A machine learning approach identifies cellular senescence on transcriptome data of human cells in vitro.

Although cellular senescence has been recognized as a hallmark of aging, it is challenging to detect senescence cells (SnCs) due to their high level of heterogeneity at the molecular level. Machine learning (ML) is likely an ideal approach to address this challenge because of its ability to recognize complex patterns that cannot be characterized by one or a few features, from high-dimensional data. To test this, we evaluated the performance of four ML algorithms including support vector machines (SVM), random forest (RF), decision tree (DT), and Soft Independent Modelling of Class Analogy (SIMCA), in distinguishing SnCs from controls based on bulk RNA sequencing data.

miR-96-5p expression is sufficient to induce and maintain the senescent cell fate in the absence of stress.

Senescence is a cell fate driven by different types of stress that results in exit from the cell cycle and expression of an inflammatory senescence-associated secretory phenotype (SASP). Here, we demonstrate that stable overexpression of miR-96-5p was sufficient to induce cellular senescence in the absence of genotoxic stress, inducing expression of certain markers of early senescence including SASP factors while repressing markers of deep senescence including LINE-1 and type 1 interferons. Stable miR-96-5p overexpression led to genome-wide changes in heterochromatin followed by epigenetic activation of p16, p21, and SASP expression, induction of a marker of DNA damage, and induction of a transcriptional signature similar to other senescent lung and endothelial cell types.

Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge.

Persistence of a Frameshifting Deletion in SARS-CoV-2 ORF7a for the Duration of a Major Outbreak.

Australia experienced widespread COVID-19 outbreaks from infection with the SARS-CoV-2 Delta variant between June 2021 and February 2022. A 17-nucleotide frameshift-inducing deletion in ORF7a rapidly became represented at the consensus level (Delta-ORF7a) in most Australian outbreak cases. Studies from early in the COVID-19 pandemic suggest that frameshift-inducing deletions in ORF7a do not persist for long in the population; therefore, Delta-ORF7a genomes should have disappeared early in the Australian outbreak.

Ghost Fat: Altered Female Body Perception After Bariatric Surgery.

Body perception is an individual's ability to recognize their body in attitudinal and/or dimensional aspects. We investigated women's body perceptions before and after bariatric surgery. Participants were 31 women ( age = 36.

The microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies.

The pathogenesis of human leukocyte antigen (HLA)-B27-associated diseases such as acute anterior uveitis (AAU) and ankylosing spondylitis (AS) remains poorly understood, though Gram-negative bacteria and subclinical bowel inflammation are strongly implicated. Accumulating evidence from animal models and clinical studies supports several hypotheses, including HLA-B27-dependent dysbiosis, altered intestinal permeability, and molecular mimicry. However, the existing literature is hampered by inadequate studies designed to establish causation or uncover the role of viruses and fungi.

Strategic Encounters in Innovation and Regulation: Healthcare Transformation in the Era of Digital Connectivity Comment on "What Managers Find Important for Implementation of Innovations in the Healthcare Sector - Practice Through Six Management Perspectives".

Healthcare innovations emerge and develop in institutionally dense selective environments. New projects and propositions in healthcare sectoral ecosystems can be understood as product-service compacts, that is, complex solutions that dynamically integrate tangible and intangible elements in close interaction with users' needs and the evolving regulatory context under uncertainty and ambiguity. We advance the concept of "strategic encounters" to encapsulate, capitalise and extend the contribution by Palm and Fischier's on the key enabling managerial factors for healthcare innovation implementation under conditions of imperfect foresight.

Long-term comparison between blind and ultrasound-guided corticoid injections in Morton neuroma.

Objectives: This work compares the effectiveness of blind versus ultrasound (US)-guided injections for Morton neuroma (MN) up to 3 years of follow-up.

