Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

RNase T2 restricts TLR13-mediated autoinflammation in vivo.

RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role in processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition to its positive regulatory role, RNase T2 also restricts RNA recognition through unknown mechanisms, as patients deficient in RNase T2 suffer from neuroinflammation.

A Proof-of-Concept for Safety Evaluation of Inhalation Exposure to Known Respiratory Irritants Using In Vitro and In Silico Methods.

There is increased interest in developing non-animal test systems for inhalation exposure safety assessments. However, defined methodologies are absent for predicting local respiratory effects from inhalation exposure to irritants. The current study introduces a concept for applying in vitro and in silico methods for inhalation exposure safety assessment.

Considerations and Challenges for Acute Inhalation Toxicity Testing and Classification of Zinc Sulphide Under REACH.

Zinc sulphide is a widely used inorganic powder, and its production has reached quantities greater than 1000 t/year. Therefore, in accordance with OECD guideline 436, an acute inhalation test was implemented to provide more accurate data. This study is crucial for ensuring the safety of workers exposed to zinc sulphide dust and complying with regulatory requirements for REACH.

Influenza Immunization in Very-Low-Birth-Weight Infants: Epidemiology and Long-Term Outcomes.

Background: Very-low-birth-weight infants (VLBWIs; birth weight < 1500 g) are at an increased risk of complicated influenza infection, which frequently includes pneumonia, encephalitis or even death. Data on influenza immunization and its outcome in VLBWIs are scarce. This study aimed to provide epidemiological data on influenza immunization for German VLBWIs and hypothesized that immunization would protect VLBWIs from infection-mediated neurodevelopmental impairment and preserves lung function at early school age.

Effects of Microstructured and Anti-Inflammatory-Coated Cochlear Implant Electrodes on Fibrous Tissue Growth and Neuronal Survival.

Cochlear implants are well established devices for treating severe hearing loss. However, due to the trauma caused by the insertion of the electrode and the subsequent formation of connective tissue, their clinical effectiveness varies. The aim of the current study was to achieve a long-term reduction in connective tissue growth and impedance by combining surface patterns on the electrode array with a poly-L-lactide coating containing 20% diclofenac.

Underlying Mechanisms of Chromatographic H/D, H/F, and Isomerism Effects in GC-MS.

Charge-free gaseous molecules labeled with deuterium H (D) atoms elute earlier than their protium-analogs H (H) from most stationary GC phases. This effect is known as the chromatographic H/D isotope effect (IE) and can be calculated by dividing the retention times () of the protiated ( ) to those of the deuterated () analytes: IE = /. Analytes labeled with C, N or O have almost identical retention times and lack a chromatographic isotope effect.

Artificial Intelligence in Cardiac Surgery: Transforming Outcomes and Shaping the Future.

Artificial intelligence (AI) has emerged as a transformative technology in healthcare, with its integration into cardiac surgery offering significant advancements in precision, efficiency, and patient outcomes. However, a comprehensive understanding of AI's applications, benefits, challenges, and future directions in cardiac surgery is needed to inform its safe and effective implementation. A systematic review was conducted following PRISMA guidelines.

Role of Ciliary Neurotrophic Factor in Angiotensin II-Induced Hypertension.

Background: Ciliary neurotrophic factor (CNTF), mainly known for its neuroprotective properties, belongs to the IL-6 (interleukin-6) cytokine family. In contrast to IL-6, the effects of CNTF on the vasculature have not been explored. Here, we examined the role of CNTF in AngII (angiotensin II)-induced hypertension.

Single-Session Surgical Intervention with Resection of a Primary Cranial Osteosarcoma and Cranioplasty using a 3D-Printed Craniotomy Template and Cranioplasty Molds.

Although osteosarcomas are the most frequent primary malignant bone tumors, the primary cranial manifestation of this condition is very rare with only a limited number of cases presented in the literature. We present the case of a 20-year-old male patient who underwent single-session surgical intervention for resection of right frontal osteosarcoma with a tailor-made craniotomy and cranioplasty using virtually designed 3D-printed templates and molds. Subsequently, the patient was treated according to the EURAMOS protocol and received adjuvant systemic chemotherapy.

Evaluation of equine perineural anesthesia simulators with integrated success control for veterinary education.

The skills necessary to perform diagnostic perineural anesthesia in equids belongs to one of the Day One Competences of a veterinarian, so every veterinary graduate should be able to perform them correctly. For logistical, hygienic and ethical reasons, practical exercises on cadaver limbs are not accessible to all students. Two equine distal limb simulators were developed and evaluated as an additional instructional tool to train the required skills.

Towards high atom economy in whole-cell redox biocatalysis: up-scaling light-driven cyanobacterial ene-reductions in a flat panel photobioreactor.

Light-driven biotransformations in recombinant cyanobacteria benefit from the atom-efficient regeneration of reaction equivalents like NADPH from water and light by oxygenic photosynthesis. The self-shading of photosynthetic cells throughout the reaction volume, along with the need for extended light paths, limits adequate light supply and significantly restricts the potential for upscaling. Here, we present a flat panel photobioreactor (1 cm optical path length) as a scalable system to provide efficient illumination at high cell densities.

