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In the design and assessment of thick concrete shell structures subjected to out‐of‐plane loads, there is often a need to evaluate the response of shear critical components or to evaluate the influence of combined loading on shear response. This paper first presents the results from three shear‐critical large‐scale shell strip experiments subjected to combinations of shear, moment, and axial load. The experiments were monitored with digital image correlation equipment to capture the full deformation field response throughout loading. The paper then presents a simplified three‐dimensional model to predict the shear response of shear critical shell elements. The model called the 3D SEM, is compared to the shell strip experiments presented in this paper and is used to predict the interaction of in‐plane versus out‐of‐plane shear for several series of shear critical shell tests in the literature. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion A predominantly endoscopic approach for acute admissions with choledocholithiasis with a gallbladder in situ (CGIS) resulted in prolonged hospital length of stay due to delays at investigation and treatment junctures. We initiated a quality improvement program of trans‐cystic biliary stenting to facilitate efficient patient progress to acute cholecystectomy and outpatient ERCP if required.We utilized implementation frameworks with regular re‐assessment for this quality improvement project. Patients who required both ERCP and cholecystectomy for management of CGIS were identified for comparison of total length of stay before and after implementation. The outcomes for stent insertion and ERCP were also collected for analysis.Twenty‐three trans‐cystic stents were attempted with 22 inserted successfully. The median total length of stay for all patients requiring both ERCP and cholecystectomy for management of CGIS was shorter compared to 6 months prior to implementation (5 days (range 3–18) vs. 6 days (range 5–17); P = 0.009). The median stenting time was 14 min (range 9–48). After stent insertion, more ERCPs were performed as day‐only outpatient cases (20/23 (87.0%) vs. 6/44 (13.6%) P < 0.001). The rate of pancreatic duct wire cannulation at ERCP was also lower (1/23 (4.3%) vs. 18/44 (40.9%); P = 0.002). No complications of stent insertion or ERCP were recorded in the study cohort.Implementation of trans‐cystic stents can lead to reductions in total hospital length of stay and improve ERCP processes. Our experience suggests that surgical initiatives can be successfully added to routine practice by establishing a project team and applying quality improvement principles. [ABSTRACT FROM AUTHOR]

In this work, the degradation of mono‐ and polyfluorinated phenolic compounds was demonstrated by a series of crude plant peroxidases, including horseradish root (HRP) and six members of the Cucurbita genus. Highly active samples were identified using a library screening approach in which more than 50 crude plant samples were initially evaluated for defluorination activity toward 4‐fluorophenol. The highest concentrations were observed in the HRP, pumpkin skin (PKS), and butternut squash skin (BNS), which consistently gave the highest intrinsic rates of decomposition for all the substrates tested. Although HRP exhibited a significant decrease in activity with increased fluorination of the phenolic substrate, PKS showed only minor reductions. Furthermore, in silico studies indicated that the active site of HRP poorly accommodates the steric bulk of additional fluorines, causing the substrate to dock farther from the catalytic heme and thus slowing the catalysis rate. We propose that the PKS active site might be larger, allowing closer access to the perfluorinated substrate, and therefore maintaining higher activity compared to the HRP enzyme. However, detailed kinetic characterization studies of the peroxidases are recommended. Conclusively, the high catalytic activity of PKS and its high yield per gram of tissue make it an excellent candidate for developing environmentally friendly biocatalytic methods for degrading fluorinated aromatics. Finally, the success of the library approach in identifying highly active samples for polyfluorinated aromatic compound (PFAC) degradation suggests the method may find utility in the quest for other advanced catalysts for PFAS degradation. [ABSTRACT FROM AUTHOR]

Activation, break‐in, and/or pre‐treatment protocols are generally applied to energy conversion devices before regular operation to reach stable performance. There remains much to understand about the relationships among physical properties, performance, and electrochemical pre‐treatments. Here, a design‐of‐experiments (DoE) strategy is employed to address this gap by demonstrating the influence of five pre‐treatment parameters for carbon‐supported Pt‐nanoparticle catalysts on the electrocatalytic oxygen reduction reaction (ORR). A subset of pre‐treatments, developed using a central composite design, are tested in a flow cell combined with an inductively‐coupled plasma mass spectrometer (on‐line ICP‐MS). The DoE‐based approach facilitates comprehensive insights from two orders of magnitude fewer experiments than a conventional grid search. The coupled on‐line ICP‐MS setup enables effective catalysis and real‐time catalyst dissolution data. Leveraging insights from DoE for on‐line ICP‐MS and additional characterization, a model is built between the degradation of a multi‐dimensional supported Pt surface, its performance, and applied electrochemical parameters. These investigations identify surface modifications, such as oxidation, and subsequent restructuring of Pt during pre‐treatment as a primary cause of performance deterioration during ORR. By combining DoE with advanced characterization techniques, a powerful approach is demonstrated to gain a mechanistic understanding of pre‐treatment protocols that can be broadly adapted to various reaction chemistries. [ABSTRACT FROM AUTHOR]

ABSTRACT Canine cutaneous/subcutaneous soft‐tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate‐adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl‐derived RNA from aggregate‐free sarcomas and lymph nodes. CD3, CD20, MUM‐1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) is an oncogenic virus associated with various malignancies, including classical Hodgkin lymphoma (cHL). Despite its known association, the specific role of humoral immune response to EBV remains poorly characterized in cHL. To address this, we conducted a study using a custom protein microarray to measure the antibody responses in cHL patients and matched healthy controls recruited from an East‐Asian hospital‐based case–control study. We identified 16 IgG antibodies significantly elevated in EBV‐positive cHL compared with controls, defining an "East‐Asian antibody signature of EBV‐positive cHL." We evaluated responses against these 16 antibodies in a distinct European population, leveraging data from our previous European cHL case–control study from the UK, Denmark, and Sweden. A subset of antibodies (14/16, 87.5%) from the "East‐Asian antibody signature of EBV‐positive cHL" exhibited significant associations with cHL in the European population. Conversely, we assessed the "European antibody signature of EBV‐positive cHL" identified in our prior study which consisted of 18 EBV antibodies (2 IgA, 16 IgG), in the East‐Asian population. A subset of these antibodies (15/18, 83.3%) maintained significant associations with cHL in the East‐Asian population. This cross‐comparison of antibody signatures underscores the robust generalizability of EBV antibodies across populations. Five anti‐EBV IgG antibodies (LMP‐1, TK, BALF2, BDLF3, and BBLF1), found in both population‐specific antibody signatures, represent a "core signature of EBV‐positive cHL." Our findings suggest that the antibody responses targeting these core EBV proteins reflect a specific EBV gene expression pattern, serving as potential biomarkers for EBV‐positive cHL independent of population‐specific factors. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Neonatal resuscitation airway training can be difficult as there is no feedback on the face mask technique. “JUNO” is a training respiratory function monitor that provides feedback on mask leak, ventilatory rate, and tidal volume.To evaluate whether the use of the JUNO improves face mask ventilation techniques in manikin models.We conducted an observational cross‐over study with our unit staff. Following instructions, each participant performed a single‐person technique, followed by a two‐person technique with no JUNO feedback. This was repeated with JUNO feedback visible. A similar sequence was performed both in term and preterm manikins, giving a total of 8 sequences. Each participant was instructed to perform 1 min of positive pressure ventilation providing 30 inflations/minute for all of the simulations. Each of the simulation data underwent a data cleaning process.Thirty‐eight subjects provided a total of 304 sequences of positive pressure ventilation. A total of 13 354 inflations were analyzed. The feedback group had significantly lower rates of inflations with leak >60%, lower rates of excessive tidal volumes, lower mean leak percentage, and a lower mean inspiratory tidal volumes. When analyzed based on the technique (single person and two‐person), similar positive results were noted in the “feedback group”, across all the strata of staff. All of the staff reported that JUNO improved their ventilation technique and would recommend it for staff training.The use of JUNO significantly improved mask ventilation consistently across manikin types, staff roles, and techniques (either single‐ or two‐person). [ABSTRACT FROM AUTHOR]

