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Digit regeneration is expedited in LG/J healer mice compared to SM/J non-healer mice
Full text linkLimb loss resulting from disease or trauma affects an estimated 185,000 Americans annually, significantly reducing their quality of life. Consequently, successful attempts to regrow missing appendages could substantially improve the prognosis for amputees. In mice, the digit tip spontaneously regenerates resected tissues following distal amputation, whereas this capacity diminishes at more proximal levels after amputation. Moreover, regenerative potential is influenced by genetic variations among inbred mouse strains: LG/J (healer) mice exhibit superior reparative potential compared to SM/J (non-healer) mice. This study investigated the response to various levels of digit amputation in these mice to determine whether this strain-dependent healing response translates to the regeneration of complex tissues. Evaluation of skeletal regrowth, cell proliferation, and differential gene and protein expression reveals that digit regeneration is more robust in LG/J mice compared to SM/J mice at multiple amputation levels, suggesting that the regenerative capacity of composite tissues is genetically heritable in mice
TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity
Full text linkLung macrophages play a pivotal role in pulmonary fibrosis, with monocyte-derived alveolar macrophages driving disease progression. However, the mechanisms regulating their pro-fibrotic behavior and survival remain unclear, and effective therapeutic strategies are lacking. Here we show that triggering receptors expressed on myeloid cells 2 are predominantly expressed on monocyte-derived alveolar macrophages in fibrotic mouse lungs and are significantly elevated in lung macrophages from patients with idiopathic pulmonary fibrosis. Deletion or knockdown of this receptor disrupts intracellular survival signaling, promotes macrophage apoptosis, and attenuates their pro-fibrotic phenotype. We further demonstrate that a lipid mediator and a high-avidity ligand of this receptor, encountered by macrophages in the alveolar milieu, enhance macrophage survival and activity. Ablation of TREM2 or blocking this receptor with soluble receptors or specific antibodies effectively alleviates lung fibrosis in male mice. These findings identify this receptor as a critical regulator of macrophage-mediated fibrosis and a promising therapeutic target for intervention
The foundational capabilities of large language models in predicting postoperative risks using clinical notes
Full text linkClinical notes recorded during a patient\u27s perioperative journey holds immense informational value. Advances in large language models (LLMs) offer opportunities for bridging this gap. Using 84,875 preoperative notes and its associated surgical cases from 2018 to 2021, we examine the performance of LLMs in predicting six postoperative risks using various fine-tuning strategies. Pretrained LLMs outperformed traditional word embeddings by an absolute AUROC of 38.3% and AUPRC of 33.2%. Self-supervised fine-tuning further improved performance by 3.2% and 1.5%. Incorporating labels into training further increased AUROC by 1.8% and AUPRC by 2%. The highest performance was achieved with a unified foundation model, with improvements of 3.6% for AUROC and 2.6% for AUPRC compared to self-supervision, highlighting the foundational capabilities of LLMs in predicting postoperative risks, which could be potentially beneficial when deployed for perioperative care
Kir7.1 is the physiological target for hormones and steroids that regulate uteroplacental function
Full text linkPreterm birth is detrimental to the well-being of both the mother and the newborn. During normal gestation, the myometrium is maintained in a quiescent state by progesterone. As a steroid hormone, progesterone is thought to modify uterine and placental morphology by altering gene expression, but another direct mode of action has long been suspected. Here, we reveal the nongenomic molecular mechanism of progesterone as the activation of human and murine inwardly rectifying potassium channel Kir7.1, which is expressed in myometrium and placental pericytes during late gestation. Kir7.1 is also activated by selective steroids, including those used to prevent premature labor, such as 17-α-hydroxyprogesterone caproate and dydrogesterone, revealing their unexpected mode of action. Our results reveal that Kir7.1 is the molecular target of both endogenous and synthetic steroids that control uterine excitability and placental function. Kir7.1, therefore, is a promising therapeutic target to support healthy pregnancy during mid and late gestation
SaLuDo: A randomized phase IIb/III study of lurbinectedin plus doxorubicin as first-line treatment in leiomyosarcoma
Full text linkPrevious phase I/II trials indicate promising activity of lurbinectedin plus doxorubicin (DOX) in leiomyosarcoma (LMS). We describe here the rationale and design of SaLuDo, an open label, randomized, multicenter, seamless phase IIb/III study to evaluate the antitumor activity and safety of lurbinectedin plus DO
Select Your Race Below
No full textDanielle Serota is a medical student. She shared a story about race and identity.
