Structure-guided design of a peripherally restricted chemogenetic system.

Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remotely controlling cellular signaling, neural activity, behavior, and physiology. Using a structure-guided approach, we provide a peripherally restricted Gi-DREADD, hydroxycarboxylic acid receptor DREADD (HCAD), whose native receptor is minimally expressed in the brain, and a chemical actuator that does not cross the blood-brain barrier (BBB). This was accomplished by combined mutagenesis, analoging via an ultra-large make-on-demand library, structural determination of the designed DREADD receptor via cryoelectron microscopy (cryo-EM), and validation of HCAD function.

Advancing dermoscopy through a synthetic hair benchmark dataset and deep learning-based hair removal.

Significance: Early detection of melanoma is crucial for improving patient outcomes, and dermoscopy is a critical tool for this purpose. However, hair presence in dermoscopic images can obscure important features, complicating the diagnostic process. Enhancing image clarity by removing hair without compromising lesion integrity can significantly aid dermatologists in accurate melanoma detection.

Artificial Intelligence for Clinical Management of Male Infertility, a Scoping Review.

Purpose Of Review: Infertility impacts one in six couples worldwide, with male infertility contributing to approximately half of these cases. However, the causes of infertility remain incompletely understood, and current methods of clinical management are cost-restrictive, time-intensive, and have limited success. Artificial intelligence (AI) may help address some of these challenges.

Polarization modulated spectroscopic ellipsometry-based surface plasmon resonance biosensor for E. coli K12 detection.

In this work, we report on the application of the polarization modulated spectroscopic ellipsometry-based surface plasmon resonance method for sensitive detection of microorganisms in Kretschmann configuration. So far, rotating analyzer and single wavelength polarization modulation methods have widely been investigated for phase sensitive surface plasmon resonance measurement. In this study, a much simpler optical setup relying on fast electro-optic phase modulator crystals is introduced for bacteria detection.

Blood flow restriction increases motor unit firing rates and input excitation of the biceps brachii during a moderate-load muscle action.

This study examined the effects of blood flow restriction (BFR) on motor unit (MU) behaviour of the biceps brachii (BB) during a single non-exhausting submaximal muscle action. Twenty adults performed maximal voluntary contractions (MVCs) of the elbow flexors, followed by an isometric trapezoidal muscle action at 40% MVC during BFR and control (CON) visits. Surface electromyographic signals recorded from the BB during the 40% MVCs were decomposed.

Integrating generative AI with ABCDE rule analysis for enhanced skin cancer diagnosis, dermatologist training and patient education.

Significance: The early detection and accurate monitoring of suspicious skin lesions are critical for effective dermatological diagnosis and treatment, particularly for reliable identification of the progression of nevi to melanoma. The traditional diagnostic framework, the ABCDE rule, provides a foundation for evaluating lesion characteristics by visual examination using dermoscopes. Simulations of skin lesion progression could improve the understanding of melanoma growth patterns.

The role of preoperative immunonutrition on morbidity and immune response after cystectomy: protocol of a multicenter randomized controlled trial (INCyst Trial).

Introduction: Cancer, malnutrition, and surgery negatively impact patient's immune system. Despite standardized surgical technique and the development of new perioperative care protocols, morbidity after cystectomy remains a serious challenge for urologists. Most common postoperative complications, such as infections and ileus, often lead to longer length of stay and worse survival.

UROPOT: study protocol for a randomized, double-blind phase I/II trial for metabolism-based potentiation of antimicrobial prophylaxis in the urological tract.

Background: Urinary tract catheters, including Double-J or ureteral stents, are prone to bacterial colonization forming biofilms and leading to asymptomatic bacteriuria. In the context of asymptomatic bacteriuria, endourological procedures causing mucosa-inducing lesions can lead to severe infections. Antibiotic prophylaxis is warranted, yet its efficacy is limited by biofilm formation on stents.

Converse Flexoelectricity in van der Waals (vdW) Three-Dimensional Topological Insulator Nanoflakes.

Low-dimensional van der Waals (vdW) three-dimensional (3D) topological insulators (TIs) have been overlooked, regarding their electromechanical properties. In this study, we experimentally investigate the electromechanical coupling of low-dimensional 3D TIs with a centrosymmetric crystal structure, where a binary compound, bismuth selenide (BiSe), is taken as an example. Piezoresponse force microscopy (PFM) results of BiSe nanoflakes show that the material exhibits both out-of-plane and in-plane electromechanical responses.

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review.

Purpose: Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols.

Methods: A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted.

A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state.

Many neurotransmitter receptors activate G proteins through exchange of GDP for GTP. The intermediate nucleotide-free state has eluded characterization, due largely to its inherent instability. Here we characterize a G protein variant associated with a rare neurological disorder in humans.

Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism.

Xylazine is in the unregulated drug supply at increasing rates, usually combined with fentanyl, necessitating understanding of its pharmacology. Despite commentary from politicians, and public health officials, it is unknown how xylazine impacts naloxone efficacy, and. few studies have examined it alone.

Okinawa-Based Nordic Diet Decreases Plasma Levels of IAPP and IgA against IAPP Oligomers in Type 2 Diabetes Patients.

Pancreas-derived islet amyloid polypeptide (IAPP) aggregates and deposits in the pancreas and periphery of Type 2 Diabetes (T2D) patients, contributing to diabetic complications. The excess IAPP can be removed by autoantibodies, and increased levels of immunoglobulin (Ig) G against IAPP have been reported in T2D patients. However, whether other Ig classes are also affected and if the levels can be managed is less known.

Risk Factors of Asymptomatic Kidney Stone Passage in Adults with Recurrent Kidney Stones.

Key Points: Asymptomatic stone passage was common in patients with recurrent calcium-containing kidney stones. Higher the number of stones at presentation, more likely it was that a kidney stone would spontaneously pass over time without causing any symptoms.

Background: Kidney stones are a common health problem and are characterized by a high risk of recurrence.

Fabrication of a low-cost benchtop optical imager for quantum dot microarray-based stress biomarker detection.

We report on a simplified optical imager to detect the presence of a stress biomarker protein, namely the Heat shock protein 90 (Hsp90). The imager consists of two elements the optical unit and the sensor, which is a custom-made biochip. Measurement is based on the masking of the streptavidin conjugated quantum dot's (Sav-QDs) fluorescence when Hsp90 attaches to it via biotinylated antibodies (Ab).

A proximity proteomics pipeline with improved reproducibility and throughput.

Proximity labeling (PL) via biotinylation coupled with mass spectrometry (MS) captures spatial proteomes in cells. Large-scale processing requires a workflow minimizing hands-on time and enhancing quantitative reproducibility. We introduced a scalable PL pipeline integrating automated enrichment of biotinylated proteins in a 96-well plate format.