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Evidence-Based Practice (EBP) has increased the availability of psychological treatments, yet many people do not benefit from therapy, some report deteriorations in symptoms, and dropout rates remain high. Precision Mental Health (PMH) is proposed as an extension of EBP by combining systematic measurement with predictive analytics to support the right intervention, at the right time, for the right person. Recent advances in Artificial Intelligence (AI) make PMH increasingly feasible in routine psychotherapy; however, the implementation of these approaches in routine care is still incipient. In this context, the present article has two main aims. First, we summarize key advances in PMH, particularly measurement-based care and data-informed decision making. Second, we introduce the NOVA project (Navigating Outcomes via Analytics), a multi-phase translational program designed to implement PMH in real-world psychological services. Guided by the Implementing Precision Methods framework, NOVA integrates (i) stakeholder-informed work on clinician acceptability and intention to use, (ii) pragmatic evaluation of decision support tools in routine care, (iii) development of robust and interpretable predictive models, and (iv) training and dissemination activities aligned with responsible innovation and professional competencies for AI-supported precision care. By detailing NOVA’s implementation pathway, we aim to provide a concrete roadmap for bridging AI innovation and psychological practice, accelerating the sustainable adoption of PMH in real-world settings.

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for many hematological malignancies, but graft-versus-host disease (GVHD) is a common complication. Low gut microbiome diversity is associated with higher GVHD risk and shorter survival in multiple studies. Recently, the BMT CTN 1703 clinical trial demonstrated superiority of a GVHD-prophylaxis regimen including post-transplant cyclophosphamide (PTCy) compared to the standard prophylaxis (tacrolimus and methotrexate, Tac/MTX) in terms of GVHD-free, relapse-free survival at one year among reduced intensity conditioning allo-HCT recipients. However, the effect of PTCy on the gut microbiome and its association with clinical outcome have not been described. Here, we report on a companion randomized clinical controlled trial (BMT CTN 1801), which collected 2575 longitudinal stool samples from 304 study participants. Samples were obtained up to weekly up to day 84 post allo-HCT and at less frequent intervals thereafter, up to 2 years. Microbiome diversity and absolute microbial load were lower in the PTCy group compared to the Tac/MTX group on days 14–28 post-HCT. However, diversity at the timepoint closest to neutrophil engraftment was not significantly associated with non-relapse mortality after one year or other clinical outcomes, contrary to expectations from previous studies. Microbial domination events, when a single species exceeds 30% relative abundance, were comparable across treatment arms and reflected both pathogen blooms as well as less severe disruptions of the microbial community. Clostridium scindens and secondary bile acid metabolism pathways were less prevalent in the PTCy arm than in the Tac/MTX arm post-HCT, yet presence of secondary bile acid metabolism pathways was associated with a lower risk of chronic GVHD. Given that PTCy was associated with a greater disruption of the microbiome as measured by diversity, absolute microbial abundance, and bile acid metabolism capability, but better clinical outcomes overall, these data suggest that the importance of the microbiome in modulating the host immune systems after allo-HCT is specific to different types of GVHD prophylaxis.

ABSTRACT The paraneurium is a distinct connective tissue sheath that loosely envelopes the epineurium. The space between the para‐ and epineurium (the subparaneurial compartment) holds significant clinical relevance, serving as a target for deposition of regional anesthesia and a potential pathway for the pathological spread of cysts and tumors. However, visualization of the paraneurial layer, as a separate structure from the epineurium, remains challenging with conventional MRI, especially in the absence of pathology. This study evaluated the visualization of the paraneurium using ultra‐high‐field 7‐Tesla (7 T) MRI compared to conventional field strengths. We assessed normal nerve anatomy and a spectrum of pathological cases, including intraneural ganglion cysts, schwannomas, intraneural perineuriomas, and metastatic melanoma. The results demonstrated that 7 T MRI provides superior resolution and delineation of the paraneurium compared to 1.5 and 3 T systems. In normal anatomy, T1‐weighted and proton density (PD) sequences provided optimal contrast between the paraneurium and surrounding adipose tissue. In contrast, for pathological cases, T2‐weighted sequences with fat suppression were superior for depicting the paraneurium and identifying subparaneurial involvement. In conclusion, 7 T MRI offers a significant advantage in identifying the thin paraneurial layer. This capability provides valuable insights into the pathogenesis of tumor spread and holds promise for improving pre‐operative planning and clinical decision‐making in peripheral nerve pathology.

