Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing.

While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile.

Development of an automated 3D high content cell screening platform for organoid phenotyping.

The use of organoid models in biomedical research has grown substantially since their inception. As they gain popularity among scientists seeking more complex and biologically relevant systems, there is a direct need to expand and clarify potential uses of such systems in diverse experimental contexts. Herein we outline a high-content screening (HCS) platform that allows researchers to screen drugs or other compounds against three-dimensional (3D) cell culture systems in a multi-well format (384-well).

Efficacy and Safety of a Preservative-Free Latanoprost Cationic Emulsion in Patients with Open-Angle Glaucoma and Concurrent Ocular Surface Disease: A Randomized Phase 2 Study.

To compare intraocular pressure (IOP), ocular surface disease (OSD) parameters, and safety in patients with open-angle glaucoma (OAG)/ocular hypertension (OH) and concurrent OSD treated with preservative-free latanoprost 0.005% cationic emulsion (PF-latanoprost-E) or travoprost-Z 0.004% ophthalmical solution containing a soft preservative system.

Mapping the genetic landscape establishing a tumor immune microenvironment favorable for anti-PD-1 response in mice and humans.

Identifying host genetic factors modulating immune checkpoint inhibitor (ICI) efficacy has been experimentally challenging because of variations in both host and tumor genomes, differences in the microbiome, and patient life exposures. Utilizing the Collaborative Cross (CC) multi-parent mouse genetic resource population, we developed an approach that fixes the tumor genomic configuration while varying host genetics. With this approach, we discovered that response to anti-PD-1 (aPD1) immunotherapy was significantly heritable in four distinct murine tumor models ( between 0.

Single nucleus transcriptomics, pharmacokinetics, and pharmacodynamics of combined CDK4/6 and mTOR inhibition in a phase 0/1 trial of recurrent high-grade glioma.

Outcomes for adult patients with a high-grade glioma continue to be dismal and new treatment paradigms are urgently needed. To optimize the opportunity for discovery, we performed a phase 0/1 dose-escalation clinical trial that investigated tumor pharmacokinetics, pharmacodynamics, and single nucleus transcriptomics following combined ribociclib (CDK4/6 inhibitor) and everolimus (mTOR inhibitor) treatment in recurrent high-grade glioma. Patients with a recurrent high-grade glioma (n = 24) harboring 1) / deletion or / amplification, 2) loss or mutations, and 3) wild-type retinoblastoma protein (Rb) were enrolled.

Challenging Dogma by Skipping the Emergency Department Thoracotomy: A Propensity Score Matched Analysis of the Trauma Quality Improvement Database.

Introduction: Survival following emergency department thoracotomy (EDT) for patients in extremis is poor. Whether intervention in the operating room instead of EDT in select patients could lead to improved outcomes is unknown. We hypothesized that patients who underwent intervention in the operating room would have improved outcomes compared to those who underwent EDT.

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations.

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics.

Self-Sustainable IoT-Based Remote Sensing Powered by Energy Harvesting Using Stacked Piezoelectric Transducer and Thermoelectric Generator.

We propose a self-powered remote multi-sensing system for traffic sensing which is powered by the collective energy harvested from the mechanical vibration of the road caused by the passing vehicles and from the temperature gradient between the asphalt of the road and the soil underneath. A stacked piezoelectric transducer converts mechanical vibrations into electrical energy and a thermoelectric generator harvests the thermal energy from the thermal gradient. Electrical energy signals from the stacked piezoelectric transducer and the thermoelectric generators are converted into usable DC power to recharge the battery using AC-DC and DC-DC converters working simultaneously.

The COVID-19 pandemic has not changed stage at presentation nor treatment patterns of head and neck cancer: A retrospective cohort study.

Objectives: To evaluate the impact of the COVID-19 lockdown measures on HNC, by comparing the stage at presentation and treatment of HNC before and after the most severe COVID-19 restrictions.

Design: A retrospective cohort study.

