Explore the vast range of titles available.

The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ , combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium. The identity and origin of adult mammary stem cells has been much debated. Here, the authors use a stochastic genetic labelling approach, together with optical tissue clearing, to visualize clonal progeny and show that unipotent stem/progenitor cells contribute to adult mammary gland development.

Background High-resolution 3D imaging of intact tissue facilitates cellular and subcellular analyses of complex structures within their native environment. However, difficulties associated with immunolabelling and imaging fluorescent proteins deep within whole organs have restricted their applications to thin sections or processed tissue preparations, precluding comprehensive and rapid 3D visualisation. Several tissue clearing methods have been established to circumvent issues associated with depth of imaging in opaque specimens. The application of these techniques to study the elaborate architecture of the mouse mammary gland has yet to be investigated. Methods Multiple tissue clearing methods were applied to intact virgin and lactating mammary glands, namely 3D imaging of solvent-cleared organs, see deep brain (seeDB), clear unobstructed brain imaging cocktails (CUBIC) and passive clarity technique. Using confocal, two-photon and light sheet microscopy, their compatibility with whole-mount immunofluorescent labelling and 3D imaging of mammary tissue was examined. In addition, their suitability for the analysis of mouse mammary tumours was also assessed. Results Varying degrees of optical transparency, tissue preservation and fluorescent signal conservation were observed between the different clearing methods. SeeDB and CUBIC protocols were considered superior for volumetric fluorescence imaging and whole-mount histochemical staining, respectively. Techniques were compatible with 3D imaging on a variety of platforms, enabling visualisation of mammary ductal and lobulo-alveolar structures at vastly improved depths in cleared tissue. Conclusions The utility of whole-organ tissue clearing protocols was assessed in the mouse mammary gland. Most methods utilised affordable and widely available reagents, and were compatible with standard confocal microscopy. These techniques enable high-resolution, 3D imaging and phenotyping of mammary cells and tumours in situ , and will significantly enhance our understanding of both normal and pathological mammary gland development.

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMP2 in the progression of dedifferentiated liposarcomas. Using disease free survival as our primary endpoint, we find that BMP2 confers poor prognosis only within the context of high BMPR1A expression. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link the BMP2/BMPR1A axis to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2 and the potential disadvantages of recombinant human BMP2 (rhBMP2) use in orthopaedic surgery. For the first time, we identify high BMP2 expression within the context of high BMPR1A expression as a biomarker of disease relapse in dedifferentiated liposarcomas.

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. Because of BMP2’s osteogenic properties, a recombinant human version (rhBMP2) has found utility as an adjuvant therapy during surgery for spinal fusions. However, the results of large-scale meta-analysis has highlighted the potential of rhBMP2 to promote new tumour formation, leading to an FDA black box warning. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMPR1A-biased BMP2 signalling in soft tissue sarcomas. Using disease free survival as our primary endpoint, we find this BMPR1A-biased BMP2 signalling confers poor overall prognosis compared both to patients with BMPR1B-biased and to the sarcoma dataset as a whole. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link this effect to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2, the need for extensive patient follow-up and the potential disadvantages of rhBMP2 use. For the first time, we identify BMPR1A-biased BMP2 signalling as a biomarker of disease relapse in dedifferentiated liposarcomas.

Post-COVID cognitive deficits, including ‘brain fog’, are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits. Longitudinal proteomic profiling of over 1,800 patients revealed two distinct profiles of blood biomarkers measured on admission to hospital for COVID-19, which predict cognitive deficits 6 and 12 months later.

Global-scale properties of Europa’s putative ocean, including its depth, thickness, and conductivity, can be established from measurements of the magnetic field on multiple close flybys of the moon at different phases of the synodic and orbital periods such as those planned for the Europa Clipper mission. The Europa Clipper Magnetometer (ECM) has been designed and constructed to provide the required high precision, temporally stable measurements over the range of temperatures and other environmental conditions that will be encountered in the solar wind and at Jupiter. Three low-noise, tri-axial fluxgate sensors provided by the University of California, Los Angeles are controlled by an electronics unit developed at NASA’s Jet Propulsion Laboratory. Each fluxgate sensor measures the vector magnetic field over a wide dynamic range (±4000 nT per axis) with a resolution of 8 pT. A rigorous magnetic cleanliness program has been adopted for the spacecraft and its payload. The sensors are mounted far out on an 8.5 m boom to form a configuration that makes it possible to measure the remaining spacecraft field and remove its contribution to data from the outboard sensor. This paper provides details of the magnetometer design, implementation and testing, the ground calibrations and planned calibrations in cruise and in orbit at Jupiter, and the methods to be used to extract Europa’s inductive response from the data. Data will be collected at nominal rates of 1 or 16 samples/s and will be processed at UCLA and delivered to the Planetary Data System in a timely manner.

