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Background: The number of cancer survivors has increased in recent decades, and the majority of them suffer from sequelae of their disease and treatment. This study, which is part of the larger research project OPTILATER, aims to explore different aspects of care services for long-term survivors (≥ 5 years after initial cancer diagnosis) in Germany. The study places an emphasis on the situation of people from different age groups, with different socio-demographic and cultural backgrounds, and sexually and gender diverse individuals. Methods: To investigate experiences related to follow-up care, focus groups (n = 2) will be conducted with members of patient advisory councils and advocacy groups, representatives of communities, healthcare workers and networks, as well as members of Associations of Statutory Health Insurance Physicians. Guided interviews will be carried out with patients and relatives (n = 40) to investigate needs, barriers and obstacles in terms of follow-up care. On this basis, additional focus groups (n = 2) will be carried out to derive possible scenarios for improving the consideration of needs. Focus groups and interviews will follow a semi-structured format and will be analysed content-analytically. Focus groups and interviews will be conducted online, recorded, transcribed, and analysed independently by two persons. Discussion: The qualitative approach is considered suitable because of the exploratory research aims. The identification of experiences and barriers can reveal disparities and optimization potential in the care of long-term cancer survivors. [ABSTRACT FROM AUTHOR]

The discovery of gravitational waves, first observed in September 2015 following the merger of a binary black hole system, has already revolutionised our understanding of the Universe. This was further enhanced in August 2017, when the coalescence of a binary neutron star system was observed both with gravitational waves and a variety of electromagnetic counterparts; this joint observation marked the beginning of gravitational multimessenger astronomy. The Einstein Telescope, a proposed next-generation ground-based gravitational-wave observatory, will dramatically increase the sensitivity to sources: the number of observations of gravitational waves is expected to increase from roughly 100 per year to roughly 100’000 per year, and signals may be visible for hours at a time, given the low frequency cutoff of the planned instrument. This increase in the number of observed events, and the duration with which they are observed, is hugely beneficial to the scientific goals of the community but poses a number of significant computing challenges. Moreover, the currently used computing algorithms do not scale to this new environment, both in terms of the amount of resources required and the speed with which each signal must be characterised. This contribution will discuss the Einstein Telescope's computing challenges, and the activities that are underway to prepare for them. Available computing resources and technologies will greatly evolve in the years ahead, and those working to develop the Einstein Telescope data analysis algorithms will need to take this into account. It will also be important to factor into the initial development of the experiment's computing model the availability of huge parallel HPC systems and ubiquitous Cloud computing; the design of the model will also, for the first time, include the environmental impact as one of the optimisation metrics.

We describe a time-resolved nascent single-cell RNA sequencing (RNA-seq) approach that measures gene-specific transcriptional noise and the fraction of active genes in S. cerevisiae. Most genes are expressed with near-constitutive behavior, while a subset of genes show high mRNA variance suggestive of transcription bursting. Transcriptional noise is highest in the cofactor/coactivator-redundant (CR) gene class (dependent on both SAGA and TFIID) and strongest in TATA-containing CR genes. Using this approach, we also find that histone gene transcription switches from a low-level, low-noise constitutive mode during M and M/G1 to an activated state in S phase that shows both an increase in the fraction of active promoters and a switch to a noisy and bursty transcription mode. Rapid depletion of cofactors SAGA and MED Tail indicates that both factors play an important role in stimulating the fraction of active promoters at CR genes, with a more modest role in transcriptional noise., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

REBa 2 Cu 3 O 7 - x (REBCO, RE = rare earth)-coated conductor is a competitive option in terms of current-carrying capacity and high-stress durability in developing high-field magnets for nuclear magnetic resonance (NMR) research. Meanwhile, a technical challenge in utilizing a stand-alone REBCO NMR magnet is an unexpected difference in the field uniformity between the designed and measured values after being constructed and charged, i.e., harmonic errors. Bortot et al., and Li et al., reported analytic evidence of the related issue. However, sufficient research has not yet been conducted, so evidence should be supplemented further. Here we report harmonic errors due to screening current and inconsistent conductor thickness, confirmed by a 400 MHz 1 H NMR magnet development project. The magnet was first charged up to its operating current, and then multiple overcharge-discharge cycles were applied, which was an empirically optimized operation protocol. A field mapping device obtained magnetic fields at designated locations in the room-temperature bore. The result showed over 100 ppm field uniformity difference between designed and measured values. A simulation model was developed considering screening current and inconsistent conductor thickness for reproducing the field distribution. Comparison of voltages and fields between simulation and measurement validated the model. Further analysis of the overcharge-discharge effect on harmonic errors demonstrated that even and odd-order harmonics are mainly attributed to screening current and geometric inconsistency while confirming the limitation of the screening current mitigation effect. Hence, we concluded that the desirable requirement of the sub-ppm level field uniformity generation might be barely possible with the current REBCO NMR magnet design approach., (© 2024. The Author(s).)