The Social Intelligence Hypothesis (SIH) is one of the leading explanations for the evolution of cognition. Since its inception a vast body of literature investigating the predictions of the SIH has accumulated, using a variety of methodologies and species. However, the generalisability of the hypothesis remains unclear. To gain an understanding of the robustness of the SIH as an explanation for the evolution of cognition, we systematically searched the literature for studies investigating the predictions of the SIH. Accordingly, we compiled 103 studies with 584 effect sizes from 17 taxonomic orders. We present the results of four meta‐analyses which reveal support for the SIH across interspecific, intraspecific and developmental studies. However, effect sizes did not differ significantly between the cognitive or sociality metrics used, taxonomy or testing conditions. Thus, support for the SIH is similar across studies using neuroanatomy and cognitive performance, those using broad categories of sociality, group size and social interactions, across taxonomic groups, and for tests conducted in captivity or the wild. Overall, our meta‐analyses support the SIH as an evolutionary and developmental explanation for cognitive variation. [ABSTRACT FROM AUTHOR]

Highly sensitive in situ hybridization procedures (RNAScope) were used to quantify the expression of three dopamine receptors (Drd1, Drd2, and Drd3) in two song control nuclei (HVC and the Area X of the basal ganglia) that are known to receive dopaminergic inputs and in the periaqueductal gray (PAG) of male and female canaries. Both sexes were treated with testosterone to ensure they would sing actively. We also determined the excitatory versus inhibitory phenotype of the cells expressing these receptors as well as their activation following a period of song production. The three receptor types were identified in each brain area, with the exception of Drd3 in Area X. The density of cells expressing each receptor varied as a function of receptor type and brain area. Surprisingly few sex differences were detected; they do not seem to explain the sex differences in testosterone‐induced song. Overall, the density of Drd‐positive cells was much lower in PAG than in the two song control nuclei. In HVC, the majority of cells expressing the three receptor subtypes were VGlut2‐positive, whereas colocalization with Vglut2 occurred in few cells in Area X and in an intermediate proportion of cells in PAG. The number of inhibitory cells expressing dopamine receptors was limited. Most dopaminoceptive cells in Area X did not express either excitatory or inhibitory markers. Finally, cellular activation during singing behavior, as measured by the expression of Egr1, was observed in cells expressing each of the three dopamine receptor subtypes, except Drd3 in the PAG. [ABSTRACT FROM AUTHOR]

Segmented barrier islands can be found in regions with small tidal ranges. In contrast to tidally dominated barriers, where inlet dynamics are thought to control island length scales, the controls on barrier island length scales in wave‐dominated environments have not been quantified. These microtidal barriers typically have a curved shoreline, suggesting the influence of wave‐driven alongshore sediment transport. Microtidal barriers are also typically hydrodynamically isolated from one another, as weak tidal flows limit interactions between adjoining barriers. To better understand the controls on and scales of barrier segmentation in the relative absence of tides, here we develop a theoretical framework to estimate the alongshore length scales at which a barrier will either breach or heal following a disturbance in the barrier morphology. The non‐dimensional framework compares the timescales of overwash (advective) and alongshore sediment transport (diffusive) processes along barrier island chains. We then apply this framework to modern barrier islands in the microtidal Gulf of Mexico using wave hindcast data and the lengths, widths, heights, and lagoon depths measured from remotely sensed geospatial data and topobathymetric data. We find that most of these barriers are currently longer than their critical length scale, often as a result of coastal restoration efforts. Our critical length scale analysis suggests that most of the Gulf of Mexico barriers are vulnerable to segmentation despite coastal restoration efforts intended to protect fisheries and the mainland coasts. Plain Language Summary: Barrier islands provide valuable protection for mainland communities, marine fisheries, and coastal ecology. Restoration efforts are frequently enacted to preserve barrier islands, particularly after storm‐induced breaches segment a barrier into two or more shorter islands. Stable barrier island length scales have been predicted in environments with large tides, where barriers are separated by inlets; however, the characteristic stable length of barriers has not been quantified for environments with small tidal ranges. In these micro‐tidal environments, barriers are primarily shaped by two mechanisms of sediment transport: (a) overwash, which moves sediment from the nearshore environment on top of and behind barriers and (b) wave‐driven alongshore sediment transport, which smooths the shoreline. Here, we present a theoretical framework to evaluate the ability of barrier islands to heal when breached, based on a comparison of timescales for barrier rollover by overwash and shoreline smoothing through alongshore sediment transport. We then apply this analysis to barrier islands in the Gulf of Mexico, finding that many of these barriers are overly long, which suggests that they are vulnerable to segmentation despite (or perhaps due to) coastal restoration. Key Points: We assess the vulnerability of micro‐tidal barriers to segmentation by comparing the timescales of island rollover and alongshore diffusionThe comparison defines a critical length scale over which barriers should be vulnerable to segmenting into smaller islandsMany Gulf of Mexico islands are longer than predicted critical length scales—these long islands tend to be anthropogenically modified [ABSTRACT FROM AUTHOR]

Electrical and electronic equipment (EEE) have revolutionized our lives, however, their associated waste (WEEE) presents a global challenge because at this time EEE relies heavily on metals that are not commonly found in the living environment (Biosphere), which find their way into the environment during both production/disposal of EEE/WEEE. The use of organic components in EEE is increasingly common, particularly with the growing interest in flexible electronics. Here we describe an approach to device design employing in silico toxicity screening to assess the toxicity of the components chosen for use in EEE that is exemplified using inorganic and organic components known in the literature for the production of prototype organic light‐emitting electrochemical cells. This approach could easily be employed to screen a variety of components for which datasets to produce safety data sheets (SDSs) don't yet exist because they have not been produced in large scale or in a regulatory environment which necessitates this. The approach has significant potential to improve high throughput screening of components for EEE that are "safe‐by‐design", potentially in combination with AI and ML approaches. [ABSTRACT FROM AUTHOR]

