MR Imaging-Guided Focused Ultrasound-Clinical Applications in Managing Malignant Gliomas.

Malignant gliomas (MGs) are the most common primary brain tumors in adults. Despite recent advances in understanding the biology and potential therapeutic vulnerabilities of MGs, treatment options remain limited as the delivery of drugs is often impeded by the blood-brain barrier (BBB), and safe, complete surgical resection may not always be possible, especially for deep-seated tumors. In this review, the authors highlight emerging applications for MR imaging-guided focused ultrasound (MRgFUS) as a noninvasive treatment modality for MGs.

MR-guided Focused Ultrasound Thalamotomy for Chronic Pain.

MR-guided focused ultrasound (FUS) represents a promising alternative for patients with chronic neuropathic who have failed medical management and other treatment options. Early single-center experience with chronic neuropathic pain and trigeminal neuralgia has demonstrated favorable long-term outcomes. Excellent safety profile with low risk of motor and sensory complications and so far anecdotal permanent neurologic deficits make FUS a powerful tool to treat patients who are otherwise hopeless.

Transcranial Focused Ultrasound: A History of Our Future.

The history of focused ultrasound is a parallel history of neuroradiology, functional neurosurgery, and physics and engineering. Multiple pioneers collaborated as ultrasound transitioned from a wartime technology to a therapeutic one, particularly in using it to ablate the brain to treat movement disorders. Several competing technologies ensured that this "ultrasonic neurosurgery" remained in a lull.

First Demonstration of PDE11A4 Target Engagement for Potential Treatment of Age-Related Memory Disorders.

PDE11A4 is a target of interest for the treatment of age-related memory disorders. A previous report from our laboratories described an amide series of potent, selective PDE11A4 inhibitors that was metabolically unstable. Investigation of heterocyclic amide isosteres for the labile amide moiety revealed distinct structure-activity relationships and identified several compounds with potency comparable to the amide series.

A breath-based in vitro diagnostic assay for the detection of lower respiratory tract infections.

An accurate diagnosis is critical to reducing mortality in people with lower respiratory tract infections (LRTIs). Current microbiological culture is time-consuming, and nucleic acid amplification-based molecular technologies cannot distinguish between colonization and infection. Previously, we described developing a sampling system for effectively capturing biomolecules from human breath.

Comparing approaches for chemoprevention for school-based malaria control in Malawi: an open label, randomized, controlled clinical trial.

Background: School-age children in sub-Saharan Africa suffer an underappreciated burden of malaria which threatens their health and education. To address this problem, we compared the efficacy of two school-based chemoprevention approaches: giving all students intermittent preventive treatment (IPT) or screening and treating only students with detected infections (IST).

Methods: In a three-arm, open-label, randomized, controlled trial (NCT05244954) in Malawi, 746 primary school students, aged 5-19 years, were individually randomized within each grade-level to IPT (n = 249), IST with a high-sensitivity rapid diagnostic test (hs-RDT, n = 248), or control (n = 249).

Regulation of macrophage fibrinolysis during venous thrombus resolution.

Background: Venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is a serious cardiovascular disease with significant mortality and morbidity. Clinically, patients with faster resolution of a venous thrombi have improved prognosis. Urokinase-plasminogen activator (uPA), produced by macrophages, is a key mediator of fibrinolysis required for resolving venous thrombi and restoring vascular integrity.

Increased Sensitivity to Effort and Perception of Effort in People with Schizophrenia.

Objective: Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations, calculations weighing the costs vs. the benefits of actions. Several reports have shown that people with schizophrenia display a reduced willingness to exert effort for monetary rewards when compared to controls.

Changes in Corticospinal Tract Consistency after Dry Needling in a Stroke Patient.

Background: Dry needling (DN) is a technique employed to mitigate spasticity and enhance functionality in stroke patients. We report the impact of DN on both corticospinal tract (CST) consistency and wrist flexors spasticity of an individual affected by stroke.

Case: The participant was a 57-year-old male who had experienced an ischemic stroke 9 months prior.

Rapid reconfiguration of cortical networks after repeated exposure to visual-vestibular conflicts.

Visual-vestibular conflicts can induce motion sickness and further postural instability. Visual-vestibular habituation is recommended to reduce the symptoms of motion sickness and improve postural stability with an altered multisensory reweighting progress. However, it is unclear how the human brain reweights multisensory information after repeated exposure to visual-vestibular conflicts.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Purpose: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations.

Methods: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education).

CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published.

IFNλ signaling in neutrophils enhances the pathogenesis of Bordetella pertussis infection.

Interferon lambda (IFN-λ) plays diverse roles in bacterial infections. Previously we showed that IFN-λ is induced in the lungs of B. pertussis-infected adult mice and exacerbates inflammation.

Out-of-Distribution Detection and Radiological Data Monitoring Using Statistical Process Control.

Machine learning (ML) models often fail with data that deviates from their training distribution. This is a significant concern for ML-enabled devices as data drift may lead to unexpected performance. This work introduces a new framework for out of distribution (OOD) detection and data drift monitoring that combines ML and geometric methods with statistical process control (SPC).

Combined Physics- and Machine-Learning-Based Method to Identify Druggable Binding Sites Using SILCS-Hotspots.

Identifying druggable binding sites on proteins is an important and challenging problem, particularly for cryptic, allosteric binding sites that may not be obvious from X-ray, cryo-EM, or predicted structures. The Site-Identification by Ligand Competitive Saturation (SILCS) method accounts for the flexibility of the target protein using all-atom molecular simulations that include various small molecule solutes in aqueous solution. During the simulations, the combination of protein flexibility and comprehensive sampling of the water and solute spatial distributions can identify buried binding pockets absent in experimentally determined structures.

Force Field Limitations of All-Atom Continuous Constant pH Molecular Dynamics.

All-atom constant pH molecular dynamics simulations offer a powerful tool for understanding pH-mediated and proton-coupled biological processes. As the protonation equilibria of protein sidechains are shifted by electrostatic interactions and desolvation energies, p values calculated from the constant pH simulations may be sensitive to the underlying protein force field and water model. Here we investigated the force field dependence of the all-atom particle mesh Ewald (PME) continuous constant pH (PME-CpHMD) simulations of a mini-protein BBL.