Background: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs., Methods: For patients with large AVMs treated by time-staged GKS over 10 years, time-staged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis., Results: Ninety-six patients were analyzed. For AVMs in the 10-20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20-30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10-20 mL, 20-30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively. Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH., Conclusion: Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

The nexus between eosinophils and microbes is attracting increasing attention. We previously showed that airway administration of sterile microbial products contained in dust collected from traditional dairy farms virtually abrogated bronchoalveolar lavage (BAL) eosinophilia and other cardinal asthma phenotypes in allergen-sensitized specific pathogen-free (SPF) mice. Interestingly, comparable inhibition of allergen-induced BAL eosinophilia and promotion of airway barrier integrity were found upon administration of a sterile, pharmacological-grade bacterial lysate, OM-85, to the airway compartment of allergen-sensitized SPF mice. Here, we asked whether intrinsic properties of airway-delivered microbial products were sufficient to inhibit allergic lung inflammation or whether these effects were mediated by reprogramming of the host microbiota. We compared germ-free (GF) mice and offspring of GF mice associated with healthy mouse gut microbiota and maintained under SPF conditions for multiple generations (Ex-GF mice). These mice were treated intranasally with OM-85 and evaluated in the ovalbumin and Alternaria models of allergic asthma focusing primarily on BAL eosinophilia. Levels of allergen-induced BAL eosinophilia were comparable in GF and conventionalized Ex-GF mice. Airway administration of the OM-85 bacterial lysate was sufficient to inhibit allergen-induced lung eosinophilia in both Ex-GF and GF mice, suggesting that host microbiota are not required for the protective effects of bacterial products in these models and local airway exposure to microbial products is an effective source of protection. OM-85-dependent inhibition of BAL eosinophilia in GF mice was accompanied by suppression of lung type 2 cytokines and eosinophil-attracting chemokines, suggesting that OM-85 may work at least by decreasing eosinophil lung recruitment., Competing Interests: Conflict of interest statement. D.V. and V.P. are inventors in PCT/EP2019/074562 (“Method of Treating and/or Preventing Asthma, Asthma Exacerbations, Allergic Asthma and/or Associated Conditions with Microbiota Related to Respiratory Disorders”). The rest of the authors have no relevant conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

The novel Oxathiazinane derivative GP-2250 (Misetionamide) displays antineoplastic activity in vitro and in vivo, as previously shown in pancreatic cancer cells and in patient-derived mouse xenografts (PDX). Currently, GP 2250 is under phase I clinical trial in pancreatic ductal adenocarcinoma (PDAC). GP-2250 in combination with Gemcitabine displays a high synergistic capacity in various primary and established pancreatic cancer cell lines. Additionally, in the eight PDX models tested, the drug combination was superior in reducing tumor volume with an aggregate tumor regression (ATR) of 74% compared to Gemcitabine alone (ATR: 10%). Similarly, in a PDX maintenance setting following two weeks of treatment with nab-Paclitaxel plus Gemcitabine, the combination of GP-2250 plus Gemcitabine resulted in outstanding tumor control (ATR: 79%) compared to treatment with Gemcitabine alone (ATR: 60%). Furthermore, GP-2250 reduced the ratio of tumor-initiating CD133 + markers on the surface of PDAC cells in spheroid cultures, indicating a possible mechanism for the synergistic effect of both substances. Considering the high tolerability of GP 2250, these results may open up a new approach to maintenance therapy with GP-2250/Gemcitabine combination following nab-Paclitaxel plus Gemcitabine as first-line treatment.

Statement of Problem: Scan bodies play a crucial role in the accuracy of digital implant scans by serving as implant-positioning transfer devices. Previous literature has demonstrated the effects of scan body characteristics on the accuracy of digital implant scans. However, the optimal application methods of scan bodies to enhance scanning accuracy remain unclear., Purpose: The purpose of this systematic review was to determine the optimal application methods of scan bodies to enhance the accuracy of digital implant scans., Material and Methods: An electronic search was conducted by using the PubMed (MEDLINE), Web of Science, Cochrane Library, and Embase databases from November 2018 to 2023. Relevant references from the included studies were further screened manually for eligibility. Following the population, intervention, comparison, and outcome (PICO) criteria, a research question focused on identifying the optimal application method for effectively using scan bodies to enhance scanning accuracy was developed. Specific inclusion criteria involved in vitro and in vivo studies. The Checklist for Reporting In Vitro Studies (CRIS) guidelines were followed and the assessment of the risk of bias in the included studies was conducted., Results: Sixteen articles that met the eligibility criteria were included in this systematic review. Two studies investigated the effect of scan body bevel orientation on the accuracy of digital implant scans, and 3 examined the impact of tightening torque on scan bodies. Among the studies focusing on completely edentulous arches, 5 recommended the use of auxiliary geometric devices on the dental arch to enhance scanning accuracy. However, 2 studies reported no improvements in accuracy after splinting scan bodies with thread., Conclusions: Different techniques for applying scan bodies, such as configuring bevel orientation, adjusting tightening torque, and attaching auxiliary geometric devices, influence the accuracy of digital implant scans. For scanning completely edentulous arches, attaching auxiliary devices to scan bodies to cover the edentulous ridge effectively enhances scanning accuracy., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Converging evidence indicates that both dopamine and glutamate neurotransmission within the nucleus accumbens (NAc) play a role in psychostimulant self-administration and relapse in rodent models. Increased NAc dopamine release from ventral tegmental area (VTA) inputs is critical to psychostimulant self-administration and NAc glutamate release from prelimbic prefrontal cortex (PFC) inputs synapsing on medium spiny neurons (MSNs) is critical to reinstatement of psychostimulant-seeking after extinction. The regulation of the activity of MSNs by VTA dopamine inputs has been extensively studied, and recent findings have demonstrated that VTA glutamate neurons target the NAc medial shell. Here, we determined whether the mesoaccumbal glutamatergic pathway plays a role in psychostimulant conditioned place preference and self-administration in mice. We used optogenetics to induce NAc release of glutamate from VTA inputs during the acquisition, expression, and reinstatement phases of cocaine- or methamphetamine-induced conditioned place preference (CPP), and during priming-induced reinstatement of cocaine-seeking behavior. We found that NAc medial shell release of glutamate resulting from the activation of VTA glutamatergic fibers did not affect the acquisition of cocaine-induced CPP, but it blocked the expression, stress- and priming-induced reinstatement of cocaine- and methamphetamine CPP, as well as it blocked the priming-induced reinstatement of cocaine-seeking behavior after extinction. These findings indicate that in contrast to the well-recognized mesoaccumbal dopamine system that is critical to psychostimulant reward and relapse, there is a parallel mesoaccumbal glutamatergic system that suppresses reward and psychostimulant-seeking behavior., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Magnetic Particle Imaging (MPI) is an emerging tomographic modality that allows for precise three-dimensional (3D) mapping of magnetic nanoparticles (MNPs) concentration and distribution. Although significant progress has been made towards improving MPI since its introduction, scaling it up for human applications has proven challenging. High-quality images have been obtained in animal-scale MPI scanners with gradients up to 7 T/m/μ 0 , however, for MPI systems with bore diameters around 200 mm the gradients generated by electromagnets drop significantly to below 0.5 T/m/μ 0 . Given the current technological limitations in image reconstruction and the properties of available MNPs, these low gradients inherently impose limitations on improving MPI resolution for higher precision medical imaging. Utilizing superconductors stands out as a promising approach for developing a human-scale MPI system. In this study, we introduce, for the first time, a human-scale amplitude-modulated (AM) MPI system with superconductor-based selection coils. The system achieves an unprecedented magnetic field gradient of up to 2.5 T/m/μ 0 within a 200 mm bore diameter, enabling large fields of view of 100 × 130 × 98 mm 3 at 2.5 T/m/μ 0 for 3D imaging. While obtained spatial resolution is in the order of previous animal-scale AM MPIs, incorporating superconductors for achieving such high gradients in a 200 mm bore diameter marks a major step toward clinical MPI.