Background: Recently, radio‐frequency ablation has been used to modulate slow‐wave activity in the porcine stomach. Gastric ablation is, however, still in its infancy compared to its history in the cardiac field, and electrophysiological studies have been restricted to temperature‐controlled, non‐irrigated ablation. Power‐controlled, irrigated ablation may improve lesion formation at lower catheter‐tip temperatures that produce the desired localized conduction block. Methods and Results: Power‐controlled, irrigated radio‐frequency ablation was performed on the gastric serosal surface of female weaner pigs (n = 5) in vivo. Three combinations of power (10–15 W) and irrigation settings (2–5 mL min−1) were investigated. A total of 12 linear lesions were created (n = 4 for each combination). Slow waves were recorded before and after ablation using high‐resolution electrical mapping. Key Results: Irrigation maintained catheter‐tip temperature below 50°C. Ablation induced a complete conduction block in 8/12 cases (4/4 for 10 W at 2 mL min−1, 1/4 for 10 W at 5 mL min−1, 3/4 for 15 W at 5 mL min−1). Blocks were characterized by a decrease in signal amplitude at the lesion site, along with changes in slow‐wave propagation patterns, where slow waves terminated at and/or rotated around the edge of the lesion. Conclusions and Inferences: Power‐controlled, irrigated ablation can successfully modulate gastric slow‐wave activity at a reduced catheter‐tip temperature compared to temperature‐controlled, non‐irrigated ablation. Reducing the irrigation rate is more effective than increasing power for blocking slow‐wave activity. These benefits suggest that irrigated ablation is a suitable option for further translation into a clinical intervention for gastric electrophysiology disorders. [ABSTRACT FROM AUTHOR]

Secondary forests represent a significant proportion of global forest cover, with over 70% of forests in East Asia classified as regenerating. While succession has been studied extensively in temperate systems, trajectories of subtropical succession remain poorly characterized in highly disturbed, urban‐adjacent forests. Investigating the additive beta diversity components of turnover and nestedness may reveal community assembly mechanisms driving secondary succession. The present study investigates plant community assembly along a successional gradient from 7 to 70 years following the onset of succession in secondary subtropical forests in Hong Kong, China. Plant survey data for 28 plots were analysed, generating additive Simpsons turnover and nestedness beta diversity metrics. Dissimilarity matrices were generated and modelled as a function of environmental matrices including forest plant community age (years following onset of secondary succession), inter‐community distance (metres), and soil moisture saturation (%) across three elevational bands using generalized dissimilarity models. Nonmetric multidimensional scaling of plant communities was conducted with Bray–Curtis dissimilarity matrices. Inter‐community distance and successional age differentially influenced plant species turnover between lowland and Montane forest types. Models of nestedness found that plot age and soil moisture saturation were significant drivers of nestedness patterns in plant communities across elevational classes. Turnover represented a higher proportion of Sorensen beta diversity than nestedness, while ANOSIM found significant differentiation between plant communities at different successional stages. Turnover patterns suggest a deterministic model of community assembly, with strong patterns of species replacement between communities at fine spatial scales and successional stages, as well as clear compositional shifts between lowland and montane forest types. NMDS analysis and functional compositional assessments suggested a transition from early successional communities with a high proportion of shrub species, to later successional communities with a higher proportion of tree species, with an increase in species turnover with greater age dissimilarity. [ABSTRACT FROM AUTHOR]

In 2016, the United Kingdom voted to exit the European Union, which was surrounded by political and social uncertainty. The United Kingdom now negotiates its own trade agreements, and in March 2023, it agreed to join the Comprehensive and Progressive Trans‐Pacific Partnership Agreement (CPTPP). A health impact assessment (HIA) was undertaken in 2022–23 to predict the potential impact of the CPTPP on the health and well‐being of the Welsh Population. This paper explores the HIA findings and highlights the value of the approach in engaging with stakeholders and informing policymakers. This HIA followed a standard five‐step approach which involved a literature review to identify potential health impacts, qualitative interviews with cross‐sectoral stakeholders and the development of a community health profile. The HIA identified potential impacts across the wider determinants of health and specific vulnerable population groups. Investor state dispute settlement mechanisms, economic uncertainty and loss of regulatory policy space were identified as key pathways for health impacts. The findings have been beneficial in informing decision‐makers to prepare for the CPTPP in Wales using an evidence‐informed approach. This work has demonstrated the value of a HIA approach that uses a transparent process to mobilise a wide range of evidence, resulting in transferrable learning. [ABSTRACT FROM AUTHOR]

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron‐containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle‐to‐organelle contacts. For example, the contact sites that mediate mitochondria–LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria–LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age‐related changes in LD morphology and mitochondria–lipid interactions in BAT. We examined the three‐dimensional morphology of mitochondria and LDs in young (3‐month) and aged (2‐year) murine BAT using serial block face‐scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle–organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT. [ABSTRACT FROM AUTHOR]

Background and purpose: This study was undertaken to compare the performance of plasma p‐tau181 with that of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD). Methods: We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests. Receiver operating characteristic analyses were used to determine the diagnostic accuracy of plasma p‐tau181 and [18F]FDG‐PET using clinical diagnosis and core AD biomarkers ([18F]florbetapir‐PET and cerebrospinal fluid [CSF] p‐tau181) as reference standards. Differences in the diagnostic accuracy between plasma p‐tau181 and [18F]FDG‐PET were determined by bootstrap‐based tests. Correlations of [18F]FDG‐PET and plasma p‐tau181 with CSF p‐tau181, amyloid β (Aβ) PET, and cognitive performance were evaluated to compare associations between measurements. Results: We observed that both plasma p‐tau181 and [18F]FDG‐PET identified individuals with positive AD biomarkers in CSF or on Aβ‐PET. In the MCI group, plasma p‐tau181 outperformed [18F]FDG‐PET in identifying AD measured by CSF (p = 0.0007) and by Aβ‐PET (p = 0.001). We also observed that both plasma p‐tau181 and [18F]FDG‐PET metabolism were associated with core AD biomarkers. However, [18F]FDG‐PET uptake was more closely associated with cognitive outcomes (Montreal Cognitive Assessment, Mini‐Mental State Examination, Clinical Dementia Rating Sum of Boxes, and logical memory delayed recall, p < 0.001) than plasma p‐tau181. Conclusions: Overall, although both plasma p‐tau181 and [18F]FDG‐PET were associated with core AD biomarkers, plasma p‐tau181 outperformed [18F]FDG‐PET in identifying individuals with early AD pathophysiology. Taken together, our study suggests that plasma p‐tau181 may aid in detecting individuals with underlying early AD. [ABSTRACT FROM AUTHOR]

