Basic Science and Pathogenesis.

Background: SNX19 is a key player in endolysosomal and autophagy pathways, which have been extensively reported in neuronal dysfunction and neurodegenerative diseases. Although genetic and cellular evidence suggests SNX19 contributes to neuropathology, the underlying mechanisms remain unknown. Here, we propose to study the mechanism in aging postmortem brain tissue at single cell level and model SNX19 in human induced pluripotent stem cell (hiPSCs) derived brain organoids.

Detection of Apple Proliferation Disease Using Hyperspectral Imaging and Machine Learning Techniques.

Apple proliferation is among the most important diseases in European fruit production. Early and reliable detection enables farmers to respond appropriately and to prevent further spreading of the disease. Traditional phenotyping approaches by human observers consider multiple symptoms, but these are difficult to measure automatically in the field.

Neurotoxicity and Rare Adverse Events in BCMA-Directed CAR T Cell Therapy: A Comprehensive Analysis of Real-World FAERS Data.

Chimeric antigen receptor T (CAR T) cell therapies have emerged as a valuable treatment modality for patients with plasma cell disorders. As the population of patients receiving CAR T therapies grows, the identification and management of associated rare toxicities become increasingly crucial. This study aims to identify safety signals associated with commercial anti-B-cell maturation antigen (BCMA) CAR T therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Persistent Social Inequality in Adolescent Health Indicators 1991-2022: Trend Study From Denmark.

Objectives: To examine trends in socioeconomic inequality in adolescent health over three decades, across fifteen health indicators: overweight, underweight, headache, stomachache, backpain, emotional symptoms, difficulties falling asleep, loneliness, low life satisfaction, low self-rated heath, smoking, drunkenness, physical inactivity, low vegetable intake, and inadequate toothbrushing.

Methods: The Health Behaviour in School-aged Children (HBSC) study in Denmark included nine identical surveys of 11-15-year-olds from 1991 to 2022, n = 35,423. For each health indicator, we measured absolute and relative socioeconomic inequality by prevalence differences and odds ratios between low and high socioeconomic groups.

Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma.

Interferon-alpha has activity against multiple myeloma. Modakafusp alfa is an immunocytokine comprising two attenuated interferon-alpha2b molecules and an anti-CD38 IgG4 antibody, targeting delivery of interferon-alpha to CD38+ immune and myeloma cells. This phase I/II trial (NCT03215030) enrolled patients with relapsed/refractory multiple myeloma with ≥3 prior lines of treatment and refractory to or intolerant of ≥1 proteasome inhibitor and ≥1 immunomodulatory drug.

Design of an international, phase IV, open-label study of simoctocog alfa in women/girls with hemophilia A undergoing surgery (NuDIMENSION).

Background: Although hemophilia A mainly affects males, carriers (defined as females with hemophilia A, as well as symptomatic or asymptomatic hemophilia A carriers) are at risk of excessive bleeding, particularly during trauma or during surgical procedures. Clinical trials have focused on male patients with severe disease, and data for females are limited. Improved, evidence-based treatment guidelines for management of hemophilia A carriers are required.

Efficacy of emicizumab in patients with severe haemophilia A without factor VIII inhibitors in Germany: evaluation of real-life data documented by the smart medication eDiary.

Background: Systematically documented data on real-world use of emicizumab, a bispecific antibody factor (F)VIII mimetic, are still lacking in people with severe haemophilia A (PwSHA). Smart medication, a real-time, online platform, monitors treatment administration and outcomes for people with haemophilia A in Germany.

Objective: To evaluate annualised bleeding rates (ABRs) and annualised joint bleeding rates (AJBRs), using data documented in the smart medication eDiary, for PwSHA receiving emicizumab.

Cancer cells impair monocyte-mediated T cell stimulation to evade immunity.

The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses. Within the tumour microenvironment, CD8 T cells undergo full effector differentiation and acquire cytotoxic anti-tumour functions in specialized niches. Although interactions with type 1 conventional dendritic cells have been implicated in this process, the underlying cellular players and molecular mechanisms remain incompletely understood.

Solvent-Directed Social Chiral Self-Sorting in PdL Coordination Cages.

