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BackgroundThe development of treatments for freezing of gait (FOG) in Parkinson's disease (PD) requires experimental study set-ups in which FOG is likely to occur, and is amenable to therapeutic interventions. We explore whether the 'Auditory Stroop Task' (AST) can be used to increase cognitive load (and thereby elicit FOG), simultaneously with visual cues (as a therapeutic intervention for FOG). We additionally examined how these two contrasting effects might interact in affecting gait and FOG parameters.ObjectivesWe investigated whether: (1) the 'Auditory Stroop Task' (AST) influences gait in healthy elderly and persons with PD who experience FOG, and increases the frequency of FOG events among PD patients; (2) the AST and visual cues interact; and (3) different versions of the AST exert different cognitive loads.MethodsIn 'Experiment 1', 19 healthy elderly subjects performed a walking task while performing a high and low load version of the AST. Walking with a random numbers task, and walking without cognitive load served as control conditions. In 'Experiment 2', 20 PD patients with FOG and 18 healthy controls performed a walking task with the AST, and no additional cognitive load as control condition. Both experiments were performed with and without visual cues. Velocity, cadence, stride length, and stride time were measured in all subjects. FOG severity was measured in patients.ResultsCompared to the control conditions, the AST negatively affected all gait parameters in both patients and controls. The AST did not increase the occurrence of FOG in patients. Visual cues reduced the decline in stride length induced by cognitive load in both groups. Both versions of the AST exerted similar effects on gait parameters in controls.ConclusionsThe AST is well-suited to simulate the effects of cognitive load on gait parameters, but not FOG severity, in gait experiments in persons with PD and FOG.

This dataset quantifies storm intensity of approximately 130 unique historical storms along the New Jersey coastline from 1980 to 2014 for three separate sea level conditions. Namely, (1) as observed in the historical record; (2) detrended to 1997 mean sea level and (3) adjusted to the 2050 and 2100 sea level rise scenarios presented in the International Panel on Climate Change's (IPCC) Sixth Assessment Report (AR6). Projected sea level scenarios are adjusted to include local vertical land movement. Storm intensity is quantified in terms of erosion potential, considering the combination of total water level, wave heights, and storm duration. The observational dataset includes both tropical and extratropical storms and quantifies both the cumulative (duration) and peak (single hour) storm intensity for each storm and sea level rise (SLR) condition. Additionally, hourly time series of wave characteristics and water levels are provided at 13 locations along the New Jersey coast, facilitating hydrodynamic forcing of nearshore models. The dataset provides the means and methods to directly compare historical storms under future SLR conditions.

Abstract Background Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. Introduction Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. Methods Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. Results The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). Conclusion Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.

Abstract Background Cranial radiotherapy (cRT) can induce hormonal deficiencies as a consequence of significant doses to the hypothalamic-pituitary (HP) axis. In contrast to profound endocrinological follow-up data from survivors of childhood cancer treated with cRT, little knowledge exists for adult cancer patients. Methods A systematic search of the literature was conducted using the PubMed database and the Cochrane library offering the basis for our debate of the relevance of HP axis impairment after cRT in adult cancer patients. Against the background of potential relevance for patients receiving whole brain radiotherapy (WBRT), a particular focus was set on the temporal onset of hypopituitarism and the radiation dose to the HP axis. Results Twenty-eight original papers with a total of 1728 patients met the inclusion criteria. Radiation doses to the HP area ranged from 4 to 97 Gray (Gy). Hypopituitarism incidences ranged from 20 to 93% for adult patients with nasopharyngeal cancer or non-pituitary brain tumors. No study focused particularly on hypopituitarism after WBRT. The onset of hypopituitarism occurred as early as within the first year following cRT (range: 3 months to 25.6 years). However, since most studies started follow-up evaluation only several years after cRT, early onset of hypopituitarism might have gone unnoticed. Conclusion Hypopituitarism occurs frequently after cRT in adult cancer patients. Despite the general conception that it develops only after several years, onset of endocrine sequelae can occur within the first year after cRT without a clear threshold. This finding is worth debating particularly in respect of treatment options for patients with brain metastases and favorable survival prognoses.

Breaching or overtopping of coastal dunes is associated with greater upland damages. Reliable tools are needed to efficiently assess the likelihood of dune erosion during storm events. Existing methods rely on numerical modeling (extensive investment) or insufficiently parameterize the system. To fill this gap, a fragility curve model using a newly developed dune Engineering Demand Parameter (EDP) is introduced. Conceptually, the EDP is similar to the Shield’s parameter in that it represents the ratio of mobilizing terms to stabilizing terms. Physically, the EDP is a measure of storm intensity over the dune’s resilience. To highlight potential applications, the proposed EDP fragility curve models are fit to a spatially and temporally robust dataset and used to predict dune response subjected to varying storm intensities including both extratropical and tropical storm. This approach allows for the probabilistic prediction of dune impacts through an innovative, computationally efficient model. Several different forms of the EDP are tested to determine the best schematization of the dune resilience. The final recommended EDP is the Peak Erosion Intensity (PEI) raised to the fourth power over the product of the dune volume and berm-width squared. Including both storm intensity and resilience terms in the EDP enables comparison of different beach configurations in different storm events fulfilling a need existing vulnerability assessors cannot currently account for directly.

Information on the origin of pollution constitutes an essential step of air quality management as it helps identifying measures to control air pollution. In this work, we review the most widely used source-apportionment methods for air quality management. Using theoretical and real-case datasets we study the differences among these methods and explain why they result in very different conclusions to support air quality planning. These differences are a consequence of the intrinsic assumptions that underpin the different methodologies and determine/limit their range of applicability. We show that ignoring their underlying assumptions is a risk for efficient/successful air quality management as these methods are sometimes used beyond their scope and range of applicability. The simplest approach based on increments (incremental approach) is often not suitable to support air quality planning. Contributions obtained through mass-transfer methods (receptor models or tagging approaches built in air quality models) are appropriate to support planning but only for specific pollutants. Impacts obtained via “brute-force” methods are the best suited but it is important to assess carefully their application range to make sure they reproduce correctly the prevailing chemical regimes. Keywords: Urban air pollution, Source allocation, Source apportionment, Increment, Contribution, Impact, Air quality planning, Brute force, Mitigation strategy

A comprehensive case study of Keansburg Inlet (New Jersey, USA) is presented with the objective of evaluating inlet management alternatives and assessing the influence of an operational flood gate on channel shoaling. The goal of the research is determining the most effective strategy for minimizing the frequency of maintenance dredging. This study compares the effectiveness of (1) traditional structural solutions; (2) modified dredging templates; and (3) assesses the influence of the flood gate operations during conditions representative of a typical year. Alternative analysis is completed using a coupled hydrodynamic–wave model (Delft3D-Flexible Mesh (FM)) with Real Time Control to simulate morphological changes. The model was calibrated and evaluated using collected field data. Water levels are reproduced within 6% of the spring tide range with lag times less than 20 min. The model results and observations suggest sediment transport is dominated by wave action with pronounced variations in dominant wave direction. The results indicate that changes to the operational dredging, or what the authors have termed broadly as “adaptive dredging techniques”, appear to deliver the most promising improvement. Model results suggest that the current operational procedures of the flood gate do not significantly alter the channel infilling rates and patterns during typical (i.e., non-extreme event) conditions.

The ethmoidal region of the skull houses one of the most important sense organs of mammals, the sense of smell. Investigation of the ontogeny and comparative anatomy of internal nasal structures of the macrosmatic order Scandentia is a significant contribution to the understanding of the morphotype of Scandentia with potential implications for our understanding of the primate nasal morphological pattern. For the first time perinatal and adult stages of Ptilocercus lowii and selected Tupaia species were investigated by serial histological sections and high-resolution computed tomography (μCT), respectively. Scandentia show a very common olfactory turbinal pattern of small mammals in having two frontoturbinals, three ethmoturbinals, and one interturbinal between the first and second ethmoturbinal. This indicates a moderately developed sense of smell (moderately macrosmatic). The observed septoturbinal is probably an apomorphic character of Scandentia. A general growth in length occurs during postnatal ontogeny; thus the adult ethmoidal region is proportionally longer compared to the rest of the skull. Throughout ontogeny Ptilocercus has a proportionally longer nasal cavity than Tupaia. Major differences exist between Ptilocercus and Tupaia in regard to the proportions of the nasal cavity which correlate with the position of the orbits. Compared to Tupaia, Ptilocercus shows more anteriorly oriented orbits and has a proportionally longer nasal capsule than Tupaia and based on anatomy probably a higher level of olfactory discrimination. Furthermore, Ptilocercus has a platybasic skull base that resembles a derived feature of Ptilocercidae. In contrast, Tupaia has a distinct septum interorbitale leading to a tropibasic skull, a pattern that is a plesiomorphic character of Tupaiidae and Scandentia in general. This finding helps us to understand the septum interorbitale pattern in Primates. Our results indicate that differences among the investigated Scandentia species are correlated with adaptations to foraging and behavioural biology.

Belgium is one of the areas within Europe experiencing the highest levels of air pollution. A high-resolution (3 km) modelling experiment is employed to provide guidance to policymakers about expected air quality changes in the near future (2026–2035). The regional air quality model AURORA (Air quality modelling in Urban Regions using an Optimal Resolution Approach), driven by output from a regional climate model, is used to simulate several 10-year time slices to investigate the impact of climatic changes and different emission scenarios on near-surface O3 concentrations, one of the key indices for air quality. Evaluation of the model against measurements from 34 observation stations shows that the AURORA model is capable of reproducing 10-year mean concentrations, daily cycles and spatial patterns. The results for the Representative Concentration Pathways (RCP)4.5 emission scenario indicate that the mean surface O3 concentrations are expected to increase significantly in the near future due to less O3 titration by reduced NOx emissions. Applying an alternative emission scenario for Europe is found to have only a minor impact on the overall concentrations, which are dominated by the background changes. Climate change alone has a much smaller effect on the near-surface O3 concentrations over Belgium than the projected emission changes. The very high horizontal resolution that is used in this study results in much improved spatial correlations and simulated peak concentrations compared to a standard 25 km simulation. An analysis of the number of peak episodes during summer revealed that the emission reductions in RCP4.5 result in a 25% decrease of these peak episodes.

Rationale. Cystic fibrosis related diabetes (CFRD) is the most common comorbidity in patients with CF. In spite of increased screening, diagnosis, and treatment of CFRD, the mortality rate in patients with CFRD still far exceeds the mortality rate in those without CFRD. Guidelines suggest that screening for CFRD be performed annually using the 2-hour 75-gram oral glucose tolerance test (OGTT). Adherence to recommended screening has been poor, with only approximately one-quarter of adults with CF undergoing OGTT in 2014. Use of continuous glucose monitoring (CGM) for diagnosis may become an alternative. Objectives. Our objective was to determine whether abnormal CGM predicts subsequent development of CFRD, lung function, and body mass index (BMI) decline and increased rate of CF pulmonary exacerbations in adults with CF. Methods. In a prospective single center pilot trial from September 2009 to September 2010, 21 adult patients due for routine OGTT were recruited to complete simultaneous 3-day CGM and 2-hour 75 gram OGTT. Subsequently, clinical information was reviewed from 2008 to 2015. Conclusions. There was a moderate correlation between interpreted results of 2-hour OGTT and CGM (p=0.03); CGM indicated a greater level of glucose impairment than OGTT. Glucose >200 mg/dL by CGM predicted development of CFRD (p=0.0002).

A standardized methodology for the validation of short-term air quality forecast applications was developed in the framework of the Forum for Air quality Modeling (FAIRMODE) activities. The proposed approach, focusing on specific features to be checked when evaluating a forecasting application, investigates the model's capability to detect sudden changes in pollutant concentration levels, predict threshold exceedances and reproduce air quality indices. The proposed formulation relies on the definition of specific forecast modelling quality objectives and performance criteria, defining the minimum level of quality to be achieved by a forecasting application when it is used for policy purposes. The persistence model, which uses the most recent observed value as the predicted value, is used as a benchmark for the forecast evaluation. The validation protocol has been applied to several forecasting applications across Europe, using different modelling paradigms and covering a range of geographical contexts and spatial scales. The method is successful, with room for improvement, in highlighting shortcomings and strengths of forecasting applications. This provides a useful basis for using short-term air quality forecasts as a supporting tool for providing correct information to citizens and regulators.

Abstract Background When improving the health of local and regional populations, cross-sector collaboration between different policy domains, non-governmental organisations and citizens themselves is needed. Previously, enabling factors and strategies have been identified to improve cross-sector collaboration for health. However, few longitudinal studies have been conducted to understand how the implementation of strategies for cross-sector collaboration changes throughout the collaboration process. The aim of this study is therefore to learn more about the different strategies that were implemented throughout three cross-sector collaboration projects for a healthy living environment. Methods The realist evaluation approach was used to understand how the implemented strategies worked, in which context, why and with what outcomes. Project partners were asked to reflect on their implemented strategies at two different moments in the project timelines, and quarterly updates with project leaders were held. In addition two reference panels were organised for data triangulation. Results Three key insights for successful cross-sector collaboration throughout projects for a healthy living environment were identified, namely 1. Investing in trust among the partners and faith in the project has a positive influence on continuing the collaboration throughout the project; 2. Making stakeholders actively participate throughout the project requires additional strategies after the onset of the project, and 3. Defining roles, tasks, and other prerequisites at the start of the project helps in pursuing the project over time, but needs re-examination throughout the project. These key insights were based on multiple examples of implemented strategies, linked to context, mechanisms and outcomes. Conclusions This study shows the different strategies that can be employed as the collaboration in projects for a healthy living environment progresses. We found that ‘trust’ does not merely include the relationships built between the partners, but at the onset of projects can also be based on faith in the project itself. In addition, as it can be difficult to foresee the right investments and strategies at the onset of the project, frequent reflection moments to choose fitting strategies might benefit regional partners in their cross-sector collaboration for health.

