Control of BKPyV-DNAemia by a Tailored Viro-Immunologic Approach Does Not Lead to BKPyV-Nephropathy Progression and Development of Donor-Specific Antibodies in Pediatric Kidney Transplantation.

Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome.

Bacterial Multiresistance and Microbial Diversity of Milk Received by a University Hospital Milk Bank.

Breastfeeding is fundamental for the development and protection of the newborn, and microorganisms present in breast milk are associated with the development of the infant's intestinal microbiota. However, there are factors that interfere with breastfeeding, resulting in the need to supply donated milk to milk banks for these children. Even though there is a restriction on medications prescribed for pregnant and breastfeeding women, some antimicrobials are accepted, as long as they are used correctly and as they can increase the selection pressure for resistant bacteria.

HERVs Endophenotype in Autism Spectrum Disorder: Human Endogenous Retroviruses, Specific Immunoreactivity, and Disease Association in Different Family Members.

Increasing evidence indicates that human endogenous retroviruses (HERVs) are important to human health and are an underexplored component of many diseases. Certain HERV families show unique expression patterns and immune responses in autism spectrum disorder (ASD) patients compared to healthy controls, suggesting their potential as biomarkers. Despite these interesting findings, the role of HERVs in ASD needs to be further investigated.

The Epigenetic Machinery and Energy Expenditure: A Network to Be Revealed.

Mendelian disorders of the epigenetic machinery (MDEMs) include a large number of conditions caused by defective activity of a member of the epigenetic machinery. MDEMs are characterized by multiple congenital abnormalities, intellectual disability and abnormal growth. that can be variably up- or down-regulated.

The Prevalence and Clinical Characteristics of -Associated Hearing Loss in 15,684 Hearing Loss Patients.

belongs to the unconventional myosin superfamily, and the myosin IIIa protein localizes on the tip of the stereocilia of vestibular and cochlear hair cells. Deficiencies in have been reported to cause the deformation of hair cells into abnormally long stereocilia with an increase in spacing. is a rare causative gene of autosomal recessive sensorineural hearing loss (DFNB30), with only 13 cases reported to date.

Genotype-Phenotype Correlations of Nance-Horan Syndrome in Male and Female Carriers of a Novel Variant.

Background: Nance-Horan syndrome (NHS) is a rare, frequently underdiagnosed, X-linked disease caused by mutations in the NHS gene. In males, it causes bilateral dense pediatric cataracts, dental anomalies, and facial dysmorphisms. Females traditionally have a more subtle phenotype with discrete lens opacities as an isolated feature.

Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons.

Background/objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the smallest of the three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843).

Genome-Wide Insights into Internalizing Symptoms in Admixed Latin American Children.

Background/objectives: Internalizing disorders, including depression and anxiety, are major contributors to the global burden of disease. While the genetic architecture of these disorders in adults has been extensively studied, their early-life genetic mechanisms remain underexplored, especially in non-European populations. This study investigated the genetic mechanisms underlying internalizing symptoms in a cohort of Latin American children.

Expanding the Molecular Spectrum of Missense Variants: Clinical Insights and Literature Review.

Background/objectives: The failure of physiological left-right (LR) patterning, a critical embryological process responsible for establishing the asymmetric positioning of internal organs, leads to a spectrum of congenital abnormalities characterized by laterality defects, collectively known as "heterotaxy". biallelic variants have recently been associated with heterotaxy syndrome and congenital heart defects (CHD). However, the genotype-phenotype correlations and the underlying pathogenic mechanisms remain poorly understood.

Novel Variants and Clinical Features of Hearing Loss in a Large Japanese Cohort.

Background/objectives: The gene is responsible for autosomal recessive non-syndromic sensorineural hearing loss and is assigned as DFNB18B. To date, 44 causative variants have been reported to cause non-syndromic hearing loss. However, the detailed clinical features for -associated hearing loss remain unclear.

The Heterozygous p.A684V Variant in the Gene Is a Mutational Hotspot Causing a Severe Hearing Loss Phenotype.

Background/objectives: A heterozygous mutation in the gene is responsible for autosomal dominant non-syndromic hearing loss (DFNA6/14/38) and Wolfram-like syndrome, which is characterized by bilateral sensorineural hearing loss with optic atrophy and/or diabetes mellitus. However, detailed clinical features for the patients with the heterozygous p.A684V variant remain unknown.

Sickle Cell Disease in the Islands of Zanzibar: Patients' Characteristics, Management, and Clinical Outcomes.

Background: This study aimed to describe Sickle Cell Disease (SCD) phenotypes, sociodemographic characteristics, healthcare, and clinical outcomes of patients with SCD attending Mnazi Mmoja Hospital (MMH) in Zanzibar.

Methods: Individuals who visited MMH between September 2021 and December 2022 and were known or suspected to have SCD were enrolled in the clinic. Sociodemographic characteristics and clinical features were documented, and laboratory tests were performed.

Production of Amyloid-β in the Aβ-Protein-Precursor Proteolytic Pathway Is Discontinued or Severely Suppressed in Alzheimer's Disease-Affected Neurons: Contesting the 'Obvious'.

A notion of the continuous production of amyloid-β (Aβ) via the proteolysis of Aβ-protein-precursor (AβPP) in Alzheimer's disease (AD)-affected neurons constitutes both a cornerstone and an article of faith in the Alzheimer's research field. The present Perspective challenges this assumption. It analyses the relevant empirical data and reaches an unexpected conclusion, namely that in AD-afflicted neurons, the production of AβPP-derived Aβ is either discontinued or severely suppressed, a concept that, if proven, would fundamentally change our understanding of the disease.

