Incidence of Adjacent Synchronous Ipsilateral Infiltrating Carcinoma and/or Ductal Carcinoma In Situ in Patients Diagnosed with Flat Epithelial Atypia by Core Needle Biopsy (TBCRC 034).

Background: Flat epithelial atypia (FEA), a rare breast proliferative lesion, is often diagnosed following core biopsy (CB) of mammographic microcalcifications. In the prospective multi-institution TBCRC 034 trial, we investigate the upgrade rate to ductal carcinoma in situ (DCIS) or invasive cancer following excision for patients diagnosed with FEA on CB.

Patients And Methods: Patients with a breast imaging reporting and data system (BI-RADS) ≤ 4 imaging abnormality and a concordant CB diagnosis of FEA were identified for excision.

The Landmark Series: Neoadjuvant Radiotherapy in Extremity Soft Tissue Sarcoma-The Way to Hypofractionation.

For patients with nonmetastatic soft tissue sarcoma (STS) who are at high risk of local recurrence, the standard of care for limb-conserving local management is combined radiotherapy and surgery. Radiotherapy for STS entails 5 weeks of conventionally fractionated radiotherapy (25 × 2 Gy) preoperatively or 6 or more weeks postoperatively. There is growing interest in the use of preoperative hypofractionated regimes, viz.

Defining Textbook Outcomes for Minimally Invasive Surgical Resection of Small Gastrointestinal Stromal Tumors (GIST) of the Stomach.

Background: Textbook outcome (TO) has been utilized to assess the quality of surgical care. This study aimed to define TO rates for minimally invasive gastric gastrointestinal stromal tumor (GIST) resections in a bi-institutional cohort.

Methods: Patients with gastric GIST (≤ 5 cm) who underwent laparoscopic or robotic resection (January 2014 to January 2024) were retrospectively identified from two GIST centers.

The Age-Old Question in Nipple-Sparing Mastectomy: Is Older Age a Contraindication?

Background: Nipple-sparing mastectomy (NSM) is infrequently performed in older women, at least in part owing to concerns regarding age-related complications. We describe postoperative outcomes of NSM in older women and risk factors for complications, with the goal of informing patient selection and decision-making.

Patients And Methods: Cases of NSM with immediate implant-based reconstruction were identified from an institutional database (2009-2019).

The Effect of Vaccination on the Competitive Advantage of Two Strains of an Infectious Disease.

We investigate the impact of differential vaccine effectiveness, waning immunity, and natural cross-immunity on the capacity for vaccine-induced strain replacement in two-strain models of infectious disease spread. We focus specifically on the case where the first strain is more transmissible but the second strain is more immune-resistant. We consider two cases on vaccine-induced immunity: (1) a monovalent model where the second strain has immune escape with respect to vaccination; and (2) a bivalent model where the vaccine remains equally effective against both strains.

Group 3 Innate Lymphoid Cells: A Potential Therapeutic Target for Steroid Resistant Asthma.

Asthma is a chronic airway inflammatory disease that affects millions globally. Although glucocorticoids are a mainstay of asthma treatment, a subset of patients show resistance to these therapies, resulting in poor disease control and increased morbidity. The complex mechanisms underlying steroid-resistant asthma (SRA) involve Th1 and Th17 lymphocyte activity, neutrophil recruitment, and NLRP3 inflammasome activation.

Identification of immune suppressor candidates utilizing comparative transcriptional profiling in histiocytic sarcoma.

Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model.

Overexpression of miR17 ~ 92 in Myeloid Cells in Mice Increased Bone Mass Through Reduced Bone Resorption and Increased Bone Formation in Sex-Dependent Manner.

This study assessed the feasibility of miR17 ~ 92-based antiresorptive strategy by determining the effects of conditional transgenic (cTG) overexpression of miR17 ~ 92 in myeloid cells on bone and osteoclasts. Osteoclasts of male and female cTG mutant mice each showed 3- to fivefold overexpression of miR17 ~ 92 cluster genes compared to those of age- and sex-matched wildtype (WT) littermates. Male but not female cTG mutant mice had more trabecular and cortical bones as well as lower bone resorption reflected by reduction in osteoclast number and resorbing surface.

Breaking Barriers in Huntington's Disease Therapy: Focused Ultrasound for Targeted Drug Delivery.

Huntington's disease (HD) is a progressive neurodegenerative disease resulting from a mutation in the huntingtin (HTT) gene and characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Currently, no disease-modifying treatments are available. Recent research has developed therapeutic agents that may have the potential to directly target the disease pathology, such as gene silencing or clearing the mutant protein.

Spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins.

Plasma thyroid hormone (TH) binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB), carry THs to extrathyroidal sites, where THs are unloaded locally and then taken up via membrane transporters into the tissue proper. The respective roles of THBPs in supplying THs for tissue uptake are not completely understood. To investigate this, we developed a spatial human physiologically based kinetic (PBK) model of THs, which produces several novel findings.

Health state utilities associated with invasive pneumococcal disease, pneumonia, and recurrent acute otitis media in young children.

Purpose: Cost-utility analyses examining the value of new vaccines for pneumococcal disease will require health state utilities as inputs. Existing utilities for pneumococcal infections in young children are limited. The purpose of this study was to estimate health state utilities associated with pneumococcal infections in young children.