Background: Assessment of measurable residual disease (MRD) is an essential prognostic tool for B-lymphoblastic leukaemia (B-ALL). In this study, we evaluated the utility of next-generation sequencing (NGS)-based MRD assessment in real-world clinical practice., Method: The study included 93 paediatric patients with B-ALL treated at our institution between January 2017 and June 2022. Clonality for IGH or IGK rearrangements was identified in most bone marrow samples (91/93, 97.8%) obtained at diagnosis., Results: In 421 monitoring samples, concordance was 74.8% between NGS and multiparameter flow cytometry and 70.7% between NGS and reverse transcription-PCR. Elevated quantities of clones of IGH alone (P < 0.001; hazard ratio [HR], 22.2; 95% confidence interval [CI], 7.1-69.1), IGK alone (P = 0.011; HR, 5.8; 95% CI, 1.5-22.5), and IGH or IGK (P < 0.001; HR, 7.2; 95% CI, 2.6-20.0) were associated with an increased risk of relapse. Detection of new clone(s) in NGS was also associated with inferior relapse-free survival (P < 0.001; HR, 18.1; 95% CI, 3.0-108.6). Multivariable analysis confirmed age at diagnosis, BCR::ABL1-like mutation, TCF3::PBX1 mutation, and increased quantity of IGH or IGK clones during monitoring as unfavourable factors., Conclusion: In conclusion, this study highlights the usefulness of NGS-based MRD as a routine assessment tool for prognostication of paediatric patients with B-ALL., (© 2024. The Author(s).)

Platinum ditelluride (1 T -PtTe 2 ) is a two-dimensional (2D) topological semimetal with a distinctive band structure and flexibility of van der Waals integration as a promising candidate for future electronics and spintronics. Although the synthesis of large-scale, uniform, and highly crystalline films of 2D semimetals system is a prerequisite for device application, the synthetic methods meeting these criteria are still lacking. Here, we introduce an approach to synthesize highly oriented 2D topological semimetal PtTe 2 using a thermally assisted conversion called tellurization, which is a cost-efficient method compared to the other epitaxial deposition methods. We demonstrate that achieving highly crystalline 1 T -PtTe 2 using tellurization is not dependent on epitaxy but rather relies on two critical factors: (i) the crystallinity of the predeposited platinum (Pt) film and (ii) the surface coverage ratio of the Pt film considering lateral lattice expansion during transformation. By optimizing the surface coverage ratio of the epitaxial Pt film, we successfully obtained 2 in. wafer-scale uniformity without in-plane misalignment between antiparallelly oriented domains. The electronic band structure of 2D topological PtTe 2 is clearly resolved in momentum space, and we observed an interesting 6-fold gapped Dirac cone at the Fermi surface. Furthermore, ultrahigh electrical conductivity down to ∼3.8 nm, which is consistent with that of single crystal PtTe 2 , was observed, proving its ultralow defect density.

Stretchable organic light-emitting diodes (OLEDs) have emerged as promising optoelectronic devices with exceptional degree of freedom in form factors. However, stretching OLEDs often results in a reduction in the geometrical fill factor (FF), that is the ratio of an active area to the total area, thereby limiting their potential for a broad range of applications. To overcome these challenges, we propose a three-dimensional (3D) architecture adopting a hidden active area that serves a dual role as both an emitting area and an interconnector. For this purpose, an ultrathin OLED is first attached to a 3D rigid island array structure through quadaxial stretching for precise, deformation-free alignment. A portion of the ultrathin OLED is concealed by letting it 'fold in' between the adjacent islands in the initial, non-stretched condition and gradually surfaces to the top upon stretching. This design enables the proposed stretchable OLEDs to exhibit a relatively high FF not only in the initial state but also after substantial deformation corresponding to a 30% biaxial system strain. Moreover, passive-matrix OLED displays that utilize this architecture are shown to be configurable for compensation of post-stretch resolution loss, demonstrating the efficacy of the proposed approach in realizing the full potential of stretchable OLEDs., (© 2024. The Author(s).)

