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Developing standardized methodology to allow efficient and cost‐effective ecological data collection, particularly at scale, is of critical importance for understanding species' declines. Remote camera networks can enable monitoring across large spatiotemporal scales and at relatively low researcher cost, but manually analysing images and extracting biologically meaningful data is time‐consuming. Citizen science image analysis could reduce researcher workload and increase output from large datasets, while actively raising awareness of ecological and conservation issues. Nevertheless, testing the validity of citizen science data collection and the retention of volunteers is essential before integrating these approaches into long‐term monitoring programmes. In this study, we used data from a Zooniverse citizen science project, Seabird Watch, to investigate changes in breeding timing of a globally declining seabird species, the Black‐legged Kittiwake Rissa tridactyla. Time‐lapse cameras collected >200 000 images between 2014 and 2023 across 11 locations covering the species' North Atlantic range (51.7°N–78.9°N), with over 35 000 citizen science volunteers 'tagging' adult and juvenile Kittiwakes in images. Most volunteers (81%) classified images for only a single day, and each volunteer classified a median of five images, suggesting that high volunteer recruitment rates are important for the project's continued success. We developed a standardized method to extract colony arrival and departure dates from citizen science annotations, which did not significantly differ from manual analysis by a researcher. We found that Kittiwake colony arrival was 2.6 days later and departure was 1.2 days later per 1° increase in latitude, which was consistent with expectations. Year‐round monitoring also showed that Kittiwakes visited one of the lowest latitude colonies, Skellig Michael (51.8°N), during winter, whereas birds from a colony at similar latitude, Skomer Island (51.7°N), did not. Our integrated time‐lapse camera and citizen science system offers a cost‐effective means of measuring changes in colony attendance and subsequent breeding timing in response to environmental change in cliff‐nesting seabirds. This study is of wide relevance to a broad range of species that could be monitored using time‐lapse photography, increasing the geographical reach and international scope of ecological monitoring against a background of rapidly changing ecosystems and challenging funding landscapes. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess if dicloxacillin/flucloxacillin reduces the therapeutic efficacy of direct oral anticoagulants (DOACs) and the underlying molecular mechanism. Methods: In a randomized, crossover study, we assessed whether dicloxacillin reduces oral absorption of drugs through P‐glycoprotein (P‐gp) during 10 and 28 days of treatment. To study the impact of dicloxacillin/flucloxacillin on intestinal and hepatic expression of P‐gp in vitro, we usd LS174T cells and 3D spheroids of primary human hepatocytes. Finally, we used nationwide Danish health registries and the UK's Clinical Practice Research Datalink to estimate hazard ratios (HRs) for the risk of stroke and systemic embolism following dicloxacillin/flucloxacillin exposure among DOAC users, using phenoxymethylpenicillin and amoxicillin as active comparators. Results: Dicloxacillin reduced the area under the curve of dabigatran to a geometric mean ratio 10 days of 0.67 (95% confidence interval [CI]: 0.42–1.1) and geometric mean ratio 28 days of 0.72 (95% CI: 0.39–1.4), suggesting reduced oral absorption via increased P‐gp expression. In vitro, dicloxacillin raised P‐gp expression in both intestinal and liver cells, while flucloxacillin only affected liver cells. In the pharmacoepidemiologic study, dicloxacillin and flucloxacillin were not associated with increased risk of stroke/systemic embolism (dicloxacillin vs. phenoxymethylpenicillin HR: 0.93, 95% CI: 0.72–1.2; flucloxacillin vs. amoxicillin HR: 0.89, 95% CI: 0.51–1.5). Conclusions: Dicloxacillin increases expression of intestinal P‐gp, leading to reduced oral absorption of dabigatran. However, concomitant use of dicloxacillin/flucloxacillin was not associated with stroke and systemic embolism among DOAC users, suggesting no clinical impact from the drug–drug interaction between dicloxacillin/flucloxacillin and DOACs. [ABSTRACT FROM AUTHOR]

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The translation of pre‐clinical anti‐cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose‐limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off‐target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as delivery vehicles include the induction of a protracted immune response that results in their rapid systemic clearance, manufacturing cost, lack of stability, and their biocompatibility. Extracellular vesicles (EVs) are a heterogeneous class of endogenous biologically produced lipid bilayer nanoparticles that mediate intercellular communication by carrying bioactive macromolecules capable of modifying cellular phenotypes to local and distant cells. By genetic, chemical, or metabolic methods, extracellular vesicles (EVs) can be engineered to display targeting moieties on their surface while transporting specific cargo to modulate pathological processes following uptake by target cell populations. This review will survey the types of EVs, their composition and cargoes, strategies employed to increase their targeting, uptake, and cargo release, and their potential as targeted anti‐cancer therapeutic delivery vehicles. [ABSTRACT FROM AUTHOR]

Long‐term sample stability of five atypical antipsychoticdrugs risperidone, paliperidone, clozapine, quetiapine and olanzapine and the antidepressant drug mirtazapine in serum was studied by use of a newly developed and validated analytical method based on solid‐phase extraction and liquid chromatography–tandem mass spectrometry. Ascorbic acid was used as an antioxidative agent to stabilize olanzapine during storage and sample preparation. We assessed analyte stability on long‐term storage in serum samples at 25°C, 5°C, −20°C and −80°C, and during five freeze–thaw cycles. Analytes were stable for 23 days at room temperature except for olanzapine and mirtazapine (17 days). All analytes were stable for at least 30 days at 5°C. All analytes were stable for 270 days at −20°C, except for paliperidone and mirtazapine with 60 days and 180 days, respectively. All analytes were stable for 270 days at −80°C. Furthermore, all analytes were stable for five freeze–thaw cycles. We recommend storage at −80°C when samples drawn for analysis of antipsychotic drugs are stored for more than 60 days, whereas a temperature of −20°C is sufficient for storage less than 60 days. [ABSTRACT FROM AUTHOR]

Stamp seals of the Dilmun type have kept their characteristic shape and boss decoration of three lines and four dotted circles for several 100 years. Although the carving of the shape of the seal and the design on the obverse normally reveal a confident experience, the cutting of the three lines on the reverse is generally irregular and clumsy. It is suggested that the former was in the hands of a professional seal carver, whereas the latter was carried out by the seal owner, perhaps as a sign of allegiance to the king. [ABSTRACT FROM AUTHOR]

Objective: Tumour necrosis factor (TNF)‐α is a proinflammatory marker and has been shown to affect mitochondrial function in different tissues. We investigated the effect on adipose tissue (AT) inflammation and mitochondrial respiration in patients with hidradenitis suppurativa (HS) after 12 weeks of treatment with adalimumab, a TNF‐α inhibitor. Methods: We sampled blood and an AT biopsy from 13 patients with HS and 10 control subjects after an overnight fast. The patients were retested after at least 12 weeks of treatment with adalimumab (40 mg/week). We measured macrophage content and mitochondrial respiration in the AT and interleukin (IL)‐1β, IL‐6, IL‐10, high‐sensitivity C‐reactive protein (hsCRP), interferon‐γ, TNF‐α, adiponectin and leptin in plasma. Clinical scores and Dermatology Quality of Life Index (DLQI) were assessed. Results: We found a higher anti‐inflammatory macrophage content (CD206+) in the patient group compared with the control group, but no differences between before and after the intervention. No difference in mitochondrial respiration was observed. We observed higher plasma IL‐6 and hsCRP concentrations in patients with HS compared to controls, with no differences before and after the intervention. The difference between controls and HS patients was abolished after the intervention. HS patients improved their DLQI after the intervention with no change in clinical scores. Conclusion: Treatment with adalimumab in patients with HS does not alter AT inflammation or mitochondrial respiratory capacity; however, we did see a higher content of anti‐inflammatory macrophages in the patient group compared with the control group. [ABSTRACT FROM AUTHOR]

