels to control blood flow and blood pressure. Here, we describe an in silico model, which we call the 'Hernandez-Hernandez model', of electrical and Ca2+ signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca2+ signaling during the development of myogenic tone in arterial blood vessels. Although experimental data suggest that KV1.5 channel currents have similar amplitudes, kinetics, and voltage dependencies in male and female myocytes, simulations suggest that the KV1.5 current is the dominant current regulating membrane potential in male myocytes. In female cells, which have larger KV2.1 channel expression and longer time constants for activation than male myocytes, predictions from simulated female myocytes suggest that KV2.1 plays a primary role in the control of membrane potential. Over the physiological range of membrane potentials, the gating of a small number of voltage-gated K+ channels and L-type Ca2+ channels are predicted to drive sex-specific differences in intracellular Ca2+ and excitability. We also show that in an idealized computational model of a vessel, female arterial smooth muscle exhibits heightened sensitivity to commonly used Ca2+ channel blockers compared to male. In summary, we present a new model framework to investigate the potential sex-specific impact of antihypertensive drugs.

BackgroundPatients who undergo lumbar discectomy may experience ongoing lumbosacral radiculopathy (LSR) and seek spinal manipulative therapy (SMT) to manage these symptoms. We hypothesized that adults receiving SMT for LSR at least one year following lumbar discectomy would be less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT, over two years' follow-up.MethodsWe searched a United States network of health records (TriNetX, Inc.) for adults aged ≥ 18 years with LSR and lumbar discectomy ≥ 1 year previous, without lumbar fusion or instrumentation, from 2003 to 2023. We divided patients into two cohorts: (1) chiropractic SMT, and (2) usual care without chiropractic SMT. We used propensity matching to adjust for confounding variables associated with lumbar spine reoperation (e.g., age, body mass index, nicotine dependence), calculated risk ratios (RR), with 95% confidence intervals (CIs), and explored cumulative incidence of reoperation and the number of SMT follow-up visits.ResultsFollowing propensity matching there were 378 patients per cohort (mean age 61 years). Lumbar spine reoperation was less frequent in the SMT cohort compared to the usual care cohort (SMT: 7%; usual care: 13%), yielding an RR (95% CIs) of 0.55 (0.35-0.85; P = 0.0062). In the SMT cohort, 72% of patients had ≥ 1 follow-up SMT visit (median = 6).ConclusionsThis study found that adults experiencing LSR at least one year after lumbar discectomy who received SMT were less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT. While these findings hold promise for clinical implications, they should be corroborated by a prospective study including measures of pain, disability, and safety to confirm their relevance. We cannot exclude the possibility that our results stem from a generalized effect of engaging with a non-surgical clinician, a factor that may extend to related contexts such as physical therapy or acupuncture.RegistrationOpen Science Framework ( https://osf.io/vgrwz ).

Layered double hydroxide (LDH) phases that form during cement hydration can incorporate a variety of interlayer anions in their interlayer positions. Here, a range of phases of general formula [MII(1−x)MIII(x)(OH)2][An−]x/n·zH2O were synthesized, where MII = Mg2+ (hydrotalcite) or Ca2+ (AFm), MIII = Al3+ such that [MII/Al] = 2 (Ca and Mg, atomic units) or 3 (Mg only), and A = Cl−, Br−, or I−. All the synthesized phases were characterized to assess their composition, density, and crystal structure. By approach from undersaturation, the solubility data of these compounds was measured at 5, 25, and 60°C. This thermochemical data was used to successfully model their formation using thermodynamic modeling and to infer the fields of stability of these compounds for conditions of relevance to cementitious systems. It is seen that halide-containing hydrotalcite phases strongly compete with hydroxide-containing hydrotalcite, with the latter prevailing at high pH. In contrast, halide-containing AFm compounds are more stable compared with hydroxide-containing AFm compositions.

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.

The LIGO/Virgo collaboration published the catalogs GWTC-1, GWTC-2.1, and GWTC-3 containing candidate gravitational-wave (GW) events detected during its runs O1, O2, and O3. These GW events can be possible sites of neutrino emission. In this paper, we present a search for neutrino counterparts of 90 GW candidates using IceCube DeepCore, the low-energy infill array of the IceCube Neutrino Observatory. The search is conducted using an unbinned maximum likelihood method, within a time window of 1000 s, and uses the spatial and timing information from the GW events. The neutrinos used for the search have energies ranging from a few GeV to several tens of TeV. We do not find any significant emission of neutrinos, and place upper limits on the flux and the isotropic-equivalent energy emitted in low-energy neutrinos. We also conduct a binomial test to search for source populations potentially contributing to neutrino emission. We report a nondetection of a significant neutrino-source population with this test.

