Search

Aims: Psychosocial impacts of early continuous glucose monitoring (CGM) initiation in youth soon after type 1 diabetes diagnosis are underexplored. We report parent/guardian and youth patient‐reported outcomes (PROs) that measure psychosocial states for families in 4T Study 1. Materials and Methods: Of the 133 families in the 4T Study 1, 132 parent/guardian and 66 youth (≥11 years) were eligible to complete PROs. PROs evaluated included diabetes distress, global health, diabetes technology attitudes and CGM benefits/burden scales. Temporal trends of PROs were assessed via generalised linear mixed effects regression. Sociodemographic and clinical characteristics associated with PROs were evaluated. Psychosocial associations were evaluated by regressing parental distress on youth distress. Results: PRO completion rates were 85.6% and varied between parent/guardian and youth. Throughout the study, parent/guardian and youth distress remained low and youth had increased technology acceptance (p = 0.046). Each additional month of CGM use was associated with a 14% decrease in the odds of experiencing diabetes distress (aOR = 0.86, 95% CI [0.76, 0.99], p = 0.029). Additionally, higher time‐in‐range was associated with decreased diabetes distress (p = 0.048). Age, diabetic ketoacidosis at diagnosis, gender, ethnicity, insurance status and language spoken were not associated with PROs. Conclusions: Initiation of CGM shortly after type 1 diabetes diagnosis does not have unintended negative psychological consequences. Longer duration of CGM use was associated with decreased youth distress and technology acceptance increased throughout the study. [ABSTRACT FROM AUTHOR]

Summary: Here, we investigated the molecular genetic basis of mite domatia, structures on the underside of leaves that house mutualistic mites, and intraspecific variation in domatia size in Vitis riparia (riverbank grape).Domatia and leaf traits were measured, and the transcriptomes of mite domatia from two genotypes of V. riparia with distinct domatia sizes were sequenced to investigate the molecular genetic pathways that regulate domatia development and intraspecific variation in domatia traits.Key trichome regulators as well as auxin and jasmonic acid are involved in domatia development. Genes involved in cell wall biosynthesis, biotic interactions, and molecule transport/metabolism are upregulated in domatia, consistent with their role in domatia development and function.This work is one of the first to date that provides insight into the molecular genetic bases of mite domatia. We identified key genetic pathways involved in domatia development and function, and uncovered unexpected pathways that provide an avenue for future investigation. We also found that intraspecific variation in domatia size in V. riparia seems to be driven by differences in overall leaf development between genotypes. [ABSTRACT FROM AUTHOR]

Background: Laryngeal chondroradionecrosis (LCRN) is a rare but severe complication of radiation therapy. The study aimed to review the management of LCRN and evaluate the clinical benefit of hyperbaric oxygen therapy (HBOT). Methods: We retrospectively analyzed all radiation‐induced LCRN patients between 2006 and 2019 at a tertiary medical center. Diagnosis was based on signs and symptoms of Chandler's classification, imaging, and/or histopathology report. The primary outcome was improvement in Chandler's grade after HBOT. Results: Of 678 irradiated laryngeal cancer patients, 29 (4.3%) were diagnosed with LCRN. The most common primary management was tracheostomy with intravenous steroids and antibiotics (59%). Ten patients received HBOT (34.5%), and six underwent total laryngectomy (21%). In HBOT‐treated patients, Chandler's grade significantly improved from a median of 4 (range 2–4) to 2.5 (range 1–4; p = 0.005). Conclusions: HBOT may benefit in the management of patients with persistence and unresponsive symptoms of LCRN following radiation therapy for laryngeal SCC. [ABSTRACT FROM AUTHOR]

We applied state‐of‐the‐art seismic processing and imaging techniques to crustal‐scale seismic reflection data from the BELCORP/DEKORP87 lines 1A and 1B. The aim of the presented work was to identify structural evidence in the Earth's crust and upper mantle related to the ongoing magmatic activity in the Quaternary West Eifel Volcanic Field (WEVF) in Central Europe where ca. 70 eruptions happened since 65 ka. Following careful signal‐processing, Fresnel volume migration was applied and yielded images with exceptionally strong lithospheric reflectors in the SE of the WEVF. Sparse signal representation revealed numerous reversed polarities. Using petrophysical relations, the corresponding reflections can be interpreted as reflections from melt and/or volatile‐bearing (supercritical CO2) zones which appear as horizontally elongated lens‐shaped sills. Furthermore, we observed reflections with similarly inverted polarities from structural features located around the Moho at of 31 km depth, indicating fluids or melts from the uppermost mantle and supporting magmatic underplating models. Plain Language Summary: We re‐processed a more than 35 years‐old seismic dataset with new processing methods to search for active magmatic structures in the Earth's crust and upper mantle, Western Germany. There, in the Eifel mountains, volcanic eruptions happened until just 11,000 years ago. This young age, current volcanic gas emissions, current wide‐spread uplift, and hints of magmatic processes at depth indicate that the volcanic processes are dormant but not extinct. A possible reawaking of volcanic eruptions would present a significant hazard in Central Europe, with the potential for severe impact on air traffic for example, The reprocessing of seismic data finds strongly reflecting structures at depths of 10–30 km beneath the youngest part of the West Eifel Volcanic Field. The observation of reversed signal amplitudes is a strong indication that some reflectors consist of magmatic melt, fluids, or gas. Thus, future hazard assessments should consider the presence of this magmatic material in the Earth's crust. Key Points: Quaternary volcanism in the Eifel region, Germany, still has active magmatic structures in the lower lithosphereDeep seismic reflection imaging reveals a rich inventory of sill‐like structures beneath a volcanic field in the EifelReflections with negative‐amplitude polarity from 15 km depth and the Moho are related to upwelling melts or fluids from the upper mantle [ABSTRACT FROM AUTHOR]

