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Abstract Background Comparative pharmacokinetics and pharmacodynamics (PK/PD) of apixaban and rivaroxaban have not been studied in dogs and the propensity of these drugs to cause hypercoagulability after discontinuation is unknown. Hypothesis Compare the PK/PD of clinical dosing regimens of PO apixaban and rivaroxaban administered repeatedly to healthy dogs and assess the effect of abrupt drug discontinuation on coagulation. Animals Six University‐owned, purpose‐bred, middle‐aged, mixed‐breed dogs (4 male, 2 female). Methods Dogs were given apixaban or rivaroxaban PO at 0.5 mg/kg q12h for 7 days with a 14‐day washout period between drugs. Plasma drug concentrations were quantitated, and anticoagulant effects were measured using clotting times, calibrated anti‐Xa bioactivity assays, and measurements of thrombin generation. The potential for rebound hypercoagulability was assessed by measuring D‐dimers, thrombin‐antithrombin (TAT) complexes, and antithrombin activity after drug discontinuation. Results Plasma drug concentrations and anti‐Xa bioactivities were closely correlated for both drugs, but drug concentrations varied considerably among dogs, despite consistent dose regimens. Thrombin generation variables were significantly correlated with the anti‐Xa bioactivity of both drugs and no significant differences in the effects of apixaban and rivaroxaban on thrombin generation were observed. Drug discontinuation had no effect on D‐dimer concentrations. The concentration of TAT complexes decreased after apixaban discontinuation and did not change after rivaroxaban discontinuation. Conclusions and Clinical Importance Repeated PO administration of apixaban or rivaroxaban to healthy dogs produced comparable anticoagulant effects measured by inhibition of thrombin formation. Rebound hypercoagulability after drug discontinuation was not observed and weaning of these drugs in clinical patients might not be necessary.

Abstract RLYB212 is a human monoclonal anti‐human platelet antigen (HPA)‐1a immunoglobulin gamma 1 in clinical development as a subcutaneous injection for the prevention of maternal alloimmunization to fetal HPA‐1a leading to fetal and neonatal alloimmune thrombocytopenia (FNAIT). This analysis developed a target‐mediated drug disposition (TMDD) model to simultaneously characterize RLYB212 pharmacokinetics (PK) and HPA‐1a‐positive platelet dynamics in HPA‐1b/b (HPA‐1a‐negative) volunteers. The model was then used to perform simulations to inform a dosing regimen in a phase II clinical study in pregnant women, where simulations accounted for physiological changes throughout pregnancy. Allometric scaling (0.75) for clearance and intercompartment transfer rate and volume (1) was included in the base model to account for variations in body weight. A 0.06 mg RLYB212 dose with a loading dose of 0.12 mg was identified as the optimal dosing regimen of RLYB212, which maintained exposures below the target upper boundary of ~10 ng/mL throughout pregnancy. This work presents an application of the TMDD model that advances the quantitative clinical pharmacology toolkit to understand monoclonal antibody PK in pregnancy.

Abstract Effective approaches are needed to conserve the planet's remaining wildlife and wilderness landscapes, especially concerning global biodiversity conservation targets. Here, we present a new software system called EarthRanger: an open‐source platform built to help monitor, research and manage ecosystems. EarthRanger consists of seven main components (Core Server, API, Storage, Gundi, Web App, Mobile App, Ecoscope) that provide functionality for data (i) aggregation & collection, (ii) storage & management, (iii) real‐time and post hoc analysis, (iv) visualisation and (v) dissemination. The mobile application provides field‐based data recording and visualisation tools. EarthRanger may be deployed for single project use or can aggregate across multiple geographies as a centralised hub. EarthRanger can be used to collect standardised tracking data (e.g. from wildlife collars, vehicles and ranger patrols) and configurable event information (e.g. a singular recording with associated user‐defined attribute information such as a wildlife sighting or encounter with a poacher). Since development began in 2015, the platform has (at the time of writing) been deployed at over 500 sites across 70 countries and with myriad configurations and objectives. EarthRanger has improved the ability to monitor data feeds and manage conservation‐related operations in real time. For instance, the deployment of EarthRanger by African Parks has led to the removal of over 50,000 snares, steady population growth of key species of concern and near cessation of poaching. In Liwonde's protected area, enhanced mitigation efforts supported by EarthRanger reduced the number of deaths from wildlife conflict by more than 91%. EarthRanger is also providing a platform to enhance standardisation, aggregation, transfer and long‐term storage of ecological information and promote collaboration between groups conducting protected area management and ecology and biodiversity research.

Abstract Objective To characterize the experience of people with epilepsy and aligned healthcare workers (HCWs) during the first 18 months of the COVID‐19 pandemic and compare experiences in high‐income countries (HICs) with non‐HICs. Methods Separate surveys for people with epilepsy and HCWs were distributed online in April 2020. Responses were collected to September 2021. Data were collected for COVID‐19 infections, the effect of COVID‐related restrictions, access to specialist help for epilepsy (people with epilepsy), and the impact of the pandemic on work productivity (HCWs). The frequency of responses for non‐HICs and HICs were compared using non‐parametric Chi‐square tests. Results Two thousand one hundred and five individuals with epilepsy from 53 countries and 392 HCWs from 26 countries provided data. The same proportion of people with epilepsy in non‐HICs and HICs reported COVID‐19 infection (7%). Those in HICs were more likely to report that COVID‐19 measures had affected their health (32% vs. 23%; p

Abstract Background Preclinical rheumatoid arthritis (Pre‐RA) is defined as the early stage before the development of clinical RA. While cachexia is a well‐known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre‐RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre‐RA with the matched controls. Methods In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre‐RA and propensity score (PS)‐matched control groups. Pre‐RA was retrospectively defined as the absence of RA from baseline to year‐2, with progression to physician‐diagnosed clinical RA between years 3–8 of the follow‐up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year‐2 follow‐ups of the cohort. The outcomes were the differences between Pre‐RA and control groups in the 2‐year rate of change for thigh muscle composition [cross‐sectional area (CSA) and intramuscular adipose tissue (Intra‐MAT)] and adiposity [intermuscular adipose tissue (Inter‐MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed‐effect regression models were used for comparison. Results After 1:3 PS‐matching of the groups for confounding variables (demographics, risk factors, co‐morbidities, and knee osteoarthritis status), 408 thighs (102 Pre‐RA and 306 control) of 322 participants were included (age mean ± SD: 61.7 ± 8.9 years; female/male: 1.8). Over a 2‐year period, Pre‐RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): −180.13 mm2/2‐year, −252.80 to −107.47, P‐value

