IntroductionAttention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental paediatric disorders and persists into adulthood, although it is frequently underdiagnosed and underrecognized in adult populations. In this context, the prevalence of pharmacologically treated individuals diagnosed with ADHD represents an important quality indicator for ADHD management.AimTo estimate the pooled prevalence of pharmacologically treated individuals with ADHD in different age groups in Europe and worldwide.MethodsA comprehensive search of PubMed/MEDLINE was conducted to identify relevant articles published up to October 4, 2024. The present systematic review and meta-analysis examined ADHD prevalence using clinically confirmed diagnoses and treatment data from official records. The exclusion criteria included studies that lacked clinical confirmation of ADHD and/or relied exclusively on parental reports for diagnostic or medication information. The prevalence of pharmacologically treated individuals with ADHD was calculated as a percentage, with a 95% confidence interval (CI). A meta-analysis was performed in R using a random-effects model. Heterogeneity was calculated using I². Prediction intervals were additionally computed to reflect the expected range of prevalence in future studies. Risk of bias was assessed for all included studies using a standardized, previously published methodology. The study was prospectively registered in PROSPERO (CRD42020200220) and adhered to the PRISMA guidelines for systematic review and meta-analysis (2020).ResultsThe systematic review identified 13 studies (12 studies included in the meta-analysis) with substantial variation in age-specific reporting. The pooled prevalence of pharmacologically treated ADHD was 73.4% (95% CI: 63.4–81.5), with extremely high between-study heterogeneity and wide 95% prediction interval (29.6%–94.5%), reflecting substantial variation across settings. The pooled prevalence estimate should be interpreted with caution due to substantial between-study heterogeneity and is not intended for direct clinical inference. Geographic analyses revealed no significant variation across countries. Sex-stratified analyses showed no significant difference between males and females, although point estimates were slightly higher in males.ConclusionThe prevalence of pharmacological treatment among individuals with ADHD appears to vary across age groups and settings Overall, findings indicate substantial variation in pharmacological treatment of ADHD by age, with consistently high heterogeneity limiting the precision of pooled estimates.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020200220.
New York boys club has a time-tested recipe to protect members’ mental health
NEW YORK — A couple of years ago, a reporter approached the Boys’ Club of New York looking to interview some of its middle-schoolers for a story about the mental health crisis in boys.
It’s easy to see why. Many of the about 2,500 boys who participate in the 150-year-old organization’s after-school and weekend activities come from disadvantaged socioeconomic backgrounds, often living in single-parent households or facing the threat of immigration enforcement. With limited access to academic and developmental support, the risk factors are plentiful.
An end-to-end pipeline for automated fetal brain segmentation and biometry from 3D SSFP MRI
Fetal magnetic resonance imaging (MRI) plays an essential role for the evaluation of fetal abnormalities, offering improved visualization of developing brain structures and superior soft tissue contrast in comparison to other imaging modalities. Accurate and reproducible assessment of fetal brain biometry is critical for diagnosing neurodevelopmental abnormalities. However, these measurements typically rely on manual segmentation, which is time-consuming, labor-intensive, prone to error and dependent on the interpreting radiologist’s expertise and experience. Recent advancements have enabled automated analysis primarily on Half-Fourier Acquisition Single-shot Turbo spin-Echo (HASTE) sequences, yet these acquisitions are susceptible to inter-slice misalignment and often require time-consuming super-resolution reconstruction. In contrast, 3D Steady-State Free Precession (SSFP) imaging offers smaller slice thickness, improving through-plane resolution, along with reduced motion sensitivity and whole-body coverage in a single scan. In this study, we present an end-to-end deep learning pipeline for automated segmentation and biometry of the fetal brain from whole-body SSFP MRI. The dataset includes manual annotations of the fetal head, brain parenchyma and extraaxial cerebrospinal fluid (CSF). The framework employs nnU-Net for robust head localization and multi-structure segmentation, along with principal component analysis (PCA)-based reorientation and head circumference estimation. A Tri-Attention U-Net architecture was evaluated as a standalone model and within the nnU-Net framework. The final pipeline consists of a Tri-Attention nnU-Net for head localization and nnU-Net for multi-structure segmentation. The pipeline achieved mean Dice similarity coefficients (DSC) of 94.48, 93.58 and 82.75% for the head, brain parenchyma and extraaxial CSF, respectively. These findings demonstrate the feasibility of accurate, fully automated fetal brain biometry from SSFP MRI with potential to reduce inter-observer variability, streamline clinical workflows and enhance clinical decision-making through fast and reproducible quantitative assessment.
