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Abstract Background Cancer survivors (CS) comprise a particularly high-risk group for both de-novo and recurrent malignancies after solid organ transplantation. Case presentation We report a case of relapsed melanoma, presented as metastatic disease seven months after heart transplantation in a patient who had an early-stage melanoma resected 25 years prior. Treatment with a combination of dabrafenib, a BRAF inhibitor, and trametinib, a mitogen-activated protein kinase (MEK) inhibitor resulted in a near-complete metabolic response, without major adverse effects. Conclusion This case demonstrates the increased risk of recurrence in CS with melanoma, which can persist decades after cancer diagnosis. These patients may be amenable to treatment using modern treatment modalities in oncology.

Abstract White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1’s function during differentiation. These findings underscore PATZ1’s regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development.

Abstract Background Recruitment to residency programs in hospitals located in other than major hubs (“remotely located”) is a challenge in many countries. In 2011, the Israeli Ministry of Health launched a 10-year financial incentive to encourage physicians to enroll in residency programs in such hospitals. Nearly 1 billion New Israeli Shekels (260 million US$) were invested in that program which had only limited success. As a new physician association’s collective agreement is impending, we aimed to measure the effectiveness of selected incentives in attracting medical school graduates to residencies in remotely located hospitals. Methods This study included Israeli medical students in their final year of medical school. We used an online questionnaire with multiple-choice demographic questions and a 5-point Likert scale to gauge the effect of various incentives on their preference for residency location. Results Between July and November 2022, 522 students responded (405 studied in Israeli medical schools [out of 705 students] and 117 in foreign medical schools [out of 1936 students]). Forty-two percent had at least one clerkship in a remotely located hospital, and 24% had included at least one remotely located hospital among their top five choices for internship. Only 13% reported that they prefer a residency program in those institutions. The incentive selected by students as most persuasive was government assistance in acceptance to and financial support for a fellowship abroad, followed by a financial grant and fewer on-call hours. Only 7% of the students indicated that no incentive would influence them to choose a remotely located hospital for their residency training. Medical education in a remotely located university and the choice of at least one remotely located hospital among the top five choices for internship were significantly associated with positive incentive receptivity, whereas male sex and older age were associated with negative receptivity. Conclusion This study on the attitudes of Israeli medical school graduates toward incentives aimed at attracting them to residencies in remotely located institutions revealed that career development opportunities and assistance in obtaining fellowships might influence their choice.

The fraction of urban volatile organic compound (VOC) emissions attributable to fossil fuel combustion has been declining in many parts of the world, resulting in a need to better constrain other anthropogenic sources of these emissions. During the National Institute of Environmental Research (NIER) and National Aeronautics and Space Administration (NASA) Korea-United States Air Quality (KORUS-AQ) field study in Seoul, South Korea, during May–June 2016, air quality models underestimated ozone, formaldehyde, and peroxyacetyl nitrate (PAN), indicating an underestimate of VOCs in the emissions inventory. Here, we use aircraft observations interpreted with the GEOS-Chem chemical transport model (version 13.4.0) to assess the need for increases in VOC emissions and for a revised chemical mechanism to improve treatment of VOC speciation and chemistry. We find that the largest needed VOC emissions increases are attributable to compounds associated with volatile chemical products, liquefied petroleum gas (LPG) and natural gas emissions, and long-range transport. Revising model chemistry to better match observed VOC speciation together with increasing model emissions of underestimated VOC species increased calculated OH reactivity by +2 s−1 and ozone production by +2 ppb h−1. Ozone increased by +6 ppb below 2 km and +9 ppb at the surface, and formaldehyde and acetaldehyde increased by +30 % and +120 % aloft, respectively, all in better agreement with observations. The larger increase in acetaldehyde was attributed to ethanol emissions, which we found to be as important for ozone production as isoprene or alkenes. The increased acetaldehyde significantly reduced the model PAN bias. The need for additional unmeasured VOCs, however, was indicated by a remaining model bias of −0.8 ppb in formaldehyde and a −57 % and −52 % underestimate in higher peroxynitrates (PNs) and alkyl nitrates (ANs), respectively. We added additional chemistry to the model to represent an additional six PNs from observed VOCs but were unable to account for the majority of missing PNs. However, four of these PNs were modeled at concentrations similar to other commonly measured PNs (> 2 % of PAN) indicating that these should be measured in future campaigns and considered from other VOC emission sources (e.g., fires). We hypothesize that emissions of oxygenated VOCs (OVOCs) such as ≥ C5 aldehydes from cooking and/or alkenes associated with volatile chemical products could produce both PNs and ANs and improve remaining model biases. Emerging research on the emissions and chemistry of these species will soon allow for modeling of their impact on local and regional photochemistry.