Setting: A regional cancer network serving a patient population of 2.

Single-cell analysis of endometriosis reveals a coordinated transcriptional programme driving immunotolerance and angiogenesis across eutopic and ectopic tissues.

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus. It affects many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, which limits early diagnosis and treatment.

Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.

A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates.

Background complexity can mitigate poor camouflage.

Avoiding detection through camouflage is often key to survival. However, an animal's appearance is not the only factor affecting conspicuousness: background complexity also alters detectability. This has been experimentally demonstrated for both artificially patterned backgrounds in the laboratory and natural backgrounds in the wild, but only for targets that already match the background well.

Targeting p21 highly expressing cells in adipose tissue alleviates insulin resistance in obesity.

Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2 diabetes. Limited mechanism-based strategies exist to alleviate insulin resistance. Here, using single-cell transcriptomics, we identify a small, critically important, but previously unexamined cell population, p21 highly expressing (p21) cells, which accumulate in adipose tissue with obesity.

Neurokinin B-Expressing Neurons of the Central Extended Amygdala Mediate Inhibitory Synaptic Input onto Melanin-Concentrating Hormone Neuron Subpopulations.

The lateral hypothalamic area (LHA) is a highly conserved brain region critical for maintaining physiological homeostasis and goal-directed behavior. LHA neurons that express melanin-concentrating hormone (MCH) are key regulators of arousal, energy balance, and motivated behavior. However, cellular and functional diversity among LHA neurons is not well understood.

A case of Clival Tuberculosis and associated meningitis.

Herein we report a 30-year-old man presenting with fevers, headaches and weight loss. On admission he was disorientated and demonstrated no focal signs of neurological deficit. Magnetic resonance imaging revealed a large area of abnormal bone marrow signal centred within the clivus with extension into the sphenoid sinus and signs of associated basal meningitis.

Somatostatin-expressing parafacial neurons are CO/H sensitive and regulate baseline breathing.

Glutamatergic neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating breathing in response to tissue CO/H. The RTN and greater parafacial region may also function as a chemosensing network composed of CO/H-sensitive excitatory and inhibitory synaptic interactions. In the context of disease, we showed that loss of inhibitory neural activity in a mouse model of Dravet syndrome disinhibited RTN chemoreceptors and destabilized breathing (Kuo et al.

Mydriasis with micro-array print touch-free tropicamide-phenylephrine fixed combination MIST: pooled randomized Phase III trials.

Prospective, double-masked, controlled, cross-over superiority studies. Eligible volunteers in two pooled Phase III trials received microdosed mydriatics. MIST-1 study subjects received fixed-combination TR-PH, phenylephrine 2.

The role of antibiotics in the surgical management of paediatric obstructive sleep apnoea (OSA): a cohort study.

Purpose: Obstructive sleep apnoea (OSA) describes an irregular night-time breathing pattern that is present in approximately 1.8% of children and can have a negative impact on quality of life. The use of antibiotics postoperatively is controversial.

Delivering online alternatives to the anatomy laboratory: Early experience during the COVID-19 pandemic.

Social distancing measures due to the COVID-19 pandemic will make anatomy dissecting room practicals difficult, if not impossible to run at some institutions in the upcoming academic year. The learning community that exists within physical anatomy practicals needs to be moved online. Virtual replacement of visuo-spatial and social elements of learning anatomy pose particular challenges to educators.

Dissecting a department of surgery: Exploring organizational culture and competency expectations.

Introduction: In order to recruit high-potential trainees, surgery residency and fellowship programs must first understand what competencies and attributes are required for success in their respective programs. This study performed a systematic analysis to define organizational culture and competency expectations across training programs within one academic surgery department.

Methods: Subject matter experts rated the importance and frequency of 22 competencies and completed a 44-item organizational culture inventory along 1 to 5 Likert-type scales.

Cellular taxonomy and spatial organization of the murine ventral posterior hypothalamus.

The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance, and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single-cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell populations in the mouse VPH.