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This review aimed to summarize the current literature on antibiotic distribution in orthopedically relevant tissues and settings where dynamic sampling methods have been used. PubMed and Embase databases were systematically searched. English‐published studies between 2004 and 2024 involving systemic antibiotic administration in orthopedically relevant tissues and settings based on dynamic measurements were included. In total, 5385 titles were identified. After title and abstract screening, 97 eligible studies (43 different antibiotic drugs) were included. The studies covered both preclinical (42%) and clinical studies including healthy and infected tissues (21%) and prophylactic and steady‐state situations (35%). Microdialysis emerged as the predominant sampling method in 98% of the studies. Most of the presented antibiotics (80%) were only assessed once or twice. Among the most extensively studied antibiotics were cefuroxime (18 studies), linezolid (9 studies) and vancomycin (9 studies). This review presents valuable insights into the microenvironmental distribution of antibiotics in orthopedically relevant target tissues and settings and seeks to provide a basis for improving dosing recommendations and treatment outcomes. However, it is important to acknowledge that our findings are limited to the specific drug, dosing regimens, administration method and target tissue, and are crucially linked to the selected PK/PD target. [ABSTRACT FROM AUTHOR]

Purpose: Etoposide to standard R‐CHOP is used for high‐risk diffuse large B‐cell lymphoma (DLBCL) in some countries. Due to the lack of randomized trials, a real‐world data study using matching methods was used to test the potential effectiveness of R‐CHOEP over R‐CHOP. Patients and Methods: This study included patients from the Danish Lymphoma Register diagnosed between 2006 and 2020 at the age of 18–60 years with de novo DLBCL and age‐adjusted IPI ≥2. R‐CHOEP treated patients were matched 1:1 without replacement to R‐CHOP treated patients using a hybrid exact and genetic matching technique. Primary endpoints were progression‐free survival (PFS) and overall survival (OS). Results: In total, 396 patients were included; 213 received R‐CHOEP and 183 received R‐CHOP. Unadjusted 5‐year PFS and OS for R‐CHOEP were 69% (95% Confidence intervals [CI]; 63%–76%) and 79% (CI;73%–85%) versus 62% (CI;55%–70%) and 76% (CI;69%–82%) for R‐CHOP (log‐rank test, PFS p =.25 and OS p =.31). A total of 127 patients treated with R‐CHOEP were matched to 127 patients treated with R‐CHOP. Matching‐adjusted 5‐year PFS and OS were 65% (CI; 57%–74%) and 79% (CI; 72%–84%) for R‐CHOEP versus 63% (CI; 55%–73%) and 79% (CI;72%–87%) for R‐CHOP (log‐rank test, PFS p =.90 and OS p =.63). Conclusion: The present study did not confirm superiority of R‐CHOEP over R‐CHOP for young patients with high‐risk DLBCL. [ABSTRACT FROM AUTHOR]

SUMMARY: Barley produces several specialized metabolites, including five α‐, β‐, and γ‐hydroxynitrile glucosides (HNGs). In malting barley, presence of the α‐HNG epiheterodendrin gives rise to undesired formation of ethyl carbamate in the beverage production, especially after distilling. Metabolite‐GWAS identified QTLs and underlying gene candidates possibly involved in the control of the relative and absolute content of HNGs, including an undescribed MATE transporter. By screening 325 genetically diverse barley accessions, we discovered three H. vulgare ssp. spontaneum (wild barley) lines with drastic changes in the relative ratios of the five HNGs. Knock‐out (KO)‐lines, isolated from the barley FIND‐IT resource and each lacking one of the functional HNG biosynthetic genes (CYP79A12, CYP71C103, CYP71C113, CYP71U5, UGT85F22 and UGT85F23) showed unprecedented changes in HNG ratios enabling assignment of specific and mutually dependent catalytic functions to the biosynthetic enzymes involved. The highly similar relative ratios between the five HNGs found across wild and domesticated barley accessions indicate assembly of the HNG biosynthetic enzymes in a metabolon, the functional output of which was reconfigured in the absence of a single protein component. The absence or altered ratios of the five HNGs in the KO‐lines did not change susceptibility to the fungal phytopathogen Pyrenophora teres causing net blotch. The study provides a deeper understanding of the organization of HNG biosynthesis in barley and identifies a novel, single gene HNG‐0 line in an elite spring barley background for direct use in breeding of malting barley, eliminating HNGs as a source of ethyl carbamate formation in whisky production. [ABSTRACT FROM AUTHOR]

One key aspect for the development of functional molecular electronic devices is the ability to precisely tune and reversibly switch the conductance of individual molecules in electrode‐molecule‐electrode junctions in response to external stimuli. In this work, we present a new approach to access molecular switches by deliberately controlling the flexibility in the molecular backbone. We here describe two new conductance switches based on bis(triarylamines) that rely on the reversible toggling between two conformers, each associated with vastly different conductances. By molecular design, we were able to realize an on/off ratio Ghigh/Glow of ~103, which is one of the largest values reported to date. Flicker noise analysis and molecular transport calculations indicate that on/off switching relies on a change of the conduction pathway and vast differences in molecule‐electrode coupling. We thereby provide a new scaffold for further development of molecular conductance switches that are both efficient and easily refined. [ABSTRACT FROM AUTHOR]

Within the last decade, a construction‐friendly design principle using flexible wire ropes instead of traditional u‐bars for connecting wall elements has gained popularity. However, anchoring wire ropes in T and L connections remains a complex challenge. Here, the wire ropes stick out of the side of the wall element and are bent in the anchorage zone. This paper presents the findings of an extensive experimental program with 40 specimens, investigating the anchorage capacity of wire ropes in wall elements under these conditions. The study reveals that specially designed reinforcements significantly increase the anchorage capacity, while traditional wall reinforcements have minimal impact. Failure mechanisms primarily involve concrete cone failures, providing valuable insights for construction‐friendly connections. Based on the observed failure mechanism, the paper presents an analytical failure mechanism. The model is based on the upper‐bound theorem of plasticity theory. The model predicts both the capacity and the failure mechanism with satisfactory accuracy. [ABSTRACT FROM AUTHOR]

Oral candidiasis (OC), a prevalent opportunistic infection of the oral mucosa, presents a considerable health challenge, particularly in individuals with compromised immune responses, advanced age, and local predisposing conditions. A considerable part of the population carries Candida in the oral cavity, but only few develop OC. Therefore, the pathogenesis of OC may depend on factors other than the attributes of the fungus, such as host factors and other predisposing factors. Mucosal trauma and inflammation compromise epithelial integrity, fostering a conducive environment for fungal invasion. Molecular insights into the immunocompromised state reveal dysregulation in innate and adaptive immunity, creating a permissive environment for Candida proliferation. Detailed examination of Candida species (spp.) and their virulence factors uncovers a nuanced understanding beyond traditional C. albicans focus, which embrace diverse Candida spp. and their strategies, influencing adhesion, invasion, immune evasion, and biofilm formation. Understanding the pathophysiological microenvironments in OC is crucial for the development of targeted therapeutic interventions. This review aims to unravel the diverse pathophysiological microenvironments influencing OC development focusing on microbial, host, and predisposing factors, and considers Candida resistance to antifungal therapy. The comprehensive approach offers a refined perspective on OC, seeking briefly to identify potential therapeutic targets for future effective management. [ABSTRACT FROM AUTHOR]

Purpose: To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best‐corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. Methods: In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term‐born controls were examined with spectral‐domain optical coherence tomography and BCVA at age 31–43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. Results: The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 μm (28.2) and 272.4 μm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 μm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. Conclusion: Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function. [ABSTRACT FROM AUTHOR]

