Feasibility and Acute Toxicity of Hypo-Fractionated Radiotherapy on 0.35T MR-LINAC: The First Prospective Study in Spain.

This observational, descriptive, longitudinal, and prospective basket-type study (Registry #5289) prospectively evaluated the feasibility and acute toxicity of hypo-fractionated radiotherapy on the first 0.35T MR-LINAC in Spain. A total of 37 patients were included between August and December 2023, primarily with prostate tumors (59.46%), followed by pancreatic tumors (32.44%). Treatment regimens typically involved extreme hypo-fractionated radiotherapy, with precise dose delivery verified through quality assurance measures. Acute toxicity assessment at treatment completion revealed manageable cystitis, with one case persisting at the three-month follow-up. Gastrointestinal toxicity was minimal. For pancreatic tumors, daily adaptation of organ-at-risk (OAR) and gross tumor volume (GTV) was practiced, with median doses to OAR within acceptable limits. Three patients experienced gastrointestinal toxicity, mainly nausea. Overall, the study demonstrates the feasibility and safety of extreme hypo-fractionated radiotherapy on a 0.35T MR-LINAC, especially for challenging anatomical sites like prostate and pancreatic tumors. These findings support the feasibility of MR-LINAC-based radiotherapy in delivering precise treatments with minimal toxicity, highlighting its potential for optimizing cancer treatment strategies.

Technical Note: Improving the workflow in a carbon ion therapy center with custom software for enhanced patient care.

Carbon-ion radiation therapy (CIRT) is an up-and-coming modality for cancer treatment. Implementation of CIRT requires collaboration among specialists like radiation oncologists, medical physicists, and other healthcare professionals. Effective communication among team members is necessary for the success of CIRT. However, the current workflows involving data management, treatment planning, scheduling, and quality assurance (QA) can be susceptible to errors, leading to delays and decreased efficiency. With the aim of addressing these challenges, a team of medical physicists developed an in-house workflow management software using FileMaker Pro. This tool has streamlined the workflow and improved the efficiency and quality of patient care.

The Role of Large Language Models in Transforming Emergency Medicine: Scoping Review.

BACKGROUND: Artificial intelligence (AI), more specifically large language models (LLMs), holds significant potential in revolutionizing emergency care delivery by optimizing clinical workflows and enhancing the quality of decision-making. Although enthusiasm for integrating LLMs into emergency medicine (EM) is growing, the existing literature is characterized by a disparate collection of individual studies, conceptual analyses, and preliminary implementations. Given these complexities and gaps in understanding, a cohesive framework is needed to comprehend the existing body of knowledge on the application of LLMs in EM. OBJECTIVE: Given the absence of a comprehensive framework for exploring the roles of LLMs in EM, this scoping review aims to systematically map the existing literature on LLMs' potential applications within EM and identify directions for future research. Addressing this gap will allow for informed advancements in the field. METHODS: Using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) criteria, we searched Ovid MEDLINE, Embase, Web of Science, and Google Scholar for papers published between January 2018 and August 2023 that discussed LLMs' use in EM. We excluded other forms of AI. A total of 1994 unique titles and abstracts were screened, and each full-text paper was independently reviewed by 2 authors. Data were abstracted independently, and 5 authors performed a collaborative quantitative and qualitative synthesis of the data. RESULTS: A total of 43 papers were included. Studies were predominantly from 2022 to 2023 and conducted in the United States and China. We uncovered four major themes: (1) clinical decision-making and support was highlighted as a pivotal area, with LLMs playing a substantial role in enhancing patient care, notably through their application in real-time triage, allowing early recognition of patient urgency; (2) efficiency, workflow, and information management demonstrated the capacity of LLMs to significantly boost operational efficiency, particularly through the automation of patient record synthesis, which could reduce administrative burden and enhance patient-centric care; (3) risks, ethics, and transparency were identified as areas of concern, especially regarding the reliability of LLMs' outputs, and specific studies highlighted the challenges of ensuring unbiased decision-making amidst potentially flawed training data sets, stressing the importance of thorough validation and ethical oversight; and (4) education and communication possibilities included LLMs' capacity to enrich medical training, such as through using simulated patient interactions that enhance communication skills. CONCLUSIONS: LLMs have the potential to fundamentally transform EM, enhancing clinical decision-making, optimizing workflows, and improving patient outcomes. This review sets the stage for future advancements by identifying key research areas: prospective validation of LLM applications, establishing standards for responsible use, understanding provider and patient perceptions, and improving physicians' AI literacy. Effective integration of LLMs into EM will require collaborative efforts and thorough evaluation to ensure these technologies can be safely and effectively applied.