Methods: This is an evaluator-blinded randomised trial in which 33 patients with MN were injected by an experienced orthopaedic surgeon based on anatomical landmarks (blind injection, group 1) and 38 patients were injected by an experienced musculoskeletal radiologist under US guidance (group 2). Patients were assessed using the visual analogue scale and the Manchester Foot Pain and Disability index (MFPDI).

Serine 26 in Early Growth Response-1 Is Critical for Endothelial Proliferation, Migration, and Network Formation.

Background Vascular endothelial cell proliferation, migration, and network formation are key proangiogenic processes involving the prototypic immediate early gene product, Egr-1 (early growth response-1). Egr-1 undergoes phosphorylation at a conserved Ser26 but its function is completely unknown in endothelial cells or any other cell type. Methods and Results A CRISPR/Cas9 strategy was used to introduce a homozygous Ser26>Ala mutation into endogenous Egr-1 in human microvascular endothelial cells.

Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging.

Aging drives progressive loss of the ability of tissues to recover from stress, partly through loss of somatic stem cell function and increased senescent burden. We demonstrate that bone marrow-derived mesenchymal stem cells (BM-MSCs) rapidly senescence and become dysfunctional in culture. Injection of BM-MSCs from young mice prolonged life span and health span, and conditioned media (CM) from young BM-MSCs rescued the function of aged stem cells and senescent fibroblasts.

Truncated YY1 interacts with BASP1 through a 339KLK341 motif in YY1 and suppresses vascular smooth muscle cell growth and intimal hyperplasia after vascular injury.

Aims: In-stent restenosis and late stent thrombosis are complications associated with the use of metallic and drug-coated stents. Strategies that inhibit vascular smooth muscle cell (SMC) proliferation without affecting endothelial cell (EC) growth would be helpful in reducing complications arising from percutaneous interventions. SMC hyperplasia is also a pathologic feature of graft stenosis and fistula failure.

Thermostable small-molecule inhibitor of angiogenesis and vascular permeability that suppresses a pERK-FosB/ΔFosB-VCAM-1 axis.

Vascular permeability and angiogenesis underpin neovascular age-related macular degeneration and diabetic retinopathy. While anti-VEGF therapies are widely used clinically, many patients do not respond optimally, or at all, and small-molecule therapies are lacking. Here, we identified a dibenzoxazepinone BT2 that inhibits endothelial cell proliferation, migration, wound repair in vitro, network formation, and angiogenesis in mice bearing Matrigel plugs.

Ancient genomes in South Patagonia reveal population movements associated with technological shifts and geography.

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data.

Predicting habitat use by the Argentine hake Merluccius hubbsi in a warmer world: inferences from the Middle Holocene.

Fish skeletal remains recovered from two archaeological sites dated in the Middle Holocene of Tierra del Fuego (Argentina) were analysed to describe habitat use patterns by hake in the past and predict changes in a warmer world. Mitochondrial DNA was successfully extracted and amplified from 42 out of 45 first vertebra from ancient hake and phylogenetic analysis assigned all haplotypes to Argentine hake (Merluccius hubbsi). According to osteometry, the Argentine hake recovered from the archaeological site were likely adults ranging 37.

SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs.

Cell senescence is one of the hallmarks of aging known to negatively influence a healthy lifespan. Drugs able to kill senescent cells specifically in cell culture, termed senolytics, can reduce the senescent cell burden in vivo and extend healthspan. Multiple classes of senolytics have been identified to date including HSP90 inhibitors, Bcl-2 family inhibitors, piperlongumine, a FOXO4 inhibitory peptide and the combination of Dasatinib/Quercetin.

Extracellular signal-regulated kinase-1 phosphorylates early growth response-1 at serine 26.

Egr-1, an immediate-early gene product and master regulator was originally described as a phosphoprotein following its discovery in the 1980s. However specific residue(s) phosphorylated in Egr-1 remain elusive. Here we phosphorylated recombinant Egr-1 in vitro with ERK1 prior to mass spectrometry, which identified phosphorylation of Ser and Ser with the latter ∼12 times more abundant than Ser.

