Implanted adipose progenitor cells as physicochemical regulators of breast cancer.

Multipotent adipose-derived stem cells (ASCs) are increasingly used for regenerative purposes such as soft tissue reconstruction following mastectomy; however, the ability of tumors to commandeer ASC functions to advance tumor progression is not well understood. Through the integration of physical sciences and oncology approaches we investigated the capability of tumor-derived chemical and mechanical cues to enhance ASC-mediated contributions to tumor stroma formation. Our results indicate that soluble factors from breast cancer cells inhibit adipogenic differentiation while increasing proliferation, proangiogenic factor secretion, and myofibroblastic differentiation of ASCs. This altered ASC phenotype led to varied extracellular matrix (ECM) deposition and contraction thereby enhancing tissue stiffness, a characteristic feature of breast tumors. Increased stiffness, in turn, facilitated changes in ASC behavior similar to those observed with tumor-derived chemical cues. Orthotopic mouse studies further confirmed the pathological relevance of ASCs in tumor progression and stiffness in vivo. In summary, altered ASC behavior can promote tumorigenesis and, thus, their implementation for regenerative therapy should be carefully considered in patients previously treated for cancer.

Exploring the Usage of ChatGPT Among Medical Students in the United States.

OBJECTIVES: Chat Generative Pretrained Transformer (ChatGPT) is a large language model developed by OpenAI that has gained widespread interest. It has been cited for its potential impact on health care and its beneficial role in medical education. However, there is limited investigation into its use among medical students. In this study, we evaluated the frequency of ChatGPT use, motivations for use, and preference for ChatGPT over existing resources among medical students in the United States. METHODS: Data was collected from an original survey consisting of 14 questions assessing the frequency and usage of ChatGPT in various contexts within medical education. The survey was distributed via email lists, group messaging applications, and classroom lectures to medical students across the United States. Responses were collected between August and October 2023. RESULTS: One hundred thirty-one participants completed the survey and were included in the analysis. Of the total, 48.9% respondents responded that they have used ChatGPT in medical studies. Among ChatGPT users, 43.7% of respondents report using ChatGPT weekly, several times per week, or daily. ChatGPT is most used for writing, revising, editing, and summarizing purposes. 37.5% and 41.3% of respondents reported using ChatGPT more than 25% of the working time for these tasks respectively. Among respondents who have not used ChatGPT, more than 50% of respondents reported they were extremely unlikely or unlikely to use ChatGPT across all surveyed scenarios. ChatGPT users report they are more likely to use ChatGPT over directly asking professors or attendings (45.3%), textbooks (42.2%), and lectures (31.7%), and least likely to be used over popular flashcard application Anki (11.1%) and medical education videos (9.5%). CONCLUSIONS: ChatGPT is an increasingly popular resource among medical students, with many preferring ChatGPT over other traditional resources such as professors, textbooks, and lectures. Its impact on medical education will only continue to grow as its capabilities improve.

Unilateral double facial artery: an anatomic variant and clinical implications.

Background: This paper reports a rare anatomical variant of the facial artery (FA) - namely, a double FA pattern - which has significant implications in a wide range of surgical and aesthetic medicine disciplines. Case: The study involves a case report and literature review of the FA and its variants. The case is that of a 61-year-old female cadaver with a unilateral FA variant branching pattern discovered during a cadaveric dissection for an anatomy course. Discussion: The dissection revealed an unusual supply of the typical FA distribution by two separate branches from either side of the maxillary artery. The first branch, termed FA1, followed a typical FA course arising from the external carotid to supply the lower portion of the face via lingual, inferior labial, and mental arterial branches. The second branch, termed FA2, arose superior to the maxillary artery near the origin of a typical transverse facial artery, to supply the upper portion of the face via superior labial, lateral nasal, and angular arterial branches. No direct communication between the two branches was observed grossly via dissection. The observed branching pattern has not previously been reported in literature and has critical implications for surgical planning and intervention. Conclusion: This study emphasizes the importance of understanding variant FA anatomy in procedures requiring precise anatomical knowledge of arterial supply to the face. Duplicate and/or secondary facial arteries necessitate careful consideration for their potential consequences on the success of surgery of the head and neck, dermal fillers, and embolization for epistaxis procedures.