ForCEPSS-A framework for cardiac electrophysiology simulations standardization.

BACKGROUND AND OBJECTIVE: Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. METHODS AND RESULTS: Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP1 Plank et al. (2021) and the Python-based carputils2 framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. CONCLUSION: ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments.

Transferring emergence profile and position of interim restorative implant fixture. A novel digital technique.

The present technical article describes a protocol to digitally reproduce the emergence profile of an interim implant prosthesis (IP) and to transfer its macrogeometry into the definitive restoration. The purpose of this protocol was to minimize alterations in the gingival architecture developed during the interim restorative phase of a single implant that could potentially jeopardize its esthetic outcome. The process included obtaining an intraoral scan with the interim IP in situ, a duplicate of this intraoral scan that was used to capture the exact position of the implant, and an extraoral scan of the prosthesis. These data could then be imported into IOS software to create a model where the patients' soft tissue was incorporated with precision, allowing for the fabrication of a definitive crown with an optimal soft tissue adaptation. As there are few articles in the scientific literature that have reported a consistent method to replicate the emergence profile of an interim IP, the present technical article aims to highlight the potential of utilizing the emergence profile of an interim IP created by IOS software.

Towards Machine-FAIR: Representing software and datasets to facilitate reuse and scientific discovery by machines.

OBJECTIVE: To use software, datasets, and data formats in the domain of Infectious Disease Epidemiology as a test collection to evaluate a novel M1 use case, which we introduce in this paper. M1 is a machine that upon receipt of a new digital object of research exhaustively finds all valid compositions of it with existing objects. METHOD: We implemented a data-format-matching-only M1 using exhaustive search, which we refer to as M1DFM. We then ran M1DFM on the test collection and used error analysis to identify needed semantic constraints. RESULTS: Precision of M1DFM search was 61.7%. Error analysis identified needed semantic constraints and needed changes in handling of data services. Most semantic constraints were simple, but one data format was sufficiently complex to be practically impossible to represent semantic constraints over, from which we conclude limitatively that software developers will have to meet the machines halfway by engineering software whose inputs are sufficiently simple that their semantic constraints can be represented, akin to the simple APIs of services. We summarize these insights as M1-FAIR guiding principles for composability and suggest a roadmap for progressively capable devices in the service of reuse and accelerated scientific discovery. CONCLUSION: Algorithmic search of digital repositories for valid workflow compositions has potential to accelerate scientific discovery but requires a scalable solution to the problem of knowledge acquisition about semantic constraints on software inputs. Additionally, practical limitations on the logical complexity of semantic constraints must be respected, which has implications for the design of software.

Improving routine use of clinical pathway decision support through integration of an EHR with a clinical library resource designed to provide evidence-based guidance within oncology workflows.

BACKGROUND: The rapid evolution, complexity, and specialization of oncology treatment makes it challenging for physicians to provide care based on the latest and best evidence. We hypothesized that physicians would use evidence-based trusted care pathways if they were easy to use and integrated into clinical workflow at the point of care. METHODS: Within a large integrated care delivery system, we assembled clinical experts to define and update drug treatment pathways, encoded them as flowcharts in an online library integrated with the electronic medical record, communicated expectations that clinicians would use these pathways for every eligible patient, and combined data from multiple sources to understand usage over time. RESULTS: We were able to achieve > 75% utilization of eligible protocols ordered through these pathways within two years, with > 90% of individual oncologists having consulted the pathway at least once, despite no requirements or external incentives associated with pathway usage. Feedback from users contributed to improvements and updates to the guidance. CONCLUSIONS: By making our clinical decision support easily accessible and actionable, we find that we have made considerable progress toward our goal of having physicians consult the latest evidence in their treatment decisions.

Postprocessing Workflow for Laboratory Diffraction Contrast Tomography: A Case Study on Chromite Geomaterials.

