Single-cell RNA flow cytometry to assess intratumoral production of cytokines/chemokines.

The tumor microenvironment (TME) consists of complex interactions between cellular and extracellular components, among which the immune system is known to play an integral role in disease progression and response to therapy. Cytokines and chemokines are cell signaling proteins used by immune cells to communicate with each other as well as with other cell types in the body. These proteins control systemic and local immune responses and levels of cytokines/chemokines in the TME have been associated with tumor outcomes.

Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials And Methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

MnSOD non-acetylation mimic knock-in mice exhibit dilated cardiomyopathy.

Manganese superoxide dismutase (MnSOD/SOD2) is an essential mitochondrial enzyme that detoxifies superoxide radicals generated during oxidative respiration. MnSOD/SOD2 lysine 68 acetylation (K68-Ac) is an important post-translational modification (PTM) that regulates enzymatic activity, responding to nutrient status or oxidative stress, and elevated levels have been associated with human illness. To determine the in vivo role of MnSOD-K68 in the heart, we used a whole-body non-acetylation mimic mutant (MnSOD) knock-in mouse.

Super-resolution microscopy as drug discovery tool.

At the turn of the century a fundamental resolution barrier in fluorescence microscopy known as the diffraction limit was broken, giving rise to the field of super-resolution microscopy. Subsequent nanoscopic investigation with visible light revolutionised our understanding of how previously unknown molecular features give rise to the emergent behaviour of cells. It transpires that the devil is in these fine molecular details, and essential nanoscale processes were found everywhere researchers chose to look.

Biosorption of rhodamine B and sunset yellow dyes on cross-linked chitosan-alginate biocomposite beads: Experimental and theoretical studies.

This research explores the biosorption of Rhodamine B (Rd-B) and Sunset Yellow (SY) dyes using cross-linked chitosan-alginate (Ch-A) biocomposite beads, combining experimental investigations with theoretical studies to elucidate the biosorption mechanisms. The biocomposite beads were synthesized through an eco-friendly cross-linking method, and their structural properties were characterized using various characterization techniques. Complementary theoretical studies using Monte Carlo (MC) simulations and molecular dynamics (MD) calculations provided insights into the molecular interactions between the dyes and the biocomposite beads.

Role of the International Society of Liquid Biopsy (ISLB) in establishing quality control frameworks for clinical integration.

Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, widespread adoption is hindered by a lack of standardized protocols, requiring robust quality control and harmonized workflows. Large-scale studies are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) assays tailored to different disease stages.

Survival outcomes comparing minimally invasive versus open cytoreductive surgery in recurrent adult-type granulosa cell tumors.

Background: Adult-type granulosa cell tumors are a rare form of ovarian cancer, 30% of which will recur. Cytoreductive surgery is often performed at the time of a first recurrence, but little is known about the impact of open versus minimally invasive surgical approaches on survival outcomes.

Objective: To examine associations between surgical approach, clinical variables, and survival outcomes among patients with adult-type granulosa cell tumors who underwent cytoreductive surgery at the time of first recurrence.

Assessing Surgical Competency Among Fellows in Vitreoretinal Surgery: A Survey of Fellowship Program Directors and Fellows.

Purpose: We surveyed vitreoretinal (VR) fellowship program directors (PDs) to elucidate how they assess surgical competency among VR fellows. In addition, we also surveyed fellowship program graduates for the years 2022 and 2023 regarding assessment metrics and tools used during VR fellowship training.

Design: Web-based, cross-sectional descriptive study.

Retinal structural alterations in patients with epilepsy taking antiepileptic drugs: A systematic review and meta-analysis of OCT findings.

The impact of various neurodegenerative diseases on the retina has been investigated in recent years using optical coherence tomography (OCT). Epilepsy, classified as a neurodegenerative disorder, has been indicated to affect the structural integrity of the retina. Moreover, there is ongoing debate regarding the relative contribution of disease pathogenesis and the consumption of anti-epileptic drugs (AEDs) to these retinal changes.

Immunogenicity and safety of a monovalent omicron XBB.1.5 SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose in US adults: interim analysis of a single-arm phase 2/3 study.

Background: Authorities globally recommended a monovalent omicron XBB.1.5-based COVID-19 vaccine for the 2023-24 season.

Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.

Synergistic suppression of cell growth: Phenmiazine derivatives targeting p53 and MDM2 unveiled through hybrid computational method.

