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The aim of this study is to determine how students believe their learning-related experiences (i.e., attention, affect, and time perception) have changed over the course of the pandemic. This study documented students' (N[subscript analyzed] = 191) relative judgments of change between their "current" experiences (measured April 2022) and their remembered experiences from three different timepoints: (1) before the pandemic-related restrictions (before March 2020; pre-restriction); (2) immediately after the restrictions were implemented (spring 2020; early restriction); and (3) immediately after they were lifted (~ winter/spring 2022; post-restriction). This study also captured how students predicted their experiences would change in the future. Roughly 2 years after pandemic-related restrictions were introduced, students reported perceiving reductions in their attention, affect, and time-perception compared to their remembered pre- and early restriction learning-related experiences. They also reported perceived reductions in their attention and affect even as pandemic-related restrictions were beginning to lift, though these declines were slightly attenuated. Regarding the future, students were optimistic that their learning-related experiences would improve in the coming months. These findings can support the creation of future approaches targeting the improvement of attention, affect, and productivity in learning and performance-based environments.

Abstract The Fezouata Biota (Morocco) is a Burgess Shale-type (BST) assemblage that provides a wealth of information on Early Ordovician ecosystems. Much work has been done to compare the preservation of the Fezouata Biota to other BSTs. However, studies investigating preservation variations within the Fezouata Biota are rare. Here, we use probabilities to investigate the preservation of various ecological categories of Fezouata eumetazoans. Complex taphonomic processes and phylum-specific constraints have led to the better preservation of predators/scavengers in this biota. However, no differences in preservation are observed between vagile and sessile taxa. Importantly, Tremadocian taxa are better preserved than Floian ones. As such, this study highlights the gradual closure of the BST window of preservation in the Zagora region of Morocco and constitutes a benchmark for future palaeoecological and evolutionary studies on the Fezouata Biota.

Objectives: Despite clinical relevance, commercially available molecular tools for accurate β-lactamase detection are limited. In this study, we evaluated the performance of the ARM-DⓇ Kit, β-Lactamase, a commercially available multiplex PCR assay designed to detect nine β-lactamase genes, including the five major plasmid-mediated carbapenemases, ESBL and AmpC genes circulating in the United States. Methods: A diverse collection of 113 Gram-negative isolates, including 42 with multiple β-lactamases genes, was selected from the U.S. Centers for Disease Control and Prevention (CDC) & Food and Drug Administration (FDA) Antimicrobial Resistance Isolate Bank, to represent the most frequently detected bacterial species carrying plasmid-mediated β-lactam resistance genes. Results: Results were compared with whole genome sequence data. Of 164 β-lactamase gene targets with 49 unique variants, all were detected correctly without any cross-reactivity. The sensitivity and specificity were 100% (164/164) and 99.9% (852/853), respectively. Conclusion: The ARM-DⓇ Kit, β-Lactamase detected a wide range of β-lactamase genotypes at a low upfront cost. The Streck assay represents a suitable, comprehensive tool for the detection of key β-lactamase resistance genes of public health concern in the United States.

Abstract Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults. The present study derived BPV metrics from continuous beat-to-beat blood pressure monitoring data. Two sequential 7 min waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed. All sequence and dispersion based BPV metrics displayed good test–retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC = 0.87 and 0.82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group. In conclusion, beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained in older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.

Abstract Hailstorms are analyzed across the United States using explicit hailstone size calculations from convection-permitting regional climate simulations for historical, mid-century, and end of twenty-first-century epochs. Near-surface hailstones

Abstract The equilibrium theorem provided a fundamental framework for understanding species’ distributions and movement in fragmented ecosystems. Wetland-dependent avian species are model organisms to test insular predictions within protected area networks because their mobility allows surveillance of isolated patches without landscape barriers. We hypothesized size and isolation would influence functional connectivity of sanctuaries by GPS-marked wintering mallards (Anas platyrhynchos) within a mesocosm protected sanctuary area network. We evaluated functional connectivity and sanctuary use, measured by movements between sanctuaries, using a multistate modeling framework. Proximity drove connectivity, underscoring that patch isolation—not size—influenced connectivity, even for an avian species with no ascertainable landscape resistance or barriers. We also found that sanctuary use increased overwintering survival by reducing harvest mortality. Our test of equilibrium theory predictions demonstrated that isolation of protected sanctuary areas supersedes their size in determining functional connectivity for mallards and access to these areas may have direct fitness consequences. Our findings could refine land acquisition, restoration, and management practices with equal or greater emphasis on adjacency in protected area network design, especially for wetland-dependent migratory gamebirds.

