Phosphorylation-dependent WRN-RPA interaction promotes recovery of stalled forks at secondary DNA structure.

The WRN protein is vital for managing perturbed replication forks. Replication Protein A strongly enhances WRN helicase activity in specific in vitro assays. However, the in vivo significance of RPA binding to WRN has largely remained unexplored.

Sanctuary for vulnerable Arctic species at the Borealis Mud Volcano.

Borealis is a recently discovered submerged mud volcano in the Polar North Atlantic, differing from the numerous methane seepages previously identified in the region. Here we show in situ observations from a remotely operated vehicle (ROV), capturing the release of warm (11.5 °C) Neogene sediments and methane-rich fluids from a gryphon at Borealis.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: an international multicentre retrospective cohort study.

Background: Most patients undergoing pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) develop recurrence. No previous studies have investigated predictors of local-only recurrence following PD for PDAC. Our study aimed to determine timing, pattern and predictors of any-site and local-only recurrence following PD for PDAC.

Extended cognitive load induces fast neural responses leading to commission errors.

Extended performance of cognitively demanding tasks induces cognitive fatigue manifested with an overall deterioration of behavioral performance. In particular, long practice with tasks requiring impulse control is typically followed by a decrease in self-control efficiency, leading to performance instability. Here, we show that this is due to changes in activation modalities of key task-related areas occurring if these areas previously underwent intensive use.

A role for mitochondria-ER crosstalk in amyotrophic lateral sclerosis 8 pathogenesis.

Protein aggregates in motoneurons, a pathological hallmark of amyotrophic lateral sclerosis, have been suggested to play a key pathogenetic role. ALS8, characterized by ER-associated inclusions, is caused by a heterozygous mutation in VAPB, which acts at multiple membrane contact sites between the ER and almost all other organelles. The link between protein aggregation and cellular dysfunction is unclear.

Expanding the phenotypic spectrum of PROS: reclassifying isolated lateralised overgrowth.

Lateralised overgrowth (LO) is characterised by the asymmetric increase in the size of any part of the body exceeding 10% compared with the unaffected contralateral one. LO is a key feature in various syndromic overgrowth disorders, such as Beckwith-Wiedemann spectrum and -related overgrowth spectrum (PROS). However, it can also present as isolated (ILO).

Safety of interleukin inhibitors in patients with plaque psoriasis and history of neoplasms: a multicenter retrospective study - IL PSO (Italian landscape psoriasis).

Interleukin (IL) inhibitors are increasingly used in the management of moderate-to-severe plaque psoriasis. However, their use in patients with a history of cancer is debated. We conducted a multicenter retrospective study across nine Italian Dermatology Units to assess the real-world effectiveness and safety of IL inhibitors (IL-23, IL-17, IL-12/23) in 136 oncological patients with moderate-to-severe plaque psoriasis.

The Autonomic Nervous System and Inflammation in Chronic Kidney Disease.

The autonomic nervous system plays a crucial role in regulating physiological processes and maintaining homeostasis through its two branches: the sympathetic nervous system (SNS) and the parasympathetic nervous system. Dysregulation of the autonomic system, characterized by increased sympathetic activity and reduced parasympathetic tone, is a common feature in chronic kidney disease (CKD) and cardiovascular disease. This imbalance contributes to a pro-inflammatory state, exacerbating disease progression and increasing the risk for cardiovascular events.

How to: share and reuse data - challenges and solutions from PrIMAVeRa project.

Background: Data sharing accelerates scientific progress and improves evidence quality. Even though journals and funding institutions require investigators to share data, only a small part of studies made their data publicly available upon publication. The procedures necessary to share retrospective data for re-use in secondary data analysis projects can be cumbersome.

Informed Consent and Shared Decision-Making in Modern Medicine. Case-based Approach, Current Gaps and Practical Proposal.

Advances in personalized medicine and Systems Biology have introduced probabilistic models and error discovery to cardiovascular care, aiding disease prevention and procedural planning. However, clinical application faces cultural, technical, and methodological hurdles. Patient autonomy remains essential, with shared decision-making (SDM) gaining importance in managing complex cardiovascular treatment options.

Prospective Validation of CAR-HEMATOTOX and a simplified version predict Survival in Patients with Large B-Cell Lymphoma treated with anti-CD19 CAR T-cells: data from CART-SIE study.

Background: Anti-CD19 CAR T-cells have revolutionized outcomes in relapsed/refractory large B-cell lymphomas. Long-term follow-up underscored the role of hematological toxicity in non-relapse mortality, largely driven by infections, leading to the development of the CAR-HEMATOTOX (HT) score for predicting neutropenia. The European scientific community (EHA/EBMT) later reached a consensus, defining a new entity: immune effector cell-associated hematotoxicity (ICAHT).