Background: Many young adults report poor diet quality. However, research evaluating whether young adult males and females differ in diet quality is limited. Additionally, although diet quality has a known inverse association with body mass index (BMI), it is unclear whether this association is observed in young adults and whether it varies by gender. The present study aimed to evaluate gender differences in diet quality in young adults, as well as the associations between diet quality and BMI. Methods: Data collected via the Healthy Eating Quiz (HEQ) in respondents aged 18–35 years between July 2019 and December 2021 were analysed, including demographics, and diet quality calculated using the Australian Recommended Food Score (ARFS). Differences in characteristics were analysed using a two‐sample t‐test, chi‐squared and one‐way analysis of covariance. Linear regressions were performed to estimate associations between diet quality and BMI. An interaction term was included in the model to test differences between genders. Results: The respondents (n = 28,969) were predominantly female (70.8%) with a mean ± SD age of 25.9 ± 5.0 years and BMI of 24.6 ± 5.2 kg/m2. The mean ± SD ARFS was significantly different between females and males (33.1 ± 8.6 vs. 31.4 ± 9.3 points out of 70; p < 0.001). Diet quality had a small, significant inverse association with BMI in both genders. The interaction effect between diet quality score and gender in predicting BMI was significant (p < 0.001), suggesting the impact of diet quality on BMI varies by gender, with lower diet quality more strongly associated with higher BMI in females compared to males. Conclusion: Interventions that target young adults are needed to improve diet quality and its potential contribution to BMI status. As a result of the small observed effect sizes, caution should be applied in interpreting these findings. Key points: Young male and female adults (18–35 years) demonstrate significantly different diet quality, with females scoring higher.Diet quality and body mass index (BMI) were inversely associated in both males and females, but the impact of diet quality on BMI varies by gender.Dietary interventions in young adults are needed to improve diet quality and the contribution to BMI status. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pyroglutamic acidosis (PGA) or 5‐Oxoprolinuria is an uncommon and often overlooked cause of high anion gap metabolic acidosis (HAGMA). This case highlights the importance of systematically approaching HAGMA, and to consider PGA as a differential diagnosis when medications that disrupt the γ‐glutamyl cycle such as flucloxacillin and paracetamol are present. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The established cerebrospinal fluid (CSF) phosphorylated tau181 (p‐tau181) may not reliably reflect concomitant Alzheimer's disease (AD) and primary age‐related tauopathy (PART) found in Creutzfeldt–Jakob disease (CJD) at autopsy. METHODS: We investigated CSF N‐terminal p‐tau181, p‐tau217, and p‐tau231 with in‐house Simoa assays in definite CJD (n = 29), AD dementia (n = 75), mild cognitive impairment (MCI) due to AD (n = 65), and subjective cognitive decline (SCD, n = 28). Post‐mortem examination performed in patients with CJD 1.3 (0.3–14.3) months after CSF collection revealed no co‐pathology in 10, concomitant AD in 8, PART in 8, and other co‐pathologies in 3 patients. RESULTS: N‐terminal p‐tau was increased in CJD versus SCD (p < 0.0001) and correlated with total tau (t‐tau) in the presence of AD and PART co‐pathology (rho = 0.758–0.952, p ≤ 001). Concentrations in CJD+AD were indistinguishable from AD dementia, with the largest fold‐change in p‐tau217 (11.6), followed by p‐tau231 and p‐tau181 (3.2–4.5). DISCUSSION: Variable fold‐changes and correlation with t‐tau suggest that p‐tau closely associates with neurodegeneration and concomitant AD in CJD. Highlights: N‐terminal phosphorylated tau (p‐tau) biomarkers are increased in Creutzfeldt–Jakob disease (CJD) with and without concomitant AD.P‐tau217, p‐tau231, and p‐tau181 correlate with total tau (t‐tau) and increase in the presence of amyloid beta (Aβ) co‐pathology.N‐terminal p‐tau181 and p‐tau231 in Aβ‐negative CJD show variation among PRNP genotypes.Compared to mid‐region–targeting p‐tau181, cerebrospinal fluid (CSF) N‐terminal p‐tau has greater potential to reflect post‐mortem neuropathology in the CJD brain. [ABSTRACT FROM AUTHOR]

Serial crystallography (SX) involves combining observations from a very large number of diffraction patterns coming from crystals in random orientations. To compile a complete data set, these patterns must be indexed (i.e. their orientation determined), integrated and merged. Introduced here is TORO (Torch‐powered robust optimization) Indexer, a robust and adaptable indexing algorithm developed using the PyTorch framework. TORO is capable of operating on graphics processing units (GPUs), central processing units (CPUs) and other hardware accelerators supported by PyTorch, ensuring compatibility with a wide variety of computational setups. In tests, TORO outpaces existing solutions, indexing thousands of frames per second when running on GPUs, which positions it as an attractive candidate to produce real‐time indexing and user feedback. The algorithm streamlines some of the ideas introduced by previous indexers like DIALS real‐space grid search [Gildea, Waterman, Parkhurst, Axford, Sutton, Stuart, Sauter, Evans & Winter (2014). Acta Cryst. D70, 2652–2666] and XGandalf [Gevorkov, Yefanov, Barty, White, Mariani, Brehm, Tolstikova, Grigat & Chapman (2019). Acta Cryst. A75, 694–704] and refines them using faster and principled robust optimization techniques which result in a concise code base consisting of less than 500 lines. On the basis of evaluations across four proteins, TORO consistently matches, and in certain instances outperforms, established algorithms such as XGandalf and MOSFLM [Powell (1999). Acta Cryst. D55, 1690–1695], occasionally amplifying the quality of the consolidated data while achieving superior indexing speed. The inherent modularity of TORO and the versatility of PyTorch code bases facilitate its deployment into a wide array of architectures, software platforms and bespoke applications, highlighting its prospective significance in SX. [ABSTRACT FROM AUTHOR]

The sorting and assembly machinery (SAM) Complex is responsible for assembling β‐barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block‐face‐scanning electron microscopy and computer‐assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50‐deficient myotubes from mice and humans with wild‐type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography‐Mass Spectrometry‐based metabolomics to explore differential changes in WT and Sam50‐deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50‐deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß‐Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50‐deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50‐deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle. [ABSTRACT FROM AUTHOR]

Issue Addressed: Universities are a crucial setting to address and promote optimal mental health of young Australians. However, there is a lack of knowledge of universities' views of current implementation of health and wellbeing initiatives. Therefore, we examined the views of Australian universities on the implementation of health and wellbeing policies and programs within Australian universities. Methods: An online survey of Australian universities asked respondents to rate their level of agreement with five statements pertaining to the implementation of health and wellbeing policies and programs for students within Australian universities using a 5‐point Likert scale (strongly agree to strongly disagree). Results: Eleven universities completed the survey (28.2% response rate). All respondents (n = 11) agreed that universities play a crucial role in supporting the health and wellbeing of their students and report access to sufficient expertise to do this. Approximately three‐quarters (8/11) agreed that universities know what policies and programs to implement to support their students' health and wellbeing. There was less agreement that universities have sufficient resources (2/11 agree) or access to sufficient information about the health and wellbeing of their student population (3/11 agree) to support the implementation of health and wellbeing policies and programs. Conclusions: Australian universities demonstrated strong organisational commitment to supporting the health and wellbeing of their students but highlighted some key barriers to implementation. So What?: Findings from this preliminary research highlight potential barriers and facilitators to the implementation of health and wellbeing policies and programs in Australian universities, and potential foci for future research. [ABSTRACT FROM AUTHOR]

