Classification of Fibro-osseous Tumors in the Craniofacial Bones using DNA Methylation and Copy Number Alterations.

Fibro-osseous tumors of the craniofacial bones are a heterogeneous group of lesions comprising cemento-osseous dysplasia (COD), cemento-ossifying fibroma (COF), juvenile trabecular ossifying fibroma (JTOF), psammomatoid ossifying fibroma (PsOF), fibrous dysplasia (FD), and low-grade osteosarcoma (LGOS) with overlapping clinicopathological features. However, their clinical behavior and treatment differ significantly, underlining the need for accurate diagnosis. Molecular diagnostic markers exist for subsets of these tumors, including GNAS mutations in FD, SATB2 fusions in PsOF, mutations involving the RAS-MAPK signaling pathway in COD, and MDM2 amplification in LGOS.

Monitoring M-Protein, Therapeutic Antibodies, and Polyclonal Antibodies in a Multiparametric Mass Spectrometry Assay Provides Insight into Therapy Response Kinetics in Patients with Multiple Myeloma.

Multiple Myeloma (MM) is a hematologic malignancy caused by clonally expanded plasma cells that produce a monoclonal immunoglobulin (M-protein), a personalized biomarker. Recently, we developed an ultra-sensitive mass spectrometry method to quantify minimal residual disease (MS-MRD) by targeting unique M-protein peptides. Therapeutic antibodies (t-Abs), key in MM treatment, often lead to deep and long-lasting responses.

Adenovirus-Neutralizing and Infection-Promoting Activities Measured in Serum of Human Brain Cancer Patients Treated with Oncolytic Adenovirus Ad5-∆24.RGD.

Oncolytic adenoviruses derived from human serotype 5 (Ad5) are being developed to treat cancer. Treatment efficacy could be affected by pre-existing or induced neutralizing antibodies (NAbs), in particular in repeat administration strategies. Several oncolytic adenoviruses that are currently in clinical development have modified fiber proteins to increase their infectivity.

Non-Invasive Determination of the Paternal Inheritance in Pregnancies at Risk for β-Thalassaemia by Analyzing Cell-Free Fetal DNA Using Targeted Next-Generation Sequencing.

Non-invasive prenatal testing (NIPT) has been widely adopted for the screening of chromosomal abnormalities; however, its adoption for monogenic disorders, such as β-thalassaemia, has proven challenging. Haemoglobinopathies are the most common monogenic disorders globally, with β-thalassaemia being particularly prevalent in Cyprus. This study introduces a non-invasive prenatal haplotyping (NIPH) assay for β-thalassaemia, utilizing cell-free DNA (cfDNA) from maternal plasma.

The Impact of Postoperative Prophylactic Medication on Long-Term Surgical, Severe Endoscopic and Endoscopic or Radiologic Recurrence Following Primary Ileocecal Resection in Patients With Crohn's Disease.

Background: The impact of prophylactic medication following ileocecal resection (ICR) for Crohn's disease (CD) merits further elucidation. Prophylactic medication following ileocecal resection (ICR) is recommended in patients with Crohn's disease (CD), particularly in patients at increased risk of recurrence, but the impact on long-term outcomes needs to be further elucidated.

Aim: To evaluate the effect of postoperative prophylactic medication on long-term prognosis.

One Health preparedness and response for mosquito-borne viruses: a stakeholder- and social network-analysis in the Netherlands.

Background: The emergence of mosquito-borne viruses (MBVs) in Europe emphasizes the need for preparedness and response plans. This requires knowledge integration and collaboration across the human, animal, vector, and environmental health domains, aligning with the One Health approach. Despite the importance of a One Health approach, engaging stakeholders from each domain remains challenging.

Defining Hyperphagia for Improved Diagnosis and Management of MC4R Pathway-Associated Disease: A Roundtable Summary.

