Meniscal forces and knee kinematics are affected by tibial slope modifying high tibial osteotomy.

Purpose: To quantify the effect of increasing the posterior tibial slope (PTS) on knee kinematics and the resultant medial and lateral meniscal forces.

Methods: In this controlled laboratory study, a 6 degrees of freedom (DOF) robotic testing system was used to apply external loading conditions to seven fresh-frozen human cadaveric knees: (1) 200-N axial compressive load, (2) 5-N m internal tibial +10-N m valgus torque and (3) 5-N m external tibial + 10-N m varus torque. Knee kinematics and the resultant medial and lateral meniscal forces were acquired for two PTS states: (1) native PTS and (2) increased PTS.

Donor C1 Group KIR-ligand inferiority is linked to increased mortality in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide.

Background Aims: In HLA-identical hematopoietic stem cell transplantation (HSCT), HLA-C1 group killer cell immunoglobulin-like receptor (KIR) ligands have been linked to graft-versus-host disease, whereas C2 homozygosity was associated with increased relapses. The differential impact of the recipients versus the donor's HLA-C KIR ligands cannot be determined in HLA-identical HSCT but may be elucidated in the haploidentical setting, in which HLA-C (including the HLA-C KIR ligand group) mismatching is frequently present.

Methods: We retrospectively investigated the effect of recipient versus donor C1 ligand content on survival and complications in post-transplant cyclophosphamide (PTCy)-based haploidentical HSCT (n = 170).

Special screw corridors and imaging in pelvic ring trauma.

Adequate intraoperative visualization is mandatory for implant application in pelvic ring injuries. Several fluoroscopic X-ray views are in practical use. The gold standard primary X-ray is the anteroposterior view of the pelvis.

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.

Intra-individual variability in ancient plasmodium DNA recovery highlights need for enhanced sampling.

Malaria has been a leading cause of death in human populations for centuries and remains a major public health challenge in African countries, especially affecting children. Among the five Plasmodium species infecting humans, Plasmodium falciparum is the most lethal. Ancient DNA research has provided key insights into the origins, evolution, and virulence of pathogens that affect humans.

The dynamics of higher-order novelties.

Studying how we explore the world in search of novelties is key to understand the mechanisms that can lead to new discoveries. Previous studies analyzed novelties in various exploration processes, defining them as the first appearance of an element. However, novelties can also be generated by combining what is already known.

Altered thrombin generation with prothrombin complex concentrate is not detected by viscoelastic testing: an in vitro study.

Background: Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity.

Establishment of the REMBAC-cassette, a rapid, efficient and manifold BacMam tool for recombinant protein expression.

Efficient recombinant protein production requires mammalian stable cell lines or often relies on inefficient transfection processes. Baculoviral transduction of mammalian cells (BacMam) offers cost-effective and robust gene transfer and straightforward scalability. The advantages over conventional approaches are, no need of high biosafety level laboratories, efficient transduction of various cell types and transfer of large transgenes into host cells.

Host hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury.

Background & Aims: Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood.

The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells.

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for targeting "undruggable" proteins, and several PROTACs have reached the stage of clinical candidates. However, the roles of cellular transmembrane transporters in PROTAC uptake and efflux remain underexplored.

Drug-drug interactions between palbociclib and proton pump inhibitors in early breast cancer: an exploratory analysis of PALLAS (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

Background: Concomitant intake of proton pump inhibitors (PPIs) may create drug-drug interactions, potentially impacting efficacy of anticancer agents. In the phase III PALLAS trial, the addition of palbociclib capsules to standard adjuvant endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer did not improve invasive disease-free survival (iDFS). We explored whether concomitant use of PPIs affected survival outcomes in patients treated with palbociclib in PALLAS.

Ethnic origin in cancer clinical trials: overrated or understated? A comprehensive analysis of cancer clinical trials leading to FDA and EMA approvals between 2020 and 2022.

Background: Ethnic diversity in cancer clinical trials is essential to ensure that therapeutic advances are equitable and broadly applicable in multicultural societies. Yet, missing consensus on the documentation of ethnic origin, partially based on the complexity of the terminology and fear of discrimination, leads to suboptimal patient management of minority populations. Additionally, eligibility criteria, such as stringent laboratory cut-offs, often fail to account for variations across ethnic groups, potentially excluding patients without evidence-based justification.

Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis.

Background: Brain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody-drug conjugates has been reported, but the size of individual studies has been small.

