Brain-wide neuronal circuit connectome of human glioblastoma.

Glioblastoma (GBM) infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression. Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic. The extent of GBM integration into the brain-wide neuronal circuitry remains unclear.

Factors Associated with Nonspecialist Quality of Delivery within a Family Strengthening Intervention in Rwanda: a Parallel Latent Growth Model.

In task-shared, mental health, and psychosocial support interventions, monitoring the quality of delivery (fidelity and competence) of nonspecialist providers is critical. Quality of delivery is frequently reported in brief, summary statistics, and while both fidelity and competence scores tend to be high, rarely have factors associated with quality of delivery in low-resource, mental health, and psychosocial support interventions been examined using inferential statistics. Understanding both modifiable and non-modifiable predictors of quality of delivery is important for adapting training and supervision approaches throughout intervention delivery.

Chemistry, manufacturing and controls strategies for using novel excipients in lipid nanoparticles.

Lipid nanoparticles (LNPs) for nucleic acid delivery often use novel lipids as functional excipients to modulate the biodistribution, pharmacokinetics, pharmacodynamics and efficacy of the nucleic acid. Novel excipients used in pharmaceutical products are subject to heightened regulatory scrutiny and often require data packages comparable to an active pharmaceutical ingredient. Although these regulatory requirements may help to ensure patient safety they also create economic and procedural barriers that can disincentivize innovation and delay clinical investigation.

Dipolar wavevector interference induces a polar skyrmion lattice in strained BiFeO films.

Skyrmions can form regular arrangements, so-called skyrmion crystals (SkXs). A mode with multiple wavevectors q then describes the arrangement. While magnetic SkXs, which can emerge in the presence of Dzyaloshinskii-Moriya interaction, are well established, polar skyrmion lattices are still elusive.

Pediatric erythromelalgia from multidisciplinary perspectives: a scoping review.

Erythromelalgia is a rare, chronic pain disorder characterized by the triad of intense burning sensation, warmth, and redness, primarily involving the hands and feet, and usually alleviated by cold and worsened by heat. The objective of this scoping review was to: 1) map the existing literature on erythromelalgia in youth, 2) identify knowledge gaps, and 3) inform directions for future research in pediatric erythromelalgia. One hundred and sixty-seven studies reporting 411 cases of childhood-onset erythromelalgia were identified.

The flavonoid metabolic pathway genes Ac4CL1, Ac4CL3 and AcHCT1 positively regulate the kiwifruit immune response to Pseudomonas syringae pv. actinidiae.

Psa primarily utilises the type III secretion system (T3SS) to deliver effector proteins (T3Es) into host cells, thereby regulating host immune responses. However, the mechanism by which kiwifruit responds to T3SS remains unclear. To elucidate the molecular reaction of kiwifruit plants to Psa infection, M228 and mutant M228△hrcS strains were employed to inoculate Actinidia chinensis var.

System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring.

Three-dimensional subcellular imaging is essential for biomedical research, but the diffraction limit of optical microscopy compromises axial resolution, hindering accurate three-dimensional structural analysis. This challenge is particularly pronounced in label-free imaging of thick, heterogeneous tissues, where assumptions about data distribution (e.g.

Distinct molecular and clinical features of specific variants of KRAS codon 12 in pancreatic adenocarcinoma.

PURPOSE Oncogenic mutations in KRAS have been identified in > 85% of pancreatic ductal adenocarcinoma (PDAC) cases. G12D, G12V, and G12R are the most frequent variants. Using large clinical and genomic databases, this study characterizes prognostic and molecular differences between KRAS variants, focusing on KRAS G12D and G12R.

Aging-dependent temporal regulation of MIR156 epigenetic silencing by CiLDL1 and CiNF-YB8 in chrysanthemum.

Temporal decline in microRNA miR156 expression is crucial for the transition to, and maintenance of, the adult phase and flowering competence in flowering plants. However, the molecular mechanisms underlying the temporal regulation of miR156 reduction remain largely unknown. Here, we investigated the epigenetic mechanism regulating the temporal silencing of cin-MIR156 in wild chrysanthemum (Chrysanthemum indicum), focusing on the role of the lysine-specific demethylase CiLDL1 and the nuclear factor Y complex.

Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07523LS in Newborn Infants Exposed to HIV-1.

Background: Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07523LS.

Methods: VRC07523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (Cohort 1; N=11, enrolled in USA) and breastfed (Cohort 2; N=11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1.

Immune Microenvironment in Breast Cancer Metastasis.

Metastatic disease is the final stage of breast cancer that accounts for vast majority of patient death. Mounting data over recent years strongly support the critical roles of the immune microenvironment in determining breast cancer metastasis. The latest single-cell studies provide further molecular evidence illustrating the heterogeneity of this immune microenvironment.

Classification of Breast Cancer Through the Perspective of Cell Identity Models.