Abstract Background Cachexia, a syndrome with high prevalence in non‐small cell lung cancer patients, impairs quality of life and reduces tolerance and responsiveness to cancer therapy resulting in decreased survival. Optimal nutritional care is pivotal in the treatment of cachexia and a recommended cornerstone of multimodal therapy. Here, we investigated the therapeutic effect of an intervention diet consisting of a specific combination of high protein, leucine, fish oil, vitamin D, galacto‐oligosaccharides, and fructo‐oligosaccharides on the development and progression of cachexia in an orthotopic lung cancer mouse model. Methods Eleven‐week‐old male 129S2/Sv mice were orthotopically implanted with 344P lung epithelial tumour cells or vehicle (control). Seven days post‐implantation tumour‐bearing (TB) mice were allocated to either intervention‐ or isocaloric control diet. Cachexia was defined as 5 days of consecutive body weight loss, after which mice were euthanized for tissue analyses. Results TB mice developed cachexia accompanied by significant loss of skeletal muscle mass and epididymal fat mass compared with sham operated mice. The cachectic endpoint was significantly delayed (46.0 ± 15.2 vs. 34.7 ± 11.4 days), and the amount (−1.57 ± 0.62 vs. −2.13 ± 0.57 g) and progression (−0.26 ± 0.14 vs. −0.39 ± 0.11 g/day) of body weight loss were significantly reduced by the intervention compared with control diet. Moreover, systemic inflammation (pentraxin‐2 plasma levels) and alterations in molecular markers for proteolysis and protein synthesis, indicative of muscle atrophy signalling in TB‐mice, were suppressed in skeletal muscle by the intervention diet. Conclusions Together, these data demonstrate the potential of this multinutrient intervention, targeting multiple components of cachexia, as integral part of lung cancer management.

Abstract Assessing the dynamics of forest structure complexity is a critical task in times of global warming, biodiversity loss and increasing disturbances in order to ensure the resilience of forests. Recent studies on forest biodiversity and forest structure emphasize the essential functions of deadwood accumulation and diversification of light conditions for the enhancement of structural complexity. The implementation of an experimental patch‐network in managed broad‐leaved forests within Germany enables the standardized analysis of various aggregated and distributed treatments characterized through diverse deadwood and light structures. To monitor the dynamics of enhanced forest structure complexity as seasonal and trend components, dense time‐series from high spatial resolution imagery of Sentinel‐1 (Synthetic‐Aperture Radar, SAR) and Sentinel‐2 (multispectral) are analyzed in time‐series decomposition models (BEAST, Bayesian Estimator of Abrupt change, Seasonal change and Trend). Based on several spatial statistics and a comprehensive catalog on spectral indices, metrics from Sentinel‐1 (n = 84) and Sentinel‐2 (n = 903) are calculated at patch‐level. Metrics best identifying the treatment implementation event are assessed by change point dates and probability scores. Heterogeneity metrics of Sentinel‐1 VH and Sentinel‐2 NMDI (Normalized Multi‐band Drought Index) capture the treatment implementation event most accurately, with clear advantages for the identification of aggregated treatments. In addition, aggregated structures of downed or no deadwood can be characterized, as well as more complex standing structures, such as snags or habitat trees. To conclude, dense time‐series of complementary high spatial resolution sensors have the potential to assess various aggregated forest structure complexities, thus supporting the continuous monitoring of forest habitats and functioning over time.

Abstract Clinical trials seeking to delay or prevent the onset of type 1 diabetes (T1D) face a series of pragmatic challenges. Despite more than 100 years since the discovery of insulin, teplizumab remains the only FDA‐approved therapy to delay progression from Stage 2 to Stage 3 T1D. To increase the efficiency of clinical trials seeking this goal, our project sought to inform T1D clinical trial designs by developing a disease progression model‐based clinical trial simulation tool. Using individual‐level data collected from the TrialNet Pathway to Prevention and The Environmental Determinants of Diabetes in the Young natural history studies, we previously developed a quantitative joint model to predict the time to T1D onset. We then applied trial‐specific inclusion/exclusion criteria, sample sizes in treatment and placebo arms, trial duration, assessment interval, and dropout rate. We implemented a function for presumed drug effects. To increase the size of the population pool, we generated virtual populations using multivariate normal distribution and ctree machine learning algorithms. As an output, power was calculated, which summarizes the probability of success, showing a statistically significant difference in the time distribution until the T1D diagnosis between the two arms. Using this tool, power curves can also be generated through iterations. The web‐based tool is publicly available: https://app.cop.ufl.edu/t1d/. Herein, we briefly describe the tool and provide instructions for simulating a planned clinical trial with two case studies. This tool will allow for improved clinical trial designs and accelerate efforts seeking to prevent or delay the onset of T1D.

Abstract Background Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia. Methods Rectus abdominis muscle biopsies were collected during surgery of patients with pancreatic ductal adenocarcinoma (n = 10 without cachexia, n = 20 cachectic without inflammation (CRP

Abstract Aims Chronic systolic heart failure (CHF) is a major health burden. A relevant number of patients shows asymptomatic left ventricular dysfunction (ALVSD) before symptomatic CHF or becomes asymptomatic after initiating heart failure therapy. Clinical course, prognosis, and response to pharmacological and device‐based treatment are largely unknown in these two distinct groups of patients. Current pharmacological and interventional therapies do neither properly address the underlying pathophysiology nor prevent malignant loss of function. New therapeutic paradigms are needed to stop the progression from asymptomatic to symptomatic heart failure. Key questions are what causes progression of clinically asymptomatic New York Heart Association (NYHA) I heart failure to overt heart failure (>NYHA I) in some but not all patients and the underlying reasons for this transition. This requires the identification of disease mechanisms and biomarkers that predict outcome in well‐defined cohorts for innovative preclinical and clinical trials. Methods and results TransitionCHF is a prospective, multicentre, longitudinal pathophysiological evaluation cohort study in patients with asymptomatic systolic dysfunction NYHA I and left ventricular ejection fraction ≤40%. The cohort comprises both incidental findings and patients who had become asymptomatic after a previous symptomatic event. TransitionCHF has recruited 1000 patients with ALVSD caused by various aetiologies in 20 university heart failure clinics across Germany. Both patients with and without comorbidities at study entry will be recruited. Patients will be systematically investigated and followed up annually over the course of the study. The primary composite endpoint is time to hospitalization for heart failure and cardiovascular death. The secondary endpoints assess time to all‐cause mortality, to cardiovascular mortality, to heart failure mortality, to all‐cause hospitalization, to heart failure hospitalization, and to recurrent heart failure hospitalizations, as well as time to assist device implantation/transplantation. Additional investigations focusing on biomarkers, comorbidities, gender aspects, nutrition, and functional parameters including quality of life will be performed. Conclusions TransitionCHF will provide a more thorough pathophysiological understanding of the progression of asymptomatic systolic dysfunction into symptomatic heart failure that will help develop therapies tailored to prevent progressive heart failure.

Abstract In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image‐guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in‐person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post‐ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.