Course‐based undergraduate research experiences (CUREs) can be a powerful tool in broadening participation in undergraduate research. In this paper, we review the benefits of and barriers to undergraduate research experiences and explore how CUREs can mitigate some of those issues. As a part of the NSF‐supported Biological Collections in Ecology and Evolution Network (BCEENET) activities, a series of network meetings produced a set of recommendations to increase the accessibility of CUREs for all students at all institution types. We use BCEENET CUREs that focus on digitized natural history collections data to illustrate how leveraging adaptable open educational resources that use freely available data and analysis tools can increase accessibility of undergraduate research. We also discuss how inclusive networks of educators and research collaborators can support broadening CURE implementation. [ABSTRACT FROM AUTHOR]

Close‐kin mark–recapture (CKMR) is a method that allows estimating population census size, among other parameters, through the observed number of pairs that are close‐kin including parent–offspring pairs (POPs) and half‐sibling pairs (HSPs). CKMR models are capable of estimating abundance, fecundity and survival at age using POPs and HSPs from different cohorts. The link between effective population size (Ne) and the number of 'within‐cohort' sibling pairs has been noted before but how to actually achieve such an estimate with CKMR has not been previously demonstrated.We show it is possible to use the number of 'within‐cohort' sibling pairs along with POPs and 'different‐cohort' HSPs to estimate Ne. These can be combined with an estimate of annual variance in number of offspring to estimate the lifetime variance of total reproductive success which can be used to find Ne. We show that the variance in number of offspring produced by adults in a given year is related to the within‐cohort comparisons.Our approach is demonstrated on an individual‐based simulation where we show that the CKMR Ne estimate offers similar results to Ne estimated from methods like linkage disequilibrium.Our methods allow estimating Ne using CKMR while also estimating demographic parameters. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence of elevated arterial stiffness and associations to known and potentially novel risk factors in a modern European technology‐based cohort of children and adolescents with type 1 diabetes. Research Design and Methods: Cross‐sectional study, including 127 children recruited from Pediatric Diabetes Departments across Eastern Denmark between May 2022 and January 2024. Arterial stiffness was assessed as carotid–femoral pulse‐wave‐velocity (cfPWV) using the Sphygmocor XCEL system. Unadjusted and adjusted linear regression models explored associations between cfPWV and other risk factors. Adjustments included age, sex, diabetes duration, time‐in‐range, hemoglobin A1c (HbA1c), body mass index (BMI) z‐score, low‐density lipoprotein (LDL)‐cholesterol, and mean arterial pressure (MAP). Results: Median (interquartile range [IQR]) age was 14.2 years (12.0, 16.4), diabetes duration was 4.7 years (2.7, 8.4), HbA1c level was 7.0% (6.5, 7.9), (53 mmol/l: 48–63), time‐in‐range was 63% (53–75), and 52% were male. The majority were treated with continuous‐subcutaneous‐insulin‐infusion (82%), and all (except two) used continuous‐glucose‐monitors. The prevalence of elevated arterial stiffness (cfPWV z‐score over the 90th percentile) was 16%. Unadjusted analyses demonstrated higher cfPWV was associated with longer diabetes duration, higher age, HbA1c, MAP, and liver stiffness, and lower time‐in‐range and insulin sensitivity. Higher cfPWV remained associated with higher age (standardized β (confidence interval (CI) 95%): 0.38 (0.27, 0.48); p < 0.001) and lower time‐in‐range (−0.15 ((−0.26), (−0.03)); p < 0.011) after adjustment. Conclusions: Despite modern treatment technology and better overall metabolic control, children and adolescents with type 1 diabetes present with a high prevalence of elevated arterial stiffness. Higher arterial stiffness was associated with higher age and lower time‐in‐range, independent of other risk factors, including HbA1c. [ABSTRACT FROM AUTHOR]

Background: The development of artificial intelligence (AI) is rapidly expanding, showing promise in the dermatological field. Skin checks are a resource‐heavy challenge that could potentially benefit from AI‐tool assistance, particularly if provided in widely available AI solutions. A novel smartphone application(app)‐based AI system, "SCAI," was developed and trained to recognize spots in paired images of skin, pursuing identification of new skin lesions. This pilot study aimed to investigate the feasibility of the SCAI‐app to identify simulated skin changes in vivo. Materials and methods: The study was conducted in a controlled setting with healthy volunteers and standardized, simulated skin changes (test spots), consisting of customized 3‐mm adhesive spots in three colors (black, brown, and red). Each volunteer had a total of eight test spots adhered to four areas on back and legs. The SCAI‐app collected smartphone‐ and template‐guided standardized images before and after test spot application, using its backend AI algorithms to identify changes between the paired images. Results: Twenty‐four volunteers were included, amounting to a total of 192 test spots. Overall, the detection algorithms identified test spots with a sensitivity of 92.0% (CI: 88.1–95.9) and a specificity of 95.5% (CI: 95.0–96.0). The SCAI‐app's positive predictive value was 38.0% (CI: 31.0–44.9), while the negative predictive value was 99.7% (CI: 99.0–100). Conclusion: This pilot study showed that SCAI‐app could detect simulated skin changes in a controlled in vivo setting. The app's feasibility in a clinical setting with real‐life skin lesions remains to be investigated, where the challenge with false positives in particular needs to be addressed. [ABSTRACT FROM AUTHOR]

Purpose: Absorbable interference screws for anterior cruciate ligament reconstruction (ACLR) can lead to tunnel widening and cyst formation. The Biosure Regenesorb interference screw (Smith & Nephew). has been developed with an optimised calcium phosphate/polymer composition to promote bone formation during resorption. The present study aims to investigate screw resorption, new bone formation, and tunnel geometry following ACLR with Biosure Regenesorb screw tibial fixation. Methods: The study is a prospective single‐centre case series of 12 patients with ACL lesions and treated with ACLR using hamstring tendon autograft with Biosure Regenesorb interference screw tibial fixation with a two‐year follow‐up period. The Biosure Regenesorb consists of 65% polylactide‐glycolic acid poly. 20% calcium sulphate and 15% tricalcium phosphate. Primary endpoint: Tunnel volume. implant volume and new bone formation in the tibial tunnel is evaluated by quantitative computed tomography (CT) scanning. Secondary endpoints: Arthrometric knee laxity, International Knee Documentation Committee (IKDC) and Knee Osteoarthritis and Injury Outcome Scores (KOOS) and Tegner activity scale. Results: Screw volume decreased to 44% within the two‐year follow‐up period while tunnel volume remained unchanged. Only a minor amount (<1% of tunnel volume) of new bone formation in the screw remnants was observed. Sagittal knee laxity at one year was 0.9 mm. The IKDC score increased by 15 points and the KOOS sport and KOOS quality of life scores increased by 25 and 26 points. respectively. Conclusion: ACLR using Biosure Regenesorb interference screw does not result in tunnel widening. showing a screw resorption of 44% after two years and minor new bone formation. Knee stability and subjective outcome improvements are as expected after other ACLR methods. Level of evidence: IV. [ABSTRACT FROM AUTHOR]

Purpose: To translate and cross‐culturally adapt PREP2 into Danish and to investigate the face validity and reliability of Danish PREP2 through cognitive interviewing, Rasch and reliability analyses. Methods: The Danish PREP2 was translated using a standardized procedure and then pretested following the Three‐Steps‐Interviews (TSTI) process. A total of 15 myopic children aged 7–14 wearing either orthokeratology lenses (ortho‐k) or single‐vision spectacles (SVS) were included in pretesting comprising cognitive interviews and Rasch analysis. Data from cognitive interviewing was analysed thematically according to Collins. Rasch analysis was used to pretest the psychometric properties in terms of person‐ and item‐fit statistics. Reliability was assessed via test–retest using Intra‐class correlation coefficient (ICC) in the CONTROL study population, which consisted of 60 Danish children aged 7–14 years wearing either ortho‐k or SVS. Results: Fifteen children participated in pilot studies comprising of cognitive interviewing and Rasch analysis and 44 out of 60 CONTROL children participated in test–retest reliability analysis. The translation process resulted in a Danish version of PREP2 corroborating the original. Pretesting highlighted issues in the contextualization of items and in marking responses. Thus, we introduced a digital format with help texts. Cognitive interviewing identified issues in the following Collins' themes: comprehension (understanding of concepts), judgement (ambiguity of items) and response (selecting answers). Rasch analysis indicated that help texts were useful for clarifying context. The ICC was 0.77 (95% CI: 0.66–0.85). Conclusions: The cross‐cultural adaptation of PREP2 was satisfactory and issues were identified and corrected through pretesting. The test–retest reliability showed substantial consistency. The instrument could be validated in a more generalizable setting in future studies. Trial registration: NCT03246464 (CONTROL study). [ABSTRACT FROM AUTHOR]