Purpose Of Review: Hyperphagia is a condition associated with rare obesity-related diseases, presenting as a pathologic, insatiable hunger accompanied by abnormal food-seeking behaviors. In October 2023, a group of researchers and clinicians with expert knowledge on hyperphagia convened at the annual ObesityWeek meeting to discuss the need for a unified definition of hyperphagia and key items necessary to improve the identification, assessment, and treatment of hyperphagia in patients with melanocortin 4 receptor (MC4R) pathway-associated diseases.

Recent Findings: The definition of hyperphagia proposed by this group is a pathologic, insatiable hunger accompanied by abnormal food-seeking behaviors.

Discontinuation of anticoagulants and occurrence of bleeding and thromboembolic events in vitamin K antagonist users with a life-limiting disease.

Background: Data on risks and benefits of long-term anticoagulants in patients with a life-limiting disease are limited. This cohort study aims to describe (dis)continuation of anticoagulants and incidences of bleeding and thromboembolic events in vitamin K antagonist (VKA) users with a life-limiting disease.

Methods: Data from five Dutch anticoagulation clinics were linked to data from Statistics Netherlands and the Netherlands Cancer registry.

DDAVP response and its determinants in bleeding disorders: a systematic review and meta-analysis.

Desmopressin (DDAVP) can be used to prevent or stop bleeding. However, large inter-individual variability is observed in DDAVP response and determinants are largely unknown. In this systematic review and meta-analysis we aim to identify the response to DDAVP, and the factors that determine DDAVP response in patients.

TCR transgenic clone selection guided by immune receptor analysis and single-cell RNA expression of polyclonal responders.

Since the precursor frequency of naive T cells is extremely low, investigating the early steps of antigen-specific T cell activation is challenging. To overcome this detection problem, adoptive transfer of a cohort of T cells purified from T cell receptor (TCR) transgenic donors has been extensively used but is not readily available for emerging pathogens. Constructing TCR transgenic mice from T cell hybridomas is a labor-intensive and sometimes erratic process, since the best clones are selected based on antigen-induced CD69 upregulation or IL-2 production in vitro, and TCR chains are polymerase chain reaction (PCR)-cloned into expression vectors.

Sex differences in atrial potential morphology.

Background: Areas of conduction disorders play an important role in both initiation and perpetuation of AF and can be recognized by specific changes in unipolar potential morphology. For example, EGM fractionation may be caused by asynchronous activation of adjacent cardiomyocytes because of structural barriers such as fibrotic strands. However, it is unknown whether there are sex differences in unipolar potential morphology.

Exposure to residential air pollution and the development of functional connectivity of brain networks throughout adolescence.

Background: A few studies linked air pollution to differences in functional connectivity of resting-state brain networks in children, but how air pollution exposure affects the development of brain networks remains poorly understood. Therefore, we studied the association of air pollution exposure from birth to 3 years and one year before the first imaging assessment with the development of functional connectivity across adolescence.

Methods: We utilized data from 3,626 children of the Generation R Study (The Netherlands).

Newborn Screening by DNA-First: Systematic Evaluation of the Eligibility of Inherited Metabolic Disorders Based on Treatability.

The biomarker-based Dutch Newborn Screening (NBS) panel (as of 2024) comprises 19 inherited metabolic disorders (IMDs). With the use of next-generation sequencing (NGS) as a first-tier screen, NBS could expand to include IMDs that lack a reliable biochemical footprint in dried blood spots, while also reducing secondary findings. To be eligible for inclusion in NBS, an IMD needs to fulfill the Wilson and Jungner criteria, with treatability being one of the most important criteria.

Supravalvular aortic stenosis repair in a 3-year-old child with Williams syndrome using an interdigitating slide aortoplasty.

Several techniques for the surgical correction of congenital supravalvular aortic stenosis have been devised. We describe the step-by-step surgical approach of a slide aortoplasty to correct localized supravalvular aortic stenosis in a 3-year-old child with Williams syndrome.