Abstract Surface freshening of the Southern Ocean driven by meltwater discharge from the Antarctic ice sheet has been shown to influence global climate dynamics. However, most climate models fail to account for spatially and temporally varying freshwater inputs from ice sheets, introducing significant uncertainty into climate projections. We present the first historically calibrated projections of Antarctic freshwater fluxes (sub‐shelf melting, calving, and surface meltwater runoff) to 2300 that can be used to force climate models lacking interactive ice sheets. Our findings indicate substantial changes in the magnitude and partitioning of Antarctic freshwater discharge over the coming decades and centuries, particularly under very‐high warming scenarios, driven by the progressive collapse of the West Antarctic ice shelves. We project a shift in the form and location of Antarctic freshwater sources, as liquid sub‐shelf melting increases under the two climate scenarios considered, and surface meltwater runoff could potentially become a dominant contributor under extreme atmospheric warming.

Abstract Economics is the study of the allocation of scarce resources to meet human wants and needs and has a critical role to play in addressing challenges related to environmental sustainability, community resilience, and food security. In the context of aquaculture, the key to such a discussion is understanding the linkages of aquaculture farming businesses with other economic sectors and how policy decisions that affect aquaculture result in economic ripples throughout local, regional, and national economies. The only previous national estimates of the economic contributions of U.S. aquaculture are nearly 30 years old. The current study was based on comprehensive data from detailed farm‐level surveys (that captured 77% of the total value of U.S. aquaculture) supplemented by information from publications on the remaining aquaculture sectors. The economic contributions measured in this study were limited to those at the farm level and do not include subsequent impacts that occur as farmed products move through processing, distribution, food service, and retail sectors in the U.S. economy. Results showed that U.S. aquaculture farms contributed $4 billion annually and supported more than 22,000 jobs each year. Labor income and value‐added contributions were $1 billion and $3 billion, respectively. Analysis of the linkages of U.S. aquaculture production activities with other economic sectors showed that nearly all (96%) economic sectors were supported to some degree by U.S. aquaculture farms. Foodfish farms generated the greatest contributions, followed by mollusk farms. Freshwater aquaculture farms contributed twice that of the contributions of marine aquaculture because of the greater size of the freshwater aquaculture sector. Growth of both freshwater and marine sectors would increase overall contributions to the economy. Constraints to growth of aquaculture include regulatory barriers that have restricted existing sectors from meeting current demand for their products. The lack of an adequate regulatory framework for offshore marine aquaculture has constrained its growth and development, especially with respect to the rest of the world. Streamlined regulations implemented in a more timely and efficient manner could result in substantially greater economic contributions from existing U.S. aquaculture farms. The total economic impact of U.S. aquaculture production is likely three to four times greater than the farm‐level impacts estimated in this study as a result of impacts that occur as aquaculture products move downstream through various marketing channels. Additional research is needed to measure the impacts of U.S. aquaculture products in the processing, distribution, food service, supermarket, and restaurant levels of the marketing chain to fully capture the total economic contributions from U.S. aquaculture.

Abstract Following an application from Alzchem Trostberg GmbH, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Austria, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to creatine and improvement in cognitive function. The Panel considers that the food constituent, creatine, is sufficiently characterised. An improvement in cognitive function in one or more of its domains is a beneficial physiological effect. The applicant identified 21 human intervention studies on creatine supplementation and measures of cognitive function through a literature search. Two additional studies published after the search was conducted were identified through the reference list of a meta‐analysis. In weighing the evidence, the Panel took into account that the acute effect of creatine on working memory, observed in two studies at 20 g/day for 5–7 days, was not seen at lower doses (2.2–14 g/day), or with continuous consumption (5 g/day for 6 weeks following a 5‐day loading phase). Furthermore, the effect on response inhibition at 20 g/day for 7 days was an isolated finding among 10 intervention studies in healthy individuals, with no effects observed on other cognitive domains. The Panel also considered that the three intervention studies conducted in diseased individuals do not support an effect of creatine supplementation on cognition, and that the available evidence for a mechanism by which creatine could exert the claimed effect is weak. The Panel concludes that a cause‐and‐effect relationship has not been established between creatine supplementation and an improvement in cognitive function in one or more of its domains.

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of Tiger nuts (Cyperus esculentus) oil as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tiger nuts (C. esculentus) is an edible tuber with history of consumption as food. The NF is the oil obtained from the nuts through cold pressing of the seeds flour. Oleic acid is the major component, representing 65%–69% of the oil's total fatty acids. The applicant proposed to use the NF as an ingredient in several food categories, and as a cooking oil or added as a condiment. The Panel notes that there are no safety concerns regarding stability if the NF complies with the proposed specification limits during its entire shelf‐life. Taking into consideration the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The Panel considers that, based on the production process, composition of the NF, history of use of and composition of the source, no toxicological studies are required on the NF. The Panel concludes that the NF is safe under the proposed conditions of use.

Abstract Vitamins and essential minerals are micronutrients that are required for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. A tolerable upper intake level (UL) is a science‐based reference value that supports policy‐makers and other relevant actors in managing the risks of excess nutrient intake. EFSA's principles for establishing ULs for vitamins and minerals were originally developed by the Scientific Committee on Food in 2000. This guidance from the EFSA Panel on Nutrition, Novel Foods and Food Allergens provides an updated framework for UL assessments. A draft was published in 2022 and underwent a 2‐year piloting period. The present document incorporates revisions based on the experience gained through its practical implementation. It covers aspects related to the planning of the risk assessment (problem formulation and definition of methods) and its implementation (evidence retrieval, appraisal, synthesis, integration, uncertainty analysis). As in the previous framework, the general principles developed for the risk assessment of chemicals in food are applied, i.e. hazard identification, hazard characterisation, intake assessment, risk characterisation. Specific to nutrients are their biochemical and physiological roles and the specific and selective mechanisms that maintain the systemic homeostasis and accumulation of the nutrient in the body. Such considerations must also be taken into account when conducting risk assessments of nutrients.

ABSTRACT Ungulates serve as the primary carrion source for facultative scavengers in European ecosystems. In the absence of large carnivores, such as wolves (Canis lupus), human hunting leftovers are the main source of carrion for these scavengers. Additionally, wild boars (Sus scrofa) are heavily culled in many ecosystems and are both a significant prey species for wolves as well as a key scavenger. Nowadays, wolves and wild boars are re‐establishing their historical home ranges. However, it remains unclear how their presence influences the population dynamics of facultative scavengers under different scenarios of human hunting strategies. We simulated the biomass densities of all states in the trophic web including European scavengers and wolves using an ordinary differential equations (ODE) model. The presence of wolves led to a positive trend in scavenger biomass in general. However, in general, we found that plant‐based resources were more important for scavenger dynamics than carrion, regardless of whether the carrion originated from human hunting or wolf predation. Only when wolves were absent but boars present, the human hunting strategy became important in determining scavenger dynamics via carrion supply. In conclusion, our model indicates that population dynamics of facultative scavengers are not mainly driven by the availability of carrion, but rather by the presence of and competition for vegetation. Furthermore, our simulations highlight the importance of adapting human hunting strategies in accordance with the re‐establishment of wolf and boar as these can cause fluctuating population patterns over the years.

