Recent experimental observations obtained in reduced in vitro systems have reported direct proximity between bacteria and neuronal cells associated with intracellular Ca2+ dynamics and transcriptomic alterations. In particular, studies involving Lactiplantibacillus plantarum and primary cortical neuronal cultures have described bacterial adhesion to neuronal surfaces together with modulation of neuroplasticity-associated proteins and gene networks related to cellular signaling and neuronal regulation. Current models of the microbiota–gut–brain axis primarily emphasize indirect communication mediated through metabolites, immune pathways, neuroendocrine signaling, vagal pathways, extracellular vesicles, and soluble mediators. Although these mechanisms possess substantial explanatory value, certain early cellular responses observed under conditions of direct bacteria–neuron proximity may not be fully interpretable exclusively through soluble signaling mechanisms. This manuscript proposes a conceptual perspective in which the neuronal membrane is considered a dynamic cellular interface potentially sensitive to localized mechanical, physicochemical, or membrane-associated perturbations generated under conditions of direct biological proximity. Within this context, intracellular Ca2+ dynamics are interpreted as possible early cellular responses that may emerge in association with membrane-associated perturbation. Potential candidate mechanisms including mechanosensitive ion channels, localized membrane perturbation, adhesion-associated signaling, cytoskeletal remodeling, membrane reorganization, and local physicochemical microenvironmental alterations are discussed together with alternative explanations involving soluble mediators, immune activation, extracellular vesicles, osmotic or ionic perturbations, and generalized cellular stress responses. Importantly, the currently available evidence derives exclusively from reduced experimental systems and does not establish physiological relevance or demonstrated neuromodulation in vivo. Rather than proposing an alternative model of microbiota–brain communication, this perspective aims to refine interpretation of emerging neurobacterial interface observations by defining experimentally testable hypotheses and mechanistically plausible questions for future investigation.
Correction: Positive effect of microvascular proliferation on functional recovery in experimental cervical spondylotic myelopathy
Applications of machine learning algorithms to detect digital addiction: a meta-analysis
Digital addiction (DA) has emerged as a significant global concern, yet traditional diagnostic methods relying on self-report questionnaires face subjective bias and threshold inconsistencies. Recent advances in machine learning (ML) offer promising alternatives for automated DA detection. This study conducted a systematic meta-analysis of 64 eligible studies (75 independent datasets; N = 165,624), employing both single-group proportion and bivariate diagnostic test accuracy (DTA) models. The pooled classification accuracy was 0.87 (95% CI [0.85, 0.90]), and the DTA framework yielded a robust AUC of 0.92, with balanced sensitivity and specificity (both 0.86). Subgroup analyses showed high accuracy across subtypes, particularly for internet (0.90) and social media addiction (0.86). Accuracy was comparable between survey-based and physiological data, though physiological markers demonstrated superior specificity (0.90). These findings underscore the potential of ML-driven tools as scalable screening instruments while emphasizing the need for representative sampling and standardized diagnostic criteria to advance digital mental health practice.
The impacts of a justice-focused body image program for early adolescents
To address gaps in universal, diversity-focused eating disorders prevention with early adolescents, our team co-created an evidence-informed body image intervention through a community-engaged, participatory research process. The Body Justice intervention and associated research were co-created by a team of middle school students and staff and undergraduate students and faculty in the Pacific Northwest United States. The intervention includes eight brief lessons (six hours total) with culturally-tailored content rooted in cognitive dissonance and media literacy (e.g., cultural appearance ideals, diversity representation within media, food culture). The intervention was delivered with 7th grade students over three years (N = 333; 49% students of color; 53% cisgender boys, 36% cisgender girls, 12% gender diverse; 27% sexually diverse) using college student leaders (near peers) and middle school student co-leaders. Student satisfaction immediately after the intervention was moderate overall and higher for students of color, sexually diverse students, and cisgender girls and gender diverse students compared to their peers with majority identities. Across the sample, there was a significant reduction in unhealthy weight control behaviors from baseline to two-month follow-up with similar improvement among subgroups except for students of color, who had smaller reductions over time compared to their white peers. Across the sample, there was a significant reduction in internalized appearance norms from pre to post-intervention and through follow-up. These reductions were similar across gender, but the change was significant only for white students and straight students. There was no overall improvement in perceived appearance pressure from social media over time, but subgroup analyses revealed that students of color experienced improvement over time unlike other subgroups. In general, subgroup analyses should be interpreted cautiously due to concerns about adequate power. These results suggest that the Body Justice curriculum was delivered effectively and was well-liked by middle school students with marginalized identities. While aspects of the intervention were beneficial (e.g., a reduction in unhealthy weight control behaviors over time), findings suggest potentially differential results across identity subgroups. This has implications for collaborative school-based research, body image and eating disorders prevention, and community-engaged methods to foster equity.