Contrary to the dominant narrative of the historical formation of democracy in Denmark, which emphasises a smooth and gradual linear transition to democracy and modernity, this paper accentuates a discontinuous and contentious road towards democratisation. Based on quantitative and qualitative sources, this article identifies four major waves of popular mobilisation that paved the way for the introduction and expansion of political rights. The first wave of popular protest began in the 1830s and culminated in 1848 with the fall of absolutism and the transition to constitutional monarchy. The next protest wave from 1885 to 1887 arose from the so‐called 'constitutional struggle' and mobilised hundreds of thousands of ordinary Danes and contributed to the nationalisation and parliamentarisation of the political system. The third wave unfolded around the end of the Second World War, while the hitherto last wave of popular struggle erupted in 1968 with the youth rebellion. The analysis shows that 'democracy' was the central issue of contention in all four protest waves and supports the main thesis that periods of intense interaction between popular protest and the state have had a decisive formative influence on the genesis and further development of Danish democracy. [ABSTRACT FROM AUTHOR]

Cyclisation of peptides by forming thioether (lanthionine), disulfide (cystine) or methylene thioacetal bridges between side chains is established as an important tool to stabilise a given structure, enhance metabolic stability and optimise both potency and selectivity. However, a systematic comparative study of the effects of differing bridging modalities on peptide conformation has not previously been carried out. In this paper, we have used the NMR deconvolution algorithm, NAMFIS, to determine the conformational ensembles, in aqueous solution, of three cyclic analogues of angiotensin(1–7), incorporating either disulfide, or non‐reducible thioether or methylene thioacetal bridges. We demonstrate that the major solution conformations are conserved between the different bridged peptides, but the distribution of conformations differs appreciably. This suggests that subtle differences in ring size and bridging structure can be exploited to fine‐tune the conformational properties of cyclic peptides, which may modulate their bioactivities. [ABSTRACT FROM AUTHOR]

Peracetic acid (PAA) has a long history as an efficacious and eco‐friendly disinfectant. It was first synthesised in 1902, and since then a wide range of applications has been developed in various industries. Aquaculture is a more recent industry wherein the potential of PAA is significant. As the global demand for sustainable development increases, there has likewise been growing interest in using PAA in aquaculture as an alternative to less environmentally friendly practices. PAA has no carcinogenic risk to humans (unlike formalin), has negligible harmful by‐products (unlike chlorine‐based disinfectants) and with appropriate precautions, the risks of causing severe human health damage is easier to control than ozone. Fish show strong physiological recovery and adaptation to PAA, whereas susceptible life stages of pathogens are highly vulnerable, enabling a safe and efficacious disinfection of the entire culture water and not the flow‐restricted disinfection by such processes as ultraviolet radiation or ozone. The effective concentration of PAA against many fish pathogens is usually below 2 mg L−1, which is tolerable for most fish, and it has very low environmental risk due to rapid degradation. However, such degradation and the hydrodynamics in production‐scale aquaculture systems complicate the practical use of PAA. In this review, we summarise key results of safe concentrations of PAA and its effectiveness specifically for fish farmers. We also outline major difficulties and possible solutions for practical uses of PAA. We intend to bring global attention to this compound and inspire future possibilities for its sustainable use as a water disinfectant in aquaculture. [ABSTRACT FROM AUTHOR]

After COVID‐19 long term respiratory symptoms and reduced lung function including maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) have been reported. However, no studies have looked at MIP and MEP in all disease groups and the reference materials collection methods differ substantially. We aimed to determine MIP and MEP in individuals after COVID‐19 infection with different disease severity using reference material of healthy control group obtained using the same standardized method. Patients with COVID‐19 were included March 2020–March 2021 at Rigshospitalet, Denmark. MIP and MEP were measured using microRPM. Predicted MIP and MEP were calculated using reference material obtained from 298 healthy adults aged 18–97 years using the same method. In SECURe, 145 participants were measured median 5 months after COVID‐19 diagnosis and of these 16% had reduced MIP and/or MEP. There was reduced spirometry and total lung capacity, but not reduced diffusion capacity in those with abnormal MIP and/or MEP compared with normal MIP and MEP. Of those with reduced MIP and/or MEP at 5 months, 80% still had reduced MIP and/or MEP at 12 months follow‐up. In conclusion, few have reduced MIP and/or MEP 5 months after COVID‐19 and little improvement was seen over time. [ABSTRACT FROM AUTHOR]

The consequences of short‐term disuse are well known, but effective countermeasures remain elusive. This study investigated the effects of neuromuscular electrical stimulation (NMES) during 5 days of bed rest on retaining lower limb muscle mass and muscle function in healthy young and old participants. One leg received NMES of the quadriceps muscle (3 × 30min/day) (NMES), and the other served as a control (CON). Isometric quadriceps strength (MVC), rate of force development (RFD), lower limb lean mass, and muscle thickness were assessed pre‐and post‐intervention. Muscle thickness remained unaltered with NMES in young and increased in old following bed rest, while it decreased in CON legs. In old participants, mid‐thigh lean mass (MTLM) was preserved with NMES while decreased in CON legs. In the young, only a tendency to change with bed rest was detected for MTLM. MVC and early‐phase RFD decreased in young and old, irrespective of NMES. In contrast, late‐phase RFD was retained in young participants with NMES, while it decreased in young CON legs, and in the old, irrespective of NMES. NMES during short‐term bed rest preserved muscle thickness but not maximal muscle strength. While young and old adults demonstrated similar adaptive responses in preventing the loss of skeletal muscle thickness, RFD was retained in the young only. [ABSTRACT FROM AUTHOR]

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub‐surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D‐OCT) to characterize microvessels in AK I‐III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I‐III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D‐OCT. On D‐OCT, vessel shapes, −pattern and ‐direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D‐OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty‐seven patients with AK I‐III (n = 207) and PD (n = 87) were included. Qualitative D‐OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 μm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non‐specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II‐III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I‐II than PD (p ≤ 0.025), whereas diameter remained constant. D‐OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D‐OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades. [ABSTRACT FROM AUTHOR]

Step selection functions (SSFs) are used to jointly describe animal movement patterns and habitat preferences. Recent work has extended this framework to model inter‐individual differences, account for unexplained structure in animals' space use and capture temporally varying patterns of movement and habitat selection.In this paper, we formulate SSFs with penalised smooths (similar to generalised additive models) to unify new and existing extensions, and conveniently implement the models in the popular, open‐source mgcv R package.We explore non‐linear patterns of movement and habitat selection, and use the equivalence between penalised smoothing splines and random effects to implement individual‐level and spatial random effects. This framework can also be used to fit varying‐coefficient models to account for temporally or spatially heterogeneous patterns of selection (e.g. resulting from behavioural variation), or any other non‐linear interactions between drivers of the animal's movement decisions.We provide the necessary technical details to understand several key special cases of smooths and their implementation in mgcv, showcase the ecological relevance using two illustrative examples and provide R code to facilitate the adoption of these methods. This paper offers a broad overview of how smooth effects can be applied to increase the flexibility and biological realism of SSFs. [ABSTRACT FROM AUTHOR]

