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Objectives: Higher education students experience elevated levels of suicidal ideation, but often face barriers in accessing support. The Mental Imagery for Suicidality in Students Trial (MISST; ISRCTN13621293; NCT05296538) tested the feasibility and acceptability of a six-session imagery-based approach called Broad-Minded Affective Coping (BMAC). This qualitative evaluation explored the experiences of MISST participants and staff., Design: A qualitative study using one-to-one qualitative interviews with participants and staff recruited from MISST. Reflexive thematic analysis was used to explore trial participant and staff experiences to inform a future definitive trial., Methods: Student participants (n = 16), research assistants (n = 4) and the trial therapist (n = 1) were interviewed and transcripts analysed using reflexive thematic analysis., Results: Four key themes were identified. The first theme highlights the value and challenges for students in talking about suicide. The ways in which communication and rapport can be built to facilitate this conversation are explored in theme 2. Theme 3 explains how working with the BMAC therapist increased participants' awareness of their current mood, drew their attention to positive moments in their lives and helped them to actively recall these moments to interrupt negative cycles of rumination and suicidal ideation. The extent to which the BMAC is 'fit for purpose' is outlined in theme 4, generating specific recommendations for future intervention development., Conclusions: The BMAC offers a positive, time-limited, structured intervention that is well suited to meet the needs of higher education students experiencing suicidal ideation. Further research is needed to test the effectiveness on mental health and suicide-related outcomes., (© 2024 The Author(s). Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

The impact of saltwater intrusion on coastal forests and farmland is typically understood as sea-level-driven inundation of a static terrestrial landscape, where ecosystems neither adapt to nor influence saltwater intrusion. Yet recent observations of tree mortality and reduced crop yields have inspired new process-based research into the hydrologic, geomorphic, biotic, and anthropogenic mechanisms involved. We review several negative feedbacks that help stabilize ecosystems in the early stages of salinity stress (e.g., reduced water use and resource competition in surviving trees, soil accretion, and farmland management). However, processes that reduce salinity are often accompanied by increases in hypoxia and other changes that may amplify saltwater intrusion and vegetation shifts after a threshold is exceeded (e.g., subsidence following tree root mortality). This conceptual framework helps explain observed rates of vegetation change that are less than predicted for a static landscape while recognizing the inevitability of large-scale change.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as "adaptive coding." Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Flooding and salinization triggered by storm surges threaten the survival of coastal forests. The forest root zone (top 40 cm of soil) is the most affected by surge flooding. Determining the effect of a storm surge on edaphic conditions is essential to estimate vegetation response. Pre-storm soil hydrology could mitigate or enhance the salinization effect, ultimately determining the resilience of the forest. Here we assess the influence of pre-storm soil water content and salinity on storm surge effects in coastal vegetated areas. A 1D model (HYDRUS-1D) is used to simulate saltwater infiltration from above through the unsaturated zone. Different water content and concentration scenarios, along with scenarios with variable storm surge salt concentration, storm surge height and storm surge flooding duration are considered. In soils characterized by silt and clay, the maximum salinized soil depth increases as water content increases, affecting the top 40 cm of soil, except for clay loam soil, for which only the top 20 cm are salinized. In sandy soils, the salinization process involves the entire soil column. The contribution of water content to salinization varies from 12 % to 30 % along the top 40 cm in fine soils. In fine soils, the storm-surge height also becomes relevant. A study case is presented to support the numerical results. Field data confirm that soil water content controls the salinization of the root zone in clay and silt soils. Overall, we conclude that the root zones of coastal forests with clay and silt soils and low water content are the most at risk during storm surges. These events have the potential to radically change edaphic conditions and affect ecosystems., 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.)

This review aimed to develop a conceptual model of the therapeutic alliance in the context of psychotherapy and suicidal experiences from therapist and client perspectives. The protocol was pre-registered on PROSPERO (CRD42021268273). MEDLINE, PsycINFO, Web of Science, Embase and CINAHL were systematically searched from database inception to April 2024. Eligible studies were peer-reviewed, qualitative, and included client and/or therapist's perspectives of the therapeutic alliance in the context of psychotherapy and suicidal experiences. Studies were critically appraised and analysed using a meta-ethnography approach involving a reciprocal translation of studies and line of argument synthesis. Thirty-seven papers were included, generating two overarching themes; 'Working on the edge' and 'Being ready, willing, and able to build an alliance in the context of suicidal experiences'. Therapeutic alliance in the context of suicidal experiences is unique, fluid, potentially lifesaving, and influenced by multiple inter-connected internal and external processes and systems. Clinical implications emphasise the need to improve training, supervision, and support for therapists to equip them with the additional skills required in navigating the intricacies of the therapeutic alliance with clients who have suicidal experiences. Flexibly interweaving risk assessment into therapeutic conversation was beneficial to the alliance with suicidal clients and enhanced their safety., Competing Interests: Declaration of competing interest PG and DP are among other co-authors of a suicide-focussed CBT treatment manual for people with psychosis (Tarrier et al., 2013), which is published under copyright as a book. Cognitive Behavioural Suicide Prevention Therapy has been applied, adapted, and assessed in pilot and phase 2 trials for several high-risk populations. The authors of the review have been and/or are currently funded to work on these trials and have published work arising from these trials., (Copyright © 2024. Published by Elsevier Ltd.)

This editorial provides an overview of the challenges and benefits of working as and supervising trial therapists from the perspective of investigators and trial therapists. Key differences between trial therapy and standard care are considered, with recommendations for best practice.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased towards the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published datasets to reveal pathways supported by orthogonal datasets, including transcriptional regulation, epigenetic modifications, and MAPK signalling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 27 proteins that were determined to impact assembly and release. Additionally, a subset of proteins were tested across other coronaviruses revealing 17 potential pan-coronavirus targets. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry, and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo . These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals., Competing Interests: COMPETING INTERESTS STATEMENT J.F.H. has received research support, paid to Northwestern University, from Gilead Sciences, and is a paid consultant for Merck. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, Astrazeneca and Novavax. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. All other authors declare no competing interests.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: This article reviews process and performance of an innovative effort leveraging virtual health to manage unmet demand for behavioral health and substance use disorder services across a large military region. This effort began in June 2022 and included nearly all of the Defense Health Agency Region-Europe's military behavioral health and substance abuse clinics participating. The two goals of improving access to behavioral health and substance use services for active duty service members and improving utilization of the military clinics were employed. Operational and remote locations with known care gaps could access services as well. Connecting services to the point of need is an established strength of virtual health delivery systems of care., Materials and Methods: A team consisting of clinical leaders and Virtual Medical Center-Europe staff developed a centralized screening process and simple business rules. When a clinic was unable to meet its access-to-care standard of 28 days, the patient requesting or referral from a remote location, was offered a virtual video option with a provider from another clinic with availability. Centralized screening was created and staffed by three technicians. The Behavioral Health Integrated Support Network (BHISN) screening clinic assessed appropriateness of virtual care using established exclusion criteria. Once screened, the patient was scheduled for an appointment with one of the 31 therapists in 14 participating clinics in a 3- to 5-day window. The military health system's video connect platform was used., Results: Between June 2022 and November 2023, 131 patients who were unable to find routine care in their home clinic were screened, scheduled, and completed a virtual visit with one of the 31 participating therapists from 14 behavioral health and substance use clinics. Seventy-eight (59%) participants were active duty empaneled to military treatment facilities in Europe and 53 (39%) were active duty enrolled in Tricare Prime Remote and deployed to remote locations with limited care. Forty-four percent of patients were recommended for continued virtual therapy or counseling kept their first follow-up demonstrating good follow-up care using a virtual option. The overall no-show rate was low at 7%. Care and consultation were successfully delivered using video visits to location in 18 countries in three geographic Europe, the Middle East and, Africa., Conclusion: The Virtual Medical Center-Europe, Army Europe Behavioral Health, and Substance Use leadership work collaboratively to plan and optimize program performance. For BHISN to function as intended requires key dedicated support staff, such as mental health and social services assistants to screen and coordinate virtual care. Scheduling can be performed by a central cell requiring clinics to relinquish some local control in the interest of meeting patient demand in large and diverse area that covers three continents. BHISN shows promising initial success by providing a process of managing demand and connecting requests for behavioral health and substance use care leveraging capacity from all clinics using a virtual video service in a diverse operating environment., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

This study aimed to understand young gay men's experiences of social support, relationships, community networks, talking about psychological distress, and their impact on distress and wellbeing. Eight verbatim transcriptions from semi-structured interviews with gay men aged 18-35 years were analyzed using Interpretative Phenomenological Analysis. Three super-ordinate themes were developed; 1) Growing up gay in a straight world: Developmental traumas, regarding men's experiences of homophobic abuse and exclusion and the internalized impact on their identities and identity concealment. 2) Belonging and not belonging within LGBTQ+ communities, encompassing men's varied experiences of LGBTQ+ communities and the corresponding impacts upon their wellbeing. 3) Relational responses to rejection, describing how men made sense of and managed their relationships within the context of the developmental traumas they had experienced growing up as gay men. These findings illuminate the psychological impact of experiencing multiple developmental traumas related to one's identity as a gay man, and how this influences lifelong relational behavior; and how experiences of social support, relationships and LGBTQ+ communities influence men's mental health. They provide a strong rationale for psychological interventions to acknowledge and address gay men's unique and adverse social experiences within their relationships, communities and societies.