Abstract Fossilization, or the transition of an organism from the biosphere to the geosphere, is a complex mechanism involving numerous biological and geological variables. Bacteria are one of the most significant biotic players to decompose organic matter in natural environments, early on during fossilization. However, bacterial processes are difficult to characterize as many different abiotic conditions can influence bacterial efficiency in degrading tissues. One potentially important variable is the composition and nature of the sediment on which a carcass is deposited after death. We experimentally examined this by decaying the marine shrimp Palaemon varians underwater on three different clay sediments. Samples were then analyzed using 16S ribosomal RNA sequencing to identify the bacterial communities associated with each clay system. Results show that samples decaying on the surface of kaolinite have a lower bacterial diversity than those decaying on the surface of bentonite and montmorillonite, which could explain the limited decay of carcasses deposited on this clay. However, this is not the only role played by kaolinite, as a greater proportion of gram-negative over gram-positive bacteria is observed in this system. Gram-positive bacteria are generally thought to be more efficient at recycling complex polysaccharides such as those forming the body walls of arthropods. This is the first experimental evidence of sediments shaping an entire bacterial community. Such interaction between sediments and bacteria might have contributed to arthropods’ exquisite preservation and prevalence in kaolinite-rich Lagerstätten of the Cambrian Explosion.

Abstract Complex oxides offer rich magnetic and electronic behavior intimately tied to the composition and arrangement of cations within the structure. Rare earth iron garnet films exhibit an anisotropy along the growth direction which has long been theorized to originate from the ordering of different cations on the same crystallographic site. Here, we directly demonstrate the three-dimensional ordering of rare earth ions in pulsed laser deposited (EuxTm1-x)3Fe5O12 garnet thin films using both atomically-resolved elemental mapping to visualize cation ordering and X-ray diffraction to detect the resulting order superlattice reflection. We quantify the resulting ordering-induced ‘magnetotaxial’ anisotropy as a function of Eu:Tm ratio using transport measurements, showing an overwhelmingly dominant contribution from magnetotaxial anisotropy that reaches 30 kJ m−3 for garnets with x = 0.5. Control of cation ordering on inequivalent sites provides a strategy to control matter on the atomic level and to engineer the magnetic properties of complex oxides.

Abstract Background Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer’s disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. Methods Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ42, Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. Results All autonomic networks were positively associated with Aβ42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. Conclusion The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

Abstract Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2+ fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2+ fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2+ myeloid cells, CCR7+ LAMP3+ dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2+ fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an in-depth view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.

Quiescence is a reversible cell cycle exit traditionally thought to be associated with a metabolically inactive state. Recent work in muscle cells indicates that metabolic reprogramming is associated with quiescence. Whether metabolic changes occur in cancer to drive quiescence is unclear. Using a multi-omics approach, we found that the metabolic enzyme ACSS2, which converts acetate into acetyl-CoA, is both highly upregulated in quiescent ovarian cancer cells and required for their survival. Indeed, quiescent ovarian cancer cells have increased levels of acetate-derived acetyl-CoA, confirming increased ACSS2 activity in these cells. Furthermore, either inducing ACSS2 expression or supplementing cells with acetate was sufficient to induce a reversible quiescent cell cycle exit. RNA-Seq of acetate treated cells confirmed negative enrichment in multiple cell cycle pathways as well as enrichment of genes in a published G0 gene signature. Finally, analysis of patient data showed that ACSS2 expression is upregulated in tumor cells from ascites, which are thought to be more quiescent, compared to matched primary tumors. Additionally, high ACSS2 expression is associated with platinum resistance and worse outcomes. Together, this study points to a previously unrecognized ACSS2-mediated metabolic reprogramming that drives quiescence in ovarian cancer. As chemotherapies to treat ovarian cancer, such as platinum, have increased efficacy in highly proliferative cells, our data give rise to the intriguing question that metabolically-driven quiescence may affect therapeutic response.

The rapid early diversification of arthropods has made understanding internal relationships within the group fiendish. Particularly unresolved is the origin of Euchelicerata, a clade consisting of the Prosomapoda (comprising the extant Xiphosura and Arachnida and the extinct Chasmataspidida, Eurypterida and synziphosurines) and the extinct Offacolidae. Here we describe new material of the Silurian ‘synziphosurine’ Bunaia woodwardi Clarke, 1919 that reveals previously unknown features of its ventral anatomy: a pair of elongated chelicerae in the prosoma, followed posteriorly by five pairs of biramous appendages, a first pre-abdomen somite bearing a pair of paddle-like uniramous appendages (exopods) and a ventral pretelsonic process. Phylogenetic analyses retrieve B. woodwardi as a member of Offacolidae closely related to Setapedites abundantis from the Early Ordovician Fezouata Biota. An anatomical comparison of the pretelsonic process of B. woodwardi, also present in Setapedites, with the posterior trunk morphologies of other Offacolidae, Habeliida and Vicissicaudata, suggests a possible homologous appendicular origin. This proposed apomorphic character supports a monophyletic Arachnomorpha, formed of Vicissicaudata, Habeliida and Euchelicerata. The establishment of this new homology could help to clarify the highly enigmatic phylogeny at the base of the euchelicerates as well as the sequence of character acquisition during their early evolution.