Abstract The sympathetic nervous system controls bodily functions including vascular tone, cardiac rhythm, and the “fight-or-flight response”. Sympathetic chain ganglia develop in parallel with preganglionic motor nerves extending from the neural tube, raising the question of whether axon targeting contributes to sympathetic chain formation. Using nerve-selective genetic ablations and lineage tracing in mouse, we reveal that motor nerve-associated Schwann cell precursors (SCPs) contribute sympathetic neurons and satellite glia after the initial seeding of sympathetic ganglia by neural crest. Motor nerve ablation causes mispositioning of SCP-derived sympathoblasts as well as sympathetic chain hypoplasia and fragmentation. Sympathetic neurons in motor-ablated embryos project precociously and abnormally towards dorsal root ganglia, eventually resulting in fusion of sympathetic and sensory ganglia. Cell interaction analysis identifies semaphorins as potential motor nerve-derived signaling molecules regulating sympathoblast positioning and outgrowth. Overall, central innervation functions both as infrastructure and regulatory niche to ensure the integrity of peripheral ganglia morphogenesis.

Abstract Background Enamel is highly transparent at short wavelength infrared imaging (SWIR) wavelengths allowing the detection of dental decay without the need for ionizing radiation. The purpose of this study was to use SWIR imaging methods including cross polarization optical coherence tomography (CP-OCT), occlusal transillumination (SWIR-OT), proximal transillumination (SWIR-PT), and occlusal reflectance (SWIR-R) to image interproximal lesions in vivo and compare the sensitivity with radiography. Methods Participants (n = 30) aged 18–80 each with a radiopositive interproximal lesion scheduled for restoration were enrolled in the study. Studies have shown that the opposing proximal surfaces across the contact will likely also have lesions. SWIR images were acquired of the adjoining teeth at each contact with an interproximal lesion scheduled for restoration. Lesion presence and depth were assessed on each side of the contact for radiography and each SWIR imaging method. Lesions on radiographs and in CP-OCT images were identified by a single examiner while lesions in SWIR images were identified by a contrast threshold via semi-automatic image segmentation. Results All SWIR imaging methods had significantly higher sensitivity (P

Abstract Sero-monitoring provides context to the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and changes in population immunity following vaccine introduction. Here, we describe results of a cross-sectional hospital-based study of anti-spike seroprevalence in New York City (NYC) from February 2020 to July 2022, and a follow-up period from August 2023 to October 2023. Samples from 55,092 individuals, spanning five epidemiological waves were analyzed. Prevalence ratios (PR) were obtained using Poisson regression. Anti-spike antibody levels increased gradually over the first two waves, with a sharp increase during the 3rd wave coinciding with SARS-CoV-2 vaccination in NYC resulting in seroprevalence levels >90% by July 2022. Our data provide insights into the dynamic changes in immunity occurring in a large and diverse metropolitan community faced with a new viral pathogen and reflects the patterns of antibody responses as the pandemic transitions into an endemic stage.

Abstract Neuromodulation using high frequency (>1 kHz) electric stimulation (HFS) enables preferential activation or inhibition of individual neural types, offering the possibility of more effective treatments across a broad spectrum of neurological diseases. To improve effectiveness, it is important to better understand the mechanisms governing activation and inhibition with HFS so that selectivity can be optimized. In this study, we measure the membrane potential (Vm) and spiking responses of ON and OFF α-sustained retinal ganglion cells (RGCs) to a wide range of stimulus frequencies (100–2500 Hz) and amplitudes (10–100 µA). Our findings indicate that HFS induces shifts in Vm, with both the strength and polarity of the shifts dependent on the stimulus conditions. Spiking responses in each cell directly correlate with the shifts in Vm, where strong depolarization leads to spiking suppression. Comparisons between the two cell types reveal that ON cells are more depolarized by a given amplitude of HFS than OFF cells—this sensitivity difference enables the selective targeting. Computational modeling indicates that ion-channel dynamics largely account for the shifts in Vm, suggesting that a better understanding of the differences in ion-channel properties across cell types may improve the selectivity and ultimately, enhance HFS-based neurostimulation strategies.

