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An incongruence exists between the growing job opportunities in rural areas and the educational opportunities provided to rural students, especially in science, technology, engineering, and mathematics (STEM) fields. Positive change is possible, however. As one means to tackle this complex issue, this study sought to understand the perceptions and experiences of students who graduated from rural high schools and pursued STEM majors in college as exemplars of rural students who pursued postsecondary education in STEM disciplines. This phenomenological study explored how college students in STEM majors perceived their rural schools and communities as influencing their academic journeys. Rather than focusing only on deficits and inequities associated with rurality, this study employed the rural cultural wealth (RCW) framework to highlight the agency and capital rural students employed within their journeys. Qualitative data analysis revealed that participants' comments about their rural schools and communities were diverse. The findings also aligned and extended current literature and the RCW framework. These insights into these STEM students' rural backgrounds and academic journeys were then used to create recommendations for future P-20 educational research, practices, and policies.

This article explores the possibilities for decolonizing approaches to intercultural learning for international students in Canada. In this article the authors present the findings from a series of photovoice workshops conducted as a part of a larger mixed-methods project that explores how informal and everyday pedagogies shape international students' mobility decisions in the Atlantic Canadian province of Nova Scotia. Participants' collaborative analysis of their own photographs reveal how everyday citizenship learning emerges from international students' affective relationships to place in such a way that obscures how international education is implicated in processes of settler colonialism. However, evidence suggests that participants' sense of belonging is deeply implicated in their connections to place, highlighting potential opportunities for integrating international students in current initiatives to "decolonize" higher education in the Canadian context.

Artificial Intelligence (AI) has threatened higher education (HE). In doing so it has granted a portal that makes visible the dominant paradigm that has long defined what "intelligence" is and the narrow set of knowledges and literacies sanctioned for its pursuit. In this paper, we orient our thinking from this clarifying moment, asking: beyond these limits, what intelligences should educators value and nurture for sustainable and anti-colonial futures, and how might we support these through educational practices in HE? We also pause to reflect on the ways in which AI might move learners' pursuits of intelligence in more expansive directions. This orientation, we argue, provides a means to unsettle the hierarchies of intelligence that we live with/out, and a pathway to (re)direct AI's potential toward just and hopeful ends.

Candida parapsilosis is known to cause severe and persistent outbreaks in clinical settings. Patients infected with multidrug-resistant C. parapsilosis (MDR Cp) isolates were identified in a large Turkish hospital from 2017-2020. We subsequently identified three additional patients infected with MDR Cp isolates in 2022 from the same hospital and two echinocandin-resistant (ECR) isolates from a single patient in another hospital. The increasing number of MDR and ECR isolates contradicts the general principle that the severe fitness cost associated with these phenotypes could prevent their dominance in clinical settings. Here, we employed a multidimensional approach to systematically assess the fitness costs of MDR and ECR C. parapsilosis isolates. Whole-genome sequencing revealed a novel MDR genotype infecting two patients in 2022. Despite severe in vitro defects, the levels and tolerances of the biofilms of our ECR and MDR isolates were generally comparable to those of susceptible wild-type isolates. Surprisingly, the MDR and ECR isolates showed major alterations in their cell wall components, and some of the MDR isolates consistently displayed increased tolerance to the fungicidal activities of primary human neutrophils and were more immunoevasive during exposure to primary human macrophages. Our systemic infection mouse model showed that MDR and ECR C. parapsilosis isolates had comparable fungal burden in most organs relative to susceptible isolates. Overall, we observed a notable increase in the genotypic diversity and frequency of MDR isolates and identified MDR and ECR isolates potentially capable of causing persistent outbreaks in the future.