This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs)

Abstract Background The start of complementary feeding in infancy plays an essential role in promoting healthy eating habits. Evidence shows that it is important what infants are offered during this first introduction of solid foods: e.g. starting exclusively with vegetables is more successful for vegetable acceptance than starting with fruits. How infants are introduced to solid foods also matters: if parents are sensitive and responsive to infant cues during feeding, this may promote self-regulation of energy intake and a healthy weight. However, the effectiveness of the what and the how of complementary feeding has never been experimentally tested in the same study. In the current project the what and how (and their combination) are tested in one study to determine their relative importance for fostering vegetable acceptance and self-regulation of energy intake in infants. Methods A four-arm randomized controlled trial (Baby’s First Bites (BFB)) was designed for 240 first-time Dutch mothers and their infants, 60 per arm. In this trial, we compare the effectiveness of (a) a vegetable-exposure intervention focusing on the what in complementary feeding; (b) a sensitive feeding intervention focusing on the how in complementary feeding, (c) a combined intervention focusing on the what and how in complementary feeding; (d) an attention-control group. All mothers participate in five sessions spread over the first year of eating solid foods (child age 4–16 months). Primary outcomes are vegetable consumption, vegetable liking and self-regulation of energy intake. Secondary outcomes are child eating behaviors, child anthropometrics and maternal feeding behavior. Outcomes are assessed before, during and directly after the interventions (child age 18 months), and when children are 24 and 36 months old. Discussion The outcomes are expected to assess the impact of the interventions and provide new insights into the mechanisms underlying the development of vegetable acceptance, self-regulation and healthy eating patterns in infants and toddlers, as well as the prevention of overweight. The results may be used to improve current dietary advice given to parents of their young children on complementary feeding. Trial registration The trial was retrospectively registered during inclusion of participants at the Netherlands National Trial Register (identifier NTR6572) and at ClinicalTrials.gov (NCT03348176). Protocol issue date: 1 April 2018; version number 1.

Abstract Background Prostate cancer is the most commonly diagnosed cancer in men. Radiotherapy represents one major treatment option in different therapeutic settings. As patients increasingly rely on internet-based medical information, we examined the quality of information on radiotherapy and prostate cancer in websites used by laypersons. Methods An Internet search from a patients` perspective was carried out using different search engines (Google, Yahoo and Bing, search terms: “prostate cancer” and “radiotherapy”). The quality of search results was analyzed with regard to the DISCERN score, HON code certification, the JAMA criteria and the ALEXA traffic rank. Results In general, websites were of good quality. The highest quality was found for websites operated by charity organizations. No significant differences in results obtained via the above-mentioned tools were seen for the examined search engines, but Google revealed the most stable search results in terms of temporal changes. Conclusion Patients with prostate cancer can sufficiently inform themselves on general treatment options including radiotherapy on websites directed at laypersons. However, no simple strategy could identify high quality websites in general. For treating physicians, it is important to support patients in interpreting and ranking the vast quantity of information.

The need for a new surveillance approach to understand the clinical outcomes and behaviors of people in care for HIV evolved from the new challenges for monitoring clinical outcomes in the HAART era, the impact of the epidemic on an increasing number of areas in the US, and the need for representative data to describe the epidemic and related resource utilization and needs. The Institute of Medicine recommended that the Centers for Disease Control and Prevention and the Heath Resources and Services Administration coordinate efforts to survey a random sample of HIV-infected persons in care, in order to more accurately measure the need for prevention and care services. The Medical Monitoring Project (MMP) was created to meet these needs. This manuscript describes the evolution and design of MMP, a new nationally representative clinical outcomes and behavioral surveillance system, and describes how MMP data will be used locally and nationally to identify care and treatment utilization needs, and to plan for prevention interventions and services.

Introduction: In patients undergoing percutaneous coronary intervention (PCI), personalised medicine is key to the secondary prevention of ischaemic and bleeding events. To provide an extensive overview of the quality of secondary prevention and of personalised medicine, a consortium in the southeastern region of the Netherlands has created a PCI registry: the South-East Netherlands Heart Registry (Zuid-Oost Nederland Hart Registratie, ZON-HR)., Aim: To visualise and improve personalised secondary prevention post-PCI, focussing on key elements such as antiplatelet treatment, cholesterol management and comorbidities such as diabetes mellitus., Design and Population: A prospective multicentre registry of all consecutive patients undergoing PCI at 4 participating PCI centres and 3 referral centres., Treatment: Interventional procedures and concomitant pharmaceutical treatment are performed in accordance with the guidelines. The ZON-HR promotes risk stratification after PCI using a simplified protocol for a personalised antiplatelet strategy., Data Collection and Quality: Demographics, laboratory values, baseline procedural characteristics and pharmaceutical treatment data are collected. Outcomes include thromboembolic and bleeding complications and medication changes. Data are pseudonymised, and a clinical event committee will review 20% of the adverse events (randomly selected)., Strengths and Weaknesses: This registry represents the entire PCI population and visualises gaps in secondary prevention. Weaknesses are the collection of outcomes and medication changes using mostly patient-reported outcomes., Conclusion: The ZON-HR is a comprehensive PCI registry that provides baseline and follow-up data of a large PCI cohort in the southeastern region of the Netherlands. The ZON-HR aims to improve secondary prevention after PCI and augment personalised treatment that focusses on key elements of secondary prevention., Competing Interests: Conflict of interest: P.J.C. Winkler has received an unrestricted grant from Boehringer Ingelheim. P. Damman has received research grants from Abbott, Philips and AstraZeneca and is a deputy editor of the Netherlands Heart Journal. A.W.J. van ’t Hof has received unrestricted grants from AstraZeneca, Medtronic, Abbott Vascular and Boehringer Ingelheim and is an associate editor of the Netherlands Heart Journal. R.J.M. van Geuns has received grants and personal fees from Boston Scientific, Abbott Vascular, AstraZeneca and Amgen and grants from Infraredx. The other authors report no competing interests or disclosures. E.C. I. Woelders, D.A. M. Peeters, S. Janssen, J.J. P. Luijkx and W.S. Remkes declare that they have no competing interests., (© 2025. The Author(s).)

