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We present a parallel combination of existing, well-known and robust software used in modelling the neotectonics of planetary lithosphere, which we call ShellSet. An added parallel framework allows multiple models to be run at the same time with varied input parameters. Additionally, we have included a grid search option to automatically generate models within a given parameter space. ShellSet offers significant advantages over the original programs through its simplicity, efficiency and speed. We demonstrate the performance improvement obtained by ShellSet's parallel framework by presenting timing and speedup information for a parallel grid search, varying the number of processes and models, on both a typical computer and a high-performance computing cluster node. A possible use case for ShellSet is shown using two examples in which we improve on an existing global model. In the first example we improve the model using the same data, and in the second example we further improve the model through the addition of a new scoring dataset. The necessary ShellSet program version along with all the required input and post-processing files needed to recreate the results presented in this article are available at https://doi.org/10.5281/zenodo.7986808 (May et al., 2023).

Spaceborne lidar provides a unique opportunity to supplement the field plot measurements of national forest inventories (NFIs) by providing dense measurements of vertical canopy structure. For full waveform instruments such as the Global Ecosystem Dynamics Investigation (GEDI), measurements take the form of reflected energy as a function of height within an observed footprint. Many forest attributes cannot be directly computed from the waveforms, and thus statistical models relating the measurements to target attributes must be trained using field plot data. Because the discrete footprint samples produced by spaceborne lidar instruments have little chance of collocation with pre-existing field plots, model calibration remains a primary challenge. We leveraged the density and spatial correlation of GEDI observations to make predictions of the cumulative waveform over 326,787 NFI plots distributed across the contiguous United States. The predictions yield probability distributions, giving not only a predicted waveform but quantification of prediction uncertainty. The product of this work is a data set comprised of the NFI plots paired with the predictive waveform distributions. The predicted waveforms and their uncertainties can be used to train models with “error-in-variables” techniques that account for and filter the uncertainty in the predicted waveforms. This data set and the corresponding techniques allow statistically rigorous model training without requirements of collocation, yielding downstream forest attribute predictions that are consistent with NFI measurements and estimates. We demonstrate the data set by training a model for forest above ground biomass density (AGBD) and then use the model to produce a spatially complete 1 km map of AGBD for the contiguous United States. We further compare our AGBD predictions to US NFI estimates at a 64,000 hectare scale, showing the increase in precision to be proportional to the collection of almost 500,000 additional NFI plots across forested regions of CONUS.

Dopamine has multiple physiological functions including feed intake control in which it can act as an anorectic or orexigenic agent. This study had the objective to evaluate intra-abomasal administration of L-DOPA (levodopa; L-3,4-dihydroxyphenylalanine) from -Mucuna pruriens on circulating catecholamines, indicators of energy metabolism and feed intake in cattle. Eight Holstein steers (340 ± 20 kg) fitted with ruminal cannula were used in a replicated 4 x 4 Latin Square design experiment. Intra-abomasal infusion of L-DOPA at 0, 0.5, 1 and 2 mg/kg BW was carried out for seven days and blood samples were collected at 0, 30, 60, 120, 240 and 480 min from L-DOPA infusion on day 7. The area under the curve (AUC) of plasma L-DOPA and free dopamine increased quadratically with the administration of L-DOPA. However, the AUC of plasma total dopamine had a positive linear response with the increase of L-DOPA. Conversely, the serum 5-hydroxytriptophan (5-HTP), plasma serotonin, serum serotonin, serum tyrosine, plasma glucose and plasma free fatty acids were not affected by the intra-abomasal infusion of L-DOPA. The circulating concentration of the epinephrine, norepinephrine, serotonin, glucose and free fatty acids did not change with L-DOPA infusion. It can be concluded that intra-abomasal L-DOPA administration produced a strong increase in circulating dopamine with no change in energy metabolites and feed intake in cattle.

Background: Studies have shown conflicting results on the efficacy of tocilizumab (TCZ) for patients with COVID-19, with many confounders of clinical status and limited duration of the observation. Here, we evaluate the real-world long-term efficacy of TCZ in COVID-19 patients. Methods: We conducted a retrospective study of hospitalized adult patients with COVID-19 using a large US-based multicenter COVID-19 database (Cerner Real-World Data; updated in September, 2020). The TCZ group was defined as patients who received at least one dose of the drug. Matching weight (MW) and a propensity score weighting method were used to balance confounding factors. Results: A total of 20,399 patients were identified. 1,510 and 18,899 were in the TCZ and control groups, respectively. After MW adjustment, no statistically significant differences in all-cause mortality were found for the TCZ vs. control group (Hazard Ratio [HR]:0.76, p=0.06). Survival curves suggested a better trend in short-term observation, driven from a subgroup of patients requiring oxygen masks, BIPAP or CPAP. Conclusion: We observed a temporal (early) benefit of TCZ, especially in patients on non-invasive high-flow supplemental oxygen. However, the benefit effects faded with longer observation. The long-term benefits and risks of TCZ should be carefully evaluated with follow-up studies.

