Mechanochemical topological defects in an active nematic.

We propose a reaction-diffusion system that converts topological information of an active nematic into chemical signals. We show that a curvature-activated reaction dipole is sufficient for creating a system that dynamically senses topology by producing a concentration field possessing local extrema coinciding with ±1/2 defects. The enabling term is analogous to polarization charge density seen in dielectric materials.

Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.

Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study.

Phase transition in a kinetic mean-field game model of inertial self-propelled agents.

The framework of mean-field games (MFGs) is used for modeling the collective dynamics of large populations of non-cooperative decision-making agents. We formulate and analyze a kinetic MFG model for an interacting system of non-cooperative motile agents with inertial dynamics and finite-range interactions, where each agent is minimizing a biologically inspired cost function. By analyzing the associated coupled forward-backward in a time system of nonlinear Fokker-Planck and Hamilton-Jacobi-Bellman equations, we obtain conditions for closed-loop linear stability of the spatially homogeneous MFG equilibrium that corresponds to an ordered state with non-zero mean speed.

Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors.

Parkinson's disease is a neurodegenerative condition characterized by slow movement (bradykinesia), tremors, and muscle stiffness. These symptoms occur due to the degeneration of dopamine- producing neurons in the substantia nigra region of the brain, leading to reduced dopamine levels. The development of Parkinson's Disease (PD) involves a combination of genetic and environmental factors.

Targeting erbB Pathways in Breast Cancer: Dual Kinase Inhibition for Brain Metastasis and Prevention of p185HER2/Neu Tumor Development.

Background: Breast cancer predominantly affects women and poses challenges in the treatment of both local and advanced diseases. In a previous study, we reported the effectiveness of ER121, a structurally resolved small compound specifically designed to target human cancers expressing or overexpressing mutant EGFR and HER2.

Purpose: The objective of this study is to assess the efficacy and toxicity of ER121 in metastatic and triple negative breast cancer (TNBC, HER2+) cells and tumor models.

Artificial Intelligence Assisted Surgical Scene Recognition: A Comparative Study Amongst Healthcare Professionals.

Objective: This study aimed to compare the ability of a deep-learning platform (the MACSSwin-T model) with healthcare professionals in detecting cerebral aneurysms from operative videos. Secondly, we aimed to compare the neurosurgical team's ability to detect cerebral aneurysms with and without AI-assistance.

Background: Modern microscopic surgery enables the capture of operative video data on an unforeseen scale.

Skull Base Repair following Resection of Vestibular Schwannoma: A Systematic Review (Part 1: The Retrosigmoid Approach).

 Despite advances in skull-base reconstruction techniques, cerebrospinal fluid (CSF) leaks remain a common complication following retrosigmoid (RS) vestibular schwannoma (VS) surgery. We aimed to review and classify the available strategies used to prevent CSF leaks following RS VS surgery.  A systematic review, including studies of adults undergoing RS VS surgery since 2000, was conducted.

Skull Base Repair following Resection of Vestibular Schwannoma: A Systematic Review (Part 2: The Translabyrinthine Approach).

 Despite advances in skull base reconstruction techniques, cerebrospinal fluid (CSF) leaks remain a relatively common complication after translabyrinthine (TL) vestibular schwannoma (VS) surgery. We conducted a systematic review to synthesize the repair techniques and materials used in TL VS surgery to prevent CSF leaks.  A systematic review of studies published since 2000 reporting techniques to prevent CSF leaks during adult TL VS surgery was conducted.

Nuclear instance segmentation and tracking for preimplantation mouse embryos.

For investigations into fate specification and morphogenesis in time-lapse images of preimplantation embryos, automated 3D instance segmentation and tracking of nuclei are invaluable. Low signal-to-noise ratio, high voxel anisotropy, high nuclear density, and variable nuclear shapes can limit the performance of segmentation methods, while tracking is complicated by cell divisions, low frame rates, and sample movements. Supervised machine learning approaches can radically improve segmentation accuracy and enable easier tracking, but they often require large amounts of annotated 3D data.

Exploring the impact and influence of melanin on frequency-domain near-infrared spectroscopy measurements.

Significance: Near-infrared spectroscopy (NIRS) is a non-invasive optical method that measures changes in hemoglobin concentration and oxygenation. The measured light intensity is susceptible to reduced signal quality due to the presence of melanin.

Aim: We quantify the influence of melanin concentration on NIRS measurements taken with a frequency-domain near-infrared spectroscopy system using 690 and 830 nm.

Cell-specific effects of temporal interference stimulation on cortical function.

Temporal interference (TI) stimulation is a popular non-invasive neurostimulation technique that utilizes the following salient neural behavior: pure sinusoid (generated in off-target brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in target brain regions) does. To understand its effects and mechanisms, we examine responses of different cell types, excitatory pyramidal (Pyr) and inhibitory parvalbumin-expressing (PV) neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation.

Mapping the Clinical Pathway for Patients Undergoing Vestibular Schwannoma Resection.

Background: The introduction of the electronic health record (EHR) has improved the collection and storage of patient information, enhancing clinical communication and academic research. However, EHRs are limited by data quality and the time-consuming task of manual data extraction. This study aimed to use process mapping to help identify critical data entry points within the clinical pathway for patients with vestibular schwannoma (VS) ideal for structured data entry and automated data collection to improve patient care and research.

