BackgroundFreezing of gait (FOG) is one of the most debilitating motor symptoms in Parkinson’s disease (PD), affecting a substantial proportion of people with PD. Numerous hypothetical mechanisms exist, attempting to explain FOG. Current evidence originated from stationary measures in lying positions, limiting the understanding of neurophysiological changes elicited by FOG episodes during regular locomotion. Neurophysiological aspects of FOG, especially in response to vibrotactile cueing, have been explored only by a few studies. To address this gap, the current study aims to investigate FOG episodes in people with PD and the impact of vibrotactile cueing while walking through virtual environments on a self-paced treadmill.MethodsThirty people with Parkinson’s Disease and FOG will be recruited. They will undergo screening and familiarization before performing different walking tests in virtual reality using the Gait Real-time Analysis Interactive Lab (GRAIL). Participants will perform two experimental blocks, each consisting of four walking trials of approximately 10 min. A break of 10 to 30 min will be provided between blocks. Walking with or without vibrotactile cueing will be performed in alternation. During walking, electrocortical (EEG), hemodynamic (fNIRS), kinematic data (3D motion capture), and kinetic data (force plates) will be recorded. Data will be analyzed to investigate spatiotemporal and frequency characteristics of electrocortical and hemodynamic brain activity related to FOG and the impact of vibrotactile cueing on neural signatures and gait improvements in FOG.DiscussionCombining neurophysiological measurements of EEG and fNIRS paired with kinematics and kinetics will provide insights into the cortical and behavioral changes associated with FOG and vibrotactile cueing, to derive results that can be used for the design of intervention strategies for treating PD.Study protocol registrationhttps://drks.de/search/de/trial/DRKS00034584, identifier DRKS00034584.
Texas Biomed Enters Into a CRADA with U.S. Dept. of War to Help Protect Against Biological Threats
Texas Biomedical Research Institute signed a cooperative research and development agreement (CRADA) with the U.S. Department of War to help protect service members and civilians from emerging and high-consequence biological threats.
The agreement with the Capability Program Executive for Chemical, Biological, Radiological, and Nuclear Defense (CPE CBRND), which manages the nation’s investments in chemical, biological, radiological, and nuclear (CBRN) defense diagnostics and medical countermeasures (MCMs), establishes a collaborative framework to accelerate the development, testing, and validation of medical countermeasures while strengthening national preparedness, according to Cory Hallam, PhD, professor and executive vice president of Applied Science and Innovation at Texas Biomed.
“We are proud to offer our unique scientific capabilities to support the nation’s biodefense mission,” said Hallam. “Texas Biomed excels in reducing the time between scientific insight and operational impact, which is critical for proactive preparedness and responding quickly when threats emerge.”
Collaborative framework
The CRADA establishes a framework for Texas Biomed and CPE CBRND to collaborate on MCM projects that protect global populations, including U.S. soldiers serving at home and abroad. The agreement recognizes Texas Biomed’s operational impact capabilities, including high containment research and adherence to Good Laboratory Practice standards that support FDA regulatory requirements.
The Institute is also home to one of the nation’s seven National Primate Research Centers, offering expertise in translational studies and model development.
The CRADA framework is intended to ensure that critical resources for biological threats, whether from naturally emerging diseases or engineered risks, are continuously ready and available on demand, rather than episodically, continued Hallam.
“This is a long-term investment in resilience,” added Larry Schlesinger, MD, president and CEO of Texas Biomed. “As biological threats continue to evolve, partnerships like this are increasingly essential. Under this agreement, we have the potential to build new joint capabilities that will serve the nation not just today, but for decades to come.”
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Autistic- and attention-deficit/hyperactivity disorder-like traits: differential associations with burnout, depression and anxiety, and empathy among Japanese junior residents
IntroductionBurnout, depression, and anxiety are major concerns among physicians because they affect individual well-being, patient care, and healthcare systems. Neurodevelopmental traits, including autistic-like traits (ALTs) and attention-deficit/hyperactivity disorder (ADHD)-like traits (ADHLTs), may increase vulnerability to psychological distress. However, little is known about how these traits relate to burnout, depression and anxiety, and empathy among junior residents.MethodsIn this cross-sectional study, 148 junior residents from two teaching hospitals in Japan completed validated measures of ALTs (21-item Japanese version of the Autism-Spectrum Quotient), ADHLTs (Adult ADHD Self-Report Scale Screener), burnout (Maslach Burnout Inventory), depression and anxiety (Hospital Anxiety and Depression Scale), physician–patient empathy (Jefferson Scale of Physician Empathy), and psychological flexibility and inflexibility processes (Valuing Questionnaire, Cognitive Fusion Questionnaire-7, and Work-related Acceptance and Action Questionnaire). Associations were examined using multivariable logistic and linear regression analyses. Exploratory statistical mediation analyses using structural equation modeling examined indirect associations through psychological flexibility and inflexibility processes.ResultsThe prevalence of ALTs and ADHLTs was 23.6% for each trait. ALTs were associated with lower personal accomplishment, a burnout dimension; higher depression and anxiety; and lower physician–patient empathy. ADHLTs were associated with greater emotional exhaustion, another burnout dimension. In exploratory statistical mediation analyses, progress toward values, a core process of psychological flexibility, showed a significant indirect association between ALTs and personal accomplishment, and the direct association was attenuated and no longer statistically significant after including the process variables. Significant indirect associations through progress toward values were also observed for the associations of ALT with depression and anxiety and empathy. Cognitive fusion, a core process of psychological inflexibility, showed a significant indirect association between ADHLTs and emotional exhaustion. Overall, neurodevelopmental traits were associated with distinct patterns of psychological functioning, suggesting variability in both vulnerability and adaptive processes.DiscussionNeurodevelopmental traits such as ALTs and ADHLTs were significantly associated with burnout dimensions, depression and anxiety, and physician–patient empathy among junior residents. Psychological flexibility and inflexibility processes, particularly progress toward values and cognitive fusion, may be relevant to these associations. Process-based support strategies may warrant further investigation for residents with elevated neurodevelopmental traits.Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R00005, identifier UMIN000046897.
