Atypical free sialic acid storage disorder associated with tissue specific mosaicism of SLC17A5.

Free sialic acid storage disorder (FSASD) is a rare autosomal recessive lysosomal storage disease caused by pathogenic SLC17A5 variants with variable disease severity. We performed a multidisciplinary evaluation of an adolescent female with suspected lysosomal storage disease and conducted comprehensive studies to uncover the molecular etiology. The proband exhibited intellectual disability, a storage disease gestalt, and mildly elevated urine free sialic acid levels.

Relationship Between Perceived COVID-19 Risk and Change in Perceived Breast Cancer Risk: Prospective Observational Study.

Background: Whether COVID-19 is associated with a change in risk perception about other health conditions is unknown. Because COVID-19 occurred during a breast cancer study, we evaluated the effect of COVID-19 risk perception on women's breast cancer risk perception.

Objective: This study aims to evaluate the relationship between perceived risk of COVID-19 and change in perceived breast cancer risk.

Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy.

Adoptive cell transfer (ACT) is a therapeutic strategy to augment antitumor immunity. Here, we report that ex vivo treatment of mouse CD8 T cells with dimethyloxalylglycine (DMOG), a stabilizer of hypoxia-inducible factors (HIFs), induced HIF binding to the genes encoding the costimulatory receptors CD81, GITR, OX40, and 4-1BB, leading to increased expression. DMOG treatment increased T cell killing of melanoma cells, which was further augmented by agonist antibodies targeting each costimulatory receptor.

Mentoring to address differential attainment of international medical graduates in GP training.

Introduction: International Medical Graduates (IMGs) form an important and valued part of the United Kingdom's (UK) medical workforce but many experience difficult transitions into the National Health Service workforce. Mentoring could support IMGs as they transition into their role as General Practice (GP) trainees but there is a lack of evidence about whether mentoring is an effective intervention for this group.

Aim: To evaluate the effectiveness of the NHS Education for Scotland (NES) GP mentoring programme from the perspective of mentors and mentees.

'Bitesize' primary care focused education programme for GP trainees in their hospital component: an evaluation of a national teaching pilot.

There is need for a greater connection between General Practice and GP trainees in their hospital component of training. Currently, in Scotland, there are no national education programmes specifically designed for GP trainees during their hospital component of training. Our aim was to develop and evaluate the feasibility of a national online 'bitesize' education programme delivered live for GP trainees in their hospital component of training.

Hypoxia-inducible factor 1 recruits FACT and RNF20/40 to mediate histone ubiquitination and transcriptional activation of target genes.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40).

Association of Sleep Characteristics with Tinnitus and Hearing Loss.

Objective: The impact of poor sleep on tinnitus has been mainly attributed to central processes. There is an association between sleep disorders and hearing loss, but whether hearing levels mediate the association between sleep disorders and tinnitus is unknown. This study investigates the association between sleep characteristics, tinnitus, and hearing loss.

Pathogenic Potential of and : A Case Report.

and have been considered normal aural flora. Their significance in active infection is controversial. We examined a series of patients presenting with acute and chronic otitis media whose ear canal culture isolated and and explored possible pathogenicity, associated factors, and outcomes.

The everchanging Sky-Tower - an apparent giant.

For over a quarter-century, the Sky-Tower has dominated the skyline of Auckland Tāmaki Makaurau. Despite its imposing height, observers anecdotally report odd fluctuations in how big it appears. From certain angles, it can look positively stumpy.

Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss in Children: Identification Following Universal Newborn Hearing Screening, Effect of Antiviral Treatment, and Long-Term Hearing Outcomes.

Objectives: Congenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of children with cCMV in relation to their newborn hearing screening findings, and their use of antiviral therapy.

Design: The study was based on a retrospective chart review using a database of pediatric patients (N = 445) seen at the University of Minnesota Lions clinic.

LIN28B and Let-7 in Diffuse Midline Glioma: A Review.

Diffuse midline glioma (DMG) is the most lethal of all childhood cancers. DMGs are driven by histone-tail-mutation-mediated epigenetic dysregulation and partner mutations in genes controlling proliferation and migration. One result of this epigenetic and genetic landscape is the overexpression of LIN28B RNA binding protein.

Magnetic Resonancy Imaging Safety in Active Osseointegrated (Osia®) and Cochlear Implants: New Technology Creating Confusion.

Objective: There is increased confusion regarding MRI-compatible CIs and BAHAs. This report describes two cases when patients underwent MRIs with non-MRI compatible devices.

Results: One patient with bilateral Cochlear Osias experienced dislocation of both internal magnets after 1.

