The potential of muscarinic M and M receptor activators for the treatment of cognitive impairment associated with schizophrenia.

Cognitive impairment is a core symptom of schizophrenia and a major determinant of poor long-term functional outcomes. Despite considerable efforts, we do not yet have any approved pharmacological treatments for cognitive impairment associated with schizophrenia (CIAS). A combination of advances in pre-clinical research and recent clinical trial findings have led to a resurgence of interest in the cognition-enhancing potential of novel muscarinic acetylcholine receptor (mAChR) agonists in schizophrenia.

Role of Hypoperfusion Intensity Ratio in Vessel Occlusions: A Review on Safety and Clinical Outcomes.

The hypoperfusion intensity ratio (HIR) is a quantitative metric used in vascular occlusion imaging to evaluate the extent of brain tissue at risk due to hypoperfusion. Defined as the ratio of tissue volume with a time-to-maximum (Tmax) of >10 seconds to that of >6 seconds, HIR assists in differentiating between the salvageable penumbra and the irreversibly injured core infarct. This review explores the role of HIR in assessing clinical outcomes and guiding treatment strategies, including mechanical thrombectomy and thrombolytic therapy, for patients with large vessel occlusions (LVOs).

SLC16A8 is a causal contributor to age-related macular degeneration risk.

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter.

Noninvasive in vivo photoacoustic detection of malaria with Cytophone in Cameroon.

Current malaria diagnostics are invasive, lack sensitivity, and rapid tests are plagued by deletions in target antigens. Here we introduce the Cytophone, an innovative photoacoustic flow cytometer platform with high-pulse-rate lasers and a focused ultrasound transducer array to noninvasively detect and identify malaria-infected red blood cells (iRBCs) using specific wave shapes, widths, and time delays generated from the absorbance of laser energy by hemozoin, a universal biomarker of malaria infection. In a population of Cameroonian adults with uncomplicated malaria, we assess our device for safety in a cross-sectional cohort (n = 10) and conduct a performance assessment in a longitudinal cohort (n = 20) followed for 30 ± 7 days after clearance of parasitemia.

The use of 7T MRI in multiple sclerosis: review and consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

The use of ultra-high-field 7-Tesla (7T) MRI in multiple sclerosis (MS) research has grown significantly over the past two decades. With recent regulatory approvals of 7T scanners for clinical use in 2017 and 2020, the use of this technology for routine care is poised to continue to increase in the coming years. In this context, the North American Imaging in MS Cooperative (NAIMS) convened a workshop in February 2023 to review the previous and current use of 7T technology for MS research and potential future research and clinical applications.

Innovative COVID-19 Point-of-Care Diagnostics Suitable for Tuberculosis Diagnosis: A Scoping Review.

Rapid and accurate point-of-care (POC) tuberculosis (TB) diagnostics are crucial to bridge the TB diagnostic gap. Leveraging recent advancements in COVID-19 diagnostics, we explored adapting commercially available POC SARS-CoV-2 tests for TB diagnosis in line with the World Health Organization (WHO) target product profiles (TPPs). A scoping review was conducted following PRISMA-ScR guidelines to systematically map POC antigen and molecular SARS-CoV-2 diagnostic tests potentially meeting the TPPs for TB diagnostic tests for peripheral settings.

Outcomes and Recurrence Rates Among Patients With Provoked and Cryptogenic Cerebral Venous Thrombosis: Analysis of the ACTION CVT.

Background And Objectives: Cerebral venous thrombosis (CVT) is a rare cause of stroke. While the standard treatment is anticoagulation, the type and duration of anticoagulation depends on the underlying etiology. This study aims to identify prevalence, risk factors, and recurrent venous thromboembolism (VTE) rates among patients with idiopathic (cryptogenic) CVT and CVT provoked by transient (peripartum, hormonal treatment, infection, trauma) and persistent (cancer, thrombophilia) factors.

Extensive Biotransformation Profiling of AZD8205, an Anti-B7-H4 Antibody-Drug Conjugate, Elucidates Pathways Underlying Its Stability .

