Database resources of the National Center for Biotechnology Information.

The National Center for Biotechnology Information (NCBI) provides online information resources for biology, including the GenBank® nucleic acid sequence database and the PubMed® database of citations and abstracts published in life science journals. NCBI provides search and retrieval operations for most of these data from 35 distinct databases. The E-utilities serve as the programming interface for most of these databases. Resources receiving significant updates in the past year include PubMed, PMC, Bookshelf, SciENcv, the NIH Comparative Genomics Resource (CGR), NCBI Virus, SRA, RefSeq, foreign contamination screening tools, Taxonomy, iCn3D, ClinVar, GTR, MedGen, dbSNP, ALFA, ClinicalTrials.gov, Pathogen Detection, antimicrobial resistance resources, and PubChem. These resources can be accessed through the NCBI home page at https://www.ncbi.nlm.nih.gov.

RefSeq Functional Elements as experimentally assayed nongenic reference standards and functional interactions in human and mouse.

Eukaryotic genomes contain many nongenic elements that function in gene regulation, chromosome organization, recombination, repair, or replication, and mutation of those elements can affect genome function and cause disease. Although numerous epigenomic studies provide high coverage of gene regulatory regions, those data are not usually exposed in traditional genome annotation and can be difficult to access and interpret without field-specific expertise. The National Center for Biotechnology Information (NCBI) therefore provides RefSeq Functional Elements (RefSeqFEs), which represent experimentally validated human and mouse nongenic elements derived from the literature. The curated data set is comprised of richly annotated sequence records, descriptive records in the NCBI Gene database, reference genome feature annotation, and activity-based interactions between nongenic regions, target genes, and each other. The data set provides succinct functional details and transparent experimental evidence, leverages data from multiple experimental sources, is readily accessible and adaptable, and uses a flexible data model. The data have multiple uses for basic functional discovery, bioinformatics studies, genetic variant interpretation; as known positive controls for epigenomic data evaluation; and as reference standards for functional interactions. Comparisons to other gene regulatory data sets show that the RefSeqFE data set includes a wider range of feature types representing more areas of biology, but it is comparatively smaller and subject to data selection biases. RefSeqFEs thus provide an alternative and complementary resource for experimentally assayed functional elements, with future data set growth expected.

The Sequence Read Archive: a decade more of explosive growth.

The Sequence Read Archive (SRA, https://www.ncbi.nlm.nih.gov/sra/) stores raw sequencing data and alignment information to enhance reproducibility and facilitate new discoveries through data analysis. Here we note changes in storage designed to increase access and highlight analyses that augment metadata with taxonomic insight to help users select data. In addition, we present three unanticipated applications of taxonomic analysis.

Combined Ethylene Glycol Poisoning with Methemoglobinemia Due to Antifreeze Ingestion.

BACKGROUND: Antifreeze poisoning is potentially life-threatening and often requires multiple antidotal therapies and hemodialysis. Ethylene or propylene glycol toxicity is commonly caused by antifreeze ingestion. However, ingestion of antifreeze is typically not associated with methemoglobinemia. Currently, only one other case of antifreeze ingestion causing combined ethylene glycol poisoning and methemoglobinemia has been reported. CASE REPORT: A 56-year-old man presented after a witnessed, intentional, large-volume antifreeze ingestion. Evaluation revealed dark brown blood and significantly elevated methemoglobin and ethylene glycol levels. He was successfully treated with methylene blue, fomepizole, and hemodialysis. No other potential cause for methemoglobinemia was elucidated, and further research indicated that minor components of the specific antifreeze product served as an oxidizing agent. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the impact of minor, unreported product components that may significantly contribute to clinical toxicity, as well as the need to remain vigilant when reviewing product information and potential limitations therein.

Influence of Pennsylvania liquor store closures during the COVID-19 pandemic on alcohol withdrawal consultations.