The article discusses the impact of aerobic training on interleukin-15 (IL-15) response to acute exercise in cancer survivors. It highlights the role of IL-15 in immune system function and its potential as a therapeutic target for cancer treatment. The study found that acute exercise significantly increased circulating IL-15 concentrations, while chronic IL-15 levels remained unchanged after high-intensity interval training (HIIT). The findings suggest that continuous training may not enhance the beneficial effects of IL-15, emphasizing the importance of short-term exercise effects in cancer prevention and therapy. [Extracted from the article]

A non‐exercise method equation using seismocardiography for estimating V̇O2peak (SCG V̇O2peak) has previously been validated in healthy subjects. However, the performance of the SCG V̇O2peak within a trained population is unknown, and the ability of the model to detect changes over time is not well elucidated. Forty‐seven sub‐elite football players were tested at the start of pre‐season (SPS) and 36 players completed a test after eight weeks at the end of the pre‐season (EPS). Testing included an SCG V̇O2peak estimation at rest and a graded cardiopulmonary exercise test (CPET) on a treadmill for determination of V̇O2peak. Agreement between SCG V̇O2peak and CPET V̇O2peak showed a large underestimation at SPS (bias ± 95% CI: −9.9 ± 1.8, 95% Limits of Agreement: 2.2 to −22.0 mL·min−1 kg−1). At EPS no interaction (p = 0.3590) but a main effect of time (p < 0.0001) and methods (p < 0.0001) was observed between SCG and CPET V̇O2peak. No correlation in V̇O2peak changes was observed between SCG and CPET (r = −20.0, p = 0.2484) but a fair agreement in classifying the correct directional change in V̇O2peak with the SCG method was found (Cohen's κ coefficient = 0.28 ± 0.25). Overall, the SCG V̇O2peak method lacks accuracy and despite being able to estimate group changes, it was incapable of detecting individual changes in V̇O2peak following a pre‐season period in sub‐elite football players. The SCG algorithm needs to be further adjusted and the accuracy and precision improved for the method to be applicable for use within a trained population. Highlights: This is the first time a non‐exercise method using seismocardiography for the estimation of V̇O2peak has been validated in sub‐elite football players.The seismocardiography V̇O2peak method lacks accuracy within a trained population as it underestimates V̇O2peak compared to the gold standard measurement in sub‐elite football players.The seismocardiography V̇O2peak method can estimate the group changes in V̇O2peak following the pre‐season training period in sub‐elite football players. However, it is incapable of detecting individual changes.Adjustment of the seismocardiography V̇O2peak algorithm is needed and the accuracy and precision improved for the method to be applicable for use within a trained population. [ABSTRACT FROM AUTHOR]

Amphibians and fishes play a central role in shaping the structure and function of freshwater environments. These organisms have a limited capacity to disperse across different habitats and the thermal buffer offered by freshwater systems is small. Understanding determinants and patterns of their physiological sensitivity across life history is, therefore, imperative to predicting the impacts of climate change in freshwater systems. Based on a systematic literature review including 345 experiments with 998 estimates on 96 amphibian (Anura/Caudata) and 93 freshwater fish species (Teleostei), we conducted a quantitative synthesis to explore phylogenetic, ontogenetic, and biogeographic (thermal adaptation) patterns in upper thermal tolerance (CTmax) and thermal acclimation capacity (acclimation response ratio, ARR) as well as the influence of the methodology used to assess these thermal traits using a conditional inference tree analysis. We found globally consistent patterns in CTmax and ARR, with phylogeny (taxa/order), experimental methodology, climatic origin, and life stage as significant determinants of thermal traits. The analysis demonstrated that CTmax does not primarily depend on the climatic origin but on experimental acclimation temperature and duration, and life stage. Higher acclimation temperatures and longer acclimation times led to higher CTmax values, whereby Anuran larvae revealed a higher CTmax than older life stages. The ARR of freshwater fishes was more than twice that of amphibians. Differences in ARR between life stages were not significant. In addition to phylogenetic differences, we found that ARR also depended on acclimation duration, ramping rate, and adaptation to local temperature variability. However, the amount of data on early life stages is too small, methodologically inconsistent, and phylogenetically unbalanced to identify potential life cycle bottlenecks in thermal traits. We, therefore, propose methods to improve the robustness and comparability of CTmax/ARR data across species and life stages, which is crucial for the conservation of freshwater biodiversity under climate change. [ABSTRACT FROM AUTHOR]

Purpose: In Football, the high‐intensity running bouts during matches are considered decisive. Interestingly, recent studies showed that peak fat oxidation rates (PFO) are higher in football players than other athletes. This study aimed to investigate whether PFO increases following a pre‐season. Secondarily, and due to COVID‐19, we investigated whether PFO is related to the physical performance in a subgroup of semi‐professional male football players. Methods: Before and after 8 weeks of pre‐season training, 42 sub‐elite male football players (18 semi‐professionals and 24 non‐professionals) had a dual‐energy x‐ray absorptiometry scan and performed a graded exercise test on a treadmill for the determination of PFO, the exercise intensity eliciting PFO (Fatmax) and peak oxygen uptake (V̇O2peak). Additionally, the semi‐professional players performed a Yo‐Yo Intermittent Recovery Test level 2 (YYIR2) before and after pre‐season training to determine football‐specific running performance. Results: PFO increased by 11 ± 10% (mean ± 95% CI), p = 0.031, and V̇O2peak increased by 5 ± 1%, p < 0.001, whereas Fatmax was unchanged (+12 ± 9%, p = 0.057), following pre‐season training. PFO increments were not associated with increments in V̇O2peak (Pearson's r2 = 0.00, p = 0.948) or fat‐free mass (FFM) (r2 = 0.00, p = 0.969). Concomitantly, YYIR2 performance increased in the semi‐professional players by 39 ± 17%, p < 0.001, which was associated with changes in V̇O2peak (r2 = 0.35, p = 0.034) but not PFO (r2 = 0.13, p = 0.244). Conclusions: PFO, V̇O2peak, and FFM increased following pre‐season training in sub‐elite football players. However, in a subgroup of semi‐professional players, increments in PFO were not associated with improvements in YYIR2 performance nor with increments in V̇O2peak and FFM. [ABSTRACT FROM AUTHOR]

Introduction: Liver fat (LF) and visceral adipose tissue (VAT) content decreases with training, however, this has mainly been investigated in sedentary obese or healthy participants. The aim of this study was to investigate the effects of repeated prolonged exercise on LF and VAT content in well‐trained older men and to compare baseline LF and VAT content to recreationally active older men. Method: A group of five well‐trained older men were tested before and after cycling a total distance of 2558 km in 16 consecutive days. VAT content and body composition was measured using DXA before a bicycle ergometer test was performed to determine maximal fat oxidation (MFO), maximal oxygen consumption (VO2max$$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$), and the relative intensity at which MFO occurred (Fatmax). LF content was measured on a separate day using MRI. For comparison of baseline values, a control group of eight healthy age‐ and BMI‐matched recreationally active men were recruited. Results: The well‐trained older men had lower VAT (p = 0.02), and a tendency toward lower LF content (p = 0.06) compared with the control group. The intervention resulted in decreased LF content (p = 0.02), but VAT, fat mass, and lean mass remained unchanged. VO2max$$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$, MFO, and Fatmax were not affected by the intervention. Conclusion: The study found that repeated prolonged exercise reduced LF content, but VAT and VO2max$$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ remained unchanged. Aerobic capacity was aligned with lower LF and VAT in older active men. [ABSTRACT FROM AUTHOR]

Aim: There is currently an increased focus on competency‐based training, in which training and assessment play a crucial role. The aim of this systematic review is to create an overview of hands‐on training methods and assessment tools for appendicectomy and colon and rectal surgery procedures using either an open, laparoscopic or robot‐assisted approach. Method: A systematic review of Medline, Embase, Cochrane and Scopus databases was conducted following the PRISMA guidelines. We conducted the last search on 9 March 2023. All published papers describing hands‐on training, evaluation of performance data and development of assessment tools were eligible. The quality of studies and the validity evidence of assessment tools are reported. Results: Fifty‐one studies were identified. Laparoscopic assessment tools are abundant, but the literature still lacks good‐quality assessment tools for open appendicectomy, robotic colectomy and open rectal surgery. Overall, there is a lack of discussion regarding the establishment of pass/fail standards and the consequences of assessment. Virtual reality simulation is used more for appendicectomy than colorectal procedures. Only a few of the studies investigating training were of acceptable quality. There is a need for high‐quality studies in open and robotic‐assisted colon surgery and all approaches to rectal surgery. Conclusion: This review provides an overview of current training methods and assessment tools and identifies where more research is needed based on the quality of the studies and the current validity evidence. [ABSTRACT FROM AUTHOR]