Abstract Dense and aligned Collagen I fibers are associated with collective cancer invasion led by protrusive tumor cells, leader cells. In some breast tumors, a population of cancer cells (basal-like cells) maintain several epithelial characteristics and express the myoepithelial/basal cell marker Keratin 14 (K14). Emergence of leader cells and K14 expression are regarded as interconnected events triggered by Collagen I, however the underlying mechanisms remain unknown. Using breast carcinoma organoids, we show that Collagen I drives a force-dependent loop, specifically in basal-like cancer cells. The feed-forward loop is centered around the mechanotransducer Yap and independent of K14 expression. Yap promotes a transcriptional program that enhances Collagen I alignment and tension, which further activates Yap. Active Yap is detected in invading breast cancer cells in patients and required for collective invasion in 3D Collagen I and in the mammary fat pad of mice. Our work uncovers an essential function for Yap in leader cell selection during collective cancer invasion.

Abstract Background Public libraries in the United States have experienced increases in opioid-related substance use in their communities and on their premises. This includes fatal and non-fatal overdose events. Some libraries have adopted response measures in their branches to deter substance use or prevent overdose. A small number of libraries around the nation have decided to stock the opioid antagonist naloxone (Narcan) for staff to administer to patrons who experience overdose. This response measure has generated extensive media attention. Although Ohio ranks fourth in age-adjusted drug mortality rate in the United States, there has been no investigation of whether Ohio libraries are observing opioid-related transactions, consumption, and/or overdose events, or which measures they have adopted in response to these activities. We conducted a multimethod survey with Ohio public library directors to identify the response measures they have adopted. We present descriptive findings from the quantitative and qualitative items in our survey. Methods We conducted a cross-sectional 54-item multimethod survey of public library system directors (one per system) in Ohio. Directors of each of Ohio’s public library systems were invited to participate via email. Results Of 251 library systems, 56 responded (22.3% response rate), with 34 respondents (60.7%) indicating awareness of opioid-related transactions, consumption, and/or overdose on their premises. Most (n = 43, 76.8%) did not stock naloxone in their buildings. Over half (n = 34, 60.7%) reported implementing one or more non-naloxone response measures. These measures focus on improving security for staff and patrons, deterring opioid-related transactions (purchases and exchanges) and consumption, and providing educational events on substance use. Nearly half (n = 25, 47.2%) partner with community organizations to provide opioid response measures. A similar proportion reported adequate funding to respond to opioid-related substance use (n = 23, 45.1%), and most (n = 38, 74.5%) reported adequate support from their boards and communities. Few respondents have implemented evaluations of their response measures. Conclusions Ohio public libraries are responding to evidence of opioid-related transactions, consumption, and/or overdose on their premises with a range of measures that focus on substance use prevention and deterrence. Most Ohio library systems do not stock naloxone. Respondents indicated they prefer to call 911 and let first responders handle overdose events. The majority of respondents indicated their library systems have political capacity to respond to evidence of opioid-related substance use on their premises, but have limited operational and functional capacity. Findings suggest the need to revisit assumptions that public libraries are willing to stock naloxone to respond to overdose events, and that libraries have the resources to respond robustly to opioid-related transactions, consumption, and/or overdose on their premises.

Introduction:. This study aimed to identify research areas that demand attention in multimodal data-driven surgery for improving data management in minimally invasive surgery. Background:. New surgical procedures, high-tech equipment, and digital tools are increasingly being introduced, potentially benefiting patients and surgical teams. These innovations have resulted in operating rooms evolving into data-rich environments, which, in turn, requires a thorough understanding of the data pipeline for improved and more intelligent real-time data usage. As this new domain is vast, it is necessary to identify where efforts should be focused on developing seamless and practical data usage. Methods:. A modified electronic Delphi approach was used; 53 investigators were divided into the following groups: a research group (n=9) for problem identification and a narrative literature review, a medical and technical expert group (n=14) for validation, and an invited panel (n=30) for two electronic survey rounds. Round 1 focused on a consensus regarding bottlenecks in surgical data science areas and research gaps, while round 2 prioritized the statements from round 1, and a roadmap was created based on the identified essential and very important research gaps. Results:. Consensus panelists have identified key research areas, including digitizing operating room (OR) activities, improving data streaming through advanced technologies, uniform protocols for handling multimodal data, and integrating AI for efficiency and safety. The roadmap prioritizes standardizing OR data formats, integrating OR data with patient information, ensuring regulatory compliance, standardizing surgical AI models, and securing data transfers in the next generation of wireless networks. Conclusions:. This work is an international expert consensus regarding the current issues and key research targets in the promising field of data-driven surgery, highlighting the research needs of many operating room stakeholders with the aim of facilitating the implementation of novel patient care strategies in minimally invasive surgery.

Abstract Objectives The network approach to psychopathology posits that mental disorders emerge from dynamic interactions among psychopathology‐relevant variables. Ecological Momentary Assessment (EMA) is frequently used to assess these variables in daily life. Considering the transdiagnostic nature of the network approach to psychopathology, this study describes the development of a transdiagnostic EMA protocol for psychopathology. Methods First, 96 clinicians completed an online survey, providing three EMA constructs for up to three disorders they specialize in, and three EMA constructs relevant across disorders (transdiagnostic constructs). Second, 12 focus groups were conducted with clinical experts for specific types of diagnoses (e.g., mood disorders, anxiety disorders). Finally, a selection of items was reached by consensus. Two raters independently coded the online survey responses with an inter‐rater agreement of 87.3%. Results Jaccard indices showed up to 52.6% overlap in EMA items across types of diagnoses. The most frequently reported transdiagnostic constructs were mood, sleep quality, and stress. A final set of EMA items is created based on items' frequency and informativeness, ensuring completeness across diagnoses and minimizing burden. Conclusions The described procedure resulted in a feasible EMA protocol to examine psychopathology transdiagnostically. Feasibility was helped by the overlap in mentioned symptoms across disorders. Such overlap raises questions about the validity of DSM categories.

Targeted alpha therapy (TαT) represents an emerging and cutting-edge treatment option for patients dealing with highly challenging metastatic cancer diseases. Critically, the limited supply of alpha-particle-emitting radionuclides, so-called alpha in vivo nanogenerators, hampers wider utilization of TαT in clinical settings. This could effectively be circumvented by alternative production routes, including straightforward purification and reformulation strategies. Radionuclide generators offering great potential in simple and robust elution strategies can be provided that still adhere to high radioisotopic, radionuclidic, and radiochemical purity criteria. This study takes a first step towards novel separation strategies by providing additional sources of alpha in vivo nanogenerators for TαT through experiments with various metal surrogates. With different systems, 232Th/natBa was used as a radionuclide generator analogue to 227Th/223Ra, and 232Th/natBa/natLa was used as a triplet analogue to 229Th/225Ra/225Ac. Three selective resins (UTEVA, TEVA, DGA-N) were evaluated for the 232Th/natBa system. Two perturbations of the best-performing resin were further evaluated using a larger diameter column and 1 week of equilibration. For the 232Th/natBa/natLa separation system, a combined column with two selective resins (TK200, TK101) was employed and evaluated. The results thus obtained pave the way for alternative separation strategies in radioactive proof-of-concept validation in the near future.

Public libraries support community health needs, including responding to the opioid epidemic with events, services, and information. However, we lack insight into why libraries respond to problematic opioid use in their communities, what tensions are associated with responding to community opioid use, and how their responses fit within the scope of public libraries. We conducted a multimethod study to solicit the perspectives of Ohio public library directors. They characterized responding to the opioid epidemic in their communities as aligning with both the mission and attributes of public libraries, while also facing tensions that emerged from balancing the demand for expansive social services with pressure to protect the sanctity of libraries. [ABSTRACT FROM AUTHOR]