Abstract Background Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists’ experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett’s esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions. Methods We retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking. Results Two patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 μm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up. Conclusions Our results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

Historically, ecological monitoring of marine habitats has primarily relied on labour-intensive, non-automated survey methods. The field of passive acoustic monitoring (PAM) has demonstrated the potential of this practice to automate surveying in marine habitats. This has primarily been through the use of ‘ecoacoustic indices’ to quantify attributes from natural soundscapes. However, investigations using individual indices have had mixed success. Using PAM recordings collected at one of the world’s largest coral reef restoration programmes, we instead apply a machine-learning approach across a suite of ecoacoustic indices to improve predictive power of ecosystem health. Healthy and degraded reef sites were identified through live coral cover surveys, with 90–95% and 0–20% cover respectively. A library of one-minute recordings were extracted from each. Twelve ecoacoustic indices were calculated for each recording, in up to three different frequency bandwidths (low: 0.05–0.8 kHz, medium: 2–7 kHz and broad: 0.05–20 kHz). Twelve of these 33 index-frequency combinations differed significantly between healthy and degraded habitats. However, the best performing single index could only correctly classify 47% of recordings, requiring extensive sampling from each site to be useful. We therefore trained a regularised discriminant analysis machine-learning algorithm to discriminate between healthy and degraded sites using an optimised combination of ecoacoustic indices. This multi-index approach discriminated between these two habitat classes with improved accuracy compared to any single index in isolation. The pooled classification rate of 1000 cross-validated iterations of the model had a 91.7% 0.8, mean SE) success rate at correctly classifying individual recordings. The model was subsequently used to classify recordings from two actively restored sites, established >24 months prior to recordings, with coral cover values of 79.1% (±3.9) and 66.5% (±3.8). Of these recordings, 37/38 and 33/39 received a classification as healthy respectively. The model was also used to classify recordings from a newly restored site established

Earth Observation data are uniquely positioned to estimate forest aboveground biomass density (AGBD) in accordance with the United Nations Framework Convention on Climate Change (UNFCCC) principles of ‘transparency, accuracy, completeness, consistency and comparability’. However, the use of space-based AGBD maps for national-level reporting to the UNFCCC is nearly non-existent as of 2023, the end of the first global stocktake (GST). We conduct an evidence-based comparison of AGBD estimates from the NASA Global Ecosystem Dynamics Investigation and ESA Climate Change Initiative, describing differences between the products and National Forest Inventories (NFIs), and suggesting how science teams must align efforts to inform the next GST. Between the products, in the tropics, the largest differences in estimated AGBD are primarily in the Congolese lowlands and east/southeast Asia. Where NFI data were acquired (Peru, Mexico, Lao PDR and 30 regions of Spain), both products show strong correlation to NFI-estimated AGBD, with no systematic deviations. The AGBD-richest stratum of these, the Peruvian Amazon, is accurately estimated in both. These results are remarkably promising, and to support the operational use of AGB map products for policy reporting, we describe targeted ways to align products with Intergovernmental Panel on Climate Change (IPCC) guidelines. We recommend moving towards consistent statistical terminology, and aligning on a rigorous framework for uncertainty estimation, supported by the provision of open-science codes for large-area assessments that comprehensively report uncertainty. Further, we suggest the provision of objective and open-source guidance to integrate NFIs with multiple AGBD products, aiming to enhance the precision of national estimates. Finally, we describe and encourage the release of user-friendly product documentation, with tools that produce AGBD estimates directly applicable to the IPCC guideline methodologies. With these steps, space agencies can convey a comparable, reliable and consistent message on global biomass estimates to have actionable policy impact.