Texture stands as a fundamental descriptor in the realms of geology and earth and planetary science. Beyond offering insights into the geological processes underlying mineral formation, its characterization plays a pivotal role in advancing engineering applications, notably in mining, mineral processing, and metal extraction, by providing quantitative data for predictive modeling. Laboratory diffraction contrast tomography (LabDCT), a recently developed 3D characterization technique, offers nondestructive measurement of grain phases including their morphology, distribution, and crystal orientation. It has recently shown its potential to assess 3D textures in complex natural rock samples. This study looks at improving on previous work by examining the artifacts and presents a novel postprocessing workflow designed to correct them. The workflow is developed to rectify inaccurate grain boundaries and interpolate partially reconstructed grains to provide more accurate results and is illustrated using multi-scan examples on chromite sands and natural chromitite from the Upper Group 2 Reef layer in South Africa. The postcorrected LabDCT results were validated through qualitative and quantitative assessment using 2D electron back-scattered diffraction on polished sample surfaces. The successful implementation of this postprocessing workflow underscores its substantial potential in achieving precise textural characterization and will provide valuable insights for both earth science and engineering applications.

Volumetric Analysis of Peri-implant Tissue Change Over Time: Validating an Innovative 3D Method.

PURPOSE: To validate an innovative 3D volumetric method of evaluating tissue changes proposed by Lee et al in 2020 by comparing the results of this method-in which the scanned peri-implant surfaces were transformed, visualized, and analyzed as 3D objects-to the results reported by an existing method based on calculation of the mean distance between measured surfaces. The null hypothesis was that there was no statistically significant difference between the two methods. Additionally, the present study evaluated peri-implant tissue changes 5 years after single implant placement in the esthetic zone. MATERIALS AND METHODS: Both methods were applied to 11 oral implant site casts (6 maxillary central incisor sites, 5 maxillary lateral incisor sites) taken from 11 patients at crown placement and at follow-up examinations 5 years later. The methods are based on digital workflows in which the reference and 5-year casts are scanned and the resulting STL files are superimposed and analyzed for three regions of interest (mesial papilla, central area, and distal papilla). The volumetric changes reported by the Lee et al method and the mean distance method were calculated and compared using the Spearman rank correlation coefficient (P < .01) and the Wilcoxon signed-rank test (P < .05). RESULTS: The correlation between the two sets of measurements was very high (Spearman rank correlation coefficient = 0.885). The new volumetric method indicated a mean volume loss of 2.82 mm3 (SD: 5.06), while the method based on the measurement of mean distance showed a mean volume loss of 2.92 mm3 (SD: 4.43; Wilcoxon signed-rank test result: P = .77). No statistically significant difference was found. The two methods gave equivalent results, and the null hypothesis was accepted. CONCLUSIONS: The new volumetric method was validated and can be considered a trustworthy tool.

An On-Farm Workflow for Predictive Management of Paralytic Shellfish Toxin-Producing Harmful Algal Blooms for the Aquaculture Industry.

Paralytic shellfish toxins (PSTs) produced by marine dinoflagellates significantly impact shellfish industries worldwide. Early detection on-farm and with minimal training would allow additional time for management decisions to minimize economic losses. Here, we describe and test a standardized workflow based on the detection of sxtA4, an initial gene in the biosynthesis of PSTs. The workflow is simple and inexpensive and does not require a specialized laboratory. It consists of (1) water collection and filtration using a custom gravity sampler, (2) buffer selection for sample preservation and cell lysis for DNA, and (3) an assay based on a region of sxtA, DinoDtec lyophilized quantitative polymerase chain reaction (qPCR) assay. Water samples spiked with Alexandrium catenella showed a cell recovery of >90% when compared to light microscopy counts. The performance of the lysis method (90.3% efficient), Longmire's buffer, and the DinoDtec qPCR assay (tested across a range of Alexandrium species (90.7-106.9% efficiency; r2 > 0.99)) was found to be specific, sensitive, and efficient. We tested the application of this workflow weekly from May 2016 to 30th October 2017 to compare the relationship between sxtA4 copies L-1 in seawater and PSTs in mussel tissue (Mytilus galloprovincialis) on-farm and spatially (across multiple sites), effectively demonstrating an ∼2 week early warning of two A. catenella HABs (r = 0.95). Our tool provides an early, accurate, and efficient method for the identification of PST risk in shellfish aquaculture.

Transcription Factors behind MYB98 Regulation: What Does the Discovery of SaeM Suggest?

MYB98 is master regulator of the molecular network involved in pollen tube attraction. Until recently, it was unclear how this gene exhibits exclusively synergid cell-specific expression in ovule. Our recent study has established that a 16-bp-long SaeM element is crucial for its synergid cell-specific expression in ovule, and an 84-bp-long fragment harboring SaeM is sufficient to drive the process. In this study, we have developed a workflow to predict functional roles of potential transcription factors (TFs) putatively binding to the promoter region, taking MYB98 promoter as a test subject. After sequential assessment of co-expression pattern, network analysis, and potential master regulator identification, we have proposed a multi-TF model for MYB98 regulation. Our study suggests that ANL2, GT-1, and their respective homologs could be direct regulators of MYB98 and indicates that TCP15, TCP16, FRS9, and HB34 are likely master regulators of the majority of the TFs involved in its regulation. Comprehensive studies in the future are expected to offer more insights into such propositions. Developed workflow can be used while designing similar regulome-related studies for any other species and genes.

Evaluating free segmentation tools for CBCT-derived models: Cost-effective solutions.

OBJECTIVES: This study evaluated the segmentation accuracy and reliability of free software packages and compared them with commercial alternatives. MATERIAL AND METHODS: A total of 36 stone models were scanned using a desktop scanner and then imaged by cone beam computed tomography (CBCT). The CBCT volumes were segmented using 2 free software packages (3D Slicer and Blue Sky Plan) and 2 commercial software packages (Mimics and OnDemand3D). Stereolithography (STL) files generated by the desktop scanner were used as the control group (reference models). The accuracy of segmentation was evaluated by (1) comparing 6 linear measurements taken from each STL model generated by the 4 software packages with that obtained by the scanner, and (2) deviation analysis of each STL model generated by the 4 software packages with that obtained by the scanner. Absolute error and percentage error, repeated measures anova and Friedman test followed by post hoc analysis, intraclass correlation coefficient (ICC), and Pearson's r were used to evaluate the accuracy of the tested software packages. RESULTS: There was no statistically significant difference in all intra-arch measurements obtained using the four software packages. Measurements obtained using the free software packages and the scanner showed excellent positive correlation, ranging from 0.825 to 0.988, confirming equivalence with commercial software packages. CONCLUSION: Within the settings of the current study, accurate and time-saving segmentations with high positive correlation could be performed using the tested free segmentation software packages (3D Slicer and Blue Sky Plan). Nevertheless, further evaluation is necessary to gage their accuracy using different CBCT modalities.

Impact of Scanbody Geometry and CAD Software on Determining 3D Implant Position.

The implementation of CAD software in the digital production of implant prosthetics stands as a pivotal aspect of clinical dentistry, necessitating high precision in the alignment of implant scanbodies. This study investigates the influence of scanbody geometry and the method of superimposing in CAD software when determining 3D implant position. A standardized titanium model with three bone-level implants was digitized to create reference STL files, and 10 intraoral scans were performed on Medentika and NT-Trading scanbodies. To determine implant position, the generated STL files were imported into the Exocad CAD software and superimposed-automatically and manually-with the scanbody geometries stored within the software's shape library. Position accuracy was determined by a comparison of the 3D-defined scanbody points from the STL matching files with those from the reference STL files. The R statistical software was used for the evaluation of the data. In addition, mixed linear models and a significance level of 0.05 were applied to calculate the p-values. The manual overlay method was significantly more accurate than the automatic overlays for both scanbody types. The Medentika scanbodies showed slightly superior precision compared to the NT-Trading scanbodies. Both scanbody geometry and the type of alignment in the CAD software significantly affect digital workflow accuracy. Manual verification and adjustment of the automatic alignment process are essential for precise implant positioning.

Computational exploration of novel antimicrobial modalities targeting fucose-binding lectins and ribosomes in Mycobacterium smegmatis using tRNA-encoded peptides.

