Animal and vegetal materials of mouse oocytes segregate at first zygotic cleavage: a simple mechanism that makes the two-cell blastomeres differ reciprocally from the start.

Recent advances in embryology have shown that the sister blastomeres of two-cell mouse and human embryos differ reciprocally in potency. An open question is whether the blastomeres became different as opposed to originating as different. Here we wanted to test two relevant but conflicting models: one proposing that each blastomere contains both animal and vegetal materials in balanced proportions because the plane of first cleavage runs close to the animal-vegetal axis of the fertilized oocyte (meridional cleavage); and the other model proposing that each blastomere contains variable proportions of animal and vegetal materials because the plane of the first cleavage can vary - up to an equatorial orientation - depending on the topology of fertilization.

Validation requirements for AI-based intervention-evaluation in aging and longevity research and practice.

The field of aging and longevity research is overwhelmed by vast amounts of data, calling for the use of Artificial Intelligence (AI), including Large Language Models (LLMs), for the evaluation of geroprotective interventions. Such evaluations should be correct, useful, comprehensive, explainable, and they should consider causality, interdisciplinarity, adherence to standards, longitudinal data and known aging biology. In particular, comprehensive analyses should go beyond comparing data based on canonical biomedical databases, suggesting the use of AI to interpret changes in biomarkers and outcomes.

Post Hoc Analysis Comparing the Safety and Efficacy of PrabotulinumtoxinA in Millennials and Nonmillennials With Moderate to Severe Glabellar Lines.

Background: Millennials accept and invest in aesthetic procedures more than older generations.

Objective: To compare efficacy outcomes between millennial and nonmillennial patients after treatment of glabellar lines with prabotulinumtoxinA.

Materials And Methods: This was a post hoc analysis of 3 Phase III studies of 20 U prabotulinumtoxinA for the treatment of moderate to severe glabellar lines.

Botulinum Toxin Accessory Proteins: Are They Just an Accessory?

Background: Botulinum neurotoxins produced by Clostridium botulinum consist of a complex of a core neurotoxin protein and one or more nontoxin accessory proteins. The accessory proteins are generally thought to protect the neurotoxin from the gastric environment in botulism poisoning, dissociating away upon absorption. Other than their questionable immunogenicity, they are rarely mentioned in botulinum toxin therapy.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway.

The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell's capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has been shown to be successful in achieving both therapeutic efficacy and safety across various cancer models; however, the molecular mechanisms driving its selective antitumor effects remain unclear. Here, we show for the first time that ISR plasticity relies on PP2A activation to regulate drug response and dictate cellular fate under conditions of chronic stress.

Safety and Duration of Effect of 40-Unit PrabotulinumtoxinA-xvfs for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients: A Phase II, Multicenter, Randomized, Double-Blind, Active-Controlled Trial.

Background: Extending the duration of effect of botulinum toxins-by administering doses beyond those of the approved labels-has been an area of increasing interest in the field of aesthetics.

Objectives: The aim of this study was to investigate the safety and duration of effect of 40-unit (U) prabotulinumtoxinA-xvfs (twice the approved dose and concentration) for the treatment of moderate-to-severe glabellar lines.

Methods: A total of 154 adult patients were randomized 1:1:1 to a single treatment of either 40 U prabotulinumtoxinA-xvfs (PRA 40, 5 injections of 8 U/0.

Clutter rejection in passive non-line-of-sight imaging via blind multispectral unmixing.

Passive non-line-of-sight imaging methods that utilize scattered light to "look around corners" are often hindered by unwanted sources that overwhelm the weaker desired signal. Recent approaches to mitigate these "clutter" sources have exploited dependencies in the spectral content, or color, of the scattered light. A particularly successful method utilized blind source separation methods to isolate the desired imaging signal with minimal prior information.

Human Ageing Genomic Resources: updates on key databases in ageing research.

Ageing is a complex and multifactorial process. For two decades, the Human Ageing Genomic Resources (HAGR) have aided researchers in the study of various aspects of ageing and its manipulation. Here, we present the key features and recent enhancements of these resources, focusing on its six main databases.

scDiffCom: a tool for differential analysis of cell-cell interactions provides a mouse atlas of aging changes in intercellular communication.