ABSTRACT Florida, USA is a hotspot of biological invasions with over 500 non‐native species reported. Reptiles encompass most of the non‐native wildlife with over 50 species established, many of which are sympatric and are identified as invasive due to their impacts to the environment, economy, and human health and safety. Reports of new non‐native reptiles occur, and many established non‐native reptiles continue to expand their ranges in Florida, increasing the need for multitaxa detection and monitoring capabilities. Invasive constrictor snakes are a primary focus of management efforts due to life history traits that favor successful establishment and dispersal in Florida as well as their impacts to native wildlife and Everglades restoration efforts. While traditional survey methods that rely on visual detections fail to reliably detect invasive constrictors, environmental DNA (eDNA) has proven to be a promising method for detection of cryptic and rare species across the landscape. To address emerging needs for multispecies detection and monitoring in Florida, we developed the first tetraplex dPCR assay designed for detection of four species of invasive constrictor snakes, including Burmese pythons (Python bivittatus), northern African pythons (P. sebae), boa constrictors (Boa constrictor), and rainbow boas (Epicrates cenchria). In this tetraplex assay, no cross‐amplification across species was documented. This assay serves as a valuable tool for faster and more accurate monitoring efforts of these invasive species in South Florida. Additionally, eDNA samples comprised of soil and water both tested positive for Burmese python DNA under controlled and semicontrolled conditions with DNA being detectable up to 2‐weeks post removal in soil samples. Water samples yielded positive detection as quickly as 5 min after exposure to the organism. These data highlight the utility and sensitivity of this protocol for eDNA monitoring.

Abstract Sensors that can accurately assess oxygen (O2) concentrations in real time are crucial for a wide range of applications spanning personal health monitoring, environmental protection, and industrial process development. Here a high‐performance chemiresistive sensor that allows for the rapid detection of O2 at room temperature under visible light illumination is described. Inspired by the operating principles of dye‐sensitized solar cells, the chemiresistor is based on a single‐walled carbon nanotube‐titania hybrid (SWCNT‐TiO2) bearing a molecular Re‐based photosensitizer [(Pbpy)(CO)3ReBr] (Pbpy = 4,4′‐[P(O)(OH)2]2‐2,2′‐bipyridine). The resulting SWCNT‐TiO2‐Re composite undergoes photoinduced charge transfer that is sensitive to ppb levels of O2, thereby yielding a rapid and reversible chemiresistive response. Owing to its unique mode of operation and robust components, the sensor shows a high degree of selectivity for O2 over a range of interferants, humidity tolerance, and multimonth benchtop stability. The approach presented herein demonstrates the translatability of concepts in light harvesting to the development of robust, rapid, and low‐power sensing technologies.

Abstract Thermal‐responsive hydrogels are developed as ion‐conductive switchs for energy storage devices, however, the molecule mechanism of switch on/off remains unclear. Here, poly(N‐isopropylacrylamide‐co‐acrylamide) hydrogel is synthesized as a model material and nanodiamond (ND) based quantum sensing for phase change study is developed. First, micro‐scale phase separation with cross‐linked mesh structure after sol‐gel transition is visualized in situ and water molecules are trapped by polymer chains and on a chemically “frozen” state. Then, the nano‐scale inhomogeneous distributions of viscosity, thermal conductivity and ionic mobility in hydrogel at high temperature are observed by measuring the rotation, translation and zero‐field splitting of NDs. Besides, the ionic mobility of hydrogel is found to be dependent not only on temperature but also on polymer concentration. These observations suggested that the physical “wall” induced by inhomogeneous phase separation at microscopic scale blocked the ion conduction pathways, providing a potential intrinsic explanation for ion migration shut‐down of ionic hydrogels at high temperature.

Abstract Objectives This study aimed to assess the diagnostic management and follow‐up imaging for glioma patients across Belgian hospitals by calculating process indicators. Methods Patients with newly diagnosed glioma in Belgium (2016–2019) were selected from the Belgian Cancer Registry. The National Social Security Number served as unique patient identifier, linking the Registry to vital status and reimbursement data. Nine measurable process related to diagnosis and follow‐up imaging were identified, with reformulations for 7 due to data limitations. For each indicator, technical documentation sheets, containing all required details (rationale, numerator and denominator, target, limitations, benchmarking, subgroup analyses) were developed, reviewed by a multidisciplinary expert panel, and validated in six pilot hospitals. Per indicator, patients were assigned to the most relevant hospital per indicator using allocation algorithms. Results Results for process indicators assessing MRI use in glioma diagnosis and follow‐up aligned with predefined targets (90%), except for early postoperative MRI (48.5% vs. target 90%). Mandatory reporting of the WHO performance status (89.3% vs. target 100%) and performance of full‐spine (43.6% vs. target 90%) and follow‐up MRI (73.5% vs. target 90%) in ependymoma were suboptimal. The largest variability across centers was noted for the indicator on early postoperative MRI. Conclusion This calculation of process indicators identified opportunities for improvement in diagnosis and follow‐up imaging for glioma patients in Belgium. Monitoring indicator results and providing individual feedback reports to the Belgian hospitals invites neuro‐oncology care teams and hospital managements to reflect on their results and to take measures to continuously improve care for glioma.

ABSTRACT Backround Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing. Methods To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). Results AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%–100%), urothelial carcinoma (74.6%–100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%–99.6%), and pancreaticobiliary cancers (65.2%–98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%–77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (p

ABSTRACT Objective This study aims to describe patterns, sources, and reasons for cannabis use among cancer patients during active treatment (+CDTX) compared to no‐use during active treatment (−CDTX). Methods Data are from 385 surveys collected via REDCap during phase I of an ongoing study among adult cancer patients seen at an NCI‐designated comprehensive cancer center within the last 5 years of treatment. A harmonized survey was created with 11 other NCI centers to assess cannabis use patterns, sources, and reasons for use. Sociodemographics and cancer details were also collected via self‐report. Descriptive statistics were calculated and stratified by +/−CDTX. Chi‐squared tests were conducted to compare proportions between groups. Results Among the sample [49.5 years (SD 15.9); 53.0% male; and 41.6% Hispanic/Latino], 41.0% + CDTX and 59.0% −CDTX. A majority (71.8%) of +CDTX initiated use before diagnosis versus 44.1% in −CDTX (p

Abstract Human–elephant conflict is growing in Africa as human populations and development increases, creating disturbance to elephant habitats. Beehive fences have been trialed as a coexistence tool with some success but all studies have looked at small sample sizes over a short time period. Our study analyses the behavior of African elephants (Loxodonta africana) that approached a network of beehive fence protected farms in two conflict villages over 9 years next to Tsavo East National Park. We compare differences in elephant raids and beehive occupation rates annually, during a drought, and during peak crop production seasons. Out of 3999 elephants approaching our study farms 1007 elephants broke the beehive fence and entered the protected farm areas (25.18%). This was significantly less than the 2649 encounters where elephants remained either outside the farm boundary or broke into the control farms (66.24%). A further 343 elephants entered the farm by walking through a gap at the end of a fence (8.56%). The annual beehive fence break‐through rates averaged 23.96% (±SE 3.15) resulting in a mean of 76.04% elephants deterred from beehive fences protected farm plots. Over six peak crop growing seasons the beehive fences kept between 78.3% and 86.3% of elephants out of the farms and crops. The beehive fences produced one ton of honey sold for $2250; however, a drought caused a 75% reduction in hive occupation rates and honey production for 3 years after negatively impacting honey profits and the effectiveness of the fences. Beehive fences are very effective at reducing up to 86.3% of elephant crop‐raids during peak crop seasons after good rainfall, but any increase in elephant habitat disturbance or the frequency and duration of droughts could reduce their effectiveness as a successful coexistence tool.