Omalizumab for management of hypersensitivity reactions to anticancer drugs.

Hypersensitivity reactions to anticancer drugs include treatment-limiting toxicity. Standard drug desensitisation offers temporary tolerance and hence requires repetition. We used omalizumab, an anti-immunoglobulin E antibody, to overcome immediate and delayed hypersensitivity reactions to various anticancer drugs.

Relevance of learning health systems to physiatrists and its synergy with implementation science: A commentary.

As health care attempts to bridge the gap between evidence and practice, the concept of the learning health system (LHS) is becoming increasingly relevant. LHS integrates evidence with health systems data, driving health care quality and outcomes through updates in policy, practice, and care delivery. In addition, LHS research is becoming critically important as there are several initiatives underway to increase research capacity, expertise, and implementation, including attempts to stimulate increasing numbers of LHS researchers.

Emerging Applications of Plant Antimicrobials in the Food Industry.

Food safety is a global concern with significant public health implications. Improper food handling can harbor a wide range of pathogenic organisms. Antimicrobial agents are crucial for controlling microbes and ensuring food safety and human health.

Regulatory landscape and challenges in CAR-T cell therapy development in the US, EU, Japan, and India.

Chimeric Antigen Receptor-T cell (CAR-T) therapy has evolved as a revolutionary cancer treatment modality, offering remarkable clinical responses by harnessing the power of a patient's immune system to target and eliminate cancer cells. However, the development and commercialization of CAR-T cell therapies are accompanied by complex regulatory requirements and challenges. This therapy falls under the regulatory category of advanced therapy medicinal products.

Recent Developments in the Antimicrobial Potential of Some Nitrogenous Heterocycles and their SAR Studies: A Review.

Background: Infection remains a significant global health concern, with millions of new cases and deaths occurring due to infectious diseases. Currently, chemoprophylaxis and chemotherapy are the primary treatments, but side effects and toxicities pose challenges. Pathogenic microorganisms have developed resistance to antimicrobial medications.

Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy.

Development and Validation of Fast and Sensitive RP-HPLC Stability-Indicating Method for Quantification of Piroxicam in Bulk Drug.

A simple, rapid, sensitive, and cost-effective green solvent-assisted reverse-phase high-performance liquid chromatographic technique, coupled with a photodiode array detector, was developed and validated for the estimation of piroxicam (PRXM). The chromatographic separation was achieved by using a C-18 (250 × 4.6) mm, 5-μm stationary phase and a mobile phase consisting of methanol and 0.

Effect of exogenous melatonin implant on post-thaw semen quality of buffalo bulls.

Melatonin is an intracellular antioxidant of sperm membrane that protects the cells from lipid peroxidation. Yet, its role as an antioxidant on semen quality of buffalo bulls is still obscure. The present study was undertaken to assess the effect of exogenous melatonin implant (18 mg/50 kg bodyweight) on post-thaw sperm characteristics, oxidative stress, endocrinological profiles and fertility of buffalo bulls.

Association of electrocardiographic and echocardiographic variables with neurological outcomes after ischemic Stroke.

Background: Cardiac dysfunction is often seen following neurological injury. Data regarding cardiac involvement after ischemic stroke is sparse. We investigated the association of electrocardiographic (ECG) and echocardiographic variables with neurological outcomes after an acute ischemic stroke.

Anti-PD-(L)1 plus BRAF/MEK inhibitors (triplet therapy) after failure of immune checkpoint inhibition and targeted therapy in patients with advanced melanoma.

Background: Effective treatment options are limited for patients with advanced melanoma who have progressed on immune checkpoint inhibitors (ICI) and targeted therapies (TT). Preclinical models support the combination of ICI with TT; however, clinical trials evaluating the efficacy of triplet combinations in first-line setting showed limited advantage compared to TT only.

Methods: We conducted a retrospective, multicenter study, that included patients with advanced melanoma who were treated with BRAF/MEK inhibitors in combination with an anti-PD-(L)1 antibody (triplet therapy) after failure of at least one anti-PD-(L)1-based therapy and one TT in seven major melanoma centers between February 2016 and July 2022.

Molecular Profiling and the Impact of Treatment on Outcomes in Adenoid Cystic Carcinoma Type I and II.

Purpose: Adenoid cystic carcinoma (ACC) is an uncommon salivary gland cancer with no approved therapies available to treat advanced, incurable disease. Recent molecular profiling efforts have identified two important subtypes: the more aggressive ACC-I is characterized by Notch pathway alterations and MYC amplification whereas ACC-II demonstrates a more indolent phenotype and TP63 overexpression.

Experimental Design: This retrospective observational cohort study involved de-identified samples from 438 patients with ACC with tumor samples sent for commercially-available molecular profiling (Caris Life Sciences).

The DCM Project Portal: A direct-to-participant platform of The DCM Research Project.

Study Objective: To develop a digital platform to conduct family-based, dilated cardiomyopathy (DCM) genetic research.

Design: The DCM Project Portal, a direct-to-participant electronic recruitment, consent, and communication tool, was designed using prior experience with traditional enrollment methods and characteristics and feedback of current participants.

Participants: DCM patients (probands) and their family members enrolled from June 7, 2016 to March 15, 2020 at 25 US advanced heart failure programs.