tRNA-Encoded Peptides (tREPs), encoded by small open reading frames (smORFs) within tRNA genes, have recently emerged as a new class of functional peptides exhibiting antiparasitic activity. The discovery of tREPs has led to a re-evaluation of the role of tRNAs in biology and has expanded our understanding of the genetic code. This presents an immense, unexplored potential in the realm of tRNA-peptide interactions, paving the way for groundbreaking discoveries and innovative applications in various biological functions. This study explores the antimicrobial potential of tREPs against protein targets by employing a computational method that uses verified data sources and highly recognized predictive algorithms to provide a sorted list of likely antimicrobial peptides, which were then filtered for toxicity, cell permeability, allergenicity and half-life. These peptides were then docked with screened protein targets and computationally validated using molecular dynamics (MD) simulations for 150 ns and the binding free energy was estimated. The peptides Pep2 (VVLWRKPRVRKTG) and Pep6 (HRLRLRRRKPWW) exhibited good binding affinities of -110.5 +/- 2.5 and -129.0 +/- 3.9, respectively, with RMSD values of 0.4 and 0.25 nm against the fucose-binding lectin (7NEF) and the 30S ribosome of Mycobacterium smegmatis (5O5J) protein targets. The 7NEF-Pep2 and 5O5J-Pep6 complexes indicated higher negative binding free energies of -52.55 kcal/mol and -55.52 kcal/mol respectively, as calculated by Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA). Thus, the tREPs derived peptides designed as a part of this study, provide novel approaches for potential anti-bacterial therapeutic modalities.Communicated by Ramaswamy H. Sarma.

Challenges With Robot-Assisted Surgery Setup for Complex Minimally Invasive Upper Gastrointestinal Surgery.

BACKGROUND: The utilization of robot-assisted approaches to surgery has increased significantly over the last two decades. This has introduced novel complexities into the operating room environment, requiring management of new challenges and workflow adaptation. This study aimed to analyze challenges in the surgical setup for complex upper gastrointestinal robot-assisted surgery (UGI-RAS) and identify opportunities for solutions. METHODS: Direct observations of surgical setup processes for UGI-RAS were performed by a trained Human Factors researcher at a non-profit academic medical center in Southern California. Setup tasks were subdivided into five phases: (1) before wheels-in; (2) patient transfer and anesthesia induction; (3) patient preparation; (4) surgery preparation; and (5) robot docking. Start/end times for each phase/task were documented along with workflow disruption (FD) narratives and timestamps. Setup tasks and FDs were analyzed using descriptive statistics. RESULTS: Twenty UGI-RAS setup procedures were observed between May-November 2023: sleeve gastrectomy +/- hiatal hernia repair (n = 9, 45.00%); para-esophageal hernia repair +/- fundoplication (n = 8, 40.00%); revision to Roux-en-Y gastric bypass (n = 2, 10.00%); and gastric band removal (n = 1, 5.00%). Frequent FDs included planning breakdowns (n = 20, 29.85%), equipment/supply management (n = 17, 25.37%), patient care coordination (n = 8, 11.94%), and equipment challenges (n = 8, 11.94%). Eleven of 20 observations were first-start cases, of which 10 experienced delayed starts. DISCUSSION: Interventions aimed at improving workflows during UGI-RAS setup include performing pre-operative team huddles and conducting trainings aimed at team coordination and equipment challenges. These solutions could result in improved teamwork, efficiency, and communication while reducing case start delays and turnover time.

Comparison of periprocedural and procedure room times between moderate sedation and monitored anesthesia care in interventional radiology.

Objectives: In recent years, there has been increased utilization of monitored anesthesia care (MAC) in interventional radiology (IR) departments. The purpose of this study was to compare pre-procedure bed, procedure room, and post-procedure bed times for IR procedures performed with either nurse-administered moderate sedation (MOSED) or MAC. Material and Methods: An institutional review board-approved single institution retrospective review of IR procedures between January 2010 and September 2022 was performed. Procedures performed with general anesthesia or local anesthetic only, missing time stamps, or where <50 cases were performed for both MAC and MOSED were excluded from the study. Pre-procedure bed, procedure room, post-procedure bed, and total IR encounter times were compared between MAC and MOSED using the t-test. The effect size was estimated using Cohen's d statistic. Results: 97,480 cases spanning 69 procedure codes were examined. Mean time in pre-procedure bed was 27 min longer for MAC procedures (69 vs. 42 min, P < 0.001, d = 0.95). Mean procedure room time was 11 min shorter for MAC (60 vs. 71 min, P < 0.001, d = 0.48), and mean time in post-procedure bed was 10 min longer for MAC (102 vs. 92 min, P < 0.001, d = 0.22). Total IR encounter times were on average 27 min longer for MAC cases (231 vs. 204 min, P < 0.001, d = 0.41). Conclusion: MAC improves the utilization of IR procedure rooms, but at the cost of increased patient time in the pre- and post-procedure areas.

