Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies.

Electronic health records (EHRs) were implemented to improve quality of care and patient outcomes. This study assessed the relationship between EHR-adoption and patient outcomes.We performed an observational study using State Inpatient Databases linked to American Hospital Association survey, 2011. Surgical and medical patients from 6 large, diverse states were included. We performed univariate analyses and developed hierarchical regression models relating level of EHR utilization and mortality, readmission rates, and complications. We evaluated the effect of EHR adoption on outcomes in a difference-in-differences analysis, 2008 to 2011.Medical and surgical patients sought care at hospitals reporting no EHR (3.5%), partial EHR (55.2%), and full EHR systems (41.3%). In univariate analyses, patients at hospitals with full EHR had the lowest rates of inpatient mortality, readmissions, and Patient Safety Indicators followed by patients at hospitals with partial EHR and then patients at hospitals with no EHR (P < 0.05). However, these associations were not robust when accounting for other patient and hospital factors, and adoption of an EHR system was not associated with improved patient outcomes (P > 0.05).These results indicate that patients receiving medical and surgical care at hospitals with no EHR system have similar outcomes compared to patients seeking care at hospitals with a full EHR system, after controlling for important confounders.To date, we have not yet seen the promised benefits of EHR systems on patient outcomes in the inpatient setting. EHRs may play a smaller role than expected in patient outcomes and overall quality of care.

Widely-prescribed prodrug opioids (e.g., hydrocodone) require conversion by liver enzyme CYP-2D6 to exert their analgesic effects. The most commonly prescribed antidepressant, selective serotonin reuptake inhibitors (SSRIs), inhibits CYP-2D6 activity and therefore may reduce the effectiveness of prodrug opioids. We used a machine learning approach to identify patients prescribed a combination of SSRIs and prodrug opioids postoperatively and to examine the effect of this combination on postoperative pain control. Using EHR data from an academic medical center, we identified patients receiving surgery over a 9-year period. We developed and validated natural language processing (NLP) algorithms to extract depression-related information (diagnosis, SSRI use, symptoms) from structured and unstructured data elements. The primary outcome was the difference between preoperative pain score and postoperative pain at discharge, 3-week and 8-week time points. We developed computational models to predict the increase or decrease in the postoperative pain across the 3 time points by using the patient's EHR data (e.g. medications, vitals, demographics) captured before surgery. We evaluate the generalizability of the model using 10-fold cross-validation method where the holdout test method is repeated 10 times and mean area-under-the-curve (AUC) is considered as evaluation metrics for the prediction performance. We identified 4,306 surgical patients with symptoms of depression. A total of 14.1% were prescribed both an SSRI and a prodrug opioid, 29.4% were prescribed an SSRI and a non-prodrug opioid, 18.6% were prescribed a prodrug opioid but were not on SSRIs, and 37.5% were prescribed a non-prodrug opioid but were not on SSRIs. Our NLP algorithm identified depression with a F1 score of 0.95 against manual annotation of 300 randomly sampled clinical notes. On average, patients receiving prodrug opioids had lower average pain scores (p<0.05), with the exception of the SSRI+ group at 3-weeks postoperative follow-up. However, SSRI+/Prodrug+ had significantly worse pain control at discharge, 3 and 8-week follow-up (p < .01) compared to SSRI+/Prodrug- patients, whereas there was no difference in pain control among the SSRI- patients by prodrug opioid (p>0.05). The machine learning algorithm accurately predicted the increase or decrease of the discharge, 3-week and 8-week follow-up pain scores when compared to the pre-operative pain score using 10-fold cross validation (mean area under the receiver operating characteristic curve 0.87, 0.81, and 0.69, respectively). Preoperative pain, surgery type, and opioid tolerance were the strongest predictors of postoperative pain control. We provide the first direct clinical evidence that the known ability of SSRIs to inhibit prodrug opioid effectiveness is associated with worse pain control among depressed patients. Current prescribing patterns indicate that prescribers may not account for this interaction when choosing an opioid. The study results imply that prescribers might instead choose direct acting opioids (e.g. oxycodone or morphine) in depressed patients on SSRIs.

High-value cancer care balances effective treatment with preservation of quality of life. Chemotherapy is known to affect patients' physical and psychological well-being negatively. Patient-reported outcomes (PROs) provide a means to monitor declines in a patients' well-being during treatment.

As artificial intelligence (AI) makes continuous progress to improve quality of care for some patients by leveraging ever increasing amounts of digital health data, others are left behind. Empirical evaluation studies are required to keep biased AI models from reinforcing systemic health disparities faced by minority populations through dangerous feedback loops. The aim of this study is to raise broad awareness of the pervasive challenges around bias and fairness in risk prediction models. We performed a case study on a MIMIC-trained benchmarking model using a broadly applicable fairness and generalizability assessment framework. While open-science benchmarks are crucial to overcome many study limitations today, this case study revealed a strong class imbalance problem as well as fairness concerns for Black and publicly insured ICU patients. Therefore, we advocate for the widespread use of comprehensive fairness and performance assessment frameworks to effectively monitor and validate benchmark pipelines built on open data resources.

Despite compelling evidence that statins are safe, are generally well tolerated, and reduce cardiovascular events, statins are underused even in patients with the highest risk. Social media may provide contemporary insights into public perceptions about statins.

Limited sharing of data sets that accurately represent disease and patient diversity limits the generalizability of artificial intelligence (AI) algorithms in health care.

With growing availability of digital health data and technology, health-related studies are increasingly augmented or implemented using real world data (RWD). Recent federal initiatives promote the use of RWD to make clinical assertions that influence regulatory decision-making. Our objective was to determine whether traditional real world evidence (RWE) techniques in cardiovascular medicine achieve accuracy sufficient for credible clinical assertions, also known as "regulatory-grade" RWE.

