Trochleoplasty Utilization in the Management of Patellofemoral Instability: Results From an International Survey of Surgeons.

Background: Considerable variability exists in the described clinical and radiographic indications for use, surgical techniques, postoperative management, and risk profile after trochleoplasty for the management of patellofemoral instability (PFI). In areas of clinical uncertainty, a cohesive summary of expert opinion and identification of areas of variation in current practice can be useful in guiding current practice and future research efforts.

Purpose: To assess the current indications for use, surgical techniques, postoperative rehabilitation practices, and observed complication profile for trochleoplasty in the management of PFI among surgeons who perform this procedure.

High clinical utility of long-read sequencing for precise diagnosis of congenital adrenal hyperplasia in 322 probands.

Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.

Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.

Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.

Background: BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.

Objective: The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.

Differentially Expressed Nedd4-binding Protein Ndfip1 Protects Neurons Against Methamphetamine-induced Neurotoxicity.

To identify factors involved in methamphetamine (METH) neurotoxicity, we comprehensively searched for genes which were differentially expressed in mouse striatum after METH administration using differential display (DD) reverse transcription-PCR method and sequent single-strand conformation polymorphism analysis, and found two DD cDNA fragments later identified as mRNA of Nedd4 (neural precursor cell expressed developmentally downregulated 4) WW domain-binding protein 5 (N4WBP5), later named Nedd4 family-interacting protein 1 (Ndfip1). It is an adaptor protein for the binding between Nedd4 of ubiquitin ligase (E3) and target substrate protein for ubiquitination. Northern blot analysis confirmed drastic increases in Ndfip1 mRNA in the striatum after METH injections, and in situ hybridization histochemistry showed that the mRNA expression was increased in the hippocampus and cerebellum at 2 h-2 days, in the cerebral cortex and striatum at 18 h-2 days after single METH administration.

The Value of Multidisciplinary Neuro-oncological Tumor Boards to Increase the Accuracy of FET PET for Identifying Brain Tumor Relapse.

Purpose: Especially in Europe, amino acid PET is increasingly integrated into multidisciplinary neuro-oncological tumor boards (MNTBs) to overcome diagnostic uncertainties such as treatment-related changes. We evaluated the accuracy of MNTB decisions that included the O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET information compared with FET PET results alone to differentiate tumor relapse from treatment-related changes.

Patients And Methods: In a single academic center, we retrospectively evaluated 180 MNTB decisions of 151 patients with CNS WHO grade 3 or 4 gliomas (n = 122) or brain metastases (n = 29) presenting equivocal MRI findings following anticancer treatment.

Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.

Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.

AI generated synthetic STIR of the lumbar spine from T1 and T2 MRI sequences trained with open-source algorithms.

Background And Purpose: To train and evaluate an open-source generative adversarial networks (GANs) to create synthetic lumbar spine MRI STIR volumes from T1 and T2 sequences, providing a proof-of-concept that could allow for faster MRI examinations.

Materials And Methods: 1817 MRI examinations with sagittal T1, T2, and STIR sequences were accumulated and randomly divided into training, validation, and test sets. GANs were trained to create synthetic STIR volumes using the T1 and T2 volumes as inputs, optimized using the validation set, then applied to the test set.

Peritumoral Hyperintense Signal on Post-contrast FLAIR Images Surrounding Vestibular Schwannomas Following Stereotactic Radiosurgery.

Background And Purpose: Prior investigations have noted the presence of peritumoral hyperintense signal (a "halo") around vestibular schwannomas on postcontrast 3D T2 FLAIR images. This study evaluated this phenomenon in a cohort of patients undergoing stereotactic radiosurgery.

Materials And Methods: A retrospective review was completed of consecutive patients with presumed vestibular schwannomas undergoing stereotactic radiosurgery.

ADAMTS4-Specific MR Peptide Probe for the Assessment of Atherosclerotic Plaque Burden in a Mouse Model.

Introduction: Atherosclerosis is the underlying cause of multiple cardiovascular pathologies. The present-day clinical imaging modalities do not offer sufficient information on plaque composition or rupture risk. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is a strongly upregulated proteoglycan-cleaving enzyme that is specific to cardiovascular diseases, inter alia, atherosclerosis.

Unveiling patterns in spatial transcriptomics data: a novel approach utilizing graph attention autoencoder and multiscale deep subspace clustering network.

Background: The accurate deciphering of spatial domains, along with the identification of differentially expressed genes and the inference of cellular trajectory based on spatial transcriptomic (ST) data, holds significant potential for enhancing our understanding of tissue organization and biological functions. However, most of spatial clustering methods can neither decipher complex structures in ST data nor entirely employ features embedded in different layers.

Results: This article introduces STMSGAL, a novel framework for analyzing ST data by incorporating graph attention autoencoder and multiscale deep subspace clustering.

Multimodality Imaging Evaluation of Diseases of the Pulmonic Valve and Right Ventricular Outflow Tract for the Adult Cardiologist.