Kinetic and structural investigation of the 4-allyl syringol oxidase from Streptomyces cavernae.

4-Phenol oxidases are proposed to be involved in the utilization of lignin-derived aromatic compounds. While enzymes with selectivity towards 4-hydroxyphenyl and guaiacyl motifs are well described, we identified the first syringyl-specific oxidase from Streptomyces cavernae (Sc4ASO) only very recently. Here, in-depth studies were conducted to unravel the molecular origins of the outstanding selectivity of Sc4ASO.

A review of lignin as a precursor for macromonomers: Challenges and opportunities in utilizing agri-food waste.

Lignocellulosic biomass, rich in cellulose, hemicellulose, and lignin, represents a promising renewable resource. However, lignin, a complex polyphenolic material, remains underutilized despite its surplus production. This review focuses on the conversion of lignin into macromonomers for polymer production.

Brain State Forecasting for Precise Brain Stimulation: Current Approaches and Future Perspectives.

Transcranial magnetic stimulation (TMS) has the potential to yield insights into cortical functions and improve the treatment of neurological and psychiatric conditions. However, its reliability is hindered by a low reproducibility of results. Among other factors, such low reproducibility is due to structural and functional variability between individual brains.

Additively Manufactured Subperiosteal Implants for the Rehabilitations of Lateral Incisors Agenesis - a case series.

Background: Tooth agenesis, particularly the absence of upper lateral incisors, presents substantial challenges for clinicians due to the associated bone atrophy, which limits the use of traditional implant solutions. Current options, such as endosseous implants combined with guided bone regeneration (GBR), often fail due to insufficient osseointegration in atrophic bone. This study aims to evaluate the effectiveness of custom-made, additively manufactured subperiosteal implants in addressing these challenges METHODS: This retrospective study assessed 16 custom-made subperiosteal implants used in 12 patients (10 females, 2 males; mean age 25 ± 2.

Efficacy and safety of long-acting muscarinic antagonists in COPD: a meta-analysis and meta-regression with a focus on aging.

The increasing global elderly population, projected to reach 20% of individuals aged 65 and over by 2030, faces significant pulmonary challenges, including chronic obstructive pulmonary disease (COPD). Aging is associated with a natural decline in lung function and structural changes that exacerbate respiratory issues. COPD, characterized by chronic respiratory symptoms and airflow obstruction, presents a unique challenge in older patients due to the accelerated decline in lung function.

Development of nebulized inhalation delivery for fusion-inhibitory lipopeptides to protect non-human primates against Nipah-Bangladesh infection.

Nipah virus (NiV) is a lethal zoonotic paramyxovirus that can be transmitted from person to person through the respiratory route. There are currently no licensed vaccines or therapeutics. A lipopeptide-based fusion inhibitor was developed and previously evaluated for efficacy against the NiV-Malaysia strain.

Changes in Coagulation Factor XI Activity Levels in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI.

Background - Although Factor XI (FXI) inhibitors are currently tested for the prevention of thrombotic events, their early treatment could prevent thrombus consolidation in ST-segment elevation myocardial infarction (STEMI). This study aims to characterize coagulation FXI levels and their variations in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). Methods - Patients with STEMI were prospectively enrolled between December 2023 and May 2024.

Intraoperative methylene blue staining is effective as a single mapping technique in the identification of sentinel lymph nodes in dogs with low-grade mast cell tumours.

Objectives: The aim of this prospective study was to assess the association between methylene blue staining pattern and the presence of histologic nodal metastasis in dogs with low-grade mast cell tumour in low-resource settings for the efficient diagnosis of lymphatic spread.

Methods: Dogs with a single, cytologically low-grade mast cell tumour and no documented distant metastases were prospectively included and underwent surgery. Along with primary mast cell tumour removal, intraoperative sentinel lymph node mapping with peritumoral mast cell tumour injection and regional lymph node excision, regardless of whether blue dye was visible in the lymph node, were performed.

State of the Art and Emerging Technologies in Vaccine Design for Respiratory Pathogens.

In this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, respiratory syncytial virus (RSV), the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), , (), , and . Advancements driven by the recent coronavirus disease 2019 (COVID-19) crisis have largely focused on viruses, but effective prophylactic solutions for bacterial pathogens are also needed, especially in light of the antimicrobial resistance (AMR) phenomenon. Here, we discuss various innovative key technologies that can help address this critical need, such as (a) the development of Lung-on-Chip ex vivo models to gain a better understanding of the pathogenesis process and the host-microbe interactions; (b) a more thorough investigation of the mechanisms behind mucosal immunity as the first line of defense against pathogens; (c) the identification of correlates of protection (CoPs) which, in conjunction with the Reverse Vaccinology 2.