Dysregulation of intercellular communication is a hallmark of aging. To better quantify and explore changes in intercellular communication, we present scDiffCom and scAgeCom. scDiffCom is an R package, relying on approximately 5,000 curated ligand-receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data.

Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer.

Introduction: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.

Results: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age.

Isolating Signals in Passive Non-Line-of-Sight Imaging using Spectral Content.

In real-life passive non-line-of-sight (NLOS) imaging there is an overwhelming amount of undesired scattered radiance, called clutter, that impedes reconstruction of the desired NLOS scene. This paper explores using the spectral domain of the scattered light field to separate the desired scattered radiance from the clutter. We propose two techniques: The first separates the multispectral scattered radiance into a collection of objects each with their own uniform color.

Influence of design implant and apical depth in post-extraction sockets: an in vitro simulated study.

Background: Implant design and apical stability are principal parameters involved in achieving successful primary stability. Using polyurethane models to simulate post-extraction sockets, we investigated the effects of using differing blade designs on the primary stability of tapered implants and the impact of apical depth.

Method: Six polyurethane blocks were used to simulate post-extraction pockets.

PrabotulinumtoxinA for the treatment of glabellar lines in adults, 65 years of age and older: The fourth in a series of post hoc analyses of the phase III clinical study data.

Background: Despite the absence of Phase III clinical trial data to support their use, 3.4% of all neurotoxin treatments performed internationally for esthetic purposes in 2020 were performed in patients 65 years of age and older.

Objectives: To investigate the efficacy and safety of prabotulinumtoxinA for the treatment of moderate to severe glabellar lines in the subset of Phase III clinical trial participants who were 65 years of age and older.

Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease.

Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis.

Senescent cells can spread the senescent phenotype to other cells by secreting senescence-associated secretory phenotype factors. The resulting paracrine senescent cells make a significant contribution to the burden of senescent cell accumulation with age. Previous efforts made to characterize paracrine senescence are unreliable due to analyses being based on mixed populations of senescent and non-senescent cells.

Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats.

Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.

PrabotulinumtoxinA vs OnabotulinumtoxinA for the Treatment of Adult Males With Moderate to Severe Glabellar Lines: Post-hoc Analyses of the Phase III Clinical Study Data.

Background: Despite a growing interest among men in cosmetic procedures such as botulinum toxin, comparator clinical trial data in this population are limited.

Objectives: The authors sought to compare the efficacy and safety of prabotulinumtoxinA and onabotulinumtoxinA for the treatment of males with moderate to severe glabellar lines.

Methods: Post-hoc analyses were performed on the subpopulation of male patients treated with either a single dose of 20 U prabotulinumtoxinA (n = 25) or 20 U onabotulinumtoxinA (n = 31) in the EVB-003 Phase III glabellar line clinical study.

PrabotulinumtoxinA for Treatment of Millennials With Moderate to Severe Glabellar Lines: Post Hoc Analyses of the Phase III Clinical Study Data.

Background: The use of esthetic products by millennials is increasing, yet published clinical trial data in this population are limited.

Objective: To compare the efficacy and safety of prabotulinumtoxinA for the treatment of moderate to severe glabellar lines in millennial and nonmillennial patients.

Methods And Materials: Post hoc analyses were performed on the pooled population of all patients treated with 20U prabotulinumtoxinA in the 3 single-dose Phase III glabellar line clinical studies.

Positive Selection and Enhancer Evolution Shaped Lifespan and Body Mass in Great Apes.

Within primates, the great apes are outliers both in terms of body size and lifespan, since they include the largest and longest-lived species in the order. Yet, the molecular bases underlying such features are poorly understood. Here, we leveraged an integrated approach to investigate multiple sources of molecular variation across primates, focusing on over 10,000 genes, including approximately 1,500 previously associated with lifespan, and additional approximately 9,000 for which an association with longevity has never been suggested.

Repercussions of COVID-19 in Brazilian Dentists' Personal and Professional Routines: An Online Survey.

Aim And Objective: This study evaluated the repercussions of coronavirus disease-2019 (COVID-19) in Brazilian dentists' personal and professional routines.

Materials And Methods: Brazilian dentists were invited to participate in an online survey with questions pertaining to COVID-19 and its repercussions in dental practice. Sample calculation was performed using the Survey Monkey software (www.