Detailed analysis of cystic lesions in patients after open fetal repair and postnatal myelomeningocele closure.

Purpose: We sought to evaluate the incidence, natural history, and management of cystic spinal lesions following myelomeningocele/myeloschisis closure.

Methods: We performed a single-center retrospective review of all patients who underwent myelomeningocele/myeloschisis closure from 2013 to 2018 with follow-up to 5 years old.

Results: We analyzed 100 fetal repairs and 81 postnatal closures from 305 total surgeries.

Ipsilateral restriction of chromosome movement along a centrosome, and apical-basal axis during the cell cycle.

Little is known about how distance between homologous chromosomes are controlled during the cell cycle. Here, we show that the distribution of centromere components display two discrete clusters placed to either side of the centrosome and apical/basal axis from prophase to G interphase. 4-Dimensional live cell imaging analysis of centromere and centrosome tracking reveals that centromeres oscillate largely within one cluster, but do not cross over to the other cluster.

Prognostic immune markers in esophageal cancer patients managed with trimodal therapy.

Background: Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40-50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication.

Risk of Gastrointestinal Diseases in Osteogenesis Imperfecta: A Nationwide, Register-Based Cohort Study.

Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI.

Intravenous thrombolysis in patients with acute dizziness or imbalance and suspected ischemic stroke-systematic review.

Background: Correct identification of those patients presenting with an acute vestibular syndrome (AVS) or an acute imbalance syndrome (AIS) that have underlying posterior-circulation stroke (PCS) and thus may benefit from revascularization (intravenous thrombolysis (IVT), endovascular therapy (EVT)) is important. Treatment guidelines for AVS/AIS patients are lacking. We reviewed the evidence on acute treatment strategies in AVS/AIS focusing on predictors for IVT/EVT and outcome.

Immunometabolism In Brain Aging and Neurodegeneration: Bridging Metabolic Pathways and Immune Responses.

The complex set of interactions between the immune system and metabolism, known as immunometabolism, has emerged as a critical regulator of disease outcomes in the central nervous system. Numerous studies have linked metabolic disturbances to impaired immune responses in brain aging, neurodegenerative disorders, and brain injury. In this review, we will discuss how disruptions in brain immunometabolism balance contribute to the pathophysiology of brain dysfunction.

Thermogelation of nanoemulsions stabilized by a commercial pea protein isolate: high-pressure homogenization defines gel strength.

The impact of animal-based food production on climate change drives the development of plant-based alternatives. We demonstrate the use of colloidal thermogelation on a real nanoemulsion system to create structured gels that could be of interest for thermo-mechanical processing of next-generation plant-based food applications. We use a commercial pea protein isolate (PPI) without further purification to stabilize a 20 vol% peanut oil-in-water nanoemulsion at pH = 7 by high-pressure homogenization (HPH) and demonstrate the temperature induced gelation behavior of the nanoemulsion as a function of the HPH processing parameters.

Is the cortisol awakening response truly a response to awakening? Replication and extension using overnight sampling.

The cortisol awakening response (CAR) is a discrete component of the circadian cortisol profile. Evidence suggests that the CAR is a deviation from the pre-awakening increase in cortisol concentration, although this has yet to be replicated. Therefore, the purpose of this study was to replicate this finding and to investigate further the extent to which the CAR is distinct from the circadian profile.

The economic burden of diabetes in spinal fusion surgery: a systematic review and meta-analysis.

Purpose: This study aimed at comparing the costs of spinal fusion surgery between patients with and without diabetes.

Methods: Following PRISMA guidelines, a systematic search of four databases was conducted. A meta-analysis was performed on comparative studies examining diabetic versus non-diabetic adults undergoing cervical/lumbar fusion in terms of cost.

Slow-Coagulation Transscleral Cyclophotocoagulation in Pseudoexfoliation Glaucoma.

Purpose: To evaluate the outcomes of slow-coagulation transscleral cyclophotocoagulation (SC-TSCPC) in pseudoexfoliation glaucoma (PXG).

Methods: A single-center, retrospective non-comparative study including consecutive patients with medically uncontrolled PXG who underwent SC-TSCPC (1250-milliwatt power and 4-second duration). The primary outcome measure was surgical success (defined as intraocular pressure (IOP) between 6 - 21 mmHg with ≥20% reduction compared to baseline and no need for further glaucoma surgeries or development of vision-threatening complications).

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the leading cause of dementia worldwide. The recent announcement that lecanemab, a monoclonal antibody targeting amyloid-b, can slow down cognitive decline in AD is a great step forward in the battle against the disease. However, the modest success achieved in the clinical trial speak to the need for developing additional pharmaceutical approaches to target other key features of AD.

Basic Science and Pathogenesis.

Background: Applying single-cell RNA sequencing (scRNA-seq) to the study of neurodegenerative disease has propelled the field towards a more refined cellular understanding of Alzheimer's disease (AD); however, directly linking protein pathology to transcriptomic changes has not been possible at scale. Recently, a high-throughput method was developed to generate high-quality scRNA-seq data while retaining cytoplasmic proteins. Tau is a cytoplasmic protein and when hyperphosphorylated is integrally involved in AD progression.