A function-based mapping of sensory integration along the cortical hierarchy.

Sensory information mainly travels along a hierarchy spanning unimodal to transmodal regions, forming multisensory integrative representations crucial for higher-order cognitive functions. Here, we develop an fMRI based two-dimensional framework to characterize sensory integration based on the anchoring role of the primary cortex in the organization of sensory processing. Sensory magnitude captures the percentage of variance explained by three primary sensory signals and decreases as the hierarchy ascends, exhibiting strong similarity to the known hierarchy and high stability across different conditions.

Perspectives on Codebook: sequence specificity of uncharacterized human transcription factors.

We describe an effort ("Codebook") to determine the sequence specificity of 332 putative and largely uncharacterized human transcription factors (TFs), as well as 61 control TFs. Nearly 5,000 independent experiments across multiple and assays produced motifs for just over half of the putative TFs analyzed (177, or 53%), of which most are unique to a single TF. The data highlight the extensive contribution of transposable elements to TF evolution, both in and , and identify tens of thousands of conserved, base-level binding sites in the human genome.

Cross-platform DNA motif discovery and benchmarking to explore binding specificities of poorly studied human transcription factors.

A DNA sequence pattern, or "motif", is an essential representation of DNA-binding specificity of a transcription factor (TF). Any particular motif model has potential flaws due to shortcomings of the underlying experimental data and computational motif discovery algorithm. As a part of the Codebook/GRECO-BIT initiative, here we evaluated at large scale the cross-platform recognition performance of positional weight matrices (PWMs), which remain popular motif models in many practical applications.

Considerations for Cell Type Heterogeneity in Pediatric Salivary DNA Methylation Analyses: Comparison of Reference Panels & Stratification by Estimated Cell Type Proportion.

Saliva is a widely used sample in epigenetic research with children due to its non-invasive nature. Since DNA methylation (DNAm) profile is cell type (CT) specific, salivary DNAm associations with exposures may be influenced by CT compositions, which is highly variable in saliva as it contains immune and buccal epithelial cells (BEC). Reference-based CT deconvolution and statistically adjusting estimated CT in DNAm analyses have become an increasingly common practice.

Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors.

Background/objectives: This retrospective observational study aimed to investigate the perioperative outcome in Malignant Peripheral Nerve Sheath Tumors (MPNSTs) with and without relation to Neurofibromatosis Type 1 (NF1) and to detect possible influencing factors.

Methods: Clinical reports, histopathological evaluations, imaging, and treatment characteristics were reviewed in 35 operated MPNSTs in 33 patients. Possible predictive valuables included disease type, preoperative tumor volume, SUV and MIB-1 proliferation index, resection margins, the presence of metastasis, and whether radio-/chemotherapy was received.

Minimal Variation in Functional Connectivity in Relation to Daily Affect.

Reported associations between functional connectivity and affective disorder symptoms are minimally reproducible, which can partially be attributed to difficulty capturing highly variable clinical symptoms in cross-sectional study designs. "Dense sampling" protocols, where participants are sampled across multiple sessions, can overcome this limitation by studying associations between functional connectivity and variable clinical states. Here, we characterized effect sizes for the association between functional connectivity and time-varying positive and negative daily affect in a nonclinical cohort.

The Impact of Public Policy on Equitable Access to Technology for Children and Youth Living with Type 1 Diabetes in British Columbia, Canada.

Structural inequities impede technology uptake in marginalized populations living with type 1 diabetes (T1D). Our objective was to describe hemoglobin A1c (HbA), time in range (TIR), and pump use to evaluate the impact of a universal funding policy for continuous glucose monitoring (CGM) across levels of deprivation in children with T1D in the Canadian province of British Columbia (BC). Patients with T1D and at least one outpatient visit after June 10, 2020 (1-year before universal CGM funding) who were enrolled in the BC Pediatric Diabetes Registry were included ( = 477).

Psychosocial screening, in-patient care, and disposition planning: Clinicians' perspectives.

Objective: Our objective was to explore clinicians' views on the MyHEARTSMAP screening report; whether this report has impacted their patient care, and if so, how. MyHEARTSMAP is a psychosocial self-screening tool for youth to identify mental health concerns.

Methods: We conducted a cross-sectional study as a sub-study of the MyHEARTSMAP In-Patient randomized control trial.

Pulmonary Xe MRI: CNN Registration and Segmentation to Generate Ventilation Defect Percent with Multi-center Validation.

Rationale And Objectives: Hyperpolarized Xe MRI quantifies ventilation-defect-percent (VDP), the ratio of Xe signal-void to the anatomic H MRI thoracic-cavity-volume. VDP is associated with airway inflammation and disease control and serves as a treatable trait in therapy studies. Semi-automated VDP pipelines require time-intensive observer interactions.

Immunohistochemical study of histone protein 3 modification in pediatric osteosarcoma identifies reduced H3K27me3 as a marker of poor treatment response.