Treating addiction with an addictive drug: the ketamine paradox revisited
BackgroundSubstance use disorders (SUDs) and treatment-resistant depression (TRD) remain a major global health challenge, marked by high relapse rates and limited long-term effectiveness of existing treatments. Ketamine, a glutamatergic modulator with rapid neuroplastic effects, has emerged as a novel intervention for TRD and is increasingly investigated as an adjunctive treatment for addiction, yet concerns about its abuse liability persist.ObjectiveThis review critically evaluates ketamine’s therapeutic potential for SUDs while examining its neurobiological mechanisms, clinical efficacy, and risk of misuse within a unified risk–benefit framework.MethodsA structured narrative review conducted in accordance with the SANRA framework using the PubMed, Scopus, PsycINFO, and Web of Science databases, covering literature published until March 2026. Eligible studies included clinical trials, experimental studies, and mechanistic investigations relevant to ketamine use in addiction and depression. Evidence was synthesized thematically across the domains of efficacy, mechanisms, and safety.ResultsAcross alcohol and cocaine use disorders, ketamine combined with psychotherapy has demonstrated promising reductions in craving and increases in abstinent days in small-to moderate-sized Phase 2 trials. However, findings remain difficult to generalize due to considerable variability in dosing strategies, comparator conditions, and follow-up periods. Effects on relapse prevention have been more inconsistent and less reliably positive. Mechanistically, ketamine promotes synaptic plasticity via NMDA receptor antagonism and downstream glutamatergic signaling, potentially disrupting maladaptive reward-related memories and reversing maladaptive neurocircuitry involved in both depression and addiction. While acute adverse effects are generally transient under clinical supervision, ketamine carries a well-established risk of misuse, particularly in unsupervised or high-dose settings.ConclusionsKetamine represents a promising but still experimental intervention for both refractory depression and selected SUDs. Its clinical use depends on careful patient selection, structured delivery, and integration with psychotherapy. Although ketamine may redefine treatment paradigms for TRD and addiction, larger-scale trials and long-term safety data are essential to define its role within psychiatric and addiction treatment frameworks.
Loneliness, rumination, and adolescent psychological crisis in China: a pilot moderated mediation study
BackgroundAdolescent psychological crisis—encompassing depressive disorder, anxiety disorder, and suicidal ideation—is a major public health challenge. One in five adolescents experiences a clinically significant mental health condition globally. Loneliness is a well-documented, modifiable risk factor for these outcomes. However, the exact cognitive-emotional pathways linking loneliness to acute psychological crisis remain unclear. This is particularly true in China, where rapid social change and intense academic pressure increasingly strain adolescent mental health. We do not yet fully understand how protective resources might buffer these specific pathways.Objectives and methodsThis pilot study tests a moderated mediation model based on the Evolutionary Theory of Loneliness and the stress-vulnerability framework. We investigate ruminative thinking as a cognitive-emotional mediator between loneliness and psychological crisis. We also test whether perceived social support and psychological resilience moderate distinct stages of this pathway. Based on a pilot sample of N = 312 Chinese adolescents (ages 12–18), we use structural equation modelling (SEM), confirmatory factor analysis (CFA), and Hayes’ PROCESS Macro (Model 14) with 5, 000 bootstrap replications. Two-wave longitudinal data (n = 187, 8-week interval) were available for the depression outcome only; the anxiety and suicidal-ideation pathways were examined cross-sectionally.ResultsLoneliness is significantly associated with depressive symptoms (β = 0.43, p < 0.001), anxiety (β = 0.38, p < 0.001), and suicidal ideation (β = 0.27, p < 0.001). Ruminative thinking accounts for 40–46% of the total indirect association across all three outcomes. Social support buffers the transmission from loneliness to rumination (b = −0.16, p = 0.002, ΔR2 = 0.023), while resilience buffers the transmission from rumination to crisis (b = −0.19, p < 0.001, ΔR2 = 0.031).ConclusionsThese preliminary, exploratory findings are consistent with the possibility that ruminative thinking partially accounts for the cross-sectional association between loneliness and adolescent psychological crisis in China, and with social support and resilience attenuating this association at potentially distinct stages. Because the pilot is underpowered for the moderated mediation model and the available longitudinal evidence covers depression only, the moderation and stage-specificity results should be read as hypothesis-generating rather than confirmatory. A planned full-scale study (N ≥ 1, 200) will test these mechanisms further. We also outline initial practical implications for school-based interventions.
