Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.

Silencing of lncRNA Gm26917 Attenuates Alveolar Macrophage-mediated Inflammatory Response in LPS-induced Acute Lung Injury Via Inhibiting NKRF Ubiquitination.

The inflammatory response mediated by alveolar macrophages plays a crucial role in the development of acute lung injury. Numerous studies have reported that lncRNAs are highly expressed in acute lung injury in mouse models and cell lines, and acute lung injury (ALI) can be effectively alleviated by targeting these lncRNAs. The aim of this study was to explore the mechanism by LncRNA Gm26917 regulates the inflammatory response in alveolar macrophages during acute lung injury mouse model.

The role of MEGF10 in myoblast fusion and hypertrophic response to overload of skeletal muscle.

Biallelic mutations in multiple EGF domain protein 10 (MEGF10) gene cause EMARDD (early myopathy, areflexia, respiratory distress and dysphagia) in humans, a severe recessive myopathy, associated with reduced numbers of PAX7 positive satellite cells. To better understand the role of MEGF10 in satellite cells, we overexpressed human MEGF10 in mouse H-2k-tsA58 myoblasts and found that it inhibited fusion. Addition of purified extracellular domains of human MEGF10, with (ECD) or without (EGF) the N-terminal EMI domain to H-2k-tsA58 myoblasts, showed that the ECD was more effective at reducing myoblast adhesion and fusion by day 7 of differentiation, yet promoted adhesion of myoblasts to non-adhesive surfaces, highlighting the importance of the EMI domain in these behaviours.

Prognostic significance of right subdiaphragmatic washing cytology in patients with endometrial cancer.

Cancer cells in the right subdiaphragmatic lavage may reflect peritoneal dissemination, but its prognostic significance is unknown. This study investigated recurrence-free survival (RFS), overall survival (OS), and recurrence patterns in patients with curatively resected endometrial cancer by cytology collection site. Peritoneal cytology was collected at the beginning of surgery by washing the pelvic and right subdiaphragmatic cavity separately.

Simulated deep space exposure on seeds utilizing the MISSE flight facility.

The MISSE-Seed project was designed to investigate the effects of space exposure on seed quality and storage. The project tested the Multipurpose Materials International Space Station Experiment-Flight Facility (MISSE-FF) hardware as a platform for exposing biological samples to the space environment outside the International Space Station (ISS). Furthermore, it evaluated the capability of a newly designed passive sample containment canister as a suitable exposure unit for biological samples for preserving their vigor while exposing to the space environment to study multi-stressor effects.

A biophysical basis for the spreading behavior and limited diffusion of Xist.

Xist RNA initiates X inactivation as it spreads in cis across the chromosome. Here, we reveal a biophysical basis for its cis-limited diffusion. Xist RNA and HNRNPK together drive a liquid-liquid phase separation (LLPS) that encapsulates the chromosome.

Aberrant acetylation caused by a CDYL splicing mutation contributes to thin mid-piece related asthenoteratozoospermia and male infertility.

Objectives: Acetylated tubulin is a hallmark of flagellar stability in spermatozoa, and studies have demonstrated the ability of CDYL to function as a tubulin acetyltransferase in spermatozoa. Of note, germline conditional knockout of Cdyl can lead to asthenoteratozoospermia and infertility in male mice. However, the role of CDYL gene in human fertility remains uncharacterized.

Development of Functional and Hydrolytically Stable Vinyl Monomers as Methacrylate Dental Resin Restorative Alternatives.

Dental resin-based restorative (RBR) materials represent the most ubiquitous biomaterials utilized globally. Methacrylate (MA)-ester based monomers - present in RBRs since the 1960s - experience significantly elevated rates of failure compared to previously used silver/amalgam fillings attributed to their hydrolysis reported in both simulated and in vivo environments. There is currently no alternative RBR chemistry that matches the functional and clinical workflow considerations of MA-RBRs while addressing their limited-service lives.

Association between choroidal microvasculature in the eye and Alzheimer's disease risk in cognitively healthy mid-life adults: A pilot study.

Introduction: We explored associations between measurements of the ocular choroid microvasculature and Alzheimer's disease (AD) risk.

