Spatiotemporal dynamics of fetal liver hematopoietic niches.

Embryonic hematopoietic cells develop in the fetal liver (FL), surrounded by diverse non-hematopoietic stromal cells. However, the spatial organization and cytokine production patterns of the stroma during FL development remain poorly understood. Here, we characterized and mapped the hematopoietic and stromal cell populations at early (E12.

Incongruent virtual reality cycling exercise demonstrates a role of perceived effort in cardiovascular control.

In this study we have used a highly immersive virtual reality (VR) cycling environment where incongruence between virtual hill gradient (created by visual gradient and bike tilt angle) and actual workload (pedalling resistance) can experimentally manipulate perception of exercise effort. This therefore may provide a method to examine the role of effort perception in cardiorespiratory control during exercise. Twelve healthy untrained participants (7 men, age 26 ± 5 years) were studied during five visits.

The molecular reach of antibodies crucially underpins their viral neutralisation capacity.

Key functions of antibodies, such as viral neutralisation, depend on high-affinity binding. However, viral neutralisation poorly correlates with antigen affinity for reasons that have been unclear. Here, we use a new mechanistic model of bivalent binding to study  >45 patient-isolated IgG1 antibodies interacting with SARS-CoV-2 RBD surfaces.

A Sentinel Survey in Remote Western Thailand Indicates that School-Aged Children and Reproductive-Aged Women of the Indigenous Pwo Karen Community are Iodine Sufficient.

Indigenous peoples are often not routinely included in iodine programs because of language barriers and remote access, and may thus be at higher risk of iodine deficiency disorders, which could adversely impact their quality of life. We conducted this cross-sectional study in the remote Pwo Karen community of Thailand to determine the urinary iodine concentration (UIC) of school-aged children (SAC) and women of reproductive age (WRA) and investigate the iodine content in household salt. We measured UIC in spot urine samples from healthy SAC and WRA, administered a questionnaire, estimated daily iodine intake and collected household salt samples to determine salt iodine concentration.

Human enteric glia diversity in health and disease: new avenues for the treatment of Hirschsprung disease.

Background And Aims: The enteric nervous system (ENS), comprised of neurons and glia, regulates intestinal motility. Hirschsprung disease (HSCR) results from defects in ENS formation, yet while neuronal aspects have been extensively studied, enteric glia remain disregarded. This study aimed to explore enteric glia diversity in health and disease.

Oncogenic PIK3CA corrupts growth factor signaling specificity.

Technical limitations have prevented understanding of how growth factor signals are encoded in distinct activity patterns of the phosphoinositide 3-kinase (PI3K)/AKT pathway, and how this is altered by oncogenic pathway mutations. We introduce a kinetic, single-cell framework for precise calculations of PI3K-specific information transfer for different growth factors. This features live-cell imaging of PI3K/AKT activity reporters and multiplexed CyTOF measurements of PI3K/AKT and RAS/ERK signaling markers over time.

Elevated hematopoietic stem cell frequency in mouse alveolar bone marrow.

Hematopoietic stem cells (HSCs) are crucial for maintaining hematopoietic homeostasis and are localized within distinct bone marrow (BM) niches. While BM niches are often considered similar across different skeletal sites, we discovered that the alveolar BM (al-BM) in the mandible harbors the highest frequency of immunophenotypic HSCs in nine different skeletal sites. Transplantation assays revealed significantly increased engraftment from al-BM compared to femur, tibia, or pelvis BM, likely due to a higher proportion of alveolar HSCs.

Molecular profiling in MPN: who should have it and why?

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are a group of blood cancers that result from somatic mutations in hematopoietic stem cells, causing constitutive activation of JAK-STAT signaling pathways with consequent overproduction of 1 or more myeloid lineages. The initiating event in MPN pathogenesis is a genetic mutation, and consequently molecular profiling is central to the diagnosis, risk stratification, and, increasingly, monitoring of therapy response in persons with MPN. In this review we summarize current approaches to molecular profiling of classical MPNs (essential thrombocythemia, polycythemia vera, and myelofibrosis), using illustrative clinical case histories to demonstrate how genetic analysis is already fully integrated into MPN diagnostic classification and prognostic risk stratification.

When, which and how to switch: Navigating JAK inhibitors in myelofibrosis.

Navigating choice of JAK inhibitor (JAKi) therapy for patients with myelofibrosis who are JAKi-naïve and for those who have previously been treated with a JAKi.

Demonstration of T-Cell Monotypia Using Anti-TCRbeta1/2 (/2) Immunostaining as a Rapid and Cost-Effective Alternative to PCR-Based Clonality Studies for the Diagnosis of T-Cell Lymphoma.