Weakly interacting massive particles (WIMPs) may interact with a virtual pion that is exchanged between nucleons. This interaction channel is important to consider in models where the spin-independent isoscalar channel is suppressed. Using data from the first science run of the LUX-ZEPLIN dark matter experiment, containing 60 live days of data in a 5.5 tonne fiducial mass of liquid xenon, we report the results on a search for WIMP-pion interactions. We observe no significant excess and set an upper limit of 1.5 × 10−46 cm2 at a 90% confidence level for a WIMP mass of 33 GeV/c2 for this interaction.

Meningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow-up (median 9.9 years; range 15 days-43 years), we performed extensive molecular characterization including genome-wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5-7::ex16-17, 26 = ex4::ex2-3; 12 = ex2-3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis-free survival (MFS) (p = 0.03) and, on multivariate analysis, disease-specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p

Intrinsically motivated information seeking is an expression of curiosity believed to be central to human nature. However, most curiosity research relies on small, Western convenience samples. Here, we analyze a naturalistic population of 482,760 readers using Wikipedias mobile app in 14 languages from 50 countries or territories. By measuring the structure of knowledge networks constructed by readers weaving a thread through articles in Wikipedia, we replicate two styles of curiosity previously identified in laboratory studies: the nomadic busybody and the targeted hunter. Further, we find evidence for another style-the dancer-which was previously predicted by a historico-philosophical examination of texts over two millennia and is characterized by creative modes of knowledge production. We identify associations, globally, between the structure of knowledge networks and population-level indicators of spatial navigation, education, mood, well-being, and inequality. These results advance our understanding of Wikipedias global readership and demonstrate how cultural and geographical properties of the digital environment relate to different styles of curiosity.

The human face plays a central role in emotions and social communication. The emotional and somatic motor networks generate facial behaviors, but whether facial behaviors have representations in the structural anatomy of the human brain is unknown. We coded 16 facial behaviors in 55 healthy older adults who viewed five videos that elicited emotions and examined whether individual differences in facial behavior were related to regional variation in gray matter volume. Voxel-based morphometry analyses revealed that greater emotional facial behavior during the disgust trial (i.e. greater brow furrowing and eye tightening as well as nose wrinkling and upper lip raising) and the amusement trial (i.e. greater smiling and eye tightening) was associated with larger gray matter volume in midcingulate cortex, supplementary motor area, and precentral gyrus, areas spanning both the emotional and somatic motor networks. When measured across trials, however, these facial behaviors (and others) only related to gray matter volume in the precentral gyrus, a somatic motor network hub. These findings suggest that the emotional and somatic motor networks store structural representations of facial behavior and that the midcingulate cortex is critical for generating the predictable movements in the face that arise during emotions.

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation.

Liver X receptor-α (LXRα) regulates cellular cholesterol abundance and potently activates hepatic lipogenesis. Here we show that at least 1 in 450 people in the UK Biobank carry functionally impaired mutations in LXRα, which is associated with biochemical evidence of hepatic dysfunction. On a western diet, male and female mice homozygous for a dominant negative mutation in LXRα have elevated liver cholesterol, diffuse cholesterol crystal accumulation and develop severe hepatitis and fibrosis, despite reduced liver triglyceride and no steatosis. This phenotype does not occur on low-cholesterol diets and can be prevented by hepatocyte-specific overexpression of LXRα. LXRα knockout mice exhibit a milder phenotype with regional variation in cholesterol crystal deposition and inflammation inversely correlating with steatosis. In summary, LXRα is necessary for the maintenance of hepatocyte health, likely due to regulation of cellular cholesterol content. The inverse association between steatosis and both inflammation and cholesterol crystallization may represent a protective action of hepatic lipogenesis in the context of excess hepatic cholesterol.

Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modeling the colonic epithelium in active disease and identified two major molecular subtypes: immune-deficient infectious CD (IDICD) and stress and senescence-induced fibrostenotic CD (S2FCD). Each subtype shows internal consistency in the transcriptome, genome, and phenome. The spectrum of morphometric, phenotypic, and functional changes within the "living biobank" reveals distinct differences between the molecular subtypes. Drug screens reverse subtype-specific phenotypes, suggesting phenotyped-genotyped CD PDOs can bridge basic biology and patient trials by enabling preclinical phase "0" human trials for personalized therapeutics.