Objective: To assess the validity of the Fetal Medicine Foundation (FMF) chorionicity‐specific models for fetal growth in twin pregnancy. Methods: This was an external validation study of the FMF models using a nationwide Danish cohort of twin pregnancies. The cohort included all dichorionic (DC) and monochorionic diamniotic (MCDA) twin pregnancies with an estimated delivery date between 2008 and 2018, which satisfied the following inclusion criteria: two live fetuses at the first‐trimester ultrasound scan (11–14 weeks' gestation); biometric measurements available for the calculation of estimated fetal weight (EFW) using the Hadlock‐3 formula; and delivery of two liveborn infants. Validation involved assessing the distributional properties of the models and estimating the mean EFW Z‐score deviations. Additionally, the models were applied to pregnancies that delivered preterm and attended non‐scheduled visits (complicated pregnancies). Results: Overall, 8542 DC and 1675 MCDA twin pregnancies met the inclusion criteria. In DC twins, 17 084 fetuses were evaluated at a total of 95 346 ultrasound scans, of which 44.5% were performed at scheduled visits in pregnancies carried to 37 + 0 weeks or later. The median number of growth scans per DC twin fetus from 20 + 0 weeks onwards was four. The model showed good agreement with the validation cohort for scheduled visits in DC twins delivered at 37 + 0 weeks or later (mean ± SD EFW Z‐score, –0.14 ± 1.05). In MCDA twins, 3350 fetuses underwent 31 632 eligible ultrasound scans, of which 59.5% were performed at scheduled visits in pregnancies carried to 36 + 0 weeks or later. The median number of growth scans per MCDA twin fetus from 16 + 0 weeks onwards was 10. The model showed favorable agreement with the validation cohort for scheduled visits in MCDA twins delivered at 36 + 0 weeks or later (mean ± SD EFW Z‐score, –0.09 ± 1.01). Non‐scheduled visits and preterm delivery before 37 + 0 weeks for DC twins and before 36 + 0 weeks for MCDA twins corresponded with smaller weight estimates, which was consistent with the study's definition of complicated pregnancy. Conclusions: The FMF models provide a good fit for EFW measurements in our Danish national cohort of uncomplicated twin pregnancies assessed at routine scans. Therefore, the FMF models establish robust criteria for subsequent investigations and potential clinical applications. Future research should focus on exploring the consequences of clinical implementation, particularly regarding the identification of twins that are small‐for‐gestational age, as they are especially susceptible to adverse perinatal outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Peer support is a collaborative practice where people with lived experience of mental health conditions engage in supporting like‐minded. Peer support impacts on personal recovery and empowerment and creates value at an organisational level. However, the implementation of peer support into existing mental health services is often impeded by barriers embedded in organisational culture and support in role expectations. Non‐peer professionals' recovery orientation and attitudes towards peer support workers (PSWs) are essential factors in the implementation of peer support, and this study explored non‐peer professionals' understanding of recovery and their attitudes towards PSWs joining existing community mental health teams in one region of Denmark. In total, 17 non‐peer professionals participated in three focus groups. Thematic analysis led to three themes: (1) Recovery is a process of "getting better" and balancing personal and clinical perspectives; (2) Realising recovery‐oriented practice: a challenging task with conflicting values; and (3) Expectations and concerns about peer support workers joining the team. Recovery‐oriented practice faces challenging conditions in contemporary mental health services due to a dominant focus on biomedical aspects in care and treatment. Implementation facilitators and barriers in the employment of PSWs point towards fundamental aspects that must be present when employing PSWs in an organisation. The issues described leading up to the employment of PSWs reflected in this study underpin the importance of preparing an organisation for the employment of PSWs based on the available knowledge. [ABSTRACT FROM AUTHOR]

Penicillin is available in both an oral (penicillin V) and intravenous formulation (penicillin G), theoretically allowing for a safe transition between the two. However, the use of oral penicillin remains a topic of debate due to low and variable bioavailability. This study aimed to assess the time for which the free penicillin concentration exceeded targeted minimum inhibitory concentrations for Staphylococcus aureus and Streptococcus species (0.125, 0.25, and 0.5 mg/L) in cancellous bone and subcutaneous tissue after intravenous penicillin and oral penicillin administration. 12 female pigs (68–75 kg) were assigned, according to local standard clinical regimes, to either intravenous penicillin (1.2 g) or oral penicillin (0.8 g) treatment every 6 h over an 18 h period. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was dynamic/continually collected in the first dosing interval (0–6 h), simulating a prophylactic situation, and the third dosing interval (12–18 h), simulating a therapeutic setting. Plasma samples were collected for reference. For all investigated targets, intravenous treatment resulted in a longer mean time above relevant minimum inhibitory concentrations in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral treatment. With clinically relevant dosing, intravenous penicillin provides superior exposure compared to oral penicillin in both a prophylactic and therapeutic setting. [ABSTRACT FROM AUTHOR]

Motivation: Human activities have been reshaping the natural world for tens of thousands of years, leading to the extinction of hundreds of bird species. Past research has provided evidence of extinction selectivity towards certain groups of species, but trait information is lacking for the majority of clades, especially for prehistoric extinctions identified only through subfossil remains. This incomplete knowledge potentially obscures the structure of natural communities, undermining our ability to infer changes in biodiversity across space and time, including trends in functional and phylogenetic diversity. Biases in currently available trait data also limit our ability to identify drivers and processes of extinction. Here we present AVOTREX, an open‐access database of species traits for all birds known to have gone extinct in the last 130,000 years. This database provides detailed morphological information for 610 extinct species, along with a pipeline to build phylogenetic trees that include these extinct species. Main Types of Variables Contained: For each extinct bird species, we provide information on the taxonomy, geographic location, and period of extinction. We also present data on island endemicity, flight ability, and body mass, as well as standard measurements of external (matching the AVONET database of extant birds) and skeletal morphology from museum specimens where available. To ensure comprehensive morphological data coverage, we estimate all missing morphological measurements using a data imputation technique based on machine learning. Finally, we provide an R package to graft all extinct species onto a global phylogeny of extant species (BirdTree). Spatial Location and Grain: Global. Time Period and Grain: All known globally extinct bird species from 130,000 years ago up until 2024. Major Taxa and Level of Measurement: Birds (Class Aves), species level. Software Format: Spreadsheets (.csv) stored in Dryad. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Placental‐derived extracellular vesicles (EVs) are nano‐organelles that facilitate intercellular communication between the feto‐placental unit and the mother. We evaluated a novel Multiple Microarray analyzer for identifying surface markers on plasma EVs that predict preterm delivery and preeclampsia compared to term delivery controls.In this prospective exploratory cohort study pregnant women between 24 and 40 gestational weeks with preterm delivery (n = 16), preeclampsia (n = 19), and matched term delivery controls (n = 15) were recruited from Bnai Zion Medical Center, Haifa, Israel. Plasma samples were tested using a multiple microarray analyzer. Glass slides with 17 antibodies against EV surface receptors ‐ were incubated with raw plasma samples, detected by biotinylated secondary antibodies specific to EVs or placental EVs (PEVs), and labeled with cyanine 5–streptavidin. PBS and whole human IgG served as controls. The fluorescent signal ratio to negative controls was log 2 transformed and analyzed for sensitivity and specificity using the area under the receiver operating characteristics curves (AUROC). Best pair ratios of general EVs/PEVs were used for univariate analysis, and top pairs were combined for multivariate analysis. Results were validated by comparison with EVs purified using standard procedures.Heatmaps differentiated surface profiles of preeclampsia, preterm delivery, and term delivery receptors on total EVs and PEVs. Similar results were obtained with enriched EVs and EVs from raw plasma. Univariate analyses identified markers predicting preterm delivery and preeclampsia over term delivery controls with AUC >0.6 and sensitivity >50% at 80% specificity. Combining the best markers in a multivariate model, preeclampsia prediction over term delivery had an AUC of 0.89 (95% CI: 0.72–1.0) with 90% sensitivity and 90% specificity, marked by inflammation (TNF RII), relaxation (placenta protein 13 (PP13)), and immune‐modulation (LFA1) receptors. Preterm delivery prediction over term delivery had an AUC of 0.97 (0.94–1.0), 84% sensitivity, and 90% specificity, marked by cell adhesion (ICAM), immune suppression, and general EV markers (CD81, CD82, and Alix). Preeclampsia prediction over preterm delivery had an AUC of 0.91 (0.79–0.99) with 80% sensitivity and 90% specificity with markers for complement activation (C1q) and autoimmunity markers.The new, robust EV Multi‐Array analyzer and methodology offer a simple, fast diagnostic tool that reveals novel surface markers for major obstetric syndromes. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is characterized by immune cell infiltration in the islets of Langerhans, leading to the destruction of insulin‐producing beta cells. This destruction is driven by secreted cytokines and cytotoxic T cells inducing apoptosis in beta cells. Butyrate, a metabolite produced by the gut microbiota, has been shown to have various health benefits, including anti‐inflammatory and anti‐diabetic effects. In this study, we investigated the potential protective effects of butyrate on cytokine‐induced apoptosis in beta cells and explored the underlying mechanisms. Insulin‐secreting INS‐1E cells and isolated mouse islets were treated with interleukin‐1beta (IL‐1β) or a combination of IL‐1β and interferon‐gamma (IFN‐γ) in the presence or absence of butyrate. We analyzed apoptosis, nitric oxide (NO) levels, expression of stress‐related genes, and immune cell migration. Our results demonstrated that butyrate significantly attenuated cytokine‐induced apoptosis in both INS‐1E cells and mouse islets, accompanied by a reduction in NO levels. Butyrate also decreased the expression of endoplasmic reticulum (ER) stress markers such as Chop, phosphorylated eIF2α and Atf4, as well as some pro‐apoptotic genes including Dp5 and Puma. Butyrate reduced the cytokine‐induced expression of the chemokine genes Cxcl1 and Cxcl10 in mouse islets, as well as the chemotactic activity of THP‐1 monocytes toward conditioned media from IL‐1β‐exposed islets. In conclusion, these findings indicate that butyrate protects beta cells from cytokine‐induced apoptosis and ER stress, suggesting its potential as a therapeutic agent to prevent beta cell destruction in T1D. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Obesity is a risk factor for diabetes mellitus, which commonly coexists with pancreatitis in cats. However, obesity has not previously been associated with pancreatitis in cats.To evaluate factors affecting serum concentrations of pancreatic lipase immunoreactivity (fPLI), trypsin‐like immunoreactivity (fTLI), cobalamin and folate in clinically healthy lean, overweight and obese, or diabetic cats.Seventy‐nine client‐owned cats (27 healthy lean [LN, BCS 4‐5/9], 30 healthy overweight and obese [OW, BCS 7‐9/9], and 22 diabetic [DM]) were included.Cross‐sectional study. The cats underwent physical examination, and blood tests. Linear regression models compared differences in fPLI, fTLI, cobalamin, and folate concentrations. Fisher's exact test assessed the proportions of cats with fPLI and fTLI indicative of pancreatitis, and hypocobalaminemia. A random forest algorithm identified explanatory variables for cats having fPLI levels indicative of pancreatitis.No LN cats, while 6/30 (20%) of OW and 10/22 (45%) of DM cats had fPLI concentrations indicative of pancreatitis. Body condition score (P = .02) and body weight (P = .002) were positively associated with fPLI levels in LN and OW cats. Higher fPLI, and lower cobalamin concentrations were associated with higher age across groups.Body condition score and body weight were associated with higher fPLI levels in nondiabetic cats. A larger proportion of OW and DM cats had fPLI concentrations indicative of pancreatitis compared to LN cats. Whether this indicates subclinical pancreatitis remains to be determined. Hypocobalaminemia was less frequent in OW compared to DM cats. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Dostarlimab‐gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the programmed cell death protein‐1 (PD‐1) receptor and blocks its ligands. RUBY (NCT03981796) is a two‐part multicentre study in patients with recurrent or primary advanced endometrial cancer. The overall aims were to characterise the population pharmacokinetics (PopPK) from Part 1 of this study, identify relevant covariates of interest, and assess exposure–efficacy/safety (ER) relationships.A PopPK model developed using GARNET (NCT02715284) study data for dostarlimab monotherapy was externally validated with RUBY Part 1 study data. Subsequently, the model was updated with data across the two studies. Exposure–safety analyses for adverse events related to dostarlimab alone or in combination with standard of care (SOC) were modelled using logistic regression. Exposure–efficacy analysis included Cox proportional hazards analysis of the primary efficacy endpoint of progression‐free survival (PFS).For the model update, 7957 pharmacokinetics observations from 868 patients pooled from both RUBY and GARNET studies were available. The model was consistent with the previous model. Dostarlimab clearance was estimated to be 7.79% lower when dostarlimab was given as SOC combination therapy. However, no significant covariates were clinically relevant. Hepatic or renal impairment did not affect pharmacokinetics. Among the safety endpoints, only rash showed a small yet statistically significant effect (P < .05) in all subjects; however, this was not not deemed clinically relevant. There were no other clinically significant exposure–safety or exposure–PFS relationships.The addition of chemotherapy to dostarlimab had limited effect on dostarlimab PopPK, with no clinically significant covariates or clinically relevant exposure–safety or exposure–PFS relationships. [ABSTRACT FROM AUTHOR]

