Publications by authors named "Lazarevic V"

CD4 T helper (Th) cell differentiation depends on regulatory networks that enforce lineage commitment while suppressing alternative fates. In a recent issue of Nature, Hou et al. reveal that calcitonin gene-related peptide (CGRP) directs Th1 commitment, highlighting neuro-immune crosstalk in T cell fate decisions.

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Introduction: Chronic urticaria (CU) is defined as the presence of recurring hives and/or angioedema lasting more than 6 weeks. The precise impact of food allergies, particularly to galactose-α-1,3-galactose (α-gal) and omega-5-gliadin (O5G), on the development of CU is not well established.

Aim: The study examines the frequency of sensitisation to these allergens and their clinical significance in individuals with CU.

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Background: Critical illness is associated with an altered gut microbiota, yet its association with poor outcomes remains unclear. This study evaluates the early gut microbiota diversity changes in intensive care unit patients and its association with mortality. Additionally, it explores fecal pH as a potential biomarker for these changes.

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The aim of this prospective, international multicenter, pseudorandomized study comparing RICT HCT to standard-of-care chemotherapy in intermediate- or high-risk AML patients 50-70 years using the donor versus no-donor concept. Part 1 included only patients with potential family donors (RD) at the date of HLA-typing of the first potential sibling or CR-date, if later. Part 2 allowed the inclusion of patients without a possible sibling donor using the start of an unrelated donor (URD) search as inclusion date.

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Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS.

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Gene panel sequencing has become a common diagnostic tool for detecting somatically acquired mutations in myeloid neoplasms. However, many panels have restricted content, provide insufficient sensitivity levels, or lack clinically validated workflows. We here describe the development and validation of the Genomic Medicine Sweden myeloid gene panel (GMS-MGP), a capture-based 191 gene panel including mandatory genes in contemporary guidelines as well as emerging candidates.

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Article Synopsis
  • The standard treatment for acute myeloid leukemia (AML) has been the 7+3 regimen (cytarabine infusion with anthracycline) since the 1980s.
  • A recent study compared this standard regimen with a higher dose of cytarabine in older, high-risk AML patients, showing improved overall survival rates and remission rates in those receiving the increased dose.
  • The results indicated that those on the higher cytarabine dosage had a median overall survival of 10.7 months compared to 6.4 months for the standard dose, suggesting that the more intensive treatment leads to better outcomes for this patient group.
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Introduction: The gut barrier, comprising gut microbiota, plays a pivotal role in chronic kidney disease (CKD) progression and nutritional status. This study aimed to explore gut barrier alterations in hemodialyzed (HD) patients, non-HD (NHD) CKD patients, and healthy volunteers.

Methods: Our cross-sectional study enrolled 22 HD patients, 11 NHD patients, and 11 healthy volunteers.

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The aetiology of chronic aseptic meningitis is difficult to establish. meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS).

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Introduction: Interferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive.

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Background: Early life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels.

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Background: Hospital-acquired and ventilator-associated-pneumonia (HAP/VAP) are one of the most prevalent health-care associated infections in the intensive care unit (ICU). Culture-independent methods were therefore developed to provide faster route to diagnosis and treatment. Among these, metagenomic next-generation sequencing (mNGS) has shown considerable promise.

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Article Synopsis
  • Before using metagenomic next-generation sequencing (mNGS) in labs, researchers need to tackle some challenges related to detecting and quantifying bacteria in samples with a lot of host DNA.
  • In this study, they tested different DNA extraction methods on pig muscle tissue spiked with various bacteria to see how well these methods worked.
  • They found that while unenriched samples could quantify bacteria well, they struggled with sensitivity; however, using a modified enrichment procedure significantly improved bacterial detection and provided clearer taxonomic profiles.
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The management of ventilator-associated pneumonia and hospital-acquired pneumonia requires rapid and accurate quantitative detection of the infecting pathogen. To this end, we propose a metagenomic sequencing assay that includes the use of an internal sample processing control for the quantitative detection of 20 relevant bacterial species from bronchoalveolar lavage samples.

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We report a case of Mycoplasma genitalium endocarditis in a prosthetic heart valve of a woman who sought care in Switzerland for acute aortic valve dysfunction 3 years after valve replacement. This unusual manifestation of infection with this bacterium was diagnosed using broad-range PCR despite suspicion of a mechanical disinsertion.

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Acute myeloid leukemia (AML) is initiated and propagated by leukemia stem cells (LSCs), a self-renewing population of leukemia cells responsible for therapy resistance. Hence, there is an urgent need to identify new therapeutic opportunities targeting LSCs. Here, we performed an in vivo CRISPR knockout screen to identify potential therapeutic targets by interrogating cell surface dependencies of LSCs.

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Article Synopsis
  • * The study showed that GATA3, a transcription factor typically associated with Th2 cell differentiation, is crucial for the pathogenic function of Th17 cells in EAE, particularly in their early differentiation stages.
  • * Late deletion of GATA3 led to reduced GM-CSF production and an inability to induce EAE symptoms, suggesting GATA3 plays a critical role in maintaining the pathogenic characteristics of T-bet-expressing Th17 cells by influencing gene regulation.
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Article Synopsis
  • CD4 T helper 17 (T17) cells play a dual role in protecting barrier tissues and contributing to autoimmune conditions, like multiple sclerosis.* -
  • The transcription factor EGR2 is crucial for driving the harmful behavior of pathogenic T17 cells in the central nervous system (CNS), while it does not affect protective T17 cells elsewhere.* -
  • Deleting EGR2 specifically in T cells reduces neuroinflammation without impairing the body's ability to fight infections, highlighting its role in regulating T17 cell functions based on tissue and disease context.*
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The Swiss Pathogen Surveillance Platform (SPSP) is a shared secure surveillance platform between human and veterinary medicine, to also include environmental and foodborne isolates. It enables rapid and detailed transmission monitoring and outbreak surveillance of pathogens using whole genome sequencing data and associated metadata. It features controlled data access, complex dynamic queries, dedicated dashboards and automated data sharing with international repositories, providing actionable results for public health and the vision to improve societal well-being and health.

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, and have been recently described in the female genital tract. We present the first case of a postpartum septic arthritis of the pubic symphysis due to these organisms, identified by next generation sequencing.

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The suspicion of an origin of Parkinson's disease (PD) at the periphery of the body and the involvement of environmental risk factors in the pathogenesis of PD have directed the attention of the scientific community towards the microbiota. The microbiota represents all the microorganisms residing both in and on a host. It plays an essential role in the physiological functioning of the host.

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