Real-world outcomes of intranasal esketamine and intravenous ketamine induction therapy for treatment-resistant depression in a community clinic: a retrospective cohort study
IntroductionIntravenous (IV) ketamine and intranasal esketamine are NMDA receptor antagonists used for treatment-resistant depression (TRD). Both have demonstrated efficacy in controlled trials, but observational evidence from real-world community settings is limited.MethodsWe conducted a single-center retrospective cohort study of adults aged 18 to 65 receiving induction therapy for TRD with intranasal esketamine or IV ketamine at a community psychiatric clinic from January 1 through December 31, 2025. Patients with prior exposure to either medication or to oral ketamine derivatives were excluded. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to end of induction. Secondary outcomes included response (≥50% PHQ-9 reduction), remission (final PHQ-9 ≤4), clinically meaningful improvement (≥5 PHQ-9 reduction), induction completion, and adverse events. Within-group and per-protocol analyses were exploratory.ResultsSixty-three patients met inclusion criteria (esketamine n=37; IV ketamine n=26). Baseline PHQ-9 scores were similar (18.22±4.49 vs. 18.27±5.41; P = 0.967), as was mean change from baseline (-10.31±5.59 vs. -9.50±5.69; mean difference 0.81, 95% CI -2.12 to 3.75; P = 0.589). Response rates were 64.9% vs. 69.2% (RR 0.94, 95% CI 0.66 to 1.33; P = 0.790), remission 32.4% vs. 23.1% (RR 1.41, 95% CI 0.61 to 3.26; P = 0.573), and clinically meaningful improvement 83.8% vs 73.1% (RR 1.15, 95% CI 0.87 to 1.51; P = 0.353). Induction completion exceeded 90% in both groups; one patient per cohort discontinued from intolerable side effects, and no serious adverse events occurred. Within-group PHQ-9 reduction was large: 10.31±5.59 points (paired t[34]=10.91; P<0.001; Cohen’s d=1.84) for esketamine and 9.50±5.69 points (paired t[23]=8.18; P<0.001; Cohen’s d=1.67) for ketamine. Findings remained statistically significant and clinically large under a pre-specified baseline observation carried forward (BOCF) sensitivity analysis (Cohen’s d=1.65 and 1.45).ConclusionsInduction therapy with intranasal esketamine and intravenous ketamine was associated with robust antidepressant effects in a community outpatient setting, consistent with prior trial data. The modest sample size limits power to detect between-group differences and increases the risk of type II error; the absence of statistically significant between-group differences should therefore not be interpreted as evidence of equivalence. Protocol asymmetry between arms (esketamine: 12 sessions over 8 weeks; IV ketamine: 6 sessions over 3 weeks) further limits direct comparison of endpoint values between groups. Practical considerations including insurance coverage, cost, and administration logistics may help guide treatment selection. Longitudinal follow-up is planned to characterize treatment durability.
Autism service barriers for Latine children and their families: a participatory approach to adapting autism diagnostic care
IntroductionLatine children from families with limited English proficiency (LEP) experience barriers to timely autism diagnosis resulting in persistent health inequities. This participatory mixed-methods study examined these barriers and identified multi-level strategies to adapt diagnostic care models for Spanish-speaking Latine families.MethodsParticipants included twelve caregivers of thirteen autistic children with parent reported diagnosis of autism, twelve clinicians, and six care coordinators. All participants completed surveys and participated in qualitative interviews or focus groups.ResultsQuantitative findings revealed significant lag between caregiver’s first developmental concern and diagnosis, limited autism knowledge, and difficulty navigating care. Qualitative results highlighted systemic barriers, including clinician-patient language discordance, interpreter inaccuracies and quality variability, cultural stigma, and long waitlists. Clinicians reported challenges with communicating about autism with Spanish-speaking families and emphasized language and cultural differences as primary barriers. Caregivers described social isolation, mistrust of health systems, and emotional distress compounded by immigration-related stressors.DiscussionFindings underscore the need for structural adaptation of care approaches beyond translation services.
Biotech’s digital twin dilemma
Nature Biotechnology, Published online: 09 July 2026; doi:10.1038/s41587-026-03211-3
From virtual patients to simulated cells and organs-on-chips, digital twins are forecasting disease and guiding drug development. Scientists now must figure out how to define, validate and deploy these models.
High-quality phage assembly from metagenomes with PALACE
Nature Biotechnology, Published online: 09 July 2026; doi:10.1038/s41587-026-03188-z
PALACE combines homology features and deep learning to improve phage assembly from metagenomics.
A second chance for gene therapy to restore natural hearing
Nature Medicine, Published online: 09 July 2026; doi:10.1038/s41591-026-04512-5
The immune-privileged environment of the inner ear permits sequential bilateral gene therapy for one form of congenital deafness, which adds to growing evidence of the feasibility, safety and efficacy of this innovative curative treatment.