Numerous spatiotemporal species distribution modeling frameworks are now available to the ecological practitioner. This study compared three such frameworks accessible in the R programming language: generalized additive models with spatiotemporal smooths as implemented by mgcv, spatiotemporal generalized linear mixed models based on nearest neighbor Gaussian processes as implemented by starve, and spatiotemporal generalized linear mixed models based on the stochastic partial differential equations approach as implemented by sdmTMB. The primary focus was to compare the inferences obtained from applying these frameworks to the case study of the orange‐footed sea cucumber, Cucumaria frondosa, on the Scotian Shelf off Nova Scotia, Canada. Each model was fit to catch data (2000–2019) from Fisheries and Oceans Canada's annual Research Vessel and Snow Crab surveys. Environmental covariates were sourced from high‐resolution data layers, including physical oceanographic, bathymetric, and seafloor morphometric datasets. The three models captured variability in sea cucumber distribution that would have been overlooked without a spatiotemporal approach. Although their predictions were similar, including within C. frondosa spatial reserves, the models provided different inferences regarding covariate effects. This suggests that while practitioners primarily interested in mapping species distributions need only apply the most familiar framework, those most concerned with identifying predictive environmental covariates may benefit from comparing the output from multiple approaches. Employing multiple approaches can also serve as a validation technique. [ABSTRACT FROM AUTHOR]

Aims: Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta‐cell receptors for GLP‐1, both of which are related to the insulin production. Materials and Methods: We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide. Results: Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non‐diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP‐1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both CERS2 and CERS6. Conclusions: Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non‐diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta‐cell insulin resistance due to low levels of GLP‐1 receptors. [ABSTRACT FROM AUTHOR]

Background: Most of the shrimp side streams are discarded due to the lack of appropriate processing techniques/methodology for their utilization, which is not only a loss of potentially valuable compounds, but also leads to environmental pollution. The study aimed to employ a mechanical filter press to separate the liquid called press juice (PJ) and the solid named press cake (PC) fraction from shrimp head and shell (H&S). Results: The proximate composition was performed, including amino acids analysis, protein content, fatty acids, and the main volatile compounds. In the whole shrimp (WS), the average values of protein, lipid, dry matter, and ash content were recorded at 14.7%, 2.9%, 21.1%, and 4.8%, respectively. The protein percentage reached 10.1% in H&S, indicating considerable amount of protein leftover in the shrimp side streams (p < 0.05). The major PUFAs in WSs' sample were Eicosapentaenoic acid (EPA) (8.8%) and Docosahexaenoic acid (DHA) (7.8%). Furthermore, the values of EPA and DHA a showed nearly two‐folded increase after peeling and filter‐pressing, PC sample. Total amino acids in the WS, H&S, PJ, and PC samples were found to be 94.6, 67.7, 22.2, and 76.6 mg/g, respectively. From the nutritional point of view, non‐essential amino acids represented higher values (13.2%–56.9%) compared to essential amino acids (9.0%–37.6%). The major components of 5′‐neucleoitides in WS sample were in order of guanosine‐5′‐diphosphate (GDP) ≫ hypoxanthine (HYP) > inosine‐5′‐monophosphate (IMP) ≫ adenosine‐5′‐monophosphate (AMP) > adenosine‐5′‐diphosphate (ADP) with values of 684.4, 293.6, 201.4, 25.6 and 16.2 μg/g sample, while no inosine (INO), guanosine‐5′‐monophosphate (GMP), and guanosine‐5′‐triphosphate (GTP) were detected. Equivalent umami concentration (g MSC/100 g) was recorded as 0.63, 0.07 for WS and H&S samples and 0.015 for PJ sample, which indicates a significant drop from the shrimp raw material toward the side streams. Most volatile compounds belonged to alkenes followed by alkanes groups. Conclusion: This work showed the possibility to employ the filter press machine to obtain PJ and PC from shrimp H&S, after peeling processing. The fractions present an interesting nutritional composition and value. [ABSTRACT FROM AUTHOR]

Public opinion can have a decisive influence on conservation actions leading to a need to understand how public opinion is formed. In a survey with a representative sample of the German population, participants answered questions about foxes in two consecutive years. Different versions of a leaflet about foxes were distributed to 2448 participants before the second interview. We compared a narrative text presentation to a non‐narrative list of facts and examined the use of photographs and schematic graphs. We assessed how the presentation format and socio‐demographic factors affected the probability that participants read the leaflet. Using a before‐after/control‐impact design, we examined whether the leaflet affected people's fox‐related knowledge, attitude, and risk perception. The results show that participants were more likely to read the leaflet with increasing age and a higher educational level. Reading probability also increased with attitude toward foxes. Participants who read the leaflet completely gained more knowledge about foxes than those who read it only partly. Photographs also contributed to a higher knowledge gain, but schematic graphs did not. Moreover, participants who read a fact list gained more knowledge compared to the control condition. Furthermore, the combination of visual and textual features had an effect on attitude toward foxes. However, we found no evidence that any treatment affected risk perception. We discuss implications and derivations for science communication to improve conservation actions. [ABSTRACT FROM AUTHOR]

Purpose: Layer‐specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer‐specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD. Methods: We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer‐specific (endocardial‐, whole‐layer‐, and epicardial‐) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer‐specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression. Results: Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS < 400 (endocardial GLS: −20.5 vs. −22.7%, whole‐layer GLS: −17.7 vs. −19.4%, epicardial GLS: −15.3 vs. −16.9%, p <.001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR = 1.11 (1.03–1.20); whole‐layer GLS: OR = 1.14 (1.04–1.24); epicardial GLS: OR = 1.16 (1.05–1.29), per 1% absolute decrease). Conclusion: In this study population with patients suspected of CAD and normal systolic function, impaired layer‐specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS. [ABSTRACT FROM AUTHOR]

Background/Aim: Type 1 diabetes is an autoimmune disease that involves the development of autoantibodies against pancreatic islet beta‐cell antigens, preceding clinical diagnosis by a period of preclinical disease activity. As screening activity to identify autoantibody‐positive individuals increases, a rise in presymptomatic type 1 diabetes individuals seeking medical attention is expected. Current guidance on how to monitor these individuals in a safe but minimally invasive way is limited. This article aims to provide clinical guidance for monitoring individuals with presymptomatic type 1 diabetes to reduce the risk of diabetic ketoacidosis (DKA) at diagnosis. Methods: Expert consensus was obtained from members of the Fr1da, GPPAD, and INNODIA consortia, three European diabetes research groups. The guidance covers both specialist and primary care follow‐up strategies. Results: The guidance outlines recommended monitoring approaches based on age, disease stage and clinical setting. Individuals with presymptomatic type 1 diabetes are best followed up in specialist care. For stage 1, biannual assessments of random plasma glucose and HbA1c are suggested for children, while annual assessments are recommended for adolescents and adults. For stage 2, 3‐monthly clinic visits with additional home monitoring are advised. The value of repeat OGTT in stage 1 and the use of continuous glucose monitoring in stage 2 are discussed. Primary care is encouraged to monitor individuals who decline specialist care, following the guidance presented. Conclusions: As type 1 diabetes screening programs become more prevalent, effective monitoring strategies are essential to mitigate the risk of complications such as DKA. This guidance serves as a valuable resource for clinicians, providing practical recommendations tailored to an individual's age and disease stage, both within specialist and primary care settings. [ABSTRACT FROM AUTHOR]

