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Background: There is increasing interest in developing FPR2 agonists (compound 43, ACT‐389949 and BMS‐986235) as potential pro‐resolving therapeutics, with ACT‐389949 and BMS‐986235 having entered phase I clinical development. FPR2 activation leads to diverse downstream outputs. ACT‐389949 was observed to cause rapid tachyphylaxis, while BMS‐986235 and compound 43 induced cardioprotective effects in preclinical models. We aim to characterise the differences in ligand‐receptor engagement and downstream signalling and trafficking bias profile. Experimental Approach: Concentration‐response curves to G protein dissociation, β‐arrestin recruitment, receptor trafficking and second messenger signalling were generated using FPR2 ligands (BMS‐986235, ACT‐389949, compound 43 and WKYMVm), in HEK293A cells. Log(τ/KA) was obtained from the operational model for bias analysis using WKYMVm as a reference ligand. Docking of FPR2 ligands into the active FPR2 cryoEM structure (PDBID: 7T6S) was performed using ICM pro software. Key Results: Bias analysis revealed that WKYMVm and ACT‐389949 shared a very similar bias profile. In comparison, BMS‐986235 and compound 43 displayed approximately 5‐ to 50‐fold bias away from β‐arrestin recruitment and trafficking pathways, while being 35‐ to 60‐fold biased towards cAMP inhibition and pERK1/2. Molecular docking predicted key amino acid interactions at the FPR2 shared between WKYMVm and ACT‐389949, but not with BMS‐986235 and compound 43. Conclusion and Implications: In vitro characterisation demonstrated that WKYMVm and ACT‐389949 differ from BMS‐986235 and compound 43 in their signalling and protein coupling profile. This observation may be explained by differences in the ligand‐receptor interactions. In vitro characterisation provided significant insights into identifying the desired bias profile for FPR2‐based pharmacotherapy. [ABSTRACT FROM AUTHOR]

Polymeric supramolecular hydrogels (PSHs) leverage the thermodynamic and kinetic properties of non‐covalent interactions between polymer chains to govern their structural characteristics. As these materials are formed via endothermic or exothermic equilibria, their thermal response is challenging to control without drastically changing the nature of the chemistry used to join them. In this study, we introduce a novel class of PSHs utilizing the intercalation of double‐stranded DNA (dsDNA) as the primary dynamic non‐covalent interaction. The resulting dsDNA intercalating supramolecular hydrogels (DISHs) can be tuned to exhibit both endothermically or exothermically driven binding through strategic selection of intercalators. Bifunctional polyethylene glycol (MW~2000 Da) capped with intercalators of varying hydrophobicity, charge, and size (acridine, psoralen, thiazole orange, and phenanthridine) produced DISHs with comparable moduli (500–1000 Pa), but unique thermal viscoelastic responses. Notably, acridine‐based cross‐linkers displayed invariant and even increasing relaxation times with temperature, suggesting an endothermic binding mechanism. This methodology expands the set of structure‐properties available to biomass‐derived DNA biomaterials and promises a new material system where a broad set of thermal and viscoelastic responses can be obtained due to the sheer number and variety of intercalating molecules. [ABSTRACT FROM AUTHOR]

The UN Decade on Ecosystem Restoration will result in an unprecedented need for seeds. Agricultural production, or the growing of plants under controlled conditions to produce desired resources, can be a helpful tool for providing the quantities of seeds needed for large‐scale restoration. In some ecosystems, agricultural production of native plant seeds is part of the restoration process. This is particularly true for native plants that are similar to major food crops, such as native grasses. However, conventional crops have contrasting characteristics (e.g. fast growing, high yield for a focused use) from those desired in restored vegetation (plants capable of surviving and providing ecosystem services in variable environments). This contrast leads to significant, often opposing differences in desirable characteristics in crop versus natural systems. Examples include rapid germination in domesticated crops versus seed dormancy in wild plants, uniform germination, growth and flowering versus bet‐hedging strategies, or high seed retention versus seed dispersal. While it may be useful to maximize productivity of native plants in agricultural environments with similar trait modifications, for restoration, the demands of the natural environment should be primary, and agricultural production should aim to maximize the diversity, function, and evolutionary potential of native species. Any perceived benefits that come from the production of large quantities of inexpensive seeds that cannot meet the needs of wild communities are short‐sighted. We suggest research directions that will be needed to meld agricultural production needs with those of restoration practitioners, as a challenge for those invested in the procurement and use of wild seeds. [ABSTRACT FROM AUTHOR]

The study aimed to illustrate how contact (from match‐event data) and head acceleration event (HAE) (from instrumented mouthguard [iMG]) data can be combined to inform match limits within rugby. Match‐event data from one rugby union and rugby league season, including all competitive matches involving players from the English Premiership and Super League, were used. Playing exposure was summarised as full game equivalents (FGE; total minutes played/80). Expected contact and HAE exposures at arbitrary thresholds were estimated using match‐event and iMG data. Generalised linear models were used to identify differences in contact and HAE exposure per FGE. For 30 FGEs, forwards had greater contact than backs in rugby union (n = 1272 vs. 618) and league (n = 1569 vs. 706). As HAE magnitude increased, the differences between positional groups decreased (e.g., rugby union; n = 34 and 22 HAE >40 g for forwards and backs playing 30 FGEs). Currently, only a relatively small proportion of rugby union (2.5%) and league (7.3%) players exceeded 25 FGEs. Estimating contact and HAEs per FGE allows policymakers to prospectively plan and model estimated overall and position‐specific loads over a season and longer term. Reducing FGE limits by a small amount would currently only affect contact and HAE exposure for a small proportion of players who complete the most minutes. This may be beneficial for this cohort but is not an effective HAE and contact exposure reduction strategy at a population level, which requires individual player management. Given the positional differences, FGE limits should exist to manage appropriate HAE and contact exposure. Highlights: Estimating contact events and head acceleration events (HAEs) per full game equivalents (FGE, i.e., 80 minutes) allows policymakers to prospectively plan and model estimated overall and position‐specific loads over a season and longer term.Through retrospectively analysing FGE exposure, the findings demonstrate that only a small proportion of rugby players would be affected by a feasible reduction in FGE limits, but the difference in contact and HAE exposure for these players could be significant over the duration of a playing career.Per FGE in both rugby codes, forwards have a greater expected contact and head acceleration event exposure than backs, and thus any implemented FGE limits should at least be position group‐specific and ideally incorporate individual player management. [ABSTRACT FROM AUTHOR]

