Influenza A virus replication has a stronger dependency on Raf/MEK/ERK signaling pathway activity than SARS-CoV-2.

The recent COVID-19 pandemic again highlighted the urgent need for broad-spectrum antivirals, both for therapeutic use in acute viral infection and for pandemic preparedness in general. The targeting of host cell factors hijacked by viruses during their replication cycle presents one possible strategy for development of broad-spectrum antivirals. By inhibiting the Raf/MEK/ERK signaling pathway, a central kinase cascade of eukaryotic cells, which is being exploited by numerous viruses of different virus phyla, the small-molecule MEK inhibitor zapnometinib has the potential to address this need.

The effect of an infra-acetabular screw for anatomically shaped three-dimensional plate or standard plate designs in acetabulum fractures: a biomechanical analysis.

Background: Various plate shapes and implant configurations are used for stabilization of acetabulum fractures via anterior approaches. Little is known about the biomechanical stability of a two-dimensionally shaped "conventional" plate ("J-Plate"-JP) in comparison to three-dimensionally shaped plate configurations (3DP). In addition, the augmentary effect of an infra-acetabular lag-screw (IACS) fixation for anterior column and posterior hemi-transverse acetabulum fractures has not been clarified in comparison of JP and 3DP constructs.

Macrophage-activating lipoprotein (MALP)-2 impairs the healing of partial tendon injuries in mice.

Tendon injuries are accounted for up to 50% of musculoskeletal injuries and often result in poor outcomes. Inflammation is a major hallmark of tendon regeneration. Therefore, we analyzed in this study whether the topical application of the pro-inflammatory mediator macrophage-activating lipoprotein (MALP)-2 improves the healing of partial tendon injuries.

Salivary gland carcinoma in children and adolescents: The EXPeRT/PARTNER diagnosis and treatment recommendations.

Salivary gland carcinomas (SGCs) are rare during childhood and adolescence. Consequently, no standardized recommendations for the diagnosis and therapeutic management of pediatric SGC are available, and pediatric oncologists and surgeons generally follow adult guidelines. Complete surgical resection with adequate margins constitutes the cornerstone of treatment.

Facing the challenges of very rare tumors of pediatric age: The European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) background, goals, and achievements.

It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects.

Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection.

The European Paediatric Rare Tumours Network - European Registry (PARTNER) project for very rare tumors in children.

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created.

Thymoma and thymic carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population.

Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT).

Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy.

Role of Iron Sulfide Phases in the Stability of Noncrystalline Tetravalent Uranium in Sediments.

Uranium (U) bioremediation has been investigated as a cost-effective strategy to tackle U contamination in the subsurface. While uraninite was believed to be the only product of bioreduction, numerous studies have revealed that noncrystalline U(IV) species (NCU(IV)) are dominant. This finding brings into question the effectiveness of bioremediation because NCU(IV) species are expected to be labile and susceptible to oxidation.

Diversity of peptidoglycan structure-Modifications and their physiological role in resistance in antibiotic producers.

Peptidoglycan (PG) is a bacteria specific cell surface layer that ensures the bacterial shape and integrity. The two actinomycetes Amycolatopsis balhimycina and Microbispora sp. PTA-5024 are producers of PG targeting antibiotics.

Role of the Streptomyces spore wall synthesizing complex SSSC in differentiation of Streptomyces coelicolor A3(2).

A crucial stage of the Streptomyces life cycle is the sporulation septation, a process were dozens of cross walls are synchronously formed in the aerial hyphae in a highly coordinated manner. This process includes the remodeling of the spore envelopes to make Streptomyces spores resistant to detrimental environmental conditions. Sporulation septation and the synthesis of the thickened spore envelope in S.

Pre-clinical study on a telemetric gastric sensor for recognition of acute upper gastrointestinal bleeding: the "HemoPill monitor".

Background: Acute upper gastrointestinal bleeding is a life-threatening medical condition with a relevant risk of re-bleeding even after initial endoscopic hemostasis. The implantable HemoPill monitor contains a novel telemetric sensor to optically detect blood in the stomach allowing the surveillance of high-risk patients for re-bleedings.

Methods: In this pre-clinical porcine study, bleeding has been simulated by injecting porcine blood into the stomach of a pig through an implanted catheter using a syringe pump.

Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors.

Although all tumours are rare in childhood, there are some particularly rare paediatric cancers which have not benefited from advances made by the international paediatric oncology network. To establish a shared definition and produce a list of these entities, the European Union Joint Action on Rare Cancers (JARC) promoted a consensus effort. The definition was based on the incidence rates estimated using the information network on rare cancers (RARECAREnet) database, pooling data from 94 population-based cancer registries and 27 countries.

The FtsK-like motor TraB is a DNA-dependent ATPase that forms higher-order assemblies.

TraB is an FtsK-like DNA translocase responsible for conjugative plasmid transfer in mycelial Unlike other conjugative systems, which depend on a type IV secretion system, requires only TraB protein to transfer the plasmid as dsDNA. The γ-domain of this protein specifically binds to repeated 8-bp motifs on the plasmid sequence, following a mechanism that is reminiscent of the FtsK/SpoIIIE chromosome segregation system. In this work, we purified and characterized the enzymatic activity of TraB, revealing that it is a DNA-dependent ATPase that is highly stimulated by dsDNA substrates.

A comparison of the efficacy of immunomodulatory-free regimens in relapsed or refractory multiple myeloma: a network meta-analysis.

Treatment history influences the outcomes of subsequent therapies in patients with relapsed or refractory multiple myeloma (RRMM) and needs to be considered when deciding which treatment to use next. To assess the relative merits of immunomodulatory (IMiD)-free treatments, a systematic literature review (SLR) was conducted to identify relevant randomized controlled trials in patients with RRMM. A network meta-analysis (NMA) was performed to assess various IMiD-free regimens, including bortezomib and dexamethasone (Vd)-based treatments, and to explore differences in patient outcomes.

Balloon Guided Cement Augmentation of Iliosacral Screws in the Treatment of Insufficiency Fractures of the Sacrum - Description of a New Method and Preliminary Results.

PURPOSE OF THE STUDY Fragility fractures of the pelvic ring in the elderly population are a serious problem in orthopaedics. The treatment options range from conservative treatment to diverse operative options. We present a balloon guided new technique of implanting cement augmented screws aiming at improved implant anchorage and reduced cement leakage.

Daratumumab plus bortezomib and dexamethasone bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR.

Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A analysis based on treatment history and longer follow up is presented. After 19.

The pSG5-based thermosensitive vector family for genome editing and gene expression in actinomycetes.

Actinomycetes are the most important producers of secondary metabolites for medical, agricultural and industrial applications. Efficient engineering of bacterial genomes to improve their biosynthetic capabilities largely depends on the available arsenal of tools and vectors. One of the most widely used vector systems for actinomycetes is derived from the Streptomyces ghanaensis DSM2932 plasmid pSG5.

The UK Centre for Astrobiology: A Virtual Astrobiology Centre. Accomplishments and Lessons Learned, 2011-2016.

The UK Centre for Astrobiology (UKCA) was set up in 2011 as a virtual center to contribute to astrobiology research, education, and outreach. After 5 years, we describe this center and its work in each of these areas. Its research has focused on studying life in extreme environments, the limits of life on Earth, and implications for habitability elsewhere.

Design, Synthesis, and Biological Evaluation of Novel Type I/ p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine.

We recently reported 1a (skepinone-L) as a type I p38α MAP kinase inhibitor with high potency and excellent selectivity in vitro and in vivo. However, as a type I inhibitor, it is entirely ATP-competitive and shows just a moderate residence time. Thus, the scope was to develop a new class of advanced compounds maintaining the structural binding features of skepinone-L scaffold like inducing a glycine flip at the hinge region and occupying both hydrophobic regions I and II.

TNFα induced up-regulation of Na,K,2Cl cotransporter NKCC1 in hepatic ammonia clearance and cerebral ammonia toxicity.

The devastating consequences of hepatic failure include hepatic encephalopathy, a severe, life threatening impairment of neuronal function. Hepatic encephalopathy is caused by impaired hepatic clearance of NH. Cellular NH uptake is accomplished mainly by the Na,K,2Cl cotransporter.

Comparison of Ventricular Inducibility with Late Gadolinium Enhancement and Myocardial Inflammation in Endomyocardial Biopsy in Patients with Dilated Cardiomyopathy.

Background: Risk stratification of patients with non-ischemic dilated cardiomyopathy remains a matter of debate in the era of device implantation.

Objective: We investigated associations between histopathological findings, contrast-enhanced cardiac MRI and the inducibility of ventricular tachycardia (VT) or fibrillation (VF) in programmed ventricular stimulation.

Methods: 56 patients with impaired left ventricular ejection fraction (LVEF≤50%, mean 36.