Background Patients with Kawasaki disease (KD) with coronary artery involvement require long‐term cardiac care. Although respective evidence‐based recommendations are missing, cardiac catheterization is still considered the gold standard for diagnosing detailed coronary pathology. Therefore, to better understand coronary artery pathology development, we conducted a survey to document and evaluate cardiac catheterization data in a European population. Methods and Results We retrospectively analyzed cardiac catheterization data from KD children from the year 2010 until April 2023. This registry covers basic acute‐phase clinical data, and more importantly, detailed information on morphology, distribution, and the development of coronary artery pathologies. A total of 164 mainly White patients (65% boys) were included. A relevant number of patients had no coronary artery aneurysm (CAA) at the cardiac catheterization, indicating that distal CAAs were almost exclusively detected alongside proximal CAAs. Patients with multiple CAAs revealed a significant positive correlation between the number of CAAs and their dimensions in diameter and in length. Location of the CAA within the coronary artery, age at onset of KD, or natal sex did not significantly influence CAA diameters, but CAAs were longer in older children and in boys. Conclusions That distal CAAs were only present together with proximal ones will hopefully reduce diagnostic CCs in patients with KD without echocardiographically detected proximal CAAs. Furthermore, this study gives valuable insights into dimensional specifics of CAAs in patients with KD. As an ongoing registry, future analyses will further explore long‐term outcomes and performed treatments, helping to refine clinical long‐term strategies for patients with KD. REGISTRATION URL: https://drks.de/; Unique Identifier: DRKS00031022.

The National Heart, Lung, and Blood Institute convened a virtual workshop in September 2022 to discuss “Optimal Instruments for Measurement of Diet, Physical Activity, and Sleep.” This report summarizes the proceedings, identifying current research gaps and future directions for measuring different lifestyle behaviors in adult population‐based studies. Key discussions centered on integrating report‐based methods, like questionnaires, with device‐based assessments, including wearables and physiological measures such as biomarkers and omics to enhance self‐reported metrics and better understand the underlying biologic mechanisms of chronic diseases. Emphasis was placed on the need for data harmonization, including the adoption of standard terminology, reproducible metrics, and accessible raw data, to enhance the analysis through artificial intelligence and machine learning techniques. The workshop highlighted the importance of standardizing procedures for integrated behavioral phenotypes using time‐series data. These efforts aim to refine data accuracy and comparability across studies and populations, thereby advancing our understanding of lifestyle behaviors and their impact on chronic disease outcomes over the life course.

Abstract The outcomes of speciation across organismal dimensions (e.g., ecological, genetic, phenotypic) are often assessed using phylogeographic methods. At one extreme, reproductively isolated lineages represent easily delimitable species differing in many or all dimensions, and at the other, geographically distinct genetic segments introgress across broad environmental gradients with limited phenotypic disparity. In the ambiguous gray zone of speciation, where lineages are genetically delimitable but still interacting ecologically, it is expected that these lineages represent species in the context of ontology and the evolutionary species concept when they are maintained over time with geographically well‐defined hybrid zones, particularly at the intersection of distinct environments. As a result, genetic structure is correlated with environmental differences and not space alone, and a subset of genes fail to introgress across these zones as underlying genomic differences accumulate. We present a set of tests that synthesize species delimitation with the speciation process. We can thereby assess historical demographics and diversification processes while understanding how lineages are maintained through space and time by exploring spatial and genome clines, genotype‐environment interactions, and genome scans for selected loci. Employing these tests in eight lineage‐pairs of snakes in North America, we show that six pairs represent 12 “good” species and that two pairs represent local adaptation and regional population structure. The distinct species pairs all have the signature of divergence before or near the mid‐Pleistocene, often with low migration, stable hybrid zones of varying size, and a subset of loci showing selection on alleles at the hybrid zone corresponding to transitions between distinct ecoregions. Locally adapted populations are younger, exhibit higher migration, and less ecological differentiation. Our results demonstrate that interacting lineages can be delimited using phylogeographic and population genetic methods that properly integrate spatial, temporal, and environmental data.

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of an extension of use of oil from Schizochytrium limacinum (strain FCC‐3204) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The extension of use pertains to the use of the NF as a food ingredient in protein products at a maximum use level of 1 g of docosahexaenoic acid (DHA) in 100 g of product. The Panel considers that the information provided on the composition and the production process is sufficiently described and does not raise safety concerns. S. limacinum was attributed the qualified presumption of safety (QPS) status with the qualification ‘for production purposes only’. Data provided demonstrated the absence of viable cells in the NF. Under the proposed extension of use, the highest intake estimate (at the 95th percentile) of DHA from the NF in protein products is 6.3 mg DHA/kg bw per day for adolescents. The Panel notes that the exposure to DHA from the new intended use of the NF in protein products is very low compared to the exposure to DHA from the already authorised food categories (excluding food supplements). The Panel concludes that the NF (oil from S. limacinum (FCC‐3204)) is safe under the new intended use.

Abstract Biological Nitrification Inhibition (BNI) encompasses primarily NH4+‐induced release of secondary metabolites to impede the rhizospheric nitrifying microbes from performing nitrification. The intermediate wheatgrass Thinopyrum intermedium (Kernza®) is known for exuding several nitrification inhibition traits, but its BNI potential has not yet been identified. We hypothesized Kernza® to evince BNI potential through the presence and release of multiple BNI metabolites. The presence of BNI metabolites in the biomass of Kernza® and annual winter wheat (Triticum aestivum) and in the root exudates of hydroponically grown Kernza®, were fingerprinted using HPLC‐DAD and GC–MS/MS analyses. Growth bioassays involving ammonia‐oxidizing bacteria (AOB) and archaea (AOA) strains were conducted to assess the influence of the crude root metabolome of Kernza® and selected metabolites on nitrification. In most instances, significant concentrations of various metabolites with BNI potential were observed in the leaf and root biomass of Kernza® compared to annual winter wheat. Furthermore, NH4+ nutrition triggered the exudation of various phenolic BNI metabolites. Crude root exudates of Kernza® inhibited multiple AOB strains and completely inhibited N. viennensis. Vanillic acid, caffeic acid, vanillin, and phenylalanine suppressed the growth of all AOB and AOA strains tested, and reduced soil nitrification, while syringic acid and 2,6‐dihydroxybenzoic acid were ineffective. We demonstrated the considerable role of the Kernza® metabolome in suppressing nitrification through active exudation of multiple nitrification inhibitors.