The storage and management of stockpiles of materials is a fundamental process in large scale activities such as mining, civil engineering, and in the management of waste landfill sites. Following the evolution of stocks has always been important, and advancements in remote sensing technology are not only facilitating this, but also making it possible in near real-time. Nowadays, this monitoring appears to be performed almost exclusively using UAV based techniques. This paper proposes to apply a simple Shape-from-Shading method on low resolution satellite images provided by PlanetScope to monitor the evolution of the volume of stockpiles. The proposed Shape-from-Shading formulation makes it possible to handle occluding objects in the scene. The loss in accuracy due to the low resolution of PlanetScope images is well compensated by the daily revisit frequency and by the fact that spaceborne acquisitions require no human supervision. With satellites it is also easy to follow simultaneously several stocking sites all over the world. We test our method on two coal storage sites and demonstrate that the stockpiles are well detected.

Carbon 1s excitation of methane, CH _4 , has been studied in the gas phase using the ion trap integrated with the photon–ion instrument at PETRA III/DESY and soft X-rays from the beamline P04. The created photoions are stored within the ion trap so that in further steps the photoions can undergo reactions with neutral methane molecules. The ionic photoproducts as well as reaction products created thereby are mass-over-charge analyzed by an ion time-of-flight spectrometer. Besides the photoions, product ions with up to three carbon atoms are found. In contrast to experiments using vacuum ultraviolet radiation, especially highly reactive product ions with a small number of hydrogen atoms such as ${{\rm{C}}}_{2}{{\rm{H}}}_{2}^{+}$ and ${{\rm{C}}}_{2}{{\rm{H}}}_{3}^{+}$ are found, which are important precursors for larger hydrocarbons such as C _6 H _6 . Possible production routes of the product ions are analyzed on the basis of a model that considers the probabilities for photofragmentation and the first subsequent chemical reaction step. The model indicates that the high degree of fragmentation by photons with energies around 280 eV is favoring these products. The results of the measurements show that the products like ${{\rm{C}}}_{2}{{\rm{H}}}_{2}^{+}$ and ${{\rm{C}}}_{2}{{\rm{H}}}_{3}^{+}$ can be generated by a single collision of the ionization product with neutral methane. The results suggest that soft X-rays might be important for chemical reactions in planetary atmospheres, which has usually not been taken into account. However, due to the high degree of fragmentation and large cross sections involved, they can have a large influence even when the corresponding photon flux is rather small.

Abstract Background RGM medium is an agar-based, selective culture medium designed for the isolation of nontuberculous mycobacteria (NTM) from the sputum of patients with cystic fibrosis (CF). We evaluated RGM medium for the detection of NTM in patients with CF (405 samples), bronchiectasis (323 samples) and other lung diseases necessitating lung transplantation (274 samples). Methods In total, 1002 respiratory samples from 676 patients were included in the study. Direct culture on RGM medium, with incubation at two temperatures (30 °C and 37 °C), was compared with conventional culture of decontaminated samples for acid-fast bacilli (AFB) using both a solid medium (Löwenstein-Jensen medium) and a liquid medium (the Mycobacterial Growth Indicator Tube; MGIT). Results For all three patient groups, significantly more isolates of NTM were recovered using RGM medium incubated at 30 °C than by any other method (sensitivity: 94.6% vs. 22.4% for conventional AFB culture; P < 0.0001). Significantly more isolates of Mycobacterium abscessus complex were isolated on RGM at 30 °C than by AFB culture (sensitivity: 96.1% vs. 58.8%; P < 0.0001). The recovery of Mycobacterium avium complex was also greater using RGM medium at 30 °C compared to AFB culture (sensitivity: 83% vs. 70.2%), although this difference was not statistically significant and a combination of methods was necessary for optimal recovery (P = 0.21). Conclusions In the largest study of RGM medium to date, we reaffirm its utility for isolation of NTM from patients with CF. Furthermore; we show that it also provides an effective tool for culture of respiratory samples from patients with bronchiectasis and other lung diseases.

