St. Jude Children's Research Hospital

Uneven TCR chain pairing constraints govern epitope recognition

Combinatorial pairing of independently recombined T cell receptor (TCR) α- and β-chains is central to diversifying the TCR repertoire. Although sequence motifs in one chain correlate with epitope recognition, the extent to which a single chain dictates specificity remains unclear...

Early-life colonization with Clostridioides difficile remodels the developing gut

Clostridioides difficile causes severe disease in adults but commonly colonizes infants asymptomatically. The consequences of early-life colonization on host development remain unknown. In a neonatal mouse model, C. difficile colonization drove proinflammatory and tissue repair r...

Risk factors for Cefepime Resistance in Bacteria Causing Gram-negative Bloodstream Infections in a Children’s Cancer Center

Abstract Background Strategies that seek to provide timely and effective therapy for febrile neutropenia (FN) in children with cancer or hematopoietic cell therapy (HCT) are threatened by increasing rates of antimicrobial resistance (AR). At our institution clinically stable pati...

Impact of virus and bacteria co-detection in children with severe malaria

Abstract Background Malaria is a leading cause of death in children under five years of age worldwide. Clinically, malaria, pneumonia, and other febrile illnesses often present with similar symptoms, complicating management. The extent to which respiratory pathogens influence the...

Patient outcomes associated with carbapenem-sparing management of febrile neutropenia

Abstract Background Febrile neutropenia (FN) guidelines recommend that local epidemiology inform empiric antibacterial treatment, but that efforts be made to restrict carbapenem administration to unstable patients. At our institution most stable patients are treated with cefepime...

Silent Verb Generation During fMRI Reveals Post-Radiotherapy Alterations in Cerebellar–Cerebral Language Regions in Patients Treated for Medulloblastoma

Background: Medulloblastoma is the most common malignant pediatric brain tumor. Although radiotherapy improves survival, it is often associated with neurocognitive impairments affecting language and executive functions in developing brains. We investigated treatment-related chang...

The ageing immune system and its battle with viruses

Graphical Abstract Virus-specific immunity and correlates of protection change across human life: children encounter first infections/vaccinations when they are immunologically naïve, whereas cumulative exposure histories in older adults shape their immunity.

Managing What You Cannot Measure: Anesthetic Implications of Takayasu’s Arteritis in Hypertensive Intracranial Hemorrhage

ABSTRACT: Takayasu's arteritis is a rare inflammatory vasculopathy affecting medium- and large-caliber arteries, often presenting as cerebrovascular incidents in young individuals, primarily due to uncontrolled hypertension. The following is the case of a young male with no known...

Mitophagy and Noncoding RNA Regulation in Type 2 Diabetes Mellitus: Molecular Mechanisms, Tissue-Specific Evidence and Translational Perspective

Despite significant therapeutic advances, T2DM remains a global public health challenge that leads to multiple complications, including cardiovascular, renal, hepatic, and neurodegenerative disorders. Mitochondrial dysfunction and impaired mitophagy remain fundamental, yet incomp...

Paediatric therapeutic development workshop on osteosarcoma

The fourth Paediatric Therapeutic Development Workshop focused on osteosarcoma, the most common primary bone cancer in children and young adults. Current treatment of osteosarcoma comprises surgery and chemotherapy. Outcome has shown very little improvement over the last four dec...

Decoding TnsC Filament Assembly in CRISPR-Associated Transposons Using Interpretable Deep Learning and Molecular Simulations

Abstract CRISPR-associated transposons (CASTs) enable programmable DNA integration, yet how the TnsC regulator forms processive filaments on DNA to coordinate RNA-guided transposition in type V-K CAST systems remains unknown. Here, we integrate large-scale molecular simulations,...

Splicing genes as main targets of differential splicing

Abstract Splicing of transcripts via the spliceosome machinery is a complex process involving a multitude of proteins and short noncoding RNAs. In addition to full-length transcripts with all exons in the genomically encoded order, alternatively spliced transcripts can also be pr...

Optimizing safety and efficacy of asparaginase and blinatumomab therapy in frontline acute lymphoblastic leukemia regimens in diverse health care settings—international expert consensus

Frontline blinatumomab combined with chemotherapy has resulted in improved outcomes in both pediatric and adult patients with acute lymphoblastic leukemia and is considered the new cornerstone of acute lymphoblastic leukemia treatment. The role of asparaginase in this new landsca...

Beyond the scaffold: Glia as architects of the neural extracellular matrix

Astrocytes, oligodendrocyte lineage cells, and microglia dynamically shape the neural extracellular matrix (ECM) across brain development and aging. Recent findings highlight the potential of glial regulation of the ECM as a framework for understanding circuit formation and ident...

Longitudinal evaluation of sleep disturbances in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

Abstract Purpose The current study examines longitudinal changes in sleep disturbances and the risks they pose for new-onset health conditions in survivors of childhood cancer. Methods Five-year survivors ( N = 1081; median [range] age 50.0 [45.2–55.0] years) and siblings ( N = 2...

ZPY-CpG-Ch, a broad coverage vaccine against Streptococcus pneumoniae

Existing licensed pneumococcal vaccines, including Prevnar-13 and its higher-valency successors, have played a major role in reducing invasive pneumococcal disease worldwide. However, their effectiveness is increasingly threatened by the rise of multidrug-resistant strains and th...

MBNL1 hijacks a structured single-stranded distal DNA element to sustain FLT3 expression in KMT2A-rearranged leukemias

The molecular mechanisms by which KMT2A-rearranged (KMT2A-r) leukemias maintain the oncogenic FLT3 expression remain largely unclear, limiting therapeutic opportunities. Here, we identify the RNA binding protein MBNL1 as an unexpected positive regulator of FLT3 by DepMap dataset...

Designing Reliable Care Through Clinical Pathways: A Human Factors Framework

Background/Objectives: Healthcare delivery systems are inherently complex, and efforts to improve quality and safety often fail to achieve sustained, system-wide impact because of misalignment between work system design, care processes, and clinical practice. This article present...