Role of imaging methods in diagnosis and treatment of Morton's neuroma.

Among the many causes of forefoot pain, Morton's neuroma (MN) is often suspected, particularly in women, due to its high incidence. However, there remain controversies about its relationship with symptomatology and which diagnostic and treatment choices to choose. This article mainly focuses on the role of the various imaging methods and their abilities to support an accurate diagnosis of MN, ruling out other causes of forefoot pain, and as a way of providing targeted imaging-guided therapy for patients with MN.

Osteoporotic vertebral endplate and cortex fractures: A pictorial review.

Unlabelled: Despite years' research, the radiographic criteria for osteoporotic vertebral fracture and its grading remain debated. The importance of identifying vertebral endplate/cortex fracture (ECF) is being recognised; however, evaluation of osteoporotic ECF requires training and experience. This article aims to serve as a teaching material for radiologists/physicians or researchers to evaluate osteoporotic ECF.

CT-guided radiofrequency ablation in patients with aneurysmal bone cysts.

Introduction: Aneurysmal bone cyst (ABC) is one of most therapeutic challenging lesions for orthopedic surgeons specially in large-sized lesions and lesions, which are very close to important neurovascular structures. In the present study, we express our experience in the treatment of aneurysmal bone cyst by radiofrequency thermal ablation (RFTA).

Methods: In the last two years, we have treated 20 cases (12 males & 8 females) presented with painful aneurysmal bone cysts in different anatomical locations, the age mean (±SD) is 18.

Developing Neolignans as Proangiogenic Agents: Stereoselective Total Syntheses and Preliminary Biological Evaluations of the Four Guaiacylglycerol 8--4'-Coniferyl Ethers.

Stereoselective total syntheses of the four stereoisomeric forms of guaiacylglycerol 8--4'-coniferyl ether, viz., compounds , -, , and -, have been established. The key step involves an Evans/Seebach auxiliary-controlled and syn-selective aldol process followed, in the reaction sequences leading to the anti-compounds, by a Mitsunobu reaction involving a benzylic alcohol residue.

Identifying osteoporotic vertebral endplate and cortex fractures.

Osteoporosis is the most common metabolic bone disease, and vertebral fractures (VFs) are the most common osteoporotic fracture. A single atraumatic VF may lead to the diagnosis of osteoporosis. Prevalent VFs increase the risk of future vertebral and non-vertebral osteoporotic fracture independent of bone mineral density (BMD).

Taking advantage of an unerupted third molar: a case report.

Introduction:: Treatments with dental surgery seek to displace tooth to the correct position within the dental arch.

Objective:: To report a clinical case that took advantage of an unerupted third molar.

Case History:: A male patient, 18 years of age, was referred by his dentist to evaluate the third molars.

The Association between t-PA Administration and In-Hospital Mortality following Acute Ischemic Stroke in Puerto Rican Patients.

Objective: Despite being the standard of care, thrombolytic therapy with tissue plasminogen activator (t-PA) is currently administered to only 5% of acute ischemic stroke (AIS) patients in the United States. Published scientific information regarding both the use of t-PA for AIS in Hispanic patients and its impact on short-term mortality is scarce. The objectives of this study are to investigate, among Puerto Rican patients hospitalized with AIS, the rate of t-PA administration, and the risk of in-hospital mortality in patients who received t-PA vs.

Temperature and toxic Tau in Alzheimer's disease: new insights.

Alzheimer's disease (AD), the most common dementia in the elderly, is characterized by cognitive impairment and severe autonomic symptoms such as disturbance in core body temperature (Tc), which may be predictors or early events in AD onset. Inclusions of phosphorylated Tau (p-Tau) are a hallmark of AD and other neurodegenerative disorders called "Tauopathies." Animal and human studies show that anesthesia augments p-Tau levels through reduction of Tc, with implications for AD.