Sequential STING and CD40 agonism drives massive expansion of tumor-specific T cells in liposomal peptide vaccines.

The clinical use of cancer vaccines is hampered by the low magnitude of induced T-cell responses and the need for repetitive antigen stimulation. Here, we demonstrate that liposomal formulations with incorporated STING agonists are optimally suited to deliver peptide antigens to dendritic cells in vivo and to activate dendritic cells in secondary lymphoid organs. One week after liposomal priming, systemic administration of peptides and a costimulatory agonistic CD40 antibody enables ultrarapid expansion of T cells, resulting in massive expansion of tumor-specific T cells in the peripheral blood two weeks after priming.

B(CF)-Catalyzed Regiodivergent Thioetherifications of Alkenes via Thiiranium Intermediates: Experimental and Computational Insights.

Precise control of selective alkene functionalization is a continuing challenge in the chemical community. In this study, we develop a substitution-controlled regiodivergent thioetherification of di- or trisubstituted alkenes using 10 mol % tris(pentafluorophenyl)borane [B(CF)] as a catalyst and N-thiosuccinimide as a sulfenylating reagent. This metal-free borane catalyzed C-S bond forming method is utilized for a Csp-H sulfenylation reaction to synthesize an array of diphenylvinylsulfide derivatives with good to excellent yields (25 examples, up to 91 % yield).

Identification and characterisation of pathogenic and non-pathogenic FGF14 repeat expansions.

Repeat expansions in FGF14 cause autosomal dominant late-onset cerebellar ataxia (SCA27B) with estimated pathogenic thresholds of 250 (incomplete penetrance) and 300 AAG repeats (full penetrance), but the sequence of pathogenic and non-pathogenic expansions remains unexplored. Here, we demonstrate that STRling and ExpansionHunter accurately detect FGF14 expansions from short-read genome data using outlier approaches. By combining long-range PCR and nanopore sequencing in 169 patients with cerebellar ataxia and 802 controls, we compare FGF14 expansion alleles, including interruptions and flanking regions.

Electrocatalytic continuous flow chlorinations with iodine(I/III) mediators.

Electrochemistry offers tunable, cost effective and environmentally friendly alternatives to carry out redox reactions with electrons as traceless reagents. The use of organoiodine compounds as electrocatalysts is largely underdeveloped, despite their widespread application as powerful and versatile reagents. Mechanistic data reveal that the hexafluoroisopropanol assisted iodoarene oxidation is followed by a stepwise chloride ligand exchange for the catalytic generation of the dichloroiodoarene mediator.

Indicators of technostress, their association with burnout and the moderating role of support offers among nurses in German hospitals: a cross-sectional study.

Objectives: To examine the level of indicators of technostress among nurses with and without a leadership position, the relationship between indicators of technostress and burnout and the moderating role of support offered by employers. The availability of support offers and further needs of nurses were also explored.

Design: Cross-sectional online survey.

Correction: An un-forgotten classic: the nitro-Mannich reaction between nitrones and silyl nitronates catalysed by B(CF).

[This corrects the article DOI: 10.1039/D3SC05672D.].

Continuous Flow Electroselenocyclization of Allylamides and Unsaturated Oximes to Selenofunctionalized Oxazolines and Isoxazolines.

The synthesis of selenofunctionalized oxazolines and isoxazolines from -allyl benzamides and unsaturated oximes with diselenides was studied by utilizing a continuous flow electrochemical approach. At mild reaction conditions and short reaction times of 10 min product yields of up to 90% were achieved including a scale-up reaction. A broad substrate scope was studied and the reaction was shown to have a wide functional group tolerance.

Same job, same working conditions? A cross-sectional study to examine the similarities and differences of the working situation in ambulatory and residential youth welfare workers.

Background: Employees in social work exhibit high rates of sick leave due to mental health issues. Additionally, work-related demands in youth welfare have increased in recent years. Particularly in light of the escalating shortage of skilled professionals in this field, this trend becomes especially critical.

NEMO/NF-κB signaling functions as a double-edged sword in PanIN formation versus progression to pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is marked by a dismal survival rate, lacking effective therapeutics due to its aggressive growth, late-stage diagnosis, and chemotherapy resistance. Despite debates on NF-κB targeting for PDAC treatment, no successful approach has emerged.

Methods: To elucidate the role of NF-κB, we ablated NF-κB essential modulator (NEMO), critical for conventional NF-κB signaling, in the pancreata of mice that develop precancerous lesions (KC mouse model).

Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment.

5q-associated spinal muscular atrophy (SMA) is a motoneuron disease caused by mutations in the survival motor neuron 1 (SMN1) gene. Adaptive immunity may contribute to SMA as described in other motoneuron diseases, yet mechanisms remain elusive. Nusinersen, an antisense treatment, enhances SMN2 expression, benefiting SMA patients.

Deville rebooted - practical NO synthesis.

Dinitrogen pentoxide (NO), the anhydride of nitric acid, was synthesised by Henri Étienne Sainte-Claire Deville in Paris in 1849 using silver nitrate and chlorine gas. Herein, we revisit, optimise, and modify Deville's method using photocatalysis to enable a safe, clean, practical, and reproducible alternative for NO synthesis in quantitative yields. Moreover, it is predicted that the modifications can accommodate an industrial scale-up, but the silver chloride generated must be recycled.

Diverse Reactivity of Amidinate-Supported Boron Centers with the Hypersilyl Anion and Access to a Monomeric Secondary Boron Hydride.

Diverse reactivity of the bulky tris(trimethylsilyl)silyl substituent [Si(SiMe)], also known as the hypersilyl group, was observed for amidinate-supported dichloro- and phenylchloroborane complexes. Treatment of the dichloroborane with potassium tris(trimethylsilyl)silyl led to the activation of the backbone β-carbon center and formation of saturated four-membered heterocyclic chloroboranes R'{Si(SiMe)}C(NR)BCl [R' = Ph, R = Cy (); R' = Ph, R = Pr (); R' = Bu, R = Cy ()], whereas the four-membered amidinate hypersilyl-substituted phenyl borane {PhC(NCy)B(Ph)[Si(SiMe)]} was observed for the case of an amidinate-supported phenylchloroborane. The highly deshielded B NMR spectroscopic resonance and the distinct difference in the Si NMR spectrum confirmed the presence of a σ-donating hypersilyl effect on compounds , , and .

Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach.

Background: Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles.

Methods: Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP).

Digital stress perception among German hospital nurses and associations with health-oriented leadership, emotional exhaustion and work-privacy conflict: a cross-sectional study.

Background: The use of digital information and communication technologies (ICT) can be accompanied by increased technostress for nursing staff, which in turn can be associated with health consequences. In addition, the use-related constant accessibility through ICT can have a negative impact on health-related recovery and regeneration phases. Health-promoting behaviors of supervisors can influence health complaints and conflicts between employees' work and private lives.

Rare Missense Variants in KCNJ10 Are Associated with Paroxysmal Kinesigenic Dyskinesia.

Background: Although the group of paroxysmal kinesigenic dyskinesia (PKD) genes is expanding, the molecular cause remains elusive in more than 50% of cases.

Objective: The aim is to identify the missing genetic causes of PKD.

Methods: Phenotypic characterization, whole exome sequencing and association test were performed among 53 PKD cases.

An un-forgotten classic: the nitro-Mannich reaction between nitrones and silyl nitronates catalysed by B(CF).

Herein we report the B(CF)-catalysed nitro-Mannich reaction between nitrones and silyl nitronates, affording silyl-protected α-nitro hydroxylamines with yields up to 99% and diastereoselectivities up to 99 : 1. Crucially, the obtained products can be converted into 1,2-diamines under simple reductive conditions. This work provides a new orthogonal method to the existing routes for the instalment of a nitro moiety under Lewis acid catalysed conditions, and expands the state-of-the-art substrate scope with respect to the silyl nitronates.

The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study.

Background And Objectives: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL).

Methods: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort.

Glial cells react to closed head injury in a distinct and spatiotemporally orchestrated manner.

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. Acute neuroinflammation is a prominent reaction after TBI and is mostly initiated by brain-resident glial cells such as microglia, NG2-glia and astrocytes. The magnitude of this reaction paves the way for long-lasting consequences such as chronic neurological pathologies, for which therapeutic options remain limited.

Does Spinocerebellar ataxia 27B mimic cerebellar multiple system atrophy?

Background: Whether spinocerebellar ataxia 27B (SCA27B) may present as a cerebellar multiple system atrophy (MSA-C) mimic remains undetermined.

Objectives: To assess the prevalence of FGF14 (GAA) expansions in patients with MSA-C, to compare SCA27B and MSA-C clinical presentation and natural history.

Methods: FGF14 expansion screening combined with longitudinal deep-phenotyping in a prospective cohort of 195 patients with sporadic late-onset cerebellar ataxia.