Gender-specific symptom outcomes on cariprazine treatment: a 12-month naturalistic longitudinal follow-up study in schizophrenia
IntroductionA growing body of literature is focusing on third-generation antipsychotics and their unique characteristics, but few studies have examined gender as a crucial factor in response profiles. The present study aims to address this gap by analyzing the outcomes of 12-month naturalistic treatment with cariprazine to elucidate changes in specific psychopathological domains between men and women.MethodsThe present 12-month longitudinal naturalistic study involved a sample of individuals diagnosed with schizophrenia according to the DSM-5-TR treated with cariprazine at the outpatients’ psychiatric services of a major university and community hospitals in Italy. The assessments conducted included sociodemographic data, the Structured Clinical Interview for the DSM-5 (SCID-5), and the Positive and Negative Symptom Scale (PANSS) Total and Subscale scores, as well as the PANSS-derived Marder factors. The PANSS was administered at three time points: before starting the treatment with cariprazine (T0), after 6 months (T1), and after 12 months (T2).ResultsFifteen male and 17 female subjects were assessed at the three time points. The mean dose of cariprazine was 4.2 ± 1.3 mg for men and 4.0 ± 1.5 mg for women. Both genders exhibited improvements in all PANSS subscale symptoms after 6 and 12 months of cariprazine treatment compared to the baseline, with the only exception of the Uncontrolled hostility/excitement Marder factor among men. Progressive improvements through time points in symptom subscales were found in both sexes, reaching numerical differences in every PANSS subscale in both sexes at T2. Gender specifc response profiles emerged after 6 and 12 months of treatment in the PANSS subscales and items in men and women.DiscussionCariprazine exhibited significant efficacy in both sexes, with no significant differences between men and women despite a gender specific response profile emerged. Additional studies are needed to further investigate the efficacy profile and long-term outcome of cariprazine treatment by gender.
TIC-XNet: a structured evidence translation framework for interpretable multimodal pediatric tic event detection with improved temporal alignment and fidelity
ObjectivesThis study aimed to develop an interpretable multimodal framework for detecting tic events in children with tic disorders by translating model decisions into structured, time-aligned evidence from synchronized video and physiological signals.MethodsTIC-XNet was developed to jointly analyze synchronized video, heart rate, and electrodermal activity signals and to generate structured evidence outputs. Recordings from 417 children with clinically diagnosed tic disorders were collected during structured clinical assessments and home-based observations. TIC-XNet was compared with a prediction-only black-box model and a post-hoc explainable model under matched predictive backbones and identical training settings.ResultsWithin the evaluated internal subject-level split, TIC-XNet achieved the best performance on the pooled shared test set, with a window-level AUC of 0.915 ± 0.019, higher event-level recall and precision, fewer missed events, and lower post-buffering prediction latency than the comparator models. Its translated outputs also showed higher decision fidelity, greater stability under perturbation, and closer temporal alignment with expert-annotated tic onsets. Subject-level translated numerical signals were associated with tic severity.ConclusionsThese findings indicate that evidence translation can support more interpretable multimodal detection of tic events in children with tic disorders while remaining compatible with strong predictive performance.
Developmental high-risk criteria for severe mental illness: a neurodevelopmental framework for premorbid detection
Mapping and engineering the human cell–cell interactome
Nature Biotechnology, Published online: 23 June 2026; doi:10.1038/s41587-026-03177-2
Di Carlo and colleagues discuss technologies required to map and engineer the human cell–cell interactome and the therapeutic avenues such an atlas could unlock.
Efficient generation of epitope-targeted antibodies with Germinal
Nature Biotechnology, Published online: 23 June 2026; doi:10.1038/s41587-026-03187-0
Germinal achieves epitope-targeted, de novo complementarity-determining region design with high experimental success rates.
Shifting the goalposts in obesity drug development
Nature Medicine, Published online: 23 June 2026; doi:10.1038/s41591-026-04462-y
Obesity drug development must move beyond an emphasis on ever-greater weight loss to prioritize tolerability, sustainable benefits and medication persistence; two recent trials exemplify this shift, with more underway.