Methods: We measured the choroidal vasculature appearing in optical coherence tomography (OCT) scans of 69 healthy, mid-life individuals in the PREVENT Dementia cohort. The cohort was prospectively split into low-, medium-, and high-risk groups based on the presence of known risk factors (apolipoprotein E [] ε4 genotype and family history of dementia [FH]).

Association of Total Mortality and Cardiovascular Endpoints With the Timing of the First and Second Systolic Peak of the Aortic Pulse Wave.

Prognostic significance of the timing in the cardiac cycle of the first (TP1) and second (TP2) systolic peak of the central aortic pulse wave is ill-defined. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of adverse health outcomes associated with TP1 and TP2, estimated by the SphygmoCor software, were assessed in the International Database of Central Arterial Properties for Risk Stratification (IDCARS) (n = 5529). Model refinement was assessed by the integrated discrimination (ID) and net reclassification (NR) improvement.

Laparoscopic jejunostomy during McKeown minimally invasive esophagectomy: a propensity score analysis.

Background: Nutrition is a key factor limiting the rapid recovery of patients undergoing esophagectomy, but there is as yet no consensus on the optimal route of nutritional support. This study aimed to evaluate the potential benefits of laparoscopic jejunostomy (Lap-J) in comparison to conventional nasoenteral tube (NT) feeding in patients who underwent McKeown minimally invasive esophagectomy (MIE).

Methods: A total of 577 consecutive patients with esophageal squamous cell carcinoma (ESCC) who underwent McKeown MIE were included in this single-center retrospective study.

Development and current status of anti-reflux esophagogastrostomy after proximal gastrectomy: a literature review.

Background: The selection of an appropriate gastrointestinal (GI) reconstruction procedure after proximal gastrectomy (PG) has long been a challenge. Surgeons have had a long history of exploring anti-reflux gastroesophageal anastomosis. The aim of this article is to systematically summarize the anti-reflux principles of GI reconstructive procedures through a review of the previous literature and to provide a theoretical basis for clinicians to select or innovate procedures.

Efficacy and tolerability of neoadjuvant therapy with Talimogene laherparepvec in cutaneous basal cell carcinoma: a phase II trial (NeoBCC trial).

We present a single-arm, phase II, neoadjuvant trial with the oncolytic virus talimogene laherparepvec (T-VEC) in 18 patients with difficult-to-resect cutaneous basal cell carcinomas. The primary end point, defined as the proportion of patients, who after six cycles of T-VEC (13 weeks), become resectable without the need for plastic reconstructive surgery, was already achieved after stage I (9 of 18 patients; 50.0%); thus the study was discontinued for early success.

Motion-Onset Visually Evoked Potentials (VEPs) are Amplified in The Deaf.

The loss of a sensory modality triggers a phenomenon known as cross-modal plasticity, where areas of the brain responsible for the lost sensory modality are reorganized and repurposed to the benefit of the remaining modalities. After perinatal or congenital deafness, superior visual motion detection abilities have been psychophysically identified in both humans and cats, and this advantage has been causally demonstrated to be mediated by reorganized auditory cortex. In our study, we investigated visually evoked potentials (VEPs) in response to motion-onset stimuli of varying speeds in both hearing and perinatally deafened cats under light anesthesia.

Chapter 6: SYNDROMIC PRIMARY HYPERPARATHYROIDISM.

Syndromic primary hyperparathyroidism has several features in common: younger age at diagnosis when compared with sporadic primary hyperparathyroidism, often synchronous or metachronous multi-glandular involvement, higher possibility of recurrence, association with other endocrine or extra-endocrine disorders, and suggestive family background with autosomal dominant inheritance. Hyperparathyroidism in multiple endocrine neoplasia type 1 is the most common syndromic hyperparathyroidism. It is often asymptomatic in adolescents and young adults, but may be responsible for recurrent lithiasis and/or bone loss.

Exit interviews from two randomised placebo-controlled phase 3 studies with caregivers of young children with autism spectrum disorder.