Herbarium specimens are increasingly being used as sources of information to understand the ecology and evolution of plants and their associated microbes. Most studies have used specimens as a source of genetic material using culture‐independent approaches. We demonstrate that herbarium specimens can also be used to culture nodule‐associated bacteria, opening the possibility of using specimens to understand plant–microbe interactions at new spatiotemporal scales. We used historic and contemporary nodules of a common legume, Medicago lupulina, to create a culture collection. We were able to recover historic bacteria in 15 genera from three specimens (collected in 1950, 2004, and 2015). This work is the first of its kind to isolate historic bacteria from herbarium specimens. Future work should include inoculating plants with historic strains to see if they produce nodules and if they affect plant phenotype and fitness. Although we were unable to recover any Ensifer, the main symbiont of Medicago lupulina, we recovered some other potential nodulating species, as well as many putative growth‐promoting bacteria. [ABSTRACT FROM AUTHOR]

Tendon allograft and xenograft processing often involves one or more steps of freezing and thawing. As failure strength is an important graft consideration, this study aimed to evaluate effects on failure properties when varying freeze‐thaw conditions. Kangaroo tendons, a potential xenograft source, were used to evaluate changes in ultimate tensile strength (UTS), failure strain and elastic modulus after exposure to different freezer‐storage temperatures (−20°C vs. −80°C), storage durations (1, 3, 6, 9, or 12 months), number of freeze‐thaw cycles (1, 2, 3, 4, 5, or 10), or freeze‐thaw temperature ranges (including freezing in liquid nitrogen to thawing at 37°C). Tendons stored for 6 or more months had significantly increased UTS and elastic modulus compared with 1 or 3 months of storage. This increase occurred irrespective of the freezing temperature (−20°C vs. −80°C) or the number of freeze‐thaw cycles (1 vs. 10). In contrast, UTS, failure strain and the elastic modulus were no different between storage temperatures, number of freeze‐thaw cycles and multiple freeze‐thaw cycles across a range of freeze and thaw temperatures. Common freeze‐thaw protocols did not negatively affect failure properties, providing flexibility for graft testing, storage, transportation and decellularisation procedures. However, the change in properties with the overall storage duration has implications for assessing the consistent performance of grafts stored for short versus extended periods of time (<6 months vs. >6 months), and the interpretation of data obtained from tissues of varying or unknown storage durations. [ABSTRACT FROM AUTHOR]

With the growing importance of identity development, it is important to see the intersections that occur with one's identity as both a leader and as bisexual. Leader identity and bisexual identity development can occur in tandem, with critical moments influencing both dually occurring identity development processes. By understanding the need that the field of leadership education has to explore the development of bisexual leaders and leadership educators, the authors discuss the need to center minoritized identities in our scholarship and practice within the field. [ABSTRACT FROM AUTHOR]

While biallelic POLR3A loss‐of‐function variants are traditionally linked to hypomyelinating leukodystrophy, patients with a specific splice variant c.1909+22G>A manifest as adolescent‐onset spastic ataxia without overt leukodystrophy. In this study, we reported eight new cases, POLR3A‐related disorder with c.1909+22 variant. One of these patients showed expanded phenotypic spectrum of generalised dystonia and her sister remained asymptomatic except for hypodontia. Two patients with dystonic arm tremor responded to deep brain stimulation. In our systemic literature review, we found that POLR3A‐related disorder with c.1909+22 variant has attenuated disease severity but frequency of dystonia and upper limb tremor did not differ among genotypes. [ABSTRACT FROM AUTHOR]

Tumor suppressor p53 (TP53) is frequently mutated in cancer, often resulting not only in loss of its tumor-suppressive function but also acquisition of dominant-negative and even oncogenic gain-of-function traits. While wild-type p53 levels are tightly regulated, mutants are typically stabilized in tumors, which is crucial for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. Most regulators of wild-type p53 also regulate p53 mutants, except for p53 R337H regulators, which are largely private to this mutant. Mechanistically, FBXO42 emerged as a positive regulator for a subset of p53 mutants, working with CCDC6 to control USP28-mediated mutant p53 stabilization. Additionally, C16orf72/HAPSTR1 negatively regulates both wild-type p53 and all tested mutants. C16orf72/HAPSTR1 is commonly amplified in breast cancer, and its overexpression reduces p53 levels in mouse mammary epithelium leading to accelerated breast cancer. This study offers a network perspective on p53 stability regulation, potentially guiding strategies to reinforce wild-type p53 or target mutant p53 in cancer. Synopsis: Genome-wide p53 protein stability screens provide a comprehensive network view of the processes regulating wild type and mutant p53 and uncover potential targets for reinforcing wild-type p53 or targeting mutant p53 in cancer. Most proteins regulating wild-type p53 also affect mutant p53, except for p53 R337H, which harbors a distinct set of regulators. FBXO42 is a novel positive regulator for a subset of p53 mutants and collaborates with CCDC6 in regulating USP28-mediated stabilization of mutant p53. Loss of FBXO42 or CCDC6 reduces metastasis of p53 mutant pancreatic cancer cells, similar to depletion of mutant p53 itself. C16orf72/HAPSTR1 is a negative regulator affecting the stability of both wild-type and mutant p53, depending on its nuclear localization and the activity of the E3 ubiquitin ligase HUWE1. C16orf72/HAPSTR1 is a proto-oncogene and its overexpression reduces p53 levels and accelerates tumor growth in a p53 wild-type breast cancer mouse model. Genome-wide p53 protein stability screens provide a comprehensive network view of the processes regulating wildtype and mutant p53 and uncover potential targets for reinforcing wild-type p53 or targeting mutant p53 in cancer. [ABSTRACT FROM AUTHOR]

The homeless population remains understudied, and their victimisation is unreported, especially homeless victims of homicide. With the number of people faced with homelessness increasing, the heightened rates of victimisation for violent crimes throughout this population becomes even more concerning. A review of the literature revealed an absence of meaningful research beyond basic descriptive statistics of rates of homeless homicide in the UK. The current study explores the behavioural variation and risk factors associated with the victims and perpetrators of 19 cases of homeless homicide in the UK. A content analysis was first conducted to derive 22 case variables. Smallest Space Analysis was then employed to analyse the cases according to the variables selected. The themes produced in the SSA output were comparable to that of Canter's Victim Role Model: Victim as Object, Victim as Person and Victim as Vehicle. The current study lays a foundation for developing an understanding of the variation in behaviour across cases of homeless homicide and may serve to inform preventative measures. [ABSTRACT FROM AUTHOR]

The article "A body of one's own: A trans history of Argentina" by Patricio Simonetto explores the history of transgender and gender-diverse individuals in Argentina amidst the country's complex national history. The author delves into the challenges of applying modern terminology to historical contexts and highlights the diverse experiences and identities within the transgender community. The book sheds light on the local rituals and global influences shaping the transgender experience in Argentina, emphasizing the importance of understanding the nuances and complexities of gender identity. [Extracted from the article]

Targeting immunosuppressive metastatic cancer cells is a key challenge in therapy. We recently have shown that a rigid‐rod aromatic, pBP−NBD, that responds to enzymes and kill immunosuppressive metastatic osteosarcoma (mOS) and castration resistant prostate cancer (CRPC) cells in mimetic bone microenvironment. However, pBP−NBD demonstrated moderate efficacy against CRPC cells. To enhance activity, we incorporated the unnatural amino acid L‐ or D‐4,4′‐biphenylalanine (L‐ or D−BiP) into pBP−NBD, drastically increasing cellular uptake and CRPC inhibition. Specifically, we inserted BiP into pBP−NBD to target mOS (Saos2 and SJSA1) and CRPC (VCaP and PC3) cells with overexpressed phosphatases. Our results show that the D‐peptide backbone with an aspartate methyl diester at the C‐terminal offers the highest activity against these immunosuppressive mOS and CRPC cells. Importantly, imaging shows that the peptide assemblies almost instantly enter the cells and accumulate primarily within the endoplasmic reticulum of Saos2, SJSA1, and PC3 cells and at the lysosomes of VCaP cells. By using BiP to boost cellular uptake and self‐assembly within cancer cells, this work illustrates an unnatural hydrophobic amino acid as a versatile and effective residue to boost endocytosis of synthetic peptides for intracellular self‐assembly. [ABSTRACT FROM AUTHOR]

Apparent treatment‐resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with three antihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90 mmHg and taking ≥3 antihypertensives) from the United States–based Optum® de‐identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3 antihypertensive classes within 30 days between January 1, 2015 and June 30, 2021, and two office BP measures recorded 1–90 days apart within 30 days to 11 months after the index regimen date. Of a total 18 797 070 patients identified with any hypertension, 71 100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22 risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80 years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre‐existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5‐year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high‐risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5‐year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high‐risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation remains the treatment of choice for children with kidney failure (KF). In South Africa, kidney replacement therapy (KRT) is restricted to children eligible for transplantation. This study reports on the implementation of the Paediatric Feasibility Assessment for Transplantation (pFAT) tool, a psychosocial risk score developed in South Africa to support transparent transplant eligibility assessment in a low‐resource setting. Methods: Single‐center retrospective descriptive analysis of children assessed for KRT using pFAT tool from 2015 to 2021. Results: Using the pFAT form, 88 children (median [range] age 12.0 [1.1 to 19.0] years) were assessed for KRT. Thirty (34.1%) children were not listed for KRT, scoring poorly in all domains, and were referred for supportive palliative care. Fourteen of these 30 children (46.7%) died, with a median survival of 6 months without dialysis. Nine children were reassessed and two were subsequently listed. Residing >300 km from the hospital (p =.009) and having adherence concerns (p =.003) were independently associated with nonlisting. Of the 58 (65.9%) children listed for KRT, 40 (69.0%) were transplanted. One‐year patient and graft survival were 97.2% and 88.6%, respectively. Only one of the four grafts lost at 1‐year posttransplant was attributed to psychosocial issues. Conclusions: Short‐term outcomes among children listed using the pFAT form are good. Among those nonlisted, the pFAT highlights specific psychosocial/socioeconomic barriers, over which most children themselves have no power to change, which should be systemically addressed to permit eligibility of more children and save lives. [ABSTRACT FROM AUTHOR]

Objective: To describe primary care provider (PCP) practices for the assessment and management of females with urinary incontinence (UI), and appraise these practices relative to recommendations made in high‐quality clinical guidelines. Methods: Studies were searched in four databases (MEDLINE, EMBASE, CINAHL, Web of Science) from their respective inception dates to 6 March 2023. All studies describing UI evaluation and management practices used by PCPs for female patients were eligible. Two reviewers independently selected studies assessed their quality and extracted data. A narrative synthesis of included studies was performed to describe practices. Relevant evaluation and management practices were then compared to recommendations that were consistent across current high‐quality UI guidelines. Pharmacotherapy, referrals, and follow‐ups were reported descriptively only. Results: A total of 3475 articles were retrieved and, among those, 31 were included in the review. The majority reported a poor–moderate adherence to performing a pelvic examination (reported adherence range: 23–76%; based on eight studies), abdominal examination (0–87%; three studies), pelvic floor muscle assessment (9–36%; two studies), and bladder diary (0–92%; nine studies), while there was high adherence to urine analysis (40–97%; nine studies). For the conservative management of UI, studies revealed a poor–moderate adherence to recommendations for pelvic floor muscle training (5–82%; nine studies), bladder training (2–53%; eight studies) and lifestyle interventions (1–71%; six studies). Regarding pharmacotherapy, PCPs predominantly prescribed antimuscarinics (2–46%; nine studies) and oestrogen (2–77%; seven studies). Lastly, PCPs referred those reporting UI to medical specialists (5–37%; 14 studies). Referrals were generally made <30 days after diagnosis with urologists being the most sought out professional to assess and treat UI. Conclusion: This review revealed poor–moderate adherence to clinical practice guideline recommendations. While these findings reflect high variability in reporting, the key message is that most aspects of patient care for female UI provided by PCPs needs to improve. [ABSTRACT FROM AUTHOR]

Many animal species depend on sound to communicate with conspecifics. However, human‐generated (anthropogenic) noise may mask acoustic signals and so disrupt behavior. Animals may use various strategies to circumvent this, including shifts in the timing of vocal activity and changes to the acoustic parameters of their calls. We tested whether pied tamarins (Saguinus bicolor) adjust their vocal behavior in response to city noise. We predicted that both the probability of occurrence and the number of long calls would increase in response to anthropogenic noise and that pied tamarins would temporally shift their vocal activity to avoid noisier periods. At a finer scale, we anticipated that the temporal parameters of tamarin calls (e.g., call duration and syllable repetition rate) would increase with noise amplitude. We collected information on the acoustic environment and the emission of long calls in nine wild pied tamarin groups in Manaus, Brazil. We found that the probability of long‐call occurrence increased with higher levels of anthropogenic noise, though the number of long calls did not. The number of long calls was related to the time of day and the distance from home range borders—a proxy for the distance to neighboring groups. Neither long‐call occurrence nor call rate was related to noise levels at different times of day. We found that pied tamarins decreased their syllable repetition rate in response to anthropogenic noise. Long calls are important for group cohesion and intergroup communication. Thus, it is possible that the tamarins emit one long call with lower syllable repetition, which might facilitate signal reception. The occurrence and quantity of pied tamarin' long calls, as well as their acoustic proprieties, seem to be governed by anthropogenic noise, time of the day, and social mechanisms such as proximity to neighboring groups. Highlights: Anthropogenic noise may mask animal sounds and to circumvent this, animals may use various behavioral strategies.Pied tamarins increase call occurrence and reduce syllable repetition rate in response to anthropogenic noise.The number of calls emitted was not related to anthropogenic noise levels, but the time of day and the distance from the border of their home ranges, proxy for the distance to neighboring groups. [ABSTRACT FROM AUTHOR]