This article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools , status, and future directions. CM4AI is the Functional Genomics Data Generation Project in the U.S. National Institute of Health's (NIH) Bridge2AI program. Its overarching mission is to produce ethical, AI-ready datasets of cell architecture, inferred from multimodal data collected for human cell lines, to enable transformative biomedical AI research.

The link between imprisonment and adverse mental health is well established and linked to both recidivism and prison misconduct, with negative consequences for prisoners, the prison system and society. To help minimise these impacts, appropriate mental health interventions are required. However, owing to finite resources to deliver healthcare in prisons, interventions must be both clinically and cost-effective. A systematic literature search was conducted using various medical and economic databases. The search aimed to identify full economic evaluations (comparing costs and consequences of two or more interventions) of mental health interventions for adult prisoners during incarceration. Results were intended to identify evidence gaps and highlight areas for future research. Only one publication met all eligibility requirements, with several limitations identified. This finding highlighted a clear lack of cost-effectiveness evidence for use by decision makers within the prison setting. This emphasises the need for future research to incorporate economic evaluation during the early stages of research design. Research should aim to incorporate both intervention costs and wider healthcare resource use, which may be affected, and generic outcomes, such as quality-adjusted life years (QALYs), which enable comparison across various disease areas and against pre-determined thresholds., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Aims and Method: This study aimed to develop and articulate a logic model and programme theories for implementing a new cognitive-behavioural suicide prevention intervention for men in prison who are perceived to be at risk of death by suicide. Semi-structured one-to-one interviews with key stakeholders and a combination of qualitative analysis techniques were used to develop programme theories., Results: Interviews with 28 stakeholders resulted in five programme theories, focusing on: trust, willingness and engagement; readiness and ability; assessment and formulation; practitioner delivering the 'change work' stage of the intervention face-to-face in a prison environment; and practitioner training, integrating the intervention and onward care. Each theory provides details of what contextual factors need to be considered at each stage, and what activities can facilitate achieving the intended outcomes of the intervention, both intermediate and long term., Clinical Implications: The PROSPECT implementation strategy developed from the five theories can be adapted to different situations and environments.

Background: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD., Methods: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation., Results: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11., Conclusion: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in both cases. Overall, DHG-H3 K27 is an unusual group of diffuse gliomas that shows similar clinical, histopathological, genomic, and epigenetic features to DMG-H3 K27 as well as enrichment for activating alterations in MAPK pathway genes. These findings suggest that DHG-H3 K27 is closely related to DMG-H3 K27 and may represent an unusual presentation of DMG-H3 K27 without apparent midline involvement and with frequent MAPK pathway activation. Detailed reports of additional cases with clinical follow-up will be important to expand our understanding of this unusual group of diffuse gliomas and to better define the clinical outcome and how to classify DHG-H3 K27., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)

Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR-Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate PDE10A as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro. Cell culture analysis showed that decreased Pde10a expression led to increased PI3K/AKT signaling in a Pten-independent manner, a response blocked by selective PI3K inhibitors. Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboring PDE10A loss have worse outcomes and potentially increased sensitivity to PI3K inhibition., (© 2024 Nuechterlein et al.; Published by Cold Spring Harbor Laboratory Press.)

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Suicide is the leading cause of death in mothers postpartum and one of the most common causes of death during pregnancy. Mental health professionals who work in perinatal services can offer insights into the factors they perceive as being linked to mothers' suicidal ideation and behaviour, support offered to mothers and improvements to current practices. We aimed to explore the experiences and perceptions of perinatal mental health professionals who have worked with suicidal mothers during the perinatal period., Method: Semi-structured interviews were conducted face-to-face or via telephone with mental health professionals working in perinatal mental health inpatient or community services across England. Data were analysed using reflexive thematic analysis., Results: From the professionals' (n = 15) accounts three main themes were developed from their interview data. The first, factors linked to suicidal ideation and behaviour, overarched two sub-themes: (1.1) the mother's context and (1.2) what the baby represents and what this means for the mother. These sub-themes described factors that professionals assessed or deemed contributory in relation to suicidal ideation and behaviour when a mother was under their care. The second main theme, communicating about and identifying suicidal ideation and behaviour, which outlined how professionals enquired about, and perceived, different suicidal experiences, encapsulated two sub-themes: (2.1) how to talk about suicide and (2.2) types of suicidal ideation and attempts. The third main theme, reducing suicidal ideation through changing how a mother views her baby and herself, focused on how professionals supported mothers to reframe the ways in which they viewed their babies and in turn themselves to reduce suicidal ideation., Conclusion: Professionals highlighted many factors that should be considered when responding to a mother's risk of suicide during the perinatal period, such as the support around her, whether the pregnancy was planned and what the baby represented for the mother. Professionals' narratives stressed the importance of adopting a tailored approach to discussing suicidal experiences with mothers to encourage disclosure. Our findings also identified psychological factors that professionals perceived as being linked to suicidal outcomes for mothers, such as self-efficacy; these factors should be investigated further., (© 2024. The Author(s).)

Background: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood., Methods: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code., Results: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p<0.0001), total bilirubin (1.06, 1.04-1.08, p<0.0001), and albumin (0.44, 0.33-0.61, p<0.0001). AA race did not affect the performance of prognostic models., Conclusions: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Introduction: Suicide is the leading direct cause of maternal death in the year following birth and the second leading cause during pregnancy, in the UK and Ireland. Currently no evidence-based psychological interventions exist specifically designed to reduce mothers' suicidal experiences during the perinatal period. Reducing suicidal ideation and behaviour in mothers is a priority to prevent deaths and lessen the distress felt by mothers and their families. As Q-methodology measures the consensus and disagreement between individuals on a given topic, the current study used Q-methodology to elicit the priorities for a future psychological intervention aimed at reducing suicidal ideation and behaviour during the perinatal period, from the collective perspectives of both mothers and professionals., Method: As part of this Q-methodology study, we developed a Q-set of 75 statements pertaining to possible elements of a psychological intervention that might help reduce a mother's suicidal ideation and behaviour during the perinatal period. Mothers and professionals were recruited via perinatal mental health services and social media advertisements., Results: Twenty-one mothers and 11 perinatal mental health professionals ranked each Q-set statement depending on its perceived importance in developing a new intervention. A centroid factor analysis was conducted and two factors, which accounted for 42% of the overall variance, were identified: Factor 1 "supporting the mother to create distance between herself and the appeal of suicide" and Factor 2 " establishing positive connections with the therapist, the baby and motherhood ." All participants believed that developing plans to keep the mother safe from suicide was the most important aspect for inclusion in a future intervention. Participants who loaded onto Factor 1 also prioritised supporting mothers to learn more about triggers for their suicidal ideation and behaviour. Ensuring a robust therapeutic alliance was more important for those who loaded onto Factor 2., Conclusion: This is the first study using Q-methodology to explore the psychological intervention priorities of mothers and professionals. Findings indicate clear priorities in terms of planning and coping during a crisis, endorsed by all participants, and provide an initial step in the development of a new perinatal suicide prevention intervention., 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 © 2023 Reid, Pratt, Edge and Wittkowski.)

Purpose of Review: The purpose of this review is to describe the commonly used molecular diagnostics and illustrate the prognostic importance to the more accurate diagnosis that also may uncover therapeutic targets., Recent Findings: The most recent WHO Classification of Central Nervous System Tumours (2021) lists over 100 distinct tumor types. While traditional histology continues to be an important component, molecular testing is increasingly being incorporated as requisite diagnostic criteria. Specific molecular findings such as co-deletion of the short arm of chromosome 1 (1p) and long arm of chromosome 19 (19q) now define IDH-mutant gliomas as oligodendroglioma. In recent years, DNA methylation profiling has emerged as a dynamic tool with high diagnostic accuracy. The integration of specific genetic (mutations, fusions) and epigenetic (CpG methylation) alterations has led to diagnostic refinement and the discovery of rare brain tumor types with distinct clinical outcomes. Molecular profiling is anticipated to play an increasing role in routine surgical neuropathology, although costs, access, and logistical concerns remain challenging., Summary: This review summarizes the current state of molecular testing in neuro-oncology highlighting commonly used and developing technologies, while also providing examples of new tumor types/subtypes that have emerged as a result of improved diagnostic precision., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

SARS-CoV-2 directly targets alveolar epithelial cells and can lead to surfactant deficiency. Early reports suggested surfactant replacement may be effective in improving outcomes. The aim of the study to assess the feasibility and efficacy of nebulized surfactant in mechanically ventilated COVID-19 patients. Patients were randomly assigned to receive open-labelled bovine nebulized surfactant or control (ratio 3-surfactant: 2-control). This was an exploratory dose-response study starting with 1080 mg of surfactant delivered at 3 time points (0, 8 and 24 h). After completion of 10 patients, the dose was reduced to 540 mg, and the frequency of nebulization was increased to 5/6 time points (0, 12, 24, 36, 48, and an optional 72 h) on the advice of the Trial Steering Committee. The co-primary outcomes were improvement in oxygenation (change in PaO 2 /FiO 2 ratio) and ventilation index at 48 h. 20 patients were recruited (12 surfactant and 8 controls). Demographic and clinical characteristics were similar between groups at presentation. Nebulized surfactant administration was feasible. There was no significant improvement in oxygenation at 48 h overall. There were also no differences in secondary outcomes or adverse events. Nebulized surfactant administration is feasible in mechanically ventilated patients with COVID-19 but did not improve measures of oxygenation or ventilation., (© 2023. The Author(s).)