Objectives: To examine the advanced practice nurse workforce in Swiss cancer care and how their roles are being implemented (eg, role structures, processes) to achieve optimal outcomes for patients and their families, care organizations, and the broader health care system., Methods: A cross-sectional study was conducted. The sample included master-prepared advanced practice nurses in cancer care, who completed an online questionnaire from December 2021 to January 2022. Thirty-nine items assessed structures (eg, role characteristics, utilization), processes (eg, role activities, interventions), and perceived outcomes (eg, for patients, the health care system) of advanced practice nurses in Swiss cancer care. Data from closed questions were analyzed using descriptive statistics. Data from open-ended questions were organized and summarized into categories related to domains of advanced practice nursing and its reported frequency by the advanced practice nurses., Results: The participating advanced practice nurses (n = 53), worked in half of the 26 Swiss cantons. Interventions were identified within nine categories, of which most were targeted to patients and their families (n = 7), followed by health care professionals (n = 2). Perceived positive outcomes were patient symptom management, length of hospital stay, and health care costs. Participants felt less confident in cancer care (eg, autonomous practice) and reported 15 professional development needs (eg, medical interventions, teaching)., Conclusions: This study provides a comprehensive examination of 53 advanced practice nurses, detailing the characteristics of their roles and utilization across various jurisdictions and health care settings. The results highlight the diverse dimensions of advanced practice nursing and its potential to enhance cancer services and outcomes in Switzerland. Opportunities for role development support and expansion are identified., Implications for Nursing Practice: More systematic health human resource planning is needed to expand the deployment of advanced practice nurses across jurisdictions, practice settings, and more diverse patient populations. Role development needs show the desire for specialized educational preparation in cancer care., 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., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Purpose: With the slice thickness routinely used in elbow MRI, small or subtle lesions may be overlooked or misinterpreted as insignificant. To compare 1 mm slice thickness MRI (1 mm MRI) with deep learning reconstruction (DLR) to 3 mm slice thickness MRI (3 mm MRI) without/with DLR, and 1 mm MRI without DLR regarding image quality and diagnostic performance for elbow tendons and ligaments., Methods: This retrospective study included 53 patients between February 2021 and January 2022, who underwent 3 T elbow MRI, including T2-weighted fat-saturated coronal 3 mm and 1 mm MRI without/with DLR. Two radiologists independently assessed four MRI scans for image quality and artefacts, and identified the pathologies of the five elbow tendons and ligaments. In 19 patients underwent elbow surgery after elbow MRI, diagnostic performance was evaluated using surgical records as a reference standard., Results: For both readers, 3 mm MRI with DLR had significant higher image quality scores than 3 mm MRI without DLR and 1 mm MRI with DLR (all P < 0.01). For common extensor tendon and elbow ligament pathologies, 1 mm MRI with DLR showed the highest number of pathologies for both readers. The 1 mm MRI with DLR had the highest kappa values for all tendons and ligaments. For reader 1, 1 mm MRI with DLR showed superior diagnostic performance than 3 mm MRI without/with DLR. For reader 2, 1 mm MRI with DLR showed the highest diagnostic performance; however, there was no significant difference., Conclusions: One mm MRI with DLR showed the highest diagnostic performance for evaluating elbow tendon and ligament pathologies, with similar subjective image qualities and artefacts., 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 Elsevier B.V. All rights reserved.)

Correlating transcriptional profiles with imaging-derived phenotypes has the potential to reveal possible molecular architectures associated with cognitive functions, brain development and disorders. Competitive null models built by resampling genes and self-contained null models built by spinning brain regions, along with varying test statistics, have been used to determine the significance of transcriptional associations. However, there has been no systematic evaluation of their performance in imaging transcriptomics analyses. Here, we evaluated the performance of eight different test statistics (mean, mean absolute value, mean squared value, max mean, median, Kolmogorov-Smirnov (KS), Weighted KS and the number of significant correlations) in both competitive null models and self-contained null models. Simulated brain maps (n = 1,000) and gene sets (n = 500) were used to calculate the probability of significance (Psig) for each statistical test. Our results suggested that competitive null models may result in false positive results driven by co-expression within gene sets. Furthermore, we demonstrated that the self-contained null models may fail to account for distribution characteristics (e.g., bimodality) of correlations between all available genes and brain phenotypes, leading to false positives. These two confounding factors interacted differently with test statistics, resulting in varying outcomes. Specifically, the sign-sensitive test statistics (i.e., mean, median, KS, Weighted KS) were influenced by co-expression bias in the competitive null models, while median and sign-insensitive test statistics were sensitive to the bimodality bias in the self-contained null models. Additionally, KS-based statistics produced conservative results in the self-contained null models, which increased the risk of false negatives. Comprehensive supplementary analyses with various configurations, including realistic scenarios, supported the results. These findings suggest utilizing sign-insensitive test statistics such as mean absolute value, max mean in the competitive null models and the mean as the test statistic for the self-contained null models. Additionally, adopting the confounder-matched (e.g., coexpression-matched) null models as an alternative to standard null models can be a viable strategy. Overall, the present study offers insights into the selection of statistical tests for imaging transcriptomics studies, highlighting areas for further investigation and refinement in the evaluation of novel and commonly used tests., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by uncontrolled proliferation of myeloid precursor cells within bone marrow. Despite advances in understanding of its molecular underpinnings, AML remains a therapeutic challenge due to its high relapse rate and clonal evolution., Methods: In this retrospective study, we analyzed data from 24 AML patients diagnosed at a single institution between January 2017 and August 2023. Comprehensive genetic analyses, including chromosomal karyotyping, next-generation sequencing, and gene fusion assays, were performed on bone marrow samples obtained at initial diagnosis and relapse. Clinical data, treatment regimens, and patient outcomes were also documented., Results: Mutations in core genes of FLT3, NPM1, DNMT3A, and IDH2 were frequently discovered in diagnostic sample and remained in relapse sample. FLT3-ITD, TP53, KIT, RUNX1, and WT1 mutation were acquired at relapse in one patient each. Gene fusion assays revealed stable patterns, while chromosomal karyotype analyses indicated a greater diversity of mutations in relapsed patients. Clonal evolution patterns varied, with some cases showing linear or branching evolution and others exhibiting no substantial change in core mutations between diagnosis and relapse., Conclusions: Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses., (© 2024. The Author(s).)

