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When fields lack consensus standard methods and accessible ground truths, reproducibility can be more of an ideal than a reality. Such has been the case for functional neuroimaging, where there exists a sprawling space of tools and processing pipelines. We provide a critical evaluation of the impact of differences across five independently developed minimal preprocessing pipelines for functional magnetic resonance imaging. We show that, even when handling identical data, interpipeline agreement was only moderate, critically shedding light on a factor that limits cross-study reproducibility. We show that low interpipeline agreement can go unrecognized until the reliability of the underlying data is high, which is increasingly the case as the field progresses. Crucially we show that, when interpipeline agreement is compromised, so too is the consistency of insights from brain-wide association studies. We highlight the importance of comparing analytic configurations, because both widely discussed and commonly overlooked decisions can lead to marked variation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Cell death and inflammation are closely linked arms of the innate immune response to combat infection and tissue malfunction. Recent advancements in our understanding of the intricate signals originating from dying cells have revealed that cell death serves as more than just an end point. It facilitates the exchange of information between the dying cell and cells of the tissue microenvironment, particularly immune cells, alerting and recruiting them to the site of disturbance. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is emerging as a critical stress sentinel that functions as a molecular switch, governing cellular survival, inflammatory responses and immunogenic cell death signalling. Its tight regulation involves multiple layers of post-translational modifications. In this Review, we discuss the molecular mechanisms that regulate RIPK1 to maintain homeostasis and cellular survival in healthy cells, yet drive cell death in a context-dependent manner. We address how RIPK1 mutations or aberrant regulation is associated with inflammatory and autoimmune disorders and cancer. Moreover, we tease apart what is known about catalytic and non-catalytic roles of RIPK1 and discuss the successes and pitfalls of current strategies that aim to target RIPK1 in the clinic., (© 2023. Springer Nature Limited.)

High-content image-based cell phenotyping provides fundamental insights into a broad variety of life science disciplines. Striving for accurate conclusions and meaningful impact demands high reproducibility standards, with particular relevance for high-quality open-access data sharing and meta-analysis. However, the sources and degree of biological and technical variability, and thus the reproducibility and usefulness of meta-analysis of results from live-cell microscopy, have not been systematically investigated. Here, using high-content data describing features of cell migration and morphology, we determine the sources of variability across different scales, including between laboratories, persons, experiments, technical repeats, cells, and time points. Significant technical variability occurred between laboratories and, to lesser extent, between persons, providing low value to direct meta-analysis on the data from different laboratories. However, batch effect removal markedly improved the possibility to combine image-based datasets of perturbation experiments. Thus, reproducible quantitative high-content cell image analysis of perturbation effects and meta-analysis depend on standardized procedures combined with batch correction., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Introduction: Complex pathologies involving the aortic arch can be treated using the frozen elephant trunk (FET) technique, which is versatile and continues to be improved with different innovations to further reduce, for example, circulatory arrest time and the need for hypothermia. FET may or may not be a definitive repair, however. Distal extension or completion-especially endovascular-is common but not well described in the literature. This review describes the considerations that are necessary during FET planning and preparation, how pathology specifics and sizing decisions will affect the subsequent need for treatment, and how outcomes might be better reported to improve understanding of the advantages and limitations of the technique., Materials and Methods: This literature review was performed to identify reports of second-stage endovascular completion after FET repair, and included any literature that described such interventions after index FET, for any aortic arch pathology., Results: Secondary intervention after FET is an important parameter to establish the success or failure of the index procedure. However, unplanned extensions are often reported with insufficient detail and follow up, and studies rarely differentiate between unplanned or adjunctive procedures. In addition, prediction of the need for extension is complicated by the response of the pathology to the index procedure., Conclusion: FET is a versatile, established surgical technique that allows for several applications in different pathologies and innovative adaptations. How, when, and why FET is extended needs to be reported in greater detail, with specific consideration given to the interaction of FET and endovascular devices in sizing, integrity, and possible complications.

Background: Universal access to assessment and treatment of mental health and learning disorders remains a significant and unmet need. There are many people without access to care because of economic, geographic, and cultural barriers, as well as the limited availability of clinical experts who could help advance our understanding and treatment of mental health., Objective: This study aims to create an open, configurable software platform to build clinical measures, mobile assessments, tasks, and interventions without programming expertise. Specifically, our primary requirements include an administrator interface for creating and scheduling recurring and customized questionnaires where end users receive and respond to scheduled notifications via an iOS or Android app on a mobile device. Such a platform would help relieve overwhelmed health systems and empower remote and disadvantaged subgroups in need of accurate and effective information, assessment, and care. This platform has the potential to advance scientific research by supporting the collection of data with instruments tailored to specific scientific questions from large, distributed, and diverse populations., Methods: We searched for products that satisfy these requirements. We designed and developed a new software platform called MindLogger, which exceeds the requirements. To demonstrate the platform's configurability, we built multiple applets (collections of activities) within the MindLogger mobile app and deployed several of them, including a comprehensive set of assessments underway in a large-scale, longitudinal mental health study., Results: Of the hundreds of products we researched, we found 10 that met our primary requirements with 4 that support end-to-end encryption, 2 that enable restricted access to individual users' data, 1 that provides open-source software, and none that satisfy all three. We compared features related to information presentation and data capture capabilities; privacy and security; and access to the product, code, and data. We successfully built MindLogger mobile and web applications, as well as web browser-based tools for building and editing new applets and for administering them to end users. MindLogger has end-to-end encryption, enables restricted access, is open source, and supports a variety of data collection features. One applet is currently collecting data from children and adolescents in our mental health study, and other applets are in different stages of testing and deployment for use in clinical and research settings., Conclusions: We demonstrated the flexibility and applicability of the MindLogger platform through its deployment in a large-scale, longitudinal, mobile mental health study and by building a variety of other mental health-related applets. With this release, we encourage a broad range of users to apply the MindLogger platform to create and test applets to advance health care and scientific research. We hope that increasing the availability of applets designed to assess and administer interventions will facilitate access to health care in the general population., (©Arno Klein, Jon Clucas, Anirudh Krishnakumar, Satrajit S Ghosh, Wilhelm Van Auken, Benjamin Thonet, Ihor Sabram, Nino Acuna, Anisha Keshavan, Henry Rossiter, Yao Xiao, Sergey Semenuta, Alessandra Badioli, Kseniia Konishcheva, Sanu Ann Abraham, Lindsay M Alexander, Kathleen R Merikangas, Joel Swendsen, Ariel B Lindner, Michael P Milham. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 11.11.2021.)

