Multi-institutional development and testing of attention-enhanced deep learning segmentation of thyroid nodules on ultrasound.

Purpose: Thyroid nodules are common, and ultrasound-based risk stratification using ACR's TIRADS classification is a key step in predicting nodule pathology. Determining thyroid nodule contours is necessary for the calculation of TIRADS scores and can also be used in the development of machine learning nodule diagnosis systems. This paper presents the development, validation, and multi-institutional independent testing of a machine learning system for the automatic segmentation of thyroid nodules on ultrasound.

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.

Putative biomarkers of hepatic dysfunction in critically ill sepsis patients.

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach.

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.

Mechanism of Sirtuin1-Mediated Deacetylation of p65-Mediated Ferroptosis of Hippocampal Neurons in Cerebral Injury after Cardiopulmonary Resuscitation in Rats.

Objective: Post-resuscitation brain injury is a common sequela after cardiac arrest (CA). Increasing sirtuin1 (SIRT1) has been involved in neuroprotection in oxygen-glucose deprivation (OGD) neurons, and we investigated its mechanism in post-cardiopulmonary resuscitation (CPR) rat brain injury by mediating p65 deacetylation modification to mediate hippocampal neuronal ferroptosis.

Methods: Sprague-Dawley rat CA/CPR model was established and treated with Ad-SIRT1 and Ad-GFP adenovirus vectors, or Erastin.

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.

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.

Integration of Immune Cell-Target Cell Conjugate Dynamics Changes the Time Scale of Immune Control of Cancer.

The human immune system can recognize, attack, and eliminate cancer cells, but cancers can escape this immune surveillance. Variants of ecological predator-prey models can capture the dynamics of such cancer control mechanisms by adaptive immune system cells. These dynamical systems describe, e.

The transcription factor NnNAC100 positively regulates amylopectin biosynthesis by activating NnSBEII in the rhizome of Nelumbo nucifera Gaertn.

NnNAC100-NnSBEII modules enhance starch content of the rhizome in Nelumbo nucifera Gaertn. Nelumbo nucifera Gaertn. is a popular aquatic vegetable and traditional Chinese medicine whose quality and taste are mainly determined by the starch.

Nanostructural Analysis of Age-Related Changes Affecting Human Dentin.

Human dentin performs its function throughout life, even though it is not remodeled like bone. Therefore, dentin must have extreme durability against daily repetitive loading. Elucidating its durability requires a comprehensive understanding of its shape, structure, and anisotropy at various levels of its structure.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the most common tauopathy and characterized by the progressive accumulation of Aß and tau. Tau is expressed in two major isoforms containing either 3 or 4 c-terminal repeats labeled as 3R and 4R tau. While these two isoforms occur in roughly equimolar ratios in AD, most research focus and mouse models of tau center only the 4Rtau protein and not 3Rtau.

Basic Science and Pathogenesis.

Background: Aging drives cellular and cognitive impairments in the adult brain. It is imperative to gain mechanistic insight into what drives aging phenotypes in the brain in order to maintain, and even restore, functional integrity in the elderly.

Method: We, and others, have shown that systemic interventions - such as heterochronic parabiosis (in which a young and old circulatory system are joined) and administration of young blood or exercise induced blood factors - can reverse age-related impairments in regenerative, synaptic and inflammatory processes, as well as rescue cognitive faculties in the aged brain.

Basic Science and Pathogenesis.

Background: The classic mode of STING activation is through binding the cyclic dinucleotide 2'3'-cyclic GMP-AMP (cGAMP), produced by the DNA sensor cyclic GMP-AMP synthase (cGAS), which is important for the innate immune response to microbial infection and autoimmune disease. Modes of STING activation that are independent of cGAS are much less well understood. We wanted to explore the interactome of STING on the organelles during its trafficking route and to understand the regulatory network of STING signaling.

Basic Science and Pathogenesis.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder involving pathological deposition of tau that includes glial inclusions and specific regional vulnerability patterns. Therapeutic developments are hampered by incomplete understanding of disease mechanisms. Few studies have examined its cell type-specific effects.

