A machine learning approach identifies cellular senescence on transcriptome data of human cells in vitro.

Although cellular senescence has been recognized as a hallmark of aging, it is challenging to detect senescence cells (SnCs) due to their high level of heterogeneity at the molecular level. Machine learning (ML) is likely an ideal approach to address this challenge because of its ability to recognize complex patterns that cannot be characterized by one or a few features, from high-dimensional data. To test this, we evaluated the performance of four ML algorithms including support vector machines (SVM), random forest (RF), decision tree (DT), and Soft Independent Modelling of Class Analogy (SIMCA), in distinguishing SnCs from controls based on bulk RNA sequencing data.

Circadian Disruption in Glaucoma: Causes, Consequences, and Countermeasures.

This review explores the intricate relationship between glaucoma and circadian rhythm disturbances. As a principal organ for photic signal reception and transduction, the eye plays a pivotal role in coordinating the body's circadian rhythms through specialized retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs). These cells are critical in transmitting light signals to the suprachiasmatic nucleus (SCN), the central circadian clock that synchronizes physiological processes to the 24-hour light-dark cycle.

Characterization of gallbladder disease in metachromatic leukodystrophy across the lifespan.

Metachromatic leukodystrophy (MLD) is a progressive demyelinating disorder resulting from the toxic accumulation of sulfatides. The stereotyped neurodegeneration of MLD is well understood, and cases are categorized into subtypes by age at neurologic onset: late infantile (LI), juvenile (J), and adult. The systemic burden of disease, such as gallbladder involvement, however, is less well characterized.

SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.

Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.

Cyclic quantum annealing: searching for deep low-energy states in 5000-qubit spin glass.

Quantum computers promise a qualitative speedup in solving a broad spectrum of practical optimization problems. The latter can be mapped onto the task of finding low-energy states of spin glasses, which is known to be exceedingly difficult. Using D-Wave's 5000-qubit quantum processor, we demonstrate that a recently proposed iterative cyclic quantum annealing algorithm can find deep low-energy states in record time.

The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.

Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G cell-cycle arrest. Ser31 is proximal to the H3.

Unraveling the Growth Dynamics of Rutile SnGeO Using Theory and Experiment.

Rutile GeO and related materials are attracting interest due to their ultrawide band gaps and potential for ambipolar doping in high-power electronic applications. This study examines the growth of rutile SnGeO films through oxygen-plasma-assisted hybrid molecular beam epitaxy (hMBE). The film composition and thickness are evaluated across a range of growth conditions, with the outcomes rationalized by using density functional theory calculations.

Psychosocial Factors Affecting Wellbeing and Sources of Support of Young Adult Cancer Survivors: A Scoping Review.

Background/objectives: To identify and analyze what is known about the psychosocial factors affecting the wellbeing and sources of support of young adult (YA) cancer survivors.

Methods: The search strategy included Neoplasms, young adults, psycho* or emotional well* or mental health. The OVID Medline and CINAHL databases were searched.

Comparing Polymerization Shrinkage Measurement Methods for Universal Shade Flowable Resin-Based Composites.

Universal shade flowable composites have been introduced to mimic tooth structure with reduced color mismatch and reduced chair time and cost. However, the polymerization shrinkage of resin material may lead to sensitivity and restoration failure. The purpose of this study was to compare the polymerization shrinkage of recently introduced universal shade flowable resin-based composites using both wet and dry density methods.

Immune Checkpoint Inhibitor-Associated Celiac Disease: A Retrospective Analysis and Literature Review.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade, which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects.

Teaching therapy decision-making to medical students: a prospective mixed-methods evaluation of a curricular innovation.

Background: Therapy decision-making (TDM) is an essential medical skill. However, teaching therapeutic reasoning poses significant challenges. We present a comprehensive TDM course for medical students and report on student satisfaction with the educational strategies, their perceived importance of various TDM domains, and their self-efficacy in incorporating these elements into clinical decisions.

Enhancement of detoxification of xenobiotic aromatic amine dyes by N-acetyltransferase 1 (NAT1) enzyme on human keratinocytes cells through structural modification.

The metabolic conversion of aromatic amines to N-acetylated forms in skin and keratinocytes depends on N-acetyltransferase-1 (NAT1). Common hair color ingredient such as para-phenylenediamine (PPD) causes allergic contact dermatitis. We explored how different electronic substituents on PPD aided NAT1 enzyme biotransform oxidative arylamine (AA) compounds G1-G13 by N-acetylation, NAT-1 activity assays, metabolism, and in vitro clearance investigations in human keratinocytes, while identifying NAT-1 protein levels by Western blot and qRT-PCR.

A minority of Th1 and Tfh effector cells express survival genes shared by memory cell progeny that require IL-7 or TCR signaling to persist.

It is not clear how CD4 memory T cells are formed from a much larger pool of earlier effector cells. We found that transient systemic bacterial infection rapidly generates several antigen-specific T helper (Th)1 and T follicular helper (Tfh) cell populations with different tissue residence behaviors. Although most cells of all varieties had transcriptomes indicative of cell stress and death at the peak of the response, some had already acquired a memory cell signature characterized by expression of genes involved in cell survival.

