Impacts of hazardous noise levels on hearing loss and tinnitus in dental professionals.

Background: Hazardous noise exposure is an important health concern in many workplaces and is one of the most common work-related injuries in the United States. Dental professionals are frequently exposed to high levels of occupational noise in their daily work environment. This noise is generated by various dental handpieces such as drills, suctions, and ultrasonic scalers.

De-escalation of surgical and radiation treatment in elderly luminal breast cancer patients, single institution report and review of the evidence.

Background: De-intensification of anti-cancer therapy without significantly affecting outcomes is an important goal. Omission of axillary surgery or breast radiation is considered a reasonable option in elderly patients with early-stage breast cancer and good prognostic factors. Data on avoidance of both axillary surgery and radiation therapy (RT) is scarce and inconclusive.

SMORE: spatial motifs reveal patterns in cellular architecture of complex tissues.

Deciphering the link between tissue architecture and function requires methods to identify and interpret patterns in spatial arrangement of cells. We present SMORE, an approach to detect patterns in sequential arrangements of cells and examine their associated gene expression specializations. Applied to retina, brain, and embryonic tissue maps, SMORE identifies novel spatial motifs, including one that offers a new mechanism of action for type 1b bipolar cells.

Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.

Background: PSEN1, PSEN2, and APP mutations cause Alzheimer's disease (AD) with an early age at onset (AAO) and progressive cognitive decline. PSEN1 mutations are more common and generally have an earlier AAO; however, certain PSEN1 mutations cause a later AAO, similar to those observed in PSEN2 and APP.

Methods: We examined whether common disease endotypes exist across these mutations with a later AAO (~ 55 years) using hiPSC-derived neurons from familial Alzheimer's disease (FAD) patients harboring mutations in PSEN1, PSEN2, and APP and mechanistically characterized by integrating RNA-seq and ATAC-seq.

KDM6A facilitates Xist upregulation at the onset of X inactivation.

Background: X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions.

A prospective, multicenter analysis of the integrated 31-gene expression profile test for sentinel lymph node biopsy (i31-GEP for SLNB) test demonstrates reduced number of unnecessary SLNBs in patients with cutaneous melanoma.

Background: National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for patients with > 10% risk of positivity, consider SLNB with 5-10% risk, and foregoing with < 5% risk. The integrated 31-gene expression profile (i31-GEP) algorithm combines the 31-GEP with clinicopathologic variables, estimating SLN positivity risk.

Methods: The i31-GEP SLNB risk prediction accuracy was assessed in patients with T1-T2 tumors enrolled in the prospective, multicenter DECIDE study (n = 322).

Mixed method study of feasibility and acceptability of electronic screening for measurement-based symptom monitoring of veterans accessing mental health treatment in VA community care program settings.

Background: 2022 survey data showed 29% of Veterans utilized Veterans Affairs (VA) paid health care at a non-VA facility, 6% higher than in 2021. Despite an increase in the number of Veterans accessing care in the community via the MISSION Act Community Care Program (CCP), there is limited information on the quality of mental health care delivered to Veterans in these settings. Further, Veterans report barriers to quality care, including poor communication between CCP and VA providers, which can result in negative patient outcomes.

Acute administration of NLX-101, a Serotonin 1A receptor agonist, improves auditory temporal processing during development in a mouse model of Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is a leading known genetic cause of intellectual disability and autism spectrum disorders (ASD)-associated behaviors. A consistent and debilitating phenotype of FXS is auditory hypersensitivity that may lead to delayed language and high anxiety. Consistent with findings in FXS human studies, the mouse model of FXS, the Fmr1 knock out (KO) mouse, shows auditory hypersensitivity and temporal processing deficits.

GLiDe: a web-based genome-scale CRISPRi sgRNA design tool for prokaryotes.

Background: CRISPRi screening has become a powerful approach for functional genomic research. However, the off-target effects resulting from the mismatch tolerance between sgRNAs and their intended targets is a primary concern in CRISPRi applications.

Results: We introduce Guide Library Designer (GLiDe), a web-based tool specifically created for the genome-scale design of sgRNA libraries tailored for CRISPRi screening in prokaryotic organisms.