Background/aim: Hypo-fractionated radiotherapy (HF-RT) is gaining popularity in prostate cancer treatment. HF-RT can lead to cystitis, particularly in cases with small bladder volumes. This study evaluated the bladder volume during a course of moderate HF-RT. This knowledge is required for the protocol of a prospective trial., Patients and Methods: Seventy-six patients receiving HF-RT (20×3.0 Gy) for prostate cancer were retrospectively evaluated. The number of HF-RT sessions with a bladder volume <200 ml and corresponding risk factors were investigated., Results: Mean and median numbers of sessions with a bladder volume <200 ml were 13.4 (±6.7) and 16.0 (interquartile range=8.0-19.0), respectively. Higher numbers of radiotherapy sessions with a bladder volume <200 ml were associated with a pre-radiotherapy volume <200 ml (p<0.001). Mean numbers of sessions with a bladder volume <200 ml were 16.0 (±5.5) in patients with a pre-radiotherapy bladder volume <200 ml and 7.9 (±5.9) in patients with a bladder volume ≥200 ml, respectively., Conclusion: Bladder volume was <200 ml during many HF-RT sessions. Patients with a pre-radiotherapy bladder volume <200 ml may benefit from an app reminding them to drink water before their HF-RT sessions., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Abnormalities in dorsolateral prefrontal cortex (DLPFC) oscillations are neurophysiological signatures of schizophrenia thought to underlie its cognitive deficits. Transcranial magnetic stimulation with electroencephalography (TMS-EEG) provides a measure of cortical oscillations unaffected by sensory relay functionality and/or patients' level of engagement, which are important confounding factors in schizophrenia. Previous TMS-EEG work showed reduced fast, gamma-range oscillations and a slowing of the main DLPFC oscillatory frequency, or natural frequency, in chronic schizophrenia. However, it is unclear whether this DLPFC natural frequency slowing is present in early-course schizophrenia (EC-SCZ) and is associated with symptom severity and cognitive dysfunction., Methods: We applied TMS-EEG to the left DLPFC in 30 individuals with EC-SCZ and 28 healthy control participants. Goal-directed working memory performance was assessed using the AX-Continuous Performance Task. The EEG frequency with the highest cumulative power at the stimulation site, or natural frequency, was extracted. We also calculated the local relative spectral power as the average power in each frequency band divided by the broadband power., Results: Compared with the healthy control group, the EC-SCZ group had reduced DLPFC natural frequency (p = .0000002, Cohen's d = -2.32) and higher DLPFC beta-range relative spectral power (p = .0003, Cohen's d = 0.77). In the EC-SCZ group, the DLPFC natural frequency was inversely associated with negative symptoms. Across all participants, the beta band relative spectral power negatively correlated with AX-Continuous Performance Task performance., Conclusions: DLPFC oscillatory slowing is an early pathophysiological biomarker of schizophrenia that is associated with its symptom severity and cognitive impairments. Future work should assess whether noninvasive neurostimulation, including repetitive TMS, can ameliorate prefrontal oscillatory deficits and related clinical functions in patients with EC-SCZ., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Tuberculosis (TB) remains a significant global health threat with high mortality and efforts to meet WHO End TB Strategy milestones are off-track. It has become clear that TB is not a dichotomous infection with latent and active forms but presents along a disease spectrum. Subclinical TB plays a larger role in transmission than previously thought. Aerosol studies have shown that undiagnosed TB patients, even with paucibacillary disease, can be highly infectious and significantly contribute to TB spread. Encouraging clinical results have been seen with the M72/AS01 E vaccine. If preliminary results can be confirmed in ongoing larger trials, modelling shows the vaccine can positively impact the epidemic. TB preventive therapy (TPT), especially for high-risk groups like people living with HIV and household contacts of drug-resistant TB patients, has shown efficacy but implementation is resource intensive. Treatment options for infectious patients have grown rapidly. New shorter, all-oral treatment regimens represent a breakthrough, but progress is threatened by rising resistance to bedaquiline. Many new chemical entities are entering clinical trials and raise hopes for all-new regimens that could overcome rising resistance rates to conventional agents. More research is needed on the management of complex cases, such as central nervous system TB and severe HIV-associated TB. Post-TB lung disease (PTLD) is an under-recognised but growing concern, affecting millions of survivors with lasting respiratory impairment and increased mortality. Continued investment in development of TB vaccines and therapeutics, treatment shortening, and management of TB sequelae is critical to combat this ongoing public health challenge., (© 2025 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Childhood leukemia accounts for 30% of all pediatric cancer cases with acute lymphoblastic leukemia (ALL) being the most common subtype. Involvement of the gut microbiome in ALL development has recently garnered interest due to an increasing recognition of the key contribution the microbiome plays in maintaining the immune system's homeostatic balance. Commensal gut microbiota provide a first line of defense against different pathogens and gut microbiome immaturity has been implicated in ALL pathogenesis. Several environmental factors such as nutrition, mode of delivery, breastfeeding and, early social or livestock contacts are known to alter the composition of the gut microbiota. Variations in these factors influence the risk of childhood leukemia onset. This review aims to elucidate the risk factors influencing microbial composition in the context of childhood ALL. The link between gut microbiome diversity and childhood ALL offers the opportunity to develop risk-reducing strategies that can be communicated to a broad target population of (future) parents and caregivers for childhood leukemia prevention. Here, we summarize evidence on how promoting a diverse gut microbiome in newborns through simple measures such as increasing social contacts early in life may decrease the risk of developing ALL in these children later on., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Kameri, Jepsen, Stachura, Rüchel, Bhave, Benitez, Crispi, Gratacos, Dragano, Janssen, Borkhardt, Pandyra, Kögler and Fischer.)

Land-use changes threaten ecosystems and are a major driver of species loss. Plants may adapt or migrate to resist global change, but this can lag behind rapid anthropogenic changes to the environment. Our data show that natural modulations of the microbiome of grassland plants in response to experimental land-use change in a common garden directly affect plant phenotype and performance, thus increasing plant tolerance. In contrast, direct effects of fertilizer application and mowing on plant phenotypes were less strong. Land-use intensity-specific microbiomes caused clearly distinguishable plant phenotypes also in a laboratory experiment using gnotobiotic strawberry plants in absence of environmental variation. Therefore, natural modulations of the plant microbiome may be key to species persistence and ecosystem stability. We argue that a prerequisite for this microbiome-mediated tolerance is the availability of diverse local sources of microorganisms facilitating rapid modulations in response to change. Thus, conservation efforts must protect microbial diversity, which can help mitigate the effects of global change and facilitate environmental and human health., (© The Author(s) 2025. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Immunoassays play an important role in drug development of products targeting the immune system. Consistent quality of the results from an immunoassay is essential to make unbiased and accurate claims about the drug product during preclinical and clinical development stages. Assay qualification and validation shed light on the performance of the assay. It is the first evaluation and the verification, respectively, of the assay's performance. This tutorial explains and illustrates the calculation methodology for important assay qualification parameters including precision, relative accuracy, linearity, the lower limit of quantification (LLOQ), the upper limit of quantification (ULOQ), the assay range and dilutability. This tutorial focuses on assays used for (pre-) clinical purposes, characterized by a lognormal distribution of the measurements on its original untransformed scale and by the lack of well characterized reference material. Statistical calculations are illustrated with qualification data from an enzyme-linked immunosorbent assay (ELISA) vaccine immunoassay., (© 2024 John Wiley & Sons Ltd.)

Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site. Outcomes included local recurrence (LR), progression-free survival (PFS), and overall survival (OS). Cumulative incidence analysis was used for LR, Kaplan-Meier estimates for PFS and OS. Covariables included patient, disease, and SRT characteristics. We performed univariable and multivariable analyses (MVA). Among 444 patients, 751 metastases were treated with SRT. Of these, 73% were intracranial and 27% extracranial lesions. Oligometastatic disease (OMD) was present in 66% of the patients. LR after two years occurred significantly more often in intracranial (25%) versus extracranial lesions (7%). In MVA of patients with OMD treated for intracranial sites, higher performance status was significantly associated with longer PFS. Further, higher performance status, biologic subtype (HR-pos./HER2-pos.), and MDT to all sites were significantly associated with longer OS. In MVA of oligometastatic patients treated for extracranial sites, biologic subtype (HR-neg./HER2-pos.) and synchronous metastasis were associated with significantly longer PFS, whereas higher grading was associated with significantly shorter PFS. Moreover, biologic subtype (HR-neg./HER2-neg.) was associated with significantly shorter OS. In conclusion, the role of MDT for breast cancer may vary per clinical scenario. Patients with OMD treated for intracranial lesions who had MDT to all sites showed superior OS. Our results should be validated prospectively., Competing Interests: Declarations. Competing interests: AF has received honoraria from Merck Sharp & Dome. DKa has received research funding from Merck KGaA and Deutsche Krebshilfe; DKr has received honoraria from Astra Zeneca, best practice onkologie, ESO, ESMO, Gilead, medupdate, Merck Sharp & Dohme, Novartis, onkowissen.TV and Pfizer; EG has received honoraria from Astra Zeneca, Novocure, IntraOp and research funding from Astra Zeneca, Novocure, IntraOp and Deutsche Krebshilfe; FW received speaker fees from AstraZeneca, Varian Medical Systems and Merck Sharp & Dohme and travel support for attending meetings from Varian Medical Systems, Novocure GmbH, Fraunhofer MEVIS and Micropos Medical as well as compensation for advisory boards from Novocure GmbH and Merck Sharp & Dohme; JHR received speaker fees from Pfizer Inc., Astra Zeneca, Sanofi and ViewRay Inc., travel reimbursement from Varian Medical Systems as well as research grants from IntraOP Medical and Varian Medical Systems outside the submitted work; MND has received speaker honoraria from Astra Zeneca outside the scope of this study All other authors have no competing interests to declare. Ethical approval: Approval from local ethics committees was acquired for each participating center after approval for the leading study center (Kiel, Germany D582/20)., (© 2024. The Author(s).)

Longitudinal studies are crucial for understanding complex microbiome dynamics and their link to health. We introduce TEMPoral TEnsor Decomposition (TEMPTED), a time-informed dimensionality reduction method for high-dimensional longitudinal data that treats time as a continuous variable, effectively characterizing temporal information and handling varying temporal sampling. TEMPTED captures key microbial dynamics, facilitates beta-diversity analysis, and enhances reproducibility by transferring learned representations to new data. In simulations, it achieves 90% accuracy in phenotype classification, significantly outperforming existing methods. In real data, TEMPTED identifies vaginal microbial markers linked to term and preterm births, demonstrating robust performance across datasets and sequencing platforms., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Rob Knight is a scientific advisory board member and consultant for BiomeSense, Inc., has equity, and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant for DayTwo and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma and has equity and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. Cameron Martino is the founder of Leaven Foods, Inc., and has equity. Gregory Buck is on the Scientific Advisory Board for Juno LTC., (© 2024. The Author(s).)

Background: The microbiome greatly affects health and wellbeing. Evolutionarily, it is doubtful that a host would rely on chance alone to pass on microbial colonization to its offspring. However, the literature currently offers only limited evidence regarding two alternative hypotheses: active microbial shaping by host genetic factors or transmission of a microbial maternal legacy., Results: To further dissect the influence of host genetics and maternal inheritance, we collected two-cell stage embryos from two representative wild types, C57BL6/J and BALB/c, and transferred a mixture of both genotype embryos into hybrid recipient mice to be inoculated by an identical microbiome at birth., Conclusions: Observing the offspring for six generations unequivocally emphasizes the impact of host genetic factors over maternal legacy in constant environments, akin to murine laboratory experiments. Interestingly, maternal legacy solely controlled the microbiome in the first offspring generation. However, current evidence supporting maternal legacy has not extended beyond this initial generation, resolving the aforementioned debate. Video Abstract., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures on animals were performed in accordance with the European Guidelines for use and care of laboratory animals: European Commission Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Experiments were approved by the State Office for Nature, Environment and Consumer Protection (LANUV, State of North Rhine-Westphalia, Germany) under the number 81-02.04.2017.A383. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Low cardiorespiratory fitness (CRF) increases the risk of postoperative morbidity and mortality following major surgery. Assessing CRF preoperatively, by measuring peak oxygen uptake (VO 2peak ) during cardiopulmonary exercise testing (CPET), is valuable yet not widely available. This study aimed to assess whether questionnaires could be used preoperatively to identify high-risk surgical patients., Methods: Healthy participants and patients who underwent CPET completed the FitMáx, Duke Activity Status Index (DASI), the modified 4-questions DASI (M-DASI-4Q), Veterans-Specific Activity Questionnaire (VSAQ), and Metabolic Equivalents of Task (MET) questionnaire. Questionnaire-VO 2peak was compared with CPET-VO 2peak . Overall performance of the questionnaires was assessed by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Furthermore, corresponding to the Youden index or pre-specified levels, sensitivity, specificity, and predictive values were determined., Results: In total, 361 participants were included. All questionnaires showed high AUC values to identify high-risk patients, defined on the basis of CPET-VO 2peak thresholds. FitMáx and VSAQ demonstrated superior results compared to the other questionnaires. Based on the Youden index, the optimal questionnaire-VO 2peak cut-off values were 20.6, 21.3, and 26.1 ml·kg -1 ·min -1 for the FitMáx and 16.3, 18.2, and 20.4 ml·kg -1 ·min -1 for the VSAQ corresponding to the VO 2peak thresholds 16.0, 18.2 and 24.5 ml·kg -1 ·min -1 respectively., Conclusion: The ability to identify high-risk surgical patients preoperatively (defined by the CPET-VO 2peak thresholds) by the FitMáx and the VSAQ indicates that they could be used to identify high-risk surgical patients. Patients with a poor predicted VO 2peak  ≤ 21.3 and ≤ 18.2 ml·kg -1 ·min -1 , respectively for FitMáx and VSAQ, should be referred to formal preoperative (cardiopulmonary) exercise testing., Trial Registration: The study was registered as NL-OMON23304 in the Overview of Medical Research in the Netherlands, retrospectively at 28-04-2020., Competing Interests: Declarations. Ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethical approval for this study (reference number N18.051) was provided by the authorised Medical Research Ethics Committee of the MMC, Veldhoven, the Netherlands on 30 April 2018. Informed consent for participation was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: In recent years, ultra-high dose rate (UHDR) irradiation has emerged as a promising innovative approach to cancer treatment. Characteristic feature of this regimen, commonly referred to as FLASH effect, demonstrated primarily for electrons, photons, or protons, is the improved normal tissue sparing, whereas the tumor control is similar to the one of the conventional dose-rate (CDR) treatments. The FLASH mechanism is, however, unknown. One major question is whether this effect is maintained when using densely ionizing (high-LET) heavy nuclei., Methods Materials: Here, we report the effects of 20 Gy UHDR heavy ion irradiation in clinically relevant conditions, ie, at high-LET in the spread-out Bragg peak of a 12 C beam using an osteosarcoma mouse model., Results: We show that UHDR irradiation was less toxic in the normal tissue compared with CDR while maintaining tumor control. The immune activation was also comparable in UHDR and CDR groups. Both UHDR and CDR exposures steered the metagenome toward a balanced state., Conclusions: These results suggest that the UHDR irradiations can improve the safety and effectiveness of heavy ion therapy, and provide a crucial benchmark for current mechanistic FLASH models. However, additional experiments are needed to validate these findings across other animal and tumor models., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Population models can be a useful tool for ecological risk assessment to increase ecological realism. In the present study, population models were used to extrapolate toxicity test results of four metals (Ag, Cu, Ni, Zn) to the population level. In total, three primary producers, five invertebrate species, and five fish species were covered. The ecological modeling-based laboratory to population effect extrapolation factor (ECOPEX factor), defined as the ratio of the predicted 10% effect concentration (EC10) at the population level and the observed EC10 for the laboratory toxicity test, ranged from 0.7 to 78.6, with a median of 2.8 (n = 27). Population modeling indicated clearly higher effect concentrations in most of the cases (ECOPEX factor >2 in 14 out of 27 cases), but in some cases the opposite was observed (in three out of 27 cases). We identified five main contributors to the variability in ECOPEX factors: (1) uncertainty about the toxicity model, (2) uncertainty about the toxicity mechanism of the metal, (3) uncertainty caused by test design, (4) impact of environmental factors, and (5) impact of population endpoint chosen. Part of the uncertainty results from a lack of proper calibration data. Nonetheless, extrapolation with population models typically reduced the variability in EC10 values between tests. To explore the applicability of population models in a regulatory context, we included population extrapolations in a species sensitivity distribution for Cu, which increased the hazardous concentration for 5% of species by a factor 1.5 to 2. Furthermore, we applied a fish population model in a hypothetical Water Framework Directive case using monitored Zn concentrations. This article includes recommendations for further use of population models in (metal) risk assessment. Environ Toxicol Chem 2024;43:2308-2328. © 2024 SETAC., (© 2024 SETAC.)