Background: Radiation delivery with ultra‐high dose rate (FLASH) radiotherapy (RT) holds promise for improving treatment outcomes and reducing side effects but poses challenges in radiation delivery accuracy due to its ultra‐high dose rates. This necessitates the development of novel imaging and verification technologies tailored to these conditions. Purpose: Our study explores the effectiveness of proton‐induced acoustic imaging (PAI) in tracking the Bragg peak in three dimensions and in real time during FLASH proton irradiations, offering a method for volumetric beam imaging at both conventional and FLASH dose rates. Methods: We developed a three‐dimensional (3D) PAI technique using a 256‐element ultrasound detector array for FLASH dose rate proton beams. In the study, we tested protoacoustic signal with a beamline of a FLASH‐capable synchrocyclotron, setting the distal 90% of the Bragg peak around 35 mm away from the ultrasound array. This configuration allowed us to assess various total proton radiation doses, maintaining a consistent beam output of 21 pC/pulse. We also explored a spectrum of dose rates, from 15 Gy/s up to a FLASH rate of 48 Gy/s, by administering a set number of pulses. Furthermore, we implemented a three‐dot scanning beam approach to observe the distinct movements of individual Bragg peaks using PAI. All these procedures utilized a proton beam energy of 180 MeV to achieve the maximum possible dose rate. Results: Our findings indicate a strong linear relationship between protoacoustic signal amplitudes and delivered doses (R2 = 0.9997), with a consistent fit across different dose rates. The technique successfully provided 3D renderings of Bragg peaks at FLASH rates, validated through absolute Gamma index values. Conclusions: The protoacoustic system demonstrates effectiveness in 3D visualization and tracking of the Bragg peak during FLASH proton therapy, representing a notable advancement in proton therapy quality assurance. This method promises enhancements in protoacoustic image guidance and real‐time dosimetry, paving the way for more accurate and effective treatments in ultra‐high dose rate therapy environments. [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS) is a well‐studied illness defined by clinical features (e.g., headache and nausea), as assessed by the Lake Louise score (LLS). Although obvious in its severe form, early stages of AMS are poorly defined and easily confused with common travel‐related conditions. Measurement of hypoxaemia, the cause of AMS, should be helpful, yet to date its utility for identifying AMS susceptibility remains unclear. This study quantified altitude‐induced hypoxaemia in individuals during an ascent to 4800 m to determine the utility of nocturnal pulse oximetry measurements for prediction of AMS. Eighteen individuals (36 ± 16 years of age) ascended to 4800 m over 12 days. Symptomology of AMS was assessed each morning via LLS criteria, with participants categorized as either AMS‐positive (LLS ≥ 3 with headache) or AMS‐negative. Overnight peripheral oxygen saturations (ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$) were recorded continuously (1 Hz) using portable oximeters. Derivatives of these recordings were compared between AMS‐positive and ‐negative subjects (Mann–Whitney U‐test). Exploratory analyses (Pearson's) were conducted to investigate relationships between overnight parameters and AMS severity. Overnight derivatives, including ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$, heart rate/ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$, variance, oxygen desaturation index, hypoxic burden and total sleep time at <80% SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$, all differed significantly between AMS‐positive and ‐negative subjects (all P < 0.01), with cumulative/relative frequency plots highlighting these differences visually. Exploratory analysis revealed that ov‐SpO2${{S}_{{\mathrm{p}}{{{\mathrm{O}}}_2}}}$ from 3850 m was correlated with peak LLS at 4800 m (r = 0.58–0.61). The findings highlight the potential for overnight oximetry to predict AMS susceptibility during ascent to high altitude. Further investigation is required to develop, evaluate and optimize predictive models to improve AMS management and prevention. What is the central question of this study?Early stages of acute mountain sickness are poorly defined, with existing assessment methods for the illness being highly ineffective. Can overnight pulse oximetry be used as a detection and prediction tool for deterioration in acute mountain sickness?What is the main finding and its importance?Overnight oximetry measurements from 3850 m were significantly correlated with acute mountain sickness severity at 4800 m (3 days later), whereas Lake Louise scores from the same time points were unrelated. These findings highlight the potential for pulse oximetry recorded from lower camps to be predictive of acute mountain sickness severity at higher altitude. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off‐label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High‐performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two‐compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <−.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine. [ABSTRACT FROM AUTHOR]

Crop pests and pathogens annually cause over $220 billion in global crop damage, with insects consuming 5%–20% of major grain crops. Current crop pest and disease control strategies rely on insecticidal and fungicidal sprays, plant genetic resistance, transgenes, and agricultural practices. Double‐stranded RNA (dsRNA) is emerging as a novel sustainable method of plant protection as an alternative to traditional chemical pesticides. Successful commercialization of dsRNA‐based biocontrols requires the economical production of large quantities of dsRNA combined with suitable delivery methods to ensure RNAi efficacy against the target pest. In this study, we have optimized the design of plasmid DNA constructs to produce dsRNA biocontrols in Escherichia coli, by employing a wide range of alternative synthetic transcriptional terminators before measurement of dsRNA yield. We demonstrate that a 7.8‐fold increase of dsRNA was achieved using triple synthetic transcriptional terminators within a dual T7 dsRNA production system compared to the absence of transcriptional terminators. Moreover, our data demonstrate that batch fermentation production dsRNA using multiple transcriptional terminators is scalable and generates significantly higher yields of dsRNA generated in the absence of transcriptional terminators at both small‐scale batch culture and large‐scale fermentation. In addition, we show that application of these dsRNA biocontrols expressed in E. coli cells results in increased insect mortality. Finally, novel mass spectrometry analysis was performed to determine the precise sites of transcriptional termination at the different transcriptional terminators providing important further mechanistic insight. [ABSTRACT FROM AUTHOR]

Lung carcinoids (L‐CDs) are rare, poorly characterised neuroendocrine tumours (NETs). L‐CDs are more common in women and are not the consequence of cigarette smoking. They are classified histologically as typical carcinoids (TCs) or atypical carcinoids (ACs). ACs confer a worse survival. Histological classification is imperfect, and there is increasing interest in molecular markers. We therefore investigated global transcriptomic and epigenomic profiles of 15 L‐CDs resected with curative intent at Royal Brompton Hospital. We identified underlying mutations and structural abnormalities through whole‐exome sequencing (WES) and single nucleotide polymorphism (SNP) genotyping. Transcriptomic clustering algorithms identified two distinct L‐CD subtypes. These showed similarities either to pancreatic or neuroendocrine tumours at other sites and so were named respectively L‐CD‐PanC and L‐CD‐NeU. L‐CD‐PanC tumours featured upregulation of pancreatic and metabolic pathway genes matched by promoter hypomethylation of genes for beta cells and insulin secretion (p < 1 × 10−6). These tumours were centrally located and showed mutational signatures of activation‐induced deaminase/apolipoprotein B editing complex activity, together with genome‐wide DNA methylation loss enriched in repetitive elements (p = 2.2 × 10−16). By contrast, the L‐CD‐NeU group exhibited upregulation of neuronal markers (adjusted p < 0.01) and was characterised by focal spindle cell morphology (p = 0.04), peripheral location (p = 0.01), high mutational load (p = 2.17 × 10−4), recurrent copy number alterations, and enrichment for ACs. Mutations affected chromatin remodelling and SWI/SNF complex pathways. L‐CD‐NeU tumours carried a mutational signature attributable to aflatoxin and aristolochic acid (p = 0.05), suggesting a possible environmental exposure in their pathogenesis. Immunologically, myeloid and T‐cell markers were enriched in L‐CD‐PanC and B‐cell markers in L‐CD‐NeU tumours. The substantial epigenetic and non‐coding differences between L‐CD‐PanC and L‐CD‐NeU open new possibilities for biomarker selection and targeted treatment of L‐CD. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

