Ertugliflozin to Reduce Arrhythmic Burden in Patients with ICDs/CRT-Ds.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial pleiotropic effects, contributing to improved cardiovascular and renal outcomes for patients with and without diabetes. The impact of SGLT2is on arrhythmic burden remains largely unexplored through randomized trials. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, we investigated the effects of ertugliflozin on arrhythmic burden among patients with heart failure with an ejection fraction less than 50%. All patients had an implantable cardioverter-defibrillator (ICD) with or without a cardiac resynchronization therapy device (CRT-D) and were randomized (1:1) to receive either ertugliflozin 5 mg once daily or placebo. The primary end point was the number of incident sustained (>30 seconds) ventricular tachycardia or ventricular fibrillation events from baseline to week 52. Secondary end points included the total number of non-sustained ventricular tachycardias, appropriate ICD therapies, changes in N-terminal pro-brain-type natriuretic peptide (NTproBNP) levels, and the number of heart failure hospitalizations. RESULTS: Randomization was prematurely terminated, after class IA guideline recommendations were published for SGLT2is in patients with heart failure regardless of the ejection fraction. The final analysis included 46 patients (11% of the originally planned sample size). The yearly rate of the primary end point was 3.5 (95% confidence interval [CI] 2.8 to 4.4) with ertugliflozin compared with 13.3 with placebo (95% CI 11.8 to 14.8; rate ratio 0.16, 95% CI 0.04 to 0.61; P<0.001). There were no apparent differences in appropriate ICD therapies, hospitalizations, NTproBNP levels, or predefined adverse and serious adverse events. CONCLUSIONS: Ertugliflozin reduced sustained ventricular tachycardia or ventricular fibrillation events in adults with heart failure and an ICD compared with placebo; however, our trial ended early and thus results should be interpreted with caution. (Funded by Investigator-initiated Studies Program of Merck Sharp & Dohme Corp and Pfizer; EudraCT number, 2020-002581-14; ClinicalTrials.gov number NCT04600921.).

Leveraging Generative AI to Accelerate Biocuration of Medical Actions for Rare Disease.

BACKGROUND: Structured representations of clinical data can support computational analysis of individuals and cohorts, and ontologies representing disease entities and phenotypic abnormalities are now commonly used for translational research. The Medical Action Ontology (MAxO) provides a computational representation of treatments and other actions taken for the clinical management of patients. Currently, manual biocuration is used to assign MAxO terms to rare diseases, enabling clinical management of rare diseases to be described computationally for use in clinical decision support and mechanism discovery. However, it is challenging to scale manual curation to comprehensively capture information about medical actions for the more than 10,000 rare diseases. METHODS: We present AutoMAxO, a semi-automated workflow that leverages Large Language Models (LLMs) to streamline MAxO biocuration for rare diseases. AutoMAxO first uses LLMs to retrieve candidate curations from abstracts of relevant publications. Next, the candidate curations are matched to ontology terms from MAxO, Human Phenotype Ontology (HPO), and MONDO disease ontology via a combination of LLMs and post-processing techniques. Finally, the matched terms are presented in a structured form to a human curator for approval. RESULTS: We used this approach to process 4,918 unique medical abstracts and identified annotations for 21 rare genetic diseases, we extracted 18,631 candidate disease-treatment curations, 538 of which were confirmed and transferred to the MAxO annotation dataset. CONCLUSION: The results of this project underscore the potential of generative AI to accelerate precision medicine by enabling a robust and comprehensive curation of the primary literature to represent information about diseases and procedures in a structured fashion. Although we focused on MAxO in this project, similar approaches could be taken for other biomedical curation tasks.

Intramedullary versus locking plate fixation for proximal humerus fractures: indications and technical considerations.