Key points Altered autonomic input to the heart plays a major role in atrial fibrillation (AF). Autonomic neurons termed ganglionated plexi (GP) are clustered on the heart surface to provide the last point of neural control of cardiac function. To date the properties of GP neurons in humans are unknown. Here we have addressed this knowledge gap in human GP neuron structure and physiology in patients with and without AF. Human right atrial GP neurons embedded in epicardial adipose tissue were excised during open heart surgery performed on both non‐AF and AF patients and then characterised physiologically by whole cell patch clamp techniques. Structural analysis was also performed after fixation at both the single cell and at the entire GP levels via three‐dimensional confocal imaging. Human GP neurons were found to exhibit unique properties and structural complexity with branched neurite outgrowth. Significant differences in excitability were revealed between AF and non‐AF GP neurons as measured by lower current to induce action potential firing, a reduced occurrence of low action potential firing rates, decreased accommodation and increased synaptic density. Visualisation of entire GPs showed almost all neurons are cholinergic with a small proportion of noradrenergic and dual phenotype neurons. Phenotypic distribution differences occurred with AF including decreased cholinergic and dual phenotype neurons, and increased noradrenergic neurons. These data show both functional and structural differences occur between GP neurons from patients with and without AF, highlighting that cellular plasticity occurs in neural input to the heart that could alter autonomic influence on atrial function. The autonomic nervous system plays a critical role in regulating heart rhythm and the initiation of AF; however, the structural and functional properties of human autonomic neurons in the autonomic ganglionated plexi (GP) remain unknown. Here we perform the first whole cell patch clamp electrophysiological and large tissue confocal imaging analysis of these neurons from patients with and without AF. Our data show human GP neurons are functionally and structurally complex. Measurements of action potential kinetics show higher excitability in GP neurons from AF patients as measured by lower current to induce action potential firing, reduced low firing action potential rates, and decreased action potential accommodation. Confocal imaging shows increased synaptic density and noradrenergic phenotypes in patients with AF. Both functional and structural differences occur in GP neurons from patients with AF that could alter autonomic influence on atrial rhythm. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPSvenous) for the diagnosis and monitoring of neurodegenerative diseases in remote settings. METHODS: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p‐tau181 and p‐tau217) were measured in paired DPSvenous and ethylenediaminetetraacetic acid plasma samples with single‐molecule array. In the validation cohort, a subset of participants (n = 99) had cerebrospinal fluid (CSF) biomarkers. RESULTS: All DPSvenous and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPSvenous GFAP, NfL, p‐tau181, and p‐tau217 differed between CSF Aβ‐positive and ‐negative individuals and were associated with worsening cognition. DISCUSSION: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPSvenous extends the utility of blood‐based biomarkers to remote settings with simplified sampling conditions, storage, and logistics. Highlights: A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPSvenous).DPSvenous biomarkers correlated with standard procedures and cognitive status.DPSvenous biomarkers had a good diagnostic accuracy discriminating amyloid status.Our findings show the potential interchangeability of DPSvenous and plasma sampling.DPSvenous may facilitate remote and temperature‐independent sampling for AD biomarker measurement.Innovative tools for blood biomarker sampling may help recognizing the earliest changes of AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations with high cerebral small vessel disease (CSVD) concomitance remains unclear. METHODS: Using a Singapore‐based cohort of cognitively impaired subjects, we assessed associations between plasma GFAP and neuroimaging measures of brain amyloid and CSVD, including white matter hyperintensities (WMH). We also examined the diagnostic performance of plasma GFAP in detecting brain amyloid beta positivity (Aβ+). RESULTS: When stratified by WMH status, elevated brain amyloid was associated with higher plasma GFAP only in the WMH– group (β = 0.383; P < 0.001). The diagnostic performance of plasma GFAP in identifying Aβ+ was significantly higher in the WMH– group (area under the curve [AUC] = 0.896) than in the WMH+ group (AUC = 0.712, P = 0.008). DISCUSSION: The biomarker utility of plasma GFAP in detecting brain amyloid pathology is dependent on the severity of concomitant WMH. Highlight: Glial fibrillary acidic protein (GFAP)'s association with brain amyloid is unclear in populations with high cerebral small vessel disease (CSVD).Plasma GFAP was measured in a cohort with CSVD and brain amyloid.Plasma GFAP was better in detecting amyloid in patients with low CSVD versus high CSVD.Biomarker utility of GFAP in detecting brain amyloid depends on the severity of CSVD. [ABSTRACT FROM AUTHOR]

Humid dunes slacks are a highly threatened habitat, listed as vulnerable in the EU habitat red list. Accelerated successional processes in dune systems have resulted in the loss and degradation of ideal conditions for specialist dune slack species, hence the need for conservation management. We investigated the restoration of a dune slack in North Wales, UK, where vegetation and soil removal to 10 cm depth was undertaken to reinstate nutrient‐poor, open and damp conditions. We assessed the outcomes of the management for dune slack communities over the 18 years since restoration. We also assessed the differences between restored and unrestored areas of dune slacks. The dunes were restored in the winter of 2004/2005, after which we conducted vegetation surveys in fixed quadrats for most years in the restored and adjacent, un‐restored dune slacks. Species diversity and plant community composition changes over time were assessed using Shannon's index, multivariate analysis and indicator species analysis. Comparisons between the restored and unrestored areas of the dune slacks were also made. Ellenberg indicator values (EIVs) were examined to identify potential environmental drivers of post management successional changes. After 18 years the restored dune slacks developed a species‐rich and diverse community. compared to the unrestored slacks. The establishment of species occurred rapidly in the first three years, followed by continued but slower increases in species richness and diversity. This is due to the addition of new species without losses of established species. EIVs show no significant difference over time suggesting the restored areas are still at an early stage of succession. Distinct stages of community change since restoration are characterised by different indicator species. Plants are likely to be largely recruited from an existing seed bank. Restoration by turf removal may be suitable for other low nutrient, species rich habitats dependent upon fluctuating groundwater levels. [ABSTRACT FROM AUTHOR]

Forest litter decomposition is an essential component of global carbon and nutrient turnover. Invertebrates play important roles in litter decomposition, but the regional pattern of their effects is poorly understood. We examined 476 case studies across 93 sites and performed a meta‐analysis to estimate regional effects of invertebrates on forest litter decomposition. We then assessed how invertebrate diversity, climate and soil pH drive regional variations in invertebrate‐mediated decomposition. We found that (1) invertebrate contributions to litter decomposition are 1.4 times higher in tropical and subtropical forests than in forests elsewhere, with an overall contribution of 31% to global forest litter decomposition; and (2) termite diversity, together with warm, humid and acidic environments in the tropics and subtropics are positively associated with forest litter decomposition by invertebrates. Our results demonstrate the significant difference in invertebrate effects on mediating forest litter decomposition among regions. We demonstrate, also, the significance of termites in driving litter mass loss in the tropics and subtropics. These results are particularly pertinent in the tropics and subtropics where climate change and human disturbance threaten invertebrate biodiversity and the ecosystem services it provides. [ABSTRACT FROM AUTHOR]