European Guideline on Chronic Nausea and Vomiting-A UEG and ESNM Consensus for Clinical Management.

Introduction: Chronic nausea and vomiting are symptoms of a wide range of gastrointestinal and non-gastrointestinal conditions. Diagnosis can be challenging and requires a systematic and well-structured approach. If the initial investigation for structural, toxic and metabolic disorders is negative, digestive motility and gut-brain interaction disorders should be assessed.

Nonhuman primate antigenic cartography of SARS-CoV-2.

Virus neutralization profiles against primary infection sera and corresponding antigenic cartography are integral part of the COVID-19 and influenza vaccine strain selection processes. Human single variant exposure sera have previously defined the antigenic relationships among SARS-CoV-2 variants but are now largely unavailable due to widespread population immunity. Therefore, antigenic characterization of future SARS-CoV-2 variants will require an animal model, analogous to using ferrets for influenza virus.

Listen to Me! Target Perceptions of Digital Hate: A Scoping Review of Recent Research.

Digital hate is typically targeted toward individuals or groups based on distinct attributes. Despite numerous studies on targets of digital hate, there is a lack of a systematic meta-perspective on targets' perceptions of digital hate. Therefore, this scoping review aims to assess available definitions and characteristics of targets, consequences of digital hate together with targets' reactions and coping strategies, dominant methodologies, and identified future outlooks of digital hate victimization research.

Behind the scenes of EQA-characteristics, capabilities, benefits and assets of external quality assessment (EQA).

The main stakeholders in external quality assessment (EQA) programs are the participants, in whose interests these challenges are ultimately organised. EQA schemes in the medical field contribute to improving the quality of patient care by evaluating the analytical and diagnostic quality of laboratory and point-of-care tests (POCT) by independent third parties and, if necessary, pointing out erroneous measurement results and analytical or diagnostic improvement potential. Other benefits include the option of using EQA samples for other important laboratory procedures, such as the verification or validation of diagnostic medical devices (IVD-MDs), a contribution to the estimation of measurement uncertainty, a means of training and educating laboratory staff through educational EQA programmes or samples, or even for independent and documented monitoring of staff competence, such as on samples with unusual or even exceptional characteristics.

Characterizing the In Utero Phenome of the Chiari II Malformation-A Network Medicine Approach, Using Fetal MRI.

Objective: To apply a network medicine-based approach to analyze the phenome of the prenatal fetal MRI and biometric findings in the Chiari II malformation (CM II) to detect specific patterns and co-occurrences.

Method: A single-center retrospective review of fetal MRI scans obtained in fetuses with CM II was performed. Co-occurrence analysis was utilized to generate a phenotypic comorbidity matrix and visualized by Gephi software.

Metabolic Profiling of Individuals with Missing Teeth and Tooth Loss.

Missing teeth have been linked to incident cardiovascular disease, diabetes, and all-cause mortality. Our previous study revealed that signs of oral infections and inflammatory conditions (i.e.

Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases.

Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases.

Working with technical purity: simulation of red tattoo pigment metabolism by online-liquid chromatography-electrochemistry-mass spectrometry.

Tattooing is a popular form of body art that has evolved from ancient times into being part of modern society. The understanding of biotransformation processes of coloring tattoo pigments in human skin is limited although skin reactions to tattoos with unknown culprits occur. Electrochemistry coupled to mass spectrometry (EC-MS) has widely been used as a tool for a purely instrumental approach to simulating the enzymatic biotransformation of xenobiotics.

LC-HRMS screening procedure for the detection of 11 different classes of prohibited substances in dried urine spots for doping control purposes.

Dried urine spots have recently been proposed as an alternative matrix in the anti-doping field. Drying urine may open the opportunity to limit microbial and thermal degradation of the prohibited substances during transportation to the anti-doping laboratories without the need for refrigeration or freezing. In this study, a multi-targeted initial testing procedure was developed for the determination of 237 prohibited drugs/metabolites from 11 different classes in dried urine spots.

Evaluation of Efficacy and Safety of miraDry Procedure in the Treatment of Primary Axillary Hyperhidrosis.

Introduction: Primary axillary hyperhidrosis significantly impacts the quality of life of affected individuals. miraDry, a non-invasive local precisely controlled thermal energy procedure, represents a promising treatment option. This retrospective analysis aimed to evaluate the treatment success and patient safety following miraDry procedure in the treatment of primary axillary hyperhidrosis.