Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion.

Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor-exhausted T (Tex_prog) cells better reflect immunotherapeutic responsivity. Here, we examined the intratumoral cellular interactions that govern the transition to terminal T cell exhaustion. We defined a metric reflecting the intratumoral progenitor exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers.

Combination checkpoint blockade and laser interstitial thermal therapy in radiographically progressive non-small cell lung cancer brain metastases.

Background: Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment being employed frequently for radiographically progressive brain metastases. Considerable interest exists in combining LITT-mediated in situ vaccination to license immune checkpoint blockade (ICB). No studies have examined the clinical feasibility of this combination in brain metastases.

Why Do Patients Opt for the Emergency Department over Other Care Choices? A Multi-Hospital Analysis.

Introduction: There are several options for receiving acute care besides emergency departments (ED), such as primary care physician (PCP) offices, urgent care centers (UCC), and telehealth services. It is unknown whether these alternative modes of care have decreased the number of ED visits for patients or whether they are considered before visiting the ED. A comprehensive study considering all potential methods of care is needed to address the evolving landscape of healthcare.

Enabling osteoporosis treatment in post-acute care: An algorithm for providers.

Approximately 60 % of older adults with a hospitalized fracture receive post-acute care in a skilled nursing facility (SNF), yet fewer than 10-20 % receive osteoporosis treatment following a fracture. This study sought to understand SNF providers' perspectives on osteoporosis treatment and to receive feedback on a pocketcard to guide osteoporosis treatment in the post-acute care setting. We interviewed 17 SNF providers with 2+ years of post-acute care experience from 13 states.

Reconfigurable origami with variable stiffness joints for adaptive robotic locomotion and grasping.

With its compactness and foldability, origami has recently been applied to robotic systems to enable versatile robots and mechanisms while maintaining a low weight and compact form. This work investigates how to generate different motions and shapes for origami by tuning its creases' stiffness on the fly. The stiffness tuning is realized by a composite material made by sandwiching a thermoplastic layer between two shape memory polymer layers.

Single-molecule detection and super-resolution imaging with a portable and adaptable 3D-printed microscopy platform (Brick-MIC).

Over the past decades, single-molecule and super-resolution microscopy have advanced and represent essential tools for life science research. There is, however, a growing gap between the state of the art and what is accessible to biologists, biochemists, medical researchers, or labs with financial constraints. To bridge this gap, we introduce Brick-MIC, a versatile and affordable open-source 3D-printed microspectroscopy and imaging platform.

Phytoplankton cell-states: multiparameter fluorescence lifetime flow-based monitoring reveals cellular heterogeneity.

Phytoplankton are a major source of primary productivity. Their photosynthetic fluorescence are unique measures of their type, physiological state, and response to environmental conditions. Changes in phytoplankton photophysiology are commonly monitored by bulk fluorescence spectroscopy, where gradual changes are reported in response to different perturbations, such as light intensity changes.

Evidence for a compact σ conformation and .

The initiation of transcription in Escherichia coli () is facilitated by promoter specificity factors, also known as σ factors, which may bind a promoter only as part of a complex with RNA polymerase (RNAP). By performing cross-linking mass spectrometry (CL-MS) of apo-σ, we reveal structural features suggesting a compact conformation compared to the known RNAP-bound extended conformation. Then, we validate the existence of the compact conformation using CL-MS by identifying cross-links similar to those found , which deviate from the extended conformation only during the stationary phase of bacterial growth.

Enumerating low-frequency nonphononic vibrations in computer glasses.

In addition to Goldstone phonons that generically emerge in the low-frequency vibrational spectrum of any solid, crystalline or glassy, structural glasses also feature other low-frequency vibrational modes. The nature and statistical properties of these modes-often termed "excess modes"-have been the subject of decades-long investigation. Studying them, even using well-controlled computer glasses, has proven challenging due to strong spatial hybridization effects between phononic and nonphononic excitations, which hinder quantitative analyses of the nonphononic contribution DG(ω) to the total spectrum D(ω), per frequency ω.

Elasticity of self-organized frustrated disordered spring networks.

There have been some interesting recent advances in understanding the notion of mechanical disorder in structural glasses and the statistical mechanics of these systems' low-energy excitations. Here we contribute to these advances by studying a minimal model for structural glasses' elasticity in which the degree of mechanical disorder-as characterized by recently introduced dimensionless quantifiers-is readily tunable over a very large range. We comprehensively investigate a number of scaling laws observed for various macro, meso and microscopic elastic properties, and rationalize them using scaling arguments.

Effects of coordination and stiffness scale separation in disordered elastic networks.

Many fibrous materials are modeled as elastic networks featuring a substantial separation between the stiffness scales that characterize different microscopic deformation modes of the network's constituents. This scale separation has been shown to give rise to emergent complexity in these systems' linear and nonlinear mechanical response. Here we study numerically a simple model featuring said stiffness scale separation in two-dimensions and show that its mechanical response is governed by the competition between the characteristic stiffness of collective nonphononic soft modes of the stiff subsystem, and the characteristic stiffness of the soft interactions.

A comparison of outcomes including bile duct injury of subtotal cholecystectomy versus open total cholecystectomy as bailout procedures for severe cholecystitis: A multicenter real-world study.

Background: Dense inflammation obscuring the hepatocystic anatomy can hinder the ability to perform a safe standard laparoscopic cholecystectomy in severe cholecystitis, requiring use of a bailout procedure. We compared clinical outcomes of laparoscopic and open subtotal cholecystectomy against the traditional standard of open total cholecystectomy to identify the optimal bailout strategy for the difficult gallbladder.

Methods: A multicenter, multinational retrospective cohort study of patients who underwent bailout procedures for severe cholecystitis.

Elasticity and rheology of auxetic granular metamaterials.

The flowing, jamming, and avalanche behavior of granular materials is satisfyingly universal and vexingly hard to tune: A granular flow is typically intermittent and will irremediably jam if too confined. Here, we show that granular metamaterials made from particles with a negative Poisson's ratio yield more easily and flow more smoothly than ordinary granular materials. We first create a collection of auxetic grains based on a re-entrant mechanism and show that each grain exhibits a negative Poisson's ratio regardless of the direction of compression.

Public support for and concerns regarding pediatric dose optimization for seizures in emergency medical services: An exception from informed consent (EFIC) trial.

Background: Federal regulations allow exception from informed consent (EFIC) to study emergent conditions when obtaining prospective consent is not feasible. Little is known about public views on including children in EFIC studies. The Pediatric Dose Optimization for Seizures in EMS (PediDOSE) trial implements age-based, standardized midazolam dosing for pediatric seizures.

The outcomes of treatment for homebound adults with complex medical conditions in a hospital-at-home unit in the southern district of Israel.

Background: A model of hospital-at-home services called the Home Care Unit ("the unit") has been implemented in the southern region of the Clalit Healthcare Services in Israel. The aim of the present study was to characterize this service model.

Methods: A retrospective cross-over study.

Rapid and specific detection of single nanoparticles and viruses in microfluidic laminar flow via confocal fluorescence microscopy.

Mainstream virus detection relies on the specific amplification of nucleic acids via polymerase chain reaction, a process that is slow and requires extensive laboratory expertise and equipment. Other modalities, such as antigen-based tests, allow much faster virus detection but have reduced sensitivity. In this study, we report the development of a flow virometer for the specific and rapid detection of single nanoparticles based on confocal microscopy.

Single-molecule detection and super-resolution imaging with a portable and adaptable 3D-printed microscopy platform (Brick-MIC).

Over the past decades, single-molecule and super-resolution microscopy have advanced and represent essential tools for life science research. There is,however, a growing gap between the state-of-the-art and what is accessible to biologists, biochemists, medical researchers or labs with financial constraints. To bridge this gap, we introduce Brick-MIC, a versatile and affordable open-source 3D-printed micro-spectroscopy and imaging platform.

Scaling regimes and fluctuations of observables in computer glasses approaching the unjamming transition.

Under decompression, disordered solids undergo an unjamming transition where they become under-coordinated and lose their structural rigidity. The mechanical and vibrational properties of these materials have been an object of theoretical, numerical, and experimental research for decades. In the study of low-coordination solids, understanding the behavior and physical interpretation of observables that diverge near the transition is of particular importance.

Cutaneous Components Leading to Pruritus, Pain, and Neurosensitivity in Atopic Dermatitis: A Narrative Review.

Atopic dermatitis (AD) is a chronic, relapsing immunoinflammatory skin condition characterized by sensations such as pruritis, pain, and neuronal hypersensitivity. The mechanisms underlying these sensations are multifactorial and involve complex crosstalk among several cutaneous components. This review explores the role these components play in the pathophysiology of atopic dermatitis.

Similarities and differences in peripheral itch and pain pathways in atopic dermatitis.

Atopic dermatitis (AD) is predominantly characterized by intense itching, but concomitant skin pain is experienced by more than 40% of patients. Patients with AD display considerable somatosensory aberrations, including increased nerve sensitivity to itch stimuli (hyperknesis), perception of itch from innocuous stimuli (alloknesis), or perception of pain from innocuous stimuli (allodynia). This review summarizes the current understanding of the similarities and differences in the peripheral mechanisms underlying itch and pain in AD.

Detecting low-energy quasilocalized excitations in computer glasses.

Soft, quasilocalized excitations (QLEs) are known to generically emerge in a broad class of disordered solids and to govern many facets of the physics of glasses, from wave attenuation to plastic instabilities. In view of this key role of QLEs, shedding light upon several open questions in glass physics depends on the availability of computational tools that allow one to study QLEs' statistical mechanics. The latter is a formidable task since harmonic analyses are typically contaminated by hybridizations of QLEs with phononic excitations at low frequencies, obscuring a clear picture of QLEs' abundance, typical frequencies, and other important micromechanical properties.