INTRODUCTION: The American College of Gastroenterology assembled a multidisciplinary task force to evaluate the current state and future direction of artificial intelligence (AI) in gastroenterology, hepatology, and endoscopy leading to the development of consensus-based recommendations for responsible AI integration in clinical practice. METHODS: A total of 32 subject-matter experts and 12 industry partners, representing diverse practice settings and expertise, conducted subgroup literature reviews across 5 key areas (endoscopy, practice management clinical applications, training and education, inflammatory bowel disease and liver disease, ethics and equity). Draft statements were developed and rated on a 5-point Likert scale using a modified Delphi process. A consensus was set at ≥70% combined agreement. Nonconsensus items were revised and revoted electronically. RESULTS: A total of 43 statements, 40 (93%) reached consensus in round 1 and the remaining 3 achieved consensus after round 2. Evidence supports computer-aided detection improving adenoma detection rate and miss rate in controlled studies, with mixed real-world impact and insufficient long-term outcomes (e.g., interval colon cancer rate). Recommendations emphasize thorough validation and reduction of bias by heterogeneous Data sets. Outside endoscopy, ambient AI scribes, natural language processing (NLP)-enabled coding, workflow optimization, and previous authorization support show potential. Training recommendations endorse a structured AI curriculum while preserving independent procedural competence to avoid deskilling. In inflammatory bowel disease and hepatology, AI could help improve diagnostic accuracy, help predict risk of disease progression, and help guide therapy. Equity, governance, and reimbursement statements call for chain-of-custody data protections, specialty-society oversight, and payment models that reward quality and cost reduction. DISCUSSION: This consensus outlines how AI can augment rather than replace clinical expertise while promoting safety, transparency, interoperability, and equity. Priorities include pragmatic and prospective trials, multi-institutional data-sharing consortia, bias mitigation, and workforce training to enable trustworthy and clinically impactful AI adoption in gastroenterology, liver, and endoscopy care.

Objectives Female sex and anticitrullinated protein antibodies (ACPA) are associated with higher disease activity in rheumatoid arthritis (RA). Since disease-related inflammation is linked to cardiovascular risk, we explored whether sex and ACPA influenced the association between disease activity at study entry and cardiovascular risk in established RA. Methods We evaluated 4008 patients with prevalent RA from an international observational cohort enrolled between 1985 and 2012. Outcomes included major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction and stroke) and ischaemic cardiovascular events (iCVE: MACE, angina, revascularisation, transient ischaemic attack and peripheral arterial disease). Follow-up accrued from enrolment until the first event or censoring. Multivariable Cox models stratified by centre risk evaluated disease activity, sex, ACPA and their interactions. Results We documented 193 MACE and 299 iCVE. Disease activity and sex were associated with MACE (all p≤0.017) and iCVE (p≤0.005) but ACPA was only associated with MACE (p=0.043). A three-way interaction on MACE (p=0.034) but not iCVE was noted. Among ACPA-negative patients, disease activity was associated with MACE in males (HR 1.57 (95% CI 1.14 to 2.16)) but not females (p-for-interaction=0.022). Among ACPA-positive patients, neither the disease activity x sex interaction (p=0.929), nor main effect of disease activity on MACE (p=0.124) was significant, but male sex was (HR 1.61 (95% CI 1.15 to 2.27)). Among females, neither disease activity x ACPA interaction (p=0.523) nor disease activity (p=0.319) was significant for MACE, but ACPA was (HR 1.57 (95% CI 1.02 to 2.42)). Conclusions The effect of disease activity at enrolment on cardiovascular risk in prevalent RA varies across patient groups with different sex and ACPA characteristics.

BACKGROUND Recently, the distribution of subparaneurial ganglion cysts involving the common peroneal and tibial nerves was described based on MRI analysis. Crossover in extreme cases was observed at the sciatic bifurcation through a mechanism comparable to a geyser, enabled by fenestrations in the epi- and paraneurium at the level of the bifurcation. The goal of this study was to investigate whether the geyser theory for crossover holds for other locations. OBSERVATIONS The authors’ prospectively maintained database of > 1100 cases of intraneural ganglion cysts in the world’s literature was queried for the existence of subparaneurial ganglion cysts at locations other than the knee. A previously unrecognized case involving the ulnar nerve originating from the elbow joint was found. Reinterpretation of the patient’s MRI studies showed circumferential subparaneurial distribution of a cyst over a long distance. Based on their previously reported geyser theory, the authors wondered if crossover had occurred at the level of the medial cord. A fenestration in the epi- and paraneurium at this level was confirmed on histological analysis of a normal cadaveric specimen. LESSONS This illustrative case shows that the geyser theory also holds in other locations. Surgical treatment of these subparaneurial cysts still follows the principles of the unified articular theory. https://thejns.org/doi/10.3171/CASE25671