PurposeTo examine patient and hospital characteristics related to seasonal fluctuation in in vitro fertilization (IVF).MethodsThis retrospective cohort study examined 33,077 oocyte retrievals identified in the National Ambulatory Surgery Sample. Exposure assignment was monthly IVF encounters: low-volume months (<25%ile), mid-volume months (≥25/<75%ile), and high-volume months (>75%ile). Main outcomes were patient and hospital characteristics related to the exposure groups, assessed with a multinomial regression model.ResultsThe median IVF encounters were 977 per month, ranging from 657 to 1074 (absolute-difference 417). January, July, and December were the lowest-quartile volume months, ranging from 657 to 710 encounters per month (low-volume months). May, August, and November were the top-quartile volume months, ranging from 1049 to 1074 encounters per month (high-volume months). In a multivariable analysis, patients undergoing IVF in the low-volume months were younger and less likely to have infertility or comorbidities. Patients undergoing IVF in the high-volume months were more likely to have lower household income and receive IVF at urban teaching facilities. Northeastern residents were less likely to have IVF in the low-volume months but more likely to have IVF in the high-volume months. Sensitivity analyses showed that the lowest-to-highest variability in monthly IVF encounters was higher in Northeast region compared to other regions (320 vs 50–128); infertility patients compared to those without (317 vs 190); privately insured patients compared to self-pay (227 vs 156); and older patients compared to younger (234 vs 192).ConclusionThis study suggests substantial seasonal fluctuation in IVF oocyte retrieval in the USA based on patient and hospital factors.

Objective There is a rising effort for hospital emergency departments (EDs) to offer and expand substance use disorder (SUD) services. This state-wide evaluation studies SUD services offered along the continuum of implementation across Kentucky’s EDs to inform future state efforts to build ED bridge programs. Methods We conducted a mixed-methods study using an online survey of all Kentucky Emergency Department Directors between January and May of 2023. We created a hospital-level dataset which we used to summarize quantitative questions and thematically analyze open-ended responses. Results Our sample included 85 unique respondents (89% of all eligible Kentucky hospitals). Nine (11%) had active bridge programs to initiate opioid use disorder patients on buprenorphine. Respondents reported that the most challenging SUD-related services for EDs to implement were buprenorphine induction for opioid use disorder treatment ( n  = 36, 42%), referrals to community-based providers ( n  = 34, 40%), and providing social work services ( n  = 25, 29%). Respondents noted that the implementation and improvement of screening protocols were needed to better identify patients with SUD, expressed concerns about care continuity, and explicitly conveyed the need and desire for additional supports to provide SUD care. Conclusions The landscape of Kentucky’s ED SUD supports shows several hospitals that offer services along the continuum of SUD care, and highlights the importance of technical assistance and financial resources to ensure the continuum is broadly available. Kentucky’s experience speaks to broader national challenges in supporting SUD in EDs – specifically the need for financial resources, buy-in and education, and creating referral relationships to ensure care continuity.

This work evaluates the effectiveness of in situ and ex situ passivation methods for mitigating the pyrophoricity of uranium–6 wt.% niobium spherical powders produced via the hydride–dehydride process coupled with plasma spheroidization. Oxide layer thickness was characterized using STEM/EDX, and pyrophoricity was assessed by a UN-recommended test method, which involves directly dropping the powders in the air. In situ passivation, performed by introducing flowing oxygen during spheroidization, produced oxide layers ranging from tens to hundreds of nanometers but resulted in inconsistent pyrophoricity mitigation at lower oxygen flow rates. Ex situ passivation, achieved by slow oxygen exposure over several months, formed uniform oxide layers of approximately 20 nm and consistently mitigated pyrophoricity. Despite requiring higher bulk oxygen content, in situ passivation enables faster processing and control of oxygen, while ex situ passivation achieves superior oxide uniformity with lower oxygen incorporation. These findings highlight the trade-offs between passivation methods and provide a foundation for improving the safety and scalability of reactive metal powder production.

This study aimed to evaluate the outcomes of a hands-on simulation-based course with emphasis on procedural techniques, clinical reasoning, and communication skills developed to improve junior Otolaryngology - Head and Neck Surgery (OHNS) residents' preparedness in managing otolaryngologic emergencies. Junior OHNS residents and faculty from residency programs in California, Nevada, and Arizona participated in this workshop in 2020 and 2021. The stations featured airway management techniques, ultrasound-guided needle aspiration, nasoseptal hematoma evacuation, and facial fracture repair using various models and cadavers. Participants completed a pre-workshop survey, post-workshop survey, and 2-month follow-up survey that assessed resident anxiety and confidence in three OHNS emergency situations across knowledge, manual skills, and teamwork using a 5-point Likert scale. Pre-workshop surveys reported the least anxiety and most confidence in teamwork, but the most anxiety and least confidence in technical skills and knowledge related to foreign body retrieval and airway management. Immediately post-workshop participants reported significant reductions in anxiety and increases in confidence, largest in the manual skills domain, in foreign body retrieval (anxiety: -0.99, confidence: +0.95,  < .01) and airway management stations (anxiety: -0.68, confidence: +1.07,  < .01). Data collected for the epistaxis station showed decreasing confidence and increasing anxiety following the workshop. Our findings demonstrate the effectiveness of a workshop in preparing junior residents in potentially lifesaving otolaryngologic techniques that residents will encounter. Optimizing use of simulation centered training can inform the future of residency education, improving confidence and decreasing anxiety in residents responsible for the safety of patients. III.