Perfusion Technologies Gain Momentum in Biomanufacturing
Perfusion-based manufacturing is gaining traction across the biopharmaceutical industry as companies seek to boost biologics output, improve product quality, and increase manufacturing flexibility without expanding facility footprints. Long viewed as a promising but operationally complex alternative to fed-batch production, perfusion is benefiting from a wave of technological advances that are making the approach more practical and economically attractive for commercial-scale manufacturing.
“Perfusion helps maintain cells at very high viable cell densities,” said Charles Solanke, senior scientist of upstream process development at Cytovance Biologics. “This produces significantly more product per unit bioreactor volume compared to traditional fed-batch processes.”
One of perfusion’s key advantages is its ability to continuously harvest product while maintaining healthy cell cultures. “Continuous removal of toxic metabolites creates a more stable environment,” Solanke notes. “This supports prolonged culture duration and high cell viability.”
Product-quality improvements are emerging as another major driver of adoption. Because biologics are harvested continuously, manufacturers can reduce variability in critical quality attributes, such as glycosylation patterns and aggregation profiles.
Technological developments are further expanding the performance ceiling of perfusion operations. High-intensity perfusion media can now support cell densities reaching 100–200 million cells per milliliter, enabling substantially greater productivity than previous generations of processes. At the same time, advances in alternating tangential flow (ATF) and tangential flow filtration (TFF) technologies improve cell-retention performance and reduce filter fouling, which is one of the most persistent challenges in long-duration perfusion runs.
Automation is also reshaping the field. Real-time monitoring technologies—including Raman spectroscopy, capacitance probes, soft sensors, and advanced process-analytical technology—are increasingly being integrated into commercial processes to provide continuous insight into culture conditions. “Real-time monitoring and process control help maintain stable culture conditions,” Solanke said. “The advances have also helped improve process robustness and manufacturing reliability.”
Despite the progress, challenges remain. Perfusion systems typically require higher media consumption, more sophisticated process controls, and additional equipment investments than conventional fed-batch operations. Extended run durations can also increase contamination risks if robust aseptic controls are not maintained.
Looking ahead, industry efforts are increasingly focused on developing cell lines specifically optimized for ultra-high-density perfusion cultures, reducing media consumption through concentrated formulations, and deploying fully autonomous process control systems. “The integration of fully automated perfusion control systems represents a promising opportunity,” Solanke said. “Together, these advancements have the potential to make perfusion processes more productive, cost-effective, and easier to operate.”
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Neonatal propofol exposure impairs synaptic plasticity and cognition, associated with BAG3 upregulation and disrupted synaptic protein homeostasis
BackgroundPropofol is widely used in pediatric anesthesia, but it has been implicated in adverse effects on brain development following repeated early-life exposure. Bag3, a co-chaperone protein involved in proteostasis and the neuronal stress response, may play a critical role in regulating synaptic function during early brain maturation.MethodsNeonatal mice were treated with propofol on postnatal days 5–7. Hippocampal neurogenesis was assessed via BrdU immunofluorescence. Synaptic proteins (PSD95, SNAP25) and Bag3 expression were measured by Western blotting. Behavioral performance in adolescence was evaluated using open-field, elevated plus-maze, Morris water maze, Y-maze, and T-maze tests.ResultsPropofol exposure significantly reduced proliferative activity (BrdU incorporation) in the dentate gyrus and decreased PSD95 and SNAP25 expression in both the cortex and hippocampus. Bag3 expression was markedly upregulated, accompanied by a mild increase in its phosphorylated form. Behaviorally, propofol-treated mice showed anxiety-like behavior and impairments in spatial learning and working memory.ConclusionThese findings suggest that early-life exposure to propofol impairs neurogenesis and synaptic plasticity. This process is temporally associated with the upregulation of stress-responsive co-chaperone BAG3, which precedes the of synaptic protein homeostasis. While causal relationship remains to be established, these findings identifies BAG3 as a candidate correlative marker of anesthetic-induced neurotoxicity and highlights it as a target for future mechanistic studies.