The trial aimed to examine the effect of eight weeks preoperative low‐load blood flow restricted resistance training (BFR‐RT) on physical function, lower limb strength, and patient‐reported outcomes in knee OA patients 3 and 12 months after total knee arthroplasty (TKA) compared with preoperative usual care. An assessor blinded randomized controlled trial (RCT) was conducted. Eighty‐six patients scheduled for TKA who were allocated to 8 weeks BFR‐RT on the affected leg 3x/week or preoperative usual care involving no exercise (CON). Primary outcome: 30‐s sit to stand (30STS). Secondary outcomes: Timed Up&Go, 40‐m walk test (40mWT), knee range of motion (ROM) 1‐repetition maximum (1RM) leg press and knee extensor strength, maximal isometric contraction (MVIC) for the knee extensors and flexors, Knee injury and Osteoarthritis Outcome Score (KOOS), and Euroqol 5‐dimensions (EQ‐5D‐L5) questionnaire. Data were collected at baseline (12 weeks pre‐surgery), ~3 days pre‐surgery, 3 and 12 months postoperatively. Intention‐to‐treat analysis revealed no significant between‐group differences in the change from baseline to 3 and 12 months postoperatively on 30STS, TUG, or 40mFWT. Significant between‐group differences were observed at 3 but not 12 months postoperatively for the corresponding changes in 1RM leg press strength, 1RM knee extensor strength, and MVIC knee extensor favoring BFR‐RT. No between‐group differences were observed for the delta changes from baseline in knee ROM, KOOS subscales or EQ‐5D‐L5 at any postoperative time points. These findings suggest that preoperative BFR‐RT offered no superior effects compared with usual preoperative care on postoperative physical function or patient‐reported outcomes. Preoperative BFR‐RT produced amplified gains in lower limb muscle strength at 3 months postoperatively. Trial Registration: NCT04081493 [ABSTRACT FROM AUTHOR]

Semi‐synthetic cannabinoids (SSCs) are derivatives of phytocannabinoids with slight chemical modifications. SSCs have appeared as legal alternatives to tetrahydrocannabinol (Δ9‐THC) in recent years. This study investigates the prevalence of SSCs in seized drug samples from Danish police and custom authorities seized in Eastern Denmark in the period 2018–2023. Screening data obtained by gas chromatography–mass spectrometry (GC–MS) were reprocessed to enable detection of SSCs. Seized drug samples were categorized into six types of formulations. Δ8‐THC was the first SSC observed and appeared in 2019 followed by hexahydrocannabinol (HHC), tetrahydrocannabidiol (H4‐CBD), hexahydrocannabinol acetate (HHC‐O‐Acetate), hexahydrocannabiphorol (HHCP) and tetrahydrocannabiphorol (Δ9‐THCP). Only one sample positive for SSCs was observed before the third quarter of 2021, with positive samples increasing from third quarter of 2022. Over the study period, a total of 15% (n = 216) of seized cannabis products were positive for SSCs. HHC was the most frequently identified SSC and found in 10% (n = 137) of samples, followed by H4‐CBD at 4% (n = 53), Δ8‐THC at 3% (n = 44), and HHC‐O‐Acetate, HHCP, and THCP each at 1% (n = 10–20). SSCs appeared in 56% of E‐cigarette products, 20% of hashish, 17% of concentrates, 10% of edibles, and 10% of plant materials. In conclusion, SSCs represent a new type of cannabinoids with a rapidly growing popularity and with specific compounds dominating at different periods. Some of the observed trends were likely influenced by the scheduling of HHC in May of 2023 in Denmark. [ABSTRACT FROM AUTHOR]