Effect of baseline values on inpatient rehabilitation outcomes after total knee arthroplasty: a retrospective observational study.

Objective: To compare inpatient rehabilitation outcomes after total knee arthroplasty (TKA) between groups with different baseline scores.

Design: A retrospective observational study.

Subjects: Patients with knee osteoarthritis who have previously undergone unilateral TKA.

Drug interactions in a sample of inpatients diagnosed with cannabis use disorder.

The majority of patients with cannabis use disorder (CUD) regularly take medication. Cannabinoids influence metabolism of some commonly prescribed drugs. However, little is known about the characteristics and frequency of potential cannabis-drug (CDIs) and drug-drug interactions (DDIs) in patients with CUD.

Probing the properties of PTEN specific botulinum toxin type E mutants.

Botulinum neurotoxins (BoNT) are established biopharmaceuticals for neuromuscular and secretory conditions based on their ability to block neurotransmitter release from neurons by proteolyzing specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Recently, a mutant catalytic domain of serotype E (LC/E) exhibiting 16 mutations was reported to cleave the phosphatase and tensin homolog (PTEN). This molecule represents an attractive new target in neurons as several reports support PTEN knockdown as a strategy to stimulate axonal regeneration after injury.

Standardized Reporting of HCC with LI-RADS and mRECIST: Update on the Situation in Germany.

Online survey about the current status of CT protocols in hepatocellular carcinoma (HCC) in the year 2023/2024. Moreover, the usage of structured reporting using LI-RADS and mRECIST was surveyed and the results were compared with a survey from 2020.Radiologists working in outpatient or inpatient care in Germany were invited.

Free-Breathing Respiratory Triggered High-Pitch Lung CT: Insights From Phantom and Patient Scans.

Objective: Respiratory motion can affect image quality and thus affect the diagnostic accuracy of CT images by masking or mimicking relevant lung pathologies. CT examinations are often performed during deep inspiration and breath-hold to achieve optimal image quality. However, this can be challenging for certain patient groups, such as children, the elderly, or sedated patients.

TIGIT-expression on natural killer cell subsets is an early indicator of alleviating liver inflammation following bulevirtide treatment in chronic hepatitis D.

Background Aims: Bulevirtide (BLV) is a novel and the only approved treatment option for patients with chronic hepatitis D (CHD). BLV alleviates liver inflammation already early during treatment when only minor HDV RNA changes are observed. We hypothesized that BLV-treatment may influence immune cells in CHD patients and performed a high-resolution analysis of natural killer (NK) cells before and during BLV-therapy.

Antibacterials with Novel Chemical Scaffolds in Clinical Development.

The rise of antimicrobial resistance represents a significant global health threat, driven by the diminishing efficacy of existing antibiotics, a lack of novel antibacterials entering the market, and an over- or misuse of existing antibiotics, which accelerates the evolution of resistant bacterial strains. This review focuses on innovative therapies by highlighting 19 novel antibacterials in clinical development as of June 2024. These selected compounds are characterized by new chemical scaffolds, novel molecular targets, and/or unique mechanisms of action, which render their potential to break antimicrobial resistance particularly high.

Exhalation of Rn-219 by patients treated with Radium-223.

Background: Treatment with Ra-223 dichloride is approved for the therapy of castration resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases in Europe since 2013, and Ra-223 is under discussion for labelling other molecules and nanoparticles. The direct progeny of Ra-223 is Rn-219, also known as actinon, a radioactive noble gas with a half-life of 3.98 s.

Microvascular reconstruction in oral and maxillofacial surgery: a Europe-wide data collection.

Purpose: This study aims to analyze microvascular reconstruction in Oral and Maxillofacial Surgery (OMFS) in Europe.

Methods: Based on previous studies, a dynamic online questionnaire was developed and subjected to internal and external evaluation. The questionnaire comprised multiple-choice, rating, and open-ended questions, addressing general and specific aspects and the impacts of the COVID-19 pandemic on microvascular reconstruction in OMFS in Europe.

Impact of diabetes mellitus type two on incidence and progression of Parkinson's disease: a systematic review of longitudinal patient cohorts.

Parkinson's disease (PD) is a chronic neurodegenerative disease of the elderly. Patients suffer from progressive motor and non-motor symptoms. Further, PD patients often present geriatric features like multimorbidity and polypharmacotherapy.

Identification of a Biosynthetic Gene Cluster for the Production of the Blue-Green Pigment Xylindein by the Fungus .

Xylindein is a blue-green pigment produced by the fungi and Its stunning color and optoelectronic properties make xylindein valuable for textiles and as a natural semiconductor material. However, producing xylindein from culture broths remains challenging because of the slow growth of the species and the poor solubility of xylindein in organic solvents. An alternative production route for obtaining pure xylindein is heterologous expression of the xylindein biosynthetic genes.

Investigating the influence of a bubble curtain on the underwater sound wave field generated by offshore pile driving.

Pile driving for offshore wind turbines typically generates high sound levels in the water column. Bubble curtains are frequently employed to protect marine fauna. This study aims to investigate the effect of a bubble curtain on the generated sound wave field.

Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection.

Background And Aims: Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection.