Unconventional Imaging Methods in Psoriatic Arthritis.

Purpose Of Review: Psoriatic arthritis (PsA) is a complex heterogeneous inflammatory disease that affects about one-third of patients with psoriasis. PsA leads to significant physical impairment and reduced quality of life. Therefore, early diagnosis and intervention are critical for improving long-term outcomes.

Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.

The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).

Improving Photocatalytic Hydrogen Generation via Polycitric Acid-based Carbon Nanodots.

Bottom-up syntheses of carbon nanodots (CND) using solvothermal treatment of citric acid are known to afford nanometer-sized, amorphous polycitric acid-based materials. The addition of suitable co-reactants in the form of in-situ synthesized N-hetero-π-conjugated chromophores facilitates hereby the overall functionalization. Our incentive was to design a CND model that features phenazine (P-CND) - a well-known N-hetero-π-conjugated chromophore - to investigate the influence of the CND matrix on its redox chemistry as well as photochemistry.

Different Pathways of Externalising Behaviour Problems From Preschool to Youth: A Test of Risk and Protective Factors and Potential Origins.

Background: This article is dedicated to David Farrington who was a giant in criminology and, in particular, a pioneer in studying developmental pathways of delinquent and antisocial behaviour. Numerous studies followed his work. Systematic reviews of his and others' research described between two and seven (mainly 3-5) trajectories.

Expression of vesiculation-related genes is associated with a tumor-promoting microenvironment: a pan-cancer analysis.

Background: Small extracellular vesicles (sEV) released by tumor cells (tumor-derived sEV; TEX) mediate intercellular communication between tumor and non-malignant cells and were shown to impact disease progression. This study investigates the relationship between the expression levels of the vesiculation-related genes linked to sEV production and the tumor microenvironment (TME).

Methods: Two independent gene sets were analyzed, both previously linked to sEV production in various non-malignant or malignant cells.

Paucity of viral infection symptoms in patients with immune-mediated inflammatory diseases.

Objectives: Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.

Design: A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.

Mode of Metal Ligation Governs Inhibition of Carboxypeptidase A.

Carboxypeptidase is a Zn-dependent protease that specifically recognises and hydrolyses peptides with a hydrophobic side chain at the C-terminal residue. According to hydrolysis mechanisms proposed in the literature, catalysis requires a water molecule to be close to the Zn ion so as to be activated as a nucleophile. Among small molecules that resemble the slowly hydrolysed Gly-Tyr peptide, which have been previously designed as inhibitors and characterised structurally, a variant with the terminal amino acid in a D-configuration has been the most effective.

Functional and Biological Characterization of the LGR5Δ5 Splice Variant in HEK293T Cells.

The regulator of the canonical Wnt pathway, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), is expressed in the stem cell compartment of several tissues and overexpressed in different human carcinomas. The isoform of the stem cell marker LGR5, named LGR5Δ5 and first described by our group, is associated with prognosis and metastasis in oral squamous cell carcinoma (OSCC) and soft tissue sarcoma (STS). In a proof-of-principle analysis, the function of LGR5Δ5 was investigated in HEK293T cells, a model cell line of the Wnt pathway, compared to full-length LGR5 (FL) expression.

Effect of Metformin on Meibomian Gland Epithelial Cells: Implications in Aging and Diabetic Dry Eye Disease.

Background: Metformin, a commonly prescribed medication for managing diabetes, has garnered increasing interest as a potential therapeutic option for combating cancer and aging.

Methods: The current study investigated the effects of metformin treatment on human meibomian gland epithelial cells (hMGECs) at morphological, molecular, and electron microscopy levels. HMGECs were stimulated in vitro with 1 mM, 5 mM, and 10 mM metformin for 24, 48, and 72 h.

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.

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.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Surveillance of drug prescribing: why outliers miss their targets - a qualitative study.

Background: Rising costs are a challenge for healthcare systems. To keep expenditure for drugs under control, in many healthcare systems, drug prescribing is continuously monitored. The Bavarian Drug Agreement (German: Wirkstoffvereinbarung or WSV) for the ambulatory sector in Bavaria (the federal state of Germany) was developed for this purpose.

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.