How much time do emergency department physicians spend on medication-related tasks? A time- and-motion study.

BACKGROUND: Medication-related problems are an important cause of emergency department (ED) visits, and medication errors are reported in up to 60% of ED patients. Procedures such as medication reconciliation and medication review can identify and prevent medication-related problems and medication errors. However, this work is often time-consuming. In EDs without pharmacists, medication reconciliation is the physician's responsibility, in addition to the primary assignments of examining and diagnosing the patient. The aim of this study was to identify how much time ED physicians spend on medication-related tasks when no pharmacists are present in the EDs. METHODS: An observational time-and-motion study of physicians in three EDs in Northern Norway was conducted using Work Observation Method by Activity Timing (WOMBAT) to collect and time-stamp data. Observations were conducted in predefined two-hour observation sessions with a 1:1 relationship between observer and participant, during Monday to Friday between 8 am and 8 pm, from November 2020 to October 2021. RESULTS: In total, 386 h of observations were collected during 225 observation sessions. A total of 8.7% of the physicians' work time was spent on medication-related tasks, of which most time was spent on oral communication about medications with other physicians (3.0%) and medication-related documentation (3.2%). Physicians spent 2.2 min per hour on medication reconciliation tasks, which includes retrieving medication-related information directly from the patient, reading/retrieving written medication-related information, and medication-related documentation. Physicians spent 85.6% of the observed time on non-medication-related clinical or administrative tasks, and the remaining time was spent standby or moving between tasks. CONCLUSION: In three Norwegian EDs, physicians spent 8.7% of their work time on medication-related tasks, and 85.6% on other clinical or administrative tasks. Physicians spent 2.2 min per hour on tasks related to medication reconciliation. We worry that patient safety related tasks in the EDs receive little attention. Allocating dedicated resources like pharmacists to contribute with medication-related tasks could benefit both physicians and patients.

Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging.

Deciphering cellular components and the spatial interaction network of the tumor immune microenvironment (TIME) of solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate spatial complexity in a holistic manner. We established and cross-validated a comprehensive immunophenotyping panel comprising over 121 markers for multiplexed tissue imaging using MACSima™ imaging cyclic staining (MICS) alongside an end-to-end analysis workflow. Applying this panel and workflow to primary cancer tissues, we characterized tumor heterogeneity, investigated potential therapeutical targets, conducted in-depth profiling of cell types and states, sub-phenotyped T cells within the TIME, and scrutinized cellular neighborhoods of diverse T cell subsets. Our findings highlight the advantage of spatial profiling, revealing immunosuppressive molecular signatures of tumor-associated myeloid cells interacting with neighboring exhausted, PD1high T cells in the TIME of hepatocellular carcinoma (HCC). This study establishes a robust framework for spatial exploration of TIMEs in solid tumors and underscores the potency of multiplexed tissue imaging and ultra-deep cell phenotyping in unraveling clinically relevant tumor components.

Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans.

BACKGROUND: Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans. RESULTS: To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow.We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans. CONCLUSIONS: The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data.

Integration of electronic project management software in an investigational drug service pharmacy within an academic medical center.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: An investigational drug services (IDS) pharmacy plays a vital role in supporting clinical trial research by ensuring the safe and efficient management of investigational products. This article describes the implementation of an electronic project management software to improve an IDS pharmacy's study protocol work. The article describes the implementation of the software and how this approach addressed specific challenges, including project oversight, process standardization, documentation, reporting, accountability, and intrateam communication. SUMMARY: We describe an electronic project management software system used to streamline and standardize the work associated with study protocols. This software provides an organized and customizable workspace to manage tasks associated with each study protocol. The software automates task creation, tracks progress, and ensures comprehensive record keeping. Additionally, the software fosters effective communication within the team and offers real-time reporting to assess team productivity and progress. We have observed improved consistency, enhanced revenue, including approximately $18,000 in additional fee capture, and increased collaboration among pharmacy team members. CONCLUSION: Implementing an electronic project management software has proven highly beneficial in the IDS pharmacy. The software has significantly improved workflow efficiency by addressing challenges in study protocol management. While initial setup and training required time and resources, the long-term benefits in project oversight, collaboration, and revenue capture justify the investment. An electronic project management software is a valuable tool in managing the complexity of study protocol activities and supports the pharmacy's crucial role in advancing clinical research.