Objectives: This study aimed to investigate whether a significant trend regarding inpatient falls in Swiss acute care hospitals between 2011 and 2019 could be confirmed on a national level, and whether the trend persists after risk adjustment for patient-related fall risk factors., Design: A secondary data analysis was conducted based on annual multicentre cross-sectional studies carried out between 2011 and 2019., Setting: All Swiss acute care hospitals were obliged to participate in the surveys. Except for emergency departments, outpatient wards and recovery rooms, all wards were included., Participants: All inpatients aged 18 or older who had given their informed consent and whose data were complete and available were included., Outcome Measure: Whether a patient had fallen in the hospital was retrospectively determined on the survey day by asking patients the following question: Have you fallen in this institution in the last 30 days?, Results: Based on data from 110 892 patients from 222 Swiss hospitals, a national inpatient fall rate of 3.7% was determined over the 9 survey years. A significant linear decreasing trend (p=0.004) was observed using the Cochran-Armitage trend test. After adjusting for patient-related fall risk factors in a two-level random intercept logistic regression model, a significant non-linear decreasing trend was found at the national level., Conclusions: A significant decrease in fall rates in Swiss hospitals, indicating an improvement in the quality of care provided, could be confirmed both descriptively and after risk adjustment. However, the non-linear trend, that is, an initial decrease in inpatient falls that flattens out over time, also indicates a possible future increase in fall rates. Monitoring of falls in hospitals should be maintained at the national level. Risk adjustment accounts for the observed increase in patient-related fall risk factors in hospitals, thus promoting a fairer comparison of the quality of care provided over time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34 + cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049-2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681-7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205-3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934-76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH.

Background: We aimed to investigate the clinical, imaging and fluid biomarker characteristics in patients with antidiacylglycerol lipase alpha (DAGLA)-autoantibody-associated cerebellitis., Methods: Serum and cerebrospinal fliud (CSF) samples from four index patients were subjected to comprehensive autoantibody screening by indirect immunofluorescence assay (IIFA). Immunoprecipitation, mass spectrometry and recombinant protein assays were used to identify the autoantigen. Sera from 101 patients with various neurological symptoms and a similar tissue staining pattern as the index patient samples, and 102 healthy donors were analysed in recombinant cell-based IIFA (RC-IIFA) with the identified protein. Epitope characterisation of all positive samples was performed via ELISA, immunoblot, immunoprecipitation and RC-IIFA using different DAGLA fragments., Results: All index patients were relatively young (age: 18-34) and suffered from pronounced gait ataxia, dysarthria and visual impairments. Paraclinical hallmarks in early-stage disease were inflammatory CSF changes and cerebellar cortex hyperintensity in MRI. Severe cerebellar atrophy developed in three of four patients within 6 months. All patient samples showed the same unclassified IgG reactivity with the cerebellar molecular layer. DAGLA was identified as the target antigen and confirmed by competitive inhibition experiments and DAGLA-specific RC-IIFA. In RC-IIFA, serum reactivity against DAGLA was also found in 17/101 disease controls, including patients with different clinical phenotypes than the one of the index patients, and in 1/102 healthy donors. Epitope characterisation revealed that 17/18 anti-DAGLA-positive control sera reacted with a C-terminal intracellular DAGLA 583-1042 fragment, while the CSF samples of the index patients targeted a conformational epitope between amino acid 1 and 157., Conclusions: We propose that anti-DAGLA autoantibodies detected in CSF, with a characteristic tissue IIFA pattern, represent novel biomarkers for rapidly progressive cerebellitis., Competing Interests: Competing interests: RM, MS, NR, CR, LS, SH, YD, CP and LK are employees of EUROIMMUN, a company that manufactures diagnostic tests and instruments. RM, MS, SH, YD, CP, FB and LK have patent applications, concerning the detection of an autoantibody against DAGLA issued and pending. KB, IS, MC, MJ-L, FR, GL, DR, TS, MPW, KG, MO, CIB, SN, K-PW, VvP, BT and K-WS report no competing interests to the work described., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

HER2 is a crucial therapeutic target in breast cancer, and the survival rate of breast cancer patients has increased because of this receptor's inhibition. However, tumors have shown resistance to this therapeutic strategy due to oncogenic mutations that decrease the binding of several HER2-targeted drugs, including lapatinib, and confer resistance to this drug. Neratinib can overcome this drug resistance and effectively inhibit HER2 signaling and tumor growth. In the present study, we examined the efficacy of lapatinib and neratinib using breast cancer cells by Raman microscopy combined with a deep wavelet scattering-based multivariate analysis framework. This approach discriminated between control cells and drug-treated cells with high accuracy, compared to classical principal component analysis. Both lapatinib and neratinib induced changes in the cellular biochemical composition. Furthermore, the Raman results were compared with the results of several in vitro assays. For instance, drug-treated cells exhibited (i) inhibition of ERK and AKT phosphorylation, (ii) inhibition of cellular proliferation, (iii) cell-cycle arrest, and (iv) apoptosis as indicated by western blotting, real-time cell analysis (RTCA), cell-cycle analysis, and apoptosis assays. Thus, the observed Raman spectral changes are attributed to cell-cycle arrest and apoptosis. The results also indicated that neratinib is more potent than lapatinib. Moreover, the uptake and distribution of lapatinib in cells were visualized through its label-free marker bands in the fingerprint region using Raman spectral imaging. These results show the prospects of Raman microscopy in drug evaluation and presumably in drug discovery.