Background: Suicidal thoughts, acts, plans and deaths are considerably more prevalent in people with non-affective psychosis, including schizophrenia, compared to the general population. Social isolation and interpersonal difficulties have been implicated in pathways which underpin suicidal experiences in people with severe mental health problems. However, the interactions between psychotic experiences, such as hallucinations and paranoia, suicidal experiences, and the presence, and indeed, absence of interpersonal relationships is poorly understood and insufficiently explored. The current study sought to contribute to this understanding., Methods: An inductive thematic analysis was conducted on transcripts of 22, individual, semi-structured interviews with adult participants who had both non-affective psychosis and recent suicidal experiences. A purposive sampling strategy was used. Trustworthiness of the analysis was assured with researcher triangulation., Results: Participants relayed both positive and negative experiences of interpersonal relationships. A novel conceptual model is presented reflecting a highly complex interplay between a range of different suicidal experiences, psychosis, and aspects of interpersonal relationships. Three themes fed into this interplay, depicting dynamics between perceptions of i. not mattering and mattering, ii. becoming disconnected from other people, and iii. constraints versus freedom associated with sharing suicidal and psychotic experiences with others., Conclusion: This study revealed a detailed insight into ways in which interpersonal relationships are perceived to interact with psychotic and suicidal experiences in ways that can be both beneficial and challenging. This is important from scientific and clinical perspectives for understanding the complex pathways involved in suicidal experiences., Trial Registration: ClinicalTrials.gov (NCT03114917), 14 th April 2017. ISRCTN (reference ISRCTN17776666 .); 5 th June 2017). Registration was recorded prior to participant recruitment commencing., (© 2023. The Author(s).)

Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated in two completed multisite clinical studies. Patients treated with ONC201 following initial radiation but prior to recurrence demonstrated a median overall survival of 21.7 months, whereas those treated after recurrence had a median overall survival of 9.3 months. Radiographic response was associated with increased expression of key tricarboxylic acid cycle-related genes in baseline tumor sequencing. ONC201 treatment increased 2-hydroxyglutarate levels in cultured H3K27M-DMG cells and patient CSF samples. This corresponded with increases in repressive H3K27me3 in vitro and in human tumors accompanied by epigenetic downregulation of cell cycle regulation and neuroglial differentiation genes. Overall, ONC201 demonstrates efficacy in H3K27M-DMG by disrupting integrated metabolic and epigenetic pathways and reversing pathognomonic H3K27me3 reduction., Significance: The clinical, radiographic, and molecular analyses included in this study demonstrate the efficacy of ONC201 in H3K27M-mutant DMG and support ONC201 as the first monotherapy to improve outcomes in H3K27M-mutant DMG beyond radiation. Mechanistically, ONC201 disrupts integrated metabolic and epigenetic pathways and reverses pathognomonic H3K27me3 reduction. This article is featured in Selected Articles from This Issue, p. 2293., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Platelets are rapidly deployed to infection sites and respond to pathogenic molecules via pattern recognition receptors (TLR, NLRP). Dickkopf1 (DKK1) is a quintessential Wnt antagonist produced by a variety of cell types including platelets, endothelial cells, and is known to modulate pro-inflammatory responses in infectious diseases and cancer. Moreover, DKK1 is critical for forming leukocyte-platelet aggregates and induction of type 2 cell-mediated immune responses. Our previous publication showed activated platelets release DKK1 following Leishmania major recognition., Results: Here we probed the role of the key surface virulence glycoconjugate lipophosphoglycan (LPG), on DKK1 production using null mutants deficient in LPG synthesis ( Δlpg1- and Δlpg2- ). Leishmania -induced DKK1 production was reduced to control levels in the absence of LPG in both mutants and was restored upon re-expression of the cognate LPG1 or LPG2 genes. Furthermore, the formation of leukocyte-platelet aggregates was dependent on LPG. LPG mediated platelet activation and DKK1 production occurs through TLR1/2., Conclusion: Thus, LPG is a key virulence factor that induces DKK1 production from activated platelets, and the circulating DKK1 promotes Th2 cell polarization. This suggests that LPG-activated platelets can drive innate and adaptive immune responses to Leishmania infection., 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 © 2023 Ihedioha, Sivakoses, Beverley, McMahon-Pratt and Bothwell.)

