Partial AUCs in Long-Acting Injectables: Rationale, Challenges, Variability, Usefulness, and Clinical Relevance.

Regulatory authorities typically require bioequivalence to be demonstrated by comparing pharmacokinetic parameters like area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C). Because in certain cases, AUC and C alone may not be adequate to identify formulation differences in early and/or late segments of the dosing interval, partial AUCs (pAUCs) have been proposed as additional metrics to evaluate bioequivalence. Even though cut-off points for pAUCs are usually decided based on clinical relevance, the identification of the correct cut-off range remains elusive in many other cases and tends to contribute to increased pAUC estimate variabilities.

High-throughput determination of exchange rates of unmodified and PTM-containing peptides using HX-MS.

Despite the widespread use of MS for hydrogen/deuterium exchange measurements, no systematic, large-scale study has been conducted to compare the observed exchange rates in protein-derived, unstructured peptides measured by MS to the predicted exchange rates calculated from NMR-derived values and how neighboring residues and post-translational modifications influence those exchange rates. In this study, we sought to test the accuracy of predicted values by performing hydrogen exchange measurements on whole cell digests to generate an unbiased dataset of 563 unique peptides derived from naturally-occurring protein sequences. A remarkable 97% of observed exchange rates of peptides are within two-fold of predicted values.

Sex Estimation Through Orbital Measurements: A Machine Learning Approach for Forensic Science.

Background: Sex estimation has been extensively investigated due to its importance for forensic science. Several anatomical structures of the human body have been used for this process. The human skull has important landmarks that can serve as reliable sex estimation predictors.

Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank.

Bone marrow adipose tissue is a distinct adipose subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates of this tissue are unclear, and its genetic determinants remain unknown. Here, we use deep learning to measure bone marrow adiposity in the femoral head, total hip, femoral diaphysis, and spine from MRI scans of approximately 47,000 UK Biobank participants, including over 41,000 white and over 6300 non-white participants.

A hybrid encryption framework leveraging quantum and classical cryptography for secure transmission of medical images in IoT-based telemedicine networks.

In the era of the Internet of Things (IoT), the transmission of medical reports in the form of scan images for collaborative diagnosis is vital for any telemedicine network. In this context, ensuring secure transmission and communication is necessary to protect medical data to maintain privacy. To address such privacy concerns and secure medical images against cyberattacks, this research presents a robust hybrid encryption framework that integrates quantum, and classical cryptographic methods.

Chemical perturbations impacting histone acetylation govern colorectal cancer differentiation.

Dysregulated epigenetic programs that restrict differentiation, reactivate fetal genes, and confer phenotypic plasticity are critical to colorectal cancer (CRC) development. By screening a small molecule library targeting epigenetic regulators using our dual reporter system, we found that inhibiting histone deacetylase (HDAC) 1/2 promotes CRC differentiation and anti-tumor activity. Comprehensive biochemical, chemical, and genetic experiments revealed that on-target blockade of the HDAC1/2 catalytic domain mediated the differentiated phenotype.

Disrupted uromodulin trafficking is rescued by targeting TMED cargo receptors.

The trafficking dynamics of uromodulin (UMOD), the most abundant protein in human urine, play a critical role in the pathogenesis of kidney disease. Monoallelic mutations in the UMOD gene cause autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), an incurable genetic disorder that leads to kidney failure. The disease is caused by the intracellular entrapment of mutant UMOD in kidney epithelial cells, but the precise mechanisms mediating disrupted UMOD trafficking remain elusive.

Deep learning for cardiac imaging: focus on myocardial diseases, a narrative review.

The integration of computational technologies into cardiology has significantly advanced the diagnosis and management of cardiovascular diseases. Computational cardiology, particularly, through cardiovascular imaging and informatics, enables a precise diagnosis of myocardial diseases utilizing techniques such as echocardiography, cardiac magnetic resonance imaging, and computed tomography. Early-stage disease classification, especially in asymptomatic patients, benefits from these advancements, potentially altering disease progression and improving patient outcomes.

SmartHypnos: An Android application for low-cost sleep self-monitoring and personalized recommendation generation.

Background And Objective: Sleep is an essential biological function that is critical for a healthy and fulfilling life. Available sleep quality assessment tools contain long questionnaires covering a long period of time, not taking into account daily physical activity patterns and individual lifestyles.

Methods: In this paper we present SmartHypnos, an Android application that supports low-end devices.

A convolutional attention model for predicting response to chemo-immunotherapy from ultrasound elastography in mouse tumor models.

Background: In the era of personalized cancer treatment, understanding the intrinsic heterogeneity of tumors is crucial. Despite some patients responding favorably to a particular treatment, others may not benefit, leading to the varied efficacy observed in standard therapies. This study focuses on the prediction of tumor response to chemo-immunotherapy, exploring the potential of tumor mechanics and medical imaging as predictive biomarkers.

Identifying mitigating strategies for endothelial cell dysfunction and hypertension in response to VEGF receptor inhibitors.

Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer survival but are associated with treatment-limiting hypertension, often attributed to endothelial cell (EC) dysfunction. Using phosphoproteomic profiling of VEGFRi-treated ECs, drugs were screened for mitigators of VEGFRi-induced EC dysfunction and validated in primary aortic ECs, mice, and canine cancer patients. VEGFRi treatment significantly raised systolic blood pressure (SBP) and increased markers of endothelial and renal dysfunction in mice and canine cancer patients.

Successful weaning from parenteral nutrition in a short bowel syndrome patient with high-output stoma through restricted oral diet: a case report.

A restricted oral diet plays a significant role in the nutritional management of patients with Short Bowel Syndrome (SBS). SBS patients often experience increased intestinal output, especially if they are classified as net "secretors" (typically having less than 100 cm of residual jejunum). This means they lose more water and sodium from their stoma than they take in by mouth.

Can generative AI replace immunofluorescent staining processes? A comparison study of synthetically generated cellpainting images from brightfield.

Cell imaging assays utilising fluorescence stains are essential for observing sub-cellular organelles and their responses to perturbations. Immunofluorescent staining process is routinely in labs, however the recent innovations in generative AI is challenging the idea of wet lab immunofluorescence (IF) staining. This is especially true when the availability and cost of specific fluorescence dyes is a problem to some labs.

Clinical Impact of C-myc Oncogenic Diversity on Solid and Lymphoid Malignancies.

Introduction: Onset and progression of malignant tumors is a multistep process including a variety of gross chromosomal and specific genes' deregulation. Among oncogenes that are frequently altered in solid and also in hematological malignancies, the C-myc (gene locus: 8q24.21) plays a pivotal role.

Gender diversity in the National Joint Registry.

Aims: Our primary aim was to establish the proportion of female orthopaedic consultants who perform arthroplasty via cases submitted to the National Joint Registry (NJR), which covers England, Wales, Northern Ireland, the Isle of Man, and Guernsey. Secondary aims included comparing time since specialist registration, private practice participation, and number of hospitals worked in between male and female surgeons.

Methods: Publicly available data from the NJR was extracted on the types of arthroplasty performed by each surgeon, and the number of procedures of each type undertaken.

Cardiac magnetic resonance for ventricular arrhythmias: a systematic review and meta-analysis.

Background: Cardiac magnetic resonance (CMR) allows comprehensive myocardial tissue characterisation, revealing areas of myocardial inflammation or fibrosis that may predispose to ventricular arrhythmias (VAs). With this study, we aimed to estimate the prevalence of structural heart disease (SHD) and decipher the prognostic implications of CMR in selected patients presenting with significant VAs.

Methods: Electronic databases were searched for studies enrolling adult patients that underwent CMR for diagnostic or prognostic purposes in the setting of significant VAs.

Overview of Small Molecules as Fluorescent Probes of .

Tuberculosis (TB) remains one of the leading infectious causes of death worldwide. Detecting and precisely quantifying viable () is crucial for comprehending mycobacterial pathogenicity; the progression and outcomes of tuberculosis; and the action, efficacy, and resistance of drugs. Fluorescent probes have emerged as indispensable tools for studying the intricate structure and dynamic interactions of with its host environment.

Treatment Adherence and Health Status of Patients With COPD Under Treatment With Salmeterol/Fluticasone via the Elpenhaler® Device: The AHEAD Study.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous progressive lung condition characterized by long-term respiratory symptoms and airflow limitation. Appropriate bronchodilation is the cornerstone of COPD treatment, leading to better health status as well as benefits in prognosis and mortality.

Methods: In the current open, noninterventional, observational study, 716 patients diagnosed with COPD of variable severity were administered a fixed-dose combination (FDC) of fluticasone propionate and salmeterol (500 + 50 mcg) through the Elpenhaler® device.

Sparing the Hippocampus in Prophylactic Cranial Irradiation Using Three Different Linear Accelerators: A Comparative Study.

Hippocampus protection, as an organ at risk in brain radiotherapy, might protect patients' quality of life. Prophylactic cranial irradiation (PCI) has been used traditionally in small cell lung cancer (SCLC) patients as it increases survival. This study aimed to discover the contributing parameters for a successful PCI with simultaneous protection of the hippocampus by using three different treatment machines.

Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3.

KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain.

An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.

Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their association and function in gene regulation. More recently, IDRs have been shown to promote multivalent protein-protein interactions between coregulators and TFs to drive their association into condensates. By contrast, here we demonstrate how the IDR of the corepressor LSD1 excludes TF association, acting as a dynamic conformational switch that tunes repression of active cis-regulatory elements.

Effects of fluid composition in fluid injection experiments in porous media.

Experiments on fluid flow in porous media, using fluids loaded with solids of various grain sizes, have been conducted in a modified Hele-Shaw setup. This setup utilised weakly cemented porous media with specific hydraulic and mechanical properties. Fluid injection in coarse granular media with clean or low-concentration fine particles, results in infiltration only, with pressure close to the material tensile strength, while injection in finer granular material causes damage alongside infiltration, with the fluid pressure still close to the material tensile strength.