Lung cancer is the leading cause of mortality in both men and women due to genetic and epigenetic modifications. Our study focuses on fabricating phenmiazine ring leads by a functional group-based drug design to inhibit p53 -7A1W and MDM2-7AU9 proteins responsible for cancer cell growth. One hundred molecules are designed and allowed to bind inside the active site of 7A1W and 7AU9 protein using a glide dock platform and subjected to find MMGBSA.

Forest restoration improves habitat and water quality in tropical streams: A multiscale landscape assessment.

Forest restoration has been a common practice to safeguard water quality and stream health but it is unclear to which extent and pace forest restoration recovers stream ecosystem structure and functions. Also, stream health might be affected by the forest restoration type and the quality of the interventions. Here, we sought to evaluate the recovery of stream habitat and water quality through forest restoration in catchments dominated by pasturelands, and explored the relationship between landscape structure and stream ecosystem recovery.

Protecting monoclonal antibodies via competitive interfacial adsorption of nonionic surfactants.

Hypothesis: Bioengineered monoclonal antibodies (mAbs) have gained significant recognition as medical therapies. However, during processing, storage and use, mAbs are susceptible to interfacial adsorption and desorption, leading to structural deformation and aggregation, and undermining their bioactivity. To suppress antibody surface adsorption, nonionic surfactants are commonly used in formulation.

Microfluidics-enabled core/shell nanostructure assembly: Understanding encapsulation processes via particle characterization and molecular dynamics.

In the realm of hybrid nanomaterials, the construction of core/shell nanoparticles offer an effective strategy for encompassing a particle by a polymeric or other suitable material, leading to a nanocomposite with distinct features within its structure. The polymer shell can be formed via nanoprecipitation, optimized by manipulating fluid flow, fluid mixing, modulating device features in microfluidics. In addition to the process optimization, success of polymer assembly in encapsulation strongly lies upon the favorable molecular interactions originating from the diverse chemical environment shared between core and shell materials facilitating formation of core/shell nanostructure.

Catching the glucocorticoid receptor in the act: Lessons from fluorescence fluctuation methods.

Technological innovation can drive scientific inquiry by allowing researchers to answer questions that were once out of reach. Eukaryotic mRNA synthesis was not so long ago thought of as a deterministic, sequential process in which transcriptional regulators and general transcription factors assemble in an orderly fashion into chromatin to, ultimately, activate RNA polymerase II. Advances in fluorescence microscopy techniques have revealed a much more complex scenario, wherein transcriptional regulators dynamically engage with chromatin in a more stochastic, probabilistic way.

Association of experienced stigma in healthcare settings with health outcomes among Black women living with HIV: Mediating roles of internalized stigma, anticipated stigma, and trust in HIV care.

Background: Black women living with HIV (WLHIV) often have suboptimal ART adherence due to a multitude of social and structural barriers, including HIV-related stigma. Trust in healthcare providers plays a significant role in adhering to ART and is likely lower among Black WLHIV compared to their White counterparts. This study examined the relationship between experienced stigma in healthcare settings and ART adherence and viral suppression through anticipated stigma in healthcare settings, internalized stigma, and medical mistrust.

Vitamin D-related genetic variants and prostate cancer risk in Black men.

Background: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. Black men, however, have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine critical genes in the vitamin D pathway and prostate cancer risk in Black men.

Guidelines to minimize risk when dry needling the rectus capitus posterior major muscle.

Background: Headache disorders are prevalent often leading to disability. The rectus capitus posterior major muscle (RCPMaj) may contribute to headache symptoms via nociceptive convergence and myodural bridging.

Objectives: To establish guidelines for needle length and needle angle to mitigate risks during dry needling RCPMaj.

Exploring Dynamics and Intermolecular Interactions in Binary Mixtures of Reline and DMSO: An Investigation Using Nuclear Magnetic Resonance and Infrared Spectroscopic Techniques.

Reline, which is composed of choline chloride and urea in a molar ratio of 1:2, is the first and most extensively studied deep eutectic solvent (DES). In certain applications, reline is blended with organic solvents, dimethyl sulfoxide (DMSO) in most cases, to gain improved properties. Therefore, it is crucial to have a profound understanding of the impact of DMSO on the dynamics and structures of the species in the binary mixtures.