BackgroundIdentification of people with HIV from electronic health record (EHR) data is an essential first step in the study of important HIV outcomes, such as risk assessment. This task has been historically performed via manual chart review, but the increased availability of large clinical data sets has led to the emergence of phenotyping algorithms to automate this process. Existing algorithms for identifying people with HIV rely on a combination of International Classification of Disease codes and laboratory tests or closely mimic clinical testing guidelines for HIV diagnosis. However, we found that existing algorithms in the literature missed a significant proportion of people with HIV in our data. ObjectiveThe aim of this study is to develop and evaluate HIV-Phen, an updated criteria-based HIV phenotyping algorithm. MethodsWe developed an algorithm using HIV-specific laboratory tests and medications and compared it with previously published algorithms in national and local data sets to identify cohorts of people with HIV. Cohort demographics were compared with those reported in the national and local surveillance data. Chart reviews were performed on a subsample of patients from the local database to calculate the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the algorithm. ResultsOur new algorithm identified substantially more people with HIV in both national (up to an 85.75% increase) and local (up to an 83.20% increase) EHR databases than the previously published algorithms. The demographic characteristics of people with HIV identified using our algorithm were similar to those reported in national and local HIV surveillance data. Our algorithm demonstrated improved sensitivity over existing algorithms (98% vs 56%-92%) while maintaining a similar overall accuracy (96% vs 80%-96%). ConclusionsWe developed and evaluated an updated criteria-based phenotyping algorithm for identifying people with HIV in EHR data that demonstrates improved sensitivity over existing algorithms.

Purpose: In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC., Methods: Using 416 LUSC tumor samples in the Cancer Genome Atlas (TCGA), we assessed genomic and transcriptomic profiles by ancestry. We replicated our analyses in pan-cancer data from TCGA, the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE), and Columbia University Medical Center., Results: We found increased MYC amplification, LUSC-specific MYC enhancer amplification, and chromosome arm 8q (chr8q) gain to be significantly associated with genetic AFR (African) ancestry in LUSC in TCGA. Furthermore, expression of MYC target genes was significantly enriched in AFR samples. Local ancestry analysis identified correlation of chr8q gain with AFR ancestry at the MYC locus in TCGA. We also found a significant correlation between chr8q and AFR ancestry in multiple cancer types and pan-cancer in TCGA. Similarly, in a pan-cancer subset of AACR GENIE data, we found a significant correlation between chr8q gain and race., Conclusion: Together, our data suggest that ancestry may influence amplification of not only MYC but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti- MYC therapeutic approaches.

Background: Mentorship is the foundation for training and career development. However, only about half of interventional radiology (IR) residency programs in the United States have a formal mentorship program at their institution. A new tiered mentorship program was introduced at our institution., Methods: A structured mentorship program was created at our institution in 2020 for IR residents to pair 1-2 faculty advisors with a group of residents, one from each PGY class, based on personal interests and career paths. A quality improvement survey with Likert scale format (1-5) was sent to IR residents and faculty members., Results: Responses were recorded from 11 IR residents in addition to all 6 IR faculty mentors. IR respondents reported satisfaction with feeling more assimilated in the department and all would recommend the current mentorship model to other institutions. Most respondents agreed the program made them comfortable conducting effective mentorship relationships as an attending and that the tiered structured of being mentee and mentor simultaneously was beneficial. Both IR residents and faculty agreed that the program helped prevent burnout., Conclusions: The tiered mentorship model has had a positive impact on the IR program by providing structured mentoring and longitudinal relationships. The most notable benefits for IR residents is the early integration into the program, sustained mentorships relationships, and the prevention of burnout. Similar models can help other programs establish structured faculty and peer mentorship for residents early in training., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ectopic pregnancies are one of the most common causes of obstetric mortality worldwide. Interstitial ectopic pregnancies, defined as an extracavitary pregnancy within the portion of the Fallopian tube that transverses the myometrium, have reported mortality rates approximately seven times higher than all types of ectopic pregnancy combined. In contrast, intracavitary eccentric gestations, often labeled as "cornual" or "angular" pregnancies, have reportedly high rates of live birth. Unfortunately, the terms "interstitial," "cornual," and "angular" have long been used with varying diagnostic criteria and often interchangeably to describe a pregnancy near the uterotubal junction. The inconsistency in nomenclature and lack of clear diagnostic criteria to distinguish among these pregnancies has resulted in a paucity of data to provide accurate prognostic information and guide appropriate management. This review article aims to provide historical context for the terms "interstitial," "cornual," and "angular;" discuss previous and more recent innovations of diagnostic methods; and provide recommendations for concise terminology and inform management., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear., Purpose: This systematic review and meta-analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models., Methods: Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random-effects models. Heterogeneity was presented as I 2 . Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results' robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis., Results: Forty studies involving 1543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = -19.12 μmol/l, 95 % CI: -25.02 to -13.23), BUN (MD = -6.72 mmol/l, 95 % CI: -9.32 to -4.12), urinary albumin excretion rate (SMD = -2.74, 95 % CI: -3.57, -1.90), histological changes (SMD = -2.25, 95 % CI: -3.19 to -1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95 % CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = -3.58, 95 % CI: -5.21 to -1.95). AM treatment also decreased fibrosis markers (i.e. TGF-β1, CTGF, collagen IV, Wnt4 and β-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group., Conclusion: AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

Background: There is increasing global evidence on the impact of advanced nursing and midwifery practitioners, and Kenya's healthcare system has an excellent opportunity to develop scopes of practice and other regulatory frameworks for the integration of these roles., Objective: The primary purpose of this gap analysis was to explore the existing evidence on opportunities and threats toward the integration of the advanced practice nursing (APN) and advanced practice midwifery (APM) roles in Kenya's healthcare system., Methods: The study team conducted a structured electronic database search of PubMed, CINAHL, Scopus, EBSCOhost Academic Search Complete, and PsycINFO to retrieve articles and credible websites for reports highlighting the opportunities and threats toward the integration of the APN and APM roles in Kenya's healthcare systems. The retrieved articles were screened for relevance and synthesized for reporting using the traditional literature review approach., Results: The Kenya Health Policy Framework 2014-2030, growing population needs, and implementation of universal health coverage provide an opportunity to harness and leverage advanced practice roles in nursing and midwifery. There is also momentum to develop advanced practice because of strategic alliances and global evidence showing the contributions and quality of services offered by advanced practice nurses and advanced practice midwives. However, lack of financial support, structural challenges, and lack of national policies, regulations, and legislation continue to obstruct progress., Conclusion and Implications for Nursing Policy: Developing scopes of practice for APN and APM in Kenya will benefit the professions, the country's healthcare delivery system, and the population. Achieving universal health coverage depends on a health workforce trained and practicing at optimal levels in tandem with education and training to deliver quality care., (© 2024 The Authors. International Nursing Review published by John Wiley & Sons Ltd on behalf of International Council of Nurses.)

Germline and somatic mutations can give rise to proteins with altered activity, including both gain and loss-of-function. The effects of these variants can be captured in disease-specific reactions and pathways that highlight the resulting changes to normal biology. A disease reaction is defined as an aberrant reaction in which a variant protein participates. A disease pathway is defined as a pathway that contains a disease reaction. Annotation of disease variants as participants of disease reactions and disease pathways can provide a standardized overview of molecular phenotypes of pathogenic variants that is amenable to computational mining and mathematical modeling. Reactome (https://reactome.org/), an open source, manually curated, peer-reviewed database of human biological pathways, in addition to providing annotations for >11 000 unique human proteins in the context of ∼15 000 wild-type reactions within more than 2000 wild-type pathways, also provides annotations for >4000 disease variants of close to 400 genes as participants of ∼800 disease reactions in the context of ∼400 disease pathways. Functional annotation of disease variants proceeds from normal gene functions, described in wild-type reactions and pathways, through disease variants whose divergence from normal molecular behaviors has been experimentally verified, to extrapolation from molecular phenotypes of characterized variants to variants of unknown significance using criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Reactome's data model enables mapping of disease variant datasets to specific disease reactions within disease pathways, providing a platform to infer pathway output impacts of numerous human disease variants and model organism orthologs, complementing computational predictions of variant pathogenicity. Database URL: https://reactome.org/., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Health advances due to developments in genomic medicine are unequally experienced in the USA; racial differences in the uptake of genetic testing are one factor in this disparity. In collaboration with Black patients and diverse health care providers, we are developing a patient-centered video intervention to increase cancer genetic testing among eligible Black Americans. The objective of the pilot work is to explore the acceptability of and support for the intervention and key content components., Methods: In order to create a patient-centered video intervention prototype, we conducted a targeted, secondary analysis of 47 coded transcripts from video-taped qualitative interviews with people with a known genetic or inherited cancer risk. The review focused on decision-making, testing experiences, and perceived value of genetic testing. We subsequently generated a 15-min video montage of content from 9 diverse (age, gender, race) participants. We used the prototype video as prompt material for semi-structured interviews with 10 Black patients who had undergone genetic testing in the last 2 years and 10 racially diverse providers (genetic counselors, a nurse, and medical oncologists) who provide management recommendations for high-risk patients. Interviews sought to understand the acceptability of a video intervention to enhance informed decision-making by Black patients and key elements for intervention efficacy., Results: Study participants were generally positive about the prototype video and provided guidance for intervention development. Interviewed patients prioritized perceived authenticity and relatability of video participants. The presentation of patients' perspectives on testing, their experiences of testing, and the benefits of having test results were all seen as useful. The benefits of testing for self and family were identified as important considerations. Privacy concerns and science skepticism were identified as germane issues, with guidance to present barriers to testing alongside possible solutions. The inclusion of clinicians was seen as potentially useful but with caution that clinicians are not universally trusted., Conclusions: Study findings provided critical input for the creation of a professionally produced, tailored intervention video for a randomized clinical trial with Black Americans to evaluate the influence on uptake of genetic testing. The interviews suggest the acceptability and potential utility of an authentic, realistic, and tailored, patient-centered video intervention to increase consideration and uptake of genetic testing., (© 2024. The Author(s).)