During the COVID‐19 pandemic, the imposition of moralistically justified costs on unvaccinated individuals was used to incentivize vaccination uptake. Here, we ask whether such a strategy creates adverse consequences in the form of lowered trust in the pandemic response among unvaccinated individuals, which could jeopardize their compliance with the broader set of health interventions. As our empirical case, we use a press conference held by the Danish government on 8 November 2021, where COVID‐19‐vaccination passports were reintroduced, in part, to pressure unvaccinated people to take up the vaccine. We analyse the effects of the press conference using daily, nationally representative survey data (total N = 24,934) employing a difference‐in‐differences design. We demonstrate that the press conference decreased the trust in the pandemic management by 11 percentage points among unvaccinated individuals, while trust remained high among vaccinated individuals. Moralistic cost imposition also reduced collective action motivation and coping appraisal among unvaccinated individuals, and, while it increased societal threat appraisal among vaccinated people, it failed to do so among unvaccinated individuals. Our findings imply that decision‐makers using moralized cost imposition as a health intervention should be aware of its potential unintended adverse consequences. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to interpret plasma renin concentrations (PRCs) correctly in a clinical setting, it is essential to understand to what extent physical activity influences the concentration. Reference values for different postural positions exist for adults, but data for children are sparse. In this study, the effect of 30 min of rest on plasma renin concentrations in paediatric patients was examined. Methods: In total, 41 paediatric patients, undergoing either arginine or clonidine provocation tests for growth hormone deficiency, were included. For each stimulation test, two blood samples were drawn. One at time 0 min and one after 30 min of rest. In total, renin concentrations were determined in 86 serum samples. Results: Renin concentrations decreased from 0 to 30 min with a median value of −20.5% (inter‐quartile range: −33.0% to −12.8%). This decrease was not dependent on sex, age, medication or comorbidity, and the variance of renin did not differ between 0 and 30 min. Conclusion: Renin concentrations in children differ according to postural position, which is comparable to adults. Thus, the clinical interpretation of renin results needs to consider the preanalytical conditions applied in the local reference population. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is a highly prevalent condition that comprise a large portion of outpatient practice, challenging the diagnosis and treatment. However, the diagnostic tools are limited to clinical history, physical examination and imaging. Degenerative disc disease (DDD) is a significant cause of LBP, and emerging literature confirms the elevated levels of biomarkers in the discs. These biomarkers may serve as a tool for diagnosis, but may also be useful in predicting the treatment outcome. Here, we examine the expression of various cytokines on 1‐year recovery from patients with LBP. Methods: Patient‐reported outcome (PRO) in terms of pain intensity (VAS), disability (ODI), and quality of life (Eq‐5D) is collected from 44 patients at baseline and 12 months after surgery to study the influence of baseline TNF‐α, IL‐1β, and IL‐6 mRNA expression in both annulus fibrosus (AF) and nucleus pulposus (NP). Results: Between baseline and follow‐up, our cohort showed improvement in VAS back pain (p < 0.001), VAS leg pain (p < 0.001), ODI (p = 0.02), and Eq‐5D (p = 0.01). Baseline levels of IL‐1 β was positively correlated with VAS back pain scores in AF (p = 0.05) and NP (p = 0.01) at 1‐year follow‐up. TNF‐α expression at baseline was also positively correlated to ODI scores (p = 0.01) at follow‐up and inversely correlated to improvements in ODI score between baseline and follow‐up, suggesting that high TNF‐α expression at baseline is associated with poor outcomes from surgery. Conclusion: The results from our study support that TNF‐α expression at baseline can serve as a very important predictor of treatment response from lumbar fusion surgery. [ABSTRACT FROM AUTHOR]

A growing and increasingly globalised human population, requiring the movement of goods and commodities, is placing increasing demands on the maritime industry, resulting in a concurrent increase in global shipping activities. This has consequences for the marine environment, particularly for species vulnerable to the impacts of vessel traffic. For example, vessel collisions can result in sub‐lethal or fatal injuries for marine mammals, whilst vessel noise can cause acoustic masking that effectively reduces an animal's listening space, potentially impacting their communication, navigation and foraging capacity.While a number of parallel approaches to mapping collision risk to large whales have arisen, these methods vary in their focus, usually on either co‐occurrence, collision probability, or probability of mortality. However, little attention has been given to the implications of methodological choice and data selection on subsequent risk predictions.To assess differences between these approaches, we used a standardised input dataset comprised of telemetry‐point data from tagged bowhead whales, and satellite‐based Automated Identification System (AIS) data of spatial vessel movements covering the Davis‐Baffin Arctic Marine Area. We applied this data to eight different, previously published analyses for deriving areas of vessel risk.We found that the choice of risk mapping approach affected the location, and total area, identified as 'high risk', and that more computationally complex approaches did not necessarily equate to different predictions. There was considerable variation in the total area of 'high risk' predicted within each map (range = 20–42,246 km2).Synthesis and Applications. The results underscore the importance of methodological transparency, informed data selection and careful interpretation when predicting collision risk. We provide practical recommendations for enhancing transparency when predicting risk, and discuss choice of approach suitable for different situations or management applications. It is critical that managers and policy makers are aware of the implications of applying different approaches when interpreting risk evaluation outputs. [ABSTRACT FROM AUTHOR]

Previous studies have linked growing up in vulnerable neighbourhoods to worse health and social outcomes in adulthood but with mixed findings regarding the impact on young people's employment status, and with studies often limited by models that did not optimally distinguish neighbourhood‐ from individual‐ or family‐level effects. The aim of this study was to examine the long‐term associations between living in a vulnerable Danish neighbourhood in adolescence and later employment status in emerging adulthood and to compare the relative importance of the family and neighbourhood contexts. Danish population register data were used to follow 390,574 individuals nested in 301,227 families, which were nested in 7,937 neighbourhoods from age 10–15 in 2009 to age 20–25 in 2019. Three‐level logistic regression models stratified by native and immigrant/descendant status were applied to estimate the general and specific family and neighbourhood contextual effects. The results showed higher general contextual effects attributed to the family context than to neighbourhoods, with vulnerable neighbourhoods explaining only a small part of the neighbourhood variance. After controlling for individual‐ and family‐level covariates, living in a vulnerable neighbourhood in adolescence was associated with a higher risk of not being in education or employment in emerging adulthood for both native Danes and immigrants/descendants. The findings indicate that growing up in a vulnerable neighbourhood may have a long‐term impact on employment status but with a much larger influence attributed to the family context than to adolescents' neighbourhood context. [ABSTRACT FROM AUTHOR]

Using Unoccupied Aerial Systems (UAS) equipped with optical RGB cameras and Doppler radar, surface velocity can be efficiently measured at high spatial resolution. UAS‐borne Doppler radar is particularly attractive because it is suitable for real‐time velocity determination, because the measurement is contactless, and because it has fewer limitations than image velocimetry techniques. In this paper, five cross‐sections (XSs) were surveyed within a 10 km stretch of Rönne River in Sweden. Ground‐truth surface velocity observations were retrieved with an electromagnetic velocity sensor (OTT MF Pro) along the XS at one m spacing. Videos from a UAS RGB camera were analyzed using both Particle Image Velocimetry (PIV) and Space‐Time Image Velocimetry (STIV) techniques. Furthermore, we recorded full waveform signal data using a Doppler radar at multiple waypoints across the river. An algorithm fits two alternative models to the average amplitude curve to derive the correct river surface velocity based on Gaussian models with: (a) one peak, and (b) two peaks. Results indicate that river flow velocity and propwash velocity caused by the drone can be found in XS where the flow velocity is low, while the drone‐induced propwash velocity can be neglected in fast and highly turbulent flows. To verify the river flow velocity derived from Doppler radar, a mean PIV value within the footprint of the Doppler radar at each waypoint was calculated. Finally, quantitative comparisons of OTT MF Pro data with STIV, mean PIV and Doppler radar revealed that UAS‐borne Doppler radar could reliably measure the river surface velocity. Plain Language Summary: Based on the Doppler effect occurring when electromagnetic waves are reflected by a moving target, a Doppler radar can measure the river surface flow velocity. Doppler radars mounted on Unoccupied Aerial Systems (UAS) are attractive because they are suitable for real‐time velocity determination and contactless measurement under a wide variety of environmental conditions and river sites. Here, five selected cross‐sections were surveyed within a 10 km stretch of Rönne River in Sweden by using UAS Doppler radar. The recorded raw Doppler radar signals were processed to obtain the river surface velocity and the drone‐induced propwash velocity. To validate the Doppler results, river surface velocity was recorded in situ and using image‐cross correlation techniques as well. Comparisons of flow velocities derived from different techniques indicated that the UAS Doppler radar can reliably measure the river surface velocity with the footprint resolution. This paper provided processing procedures for the raw Doppler radar signals, which are useful for further development of UAS‐borne Doppler radar. Key Points: Unoccupied Aerial Systems Doppler radar can measure river surface flow velocityWe pick the correct river surface velocity from the raw Doppler spectra, using either a Gaussian one peak model, or a Gaussian two peak modelParticle Image Velocimetry results within the Doppler footprint verify the estimated velocities from Doppler radar [ABSTRACT FROM AUTHOR]