CREB gene family (ATF1, CREB1, CREM) fusions with either EWSR1 or FUS gene partners drive the pathogenesis of a wide range of neoplasms, including various soft tissue tumors, intracranial myxoid mesenchymal tumors (IMMTs), hyalinizing clear cell carcinoma (HCCC), and rare mesotheliomas. Recently, a SMARCA2::CREM fusion was reported in one case each of IMMT and HCCC. In this study, we expand the clinicopathologic and molecular spectrum of these neoplasms by describing three additional cases with SMARCA2::CREM and one with a novel SMARCA4::CREM fusion, highlighting the recurrent potential of additional CREB gene fusion partners beyond FET family members. To evaluate if these fusions define a new pathologic entity, we performed a comprehensive genomic and methylation analysis and compared the results to other related tumors. Tumors occurred in children and young adults (median age 20 years) and spanned a broad anatomic distribution, including soft tissue, intracranial, head and neck, and prostatic urethra. Microscopically, the tumors shared an undifferentiated round to epithelioid cell phenotype and a hyalinized fibrous stroma. Immunohistochemically, a polyphenotypic profile was observed, with variable expression of SOX10, desmin, and/or epithelial markers. No targetable genomic alterations were found using panel‐based DNA sequencing. By DNA methylation and transcriptomic analyses, tumors grouped closely to FET::CREB entities, but not with SMARCA4/SMARCB1‐deficient tumors. High expression of CREM by immunohistochemistry was also documented in these tumors. Patients experienced local recurrence (n = 2), locoregional lymph node metastases (n = 2), and an isolated visceral metastasis (n = 1). Overall, our study suggests that SMARCA2/4::CREM fusions define a distinct group of neoplasms with round cell to epithelioid histology, a variable immunoprofile, and a definite risk of malignancy. Larger studies are needed to further explore the pathogenetic relationship with the FET::CREB family of tumors. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Species range shifts due to climate alterations have been increasingly well‐documented. Although amphibians are one of the most sensitive groups of animals to environmental perturbations due to climate change, almost no studies have offered evidence of poleward distribution shifts in this taxon in response to climate warming. Range shifts would be facilitated by variation in traits associated with the ability of species to persist and/or shift their range in the face of climate change, but the extent and consequences of intraspecific variation in these traits is unclear. We studied the role of intraspecific variation in the ongoing range shift of green treefrogs (Hyla cinerea) in response to climate change. We explored factors that are often associated with range shifts to test the hypothesis that there are differences in these traits between recently range‐expanded and nearby historical populations. We then tested the consequences of intraspecific variation for modelling climate‐induced range shifts by comparing species distribution models (SDMs) that used as input either data from the entire species range or separate inputs from ‘subpopulations’ corresponding to the historical range or the recently expanded range. We expected that building a separate SDM for each population would more accurately characterize the species range if historical and expanded populations differed in traits related to their response to climate. We found that critical thermal minimum decreased and thermal breadth increased with latitude, but the effect of latitude was significantly stronger for expanded populations compared to historical populations. Additionally, we found that individuals from expanded populations had longer leg lengths when compared to their historical counterparts. Finally, we found higher model accuracy for one of the population‐level SDMs than the species‐level SDM. Our results suggest that thermal tolerance and dispersal morphologies are associated with amphibian distributional shifts as these characteristics appear to facilitate rapid range expansion of a native anuran. Additionally, our modelling results emphasize that SDM accuracy could be improved by dividing a species range to consider potential differences in traits associated with climate responses. Future research should identify the mechanisms underlying intraspecific variation along climate gradients to continue improving SDM prediction of range shifts under climate change. [ABSTRACT FROM AUTHOR]

H13 tool steel and copper (Cu) functionally gradient materials (FGMs) have been manufactured using laser‐directed energy deposition (L‐DED). Differential scanning calorimetry analysis of H13‐Cu blends shows clear separation of the Fe‐rich and Cu‐rich liquids due to the Fe–Cu miscibility gap. Also, in the analysis, it is determined that there is a large solidification range that will promote solidification cracking. A compositional gradient is produced by changing the powder feed rates in situ within the L‐DED system, to create six different compositions, beginning with 100% H13 at the substrate and ending at 100% Cu. Single‐track clads and three‐layer clad tracks of various H13‐Cu blends are successfully printed onto a wrought H13 substrate. The cross section of the clad samples containing Cu experiences vertical cracking, indicative of solidification cracking. Rectangular FGM samples of H13‐Cu are successfully printed onto a wrought H13 substrate using two different laser powers, namely 400 and 460 W; however, these samples experience major porosity and detrimental transverse cracking issues situated in the ≈25 and ≈45 wt% Cu sections. This is attributed to the Fe–Cu miscibility gap, difference in coefficient of thermal expansion, and Cu being known to promote cracking in steels. Some potential solutions to these issues are discussed. [ABSTRACT FROM AUTHOR]

Background Purpose Material and methods Results Conclusions Patients with locally advanced prostate cancer require the prostate and pelvic lymph nodes to be irradiated simultaneously during radiation therapy treatment. However, relative motion between treatment targets decreases dosimetric conformity. Current treatment methods mitigate this error by having large treatment margins and often prioritize the prostate at patient setup at the cost of lymph node coverage.Treatment accuracy can be improved through real‐time multi‐target adaptation which requires simultaneous motion monitoring of both the prostate and lymph node targets. This study developed and evaluated an intrafraction pelvic bone motion monitoring method as a surrogate for pelvic lymph node displacement to be combined with prostate motion monitoring to enable multi‐target six‐degrees‐of‐freedom (6DoF) tracking using 2D kV projections acquired during treatment.A method to monitor pelvic bone translation and rotation was developed and retrospectively applied to images from 20 patients treated in the TROG 15.01 Stereotactic Prostate Ablative Radiotherapy with Kilovoltage Intrafraction Monitoring (KIM) trial. The pelvic motion monitoring method performed template matching to calculate the 6DoF position of the pelvis from 2D kV images. The method first generated a library of digitally reconstructed radiographs (DRRs) for a range of imaging angles and pelvic rotations. The normalized 2D cross‐correlations were then calculated for each incoming kV image and a subset of DRRs and the DRR with the maximum correlation coefficient was used to estimate the pelvis translation and rotation. Translation of the pelvis in the unresolved direction was calculated using a 3D Gaussian probability estimation method. Prostate motion was measured using the KIM marker tracking method. The pelvic motion monitoring method was compared to the ground truth obtained from a 6DoF rigid registration of the CBCT and CT.The geometric errors of the pelvic motion monitoring method demonstrated sub‐mm and sub‐degree accuracy and precision in the translational directions (TLR${{T}_{{\mathrm{LR}}}}$, TSI${{T}_{{\mathrm{SI}}}}$, TAP${{T}_{{\mathrm{AP}}}}$) and rotational directions (RLR${{R}_{{\mathrm{LR}}}}$, RSI${{R}_{{\mathrm{SI}}}}$, RAP${{R}_{{\mathrm{AP}}}}$). The 3D relative displacement between the prostate and pelvic bones exceeded 2, 3, 5, and 7 mm for approximately 66%, 44%, 12%, and 7% of the images.Accurate intrafraction pelvic bone motion monitoring in 6DoF was demonstrated on 2D kV images, providing a necessary tool for real‐time multi‐target motion‐adapted treatment. [ABSTRACT FROM AUTHOR]

To meet climate targets, consumption‐based household emissions need to fall rapidly. An important but still poorly understood question is whether generational change could contribute to decreases in emissions. It is sometimes assumed that younger generations such as Millennials and Generation Z are more concerned about climate change and have greener lifestyles than previous generations of the Silent Generation, Baby boomers, and Generation X, but carbon footprinting analysis typically focuses on age groups rather than comparing generations over time. This paper provides a first assessment of the change in consumption‐based carbon footprints of the Silent, Baby boomer, Generation X, and Millennial generations within the United Kingdom between 2001 and 2020 and a comparison of the footprints of different generational groups. The analysis is based on environmentally extended input–output analysis, using the Living Costs and Food Survey and emission data from the UK multi‐regional input–output database. We find some evidence for the hypothesis that younger generations have smaller footprints than older generations as Generation X and Millennial households have smaller carbon footprints compared to the generation before them at a similar life stage. We find that factors such as decarbonization, household occupancy, total expenditure, and changing consumption patterns contribute to the UK's changing carbon consumption emissions between 2001 and 2020, and the importance of these factors varies for different generational groups. However, future research that uses a longer time series is required to assess generational differences in carbon footprints over the whole lifespan of several generations. [ABSTRACT FROM AUTHOR]

The catalytic hydrogenation of CO2 to formate was achieved using the previously reported dichloro(η6‐p‐cymene){diphenyl(3‐methyl‐2‐indolyl)phosphine}ruthenium (1) as a catalyst under mild conditions. In this complex, the phosphorus‐based ligand adopts a κ1‐P coordination mode. The catalytic activity was achieved in the presence of DBU as a base providing a TONmax value of 3,800. In order to explore potential transformations occurring within the catalytic reactions, a series of stoichiometric tests were performed. Complex 1 was reacted with DBU to form chloro(η6‐p‐cymene){diphenyl(3‐methyl‐2‐indolide)phosphine}ruthenium (2). Structural characterization of complex 2 confirmed a κ2‐P,N coordination mode for the ligand resulting in a four membered metallacycle. Reaction of 2 with H2 led to the formation of hydrochloro(η6‐p‐cymene){diphenyl(3‐methyl‐indolyl)phosphine}ruthenium (3), albeit not with a clean conversion. This is the product resulting from the formal addition of hydrogen across the Ru−N bond of the metallacycle. Complex 3 was also synthesized via an alternative route involving the reaction of complex 1 with Me2NH • BH3 as a means of converting Ru−Cl to Ru−H [ABSTRACT FROM AUTHOR]

The COVID‐19‐Associated Hospitalization Surveillance Network (COVID‐NET) was established in March 2020 to monitor trends in hospitalizations associated with SARS‐CoV‐2 infection. COVID‐NET is a geographically diverse population‐based surveillance system for laboratory‐confirmed COVID‐19‐associated hospitalizations with a combined catchment area covering approximately 10% of the US population. Data collected in COVID‐NET includes monthly counts of hospitalizations for persons with confirmed SARS‐CoV‐2 infection who reside within the defined catchment area. A Bayesian modeling approach is proposed to estimate US national COVID‐associated hospital admission rates based on information reported in the COVID‐NET system. A key component of the approach is the ability to estimate uncertainty resulting from extrapolation of hospitalization rates observed within COVID‐NET to the US population. In addition, the proposed model enables estimation of other contributors to uncertainty including temporal dependence among reported COVID‐NET admission counts, the impact of unmeasured site‐specific factors, and the frequency and accuracy of testing for SARS‐CoV‐2 infection. Based on the proposed model, an estimated 6.3 million (95% uncertainty interval (UI) 5.4–7.3 million) COVID‐19‐associated hospital admissions occurred in the United States from September 2020 through December 2023. Between April 2020 and December 2023, model‐based monthly admission rate estimates ranged from a minimum of 1 per 10,000 population (95% UI 0.7–1.2) in June of 2023 to a highest monthly level of 16 per 10,000 (95% UI 13–19) in January 2022. [ABSTRACT FROM AUTHOR]

Background: We investigated whether a novel 8‐week personalised health behaviour support programme, focusing on the stability of symptoms and strategies to improve activities of daily living, was feasible and acceptable in adults with post‐COVID syndrome. Methods: In this randomised, controlled, pilot feasibility trial, 32 adults with post‐COVID syndrome (continued symptoms for ≥ 12 weeks) were randomised 1:1 to receive personalised health behaviour support (self‐reported physical activity and symptom diaries, plus seven one‐to‐one remotely delivered personalised self‐management support sessions), once weekly for 8‐weeks, or usual care (referral to online 'your COVID‐19 recovery' programme). The primary outcome was the feasibility of recruiting and randomising adults with post‐COVID syndrome. The secondary outcomes were to assess the acceptability and safety of the intervention and various outcome measures. Results: Of the 48 adults who expressed interest in the study, 32 (67%) were eligible and completed the baseline assessment. All 32 adults were willing to be randomised to either the personalised health behaviour support programme (n = 17) or usual care (n = 15) and 27 (age: 45 ± 12 years) adults completed follow‐up at 9 weeks. The intervention was deemed feasible, with high adherence (92% and 94% completion rates for the physical activity and symptom diaries, respectively) and excellent acceptability rates (94% 'liked the intervention a lot'). The intervention was deemed safe, with no symptom exacerbations reported. Conclusion: An 8‐week personalised health behaviour support programme was feasible for adults with post‐COVID syndrome, with good adherence and acceptability rates. Early pilot data from this small sample also suggests meaningful improvements in physical activity, fatigue and respiratory symptoms. Patient or Public Contribution: People living with post‐COVID syndrome were involved from the outset with the study design, review of study documentation and interpretation of the data following completion. Furthermore, several participants have supported the local dissemination of findings following the completion of the study. [ABSTRACT FROM AUTHOR]

Introduction: Research has found that a high percentage of people with diabetes experience stigma, with perceptions of stigma being significantly higher among people with Type 1 diabetes compared to those with Type 2 diabetes. These experiences of diabetes stigma can lead to psychological, behavioural and medical consequences. The aim of the current study was to explore the perceptions of diabetes stigma and propose strategies for addressing this from the perspective of key stakeholders. Methods: A mixed methods design was used, commencing with an online qualitative survey (n = 128) and followed by a World Café (n = 11), where attendees reflected on their own experiences with stigma and discussed the survey findings. Results: The survey indicated that 75% of those with Type 1 diabetes and 51% with Type 2 had experienced diabetes stigma. The World Café identified three main areas that participants felt impacted their experiences with stigma or had the potential to help improve stigma: healthcare interactions, public awareness and media representations. Conclusions: The findings supported previous research showing that diabetes stigma is prevalent among people with diabetes. The World Café was an excellent means of sharing knowledge and experiences among stakeholders, the findings of which will inform strategies to bring about change. Patient or Public Contribution: World Café is a collaborative method where stakeholders contribute to the production and analysis of data through rounds of discussion and feedback. [ABSTRACT FROM AUTHOR]

Objective: Preeclampsia (PE) is associated with hypertension (HTN) during pregnancy and activated CD4+ T cells, inflammatory cytokines, and autoantibodies to the angiotensin II type I receptor (AT1‐AA). Having had COVID‐19 (CV) during pregnancy is associated with an increased incidence of a PE‐like phenotype. Both PE and CV have long‐lasting neurological implications and studies show that nonpregnant COVID patients produce AT1‐AA. We have shown that CD4+ T cells from PE women cause a PE phenotype in nude athymic rats. In this study, we sought to examine the role of CD4+ T cells from PE with a CV History (Hx) to contribute to a PE phenotype and to determine the importance of CD4+ T cells in cognitive dysfunction during pregnancy. Methods: At delivery, blood and placentas were collected, and one million placental CD4+ T cells from each PE and each normotensive patient, with (NT) or without (NP) a CV (Hx) during pregnancy, were isolated, purified, and injected i.p. into a gestational day (GD) 12 pregnant nude athymic rat (one patient/rat). At GD19, blood pressure (MAP) and circulating factors were assessed in recipient rats. Cognitive function and memory were assessed using Novel Object Recognition and Barnes Maze tests, respectively. Placental ACE‐2 activity and AT1‐AA were measured from COVID Hx patients. A one‐ or two‐way ANOVA with Bonferroni's multiple comparisons test was used for statistical analysis. Results: Blood pressure was increased in patients with PE, with or without COVID, compared to NT patients. There were no significant changes in placental ACE activity in patients with COVID Hx with or without PE. AT1‐AA was elevated in PE patients and in both PE and NT COVID Hx compared to control NP. In pregnant recipient rats, MAP increased in CV Hx PE (113 ± 2, n = 8) compared to CV Hx NT (101 ± 5, n = 6). PE and PE CV Hx CD4+ T Cell recipient rats exhibited impaired memory and cognitive dysfunction (p < 0.05), compared to control groups. Recipient rats of PE CV Hx CD4+ T cells had elevated AT1‐AA compared to NT CV Hx recipients. Both COVID Hx groups and recipients of PE CD4+ T cells had elevated TNF alpha compared to NP. Conclusion: Our findings indicate that pregnant patients with a Hx of COVID during pregnancy produce AT1‐AA, with or without PE. Recipients of CD4+ T cells from PE with or without a CV Hx during pregnancy cause HTN and elevated AT1‐AA. TNF‐α is elevated in PE and in CV Hx NT and PE recipients. Interestingly, recipients of T cells from PE patients with or without a Hx of CV had worse cognitive function during pregnancy, compared to recipient rats of NP CD4+ T cells. These data demonstrate the importance of CD4+ T cells in HTN and impaired neurological function during PE in the presence or absence of a prior COVID‐19 infection during pregnancy. [ABSTRACT FROM AUTHOR]