The continuous rise in bacterial infections and antibiotic resistance is the driving force behind the search for new antibacterial agents with novel modes of action. Antimicrobial peptides (AMPs) have recently gained attention as promising antibiotic agents with the potential to treat drug-resistant infections. Several AMPs have shown a lower propensity towards developing resistance compared to conventional antibiotics. However, these peptides, especially acyldepsipeptides (ADEPs) present with unfavorable pharmacokinetic properties, such as high toxicity and low bioavailability. Different ways to improve these peptides to be drug-like molecules have been explored, and these include using biocompatible nano-carriers. ADEP1 analogues (SC005-8) conjugated to gelatin-capped Silver/Indium/Sulfide (AgInS 2 ) quantum dots (QDs) improved the antibacterial activity against Gram-negative ( Escherichia coli and Pseudomonas aeruginosa ), and Gram-positive ( Bacillus subtilis , Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus ) bacteria. The ADEP1 analogues exhibited minimum inhibition concentrations (MIC) between 63 and 500 µM, and minimum bactericidal concentrations (MBC) values between 125 and 750 µM. The AgInS 2 -ADEP1 analogue conjugates showed enhanced antibacterial activity as evident from the MIC and MBC values, i.e., 1.6-25 µM and 6.3-100 µM, respectively. The AgInS 2 -ADEP1 analogue conjugates were non-toxic against HEK-293 cells at concentrations that showed antibacterial activity. The findings reported herein could be helpful in the development of antibacterial treatment strategies.