Abstract Background Anxiety disorders (ANX) affect 30–60% of individuals with bipolar disorder (BD), yet limited research has systematically examined clinical characteristics and treatment patterns in this comorbid population. This study investigated demographic, clinical, and pharmacotherapeutic differences between individuals with BD with and without comorbid ANX. Methods Cross-sectional data from 2,225 adults with BD enrolled in the Mayo Clinic Bipolar Disorder Biobank were analyzed. Participants were assessed for comorbid ANX, demographics, clinical characteristics, medication use, and treatment response using the Alda-A scale. Results Overall, 61% (n = 1,366) had comorbid ANX. Individuals with BD + ANX were younger (40.4 vs. 43.6 years, p < 0.001), more likely female (66.6% vs. 54.8%, p < 0.001), and exhibited higher rates of rapid cycling (64.2% vs. 45.2%, p < 0.001), suicide attempts (40.4% vs. 24.8%, p < 0.001), substance use disorders (63.5% vs. 54.8%, p < 0.001), and somatic comorbidities (MCIRS: 6.68 vs. 5.42, p < 0.001). Pharmacotherapeutically, BD + ANX individuals were less likely to receive lithium (37.1% vs. 47.8%, p = 0.005) and valproic acid (21.7% vs. 29.6%, p = 0.047), but more likely to receive antidepressants (53.8% vs. 39.5%, p < 0.001), benzodiazepines (39.9% vs. 26.6%, p < 0.001), and gabapentinoids (8.5% vs. 4.5%, p < 0.001). Notably, 17.3% of BD + ANX individuals received antidepressants without mood stabilizer coverage. Treatment response (Alda-A) scores were significantly lower in BD + ANX for lithium (4.91 vs. 6.05, p < 0.001), mood-stabilizing anticonvulsants (5.09 vs. 6.22, p < 0.001), and second-generation antipsychotics (4.67 vs. 5.73, p < 0.001). Similar patterns were observed in both BD-I and BD-II subtypes. Conclusions Individuals with BD + ANX represent a more severely affected subgroup with distinct prescribing patterns favoring antidepressants over mood stabilizers and attenuated mood stabilizers response. These findings highlight the need for anxiety-informed treatment algorithms recognizing anxiety comorbidity as a negative prognostic factor.

Abstract Background Liver surgery carries a high risk of complications due to the complex interplay of patient-related factors, disease characteristics, and liver function. Expertise is essential for healthcare professionals managing hepatobiliary patients. This European consensus provides evidence-based guidance on selected aspects of peri- and postoperative care. Methods A modified Delphi process was used to achieve consensus, with a 70% agreement threshold. The expert panel comprised hepatobiliary surgeons, anaesthetists, hepatologists, a specialist nurse, and a physiotherapist. A systematic literature search was conducted in PubMed/MEDLINE, Embase, Web of Science, and Cochrane databases. Six topics were addressed: thromboprophylaxis; perioperative antibiotics; prehabilitation/nutrition/mobilization; bile leak including bilioenteric anastomosis leaks; post-hepatectomy haemorrhage; and post-hepatectomy liver failure (PHLF). Evidence appraisal and statement development followed Scottish Intercollegiate Guidelines Network methodology. A patient representative reviewed the guideline. Results Searching the literature yielded 204 included publications from an initial 6514. Thirty-two statements were formulated with a median evidence level of 2. Evidence strength varied by topic with noticeably lower evidence levels in complex surgery settings and less prevalent conditions. In some topics, study heterogeneity and specific inclusion criteria resulted in conditional recommendations, despite high-level evidence. Notably, the weakest evidence was found for perioperative thromboprophylaxis and PHLF management. Strong recommendations were formulated for prehabilitation, early postoperative mobilization, and avoidance of routine drain use. Several evidence gaps warranting multicentre studies were identified. Conclusion Optimizing peri- and postoperative care after liver resection remains challenging. Standardizing key practices and addressing evidence gaps through collaborative research are vital to improve outcomes.