Background: Inpatient falls in hospitals are an acknowledged indicator of quality of care. International comparisons could highlight quality improvement potential and enable cross-national learning. Key to fair cross-national comparison is the availability of a risk adjustment model validated in an international context. This study aimed to 1) ascertain that the variables of the inpatient fall risk adjustment model do not interact with country and thus can be used for risk adjustment, 2) compare the risk of falling in hospitals between Switzerland and Austria after risk adjustment., Methods: The data on inpatient falls from Swiss and Austrian acute care hospitals were collected on a single measurement day in 2017, 2018 and 2019 as part of an international multicentre cross-sectional study. Multilevel logistic regression models were used to screen for interaction effects between the patient-related fall risk factors and the countries. The risks of falling in hospital in Switzerland and in Austria were compared after applying the risk-adjustment model., Results: Data from 176 hospitals and 43,984 patients revealed an inpatient fall rate of 3.4% in Switzerland and 3.9% in Austria. Two of 15 patient-related fall risk variables showed an interaction effect with country: Patients who had fallen in the last 12 months (OR 1.49, 95% CI 1.10-2.01, p = 0.009) or had taken sedatives/psychotropic medication (OR 1.40, 95% CI 1.05-1.87, p = 0.022) had higher odds of falling in Austrian hospitals. Significantly higher odds of falling were observed in Austrian (OR 1.38, 95% CI 1.13-1.68, p = 0.002) compared to Swiss hospitals after applying the risk-adjustment model., Conclusions: Almost all patient-related fall risk factors in the model are suitable for a risk-adjusted cross-country comparison, as they do not interact with the countries. Further model validation with additional countries is warranted, particularly to assess the interaction of risk factors "fall in the last 12 months" and "sedatives/psychotropic medication intake" with country variable. The study underscores the crucial role of an appropriate risk-adjustment model in ensuring fair international comparisons of inpatient falls, as the risk-adjusted, as opposed to the non-risk-adjusted country comparison, indicated significantly higher odds of falling in Austrian compared to Swiss hospitals., (© 2024. The Author(s).)

The social support provided by chatbots is typically designed to mimic the way humans support others. However, individuals have more conflicting attitudes toward chatbots providing emotional support (e.g., empathy and encouragement) compared to informational support (e.g., useful information and advice). This difference may be related to whether individuals associate a certain type of support with the realm of the human mind and whether they attribute human-like minds to chatbots. In the present study, we investigated whether perceiving human-like minds in chatbots affects users' acceptance of various support provided by the chatbot. In the experiment, the chatbot posed questions about participants' interpersonal stress events, prompting them to write down their stressful experiences. Depending on the experimental condition, the chatbot provided two kinds of social support: informational support or emotional support. Our results showed that when participants explicitly perceived a human-like mind in the chatbot, they considered the support to be more helpful in resolving stressful events. The relationship between implicit mind perception and perceived message effectiveness differed depending on the type of support. More specifically, if participants did not implicitly attribute a human-like mind to the chatbot, emotional support undermined the effectiveness of the message, whereas informational support did not. The present findings suggest that users' mind perception is essential for understanding the user experience of chatbot social support. Our findings imply that informational support can be trusted when building social support chatbots. In contrast, the effectiveness of emotional support depends on the users implicitly giving the chatbot a human-like mind., 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 © 2024 Lee and Hahn.)

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G&#95;{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G&#95;{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Sprays are used both in workplace and consumer settings. Although spraying has advantages, such as uniform distribution of substances on surfaces in a highly efficient manner, it is often associated with a high inhalation burden. For an adequate risk assessment, this exposure has to be reliably quantified. Exposure models of varying complexity are available, which are applicable to spray applications. However, a need for improvement has been identified. In this contribution, a simple 2-box approach is suggested for the assessment of the time-weighted averaged exposure concentration (TWA) using a minimum of input data. At the moment, the model is restricted to binary spray liquids composed of a non-volatile fraction and volatile solvents. The model output can be refined by introducing correction factors based on the classification and categorization of two key parameters, the droplet size class and the vapor pressure class of the solvent, or by using a data set of experimentally determined airborne release fractions related to the used spray equipment. A comparison of model results with measured data collected at real workplaces showed that this simple model based on readily available input parameters is very useful for screening purposes. The generic 2-box spray model without refinement overestimates the measurements of the considered scenarios in approximately 50% of the cases by more than a factor of 100. The generic 2-box model performs better for room spraying than for surface spraying, as the airborne fraction in the latter case is clearly overestimated. This conservatism of the prediction was significantly reduced when correction factors or experimentally determined airborne release fractions were used in addition to the generic input parameters. The resulting predictions still overestimate the exposure (ratio tool estimate to measured TWA > 10) or they are accurate (ratio 0.5-10). If the available information on boundary conditions (application type, equipment) does not justify the usage of airborne release fraction, room spraying should be used resulting in the highest exposure estimate. The model scope may be extended to (semi)volatile substances. However, acceptance may be compromised by the limited availability of measured data for this group of substances and thus may have limited potency to evaluate the model prediction., 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 © 2024 Hahn, Schwarz, Nowak, Schwarz, Meyer and Koch.)