A family of Pd cages prepared from ligands based on an axially chiral diamino-[1,1'-biazulene] motif (serving as a unique azulene-based surrogate of the ubiquitous BINOL moiety) is reported. We show that preparing a cage starting from the racemate of a shorter bis-monodentate ligand derivative, equipped with pyridine donor groups, leads to integrative ("social") chiral self-sorting, exclusively yielding the product, but only in a selection of solvents. This phenomenon is driven by individual solvent molecules acting as hydrogen bonding tethers between the amino groups of neighboring ligands, thereby locking the final coordination cage in a single isomeric form.

Interplay of Stereochemistry and Charge Governs Guest Binding in Flexible ZnL Cages.

Here, we report the synthesis of a family of chiral ZnL tetrahedral cages by subcomponent self-assembly. These cages contain a flexible trialdehyde subcomponent that allows them to adopt stereochemically distinct configurations. The incorporation of enantiopure 1-phenylethylamine produced Δ and Λ enantiopure cages, in contrast to the racemates that resulted from the incorporation of achiral 4-methoxyaniline.

Csk controls leukocyte extravasation via local regulation of Src family kinases and cortactin signaling.

C-terminal Src kinase (Csk) targets Src family kinases (SFKs) and thereby inactivates them. We have previously shown that Csk binds to phosphorylated tyrosine 685 of VE-cadherin, an adhesion molecule of major importance for the regulation of endothelial junctions. This tyrosine residue is an SFK target, and its mutation (VE-cadherin-Y685F) inhibits the induction of vascular permeability in various inflammation models.

The burden of all-cause mortality following influenza-associated hospitalizations, FluSurv-NET, 2010-2019.

Background: While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited.

London dispersion driven compaction of coordination cages in the gas-phase - a combined ion mobility and theoretical study.

Large self-assembled systems (such as metallosupramolecular rings and cages) can be difficult to structurally characterize, in particular when they show a highly dynamic behavior. In the gas-phase, Ion Mobility Spectrometry (IMS), in tandem with Electrospray Ionization Mass Spectrometry (ESI MS), can yield valuable insights into the size, shape and dynamics of such supramolecular assemblies. However, the detailed relationship between experimental IMS data and the actual gas-phase structure is still poorly understood for soft and flexible self-assemblies.

A plain language summary of the final analysis of the GRIFFIN study of daratumumab plus lenalidomide, bortezomib, and dexamethasone for people with newly diagnosed multiple myeloma.

What Is This Summary About?: This summary describes the final analysis of the GRIFFIN study. In this study, participants were newly diagnosed with a type of blood and bone marrow cancer called multiple myeloma, had never received any treatment, and were able to undergo an autologous stem cell transplant. The GRIFFIN study looked at adding the drug daratumumab (D) to a combination of standard treatments called RVd (lenalidomide [R], bortezomib [V], and dexamethasone [d]) during the treatment phases induction and consolidation, followed by daratumumab and lenalidomide (D-R) maintenance.

Mental Health and Medicine Use for Headache: A Nationally Representative Study of Adolescents in Denmark.

Purpose: This study examined the prevalence of headache medicine use among Danish adolescents and explores the link between mental health, frequent headaches, and medicine use for headache. We hypothesized that poor mental health increases headache occurrence, leading to greater medicine use.

Methods: The 2022 Danish Health Behaviour in School-aged Children (HBSC) study surveyed 5292 students aged 11, 13, and 15.

Development and Validation of an LC-MS/MS Assay for the Quantitation of MO-OH-Nap Tropolone in Mouse Plasma: Application to In Vitro and In Vivo Pharmacokinetic Studies.

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitation of MO-OH-Nap tropolone (MO-OH-Nap) in mouse plasma. MO-OH-Nap is an α-substituted tropolone with anti-proliferative properties in various cancer cell lines. Detection and separation of analytes was achieved on an ACE Excel C18 (1.

Simultaneous recordings from vestibular Type I hair cells and their calyceal afferents in mice.

The vestibular hair cell receptors of anamniotes, designated Type II, are presynaptic to bouton endings of vestibular nerve distal neurites. An additional flask-shaped hair cell receptor, Type I, is present in amniotes, and communicates with a chalice-shaped afferent neuritic ending that surrounds the entire hair cell except its apical neck. Since the full repertoire of afferent fiber dynamics and sensitivities observed throughout the vertebrate phyla can be accomplished through Type II hair cell-bouton synapses, the functional contribution(s) of Type I hair cells and their calyces to vestibular performance remains a topic of great interest.