ABSTRACT Background Mood episodes in bipolar disorder (BD) follow a seasonal pattern in approximately 25% of patients. We aimed to examine the associations of specific seasonality patterns in BD with various clinical phenotypes and treatment‐related outcomes. Methods Patients from the Mayo Clinic Bipolar Disorder Biobank with available seasonality data were included in the study. Among those reporting any seasonality, participants were further categorized into four seasonality groups: fall/winter depression, spring/summer (hypo)mania, biphasic (fall/winter depression with spring/summer (hypo)mania), and equinoctial seasonality (any mood episode occurring in spring or fall). Regression models were used, treating seasonality patterns as the predictor of clinical phenotypes (BD subtype, early onset, history of psychosis, suicide attempt, rapid cycling), lifetime medication exposure (number of unique antidepressants, antipsychotics, and any psychotropics) and treatment response to mood stabilizers (Alda A score). Results Among 1702 patients with BD (61.5% female, mean age = 41.43 ± 14.73 years), 44.6% reported seasonal mood episodes. Individuals with any seasonality were more likely to have BD‐I (OR = 1.29, p = 0.024), early onset (OR = 1.29, p = 0.026), exposure to higher lifetime number of antipsychotics (IRR = 1.20, p < 0.001) and any psychotropics (IRR = 1.13, p < 0.001). Fall/winter depression was associated with a higher lifetime number of antidepressants (IRR = 1.18, p = 0.021), any psychotropics (IRR = 1.14, p = 0.013), worse response to lithium ( β = −0.82, p = 0.029) and all mood stabilizers ( β = −0.69, p = 0.014). Spring/summer (hypo)mania showed negative associations with rapid cycling (OR = 0.36, p < 0.001) and lifetime number of antidepressants (IRR = 0.70, p = 0.013). Equinoctial seasonality was linked to a history of psychosis (OR = 1.76, p = 0.004). Conclusion Seasonality in BD is associated with distinct clinical features and treatment‐related outcomes. Specific seasonality patterns, particularly fall/winter depression, may reflect a more complex and difficult‐to‐treat illness course. These findings highlight the need for research to better characterize seasonality subtypes beyond a binary “seasonal” vs. “non‐seasonal” classification and to explore how these patterns influence the illness course and management of BD.

Abstract Background Neurodegenerative tauopathies, characterized by the aggregation of misfolded tau protein, poses a significant clinical and scientific challenge. Tau interaction with other proteins affects the formation of ‘tau‐seed’ but less is known about its effects on tau‐seed properties. Our previous study revealed that Bassoon (BSN), a presynaptic protein, interacts with tau‐seed, exacerbating its toxicity. A parallel study also associated missense mutations in BSN with tau aggregation in patients, prompting an investigation into the influence of BSN and its mutations in neurodegeneration for potential therapeutic insights. Method We generated a knock‐in mouse model (BSNKI) harboring the disease‐associated p.Pro3866Ala mutation in endogenous Bsn. Cognitive and motor abilities were evaluated throughout the lifespan of heterozygous and homozygous BSNKI mice, along with analyses of BSN and tau patterns, gliosis, and gene expression changes in their brains. Additionally, we conducted single‐nucleic RNA sequencing to identify changes at the cellular level. Result BSNKI mice displayed progressive motor and memory impairments on the rotarod and fear conditioning assays, respectively. At 10 months, their brains displayed somatic BSN and pathological tau accumulation, with the gene expression changes indicating alterations of microglia, classical complement cascade, and synapse pruning pathways, as well as dysregulation of protein quality control pathways. Neuropathological data suggests that the BSN P3866A mutation instigates robust microglia activation, increased microglia‐mediated synapse engulfment, and a co‐deposition of proteasomal subunits with BSN. Furthermore, snRNA‐seq data suggest changes in neuronal populations and cell signaling. Conclusion Our BSNKI mouse model revealed the contributions of BSN P3866A mutation to tau pathogenesis and neurodegeneration. BSNKI animals displayed progressive motor and memory impairments, deposits of endogenous tau and BSN, as well as changes in gene expression and neuronal populations. Notably, BSN likely plays a dual role, promoting tau aggregation and sequestering protein degradation molecules, leading to tau and protein accumulation at the soma and synapse, which in turn could trigger neuroinflammation and other cellular changes. These findings propose BSN as a promising therapeutic target for tauopathies, underscoring the need for further exploration to elucidate underlying mechanisms and therapeutic implications.