The ubiquitin-conjugating enzyme UBE2D maintains a youthful proteome and ensures protein quality control during aging by sustaining proteasome activity.

Ubiquitin-conjugating enzymes (E2s) are key for protein turnover and quality control via ubiquitination. Some E2s also physically interact with the proteasome, but it remains undetermined which E2s maintain proteostasis during aging. Here, we find that E2s have diverse roles in handling a model aggregation-prone protein (huntingtin-polyQ) in the Drosophila retina: while some E2s mediate aggregate assembly, UBE2D/effete (eff) and other E2s are required for huntingtin-polyQ degradation.

Persisting Toward a Career in Biomedical Research: A Black, Male Scientists' Becoming-Scientist-With Multiple Spatial Configurations.

This study explores the process of becoming-scientist-with, a dynamic and relational concept that redefines science identity development as a nonlinear, evolving journey. Focused on a Black male student, Travis, the study examines how his science identity was shaped through entanglements with various material and discursive forces across multiple science, technology, engineering, math, and medicine (STEMM) learning spaces. Becoming-scientist-with is conceptualized as a continual negotiation of identity within these environments, emphasizing the roles of power, systemic racism, and institutional practices in shaping students' experiences.

Insulin-Induced Lipohypertrophy Treated With Liposuction: A Review of Case Reports.

Lipohypertrophy is the most reported cutaneous complication of insulin injection. In cases refractory to conservative management, liposuction has been proposed as a treatment. This review aims to evaluate the use of liposuction for the treatment of insulin-induced lipohypertrophy.

Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).

The fungal microbiota modulate neonatal oxygen-induced lung injury.

Background: The immature lungs of very preterm infants are exposed to supraphysiologic oxygen, contributing to bronchopulmonary dysplasia (BPD), a chronic lung disease that is the most common morbidity of prematurity. While the microbiota significantly influences neonatal health, the relationship between the intestinal microbiome, particularly micro-eukaryotic members such as fungi and yeast, and lung injury severity in newborns remains unknown.

Results: Here, we show that the fungal microbiota modulates hyperoxia-induced lung injury severity in very low birth weight premature infants and preclinical pseudohumanized and altered fungal colonization mouse models.

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on "bystander" genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed.

Evidence-Based Surgical Guidelines for Treating Children With Rhabdomyosarcoma.

Background: Surgery remains the cornerstone of treatment for rhabdomyosarcoma (RMS) in children. However, there is considerable variation in surgical management practices worldwide, highlighting the need for standardized Clinical Practice Guidelines (CPG).

Methods: The CPG development involved assembling a multidisciplinary group, prioritizing 10 key topic areas, conducting evidence searches, and synthesizing findings.

Characterizing olfactory brain responses in young infants.

Odor perception plays a critical role in early human development, but the underlying neural mechanisms are not fully understood. To investigate these, we presented appetitive and aversive odors to infants of both sexes at one month of age while recording functional magnetic resonance imaging (fMRI) and nasal airflow data. Infants slept during odor presentation to allow MRI scanning.

Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.

Background: CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.

Methods: We assessed perceived cognition (Functional Assessment of Cancer Therapy - Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up.

Elective Discontinuation of Larotrectinib in Pediatric Patients With TRK Fusion Sarcomas and Related Mesenchymal Tumors.

Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.

Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial.

Importance: In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.

Objective: To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.

Ciliary Body Medulloepithelioma: Clinical and Pathologic Challenges with a Focus on Molecular Genetics.

Objective: Ciliary body medulloepithelioma (CBME), a pediatric intraocular tumor with potential for locally aggressive behavior and metastasis, may present with a diverse spectrum of clinical and histopathologic features leading to diagnostic and management challenges. Examination of unusual CBME cases highlights challenges and modern diagnostic techniques which facilitate accurate diagnosis and guide management.

Methods: A retrospective clinicopathologic analysis of 6 patients with unusual clinical or pathologic features of CBME was performed.

Emergence of a novel reassortant highly pathogenic avian influenza clade 2.3.4.4b A(H5N2) Virus, 2024.

Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.

Investigation of Genomic and Transcriptomic Risk Factors of Clopidogrel Response in African Americans.

Clopidogrel, an anti-platelet drug, is used to prevent thrombosis after percutaneous coronary intervention. Clopidogrel resistance results in recurring ischemic events, with African Americans (AA) suffering disproportionately. The aim of this study was to discover novel biomarkers of clopidogrel resistance in African Americans using genome and transcriptome data.

Genetic Services in Appalachia Conference Series.