The value of place‐based initiatives in the design and delivery of human services has long been recognised, but the need for hybrid service delivery to clients—that is any combination of online and in‐person modalities—has become more apparent in the wake of the COVID‐19 pandemic. At face value, there may be a perceived contradiction between the reliance on geographical place in place‐based initiatives and online service delivery. Yet, it is inevitable that human services will increasingly be delivered in a hybrid form—even in the context of place‐based initiatives. This exploratory study included a modified Delphi method and deliberative panels with policymakers, service providers, and academics with experience and/or knowledge of hybrid place‐based initiatives. A central finding was the lack of respondents' shared understanding and ability to link the three central intersecting ideas being examined in this research: 'hybrid' and 'place‐based' and 'human services'. The principles underpinning place‐based initiatives need to be retained when incorporating online service delivery within place‐based initiatives. This reflects the need to develop a shared lexicon on hybrid place‐based initiatives and more creative understandings and interpretations of the relationship between people and place. Points for practitioners: Increasingly, human services are being designed, implemented, and delivered through place‐based initiatives, yet the success of place‐based initiatives often relies on more than just face‐to‐face service delivery.The COVID‐19 pandemic shifted many human services online, but how this has impacted on place‐based initiatives and their defining features of co‐location, collaboration, and co‐design has not been explored to date.Following the pandemic, both service providers and clients see the benefit in retaining and integrating face‐to‐face and online services, without understanding how best to achieve this with place‐based initiatives.This study draws on practices developed during the pandemic to understand how to best provide hybrid services (integrating in‐person and online services) and shows the relevance of hybrid services to place‐based initiatives and considerations moving forward. [ABSTRACT FROM AUTHOR]

Invasive alien species (IAS) are one of the most serious threats to global biodiversity and one of the leading causes of federal protection required for native species under the United States Endangered Species Act (ESA). Our goal was to document how IAS impact threatened and endangered species (T&ES) under the ESA to improve recovery efforts. We reviewed Federal Register listing decisions for 1,545 T&ES listed under the ESA and found that 58% were impacted by IAS. Pacific Island T&ES (97%) face greater threats from IAS compared to Mainland (38%) and Atlantic Island T&ES (22%), but the number of IAS impacting T&ES has increased over time in all 3 geographic areas, except for animals on Atlantic Islands. On Pacific Islands, we found that IAS impacted T&ES most through adverse habitat modification and competition, mainly through invasive plants. Negative interactions caused by IAS on the Mainland were mainly from invasive fish and plants, while on the Atlantic Islands they were caused by invasive mammals and plants. The IAS causing the greatest number of negative interactions included rats (Rattus), wild pigs (Sus), goats (Capra), fish (e.g., Lepomis and Micropterus), and various genera of plants (e.g., Schinus, Rubus, and Psidium). Based on our findings, immediate actions are needed to protect native biodiversity in the U.S. from IAS, especially on Pacific Islands. Such management actions include eradication of IAS, restoration of native habitat, development of robust policies that aim to prevent the further spread and establishment of IAS, and effective decision support tools. These actions will require coordinated leadership to improve recovery of T&ES, especially given the synergistic impacts of international trade and climate change. [ABSTRACT FROM AUTHOR]

Purpose: This work proposes a "hybrid" RF pulse design method for parallel transmit (pTx) systems to simultaneously control flip angle and root‐mean‐squared B1+$$ {\mathrm{B}}_1^{+} $$ (B1rms$$ {B}_1^{\mathrm{rms}} $$). These pulses are generally only designed for flip angle, however, this can lead to uncontrolled B1rms$$ {B}_1^{\mathrm{rms}} $$, which then leads to variable magnetization transfer (MT) effects. We demonstrate the hybrid design approach for quantitative imaging where both flip angle and B1rms$$ {B}_1^{\mathrm{rms}} $$ are important. Theory and Methods: A dual cost function optimization is performed containing the normalized mean squared errors of the flip angle and B1rms$$ {B}_1^{\mathrm{rms}} $$ distributions weighted by a parameter λ$$ \lambda $$. Simulations were conducted to study the behavior of both properties when simultaneously optimizing them. In vivo experiments on a 7T MRI system with an 8‐channel pTx head coil were carried out to study the effect of the hybrid design approach on variable flip angle R1$$ {\mathrm{R}}_1 $$(= 1/T1) mapping. Results: Simulations showed that both flip angle and B1rms$$ {B}_1^{\mathrm{rms}} $$ can be homogenized simultaneously without detriment to either when compared to an individual optimization. By homogenizing flip angle and B1rms$$ {B}_1^{\mathrm{rms}} $$, R1$$ {\mathrm{R}}_1 $$ maps were more uniform (coefficient of variation 6.6% vs. 13.0%) compared to those acquired with pulses that only homogenized flip angle. Conclusion: The proposed hybrid design homogenizes on‐resonance MT effects while homogenizing the flip angle distribution, with only a small detriment in the latter compared to a pulse that just homogenizes flip angle. This improved R1$$ {\mathrm{R}}_1 $$ mapping by controlling incidental MT effects, yielding more uniform R1$$ {\mathrm{R}}_1 $$ maps. [ABSTRACT FROM AUTHOR]

Fe‐based mica minerals usually display two opposing magnetic ground states, either they behave as spin‐glasses or as layered ferrimagnets. No definite reason has been proposed as an explanation for this duality. This conundrum is unraveled by comparing the synthetic micas KFe3[MGe3]O10X2 with M═Fe and Ga, X═OH− and F−. Neutron diffraction demonstrates a 2D to 3D magnetic transition in KFe3[FeGe3]O10(OH)2 while just hints or no order at all are observed for the fluorides with M═Fe and Ga respectively. The 3D transition is triggered by the presence of iron in the intralayer tetrahedra. DFT+U calculations show that the magnetic exchange couplings between the previously believed solely magnetic octahedral layers would otherwise be frustrated without this intralayer iron. [ABSTRACT FROM AUTHOR]

This work investigates the application of poly(3,4‐ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) with polyethylene oxide (PEO) in lithium batteries (LIBs). This composite film comprising PEDOT:PSS and PEO was 3D printed onto a carbon nanofiber (CNF) substrate to serve as a layer between the polypropylene (PP) separator and the lithium anode in LIBs. The resulting CNF‐PEDOT:PSS‐PEO film exhibited superior mechanical and thermal properties compared to conventional PP separators. Mechanical tests revealed a high Young's modulus and puncture strength for the composite film. Thermal stability tests indicated that the CNF‐PEDOT:PSS‐PEO film remained stable at higher temperatures compared to the commercial PP separator, and combustion tests confirmed its superior fire‐resistance properties. In terms of conductivity, the composite film maintained comparable ionic conductivity to the commercial PP separator. Electrochemical tests demonstrated that LIBs incorporating the CNF‐PEDOT:PSS‐PEO film exhibited slight improvement in cycling performance, with a 7.9 % increase in long‐term cycling capacity compared to LIBs using only the commercial PP separator. These findings indicate that the developed CNF‐PEDOT:PSS‐PEO composite film holds promise to improve safety, while maintaining the electrochemical performance of LIBs by reducing dendrite formation and enhancing thermal stability. [ABSTRACT FROM AUTHOR]

