Circuits and mechanisms for TMS-induced corticospinal waves: Connecting sensitivity analysis to the network graph.

Transcranial magnetic stimulation (TMS) is a non-invasive, FDA-cleared treatment for neuropsychiatric disorders with broad potential for new applications, but the neural circuits that are engaged during TMS are still poorly understood. Recordings of neural activity from the corticospinal tract provide a direct readout of the response of motor cortex to TMS, and therefore a new opportunity to model neural circuit dynamics. The study goal was to use epidural recordings from the cervical spine of human subjects to develop a computational model of a motor cortical macrocolumn through which the mechanisms underlying the response to TMS, including direct and indirect waves, could be investigated.

Comparative Analysis of Silicone Mouth Swabs with Varying Hardness Levels for Optimal Plaque Removal in Elderly Oral Care.

Purpose: Silicone mouth swabs have emerged as a promising alternative to gauze, sponge brushes, and soft-bristled toothbrushes, offering a balance between gentle cleaning and effectiveness. The flexibility and softness of silicone make it a suitable material for safely cleaning the sensitive oral tissues of elderly patients. This study aims to determine the optimal hardness level of silicone that maximises cleaning effectiveness while minimising the risk of trauma to oral tissues.

Reduced auditory perception and brain response with quiet TMS coil.

Background: Electromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC).

Objective: To compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil.

Consensus Statements among European Sleep Surgery Experts on Snoring and Obstructive Sleep Apnea: Part 3 Palatal Surgery, Outcomes and Follow-Up, Complications, and Post-Operative Management.

Exploring and establishing a consensus on palatal surgery, the outcomes and follow-up after the palatal surgery, the complications of palatal surgery, and the post-operative management after palatal surgery for snoring and obstructive sleep apnea (OSA) among sleep surgeons is critical in the surgical management of patients with such conditions. Using the Delphi method, a set of statements was developed based on the literature and circulated among a panel of eight European experts. Responses included agreeing and disagreeing with each statement, and the comments were used to assess the level of consensus and to develop a revised version.

Validating alternative oxidase (AOX) gene family as efficient marker consortium for multiple-resilience in Xylella fastidiosa-infected Vitis holobionts.

AOX gene family in motion marks in-born efficiency of respiration adjustment; can serve for primer screening, genotype ranking, in vitro-plant discrimination and a SMART perspective for multiple-resilient plant holobiont selection. The bacteria Xylella fastidiosa (Xf) is a climate-dependent, global threat to many crops of high socio-economic value, including grapevine. Currently designed breeding strategies for Xf-tolerant or -resistant genotypes insufficiently address the danger of biodiversity loss by focusing on selected threats, neglecting future environmental conditions.

A novel development of advanced control approach for battery-fed electric vehicle systems.

In today's context, there is a clear preference for DC microgrids over AC microgrids due to their better compatibility with generating sources, loads, and battery energy storage systems (BESS). However, the intermittent nature of renewable resources disrupts the balance between power generation and load demand. It raises concerns regarding power management and quality in the power system.

Identification of unique cell type responses in pancreatic islets to stress.

Diabetes involves the death or dysfunction of pancreatic β-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress.

The use of an anterior-posterior atrophy index to distinguish Alzheimer's disease from frontotemporal disorders: an automated volumetric MRI Study.

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) require different treatments. Since clinical presentation can be nuanced, imaging biomarkers aid in diagnosis. Automated software such as Neuroreader (NR) provides volumetric imaging data, and indices between anterior and posterior brain areas have proven useful in distinguishing dementia subtypes in research cohorts.

Heterologous HSPC Transplantation Rescues Neuroinflammation and Ameliorates Peripheral Manifestations in the Mouse Model of Lysosomal Transmembrane Enzyme Deficiency, MPS IIIC.

