BackgroundIntravenous thrombolysis with alteplase remains the standard reperfusion strategy for acute ischemic stroke (AIS), yet many patients still experience unfavorable outcomes despite timely treatment, underscoring the need for reliable multimodal prognostic markers.ObjectiveTo identify independent clinical, laboratory, and neuroimaging predictors of unfavorable 3-month functional outcome in anterior circulation AIS treated with alteplase, and to develop, internally validate, and benchmark an integrated multivariable model in accordance with TRIPOD.MethodsThis prospective single-center cohort study enrolled 268 consecutive patients with anterior circulation AIS receiving intravenous alteplase within 4.5 h of symptom onset (March 2022–February 2025). Three-month outcome was assessed by the modified Rankin Scale (mRS 0–2 favorable; 3–6 unfavorable) using validated structured instruments administered by blinded raters. Multivariable logistic regression was performed, and the final model was internally validated by 1,000-replicate bootstrap with optimism correction and shrinkage, evaluated by decision curve analysis (DCA), rendered into a nomogram, and benchmarked head-to-head against three previously published reference models using the DeLong test.ResultsOf 268 patients, 99 (36.9%) experienced unfavorable outcomes. Seven independent predictors were identified: early neurological deterioration (adjusted OR 3.45, 95% CI 2.01–5.92), large infarction exceeding one-third of the middle cerebral artery territory (OR 2.78, 1.58–4.89), baseline NIHSS (OR 1.14 per point, 1.07–1.22), poor Tan collateral score (OR 2.31, 1.34–3.98), low clot burden score (OR 2.15, 1.28–3.61), elevated D-dimer (OR 2.19, 1.29–3.72), and elevated CRP (OR 1.87, 1.11–3.15). The model achieved an apparent AUC of 0.847 (95% CI 0.801–0.893) and an optimism-corrected AUC of 0.831 (0.785–0.877) on bootstrap validation, with satisfactory calibration (Hosmer–Lemeshow P = 0.394). DCA showed positive net benefit across threshold probabilities of 0.15–0.75, and the model exceeded the recalibrated Hu, Ping, and Lv models.ConclusionA multimodal panel integrating clinical, inflammatory, coagulation, and neuroimaging parameters independently predicts unfavorable 3-month outcome following intravenous thrombolysis in anterior circulation AIS. The findings are hypothesis-generating pending external validation in independent multicenter cohorts.
Memory-focused therapy: an integrated intervention to reduce trauma symptoms, maladaptive cognitive processes, and emotional distress in Afghan youth
BackgroundAfghan youth continue to face chronic war-related trauma, terrorist violence, and severe disruptions to education and social support systems, resulting in high rates of posttraumatic stress disorder (PTSD), depression, anxiety, and hopelessness. There is a critical need for culturally responsive, low-intensity, and feasible psychological interventions that can be delivered in low-resource and unstable settings.ObjectiveThis study conducted a preliminary evaluation of the efficacy, acceptability, and mechanisms of change associated with Memory-Focused Therapy (MFT), an integrative intervention targeting autobiographical memory processing, acceptance-based regulation, and future self-construction among youth affected by the Kaaj Education Center attack in Kabul, Afghanistan.MethodsA single-group repeated-measures design was used with 26 participants assessed at baseline, post-intervention, and three-month follow-up. Standardized measures of PTSD, depression, anxiety, stress, cognitive avoidance, cognitive fusion, resilience, and posttraumatic growth were administered. MFT was delivered in 12 structured group sessions. Additionally, qualitative data from semi-structured interviews and therapist field notes were analyzed using thematic analysis.ResultsQuantitative analyses showed significant reductions in PTSD symptoms, depression, anxiety, stress, cognitive avoidance, and cognitive fusion from baseline to post-intervention, alongside significant increases in posttraumatic growth. Several of these improvements were maintained at follow-up. Qualitative findings reflected four overarching themes: (1) facilitator experiences and implementation challenges in high-risk contexts, (2) improvements in cognitive and emotional processing, (3) growth in meaning, relationships, values, and future orientation, and (4) exposure to traumatic memories and reduced avoidance.ConclusionFindings provide preliminary evidence that MFT is a feasible, acceptable, and potentially effective intervention for trauma-affected Afghan youth. By integrating trauma memory processing, present-moment emotional regulation, and future-oriented meaning-making, MFT appears to support improvements in psychological coherence, self-continuity, and resilience. Further controlled and longitudinal studies are needed to confirm these effects and examine underlying mechanisms.