This study aimed to develop and evaluate a sarcopenia prediction model by fusing numerical features from shear-wave elastography (SWE) and gray-scale ultrasonography (GSU) examinations, using the rectus femoris muscle (RF) and categorical/numerical features related to clinical information. Both cohorts (development, 70 healthy subjects; evaluation, 81 patients) underwent ultrasonography (SWE and GSU) and computed tomography. Sarcopenia was determined using skeletal muscle index calculated from the computed tomography. Clinical and ultrasonography measurements were used to predict sarcopenia based on a linear regression model with the least absolute shrinkage and selection operator (LASSO) regularization. Furthermore, clinical and ultrasonography features were combined at the feature and score levels to improve sarcopenia prediction performance. The accuracies of LASSO were 70.57 ± 5.00-81.54 ± 4.83 (clinical) and 69.00 ± 4.52-69.73 ± 5.47 (ultrasonography). Feature-level fusion of clinical and ultrasonography (accuracy, 70.29 ± 6.63 and 83.55 ± 4.32) showed similar performance with clinical features. Score-level fusion by AdaBoost showed the best performance (accuracy, 73.43 ± 6.57-83.17 ± 5.51) in the development and evaluation cohorts, respectively. This study might suggest the potential of machine learning fusion techniques to enhance the accuracy of sarcopenia prediction models and improve clinical decision-making in patients with sarcopenia., (© 2024. The Author(s).)

Background: Patients with borderline personality disorder (BPD) present difficulties in self-regulation and interaction, which is a challenge for psychotherapists that is also addressed in BPD-specific interventions. Against this background, outpatient psychotherapists were surveyed about the factors playing a decisive role in their treatment offer for patients with BPD., Methods: Psychotherapists for adults were contacted via their email address published on the website of the Kassenärztliche Vereinigung (Association of Statutory Health Insurance Physicians), 231 of whom answered an online questionnaire. The results were analysed descriptively and examined inferentially with regard to the psychotherapists' admission behaviour., Results: Almost 90% reported that they would generally accept patients with BPD in therapy. However, of those, 85% did not have a therapy slot available. The psychotherapists' learned approach of treatment was not a decisive factor in determining whether they were willing to provide treatment. Most of the psychotherapists (85%) recommended a BPD disorder-specific therapy such as Dialectical Behavior Therapy (DBT), Mentalization-Based Treatment (MBT), Transference-Focused Psychotherapy (TFP) or Schema Therapy (ST). However, only just under 7% were certified in such a disorder-specific approach. Significant individual stress factors described by the psychotherapists were suicidal risk (70%) and potential other-directed aggression (59%). In addition, it was shown that it played a role whether the psychotherapists were trained in an additional therapy approach (with at least 16 teaching units) or not., Conclusion: The care situation for people with BPD seeking an outpatient psychotherapy place is clearly in need of improvement. This is mainly due to a general lack of available therapy places as well as various fears and anxieties, such as increased suicidality, which in turn can have a negative impact on the provision of outpatient therapy. Psychotherapists who have undergone disorder-specific further training feel less burdened by suicidal behaviour. However, since only a small number of them are able to offer BPD-specific therapies, it is essential to expand and (financially) support specific training programmes. In order to meet the demand for care, professional changes are urgently needed., Competing Interests: Weitergebildet in BPS-störungsspezifischen Ansätzen nach obigem Kriterium sind: FP, AJ, LS und MR in DBT; AJ und LS in ST; LS in MBT und TFP; zertifiziert sind: SHS und MR in TFP. SHS ist zudem Trainerin und Supervisorin am TFP Institut München, MR ist Trainer und Supervisor am TFP Institut München und leitet das Ausbildungscurriculum 2023–2025., (Thieme. All rights reserved.)

Single phenological measures, like the average rate of phenological advancement, may be insufficient to explain how climate change is driving trends in animal populations. Here, we develop a multifactorial concept of spring phenology-including the onset of spring, spring duration, interannual variability, and their temporal changes-as a driver for population dynamics of migratory terrestrial species in seasonal environments. Using this conceptual model, we found that effects of advancing spring phenology on animal populations may be buffered or amplified depending on the duration and interannual variability of spring green-up, and those effects are modified by evolutionary and plastic adaptations of species. Furthermore, we compared our modelling results with empirical data on normalized difference vegetation index-based spring green-up phenology and population trends of 106 European landbird finding similar associations. We conclude how phenological changes are expected to affect migratory bird populations across Europe and identify regions that are particularly prone to suffer population declines., (© 2024 The Authors. Ecology Letters published by John Wiley & Sons Ltd.)

Snacks and beverages are often sold in addition to meals in U.S. schools ("competitive foods"), but their current nutritional quality and compliance with national Smart Snacks standards are unknown. This study assessed competitive foods in a national sample of 90 middle and high schools. Differences in compliance by school characteristics were measured using mixed methods analysis of variance. Overall, 80% of the schools in the sample sold competitive foods; but they were less commonly available in schools with universal free school meal (UFSM) policies. A total of 840 unique products were documented and, on average, 75% were compliant with Smart Snacks standards. A total of 56% aligned with recommended added sugar limits (<10% of calories); and 340 unique products (40%) aligned with both sugar and Smart Snacks standards. Approximately one-fifth of competitive foods contained synthetic dyes, and 31% of beverages contained artificial sweeteners. Smart Snacks standards compliance was greater when competitive foods were overseen by food service departments, in comparison with others (e.g., principals, student organizations, or outside vendors [77% vs. 59% compliance; p = 0.003]). Therefore, district wellness policies should consider requiring food service departments to oversee competitive foods. Federal and state policies should limit added sugars, artificial sweeteners, and synthetic dyes. This appears to be highly feasible, given the substantial number of products that meet these criteria. UFSM policies should also be considered to support healthier school meal environments more broadly.