Graduates require employability competences, such as flexibility and team working skills, to gain and maintain employment. Online learning platforms (OLPs) can provide students with resources for reflection, which is a key competence for employability. However, little is known about the design of OLPs meant to provide reflective practices that foster students' employability competences. This research study aims to identify design principles of OLPs providing reflective practices that foster the development of employability competences. Five design principles were derived from thematic analysis following two focus group interviews with students and educational experts in this qualitative study: (1) Embed the OLP in curricular and institutional activities that foster competence development; (2) Facilitate the analysis of students' current state regarding employability competences; (3) Provide recommendations and a repository with learning activities that help students to formulate goals and plan activities; (4) Facilitate the undertaking and recording of learning activities, supported by a blend of three forms of interaction (instructor-student; student-student or student-content); and (5) Foster reflection in and on action via opportunities for applying newly learned knowledge in different settings and reviewing activities via reflective journaling and knowledge sharing. This study is the first to conceptualise design principles for an OLP that is organised to provide reflective practices for the development of employability competences. The design principles were based on students' and teachers' experiences and are grounded in theory. They can inform future research as well as practitioners developing OLPs.

Preschoolers' language abilities are associated with their social interactions in early childhood classrooms. Few studies, however, have examined associations between social interactions and objective measures of children's real-time classroom language environments, information key to informing interventions to support preschool children at risk for language delays. In this pilot study, we examined associations between objective measures of real-time language environments (input and output) recorded via the Language ENvironment Analysis (LENA) system and observations of children's positive and negative interactions with peers and teachers in an early intervention classroom for children with developmental delays (n = 9, seven girls). Mixed effects regression models revealed associations between children's language environments (input and output) and their social interactions with peers and teachers. More talkative children were more likely to have a high number of positive peer interactions. Children who received more language input from teachers were more likely to have a higher number of positive teacher--child interactions, an effect that was stronger for children with the lowest language output. The results of this pilot study build on prior research by using real-time objective measurement to examine how children's language input from peers and teachers and children's own language output supports positive interactions within early intervention classrooms.

Inquiry-based project learning is an internationally recognised pedagogical approach where children work collaboratively to research and discover the answers to their questions through discussion, representation, and evaluation. This paper explores the findings from Phase One of a qualitative study examining how this approach has been interpreted in early childhood settings in Aotearoa/New Zealand. The findings from an online questionnaire sent to all settings registered on the New Zealand national data base revealed that the international discourse surrounding this approach has been a key influence in this context. There was, however, also evidence that more localised approaches that value indigenous knowledges, in alignment with the national early childhood curriculum, Te Whariki ("Te Whariki. He whariki matauranga mo nga mokopuna o Aotearoa: Early childhood curriculum." Ministry of Education. https://www.education.govt.nz/assets/Documents/Early-Childhood/Te-Whariki-Early-Childhood-Curriculum-ENG-Web.pdf) have been developed. Whilst participants identified pedagogical and practical challenges of undertaking inquiry-based approaches, the educational value of this approach for children was also strongly championed.

Due to the increased financial pressure--exacerbated by the COVID-19 pandemic--that students in higher education need to endure, considerable attention is being drawn towards the determinants of student financial anxiety. A conflicting picture has been captured about financial literacy, which has been shown to either be associated with better financial well-being or to be unrelated to financial stress. While discerning between financial knowledge ('objective' financial literacy) and perceived ability to manage personal finances ('subjective' financial literacy), this study also explores the impact that students' attitudes towards debt may exert on their financial anxiety. In a sample of 174 university students from the UK, we measured students' financial anxiety, objective and subjective financial literacy, attitudes towards debt and perceived impact of COVID-19 on financial behaviour. Bayesian analyses revealed that only attitudes towards debt and perception of the impact of the pandemic predicted students' financial anxiety. While the evidence in regard to financial literacy was inconclusive, mediation analyses showed that objective financial literacy indirectly impacted financial anxiety by increasing fear of debt. The findings suggest that students' financial anxiety may be reduced by adopting strategies that focus on the subjective perception of debt and of economic circumstances.

