Cholesterol efflux protein, ABCA1, supports anti-cancer functions of myeloid immune cells.

Although immune therapy has seen significant advances, the majority of breast and other solid tumors do not respond or quickly develop resistance. One factor driving resistance is highly immune suppressive myeloid cells (MCs) such as macrophages. Previous work has established clinical links between cholesterol and cancer outcome, and that MC function can be regulated through disruption in cholesterol metabolism.

The ciliary protein C2cd3 is required for mandibular musculoskeletal tissue patterning.

The mandible is composed of several musculoskeletal tissues including bone, cartilage, and tendon that require precise patterning to ensure structural and functional integrity. Interestingly, most of these tissues are derived from one multipotent cell population called cranial neural crest cells (CNCCs). How CNCCs are properly instructed to differentiate into various tissue types remains nebulous.

Irreversible Electroporation of the Liver Increases the Transplant Engraftment of Hepatocytes.

Introduction: Irreversible electroporation (IRE) is a tissue ablation technology that kills cells with short electrical pulses that do not induce thermal damage, thereby preserving the extracellular matrix. Preclinical research suggests that IRE may be developed as a tool for regenerative surgery by clearing existing host cells within a solid organ and creating a supportive niche for new cell engraftment. We hypothesized that hepatocytes transplanted by injection into the portal circulation would preferentially engraft within liver parenchyma pretreated with IRE.

The structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex.

The spindle assembly checkpoint (SAC) safeguards the genome during cell division by generating an effector molecule known as the Mitotic Checkpoint Complex (MCC). The MCC comprises two subcomplexes: BUBR1:BUB3 and CDC20:MAD2, and the formation of CDC20:MAD2 is the rate-limiting step during MCC assembly. Recent studies show that the rate of CDC20:MAD2 formation is significantly accelerated by the cooperative binding of CDC20 to the SAC proteins MAD1 and BUB1.

Simplification Is Not Dominant in the Evolution of Chinese Characters.

Linguistic systems are hypothesised to be shaped by pressures towards communicative efficiency that drive processes of simplification. A longstanding illustration of this idea is the claim that Chinese characters have progressively simplified over time. Here we test this claim by analyzing a dataset with more than half a million images of Chinese characters spanning more than 3,000 years of recorded history.

Wrist Proprioception in Adults with and without Subacute Stroke.

Proprioception is critical to motor control and functional status but has received limited study early after stroke. Patients admitted to an inpatient rehabilitation facility for stroke (n = 18, mean(±SD) 12.5 ± 6.

Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions.

Human induced pluripotent stem cell (iPSC)-derived liver organoids serve as models of organogenesis, disease, drug screening, and regenerative medicine. Prevailing methods for generating organoids rely on Matrigel, whose batch-to-batch variability and xenogeneic source pose challenges to mechanistic research and translation to human clinical therapy. In this report, we demonstrate that self-assembled Matrigel-free iPSC-derived organoids developed in rotating wall vessels (RWVs) exhibit greater hepatocyte-specific functions than organoids formed on Matrigel.

Kre28-Spc105 interaction is essential for Spc105 loading at the kinetochore.

Kinetochore (KTs) are macromolecular protein assemblies that attach sister chromatids to spindle microtubules (MTs) and mediate accurate chromosome segregation during mitosis. The outer KT consists of the KMN network, a protein super-complex comprising nl1 (yeast Spc105), is12 (yeast Mtw1), and dc80 (yeast Ndc80), which harbours sites for MT binding. Within the KMN network, Spc105 acts as an interaction hub of components involved in spindle assembly checkpoint (SAC) signalling.

Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling.

Accurate chromosome segregation during cell division requires amphitelic chromosome attachment to the spindle apparatus. It is ensured by the combined activity of the spindle assembly checkpoint (SAC), a signaling mechanism that delays anaphase onset in response to unattached chromosomes, and an error correction mechanism that eliminates syntelic attachments. The SAC becomes active when Mps1 kinase sequentially phosphorylates the kinetochore protein Spc105/KNL1 and the signaling proteins that Spc105/KNL1 recruits to facilitate the production of the mitotic checkpoint complex (MCC).

EDICNet: An end-to-end detection and interpretable malignancy classification network for pulmonary nodules in computed tomography.

We present an interpretable end-to-end computer-aided detection and diagnosis tool for pulmonary nodules on computed tomography (CT) using deep learning-based methods. The proposed network consists of a nodule detector and a nodule malignancy classifier. We used RetinaNet to train a nodule detector using 7,607 slices containing 4,234 nodule annotations and validated it using 2,323 slices containing 1,454 nodule annotations drawn from the LIDC-IDRI dataset.

The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint.

During mitosis, the Spindle Assembly Checkpoint (SAC) maintains genome stability while also ensuring timely anaphase onset. To maintain genome stability, the SAC must be strong to delay anaphase even if just one chromosome is unattached, but for timely anaphase onset, it must promptly respond to silencing mechanisms. How the SAC meets these potentially antagonistic requirements is unclear.

Generating Reward Functions Using IRL Towards Individualized Cancer Screening.

Cancer screening can benefit from individualized decision-making tools that decrease overdiagnosis. The heterogeneity of cancer screening participants advocates the need for more personalized methods. Partially observable Markov decision processes (POMDPs), when defined with an appropriate reward function, can be used to suggest optimal, individualized screening policies.