Background: Understanding recovery in mental health has received significant attention and consequently, recovery has been incorporated into health policy across many countries in the Global North. In comparison, the concept of 'recovery' from suicidal thoughts and behaviours has received little attention. However, the few studies in this area appear to suggest that recovery is a complex and an idiosyncratic process with many contributing factors. This can present a challenge for clinicians and services seeking to become more recovery focused. Thus, it seems of importance to develop a consensus on how recovery from suicidal thoughts and behaviours is conceptualised., Aim: The study aimed to use the Delphi design to establish a consensus of how recovery is defined by those with lived experience of suicidal thoughts and behaviours. The Delphi method draws on the expertise of a panel, often involving clinicians, researchers and lived experience experts to develop consensus over a topic by inviting them to rate the importance of, often a series of statements to a given topic area., Method: Lived experience experts were asked to complete two rounds of questionnaires distributed online to capture their views on recovery., Results: A total of 196 individuals gave their views on the first round of the study and 97 gave their views on the second round. A final list of 110 statements was developed that 80% or more of participants defined as essential or important. Statements covered items that were important in defining, facilitation and hindering the process of recovery., Conclusion: Findings are consistent with the wider literature that suggests that recovery is an idiosyncratic process, but with many commonly shared features. Here we also show that a comprehensive definition of recovery must include factors that hinder the process of recovery. Implications and recommendations for practice, policy development and future research are discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ropaj et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The aim of the study was to explore staff views about whether and how service users should be involved in the process of team formulation., Design: This study used Q methodology to explore health care professionals' views about service user involvement in team formulation meetings., Methods: Forty staff members with experience of attending team formulation meetings completed a Q Sort in which they ranked how much they agreed or disagreed with 58 statements about service user inclusion in team formulation. Factor analysis was used to identify viewpoints within the data set., Results: A three-factor solution accounting for 60% of the variance was considered the best fit for the data. The factors were: 'A safe space for staff', 'Concerns about inclusion and collaboration' and 'Service users might find attendance harmful'. Consensus statements identified areas where all participants agreed., Conclusions: This is an important area for exploration, given the growing practice of team formulation and the professional and ethical issues raised by service user involvement. There are a range of ways to promote inclusion within the practice, and staff should always consider the individual needs of service users., (© 2023 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Objectives: Suicide is a leading cause of death worldwide. People experiencing psychosis are at increased risk of death by suicide. Talking therapies can alleviate suicidal thoughts, plans, and attempts. Therapies need to also be acceptable to recipients. The aim of this study was to investigate the views on psychological therapy for people experiencing psychosis and suicidality using the Theoretical Framework of Acceptability., Design: Qualitative interview study., Methods: Participants were recruited from a randomised controlled trial comparing suicide prevention psychological therapy with treatment as usual. Individuals had a diagnosis of non-affective psychosis and experience of suicidal thoughts, plans and/or attempts. To assess the acceptability of the therapy, semi-structured interviews were conducted with 20 participants randomised to receive therapy. Data were deductively analysed using an adaptation of the Theoretical Framework of Acceptability., Results: Interviews (Mean = 45 min) were conducted and audio recorded with 21 participants. Data were organised into six themes: 1. Affective attitude, 2. Burden, 3. Alliance, 4. Intervention coherence, 5. Perceived effectiveness, and 6. Self-efficacy. There was no evidence of issues relating to domains of ethicality and opportunity costs associated with receiving therapy., Conclusions: Talking about suicide was difficult and, at times, distressing, but it was perceived to be useful for understanding experiences. To be acceptable, it is important for therapists to ensure that clients' understanding of therapy aligns with expectations of effectiveness and to invest in building strong therapeutic alliances. Future research will benefit from examining therapists' experiences of delivering therapy through different modes (e.g. online, telephone)., (© 2023 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Yellow fever virus, transmitted by infected Aedes spp. mosquitoes, causes an acute viral hemorrhagic disease. During October 2021-February 2022, a yellow fever outbreak in some communities in Ghana resulted in 70 confirmed cases with 35 deaths (case-fatality rate 50%). The outbreak started in a predominantly unvaccinated nomadic community in the Savannah region, from which 65% of the cases came. The molecular amplification methods we used for diagnosis produced full-length DNA sequences from 3 confirmed cases. Phylogenetic analysis characterized the 3 sequences within West Africa genotype II; strains shared a close homology with sequences from Cote d'Ivoire and Senegal. We deployed more sensitive advanced molecular diagnostic techniques, which enabled earlier detection, helped control spread, and improved case management. We urge increased efforts from health authorities to vaccinate vulnerable groups in difficult-to-access areas and to educate the population about potential risks for yellow fever infections.