The Reactome Knowledgebase (https://reactome.org), an Elixir and GCBR core biological data resource, provides manually curated molecular details of a broad range of normal and disease-related biological processes. Processes are annotated as an ordered network of molecular transformations in a single consistent data model. Reactome thus functions both as a digital archive of manually curated human biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. Here we review progress towards annotation of the entire human proteome, targeted annotation of disease-causing genetic variants of proteins and of small-molecule drugs in a pathway context, and towards supporting explicit annotation of cell- and tissue-specific pathways. Finally, we briefly discuss issues involved in making Reactome more fully interoperable with other related resources such as the Gene Ontology and maintaining the resulting community resource network., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: Novel approaches are needed to ensure all patients with cancer have access to quality genetic education before genetic testing to enable informed treatment decisions. The purpose of this study was to test the use of an artificial intelligence (AI) intervention for the delivery of genetic education by non-genetic providers to patients with cancer undergoing active treatment., Methods: A conversational AI-based application was developed on the HealthFAX platform to provide tailored genetic education to patients with cancer and tested at Johns Hopkins Hospital between April 2021 and Feb 2022. Patients' responses around the adoption, use, and experience of the AI application were assessed., Results: Out of 64 individuals who consented to the study, 51 accessed the tool. The responding participants had a mean age of 61 years (ranging from 30-90 years) with 39 individuals undergoing active treatment for breast cancer and 12 for advanced prostate cancer. All patients chose to complete the tool at home. The median time between study enrollment and AI application initiation was 1 day, and the median time to complete the application was 24 min. All participants in their survey responses felt that the tool was secure, easy to use, liked the convenience of viewing it at home, and felt it provided valuable information. Eighteen percent of participants viewed the application with a family member. Ninety-eight percent of the participants completed their genetic education prior to receiving their test results. In 16%, a pathogenic variant was identified., Conclusions: The 51 patients who adopted the AI application were highly satisfied with its usability and convenience. Our results support the continued evaluation of this cost-effective AI application in a large-scale study., Implications for Cancer Survivors: Tailored pre-test genetic education can be successfully delivered to patients with cancer undergoing active treatment via an AI application at their convenience., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has had extensive economic, social, and public health impacts in the United States and around the world. To date, there have been more than 600 million reported infections worldwide with more than 6 million reported deaths. Retrospective analysis, which identified comorbidities, risk factors, and treatments, has underpinned the response. As the situation transitions to an endemic, retrospective analyses using electronic health records will be important to identify the long-term effects of COVID-19. However, these analyses can be complicated by incomplete records, which makes it difficult to differentiate visits where the patient had COVID-19. To address this issue, we trained a random Forest classifier to assign a probability of a patient having been diagnosed with COVID-19 during each visit. Using these probabilities, we found that higher COVID-19 probabilities were associated with a future diagnosis of myocardial infarction, urinary tract infection, acute renal failure, and type 2 diabetes., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Synthetic cannabinoids (SCs) make up a class of novel psychoactive substances (NPS), used predominantly in prisons and homeless communities in the U.K. SCs can have severe side effects, including psychosis, stroke, and seizures, with numerous reported deaths associated with their use. The chemical diversity of SCs presents the major challenge to their detection since approaches relying on specific molecular recognition become outdated almost immediately. Ideally one would have a generic approach to detecting SCs in portable settings. The problem of SC detection is more challenging still because the majority of SCs enter the prison estate adsorbed onto physical matrices such as paper, fabric, or herb materials. That is, regardless of the detection modality used, the necessary extraction step reduces the effectiveness and ability to rapidly screen materials on-site. Herein, we demonstrate a truly instant generic test for SCs, tested against real-world drug seizures. The test is based on two advances. First, we identify a spectrally silent region in the emission spectrum of most physical matrices. Second, the finding that background signals (including from autofluorescence) can be accurately predicted is based on tracking the fraction of absorbed light from the irradiation source. Finally, we demonstrate that the intrinsic fluorescence of a large range of physical substrates can be leveraged to track the presence of other drugs of interest, including the most recent iterations of benzodiazepines and opioids. We demonstrate the implementation of our presumptive test in a portable, pocket-sized device that will find immediate utility in prisons and law enforcement agencies around the world.