Expanding the Mutation Spectrum for Inherited Retinal Diseases.

Background/objectives: Inherited retinal diseases (IRDs) represent a diverse group of genetic disorders characterized by degeneration of the retina, leading to visual impairment and blindness. IRDs are heterogeneous, sharing common clinical features that can be difficult to diagnose without knowing the genetic basis of the disease. To improve diagnostic accuracy and advance understanding of disease mechanisms, genetic testing was performed for 103 unrelated patients with an IRD at a single clinical site between 30 August 2022 and 5 February 2024.

Relevance of Next-Generation Sequencing in the Diagnosis of Thalassemia and Hemoglobinopathies: The Experience of Four Italian Diagnostic Hubs.

Unlabelled: Thalassemias and hemoglobinopathies are among the most common genetic diseases worldwide and have a significant impact on public health. The decreasing cost of next-generation sequencing (NGS) has quickly enabled the development of new assays that allow for the simultaneous analysis of small nucleotide variants (SNVs) and copy number variants (CNVs) as deletions/duplications of α- and β-globin genes.

Background/objectives: This study highlighted the efficacy and rapid identification of all types of mutations in the α- and β-globin genes, including silent variants, using the Devyser Thalassemia NGS kit.

Novel Variants Lead to Aberrant Splicing in a Patient with Chediak-Higashi Syndrome.

The advent of next-generation sequencing (NGS) has revolutionized the analysis of genetic data, enabling rapid identification of pathogenic variants in patients with inborn errors of immunity (IEI). Sometimes, the use of NGS-based technologies is associated with challenges in the evaluation of the clinical significance of novel genetic variants. In silico prediction tools, such as SpliceAI neural network, are often used as a first-tier approach for the primary examination of genetic variants of uncertain clinical significance.

An Optimized NGS Workflow Defines Genetically Based Prognostic Categories for Patients with Uveal Melanoma.

Background: Despite advances in uveal melanoma (UM) diagnosis and treatment, about 50% of patients develop distant metastases, thereby displaying poor overall survival. Molecular profiling has identified several genetic alterations that can stratify patients with UM into different risk categories. However, these genetic alterations are currently dispersed over multiple studies and several methodologies, emphasizing the need for a defined workflow that will allow standardized and reproducible molecular analyses.

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis of proteins relevant for the manifestation of neuromuscular diseases in the following aspects: (i) evaluation of the effect of genetic variants on the corresponding protein, (ii) prediction of the underlying genetic defect based on the proteomic signature of muscle biopsies, (iii) analysis of pathophysiologies underlying different entities of muscular diseases, key for the definition of new intervention concepts, and (iv) patient stratification according to biochemical fingerprints as well as (v) monitoring the success of therapeutic interventions. This review presents-also through exemplary case studies-the various advantages of mass proteomics in the investigation of genetic muscle diseases, discusses technical limitations, and provides an outlook on possible future application concepts. Hence, proteomics is an excellent large-scale analytical tool for the diagnostic workup of (hereditary) muscle diseases and warrants systematic profiling of underlying pathophysiological processes.

Remodeling of Mitochondria-Endoplasmic Reticulum Contact Sites Accompanies LUHMES Differentiation.

Neural progenitor cells (NPCs) are often used to study the subcellular mechanisms underlying differentiation into neurons in vitro. Works published to date have focused on the pathways that distinguish undifferentiated NPCs from mature neurons, neglecting the earlier and intermediate stages of this process. Current evidence suggests that mitochondria interaction with the ER is fundamental to a wide range of intracellular processes.

Advances and Challenges in Pediatric Sepsis Diagnosis: Integrating Early Warning Scores and Biomarkers for Improved Prognosis.

Identifying and managing pediatric sepsis is a major research focus, yet early detection and risk assessment remain challenging. In its early stages, sepsis symptoms often mimic those of mild infections or chronic conditions, complicating timely diagnosis. Although various early warning scores exist, their effectiveness is limited, particularly in prehospital settings where accurate, rapid assessment is crucial.

Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases.

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis.

Cyclin G1 Regulates the Alveolarization in Models of Bronchopulmonary Dysplasia by Inhibiting AT2 Cell Proliferation.

Disrupted neonatal lung alveologenesis often leads to bronchopulmonary dysplasia (BPD), the most common chronic lung disease in children. The inhibition of type 2 alveolar (AT2) cell proliferation plays an important role in the arrest of alveologenesis. However, the mechanism of AT2 cell proliferation retardation in BPD is still not fully elucidated.

Unraveling the Molecular Mechanisms of Mosquito Salivary Proteins: New Frontiers in Disease Transmission and Control.

Mosquito-borne diseases are a group of illnesses caused by pathogens transmitted by mosquitoes, and they are globally prevalent, particularly in tropical and subtropical regions. Pathogen transmission occurs during mosquito blood feeding, a process in which mosquito saliva plays a crucial role. Mosquito saliva contains a variety of biologically active proteins that facilitate blood feeding by preventing blood clotting, promoting vasodilation, and modulating the host's immune and inflammatory responses.

Tryptophan Kynurenine Pathway-Based Imaging Agents for Brain Disorders and Oncology-From Bench to Bedside.

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11.

NADH Reductive Stress and Its Correlation with Disease Severity in Leigh Syndrome: A Pilot Study Using Patient Fibroblasts and a Mouse Model.

Nicotinamide adenine dinucleotide (NAD) is a critical cofactor in mitochondrial energy production. The NADH/NAD ratio, reflecting the balance between NADH (reduced) and NADoxidized, is a key marker for the severity of mitochondrial diseases. We recently developed a streamlined LC-MS/MS method for the precise measurement of NADH and NAD.