Recent studies exploring the impact of methylation in tumor evolution suggest that although the methylation status of many of the CpG sites are preserved across distinct lineages, others are altered as the cancer progresses. Because changes in methylation status of a CpG site may be retained in mitosis, they could be used to infer the progression history of a tumor via single-cell lineage tree reconstruction. In this work, we introduce the first principled distance-based computational method, Sgootr, for inferring a tumor's single-cell methylation lineage tree and for jointly identifying lineage-informative CpG sites that harbor changes in methylation status that are retained along the lineage. We apply Sgootr on single-cell bisulfite-treated whole-genome sequencing data of multiregionally sampled tumor cells from nine metastatic colorectal cancer patients, as well as multiregionally sampled single-cell reduced-representation bisulfite sequencing data from a glioblastoma patient. We show that the tumor lineages constructed reveal a simple model underlying tumor progression and metastatic seeding. A comparison of Sgootr against alternative approaches shows that Sgootr can construct lineage trees with fewer migration events and with more in concordance with the sequential-progression model of tumor evolution, with a running time a fraction of that used in prior studies. Lineage-informative CpG sites identified by Sgootr are in inter-CpG island (CGI) regions, as opposed to intra-CGIs, which have been the main regions of interest in genomic methylation-related analyses., (© 2023 Liu et al.; Published by Cold Spring Harbor Laboratory Press.)

The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/)., Competing Interests: Declaration of interests T.I. is co-founder of Data4Cure, Inc., is on the Scientific Advisory Board, and has an equity interest. T.I. is on the Scientific Advisory Board of Ideaya BioSciences, Inc. and has an equity interest. 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. R.W.S. is co-founder of Canal House Biosciences, LLC, is on the Scientific Advisory Board, and has an equity interest. N.J.K. is a shareholder of Tenaya Therapeutics and has received stocks from Maze Therapeutics and Interline Therapeutics; has consulting agreements with the Icahn School of Medicine at Mount Sinai, New York, Maze Therapeutics and Interline Therapeutics. The laboratory of N.J.K. has received research support from Vir Biotechnology and F. Hoffmann-La Roche., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A longstanding goal of biomedicine is to understand how alterations in molecular and cellular networks give rise to the spectrum of human diseases. For diseases with shared etiology, understanding the common causes allows for improved diagnosis of each disease, development of new therapies and more comprehensive identification of disease genes. Accordingly, this protocol describes how to evaluate the extent to which two diseases, each characterized by a set of mapped genes, are colocalized in a reference gene interaction network. This procedure uses network propagation to measure the network 'distance' between gene sets. For colocalized diseases, the network can be further analyzed to extract common gene communities at progressive granularities. In particular, we show how to: (1) obtain input gene sets and a reference gene interaction network; (2) identify common subnetworks of genes that encompass or are in close proximity to all gene sets; (3) use multiscale community detection to identify systems and pathways represented by each common subnetwork to generate a network colocalized systems map; (4) validate identified genes and systems using a mouse variant database; and (5) visualize and further investigate select genes, interactions and systems for relevance to phenotype(s) of interest. We demonstrate the utility of this approach by identifying shared biological mechanisms underlying autism and congenital heart disease. However, this protocol is general and can be applied to any gene sets attributed to diseases or other phenotypes with suspected joint association. A typical NetColoc run takes less than an hour. Software and documentation are available at https://github.com/ucsd-ccbb/NetColoc ., (© 2023. Springer Nature Limited.)

Aerosols' influences on Earth's climate have been documented by several authors. This ranges from scattering and reflecting of shortwave radiation (direct effect) which is also regarded as the "Whitehouse Effect," to the ability to act as condensation nuclei (indirect effect) which results in cloud droplet formation. This broad summary of aerosol's effect on earth's climate has in turn affected some other weather variables either positively or negatively depending on people's perspectives. This work was done in a view to ascertaining some of these claims by determining the statistical significance of some certain aerosol's relationships with some selected weather variables. This was done over six (6) stations across the West African region to represent the climatic zones from the rainforest around the coasts to the desert of the Sahel. Data used consist of aerosol types (biomass burning, carbonaceous, dust, and PM 2.5 ) and climatic types (convective precipitation, wind speed, and water vapor) over a period of 30 years, with the python and ferret programs explicitly used for the graphical analyses. Climatologically, locations close to the point source seem to record more of the presence of the pollutants than the farthest ones. Results indicated that aerosols were more pronounced in the dry months of NDJF over the rainforest region depending on the latitudinal position of the location. The relationship result showed a negative correlation between convective precipitation and aerosols, except carbonaceous. But the strongest relationship can be found between water vapor and the selected aerosol types., (© 2023. The Author(s).)