The mammary epithelium has an inner luminal layer that contains estrogen receptor (ER)-positive hormone-sensing cells and ER-negative alveolar/secretory cells, and an outer basal layer that contains myoepithelial/stem cells. Most human tumours resemble either hormone-sensing cells or alveolar/secretory cells. The most widely used molecular classification, the Intrinsic classification, assigns hormone-sensing tumours to Luminal A/B and human epidermal growth factor 2-enriched (HER2E)/molecular apocrine (MA)/luminal androgen receptor (LAR)-positive classes, and alveolar/secretory tumours to the Basal-like class.

Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Objective: Tofersen, an antisense oligonucleotide, has recently received FDA and EMA approval for treating amyotrophic lateral sclerosis (ALS) in adults with SOD1 gene mutations. This systematic review and meta-analysis synthesized evidence on tofersen's safety and efficacy in patients with SOD1-related ALS.

Methods: A comprehensive search of three databases was conducted from inception through October 2024.

Expanded Naloxone Distribution by Opioid Overdose Prevention Programs to High-Need Populations and Neighborhoods in New York City.

From 2014 to 2017, the drug overdose death rate per 100,000 in New York City (NYC) increased by 81%, with 57% of overdoses in 2017 involving the opioid fentanyl. In response, overdose education and naloxone dispensing (OEND) efforts were expanded in NYC, informed by neighborhood-level and population-level opioid overdose fatality rates. We describe the demographic and geographical distribution of naloxone by NYC opioid overdose prevention programs (OOPPs; the primary distributor of naloxone to laypersons in NYC) as OEND was expanded in NYC.

Long Noncoding RNA SNHG12 Regulates Ischemia/reperfusion (I/R)-mediated Acute Kidney Injury (AKI) Through miR-129-1-3p/Ubiquitin Specific Peptidase 25 axis.

A growing body of evidence suggests the involvement of long noncoding ribose nucleic acids (lncRNAs) in acute kidney injury (AKI). This study focused on the mechanistic role of lncRNA small nucleolar RNA host gene 12 (SNHG12) in ischemia/reperfusion (I/R)-mediated AKI. A model of hypoxia/reoxygenation (H/R) was created using human kidney cells (HK-2).

Epigenetics in Neurodegenerative Diseases.

Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e.

Epigenetics in Learning and Memory.

In animals, memory formation and recall are essential for their survival and for adaptations to a complex and often dynamically changing environment. During memory formation, experiences prompt the activation of a selected and sparse population of cells (engram cells) that undergo persistent physical and/or chemical changes allowing long-term memory formation, which can last for decades. Over the past few decades, important progress has been made on elucidating signaling mechanisms by which synaptic transmission leads to the induction of activity-dependent gene regulation programs during the different phases of learning (acquisition, consolidation, and recall).

Menopause-induced 17β-estradiol and progesterone loss increases senescence markers, matrix disassembly and degeneration in mouse cartilage.

Female individuals who are post-menopausal present with higher incidence of knee osteoarthritis (KOA) than male counterparts; however, the mechanisms underlying this disparity are unknown. The most commonly used preclinical models lack human-relevant menopausal phenotypes, which may contribute to our incomplete understanding of sex-specific differences in KOA pathogenesis. Here we chemically induced menopause in middle-aged (14-16 months) C57/BL6N female mice.

The current landscape of artificial intelligence in oral and maxillofacial surgery- a narrative review.

Objective: This narrative review aims to explore the current applications and future prospects of AI within the subfields of oral and maxillofacial surgery (OMS), emphasizing its potential benefits and anticipated challenges.

Methods: A detailed review of the literature was conducted to evaluate the role of AI in oral and maxillofacial surgery. All domains within OMS were reviewed with a focus on diagnostic, therapeutic and prognostic interventions.

B cells enhance IL-1 beta driven invasiveness in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype often characterized by high lymphocyte infiltration, including tumor-infiltrating B cells (TIBs). These cells are present even in early stages of TNBC and associated with microinvasion. This study shows that co-culturing TNBC cells with B cells increases Interleukin-1β (IL-1β) expression and secretion.

An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord.

Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling in the dorsal root ganglia (DRG) and spinal cord (SC) drive the development and maintenance of neuropathic pain (NP). However, our understanding of the NP-associated spatial molecular processing landscape of SC and the non-synaptic interactions between DRG neurons and SC cells remains limited.

Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.

Super-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.

Removal of dissolved organic carbon in the West Pacific hadal zones.

The deep oceans are environments of complex carbon dynamics that have the potential to significantly impact the global carbon cycle. However, the role of hadal zones, particularly hadal trenches (water depth > 6 km), in the oceanic dissolved organic carbon (DOC) cycle is not thoroughly investigated. Here we report distinct DOC signatures in the Japan Trench bottom water.

Hepcidin, Incident Heart Failure and Cardiac Dysfunction in Older Adults: the ARIC Study.

Aims: Hepcidin regulates plasma and tissue iron levels. We studied the association of hepcidin levels with the risk of incident heart failure (HF) and cardiac dysfunction in older adults.

Methods: We included adults from the ongoing, longitudinal Atherosclerosis Risk in Communities (ARIC) study who were free from prevalent anemia and HF at Visit 5 (2011-2013) and had available hepcidin and covariate data.