A dog presented with deep pyoderma on the paw, following treatment with ciclosporin and prednisone for immune‐mediated haemolytic anaemia. Cytological evaluation, skin biopsy, aerobic culture, next‐generation DNA sequencing and PCR were used to detect the first reported case of Burkholderia gladioli in a dog. [ABSTRACT FROM AUTHOR]

A ‘no‐ownership’ or ‘no‐self theory’ holds that there is no proper subject of experience; the ownership of experience can only be accounted for by invoking a sub‐personal entity. In the recent self‐versus‐no‐self debate, it is widely assumed that the no‐ referent view of ‘I’, which is closely associated with Wittgenstein and G. E. M. Anscombe, implies a no‐ownership theory of experience. I spell out this assumption with regard to both non‐reflective and reflective consciousness and show that it is false. If the so‐called ‘self’ is an individual, the person, nothing more is required for the ownership of sensations than the non‐reflective experiencing, undergoing, or suffering of them, whereas the sense of ‘ownership’ of reflective consciousness varies according to the type of ‘I’‐thought in question. Ownership of ‘I’‐thoughts about one’s own actions, for one thing, is a matter of being able to fit future actions to them or answer questions as to why one is doing what one does. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to determine the movement patterns of three abundant salmonids—Brown Trout Salmo trutta, Mountain Whitefish Prosopium williamsoni, and Rainbow Trout Oncorhynchus mykiss—in the Smith River watershed of Montana. Methods: We tagged 7172 fish with passive integrated transponder (PIT) tags, monitored their movements past 15 stationary PIT arrays over 4 years, and located tagged fish between arrays by conducting mobile surveys. Result: Movement patterns varied seasonally, among species, and among locations. Movement was greatest in the middle portion of the watershed, which included a pristine main‐stem canyon and lower reaches of major tributaries. Fish rarely left the canyon, but movement into the canyon from other regions was common. Mountain Whitefish were most likely to move, and Brown Trout were least likely to move. Most fish travelled less than 10 km, but some fish travelled over 100 km. Distinct movement patterns were not evident; rather, a continuous spectrum of movement behaviors was apparent. Movements by Mountain Whitefish and Rainbow Trout increased during their spawning periods. Movements peaked when mean daily water temperatures were between 11.3 and 17.1°C. Conclusion: Movements were diverse and probably contributed to metapopulation dynamics, population resiliency, and species diversity. Fish movements along stream networks connect populations across diverse landscapes, and therefore, protecting and restoring stream connectivity along inland streams such as the Smith River is critical to maintaining productive fish assemblages. Impact statementFish movement was common and diverse. Movement patterns varied seasonally, among species, and among different locations in the watershed. Some fish travelled over large portions of the watershed, and many travelled further than typical daily movements. [ABSTRACT FROM AUTHOR]

Background: Pressure offloading is a critical component of plantar foot ulcer management, including diabetes‐related foot ulcers (DFU). Conventional offloading options such as total contact casting and removable knee‐high walkers may be unsuitable or unsuccessful in patients with morbid obesity, intermittent lower limb oedema, high exudative wounds or poor mobility. A mouldable fibreglass backslab device (BSD) may be a practical alternative to be considered in these situations. Methods: Data were retrospectively collected on 28 patients (29 foot ulcers) with non‐healing ulcers who received a BSD to offload their foot ulcer as an extension to standard offloading care. Baseline data included: patient demographics, type of offloading prior to BSD application, date of ulcer onset, days ulcer present prior to BSD application and ulcer size at BSD initiation. Measures of success included ulcer size reduction 12 weeks post‐BSD application, time to complete ulcer healing in BSD, time to 50% reduction in ulcer size post‐BSD application and total number of days ulcer present. Results: The median (IQR) ulcer area and ulcer duration at baseline for 19 patients (20 ulcers) who used the BSD was 1.65 (0.4–3.8) cm2 and 531 (101–635) days. At 12 weeks, the median (IQR) ulcer area was 0.3 (0–0.55) cm2 with a median (IQR) reduction of 97 (80–100) %. Nine (45%) ulcers achieved complete wound healing (100% reduction in wound size) at 12 weeks post‐BSD application, and the remaining 11 (55%) ulcers achieved at least 50% reduction in wound size. The median (IQR) time to complete wound healing and 50% reduction in wound size was 71 (35–134) days and 24 (15–44) days, respectively. Nine patients ceased use of the BSD and reverted to conventional offloading before their wounds had healed. Of these, four patients achieved a 50% reduction in wound size at the 12‐week mark with conventional offloading. Conclusion: Our preliminary data suggests that a mouldable fibreglass BSD may be a practical offloading option in the management of DFUs, especially when conventional offloading methods are unsuccessful, unsuitable or unacceptable to patients. Higher level evidence is required to demonstrate suitability or efficacy of the BSD compared to current evidence‐based recommended offloading methods. [ABSTRACT FROM AUTHOR]

In the last two decades, the electromagnetic field of the microwave range has been successfully introduced into various branches of the agribusiness industry as one of the most promising and advanced technologies for drying manufactured products. In this regard, the article proposes a new microwave irradiation technique for drying various objects based on a surface waveguide's properties. The paper analyses the main links that make up the surface waveguide as a microwave irradiation system and shows the ways of their implementation. The article describes the advantages of applying a vibratory device for exciting a surface wave, using a re-emitting antenna array, and operating a single conductor with a dielectric coating as a surface waveguide. Such advantages make it possible to introduce microwave drying units with the required distribution of electromagnetic field energy along the irradiated material, small dimensions, high drying quality, and low price. [ABSTRACT FROM AUTHOR]

The clinical use of many potent anticancer agents is limited by their non‐selective toxicity to healthy tissue. One of these examples is vorinostat (SAHA), a pan histone deacetylase inhibitor, which shows high cytotoxicity with limited discrimination for cancerous over healthy cells. In an attempt to improve tumor selectivity, we exploited the properties of cobalt(III) as a redox‐active metal center through stabilization with cyclen and cyclam tetraazamacrocycles, masking the anticancer activity of SAHA and other hydroxamic acid derivatives to allow for the complex to reach the hypoxic microenvironment of the tumor. Biological assays demonstrated the desired low in vitro anticancer activity of the complexes, suggesting effective masking of the activity of SAHA. Once in the tumor, the bioactive moiety may be released through the reduction of the CoIII center. Investigations revealed long‐term stability of the complexes, with cyclic voltammetry and chemical reduction experiments supporting the design hypothesis of SAHA release through the reduction of the CoIII prodrug. The results highlight the potential for further developing this complex class as novel anticancer agents by masking the high cytotoxicity of a given drug, however, the cellular uptake needs to be improved. [ABSTRACT FROM AUTHOR]

In the framework of the RECCAP2 initiative, we present the greenhouse gas (GHG) and carbon (C) budget of Europe. For the decade of the 2010s, we present a bottom‐up (BU) estimate of GHG net‐emissions of 3.9 Pg CO2‐eq. yr−1 (using a global warming potential on a 100 years horizon), which are largely dominated by fossil fuel emissions. In this decade, terrestrial ecosystems acted as a net GHG sink of 0.9 Pg CO2‐eq. yr−1, dominated by a CO2 sink that was partially counterbalanced by net emissions of CH4 and N2O. For CH4 and N2O, we find good agreement between BU and top‐down (TD) estimates from atmospheric inversions. However, our BU land CO2 sink is significantly higher than the TD estimates. We further show that decadal averages of GHG net‐emissions have declined by 1.2 Pg CO2‐eq. yr−1 since the 1990s, mainly due to a reduction in fossil fuel emissions. In addition, based on both data driven BU and TD estimates, we also find that the land CO2 sink has weakened over the past two decades. A large part of the European CO2 and C sinks is located in Northern Europe. At the same time, we find a decreasing trend in sink strength in Scandinavia, which can be attributed to an increase in forest management intensity. These are partly offset by increasing CO2 sinks in parts of Eastern Europe and Northern Spain, attributed in part to land use change. Extensive regions of high CH4 and N2O emissions are mainly attributed to agricultural activities and are found in Belgium, the Netherlands and the southern UK. We further analyzed interannual variability in the GHG budgets. The drought year of 2003 shows the highest net‐emissions of CO2 and of all GHGs combined. Plain Language Summary: We have synthesized the European budgets of carbon and the greenhouse gases (GHG) carbon dioxide, methane and nitrous oxide. This synthesis includes estimates of direct emissions from fossil fuel burning, industrial production, waste management and agriculture, as well as of sources and sinks in the terrestrial biosphere. Summing up the sources and sinks of the three GHGs, we estimate for the decade of the 2010s an average annual net‐emission of 3.9 billion tons of carbon dioxide equivalents. These net‐emissions are dominated by carbon dioxide from fossil fuel emissions (4.1 billion tons of carbon dioxide). In contrast, the terrestrial biosphere acts as a net sink of carbon dioxide, the effect of which is only partly counterbalanced by net emissions of methane and nitrous oxide. The net‐effect of the terrestrial biosphere's GHG budget is a sink of 0.9 billion tons of carbon dioxide equivalents per year. Over the last three decades, European GHG emissions have declined by 1.2 billion tons carbon dioxide equivalents per year, mainly due to reductions in fossil fuel emissions. However, the sink capacity of the terrestrial biosphere has diminished since the 2000s. Key Points: We provide a bottom‐up estimate of CO2, CH4, N2O emissions of 3.9 Pg CO2‐eq. yr−1 over Europe, 2010–2019Terrestrial ecosystems acted as a greenhouse gas net sink of 0.9 Pg CO2‐eq. yr−1, dominated by CO2 sinkNet‐greenhouse gas emissions decreased by ∼1/4 since the 1990s, but land carbon sink is weakening since the 2000s [ABSTRACT FROM AUTHOR]

High‐entropy materials (HEMs) represent a revolutionary class of materials that have garnered significant attention in the field of materials science due to their extraordinary properties in diverse fields of applications such as catalysis and electrochemistry. The past decade has witnessed a substantial increase in the study of these materials, exploring new synthesis routes and compositions. What began as the synthesis of high‐entropy alloys has expanded to encompass several classes of HEMs such as oxides, hydroxides, sulfides, nitrides, and carbides, among others. Several synthesis methods have been developed to produce these materials. This review therefore highlights the fundamental concepts of HEMs, including their core effects, with a major emphasis on their scalable synthesis routes. The advantages and drawbacks of these methods are also discussed. As HEMs transition from the lab to large‐scale production, there is a growing need for cost‐effective and scalable synthesis methods with high material yield suitable for a variety of applications like hydrogen storage, catalysis, batteries, supercapacitors, and fuel cells. Hence, this review serves as an introduction to scalable synthesis routes based on crystal structure, desired elements, synthesis times, and equipment costs. [ABSTRACT FROM AUTHOR]

Antibody‐drug conjugates (ADCs) represent a novel type of targeted cancer therapy combining the specificity of monoclonal antibodies with the cytotoxicity of conventional chemotherapy. Recently, ADCs have demonstrated practice‐changing efficacy across diverse solid cancers. The anti‐NECTIN‐4 ADC enfortumab vedotin (EV) has just been approved for patients with urothelial cancer and is currently under investigation for patients with castration‐resistant prostate cancer (CRPC e.g. Phase II ENCORE trial). Our objective was to evaluate the efficacy of EV in established prostate cancer (PCa) cell lines and to examine the membranous NECTIN‐4 expression in primary tumours (PRIM) and distant metastases (MET). NECTIN‐4 was heterogeneously expressed in the panel of PCa cell lines. EV led to growth inhibition in NECTIN‐4 expressing PCa cells (22Rv1 and LNCaP), whereas the NECTIN‐4‐negative PC‐3 cells were significantly less responsive to EV, emphasizing the dependence of EV response on its target expression. Immunohistochemical staining revealed moderate membranous NECTIN‐4 expression only in a small subgroup of CRPC patients with lung and peritoneal MET [n = 3/22 with H‐score ≥100, median H‐score 140 (IQR 130–150)], while 100% of PRIM (n = 48/48) and 86.4% of common MET sites (n = 19/22), including lymph node, bone and liver MET, were NECTIN‐4 negative. In summary, EV may be effective in NECTIN‐4‐positive PCa. However, our findings demonstrate that the tumoural NECTIN‐4 expression is predominantly low in metastatic PCa, which suggests that EV may only be effective in a biomarker‐stratified subgroup. [ABSTRACT FROM AUTHOR]

High pressure high temperature treatments of the composition CaMnMnTeO6 are found to yield only an A2BB'O6‐type double perovskite (Ca0.5Mn0.5)2MnTeO6, rather than a AA'BB'O6 double double perovskite with A‐ and B‐ site cation order as found in analogs CaMnMnReO6 and CaMnMnWO6 with similar cation sizes. Double perovskite (Ca0.5Mn0.5)2MnTeO6 adopts a monoclinic structure in space group P21/n with a framework of highly tilted MnO6 and TeO6 octahedra enclosing disordered Ca2+ and Mn2+ cations. Magnetic measurements show that (Ca0.5Mn0.5)2MnTeO6 is a highly frustrated spin glass with a freezing transition at 5 K, and no long‐range spin order is apparent by neutron diffraction at 1.6 K. [ABSTRACT FROM AUTHOR]

Copyright of Biotropica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

INTRODUCTION: The "A/T/N" (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimer's disease (AD) diagnosis and can encompass additional changes such as inflammation ("I"). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau‐181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation‐related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age‐decade subgroups (57‐69, 70‐79, 80‐90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau‐181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau‐181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS‐cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age. Highlights: Plasma pTau‐181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau‐181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS‐cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate. [ABSTRACT FROM AUTHOR]

Purpose: Improved survival rates have been observed in castration‐resistant prostate cancer (CRPC) due to advancements in treatment options. However, individuals with brain metastases still have limited therapeutic options and an unfavorable prognosis. Therefore, there is an urgent need to explore new therapeutic avenues, such as antibody‐drug conjugates (ADCs), which have demonstrated significant clinical activity against active brain metastases in solid tumors. Our objective was to determine the expression levels of the ADC targets Trop‐2 and NECTIN‐4 in cerebral metastasized CRPC (mCRPC). Methods: Immunohistochemical staining of Trop‐2 and NECTIN‐4 with evaluation of H‐score was performed in CRPC brain metastases (n = 31). Additionally, we examined Trop‐2 protein expression in prostate cancer cell lines and studied their responsiveness to the anti‐Trop‐2 ADC Sacituzumab govitecan (SG) in vitro. Results: Our analysis revealed that most patients exhibited moderate to strong Trop‐2 expression [n = 27/31 with H‐score ≥100, median H‐score 220 (IQR 180–280)], while NECTIN‐4 was absent in all cerebral metastases. Mechanistically, we demonstrated that the efficacy of SG depends on Trop‐2 expression levels in vitro. Overexpression of Trop‐2 in Trop‐2‐negative PC‐3 cells led to sensitization to SG, whereas CRISPR‐Cas9‐mediated knockdown of Trop‐2 in Trop‐2‐expressing DU‐145 cells conferred resistance to SG. Conclusion: The substantial expression of Trop‐2 in cerebral metastases, along with our preclinical in vitro results, supports the efficacy of SG in treating cerebral mCRPC. Thus, our results extend the understanding of the potential of ADCs in prostate cancer treatment and provide an additional treatment strategy for the challenging subset of patients with cerebral metastases. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) and MRI based computational modelling studies provide insights into severity and recovery of ischemic stroke patients. The presence of brain lesions, however, can heavily distort and impair state‐of‐the‐art processing frameworks due to abnormal intensity values and tissue distortions. In this study, we introduce and validate the novel "Lesion Aware automated Processing Pipeline (LeAPP)." LeAPP automatically processes clinical stroke MRI data while significantly reducing the impact of pathological artefacts on processing outputs such as structural and functional connectomes (SC, FC). This helps to advance the identification of biomarkers for recovery and mechanism‐based intervention planning using MRI as well as computational approaches. We extended existing frameworks, such as the Human Connectome Project (HCP) minimal processing pipeline, introducing correction steps, and implementing and modifying functional and diffusion processing to cope with MRI acquisition protocols more typical for the clinical context. A total of 51 participants (36 patients, 15 age‐matched controls) were processed across four time points for patients (3–5, 30–40, 85–95, 340–380 days after stroke onset) and one time point for controls. We validated performance using artificial lesioned brains (N = 81), derived from healthy brains and informed by real stroke lesions. The quality of reconstructing the ground truth was quantified on whole brain level and for lesion affected and unaffected regions‐of‐interest (ROIs) for brain parcellations and for SCs. Volume based agreement was evaluated using metrics such as dice coefficient, volume difference or ROI center‐of‐gravity distance while SC based agreement was defined as the difference in network metrics (e.g., node strength, clustering coefficient, or centrality). The observed deviations in reconstructed ground truth brain parcellations and structural connectomes from lesioned brains were significantly reduced for LeAPP, compared to the performance of existing pipelines such as HCP minimal processing pipeline. For instance, in the case of lesion affected ROIS we achieved a mean dice coefficient (where a value of one represents total agreement as defined by an exact overlap of both ROIs) of 0.81 with LeAPP, compared to 0.75 for HCP (p <.0001*). Additionally, the average measured ROI distance (where a value of zero represents no difference) for lesion ROIs was 0.87 for LeAPP in contrast to 1.7 for HCP (p <.0001*), indicating an overall superior performance of LeAPP. The pipeline generates standardized output files ready for brain network modelling for instance with The Virtual Brain software. This novel open‐source automated processing framework contributes to reproducible research and provides a robust framework for automated processing of clinical stroke MRI data, supporting the identification of brain network‐based biomarkers of stroke recovery. [ABSTRACT FROM AUTHOR]

Land‐use intensification in grassland ecosystems (i.e. increased mowing frequency, intensified grazing) has a strong negative effect on biodiversity and ecosystem services. However, accurate information on grassland‐use intensity is difficult to acquire and restricted to the local or regional level. Recent studies have shown that mowing events can be mapped for large areas using satellite image time series. The transferability of such approaches, especially to mountain areas, has been little explored, however, and the relevance for ecological applications in biodiversity and conservation has hardly been investigated. Here, we used a rule‐based algorithm to produce annual maps for 2018–2021 of grassland‐management events, that is, mowing and/or grazing, for Switzerland using Sentinel‐2 and Landsat 8 satellite data. We assessed the detection of management events based on independent reference data, which we acquired from daily time series of publicly available webcams that are widely distributed across Switzerland. We further examined the relationships between the generated grassland‐use intensity measures and plant species richness and ecological indicator values derived from a nationwide field survey. The webcam‐based verification for 2020 and 2021 revealed that most detected management events were actual mowing/grazing events (≥78%), but that a substantial number of events were not detected (up to 57%), particularly grazing events at higher elevations. We found lower plant species richness and higher mean ecological indicator values for nutrients and mowing tolerance with more frequent management events and those starting earlier in the year. A large proportion of the variance was explained by our use‐intensity measures. Our findings therefore highlight that remotely assessed management events can characterise land‐use intensity at fine spatial and temporal resolutions across broad scales and can explain plant biodiversity patterns in grasslands. [ABSTRACT FROM AUTHOR]

