Label-free Aβ plaque detection in Alzheimer's disease brain tissue using infrared microscopy and neural networks.

We present a novel method for the label-free detection of amyloid-beta (Aβ) plaques, the key hallmark of Alzheimer's disease, in human brain tissue sections. Conventionally, immunohistochemistry (IHC) is employed for the characterization of Aβ plaques, hindering subsequent analysis. Here, a semi-supervised convolutional neural network (CNN) is trained to detect Aβ plaques in quantum cascade laser infrared (QCL-IR) microscopy images.

The Aging Substantia Nigra is Characterized by ROS Accumulation Potentially Resulting in Increased Neuroinflammation and Cytoskeletal Remodeling.

Aging is a progressive and irreversible process, serving as the primary risk factor for neurodegenerative disorders. This study aims to identify the molecular mechanisms underlying physiological aging within the substantia nigra, which is primarily affected by Parkinson's disease, and to draw potential conclusions on the earliest events leading to neurodegeneration in this specific brain region. The characterization of essential stages in aging progress can enhance knowledge of the mechanisms that promote the development of Parkinson's disease.

Treatment Approach for Metastatic Intracranial Germinoma: A Multi-Institutional Experience.

Background: Germinoma is the most common intracranial germ cell tumor (IGCT) in children and young adults. Treatment with 24 Gy craniospinal irradiation (CSI) with boost to 40 Gy alone results in excellent survival, irrespective of disease stage. For localized germinoma, recent studies have demonstrated the efficacy of pre-irradiation induction chemotherapy in decreasing the field and dose of radiation therapy (RT) needed for cure.

Fiber Type-Specific Proteomic Alterations in R349P Desminopathy Mice.

Introduction/aims: Desminopathies are a group of rare human myopathies and cardiomyopathies caused by pathogenic variants of the desmin gene. Here, we analyzed the effects of the R349P mutant desmin on the proteomic profiles of individual fiber types of murine skeletal muscle.

Methods: Soleus and tibialis anterior muscles from hetero- and homozygous R349P desmin knock-in mice and wild-type siblings were used to collect fiber type-specific material by laser microdissection to determine their proteomic profiles.

The association between postoperative photon radiotherapy dose and disease control and salvage treatment in pediatric and adolescent ependymoma: a multi-institutional investigation.

Purpose: We characterized the association between photon radiation dose (< 59.4 versus ≥ 59.4 Gy) and outcomes in intracranial ependymoma.

Oral supplementation with propionate is reflected in the serum of healthy individuals.

Background: Short-chain fatty acids (SCFAs), including propionic acid (PA), are key in immunological research. Supplementing PA has shown benefits for autoimmune diseases. A comprehensive understanding of the PA pharmacokinetics is essential for the optimal design and execution of studies utilizing orally administered PA.

The Protective Effect of Docosahexaenoic Acid on Mitochondria in SH-SY5Y Model of Rotenone-Induced Toxicity.

Polyunsaturated fatty acids in particular omega-3 fatty acids, such as docosahexaenoic acid (DHA), are essential nutrients and components of the plasma membrane. They are involved in various processes, including synaptic development, functionality, integrity, and plasticity, and are therefore thought to have general neuroprotective properties. Considerable research evidence further supports the beneficial effects of omega-3 fatty acids, specifically on mitochondria, through their antioxidant and anti-apoptotic properties, making them an attractive addition in treatment options for neurodegenerative disorders in which mitochondrial alterations are commonly observed.

Middle-throughput LC-MS-based Platelet Proteomics with Minute Sample Amounts Using Semiautomated Positive Pressure FASP in 384-Well Format.

Comprehensive characterization of platelets requires various functional assays and analytical techniques, including omics disciplines, each demanding a separate aliquot of the given sample. Consequently, sample material for each assay is often highly limited, necessitating the downscaling of methods to work with just a few micrograms of platelet protein.Here, we present a novel sample preparation platform for proteomics analysis using only 3 μg of purified platelet protein, corresponding to 2 × 10 platelets, which can be obtained from approximately 2 to 8 μL of blood from a healthy individual (1.

Safety and efficacy of intrathecal antibodies to Nogo-A in patients with acute cervical spinal cord injury: a randomised, double-blind, multicentre, placebo-controlled, phase 2b trial.

Background: Spinal cord injury results in permanent neurological impairment and disability due to the absence of spontaneous regeneration. NG101, a recombinant human antibody, neutralises the neurite growth-inhibiting protein Nogo-A, promoting neural repair and motor recovery in animal models of spinal cord injury. We aimed to evaluate the efficacy of intrathecal NG101 on recovery in patients with acute cervical traumatic spinal cord injury.

A Review of Protein Inference.

Protein inference is an often neglected though crucial step in most proteomic experiments. In the bottom-up proteomic approach, the actual molecules of interest, the proteins, are digested into peptides before measurement on a mass spectrometer. This approach introduces a loss of information: The actual proteins must be inferred based on the identified peptides.

Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, and Cost of the Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy Prospective Multi-Institutional Trial.

Purpose: The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost.

Methods And Materials: The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, with rates of anesthesia use and outcomes of serial standardized anxiety and quality-of-life assessments assessed among the 81 children enrolled.

Metabolic Adaptation in Epilepsy: From Acute Response to Chronic Impairment.

Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities.

Correction: Immunogenic Salivary Proteins of Triatoma infestans: Development of a Recombinant Antigen for the Detection of Low-Level Infestation of Triatomines.

[This corrects the article DOI: 10.1371/journal.pntd.

Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?

A hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier.

Optimizing Inspire Hypoglossal Nerve Stimulator Settings in Pediatric Obstructive Sleep Apnea.

Introduction: Hypoglossal nerve stimulation (HGNS) is an effective therapy for carefully selected pediatric patients with Down syndrome (DS) and obstructive sleep apnea (OSA), but optimization of device settings has been focused on stimulation settings. The potential benefits of sensing lead setting optimization have not been investigated. We describe a series of three cases of HGNS in children with DS where optimization of both the stimulation lead and sensing lead settings, as well as utilization of drug-induced sleep endoscopy (DISE), when indicated, was more effective than stimulation lead optimization alone.

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

Background: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields.

Methods: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis.

Safety and Duration of Effect of 40-Unit PrabotulinumtoxinA-xvfs for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients: A Phase II, Multicenter, Randomized, Double-Blind, Active-Controlled Trial.

Background: Extending the duration of effect of botulinum toxins-by administering doses beyond those of the approved labels-has been an area of increasing interest in the field of aesthetics.

Objectives: The aim of this study was to investigate the safety and duration of effect of 40-unit (U) prabotulinumtoxinA-xvfs (twice the approved dose and concentration) for the treatment of moderate-to-severe glabellar lines.

Methods: A total of 154 adult patients were randomized 1:1:1 to a single treatment of either 40 U prabotulinumtoxinA-xvfs (PRA 40, 5 injections of 8 U/0.

Clinical Outcomes Among Patients Treated With Stereotactic Body Radiation Therapy to Femur Metastases for Oligometastatic Disease Control or Reirradiation: Results From a Large Single-Institution Experience.

Purpose: There are limited data regarding outcomes after stereotactic body radiation therapy (SBRT) for femur metastases, which was an exclusion criteria for the Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial. We aimed to characterize clinical outcomes from a large single institution experience.

Methods And Materials: Forty-eight patients with 53 lesions were consecutively treated with femur SBRT from May 2017 to June 2022.

Immortalised murine R349P desmin knock-in myotubes exhibit a reduced proton leak and decreased ADP/ATP translocase levels in purified mitochondria.

Desmin gene mutations cause myopathies and cardiomyopathies. Our previously characterised R349P desminopathy mice, which carry the ortholog of the common human desmin mutation R350P, showed marked alterations in mitochondrial morphology and function in muscle tissue. By isolating skeletal muscle myoblasts from offspring of R349P desminopathy and p53 knock-out mice, we established an immortalised cellular disease model.

Use of Multiple Machine Learning Approaches for Selecting Urothelial Cancer-Specific DNA Methylation Biomarkers in Urine.

Diagnosing urothelial cancer (UCa) via invasive cystoscopy is painful, specifically in men, and can cause infection and bleeding. Because the UCa risk is higher for male patients, urinary non-invasive UCa biomarkers are highly desired to stratify men for invasive cystoscopy. We previously identified multiple DNA methylation sites in urine samples that detect UCa with a high sensitivity and specificity in men.

Effectiveness and Safety of Sculptra Poly-L-Lactic Acid Injectable Implant in the Correction of Cheek Wrinkles.

Background: The current study evaluated the effectiveness and safety of Sculptra injectable poly-L-lactic acid (PLLA-SCA) treatment in correcting cheek wrinkles compared with a no-treatment control.

Methods: Male/female immune-competent adults (aged >21 years) with moderate/severe cheek wrinkles, graded using the Galderma Cheek Wrinkle Scale (GCWS) at rest, were randomized 2:1 to receive PLLA-SCA injections (150 mg; 8 mL reconstitution in sterile water for injection) + 1 mL lidocaine hydrochloride (2%), administered immediately after reconstitution, or no treatment (control). Up to 3 additional treatments were allowed at monthly intervals, and follow-up was at months 7, 9, and 12.

Autoinhibition of a clamp-loader ATPase revealed by deep mutagenesis and cryo-EM.

Clamp loaders are AAA+ ATPases that facilitate high-speed DNA replication. In eukaryotic and bacteriophage clamp loaders, ATP hydrolysis requires interactions between aspartate residues in one protomer, present in conserved 'DEAD-box' motifs, and arginine residues in adjacent protomers. We show that functional defects resulting from a DEAD-box mutation in the T4 bacteriophage clamp loader can be compensated by widely distributed single mutations in the ATPase domain.