Prospective Validation of CAR-HEMATOTOX and a simplified version predict Survival in Patients with Large B-Cell Lymphoma treated with anti-CD19 CAR T-cells: data from CART-SIE study.

Background: Anti-CD19 CAR T-cells have revolutionized outcomes in relapsed/refractory large B-cell lymphomas. Long-term follow-up underscored the role of hematological toxicity in non-relapse mortality, largely driven by infections, leading to the development of the CAR-HEMATOTOX (HT) score for predicting neutropenia. The European scientific community (EHA/EBMT) later reached a consensus, defining a new entity: immune effector cell-associated hematotoxicity (ICAHT).

Influence of ESBL colonization status on gut microbiota composition during allogenic hematopoietic stem cell transplantation.

After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria.

Two FAM134B isoforms differentially regulate ER dynamics during myogenesis.

Endoplasmic reticulum (ER) plasticity and ER-phagy are intertwined processes essential for maintaining ER dynamics. We investigated the interplay between two isoforms of the ER-phagy receptor FAM134B in regulating ER remodeling in differentiating myoblasts. During myogenesis, the canonical FAM134B1 is degraded, while its isoform FAM134B2 is transcriptionally upregulated.

The transcription factor ORA59 represses hypoxia responses during Botrytis cinerea infection and reoxygenation.

Transcription factors belonging to the large ethylene response factor (ERF) family are involved in plant responses to biotic and abiotic stresses. Among the ERFs, OCTADECANOID-RESPONSIVE ARABIDOPSIS 59 (ORA59) integrates ethylene and jasmonic acid signaling to regulate resistance to necrotrophic pathogens. The ERF group ERFVII encodes oxygen-labile proteins that are required for oxygen sensing and are stabilized by hypoxia established at the site of Botrytis (Botrytis cinerea) infection.

A nuclear protein quality control system for elimination of nucleolus-related inclusions.

The identification of pathways that control elimination of protein inclusions is essential to understand the cellular response to proteotoxicity, particularly in the nuclear compartment, for which our knowledge is limited. We report that stress-induced nuclear inclusions related to the nucleolus are eliminated upon stress alleviation during the recovery period. This process is independent of autophagy/lysosome and CRM1-mediated nuclear export pathways, but strictly depends on the ubiquitin-activating E1 enzyme, UBA1, and on nuclear proteasomes that are recruited into the formed inclusions.

Critical assessment of LC3/GABARAP ligands used for degrader development and ligandability of LC3/GABARAP binding pockets.

Recent successes in developing small molecule degraders that act through the ubiquitin system have spurred efforts to extend this technology to other mechanisms, including the autophagosomal-lysosomal pathway. Therefore, reports of autophagosome tethering compounds (ATTECs) have received considerable attention from the drug development community. ATTECs are based on the recruitment of targets to LC3/GABARAP, a family of ubiquitin-like proteins that presumably bind to the autophagosome membrane and tether cargo-loaded autophagy receptors into the autophagosome.

Chemogenomics for NR1 nuclear hormone receptors.

Nuclear receptors (NRs) regulate transcription in response to ligand binding and NR modulation allows pharmacological control of gene expression. Although some NRs are relevant as drug targets, the NR1 family, which comprises 19 NRs binding to hormones, vitamins, and lipid metabolites, has only been partially explored from a translational perspective. To enable systematic target identification and validation for this protein family in phenotypic settings, we present an NR1 chemogenomic (CG) compound set optimized for complementary activity/selectivity profiles and chemical diversity.

Secondary primary malignancies after CD-19 directed CAR-T-cell therapy in lymphomas: A report from the Italian CART-SIE study.

Secondary primary malignancies (SPM) have been reported after anti-BCMA or anti-CD19 chimeric antigen receptor (CAR)-T-cell therapies. While the cytotoxic effect of antecedent therapies, including chemotherapy and radiotherapy, has been well established, few data are available on risk related to CAR-T immunotherapies. The study aimed to analyse the incidence of SPM in 651 patients enrolled in the Italian prospective observational CART-SIE study.

A microscope in your pocket: can smartphones be used to perform microsurgery?

Purpose: To evaluate the use of the latest generation smartphone camera in performing arterial microanastomosis in rats.

Methods: Ten Wistar rats were divided into 2 groups and underwent anastomosis of the right carotid artery with the aid of magnification from a microscope (group M) and a smartphone camera (group S), to compare patency in 72 hours, as well as to measure the weight of the animals, diameter of the carotid arteries and anastomosis time.

Results: There was no statistical difference between the weight of the animals or the diameter of the carotid arteries.

Root photosynthesis prevents hypoxia in the epiphytic orchid .

Orchids (Phalaenopsis spp.) growing in tropical and subtropical regions are epiphytes. As such, they grow on trees with the root system utilised to anchor themselves to tree branches.

Spatiotemporal oxygen dynamics in young leaves reveal cyclic hypoxia in plants.

Oxygen is essential for plant growth and development. Hypoxia occurs in plants due to limited oxygen availability following adverse environmental conditions as well in hypoxic niches in otherwise normoxic environments. However, the existence and functional integration of spatiotemporal oxygen dynamics with plant development remains unknown.

ECP versus ruxolitinib in steroid-refractory acute GVHD - a retrospective study by the EBMT transplant complications working party.

Introduction: Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making.

The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways.

Selective autophagy of the endoplasmic reticulum (ER), known as ER-phagy, is an important regulator of ER remodeling and essential to maintain cellular homeostasis during environmental changes. We recently showed that members of the FAM134 family play a critical role during stress-induced ER-phagy. However, the mechanisms on how they are activated remain largely unknown.

The black swan: a case of central nervous system graft-versus-host disease.

Objectives: Graft-versus-host disease (GVHD) of central nervous system is an atypical and rare manifestation of chronic GVHD, presenting with a heterogeneous spectrum of signs and symptoms. Diagnosis of neurological manifestations of GVHD can be highly challenging and remain associated with dismal prognosis, significant morbidity, and reduced quality of life.

Case Presentation: In this report, we describe a 39-year-old woman developing neurological signs and symptoms 8 months after allogeneic HSCT magnetic resonance imaging showed multifocal hyperintense lesions involving the periventricular region and frontal subcortical white matter.

The psychophysics of bouncing: Perceptual constraints, physical constraints, animacy, and phenomenal causality.

In the present study we broadly explored the perception of physical and animated motion in bouncing-like scenarios through four experiments. In the first experiment, participants were asked to categorize bouncing-like displays as physical bounce, animated motion, or other. Several parameters of the animations were manipulated, that is, the simulated coefficient of restitution, the value of simulated gravitational acceleration, the motion pattern (uniform acceleration/deceleration or constant speed) and the number of bouncing cycles.

Live-Cell High-Throughput Screen for Monitoring Autophagy Flux.

Autophagy is a cellular process implicated in the renewal of cellular components and the maintenance of cellular hemostasis and therefore associated with various types of diseases. In addition, autophagy belongs to the stress response pathways and is frequently activated by chemical compounds harboring characteristics of cell toxicity. High-throughput screens analyzing autophagy flux are therefore applied in both, the field of compound identification for targeting autophagy and compound characterization for analyzing compound toxicity.

Impact of second-degree related donor on the outcomes of T cell-replete haploidentical transplantation with post-transplant cyclophosphamide.

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957).