This article focuses on the apportionment and distribution of post‐filing pre‐conversion increases in equity of assets in a debtor's estate when a debtor converts from a Chapter 13 to a Chapter 7 bankruptcy proceeding. Through an examination of the history of the US Bankruptcy Code and adequate examination of differing approaches, this article argues that courts should adopt the position that the post‐filing increase in equity due to appreciation should inure to the estate rather than to the debtor, while the increases in equity through payback plans should inure to the debtor. This approach creates the fairest situation for a debtor, placing them in a situation where they receive the full benefits of the Chapter 13 bankruptcy proposition and provides sufficient economic benefits to creditors. [ABSTRACT FROM AUTHOR]

Neotropical primates rarely exhibit active tuberculosis. A brown howler monkey was found injured in an urban area. Histopathology revealed granulomatous inflammation in the lungs, lymph nodes, and liver. Immunohistochemistry and molecular analysis confirmed the presence of Mycobacterium tuberculosis complex. The findings highlight the importance of TB surveillance in nonhuman primates. [ABSTRACT FROM AUTHOR]

Background and aims: Smoking is recognised as an independent risk factor in the development of chronic pancreatitis (CP). Cystic fibrosis transmembrane conductance regulator (CFTR) function and ductal fluid and bicarbonate secretion are also known to be impaired in CP, so it is crucial to understand the relationships between smoking, pancreatic ductal function and the development of CP. Methods: We measured sweat chloride (Cl–) concentrations in patients with and without CP, both smokers and non‐smokers, to assess CFTR activity. Serum heavy metal levels and tissue cadmium concentrations were determined by mass spectrometry in smoking and non‐smoking patients. Guinea pigs were exposed to cigarette smoke, and cigarette smoke extract (CSE) was prepared to characterise its effects on pancreatic HCO3– and fluid secretion and CFTR function. We administered cerulein to both the smoking and non‐smoking groups of mice to induce pancreatitis. Results: Sweat samples from smokers, both with and without CP, exhibited elevated Cl– concentrations compared to those from non‐smokers, indicating a decrease in CFTR activity due to smoking. Pancreatic tissues from smokers, regardless of CP status, displayed lower CFTR expression than those from non‐smokers. Serum levels of cadmium and mercury, as well as pancreatic tissue cadmium, were increased in smokers. Smoking, CSE, cadmium, mercury and nicotine all hindered fluid and HCO3– secretion and CFTR activity in pancreatic ductal cells. These effects were mediated by sustained increases in intracellular calcium ([Ca2+]i), depletion of intracellular ATP (ATPi) and mitochondrial membrane depolarisation. Conclusion: Smoking impairs pancreatic ductal function and contributes to the development of CP. Heavy metals, notably cadmium, play a significant role in the harmful effects of smoking. Key points: Smoking and cigarette smoke extract diminish pancreatic ductal fluid and HCO3– secretion as well as the expression and function of CFTRCd and Hg concentrations are significantly higher in the serum samples of smokersCd accumulates in the pancreatic tissue of smokers [ABSTRACT FROM AUTHOR]

Objective: PTEN, a known tumor suppressor gene, is a mediator of neurodevelopment. Individuals with germline pathogenic variants in the PTEN gene, molecularly defined as PTEN hamartoma tumor syndrome (PHTS), experience a variety of neurological and neuropsychiatric challenges during childhood, including autism spectrum disorder (ASD). However, the frequency and nature of seizures and the utilization of allied health services have not been described. Methods: Young patients with PHTS and sibling controls were recruited across five centers in the United States and followed every 6–12 months for a mean of 2.1 years. In addition to the history obtained from caregivers, neurodevelopmental evaluations and structured dysmorphology examinations were conducted, and brain MRI findings, received therapies, and epilepsy characteristics were reported. Results: One hundred and seven patients with PHTS (median age 8.7 years; range 3–21 years) and 38 controls were enrolled. ASD and epilepsy were frequent among patients with PHTS (51% and 15%, respectively), with generalized epilepsy strongly associated with ASD. Patients with epilepsy often required two antiseizure medications. Neuroimaging revealed prominent perivascular spaces and decreased peritrigonal myelination in individuals with PHTS‐ASD. Allied therapy use was frequent and involved physical, occupational, speech, and social skills therapies, with 89% of all patients with PHTS, regardless of ASD diagnosis, utilizing at least one service. Interpretation: This prospective, longitudinal study highlights the wide neurological spectrum seen in young individuals with PHTS. ASD is common in PHTS, comorbid with epilepsy, and allied health services are used universally. Our findings inform care discussions with families about neurological outcomes in PHTS. [ABSTRACT FROM AUTHOR]

Brain metastases can occur in nearly half of patients with early and locally advanced (stage I–III) non‐small cell lung cancer (NSCLC). There are no reliable histopathologic or molecular means to identify those who are likely to develop brain metastases. We sought to determine if deep learning (DL) could be applied to routine H&E‐stained primary tumor tissue sections from stage I–III NSCLC patients to predict the development of brain metastasis. Diagnostic slides from 158 patients with stage I–III NSCLC followed for at least 5 years for the development of brain metastases (Met+, 65 patients) versus no progression (Met−, 93 patients) were subjected to whole‐slide imaging. Three separate iterations were performed by first selecting 118 cases (45 Met+, 73 Met−) to train and validate the DL algorithm, while 40 separate cases (20 Met+, 20 Met−) were used as the test set. The DL algorithm results were compared to a blinded review by four expert pathologists. The DL‐based algorithm was able to distinguish the eventual development of brain metastases with an accuracy of 87% (p < 0.0001) compared with an average of 57.3% by the four pathologists and appears to be particularly useful in predicting brain metastases in stage I patients. The DL algorithm appears to focus on a complex set of histologic features. DL‐based algorithms using routine H&E‐stained slides may identify patients who are likely to develop brain metastases from those who will remain disease free over extended (>5 year) follow‐up and may thus be spared systemic therapy. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Inheritance from prior exposure often complicates the interpretation of terrestrial cosmogenic nuclide (TCN) inventories in glaciated terrain. Lochnagar, a mountain in eastern Scotland, holds a clear geomorphological record of corrie glaciation and the thinning of the last Scottish ice sheet over the last ~15 ka. Yet attempts to date the main stages in deglaciation after sampling of 21 granite boulders for 10Be, 26Al and 14C from corrie moraines, an ice sheet lateral moraine and boulder spreads revealed widespread, but variable, TCN inheritance. Only the youngest boulder ages fit within the range of expected deglaciation ages. To identify the sources of geological uncertainty, we provide simple models of ice cover duration and erosion histories for plateau, corrie and strath landscape domains, identify the variable nuclide inheritance that derives from different sources for boulders in these domains, and outline the effects of rotation, splitting and erosion of boulders during glacial transport. The combined effects increase clustering around arbitrary mean TCN values that exceed deglaciation ages. A further implication is that boulders have survived beneath overriding ice sheets. Such boulder trapping at Lochnagar may have resulted from topographic controls on katabatic winds and surface ablation acting on a thinning, cold‐based ice sheet. [ABSTRACT FROM AUTHOR]