We show, for the first time, radio measurements of the depth of shower maximum (X&#95;{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X&#95;{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X&#95;{max} measurements with even a sparse radio array. With this, we show that the radio technique is capable of cosmic-ray mass composition studies, both at Auger and at other experiments.

The lateral hypothalamus (LH) is involved in feeding behavior and defense responses by interacting with different brain structures, including the Ventral Tegmental Area (VTA). Emerging evidence indicates that LH-glutamatergic neurons infrequently synapse on VTA-dopamine neurons but preferentially establish multiple synapses on VTA-glutamatergic neurons. Here, we demonstrated that LH-glutamatergic inputs to VTA promoted active avoidance, long-term aversion, and escape attempts. By testing feeding in the presence of a predator, we observed that ongoing feeding was decreased, and that this predator-induced decrease in feeding was abolished by photoinhibition of the LH-glutamatergic inputs to VTA. By VTA specific neuronal ablation, we established that predator-induced decreases in feeding were mediated by VTA-glutamatergic neurons but not by dopamine or GABA neurons. Thus, we provided evidence for an unanticipated neuronal circuitry between LH-glutamatergic inputs to VTA-glutamatergic neurons that plays a role in prioritizing escape, and in the switch from feeding to escape in mice., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: While anti-peristaltic agents are beneficial for high quality magnetic resonance enterography (MRE), their use is constrained by potential side effects and increased examination complexity. We explored the potential of deep learning-based reconstruction (DLR) to compensate for the absence of anti-peristaltic agent, improve image quality and reduce artifact. This study aimed to evaluate the need for an anti-peristaltic agent in single breath-hold single-shot fast spin-echo (SSFSE) MRE and compare the image quality and artifacts between conventional reconstruction (CR) and DLR., Methods: We included 45 patients who underwent MRE for Crohn's disease between October 2021 and September 2022. Coronal SSFSE images without fat saturation were acquired before and after anti-peristaltic agent administration. Four sets of data were generated: SSFSE CR with and without an anti-peristaltic agent (CR-A and CR-NA, respectively) and SSFSE DLR with and without an anti-peristaltic agent (DLR-A and DLR-NA, respectively). Two radiologists independently reviewed the images for overall quality and artifacts, and compared the three images with DLR-A. The degree of distension and inflammatory parameters were scored on a 5-point scale in the jejunum and ileum, respectively. Signal-to-noise ratio (SNR) levels were calculated in superior mesenteric artery (SMA) and iliac bifurcation level., Results: In terms of overall quality, DLR-NA demonstrated no significant difference compared to DLR-A, whereas CR-NA and CR-A demonstrated significant differences (P<0.05, both readers). Regarding overall artifacts, reader 1 rated DLR-A slightly better than DLR-NA in four cases and rated them as identical in 41 cases (P=0.046), whereas reader 2 demonstrated no difference. Bowel distension was significantly different in the jejunum (Reader 1: P=0.046; Reader 2: P=0.008) but not in the ileum. Agreements between the images (Reader 1: ĸ=0.73-1.00; Reader 2: ĸ=1.00) and readers (ĸ=0.66 for all comparisons) on inflammation were considered good to excellent. The sensitivity, specificity, and accuracy in diagnosing inflammation in the terminal ileum were the same among DLR-NA, DLR-A, CR-NA and CR-A (94.42%, 81.83%, and 89.69 %; and 83.33%, 90.91%, and 86.21% for Readers 1 and 2, respectively). In both SMA and iliac bifurcation levels, SNR of DLR images exhibited no significant differences. CR images showed significantly lower SNR compared with DLR images (P<0.001)., Conclusions: SSFSE without anti-peristaltic agents demonstrated nearly equivalent quality to that with anti-peristaltic agents. Omitting anti-peristaltic agents before SSFSE and adding DLR could improve the scanning outcomes and reduce time., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-738/coif). J.L. is a current employee of GE HealthCare Korea, and his contribution was limited to assisting with statistical analysis. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background and Aims: Recently, we demonstrated that a distinct pattern of structural covariance networks (SCN) from magnetic resonance imaging (MRI)-derived measurements of brain cortical thickness characterized young adults with alcohol use disorder (AUD) and predicted current and future problematic drinking in adolescents relative to controls. Here, we establish the robustness and value of SCN for identifying heavy alcohol users in three additional independent studies., Design and Setting: Cross-sectional and longitudinal studies using data from the Pediatric Imaging, Neurocognition and Genetics (PING) study (n = 400, age range = 14-22 years), the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) (n = 272, age range = 17-22 years) and the Human Connectome Project (HCP) (n = 375, age range = 22-37 years)., Cases: Cases were defined based on heavy alcohol use patterns or former alcohol use disorder (AUD) diagnoses: 50, 68 and 61 cases were identified. Controls had none or low alcohol use or absence of AUD: 350, 204 and 314 controls were selected., Measurements: Graph theory metrics of segregation and integration were used to summarize SCN., Findings: Mirroring our prior findings, and across the three data sets, cases had a lower clustering coefficient [area under the curve (AUC) = -0.029, P = 0.002], lower modularity (AUC = -0.14, P = 0.004), lower average shortest path length (AUC = -0.078, P = 0.017) and higher global efficiency (AUC = 0.007, P = 0.010). Local efficiency differences were marginal (AUC = -0.017, P = 0.052). That is, cases exhibited lower network segregation and higher integration, suggesting that adjacent nodes (i.e. brain regions) were less similar in thickness whereas spatially distant nodes were more similar., Conclusion: Structural covariance network (SCN) differences in the brain appear to constitute an early marker of heavy alcohol use in three new data sets and, more generally, demonstrate the utility of SCN-derived metrics to detect brain-related psychopathology., (© 2023 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)