Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.

Introduction: Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.

Areas Covered: Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-α) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens.

Silicon-on-insulator wavelength-selective filter with integrated detectors at the 2 µm wave band.

The short-wave infrared range is highly significant for spectroscopic sensing and upcoming optical communication applications. Integrating active and passive photonic components is essential to achieve compact optical solutions. In this paper, we show, for the first time to our knowledge, a wavelength-selective detection system based on the heterogeneous integration of two grating-coupled InGaAs photodetectors operating at the 2µm wave band, with a wavelength selectivity provided by a dual-channel Mach-Zehnder interferometer fabricated using a silicon-on-insulator (SOI) wafer.

Case Report: Management of Acanthamoeba Rhinosinusitis in a Patient with Chronic Lymphocytic Leukemia.

Infections caused by free-living amoebae pose a significant public health threat owing to growing populations of immunocompromised hosts combined with diagnostic delays, treatment difficulties, and high case fatality rates. Nasopharyngeal infections caused by Acanthamoeba are rare and the optimal treatment is not well established. We report a case of Acanthamoeba rhinosinusitis in a patient with chronic lymphocytic leukemia who presented with headaches and chronic rhinosinusitis refractory to multiple courses of antibiotics.

Associations between regional adipose tissue distribution and skeletal muscle bioenergetics in older men and women.

Objective: The aim of this study was to examine associations of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.

Methods: Cross-sectional data from 829 adults ≥70 years of age were used. Abdominal, subcutaneous, and visceral AT and thigh muscle fat infiltration (MFI) were quantified by magnetic resonance imaging.

Isolation of Nuclei from Human Intermuscular Adipose Tissue and Downstream Single-Nuclei RNA Sequencing.

Intermuscular adipose tissue (IMAT) is a relatively understudied adipose depot located between muscle fibers. IMAT content increases with age and BMI and is associated with metabolic and muscle degenerative diseases; however, an understanding of the biological properties of IMAT and its interplay with the surrounding muscle fibers is severely lacking. In recent years, single-cell and nuclei RNA sequencing have provided us with cell type-specific atlases of several human tissues.

An optoelectronic implantable neurostimulation platform allowing full MRI safety and optical sensing and communication.

A novel programmable implantable neurostimulation platform based on photonic power transfer has been developed for various clinical applications with the main focus of being safe to use with MRI scanners. The wires usually conveying electrical current from the neurostimulator to the electrodes are replaced by optical fibers. Photovoltaic cells at the tip of the fibers convert laser light to biphasic electrical impulses together with feedback signals with 54% efficiency.

Assessment of Ventilation Using Adult and Pediatric Manual Resuscitators in a Simulated Adult Patient.

Background: The bag-valve-mask (BVM) or manual resuscitator bag is used as a first-line technique to ventilate patients with respiratory failure. Volume-restricted manual resuscitator bags (eg, pediatric bags) have been suggested to minimize overventilation and associated complications. There are studies that both support and caution against the use of a pediatric resuscitator bag to ventilate an adult patient.

An anthropological history of Nepal's Female Community Health Volunteer program: gender, policy, and social change.

Background: Community health workers (CHWs) are central to Primary Health Care globally. Amidst the current flourishing of work on CHWs, there often is a lack of reference to history-even in studies of programs that have been around for decades. This study examines the 35-year trajectory of Nepal's Female Community Health Volunteers (FCHVs).

DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.

The DNA-dependent protein kinase, DNA-PK, is an essential regulator of DNA damage repair. DNA-PK-driven phosphorylation events and the activated DNA damage response (DDR) pathways are also components of antiviral intrinsic and innate immune responses. Yet, it is not clear whether and how the DNA-PK response differs between these two forms of nucleic acid stress-DNA damage and DNA virus infection.

The success rates and outcomes of mandibular third molar coronectomy: 167 cases.

Purpose: The purpose of this study was to assess success rates and to report complications of coronectomy of mandibular third molars (M3M), including intra-operative failure, pain, infection, dry socket, inferior dental alveolar (IAN) and lingual nerve (LN) injuries and re-operation rates.

Methods: Retrospective analysis of 167 coronectomies completed between January 2017 to December 2022 was undertaken.

Results: The success of coronectomy was 93%.

Associations of plasma proteomics and age-related outcomes with brain age in a diverse cohort.

Machine learning models are increasingly being used to estimate "brain age" from neuroimaging data. The gap between chronological age and the estimated brain age gap (BAG) is potentially a measure of accelerated and resilient brain aging. Brain age calculated in this fashion has been shown to be associated with mortality, measures of physical function, health, and disease.

Sinonasal and Skull Base Metastatic Renal Cell Carcinoma: A Case Series.

Metastatic lesions to the paranasal sinuses and skull base, while rare, carry a poor prognosis. Renal cell carcinoma has been reported in multiple case reports to be one of the most common distant malignancies to spread to the paranasal sinuses; however, it is often unrecognized by physicians, and thus treatment is delayed. To increase awareness of this disease process, we describe three cases of metastatic renal cell carcinoma to the sinonasal cavity, which is the largest case series in the literature to date.

Associations between regional adipose tissue distribution and skeletal muscle bioenergetics in older men and women.

Objective: Examine the association of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.

Methods: Cross-sectional data from 829 older adults ≥70 years was used. Total abdominal, subcutaneous, and visceral AT; and thigh muscle fat infiltration (MFI) was quantified by MRI.

Sirtuin 2 promotes human cytomegalovirus replication by regulating cell cycle progression.

This study expands the growing understanding that protein acetylation is a highly regulated molecular toggle of protein function in both host anti-viral defense and viral replication. We describe a pro-viral role for the human enzyme SIRT2, showing that its deacetylase activity supports HCMV replication. By integrating quantitative proteomics, flow cytometry cell cycle assays, microscopy, and functional virology assays, we investigate the temporality of SIRT2 functions and substrates.

Caloric Restriction Intervention Alters Specific Circulating Biomarkers of the Senescence-Associated Secretome in Middle-Aged and Older Adults With Obesity and Prediabetes in an 18-Week Randomized Controlled Trial.

Cellular senescence is a biological aging process that is exacerbated by obesity and leads to inflammation and age- and obesogenic-driven chronic diseases including type 2 diabetes. Caloric restriction (CR) may improve metabolic function in part by reducing cellular senescence and the pro-inflammatory senescence-associated phenotype (SASP). We conducted an ancillary investigation of an 18-week randomized controlled trial (RCT) of CR (n = 31) or Control (n = 27) in 58 middle-aged/older adults (57.