Pathogenic variants in the ryanodine receptor 1 ( RYR1 ) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype-phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient's phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype-phenotype correlations., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background/aim: Patients irradiated for prostate cancer may experience urinary toxicity, particularly if the bladder volume is small. A mobile application (app) that reminds the patients to drink water prior to each radiation fraction may help avoid small volumes. This study investigating bladder volumes during a radiotherapy course is a prerequisite for a prospective trial testing such a reminder app., Patients and Methods: Frequency of bladder volumes <200 ml and seven potential risk factors were retrospectively evaluated in 72 patients receiving external beam radiotherapy for non-metastatic prostate cancer., Results: The mean and median values of the numbers of radiation fractions with bladder volumes <200 ml were 17.8 (standard deviation=12.0) and 16.5 (interquartile range Q1-Q3=7.5-29.5) fractions, respectively. Higher numbers of fractions with volumes <200 ml were significantly associated with pre-radiotherapy bladder volumes <200 ml (p<0.001) and high-risk prostate cancer (p=0.014)., Conclusion: The proportion of bladder volumes <200 ml during the radiotherapy course was high and needs to be decreased. Pre-radiotherapy bladder volume and risk level of prostate cancer were significant risk factors for higher numbers of fractions with volumes <200 ml. These results are important for designing a prospective trial., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen. Its RNA genome consists of two negative-sense segments (L and M) with one gene each, and one ambisense segment (S) with two opposing genes separated by the noncoding "intergenic region" (IGR). These vRNAs and the complementary cRNAs are encapsidated by nucleoprotein (N). Using iCLIP2 (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to map all N-vRNA and N-cRNA interactions, we detect N coverage along the L and M segments. However, the S segment vRNA and cRNA each contain approximately 100 non-encapsidated nucleotides stretching from the IGR into the 5'-adjacent reading frame. These exposed regions are RNase-sensitive and predicted to form stem-loop structures with the mRNA transcription termination motif positioned near the top. Moreover, optimal S segment transcription and replication requires the entire exposed region rather than only the IGR. Thus, the RVFV S segment contains a central, non-encapsidated RNA region with a functional role., (© 2024. The Author(s).)

