A framework for sequential monitoring of individual N-of-1 trials and combining results across a series of sequentially monitored N-of-1 trials.

Background: N-of-1 trials compare two or more treatment options for a single participant. These trials have been used to study options for chronic conditions such as arthritis and attention deficit hyperactivity disorder. In addition, they have been suggested as a means to study interventions in rare populations that may not be tractable to include in standard clinical trials, such as treatment options for HIV-positive patients in need of organ transplant.

An inflammatory state defines a high-risk T-lineage acute lymphoblastic leukemia subgroup.

T-lineage acute lymphoblastic leukemia (ALL) is an aggressive cancer comprising diverse subtypes that are challenging to stratify using conventional immunophenotyping. To gain insights into subset-specific therapeutic vulnerabilities, we performed an integrative multiomics analysis of bone marrow samples from newly diagnosed T cell ALL, early T cell precursor ALL, and T/myeloid mixed phenotype acute leukemia. Leveraging cellular indexing of transcriptomes and epitopes in conjunction with T cell receptor sequencing, we identified a subset of patient samples characterized by activation of inflammatory and stem gene programs.

Assessment of Barriers and Enablers for Implementing a Population-Based Childhood Cancer Registry in Chennai, India.

Background: Despite most childhood cancer cases being diagnosed in low- and middle-income countries, there is a significant deficit of population-based childhood cancer registries (PBCCRs) in these regions. To address this critical gap, we established India's first dedicated PBCCR in Chennai on October 4, 2022, covering children aged 0-19. This study aims to identify the barriers and enablers to implementing the Chennai PBCCR.

Improving Sickle Cell Patient Appointment Compliance in a Hospital-based Pediatric Ophthalmology Clinic.

This quality improvement initiative aimed to reduce the no-show rate at a hospital-based tertiary sickle cell ophthalmology clinic. Missed appointments place a significant burden on the healthcare system, resulting in prolonged waiting times and underutilized clinical resources that impact the quality of care provided. Individuals with sickle cell disease commonly require multiple appointments to address the myriads of comorbidities associated with their disease.

Identifying Sequence Effects on Chain Dimensions of Disordered Proteins by Integrating Experiments and Simulations.

It has become increasingly evident that the conformational distributions of intrinsically disordered proteins or regions are strongly dependent on their amino acid compositions and sequence. To facilitate a systematic investigation of these sequence-ensemble relationships, we selected a set of 16 naturally occurring intrinsically disordered regions of identical length but with large differences in amino acid composition, hydrophobicity, and charge patterning. We probed their conformational ensembles with single-molecule Förster resonance energy transfer (FRET), complemented by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy as well as small-angle X-ray scattering (SAXS).

Evaluation of methotrexate Pharmacogenomic variation to predict acute neurotoxicity in children with acute lymphoblastic leukemia.

Background: Methotrexate is an important component of curative therapy in childhood acute lymphoblastic leukemia (ALL), but the role of genetic variation influencing methotrexate clearance and transport in toxicity susceptibility in children with ALL is not well established. Therefore, we evaluated the association between suspected methotrexate pharmacogenomic variants and methotrexate-related neurotoxicity.

Methods: This study included children (aged 2-20 years) diagnosed with ALL (2005-2019) at six treatment centers in the southwest United States.

A brain-wide map of descending inputs onto spinal V1 interneurons.

Motor output results from the coordinated activity of neural circuits distributed across multiple brain regions that convey information to the spinal cord via descending motor pathways. Yet the organizational logic through which supraspinal systems target discrete components of spinal motor circuits remains unclear. Here, using viral transsynaptic tracing along with serial two-photon tomography, we have generated a whole-brain map of monosynaptic inputs to spinal V1 interneurons, a major inhibitory population involved in motor control.

Multi-band vs. conventional diffusion-weighted MRI of the abdomen in children and young adults.

Objectives: Implementation of diffusion-weighted imaging (DWI) for abdominal imaging in children has challenges due to motion artifacts exacerbated by long acquisition times. We aimed to compare acquisition time and image quality between conventional DWI and multi-band (MB) DWI of the liver in children and young adults.

Methods: Clinical MRI exams from May 2023 to January 2024 were reviewed, including four DWI sequences: respiratory-triggered (RTr, clinical standard), free-breathing (FB), MB-DWI with shift factor 1 (MBsf1), and MB-DWI with shift factor 2 (MBsf2).

Sexual dimorphism on the acute effect of exercise in the morning vs. evening: A randomized crossover study.

Background: Mammalian cells possess molecular clocks, the adequate functioning of which is decisive for metabolic health. Exercise is known to modulate these clocks, potentially having distinct effects on metabolism depending on the time of day. This study aimed to investigate the impact of morning vs.

Genome-wide CRISPR screen identifies AraC-Dauno-Eto (ADE) response modulators that predicts outcome in pediatric AML.