<![CDATA[New data in cannabis use disorder show investigational drug PP-01 cuts irritability 42% in trials.]]>
STAT+: Compass says depression drug has long-lasting benefits
Want to stay on top of the science and politics driving biotech today? Sign up to get our biotech newsletter in your inbox.
Good morning. Plenty of news today, and also a deal that is running out soon: Buy one year of STAT+, get one year free.
Vertex makes its largest-ever deal
Vertex said yesterday it will spend $10 billion to acquire Crinetics Pharmaceuticals, a biotech developing drugs for rare endocrine disorders.
<![CDATA[Phase 3 data show COMP360 psilocybin delivers rapid, lasting relief in treatment-resistant depression; FDA filing advances toward 2027 launch.]]>
Comparative meta-analysis of task-related functional brain abnormalities in nonsuicidal self-injury and suicide attempt
BackgroundNonsuicidal self-injury (NSSI) and suicide attempt (SA) are two major self-injurious behaviors causing substantial suffering and socioeconomic burden. However, it remains unclear whether NSSI and SA are characterized by common or distinct brain dysregulations. Here, we aimed to identify shared and separable neurofunctional alterations during task engagement between NSSI and SA.MethodA coordinate-based meta-analysis was employed using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) by capitalizing on task-based functional magnetic resonance imaging (fMRI) studies comparing the brain activation between NSSI/SA individuals and controls.ResultThe search identified 10 studies for NSSI (n = 200, mean age: 22.89 years) and 16 studies for SA (n = 343, mean age: 28.65 years). After threshold-free cluster enhancement correction, NSSI individuals exhibited increased right amygdala activation relative to both controls and the SA group, as well as heightened left middle frontal gyrus and reduced left paracentral lobule activation compared to the SA group. No significant activation differences were found between SA and controls, though a less conservative threshold revealed increased left postcentral gyrus activation in the SA group. No shared functional abnormalities were identified between NSSI and SA under either corrected or uncorrected thresholds. Importantly, subgroup analyses revealed that the neurofunctional abnormalities in NSSI were primarily driven by adolescent cohorts, whereas no significant clusters emerged for the SA group across age-stratified analyses.ConclusionThese results suggest that neurofunctional abnormalities are evident in adolescent NSSI, particularly in fronto−limbic regions, with no robust findings in adult NSSI or SA subgroups. This highlights a unique developmental trajectory that necessitates age-tailored risk assessment and interventions for self-injurious behaviors.