Abstract Understanding the temporal dynamics of soil microbial biomass is crucial for assessing soil ecosystem functions and services, yet these dynamics are globally uncertain. Here, we compiled a data set of soil microbial biomass carbon (MBC) and nitrogen (MBN) from 1493 studies between 1988 and 2019 to elucidate their temporal trends and potential drivers. Results showed that global MBC and MBN significantly decreased by 0.033 Mg C ha−1 yr−1 and 0.007 Mg N ha−1 yr−1 at 0–30 cm soil depth, between 1988 and 2019, respectively, which might be primarily attributed to the warming of the climate, the increase in global precipitation, and reduction of soil organic carbon (SOC) stock. The rate of decline in MBC and MBN showed a non‐linear trend: following a decline from 1988 to 1999, it slowed down until 2014, likely due to the global warming hiatus. Afterward, the pace of decline increased again from 2015 to 2019. Boreal biomes experienced the largest decrease in soil microbial biomass with the reduction rate of MBC being 4.3 times higher than in temperate biomes, showing a higher sensitivity in boreal biomes to climate change. Grassland ecosystems also exhibited greater reductions, possibly driven by their degradation. These findings shed valuable insights on the long‐term dynamics of soil microbial biomass on a global scale over the last three decades. Furthermore, this study underscores the importance of preserving soil microbial biomass as a key strategy to mitigate the adverse effects of future climate change, thereby sustaining ecosystem health and resilience.

ABSTRACT Biocides are used to control microorganisms across different applications, but emerging resistance may pose risks for those applications. Resistance to biocides has commonly been studied using adaptive laboratory evolution (ALE) experiments with growth at subinhibitory concentrations linked to serial subculturing. It has been shown recently that Escherichia coli adapts to repeated lethal stress imposed by the biocide benzalkonium chloride (BAC) by increased survival (i.e., tolerance) and not by evolving the ability to grow at increased concentrations (i.e., resistance). Here, we investigate the contributions of evolution for tolerance as opposed to resistance for the outcome of ALE experiments with E. coli exposed to BAC. We find that BAC concentrations close to the half maximal effective concentration (EC50, 4.36 μg mL−1) show initial killing (~40%) before the population resumes growth. This indicates that cells face a two‐fold selection pressure: for increased survival and for increased growth. To disentangle the effects of both selection pressures, we conducted two ALE experiments: (i) one with initial killing and continued stress close to the EC50 during growth and (ii) another with initial killing and no stress during growth. Phenotypic characterization of adapted populations showed that growth at higher BAC concentrations was only selected for when BAC was present during growth. Whole genome sequencing revealed distinct differences in mutated genes across treatments. Treatments selecting for survival‐only led to mutations in genes for metabolic regulation (cyaA) and cellular structure (flagella fliJ), while treatments selecting for growth and survival led to mutations in genes related to stress response (hslO and tufA). Our results demonstrate that serial subculture ALE experiments with an antimicrobial at subinhibitory concentrations can select for increased growth and survival. This finding has implications for the design of ALE experiments to assess resistance risks of antimicrobials in different scenarios such as disinfection, preservation, and environmental pollution.

Abstract Sphingolipids play vital roles in metabolism and regulation. Previously, the aryl hydrocarbon receptor (AHR), a ligand‐activated transcription factor, was reported to directly regulate ceramide synthesis genes by binding to their promoters. Herein, sphingosine kinase 2 (SPHK2), responsible for producing sphingosine‐1‐phosphate (S1P), was found to interact with AHR through LXXLL motifs, influencing AHR nuclear localization. Through mutagenesis and co‐transfection studies, AHR activation and subsequent nuclear translocation was hindered by SPHK2 LXXLL mutants or SPHK2 lacking a nuclear localization signal (NLS). Similarly, an NLS‐deficient AHR mutant impaired SPHK2 nuclear translocation. Silencing SPHK2 reduced AHR expression and its target gene CYP1A1, while SPHK2 overexpression enhanced AHR activity. SPHK2 was found enriched on the CYP1A1 promoter, underscoring its role in AHR target gene activation. Additionally, S1P rapidly increased AHR expression at both the mRNA and protein levels and promoted AHR recruitment to the CYP1A1 promoter. Using mouse models, AHR deficiency compromised SPHK2 nuclear translocation, illustrating a critical interaction where SPHK2 facilitates AHR nuclear localization and supports a positive feedback loop between AHR and sphingolipid enzyme activity in the nucleus. These findings highlight a novel function of SPHK2 in regulating AHR activity and gene expression.

Abstract Background Tumor lysis syndrome (TLS) is a potentially life‐threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate‐lowering treatments, and a steroid prophase strategy. Aims This study aims to explore the impact of fractionated rituximab, an anti‐CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B‐cell non‐Hodgkin lymphoma (B‐NHL). Methods Data was retrospectively collected from 94 of 186 patients. Results Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B‐cell lymphoma (75%), Burkitt lymphoma (13%) and high‐grade B‐cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline‐containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression‐free survival was 2.6 years, and 2‐year overall survival was 33%, irrespective of TLS occurrence. Conclusion In this real‐life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Abstract The response of vegetation to climate change on a large scale should be studied at the community level rather than the species level. This necessitates a focused exploration of emerging spatial patterns. Here, we surveyed 264 sites in the Inner Mongolia typical steppe, using the “needling” method to investigate 39,600 clumps formed through the coexistence relationships of dominant species. We found that the effects of slow climate change on grassland communities can be categorized into two general trends: (1) a monotone relationship, characterized by changes in the number of dominant species, compositional diversity, and optimal patch area, and (2) a unimodal relationship, reflected in variations in the number of patches and interspecific associations. The two distinct trends, connected by optimal patch area, concurrently support both the habitat amount hypothesis and the intermediate disturbance hypothesis. These findings suggest that climate change indirectly influences the area and amount of vegetation patches by regulating the arrangement of clumps. Moreover, they indicate that it is the distribution, rather than the number, of species that serves as the front line for plant communities adapting to climate change.