Introduction: Suicide is a leading cause of death globally. People with psychosis are at increased risk of suicide death and up to half experience suicidal thoughts and/or engage in suicidal behaviors in their lifetime. Talking therapies can be effective in alleviating suicidal experiences. However, research is yet to be translated into practice, demonstrating a gap in service provision. The barriers and facilitators in therapy implementation require a thorough investigation including the perspectives of different stakeholders such as service users and mental health professionals. This study aimed to investigate stakeholders' (health professionals and service users) perspectives of implementing a suicide-focused psychological therapy for people experiencing psychosis in mental health services., Methods: Face-to-face, semi-structured interviews with 20 healthcare professionals and 18 service users were conducted. Interviews were audio recorded and transcribed verbatim. Data were analyzed and managed using reflexive thematic analysis and NVivo software., Results: For suicide-focused therapy to be successfully implemented in services for people with psychosis, there are four key aspects that need to be considered: (i) Creating safe spaces to be understood; (ii) Gaining a voice; (iii) Accessing therapy at the right time; and (iv) Ensuring a straightforward pathway to accessing therapy., Discussion: Whilst all stakeholders viewed a suicide-focused therapy as valuable for people experiencing psychosis, they also recognize that enabling successful implementation of such interventions will require additional training, flexibility, and resources to existing services., 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 © 2023 Peters, Awenat, Gooding, Harris, Cook, Huggett, Jones, Lobban, Pratt and Haddock.)

Rates of suicide and violence are higher amongst male prisoners than the general population. This study aimed to explore the emotional experiences of male prisoners in the distal and immediate lead-up to acts of suicide and violence. Nine male prisoners created drawings of their emotions in the lead-up to an act of suicide and/or violence. Accompanying verbal interview data was collected to explore the narrative of these drawings. Polytextual thematic analysis was conducted on both the visual and audio data. Three themes were found. 'The outside picture' depicted the emotions that male prisoners exhibited externally. 'The inside picture' illustrated the internal emotions felt by male prisoners which were often complex and abstract. 'The complexity of the picture' denotes the complicated relationship between emotions and suicide/violence. Male prisoners experience a range of emotions in the lead up to acts of suicide and violence, with a similar set of emotions being experienced immediately prior to both suicide and violence. This study has illustrated the benefits of using a novel and creative methodology, and has demonstrated that future research with male prisoners could benefit from adopting a participatory visual methodology., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies., Methods: Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients., Results: Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant., Conclusions: Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs., (© The Author(s) 2023. Published by Oxford University Press.)

Cytoscape is an open-source bioinformatics environment for the analysis, integration, visualization, and query of biological networks. In this perspective piece, we describe our project to bring the Cytoscape desktop application to the web while explaining our strategy in ways relevant to others in the bioinformatics community. We examine opportunities and challenges in developing bioinformatics software that spans both the desktop and web, and we describe our ongoing efforts to build a Cytoscape web application, highlighting the principles that guide our development., 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 © 2023 Pratt, Pillich and Morris.)

Background: Going to university is an important milestone in many people's lives. It can also be a time of significant challenge and stress. There are growing concerns about mental health amongst student populations including suicide risk. Student mental health and counselling services have the potential to prevent suicide, but evidence-based therapies are required that fit these service contexts. The Broad-Minded Affective Coping intervention (BMAC) is a brief (6 sessions), positive imagery-based intervention that aims to enhance students access to past positive experiences and associated emotions and cognitions. Pilot data provides preliminary support for the BMAC for students struggling with suicidal thoughts and behaviours, but this intervention has not yet been evaluated in the context of a randomised controlled trial (RCT). The Mental Imagery for Suicidality in Students Trial (MISST) is a feasibility RCT that aims to determine the acceptability and feasibility of evaluating the BMAC as an intervention for university students at risk of suicide within a larger efficacy trial. Key feasibility uncertainties have been identified relating to recruitment, retention, and missing data. Intervention acceptability and safety will also be evaluated., Method: MISST is a feasibility randomised controlled trial design, with 1:1 allocation to risk assessment and signposting plus BMAC or risk assessment and signposting alone. Participants will be university students who self-report experiences of suicidal ideation or behaviour in the past 3 months. Assessments take place at baseline, 8, 16, and 24 weeks. The target sample size is 66 participants. A subset of up to 20 participants will be invited to take part in semi-structured qualitative interviews to obtain further data concerning the acceptability of the intervention., Discussion: The BMAC intervention may provide an effective, brief talking therapy to help university students struggling with suicidal thoughts that could be readily implemented into university student counselling services. Depending on the results of MISST, the next step would be to undertake a larger-scale efficacy trial., Trial Registration: The trial was preregistered (17 December 2021) on ISRCTN (ISRCTN13621293) and ClinicalTrials.gov (NCT05296538)., (© 2023. The Author(s).)