Purpose: Rapid pain relief for patients with bone metastases can be a challenge due to the lengthy and complex radiation therapy workflow. The purpose of this study was to evaluate the time (in days) between initial radiation oncology consultation and start of palliative radiation treatment after implementing an alternative virtual simulation palliative workflow., Methods and Materials: Patients meeting strict criteria were selected for virtual simulation, which included only those with painful bone metastases who were recommended palliative radiation therapy using standard anterior-posterior/posterior-anterior or opposed lateral fields. A recent (within 30 days) diagnostic computed tomography (CT) scan clearly visualizing the target volume was required for treatment planning. For comparison, a reference group of 40 consecutive patients with bone metastases who underwent in-person CT simulation before virtual simulation implementation was reviewed., Results: Forty-five patients were treated for painful bone metastases as part of the virtual simulation program from May 2021 to October 2022. Regarding travel distance, 23 patients lived locally (<50 miles from the treatment center) and 22 patients were distant (≥50 miles from the treatment center). Average time from consultation to treatment for all patients undergoing virtual simulation was 3.7 days, compared with 7.5 days for patients undergoing in-person CT simulation (3.8 days sooner, on average; P ≤ .001). Before full implementation of the virtual simulation program, 5 eligible patients participated in a virtual simulation pilot from April 2021 to May 2021, in which each patient was contoured and planned on both a pre-existing diagnostic CT scan and a standard CT simulation scan. For virtual simulation-based plans, the average V90, V95, and V99 were 99.99%, 99.87%, and 96.70%. No significant planning target volume (PTV) coverage difference was found on subsequent in-person CT simulation scans., Conclusions: The virtual simulation program decreased the time from consultation to start of treatment by more than 50% for patients recommended palliative radiation therapy for painful bone metastases. This benefit was most significant for outpatients traveling ≥50 miles for treatment. Virtual simulation-based planning can be considered for patients anxious to proceed with radiation therapy quickly or in underserved settings with limited transportation options to regional treatment centers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: The objectives of this video are to provide a brief overview of Müllerian agenesis, discuss a case of partial vaginal agenesis with a functional uterus, and present the steps of a staged McIndoe procedure for the creation of a neovagina and utero-neovaginal unification., Methods: We give an overview of Mayer-Rokitansky-Küster-Hauser syndrome, and review its incidence, clinical presentation, diagnostic evaluation, and treatment options. We present the case of a 23-year-old woman with partial vaginal agenesis, and her clinical course through conservative management with hormonal suppression and dilator therapy leading up to urogynecological surgical treatment. We describe a staged surgical approach that highlights the value of cystoscopy and laparoscopy to better delineate our patient's anatomical variations. Additionally, a mini-laparotomy and placement of an intrauterine Malecot catheter allowed for the drainage of prominent hematometra, relief of menstrual outflow obstruction, and epithelialization of a tract between the uterus and the planned neovaginal space. Ultimately, a neovagina was created using a staged McIndoe technique, leading to utero-neovaginal unification and unobstructed menses., Conclusion: In conclusion, our approach should be considered a feasible option for anatomical restoration via the creation of a neovagina in patients with Müllerian anomalies, even in the presence of a functional uterus., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: Deep learning techniques, including convolutional neural networks (CNN), have the potential to improve breast cancer risk prediction compared to traditional risk models. We assessed whether combining a CNN-based mammographic evaluation with clinical factors in the Breast Cancer Surveillance Consortium (BCSC) model improved risk prediction., Methods: We conducted a retrospective cohort study among 23,467 women, age 35-74, undergoing screening mammography (2014-2018). We extracted electronic health record (EHR) data on risk factors. We identified 121 women who subsequently developed invasive breast cancer at least 1 year after the baseline mammogram. Mammograms were analyzed with a pixel-wise mammographic evaluation using CNN architecture. We used logistic regression models with breast cancer incidence as the outcome and predictors including clinical factors only (BCSC model) or combined with CNN risk score (hybrid model). We compared model prediction performance via area under the receiver operating characteristics curves (AUCs)., Results: Mean age was 55.9 years (SD, 9.5) with 9.3% non-Hispanic Black and 36% Hispanic. Our hybrid model did not significantly improve risk prediction compared to the BCSC model (AUC of 0.654 vs 0.624, respectively, p = 0.063). In subgroup analyses, the hybrid model outperformed the BCSC model among non-Hispanic Blacks (AUC 0.845 vs. 0.589; p = 0.026) and Hispanics (AUC 0.650 vs 0.595; p = 0.049)., Conclusion: We aimed to develop an efficient breast cancer risk assessment method using CNN risk score and clinical factors from the EHR. With future validation in a larger cohort, our CNN model combined with clinical factors may help predict breast cancer risk in a cohort of racially/ethnically diverse women undergoing screening., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Study Objective: To analyze hysterectomy trends and vaginal cuff dehiscence (VCD) rates by mode of surgery at a tertiary care medical center and to describe characteristics of VCD cases., Design: Observational retrospective cohort study., Setting: Large academic hospital and affiliated community hospital., Patients: 4722 patients who underwent hysterectomy at Columbia University Irving Medical Center between January 2010 and August 2021., Interventions: Current Procedural Terminology and International Classification of Diseases codes identified hysterectomies and VCD cases. Hysterectomy trends and VCD rates were calculated by mode of surgery. Relative risks of VCD for each mode were compared with total abdominal hysterectomy (TAH). Clinical characteristics of VCDs were reviewed., Measurements and Main Results: There were 4059 total hysterectomies. Laparoscopic hysterectomies, including total laparoscopic hysterectomies (TLHs), laparoscopic-assisted vaginal hysterectomies, and robot-assisted TLHs (RA-TLHs), increased from 41.9% in 2010 to 65.9% in 2021 (p <.001). RA-TLH increased from 5.7% in 2010 to 40.2% in 2021. Supracervical hysterectomies followed similar trends and were excluded from VCD analysis. There were 15 VCDs (overall rate 0.37%). VCD was highest after RA-TLH (0.66%), followed by TLH (0.32%) and TAH (0.27%), with no VCDs after laparoscopic-assisted vaginal hysterectomy or total vaginal hysterectomy. Compared with TAH, the relative risk for VCD after RA-TLH was 2.44 (95% confidence interval 0.66-9.00) and after TLH was 1.18 (95% confidence interval 0.24-5.83), which were not statistically significant. The mean time to dehiscence was 39 days (range 8-145 days). The most common trigger event was coitus (41%)., Conclusion: VCD rates were low (<1%) for all modes of hysterectomy, and rates after robotic and laparoscopic hysterectomy were much lower than previously reported. Although VCD rates trended higher after robotic and laparoscopic hysterectomy compared with abdominal hysterectomy, the difference was not significant. It is difficult to determine whether this finding represents true lack of difference vs a lack of power to detect a significant difference given the rarity of VCD., (Copyright © 2023 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: Due to the importance of radiologic examinations, such as X-rays or computed tomography scans, for many clinical diagnoses, the optimal use of the radiology department is 1 of the primary goals of many hospitals., Objective: This study aims to calculate the key metrics of this use by creating a radiology data warehouse solution, where data from radiology information systems (RISs) can be imported and then queried using a query language as well as a graphical user interface (GUI)., Methods: Using a simple configuration file, the developed system allowed for the processing of radiology data exported from any kind of RIS into a Microsoft Excel, comma-separated value (CSV), or JavaScript Object Notation (JSON) file. These data were then imported into a clinical data warehouse. Additional values based on the radiology data were calculated during this import process by implementing 1 of several provided interfaces. Afterward, the query language and GUI of the data warehouse were used to configure and calculate reports on these data. For the most common types of requested reports, a web interface was created to view their numbers as graphics., Results: The tool was successfully tested with the data of 4 different German hospitals from 2018 to 2021, with a total of 1,436,111 examinations. The user feedback was good, since all their queries could be answered if the available data were sufficient. The initial processing of the radiology data for using them with the clinical data warehouse took (depending on the amount of data provided by each hospital) between 7 minutes and 1 hour 11 minutes. Calculating 3 reports of different complexities on the data of each hospital was possible in 1-3 seconds for reports with up to 200 individual calculations and in up to 1.5 minutes for reports with up to 8200 individual calculations., Conclusions: A system was developed with the main advantage of being generic concerning the export of different RISs as well as concerning the configuration of queries for various reports. The queries could be configured easily using the GUI of the data warehouse, and their results could be exported into the standard formats Excel and CSV for further processing., (©Leon Liman, Bernd May, Georg Fette, Jonathan Krebs, Frank Puppe. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 22.05.2023.)