The relative importance of the different processes that determine the distribution of species and the assembly of communities is a key question in ecology. The distribution of any individual species is affected by a wide range of environmental variables as well as through interactions with other species; the resulting distributions determine the pool of species available to form local communities at fine spatial scales. A challenge in community ecology is that these interactions (e.g. competition, facilitation, etc.) often are not directly measurable. Here, we used hierarchical modelling of species communities (HMSC), a recently developed framework for joint species distribution modelling, to estimate the role of biotic effects alongside environmental factors using latent variables. We investigate the role of these factors determining species distributions in communities of Artiodactyla, Perissodactyla and Proboscidea in the Afrotropics, an area of peak species richness for hoofed mammals. We also calculate pairwise trait dissimilarity between these species, from a mixture of morphological and behavioural traits, and investigate the relationship between dissimilarity and estimated residual co‐occurrence in the model. We find that while ungulate distributions appear to be predominantly determined (~ 70%) by climatic variables, such as precipitation, a substantial proportion of the variance in ungulate species distributions (~ 30%) can also be attributed to modelled latent variables that likely represent a combination of dispersal barriers and biotic factors. Although we find only a weak relationship between residual co‐occurrence and trait dissimilarity, we suggest that our results may show evidence that biotic factors, likely influenced by historical barriers to species dispersal, are important in determining species communities over a continental area. The HMSC framework can be used to provide insight into factors affecting community assembly at broad scales, and to make more powerful predictions about future species distributions as we enter an era of increasing impacts from anthropogenic change. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To determine the pattern, degree and prevalence of optic disc optical coherence tomography (OCT) alterations in adults born preterm with very low birth weight (VLBW; birth weight < 1500 g).Optic disc OCT was assessed in 98 VLBW participants and 139 term‐born controls from birth cohorts in Finland and Norway at the mean age of 36 years. The participants had not been treated for retinopathy of prematurity and had no diagnosed brain abnormality. OCT assessment included parameters for optic disc size, neural rim and peripapillary retinal nerve fibre layer thickness (pRNFLT), and for the foveal developmental stage. Background data, visual acuity, refractive error and intraocular pressure were recorded.In the VLBW group, optic disc neural rim and pRNFLT were significantly decreased, most frequently in the nasal and inferior sectors. In 40% (95% CI: 33–47) of the VLBW eyes, nerve fibre thickness of at least one optic disc sector was below the fifth percentile of the control group, including 9% (95% CI: 6–14) subgroup falling below the first percentile, that is, clinically below normal limits. VLBW participants with nerve fibre thickness below the fifth percentile did not differ by perinatal data or foveal developmental stage from the other VLBW participants. All participants had normal visual acuity.A moderate decrease of the optic disc neural rim and pRNFLT is frequently seen in clinically healthy adults born preterm with VLBW. Awareness of the VLBW‐related optic disc nerve fibre shallowness especially in the inferior and nasal sectors is important while evaluating acquired optic disc pathology in adulthood. [ABSTRACT FROM AUTHOR]

The substituted tetrahydrofuran core is a structural motif in many biologically active and natural compounds. However, the scarcity of enantioselective methods developed towards its synthesis makes this field challenging and attractive to explore. Herein, the first Brønsted‐base catalyzed enantioselective (3+2) annulation of donor‐acceptor cyclopropanes with aldehydes and ketones affording enantioenriched 2,3,5‐substituted tetrahydrofurans is reported. The reaction concept is based on activation of racemic β‐cyclopropyl ketones by a chiral bifunctional Brønsted base which catalyzes the (3+2) annulation for a range of aldehydes and ketones. For aldehydes, the annulation furnished tetrahydrofurans in excellent yield, good diastereoselectivity and with excellent enantioselectivity up to >99 % ee. Surprisingly, aromatic aldehydes afforded the cis‐2,5‐substituted tetrahydrofurans as the major diastereoisomer, while for aliphatic aldehydes the trans‐cycloadduct was favored. The reaction also proceeds well for ketones affording spiro tetrahydrofurans in excellent yields and enantioselectivities (up to 99 % ee). Hammett studies have been conducted to elucidate the influence of the electronic nature of benzaldehydes on the stereoselectivity. Based on the diastereochemical outcome for the aldehydes, two reaction paths for aromatic and aliphatic aldehydes are proposed. Finally, two diastereoselective synthetic transformations have been conducted to demonstrate the synthetic potential of the obtained products. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusion Hypophosphatasia (HPP) is a rare inherited disease that affects multiple organ systems including bone and teeth. Limited knowledge exists on dental and oral health in patients with adult‐onset HPP (aHPP).The aim of this study was to investigate oro‐dental characteristics in patients with aHPP compared to healthy controls.This case‐control study included 20 patients with aHPP compared to 31 healthy controls. Oro‐dental manifestations were examined by standardised interviews, clinical examinations as well as radiological registrations on panoramic radiograph (OP) and cone‐beam computed tomography (CBCT) scans.The subjective experience of tooth fractures (p = 0.010), caries in permanent teeth (p = 0.032) and early loss of permanent teeth (p = 0.002) was significantly higher in patients with aHPP compared to the controls. In the aHPP group, the presence of specific teeth (p ≤ 0.045) and attrition of 11 were significantly lower (p = 0.012) compared to the controls. Opacity of a few teeth (p ≤ 0.049), presence of denticles (p = 0.024), the distance between the enamel–cement junction (CEJ) and the marginal bone level at specific sites (p ≤ 0.021) and crown height of 11 (p = 0.017) were significantly higher in patients with aHPP than in healthy controls.The results indicate that patients with aHPP have a subjective experience of having poorer dental health. Loss of permanent teeth, less attrition, tooth opacities, denticles and larger distance between CEJ and marginal bone level are possible oro‐dental findings in patients with aHPP. [ABSTRACT FROM AUTHOR]

Introduction. Dietary supplements with vitamin and calcium are recommended to nursing home residents in Denmark, but adherence to the recommendation is low. In a previous part of this study, we reported improved adherence by means of The Model for Improvement leading to increased awareness and change of workflows at two nursing homes. However, potential effects of this improved adherence are unknown. Objective. The objective of this substudy was to investigate if the improved adherence to the recommendation affected vitamin D status, muscle strength, and physical functioning of the residents. Methods. This was a 20‐week quasiexperimental study involving 40 residents from two Danish nursing homes. Baseline and endpoint measurements took place in October 2021 and March 2022, respectively. Outcomes were number of residents taking vitamin D and calcium supplements; vitamin D status; handgrip strength; and physical functioning with timed‐up‐and‐go test and 30‐second chair stand test. Results. Prevalence of vitamin D supplement users increased from 45 to 78% (mean dose 41 μg) and of calcium supplement users from 40 to 72% (mean dose 769 mg) (both P = 0.002). Among those having blood sampled at both baseline and endpoint (n = 30), mean vitamin D status increased from 66.6 ± 31.7 nmol/L to 82.8 ± 26.3 nmol/L (P < 0.001), and more residents were vitamin D sufficient at endpoint (90 vs. 63%, P = 0.021). Endpoint vitamin D status among supplement users was 88.2 ± 22.2 nmol/L, which was higher compared to nonsupplement users (55.3 ± 30.4 nmol/L, P < 0.01). No effects were seen on muscle strength or physical functioning. Conclusions. Increased supplementation with vitamin D using The Model for Improvement positively affected vitamin D status and prevalence of vitamin D sufficiency but did not affect muscle strength or physical functioning. Longer‐term studies involving more residents are needed to investigate effects of improved adherence on these outcomes. This trial is registered with NCT04956705. [ABSTRACT FROM AUTHOR]

Background: Prone position ventilation (PPV) is recommended for patients with COVID‐19 induced severe Adult Respiratory Distress Syndrome (ARDS) and is used for patients supported with V‐V ECMO as well. The purpose of this study was to describe the use of PPV in these patients focusing on physiological effects with the hypothesis that PPV could reduce oxygen need and improve dynamic compliance. Methods: This study was a nationwide retrospective analysis of all COVID‐19 patients in Denmark from March 2020 – December 2021 with severe ARDS and need of V‐V ECMO support. Data on the number of patients treated with PPV, number of PPV sessions, timing, the time spent in prone position, pulmonary physiological response types with analysis of variables affecting the response are reported. Results: Out of 68 patients 44 were treated with 220 PPV sessions and a positive clinical response was observed in 80% of patients but only in 45% of sessions. On a single session level, increased compliance was observed in 38% and increased oxygenation in only 15% of 220 sessions, with within‐patient heterogeneity. Higher dynamic compliance at the beginning of a PPV session was associated with a lower delta change in dynamic compliance during PPV. The response to a PPV session could not be predicted by the response in the prior session. Dynamic compliance did not change during the ECMO course. Conclusion: Eighty percent of patients responded positively during a PPV session, but this was not associated with overall pulmonary improvement. On a single patient level, responses were heterogenous and only 45% of sessions resulted in clinical improvement. Response in dynamic compliance was associated with starting values of compliance. [ABSTRACT FROM AUTHOR]