INTRODUCTION: Alcohol withdrawal syndrome (AWS) is a serious consequence of alcohol use disorder (AUD). Due to the current COVID-19 pandemic there was a closure of Pennsylvania (PA) liquor stores on March 17, 2020. METHODS: This is a retrospective, observational study of AWS patients presenting to a tertiary care hospital. We used descriptive statistics for continuous and categorical variables and compared AWS consults placed to the medical toxicology service for six months preceding liquor store closure to those placed between March 17, 2020 and August 31, 2020. We compared this to consults placed to the medical toxicology service placed from October 1, 2019 through March 16, 2020. Charts were identified based on consults placed to the medical toxicology service, and alcohol withdrawal was determined via chart review by a medical toxicologist. This study did not require IRB approval. We evaluated Emergency Department (ED) length of stay (LOS), weekly and monthly consultation rate, rate of admission and ED recidivism, both pre- and post-liquor store closure. RESULTS: A total of 324 AWS consults were placed during the ten month period. 142 (43.8%) and 182 (56.2%) consults were pre- and post-liquor store closure. The number of consults was not statistically significant comparing these two time frames. There was no significant difference by patient age, gender, or race or by weekly or monthly consultation rate when comparing pre- and post-liquor store periods. The median ED LOS was 7 h (95% Confidence Interval (CI) Larson et al. (2012), Pollard et al. (2020) [5, 11]) and did not significantly differ between pre- and post-liquor store periods (p = 0.78). 92.9% of AWS patients required admission without significant difference between the pre- and post-liquor store closure periods (94.4% vs. 91.8%, p = 0.36). There was a significant increase in the number of AWS patients requiring a return ED visit (Odds Ratio 2.49; 95% CI [1.38, 4.49]) post closure. CONCLUSION: There were nearly 2.5 times greater odds of ED recidivism among post-liquor store closure AWS patients compared with pre-closure AWS patients.

Sexually acquired syphilis: Historical aspects, microbiology, epidemiology, and clinical manifestations.

Syphilis is caused by infection with the spirochetal bacterium Treponema pallidum subsp. pallidum. It was first recognized in the late 15th century. Since 2000, the incidence of sexually acquired syphilis has increased substantially in the developed world, with men who have sex with men and persons living with HIV infection disproportionately affected. Clinical manifestations of syphilis are protean and often include mucocutaneous manifestations. The first article in this continuing medical education series reviews historical aspects, microbiology, epidemiology, and clinical manifestations of sexually acquired syphilis.

Sexually acquired syphilis: Laboratory diagnosis, management, and prevention.

The methods used for the laboratory diagnosis of syphilis include direct detection of Treponema pallidum subspecies pallidum and serologic testing. Serologic testing relies on both nontreponemal and treponemal tests. In newly developed reverse-sequence screening algorithms, treponemal tests are performed before nontreponemal tests. The management of syphilis requires appropriate staging, treatment, and follow-up of patients along with the prompt reporting of infections to public health authorities to assist with prevention and control efforts. Benzathine penicillin G remains the treatment of choice for all stages of syphilis. Screening of populations at higher risk for syphilis is recommended by the US Centers for Disease Control and Prevention, the US Preventive Services Task Force, and the World Health Organization. The second article in this continuing medical education series reviews the testing for and the management of sexually acquired syphilis.

Sex differences in patients with suicidal intent that are managed by toxicologists: An analysis of the Toxicology Investigators' Consortium (ToxIC) Registry.

INTRODUCTION: The Toxicology Investigator's Consortium (ToxIC) maintains a prospective case registry of all patients that have been managed at the bedside by medical toxicologists. We set out to characterize the differences in toxicological suicide attempts between men and women among adult patients with poisonings managed by medical toxicologists. METHODS: ToxIC database consults for adults aged 19-65 whose primary reasons for encounter were classified as suicide attempt were used for this study (1/2010-12/2016). Data used for analysis included primary agents of toxic exposure, routes of administration, and complications. The statistical analysis was limited to descriptive methods. RESULTS: Out of 51,440 registry cases, 33,259 cases remained for analysis after applying the ages 19-65 and removing those without complete data. Of these, there were 4827 suicide attempts (14.5% of toxicological exposures) which were sub classified by gender. There were more females (F) than males (M) whose toxicology consults were due to suicidal attempts (57.6% versus 42.4%). We also found that more males used alcohol as their primary agent (2.8%M v 1.5%F) or a nonpharmaceutical (%7.4 M v %2.3 F). CONCLUSIONS: In our study, we found that there were more females than males who attempted suicide by self-poisoning; and more of them used pharmaceuticals than males. In contrast, a greater number of males used nonpharmaceuticals such as alcohol. We did not find large sex-differences in suicide completion rates, routes of administration, or subsequent symptomologies. In summary, sex-based differences were observed between adult patients with suicidal-intent exposures/ingestions managed at the bedside by medical toxicologists.