Acute care use (ACU) is a major driver of oncologic costs and is penalized by a Centers for Medicare & Medicaid Services quality measure, OP-35. Targeted interventions reduce preventable ACU; however, identifying which patients might benefit remains challenging. Prior predictive models have made use of a limited subset of the data in the electronic health record (EHR). We aimed to predict risk of preventable ACU after starting chemotherapy using machine learning (ML) algorithms trained on comprehensive EHR data.

Undetected infection and delayed isolation of infected individuals are key factors driving the monkeypox virus (now termed mpox virus or MPXV) outbreak. To enable earlier detection of MPXV infection, we developed an image-based deep convolutional neural network (named MPXV-CNN) for the identification of the characteristic skin lesions caused by MPXV. We assembled a dataset of 139,198 skin lesion images, split into training/validation and testing cohorts, comprising non-MPXV images (n = 138,522) from eight dermatological repositories and MPXV images (n = 676) from the scientific literature, news articles, social media and a prospective cohort of the Stanford University Medical Center (n = 63 images from 12 patients, all male). In the validation and testing cohorts, the sensitivity of the MPXV-CNN was 0.83 and 0.91, the specificity was 0.965 and 0.898 and the area under the curve was 0.967 and 0.966, respectively. In the prospective cohort, the sensitivity was 0.89. The classification performance of the MPXV-CNN was robust across various skin tones and body regions. To facilitate the usage of the algorithm, we developed a web-based app by which the MPXV-CNN can be accessed for patient guidance. The capability of the MPXV-CNN for identifying MPXV lesions has the potential to aid in MPXV outbreak mitigation.

Electronic health record (EHR) based research in oncology can be limited by missing data and a lack of structured data elements. Clinical research data warehouses for specific cancer types can enable the creation of more robust research cohorts.

Opioids are commonly prescribed for postoperative pain, but may lead to prolonged use and addiction. Diabetes impairs nerve function, complicates pain management, and makes opioid prescribing particularly challenging.

Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes-luminal A, luminal B, ERBB2-associated, basal-like and normal-like-with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes.

Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species.

Court documents have proven that a manufacturer-orchestrated strategy tried to promote gabapentin by distorting evidence in randomized trials. Given this background, we aimed to assess whether implausibly large treatment effects for gabapentin and for a similar gabapentinoid, pregabalin may have been published.

To develop and test a method for automatic assessment of a quality metric, provider-documented pretreatment digital rectal examination (DRE), using the outputs of a natural language processing (NLP) framework.

Background Statins are guideline-recommended medications that reduce cardiovascular events in patients with diabetes. Yet, statin use is concerningly low in this high-risk population. Identifying reasons for statin nonuse, which are typically described in unstructured electronic health record data, can inform targeted system interventions to improve statin use. We aimed to leverage a deep learning approach to identify reasons for statin nonuse in patients with diabetes. Methods and Results Adults with diabetes and no statin prescriptions were identified from a multiethnic, multisite Northern California electronic health record cohort from 2014 to 2020. We used a benchmark deep learning natural language processing approach (Clinical Bidirectional Encoder Representations from Transformers) to identify statin nonuse and reasons for statin nonuse from unstructured electronic health record data. Performance was evaluated against expert clinician review from manual annotation of clinical notes and compared with other natural language processing approaches. Of 33 461 patients with diabetes (mean age 59±15 years, 49% women, 36% White patients, 24% Asian patients, and 15% Hispanic patients), 47% (15 580) had no statin prescriptions. From unstructured data, Clinical Bidirectional Encoder Representations from Transformers accurately identified statin nonuse (area under receiver operating characteristic curve [AUC] 0.99 [0.98-1.0]) and key patient (eg, side effects/contraindications), clinician (eg, guideline-discordant practice), and system reasons (eg, clinical inertia) for statin nonuse (AUC 0.90 [0.86-0.93]) and outperformed other natural language processing approaches. Reasons for nonuse varied by clinical and demographic characteristics, including race and ethnicity. Conclusions A deep learning algorithm identified statin nonuse and actionable reasons for statin nonuse in patients with diabetes. Findings may enable targeted interventions to improve guideline-directed statin use and be scaled to other evidence-based therapies.

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology.org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi.owl.

The Stanford Microarray Database (SMD) (http://smd.stanford.edu) is a research tool for hundreds of Stanford researchers and their collaborators. In addition, SMD functions as a resource for the entire biological research community by providing unrestricted access to microarray data published by SMD users and by disseminating its source code. In addition to storing GenePix (Axon Instruments) and ScanAlyze output from spotted microarrays, SMD has recently added the ability to store, retrieve, display and analyze the complete raw data produced by several additional microarray platforms and image analysis software packages, so that we can also now accept data from Affymetrix GeneChips (MAS5/GCOS or dChip), Agilent Catalog or Custom arrays (using Agilent's Feature Extraction software) or data created by SpotReader (Niles Scientific). We have implemented software that allows us to accept MAGE-ML documents from array manufacturers and to submit MIAME-compliant data in MAGE-ML format directly to ArrayExpress and GEO, greatly increasing the ease with which data from SMD can be published adhering to accepted standards and also increasing the accessibility of published microarray data to the general public. We have introduced a new tool to facilitate data sharing among our users, so that datasets can be shared during, before or after the completion of data analysis. The latest version of the source code for the complete database package was released in November 2004 (http://smd.stanford.edu/download/), allowing researchers around the world to deploy their own installations of SMD.

The molecular basis of renal aging is not completely understood.