Abstract Testicular large B‐cell lymphoma (TLBCL) is an infrequent and aggressive lymphoma arising in an immune‐privileged site and has recently been recognized as a distinct entity from diffuse large B‐cell lymphoma (DLBCL). We describe the genetic features of TLBCL and compare them with published series of nodal DLBCL and primary large B‐cell lymphomas of the CNS (PCNSL). We collected 61 patients with TLBCL. We performed targeted next‐generation sequencing, copy number arrays, and fluorescent in situ hybridization to assess chromosomal rearrangements in 40 cases with available material. Seventy percent of the cases showed localized stages. BCL6 rearrangements were detected in 36% of cases, and no concomitant BCL2 and MYC rearrangements were found. TLBCL had fewer copy number alterations (p

Abstract Model‐based acoustic localisation estimates the locations of underwater objects by comparing sensor measurements with model predictions. To obtain high quality predictions, propagation models need to be run for a large set of environmental parameters. However, real‐time Model‐based acoustic localisation estimations using onboard computational resources are often limited. To address this, the authors propose a Quantum annealing (QA) algorithm for enhancing underwater acoustic localisation. A restricted Boltzmann machine (RBM) is trained to predict the probability distribution of underwater targets. Advantage of this approach is that part of the computation is moved to offline‐training. Moreover, the probability distribution can potentially be sampled efficiently using a quantum annealer possibly enabling real‐time accurate target estimations being made onboard.The RBM is applied to a simplified multi‐sensor horizontal localisation problem where a constant and linear acoustic propagation is assumed. Using simulated annealing the authors show that the RBM is able to learn probability distributions that resemble target locations. Preliminary results show that training and sampling the RBM can be done using QA hardware by D‐Wave Systems.However, there remains room for improvement especially in ranging predictions. Further research into possible benefits of QA RBMs is needed to provide theoretical and practical results of a speed‐up.

Abstract Background Cutaneous metastases (CM) are a frequent finding in the follow‐up of malignant tumours. Objectives CM were examined with dermoscopy, optical coherence tomography (OCT), dynamic OCT and line‐field confocal OCT (LC‐OCT) to describe common findings. Methods In the University Hospital Carl Gustav Carus Dresden, Germany, 18 patients with 61 CM were examined with dermoscopy. CM (n = 43, 31 melanoma metastases, two metastases of renal carcinoma, five metastases of cutaneous squamous cell carcinoma and five metastases of pleomorphic dermal sarcoma) were examined with OCT (VivoSight® Michelson Diagnostics). Additional 18 melanoma metastases were examined with LC‐OCT (deepLive™; Damae Medical). Results CM were localized on the head, trunk, neck and limbs. Dermoscopy patterns were angioma‐like, nevus‐like nonglobular, nevus‐like globular, blue nevus‐like and unspecific. CM showed an ulceration, hyperkeratosis with increased entrance signal and disturbed architecture of the epidermis in OCT. In deeper metastases, the dermoepidermal junction (DEJ) was normal; in most cases it was disturbed. CM were visible as subepidermal hyporeflective roundish area, with septae, with either clear margin and shadowing or blurred margin. DOCT showed dot, coiled, serpiginous and branched vessels; there was a disarray in size and distribution and vessels were converging on the centre of the metastasis. In LC‐OCT, CM showed enhanced entrance signal and disturbed architecture of a thinned epidermis, ulceration, atypical honeycomb or cobblestone pattern as well as a broken DEJ. In the dermis, a hyporeflective roundish area with clusters of hyporeflective cells with septae, clear margin and clefting or blurred margin was visible; the hyporeflective area was surrounded by bundles of connective tissue. Subepidermal vessels differentiated in size and distribution. Inflammatory, dendritic and pagetoid cells were visible. Conclusions OCT and LC‐OCT may be useful tools for immediate diagnosis, localization of CM and monitoring under treatment in addition to conventional methods like ultrasound and histopathology.

Abstract Background Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) can yield improved diagnostic accuracy of nonmelanoma skin cancer (NMSC) in comparison with dermoscopy alone. Objectives The aim of this study was to compare the diagnostic performance of OCT and RCM together and individually with that of dermoscopy. Methods Patients with lesions suspicious for NMSC were randomized into two groups in a prospective, single‐centre study. In the intervention group (IG), every lesion was examined with dermoscopy, OCT and RCM, while in the control group (CG), every lesion was examined with dermoscopy alone. Results A total of 365 lesions of 250 patients (105 female, 145 male) were included in the study. A total of 208 basal cell carcinomas (BCCs), 65 squamous cell carcinomas (SCCs) and 31 SCCs in situ were examined histologically. The IG involved significantly fewer biopsies than the CG (14 vs. 27, p = 0.029) and required fewer additional inpatient stays due to positive biopsy results (2 vs. 12, p = 0.001). For the diagnosis of BCC, diagnostic accuracy was 81% with dermoscopy, 84% with OCT, 83% with RCM and 85% with the combination of OCT and RCM (OCT/RCM). The diagnostic accuracy of OCT for BCC subtypes was as follows: superficial, 89%; nodular, 79%; sclerodermiform, 82%; and nodular‐cystic BCC, 75%. For the diagnosis of SCC, diagnostic accuracy was 85% with dermoscopy, 87% with OCT, 89% with RCM and 87% with OCT/RCM. For the diagnosis of in situ SCC, diagnostic accuracy was 87% with dermoscopy, 89% with OCT, 89% with RCM and 91% with OCT/RCM. Conclusions Diagnostic accuracy increased with OCT and RCM and was even higher when both methods were used together. OCT and RCM could facilitate optimization of lesion management by reducing the number of punch biopsies and reducing additional inpatient stays due to positive biopsy results.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is a multifactorial, multisystemic syndrome that involves alterations in lipid metabolism. This study aimed to test whether distinct plasma lipid profiles or lipid entities or both are associated with clinical and functional echocardiographic parameters in HFpEF. Methods and results We examined the human plasma lipidome in HFpEF patients (n = 18) with left ventricular ejection fraction ≥50% and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) >125 pg/mL and control subjects (n = 12) using mass spectrometry‐based shotgun lipidomics. The cohort included 8 women and 22 men with average age of 67.8 ± 8.6 SD. The control and disease groups were not significantly different with respect to age, body mass index, systolic and diastolic blood pressure, and waist‐to‐hip ratio. The disease group experienced more fatigue (P

Abstract Background This retrospective study aimed to evaluate the precision and safety outcomes of image‐guided lung percutaneous thermal ablation (LPTA) methods, focusing on radiofrequency ablation (RFA) and microwave ablation (MWA). The study utilized an innovative angle reference guide to facilitate these techniques in the treatment of lung tumors. Methods This study included individuals undergoing LPTA with the assistance of laser angle guide assembly (LAGA) at our hospital between April 2011 and March 2021. We analyzed patient demographics, tumor characteristics, procedure details, and complications. Logistic regressions were employed to assess risk factors associated with complications. Results A total of 202 patients underwent ablation for 375 lung tumors across 275 sessions involving 495 ablations. Most procedures used RFA, especially in the right upper lobe, and the majority of ablations were performed in the prone position (49.7%). Target lesions were at a median depth of 39.3 mm from the pleura surface, and remarkably, 91.9% required only a single puncture. Complications occurred in 31.0% of ablations, with pneumothorax being the most prevalent (18.3%), followed by pain (12.5%), sweating (6.5%), fever (5.0%), cough (4.8%), hemothorax (1.6%), hemoptysis (1.2%), pleural effusion (2.0%), skin burn (0.6%), and air emboli (0.2%). The median procedure time was 21 min. Notably, smoking/chronic obstructive pulmonary disease emerged as a significant risk factor for complications. Conclusion The LAGA‐assisted LPTA enhanced safety by improving accuracy and reducing risks. Overall, this investigation contributes to the ongoing efforts to refine and improve the clinical application of these thermal ablation techniques in the treatment of lung tumors.

