Loading of CAR-T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism.

Therapies against hematological malignancies using chimeric antigen receptors (CAR)-T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer-specific solid tumor antigens. Therefore, the enrichment of tumor-antigen specific CAR-T cells in the desired region is critical for improving therapy efficacy and reducing systemic on-target/off-tumor side effects. Here, we functionalized human CAR-T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site-directed targeting.

Advances in the Treatment of Neonatal Coarctation of the Aorta.

Coarctation of the aorta (CoA) is a potentially life-threatening congenital and obstructive anomaly of the distal aortic arch. After constriction of the ductus arteriosus, neonates may develop critical CoA in the isthmus area and present with severe left ventricular dysfunction or even cardiac failure. Low cardiac output and abdominal hypoperfusion (distal to the coarctation) may lead to metabolic derangements and clinical deterioration.

Molecular Profiling of Sinonasal Adenoid Cystic Carcinoma: Canonical and Noncanonical Gene Fusions and Mutation.

Adenoid cystic carcinomas (AdCC) of salivary gland origin have long been categorized as fusion-defined carcinomas owing to the almost universal presence of the gene fusion MYB::NFIB, or less commonly MYBL1::NFIB. Sinonasal AdCC is an aggressive salivary gland malignancy with no effective systemic therapy. Therefore, it is urgent to search for potentially targetable genetic alterations associated with AdCC.

Peripartum and Perinatal Outcomes in Pregnant Women with Elevated Preconceptional Body Mass Index in a Maternity Hospital (Care Level IV).

Introduction: Preconception obesity is a risk factor for pregnancy and delivery, which is why giving birth in a perinatal center (care levels I and II) is recommended. There are currently no studies which have investigated the birth outcomes of obese patients based on the care level of the maternity hospital. This study aims to assess the effect of a higher body mass index prior to conception on maternal and fetal outcomes in a maternity hospital (care level IV).

Differences between Current Clinical Practice and Evidence-Based Guideline Recommendations Regarding Tocolysis - an Austria-wide Survey.

Introduction: To evaluate the adherence of Austrian obstetricians to national guideline recommendations by investigating data on the current practice of tocolysis regarding indications, timing and monitoring of tocolysis, choice of tocolytics and serious side effects, maintenance tocolysis, support of decision-making and recommendations at patient's discharge from the hospital.

Materials And Methods: 78 obstetric departments in Austria were invited to participate in a nationwide survey between June 5 and August 31 2023 by answering a web-based questionnaire about clinical standards. The survey was conducted approximately one year after implementation of the AWMF Guideline "Prevention and Therapy of Preterm Birth" 015‑025.

Aggressive Subtypes of Laryngeal Chondrosarcoma and their Clinical Behavior: A Systematic Review.

Introduction: Laryngeal chondrosarcoma (CS) is a rare indolent malignant tumor. High-grade (G3), dedifferentiated (DD), and myxoid (MY) CSs are considered more aggressive subtypes due to their metastatic potential and relatively poor outcomes. The aim of this systematic review is to evaluate treatment modalities and survival outcomes in patients affected by these rarer CS subtypes.

Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.

Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer's disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls.

Real-world management of patients with complete response under immune-checkpoint inhibition for advanced melanoma.

Background: Up to now, the optimal duration of immune checkpoint inhibitors (ICI) has not been evaluated in prospective studies. However, current clinical practice requires decisions to be made regarding the duration of ICI in complete responders.

Material And Methods: A survey was sent to 80 DeCOG skin cancer centers to assess how decisions are made on treatment duration of ICI in melanoma after having reached complete response, and staging intervals after ICI discontinuation.

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Higher-order transient membrane protein structures.

This study shows that five membrane proteins-three GPCRs, an ion channel, and an enzyme-form self-clusters under natural expression levels in a cardiac-derived cell line. The cluster size distributions imply that these proteins self-oligomerize reversibly through weak interactions. When the concentration of the proteins is increased through heterologous expression, the cluster size distributions approach a critical distribution at which point a phase transition occurs, yielding larger bulk phase clusters.

Evaluating a computer-based body exposure paradigm for the treatment of body image disturbance in adolescent Anorexia Nervosa: effects on the attentional bias and emotions.

Background: A diagnostic criterion of Anorexia Nervosa (AN) is body image disturbance. Body exposure therapy is a widely used approach to treat this; however, it is unclear which part of body exposure therapy is relevant for regaining a realistic perspective on the own body. This study aimed to examine the role of the attentional bias (AB), which AN patients exhibit to the most disliked parts of their body.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Compensating elastic faults in a torque-assisted knee exoskeleton: functional evaluation and user perception study.

Wearable robots are often powered by elastic actuators, which can mimic the intrinsic compliance observed in human joints, contributing to safe and seamless interaction. However, due to their increased complexity, when compared to direct drives, elastic actuators are susceptible to faults, which pose significant challenges, potentially compromising user experience and safety during interaction. In this article, we developed a fault-tolerant control strategy for torque assistance in a knee exoskeleton and investigated user experience during a walking task while emulating faults.

Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.

Objectives: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modelling the natural history, and uncovering genotype-phenotype associations.

Methods: A cross-sectional analysis of 90 published and one novel case was performed, employing a Human Phenotype Ontology-based approach.

Addressing the role of surgery in brain tumour trials: A report from the neurosurgery committee of the EORTC brain tumour group.

The Brain Tumor Group (BTG) of the European Organization for Research and Treatment of Cancer (EORTC) conducts academic clinical trials and translational research to improve clinical management of patients with primary and secondary brain tumors. The EORTC BTG has traditionally played an important role in providing evidence and thus advancing the field, albeit with a main focus on radiotherapy and pharmacotherapy in gliomas. Although examples of well-designed neuro-oncological surgical trials can be found, evidence in surgical neuro-oncology predominantly includes data from uncontrolled prospective series or retrospective cohorts.

Tagless LysoIP for immunoaffinity enrichment of native lysosomes from clinical samples.

Lysosomes are implicated in a wide spectrum of human diseases including monogenic lysosomal storage disorders (LSDs), age-associated neurodegeneration and cancer. Profiling lysosomal content using tag-based lysosomal immunoprecipitation (LysoTagIP) in cell and animal models has substantially moved the field forward, but studying lysosomal dysfunction in human patients remains challenging. Here, we report the development of the 'tagless LysoIP' method, designed to enable the rapid enrichment of lysosomes, via immunoprecipitation, using the endogenous integral lysosomal membrane protein TMEM192, directly from clinical samples and human cell lines (e.

Disturbed spatial WNT activation - a potential driver of the reticularized skin phenotype in Systemic Sclerosis (SSc).

Objectives: Little is known on the mechanisms necessary to maintain the physiological adult human skin integrity. This study aims to quantitatively describe anatomical changes in systemic sclerosis (SSc)-skin compared to controls and investigate the underlying mechanisms.

Methods: Skin morphology was histologically assessed in twenty-three SSc-patients, eighteen controls and fifteen patients with hypertrophic scars.

A Firing Cannon: Bilateral Lower Limb Ischemia as a Manifestation of Cardiac Myxoma.

 Cardiac myxomas are the most common primary cardiac neoplasms.  We present a case of a middle-aged lady with cardiac myxoma in her left atrium awaiting semi-elective surgery. During the preoperative period, the patient presented emergently with acute bilateral lower limb ischemia.

is implicated in central nervous system, orofacial and maxillofacial anomalies.

Background: Previous studies in mouse, and zebrafish embryos show strong expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 ( in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies.

Persistent humid climate favored the Qin and Western Han Dynasties in China around 2,200 y ago.

The Qin and Western Han dynasties (221 BCE to 24 CE) represent an era of societal prosperity in China. However, due to a lack of high-resolution paleoclimate records it is still unclear whether the agricultural boost documented for this period was associated with more favorable climatic conditions. Here, multiparameter analysis of annually resolved tree-ring records and process-based physiological modeling provide evidence of stable and consistently humid climatic conditions during 270 to 77 BCE in northern China.

Optimized monitoring for immune checkpoint inhibitor induced myocarditis using high-sensitivity troponin-T.

Background: Immune checkpoint inhibitor (ICI)-induced Myocarditis (irMyocarditis) is a rare adverse event with a high mortality rate of 40-50 % and which is mostly not diagnosed until clinical symptoms emerge.

Objectives: This study aims to screen patients for irMyocarditis using high-sensitivity cardiac troponin-T (hs-TnT) before and regularly during therapy with ICI.

Methods: A cohort of 280 cancer patients were prospectively screened for levels of hs-TnT at baseline and prior to every ICI infusion.

Application comparison of paediatric myocardial protection procedures in arterial switch surgery.

Background: Reliable myocardial protection is essential for a good outcome after arterial switch operation.

Patients And Methods: We evaluated 56 neonates with arterial switch operation in this retrospective study. Three types of cardioplegia were used: antegrade Custodiol® (CCC) = 22, antegrade Custodiol® plus paediatric microplegia (mix) = 14, and antegrade plus retrograde intermittently paediatric microplegia (blood) = 20.