Background: The incidence of proximal humerus fractures (PHFs) continues to increase with an aging population, and intramedullary nailing (IMN) and locking plate fixation are two commonly employed techniques for the surgical management of PHF. However, the optimal fixation method can be a source of ongoing controversy. Some influencing factors include the extent of humeral head involvement, fracture complexity, patient age, and surgeon preference. There are many studies that provide a mix of data either when comparing the two techniques or analyzing them in isolation. The aim of this review is to further elucidate the indications and technical considerations involved specifically in IMN vs. locking plate fixation for PHF to further aid orthopedic surgeons when choosing surgical management. Methods: A narrative approach was chosen for this review allowing for a comprehensive review of literature, including recent findings pertaining to the comparison of management options for PHF. A comprehensive literature search was conducted using the PubMed, Embase, and Cochrane Library databases. The inclusion criteria involved studies that discussed "proximal humerus fracture" and either "intramedullary nail" or "locking plate fixation." Results: Complications such as avascular necrosis, hardware failure, additional surgical interventions, infection, fracture redisplacement, rotator cuff rupture, and nonunion did not show significant differences between the two groups. Newer generation humeral nails have minimized early complications. As both techniques undergo further refinement and utilization when specifically indicated, functional outcomes, potential complications, and postoperative pain continue to be improved. Conclusion: The available evidence suggests that both intramedullary nails and locking plates can effectively restore shoulder function in the treatment of displaced proximal humeral fractures, with unclear superiority of either method. The choice of technique should be tailored to patient factors such as fracture type, age, bone quality, and functional expectations. Surgeon experience also plays a role. While certain presentations may exhibit trends that favor one fixation, no specific technique can be universally recommended. Both IMN and LP have shown comparable and satisfactory outcomes, and the final fixation method chosen should take into account the unique characteristics of each patient.

Evaluation of the Diagnostic Accuracy of GPT-4 in Five Thousand Rare Disease Cases.

Large language models (LLM) have shown great promise in supporting differential diagnosis, but 23 available published studies on the diagnostic accuracy evaluated small cohorts (number of cases, 30-422, mean 104) and have evaluated LLM responses subjectively by manual curation (23/23 studies). The performance of LLMs for rare disease diagnosis has not been evaluated systematically. Here, we perform a rigorous and large-scale analysis of the performance of a GPT-4 in prioritizing candidate diagnoses, using the largest-ever cohort of rare disease patients. Our computational study used 5267 computational case reports from previously published data. Each case was formatted as a Global Alliance for Genomics and Health (GA4GH) phenopacket, in which clinical anomalies were represented as Human Phenotype Ontology (HPO) terms. We developed software to generate prompts from each phenopacket. Prompts were sent to Generative Pre-trained Transformer 4 (GPT-4), and the rank of the correct diagnosis, if present in the response, was recorded. The mean reciprocal rank of the correct diagnosis was 0.24 (with the reciprocal of the MRR corresponding to a rank of 4.2), and the correct diagnosis was placed in rank 1 in 19.2% of the cases, in the first 3 ranks in 28.6%, and in the first 10 ranks in 32.5%. Our study is the largest to be reported to date and provides a realistic estimate of the performance of GPT-4 in rare disease medicine.

Preventing Infections in Reverse Shoulder Arthroplasty.

PURPOSE OF REVIEW: Reverse shoulder arthroplasty (rTSA) is a commonly performed procedure to treat degenerative conditions of the shoulder. With its growing utilization, techniques to reliably diagnose and treat prosthetic joint infection (PJI) have become increasingly important. In this review we outline the current research and prevention methods of prosthetic joint infection in rTSA. This includes preoperative considerations, intraoperative, and postoperative treatment algorithms. RECENT FINDINGS: There is currently no established standardized protocol for preoperative infection prevention or post operative management. However, recent studies have identified risk factors for infection, as well as successful prevention techniques that can be implemented to minimize infection risk. Although there is no standardized protocol currently utilized to diagnose and treat shoulder PJI, we outline a potential set of preventative measures and postoperative management strategies that clinicians can use to properly diagnose and treat patients with this difficult condition.

Characterization of mosquito host-biting networks of potential Rift Valley fever virus vectors in north-eastern KwaZulu-Natal province, South Africa.