The small splice variant of the sulfonylurea receptor protein isoform 2 A (SUR2A-55) targets mitochondria and enhances mitoKATP activity. In male mice the overexpression of this protein promotes cardioprotection, reducing myocardial injury after an ischemic insult. However, it is unclear what impact SUR2A-55 overexpression has on the female myocardium. To investigate the impact of SU2R2A-55 on the female heart, mice with cardiac specific transgenic overexpression of SUR2A-55 (TGSUR2A-55) were examined by resting echocardiography and histopathology. In addition, hearts were subjected to ischemia reperfusion (IR) injury. Female TGSUR2A-55 mice had resting LV dysfunction and worse hemodynamic recovery with increased infarct size after IR injury. RNA-seq analysis found 227 differential expressed genes between WT and TGSUR2A-55 female mouse hearts that were enriched in pathways of cellular metabolism. This was in direct contrast to male mice that had only four differentially expressed genes. Female TGSUR2A-55 mice compared to female WT mice had reduced cardiomyocyte mitochondrial membrane potential without a change in electron transport chain protein expression. In addition, isolated mitochondria from female TGSUR2A-55 hearts displayed reduced sensitivity to ATP and diazoxide suggestive of increased mitoKATP activity. In conclusion, our data suggests that female TGSUR2A-55 mice are unable to tolerate a more active mitoKATP channel leading to LV dysfunction and worse response to IR injury. This is in direct contrast to our prior report showing cardioprotection in male mice overexpressing SUR2A-55 in heart. Future research directed at examining the expression and activity of mitoKATP subunits according to sex may elucidate different treatments for male and female patients.

Background:. Minimally invasive surgical interventions for metastatic invasion of the pelvis have become more prevalent and varied. Our group hypothesized that the use of percutaneous photodynamic nails (PDNs) would result in decreased pain, improved functional outcomes and level of ambulation, and decreased use of opioid pain medication. Methods:. We performed a retrospective chart review of patients with metastatic pelvic bone disease undergoing stabilization with PDNs (IlluminOss Medical) at 2 institutions. Functional outcome measures assessed include the Combined Pain and Ambulatory Function (CPAF), Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function, and PROMIS Global Health-Physical. Pain was assessed using a visual analog scale (VAS). Outcomes were assessed preoperatively and at 6 weeks, 3 months, 6 months, and 1 year following surgery. Results:. A total of 39 patients treated with PDNs were included. No cases of surgical site infection or implant failure were identified. The median pain VAS score decreased from 8 preoperatively to 0 at the 6-week time point (p < 0.0001). The median CPAF score improved from 5.5 points preoperatively to 7 points at the 3-month mark (p = 0.0132). A significant improvement in physical function was seen at 6 months in the PROMIS Physical Function (p = 0.02) and at both 6 months (p = 0.01) and 1 year (p < 0.01) for the PROMIS Global Health-Physical. The rate of patients prescribed opioid analgesia dropped from 100% preoperatively to 20% at 6 months following surgery (p < 0.001). By 6 weeks, all patients were fully weight-bearing and able to walk independently with or without assistive devices. Conclusions:. Percutaneous stabilization of metastatic periacetabular defects using PDNs is a safe and effective palliative procedure that has been shown to improve patient mobility and provide early pain relief. Level of Evidence:. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Qualitative accounts indicate there are sensory and communication related barriers to adequate childbirth and postnatal healthcare for autistic people. However, little quantitative work has explored the topic. This online survey study explored childbirth and postnatal experiences among 384 autistic and 492 non-autistic people. Compared with non-autistic people, autistic people were more likely to find the sensory aspects of birth overwhelming, and experienced lower satisfaction with birth-related and postnatal healthcare. Autistic people were more likely to experience postnatal depression and anxiety. The findings highlight that sensory and communication adjustments should be made to birth and postnatal healthcare for autistic people. The findings indicate the need for greater autism understanding among professionals and greater postnatal mental health support for autistic people.