Introduction: The Medtronic Hugo™ Robot‐assisted Surgery (RAS) system was recently approved for clinical use. We explored the safety and feasibility of this system for endometriosis surgery. The primary outcome was safe case completion without major surgical complications (Clavien–Dindo grade ≤2) and no conversion to open surgery or laparoscopy. Material and methods: Surgeries for endometriosis performed at the Department of Gynecology, Rigshospitalet, on the Medtronic Hugo™ RAS system were included. Two experienced robotic surgeons performed all surgeries with their usual robotic team. The variables included were patient demographics, peri‐ and postoperative data, complications and 30‐day readmission rate. We used the IDEAL framework 1/2a for surgical innovation in this descriptive study. Results: The first 12 patients were included. All cases were completed without intraoperative complications or conversion. Four patients experienced Clavien–Dindo grade 1 postoperative complications. No patients were re‐admitted within 30 days. Median docking time (17 minutes), console time (87.5 minutes), blood loss (40 mL) and length of hospital stay (1 day) were acceptable compared with previous literature. Conclusions: In this pilot study, we found the Medtronic Hugo™ RAS system safe and feasible for robot‐assisted surgery for endometriosis. The advent of new robotic systems is welcomed to accelerate the development of technology that will advance surgical care for patients across the globe. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend HCV screening by 18 months of age for those exposed to HCV in utero; yet, screening occurs in the minority of children. Objectives: To evaluate the association between maternal neighbourhood‐level social determinants of health (SDOH) and paediatric HCV screening in the general population in a publicly funded healthcare system in Canada. Methods: Retrospective cohort study using administrative healthcare data held at ICES. Children born to individuals positive for HCV RNA in pregnancy from 2000 to 2016 were identified and followed for 2 years. Major SDOH were identified, and the primary outcome was HCV screening in exposed children (HCV antibody and/or RNA). Associations between SDOH and HCV screening were determined using multivariate Poisson regression models adjusting for confounding. Results: A total of 1780 children born to persons with +HCV RNA were identified, and 29% (n = 516) were screened for HCV by age two. Most mothers resided in the lowest income quintile (42%), and most vulnerable quintiles for material deprivation (41%), housing instability (38%) and ethnic diversity (26%) with 11% living in rural locations. After adjustment for confounding, maternal rural residence (risk ratio [RR] 0.82, 95% confidence interval [CI] 0.62, 1.07) and living in the highest dependency quintile (RR 0.83, 95% CI 0.65, 1.07) were the SDOH most associated with paediatric HCV screening. Younger maternal age (RR 0.98 per 1‐year increase, 95% CI 0.97, 0.99), HIV co‐infection (RR 1.69, 95% CI 1.16, 2.48) and GI specialist involvement (RR 1.18, 95% CI 1.00, 1.39) were associated with higher probabilities of screening. Conclusions: Among children exposed to HCV during pregnancy, rural residences and living in highly dependent neighbourhoods showed a potential association with a lower probability of HCV screening by the age of 2. Future work evaluating barriers to paediatric HCV screening among rural residing and dependent residents is needed to enhance the screening. [ABSTRACT FROM AUTHOR]

Freshwater ecosystems are the most threatened on Earth, with many species facing extinction. The Clanwilliam sandfish (Labeo seeberi) is South Africa's most threatened migratory freshwater fish and is endemic to the Olifants–Doring River system in the Cape Fold Ecoregion. Non‐native fish predation and river desiccation have caused a recruitment bottleneck, severely compromising juvenile survival and resulting in a declining population of aging sandfish. The Saving Sandfish Project launched an emergency head‐start intervention in 2020 to reduce extinction risk. We (1) rescued juvenile sandfish from drying pools in a key spawning tributary (the Biedouw River); (2) relocated them to 6 off‐stream reservoirs; and (3) released reservoir‐reared sandfish back into their natal river once large enough to evade non‐native fish predation. Here, we estimate survival in the reservoir environment, evaluate return rates relative to wild run size, and assess the probability of return based on conditions at release. Between 2020 and 2022, we stocked 33,391 juvenile sandfish into the 6 reservoirs. After 1 year, the estimated survival rate at one reservoir was 0.679 (range based on 95% CI: 0.385–0.973). Release and return results are presented only for the first (2020) rescue cohort. In 2021, we released 1277 sandfish from 2 reservoirs into the Biedouw River, comprising 16.6% of the 2020 rescue cohort. Mean size at release was 169 mm (SE 0.6) total length. Of those released, 994 were PIT‐tagged. A total of 77 PIT‐tagged sandfish were recorded during the 2022 spawning migration—a return rate of 7.7% of tagged releases in the first year of returns. Size of fish and distance from the Doring River at release were significant predictors of return probability, with larger fish released further from the Doring experiencing a higher probability of return. This program serves as a model for the conservation of freshwater fish where there is an imminent and high risk of extinction. [ABSTRACT FROM AUTHOR]

Abrasion of tire tread, caused by friction between vehicle tires and road surfaces, causes release of tire wear particles (TWPs) into various environmental compartments. These TWPs contribute to chemical, microplastic, and particulate matter pollution. Their fate remains largely unknown, especially regarding the extent and form in which they persist in the environment. The present study investigated (1) the biodegradability of tread particles (TPs) in the form of ground tire tread, (2) how accelerated ultraviolet (UV) weathering affects their biodegradability, and (3) which TP constituents are likely contributors to TP biodegradability based on their individual biodegradability. A series of closed‐bottle tests, with aerobic aqueous medium inoculated with activated sludge, were carried out for pristine TPs, UV‐weathered TPs, and selected TP constituents; natural rubber (NR), isoprene rubber (IR), butadiene rubber (BR), and treated distillate aromatic extracts (TDAE). Biodegradation was monitored by manometric respirometry, quantifying biological oxygen consumption over 28 days. Pristine TP biodegradability was found to be 4.5%; UV‐weathered TPs showed higher biodegradability of 6.7% and 8.0% with similar and increased inoculum concentrations, respectively. The observed TP biodegradation was mainly attributed to biodegradation of NR and TDAE, with individual biodegradability of 35.4% and 8.0%, respectively; IR and BR showed negligible biodegradability. These findings indicate that biodegradability of individual constituents is decreased by a factor of 2 to 5 when compounded into TPs. Through scanning electron microscopy analysis, biodegradation was found to cause surface erosion. Processes of TP biodegradation are expected to change throughout their lifetime as new constituents are incorporated from the road and others degrade and/or leach out. Tire emissions likely persist as particles with an increased fraction of synthetic rubbers and carbon black. Environ Toxicol Chem 2024;43:31–41. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain is common and difficult to treat. The sodium channel blocker lacosamide is efficacious in animal models of pain, but its effect on neuropathic pain in humans is inconclusive. Methods: In a multicentre, randomized, double‐blinded placebo‐controlled phenotype stratified trial, we examined if lacosamide produced better pain relief in patients with the irritable nociceptor phenotype compared to those without. The primary outcome was the change in daily average pain from baseline to last week of 12 weeks of treatment. Secondary and tertiary outcomes included pain relief, patient global impression of change and presence of 30% and 50% pain reduction. Results: The study was prematurely closed with 93 patients included and 63 randomized to lacosamide or placebo in a 2:1 ratio, of which 49 fulfilled the per protocol criteria and was used for the primary objective. We did not find a better effect of lacosamide in patients with the irritable nociceptor phenotype, the 95% CI for the primary objective was 0.41 (−1.2 to 2.0). For all patients randomized, lacosamide had no effect on the primary outcome, but significantly more patients were responders to lacosamide than during placebo, with an NNT of 4.0 (95% CI 2.3–16.1) and 5.0 (95% CI 2.8–24.5) for 30% and 50% pain reduction respectively. We did not identify any predictors for response. Lacosamide was generally well tolerated. Conclusion: We could not confirm that lacosamide was more efficacious in patients with the irritable nociceptor type, but the study was prematurely closed, so we cannot exclude a small difference. Significance: Treatment of neuropathic pain is often a trial and error process. Little is known about which patient benefit from which kind of medication. The sodium channel blocker lacosamide shows variable effect on neuropathic pain. Pain sensory phenotype, as defined by quantitative sensory testing, did not predict response to treatment with lacosamide. [ABSTRACT FROM AUTHOR]