A recent global reconnaissance of Christian higher education found a number of key themes that shaped current developments, such as the pressing challenges of secularization and nationalization but also the advantages of privatization and massification. This article provides an update to this older analysis by taking a birds-eye view of trends within the past 70 years of global Christian higher education. It reveals that privatization and massification trends do not predict new developments in countries and outliers always exist. Furthermore, it highlights some findings missed in previous analyses related to the importance of indigenous Christian groups and Christian general education.

Abstract Background Bipolar disorder has been associated with several personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however little research has investigated these traits and temperaments in relation to postpartum psychosis. The aim of this study is to establish whether aspects of personality, cognitive style and affective temperament that have been associated with bipolar disorder also confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. Methods Personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments (including cyclothymic and depressive temperaments) were compared between two groups of parous women with DSM-IV bipolar I disorder: i) 284 with a lifetime history of postpartum psychosis within 6 weeks of delivery (PP group), ii) 268 without any history of mood episodes with onset during pregnancy or within 6 months of delivery (no perinatal mood episode, No PME group). Results After controlling for current mood state, and key demographic, clinical and pregnancy-related variables, there were no statistically significant differences between the PP and No PME groups on any of the personality, cognitive style or affective temperament measures. Conclusions Personality traits, cognitive styles and affective temperaments previously shown to be associated with bipolar disorder in general were not specifically associated with the occurrence of postpartum psychosis. These factors may not be relevant for predicting risk of postpartum psychosis in women with bipolar disorder.

Abstract Background Effective collaboration between speech and language therapists (SLTs) and teachers is essential in meeting the needs of children with developmental language disorders in school, but it is difficult to achieve. Currently, many children receive inadequate speech and language therapy services and/or support in school. The aim of this study was to engage key stakeholders (SLTs, teachers, parents and children with DLD) in the co-design of their ideal speech and language therapy service and support in school. The study was undertaken in order to inform the development of a conceptual model to guide collaborative practice when working with this population. Methods A qualitative study involving a diverse range of key stakeholders and using appreciative inquiry. This is a method which enables those involved to construct their ‘ideal’ about a topic of interest. Recruitment was carried out using purposive sampling. We conducted focus groups with practitioners (SLTs and teachers) and parents as well as semi-structured interviews with children who have DLD using ‘draw and tell’ techniques. A total of five focus groups and nine interviews were conducted with participants (n = 27). Results The children described their ideal supports as those which enabled them to connect, contribute and achieve. They describe ways in which environmental barriers in school needed to be addressed to allow them to do so. The professionals primarily described ways in which the language skills of the child could be improved. Both parents and practitioner groups described the importance of strengthening networks between service providers and service users. They also highlighted the need to promote a collaborative culture if stakeholders are to work effectively together across sectors. Conclusions There were differences in perspectives about the ways in which speech and language therapy services and supports could be improved, demonstrating the importance of engaging a diverse group of stakeholders. Of note were the unique insights the children brought about the barriers they faced as a result of their difficulties. Based on our findings we propose that children should be given influence in decisions about the supports that they receive in school. Implications for policy, research and practice are discussed.