Technology-Enhanced Peer Support for Depression in Older Adults: Single-Arm Mixed Methods Feasibility Study
<strong>Background:</strong> Depression in late life is often compounded by social isolation and barriers to care. There is limited study of technology-enhanced peer support for depression among older adults. <strong>Objective:</strong> This study aimed to assess the feasibility and acceptability of a technology-enhanced peer support intervention to decrease depression among older adults. <strong>Methods:</strong> We used a mixed methods pilot study among adults aged 50 years and older with depression who received a peer support intervention called Peers+. The intervention consisted of 8 weekly video chats and unidirectional texts focused on increasing depression self-care and coping. Data obtained from screening, baseline, postintervention, and 3-month follow-up were used in the analysis to assess preliminary outcomes of the intervention. Mixed effects longitudinal models were used to assess change in depression, and qualitative data were collected and analyzed to identify key themes related to participant experiences. <strong>Results:</strong> A total of 34 older adults with a mean age of 67 (SD 9.57) years participated in the study, and 82.4% (28/34) of participants finished all 8 intervention meetings. Depressive symptoms declined over the course of the study of 35 weeks (<i>F</i><sub>1, 88.8</sub>=26.0; <i>β</i>=–.14, 95% CI –0.20 to 0.09; <i>P</i><.001). Emotional well-being (<i>β</i>=.48, 95% CI 0.26-0.70; <i>P</i><.001), social functioning (<i>β</i>=.71, 95% CI 0.33-1.09; <i>P</i><.001), self-efficacy (<i>β</i>=2.29, 95% CI 0.83-3.75; <i>P</i><.001), and coping (<i>β</i>=2.90, 95% CI 0.24-5.55; <i>P</i><.001) improved throughout the study period. Participants perceived supportive texts as reinforcing trust between peer coaches, using coping strategies, increasing social connection, and providing accountability for improving self-care. Peer coaches and older adults needed technology support for participation in the study. <strong>Conclusions:</strong> This study demonstrated the feasibility and acceptability of a peer support intervention enhanced by video chats and texts, delivered by older adult peer coaches to an ethnically diverse group of older adults with depression. Study findings indicate that ongoing and accessible technology support contributed to older adult participation and engagement.
ALS Drug Extends Survival in Mice, Targets TDP-43 Low-Complexity Domain
In a new study published in Nature Aging titled, “Therapeutic targeting of the conserved region within the low-complexity domain of TDP-43 is neuroprotective and extends survival in amyotrophic lateral sclerosis mice,” researchers from University of Arizona present a new therapeutic target to shield nerve cells from the damage of ALS.
“Current FDA-approved treatments for ALS provide only modest benefits. There is an urgent need for a real breakthrough,” said Xinglong Wang, PhD, corresponding author of the study a professor at the R. Ken Coit College of Pharmacy.
ALS is difficult to treat because diagnosis occurs after substantial nerve cell damage. Causes of ALS are unclear. Fewer than one in 10 cases are inherited through a known genetic mutation. More than 90% of cases arise sporadically with no family history or clear genetic cause. However, nearly all cases demonstrate abnormal TDP-43 aggregation inside nerve cells, which often informs post-mortem diagnosis.
“We asked a simple question that had never been tested: is there one specific part of TDP-43 that’s causing the harm, something a drug could switch off without disturbing the rest?” Wang said.
The team found a region of TDP-43 were disease-causing mutations clustered. When this region was deleted in mice, the nerve cell death caused by TDP-43 dropped sharply while normal protein function remained intact. The researchers identified experimental drug, XL20, which could latch onto the target region in the TDP-43 protein. Notably, the drug could cross the blood-brain barrier.
In mice, the XL20 extended median survival by approximately a week, protected nerve cells and reduced muscle weakness. When XL20 was tested on human motor neurons, the specialized nerve cells in the brain and spinal cord, the experimental drug reversed damage.
Wang says XL20 represents a promising candidate for future clinical development. As ALS typically develops over months to years after symptoms first appear, earlier treatment could provide greater opportunity to slow disease progression.
Additionally, the study’s findings may have applications for other neurological diseases. The same TDP-43 pathology is central to limbic-predominant age-related TDP-43 encephalopathy (LATE), a common dementia which affects roughly one in three people over 80. TDP-43 pathology is also found in more than half of Alzheimer’s patients and is associated with faster cognitive decline.
“The same TDP-43 pathology is implicated in several other neurodegenerative diseases,” Wang said. “If future studies show this approach works in those diseases as well, it could eventually benefit a much larger patient population.”
The post ALS Drug Extends Survival in Mice, Targets TDP-43 Low-Complexity Domain appeared first on GEN – Genetic Engineering and Biotechnology News.