QuICSeedR: an R package for analyzing fluorophore-assisted seed amplification assay data.

Motivation: Fluorophore-assisted seed amplification assays (F-SAAs), such as real-time quaking-induced conversion (RT-QuIC) and fluorophore-assisted protein misfolding cyclic amplification (F-PMCA), have become indispensable tools for studying protein misfolding in neurodegenerative diseases. However, analyzing data generated by these techniques often requires complex and time-consuming manual processes. In addition, the lack of standardization in F-SAA data analysis presents a significant challenge to the interpretation and reproducibility of F-SAA results across different laboratories and studies.

Surface-enhanced Raman spectroscopy: a half-century historical perspective.

Surface-enhanced Raman spectroscopy (SERS) has evolved significantly over fifty years into a powerful analytical technique. This review aims to achieve five main goals. (1) Providing a comprehensive history of SERS's discovery, its experimental and theoretical foundations, its connections to advances in nanoscience and plasmonics, and highlighting collective contributions of key pioneers.

Critical Nematic Phase with Pseudogaplike Behavior in Twisted Bilayers.

The crystallographic restriction theorem constrains two-dimensional nematicity to display either Ising (Z_{2}) or three-state-Potts (Z_{3}) critical behaviors, both of which are dominated by amplitude fluctuations. Here, we use group theory and microscopic modeling to show that this constraint is circumvented in a 30°-twisted hexagonal bilayer due to its emergent quasicrystalline symmetries. We find a critical phase dominated by phase fluctuations of a Z_{6} nematic order parameter and bounded by two Berezinskii-Kosterlitz-Thouless (BKT) transitions, which displays only quasi-long-range nematic order.

Pharmacokinetics/pharmacodynamics of glucocorticoids: modeling the glucocorticoid receptor dynamics and dose/response of commonly prescribed glucocorticoids.

Background And Purpose: The main features of the dynamics of the glucocorticoid receptor (GR) have been known for 50 years: 1) in the absence of glucocorticoid (G), the receptor is localized entirely in the cytoplasm; 2) upon G binding, GR is converted into a tightly bound G form and is rapidly imported into the nucleus where it can bind DNA and modulate transcription; 3) nuclear export of GR is very slow; and 4) the nuclear form of GR can recycle through an unbound form, back to the bound transcription modulating form without leaving the nucleus.

Experimental Approach: A kinetic model that captures these features is presented, a set of model parameters for dexamethasone is derived, and the clinical implication for the commonly used glucocorticoids is discussed.

Key Results: At the high concentrations normally used to describe G pharmacodynamics, the model reduces to the standard Michaelis-Menten equation with a that is a function of 4 model parameters.

Impact of solid content on the bulk properties of lyophilized powders.

Interest in oral delivery of biological drug products, commonly prepared through lyophilization, is surging. Typically, low solid content solutions are employed for lyophilization to enhance mass transfer and minimize drying time. Yet, this approach often results in lyophilized powders with low bulk density and poor flowability, challenging downstream processing steps that are required for oral product development.

[Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus].

To successfully apply the genome editing technology using the CRISPR/Cas9 system in the clinic, it is necessary to achieve a high efficiency of knock-in, which is insertion of a genetic construct into a given locus of the target cell genome. One of the approaches to increase the efficiency of knock-in is to modify donor DNA with the same Cas9 targeting sites (CTS) that are used to induce double-strand breaks (DSBs) in the cell genome (the double-cut donor method). Another approach is based on introducing truncated CTS (tCTS), including a PAM site and 16 proximal nucleotides, into the donor DNA.

[Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line].

The low knock-in efficiency, especially in primary human cells, limits the use of the genome editing technology for therapeutic purposes, rendering it important to develop approaches for increasing the knock-in levels. In this work, the efficiencies of several approaches were studied using a model of knock-in of a construct coding for the peptide HIV fusion inhibitor MT-C34 into the human CXCR4 locus in the CEM/R5 T cell line. First, donor DNA modification was evaluated as a means to improve the efficiency of plasmid transport into the nucleus.

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Deep profiling deconstructs features associated with memory CD8 T cell tissue residence.

Tissue-resident memory CD8 T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics.

HeatGSNs: Integrating Eigenfilters and Low-Pass Graph Heat Kernels into Graph Spectral Convolutional Networks for Brain Tumor Segmentation and Classification.

Recent studies on graph representation learning in brain tumor learning tasks have garnered significant interest by encoding and learning inherent relationships among the geometric features of tumors. There are serious class imbalance problems that occur on brain tumor MRI datasets. Impressive deep learning models like CNN- and Transformer-based can easily address this problem through their complex model architectures with large parameters.

Risk assessment methods in occupational health and hygiene: a scoping review.

Background: There are a variety of risk assessment methods to evaluate occupational hazards in the field of industrial hygiene. With the development of emerging technologies in the workforce, the previously established risk assessment methods may need to be adapted or new methods developed to address the risk of new hazards.

Methods: A scoping review was conducted consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.