Abstract Background Language and cultural discordance refer to when a physician and patient do not share the same language or culture. This can create barriers to providing high-quality care at the end-of-life (EoL). This study explores the intersections of language, culture, geography, and care model in EoL care from the perspectives of palliative care physicians. Methods In this exploratory-descriptive qualitative study, semi-structured interviews (1-h) were conducted virtually between July and November 2023. We interviewed 16 family physicians with experience providing linguistic and/or culturally discordant palliative/EoL care in various urban, suburban, and rural regions of Ontario, who practiced at community and hospital outpatient clinics, home-based care, or long-term care homes. We used reflexive thematic analysis to identify themes across the interviews guided by the intersectionality theoretical framework. Results We identified three themes 1) Visible barriers to care access due to the inability to communicate accurate information and insufficient time spent during appointments with patients; 2) Invisible barriers to care access, shaped by the Eurocentric approach to palliative care and physicians’ lack of awareness on cultural discordance; 3) Workplace supports that currently exist and interventions that physicians would like to see. Community physicians following fee-for-service models were less likely to have access to professional interpreter services. Physicians in long-term care emphasized resource limitations to providing culturally-appropriate care environments. Conclusion Cultural discordance required awareness of personal biases, while language discordance hindered basic communication. These findings will be useful in informing clinical practice guidelines and mobilizing policy-level change to improve palliative/EoL care for patients from linguistic and cultural minority groups.

Abstract Precipitation channelled down tree stems (stemflow) or into drip points of ‘throughfall’ beneath trees results in spatially concentrated inputs of water and chemicals to the ground. Currently, these flows are poorly characterised due to uncertainties about which branches redirect rainfall to stemflow or throughfall drip points. We introduce a graph theoretic algorithm that ‘prunes’ quantitative structural models of trees (derived from terrestrial LiDAR) to identify branches contributing to stemflow and those contributing to throughfall drip points. To demonstrate the method's utility, we analysed two trees with similar canopy sizes but contrasting canopy architecture and rainfall partitioning behaviours. For both trees, the branch ‘watershed’ area contributing to stemflow (under conditions assumed to represent moderate precipitation intensity) was found to be only half of the total ground area covered by the canopy. The study also revealed significant variations between trees in the number and median contribution areas of modelled throughfall drip points (69 vs. 94 drip points tree−1, with contributing projected areas of 28.6 vs. 7.8 m2 tree−1, respectively). Branch diameter, surface area, volumes and woody area index of components contributing to stemflow and throughfall drip points may play a role in the trees' differing rainfall partitioning behaviours. Our pruning algorithm, enabled by the proliferation of LiDAR observations of canopy structure, promises to enhance studies of canopy hydrology. It offers a novel approach to refine our understanding of how trees interact with rainfall, thereby broadening the utility of existing LiDAR data in environmental research.

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 Bruton’s tyrosine kinase (BTK) is an intracellular signaling enzyme that regulates B-lymphocyte and myeloid cell functions. Due to its involvement in both innate and adaptive immune compartments, BTK inhibitors have emerged as a therapeutic option in autoimmune disorders such as multiple sclerosis (MS). Brain-penetrant, small-molecule BTK inhibitors may also address compartmentalized neuroinflammation, which is proposed to underlie MS disease progression. BTK is expressed by microglia, which are the resident innate immune cells of the brain; however, the precise roles of microglial BTK and impact of BTK inhibitors on microglial functions are still being elucidated. Research on the effects of BTK inhibitors has been limited to rodent disease models. This is the first study reporting effects in human microglia. Methods Here we characterize the pharmacological and functional properties of fenebrutinib, a potent, highly selective, noncovalent, reversible, brain-penetrant BTK inhibitor, in human microglia and complex human brain cell systems, including brain organoids. Results We find that fenebrutinib blocks the deleterious effects of microglial Fc gamma receptor (FcγR) activation, including cytokine and chemokine release, microglial clustering and neurite damage in diverse human brain cell systems. Gene expression analyses identified pathways linked to inflammation, matrix metalloproteinase production and cholesterol metabolism that were modulated by fenebrutinib treatment. In contrast, fenebrutinib had no significant impact on human microglial pathways linked to Toll-like receptor 4 (TLR4) and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) signaling or myelin phagocytosis. Conclusions Our study enhances the understanding of BTK functions in human microglial signaling that are relevant to MS pathogenesis and suggests that fenebrutinib could attenuate detrimental microglial activity associated with FcγR activation in people with MS.