Background: Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed assessment on the timing of severe pain, opioid consumption, influence on activities such as mobilization, breastfeeding, and caring for the infant are difficult to conduct, especially after discharge. Short message services (SMS)‐based questionnaires may offer a low‐cost way of providing such data but with the risk of insufficient response rates. We assessed the feasibility of collecting detailed, prospective data on postoperative pain and recovery during the initial hours and days following cesarean section using SMS‐based questionnaires. Methods: Prospective Danish single‐center cohort study involving elective cesarean sections under spinal anesthesia with fentanyl and bupivacaine. The postoperative pain regimen consisted of paracetamol, NSAID and oral morphine by request. Patients received an SMS‐based questionnaire at 6, 12, 18, 24, and 48 h postoperatively, as well as on days 7 and 30. Primary outcome: Response rate and time from receiving the SMS to completion of the questionnaires. Secondary outcomes: Opioid consumption and Patient Reported Outcomes Measures on pain and recovery. Results: From December 2022 to June 2023; 100 patients were included. The response rate was 78% at 6 h postoperatively, decreasing to 63% at 24 h. The median response time from receiving to answering the SMS‐based questionnaire at 6 h after cesarean section was 23 min (IQR 2–72), decreasing to 20 min (IQR 2–78) after 24 h. Severe pain, corresponding to a Numeric Rating Scale (NRS) score >6, was reported by 57% (95% CI 65–84) at 6 h, decreasing to 28% (95% CI 34–58) at 24 h. Median opioid consumption within the first 24 h was 30 mg (IQR 20–50). Conclusion: SMS‐based questionnaires on Patient Reported Outcome Measures are a feasible and cost‐effective way of prospectively collecting frequent data with acceptable response rates, even shortly after cesarean section. Secondarily 66% of patients reported severe pain during the first 24 h following cesarean section, with the highest pain scores within the initial 12 h. Future studies should focus on optimizing pain‐management within this timeframe. [ABSTRACT FROM AUTHOR]

Background: Genomic medicine has transformed clinical genetics by utilizing high‐throughput sequencing technologies to analyze genetic variants associated with diseases. Accurate variant classification is crucial for diagnosis and treatment decisions, and various tools and software such as the Ion Reporter Software and the Illumina Nirvana Software often used in a clinical setting utilize information from the ClinVar database/archive to aid in variant interpretation. However, these existing annotation tools may lack access to the latest ClinVar data, necessitating manual variant inspection. Aims: To address this gap in developing a tool providing the latest ClinVar data for variant annotation in clinical and research settings. Materials and Methods: We introduce CANVAR, a Python‐based script that efficiently annotates variants identified from next‐generation sequencing in a clinical or research context, offering comprehensive information from the latest ClinVar database. Results: CANVAR provides accurate, up‐to‐date variant annotations, streamlining variant analysis. Discussion: The rise in genomic data requires accurate variant annotation for clinical decision‐making. Misclassification poses risks, and current tools may not always access the latest data, challenging variant interpretation. Conclusion: CANVAR contributes to enhancing variant annotation by offering comprehensive information from the latest ClinVar database for genetic variants identified through next‐generation sequencing. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim of this study was to examine the discriminative validity of the Brief Assessment of Impaired Cognition (BASIC) case‐finding instrument in a general practice (GP) setting and compare it with other widely used brief cognitive instruments. Methods: Patients aged ≥70 years were prospectively recruited from 14 Danish GP clinics. Participants were classified as having either normal cognition (n = 154) or cognitive impairment (n = 101) based on neuropsychological test performance, reported instrumental activities of daily living, and concern regarding memory decline. Comparisons involved the Mini‐Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Rowland Universal Dementia Assessment Scale (RUDAS), the Mini‐Cog, the 6‐item Clock Drawing Test (CDT‐6) and the BASIC Questionnaire (BASIC‐Q). Results: BASIC demonstrated good overall classification accuracy with an area under the receiver operating characteristic curve (AUC) of 0.88 (95% confidence interval [CI] 0.84–0.92), a sensitivity of 0.72 (95% CI 0.62–0.80) and a specificity of 0.86 (95% CI 0.79–0.91). Pairwise comparisons of the AUCs of BASIC, MMSE, MoCA and RUDAS produced non‐significant results, but BASIC had significantly higher classification accuracy than Mini‐Cog, BASIC‐Q and CDT‐6. Depending on the pretest probability of cognitive impairment, the positive predictive validity of BASIC varied from 0.83 to 0.36, and the negative predictive validity from 0.97 to 0.76. Conclusions: BASIC demonstrated good discriminative validity in a GP setting. The classification accuracy of BASIC is equivalent to more complex, time‐consuming instruments, such as the MMSE, MoCA and RUDAS, and higher than very brief instruments, such as the CDT‐6, Mini‐Cog and BASIC‐Q. [ABSTRACT FROM AUTHOR]

Species distribution models (SDMs) are widely used to project how species distributions may vary over time, particularly in response climate change. Although the fit of such models to current distributions is regularly enumerated, SDMs are rarely tested across longer time spans to gauge their actual performance under environmental change. Here, we utilise paleozoological presence/absence records to independently assess the predictive accuracy of SDMs through time. To illustrate the approach, we focused on modelling the Holocene distribution of the hartebeest, Alcelaphus buselaphus, a widespread savannah‐adapted African antelope. We applied various modelling algorithms to three occurrence datasets, including a point dataset from online repositories and two range maps representing current and 'natural' (i.e. hypothetical assuming no human impact) distributions. We compared conventional model evaluation metrics which assess fit to current distributions (i.e. True Skill Statistic, TSSc, and Area Under the Curve, AUCc) to analogous 'paleometrics' for past distributions (i.e. TSSp, AUCp, and in addition Boycep, F2‐scorep and Sorensenp). Our findings reveal only a weak correlation between the ranking of conventional metrics and paleometrics, suggesting that the models most effectively capturing present‐day distributions may not be the most reliable to hindcast historical distributions, and that the choice of input data and modelling algorithm both significantly influences environmental suitability predictions and SDM performance. We thus advocate assessment of model performance using paleometrics, particularly those capturing the correct prediction of presences, such as F2‐scorep or Sorensenp, due to the potential unreliability of absence data in paleozoological records. By integrating archaeological and paleontological records into the assessment of alternative models' ability to project shifts in species distributions over time, we are likely to enhance our understanding of environmental constraints on species distributions. [ABSTRACT FROM AUTHOR]

This paper presents findings from a series of focus group interviews with three groups of professionals in England, in the period immediately preceding the COVID‐19 global pandemic, on the information needed by professionals to support migrant children with special educational needs (SEN) in the English education system. The data gathered were subjected to a thematic analysis revealing four themes: (1) Information about the needs of migrant children with SEN, (2) Information about parents and families, (3) Information about strategies to support migrant children with SEN, (4) The importance of clear and understandable information. The findings emphasise that when information is sought about migrant children with SEN, professionals must account for and understand the different experiences that the children and their families have experienced across different educational systems and the different educational ecologies associated with migration. Ecological theory helps identify potential tensions at different levels between and within different ecologies, but also suggests ways in which these may be bridged by information gathering, trust and relationship building within and across ecologies. [ABSTRACT FROM AUTHOR]

The micro Advanced Stellar Compass is an attitude reference for the MAG investigation onboard Juno. The μASC camera head unit images the star field with a CCD that is also sensitive to particles with enough energy to pass through the camera shielding: >15 MeV electrons and >80 MeV protons. This provides the capability to monitor fluxes of high‐energy particles in Jupiter's magnetosphere. A survey of energetic electron fluxes sampled during the first 47 Juno orbits reveals instances of variations observed when Juno is traversing the M‐shell of the Galilean moons. Juno's traversal of the Europa M‐shell often results in distinctly particle signatures. We present the μASC observations of increased electron flux during the crossing of Europa's plasma wake, and depletion of energetic electron flux on the upstream side. The upstream/downstream differences indicate that the wake environment of Europa drives strong pitch angle scattering on relativistic electrons. Plain Language Summary: The attitude reference (μASC) used for the MAG investigation onboard Juno is also sensitive to particles with enough energy to pass through the camera shielding. This provides the capability to monitor fluxes of high‐energy particles in Jupiter's magnetosphere, as the Juno has done since orbit insertion. A μASC survey of electron fluxes reveals instances of variations observed when Juno is traversing the M‐shell of Jupiter's moon Europa. We present particle signatures related to the interaction with Europa and discuss the implications. Key Points: Europa's wake affects the high‐energy electron driftshell by scattering electrons into the loss‐coneIncrease in e− flux is around x2.3 at distances ∼30 RE, and is gradually dissolved as far as 20° downstreamEuropa will stop the energetic electron drift shells and will be mostly free from hard radiation on the leading side [ABSTRACT FROM AUTHOR]

