Publications by Year: 2026

PURPOSE: Participation rates in population-based health surveys have been declining for decades, with nonresponse bias being a serious threat to the validity and generalizability of results. The aim of the study was to examine differences between participants and nonparticipants invited to a psychiatric diagnostic interview survey in terms of sociodemographic and health characteristics, and use of health services for mental health problems, including diagnoses.

METHODS: The study sample for the follow-up psychiatric diagnostic interview was recruited among participants in the fourth survey of the Trøndelag Health Study (HUNT4) in Norway. Information about sociodemographic and health characteristics was gathered from the main survey, while data on health service use was collected by linking records from primary and specialist patient registries with information about participation status.

RESULTS: Male sex, younger age, being unmarried, having lower educational attainment, and having lower income were associated with higher odds for nonparticipation. Contact with the primary or specialist health services for mental health problems and hospitalization for a mental disorder more than a year before or after invitation date, were associated with lower odds for nonparticipation, especially for diagnoses indicating affective disorders, anxiety disorders, personality disorders, hyperkinetic disorders or milder mental complaints.

CONCLUSION: Contrary to most prior studies examining nonresponse bias, the results indicate that people who had been in contact with the health services for mental health problems were more inclined to participate in a survey focused on mental disorders. The direction of nonresponse bias should be carefully considered and adjusted for in population-based studies.

The application of machine learning (ML) and artificial intelligence (AI) algorithms in medical imaging is an emerging area of interest, particularly in the context of clinical decision-making. Here, we report on the overall performance (i.e., sensitivity, specificity, and accuracy) of commonly used ML/AI techniques including convolutional neural networks (CNNs), support vector machines (SVMs), random forests, and ensemble approaches on the clinically relevant task of distinguishing between Parkinson's disease (PD) participants and matched healthy controls (HC). Our systematic review includes 130 studies from six different imaging modalities - dopamine transporter scans ([123I]Ioflupane single-photon emission computed tomography (SPECT)), positron emission tomography (PET) including [18F]FDG, [18F]DOPA, and [11C]raclopride, structural magnetic resonance imaging (MRI) (T1- and T2-weighted), functional MRI, and diffusion MRI. While some findings were in line with expectations for some modalities, such as the superior performance of dopamine SPECT and PET (> 90% sensitivity, specificity, and accuracy with methods like convolutional neural networks), others were more nuanced with the best-performing class of algorithms depending on the imaging modality, and sometimes, even the data source. Overall, we summarize the emerging trends across studies for each imaging technique and provide valuable recommendations for future lines of inquiry.

OBJECTIVES: Despite the stress of having a baby in a Neonatal Intensive Care Unit (NICU), factors that promote adjustment remain unclear. We examined which resiliency factors were associated with family adjustment across the NICU journey.

STUDY DESIGN: Parents with a baby in the NICU (≤2 weeks) completed surveys at three timepoints (during admission (N = 165); 1 month later (N = 85); 3 months later (N = 55)). Surveys included sociodemographics and validated measures of emotional distress, relational outcomes, and resiliency.

RESULTS: Mixed models revealed that lower parental distress was associated with: (1) higher mindfulness; (2) more adaptive coping; (3) greater parental self-efficacy (only anxiety); and (4) increased parental time for themselves (only posttraumatic stress). Higher couple satisfaction was associated with more dyadic coping and social support. Stronger parent-child bonding was associated with greater parental self-efficacy.

CONCLUSION: Mindfulness and coping are important for parental distress. Building parental efficacy, encouraging self-care, and promoting shared coping and social support is important.

Follicular regulatory T (TFR) cells restrain follicular helper T (TFH) cell-mediated B cell responses to optimize humoral immunity while limiting autoimmunity. Here we assessed the developmental dynamics of TFR cells. We found that TFR cells undergo progressive differentiation through progenitor, early effector and late effector stages. Late effector TFR cells possessed inherent instability, and could lose expression of FoxP3 to become ExTFR cells. Expression of effector TFH programs in TFR cells preceded instability, a process that was mediated by Tcf7. A subset of ExTFR could be redeemed by re-expression of FoxP3. Extrinsically, TFH cells enhanced late effector TFR cell differentiation by diverting cells away from a default Prdm1/Blimp-1 fate to express Bcl6. Together, these data indicate that TFR cells are a dynamic and plastic cell subset, the differentiation of which is controlled by intrinsic and extrinsic programs that work together to form a feedback loop to control humoral immunity.