Anomalous Extensor Indicis Proprius Muscle Extending Beyond the Extensor Retinaculum: A Case Report.

CASE: During dissection of the upper limb of a cadaver in preparation for a first-year anatomy course, an extensor indicis proprius (EIP) variant was discovered with its muscle belly extending distal to the extensor retinaculum and beyond what has been previously described in the literature. CONCLUSION: EIP is commonly used as a tendon transfer for extensor pollicis longus rupture. Few anatomic variants of EIP have been reported in the literature, but such variants should be considered because of their consequences to the success of tendon transfer and potential implications for diagnosis of an otherwise unexplained mass of the wrist.

Appyters: Turning Jupyter Notebooks into data-driven web apps.

Jupyter Notebooks have transformed the communication of data analysis pipelines by facilitating a modular structure that brings together code, markdown text, and interactive visualizations. Here, we extended Jupyter Notebooks to broaden their accessibility with Appyters. Appyters turn Jupyter Notebooks into fully functional standalone web-based bioinformatics applications. Appyters present to users an entry form enabling them to upload their data and set various parameters for a multitude of data analysis workflows. Once the form is filled, the Appyter executes the corresponding notebook in the cloud, producing the output without requiring the user to interact directly with the code. Appyters were used to create many bioinformatics web-based reusable workflows, including applications to build customized machine learning pipelines, analyze omics data, and produce publishable figures. These Appyters are served in the Appyters Catalog at https://appyters.maayanlab.cloud. In summary, Appyters enable the rapid development of interactive web-based bioinformatics applications.

Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting.

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.

Modeling Monogenic Diabetes using Human ESCs Reveals Developmental and Metabolic Deficiencies Caused by Mutations in HNF1A.

Human monogenic diabetes, caused by mutations in genes involved in beta cell development and function, has been a challenge to study because multiple mouse models have not fully recapitulated the human disease. Here, we use genome edited human embryonic stem cells to understand the most common form of monogenic diabetes, MODY3, caused by mutations in the transcription factor HNF1A. We found that HNF1A is necessary to repress an alpha cell gene expression signature, maintain endocrine cell function, and regulate cellular metabolism. In addition, we identified the human-specific long non-coding RNA, LINKA, as an HNF1A target necessary for normal mitochondrial respiration. These findings provide a possible explanation for the species difference in disease phenotypes observed with HNF1A mutations and offer mechanistic insights into how the HNF1A gene may also influence type 2 diabetes.

Hyperactive FOXO1 results in lack of tip stalk identity and deficient microvascular regeneration during kidney injury.

Loss of the microvascular (MV) network results in tissue ischemia, loss of tissue function, and is a hallmark of chronic diseases. The incorporation of a functional vascular network with that of the host remains a challenge to utilizing engineered tissues in clinically relevant therapies. We showed that vascular-bed-specific endothelial cells (ECs) exhibit differing angiogenic capacities, with kidney microvascular endothelial cells (MVECs) being the most deficient, and sought to explore the underlying mechanism. Constitutive activation of the phosphatase PTEN in kidney MVECs resulted in impaired PI3K/AKT activity in response to vascular endothelial growth factor (VEGF). Suppression of PTEN in vivo resulted in microvascular regeneration, but was insufficient to improve tissue function. Promoter analysis of the differentially regulated genes in KMVECs suggests that the transcription factor FOXO1 is highly active and RNAseq analysis revealed that hyperactive FOXO1 inhibits VEGF-Notch-dependent tip-cell formation by direct and indirect inhibition of DLL4 expression in response to VEGF. Inhibition of FOXO1 enhanced angiogenesis in human bio-engineered capillaries, and resulted in microvascular regeneration and improved function in mouse models of injury-repair.