Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.

Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discover that hippocampal and spinal cord motor neurons of mouse and human origin localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress.

Combined Autologous Breast Reconstruction and Gynecologic Procedures: Does Timing Affect Clinical and Patient-Reported Outcomes?

Background: Patients with or at risk for breast cancer may opt for risk-reducing gynecologic surgeries, including bilateral salpingo-oophorectomies and/or total abdominal hysterectomy. The timing and safety of combining these procedures with autologous breast reconstruction (ABR) are debated. This study assesses the impact of concurrent ABR and gynecologic surgeries on clinical and patient-reported outcomes.

Moving Towards the Outpatient DIEP Flap: Factors Influencing Early Discharge.

Background: Enhanced Recovery After Surgery (ERAS) protocols can reduce the length of stay (LOS) for surgical patients, including those undergoing unilateral deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, allowing most patients to be discharged by postoperative day 2. However, some patients require a prolonged inpatient stay due to difficulty completing postoperative milestones. This study aims to identify factors associated with increased LOS after DIEP flap breast reconstruction and assess safety of earlier discharge.

Improving the Evaluation of Aesthetic Outcomes in DIEP Flap Breast Reconstruction: Validation of the Aesthetic Grading Tool.

Introduction: This study aimed to develop and validate an aesthetic grading tool (AGT) for bilateral DIEP flap breast reconstruction and investigate the correlation of BREAST-Q scores with perceived aesthetic outcomes.

Methods: The AGT utilized a Likert scale to rate aesthetic outcomes based on photographs of post-reconstruction breasts. The validation involved iterative testing with healthcare providers and patients.

Three Decades of Outpatient Plastic Surgery Safety: A Review of 42,720 Consecutive Cases.

Background: Outpatient plastic surgery offers cost-effective solutions and enhanced privacy but demands careful patient assessment for suitability and vigilant anticipation of adverse events. This study provides recommendations to enhance patient safety in outpatient settings by analyzing over 40,000 consecutive cases spanning across three decades.

Methods: We retrospectively reviewed all consecutive cases completed by board-certified plastic surgeons at an accredited outpatient surgical center between 1995-2023.

Bias-Based Bullying Among Sexual and Gender Minority Youth Living With Disabilities.

Both sexual and gender minority youth (SGMY) and youth living with disabilities are disproportionately impacted by bias-based bullying in school settings. While research has separately examined how sexual and gender minority status and disability status are associated with experiences of bullying, very little research has explored the experiences of youth living with these identities simultaneously. This study examined to what extent SGMY report differential experiences of bias-based bullying depending on various identities and the type of disability an individual reports.

Background parenchymal enhancement in CEM and MRI: Is there always a high agreement?

Introduction: Background parenchymal enhancement (BPE) refers to the physiological enhancement of breast fibroglandular tissue. This study aimed to determine the agreement of BPE evaluation between contrast enhanced mammography (CEM) and magnetic resonance imaging (MRI) and investigate potential confounders.

Materials And Methods: This retrospective, IRB-approved study included women recalled from screening or with inconclusive findings on mammography and/or ultrasound, who underwent both CEM and MRI between 2018 and 2022.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Physician inpatient handoffs-Patient and physician outcomes: A systematic review.

Background: Prior reviews have shown that interventions to improve inpatient handoffs are inconsistently associated with improvement in patient outcomes. This systematic review examines the effectiveness of inpatient handoff interventions on outcomes affecting patients and physicians, including objective measures when reported (PROSPERO ID: CRD42022309326).

Methods: Pubmed, Embase, and Cochrane Central Register of Controlled Trials were searched on January 13th, 2022.

Comprehensive Mass Spectral Libraries of Human Thyroid Tissues and Cells.

Thyroid nodules are a common endocrine condition with an increasing incidence over the decades. Data-independent acquisition has been widely utilized in discovery proteomics to identify disease biomarkers and therapeutic targets. To analyze the thyroid disease-related proteome in a high-throughput, reproducible and reliable manner, we introduce thyroid-specific peptide spectral libraries.

Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs.

Innate-like splenic marginal zone (MZ) B (MZB) cells play unique roles in immunity due to their rapid responsiveness to blood-borne microbes. How MZB cells integrate cell-extrinsic and -intrinsic processes to achieve accelerated responsiveness is unclear. We found that Delta-like1 (Dll1) Notch ligands in splenic fibroblasts regulated MZB cell pool size, migration, and function.

Cognitive Control Network and Language Reorganization in Patients with Brain Tumors.

Background And Purpose: The interaction between language and other cognitive networks in patients harboring brain tumors is poorly understood. We studied the modification of the cognitive control network (CCN) induced by brain tumors and its participation in language reorganization. We hypothesized that patients with brain tumors and reorganized language would show modification of the CCN compared to patients who remain left dominant.

Single-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice.

Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells-in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions.

A Pharmacokinetic/Toxicodynamic Model of Cisplatin Nephrotoxicity Using the Kidney Injury Molecule-1 Biomarker.

Cisplatin is a platinum-based chemotherapeutic that causes acute kidney injury in over 30% of patients. The aim of this study was to develop a population pharmacokinetic/toxicodynamic (PKTD) model of cisplatin-induced kidney injury that incorporated plasma total platinum and urinary kidney injury molecule-1 (KIM-1) concentrations. Cancer patients receiving their first or second round of cisplatin-containing chemotherapy (n=39) were prospectively randomized to a 5-HT antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) and had blood and urine collected over 10 days.

Interferon-ε loss is elusive 9p21 link to immune-cold tumors, resistant to immune-checkpoint therapy and endogenous CXCL9/10 induction.

Introduction: Copy-number (CN) loss of chromosome 9p, or parts thereof, impair immune response and confer ICT resistance by direct elimination of immune-regulatory genes on this arm, notably IFNγ genes at 9p24.1, and type-I interferon (IFN-I) genes at 9p21.3.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

MOUNTAINEER-03 phase III study design: first-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer.

Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with // wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), WT mCRC in the MOUNTAINEER trial.

Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment.

Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunction associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) is increasing. Biannual liver ultrasonography and serum α-fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.

The role of neoadjuvant systemic therapy for high grade upper tract urothelial carcinoma: Results from the upper tract collaborative network (UCAN).

Introduction: Utilization of neoadjuvant systemic therapy (NAT) prior to radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is inconsistent, and optimal patient selection for NAT is unclear. The purpose of this study was to evaluate the clinical benefit of NAT in high grade UTUC undergoing RNU.

Materials And Methods: The UTUC Collaborative Network (UCAN) identified patients who underwent RNU for high grade UTUC between 2000 and 2022.

Monoclonal gammopathy of undetermined significance and the risk of thrombotic events: Results from iStopMM, a prospective population-based screening study.

Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma and related diseases but has also been associated with thrombosis. Prior studies have not been based on screened cohorts leading to bias. We assessed the risk of thrombosis in a cohort of 75 422 individuals over 40 years old who were screened for MGUS in Iceland.

Functional genomics of primary congenital glaucoma by pathway analysis and functional characterization of CYP1B1 mutations.

CYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention.