Analysis of a cell-free DNA-based cancer screening cohort links fragmentomic profiles, nuclease levels, and plasma DNA concentrations.

The concentration of circulating cell-free DNA (cfDNA) in plasma is an important determinant of the robustness of liquid biopsies. However, biological mechanisms that lead to inter-individual differences in cfDNA concentrations remain unexplored. The concentration of plasma cfDNA is governed by an interplay between its release and clearance.

Full-color time-sequential super multi-view near-eye display with front-lit waveguide illumination.

Light field (LF) displays can offer a quasi-natural three-dimensional (3D) viewing experience by tailoring the four-dimensional light information. However, the primary drawback of conventional LF displays is their limited image quality due to restricted information. To address this limitation, time-multiplexing techniques are employed, but the resulting system configurations are often impractical for achieving compact systems.

Tubulin acetyltransferases access and modify the microtubule luminal K40 residue through anchors in taxane-binding pockets.

Acetylation at α-tubulin K40 is the sole post-translational modification preferred to occur inside the lumen of hollow cylindrical microtubules. However, how tubulin acetyltransferases access the luminal K40 in micrometer-long microtubules remains unknown. Here, we use cryo-electron microscopy and single-molecule reconstitution assays to reveal the enzymatic mechanism for tubulin acetyltransferases to modify K40 in the lumen.

The role of polo-like kinases 2 in the proteasomal and lysosomal degradation of alpha-synuclein in neurons.

Parkinson's disease (PD) is a neurodegenerative disorder caused by the degeneration of dopaminergic neurons in the brain stem. PD is mostly sporadic, but familial PD (FPD) cases are recorded in different studies. The first gene mutation that is linked to FPD is α-synuclein (α-syn).

: Explainable deep learning for multistep biomedical prediction in longitudinal data.

Highlights: Many diseases are increasingly conceptualized as multifactorial, progressive processesRobust prediction of progressive disease courses can advance risk stratification and treatment targetingRiskPath provides optimizable timeseries AI to predict progressive disease with longitudinal cohort dataEnhanced explainability and functionality facilitates risk pathway mapping and compact models.

The Bigger Picture: Identifying persons at elevated risk for a disease outcome is a key prerequisite for targeting interventions to improve health. Current risk stratification tools for common diseases are aging and achieve only moderate performance.

Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex.

In eukaryotes, the origin recognition complex (ORC) faciliates the assembly of pre-replicative complex (pre-RC) at origin DNA for replication licensing. Here we show that the N-terminal intrinsically disordered region (IDR) of the yeast Orc2 subunit is crucial for this process. Removing a segment (residues 176-200) from Orc2-IDR or mutating a key isoleucine (194) significantly inhibits replication initiation across the genome.

Research progress on sexual functioning and associated factors in childhood cancer survivors: a scoping review.

Background: Childhood Cancer Survivors (CCSs) are more likely to report sexual dysfunction than people without cancer history. Sexual functioning encompasses more than just sexual dysfunction. The scarcity of information regarding the status and influencing factors of sexual functioning in CCSs, hampers to devise suitable screening or interventions.

Assembly and activation of replicative helicases at origin DNA for replication initiation.

To initiate DNA replication, it is essential to properly assemble a pair of replicative helicases at each replication origin. While the general principle of this process applies universally from prokaryotes to eukaryotes, the specific mechanisms governing origin selection, helicase loading, and subsequent helicase activation vary significantly across different species. Recent advancements in cryo-electron microscopy (cryo-EM) have revolutionized our ability to visualize large protein or protein-DNA complexes involved in the initiation of DNA replication.

A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer.

Chromones are promising for anticancer drug development. 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound showed the highest cytotoxicity (LC 3.

Identifying intraoperative events in a simulated laparotomy video: a multinational study of inattentional blindness among anesthesiologists.

Purpose: Medical errors may be occasionally explained by inattentional blindness (IB), i.e., failing to notice an event/object that is in plain sight.

Nutraceuticals for Diabetic Retinopathy: Recent Advances and Novel Delivery Systems.

Diabetic retinopathy (DR) is a major vision-threatening disease among the working-age population worldwide. Present therapeutic strategies such as intravitreal injection of anti-VEGF and laser photocoagulation mainly target proliferative DR. However, there is a need for early effective management in patients with early stage of DR before its progression into the more severe sight-threatening proliferative stage.

Efficacy and safety of Chinese herbal medicine to prevent and treat COVID-19 household close contacts in Hong Kong: an open-label, randomized controlled trial.

Objectives: To evaluate the efficacy and safety of CHM in the prevention of COVID-19 infection and treatment for COVID-19 related symptoms.

Design: Prospective open-label randomized controlled trial.

Setting: Participants' home in Hong Kong.

Gene Mosaicism Confirmed by Next-Generation Sequencing in a Clinically Symptomatic Infant.

A 4-day-old infant was admitted for neonatal jaundice. He had persistent tachycardia and tachypnea. Initial workup showed a serum free T4 of 75.

Are Tai Chi and Qigong effective in the treatment of traumatic brain injury? A systematic review.

Background: Traumatic brain injury (TBI) adversely affects both young and old and is a growing public health concern. The common functional, psychological, and cognitive changes associated with TBI and recent trends in its management, such as recommending sub-threshold aerobic activity, and multi-modal treatment strategies including vestibular rehabilitation, suggest that Tai Chi/Qigong could be beneficial for TBI. Tai Chi and Qigong are aerobic mind-body practices with known benefits for maintaining health and mitigating chronic disease.

Lifetime dairy product consumption and breast cancer risk: a prospective cohort study by tumor subtypes.

Background: Previous literature on dairy products and risk of breast cancer is inconsistent, and the relationship may depend on the life-period of dietary assessment.

Objective: We examined dairy consumption from adolescence through later adulthood and incidence of breast cancer by menopausal status and tumor molecular subtypes in the Nurses' Health Study (NHS), a prospective cohort study.

Methods: We analyzed data from 63,847 females in the NHS collected from 1980 to 2018.

G-quadruplex ligands as therapeutic agents against cancer, neurological disorders and viral infections.

G-quadruplexes (G4s) within the human genome have undergone extensive molecular investigation, with a strong focus on telomeres, gene promoters and repetitive regulatory sequences. G4s play central roles in regulating essential biological processes, including telomere maintenance, replication, transcription and translation. Targeting these molecular processes with G4-binding ligands holds substantial therapeutic potential in anticancer treatments and has also shown promise in treating neurological, skeletal and muscular disorders.

Temporal landscape of mitochondrial proteostasis governed by the UPR.

Breakdown of mitochondrial proteostasis activates quality control pathways including the mitochondrial unfolded protein response (UPR) and PINK1/Parkin mitophagy. However, beyond the up-regulation of chaperones and proteases, we have a limited understanding of how the UPR remodels and restores damaged mitochondrial proteomes. Here, we have developed a functional proteomics framework, termed MitoPQ (Mitochondrial Proteostasis Quantification), to dissect the UPR's role in maintaining proteostasis during stress.

Synergism between CMG helicase and leading strand DNA polymerase at replication fork.

The replisome that replicates the eukaryotic genome consists of at least three engines: the Cdc45-MCM-GINS (CMG) helicase that separates duplex DNA at the replication fork and two DNA polymerases, one on each strand, that replicate the unwound DNA. Here, we determined a series of cryo-electron microscopy structures of a yeast replisome comprising CMG, leading-strand polymerase Polε and three accessory factors on a forked DNA. In these structures, Polε engages or disengages with the motor domains of the CMG by occupying two alternative positions, which closely correlate with the rotational movement of the single-stranded DNA around the MCM pore.

Watershed characteristics and chemical properties govern methyl mercury concentrations within headwater streams of boreal forests in Ontario, Canada.

Methyl mercury (MeHg) concentrations in boreal headwater streams are influenced by complex natural processes and disturbances such as forestry management. Understanding drivers of MeHg within boreal streams in Ontario, Canada, is of particular interest as there are legacy MeHg concerns. However, models accounting for the complexity of underlying processes have not yet been developed.

Combining Transoral Nasopharyngeal Brush and Plasma Epstein-Barr Virus DNA in Detecting Locally Recurrent Nasopharyngeal Carcinoma.

Objective: To evaluate the sensitivities and specificities of Epstein-Barr virus (EBV) DNA in the detection of locally recurrent or persistent nasopharyngeal carcinoma (NPC) through nasopharyngeal (NP) brush biopsy and plasma, respectively, and whether a combination of both would be superior to the individual tests.

Study Design: A case-control study was conducted from September 2016 to June 2022.

Setting: A multicentre study at 3 tertiary referral centers in Hong Kong was conducted by the Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong.