Hematopoietic stem cell transplantation for CTLA-4 insufficiency across Europe: A European Society for Blood and Marrow Transplantation Inborn Errors Working Party study.

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) insufficiency causes a primary immune regulatory disorder characterized by lymphoproliferation, dysgammaglobulinemia, and multiorgan autoimmunity including cytopenias and colitis.

Objective: We examined the outcome of hematopoietic stem cell transplantation (HSCT) for CTLA-4 insufficiency and study the impact of pre-HSCT CTLA-4 fusion protein (CTLA-4-Ig) therapy and pre-HSCT immune dysregulation on survival and immunologic outcome.

Methods: This was a retrospective study of HSCT for CTLA-4 insufficiency and 2q33.

Oesophageal intubations in anaesthetic practice across Australia and New Zealand: A webAIRS analysis of 109 incidents.

Oesophageal intubations are more common than may be realised and can potentially cause significant patient harm even if promptly identified and corrected. Reports of morbidity due to unrecognised oesophageal intubation continue to present in coroner and media reports. Therefore, it would be helpful to identify mechanisms to prevent these events and implement strategies to avoid and identify incorrect endotracheal tube placement.

Cutaneous legionellosis in an immunocompromised neonate.

Cutaneous Legionella infection is rare and primarily seen in immunosuppressed patients. Herein, we present a case of cutaneous and pulmonary legionellosis presenting with fever and erythematous subcutaneous nodules in a neonate with severe combined immunodeficiency. This case underscores the importance of considering this diagnosis and highlights the use of modern testing modalities to promptly diagnose and treat infections in immunocompromised patients.

Improving access to gene therapy for rare diseases.

Effective gene therapy approaches have been developed for many rare diseases, including inborn errors of immunity and metabolism, haemoglobinopathies and inherited blindness. Despite successful pre-clinical and clinical results, these gene therapies are not widely available, primarily for non-medical reasons. Lack of commercial interest in therapies for ultra-rare diseases, costs of development and complex manufacturing processes required for advanced therapy medicinal products (ATMPs) are some of the main problems that are restricting access.

Light-Driven Ring Slippage in [Re(η-CH)(η-CH)] and the Inertness of Its Technetium Homologue.

Here, we present the light-driven reactions of [Re(η-CH)(η-CH)] () with nitriles, phosphines, and isocyanides, which are added to via a ring slippage of the tropylium cation from η to η, forming [Re(η-CH)(η-CH)(L)] (L= acetonitrile ; 2-phenylacetonitrile ; 1,3,5-triaza-5-phosphoadamantane (PTA) ; -butyl isocyanide ; benzyl isocyanide ) and [Re(η-CH)(η-CH)(L)] with L = (ethane-1,2-diyl)bis(diphenylphosphane) (dppe) . To compare the reactivities of rhenium and technetium, we also investigated the synthesis of [Tc(η-CH)], its substitution of naphthalene with cyclohepta-1,3,5-triene to obtain [Tc(η-CH)(η-CH)], and its reactivity (or lack thereof) with light.

Induced - rearrangements in {M(CO)} complexes (M = Re, Tc) by a PNP ligand.

The - rearrangements in [MX(CO)] (M = Re, Tc) induced by a pincer-type ligand (PNP) and a "halide scavenger" are reported. The reactions of -[Tc(CO)(OH)] or [TcO] in saline both yield -[Tc(PNP)(CO)], the first example of a -{Tc(CO)} type complex. In contrast, reactions with terpyridine (terpy) only gave the facial κ-terpy complexes with Re and Tc.

Electrocatalytic Ammonia Oxidation with a Tailored Molecular Catalyst Heterogenized via Surface Host-Guest Complexation.

Macrocyclic host molecules bound to electrode surfaces enable the complexation of catalytically active guests for molecular heterogeneous catalysis. We present a surface-anchored host-guest complex with the ability to electrochemically oxidize ammonia in both organic and aqueous solutions. With an adamantyl motif as the binding group on the backbone of the molecular catalyst [Ru(bpy-NMe)(tpada)(Cl)](PF) () (where bpy-NMe is 4,4'-bis(dimethylamino)-2,2'-bipyridyl and tpada is 4'-(adamantan-1-yl)-2,2':6',2″-terpyridine), high binding constants with β-cyclodextrin were observed in solution (in DMSO-:DO (7:3), = 492 ± 21 M).

Effects of Lung Ultrasound Technique and Pleural Line Depth on In Vitro and In Vivo Measurements of Pleural Line Thickness.

Objective: The aim of the work described here was to determine the effects of imaging protocol, technique and pleural line depth on measured pleural line thickness (PLT).

Methods: Sonograms were performed on a phantom and healthy volunteers. In vitro, pleural line depth, transducer type (5-1 MHz phased array vs.

pyPept: a python library to generate atomistic 2D and 3D representations of peptides.

We present pyPept, a set of executables and underlying python-language classes to easily create, manipulate, and analyze peptide molecules using the FASTA, HELM, or recently-developed BILN notations. The framework enables the analysis of both pure proteinogenic peptides as well as those with non-natural amino acids, including support to assemble a customizable monomer library, without requiring programming. From line notations, a peptide is transformed into a molecular graph for 2D depiction tasks, the calculation of physicochemical properties, and other systematic analyses or processing pipelines.

Assessing the fast prediction of peptide conformers and the impact of non-natural modifications.

We present an assessment of different approaches to predict peptide structures using modeling tools. Several small molecule, protein, and peptide-focused methodologies were used for the fast prediction of conformers for peptides shorter than 30 amino acids. We assessed the effect of including restraints based on annotated or predicted secondary structure motifs.

Discordance Between Invasive and NonInvasive Oxygen Saturation in Critically Ill COVID-19 Patients.

Objectives: To investigate discordance in oxy-hemoglobin saturation measured both by pulse oximetry (SpO) and arterial blood gas (ABG, SaO) among critically ill coronavirus disease 2019 (COVID-19(+)) patients compared to COVID-19(-) patients.

Methods: Paired SpO and SaO readings were collected retrospectively from consecutive adult admissions to four critical care units in the United States between March and May 2020. The primary outcome was the rate of discordance (|SaO-SpO|>4%) in COVID-19(+) versus COVID-19(-) patients.

Humoral and cellular responses to SARS-CoV-2 in patients with B-cell haematological malignancies improve with successive vaccination.

Patients with haematological malignancies are more likely to have poor responses to vaccination. Here we provide detailed analysis of the humoral and cellular responses to COVID-19 vaccination in 69 patients with B-cell malignancies. Measurement of anti-spike IgG in serum demonstrated a low seroconversion rate with 27.

Binding Small Molecules to a -Dicarbonyl Tc-PNP Complex via Metal-Ligand Cooperativity.

Metal-ligand cooperativity is a powerful tool for the activation of various bonds but has rarely, if ever, been studied with the radioactive transition metal Tc. In this work, we explore this bond activation pathway with the dearomatized PNP complex -[Tc(PNP*)(CO)] (), which was synthesized by deprotonation of -[Tc(PNP)(CO)Cl] with KOBu. Analogous to its rhenium congener, the dearomatized compound reacts with CO to form the carboxy complex -[Tc(PNP-COO)(CO)] and with H to form the mono-hydride complex -[Tc(PNP)(CO)H] ().

Accurate non-covalent interaction energies on noisy intermediate-scale quantum computers second-order symmetry-adapted perturbation theory.

The calculation of non-covalent interaction energies on noisy intermediate-scale quantum (NISQ) computers appears to be challenging with straightforward application of existing quantum algorithms. For example, the use of the standard supermolecular method with the variational quantum eigensolver (VQE) would require extremely precise resolution of the total energies of the fragments to provide for accurate subtraction to the interaction energy. Here we present a symmetry-adapted perturbation theory (SAPT) method that may provide interaction energies with high quantum resource efficiency.

Spotting a potential threat: Measles among pediatric solid organ transplantation recipients.

Background: Low-vaccination rates worldwide have led to the re-emergence of vaccine-preventable infections, including measles. Immunocompromised patients, including pediatric solid organ transplant (SOT) recipients, are at risk for measles because of suboptimal vaccination, reduced or waning vaccine immunity, lifelong immunosuppression, and global re-emergence of measles.

Objectives: To review published cases of measles in pediatric SOT recipients to heighten awareness of its clinical manifestations, summarize diagnostic and treatment strategies, and identify opportunities to optimize prevention.

Discovery of a Novel Potent and Selective HSD17B13 Inhibitor, BI-3231, a Well-Characterized Chemical Probe Available for Open Science.

Genome-wide association studies in patients revealed HSD17B13 as a potential new target for the treatment of nonalcoholic steatohepatitis (NASH) and other liver diseases. However, the physiological function and the disease-relevant substrate of HSD17B13 remain unknown. In addition, no suitable chemical probe for HSD17B13 has been published yet.

Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles.

We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs).

Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field.

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field.

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles.

People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints.

Therapeutic gene editing of T cells to correct CTLA-4 insufficiency.

Heterozygous mutations in result in an inborn error of immunity with an autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications of allogeneic hematopoietic stem cell transplantation. Here, we designed a homology-directed repair (HDR) gene editing strategy that inserts the cDNA into the first intron of the genomic locus in primary human T cells.

Protocol for iterative optimization of modified peptides bound to protein targets.

Peptides are commonly used as therapeutic agents. However, they suffer from easy degradation and instability. Replacing natural by non-natural amino acids can avoid these problems, and potentially improve the affinity towards the target protein.