WAVE-DAMPENED2-LIKE4 modulates the hyper-elongation of light-grown hypocotyl cells.

Light, temperature, water, and nutrient availability influence how plants grow to maximize access to resources. Axial growth, the linear extension of tissues by coordinated axial cell expansion, plays a central role in these adaptive morphological responses. Using Arabidopsis (Arabidopsis thaliana) hypocotyl cells to explore axial growth control mechanisms, we investigated WAVE-DAMPENED2-LIKE4 (WDL4), an auxin-induced, microtubule-associated protein and member of the larger WDL gene family shown to modulate hypocotyl growth under changing environmental conditions.

Neurotology Workforce in the United States: Gender Diversity and Geographic Distribution.

Objective: The workforce of neurotology has changed with increasing numbers of accredited programs and diverse representation among trainees over the past several decades. This study aims to describe the characteristics, density, and geographic variation of the current neurotology workforce in the United States.

Study Design: Cross-sectional study.

Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis.

Intratumoral hypoxia is a microenvironmental feature that promotes breast cancer progression and is associated with cancer mortality. Plexin B3 (PLXNB3) is highly expressed in estrogen receptor-negative breast cancer, but the underlying mechanisms and consequences have not been thoroughly investigated. Here, we report that PLXNB3 expression is increased in response to hypoxia and that PLXNB3 is a direct target gene of hypoxia-inducible factor 1 (HIF-1) in human breast cancer cells.

NARF is a hypoxia-induced coactivator for OCT4-mediated breast cancer stem cell specification.

Hypoxia is a key characteristic of the breast cancer microenvironment that promotes expression of the transcriptional activator hypoxia-inducible factor 1 (HIF-1) and is associated with poor patient outcome. HIF-1 increases the expression or activity of stem cell pluripotency factors, which control breast cancer stem cell (BCSC) specification and are required for cancer metastasis. Here, we identify nuclear prelamin A recognition factor () as a hypoxia-inducible, HIF-1 target gene in human breast cancer cells.

Cost-Effectiveness of PET Directed Versus Combined Modality Therapy for Early-Stage Favorable Hodgkin's Lymphoma.

Introduction: The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Recent treatment de-escalation trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET) and have suggested a detriment in progression free survival (PFS) for patients who do not receive radiation therapy (RT) but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy versus standard of care CMT.

Association of Hearing Test History With Awareness of Hearing Loss and Hearing Aid Use in Older Adults.

This cross-sectional study aims to quantify the association between having a prior hearing test and awareness of hearing loss and hearing aid use in older US adults.

Formula Otorrhea in Pediatric Patients With Cleft Palate.

The case series details 2 unusual cases of male newborns with cleft lip and palate (CLP) that later developed formula otorrhea. Both patients underwent bilateral myringotomies with the insertion of pressure equalizing (PE) tubes for chronic otitis media with effusion (OME). Chronic otorrhea associated with feeding occurred post-PE tube insertion and the otorrhea was later confirmed to be due to reflux of formula.

Epigenomic landscape and 3D genome structure in pediatric high-grade glioma.

Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3.

Examining the relationship between processing fluency and memory for source information.

Familiarity-based processes such as processing fluency can influence memory judgements in tests of item recognition. Many conventional accounts of source memory assume minimal influence of familiarity on source memory, but recent work has suggested that source memory judgements are affected when test stimuli are processed with greater fluency as a result of priming. The present experiments investigated the relationship between fluency and the accuracy of source memory decisions.

Standardization of the liquid biopsy for pediatric diffuse midline glioma using ddPCR.

Diffuse midline glioma (DMG) is a highly morbid pediatric brain tumor. Up to 80% of DMGs harbor mutations in histone H3-encoding genes, associated with poor prognosis. We previously showed the feasibility of detecting H3 mutations in circulating tumor DNA (ctDNA) in the liquid biome of children diagnosed with DMG.

Effects of H3.3G34V mutation on genomic H3K36 and H3K27 methylation patterns in isogenic pediatric glioma cells.

Histone H3.3 mutation (H3F3A) occurs in 50% of cortical pediatric high-grade gliomas. This mutation replaces glycine 34 with arginine or valine (G34R/V), impairing SETD2 activity (H3K36-specific trimethyltransferase).

Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma.

Background: Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of the H3.

BIRC2 Expression Impairs Anti-Cancer Immunity and Immunotherapy Efficacy.

Immune checkpoint blockade (ICB) has led to therapeutic responses in some cancer patients for whom no effective treatment previously existed. ICB acts on T lymphocytes and other immune cells that are inactivated due to checkpoint signals that inhibit their infiltration and function within tumors. But for more than 80% of patients, immunotherapy has not been effective.