What happens to macromolecules ? What drives the structure-activity relationship and stability for antibody-drug conjugates (ADCs)? These interrelated questions are increasingly relevant due to the re-emerging importance of ADCs as an impactful therapeutic modality and the gaps that exist in our understanding of ADC structural determinants that underlie ADC stability. Complex macromolecules, such as ADCs, may undergo changes due to their intricate structure as biotransformations may occur on the linker, the payload, and/or at the modified conjugation site. Furthermore, the dissection of ADC metabolism presents a substantial analytical challenge due to the difficulty in the identification or quantification of minor changes on a large macromolecule.

Neuropsychological Late Effects and Quality-of-Life Outcomes in Pediatric Brain Tumor Survivors: Role of Pediatric Neurologists in Monitoring and Management.

Pediatric brain tumor (PBT) survivors are at significantly increased risk of cognitive, psychosocial, and educational/vocational sequelae that impact health-related quality of life. These complications and health morbidities result in high burden on survivors and their families, particularly those already vulnerable to disparities in health care access and outcomes. Since neurological comorbidities are common in this population, neurologists are uniquely positioned to screen, treat identified symptoms, and connect families with services and resources.

Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage.

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.

Risk of COVID-19 in Children throughout the Pandemic and the Role of Vaccination: A Narrative Review.

At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, persons ≥65 years of age and healthcare personnel represented the most vulnerable groups with respect to risk of infection, severe illness, and death. However, as the pandemic progressed, there was an increasingly detrimental effect on young children and adolescents. Severe disease and hospitalization increased over time in pediatric populations, and containment measures created substantial psychosocial, educational, and economic challenges for young people.

A Novel Step-Up Dosage Regimen for Enhancing the Benefit-to-Risk Ratio of Mosunetuzumab in Relapsed or Refractory Follicular Lymphoma.

Mosunetuzumab, a T-cell engaging bispecific antibody targeting CD20xCD3, is approved for treating relapsed/refractory follicular lymphoma. This research supports the approved intravenous clinical dose regimen, summarizing the exposure-response relationships for clinical safety and efficacy. A population pharmacokinetic model and E logistic regression exposure-response models for safety and efficacy were developed using data from 439 patients with relapsed/refractory non-Hodgkin lymphoma and 159 patients with relapsed/refractory follicular lymphoma, respectively, from a Phase I/II study (NCT02500407).

Colocalization of Cancer-Associated Biomarkers on Single Extracellular Vesicles for Early Detection of Cancer.

Detection of cancer early, when it is most treatable, remains a significant challenge because of the lack of diagnostic methods sufficiently sensitive to detect nascent tumors. Early-stage tumors are small relative to their tissue of origin, heterogeneous, and infrequently manifest in clinical symptoms. The detection of early-stage tumors is challenging given the lack of tumor-specific indicators (ie, protein biomarkers, circulating tumor DNA) to enable detection using a noninvasive diagnostic assay.

Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.

Introduction: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results.

Methods: We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Disease burden and healthcare utilization in pediatric low-grade glioma: A United States retrospective study of linked claims and electronic health records.

Background: Despite high long-term survival rates, pediatric low-grade gliomas (pLGGs) are linked with significant tumor- and treatment-associated morbidities that may persist throughout life. The aims of this descriptive cross-sectional pilot study were to characterize health conditions among a cohort of patients with pLGG and explore the feasibility of quantifying disease burden and healthcare resource utilization (HRU).

Methods: Optum Market Clarity Data were used to identify patients aged ≤18 years with an ICD-10 code for brain neoplasm, ≥1 physician notes, and with evidence of pLGG recorded between January 1, 2017 and June 30, 2018.

Conversion Therapy to Transplant or Surgical Resection in Patients with Unresectable Hepatocellular Carcinoma Treated with Boosted Dose of Yttrium-90 Radiation Segmentectomy.

Background/objectives: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC).

Methods: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.