Although immune checkpoint inhibitor therapies have revolutionized oncology, many cancers are unresponsive or develop resistance that involves transforming growth factor-β1 (TGFβ1). This multicenter, open-label, phase 1 study (DRAGON trial, SRK-181-001) evaluated safety, pharmacokinetics, pharmacodynamics, predictive biomarkers and efficacy of linavonkibart, a first-in-class fully human selective anti-latent TGFβ1 antibody with anti-programmed cell death protein 1 (PD-1) therapy. The DRAGON trial was divided into three treatment parts: part A1 (dose-escalation cohorts with single-agent linavonkibart), part A2 (dose-escalation cohorts with the combination treatment of linavonkibart and pembrolizumab) and part B (dose-expansion cohorts with the combination treatment). The primary objective of the study was to determine the safety and tolerability of linavonkibart alone and in combination with pembrolizumab. Secondary objectives included evaluation of linavonkibart pharmacokinetics for each treatment paradigm, assessment of anti-linavonkibart antibody development (parts A and B) and measurement of antitumor activity (part B) after treatment. All primary and secondary objectives were met in the study. Overall, linavonkibart had a manageable safety profile, and combined therapy with pembrolizumab was generally consistent with that of pembrolizumab monotherapy. Dermatological reactions were the only additional risk identified. Neither cytokine release syndrome nor infusion interruption was observed in any patient enrolled in DRAGON. In part A (n = 34), no dose-limiting toxicities or grade 4 or 5 treatment-related adverse events occurred (linavonkibart; ≤3,000 mg once every 3 weeks (Q3W) and 2,000 mg once every 2 weeks (Q2W)). In part B (n = 78), patients progressing on prior anti-PD-1 therapy received linavonkibart (1,500 mg Q3W/1,000 mg Q2W) with pembrolizumab (200 mg Q3W). This combination demonstrated confirmed objective response rates of 20.0%, 18.2%, 9.1% and 9.1% in anti-PD-1-resistant patients with clear cell renal cell cancer (ccRCC), melanoma, head and neck squamous cell cancer and urothelial cancer, respectively. Biomarker data provide proof of mechanism and a potential ccRCC patient selection strategy. ClinicalTrials.gov identifier: NCT04291079 .

CRISPR-based genome editing therapeutics are entering the clinic, offering transformative potential but also presenting potential risks. Preclinical-to-clinical toolkits are needed to assess the safety and efficacy of these new therapies and accelerate progress. Emerging technologies to monitor the biological effects of genome editors cover a range of biological scales, from the direct measurement of editing outcomes in DNA, to human microphysiological systems, and non-invasive in vivo imaging. Measurements of on-target and off-target editing outcomes, including sequences unique to humans, provide essential benchmarks to understand functional responses. Microphysiological systems, including organoids and organs-on-chips, enable phenotypic evaluations of editing strategies in varied organ lineages and disease states. Non-invasive imaging modalities can track the biodistribution and activities of genome editors and edited cells in vivo. Collectively, these technologies provide complementary insights across different scales, from the single nucleotide to the whole organism, bridging preclinical therapeutics development with clinical trials.