An Interpretable Deep Hierarchical Semantic Convolutional Neural Network for Lung Nodule Malignancy Classification.

While deep learning methods have demonstrated performance comparable to human readers in tasks such as computer-aided diagnosis, these models are difficult to interpret, do not incorporate prior domain knowledge, and are often considered as a "black-box." The lack of model interpretability hinders them from being fully understood by end users such as radiologists. In this paper, we present a novel interpretable deep hierarchical semantic convolutional neural network (HSCNN) to predict whether a given pulmonary nodule observed on a computed tomography (CT) scan is malignant.

Clinical phenomapping and outcomes after heart transplantation.

Background: Survival after heart transplantation (HTx) is limited by complications related to alloreactivity, immune suppression, and adverse effects of pharmacologic therapies. We hypothesize that time-dependent phenomapping of clinical and molecular data sets is a valuable approach to clinical assessments and guiding medical management to improve outcomes.

Methods: We analyzed clinical, therapeutic, biomarker, and outcome data from 94 adult HTx patients and 1,557 clinical encounters performed between January 2010 and April 2013.

A Bayesian model for estimating multi-state disease progression.

A growing number of individuals who are considered at high risk of cancer are now routinely undergoing population screening. However, noted harms such as radiation exposure, overdiagnosis, and overtreatment underscore the need for better temporal models that predict who should be screened and at what frequency. The mean sojourn time (MST), an average duration period when a tumor can be detected by imaging but with no observable clinical symptoms, is a critical variable for formulating screening policy.

Percutaneous Cryoablation for the Treatment of Recurrent Malignant Pleural Mesothelioma: Safety, Early-Term Efficacy, and Predictors of Local Recurrence.

Purpose: To determine safety and early-term efficacy of CT-guided cryoablation for treatment of recurrent mesothelioma and assess risk factors for local recurrence.

Materials And Methods: During the period 2008-2012, 24 patients underwent 110 cryoablations for recurrent mesothelioma tumors in 89 sessions. Median patient age was 69 years (range, 48-82 y).

Prediction of lung cancer incidence on the low-dose computed tomography arm of the National Lung Screening Trial: A dynamic Bayesian network.

Introduction: Identifying high-risk lung cancer individuals at an early disease stage is the most effective way of improving survival. The landmark National Lung Screening Trial (NLST) demonstrated the utility of low-dose computed tomography (LDCT) imaging to reduce mortality (relative to X-ray screening). As a result of the NLST and other studies, imaging-based lung cancer screening programs are now being implemented.

THYROSIM App for Education and Research Predicts Potential Health Risks of Over-the-Counter Thyroid Supplements.

Background: Computer simulation tools for education and research are making increasingly effective use of the Internet and personal devices. To facilitate these activities in endocrinology and metabolism, a mechanistically based simulator of human thyroid hormone and thyrotropin (TSH) regulation dynamics was developed and further validated, and it was implemented as a facile and freely accessible web-based and personal device application: the THYROSIM app. This study elucidates and demonstrates its utility in a research context by exploring key physiological effects of over-the-counter thyroid supplements.

A data-driven approach for quality assessment of radiologic interpretations.

Given the increasing emphasis on delivering high-quality, cost-efficient healthcare, improved methodologies are needed to measure the accuracy and utility of ordered diagnostic examinations in achieving the appropriate diagnosis. Here, we present a data-driven approach for performing automated quality assessment of radiologic interpretations using other clinical information (e.g.

Percutaneous cryoablation for the treatment of recurrent thymoma: preliminary safety and efficacy.

Thymoma is the most common primary tumor of the anterior mediastinum and often recurs after initial surgical resection. In this case series, percutaneous cryoablation, a locally ablative technique, was used to treat 25 mediastinal and pleural recurrent thymoma lesions in five patients. Safety and short-term efficacy data were collected.

Combating against methicillin-resistant Staphylococcus aureus - two fatty acids from Purslane (Portulaca oleracea L.) exhibit synergistic effects with erythromycin.

Objectives: The aims of this study were to identify the active ingredients from Portulaca oleracea L. (PO) that could provide synergism with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) and their possible mechanisms of resistance inhibition.

Methods: High-speed counter-current chromatography (HSCCC) coupled with gas chromatography-mass spectrometry and a panel of laboratory MRSA strains were used for checkerboard and efflux inhibitory assays.

Isolation of anti-inflammatory fractions and compounds from the root of Astragalus membranaceus.

Foot ulceration, if not treated properly, will eventually result in amputation. Inflammation may impede the wound healing process if not properly controlled. The root of Astragalus membranaceus (AR) is one of the Chinese herbs commonly found in Chinese herbal formulae used for treating foot ulcer.

Two antifungal components isolated from Fructus Psoraleae and Folium Eucalypti Globuli by bioassay-guided purification.

Fructus Psoraleae and Folium Eucalypti Globuli have long been used as Chinese medicines to treat various ailments such as asthma, eczema and dermatomycosis. In previous studies, their antifungal activities were demonstrated. The aim of the present study was to isolate active antidermatophytic compounds from their ethanolic extracts by means of bioassay-guided purification.