Introduction: Autism spectrum disorder (ASD) is characterised by difficulty with social communication and restricted, repetitive patterns of behaviour. This study aimed to improve understanding of the ASD patient experience with the treatment (bumetanide) regarding the changes in core symptoms and to assess changes considered as meaningful. To achieve this, qualitative interviews were conducted with caregivers of patients in two phase 3 clinical trials (NCT03715153; NCT03715166) of a novel ASD treatment.

Recombinant Klotho administration after myocardial infarction reduces ischaemic injury and arrhythmias by blocking intracellular calcium mishandling and CaMKII activation.

Ischaemic heart disease (IHD) remains a major cause of death and morbidity. Klotho is a well-known anti-ageing factor with relevant cardioprotective actions, at least when renal dysfunction is present, but its actions are much less known when renal function is preserved. This study investigated Klotho as a biomarker and potential novel treatment of IHD-associated complications after myocardial infarction (MI) under preserved renal function.

Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis.

A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions.

Reflections on a Dobutamine Shortage in an Academic Health System: A Roadmap for Risk Reduction.

In a landscape of increasingly frequent and severe drug shortages, this article describes an interdisciplinary strategy for managing a nationwide shortage of dobutamine in an academic health system. The authors outline an approach that centers on leveraging information technology resources, minimizing waste, conserving supply, and centralizing supply. These efforts, which enabled the organization to consistently supply dobutamine to those patients who needed it most, could form a model for health systems to follow during future drug shortages.

Feature selectivity of corticocortical feedback along the primate dorsal visual pathway.

Anatomical studies have revealed a prominent role for feedback projections in the primate visual cortex. Theoretical models suggest that these projections support important brain functions, like attention, prediction, and learning. However, these models make different predictions about the relationship between feedback connectivity and neuronal stimulus selectivity.

Early Postpartum Metabolic Heterogeneity Among Women Who Progressed to Type 2 Diabetes After Gestational Diabetes: A Prospective Cohort.

Aims: Gestational diabetes mellitus (GDM) poses a significant risk for developing type 2 diabetes mellitus (T2D) and exhibits heterogeneity. However, understanding the link between different types of post-GDM individuals without diabetes and their progression to T2D is crucial to advance personalised medicine approaches.

Materials And Methods: We employed a discovery-based unsupervised machine learning clustering method to generate clustering models for analysing metabolomics, clinical, and biochemical datasets.

Biomechanical analysis of a short femoral stem used in revision total hip replacement of a standard femoral stem.

Short-stem total hip arthroplasty (SHA) has become popular because it preserves femoral bone stock and enables the use of short femoral stems in revision total hip arthroplasty (THA). However, no study has evaluated whether a short stem in revision THA, replacing a standard stem, can provide adequate primary stability to facilitate osseous integration. In this biomechanical study, a metaphyseal anchoring SHA (Tri-Lock BPS) stem and a standard THA (Corail) stem were implanted into ten composite femurs and loaded dynamically from 300 to 1700 N with 1 Hz.

Association between acetabular coverage over femoral head and rate of joint space narrowing in non-arthritic hips.

Aims: This study was performed to investigate the association between the acetabular morphology and the joint space narrowing rate (JSNR) in the non-arthritic hip.

Methods: We retrospectively reviewed standing whole-leg radiographs of patients who underwent knee arthroplasty from February 2012 to March 2020 at our institute. Patients with a history of hip surgery, Kellgren-Lawrence grade ≥ II hip osteoarthritis, or rheumatoid arthritis were excluded.

The chromatin remodeler ADNP regulates neurodevelopmental disorder risk genes and neocortical neurogenesis.

Although chromatin remodelers are among the most important risk genes associated with neurodevelopmental disorders (NDDs), the roles of these complexes during brain development are in many cases unclear. Here, we focused on the recently discovered ChAHP chromatin remodeling complex. The zinc finger and homeodomain transcription factor ADNP is a core subunit of this complex, and de novo mutations lead to intellectual disability and autism spectrum disorder.

Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections.

Whether Omicron exposures could overcome ancestral SARS-CoV-2 immune imprinting remains controversial. Here we analyzed B cell responses evoked by sequential Omicron infections in vaccinated and unvaccinated individuals. Plasma neutralizing antibody titers against ancestral SARS-CoV-2 and variants indicate that immune imprinting is not consistently induced by inactivated or recombinant protein vaccines.