Abstract This study investigates the impact of habitual late calorie intake on glucose metabolism in adults with overweight or obesity and diet or metformin-controlled prediabetes or type 2 diabetes independently of body weight, fat mass, energy intake or diet composition. Participants (n = 26) were classified as Later Eaters (LE) if ≥45% daily calories were consumed after 5 pm and Early Eaters (EE) if not, based on daily caloric intake assessed over 2-wk. EE and LE did not differ in anthropometrics or daily energy intake, but LE consumed more carbohydrates (p = 0.038) and fats (p = 0.039) after 5 pm. Fasting glucose, insulin, and C-peptide did not differ between groups but LE exhibited higher glucose concentrations after an oral glucose tolerance test (p = 0.001), even after adjusting for body weight, fat mass, energy intake and diet composition (p

Abstract The use of supramolecular assemblies in pharmaceuticals has garnered significant interest. Recent studies have shown that the activities of antibacterial agents can be enhanced through complexation with cyclic oligomers and metal ions. Notably, these complexes sometimes possess greater therapeutic properties than the parent drugs. To develop microbiologically potent supramolecular drugs, the complexation of macrocyclic hosts with fluoroquinolone (FQ) antibiotics was investigated. FQs are a successful family of antibiotics that target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, leading to bacterial cell death through the inhibition of DNA synthesis. However, antibiotic resistance resulting from the repeated use of FQs over time has limited their effectiveness against resistant pathogens. To overcome this issue, the encapsulation of FQs in polyphenolic macrocycles was investigated. This study highlights resorcinarene, a polyphenolic host with antibacterial properties, and its ability to chemically interact with FQs. The inclusion complexation process was analyzed using NMR and FTIR techniques. The binding constants determined by 1H-NMR titration revealed that levofloxacin forms more stable complexes with resorcinarene than with β-cyclodextrin, which aligned with MD simulations. Assessment of the geometric characteristics of the inclusion complexes using 2D NMR analysis confirmed that different moieties of various FQs can fit into a single host cavity and improve activity against gram-negative bacteria. Overall, these findings suggest that encapsulation in polyphenolic macrocycles is a promising strategy for utilizing FQs against antibiotic-resistant bacteria.

Abstract Background Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data. Results An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae. Conclusions Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.

Abstract Background Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that cause chronic lung disease. Rates of NTM pulmonary disease (NTM PD) have increased over the last several decades, yet national estimates in the United States (US) have not been assessed since 2015. Methods We used a nationally representative population of Medicare beneficiaries aged ≥ 65 years to assess rates of NTM PD in a high-risk population from 2010 to 2019. Poisson generalized linear models were used to assess the annual percent change in incidence in the overall population and among key demographic groups such as sex, geography, and race/ethnicity. We evaluated the relative prevalence of various comorbid conditions previously found to be associated with NTM PD. Results We identified 59,724 cases of incident NTM PD from 2010 to 2019 from an annual mean population of 29,687,097 beneficiaries, with an average annual incidence of 20.1 per 100,000 population. NTM PD incidence was overall highest in the South and among women, Asian individuals, and persons aged ≥ 80 years relative to other studied demographic groups. The annual percent change in NTM PD incidence was highest in the Northeast, at 6.5%, and Midwest, at 5.9%, and among women, at 6.5%. Several comorbid conditions were highly associated with concurrent NTM diagnosis, including allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis. Conclusions Here we provide current estimates of NTM PD incidence and prevalence and describe increasing trends in the US from 2010 to 2019. Our study suggests a need for improved healthcare planning to handle an increased future caseload, as well as improved diagnostics and therapeutics to better detect and treat NTM PD in populations aged ≥ 65 years.

Abstract The last decade has seen significant improvements in our understanding of skyrmions current induced dynamics, along with their room temperature stabilization, however, the impact of local material inhomogeneities still remains an issue that impedes reaching the regime of steady state motion of these spin textures. Here, we study the spin-torque driven motion of skyrmions in synthetic ferrimagnetic multilayers with the aim of achieving high mobility and reduced skyrmion Hall effect. We consider Pt|Co|Tb multilayers of various thicknesses with antiferromagnetic coupling between the Co and Tb magnetization. The increase of Tb thickness in the multilayers reduces the total magnetic moment and increases the spin-orbit torques allowing to reach velocities up to 400 ms−1 for skyrmions with diameters of about 160 nm. We demonstrate that due to reduced skyrmion Hall effect combined with the edge repulsion of the magnetic track, the skyrmions move along the track without any transverse deflection. Further, by comparing the field-induced domain wall motion and current-induced skyrmion motion, we demonstrate that the skyrmions at the largest current densities present all the characteristics of a dynamical flow regime.

Due to increasing digitalization, most companies have added online retail as a new business model (BM) separate from their initial physical BM, requiring them to manage a portfolio of BMs. The literature points out that companies choose between a separation or integration strategy to manage their multiple BMs. However, business cases show that companies adopting a separation strategy may then plan for a possible integration strategy. Despite the growing knowledge in the BM portfolio literature, scholars and practitioners still lack a comprehensive understanding of the integration process of two BMs that were initially managed separately. This qualitative research draws on a cumulative multiple case study of five retailers to analyze how incumbent firms with different BMs manage their integration. We show that these firms pivoted the management of their BM portfolio.The notion of pivoting has been studied from the perspective of a single BM. In this research, we demonstrate that the process of pivoting also applies to the management of several BMs. Our results provide a generic model of the BM integration process that underlines barriers and enabling pivoting factors. Finally, by considering pivoting at this corporate level, our research adds to the ongoing discussion in strategic management regarding the way companies manage the dynamics of their BM portfolio.

The ocean's biological carbon pump plays a major role in climate and biogeochemical cycles. Photosynthesis at the surface produces particles that are exported to the deep ocean by gravity. Sediment traps, which measure deep-carbon fluxes, help to quantify the carbon stored by this process. However, it is challenging to precisely identify the surface origin of particles trapped thousands of meters deep due to the influence of ocean circulation on the sinking path of carbon. In this study, we conducted a series of numerical Lagrangian experiments in the Porcupine Abyssal Plain region of the North Atlantic and developed a machine learning approach to predict the surface origin of particles trapped in a deep-ocean sediment trap. Our numerical experiments support the predictive performance of the machine learning approach, and surface conditions appear to provide valuable information for accurately predicting the source area, suggesting a potential application with satellite data. We also identify factors that potentially affect prediction efficiency, and we show that the best predictions are associated with low kinetic energy and the presence of mesoscale eddies above the trap. This new tool could provide a better link between satellite-derived sea surface observations and deep-ocean sediment trap measurements, ultimately improving our understanding of the biological-carbon-pump mechanism.

Administrative decisions mediate whether the millions who turn to the state for social services annually can access the assistance they need. We introduce the concept of intersectional burdens—which describes how a person’s social location (including race, class, gender, age, and ability) shapes their access and use of state benefits and programs—to account for the ways mutually reinforcing systems structure experiences with the state and to better understand how inequalities are experienced, reproduced, and resisted. We illustrate the intersectional nature of associated costs by drawing on a random stratified sample of sixty-one Black, Latinx, and White women’s experiences from the American Voices Project. We find that individuals who seek public safety net assistance do not experience administrative burdens in the same way or to the same degree and that social location substantively affects how people navigate administrative burdens in public income assistance processes, health-care systems, and housing experiences.