X-Linked Autism Type 9 Caused by a Hemizygote Pathogenic Variant in the Gene: Etiological Diagnosis in an Adult Male with Moderate Intellectual Disability.

Introduction: Levocarnitine is essential for brain functioning and fatty acid metabolism and stems largely from dietary sources. The Epsilon-Trimethyllysine Hydroxylase () gene encodes the enzyme N-Trimethyllysine hydroxylase (TMLH) which catalyses the first step in the biosynthesis of carnitine. Lack of TMLH enzyme activity is associated with developmental delay and autistic behaviours described as X-linked recessive autism, type 6 (OMIM#300872).

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

The immune response to SARS-CoV-2 in COVID-19 as a recall response susceptible to immune imprinting: A prospective cohort study.

Unlabelled: The antibody response to SARS-CoV-2 does not follow the immunoglobulin isotype pattern of primary responses, conflicting with the current interpretation of COVID-19.

Methods: Prospective cohort study of 191 SARS-CoV-2 infection cases and 44 controls from the second wave of COVID-19. The study stratified patients by severity and analyzed the trajectories of SARS-CoV-2 antibodies and multiple immune variables.

A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies.

Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of therapeutics.

Variable temocillin protein binding and pharmacokinetics in different clinical conditions: Implications for target attainment.

Aims: The beta-lactam antibiotic temocillin is increasingly used to treat extended-spectrum beta-lactamase (ESBL-producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations.

Methods: The plasma pharmacokinetics were analysed using non-linear mixed-effects modelling.

Multicenter validation of a galactomannan chemiluminescence immunoassay for the diagnosis of pulmonary aspergillosis on serum of patients with hematological disease.

An accurate diagnosis of invasive aspergillosis (IA) in patients with underlying hematological malignancies relies heavily on galactomannan detection. In this study, we compared the VirCLIA chemiluminescence immunoassay (CLIA) with the frequently used Platelia enzyme-linked immunosorbent assay (ELISA) on serum from hematology patients with suspected IA. Patients were categorized according to EORTC/MSGERC 2020 definitions into proven/probable IA and possible/no IA.

Minimally invasive versus open lateral pancreaticojejunostomy in patients with painful chronic pancreatitis: systematic review.

Background: Patients with painful chronic pancreatitis combined with a dilated main pancreatic duct and a normal size pancreatic head are treated according to guidelines by lateral pancreaticojejunostomy (LPJ). This systematic review compared outcomes of minimally invasive LPJ and open LPJ.

Methods: From 1 January 2000 until 13 November 2023, series reporting on minimally invasive LPJ and open LPJ in patients with symptomatic chronic pancreatitis were included.

Expanding the Scope of Microvascular Inflammation: Unveiling Its Presence Beyond Antibody-Mediated Rejection Into T-Cell Mediated Contexts.

Microvascular inflammation (MVI) in kidney transplant biopsies is mainly associated with antibody-mediated rejection (AMR), sparking debate within the Banff Classification of Renal Allograft Pathology regarding its exclusivity. This study reviewed the literature on MVI in T cell-mediated rejection (TCMR) and analyzed MVI in our transplant population. We searched English publications in MEDLINE, Embase, Web of Science, Cochrane, and Google Scholar until June 2024, focusing on glomerulitis (g), peritubular capillaritis (ptc), or MVI in kidney transplant biopsies classified as TCMR.

Red blood cell pyruvate kinase properties in Townes and Berkeley sickle cell disease mouse models - Of mice and men.

Pyruvate kinase (PK), a key ATP-generating enzyme in glycolysis, is a target for novel sickle cell disease (SCD) therapies. Enhancing PK activity lowers 2,3-diphosphyglycerate (2,3-DPG), increases adenosine triphosphate (ATP), and may prevent red blood cell (RBC) sickling. Townes and Berkeley SCD mouse models are commonly used for the development of novel drugs for SCD, but differ from humans in 2,3-DPG and ATP levels, which could be related to underlying differences in PK properties.