ClinVar: improving access to variant interpretations and supporting evidence.

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) is a freely available, public archive of human genetic variants and interpretations of their significance to disease, maintained at the National Institutes of Health. Interpretations of the clinical significance of variants are submitted by clinical testing laboratories, research laboratories, expert panels and other groups. ClinVar aggregates data by variant-disease pairs, and by variant (or set of variants). Data aggregated by variant are accessible on the website, in an improved set of variant call format files and as a new comprehensive XML report. ClinVar recently started accepting submissions that are focused primarily on providing phenotypic information for individuals who have had genetic testing. Submissions may come from clinical providers providing their own interpretation of the variant ('provider interpretation') or from groups such as patient registries that primarily provide phenotypic information from patients ('phenotyping only'). ClinVar continues to make improvements to its search and retrieval functions. Several new fields are now indexed for more precise searching, and filters allow the user to narrow down a large set of search results.

Dermatologic care for lesbian, gay, bisexual, and transgender persons: Terminology, demographics, health disparities, and approaches to care.

More than 10 million lesbian, gay, bisexual, and transgender (LGBT) persons live in the United States. Improving their health is a public health priority. LGBT persons have specific health concerns and face health care disparities. Awareness of those issues and disparities can enable dermatologists to provide medically appropriate and culturally competent care to LGBT patients. This review highlights terminology important in caring for LGBT persons, LGBT demographics in the United States, health care disparities faced by LGBT persons, and approaches to caring for LGBT patients.

Dermatologic care for lesbian, gay, bisexual, and transgender persons: Epidemiology, screening, and disease prevention.

Lesbian, gay, bisexual, and transgender (LGBT) persons face important health issues relevant to dermatologists. Men who have sex with men (MSM) are at higher risk of certain infectious diseases, including HIV, syphilis and other sexually transmitted diseases (STDs), methicillin-resistant Staphylococcus aureus infections, and invasive meningococcal disease, and might be at higher risk of non-infectious conditions, including skin cancer. Recommendations for preventive health care, including screening for HIV and other STDs, sexual health-related vaccinations, and HIV pre-exposure prophylaxis, differ for MSM compared with non-MSM. Women who have sex with women experience disparities in STDs, including chlamydia and HPV. Transgender patients have unique, and often unmet, dermatologic needs during gender transition (also called gender affirmation), related to hormonal therapy and gender-affirming surgery. Familiarity with LGBT health issues and disease-prevention guidelines can enable dermatologists to provide medically appropriate and culturally competent care to LGBT persons.

Inconsistent Collection and Reporting of Gender Minority Data in HIV and Sexually Transmitted Infection Surveillance Across the United States in 2015.

OBJECTIVES: To describe collection and reporting of gender data, including for transgender individuals and other gender minorities, in HIV and sexually transmitted infection (STI) surveillance in the United States. METHODS: We performed a cross-sectional study of the top 50 US jurisdictions in 2015 for incident infections of HIV, gonorrhea, chlamydia, or primary and secondary syphilis. For each jurisdiction, we described gender-reporting options on HIV and STI data collection forms (also called confidential morbidity report forms) and data surveillance reports, which present aggregate data at either the county or the state level. RESULTS: Seventy-one jurisdictions were among the top 50 for at least 1 infection, and we included them. Gender minority categories appeared on 60 of 71 (85%) HIV confidential morbidity report forms and 33 of 70 (47%) STI confidential morbidity report forms, and in 22 of 71 (31%) HIV surveillance reports and 8 of 71 (11%) STI surveillance reports. CONCLUSIONS: Collection and reporting of gender data were suboptimal and inconsistent. Gender minority data were collected more often than reported, suggesting barriers to reporting. Health departments should standardize collection and reporting of gender data in HIV and STI surveillance to better inform prevention and control efforts.

ClinVar: public archive of interpretations of clinically relevant variants.

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM®, GeneReviews™, UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions.

Clonidine Overdose in a Toddler Due to Accidental Ingestion of a Compounding Cream.

A 22-month-old girl without any significant medical history accidentally consumed a small amount of a therapeutic compounding cream that contained camphor, gabapentin, clonidine, ketoprofen, and lidocaine. Upon presentation to the emergency department, the child exhibited immediate onset of altered mental status with wide fluctuation in her vital signs, which included intermittent apnea requiring bag-valve mask assistance and endotracheal intubation. Serum laboratory analysis measured a clonidine level of 2.6 ng/mL and undetectable camphor, gabapentin, and ketoprofen levels. While on mechanical ventilation, the patient exhibited hypothermia, bradycardia, and hypotension; all of which responded to supportive care. After approximately 12 hours in the intensive care unit, the patient was successfully extubated and remained asymptomatic. This unique case of a patient with brief, unintentional oral exposure to a compounding cream, who demonstrated severe toxicity despite only a measured, supratherapeutic clonidine concentration, is discussed. Emergency physicians and pediatricians should be alert to the potential for exposure of pediatric patients to these medicinal compounds. Furthermore, parents must be made aware of the potential dangers of compounded medications and ensure their proper usage and storage.

Gene: a gene-centered information resource at NCBI.

The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP.

HIV-1, human interaction database: current status and new features.

The 'Human Immunodeficiency Virus Type 1 (HIV-1), Human Interaction Database', available through the National Library of Medicine at http://www.ncbi.nlm.nih.gov/genome/viruses/retroviruses/hiv-1/interactions, serves the scientific community exploring the discovery of novel HIV vaccine candidates and therapeutic targets. Each HIV-1 human protein interaction can be retrieved without restriction by web-based downloads and ftp protocols and includes: Reference Sequence (RefSeq) protein accession numbers, National Center for Biotechnology Information Gene identification numbers, brief descriptions of the interactions, searchable keywords for interactions and PubMed identification numbers (PMIDs) of journal articles describing the interactions. In addition to specific HIV-1 protein-human protein interactions, included are interaction effects upon HIV-1 replication resulting when individual human gene expression is blocked using siRNA. A total of 3142 human genes are described participating in 12,786 protein-protein interactions, along with 1316 replication interactions described for each of 1250 human genes identified using small interfering RNA (siRNA). Together the data identifies 4006 human genes involved in 14,102 interactions. With the inclusion of siRNA interactions we introduce a redesigned web interface to enhance viewing, filtering and downloading of the combined data set.

Baclofen Toxicity in a Patient with Hemodialysis-Dependent End-Stage Renal Disease.

BACKGROUND: Oral baclofen toxicity is extremely rare, but can affect patients with renal disease due to the drug's predominant renal clearance of approximately 69-85%. Patients with severely impaired renal function typically develop symptoms soon after initiating baclofen therapy, even at relatively low doses. CASE REPORT: A 69-year-old woman with a history of hemodialysis-dependent end-stage renal disease presented to the Emergency Department with encephalopathy, ataxia, and dystonia after the addition of a recent baclofen prescription for back pain (10 mg twice daily). She had been taking baclofen as prescribed for approximately 1 week when, the day prior to admission, she had increased her dose to a total of 40 mg. Diagnostic studies demonstrated the patient had chronic, end-stage renal disease and a supratherapeutic concentration of baclofen. Signs and symptoms resolved with hemodialysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is of critical importance for emergency physicians to appreciate impaired baclofen clearance in those with underlying renal disease to obviate the potential for significant drug toxicity.