Biomarkers Could Help in Antidepressant Choice
Antidepression treatment based on a person’s individual biomarkers could help determine which of the world’s most popular medications to use, a clinical trial suggests.
The SMART Trial to Predict Anhedonia Response to Antidepressant Treatment results suggest that behavioral, brain, and clinical data could together determine the optimal antidepressant to choose before a person starts treatment.
There were no significant primary endpoint differences in depression outcomes between participants who received bupropion or sertraline based on biomarkers identified in the prior Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study.
But people negative for biomarkers with both drugs had significantly worse depression symptom trajectories than those who had at least one positive biomarker, regardless of the drug they received.
Response rates among participants with both biomarkers were almost double that of those without any biomarkers, with those who had at least one biomarker having an intermediate response.
“Our results suggest that we could boost response rate by using two sets of biomarkers previously identified in the EMBARC study, making an important contribution to advancing the goals of precision psychiatry,” reported Peter Zhukovsky, PhD, from Harvard Medical School, and co-workers in Nature Mental Health.
“Ultimately, we strongly hope these advances will enable personalized treatment guidance to accelerate and boost antidepressant benefits.”
Treatment for depression is often still trial and error, with symptoms improving in only half the people taking an antidepressant. This could be due to treatments not being chosen based on people’s individual characteristics.
Finding markers that predict response to different antidepressants could therefore provide patients and clinicians with valuable information to guide treatment choice.
The trial was among the first to investigate how treatment could be guided using clinical information such as responses to questionnaires, behavioral information such as performance in computerized tasks, and brain data such as magnetic resonance imaging (MRI) scans.
It was carried out as part of the Wellcome Leap Multi-Channel Psych Program effort to double the number of people who respond to the first treatment they try for depression via the integration of multimodal biomarkers.
Firstly, the researchers investigated biomarker models that predicted response to the selective serotonin reuptake inhibitor (SSRI) sertraline or the norepinephrine-dopamine reuptake inhibitor bupropion using the EMBARC study.
The treatment-assignment algorithm that was developed generated two marker-based indications for each patient—one for bupropion and sertraline—with the predictive model achieving a cross-validated area under the curve of 0.86 and 0.66, respectively.
The team then examined whether antidepressant response could be boosted using their created biomarker combination of a functional MRI imaging marker, reward learning and sensitivity, cognitive control, the clinical variables of depression severity and neuroticism, and the demographic variable of employment status.
After analyzing these biomarkers among participants, who had major depressive disorder, the group was randomly assigned to receive a full 8-week course of an SSRI or non-SSRI.
The primary outcome was the change in depression severity from pretreatment baseline to eight weeks after the start of treatment, with no significant differences in treatment outcomes for those assigned a drug consistent versus inconsistent with their biomarkers.
This, the researchers say was possibly due to the limited power to detect moderate effects.
However, significant differences emerged in symptom reduction trajectories for those with positive markers for both medications, with a response rate of 71.4% compared with 65.4% for those with a positive biomarker for either drug and 42.9% for those with two negative markers.
The authors concluded: “We found that, relative to patients with two negative markers, those with one or two markers were characterized by significantly larger reduction in depressive symptoms, showing that biomarker-guided treatment selection can boost efficacy for two of the most widely prescribed antidepressants around the world.”
The post Biomarkers Could Help in Antidepressant Choice appeared first on Inside Precision Medicine.
Email-Delivered Digital Positive Affect Intervention for Young Adults in Zimbabwe
Conditions: Depression Symptoms
Interventions: Behavioral: Email-Delivered Positive Affect Intervention; Behavioral: Psychoeducational Control
Sponsors: Vilnius University; University of Zimbabwe
Not yet recruiting
Interventions: Behavioral: Email-Delivered Positive Affect Intervention; Behavioral: Psychoeducational Control
Sponsors: Vilnius University; University of Zimbabwe
Not yet recruiting