Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.

Alternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the cell's state and function.

Cell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis.

The ability of cells to manage consequences of exogenous proteotoxicity is key to cellular homeostasis. While a plethora of well-characterised machinery aids intracellular proteostasis, mechanisms involved in the response to denaturation of extracellular proteins remain elusive. Here we show that aggregation of protein ectodomains triggers their endocytosis via a macroendocytic route, and subsequent lysosomal degradation.

Durable response of anaplastic thyroid carcinoma to FS118, a bispecific LAG-3/PD-L1 antibody, after checkpoint inhibitor progression: a case report.

Anaplastic thyroid cancer represents a rare, highly aggressive form of thyroid cancer with a poor prognosis and an overall survival ranging from 5 to 12 months. Unfortunately, treatment options remain limited, even for patients with a targetable driver mutation. Here, we present a case of a patient with a BRAF V600E-mutated, PD-L1 positive (tumor proportion score of 95%) anaplastic thyroid cancer refractory to standard therapies, including debulking surgery, followed by chemoradiation, who had further progressed on PD-1 monotherapy, and was unable to tolerate BRAF/MEK inhibition.

Abdominal Wall Expanding System. Intraoperative Abdominal Wall Expansion as a Technique to Repair Giant Incisional Hernia and Laparostoma. New and Long-Term Results From a Three-Center Feasibility Study.

Background: The abdominal wall expanding system (AWEX) was first applied in 2012 and published in 2017. This novel technique was developed to reconstruct complex incisional hernias and residual skin-grafted laparostoma after treatment of an open abdomen, when primary midline closure was impossible. The main aim was the anatomical reconstruction of the abdominal wall and the avoidance of dissecting techniques (component separation).

Visual Field Endpoints Based on Subgroups of Points May Be Useful in Glaucoma Clinical Trials: A Study With the Humphrey Field Analyzer and Compass Perimeter.

Precis: Visual field (VF) endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogeneous data set without necessarily worsening test-retest variability and so may be useful in clinical trials.

Purpose: The purpose of this study was to characterize the outcome measures encompassing particular subsets of VF points and compare them as obtained with Humphrey [Humphrey visual field analyser (HVF)] and Compass perimeters.

Methods: Thirty patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters.

A novel EyePhone© App for improving adherence to glaucoma therapy.

Purpose: Despite advances in glaucoma treatment options, patient adherence and compliance remain very low. The EyePhone© App is a free non-commercial reminder application designed specifically for the needs of glaucoma patients. In this study, we evaluated its usefulness in improving adherence to medical treatment among glaucoma patients.

Rewiring of Cancer Cell Metabolism by Mitochondrial VDAC1 Depletion Results in Time-Dependent Tumor Reprogramming: Glioblastoma as a Proof of Concept.

Reprograming of the metabolism of cancer cells is an event recognized as a hallmark of the disease. The mitochondrial gatekeeper, voltage-dependent anion channel 1 (VDAC1), mediates transport of metabolites and ions in and out of mitochondria, and is involved in mitochondria-mediated apoptosis. Here, we compared the effects of reducing hVDAC1 expression in a glioblastoma xenograft using human-specific si-RNA (si-hVDAC1) for a short (19 days) and a long term (40 days).

"Golden Hour" quality improvement intervention and short-term outcome among preterm infants.

Objective: To evaluate the impact of a quality improvement intervention during the first hour of life ("Golden Hour") on short-term preterm neonatal outcome.

Study Design: A comprehensive protocol designed for initial stabilization and treatment of preterm infants that included cord blood sampling, use of a dedicated resuscitation room and improved team communication using Crew Resource Management tools. The infants admitted before and after implementation of the protocol were retrospectively compared in a matched case-control design.

Local delivery of mometasone furoate from an eluting endotracheal tube.

Laryngeal and tracheal morbidity is a common complication of endotracheal tube (ETT)-based airway management, and manifests as local irritation, inflammation, and edema. Systemic corticosteroids are commonly administered to manage these conditions; however, their efficacy is inadequate and limited by potential severe side effects. In the present study, a steroid delivery system for local therapy was developed to generate relatively high local drug concentrations and to improve drug efficacy.

The double benefit of Spalax p53: surviving underground hypoxia while defying lung cancer cells in vitro via autophagy and caspase-dependent cell death.

The blind subterranean mole rat, Spalax ehrenbergi, is a model organism for hypoxia tolerance. This superspecies have adapted to severe environment by altering an array of hypoxia-mediated genes, among which an alteration in the p53 DNA binding domain (corresponding to R174K in humans) that hinders its transcriptional activity towards apoptotic genes. It is well accepted that apoptosis is not the only form of programmed cell death and that mechanisms that depend on autophagy are also involved.

Short-term morbidities and neurodevelopmental outcomes in preterm infants exposed to magnesium sulphate treatment.

Aim: The aim of the study is to examine whether baseline serum Mg concentration has an impact on short-term and long-term outcomes in preterm infants exposed antenatally to MgSO4.

Methods: Participants included all infants admitted to the neonatal intensive care unit at <32 weeks of gestational age. Infant serum Mg concentration (iMgC) was examined immediately after birth in those exposed to maternal MgSO4.

Light-induced cation exchange for copper sulfide based CO2 reduction.

Copper(I)-based catalysts, such as Cu2S, are considered to be very promising materials for photocatalytic CO2 reduction. A common synthesis route for Cu2S via cation exchange from CdS nanocrystals requires Cu(I) precursors, organic solvents, and neutral atmosphere, but these conditions are not compatible with in situ applications in photocatalysis. Here we propose a novel cation exchange reaction that takes advantage of the reducing potential of photoexcited electrons in the conduction band of CdS and proceeds with Cu(II) precursors in an aqueous environment and under aerobic conditions.

Phenotype classification of zebrafish embryos by supervised learning.

Zebrafish is increasingly used to assess biological properties of chemical substances and thus is becoming a specific tool for toxicological and pharmacological studies. The effects of chemical substances on embryo survival and development are generally evaluated manually through microscopic observation by an expert and documented by several typical photographs. Here, we present a methodology to automatically classify brightfield images of wildtype zebrafish embryos according to their defects by using an image analysis approach based on supervised machine learning.

Recombinant production of the amino terminal cytoplasmic region of dengue virus non-structural protein 4A for structural studies.

Background: Dengue virus (DENV) is a mosquito-transmitted positive single strand RNA virus belonging to the Flaviviridae family. DENV causes dengue fever, currently the world's fastest-spreading tropical disease. Severe forms of the disease like dengue hemorrhagic fever and dengue shock syndrome are life-threatening.

An N-terminal amphipathic helix in dengue virus nonstructural protein 4A mediates oligomerization and is essential for replication.

Dengue virus (DENV) causes dengue fever, a major health concern worldwide. We identified an amphipathic helix (AH) in the N-terminal region of the viral nonstructural protein 4A (NS4A). Disruption of its amphipathic nature using mutagenesis reduced homo-oligomerization and abolished viral replication.

Imbalanced neural responsivity to risk and reward indicates stress vulnerability in humans.

Trauma-related psychopathology has been associated with an intense emotional reaction to stressful event. Emotional responses have evolved to signal the presence of risks to be avoided or of rewards to be approached in the environment. Thus, individuals' sensitivity to signals of risk and reward may affect the level of stress vulnerability.

Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity.

Variations in people's vulnerability to stressful life events may rise from a predated neural sensitivity as well as from differential neural modifications in response to the event. Because the occurrence of a stressful life event cannot be foreseen, characterizing the temporal trajectory of its neural manifestations in humans has been a real challenge. The current prospective study examined the emotional experience and brain responses of 50 a priori healthy new recruits to the Israeli Defense Forces at 2 time points: before they entered their mandatory military service and after their subsequent exposure to stressful events while deployed in combat units.

PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR proteins that are expressed in reproductive and neuron-rich tissues and possess neuromodulatory activity.

We report here syntenic loci in humans and mice incorporating gene clusters coding for secreted proteins each comprising 10 cysteine residues. These conform to three-fingered protein/Ly-6/urokinase-type plasminogen activator receptor (uPAR) domains that shape three-fingered proteins (TFPs). The founding gene is PATE, expressed primarily in prostate and less in testis.

The MUC1 SEA module is a self-cleaving domain.

MUC1, a glycoprotein overexpressed by a variety of human adenocarcinomas, is a type I transmembrane protein (MUC1/TM) that soon after its synthesis undergoes proteolytic cleavage in its extracellular domain. This cleavage generates two subunits, alpha and beta, that specifically recognize each other and bind together in a strong noncovalent interaction. Proteolysis occurs within the SEA module, a 120-amino acid domain that is highly conserved in a number of heavily glycosylated mucin-like proteins.

From quantum Hall ferromagnetism to huge longitudinal resistance at the 2/3 fractional quantum Hall state.

We observe the transition from a spin-unpolarized to a polarized nu=2/3 fractional quantum Hall state at low currents (<5 nA), recently described in terms of quantum Hall ferromagnetism, versus density and parallel magnetic field. At larger currents the time and current dependent huge longitudinal resistance (HLR) is always initiated at the transition. Transport in the HLR regime is linear and the amount of current-induced nuclear polarization in the HLR is comparable to the thermal nuclear polarization at approximately 20 mK and 10 T.

Coupling and entangling of quantum states in quantum dot molecules.

We demonstrate coupling and entangling of quantum states in a pair of vertically aligned, self-assembled quantum dots by studying the emission of an interacting electron-hole pair (exciton) in a single dot molecule as a function of the separation between the dots. An interaction-induced energy splitting of the exciton is observed that exceeds 30 millielectron volts for a dot layer separation of 4 nanometers. The results are interpreted by mapping the tunneling of a particle in a double dot to the problem of a single spin.

Hidden symmetries in the energy levels of excitonic 'artificial atoms'.

Quantum dots or 'artificial atoms' are of fundamental and technological interest--for example, quantum dots may form the basis of new generations of lasers. The emission in quantum-dot lasers originates from the recombination of excitonic complexes, so it is important to understand the dot's internal electronic structure (and of fundamental interest to compare this to real atomic structure). Here we investigate artificial electronic structure by injecting optically a controlled number of electrons and holes into an isolated single quantum dot.