Background: Bone metastasis in advanced cancer is challenging because of pain, functional issues, and reduced life expectancy. Treatment planning is complex, with consideration of factors such as location, symptoms, and prognosis. Prognostic models help guide treatment choices, with Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) showing promise in predicting survival for initial spinal metastases and extremity metastases treated with surgery or radiotherapy. Improved therapies extend patient lifespans, increasing the risk of subsequent skeletal-related events (SREs). Patients experiencing subsequent SREs often suffer from disease progression, indicating a deteriorating condition. For these patients, a thorough evaluation, including accurate survival prediction, is essential to determine the most appropriate treatment and avoid aggressive surgical treatment for patients with a poor survival likelihood. Patients experiencing subsequent SREs often suffer from disease progression, indicating a deteriorating condition. However, some variables in the SORG prediction model, such as tumor histology, visceral metastasis, and previous systemic therapies, might remain consistent between initial and subsequent SREs. Given the prognostic difference between patients with and without a subsequent SRE, the efficacy of established prognostic models-originally designed for individuals with an initial SRE-in addressing a subsequent SRE remains uncertain. Therefore, it is crucial to verify the model's utility for subsequent SREs., Question/purpose: We aimed to evaluate the reliability of the SORG-MLAs for survival prediction in patients undergoing surgery or radiotherapy for a subsequent SRE for whom both the initial and subsequent SREs occurred in the spine or extremities., Methods: We retrospectively included 738 patients who were 20 years or older who received surgery or radiotherapy for initial and subsequent SREs at a tertiary referral center and local hospital in Taiwan between 2010 and 2019. We excluded 74 patients whose initial SRE was in the spine and in whom the subsequent SRE occurred in the extremities and 37 patients whose initial SRE was in the extremities and the subsequent SRE was in the spine. The rationale was that different SORG-MLAs were exclusively designed for patients who had an initial spine metastasis and those who had an initial extremity metastasis, irrespective of whether they experienced metastatic events in other areas (for example, a patient experiencing an extremity SRE before his or her spinal SRE would also be regarded as a candidate for an initial spinal SRE). Because these patients were already validated in previous studies, we excluded them in case we overestimated our result. Five patients with malignant primary bone tumors and 38 patients in whom the metastasis's origin could not be identified were excluded, leaving 584 patients for analysis. The 584 included patients were categorized into two subgroups based on the location of initial and subsequent SREs: the spine group (68% [399]) and extremity group (32% [185]). No patients were lost to follow-up. Patient data at the time they presented with a subsequent SRE were collected, and survival predictions at this timepoint were calculated using the SORG-MLAs. Multiple imputation with the Missforest technique was conducted five times to impute the missing proportions of each predictor. The effectiveness of SORG-MLAs was gauged through several statistical measures, including discrimination (measured by the area under the receiver operating characteristic curve [AUC]), calibration, overall performance (Brier score), and decision curve analysis. Discrimination refers to the model's ability to differentiate between those with the event and those without the event. An AUC ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An AUC of 0.7 is considered clinically acceptable discrimination. Calibration is the comparison between the frequency of observed events and the predicted probabilities. In an ideal calibration, the observed and predicted survival rates should be congruent. The logarithm of observed-to-expected survival ratio [log(O:E)] offers insight into the model's overall calibration by considering the total number of observed (O) and expected (E) events. The Brier score measures the mean squared difference between the predicted probability of possible outcomes for each individual and the observed outcomes, ranging from 0 to 1, with 0 indicating perfect overall performance and 1 indicating the worst performance. Moreover, the prevalence of the outcome should be considered, so a null-model Brier score was also calculated by assigning a probability equal to the prevalence of the outcome (in this case, the actual survival rate) to each patient. The benefit of the prediction model is determined by comparing its Brier score with that of the null model. If a prediction model's Brier score is lower than the null model's Brier score, the prediction model is deemed as having good performance. A decision curve analysis was performed for models to evaluate the "net benefit," which weighs the true positive rate over the false positive rate against the "threshold probabilities," the ratio of risk over benefit after an intervention was derived based on a comprehensive clinical evaluation and a well-discussed shared-decision process. A good predictive model should yield a higher net benefit than default strategies (treating all patients and treating no patients) across a range of threshold probabilities., Results: For the spine group, the algorithms displayed acceptable AUC results (median AUCs of 0.69 to 0.72) for 42-day, 90-day, and 1-year survival predictions after treatment for a subsequent SRE. In contrast, the extremity group showed median AUCs ranging from 0.65 to 0.73 for the corresponding survival periods. All Brier scores were lower than those of their null model, indicating the SORG-MLAs' good overall performances for both cohorts. The SORG-MLAs yielded a net benefit for both cohorts; however, they overestimated 1-year survival probabilities in patients with a subsequent SRE in the spine, with a median log(O:E) of -0.60 (95% confidence interval -0.77 to -0.42)., Conclusion: The SORG-MLAs maintain satisfactory discriminatory capacity and offer considerable net benefits through decision curve analysis, indicating their continued viability as prediction tools in this clinical context. However, the algorithms overestimate 1-year survival rates for patients with a subsequent SRE of the spine, warranting consideration of specific patient groups. Clinicians and surgeons should exercise caution when using the SORG-MLAs for survival prediction in these patients and remain aware of potential mispredictions when tailoring treatment plans, with a preference for less invasive treatments. Ultimately, this study emphasizes the importance of enhancing prognostic algorithms and developing innovative tools for patients with subsequent SREs as the life expectancy in patients with bone metastases continues to improve and healthcare providers will encounter these patients more often in daily practice., Level of Evidence: Level III, prognostic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Atomically precise graphene nanoribbons (GNRs) synthesized from the bottom-up exhibit promising electronic properties for high-performance field-effect transistors (FETs). The feasibility of fabricating FETs with GNRs (GNRFETs) has been demonstrated, with ongoing efforts aimed at further improving their performance. However, their long-term stability and reliability remain unexplored, which is as important as their performance for practical applications. In this work, we fabricated short-channel FETs with nine-atom-wide armchair GNRs (9-AGNRFETs). We revealed that the on-state ( I ON ) current performance of the 9-AGNRFETs deteriorates significantly over consecutive full transistor on and off logic cycles, which has neither been demonstrated nor previously considered. To address this issue, we deposited a thin ∼10 nm thick atomic layer deposition (ALD) layer of aluminum oxide (Al 2 O 3 ) directly on these devices. The integrity, compatibility, electrical performance, stability, and reliability, of the GNRFETs before and/or after Al 2 O 3 deposition were comprehensively studied. The results indicate that the observed decline in electrical device performance is most likely due to the degradation of contact resistance over multiple measurement cycles. We successfully demonstrated that the devices with the Al 2 O 3 layer operate well up to several thousand continuous full cycles without any degradation. Our study offers valuable insights into the stability and reliability of GNR transistors, which could facilitate their large-scale integration into practical applications.