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability. [ABSTRACT FROM AUTHOR]

To understand how ectotherms will respond to warming temperatures, we require information on thermal habitat quality at spatial resolutions and extents relevant to the organism. Measuring thermal habitat quality is either limited to small spatial extents, such as with ground‐based 3D operative temperature (Te) replicas, representing the temperature of the animal at equilibrium with its environment, or is based on microclimate derived from physical models that use land cover variables and downscale coarse climate data. We draw on aspects of both these approaches and test the ability of unoccupied aerial vehicle (UAV) data (optical RGB) to predict fine‐scale heterogeneity in sub‐canopy lizard (Anolis bicaorum) Te in tropical forest using random forest models. Anolis bicaorum is an endemic, critically endangered, species, facing significant threats of habitat loss and degradation, and work was conducted as part of a larger project. Our findings indicate that a model incorporating solely air temperature, measured at the centre of the 20 × 20 m plot, and ground‐based leaf area index (LAI) measurements, measured at directly above the 3D replica, predicted Te well. However, a model with air temperature and UAV‐derived canopy metrics performed slightly better with the added advantage of enabling the mapping of Te with continuous spatial extent at high spatial resolutions, across the whole of the UAV orthomosaic, allowing us to capture and map Te across the whole of the survey plot, rather than purely at 3D replica locations. Our work provides a feasible workflow to map sub‐canopy lizard Te in tropical environments at spatial scales relevant to the organism, and across continuous areas. This can be applied to other species and can represent species within the same community that have evolved a similar thermal niche. Such methods will be imperative in risk modelling of such species to anthropogenic land cover and climate change. [ABSTRACT FROM AUTHOR]

Introduction: General practitioners (GPs) have been identified as pivotal in the identification and initiation of treatment for obesity, yet effective obesity management remains challenging in general practice. Despite the growing prevalence of obesity and the central role of GPs, there is a dearth of research exploring their experiences and challenges in managing the disease. Objective: This study aimed to understand these challenges by exploring GPs' experiences and to identify factors influencing their obesity management practices to inform the development of targeted intervention strategies. Method: In‐depth interviews were conducted with 10 GPs. Data were analyzed using abductive thematic analysis underpinned by the theoretical domains framework (TDF). Findings were mapped to the behavior change wheel (BCW) and the behavior change taxonomy to identify potential future intervention strategies. Findings: Participants described multiple barriers to effective obesity management, including knowledge gaps, lack of training, patient factors, and systemic challenges. Key themes identified were the need for increased support, improved patient engagement, and system‐level changes. Conclusion: This study offers valuable insights into the challenges GPs encounter when managing obesity in general practice. Application of the TDF and BCW frameworks identified complex interactions between knowledge, beliefs, and environmental factors influencing GP behavior. These findings highlight key areas for targeted interventions to enhance obesity care and drive best practice. [ABSTRACT FROM AUTHOR]

The Northeast United States exhibits significant spatial heterogeneity in flood seasonality, with spring snowmelt‐driven floods historically dominating northern areas, while other regions show more varied flood seasonality. While it is well documented that since 1996 there has been a marked increase in extreme precipitation across this region, the response of flood seasonality to these changes in extreme precipitation and the spatial distribution of these effects remain uncertain. Here we show that, historically, snowmelt‐dominated northern regions were relatively insensitive to changes in extreme precipitation. However, with climate warming, the dominance of snowmelt floods is decreasing and thus the extreme flood regimes in northern regions are increasingly susceptible to changes in extreme precipitation. While extreme precipitation increased everywhere in the Northeastern United States in 1996, it has since returned to near pre‐1996 levels in the coastal north while remaining elevated in the inland north. Thus, the inland north region has and continues to experience the greatest changes in extreme flooding seasonality, including a substantial rise in floods outside the historical spring flood season, particularly in smaller watersheds. Further analysis reveals that while early winter floods are increasingly common, the magnitude of cold season floods (Nov‐May) have remained unchanged over time. In contrast, warm season floods (June‐Oct), historically less significant, are now increasing in both frequency and magnitude in the inland north. Our results highlight that treating the entire Northeast as a uniform hydroclimatic region conceals significant regional variations in extreme discharge trends and, more generally, climate warming will likely increase the sensitivity of historically snowmelt dominated watersheds to extreme precipitation. Understanding this spatial variability in increased extreme precipitation and increased sensitivity to extreme precipitation is crucial for enhancing disaster preparedness and refining water management strategies in affected regions. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the difference in head acceleration event (HAE) incidence between training and match‐play in women's and men's players competing at the highest level of domestic rugby union globally. Players from Women's (Premiership Women's Rugby, Farah Palmer Cup) and Men's (Premiership Rugby, Currie Cup) rugby union competitions wore instrumented mouthguards during matches and training sessions during the 2022/2023 seasons. Peak linear (PLA) and angular (PAA) acceleration were calculated from each HAE and included within generalized linear mixed‐effects models. The incidence of HAEs was significantly greater in match‐play compared to training for all magnitude thresholds in both forwards and backs, despite players spending approximately 1.75–2.5 times more time in training. For all HAEs (PLA > 5 g and PAA > 400 rad/s2), incidence rate ratios (IRRs) for match versus training ranged from 2.80 (95% CI: 2.38–3.30; men's forwards) to 4.00 (3.31–4.84; women's forwards). At higher magnitude thresholds (PLA > 25 g; PAA > 2000 rad/s2), IRRs ranged from 3.64 (2.02–6.55; PAA > 2000 rad/s2 in men's backs) to 11.70 (6.50–21.08; PAA > 2000 rad/s2 in women's forwards). Similar trends were observed in each competition. Players experienced significantly more HAEs during match‐play than training, particularly at higher magnitude thresholds. Where feasible, HAE mitigation strategies may have more scope for HAE reduction if targeted at match‐play, particularly where higher magnitude HAEs are the primary concern. However, the number of HAEs associated with different training drills requires exploration to understand if HAEs can be reduced in training, alongside optimizing match performance (e.g., enhancing contact technique). [ABSTRACT FROM AUTHOR]

Managing forests to sustain their diversity and functioning is a major challenge in a changing world. Despite the key role of understory vegetation in driving forest biodiversity, regeneration and functioning, few studies address the functional dimensions of understory vegetation response to silvicultural management.We assessed the influence of the silvicultural regimes on the functional diversity and redundancy of European forest understory. We gathered vascular plant abundance data from more than 2000 plots in European forests, each associated with one out of the five most widespread silvicultural regimes. We used generalized linear mixed models to assess the effect of different silvicultural regimes on understory functional diversity (Rao's quadratic entropy) and functional redundancy, while accounting for climate and soil conditions, and explored the reciprocal relationship between three diversity components (functional diversity, redundancy and dominance) across silvicultural regimes through a ternary diversity diagram.Intensive silvicultural regimes are associated with a decrease in functional diversity and an increase in functional redundancy, compared with unmanaged conditions. This means that although intensive management may buffer communities' functions against species or functional losses, it also limits the range of understory response to environmental changes.Policy implications. Different silvicultural regimes influence different facets of understory functional features. While unmanaged forests can be used as a reference to design silvicultural practices in compliance with biodiversity conservation targets, different silvicultural options should be balanced at landscape scale to sustain the multiple forest functions that human societies are increasingly demanding. [ABSTRACT FROM AUTHOR]