Background and Aim: Vitamin K deficiency is common in persons with kidney disease, which is a known complication of diabetes. We aimed to assess the association of vitamin K status as reflected by plasma dephosphorylated‐uncarboxylated matrix Gla protein (dp‐ucMGP) with mortality, cardiovascular disease (CVD) and progression to end‐stage kidney disease (ESKD) in persons with type 1 diabetes. Materials and Methods: We analysed plasma dp‐ucMGP in stored baseline samples from a cohort of 667 persons with type 1 diabetes (baseline visit: 2009–2011). Information on mortality and CVD was obtained through linkage to registers. Cox‐proportional hazards models were applied to estimate hazard ratios (HRs) of mortality, CVD and ESKD per one doubling of dp‐ucMGP. Results: A total of 53 deaths were recorded during follow‐up. Persons with higher dp‐ucMGP (reflecting lower vitamin K status) had higher mortality in the unadjusted model (HR: 2.06 [95% confidence interval—CI: 1.22–3.45]), but not in the fully adjusted model (HR: 0.88 [95% CI: 0.44–1.73]). Particularly, adjustment for glomerular filtration rate and urinary albumin excretion rate attenuated the HR. A similar pattern was observed in unadjusted models for incidence of CVD (HR: 1.58 [95% CI: 1.03–2.42]) and risk of ESKD (HR: 7.62 [95% CI: 4.25–13.68]). In the fully adjusted models, the HRs became statistically insignificant. Conclusion: In persons with type 1 diabetes, lower vitamin K status was associated with higher mortality, CVD and progression to ESKD, however, not after adjustment for other risk factors. Interventional studies are needed to elucidate the role of vitamin K in persons with type 1 diabetes. [ABSTRACT FROM AUTHOR]

The risk of predation is an important driver that tailors life histories in various ways. Using an evolutionary model based on hormonal control, we study how different predation regimes affect adaptive risk‐taking and growth in fish populations. Growth, metabolism and foraging in the modelled fish are regulated by three simplified hormone functions: growth hormone, orexin, and thyroid hormone. A dynamic state‐dependent optimization model finds optimal hormone profiles for adaptive growth strategies in juvenile fish. We consider a gradient from species where behaviour and metabolic activity have large consequences for risk (typically benthic and camouflaged species), to the opposite endpoint where behaviour may modify predation risk to a smaller degree (as in the pelagic). Along this gradient, the model predicts changes in the pace of life from slow to fast, enacted by up‐regulation of the three hormone functions which in turn increase foraging and metabolism and change the priorities of energy reserves versus growth. Under all types of predation risk investigated, growth is faster when food availability is higher. Energy reserves are maintained primarily during periods of poor food availability and are used to accelerate growth during periods when food availability is high. The thyroid hormone function is up‐regulated predominantly when food availability is high and has an important role in trade‐offs balancing energetic gain and survival. At the individual time scale, the hormone system improves organismic flexibility and robustness. Over the phylogenetic time scale, hormone system adaptations have also restricted the phenotypic plasticity of individuals. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is a clonal haematological malignancy affecting the myeloid lineage, with generally poor patient outcomes owing to the lack of targeted therapies. The histone lysine demethylase 4A (KDM4A) has been established as a novel therapeutic target in AML, due to its selective oncogenic role within leukaemic cells. We identify that the transcription factor nuclear factor of activated T cells 2 (NFATC2) is a novel binding and transcriptional target of KDM4A in the human AML THP‐1 cell line. Furthermore, cytogenetically diverse AML cell lines, including THP‐1, were dependent on NFATC2 for colony formation in vitro, highlighting a putative novel mechanism of AML oncogenesis. Our study demonstrates that NFATC2 maintenance of cell cycle progression in human AML cells was driven primarily by CCND1. Through RNA sequencing (RNA‐seq) and chromatin immunoprecipitation sequencing (ChIP‐seq), NFATc2 was shown to bind to the promoter region of genes involved in oxidative phosphorylation and subsequently regulate their gene expression in THP‐1 cells. Furthermore, our data show that NFATC2 shares transcriptional targets with the transcription factor c‐MYC, with MYC knockdown phenocopying NFATC2 knockdown. These data suggest a newly identified co‐ordinated role for NFATC2 and MYC in the maintenance of THP‐1 cell function, indicative of a potential means of therapeutic targeting in human AML. [ABSTRACT FROM AUTHOR]

The synthesis of a strontium hexaferrite magnet is studied using in situ synchrotron powder X‐ray diffraction (PXRD) with a 16‐ms time resolution. The precursor material is cold compacted shape‐controlled goethite and strontium carbonate. The time evolution of the phases is modeled with sequential Rietveld refinements revealing that strontium hexaferrite forms within seconds at ≈1173 K. Texture analysis is performed on selected PXRD frames throughout the experiment, and the preferred orientation introduced by cold‐pressing goethite prevails through the iron oxide phase transitions (goethite → hematite → strontium hexaferrite). Electron backscatter diffraction (EBSD) data on the final pellet confirms the preferred orientation observed with PXRD. The resulting magnet has respectable magnetic properties, considering the simplicity of the preparation method, with an energy product (BHmax) of 18.6(8) kJ m−3. [ABSTRACT FROM AUTHOR]

Despite a surge in microbiota‐focused studies in teleosts, few have reported functional data on whole metagenomes as it has proven difficult to extract high biomass microbial DNA from fish intestinal samples. The zebrafish is a promising model organism in functional microbiota research, yet studies on the functional landscape of the zebrafish gut microbiota through shotgun based metagenomics remain scarce. Thus, a consensus on an appropriate sampling method accurately representing the zebrafish gut microbiota, or any fish species is lacking. Addressing this, we systematically tested four methods of sampling the zebrafish gut microbiota: collection of faeces from the tank, the whole gut, intestinal content, and the application of ventral pressure to facilitate extrusion of gut material. Additionally, we included water samples as an environmental control to address the potential influence of the environmental microbiota on each sample type. To compare these sampling methods, we employed a combination of genome‐resolved metagenomics and 16S metabarcoding techniques. We observed differences among sample types on all levels including sampling, bioinformatic processing, metagenome co‐assemblies, generation of metagenome‐assembled genomes (MAGs), functional potential, MAG coverage, and population level microdiversity. Comparison to the environmental control highlighted the potential impact of the environmental contamination on data interpretation. While all sample types tested are informative about the zebrafish gut microbiota, the results show that optimal sample type for studying fish microbiomes depends on the specific objectives of the study, and here we provide a guide on what factors to consider for designing functional metagenome‐based studies on teleost microbiomes. [ABSTRACT FROM AUTHOR]

Aim: To compare overall, fine, and gross motor abilities in adults born preterm with very low birthweight (VLBW) and a control group of term‐born individuals. Method: In a joint assessment of the Helsinki Study of Very Low Birth Weight Adults and NTNU Low Birth Weight in a Lifetime Perspective study, data were collected with harmonized methods for 118 adults born preterm (gestational age < 37 weeks) with VLBW (≤1500 g) and 147 control individuals. The primary outcome was overall motor abilities; secondary outcomes were fine and gross motor abilities. Results: The Bruininks Motor Ability Test Short Form total score was 4.1 (95% confidence interval 2.7–6.0) points lower in adults born with VLBW than in the control group, adjusted for cohort, age, and sex. This was partly mediated by their shorter height. They also had lower scores for other fine and gross motor tests. Results were similar when participants with neurosensory impairment were excluded, and when we adjusted for additional covariates. Interpretation: Adults born preterm with VLBW had poorer overall, fine, and gross motor abilities than adults born at term. This indicates that substantial difficulties in motor function among individuals born preterm with VLBW persist into mid‐adulthood. [ABSTRACT FROM AUTHOR]