BACKGROUND: Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus with serious implications for livestock health, human health, and the economy in Africa, and is suspected to be endemic in north-eastern KwaZulu-Natal (KZN), South Africa. The vectors of RVFV in this area are poorly known, although several species, such as Aedes (Neomelaniconion) mcintoshi, Aedes (Neomelaniconion) circumluteolus, Aedes (Aedimorphus) durbanensis, and Culex (Lasioconops) poicilipes may be involved. The aim of the study was to determine the vertebrate blood meal sources of potential RVFV mosquito vectors in north-eastern KZN and to characterize the host-biting network. METHODS: Blood-fed mosquitoes were collected monthly from November 2019 to February 2023 using a backpack aspirator, CO2-baited Centers for Disease Control and Prevention (CDC) miniature light traps and tent traps, in the vicinity of water bodies and livestock farming households. The mosquitoes were morphologically identified. DNA was extracted from individual mosquitoes and used as templates to amplify the vertebrate cytochrome c oxidase I (COI) and cytochrome b (cytb) genes using conventional polymerase chain reaction (PCR). Amplicons were sequenced and queried in GenBank and the Barcode of Life Data systems to identify the vertebrate blood meal sources and confirm mosquito identifications. All mosquitoes were screened for RVFV using real time reverse transcription (RT)-PCR. RESULTS: We identified the mammalian (88.8%) and avian (11.3%) blood meal sources from 409 blood-fed mosquitoes. Aedes circumluteolus (n = 128) made up the largest proportion of collected mosquitoes. Cattle (n = 195) and nyala (n = 61) were the most frequent domestic and wild hosts, respectively. Bipartite network analysis showed that the rural network consisted of more host-biting interactions than the reserve network. All mosquitoes tested negative for RVFV. CONCLUSIONS: Several mosquito species, including Ae. circumluteolus, and vertebrate host species, including cattle and nyala, could play a central role in RVFV transmission. Future research in this region should focus on these species to better understand RVFV amplification.

Incidence of gastrointestinal bleeding with hydrocortisone use in neonates and infants less than three months of age in the neonatal intensive care unit.

OBJECTIVE: The objective of this study was to determine the incidence of hydrocortisone-associated gastrointestinal bleeding (GIB) in infants <3 months and compare rates with or without stress ulcer prophylaxis. STUDY DESIGN: Retrospective cohort study of NICU patients <3 months who received hydrocortisone for hypotension. Three logistic regressions were conducted for adjusted associations between GIB, necrotizing enterocolitis (NEC), or infection and clinical characteristics. RESULTS: Of 233 patients included, 54 (23.2%) received SUP; the majority (96.3%) received histamine-2 receptor antagonists. Median postmenstrual and postnatal age at hydrocortisone initiation was 33.3 weeks and 2 days. GIB occurred in 22 patients (9.4%), with no difference in GIB (11.1% versus 8.9%, p = 0.632) or SUP-associated adverse effects (50.0% versus 52.0%, p = 0.80) with and without SUP. SUP was not associated with GIB, NEC, or infection when controlling for confounders. CONCLUSION: GIB occurred in 9.4% of patients. SUP did not provide benefit for GIB prevention and was not associated with increased risk of adverse effects.

Moderately thermostable GH1 ß-glucosidases from hyperacidophilic archaeon Cuniculiplasma divulgatum S5.

Family GH1 glycosyl hydrolases are ubiquitous in prokaryotes and eukaryotes and are utilized in numerous industrial applications, including bioconversion of lignocelluloses. In this study, hyperacidophilic archaeon Cuniculiplasma divulgatum (S5T=JCM 30642T) was explored as a source of novel carbohydrate-active enzymes. The genome of C. divulgatum encodes three GH1 enzyme candidates, from which CIB12 and CIB13 were heterologously expressed and characterized. Phylogenetic analysis of CIB12 and CIB13 clustered them with ß-glucosidases from genuinely thermophilic archaea including Thermoplasma acidophilum, Picrophilus torridus, Sulfolobus solfataricus, Pyrococcus furiosus, and Thermococcus kodakarensis. Purified enzymes showed maximal activities at pH 4.5-6.0 (CIB12) and 4.5-5.5 (CIB13) with optimal temperatures at 50°C, suggesting a high-temperature origin of Cuniculiplasma spp. ancestors. Crystal structures of both enzymes revealed a classical (α/ß)8 TIM-barrel fold with the active site located inside the barrel close to the C-termini of ß-strands including the catalytic residues Glu204 and Glu388 (CIB12), and Glu204 and Glu385 (CIB13). Both enzymes preferred cellobiose over lactose as substrates and were classified as cellobiohydrolases. Cellobiose addition increased the biomass yield of Cuniculiplasma cultures growing on peptides by 50%, suggesting that the cellobiohydrolases expand the carbon substrate range and hence environmental fitness of Cuniculiplasma.

Seroprevalence and associated risk factors for Neospora caninum infection in dairy cattle in South Africa.