BACKGROUND: Guided by the reserve capacity model, we evaluated the unique relationships between socioeconomic status (SES), reserve capacity (helplessness, self-efficacy, social support), and negative emotions on pain in patients with Rheumatoid Arthritis (RA). METHODS: The secondary analysis used baseline, cross-sectional data from 106 adults in a clinical trial comparing behavioral treatments for RA. Patients were eligible if they were ≥ 18 years old, met the ACR criteria for RA (determined by study rheumatologist), had stable disease and drug regimens for 3 months, and did not have a significant comorbid condition. Structural equation modeling evaluated the direct effects of SES, reserve capacity (helplessness- Arthritis Helplessness Index, self-efficacy -Personal Mastery Scale, social support- Social Provisions Scale) and negative emotions (stress and depressive symptoms- Perceived Stress Scale and Hamilton Depression Rating Scale) on pain (Rapid Assessment of Disease Activity in Rheumatology-RADAR & visual analog scale-VAS), and the indirect effects of SES as mediated by reserve capacity and negative emotions. The SEM model was evaluated using multiple fit criteria: χ2 goodness-of-fit statistic, the comparative fit index (CFI), the standardized root mean square residual (SRMR), and the root mean square error of approximation (RMSEA). RESULTS: Participants were mostly female (85%), 55.45 years old on average, self-identified as white (61%), Hispanic (16%), black (13%), and other (10%), and had RA for an average of 10.63 years. Results showed that low SES contributed to worse pain, through lower reserve capacity and higher negative emotions. Mediational analyses showed that reserve capacity and negative emotions partially mediated the effect of SES on pain. The final model explained 39% of the variance in pain. CONCLUSIONS: The findings indicate that lower SES was related to worse clinical pain outcomes and negative emotions and reserve capacity (helplessness, social support, and self-efficacy) mediated the effect of SES on pain. A primary limitation is the small sample size; future studies should evaluate this model further in larger, longitudinal approaches. Interventions that target negative emotions in patients with low SES may facilitate better pain control with RA. TRIAL REGISTRATION: clinicaltrials.gov NCT00072657 01/02/2004 20/03/2009.

BackgroundStandard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.MethodsEuropean Organisation for Research and Treatment of Cancer 1709/Canadian Cancer Trials Group CE.8 was a multicenter, randomized, controlled, open-label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving the only standard treatment in the whole population and in the subgroup of patients with MGMT promoter-unmethylated tumors.ResultsThe trial was opened at 82 institutions in Europe, Canada, and the U.S. A total of 749 patients (99.9% of the planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs. 16.5 months; HR = 1.04; P = .64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR = 0.97; P = .67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs. 15.1 months, HR = 1.13; P = .27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.ConclusionsAdding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.

The Mouse Metabolic Phenotyping Center (MMPC)Live Program was established in 2023 by the National Institute for Diabetes, Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high quality phenotyping services for mouse models of diabetes and obesity. Emerging as the next iteration of the MMPC Program which served the biomedical research community for 20 years (2001-2021), MMPCLive is designed as an outwardly-facing consortium of service cores that collaborate to provide reduced-cost consultation and metabolic, physiologic, and behavioral phenotyping tests on live mice for U.S. biomedical researchers. Four MMPCLive Centers located at universities around the country perform complex and often unique procedures in vivo on a fee for service basis, typically on mice shipped from the client or directly from a repository or vendor. Current areas of expertise include energy balance and body composition, insulin action and secretion, whole body carbohydrate and lipid metabolism, cardiovascular and renal function, food intake and behavior, microbiome and xenometabolism, and metabolic pathway kinetics. Additionally, an opportunity arose to reduce barriers to access and expand the diversity of the biomedical research workforce by establishing the VIBRANT Program. Directed at researchers historically underrepresented in the biomedical sciences, VIBRANT-eligible investigators have access to testing services, travel and career development awards, expert advice and experimental design consultation, and short internships to learn test technologies. Data derived from experiments run by the Centers belongs to the researchers submitting mice for testing which can be made publicly available and accessible from the MMPCLive database following publication. In addition to services, MMPCLive staff provide expertise and advice to researchers, develop and refine test protocols, engage in outreach activities, publish scientific and technical papers, and conduct educational workshops and training sessions to aid researchers in unraveling the heterogeneity of diabetes and obesity.

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.