The consumption of seafood is driven by flavour, yet achieving its high quality remains a challenge for many species reared in recirculating aquaculture systems (RAS). A comprehensive knowledge of off‐odour sources in aquatic foods is indispensable in ensuring flavour quality standards. At the beginning of the production chain, early post‐harvest lipid oxidation products develop into endogenous off‐odours and accumulate over time. These malodours add to those already absorbed exogenously, namely from the water and feeds, although the information on the interactions between these sources is currently scarce. Despite geosmin and 2‐methylisoborneol receiving significant attention in relation to fish off‐flavour, only limited knowledge on the molecular and ecological mechanisms driving their production in aquatic environments has been reported. Moreover, RAS‐hosted bacteria have been associated with a wide range of other odour‐active compounds, such as pyrazines, terpenoids, and other degradation byproducts that are frequently overlooked when studying flavour taint in fish. The influence of aquaculture feeds on the flavour of fish flesh has been underestimated, too, both as a source of off‐odours but also as a novel modulator strategy to achieve desirable aquatic food flavours. Finally, the influence of water treatment processes widely used in RAS operations, such as advance oxidation process, ozone, ultraviolet and hydrogen peroxide disinfections, is greatly underexplored with respect to odour quality. This article reviews the current scientific evidence with supporting data on the chemical diversity of off‐odours found in aquaculture fish worldwide and their potential sources and highlights knowledge gaps that should be addressed in future research. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the engagement between healthcare professionals and users of mental healthcare at the individual level in a mental health hospital. A qualitative research design with purposive sampling was adopted. Five audio‐recorded focus group interviews were conducted with nurses and other health professionals at a mental health hospital in Copenhagen and were explored using Fairclough's discourse analysis framework. This study shows how users can be subject to paternalistic control despite the official aim that user involvement be an integral part of the care and treatment offered. As evidenced in discussions by health professionals, the users were involved in plans based on conditions determined by the health professionals who were predominantly focused on treating diseases and enabling the users to live a life independent of professional help. Our results can contribute to dealing with the challenges of incorporating user involvement as an ideology in mental health hospitals. [ABSTRACT FROM AUTHOR]

Social work is characterized as a helping profession. Consequently, the nature and purposes of social work revolve around concepts of help and helping. In this article, I explore what happens when the extended family network and friends are brought together by child welfare services to make decisions to help a child. Based on analyses of a single videotaped family group conference, this article offers insights into the challenges and complexities families face when dealing with the mandated task to devise a plan that meets the child's needs. By examining sequences of interaction where friends and family members discuss future scenarios with some cast as beneficiaries and others as benefactors, I show how some of these complexities can be captured in terms of the relationship between benefactive stance and benefactive status. The complexities include ambiguities regarding the relationship between nominated future scenarios and the problem(s) they were designed to solve. Furthermore, participants dealt with uncertainties regarding who was more inclined towards specific future scenarios and thus understood to be the actual beneficiary. Additionally, the analysis shows that social identities ascribed to recipients when resolutions to problems were linked to family members' past shortcomings complicated the acknowledgement and acceptance of assistance. [ABSTRACT FROM AUTHOR]

Starvation in diploid budding yeast cells triggers a cell-fate program culminating in meiosis and spore formation. Transcriptional activation of early meiotic genes (EMGs) hinges on the master regulator Ime1, its DNA-binding partner Ume6, and GSK-3β kinase Rim11. Phosphorylation of Ume6 by Rim11 is required for EMG activation. We report here that Rim11 functions as the central signal integrator for controlling Ume6 phosphorylation and EMG transcription. In nutrient-rich conditions, PKA suppresses Rim11 levels, while TORC1 retains Rim11 in the cytoplasm. Inhibition of PKA and TORC1 induces Rim11 expression and nuclear localization. Remarkably, nuclear Rim11 is required, but not sufficient, for Rim11-dependent Ume6 phosphorylation. In addition, Ime1 is an anchor protein enabling Ume6 phosphorylation by Rim11. Subsequently, Ume6-Ime1 coactivator complexes form and induce EMG transcription. Our results demonstrate how various signaling inputs (PKA/TORC1/Ime1) converge through Rim11 to regulate EMG expression and meiosis initiation. We posit that the signaling-regulatory network elucidated here generates robustness in cell-fate control. Synopsis: Transcriptional activation of early meiotic genes is triggered by various signaling inputs. This study unveils how the yeast GSK-3β kinase Rim11 acts as a central signal integrator, orchestrating Ume6 phosphorylation and transcriptional activation of early meiotic genes. Starvation-induced nuclear localization of GSK-3β kinase Rim11 is required for Ume6 phosphorylation. TORC1 and PKA control Rim11 localization and expression. Rim11-dependent phosphorylation of Ume6 also requires Ime1. Signal integration by Rim11 and Ime1 controls the decision to enter meiosis. Starvation induces nuclear accumulation of Rim11 that integrates signals from PKA, TORC1 and Ime1 to promote cell entry into meiosis. [ABSTRACT FROM AUTHOR]

This article presents a study on the distribution of cytochrome P450 (CYP450) alleles in the Danish population. CYP450 enzymes are important for drug metabolism, and genetic variations in the genes encoding these enzymes can impact drug response. The study compared genotype data from different genotyping platforms and found that the CYP2C19*17 and CYP2C9*2 alleles were more common than the CYP2C19*2 and CYP2C9*3 alleles. The results provide valuable insights into the genetic variability of these enzymes in the Danish population and suggest that the Illumina GSA platform could be useful for identifying drug-gene interactions. [Extracted from the article]

Addressing ecological impacts with effective conservation actions requires information on the links between human pressures and localized responses. Understanding links is a priority for many conservation contexts, including the world's fresh waters, which face intensifying threats to disproportionately high species diversity, including more than half of the world's fish species. Literature synthesis can uncover links and highlight potential research gaps, yet can be very cumbersome and time consuming. Emerging tools like text mining can improve efficiency in extracting relevant information from vast scientific outputs. This study synthesizes evidence of direct anthropogenic threats to major inland fisheries and examines driver‐impact‐response patterns using coupled automated and manual text classification methods. We screened 9336 abstracts from 45 river basins of high importance to inland fish production; 1152 abstracts contained evidence of direct threats to fish. The most common documented drivers were pollution, dams, and fishing pressure, which were most strongly linked to decreased fitness, altered reproduction, and mortality, respectively. Strong impact‐response links to pollution signal potential bias toward documenting acute threats that generate more visible and immediate impacts. The use of machine learning‐based text classification performed best in classifying extraneous information. Results can inform the development of inland fisheries indicators and threat‐based metrics, highlight possible evidence gaps in linking global drivers to fishery‐level responses, and illustrate the application of a coupled synthesis approach for improved efficiency and extraction of information relevant to conservation outcomes. The associated user and interpretation guides address accessibility and technical barriers faced by conservation scientists to improve efficiency in evidence synthesis. [ABSTRACT FROM AUTHOR]

SUMMARY: Genome annotation files play a critical role in dictating the quality of downstream analyses by providing essential predictions for gene positions and structures. These files are pivotal in decoding the complex information encoded within DNA sequences. Here, we generated experimental data resolving RNA 5′‐ and 3′‐ends as well as full‐length RNAs for cassava TME12 sticklings in ambient temperature and cold. We used these data to generate genome annotation files using the TranscriptomeReconstructoR (TR) tool. A careful comparison to high‐quality genome annotations suggests that our new TR genome annotations identified additional genes, resolved the transcript boundaries more accurately and identified additional RNA isoforms. We enhanced existing cassava genome annotation files with the information from TR that maintained the different transcript models as RNA isoforms. The resultant merged annotation was subsequently utilized for comprehensive analysis. To examine the effects of genome annotation files on gene expression studies, we compared the detection of differentially expressed genes during cold using the same RNA‐seq data but alternative genome annotation files. We found that our merged genome annotation that included cold‐specific TR gene models identified about twice as many cold‐induced genes. These data indicate that environmentally induced genes may be missing in off‐the‐shelf genome annotation files. In conclusion, TR offers the opportunity to enhance crop genome annotations with implications for the discovery of differentially expressed candidate genes during plant–environment interactions. Significance Statement: Our work has broad implications for transcriptome analyses of plant–environment interactions: differentially expressed genes may be absent in commonly used annotations and would thus be missed. As solution, we suggest merging TR‐based annotations for specific conditions with existing genome annotation files. [ABSTRACT FROM AUTHOR]