Integrated multi-omics and deep learning analysis reveals neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan
BackgroundTianwang Buxin Dan is a classical Traditional Chinese Medicine formula with documented clinical use in treating neuropsychiatric disorders, yet its molecular mechanisms remain incompletely understood.MethodsWe developed an integrated analytical framework combining transcriptomic and metabolomic profiling with deep learning to investigate the neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan. Data were collected from a para-chlorophenylalanine (PCPA)- induced insomnia rat model following formula intervention. A multi-omics feature fusion strategy incorporating autoencoder-based dimensionality reduction and cross-modal attention mechanisms was implemented to address data heterogeneity.ResultsA total of 1,847 differentially expressed genes and 286 differential metabolites were identified. The constructed deep neural network achieved 91.2% classification accuracy with an AUC of 0.956 in five-fold cross-validation, and permutation testing confirmed that performance was significantly above chance (p < 0.001). Ablation experiments demonstrated that integrated multiomics outperformed single-omics models. Tryptophan hydroxylase 2 (TPH2) upregulation and monoamine oxidase A (MAO-A) suppression were identified as key features and partially validated by qPCR and Western blot.DiscussionTianwang Buxin Dan may modulate neurotransmitter metabolism through coordinated regulation of biosynthetic and catabolic pathways. A component-target-pathway regulatory network identified 47 key molecular targets interconnected through 156 functional associations. This work provides a computational framework applicable to mechanism studies of other compound TCM formulations.
Parental broad autism phenotype traits and executive function in families of children with autism spectrum disorder
BackgroundParents of children with autism spectrum disorder (ASD) frequently exhibit subclinical Broad Autism Phenotype (BAP) traits, though their relationship with executive function (EF) remains underexplored. This study investigated associations between parental BAP traits and their EF performance.MethodsThe Broad Autism Phenotype Questionnaire (BAPQ) was used to assess the BAP traits in parents of children with ASD and parents of healthy children. Among them 20 of the high-BAP ASD parents with a total BAPQ score exceeding 3.55 and 20 of the parents of typically developing children completed executive function tests. The researchers utilized the flanker, 2-back, and Task-switching paradigm to examine their EF. Correlations analysis was used to analyze BAP-EF relationships.ResultsThe self-reported questionnaires indicated that parents of children with ASD had significantly higher BAPQ scores than non-ASD’s parents, with fathers scoring 41.21% versus 15% (χ2 = 31.628, p < 0.01), and mothers 26.25% versus 8.37% (χ2 = 25.764, p < 0.01). Parents of ASD children exhibited significantly prolonged reaction times on the Flanker task (528.95 ± 78.90 ms vs. 426.80 ± 18.40 ms, T = 15.639, p<0.01), with BAPQ total scores positively correlating with slower responses (R² = 0.2325, p = 0.0313). Paradoxically, they demonstrated accelerated 2-Back incongruent reaction times (537.60 ± 80.21 ms vs. 665.70 ± 137.17 ms, T = 6.715, p=0.001) but reduced accuracy (0.947 ± 0.037 vs. 0.983 ± 0.016, T = 16.875, p<0.01), where BAPQ again correlated with reaction times (R² = 0.2318, p = 0.0316). Crucially, these associations were absent in controls, and BAPQ scores showed no relationship with task accuracy in either group.ConclusionsBAP traits are associated with attentional control challenges (indexed by Flanker Task) and a maladaptive speed-accuracy tradeoffs during working memory demands.
KLK1 Expands Possibilities to Restore Vascular Health
Knowing that the protein tissue kallikrein-1 (KLK1) is effective in treating ischemic diseases is one thing. Manufacturing it as a recombinant protein has been quite another. So, when DiaMedica Therapeutics cracked the manufacturing aspect, it was well on its way toward commercializing KLK1 therapeutics.