This study aimed to achieve the highest percentage removal of dibenzothiophene (DBT), quinoline (QUI), and indole (IND) adsorbed by double-impregnated modified activated carbon (MAC). Modification of commercial activated carbon (AC) by sulphuric acid (H2SO4) of 15%, 30%, 45%, 60%, and 75% w/v followed by subsequent 1 zinc chloride (ZnCl2): 1 AC impregnation ratio and activated at 500 oC in a muffle furnace under self-generated atmosphere for an hour. The determination of optimized MAC was identified through the highest removal rate of DBT, QUI, and IND from adsorption experiments which were analysed using an ultraviolet-visible (UV-Vis) spectrophotometer. It was found that DBT and IND showed a removal high percentage of up to 86.23% and 82.77% respectively by using 75% H2SO4 with ZnCl2 MAC. Meanwhile, QUI favoured 30% H2SO4 with ZnCl2 MAC with a removal percentage of 33.17% which was still higher than unmodified AC. Physical and chemical properties such as the morphological structure, elemental analysis, porosity, pore size, surface functional group, percentage yield, pH, bulk density, content, ash content, and iodine number were studied for the optimized MAC. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy and Fourier transform infrared spectroscopy (FTIR) were used to characterize the MAC. Both MACs showed high percentage yields of 72.08% and 71.13% for 30% and 75% H2SO4 and ZnCl2 MAC respectively. Meanwhile, the pH was between the ranges of 5.36-5.53 for both MACs. Bulk densities were also favourable while the moisture and ash content were within acceptable limits. Iodine numbers for 30% and 75% H2SO4 and ZnCl2 MAC were 857 and 861 mg/g respectively, hence indicating that the MAC achieved high porosity and good adsorption performance. Langmuir, Freundlich, and Temkin adsorption isotherm models as well as pseudo-first order (PFO) and pseudo-second order (PSO) kinetic models were considered for understanding the adsorption mechanisms. The study revealed that DBT, QUI, and IND removal processes, followed the Langmuir adsorption isotherm model with correlation coefficients, R2 of 0.9905, 0.9791, and 0.9964 respectively. Moreover, the adsorption kinetic data of DBT, QUI, and IND provided a better fitting to the PSO kinetic model with R2 of 0.9992, 0.9987, and 0.9998 respectively. According to the Langmuir isotherm model and PSO kinetic model, the adsorption mechanisms of DBT QUI and IND were chemisorbed under monolayer formations.

Abstract Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue’s codon and codon pair usage landscape, we have established a novel resource—Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

Purpose: This study aims to increase the understanding of the starting points and presuppositions of organizational learning (OL) processes in a hospital's surgical department based on the existing theory of OL and to make visible the practical possibilities of the theory in this context. Design/methodology/approach: The study was conducted as a case study. The data were collected from personnel of the hospital's surgical department and consisted of 26 thematic interviews. The data were analyzed using qualitative theory-driven content analysis. Findings: This study found different starting points for both employee-oriented and organization-oriented learning processes that could potentially progress to different levels of the organization: from individuals to a wider group or from a large group to an individual. The starting point of employee-oriented learning processes was depicted as everyday life problems or situations or was based on the person's interest. The starting points of organization-oriented learning processes were described as achieving or maintaining the organization's expected skill levels, pursuing continuous development or pursuing the organization's specific development needs. Different kinds of presuppositions were also located within the OL processes. Originality/value: This study produced new practice-based knowledge about the starting points of OL processes and their presuppositions. In health-care organizations, learning is especially important due to intensive and complex changes, and this study provides empirical evidence on how to enhance learning.

Anatomy instructional methods varied widely during the COVID-19 pandemic and programs are assessing innovations for retention. Learning preferences were assessed among medical students dichotomized as elective dissectors (ED) or non-dissectors (ND) during the COVID-19 partial re-opening in 2020 (preclinical) and again in 2022 after clinical exposure (post-clinical) to assess the viability of elective dissection post-pandemic. A mixed-method approach was used for the assessment of test scores, learning preference surveys, learning activities rankings, and thematic analyses. No significant differences occurred in anatomy examination scores. Dissection was considered useful by both preclinical groups but significantly more so by ED, while the presence of an instructor was significantly preferred by ED although a majority of ND agreed. Elective dissection was significantly preferred by ND but also by a large minority of ED students. Pre- and post-clinical ND believed that elective dissection offered more academic flexibility, did not hinder clinical learning, and did not negatively impact medical education. The corresponding ED stated that confidence improved, clinical experiences were enhanced, and dissection was irreplaceable. Preclinical ND preferred self-learning, while ED students preferred online learning, but these differences largely disappeared post-clinically. Learning activity rankings were not significantly different among all groups (ND, ED, preclinical, and post-clinical). A hybrid laboratory with a virtual learning environment ranked highest across groups and preferences increased over time suggesting that students benefited from this instructional method during clinical exposure. The absence of laboratory experience ranked lowest, and preference decreased over time suggesting that anatomy dissection is valued.