Th17-inducing dendritic cell vaccines stimulate effective CD4 T cell-dependent antitumor immunity in ovarian cancer that overcomes resistance to immune checkpoint blockade.

Background: Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing.

Discovery of , a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist.

Transient receptor potential ankyrin 1 (TRPA1) is a voltage-dependent, ligand-gated ion channel, and activation thereof is linked to a variety of painful conditions. Preclinical studies have demonstrated the role of TRPA1 receptors in a broad range of animal models of acute, inflammatory, and neuropathic pain. In addition, a clinical study using the TRPA1 antagonist GRC-17536 (Glenmark Pharmaceuticals) demonstrated efficacy in a subgroup of patients with painful diabetic neuropathy.

Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia.

Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model.

Self-diffusion in inhomogeneous granular shearing flows.

In this Letter, we discuss how flow inhomogeneity affects the self-diffusion behavior in granular flows. Whereas self-diffusion scalings have been well characterized in the past for homogeneous shearing, the effect of shear localization and nonlocality of the flow has not been studied. We, therefore, present measurements of self-diffusion coefficients in discrete numerical simulations of steady, inhomogeneous, and collisional shearing flows of nearly identical, frictional, and inelastic spheres.

How vertical oscillatory motion above a saturated sand bed leads to heap formation.

We show how oscillations in fluid flow over a fluid-saturated and porous sediment bed leads to the development of a bedform. To understand the role of pressure fluctuations on the bed associated with flow oscillations, we analyze how the flow penetrates into and through the bed. We then calculate the corresponding vertical pressure gradients within the bed that tend to expand the bed along the vertical direction.

Watchman FLX Implantation for Challenging Left Atrial Appendage Anatomy: Case-Based Discussion.

Left atrial appendage (LAA) occlusion devices provided an acceptable and valid alternative to anticoagulation among patients with atrial fibrillation who carry high bleeding risk. Watchman device is non-inferior to oral anticoagulation to prevent cerebrovascular accidents. The presence of a longer distal portion of the older generation Watchman led to exclusion of patients with prohibitive anatomy of the LAA such as chicken-wing morphology or shallow LAA.

Vertebral Artery Interventions: A Comprehensive Updated Review.

Patients with posterior circulation ischemia due to vertebral artery stenosis account for 20 to 25% of ischemic strokes and have an increased risk of recurrent stroke. In patients treated with medical therapy alone, the risk of recurrence is particularly increased in the first few weeks after symptoms occur, with an annual stroke rate of 10 to 15%. Additionally, obstructive disease of the vertebrobasilar system carries a worse prognosis, with a 30% mortality at 2-years if managed medically without additional surgical or endovascular intervention.

Self-diffusion scalings in dense granular flows.

We report on measurements of self-diffusion coefficients in discrete numerical simulations of steady, homogeneous, collisional shearing flows of nearly identical, frictional, inelastic spheres. We focus on a range of relatively high solid volume fractions that are important in those terrestrial gravitational shearing flows that are dominated by collisional interactions. Diffusion over this range of solid fraction has not been well characterized in previous studies.

A remnant planetary core in the hot-Neptune desert.

The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors.

Evolutionary temperature compensation of carbon fixation in marine phytoplankton.

The efficiency of carbon sequestration by the biological pump could decline in the coming decades because respiration tends to increase more with temperature than photosynthesis. Despite these differences in the short-term temperature sensitivities of photosynthesis and respiration, it remains unknown whether the long-term impacts of global warming on metabolic rates of phytoplankton can be modulated by evolutionary adaptation. We found that respiration was consistently more temperature dependent than photosynthesis across 18 diverse marine phytoplankton, resulting in universal declines in the rate of carbon fixation with short-term increases in temperature.

A low-mass planet candidate orbiting Proxima Centauri at a distance of 1.5 AU.

Our nearest neighbor, Proxima Centauri, hosts a temperate terrestrial planet. We detected in radial velocities evidence of a possible second planet with minimum mass sin = 5.8 ± 1.

Chest computed tomography for staging renal tumours: validation and simplification of a risk prediction model from a large contemporary retrospective cohort.

Objectives: To externally validate a nomogram recently proposed by Larcher et al. (BJU Int. 2017; 120: 490) and to develop a simplified model with comparable accuracy to guide on the need for staging chest computed tomography (CT) for patients with new renal masses.

Efficacy and Safety of Transcarotid Transcatheter Aortic Valve Replacement: A Systematic Review.

Background: In patients who are not suitable for traditional access routes for transcatheter aortic valve replacement (TAVR) due to severe peripheral vascular disease (PVD) or prohibitive surgical risk, carotid artery (CA) access is an emerging route for TAVR. This study represents the most up to date on outcomes of carotid access TAVR.