The manufacturing breakthrough came when researchers realized that protein activity (which is essential for therapeutic benefit) was linked to certain glycosylation patterns. DiaMedica engineered the molecule to reflect those glycosylations and also made two changes to the amino acid sequence to improve manufacturability. “Then we partnered with Catalent,” Rick Pauls, president and CEO, says. “We are using its GPEx® technology with CHO cells,” which produces more cells within the same timeframe and thus lowers manufacturing costs.
Tenacity in action
This happened neither easily nor quickly. To understand the measure of this achievement, we need to look at DiaMedica’s history.
KLK1 came to DiaMedica’s attention because of liver research. “A liver physiologist cut the vagus nerve [which regulates liver metabolism] and discovered that the rats, effectively, became diabetic,” Pauls recounts. “We hypothesized that when a healthy person consumed a meal, the liver releases something that acts as an insulin sensitizer. We did some basic work and identified KLK1 as that insulin sensitizer.”
The company was founded in 2004 to develop a KLK1 therapeutic for complications related to Type II diabetes. Those trials failed. “It’s a long story,” says Pauls, that left the company “pretty close to bankrupt.”
DiaMedica, though, was tenacious. “We knew there was a human urine form of this protein that had been used for a few decades in Asia to treat acute ischemic stroke, and a porcine form treating hypertension for decades as well,” Pauls recalls. DiaMedica had the protein and the manufacturing know-how to produce active, recombinant proteins, and—with KLK1 levels low in stroke patients—a reason to pivot.
Ischemic stroke and preeclampsia
Its lead compound, DM199 (rinvecalinase alfa), is enrolling patients in Phase II/III trials for acute ischemic stroke. Called the ReMEDy2 trial, the company anticipates an interim readout near year’s end. Additionally, Phase I and II studies for preeclampsia and Phase II studies for fetal growth restriction are underway.
“This is protein restoration,” Pauls says. It targets ischemic stroke patients who have missed the three-to-four-hour post-stroke treatment window for tissue plasminogen activator (tPA) therapeutics or mechanical thrombectomy. Those patients constitute approximately 80% of acute ischemic strokes today, so “there is a huge unmet medical need,” Pauls says.
DM199 works by restoring normal levels of the KLK1 protein. KLK1, in turn, is thought to enhance the production of nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor. Pouring through their own preclinical and clinical results, the DiaMedica team noticed that DM199 consistently enhanced blood circulation and lowered blood pressure.
That realization drove the team to also target preeclampsia, a hypertensive disease of pregnancy that Pauls says may be the company’s most exciting application for investors.
Unlike approved blood pressure therapeutics, DM199 does not cross the placental barrier, a critical safety feature that protects the fetus. After examining early clinical data, DiaMedica scientists also realized that increasing blood flow to the placenta could target the root cause of the disease and perhaps gain another few weeks of crucial time in utero for the fetus.
“Today, there are no approved treatments. Mothers are given labetalol and nifedipine to control blood pressure and to extend the baby’s time in utero for only a few days.” Results are less than ideal, and the consequences can be severe.
Pauls says, “Some 40% of babies born before 28 weeks could have long-term disabilities, and 10 to 15% will have problems with eyesight for life. There’s been a real lack of drugs in development because developers are worried about harming the baby.”
An investigator-led Phase II clinical trial is enrolling. Later this year, the company plans to initiate its own Phase II study focused on early-onset preeclampsia after recently receiving regulatory clearance to start the study in Canada.
If the molecule eventually is approved for preeclampsia, DM199 seems poised to become, perhaps, the first approved treatment that offers the potential to extend gestational days and possibly address a root cause of preeclampsia.
Leveraging the pivot
Unlike many biopharmaceutical companies, DiaMedica has been able to bypass some of the usual first steps by leveraging existing studies on KLK1, as well as existing clinical data for stroke and preeclampsia.
That allows researchers to focus on humans without the translational issues inherent in animal studies. It also helps the company identify the human subgroups most likely to benefit from these treatments and the most appropriate dosing regimen early. “Having that clinical data helps de-risk our program and gives a better possibility of success,” Pauls says, because, as he points out, “Animals are not the same as people.”