Mucopolysaccharidosis III type C (MPS IIIC) is an untreatable neuropathic lysosomal storage disease caused by a genetic deficiency of the lysosomal N-acetyltransferase, HGSNAT, catalyzing a transmembrane acetylation of heparan sulfate. HGSNAT is a transmembrane enzyme incapable of free diffusion between the cells or their cross-correction, which limits development of therapies based on enzyme replacement and gene correction. Since our previous work identified neuroinflammation as a hallmark of the CNS pathology in MPS IIIC, we tested whether it can be corrected by replacement of activated brain microglia with neuroprotective macrophages/microglia derived from a heterologous HSPC transplant.

Distinct cytokine profiles in late pregnancy in Ugandan people with HIV.

During pregnancy, multiple immune regulatory mechanisms establish an immune-tolerant environment for the allogeneic fetus, including cellular signals called cytokines that modify immune responses. However, the impact of maternal HIV infection on these responses is incompletely characterized. We analyzed paired maternal and umbilical cord plasma collected during labor from 147 people with HIV taking antiretroviral therapy and 142 HIV-uninfected comparators.

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.): Third edition of the guideline for evaluating efficacy of anthelmintics in ruminants (bovine, ovine, caprine).

This guideline is aimed at those who are involved in the assessment of anthelmintic efficacy in ruminant livestock species (bovine, ovine and caprine). The intent is to provide a framework that can be adopted worldwide for the testing of anthelmintics in ruminants, such that studies carried out in different countries can be compared and thereby unnecessary duplication can be reduced. Recommendations are made for the selection, housing and feeding of study animals, the type of studies required, the method used to conduct those studies, the assessment of results and the standards for defining anthelmintic efficacy.

Physiologically based pharmacokinetics modeling and transporter proteomics to predict systemic and local liver and muscle disposition of statins.

Statins are used to reduce liver cholesterol levels but also carry a dose-related risk of skeletal muscle toxicity. Concentrations of statins in plasma are often used to assess efficacy and safety, but because statins are substrates of membrane transporters that are present in diverse tissues, local differences in intracellular tissue concentrations cannot be ruled out. Thus, plasma concentration may not be an adequate indicator of efficacy and toxicity.

Diagnosis of thrombotic thrombocytopenic purpura: easy-to-use fiber optic surface plasmon resonance immunoassays for automated ADAMTS-13 antigen and conformation evaluation.

Background: Laboratory diagnosis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains challenging when ADAMTS-13 activity ranges between 10% and 20%. To prevent misdiagnosis, open ADAMTS-13 conformation gained clinical attention as a novel biomarker, especially to diagnose acute iTTP in patients with diagnostic undecisive ADAMTS-13 activity. Plasma ADAMTS-13 conformation analysis corrects for ADAMTS-13 antigen, with both parameters being characterized in enzyme-linked immunosorbent assay (ELISA)-based reference assays requiring expert technicians.

Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.

Background: This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma.

Methods: This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at 3 dose levels (DLs; -1, 1, and 2).

Diagnosis and Treatment of Sylvian Aqueduct Syndrome.

Background: Sylvian aqueduct syndrome is a rare complication after ventriculoperitoneal (V-P) shunt surgery and is not easily diagnosed.

Methods: A 26-year-old male with obstructive hydrocephalus due to tectal glioma was treated with a V-P shunt surgery in another hospital. After the surgery, the patient developed an intractable disturbance of consciousness.

Lateral Extra-articular Tenodesis Does Not Decrease Graft Failure in Revision Anterior Cruciate Ligament Reconstruction When Combined With Quadriceps or Patellar Tendon Grafts.

Purpose: To compare return-to-sport (RTS) rates, graft failure rates, and clinical outcomes in patients who underwent revision anterior cruciate ligament reconstruction (R-ACLR) with additional lateral extra-articular tenodesis (LET) versus isolated R-ACLR.

Methods: A retrospective review of the medical records of patients who underwent R-ACLR with or without a modified Lemaire LET procedure was performed. Seventy-four patients with at least 2 years of follow-up who had high-grade positive pivot-shift test findings were included.

Humoral profiles of toddlers and young children following SARS-CoV-2 mRNA vaccination.