Background: Problematic internet use (PIU) is an increasingly worrisome issue, as youth population studies are establishing links with internalizing and externalizing problems. There is a need for a better understanding of psychiatric diagnostic profiles associated with this issue, as well as its unique contributions to impairment. Here, we leveraged the ongoing, large-scale Child Mind Institute Healthy Brain Network, a transdiagnostic self-referred, community sample of children and adolescents (ages 5-21), to examine the associations between PIU and psychopathology, general impairment, physical health and sleep disturbances., Methods: A total sample of 564 (190 female) participants between the ages of 7-15 (mean = 10.80, SD = 2.16), along with their parents/guardians, completed diagnostic interviews with clinicians, answered a wide range of self-report (SR) and parent-report (PR) questionnaires, including the Internet Addiction Test (IAT) and underwent physical testing as part of the Healthy Brain Network protocol., Results: PIU was positively associated with depressive disorders (SR: aOR = 2.43, CI: 1.22-4.74, p = .01; PR: aOR = 2.56, CI: 1.31-5.05, p = .01), the combined presentation of ADHD (SR: aOR = 1.91, CI: 1.14-3.22, p = .01; PR: n.s.), Autism Spectrum Disorder (SR: n.s.; PR: aOR = 2.24, CI: 1.34-3.73, p < .001), greater levels of impairment (SR: Standardized Beta = 4.63, CI: 3.06-6.20, p < .001; PR: Standardized Beta = 5.05, CI: 3.67-6.42, p < .001) and increased sleep disturbances (SR: Standardized Beta = 3.15, CI: 0.71-5.59, p = .01; PR: Standardized Beta = 3.55, CI: 1.34-5.75, p < .001), even when accounting for demographic covariates and psychiatric comorbidity., Conclusions: The association between PIU and psychopathology, as well as its impact on impairment and sleep disturbances, highlight the urgent need to gain an understanding of mechanisms in order to inform public health recommendations on internet use in U.S. youth.

Selective Mutism (SM) is an anxiety disorder often diagnosed in early childhood and characterized by persistent failure to speak in certain social situations but not others. Diagnosing SM and monitoring treatment response can be quite complex, due in part to changing definitions of and scarcity of research about the disorder. Subjective self-reports and parent/teacher interviews can complicate SM diagnosis and therapy, given that similar speech problems of etiologically heterogeneous origin can be attributed to SM. The present perspective discusses the potential for passive audio capture to help overcome psychiatry's current lack of objective and quantifiable assessments in the context of SM. We present supportive evidence from two pilot studies indicating the feasibility of using a digital wearable device to quantify child vocalization features affected by SM. We also highlight comparative analyses of passive audio capture and its potential to enhance diagnostic characterizations for SM, as well as possible limitations of such technologies.

Data sharing is increasingly recommended as a means of accelerating science by facilitating collaboration, transparency, and reproducibility. While few oppose data sharing philosophically, a range of barriers deter most researchers from implementing it in practice. To justify the significant effort required for sharing data, funding agencies, institutions, and investigators need clear evidence of benefit. Here, using the International Neuroimaging Data-sharing Initiative, we present a case study that provides direct evidence of the impact of open sharing on brain imaging data use and resulting peer-reviewed publications. We demonstrate that openly shared data can increase the scale of scientific studies conducted by data contributors, and can recruit scientists from a broader range of disciplines. These findings dispel the myth that scientific findings using shared data cannot be published in high-impact journals, suggest the transformative power of data sharing for accelerating science, and underscore the need for implementing data sharing universally.

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).

Members of the ezrin-radixin-moesin (ERM) family of proteins are involved in multiple aspects of cell migration by acting both as crosslinkers between the membrane, receptors and the actin cytoskeleton, and as regulators of signalling molecules that are implicated in cell adhesion, cell polarity and migration. Increasing evidence suggests that the regulation of cell signalling and the cytoskeleton by ERM proteins is crucial during cancer progression. Thus, both their expression levels and subcellular localisation would affect tumour progression. High expression of ERM proteins has been shown in a variety of cancers. Mislocalisation of ERM proteins reduces the ability of cells to form cell-cell contacts and, therefore, promotes an invasive phenotype. Similarly, mislocalisation of ERM proteins impairs the formation of receptor complexes and alters the transmission of signals in response to growth factors, thereby facilitating tumour progression. In this Commentary, we address the structure, function and regulation of ERM proteins under normal physiological conditions as well as in cancer progression, with particular emphasis on cancers of epithelial origin, such as those from breast, lung and prostate. We also discuss any recent developments that have added to the understanding of the underlying molecular mechanisms and signalling pathways these proteins are involved in during cancer progression.