The most common pediatric primary malignant bone tumor, osteosarcoma, is often described as genetically non-recurrent and heterogeneous. Neoadjuvant chemotherapy is typically followed by resection and assessment of treatment response, which helps inform prognosis. Identifying biomarkers that may impact chemotherapy response and survival could aid in upfront risk stratification and identify patients in highest need of innovative therapies for future clinical trials.

Ceftazidime-Cefazolin Empiric Therapy for Pediatric Gradenigo Syndrome.

Objective: Gradenigo Syndrome (GS), a rare complication of petrous apicitis secondary to acute otitis media, is characterized by (an often incomplete) triad of otorrhea, abducens nerve palsy, and facial pain along the trigeminal nerve distribution. There are several causative pathogens of petrous apicitis, including and species, while is the most common. However, the case report literature often describes antibiotic management of GS with antibiotics that do not cover , potentially predisposing to further intracranial complications or mortality.

Evaluating family-centred care at BC Children's Hospital: Healthcare providers' perspectives.

Background: Family-centred care (FCC) emphasizes a partnership approach to care between healthcare providers (HCPs), patients, and families. FCC provides significant benefits to both children and families; however, challenges exist in implementing FCC into practice. This study aimed to explore HCPs' FCC behaviours in multidisciplinary specialty clinics at a tertiary pediatric health care center in Canada.

Pterostilbene Targets Hallmarks of Aging in the Gene Expression Landscape in Blood of Healthy Rats.

Scope: Polyphenols from the phytoestrogen group, including pterostilbene (PTS), are known for their antioxidant, anti-inflammatory, and anti-cancer effects. In recent reports, phytoestrogens attenuate age-related diseases; however, their pro-longevity effects in healthy models in mammals remain unknown. As longevity research demonstrates age-related transcriptomic signatures in human blood, the current study hypothesizes that phytoestrogen-supplemented diet may induce changes in gene expression that ultimately confer pro-longevity benefits.

Tracking insulin- and glucagon-expressing cells in vitro and in vivo using a double reporter human embryonic stem cell line.

Human embryonic stem cell (hESC)-derived pancreatic alpha and beta cells can be used to develop cell replacement therapies to treat diabetes. However, recent published differentiation protocols yield varying amounts of alpha and beta cells amidst heterogeneous cell populations. To visualize and isolate hESC-derived alpha and beta cells, we generated a GLUCAGON-2AmScarlet and INSULIN-2A-EGFP dual fluorescent reporter (INSEGFPGCGmScarlet) hESC line using CRISPR/Cas9.

Pain and development: interacting phenomena.

For decades, clinicians and researchers have observed bidirectional relationships between child development and the pain experience in childhood. Pain in childhood is an inherently developmental phenomenon, embedded in an iterative, time-dependent process that reflects individual biological, behavioral, social, psychological, and environmental characteristics that unfold across the early life span. Childhood pain can have wide ranging effects on brain development in ways that contribute-for better and worse-to social, emotional, and cognitive well-being in childhood and on into adulthood.

24-Hour Induction of Transdermal Buprenorphine to Buprenorphine Extended-Release.

Buprenorphine is an effective treatment for opioid use disorder but can be slow when using a standard low-dose titration protocol to avoid precipitated withdrawal. This presents a substantial practical barrier in clinical practice. Recent low-dose induction strategies have attempted to simplify and shorten the process required for successful induction, including our own transdermal buprenorphine method, which achieves induction to sublingual buprenorphine/naloxone after 48 h.

Long-Term Health Outcomes of Individuals With Pseudodeficiency Alleles in IDUA May Inform Newborn Screening Practices for Mucopolysaccharidosis Type I.

Mucopolysaccharidosis type I (MPS I), a lysosomal disorder caused by variants in IDUA, was added to the Recommended Uniform Screening Panel for newborn screening in 2016. Positive screening results for MPS I are commonly due to variants known as "pseudodeficiency alleles," which decrease in vitro alpha-L-iduronidase enzyme activity but are thought to provide sufficient in vivo activity. Despite the historic assumption that these variants are biologically benign, the possibility that they could give rise to complex, multigenic, or attenuated phenotypes has not been systemically evaluated in adults.

Diabetes Mellitus Associated with Maternally Inherited Diabetes and Deafness (MIDD): From Pathogenic Variant to Phenotype.

Maternally inherited diabetes and deafness (MIDD) is a monogenic mitochondrial disorder caused by a pathogenic variant in the MT-TL1 gene encoding for a leucine transfer RNA. We propose a new hypothesis that explains how the MT-TL1 variant causes impaired glucose tolerance and diabetes in MIDD. We suggest that diabetes in MIDD primarily depends on a variable combination of insulin resistance and impaired beta cell function that seems more likely to occur in the presence of high skeletal muscle heteroplasmy and moderate beta cell heteroplasmy for m.

Symptomatology and Management of Adult Anaphylaxis according to Trigger: A Cross-Sectional Study.

Introduction: Anaphylaxis is an acute life-threatening allergy, most commonly provoked by food, venom, or drugs. There is limited data regarding differences in symptomatology between anaphylaxis provoked by different triggers. This study aimed to assess sociodemographic characteristics, clinical symptoms, and management of anaphylaxis, according to triggers in adults.