Basic Science and Pathogenesis.

Background: As humans age, some experience cognitive impairment while others do not. When impairment occurs, it varies in severity across individuals. Translationally relevant models are critical for understanding the neurobiological drivers of this variability, which is essential to uncovering the mechanisms underlying the brain's susceptibility to aging.

Basic Science and Pathogenesis.

Background: Brain accumulation of amyloid-ß (Aß) in plaques and neurons is the cause of AD neuropathology that is opposed by autologous monocyte/macrophages (MMs) in health but this defense fails in AD.

Method: RNAseq, immunochemistry of the brain, immunofluorescence, and confocal microscopy of macrophages.

Result: In the AD brain, MMs shuttle Aß from parenchyma to vessels, which develop vasculitis, causing amyloid-related imaging abnormalities (ARIAs).

Basic Science and Pathogenesis.

Background: Sleep dysfunction is commonly seen in Alzheimer's disease (AD) and Progressive Supranuclear Palsy (PSP), potentially worsening these conditions. Investigating early neuropathological changes in human sleep-promoting neurons, which often precede cognitive decline, is crucial for understanding the basis for sleep dysfunction as possible treatments yet remain underexplored. We used postmortem brains of AD and PSP patients to quantify neuronal numbers and tau burden in the intermediate nucleus of the hypothalamus (IntN), VLPO analog, known for its role in sleep maintenance.

Basic Science and Pathogenesis.

Background: Cerebrovascular alterations and innate immune activation are key features of Alzheimer's disease (AD). However, the mechanisms that link blood-brain barrier disruption to neurodegeneration are poorly understood and well-defined druggable targets at the neurovascular interface are limited.

Method: By developing a multiomic and genetic loss-of-function pipeline, we reported the transcriptomic and global phosphoproteomic landscape of blood-induced microglia activation and the causal role for fibrin in induction of neurodegenerative genes and oxidative stress pathways in innate immune cells.

Basic Science and Pathogenesis.

Background: Clinicopathological studies of Alzheimer's disease (AD) have demonstrated that synaptic or neuronal loss and clinical cognitive decline do not reliably correlate with fibrillar amyloid burden. We created a transgenic mouse model overexpressing Dutch (E693Q) mutant human amyloid precursor protein (APP) driven by the pan-neuronal Thy1 promoter. Accumulation of APP carboxyl-terminal fragments was observed in the brains of these mice, which develop an impaired learning phenotype directly proportional to brain oAβ levels.

Technology Enhanced Multidisciplinary Cancer Conferences in Gynecologic Oncology: Impact on Quality and Education.

Multidisciplinary cancer conferences (MCCs) improve patient outcomes. Our goals were to investigate the impact of a technology platform, navify® Clinical Hub for Tumor Boards (nCH) on the quality and educational value of gynecologic oncology MCCs. We conducted a prospective, mixed methods study of the gynecologic oncology MCC at a comprehensive cancer center from 2020 to 2023.

Exposure to Lead, Cadmium, Mercury and Arsenic Among Asian and Non-Asian Children and Adolescents in the United States: NHANES 2015-2018.

Higher concentrations of heavy metals were reported mainly among adult Asian persons compared to other racial/ethnic groups in earlier NHANES cycles' studies. We aimed to examine concentrations of metals among Asian children/adolescents compared to children/adolescents identifying with other racial/ethnic groups, considering socio-demographic factors and potential mediation by fish/shellfish consumption. Using NHANES data (2015-2018), 5293 participants (1-19 years) with blood/urinary measurements of lead, cadmium, mercury and arsenic were included.

BayesAge 2.0: a maximum likelihood algorithm to predict transcriptomic age.

Aging is a complex biological process influenced by various factors, including genetic and environmental influences. In this study, we present BayesAge 2.0, an upgraded version of our maximum likelihood algorithm designed for predicting transcriptomic age (tAge) from RNA-seq data.