Purpose of Review: COVID-19 is an ongoing global pandemic since it was first discovered in 2020. Cerebral vascular disease and stroke are among the most common and devastating neurological manifestations of COVID-19. This review offers an up-to-date information on the possible underlying mechanism of COVID-19-related stroke, its diagnosis, and management., Recent Findings: The thromboembolism associated with COVID-19 infection is likely related to the cytokine storm with innate immune activation, pulmonary disease leading to hypoxia-induced ischemia, thrombotic microangiopathy, endothelial damage and multifactorial activation of the coagulation cascade. Currently, there is no clear guidelines on the use of antithrombotics for the prevention and treatment of this phenomenon., Summary: COVID-19 infection can directly cause a stroke or facilitate the formation of thromboembolism in the presence of other medical conditions. Physicians treating patients with COVID-19 should stay vigilant about the signs and symptoms of stroke, detect and treat early., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Pathway databases provide descriptions of the roles of proteins, nucleic acids, lipids, carbohydrates, and other molecular entities within their biological cellular contexts. Pathway-centric views of these roles may allow for the discovery of unexpected functional relationships in data such as gene expression profiles and somatic mutation catalogues from tumor cells. For this reason, there is a high demand for high-quality pathway databases and their associated tools. The Reactome project (a collaboration between the Ontario Institute for Cancer Research, New York University Langone Health, the European Bioinformatics Institute, and Oregon Health & Science University) is one such pathway database. Reactome collects detailed information on biological pathways and processes in humans from the primary literature. Reactome content is manually curated, expert-authored, and peer-reviewed and spans the gamut from simple intermediate metabolism to signaling pathways and complex cellular events. This information is supplemented with likely orthologous molecular reactions in mouse, rat, zebrafish, worm, and other model organisms. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Browsing a Reactome pathway Basic Protocol 2: Exploring Reactome annotations of disease and drugs Basic Protocol 3: Finding the pathways involving a gene or protein Alternate Protocol 1: Finding the pathways involving a gene or protein using UniProtKB (SwissProt), Ensembl, or Entrez gene identifier Alternate Protocol 2: Using advanced search Basic Protocol 4: Using the Reactome pathway analysis tool to identify statistically overrepresented pathways Basic Protocol 5: Using the Reactome pathway analysis tool to overlay expression data onto Reactome pathway diagrams Basic Protocol 6: Comparing inferred model organism and human pathways using the Species Comparison tool Basic Protocol 7: Comparing tissue-specific expression using the Tissue Distribution tool., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)