Background: This study utilizes interviews of clinical medical physicists to investigate self‐reported shortcomings of the current weekly chart check workflow and opportunities for improvement. Methods: Nineteen medical physicists were recruited for a 30‐minute semi‐structured interview, with a particular focus placed on image review and the use of automated tools for image review in weekly checks. Survey‐type questions were used to gather quantitative information about chart check practices and importance placed on reducing chart check workloads versus increasing chart check effectiveness. Open‐ended questions were used to probe respondents about their current weekly chart check workflow, opinions of the value of weekly chart checks and perceived shortcomings, and barriers and facilitators to the implementation of automated chart check tools. Thematic analysis was used to develop common themes across the interviews. Results: Physicists ranked highly the value of reducing the time spent on weekly chart checks (average 6.3 on a scale from 1 to 10), but placed more value on increasing the effectiveness of checks with an average of 9.2 on a 1–10 scale. Four major themes were identified: (1) weekly chart checks need to adapt to an electronic record‐and‐verify chart environment, (2) physicists could add value to patient care by analyzing images without duplicating the work done by physicians, (3) greater support for trending analysis is needed in weekly checks, and (4) automation has the potential to increase the value of physics checks. Conclusion: This study identified several key shortcomings of the current weekly chart check process from the perspective of the clinical medical physicist. Our results show strong support for automating components of the weekly check workflow in order to allow for more effective checks that emphasize follow‐up, trending, failure modes and effects analysis, and allow time to be spent on other higher value tasks that improve patient safety. [ABSTRACT FROM AUTHOR]

A visible‐light‐induced, three‐component palladium‐catalyzed 1,4‐aminoarylation of butadienes with readily available aryl halides and aliphatic amines has been developed, affording allylamines with excellent E‐selectivity. The reaction exhibits exceptional control over chemo‐, regio‐, and stereoselectivity, a broad substrate scope, and high functional group compatibility, as demonstrated by the late‐stage functionalization of bioactive molecules. Mechanistic investigations are consistent with a photoinduced radical Pd(0)‐Pd(I)‐Pd(II)‐Pd(0) Heck‐Tsuji–Trost allylation cascade. [ABSTRACT FROM AUTHOR]

Rationale, Aims and Objectives: Spine pain (SP) is common and often disabling. Clinical practice guidelines discourage opioid treatment and outline the value of varied nonpharmacologic therapies (NPTs). This study elucidates the amount of variability in primary‐care clinicians' (PCPs') prescribing of opioids and in their cases' receipt of the two most common NPTs (exercise therapy and spinal manipulation). Method: The design was a retrospective cohort study examining variation in the treatment of PCPs' new SP cases, classified by receipt of (a) prescription of an opioid at the initial visit; (b) exercise therapy and/or spinal manipulation within 30 days of initial visit. The study was set in the primary care clinics at military treatment facilities of the US Military Health System in the period between October 2011 and September 2016. Results: The majority of cases did not receive a study treatment (66.3%); 19.6% of cases received only NPT within 30 days of initial visit; 11.5% were prescribed only an opioid at the initial visit with receipt of both NPT and opioid during early treatment rare (2.6%). Exercise therapy within 30 days exhibited more than a twofold difference in interquartile percentile rates (IQR) (median provision 15.8%, IQR 9.8%−22.1%). The other treatments exhibited even greater variation; specifically, spinal manipulation (median 8.5%, IQR 3.3%−15.8%), and opioid at initial visit (median 10.3%, IQR 4.4%−18.2%). The availability of physical therapists and doctors of chiropractic had significant association with several clinical provision rates. Conclusion: Among providers of spine care for a sample of Army soldiers, there was substantial variation in the early provision of exercise therapy, spinal manipulation, and opioid prescriptions. The magnitude of the case‐mix adjusted variation and its association with facility availability of providers suggests that quality of care initiatives may help reduce this variation. [ABSTRACT FROM AUTHOR]

Modern quantum technologies have matured such that they can now be used in space applications, e.g., long‐distance quantum communication. Here, the design of a compact true single photon source is presented that can enhance the secure data rates in satellite‐based quantum key distribution scenarios compared to conventional laser‐based light sources. The quantum light source is a fluorescent color center in hexagonal boron nitride. The emitter is off‐resonantly excited by a diode laser and directly coupled to an integrated photonic processor that routes the photons to different experiments performed directly on‐chip: i) the characterization of the single photon source and ii) testing a fundamental postulate of quantum mechanics, namely the relation of the probability density and the wave function (known as Born's rule). The described payload is currently being integrated into a 3U CubeSat and scheduled to launch in 2024 into low Earth orbit. Therefore the feasibility of true single photon sources and reconfigurable photonic circuits in space can be evaluated. This provides a promising route toward a high‐speed quantum network. [ABSTRACT FROM AUTHOR]

Background: Intranasal corticosteroids (INCS) are a treatment mainstay of chronic rhinosinusitis and allergic rhinitis. Current computational models demonstrate that >90% of INCS drug deposition occurs on the head of the inferior turbinate and nasal valve, rather than the actual sinuses. These models do not consider mucociliary clearance which propels mucus posteriorly, nor do they consider the absorption of the drug. The purpose of this study is to better understand the exact anatomical location where INCS are absorbed. Methods: Patients with chronic rhinosinusitis and allergic rhinitis taking fluticasone pre‐operatively who were scheduled for functional endoscopic sinus surgery and inferior turbinate reduction, respectively, were recruited. Intra‐operative tissue samples were obtained from predetermined locations within the sinonasal cavity. Mass spectrometry was then used to quantify the amount of absorption in each specific anatomic location to determine the largest amount of absorption. Results: Eighteen patients were included in our study. The greatest fluticasone absorption levels across the sinonasal anatomy were at the anterior inferior turbinate (5.7 ngl/mL), ethmoid sinus, (4.4 ng/mL), posterior inferior turbinate (3.7 ng/mL), maxillary sinus (1.3 ng/mL), and the sphenoethmoidal recess (0.72 ng/mL) respectively. Absorption was significantly higher in revision surgery compared to surgically naïve patients. Conclusions: Computation fluid dynamic models of the nasal passage are useful models to help predict intranasal particle flow. However, these models do not incorporate or consider the important mucociliary clearance system, leading to absorption of fluticasone throughout the sinonasal cavity far beyond that predicted by these models. Level of Evidence: 2 Laryngoscope, 134:1551–1555, 2024 [ABSTRACT FROM AUTHOR]