Background/objectives: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates, and diagnosis typically relies on slow, complex, and expensive multiplexed PCR reactions, requiring significant training and experience to interpret them. We aimed to raise highly specific antibodies against the two alternatively used and very similar T-cell receptor beta constant regions, TCRbeta1 and TCRbeta2, encoded by the and gene segments, respectively. We sought to demonstrate the feasibility of detecting TCRbeta1 and TCRbeta2 immunohistochemically in routine clinical (formalin-fixed, paraffin-embedded (FFPE)) tissue sections as a novel diagnostic strategy for T-cell lymphomas.

A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation.

The human brain undergoes protracted postnatal maturation, guided by dynamic changes in gene expression. Most studies exploring these processes have used bulk tissue analyses, which mask cell-type-specific gene expression dynamics. Here, using single-nucleus RNA sequencing on temporal lobe tissue, including samples of African ancestry, we build a joint pediatric and adult atlas of 75 cell subtypes, which we verify with spatial transcriptomics.

Are viral loads in the febrile phase a predictive factor of dengue disease severity?

Background: As many studies have shown conflicting results regarding the extent of viraemia and clinical disease severity, we sought to investigate if viraemia during early dengue illness is associated with subsequent clinical disease severity.

Methods: Realtime PCR was carried out to identify the dengue virus (DENV serotype), in 362 patients, presenting within the first 4 days of illness, from 2017 to 2022, in Colombo Sri Lanka. To characterize subsequent clinical disease severity, all patients were followed throughout their illness daily and disease severity classified according to WHO 1997 and 2009 disease classification.

The state-of-the-art of N-of-1 therapies and the IRDiRC N-of-1 development roadmap.

In recent years, a small number of people with rare diseases caused by unique genetic variants have been treated with therapies developed specifically for them. This pioneering field of genetic N-of-1 therapies is evolving rapidly, giving hope for the individualized treatment of people living with very rare diseases. In this Review, we outline the concept of N-of-1 individualized therapies, focusing on genetic therapies, and illustrate advances and challenges in the field using cases for which therapies have been successfully developed.

Liver cirrhosis is a risk-factor for Pneumocystis jirovecii associated mortality.

Background: Pneumocystis jirovecci pneumonia (PCP) is a life threating disease in immunodeficient patients. Liver cirrhosis itself can lead to immunodefiency, however little is known if Pneumocystis jirovecci infection affects the outcome of patients with liver cirrhosis.

Aim: We aimed to assess the predictors for Pneumocystis jirovecci-associated mortality in patients with Pneumocystis jirovecci infection treated at intensive care units.

Towards the genomic sequence code of DNA fragility for machine learning.

Genomic DNA breakages and the subsequent insertion and deletion mutations are important contributors to genome instability and linked diseases. Unlike the research in point mutations, the relationship between DNA sequence context and the propensity for strand breaks remains elusive. Here, by analyzing the differences and commonalities across myriads of genomic breakage datasets, we extract the sequence-linked rules and patterns behind DNA fragility.

The surgical, histopathological characteristics, and survival outcome of ovarian clear cell carcinoma: a retrospective case series sharing the experience of a tertiary cancer centre.

Background: Ovarian clear cell carcinoma (OCCC) is a rare and distinct subtype of epithelial ovarian cancer (EOC). It is unique in several biological aspects. This study analyzes the clinicopathological features and survival outcome of patients with OCCC, aiming to identify factors affecting recurrence, progression-free survival (PFS) and overall survival (OS).

Shaping hematopoietic cell ecosystems through galectin-glycan interactions.

Hematopoiesis- the formation of blood cell components- continually replenishes the blood system during embryonic development and postnatal lifespans. This coordinated process requires the synchronized action of a broad range of cell surface associated proteins and soluble mediators, including growth factors, cytokines and lectins. Collectively, these mediators control cellular communication, signalling, commitment, proliferation, survival and differentiation.

Goblet cell differentiation subgroups in colorectal cancer.

The poor prognosis of relatively undifferentiated cancers has long been recognized, suggesting that selection against differentiation and in favor of uncontrolled growth is one of the most powerful drivers of cancer progression. Goblet cells provide the mucous surface of the gut, and when present in colorectal cancers (CRC), the cancers are called mucinous. We have used the presence of MUC2, the main mucous product of goblet cells, and an associated gene product, TFF3, to classify a large panel of nearly 80 CRC-derived cell lines into five categories based on their levels of MUC2 and TFF3 expression.