Rates of biological invasion are increasing globally, with associated negative effects on native biodiversity and ecosystem services. Among other genetic processes, hybridisation can facilitate invasion by producing new combinations of genetic variation that increase adaptive potential and associated population fitness. Yet the role of hybridisation (and resulting gene flow) in biological invasion in invertebrate species is under‐studied. Calliphora hilli and Calliphora stygia are blowflies proposed to have invaded New Zealand separately from Australia between 1779 and 1841, and are now widespread throughout the country. Here, we analysed genome‐wide single nucleotide polymorphisms (SNPs), generating genotyping‐by‐sequencing data for 154 individuals collected from 24 populations across New Zealand and Australia to assess the extent of gene flow and hybridisation occurring within and between these blowflies and to better understand their overall population structure. We found that New Zealand populations of both species had weak genetic structure, suggesting high gene flow and an absence of dispersal limitations across the country. We also found evidence that interspecific hybridisation is occurring in the wild between C. hilli and C. stygia in both the native and invasive ranges, and that intraspecific admixture is occurring among populations at appreciable rates. Collectively, these findings provide new insights into the population structure of these two invasive invertebrates and highlight the potential importance of hybridisation and gene flow in biological invasion. [ABSTRACT FROM AUTHOR]

This study aims to estimate climatological cloudburst frequencies from daily precipitation sums for a dense network of 161 historical Danish stations covering the period 1914–2010, in order to reveal any systematic regional differences. We define a cloudburst day for a given station as a day when the maximum 1‐h precipitation sum exceeds a predefined threshold; we use the thresholds 15, 20 and 25 mm, corresponding to a cloudburst frequency around 0.42, 0.16 and 0.06 year−1, respectively. Supplementing the historical data, we use hourly data from a modern network and relate the daily probability of cloudburst occurrence to the corresponding daily precipitation using binary regression. This allows an estimation of the cloudburst frequency from a series of daily sums. To validate the methods, we use 33 stations that have been operating for 30 years or longer. For these stations, we demonstrate significant skill by comparing observed and estimated cloudburst frequencies with a jackknife procedure. By applying the model to the 161 historical series, we estimate climatological cloudburst frequencies throughout Denmark. We find large systematic regional variations across Denmark and these variations are much larger, but with a similar regional pattern, than obtained by previous work. We suggest applying the approach to the historical daily precipitation series that exist across the world. [ABSTRACT FROM AUTHOR]

Heterogeneous catalytic ammoxidation provides an eco‐friendly route for the cyanide‐free synthesis of nitrile compounds, which are important precursors for synthetic chemistry and pharmaceutical applications. However, in general such a process requires high pressures of molecular oxygen at elevated temperatures to accelerate the oxygen reduction and imine dehydrogenation steps, which is highly risky in practical applications. Here, we report an electric field enhanced ammoxidation system using a supported Fe clusters catalyst (Fe/NC), which enables efficient synthesis of nitriles from the corresponding aldehydes under ambient air pressure at room temperature (RT). A synergistic effect between the external electric field and the Fe/NC catalyst promotes the ammonia activation and the dehydrogenation of the generated imine intermediates and avoids the unwanted backwards reaction to aldehydes. This electric field enhanced ammoxidation system presents high efficiency and selectivity for the conversion of a series of aldehydes under mild conditions with high durability, rendering it an attractive process for the green synthesis of nitriles with fragile functional groups. [ABSTRACT FROM AUTHOR]

The rixosome defined in Schizosaccharomyces pombe and humans performs diverse roles in pre‐ribosomal RNA processing and gene silencing. Here, we isolate and describe the conserved rixosome from Chaetomium thermophilum, which consists of two sub‐modules, the sphere‐like Rix1‐Ipi3‐Ipi1 and the butterfly‐like Las1‐Grc3 complex, connected by a flexible linker. The Rix1 complex of the rixosome utilizes Sda1 as landing platform on nucleoplasmic pre‐60S particles to wedge between the 5S rRNA tip and L1‐stalk, thereby facilitating the 180° rotation of the immature 5S RNP towards its mature conformation. Upon rixosome positioning, the other sub‐module with Las1 endonuclease and Grc3 polynucleotide‐kinase can reach a strategic position at the pre‐60S foot to cleave and 5′ phosphorylate the nearby ITS2 pre‐rRNA. Finally, inward movement of the L1 stalk permits the flexible Nop53 N‐terminus with its AIM motif to become positioned at the base of the L1‐stalk to facilitate Mtr4 helicase‐exosome participation for completing ITS2 removal. Thus, the rixosome structure elucidates the coordination of two central ribosome biogenesis events, but its role in gene silencing may adapt similar strategies. Synopsis: The rixosome is involved in ribosome biogenesis and gene silencing. Its cryo‐EM structure explains how it can participate in pre‐60S ribosome maturation during 5S RNP rotation and ITS2 processing.Rix1 sub‐module of the rixosome functions as central hub to trigger the 5S RNP rotation on pre‐60S particles.Las1‐Grc3 endonuclease flexibly attached to the rixosome can be strategically positioned at the pre‐60S foot to perform ITS2 processing. [ABSTRACT FROM AUTHOR]

Objective: Data from South Asia indicate that for 15%–20% of suicide attempts, pesticides are purchased from shops; otherwise, pesticides are obtained from an individual's house or nearby environment. We aimed to investigate the difference between individuals who directly purchase pesticides from shops for suicide attempts and suicide deaths versus those related to accessing the pesticides from an individual's house or nearby environment. Methods: We conducted two comparative studies in rural Sri Lanka: (1) non‐fatal shop cases (n = 50) were survivors of self‐poisoning with pesticides who ingested the pesticides after purchasing them from a shop; non‐fatal domestic cases (n = 192) were survivors who accessed pesticides from their house or nearby environment. (2) fatal shop cases (n = 50) were individuals who died after ingesting pesticides they purchased for the act; fatal domestic cases (n = 102) were patients who died after ingesting pesticides they accessed at house or nearby environment. Logistic regression analysis was used to assess the characteristics which distinguished between the shop and domestic cases. Results: Data indicate that 20.7% and 32.9% of individuals who used pesticides for suicide attempts and suicide deaths had purchased them from shops, respectively. Being a non‐farmer was the main distinguishing characteristic of shop cases: adjusted odds ratios (AOR) 8.9, 95% confidence intervals (CI) 3.2–24.4 for non‐fatal shop cases, and AOR 4.0, 95% CI 1.5–10.6 for fatal shop cases. Non‐fatal shop cases also had higher suicide intent (AOR 3.0, CI 1.0–8.9), and ingesting an insecticide (AOR 4.8, CI 1.8–1.0–8.9) than non‐fatal domestic cases. Conclusion: A high suicide intent of individuals who purchase pesticides for the event explains the high proportion of such fatal cases. Such high suicide intent makes the prevention implications difficult to spell out for those individuals who purchase pesticides for self‐poisoning. However, our findings are valuable for clinicians to assess pesticide poisoning cases in hospitals. [ABSTRACT FROM AUTHOR]

We aimed to follow a nationwide cohort of patients with pulmonary embolism (PE) without any exclusions to generate information regarding long-term symptoms, investigational findings and to determine the prevalence of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that this approach would yield generalizable estimates of CTEPH prevalence and incidence. All individuals diagnosed with acute PE in Sweden in 2005 were identified using the National Patient Register. In 2007, survivors were asked to complete a questionnaire regarding current symptoms. Those with dyspnea were referred for further examinations with laboratory tests, electrocardiogram (ECG), and a ventilation/perfusion scan (V/Q scan). If CTEPH was suspected, a referral to the nearest pulmonary arterial hypertension-center was recommended. Of 5793 unique individuals with PE diagnosis in 2005, 3510 were alive at the beginning of 2007. Altogether 53% reported dyspnea at some degree whereof a large proportion had V/Q scans indicating mismatched defects. Further investigation revealed 6 cases of CTEPH and in parallel 18 cases were diagnosed outside this study. The overall prevalence of CTEPH was 0.4% (95% confidence interval [CI]: 0.2%-0.6%) and 0.7% (95% CI: 0.4%-1.0%) among the survivors. The cumulative incidence of CTEPH in the group of patients who underwent a V/Q scan was 1.1% (95% CI: 0.2%-2.0%). There was a high mortality following an acute PE, a high proportion of persistent dyspnea among survivors, whereof several had pathological findings on V/Q scans and echocardiography. Only a minority developed CTEPH, indicating that CTEPH is the tip of the iceberg of post-PE disturbances. [ABSTRACT FROM AUTHOR]

Objectives: Bacterial infection following spinal fusion is a major clinical concern with up to 20% incidence. An ultrasound‐triggered bulk‐release system to combat postsurgical bacterial survival was designed and evaluated. Methods: Polylactic acid (PLA) clips were loaded with vancomycin (VAN) and microbubbles (Sonazoid, GE HealthCare) in vitro. Stability was determined over 14 days. VAN‐loaded clips were submerged in water and insonated using a Logiq E10 scanner (GE HealthCare) with a curvilinear C6 probe. Doppler‐induced VAN release was quantified using spectrophotometry. For in vivo testing, clips were loaded with methylene blue (MeB) solution and Sonazoid. These clips were implanted into a rabbit along the spine at L2 and L5, as well as a pig at L1 and L3, then insonated in Doppler mode using the C6 probe. Results: Sonazoid microbubbles were better preserved when incubated in VAN compared with distilled water at 4°C, 25°C, and 37°C incubation temperatures (P =.0131). Contrast enhancement was observed from both solutions when incubated at 4°C storage conditions. Insonated clips achieved average cumulative VAN release of 101.8 ± 2.8% (81.4 ± 2.8 mg) after 72 hours. Uninsonated clips had only 0.3 ± 0.1% (0.3 ± 0.1 mg) average cumulative VAN release (P <.0001). Clips retrieved from the rabbit did not rupture with insonation nor produce MeB staining of surrounding tissues. In the pig, the PLA film was visibly ruptured and MeB tissue was observed following insonation, whereas the uninsonated clip was intact. Conclusion: These results demonstrate ultrasound‐triggered release of an encapsulated prophylactic solution and provide an important proof‐of‐concept for continuing large animal evaluations for translational merit. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of implantoplasty (IP) on maximum implant failure strength of narrow diameter implants of different type/design and material, with simulated advanced bone loss. Materials and Methods: Narrow, parallel‐walled implants (3.3 mm in diameter × 10 mm long) with an internal connection of different type/design [bone level (BL), tissue level (TL)] and material [Titanium grade IV (Ti), Titanium‐Zirconium alloy (TiZr)] from one specific manufacturer were used. Half of the implants were subjected to IP in their coronal 5 mm; the remaining were used as controls (seven implants per group). Dynamic loading prior to maximum load strength testing was included. Results: During dynamic loading, the fracture rate of BL implants was low and independent of IP, while that of TL implants increased significantly with IP compared with controls (p =.001). Maximum implant failure strength reduction (in %) due to IP, was 1.3%–25.4%; TiZr BL implants were least affected. Implants subjected to IP compared to those without IP as well as TL implants compared to BL implants showed a significantly lower maximum implant failure strength (p <.002); implant material was not significant (p =.845). Conclusions: Based on data from implants of one specific manufacturer, IP has a significant negative impact on the fracture strength of narrow implants suffering from advanced peri‐implantitis. TL implants have been more severely affected compared to BL implants and presented an increased risk for failure during normal chewing forces. In addition, this negative impact of IP on TL implants was independent of the implant material (i.e., Ti or TiZr). Clinical Relevance: Narrow single TL implants with advanced horizontal bone loss (e.g., 5 mm), when subjected to IP, appear to have an increased fracture risk during normal function. [ABSTRACT FROM AUTHOR]

Background: Non‐selective beta‐blockers (NSBB) are widely used in the treatment of patients with cirrhosis. Only about 50% respond with a sufficient reduction in their hepatic venous pressure gradient (HVPG) and NSBB may induce detrimental cardiac and renal effects in the presence of severe decompensation. We aimed to assess the effects of NSBB on haemodynamics using magnetic resonance imaging (MRI) and to assess if these haemodynamic changes were related to the disease severity and HVPG response. Method: A prospective cross‐over study of 39 patients with cirrhosis. Patients underwent hepatic vein catheterization and MRI with assessments of HVPG, cardiac function, systemic and splanchnic haemodynamics before and after propranolol infusion. Results: Propranolol induced significant decreases in cardiac output (−12%) and blood flow of all vascular compartments, with the largest reductions seen in the azygos venous (−28%), portal venous (−21%), splenic (−19%) and superior mesenteric artery (−16%) blood flow. Renal artery blood flow fell by −5% in the total cohort, with a more pronounced reduction in patients without ascites than in those with ascites (−8% vs. −3%, p =.01). Twenty‐four patients were NSBB responders. Their changes in HVPG after NSBB were not significantly associated with other haemodynamic changes. Conclusion: The changes in cardiac, systemic and splanchnic haemodynamics did not differ between NSBB responders and non‐responders. The effects of acute NSBB blockade on renal flow seem to depend on the severity of the hyperdynamic state, with the largest reduction in renal blood flow in compensated patients compared to decompensated patients with cirrhosis. However, future studies are needed to assess the effects of NSBB on haemodynamics and renal blood flow in patients with diuretic‐resistant ascites. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemo‐ and radiotherapy cause cellular damage to tumorous and healthy dividing cells. Chemotherapy has been shown to cause mitochondrial respiratory dysfunction in non‐tumorous tissues, but the effects on human peripheral blood mononuclear cells (PBMCs) remain unknown. Aim: We aimed to investigate mitochondrial respiration of PBMCs before and after adjuvant chemo‐ and radiotherapy in postmenopausal patients with early breast cancer (EBC) and relate these to metabolic parameters of the patients. Methods: Twenty‐three postmenopausal women diagnosed with EBC were examined before and shortly after chemotherapy with (n = 18) or without (n = 5) radiotherapy. Respiration (O2 flux per million PBMCs) was assessed by high‐resolution respirometry of intact and permeabilized PBMCs. Clinical metabolic characteristics and mitochondrial DNA (mtDNA) content of PBMCs (mtDN relative to nuclear DNA) were furthermore assessed. Results: Respiration of intact and permeabilized PBMCs from EBC patients significantly increased with adjuvant chemo‐ and radiotherapy (p = 6 × 10−5 and p = 1 × 10−7, respectively). The oxygen flux attributed to specific mitochondrial complexes and respiratory states increased by 17–43% compared to before therapy initiation. Similarly, PBMC mtDNA content increased by 40% (p = 0.002). Leukocytes (p = 0.0001), hemoglobin (p = 0.0003), and HDL cholesterol (p = 0.003) concentrations decreased whereas triglyceride (p = 0.01) and LDL (p = 0.02) concentrations increased after treatment suggesting a worsened metabolic state. None of the metabolic parameters or the mtDNA content of PBMCs correlated significantly with PBMC respiration. Conclusion: This study shows that mitochondrial respiration and mtDNA content in circulating PBMCs increase after adjuvant chemo‐ and radiotherapy in postmenopausal patients with EBC. Besides the increased mtDNA content, a shift in PBMC subpopulation proportions towards cells relying on oxidative phosphorylation, who may be less sensitive to chemotherapy, might influence the increased mitochondrial respiration observed iafter chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis. Aim: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis. Methods: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed. Results: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e′, left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01). Conclusions: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine‐conjugated BA are associated with portal hypertension. [ABSTRACT FROM AUTHOR]