Materials properties are determined by their compositions and structures. In ABO3 oxides different cation orderings lead to mainly perovskite‐ or corundum like derivatives with exciting physical properties. Sometimes, a material can be stabilized in more than one structural modification, providing a unique opportunity to explore structure‐properties relationship. Here, CoVO3 obtained in both ilmenite‐(CoVO3‐I) and LiNbO3‐type (CoVO3‐II) polymorphs at moderate (8–12 GPa) and high pressures (22 GPa), respectively are presented. Their distinctive cation distributions affect drastically the magnetic properties as CoVO3‐II shows a cluster‐glass behavior while CoVO3‐I hosts a honeycomb zigzag magnetic structure in the cobalt network. First principles calculations show that the influence of vanadium is crucial for CoVO3‐I, although it is previously considered as non‐magnetic in a dimerized spin‐singlet state. Contrarily, CoVO3‐II shows two independent interpenetrating antiferromagnetic Co‐ and ferromagnetic V‐hcp sublattices, which intrinsically frustrate any possible magnetic order. CoVO3‐II is also remarkable as the first oxide crystallizing with the LiNbO3‐type structure where both metals contain free d electrons. CoVO3 polymorphs pinpoint therefore as well to a much broader phase field of high‐pressure A‐site Cobaltites. [ABSTRACT FROM AUTHOR]

We examine how the racial wealth gap interacts with financial aid in American higher education to generate a disparate impact on college access and outcomes. Retirement savings and home equity are excluded from the formula used to estimate the amount a family can afford to pay. All else equal, omitting those assets mechanically increases the financial aid available to families that hold them. White families are more likely to own those assets and in larger amounts. We document this issue and explore its relationship with observed differences in college attendance, types of institutions attended, degrees attained, and education debt using data from the Survey of Consumer Finances (SCF), the National Postsecondary Student Aid Study (NPSAS), and the Panel Study of Income Dynamics (PSID). We show that this treatment of assets provides an implicit subsidy worth thousands of dollars annually to students from families with above‐median incomes. White students receive larger subsidies relative to Black students and Hispanic students with similar family incomes, and this gap in subsidies is associated with disadvantages in educational advancement and student loan levels. It may explain 10 percent to 15 percent of white students' advantage in these outcomes relative to Black students and Hispanic students. [ABSTRACT FROM AUTHOR]

Extraterrestrial chrome spinel and chromite extracted from the sedimentary rock record are relicts from coarse micrometeorites and rarely meteorites. They are studied to reconstruct the paleoflux of meteorites to the Earth and the collisional history of the asteroid belt. Minor element concentrations of Ti and V, and oxygen isotopic compositions of these relict minerals were used to classify the meteorite type they stem from, and thus to determine the relative meteorite group abundances through time. While coarse sediment‐dispersed extraterrestrial chrome‐spinel (SEC) grains from ordinary chondrites dominate through the studied time windows in the Phanerozoic, there are exceptions: We have shown that ~467 Ma ago, 1 Ma before the breakup of the L chondrite parent body (LCPB), more than half of the largest (>63 μm diameter) grains were achondritic and originated from differentiated asteroids in contrast to ordinary chondrites which dominated the meteorite flux throughout most of the past 500 Ma. Here, we present a new data set of oxygen isotopic compositions and elemental compositions of 136 grains of a smaller size fraction (32–63 μm) in ~467 Ma old pre‐LCPB limestone from the Lynna River section in western Russia, that was previously studied by elemental analysis. Our study constitutes the most comprehensive oxygen isotopic data set of sediment‐dispersed extraterrestrial chrome spinel to date. We also introduce a Raman spectroscopy‐based method to identify SEC grains and distinguish them from terrestrial chrome spinel with ~97% reliability. We calibrated the Raman method with the established approach using titanium and vanadium concentrations and oxygen isotopic compositions. We find that ordinary chondrites are approximately three times more abundant in the 32–63 μm fraction than achondrites. While abundances of achondrites compared to ordinary chondrites are lower in the 32–63 μm size fraction than in the >63 μm one, achondrites are approximately three times more abundant in the 32–62 μm fraction than they are in the present flux. We find that the sources of SEC grains vary for different grain sizes, mainly as a result of parent body thermal metamorphism. We conclude that the meteorite flux composition ~467 Ma ago ~1 Ma before the breakup of the LCPB was fundamentally different from today and from other time windows studied in the Phanerozoic, but that in contrast to the large size fraction ordinary chondrites dominated the flux in the small size fraction. The high abundance of ordinary chondrites in the studied samples is consistent with the findings based on coarse extraterrestrial chrome‐spinel from other time windows. [ABSTRACT FROM AUTHOR]

Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages. [ABSTRACT FROM AUTHOR]

We set out to demonstrate the feasibility of pharmacogenetic testing of DPYD and UGT1A1 and explore the clinical benefits in a community‐based cancer center. We conducted a retrospective review of 280 patients who underwent pharmacogenetic testing between November 2020 and May 2023. The primary end points included the percentage of patients with results prior to chemotherapy initiation, percentage of DPYD‐ and UGT1A1‐guided interventions implemented before chemotherapy initiation, and the turnaround time (TAT) for the pharmacogenetics results. Exploratory end points included a comparison of unplanned hospitalizations and treatment interruptions among (1) DPD phenotypes in patients who received fluoropyrimidines and (2) UGT1A1 phenotypes in patients who received irinotecan ± fluoropyrimidines. We evaluated cancer progression among patients who received DPYD‐guided dose reductions in the curative setting. More than 75% of patients had results prior to initiation of chemotherapy and 61.5% of the actionable interventions were implemented before chemotherapy, with a median TAT of 7 calendar days (IQR 5–8 calendar days). A non‐significant higher percentage of unplanned hospitalizations and treatment interruptions occurred among patients with normal DPYD compared with patients with DPYD‐guided dose reductions. A non‐significant higher frequency of treatment interruptions and dose reductions were observed in UGT1A1 intermediate metabolizer (IM) compared with UGT1A1 normal metabolizer (NM). None of the patients who received DPYD‐guided dose reductions in the curative setting experienced progression after a median follow‐up of 342 days. The real‐world evidence generated from this study demonstrates the feasibility of pre‐chemotherapy pharmacogenetic testing of DPYD and UGT1A1 in a community‐based cancer center. [ABSTRACT FROM AUTHOR]