Excerpt:
...I am a white-passing Ashkenazi Jew. In Slavic languages, Serota means “orphan.” Jewish children who were orphaned by violent pogroms in eastern Europe in the 19th century were given this name when there were no surviving family or community members to identify the child. Intrinsic to my name and my identity is the notion of otherhood
From Ashes to Purpose: A Journey of Healing and Hope
No full textAye Thant is a researcher in the Department of Neurology. She shared a story of healing and hope.
Excerpt:
It was a beautiful ordinary spring morning on February 1, 2021—the birds were singing, the sun was shining, and people were going on with their lives. Yet, beneath the calm lay chaos: internet and cellular connections were cut off with eerie silence in the air, and the junta had overthrown Burma’s democratically elected government, citing alleged voter fraud.... However, the first protest erupted right before our medical school, led by an activist physician who called for resistance. This spark ignited the nationwide Spring Revolution, and the junta quickly issued an arrest warrant for that doctor
Emerging domains for measuring health care delivery with electronic health record metadata
Full text linkThis article aims to introduce emerging measurement domains made feasible through the electronic health record (EHR) use metadata, to inform the changing landscape of health care delivery. We reviewed emerging domains in which EHR metadata may be used to measure health care delivery, outlining a framework for evaluating measures based on desirability, feasibility, and viability. We argue that EHR use metadata may be leveraged to develop and operationalize novel measures in the domains of team structure and dynamics, workflows, and cognitive environment to provide a clearer understanding of modern health care delivery. Examples of measures feasible using metadata include quantification of teamwork and collaboration, patient continuity measures, workflow conformity measures, and attention switching. By enabling measures that can be used to inform the next generation of health care delivery, EHR metadata may be used to improve the quality of patient care and support clinician well-being. Careful attention is needed to ensure that these measures are desirable, feasible, and viable
Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination
Full text linkWe investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting th
Social media as a platform for cancer care decision-making among women: Internet survey-based study on trust, engagement, and preferences
Full text linkBACKGROUND: Decision aids improve patient and clinician decision-making but are underused and often restricted to clinical settings.
OBJECTIVE: Given limited studies analyzing the feasibility of disseminating decision aids through social media, this study aimed to evaluate the acceptability, trust, and engagement of women with social media as a tool to deliver online decision aids for cancer treatment.
METHODS: To prepare for potential dissemination of a breast cancer decision aid via social media, a cross-sectional survey in February 2023 was conducted via Prime Panels, an online market research platform, of women aged 35-75 years in the United States. Demographics, health, cancer information-seeking behaviors, social media use, trust in social media for health information, as well as the likelihood of viewing cancer-related health information and clicking on decision aids through social media, were assessed. Statistical analyses included descriptive statistics, correlations, and multivariable ordinal regression.
RESULTS: Of 607 respondents, 397 (65.4%) had searched for cancer information, with 185 (46.6%) using the internet as their primary source. Facebook (Meta) was the most popular platform (511/607, 84.2%). Trust in social media for health information was higher among Black (14/72, 19.4%) and Asian respondents (7/27, 25.9%) than among White respondents (49/480, 10.2%; P=.003). Younger respondents aged 35-39 years (17/82, 20.7%) showed higher trust than those aged 70-79 years (12/70, 17.1%; P\u3c.001). Trust in social media for health information was linked to a higher likelihood of viewing cancer information and accessing a decision aid online (P\u3c.001). Participants who rated social media as Trustworthy (n=73) were more likely to view cancer information (61/73, 83.6%) and click on decision aids (61/73, 83.6%) than those who found it Untrustworthy (n=277; view: 133/277, 48.0%; click: 125/277, 45.1%). Engagement with social media positively correlated with viewing online cancer information (Spearman ρ=0.20, P\u3c.001) and willingness to use decision aids (ρ=0.21, P\u3c.001). Multivariable ordinal regression analyses confirmed that perception of social media\u27s trustworthiness is a significant predictor of engagement with decision aids (untrustworthy vs trustworthy β=-1.826, P\u3c.001; neutral vs trustworthy β=-0.926, P=.007) and of viewing cancer information (untrustworthy vs trustworthy β=-1.680, P\u3c.001, neutral vs trustworthy β=-0.581, P=.098), while age and employment status were not significant predictors.
CONCLUSIONS: This exploratory study suggests that social media platforms may increase access to health information and decision aids. No significant differences were observed between demographic variables and the use or trust in social media for health information. However, trust in social media emerged as a mediating factor between demographics and engagement with cancer information online. Before disseminating decision aids on social media, groups should identify existing trust and engagement patterns with different platforms within their target demographic