Background: There are frequent discrepancies among high‐resolution manometry (HRM), functional lumen imaging probe (FLIP), and esophagram in identifying lower esophageal sphincter (LES)‐related obstruction. We aimed to determine the frequency of those discrepancies and how they influenced clinical treatment/outcomes. Methods: We identified patients who had all three tests (HRM, FLIP, and esophagram) and endoscopy performed for evaluation of esophageal symptoms in our Center for Esophageal Diseases. Discrepancies among the tests for the presence of LES obstruction were noted, and the performance of individual tests was compared against a consensus opinion rendered by a panel of esophagologists. Binary logistical regression was performed, and ROC curves were generated for prediction of the consensus clinical diagnosis of LES obstruction. Key Results: A total of 126 patients (mean age 57.9 ± 17.0 years; 67% female) met inclusion criteria. All three tests agreed on the presence or absence of LES obstruction in only 72 (57%) patients [no LES obstruction in 57 (45%), LES obstruction in 15 (12%)]. Thirteen patients (10%) had a change in management based on additional findings on FLIP +/− esophagram not seen on HRM with 69% having symptomatic improvement after LES‐directed intervention. FLIP was the strongest predictor of a consensus diagnosis of LES obstruction by logistic regression and ROC (OR 23.36, AUC 0.796), followed by HRM (OR 15.41, AUC 0.764). Conclusions & Inference: High‐resolution manometry, functional lumen imaging probe, and esophagram each have considerable limitations for identifying LES obstruction, and discrepancies among these tests occur frequently. Multimodal testing is often required for adequate evaluation of LES‐related obstruction. [ABSTRACT FROM AUTHOR]

COVID‐19, which was first identified in 2019 in Wuhan, China, is a respiratory illness caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Although some patients infected with COVID‐19 can remain asymptomatic, most experience a range of symptoms that can be mild to severe. Common symptoms include fever, cough, shortness of breath, fatigue, loss of taste or smell and muscle aches. In severe cases, complications can arise including pneumonia, acute respiratory distress syndrome, organ failure and even death, particularly in older adults or individuals with underlying health conditions. Treatments for COVID‐19 include remdesivir, which has been authorised for emergency use in some countries, and dexamethasone, a corticosteroid used to reduce inflammation in severe cases. Biological drugs including monoclonal antibodies, such as casirivimab and imdevimab, have also been authorised for emergency use in certain situations. While these treatments have improved the outcome for many patients, there is still an urgent need for new treatments. Medicinal plants have long served as a valuable source of new drug leads and may serve as a valuable resource in the development of COVID‐19 treatments due to their broad‐spectrum antiviral activity. To date, various medicinal plant extracts have been studied for their cellular and molecular interactions, with some demonstrating anti‐SARS‐CoV‐2 activity in vitro. This review explores the evaluation and potential therapeutic applications of these plants against SARS‐CoV‐2. This review summarises the latest evidence on the activity of different plant extracts and their isolated bioactive compounds against SARS‐CoV‐2, with a focus on the application of plant‐derived compounds in animal models and in human studies. [ABSTRACT FROM AUTHOR]

This paper examines whether authentic leadership provides the resources employees need to build their psychological capacities and well‐being so that they can embrace organisational change and engage in innovative work behaviour (IWB) within non‐profit organisation (NPO). The paper builds on previous research examining the antecedents of IWB such as 'innovation‐enabling culture' and psychological capital (PsyCap). The new variables examined in this study are authentic leadership and acceptance of change. Utilising a structural equation modelling methodology, 248 surveys from Australian not‐for‐profit employees were analysed revealing that authentic leadership accounted for more than a fifth of the variance of PsyCap; PsyCap, age, and authentic leadership accounted for 40% of employees' well‐being; and age, leadership, and acceptance of change accounted for a quarter of their IWB, although acceptance of change was not directly related to IWB. The main contribution of this paper is in explaining why authentic leadership is an important ingredient for building an 'innovation‐enabling culture' for NPO employees, suggesting that such leadership provides a pathway for developing effective workplace relationships built on trust and ethical decision making. Such behaviour builds a supportive culture for developing employees' personal resources, which promotes the conditions for promoting IWB. Points for practitioners: Authentic leadership behaviour provides a platform for developing the psychological capacities of employees in non‐profit organisations (NPOs) contracted to deliver social services to Australians.Authentic leadership behaviours and psychological capital enhance employees' well‐being.Authentic leadership behaviours and psychological capital are significant building blocks of an innovation‐enabling culture in NPOs. [ABSTRACT FROM AUTHOR]

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies. Since MSKI is a broad term encompassing infections varying in pathogen, anatomical location, and implants used, there are also a wide range of animal models described modeling these disparate infections. Although some of these variations are required to adequately evaluate specific interventions, there would be enormous value in creating a unified and standardized criteria to animal testing in the treatment of MSKI. The Treatment Workgroup of the 2023 International Consensus Meeting on Musculoskeletal Infection was responsible for questions related to preclinical models for treatment of MSKI. The main objective was to review the literature related to priority questions and estimate consensus opinion after voting. This document presents that process and results for preclinical models related to (1) animal model considerations, (2) outcome measurements, and (3) imaging. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We set out to identify tau PET‐positive (A+T+) individuals among amyloid‐beta (Aβ) positive participants using plasma biomarkers. METHODS: In this cross‐sectional study we assessed 234 participants across the AD continuum who were evaluated by amyloid PET with [18F]AZD4694 and tau‐PET with [18F]MK6240 and measured plasma levels of total tau, pTau‐181, pTau‐217, pTau‐231, and N‐terminal tau (NTA‐tau). We evaluated the performances of plasma biomarkers to predict tau positivity in Aβ+ individuals. RESULTS: Highest associations with tau positivity in Aβ+ individuals were found for plasma pTau‐217 (AUC [CI95%] = 0.89 [0.82, 0.96]) and NTA‐tau (AUC [CI95%] = 0.88 [0.91, 0.95]). Combining pTau‐217 and NTA‐tau resulted in the strongest agreement (Cohen's Kappa = 0.74, CI95% = 0.57/0.90, sensitivity = 92%, specificity = 81%) with PET for classifying tau positivity. DISCUSSION: The potential for identifying tau accumulation in later Braak stages will be useful for patient stratification and prognostication in treatment trials and in clinical practice. Highlights: We found that in a cohort without pre‐selection pTau‐181, pTau‐217, and NTA‐tau showed the highest association with tau PET positivity.We found that in Aβ+ individuals pTau‐217 and NTA‐tau showed the highest association with tau PET positivity.Combining pTau‐217 and NTA‐tau resulted in the strongest agreement with the tau PET‐based classification. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changes and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p‐tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS: We employed a novel p‐tau217 immunoassay (University of Gothenburg [UGOT] p‐tau217) in four independent cohorts (n = 308) including a cerebrospinal fluid (CSF) biomarker‐classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired (CU) and mild cognitively impaired (MCI) participants (MYHAT and Pittsburgh), and a population‐based cohort of individuals with SCD (Barcelonaβeta Brain Research Center's Alzheimer's At‐Risk Cohort [β‐AARC]). RESULTS: UGOT p‐tau217 showed high accuracy (area under the curve [AUC] = 0.80–0.91) identifying amyloid beta (Aβ) pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p‐tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC = 0.91). DISCUSSION: UGOT p‐tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum. [ABSTRACT FROM AUTHOR]