Methods: A systematic review was conducted as per the Preferred Reporting Instructions for Systematic Reviews and Meta-analysis (PRISMA).

Percutaneous endovascular abdominal aneurysm repair: State-of-the art.

Endovascular repair of abdominal aortic aneurysms emerged initially as an alternative treatment strategy for patients considered to be inoperable or high risk for surgery. The evolution of endovascular techniques has made this technology a safe and less invasive alternative to open surgery for patients with suitable aortic anatomy. This manuscript reviews the current state of the art for endovascular AAA repair techniques, clinical outcomes, guideline recommendations, and future applications.

The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8 T Cell Fitness and Functionality.

Tissue-resident memory CD8 T (Trm) cells share core residency gene programs with tumor-infiltrating lymphocytes (TILs). However, the transcriptional, metabolic, and epigenetic regulation of Trm cell and TIL development and function is largely undefined. Here, we found that the transcription factor Bhlhe40 was specifically required for Trm cell and TIL development and polyfunctionality.

Bedforms Produced on a Particle Bed by Vertical Oscillations of a Plate.

We describe a new mechanism that produces bedforms and characterize the conditions under which it operates. The mechanism is associated with pressure gradients generated in a fluid saturated particle bed by a plate oscillating in the water above it. These vertical pressure gradients cause oscillatory bed failure.

Erodible, granular beds are fragile.

Geophysical flows that involve the transport of grains and the shearing of colloids and non-Brownian suspensions often take place above a substrate composed of the same particles that can be incorporated into the flow. Despite the importance of understanding such erodible beds to the phrasing of appropriate boundary conditions for the solution of continuum models, a rigorous definition of the erodible bed and the constitutive relations for the stresses within it are still lacking. Here, we use discrete-element simulations to show that the intense, intermittent forming and breaking of contact chains marks the transition to the erodible bed at a critical solid volume fraction, as in shear jamming of steady, homogeneous flows.

Unintentional removal of a developing permanent premolar during primary molar extraction: a 10-year case report.

A 14-year-old girl underwent extraction of an ankylosed primary left second molar as requested by her orthodontist. The developing mandibular left second premolar (tooth 20) was unintentionally removed during extraction of the primary molar. Immediate measures were taken to reimplant tooth 20.

Myosin efflux promotes cell elongation to coordinate chromosome segregation with cell cleavage.

Chromatid segregation must be coordinated with cytokinesis to preserve genomic stability. Here we report that cells clear trailing chromatids from the cleavage site by undergoing two phases of cell elongation. The first phase relies on the assembly of a wide contractile ring.

Surgeon leadership in the coding, billing, and contractual negotiations for fenestrated endovascular aortic aneurysm repair increases medical center contribution margin and physician reimbursement.

Background: Fenestrated endovascular aneurysm repair (FEVAR) allows endovascular treatment of thoracoabdominal and juxtarenal aneurysms previously outside the indications of use for standard devices. However, because of considerable device costs and increased procedure time, FEVAR is thought to result in financial losses for medical centers and physicians. We hypothesized that surgeon leadership in the coding, billing, and contractual negotiations for FEVAR procedures will increase medical center contribution margin (CM) and physician reimbursement.

What Works in the Treatment of Borderline Personality Disorder.

Purpose Of The Review: This review summarizes advances in treatments for adults with borderline personality disorder (BPD) in the last 5 years.

Recent Findings: Evidence-based advances in the treatment of BPD include a delineation of generalist models of care in contrast to specialist treatments, identification of essential effective elements of dialectical behavioral therapy (DBT), and the adaptation of DBT treatment to manage post-traumatic stress disorder (PTSD) and BPD. Studies on pharmacological interventions remain limited and have not provided evidence that any specific medications can provide stand-alone treatment.

Steering surface topographies of electrospun fibers: understanding the mechanisms.

A profound understanding of how to tailor surface topographies of electrospun fibers is of great importance for surface sensitive applications including optical sensing, catalysis, drug delivery and tissue engineering. Hereby, a novel approach to comprehend the driving forces for fiber surface topography formation is introduced through inclusion of the dynamic solvent-polymer interaction during fiber formation. Thus, the interplay between polymer solubility as well as computed fiber jet surface temperature changes in function of time during solvent evaporation and the resultant phase separation behavior are studied.

Erosion and deposition in depth-averaged models of dense, dry, inclined, granular flows.

We derive expressions for the rates of erosion and deposition at the interface between a dense, dry, inclined granular flow and an erodible bed. In obtaining these, we assume that the interface between the flowing grains and the bed moves with the speed of a pressure wave in the flow, for deposition, or with the speed of a disturbance through the contacting particles in the bed, for erosion. We employ the expressions for the rates of erosion and deposition to show that after an abrupt change in the angle of inclination of the bed the characteristic time for the motion of the interface is much shorter than the characteristic time of the flow.