Synthesis of tertiary alkyl amines via photoinduced copper-catalysed nucleophilic substitution.

In view of the high propensity of tertiary alkyl amines to be bioactive, the development of new methods for their synthesis is an important challenge. Transition-metal catalysis has the potential to greatly expand the scope of nucleophilic substitution reactions of alkyl electrophiles; unfortunately, in the case of alkyl amines as nucleophiles, only one success has been described so far: the selective mono-alkylation of primary amines to form secondary amines. Here, using photoinduced copper catalysis, we report the synthesis of tertiary alkyl amines from secondary amines and unactivated alkyl electrophiles, two readily available coupling partners.

Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.

Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.

Magnetic resonance imaging of hepatocellular carcinoma: a spectrum of uncommon morphologic subtypes, unusual imaging patterns and mimics.

Advances in imaging techniques have evolved, allowing for early noninvasive diagnosis and improved management of high-risk patients with hepatocellular carcinoma (HCC). The hallmark imaging features of HCC on multiphasic cross-sectional imaging can be explained by the multistep process of hepatocarcinogenesis and is seen in 60% of cases. However, approximately 40% of cases do not abide by the classic imaging appearance and may pose a diagnostic challenge for radiologists.

Establishing bio-logging data collections as dynamic archives of animal life on Earth.

Rapid growth in bio-logging-the use of animal-borne electronic tags to document the movements, behaviour, physiology and environments of wildlife-offers opportunities to mitigate biodiversity threats and expand digital natural history archives. Here we present a vision to achieve such benefits by accounting for the heterogeneity inherent to bio-logging data and the concerns of those who collect and use them. First, we can enable data integration through standard vocabularies, transfer protocols and aggregation protocols, and drive their wide adoption.

Building a growing genomic repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome.

Time-resolved fluorescence measurements of dissolved organic matter (DOM) as a function of environmental parameters in estuarine waters.

Fluorescent lifetimes of dissolved organic matter (DOM) and associated physicochemical parameters were measured over 14 months in an estuary in Southern California, USA. Measurements were made on 77 samples from sites near the inlet, mid-estuary, and outlet to maximize the range of physicochemical variables. Time-resolved fluorescence data were well fit to a triexponential model with an intermediate lifetime component (τ: 1 to 5 ns), a long lifetime component (τ: 2 to 15 ns), and a short lifetime component (τ: < 1 ns).

Pro-inflammatory macrophage activation does not require inhibition of oxidative phosphorylation.

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Oxidative phosphorylation sharply decreases upon classical macrophage activation, as mitochondria are thought to shift from ATP production towards accumulating signals that amplify effector function. However, evidence is conflicting regarding whether this collapse in respiration is essential or dispensable.

ATM and IRAK1 orchestrate two distinct mechanisms of NF-κB activation in response to DNA damage.

DNA damage in cells induces the expression of inflammatory genes. However, the mechanism by which cells initiate an innate immune response in the presence of DNA lesions blocking transcription remains unknown. Here we find that genotoxic stresses lead to an acute activation of the transcription factor NF-κB through two distinct pathways, each triggered by different types of DNA lesions and coordinated by either ataxia-telangiectasia mutated (ATM) or IRAK1 kinases.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Treatment advances across the cervical cancer spectrum.

Cervical cancer is preventable with screening and vaccination approaches; however, access to these preventative measures is limited both nationally and globally and thus many women will still develop cervical cancer. Novel treatments and practice-changing research have improved cervical cancer outcomes over the past few decades. In this Review, we discuss clinical trials that have refined or redefined the treatment of cervical cancers across the early stage, locally advanced, persistent, recurrent and/or metastatic disease settings.

AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides.

Non-invasive blood glucose monitoring using PPG signals with various deep learning models and implementation using TinyML.

Accurate and continuous blood glucose monitoring is essential for effective diabetes management, yet traditional finger pricking methods are often inconvenient and painful. To address this issue, photoplethysmography (PPG) presents a promising non-invasive alternative for estimating blood glucose levels. In this study, we propose an innovative 1-second signal segmentation method and evaluate the performance of three advanced deep learning models using a novel dataset to estimate blood glucose levels from PPG signals.