Disorders of the pulmonic valve (PV) receive considerably less attention than other forms of valvular heart disease. Due to the dramatically improved survival of children with congenital heart disease over the last 5 decades, there has been a steady increase in the prevalence of adults with congenital heart disease, which necessitates that clinicians become familiar with the anatomy and the evaluation of right ventricular outflow tract and PV anomalies. A multimodality imaging approach using echocardiography, cardiac computed tomography, and magnetic resonance imaging is essential for a comprehensive evaluation of the anatomy and function of the right ventricular outflow tract, PV, and supravalvular region.

Association of Pre- and Postinjury Mental Health With Long-term Clinical and Financial Outcomes.

Background: As increased attention is placed on optimizing long-term outcomes of trauma patients by addressing mental health, little is known regarding the interplay of pre- and postinjury mental health on long-term financial and functional outcomes.

Methods: Patients from 19 Level 1 and 2 trauma centers took part in serial surveys 1 to 24 months postdischarge. Preinjury mental health diagnoses were identified using trauma registry data and postinjury mental health symptoms from survey data.

Improving Understanding of Fexofenadine Pharmacokinetics to Assess Pgp Phenotypic Activity in Older Adult Patients Using Population Pharmacokinetic Modeling.

Background And Objective: Fexofenadine is commonly used as a probe substrate to assess P-glycoprotein (Pgp) activity. While its use in healthy volunteers is well documented, data in older adult and polymorbid patients are lacking. Age- and disease-related physiological changes are expected to affect the pharmacokinetics of fexofenadine.

Monitoring Excavation-Induced Deformation of a Secant Pile Wall Using Distributed Fiber Optic Sensors.

This paper investigates the use of the BOTDA (Brillouin Optical Time-Domain Analysis) technology to monitor a large-scale bored pile wall in the field. Distributed fiber optic sensors (DFOSs) were deployed to measure internal temperature and strain changes during cement grouting, hardening, and excavation-induced deformation of a secant pile wall. The study details the geological conditions and DFOS installation process.

Digital Health Technologies for Optimising Treatment and Rehabilitation Following Surgery: Device-Based Measurement of Sling Posture and Adherence.

Background: Following shoulder surgery, controlled and protected mobilisation for an appropriate duration is crucial for appropriate recovery. However, methods for objective assessment of sling wear and use in everyday living are currently lacking. In this pilot study, we aim to determine if a sling-embedded triaxial accelerometer and/or wrist-worn sensor can be used to quantify arm posture during sling wear and adherence to sling wear.

Machine Learning and Computed Tomography Radiomics to Predict Disease Progression to Upfront Pembrolizumab Monotherapy in Advanced Non-Small-Cell Lung Cancer: A Pilot Study.

Background/objectives: Pembrolizumab monotherapy is approved in Canada for first-line treatment of advanced NSCLC with PD-L1 ≥ 50% and no EGFR/ALK aberrations. However, approximately 55% of these patients do not respond to pembrolizumab, underscoring the need for the early intervention of non-responders to optimize treatment strategies. Distinguishing the 55% sub-cohort prior to treatment is a real-world dilemma.

Components of the Endosome-Lysosome Vesicular Machinery as Drivers of the Metastatic Cascade in Prostate Cancer.

Prostate cancer remains a significant global health concern, with over 1.4 million new cases diagnosed and more than 330,000 deaths each year. The primary clinical challenge that contributes to poor patient outcomes involves the failure to accurately predict and treat at the onset of metastasis, which remains an incurable stage of the disease.

An Overview of Zika Virus and Zika Virus Induced Neuropathies.

Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms.

Defecation Site Preferences and Spatial Ecological Segregation of Forest Musk Deer and Siberian Roe Deer in North China.

The forest musk deer () and Siberian roe deer () are browsers with a broad sympatric distribution in North and Southwest China. However, little is known about their spatial utilization of microhabitats and habitats. This study, conducted on Huanglong Mountain in China, analyzed the defecation site distribution, indicating preferences of forest musk deer and Siberian roe deer for their habitat demands.

Integrated analysis of miRNAs and mRNAs in thousands of single cells.

The simultaneous sequencing of multiple types of biomolecules can facilitate understanding various forms of regulation occurring in cells. Cosequencing of miRNA and mRNA at single-cell resolution is challenging, and to date, only a few such studies (examining a quite limited number of cells) have been reported. Here, we developed a parallel single-cell small RNA and mRNA coprofiling method (PSCSR-seq V2) that enables miRNA and mRNA coexpression analysis in many cells.

Fusion of FDG and FMZ PET Reduces False Positive in Predicting Epileptogenic Zone.

Background And Purpose: Epilepsy, a globally prevalent neurological disorder, necessitates precise identification of the epileptogenic zone (EZ) for effective surgical management. While the individual utilities of FDG PET and FMZ PET have been demonstrated, their combined efficacy in localizing the epileptogenic zone remains underexplored. We aim to improve the non-invasive prediction of epileptogenic zone (EZ) in temporal lobe epilepsy (TLE) by combining FDG PET and FMZ PET with statistical feature extraction and machine learning.

Tissue concepts: Supervised foundation models in computational pathology.

Due to the increasing workload of pathologists, the need for automation to support diagnostic tasks and quantitative biomarker evaluation is becoming more and more apparent. Foundation models have the potential to improve generalizability within and across centers and serve as starting points for data efficient development of specialized yet robust AI models. However, the training of foundation models themselves is usually very expensive in terms of data, computation, and time.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.