Osteomyelitis, especially multidrug-resistant cases, remains a formidable clinical challenge due to recurrent infections and antibiotic limitations. Here, we present an injectable GaCuVan&HACHO-BSA hydrogel that self-assembles in situ within the bone marrow cavity-the epicenter of trained immunity-to simultaneously eradicate pathogens, induce innate immune memory, and regenerate bone. The hydrogel captured bacteria, virulence factors, and inflammatory mediators through multivalent interactions with enhanced injectability, biocompatibility, and sustained antigen release, making it ideal for minimally invasive treatment of osteomyelitis-related bone defects. Mechanistically, adsorbed pathogen signatures activated pattern recognition receptors, triggering metabolic reprogramming (elevated succinate/ATP/lactate), HIF-1α stabilization, amplified glycolysis and inflammation (COX2/iNOS/CD86), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) production-collectively inducing trained immunity with cross-protection against homologous/heterologous reinfection. Furthermore, glycyrrhizic acid promoted bone tissue repair and modulated immune responses. By converging antimicrobial defense, innate immune memory, and tissue repair into a single platform, this work redefines osteomyelitis management and advances immunomodulatory biomaterials for clinical translation.

Previous studies have found that individuals with schizophrenia (SZ) benefit less from semantic context in verbal recall than comparison (HC) subjects. This has not been systematically studied in individuals with schizotypal personality disorder (SPD), a group that does not carry the confounding effects of chronic medication usage and/or hospitalization, but has a high genetic loading for SZ. The purpose of the current study was to examine the effect of context on verbal learning performance in men and women with DSM-5-defined SPD. The effect of semantic context on verbal recall was measured in 69 right-handed men and women with clinically-defined schizotypal personality disorder and 56 right-handed healthy controls. On a semantic facilitation task, subjects were asked to listen to and recall eight 10-word lists with increasing context, ranging from random order to text format. Verbal recall performance of male and female SPD subjects was contrasted with gender-matched HCs. Male SPD subjects benefited significantly less from context in verbal learning, while female SPDs performed similarly to controls. The current study examined the effect of gender and semantic facilitation on learning in clinically-defined SPD. The results are consistent with previous hypotheses of gender-specific left hemisphere dysfunction in male SPD, and provide further support for a primary deficit in early learning processes in this population.

The CELSR1 gene is a core component of the tissue/planar cell polarity signaling pathway. It encodes a developmentally regulated protein that belongs to the adhesion G protein-coupled receptors. Herein we describe seven subjects, from five unrelated families, featuring a neurodevelopmental disorder associated with biallelic CELSR1 variants. The main phenotypic features of this disorder are different types of brain malformations (including pachygyria, periventricular nodular heterotopia, abnormal corpus callosum, white matter abnormalities, hypoplasia of brainstem and cerebellum), variable degrees of neurodevelopmental delay and intellectual disability, behavioral disorders, and, in some subjects, epilepsy. Using whole exome sequencing, we identify five compound heterozygous variants and one homozygous variant of CELSR1 in these subjects. We infer the pathogenicity and functional effects of these variants through bioinformatic analysis, protein modelling and prediction tools. To further characterize the effects of mutant CELSR1, we generate Celsr1 knockout mice, which exhibit partial agenesis of the corpus callosum, periventricular heterotopia and irregular shape of the ventricular/subventricular zone, enlarged lateral ventricles with a fully penetrant phenotype, and increased susceptibility to seizures. These findings emphasize the importance of CELSR1 in several polarity-dependent processes during embryonic and postnatal development.

Mammals regulate the localization, composition, and activity of their native microbiota at colonization sites. Lectins residing at these sites influence microbial populations, but their functional roles are often unclear. Intelectins are found in chordates at mucosal barriers, but their functions are not well characterized. In this study, we find that mouse intelectin-2 (mItln2) and human intelectin-2 (hItln2) engage and crosslink mucins via carbohydrate recognition. Moreover, both lectins recognize microbes within native microbial communities, including gram-positive and gram-negative isolates from the respiratory and gastrointestinal tracts. This ability to engage mammalian and microbial glycans arises from calcium-coordinated binding of carbohydrate residues within mucus and microbial surfaces. Microbes, but not human cells, bound by mItln2 or hItln2, suffer a loss of viability. These findings underscore the crucial antimicrobial role of mammalian intelectin-2 in mucosal defense, where it plays offensive (microbial killing) and defensive (mucus crosslinking) roles in regulating microbial colonization.