Cytarabine, daunorubicin, and etoposide (ADE) have been the standard backbone of induction chemotherapy regimens for acute myeloid leukemia (AML) patients for over five decades. However, chemoresistance is still a major concern, and a significant proportion of AML becomes resistant to ADE treatment leading to relapse and poor survival. Therefore, there is a significant need to identify mechanisms mediating drug resistance to overcome chemoresistance.

Development of an automated CBCT-based simulation-free platform for expedited palliative radiotherapy on a conventional linear accelerator.

Background: Conventional approaches for emergent or expedited palliative radiotherapy (RT) involve the application of cumbersome vendor-provided solutions and/or multiple patient appointments to complete the RT workflow within a compressed timeframe.

Purpose: This report delineates the clinical development of an in-house, semi-automated Cone-beam computed tomography (CBCT)-based simulation-free platform for expedited palliative RT on conventional linacs, intended to supplant existing techniques employed at this institution.

Methods: The internal software, termed SimFree Wizard (SFW), was engineered utilizing a C#-based application programming interface integrated within the treatment planning system (TPS).

JUMPlib: Integrative Search Tool Combining Fragment Ion Indexing with Comprehensive TMT Spectral Libraries.

The identification of peptides is a cornerstone of mass spectrometry-based proteomics. Spectral library-based algorithms are well-established methods to enhance the identification efficiency of peptides during database searches in proteomics. However, these algorithms are not specifically tailored for tandem mass tag (TMT)-based proteomics due to the lack of high-quality TMT spectral libraries.

Deconstruction of a memory engram reveals distinct ensembles recruited at learning.

How are associative memories formed? Which cells represent a memory, and when are they engaged? By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified non-overlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented or certain mouse behaviors occurred and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the different identities of the cell ensembles active during learning, and revealed, for the first time, which ones form the core engram and are essential for memory formation and recall.

Postoperative complications after central nervous system tumor resection in pediatric patients admitted to an intensive care unit in Colombia.

Introduction: Central nervous system (CNS) tumors are the second most prevalent malignant neoplasms in childhood, with surgical resection as the primary therapeutic approach. The immediate postoperative period following CNS tumor resection requires intensive care to mitigate complications associated with high morbidity and mortality.

Objective: The primary aim of this study is to comprehensively describe the postoperative complications observed in pediatric patients who underwent primary CNS tumor resection and were subsequently admitted to the pediatric intensive care unit (PICU) at Hospital Universitario Fundación Valle del Lili in Colombia.

Long-read epigenomic diagnosis and prognosis of Acute Myeloid Leukemia.

Acute Myeloid Leukemia (AML) is an aggressive cancer with dismal outcomes, vast subtype heterogeneity, and suboptimal risk stratification. In this study, we harmonized DNA methylation data from 3,314 patients across 11 cohorts to develop the Acute Leukemia Methylome Atlas (ALMA) of diagnostic relevance that predicted 27 WHO 2022 acute leukemia subtypes with an overall accuracy of 96.3% in discovery and 90.

Supporting cardiomyopathy screening behavior in adult survivors of childhood cancer: an eHealth motivational interviewing-framed pilot intervention.

Purpose: The Healthy Hearts pilot study evaluated the effect of an eHealth motivational interviewing-framed intervention on cardiomyopathy screening-related knowledge, health beliefs, intrinsic motivation, and behavioral action steps among adult survivors of childhood cancer.

Methods: We consented N = 73 survivors to participate in a single-arm pilot study. Participants completed an online baseline survey (n = 68) assessing knowledge, health beliefs, and intrinsic motivation related to cancer therapy-induced cardiomyopathy and screening echocardiograms.

Development of a high-throughput platform for quantitation of histone modifications on a new QTOF instrument.

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The 5 histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry-based approaches, identification and quantification of modified histone peptides remains challenging due to factors such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks.

Integrating cancer into crisis: a global vision for action from WHO and partners.

More than a billion people live in fragile, conflict-affected, and vulnerable settings requiring humanitarian support, where cancer is a substantial health issue. Despite its substantial effect on populations, cancer care remains underprioritised in emergency preparedness and response frameworks and humanitarian operational planning. This Policy Review summarises the perspectives and actionable recommendations from the First Global High-Level Technical Meeting on Non-communicable Diseases in Humanitarian Settings, with a focus on cancer.

Development of tetracycline analogues with increased aqueous stability for the treatment of mycobacterial infections.

Tetracycline analogs from the minocycline family have recently shown promise for the treatment of non-tuberculous mycobacterial infections. However, current tetracycline and minocycline therapeutics can be limited by tolerability, stability, or inactivation by TetX. In this study, a series of novel 9-heteroaryl substituted minocycline analogs were designed and synthesized, which resulted in analogs with good in vitro activity against Mycobacterium tuberculosis and Mycobacterium abscessus, stability in water for more than 7 days, avoidance of TetX inactivation in M.

Rhabdoid Tumor of the Kidney and Soft Tissues: Results from National Wilms Tumor Study-5 and Children's Oncology Group Study AREN0321.

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients And Methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1).

The landscape of primary mismatch repair deficient gliomas in children, adolescents, and young adults: a multi-cohort study.

Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.