Bovine neosporosis is a widespread parasitic disease associated with significant economic losses. Its effects on the reproductive performance of cows have resulted in losses that run into the hundreds of millions of US dollars in dairy industries in various countries (Reichel et al., Int J Parasitol 43:133-142, 2013). Due to outdated and scant information on the occurrence of Neospora caninum infection in South Africa, the study aimed to determine the seroprevalence and risk factors associated with infection in dairy cattle in South Africa. A total of 1401 blood samples were randomly collected from cattle on 48 dairy farms in seven of the nine provinces in South Africa. A close-ended questionnaire was used in a cross-sectional study to obtain farm-level and animal-level data. Serological testing was done using a commercial IDvet Screen® Neospora caninum Indirect ELISA. An overall seroprevalence, adjusted for test sensitivity and specificity, of 2.3% (95% CI, 1.3-4.1) was detected and 48% (23/48) of sampled farms had at least one animal testing positive. The highest seroprevalence of N. caninum was in the KwaZulu-Natal province with 7.5% (95% CI, 3.8-14.3), and the lowest in Western Cape with 0.1% (95% CI, 0-1.2). The highest within-farm seroprevalence of 25% was detected on a farm in the North West Province. In a multivariable logistic regression model, the odds of N. caninum seropositivity were higher in Holstein-Friesian cattle when compared to other breeds. Good hygiene was identified as a protective factor. Cattle left out on pasture had increased odds of testing positive for N. caninum compared to those that were penned. The odds of testing seropositive for N. caninum was higher on farms that practised segregation of cattle into different age groups. The purchase of replacement animals was a significant risk factor, as open herds had increased odds of N. caninum seropositivity. Cattle on farms that did not have a specific calving location were more likely to be seropositive. This is the first such study in South Africa and shows that N. caninum is widely distributed in the country at a low seroprevalence, but it may be a cause of concern on certain farms.

Oxyplasma meridianum gen. nov., sp. nov., an extremely acidophilic organotrophic member of the order Thermoplasmatales.

A mesophilic, hyperacidophilic archaeon, strain M1T, was isolated from a rock sample from Vulcano Island, Italy. Cells of this organism were cocci with an average diameter of 1 µm. Some cells possessed filaments. The strain grew in the range of temperatures between 15 and 52 °C and pH 0.5-4.0 with growth optima at 40 °C and pH 1.0. Strain M1T was aerobic and chemoorganotrophic, growing on complex substrates, such as casamino acids, trypticase, tryptone, yeast and beef extracts. No growth at expenses of oxidation of elemental sulphur or reduced sulphur compounds, pyrite, or ferrous sulphate was observed. The core lipids were glycerol dibiphytanyl glycerol tetraether lipids (membrane spanning) with 0 to 4 cyclopentane moieties and archaeol, with trace amounts of hydroxy archaeol. The dominant quinone was MK-7 : 7. The genome size of M1T was 1.67 Mbp with a G+C content of 39.76 mol%, and both characteristics were well within the common range for Thermoplasmatales. The phylogenetic analysis based on 16S rRNA gene sequence placed the strain M1T within the order Thermoplasmatales with sequence identities of 90.9, 90.3 and 90.5% to the closest SSU rRNA gene sequences from organisms with validly published names, Thermoplasma acidophilum, Thermoplasma volcanium and Thermogymnomonas acidicola, respectively. Based on the results of our genomic, phylogenetic, physiological and chemotaxonomic studies, we propose that strain M1T (=DSM 116605T=JCM 36570T) represents a new genus and species, Oxyplasma meridianum gen. nov., sp. nov., within the order Thermoplasmatales.

An ontology-based knowledge graph for representing interactions involving RNA molecules.

The "RNA world" represents a novel frontier for the study of fundamental biological processes and human diseases and is paving the way for the development of new drugs tailored to each patient's biomolecular characteristics. Although scientific data about coding and non-coding RNA molecules are constantly produced and available from public repositories, they are scattered across different databases and a centralized, uniform, and semantically consistent representation of the "RNA world" is still lacking. We propose RNA-KG, a knowledge graph (KG) encompassing biological knowledge about RNAs gathered from more than 60 public databases, integrating functional relationships with genes, proteins, and chemicals and ontologically grounded biomedical concepts. To develop RNA-KG, we first identified, pre-processed, and characterized each data source; next, we built a meta-graph that provides an ontological description of the KG by representing all the bio-molecular entities and medical concepts of interest in this domain, as well as the types of interactions connecting them. Finally, we leveraged an instance-based semantically abstracted knowledge model to specify the ontological alignment according to which RNA-KG was generated. RNA-KG can be downloaded in different formats and also queried by a SPARQL endpoint. A thorough topological analysis of the resulting heterogeneous graph provides further insights into the characteristics of the "RNA world". RNA-KG can be both directly explored and visualized, and/or analyzed by applying computational methods to infer bio-medical knowledge from its heterogeneous nodes and edges. The resource can be easily updated with new experimental data, and specific views of the overall KG can be extracted according to the bio-medical problem to be studied.

From transcriptomics to digital twins of organ function.

Cell level functions underlie tissue and organ physiology. Gene expression patterns offer extensive views of the pathways and processes within and between cells. Single cell transcriptomics provides detailed information on gene expression within cells, cell types, subtypes and their relative proportions in organs. Functional pathways can be scalably connected to physiological functions at the cell and organ levels. Integrating experimentally obtained gene expression patterns with prior knowledge of pathway interactions enables identification of networks underlying whole cell functions such as growth, contractility, and secretion. These pathways can be computationally modeled using differential equations to simulate cell and organ physiological dynamics regulated by gene expression changes. Such computational systems can be thought of as parts of digital twins of organs. Digital twins, at the core, need computational models that represent in detail and simulate how dynamics of pathways and networks give rise to whole cell level physiological functions. Integration of transcriptomic responses and numerical simulations could simulate and predict whole cell functional outputs from transcriptomic data. We developed a computational pipeline that integrates gene expression timelines and systems of coupled differential equations to generate cell-type selective dynamical models. We tested our integrative algorithm on the eicosanoid biosynthesis network in macrophages. Converting transcriptomic changes to a dynamical model allowed us to predict dynamics of prostaglandin and thromboxane synthesis and secretion by macrophages that matched published lipidomics data obtained in the same experiments. Integration of cell-level system biology simulations with genomic and clinical data using a knowledge graph framework will allow us to create explicit predictive models that mechanistically link genomic determinants to organ function. Such integration requires a multi-domain ontological framework to connect genomic determinants to gene expression and cell pathways and functions to organ level phenotypes in healthy and diseased states. These integrated scalable models of tissues and organs as accurate digital twins predict health and disease states for precision medicine.

Replacing non-biomedical concepts improves embedding of biomedical concepts.

Objectives: Concept embeddings are low-dimensional vector representations of concepts such as MeSH:D009203 (Myocardial Infarction), whose similarity in the embedded vector space reflects their semantic similarity. Here, we test the hypothesis that non-biomedical concept synonym replacement can improve the quality of biomedical concepts embeddings. Materials and methods: We developed an approach that leverages WordNet to replace sets of synonyms with the most common representative of the synonym set. Results: We tested our approach on 1055 concept sets and found that, on average, the mean intra-cluster distance was reduced by 8% in the vector-space. Assuming that homophily of related concepts in the vector space is desirable, our approach tends to improve the quality of embeddings. Discussion and Conclusion: This pilot study shows that non-biomedical synonym replacement tends to improve the quality of embeddings of biomedical concepts using the Word2Vec algorithm. We have implemented our approach in a freely available Python package available at https://github.com/TheJacksonLaboratory/wn2vec.

Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia.

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.

Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes.

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.

Incidental seminoma in nonobstructive azoospermia: a case report.

Objective: To report on the incidental finding of invasive seminoma in a patient with nonobstructive azoospermia during microdissection testicular sperm extraction. Design: Case report. Patients: A single patient diagnosed with nonobstructive azoospermia underwent microdissection testicular sperm extraction, and an incidental finding of invasive seminoma was made upon histopathological analysis. Results: An incidental discovery of invasive seminoma was observed in the sample pathology obtained during the microdissection testicular sperm extraction. Consequently, the patient underwent further diagnostic workup and a radical orchiectomy. Conclusions: Men with male factor infertility are at increased risk of testicular cancer. As such, it is imperative to incorporate a thorough physical examination and relevant imaging into their diagnostic process. Additionally, it is advisable to include histopathological analysis for all individuals undergoing microdissection testicular sperm extraction.

Racial Disparities in Sports Cardiology: A Review.

Importance: Racial disparities in cardiovascular health, including sudden cardiac death (SCD), exist among both the general and athlete populations. Among competitive athletes, disparities in health outcomes potentially influenced by social determinants of health (SDOH) and structural racism remain inadequately understood. This narrative review centers on race in sports cardiology, addressing racial disparities in SCD risk, false-positive cardiac screening rates among athletes, and the prevalence of left ventricular hypertrophy, and encourages a reexamination of race-based practices in sports cardiology, such as the interpretation of screening 12-lead electrocardiogram findings. Observations: Drawing from an array of sources, including epidemiological data and broader medical literature, this narrative review discusses racial disparities in sports cardiology and calls for a paradigm shift in approach that encompasses 3 key principles: race-conscious awareness, clinical inclusivity, and research-driven refinement of clinical practice. These proposed principles call for a shift away from race-based assumptions towards individualized, health-focused care in sports cardiology. This shift would include fostering awareness of sociopolitical constructs, diversifying the medical team workforce, and conducting diverse, evidence-based research to better understand disparities and address inequities in sports cardiology care. Conclusions and Relevance: In sports cardiology, inadequate consideration of the impact of structural racism and SDOH on racial disparities in health outcomes among athletes has resulted in potential biases in current normative standards and in the clinical approach to the cardiovascular care of athletes. An evidence-based approach to successfully address disparities requires pivoting from outdated race-based practices to a race-conscious framework to better understand and improve health care outcomes for diverse athletic populations.

Cervical ripening with vaginal Misoprostol plus Hyoscine-N-Butylbromide versus vaginal Misoprostol alone among pregnant women: a double-blind randomised controlled trial.

Objective: To compare cervical ripening time with the use of vaginal Misoprostol plus Hyoscine-N-Butylbromide, with vaginal Misoprostol alone. Design: A double-blind randomized controlled trial with Pan-African Clinical Trials Registry (PACTR) approval number PACTR202112821475292. Setting: Federal Medical Centre, Asaba, Nigeria. Participants: A total of 126 eligible antenatal patients for cervical ripening were enrolled. Interventions: Participants in Group A had 25µg of vaginal misoprostol with 1ml of intramuscular placebo, and those in Group B had 25µg of vaginal misoprostol with 20mg of Intramuscular Hyoscine (1 ml). Oxytocin infusion was used when indicated, and the labour was supervised as per departmental protocol. Main outcome measure: Cervical ripening time. Results: The mean cervical ripening time was statistically significantly shorter in the hyoscine group (8.48±4.36 hours) than in the placebo group (11.40±7.33 hours); p-value 0.02, 95% CI 0.80-5.05. There was no statistically significant difference in the mean induction-delivery interval in Group A (7.38±5.28 hours) compared to Group B (7.75±5.04 hours), with a value of 0.54. The mode of delivery was comparable. However, women in Group B (53, 84.1%) achieved more vaginal deliveries than women in Group A (50, 79.4%); p-value 0.49. Thirteen women in Group A (20.6%) had a caesarean section, while ten women (15.9%) in Group B had a caesarean section (p-value 0.49, RR 0.94, CI 0.80-1.11). Adverse maternal and neonatal outcomes were not statistically significant between the two groups. Conclusion: Intramuscular hyoscine was effective in reducing cervical ripening time when used as an adjunct to vaginal Misoprostol, with no significant adverse maternal or neonatal outcome. Funding: None declared.

A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis.

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a range of associated genomic and transcriptomic data, clinical metadata, pathologic assessments of cell composition, and, in several cases, detailed pathologic annotations of neoplastic, stromal, and necrotic regions. The amenability of these images to deep learning was highlighted through three applications: (i) development of a classifier for neoplastic, stromal, and necrotic regions; (ii) development of a predictor of xenograft-transplant lymphoproliferative disorder; and (iii) application of a published predictor of microsatellite instability. Together, this PDX Development and Trial Centers Research Network image repository provides a valuable resource for controlled digital pathology analysis, both for the evaluation of technical issues and for the development of computational image-based methods that make clinical predictions based on PDX treatment studies. Significance: A pan-cancer repository of >1,000 patient-derived xenograft hematoxylin and eosin-stained images will facilitate cancer biology investigations through histopathologic analysis and contributes important model system data that expand existing human histology repositories.