This study examined the data generated as part of a seven-session webinar series that focused on genetics care provision in the medically underserved, rural Appalachian region and examined how these services have adapted to challenging practice environments. Barriers and facilitators to care in our region were considered. Data included a baseline survey of registrants, transcripts of sessions, and feedback about sessions.

Multi-center evaluation of the Alinity m HR HPV assay with liquid-based cytology cervical specimens in the United States.

Incorporating molecular testing for human papillomavirus (HPV) into the screening of cervical specimens can improve risk stratification and, in turn, patient management. Infection with a high-risk (HR) HPV genotype is associated with greater risk for persistent infection, viral integration, and progression of cervical neoplasia. Current guidelines consider HPV 16 or HPV 18 clinically actionable with referral to colposcopy; however, 12 Other HR HPV genotypes have been associated with cervical cancer risk, suggesting a benefit of extended genotyping.

Insulin Therapy for Acute Pancreatitis in a Patient With Lipase Maturation Factor 1 Mutation: A Case Report.

Acute pancreatitis is a frequent cause of hospital admission, managed with intravenous (IV) fluids, analgesia, and oral feeding when tolerated. In patients with hypertriglyceridemia-induced pancreatitis, insulin and other therapies may be necessary for disease resolution. We present a case of a patient with severe acute pancreatitis and euglycemic diabetic ketoacidosis (DKA) with known lipase maturation factor 1 (LMF1) gene mutations, which can impact insulin efficacy on triglyceride metabolism through altered lipoprotein lipase activity, successfully treated with intravenous insulin.

Performance of a Toric, Monthly, Soft Contact Lens in Digital Device Users.

Purpose: To determine the performance of TOTAL30 for Astigmatism (T30fA; Alcon; Fort Worth, TX, USA) contact lenses (CLs) in existing CL wearers who are also frequent digital device users.

Methods: This 1-month, 3-visit study recruited adult, 18- to 40-year-old subjects who were required to use daily digital devices for at least 8 hours per day. All subjects were refit into T30fA CLs.

Clinical, immunophenotypic, and genomic findings of acute myeloid leukemia with RAM immunophenotype: Comparison with other CD56-positive acute leukemias.

Background: Acute myeloid leukemia (AML) with RAM immunophenotype is a newly recognized high-risk AML immunophenotypic subcategory characterized by blasts with bright expression of CD56 and weak to absent expression of CD45, HLA-DR, and CD38, as first described by the Children's Oncology Group (COG). The relationship between AML-RAM and other CD56-positive acute leukemias is unclear. The goal of this study is to characterize the clinicopathological characteristics of AML with RAM phenotype and compare them with other CD56 co-expressing acute leukemias.

The International Association for the Study of Lung Cancer Staging Project: The Database and Proposal for the Revision of the Staging of Pulmonary Neuroendocrine Carcinoma in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

Introduction: Pulmonary high-grade neuroendocrine carcinoma (NEC) includes small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC). The seventh and eighth editions of the TNM classification for lung cancer confirmed the applicability of this staging system for SCLC. With the proposal of N2 and M1c subcategories for the ninth edition classification, we assessed the applicability to NECs.

The acute management of penetrating carotid artery injuries-A systematic review.

Background: Penetrating carotid artery injuries (CAI) are rare with high morbidity and mortality. We aimed to perform a systematic review of the published literature to evaluate the workup and management of penetrating CAI.

Methods: Studies of acute management of adult trauma patients with penetrating common or internal carotid artery injuries on MEDLINE or EMBASE from 1946 through July 2024 were included following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement methodology.

Kinematic Alignment Compared with Mechanical Alignment Techniques Results in Greater Peak Three-Dimensional Knee Joint Moments During Stair Negotiation.

Background: This study investigated the influence of surgical alignment techniques on knee joint biomechanics during stair negotiation tasks. Our hypothesis was that a more personalized joint alignment would result in reduced medial knee loading biomechanics to negotiate the stairs.

Methods: There were 28 adults (14 mechanical alignments [MA], 14 kinematic alignment [KA]) who underwent total knee arthroplasty (TKA) at least one year post-operatively and performed five stair ascent and descent trials at their preferred velocities.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Setting standards for brain collection procedures in metabolomic studies.

Current metabolomics technologies can measure hundreds of chemical entities in tissue extracts with good reliability. However, long-recognized requirements to halt enzyme activities during the initial moments of sample preparation are usually overlooked, allowing marked postmortem shifts in levels of labile metabolites representing diverse pathways. In brain many such changes occur in a matter of seconds.