Background and Aims: Chronic wounds present a growing challenge in the aging population, resulting in an extended course of treatment and an increased influx of patients with recalcitrant wounds seeking admission to hospitals. Furthermore, the general trend in patient care is toward simple and inexpensive treatment methods, feasible in an outpatient setting with little material costs. This retrospective case study aims to elucidate the operative procedure and outcomes associated with hair follicle unit transplantation utilizing punch grafts from the scalp for the management of hard-to-heal wounds., Methods: A cohort of 28 patients, comprising 20 males and eight females, with a mean age of 72.61 years (range: 48-89) and an average wound area of 82.49 cm 2 , underwent dissection of punch grafts containing hair follicles (2-3 mm in diameter) from the scalp. Subsequently, these grafts were transplanted into the wound bed. The retrospective evaluation of ulcer healing encompassed photo documentation and clinical records, while patient satisfaction was assessed through structured questionnaires., Results: In 78.6% (22) of the cases, a favorable impact on wound healing was observed, characterized by epithelization, and in 57.1% (16) of the patients, complete wound closure was achieved. With the exception of one donor site, all other sites healed without complications. The patient survey indicated that the majority of individuals subjected to the procedure did not perceive it as painful or time-consuming. Notably, 81% (17) of individuals expressed a willingness to undergo the treatment again. Even in challenging wound conditions, such as pyoderma gangrenosum, our method demonstrated a positive effect on wound healing., Conclusion: Within our cohort, the utilization of hair follicle units in the management of hard-to-heal wounds resulted in either complete or partial wound closure for the majority of patients, accompanied by minimal morbidity, reduced operation time, and a low incidence of complications and associated costs., Competing Interests: The author declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Fluorescence molecular imaging plays a vital role in image-guided surgery. In this context, the urokinase plasminogen activator receptor (uPAR) is an interesting biomarker enabling the detection and delineation of various tumor types due to its elevated expression on both tumor cells and the tumor microenvironment. In this study, anti-uPAR Nanobodies (Nbs) are generated through llama immunization with human and murine uPAR protein. Extensive in vitro characterization and in vivo testing with radiolabeled variants are conducted to assess their pharmacokinetics and select lead compounds. Subsequently, the selected Nbs are converted into fluorescent agents, and their application for fluorescence-guided surgery is evaluated in various subcutaneous and orthotopic tumor models. The study yields a panel of high-affinity anti-uPAR Nbs, showing specific binding across multiple types of cancer cells in vitro and in vivo. Lead fluorescently-labeled compounds exhibit high tumor uptake with high contrast at 1 h after intravenous injection across all assessed uPAR-expressing tumor models, outperforming a non-targeting control Nb. Additionally, rapid and accurate tumor localization and demarcation are demonstrated in an orthotopic human glioma model. Utilizing these Nbs can potentially enhance the precision of surgical tumor resection and, consequently, improve survival rates in the clinic., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Numerous studies provide critical analyses of TV minority representations but only few examine successful portrayals. Moreover, there is no consensus on what makes a given depiction successful and how to measure it. Bringing insights from representation studies and media psychology, we propose that successful representations showcase minorities in a way which may foster audience engagement with characters and improve their diversity attitudes. In the current project, we developed a quantitative content analysis codebook with the following representation strategies: portrayal of minority experiences, recognizable representation, attractive representation, psychological depth, stereotypical representation, and friendly interactions. We demonstrate our approach by analyzing the portrayal of non-heterosexual and Black characters in Sex Education . We coded all the scenes with Eric, Adam, and Jackson from the first season of the TV show. Results indicate that these characters are predominantly shown as recognizable to viewers and in friendly interactions with other people. Moreover, they are depicted with attractive personality traits, and indicators of psychological depth. They also undergo various minority experiences. Some stereotypes about gay men are shown but anti-Black stereotypes are rare. In the results' discussion, we suggest different ways of using our codebook in future studies.

Background/aim: We investigated grade ≥2 dermatitis in patients irradiated for breast cancer. This study evaluated associations between dermatitis and the season during which radiotherapy took place., Patients and Methods: Associations between the season and grade ≥2 dermatitis were retrospectively evaluated in 327 breast cancer patients. Seasons were March to May (spring), June to August (summer), September to November (autumn), and December to February (winter). Subgroup analyses were performed considering fractionation, radiation technique, treatment volume, radiation boost, and deep-inspiration breath-hold technique. Furthermore, warmer and cooler months were compared., Results: The season had no significant impact on the rate of grade ≥2 dermatitis in the entire cohort (p=0.63) nor in the subgroup analyses (p-values between 0.17 and 0.82). No significant difference in rate was found between warm and cool months., Conclusion: Grade ≥2 dermatitis was not associated with the season during which radiotherapy was performed. This factor may not be important for stratification in prospective trials., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The aim of this work was to assess the current state of digitalization in radiation oncology departments in Germany, Austria, and Switzerland., Methods: A comprehensive survey was conducted in a digital format, consisting of 53 questions that covered various aspects of digitalization including patient workflow, departmental organization, radiotherapy planning, and employee-related aspects., Results: Overall, 120 forms were eligible for evaluation. Participants were mainly physicians or medical physicists responsible for digitalization aspects in their departments. Nearly 70% of the institutions used electronic patient records, with 50% being completely paperless. However, the use of smartphone apps for electronic patient reported outcomes (ePROMs) and digital health applications (DIGA) was limited (9% and 4.9%, respectively). In total, 70.8% of the radio-oncology departments had interfaces with diagnostic departments, and 36% had digital interchanges with other clinics. Communication with external partners was realized mainly through fax (72%), e‑mails (55%), postal letters (63%), or other digital exchange formats (28%). Almost half of the institutions (49%) had dedicated IT staff for their operations., Conclusion: To the best of our knowledge, this survey is the first of its kind conducted in German-speaking radiation oncology departments within the medical field. The findings suggest that there is a varied level of digitalization implementation within these departments, with certain areas exhibiting lower rates of digitalization that could benefit from targeted improvement initiatives., (© 2023. The Author(s).)

In the framework of the Forum for Air Quality Modelling in Europe (FAIRMODE), a modelling intercomparison exercise for computing NO 2 long-term average concentrations in urban districts with a very high spatial resolution was carried out. This exercise was undertaken for a district of Antwerp (Belgium). Air quality data includes data recorded in air quality monitoring stations and 73 passive samplers deployed during one-month period in 2016. The modelling domain was 800 × 800 m 2 . Nine modelling teams participated in this exercise providing results from fifteen different modelling applications based on different kinds of model approaches (CFD - Computational Fluid Dynamics-, Lagrangian, Gaussian, and Artificial Intelligence). Some approaches consisted of models running the complete one-month period on an hourly basis, but most others used a scenario approach, which relies on simulations of scenarios representative of wind conditions combined with post-processing to retrieve a one-month average of NO 2 concentrations. The objective of this study is to evaluate what type of modelling system is better suited to get a good estimate of long-term averages in complex urban districts. This is very important for air quality assessment under the European ambient air quality directives. The time evolution of NO 2 hourly concentrations during a day of relative high pollution was rather well estimated by all models. Relative to high resolution spatial distribution of one-month NO 2 averaged concentrations, Gaussian models were not able to give detailed information, unless they include building data and street-canyon parameterizations. The models that account for complex urban geometries (i.e. CFD, Lagrangian, and AI models) appear to provide better estimates of the spatial distribution of one-month NO 2 averages concentrations in the urban canopy. Approaches based on steady CFD-RANS (Reynolds Averaged Navier Stokes) model simulations of meteorological scenarios seem to provide good results with similar quality to those obtained with an unsteady one-month period CFD-RANS simulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aim: Pneumonitis is a serious radiotherapy complication. This study, which is a prerequisite for a prospective trial, aimed to identify the prevalence of pneumonitis and risk factors in elderly patients with lung cancer., Patients and Methods: Ninety-eight lung cancer patients aged ≥65 years were included. Seventeen factors were investigated regarding grade ≥2 pneumonitis at 24 weeks following radiotherapy., Results: The prevalence of grade ≥2 pneumonitis at 24 weeks was 27.3%. On univariate analysis, a significant association was observed for mean (ipsilateral) lung dose (MLD; ≤13.0 vs. 13.1-20.0 vs. >20.0 Gy; 0% vs. 24.9% vs. 48.7%). Results were significant also for ≤13.0 vs. >13.0 Gy (0% vs. 37.1%) or ≤20.0 vs. >20.0 Gy (13.4% vs. 48.7%). MLD achieved significance on multivariate analysis., Conclusion: Elderly patients receiving MLDs >13.0 Gy, particularly >20.0 Gy, have a high risk of grade ≥2 pneumonitis. These results are important for designing a prospective trial., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial., Patients and Methods: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated., Results: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001)., Conclusion: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)