A new hydroxo‐bridged ruthenium (II) complex [{Ru(η6‐p‐cymene)(iPr2P−O)}2(μ‐OH)]Cl (2) has fortuitously been isolated from the reaction between the known ruthenium(II) complex [RuCl2(η6‐p‐cymene)(iPr2P‐OH)] (1) in either CDCl3 or CHCl3 solutions in the presence of excess DBU (1,8‐diazabicyclo(5.4.0)undec‐7‐ene) at room temperature. Complex 2 is only formed under specific conditions as an orange‐colored air and moisture stable binuclear complex. It is formed via the deprotonation of the P−OH unit in [RuCl2(η6‐p‐cymene)(iPr2P‐OH)]. Complex 2 has been fully characterized by spectroscopic and analytical methods. Its structure was determined by single crystal X‐ray diffraction which reveals a boat‐shaped motif containing a bridging hydroxide unit which undergoes hydrogen bonding with a chloride counterion. Complex 2 was utilized as a catalyst for the hydrogenation of CO2 to formic acid salt using molecular hydrogen. The catalytic reactions were performed at 100 °C in THF in the presence of DBU as a base to isolate [DBU+H][OC(O)H] salt as the final product. Using catalyst loadings down to 0.01 mol%, it was possible to hydrogenate gaseous CO2 with TONs up to 9900. [ABSTRACT FROM AUTHOR]

Ferro‐rotational (FR) materials, renowned for their distinctive material functionalities, present challenges in the growth of homo‐FR crystals (i.e., single FR domain). This study explores a cost‐effective approach to growing homo‐FR helimagnetic RbFe(SO4)2 (RFSO) crystals by lowering the crystal growth temperature below the TFR threshold using the high‐pressure hydrothermal method. Through polarized neutron diffraction experiments, it is observed that nearly 86% of RFSO crystals consist of a homo‐FR domain. Notably, RFSO displays remarkable stability in the FR phase, with an exceptionally high TFR of ≈573 K. Furthermore, RFSO exhibits a chiral helical magnetic structure with switchable ferroelectric polarization below 4 K. Importantly, external electric fields can induce a single magnetic domain state and manipulate its magnetic chirality. The findings suggest that the search for new FR magnets with outstanding material properties should consider magnetic sulfates as promising candidates. [ABSTRACT FROM AUTHOR]

This work presents a novel approach to achieve directional and normal thermal emission from epsilon‐near–zero (ENZ) materials. ENZ materials exhibit near–zero permittivity at the ENZ point, resulting in some unique properties compared to conventional optical materials including infinite wavelength, constant phase distribution, and decoupling of spatial and temporal fields inside the ENZ material. These properties are used to engineer the far‐field thermal emission from optical antennas fabricated on ENZ film in the mid‐infrared. By coupling the antenna resonance mode with the Berreman mode of the ENZ material, highly directional and normal emission is demonstrated. This approach could have significant implications for thermal management, energy conversion, and sensing applications. [ABSTRACT FROM AUTHOR]

Wastewater treatment plants are one of the major pathways for microplastics to enter the environment. In general, microplastics are contaminants of global concern that pose risks to ecosystems and human health. Here, we present a proof‐of‐concept for reduction of microplastic pollution emitted from wastewater treatment plants: delivery of recombinant DNA to bacteria in wastewater to enable degradation of polyethylene terephthalate (PET). Using a broad‐host‐range conjugative plasmid, we enabled various bacterial species from a municipal wastewater sample to express FAST‐PETase, which was released into the extracellular environment. We found that FAST‐PETase purified from some transconjugant isolates could degrade about 40% of a 0.25 mm thick commercial PET film within 4 days at 50°C. We then demonstrated partial degradation of a post‐consumer PET product over 5–7 days by exposure to conditioned media from isolates. These results have broad implications for addressing the global plastic pollution problem by enabling environmental bacteria to degrade PET. [ABSTRACT FROM AUTHOR]

Successful management requires information on pressures that threaten a species and areas where conservation actions are needed. The Baltic Proper harbour porpoise population was first listed as Critically Endangered by the International Union for the Conservation of Nature in 2008. Now, 16 years later, there is no change in conservation status despite ample conservation policy calling for its protection and an urgent need for management action to protect this population. Here, we provide an overview of the current status of the population, highlight knowledge gaps on the impact of pressures, and make recommendations for management of anthropogenic activities. Based on an exceeded limit for anthropogenic mortality, the high concentrations of contaminants in the Baltic Sea, combined with reductions in prey availability and increases in underwater noise, it is inferred that this population is likely still decreasing in size and conservation action becomes more urgent. As bycatch and unprotected underwater explosions result in direct mortality, they must be reduced to zero. Inputs of contaminants, waste, and existing and emerging noise sources should be minimised and regulated. Additionally, ecosystem‐based sustainable management of fisheries is paramount in order to ensure prey availability, and maintain a healthy Baltic Sea. Stranding networks to routinely assess individuals for genetic population assignment and health need to be expanded, to identify rare samples from this population. Knowledge is still scarce on the population‐level impact of each threat, along with the cumulative impact of multiple pressures on the population. However, the current knowledge and management instruments are sufficient to apply effective protection for the population now. While bycatch is the main pressure impacting this population, urgent conservation action is needed across all anthropogenic activities. Extinction of the Baltic Proper harbour porpoise population is a choice: decision‐makers have the fate of this genetically and biologically distinct marine mammal population in their hands. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma (UC) occurs uncommonly in cats and no association has previously been observed with long‐term indwelling urinary implants. An 18‐year‐old male castrated domestic shorthair cat initially was presented for hematuria, leading to the diagnosis of a right‐sided ureterolithiasis and severe pyelectasia on ultrasound examination, prompting right‐sided subcutaneous ureteral bypass (SUB) device placement. The cat subsequently had intermittent hematuria and dysuria, without ultrasonographic abnormality of the bladder or positive urine culture. Thirteen months later the patient developed refractory lower urinary tract signs, azotemia, a proliferative mass in the region of the cystostomy tube component of the SUB device and evidence of left ureteral obstruction. Cystostomy tube revision and left‐sided SUB device placement were performed, as well as a partial cystectomy for removal of the mass. Upon histopathology, the mass was diagnosed as a UC. To our knowledge, UC associated with a long‐term indwelling cystostomy catheter component of a SUB device has not been reported in veterinary medicine. [ABSTRACT FROM AUTHOR]

Objectives: Grotta‐Riparo di Uluzzo C (Apulia, southern Italy) is a pivotal site for investigating the evolution of the Middle Paleolithic and the earliest phases of the Upper Paleolithic in southern Italy, as the extensive stratigraphic record of this site includes a thick Mousterian sequence followed by the Uluzzian. Here, we investigate the taxonomic affinity of seven unpublished deciduous human teeth retrieved from the site of Uluzzo C in 1960. Materials and Methods: The teeth are represented by seven plaster dental casts, which are housed at the Museo Civico di Paleontologia e Paletnologia in Maglie (Lecce, Apulia). The location of the original specimens remains unknown, rendering these casts the only human remains evidence yielded by Uluzzo C to date. Based on occlusal‐view photographs and digital models of the casts, we examined the external morphology and morphometry of the teeth, comparing them to Homo sapiens and H. neanderthalensis samples. Through geometric morphometric methods and statistical analyses, we analyzed the crown outline of the deciduous molars. Results: The teeth show morphological and morphometric features that are variably found in H. neanderthalensis, H. sapiens, or both. Specifically, crown outline analysis shows that all molars fall within H. neanderthalensis variability, except for Uluzzo 853 (lower right deciduous first molar), which falls within H. sapiens variability. Discussion: This study provides the first taxonomic assessment of the hominin teeth from Uluzzo C. The results contribute additional insights into the Paleolithic peopling of southern Italy during a crucial period marked by the persistence of post‐Tyrrhenian Neanderthal techno‐complexes and the arrival of H. sapiens. [ABSTRACT FROM AUTHOR]

Transportation is a leading contributor to greenhouse gas emissions and has become a focus for climate policies. Traffic‐related air pollution disproportionately affects environmental justice (EJ) communities—neighborhoods that have disproportionate exposure to environmental hazards, but health impact assessments rarely center EJ issues or prioritize the concerns of EJ communities. One explanation for the lack of focus on EJ communities is that both policymakers and academia have often failed to engage these communities. In this paper, academic researchers collaborate with seven EJ organizations in the northeastern US, working with collaboration advisors and facilitators, to design and evaluate potential transportation emissions reduction scenarios using air quality and health benefits modeling tools. We model and estimate the benefits of these scenarios, while working to build collaborative relationships between academic researchers and EJ organizations. The two primary outputs from this process are: quantification of health benefits attributable to emission reduction scenarios of interest to EJ organizations, and enhanced trust and community building between academic researchers and EJ organizations, with reflections on strengths, challenges, and opportunities for future work. We find the largest improvements to health result from scenarios that reduce car and truck traffic. Dialog between academic researchers and EJ organizations reinforce the disconnect between regional‐scale models and local community concerns as well as the more general gaps between statistical models and lived experience. Despite these challenges, the collaboration led to more meaningful models and valued insight for community organizations, and we recommend comparable collaborations in other settings where pollution control is being planned and evaluated in EJ communities. Plain Language Summary: Transportation is a leading contributor to emissions and is a focus for climate policies. Traffic‐related air pollution disproportionately affects environmental justice (EJ) communities, but health impact assessments rarely center EJ issues or prioritize the concerns of EJ communities. One explanation for the lack of focus on EJ communities is that both policymakers and academia have often failed to engage these communities. In this paper, academic researchers collaborate with seven EJ organizations in the northeastern US, working with collaboration advisors and facilitators, to design and evaluate potential transportation emissions reduction scenarios using air quality and health benefits modeling tools. We model and estimate the benefits of these scenarios while working to build collaborative relationships between academic researchers and EJ organizations. We find the largest improvements to health result from scenarios that reduce car and truck traffic. Dialog between academic researchers and EJ organizations reinforce the disconnect between regional‐scale models and local community concerns as well as the more general gaps between statistical models and lived experience. Despite these challenges, the collaboration led to more meaningful models and valued insight for community organizations, and we recommend comparable collaborations in other settings where pollution control is being planned and evaluated in EJ communities. Key Points: Transportation is a leading contributor to greenhouse gas emissions and has recently become a focus for climate policiesHealth impact assessments rarely center environmental justice (EJ) issues or prioritize the concerns of EJ communitiesAcademic researchers and EJ communities can collaborate on scenario development to prioritize health and air quality benefits for EJ communities [ABSTRACT FROM AUTHOR]

Understanding what diversity of small‐scale fisheries translates to in practice, and what this means for management regimes seeking sustainability, continues to be a challenging undertaking. This is particularly so in the tropical Pacific Islands region, where small‐scale coastal fisheries play a significant role in domestic food and livelihood systems. A renewed regional policy focus on supporting coastal fisheries, combined with momentum built from a decades‐long 'Pacific renaissance' in community‐based fisheries management approaches, has increased resourcing and support for coastal fishery data collection and knowledge production. In this context, there is growing demand to explicitly characterise diversity and complexity of community‐based coastal fisheries to inform how national co‐management programs can adequately support the many communities within national constituencies. This study presents findings from a community‐based coastal fisheries monitoring programme implemented in ten communities across Kiribati and Vanuatu between 2019 and 2021. Findings illustrate the intra‐ and inter‐country diversity of contextual drivers, fishing practices, and fisher participation. We discuss the implications of this enhanced understanding of community‐based fisheries for applied co‐management practice in these two countries. In doing so, we add to a growing knowledge base about fishing practices in Pacific Island coastal communities and elucidate avenues through which to incorporate this knowledge into adaptive co‐management practice. [ABSTRACT FROM AUTHOR]

Background: Chronic nitrous oxide (N2O) use causes inactivation of vitamin B12, resulting in neurological and psychiatric symptoms. This case series presents all N2O‐related presentations to the emergency department at Royal Perth Hospital between June 2019 and June 2021, alongside the costs of these admissions. Case Presentation: Twenty‐two patients were identified; 68% (n = 15) were male. The median age was 22.4 years (interquartile range [IQR], 20–30). Median daily number of N2O bulbs inhaled was 150 (IQR, 64–300) with a median duration of use of 9 months (IQR, 3–12). Presentations included ataxia, paraesthesia and falls (n = 18), urinary retention (n = 3) and psychotic symptoms (n = 2). Fourteen patients had severe symptoms prompting a magnetic resonance imaging of brain and spine, confirming 12 cases of subacute combined degeneration of the spinal cord. All patients had IMI vitamin B12 therapy, while 14 had oral methionine therapy. The median length of admission was 4 days (IQR 1–23 days). The median cost of admission per day for patients where costs were accessible (n = 7) was $2061 (IQR, $1903‐$2860). Discussion and Conclusions: A case series of symptomatic chronic N2O use with severe neurological sequelae and significant costs associated per admission. Triangulation of emergency department and Ecstasy and Related Drugs Reporting System data helped prompt a swift public health response, including mandatory warning labels, limits to transaction amounts and legislative changes to the Medicines and Poisons Act to make it illegal for sale if there is a suspicion that it will be abused. [ABSTRACT FROM AUTHOR]

Mucosal‐associated invariant T (MAIT) cells are innate‐like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro‐inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti‐cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we showed that peritumoral injection of in vivo‐expanded MAIT cells into RAG1−/− mice with MC38‐derived tumours inhibits tumour growth compared to control. Multiplex cytokine analyses showed that tumours from the MAIT cell‐treated group have higher expression of markers for eosinophil‐activating cytokines, suggesting a potential association between eosinophil recruitment and tumour inhibition. In a human peripheral leukocyte co‐culture model, we showed that leukocytes stimulated with MAIT ligand showed an increase in eotaxin‐1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we showed that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil‐associated mechanisms. Our results highlight the potential of MAIT cells for non‐donor restricted colon cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Exercise is recommended for the management of metabolic dysfunction‐associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. Methods: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12–20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI‐measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. Results: Eighty‐eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5‐fold (OR [95%CI]: 4.86 [1.72, 13.8], p =.002) greater odds of ≥30% relative reduction in MRI‐measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). Conclusion: Exercise training led to clinically meaningful improvements in surrogate serum‐ and imaging‐based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight‐neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD. [ABSTRACT FROM AUTHOR]

Predatory journals and conferences are an emerging problem in scientific literature as they have financial motives, without guaranteeing scientific quality and exposure. The main objective of the ASGLOS project is to investigate the predatory e‐email characteristics, management, and possible consequences and to analyse the extent of the current problem at each academic level. To collect the personal experiences of physicians' mailboxes on predatory publishing, a Google Form® survey was designed and disseminated from September 2021 to April 2022. A total of 978 responses were analysed from 58 countries around the world. A total of 64.8% of participants indicated the need for 3 or fewer emails to acquire a criticality view in distinguishing a real invitation from a spam, while 11.5% still have doubt regardless of how many emails they get. The AGLOS Study clearly highlights the problem of academic e‐mail spam by predatory journals and conferences. Our findings signify the importance of providing academic career‐oriented advice and organising training sessions to increase awareness of predatory publishing for those conducting scientific research. [ABSTRACT FROM AUTHOR]

Background: Tissue stimulations greatly affect cell growth, phenotype, and function, and they play an important role in modeling tissue physiology. With the goal of understanding the cellular mechanisms underlying the response of tissues to external stimulations, in vitro models of tissue stimulation have been developed in hopes of recapitulating in vivo tissue function. Methods: Herein we review the efforts to create and validate tissue stimulators responsive to electrical or mechanical stimulation including tensile, compression, torsion, and shear. Results: Engineered tissue platforms have been designed to allow tissues to be subjected to selected types of mechanical stimulation from simple uniaxial to humanoid robotic stain through equal‐biaxial strain. Similarly, electrical stimulators have been developed to apply selected electrical signal shapes, amplitudes, and load cycles to tissues, lending to usage in stem cell‐derived tissue development, tissue maturation, and tissue functional regeneration. Some stimulators also allow for the observation of tissue morphology in real‐time while cells undergo stimulation. Discussion on the challenges and limitations of tissue simulator development is provided. Conclusions: Despite advances in the development of useful tissue stimulators, opportunities for improvement remain to better reproduce physiological functions by accounting for complex loading cycles, electrical and mechanical induction coupled with biological stimuli, and changes in strain affected by applied inputs. [ABSTRACT FROM AUTHOR]