Although young children generally experience mild symptoms following infection with SARS-CoV-2, severe acute and long-term complications can occur. SARS-CoV-2 mRNA vaccines elicit robust immunoglobulin profiles in children ages 5 years and older, and in adults, corresponding with substantial protection against hospitalizations and severe disease. Whether similar immune responses and humoral protection can be observed in vaccinated infants and young children, who have a developing and vulnerable immune system, remains poorly understood.

Consensus Statements among European Sleep Surgery Experts on Snoring and Obstructive Sleep Apnea: Part 1 Definitions and Diagnosis.

Seeking consensus on definitions and diagnosis of snoring and obstructive sleep apnea (OSA) among sleep surgeons is important, particularly in this relatively new field with variability in knowledge and practices. A set of statements was developed based on the literature and circulated among eight panel members of European experts, utilizing the Delphi method. Responses in agreement and disagreement on each statement and the comments were used to assess the level of consensus and develop a revised version.

Intravenous Thrombolysis Before Endovascular Treatment in Posterior Circulation Occlusions: A MR CLEAN Registry Study.

Background: The effectiveness of intravenous thrombolysis (IVT) before endovascular treatment (EVT) has been investigated in randomized trials and meta-analyses. These studies mainly concerned anterior circulation occlusions. We aimed to investigate clinical, technical, and safety outcomes of IVT before EVT in posterior circulation occlusions in a nationwide registry.

Design and Biological Evaluation of Piperazine-Bearing Nitrobenzamide Hypoxia/GDEPT Prodrugs: The Discovery of CP-506.

Off-target aerobic activation of PR-104A by human aldo-keto reductase 1C3 (AKR1C3) has confounded the development of this dual hypoxia/gene therapy prodrug. Previous attempts to design prodrugs resistant to AKR1C3 activation have resulted in candidates that require further optimization. Herein we report the evaluation of a lipophilic series of PR-104A analogues in which a piperazine moiety has been introduced to improve drug-like properties.

Integrating machine learning with pharmacokinetic models: Benefits of scientific machine learning in adding neural networks components to existing PK models.

Recently, the use of machine-learning (ML) models for pharmacokinetic (PK) modeling has grown significantly. Although most of the current approaches use ML techniques as black boxes, there are only a few that have proposed interpretable architectures which integrate mechanistic knowledge. In this work, we use as the test case a one-compartment PK model using a scientific machine learning (SciML) framework and consider learning an unknown absorption using neural networks, while simultaneously estimating other parameters of drug distribution and elimination.

Histological Characteristics and Management of Hepatitis on Immune Checkpoint Inhibitors: A Retrospective Descriptive Study.

Background And Aims: the side effects of immune checkpoint inhibitors (ICI) pose a problem for the clinical management of cancer patients. There is a lack of knowledge of the value of liver biopsy in patients with ICI-related drug-induced liver injury (ICI-DILI). The aim of this study was to explore the impact of liver biopsy on clinical management and response to corticosteroids, according to histological findings.

Impact of Time to Fixation on Outcomes of Operative Treatment of Intra-articular Distal Radius Fractures.

Background: The incidence of operative treatment of distal radius fractures (DRFs) has increased recently, but the optimal timing for surgical fixation remains unclear. We hypothesized that: (1) an increase in time to fixation of intra-articular DRFs would increase the likelihood of postoperative complications; and (2) increased time from injury to fixation would lead to longer surgical time and worse range of motion (ROM) outcomes.

Methods: We retrospectively reviewed 299 fractures in 284 adult patients who underwent open reduction and internal fixation (ORIF) of a closed, intra-articular DRF at our institution over a 10.

Rapid estimation of cortical neuron activation thresholds by transcranial magnetic stimulation using convolutional neural networks.

Background: Transcranial magnetic stimulation (TMS) can modulate neural activity by evoking action potentials in cortical neurons. TMS neural activation can be predicted by coupling subject-specific head models of the TMS-induced electric field (E-field) to populations of biophysically realistic neuron models; however, the significant computational cost associated with these models limits their utility and eventual translation to clinically relevant applications.

Objective: To develop computationally efficient estimators of the activation thresholds of multi-compartmental cortical neuron models in response to TMS-induced E-field distributions.