Abstract With the anticipated launch of the Australian Bragg Centre for Proton Therapy and Research (ABCPTR) in Adelaide, Australia, proton therapy will become a significant addition to existing cancer treatment options for Australians. The anticipated benefits will be particularly evident in rare cancers such as clival chordomas, a challenging tumour entity due to the anatomical relationship with critical structures, and proven radio‐resistance to conventional radiation therapy. The article synthesises key findings from major studies and evaluates the current evidence supporting various management strategies for clival chordomas. It also considers the influence of institutional volume and multidisciplinary team management on patient outcomes and outlines how high‐quality care can be effectively delivered within the Australian healthcare system, emphasising the potential impact of proton therapy on the treatment paradigm of clival chordomas in Australia.

Abstract Background Duchenne muscular dystrophy (DMD) is an X‐linked disorder characterized by progressive muscle weakness due to the absence of functional dystrophin. DMD patients also develop dilated cardiomyopathy (DCM). We have previously shown that DMD (mdx) mice and a canine DMD model (GRMD) exhibit abnormal intracellular calcium (Ca2+) cycling related to early‐stage pathological remodelling of the ryanodine receptor intracellular calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) contributing to age‐dependent DCM. Methods Here, we used hiPSC‐CMs from DMD patients selected by Speckle‐tracking echocardiography and canine DMD cardiac biopsies to assess key early‐stage Duchenne DCM features. Results Dystrophin deficiency was associated with RyR2 remodelling and SR Ca2+ leak (RyR2 Po of 0.03 ± 0.01 for HC vs. 0.16 ± 0.01 for DMD, P

Abstract Rural households in East Africa rely on local markets, but the influence of market food diversity and household food purchase diversity on diets has not been well‐characterized. We quantify the associations among market food diversity, household food purchase diversity and dietary diversity of mothers, fathers and children in rural Tanzania. This study uses baseline data from a randomized controlled trial, Engaging Fathers for Effective Child Nutrition and Development in Tanzania. We used the 10 food groups for women's dietary diversity to assess the seasonal availability of nutritious foods in 79 markets. Using data from 957 rural households in two districts in Mara, Tanzania, we measured household food purchase diversity over the previous month and dietary diversity among children (6–23 months), mothers and fathers. Overall, 63% of markets sold all 10 food groups throughout the year, indicating high‐market food diversity and minimal seasonality. However, only 33% of women and 35% of children met dietary diversity recommendations. Households that reported higher purchasing power (0.14, p

Abstract Despite the recent increase in landscape conservation and the design processes agencies are undertaking, there remains an implementation gap due to an inability to evaluate general strategies and account for uncertainties faced by managers. We demonstrated how a decision support process (DSP), recently developed to inform landscape conservation design, can address uncertainties and complexities inherent in landscape conservation to facilitate long‐term, large‐scale conservation planning. We applied the DSP to landscape conservation efforts within conservation opportunity areas (COA) of states in the Gulf Coastal Plains and Ozarks region. We engaged state planners within the region to identify important landscape conservation uncertainties they face in planning. We developed, simulated, and modeled the impacts of conservation addressing 3 uncertainties identified by state wildlife managers and evaluated the impacts by examining the responses of state and local populations of 2 bird species of conservation concern, prairie warbler (Setophaga discolor) and wood thrush (Hylocichla mustelina). The responses of prairie warbler populations to conservation strategies indicated that both approaches of protecting quality habitat from land‐use change and restoring and enhancing lower quality and nonhabitat improved their viability at regional, statewide, and COA scales. However, we noted that the relative effectiveness of strategies varied among states in ways that suggest a state's process for delineating COAs and what threats they face could influence which conservation approach to consider. Our findings highlight the need for regional coordination and the use of decision‐support processes to guide effective conservation at landscape scales.

Abstract Background In the phase 3 EMPOWER‐Cervical 1/GOG‐3016/ENGOT‐cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first‐line platinum‐based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. Methods Patients were enrolled regardless of programmed cell death‐ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single‐agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow‐up was 13.6 (6.0–25.3) versus 18.2 (6.0–38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0‐not evaluable) and 9.4 (5.4–14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43–1.68). Median PFS (95% CI) was 4.0 (1.4–8.2) versus 3.7 (1.8–4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50–1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44–13.99). Incidence of treatment‐emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. Discussion While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6‐month shorter median duration of follow‐up versus the overall study population.

Abstract Introduction Osteosarcoma is the most common primary malignancy of the bone. There is a lack of effective treatments for patients who experience relapsed osteosarcoma. One treatment for relapsed patients is gemcitabine and docetaxel combination chemotherapy (GEMDOX). This systematic review aimed to establish the efficacy of this chemotherapy regimen, as well as identify the common severe toxicities that are associated with it. Resistant osteosarcoma cell lines developed from MG‐63 and HOS‐143B were used to represent relapsed osteosarcoma patients in a pre‐clinical study. Results We identified 11 retrospective and Phase II studies that were suitable for inclusion in our review. 10.65% of patients had a response to gemcitabine and docetaxel combination therapy and the disease control rate was 35% (n = 197). 36%, 35.3% and 18.04% of patients experienced grade 3 or 4 neutropenia, thrombocytopenia and anaemia respectively (n = 133). Male patients (X2 = 9.14, p

Abstract The European Commission requested EFSA to update the scientific guidance for the preparation of notifications for authorisation of traditional foods, previously developed following the adoption of Regulation (EU) 2015/2283 on novel foods. This guidance document provides advice on the scientific information needed to be submitted by applicants when submitting traditional food notifications pursuant to Article 14 and traditional food applications pursuant to Article 16 of Regulation (EU) 2015/2283. The safety of a traditional food should be substantiated by data on its composition, its experience of continued use and its proposed conditions of use. Its normal consumption should not be nutritionally disadvantageous. The applicant should integrate the information on the composition and the experience of continued use and provide a concise overall consideration on how this substantiates the history of safe use of the traditional food and how this relates to the proposed conditions of use for the EU. Potential health hazards identified on the basis of compositional data and/or data from the experience of continued use should be discussed. On the basis of the information provided, EFSA will assess the safety related to the consumption of the traditional food under the proposed conditions of use.

Abstract The European Commission requested EFSA to update the scientific guidance for the preparation of applications for authorisation of novel foods, previously developed following the adoption of Regulation (EU) 2015/2283 on novel foods. This guidance document provides advice on the scientific information needed to be submitted by the applicant towards demonstrating the safety of the novel food. Requirements pertain to the description of the novel food, production process, compositional data, specifications, proposed uses and use levels and anticipated intake of the novel food. Furthermore, information needed in sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, toxicological information, nutritional information and allergenicity is also described. The applicant should integrate and interpret the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they are to be discussed in relation to the anticipated intake of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use.