Increased circulating tissue inhibitor of metalloproteinases‐1 (TIMP‐1) levels have been observed in patients with acute lung injury (ALI). However, the sex‐specific regulation of TIMP‐1 and the underlying molecular mechanisms have not been well elucidated. In this study, we found that plasma TIMP‐1 levels were significantly higher in COVID‐19 and H1N1 patients compared with those in healthy subjects (n = 25). TIMP‐1 concentrations were significantly different between males and females in each disease group. Among female but not male patients, TIMP‐1 levels significantly correlated with the PaO2/FiO2 ratio and hospital length of stay. Using the mouse model of ALI induced by the H1N1 virus, we found that TIMP‐1 is strikingly induced in PDGFRα‐positive cells in the murine lungs. Moreover, female mice showed a higher Timp‐1 expression in the lungs on day 3 postinfection. Mechanistically, we observed that estrogen can upregulate TIMP‐1 expression in lung fibroblasts, not epithelial cells. In addition, overexpression of estrogen receptor α (ERα) increased the TIMP‐1 promoter activity. In summary, TIMP‐1 is an estrogen‐responsive gene, and its promoter activity is regulated by ERα. Circulating TIMP‐1 may serve as a sex‐specific marker, reflecting the severity and worst outcomes in female patients with SARS‐CoV2‐ and IAV‐related ALI. [ABSTRACT FROM AUTHOR]

Objective: Older people with multiple sclerosis (MS) have a less active radiological and clinical presentation, but many still attain significant levels of disability; but what drives worsening disability in this group? Methods: We used data from the UK MS Register to characterize demographics and clinical features of late‐onset multiple sclerosis (LOMS; symptom onset at ≥50 years), compared with adult‐onset MS (AOMS; onset 18–49 years). We performed a pathology study of a separate MS cohort with a later onset (n = 18, mean age of onset 54 years) versus AOMS (n = 23, mean age of onset 29 years). Results: In the Register cohort, there were 1,608 (9.4%) with LOMS. When compared with AOMS, there was a lower proportion of women, a higher proportion of primary progressive MS, a higher level of disability at diagnosis (median MS impact scale 36.7 vs. 28.3, p < 0.001), and a higher proportion of gait‐related initial symptoms. People with LOMS were less likely to receive a high efficacy disease‐modifying treatment and attained substantial disability sooner. Controlling for age of death and sex, neuron density in the thalamus and pons decreased with onset‐age, whereas actively demyelinating lesions and compartmentalized inflammation was greatest in AOMS. Only neuron density, and not demyelination or the extent of compartmentalized inflammation, correlated with disability outcomes in older‐onset MS patients. Interpretation: The more progressive nature of older‐onset MS is associated with significant neurodegeneration, but infrequent inflammatory demyelination. These findings have implications for the assessment and treatment of MS in older people. ANN NEUROL 2024;95:471–486 [ABSTRACT FROM AUTHOR]

Background: We are a research team of clinical, academic and advocacy‐based researchers with and without learning disabilities, working on the Humanising Healthcare (for people with learning disabilities) project. The project is dedicated to finding and sharing healthcare practices that enhance the lives of people with learning disabilities. As part of our ethics applications to access National Health Service study sites for fieldwork, we worked together to write guiding principles for co‐producing research ethics with researchers with learning disabilities. In this paper, we introduce these Participatory Ethics Good Practice Guidelines and reflect on our collaboration. Methods: We reflect on developing the Participatory Ethics Good Practice Guidelines. These guidelines were developed during online co‐production meetings with our full research team, including advocacy‐based organisation researchers, clinical researchers and university researchers. We considered consent, understanding research, and understanding research methods during the development of these Guidelines. Findings: We present ten guidelines for co‐producing research with people with learning disabilities. Conclusions: Our findings may be helpful to researchers with learning disabilities, university and clinical researchers, funders, and those who work in research governance (e.g., ethics committees and university research departments). Accessible Summary: An Easy Read version of this accessible summary can be found in Appendix A.It is important to do disability research together with researchers with learning disabilities.Co‐production is where researchers with and without learning disabilities work as partners. Co‐produced learning disability research should be led by people with learning disabilities.An important part of doing research is thinking together about research ethics. Research ethics is about doing fair research that does not harm people with learning disabilities.We are a research team of people with and without learning disabilities. We worked together to develop 10 ideas for co‐producing research.We called these 10 ideas 'Participatory Ethics Good Practice Guidelines'. This paper includes an Easy Read version of these 10 ideas (Appendix B).Researchers with learning disabilities on our study team are not just experts in being a person with a learning disability but also experienced researchers; a point all researchers should keep in mind. [ABSTRACT FROM AUTHOR]

Ion‐acoustic waves (IAWs) commonly occur near interplanetary (IP) shocks. These waves are important because of their potential role in the dissipation required for collisionless shocks to exist. We study IAW occurrence statistically at different heliocentric distances using Solar Orbiter to identify the processes responsible for IAW generation near IP shocks. We show that close to IP shocks the occurrence rate of IAW increases and peaks at the ramp. In the upstream region, the IAW activity is highly variable among different shocks and increases with decreasing distance from the Sun. We show that the observed currents near IP shocks are insufficient to reach the threshold for the current‐driven instability. We argue that two‐stream proton distributions and suprathermal electrons are likely sources of the waves. Plain Language Summary: Ion‐acoustic waves (IAWs) are fluctuations in the electric field that occur at frequencies close to the ion plasma frequency. These waves are commonly found in the solar wind and often cluster around interplanetary (IP) shock waves. In this study, we investigate and quantify how common IAWs are in the vicinity of IP shocks. Our research revealed that IAW activity is enhanced before and after most IP shock passages. Furthermore, IAWs are more likely to be observed preceding IP shocks that are closer to the Sun. We find that the occurrence rate of IAWs shows no clear dependence on the IP shock parameters. We explore the possible mechanisms that could explain the presence of these IAWs. For instance, IAW modes can be excited by electric currents if the associated drift velocity between ions and electrons is above a certain threshold. However, the currents alone are not strong enough to generate the IAWs found near IP shocks. We discuss other potential generation mechanisms, such as velocity distributions of ions and electrons deviating from thermodynamic equilibrium. Key Points: The occurrence of Ion‐acoustic waves (IAWs) is enhanced at interplanetary (IP) shocks, peaking at the shock rampThe occurrence rate of IAWs in the upstream region of IP shocks increases with decreasing radial distance from the SunIAWs are observed upstream of an IP shock together with two‐stream protons and an electron strahl [ABSTRACT FROM AUTHOR]

Typical approaches to heterocycle construction require significant changes in synthetic strategy even for a change as minor as increasing the ring size. The ability to access multiple heterocyclic scaffolds through a common synthetic approach, simply through trivial modification of one reaction component, would enable facile access to diverse libraries of structural analogues of core scaffolds. Here, we show that urea‐derived ligands effectively promote Pd‐mediated chainwalking processes to enable remote heteroannulation for the rapid construction of six‐ and seven‐membered azaheterocycles under essentially identical reaction conditions. This method demonstrates good functional group tolerance and effectively engages sterically hindered substrates. In addition, this reaction is applicable to target‐oriented synthesis, demonstrated through the formal synthesis of antimalarial alkaloid galipinine. [ABSTRACT FROM AUTHOR]