Publications by Year: 2026

OBJECTIVE: Studies evaluating the effect of anti-inflammatory treatment on depressive symptom severity and anhedonia in depressed individuals report mixed results. In this preregistered systematic review and meta-analysis, the authors evaluated whether anti-inflammatory treatments, compared to placebo, reduce anhedonia and depressive symptom severity in depressed individuals with an inflammatory phenotype.

METHODS: The authors included randomized controlled trials of pharmacological anti-inflammatory treatments that assessed anhedonia or depressive symptom severity and recruited depressed individuals with an inflammatory phenotype or measured baseline inflammatory biomarkers that permitted post hoc analysis. A search was conducted in February 2025 of MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and PsycINFO. Multiple reviewers independently applied criteria, and discrepancies were resolved via consensus. Two reviewers independently extracted data and cross-checked for errors.

RESULTS: In randomized controlled trials (k=11) using an established cutoff for elevated inflammation (C-reactive protein ≥2 mg/L), both anhedonia (Hedges' g=0.40, 95% CI=0.08, 0.71) and depressive symptoms (Hedges' g=0.35, 95% CI=0.05, 0.64) were reduced, but no differences in treatment response (relative risk=1.28, 95% CI=0.997, 1.64) or remission rates (relative risk=1.18, 95% CI=0.71, 1.95) were observed. Results did not vary by clinical, interventional, or demographic characteristics.

CONCLUSIONS: Anti-inflammatory treatments may be safe and effective at reducing depressive symptoms and anhedonia in depressed individuals with heightened inflammation. Not accounting for inflammatory status may help explain prior mixed findings.

• It is uncertain if the 2017 ASCO recommendations on postanthracycline surveillance echocardiography impacted practice. • Release of the ASCO guidelines was not associated with changes in echocardiogram frequency with under half of patients receiving an echocardiogram within 18 months following chemotherapy initiation.

White matter hyperintensities (WMH) are an MRI-based biomarker associated with aging, Alzheimer's disease, and vascular dementia. Although the volume of WMH typically increases over time (growth) for individuals, WMH volume in some cases can also decrease (regress). This suggests the presence of active brain injury recovery mechanisms. Whether WMH regression reflects a true biological phenomenon or results from imaging artifacts or measurement errors, however, remains controversial. Here, we review published reports, following PRISMA search guidelines, describing or referring to WMH regression, the methods used to detect and quantitate regression, and proposed underlying mechanisms. Of 174 reviewed articles, 31 (26 original research studies and five case reports) were identified as directly related to WMH regression. Technical factors such as differences in longitudinal scan parameters, motion artifacts, and the interval between baseline and follow-up scans can affect WMH volume measurements. These factors may lead to inaccurate conclusions if appropriate controls are not employed. Although the use of standardized and systematic measurement protocols is essential, there is strong evidence indicating that WMH regression is a robust and biologically important phenomenon that may be influenced by clinical interventions. Further studies are needed to investigate WMH regression in relation to cerebrovascular risk mitigation and other therapeutic strategies.

Objective.The delineation of the clinical target volume (CTV) in radiotherapy is fundamentally uncertain due to the invisibility of microscopic disease on medical images. The ICRU 83 report acknowledges this by proposing a probabilistic interpretation of the CTV, but it does not define how to compute the probability of microscopic tumor presence (MTP) in tissue. This work addresses this gap by introducing a novel stochastic model that estimates the probability of MTP at the voxel level based on local spatial correlations in the voxels' neighborhood.Approach.We developed two first-principles stochastic models to simulate MTP under different assumptions, incorporating spatial correlation between neighboring voxels. The constant marginal probability (CMP) model assumes spatially uniform MTP and is suited for tumors without radial dependence on the distance from the gross tumor volume (GTV). The variable marginal probability (VMP) model introduces radial dependence, modeling decreasing MTP with distance from the GTV. The CMP model was evaluated on prostate cancer data, while the VMP model was assessed using breast and lung cancer data.Results.Both models accurately reproduced the fraction of times that MTP is present. In the prostate case, the CMP model estimated a marginal probability of MTP of 0.03, consistent with a literature report that indicates an average total microscopic tumor volume of approximately583mm3across patients. The VMP model successfully replicated the radial distribution of tumor islets, achieving mean absolute errors of 0.01 mm and 0.011 mm for breast and lung cancer distance distributions, respectively. However, not all MTP characteristics could be fully captured by the models, and in some cases discrepancies with population based tumor characteristics remain.Significance.This work introduces a statistically consistent framework that enables a probabilistic definition of the CTV. The proposed models provide a new way to capture key aspects of microscopic disease spread by introducing local voxel correlations.

This guideline provides evidence-based recommendations for clinicians, patients, and other stakeholders on the management of functional seizures. Following a National Academy of Medicine-compliant process, a multidisciplinary panel conducted a systematic review and integrated the findings with the authors' clinical experience to develop recommendations. A systematic review of the available evidence from first published articles to February 25, 2025, identified 12 Class II-III studies. The review found that psychological interventions are possibly effective in increasing the likelihood of achieving freedom from functional seizures, decreasing the frequency of functional seizures, decreasing anxiety, and improving health-related quality of life and psychosocial functioning for individuals with functional seizures. Key recommendations state that, when evaluating patients with seizure-like episodes, clinicians should seek historical and semiological information (including smartphone videos) from both patients and witnesses and may obtain video-EEG of all typical seizure-like episodes where feasible. Clinicians should evaluate patients diagnosed with functional seizures for co-occurring psychiatric disorders and co-occurring epilepsy. Clinicians should adhere to universal standards of care for patients, including speaking respectfully, refraining from unnecessary harm, and avoiding stigmatizing behavior. Clinicians should provide a specific diagnostic label and rationale for the diagnosis, should engage in shared decision making regarding the treatment plan, and should provide continuity of care to individuals diagnosed with functional seizures. When psychological interventions for functional seizures are indicated, clinicians should counsel patients regarding the potential benefits and risks of these interventions and should refer interested and appropriate patients to these interventions for the treatment of functional seizures. Clinicians should involve family, caregivers, or others in the social support network in the psychological treatment of individuals with functional seizures. Clinicians should not prescribe benzodiazepines or antiseizure medications for patients with functional seizures without co-occurring epilepsy or another indication for these medications and should counsel patients regarding the potential risks and lack of evidence of benefit for using these medications for functional seizures. Clinicians should taper off antiseizure medications for patients with functional seizures and without another indication for these medications. The guideline also identifies gaps in the available evidence and outlines potentially clinically impactful avenues for future research.

Iptacopan is a first-in-class, oral, selective inhibitor of complement factor B that has demonstrated positive efficacy across several complement-driven diseases. Here we evaluate the efficacy and safety of iptacopan monotherapy in adult patients with primary immune thrombocytopenia (ITP) and primary cold agglutinin disease (CAD). We performed a global, multicenter, phase 2 basket study enrolling patients with primary ITP or CAD after failure of ≥ 1 unique prior therapies. Primary endpoints were platelet response (≥ 50 × 109/L) for ITP and hemoglobin response (≥ 1.5 g/dL increase) for CAD sustained for ≥ 2 consecutive weeks during the first 12 weeks of iptacopan treatment, without the use of rescue therapy. Other endpoints included time to first response, duration of response, pharmacokinetics, safety/tolerability, and FACIT-Fatigue. Nineteen patients were treated with iptacopan (9 ITP, 10 CAD). Among patients with CAD, most showed improvements in hemoglobin levels, with a mean increase of 2.2 g/dL from baseline to week 12; five (50%) patients achieved the primary endpoint. Improvements were also observed for other outcomes in CAD, including lactate dehydrogenase, bilirubin, reticulocytes, and FACIT-Fatigue. Conversely, no patients with ITP met the primary endpoint. Most treatment-emergent adverse events (TEAEs) were mild, the most common being headache (21%), asthenia (16%), fatigue (16%), and petechiae (16%). Iptacopan monotherapy demonstrated encouraging preliminary efficacy in primary CAD, while no protocol-defined responses were observed in primary ITP. Iptacopan may represent a promising oral option for CAD and was well tolerated in both ITP and CAD with no unexpected safety signals. Trial Registration: ClinicalTrials.gov identifier: NCT05086744.

Apicomplexan parasites, responsible for toxoplasmosis, cryptosporidiosis and malaria, invade host cells through a unique gliding motility mechanism powered by actomyosin motors and a dynamic organelle called the conoid. Here, using cryo-electron microscopy, we determined structures of four essential complexes of the Toxoplasma gondii conoid: the preconoidal P2 ring, tubulin-based conoid fibers, and the subpellicular and intraconoidal microtubules. Our analysis identified 40 distinct conoid proteins, several of which are essential for parasite lytic growth, as revealed through genetic disruption studies. Comparative analysis of the tubulin-containing complexes sheds light on their functional specialization by microtubule-associated proteins, while the structure of the preconoidal ring pinpoints the site of actin polymerization and initial translocation, enhancing our mechanistic understanding of gliding motility and, therefore, parasite invasion.