Once the company pivoted to its current indications six or seven years ago, the challenge shifted from getting and manufacturing the active form of the protein to selecting the best indications and assembling the right team members.
“In the early days, maybe we didn’t have the right level of experience with limited capital,” he admits. Today, “we’ve been able to bring people on board who have brought drugs to market.”
Readouts due in 2027
Currently, the company is focused tightly on its clinical trials. The next step for DiaMedica is to get readouts from many of those, with five readouts on various aspects of the programs expected between now and the end of 2027. Each of those readouts will report on about 30 patients and will be factors in the design of a subsequent pivotal trial.
Additionally, an interim analysis of the first 200 patients in its acute ischemic stroke trial is expected by the end of the year, Pauls says. “If we see a drug effect that’s comparable to our Phase II trial or the data with the urine form (of KLK1) from China—which treats close to a million patients per year—we’ll be looking at completing enrollment the following quarter for stroke and then for preeclampsia. DiaMedica is dedicated to offering second chances to acute ischemic stroke patients and others who haven’t had them before, all while pivoting to new opportunities itself. Now, as trials advance, Pauls says, “I think this should be a straightforward path.”
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A dual-branch network with brain region-constrained attention for EEG emotion recognition
IntroductionElectroencephalography (EEG)-based emotion recognition provides an objective avenue for affective computing. However, the complexity of EEG signals across temporal, frequency, and spatial domains makes any single dimension inadequate.MethodsTo overcome these limitations, we propose the Brain Region-Constrained Attention Dual-Branch Network (BRAD-Net). This network adopts a parallel Spatio-Temporal and Spectral-Spatial dual-branch architecture to achieve synergistic multi-domain EEG feature learning. Within the spatio-temporal branch, we introduce a novel Brain Region-Constrained Attention mechanism, which strictly confines self-attention computation to channels belonging to the same brain region. This design not only suppresses irrelevant cross-region interference but also incorporates neuroanatomical priors of brain parcellation, thereby enabling effective and interpretable representation learning.ResultsIn subject-dependent experiments using 10-fold cross-validation on DEAP and DREAMER datasets, BRAD-Net achieves high accuracies of 97.44%, 97.70%, and 97.97% for valence, arousal, and dominance on DEAP, and 99.66%, 99.78%, and 99.80% on DREAMER, respectively. Leave-one-subject-out validation on DREAMER dataset achieves accuracies of 72.80% and 75.66% for arousal and dominance, respectively. Additionally, the BRAD-Net demonstrates strong cross-paradigm adaptability, achieving 98.21% accuracy on a depression classification dataset.ConclusionsThese findings confirm that integrating neuroanatomical priors into a dual-branch multi-dimensional learning framework effectively extracts robust and interpretable neural representations. BRAD-Net not only advances high-performance EEG emotion recognition but also provides a novel, biologically-constrained design paradigm for developing more interpretable brain-computer interface models. By demonstrating that restricting attention to within-brain-region interactions suffices for accurate emotion recognition, our work offers a new theoretical perspective on the application of brain parcellation knowledge in classification models.
Research progress on addictive features and reward circuit mechanisms in non-suicidal self-injury and the feasibility of precision neuromodulation
Non-Suicidal Self-Injury (NSSI) presents a significant public health challenge; however, its underlying neurobiological mechanisms remain insufficiently understood, limiting the development of targeted interventions. Emerging evidence suggests that NSSI exhibits core addictive features, such as compulsive urges and tolerance, which may be driven by dysfunctions in the brain’s reward circuitry. This review synthesizes current research on the neural overlaps between NSSI and addiction, specifically focusing on the dysregulation of the ventral striatum and prefrontal cortex. Based on this mechanistic framework, we propose the potential of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)—a high-dose, functional connectivity-guided transcranial magnetic stimulation protocol—as a precision treatment for NSSI. By targeting specific reward network deficits, SAINT may offer a novel, rapid-acting therapeutic strategy for patients who do not respond to conventional pharmacological or psychological interventions.