Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity.

The 1858C>T allele of the tyrosine phosphatase PTPN22 is present in 5-10% of the North American population and is strongly associated with numerous autoimmune diseases. Although research has been done to define how this allele potentiates autoimmunity, the influence PTPN22 and its pro-autoimmune allele has in anti-viral immunity remains poorly defined. Here, we use single cell RNA-sequencing and functional studies to interrogate the impact of this pro-autoimmune allele on anti-viral immunity during Lymphocytic Choriomeningitis Virus clone 13 (LCMV-cl13) infection. Mice homozygous for this allele (PEP-619WW) clear the LCMV-cl13 virus whereas wildtype (PEP-WT) mice cannot. This is associated with enhanced anti-viral CD4 T cell responses and a more immunostimulatory CD8α- cDC phenotype. Adoptive transfer studies demonstrated that PEP-619WW enhanced anti-viral CD4 T cell function through virus-specific CD4 T cell intrinsic and extrinsic mechanisms. Taken together, our data show that the pro-autoimmune allele of Ptpn22 drives a beneficial anti-viral immune response thereby preventing what is normally a chronic virus infection.

High-throughput functional annotation of natural products by integrated activity profiling.

Determining mechanism of action (MOA) is one of the biggest challenges in natural products discovery. Here, we report a comprehensive platform that uses Similarity Network Fusion (SNF) to improve MOA predictions by integrating data from the cytological profiling high-content imaging platform and the gene expression platform Functional Signature Ontology, and pairs these data with untargeted metabolomics analysis for de novo bioactive compound discovery. The predictive value of the integrative approach was assessed using a library of target-annotated small molecules as benchmarks. Using Kolmogorov-Smirnov (KS) tests to compare in-class to out-of-class similarity, we found that SNF retains the ability to identify significant in-class similarity across a diverse set of target classes, and could find target classes not detectable in either platform alone. This confirmed that integration of expression-based and image-based phenotypes can accurately report on MOA. Furthermore, we integrated untargeted metabolomics of complex natural product fractions with the SNF network to map biological signatures to specific metabolites. Three examples are presented where SNF coupled with metabolomics was used to directly functionally characterize natural products and accelerate identification of bioactive metabolites, including the discovery of the azoxy-containing biaryl compounds parkamycins A and B. Our results support SNF integration of multiple phenotypic screening approaches along with untargeted metabolomics as a powerful approach for advancing natural products drug discovery.

Functional mapping of PHF6 complexes in chromatin remodeling, replication dynamics, and DNA repair.

The Plant Homeodomain 6 gene (PHF6) encodes a nucleolar and chromatin-associated leukemia tumor suppressor with proposed roles in transcription regulation. However, specific molecular mechanisms controlled by PHF6 remain rudimentarily understood. Here we show that PHF6 engages multiple nucleosome remodeling protein complexes, including nucleosome remodeling and deacetylase, SWI/SNF and ISWI factors, the replication machinery and DNA repair proteins. Moreover, after DNA damage, PHF6 localizes to sites of DNA injury, and its loss impairs the resolution of DNA breaks, with consequent accumulation of single- and double-strand DNA lesions. Native chromatin immunoprecipitation sequencing analyses show that PHF6 specifically associates with difficult-to-replicate heterochromatin at satellite DNA regions enriched in histone H3 lysine 9 trimethyl marks, and single-molecule locus-specific analyses identify PHF6 as an important regulator of genomic stability at fragile sites. These results extend our understanding of the molecular mechanisms controlling hematopoietic stem cell homeostasis and leukemia transformation by placing PHF6 at the crossroads of chromatin remodeling, replicative fork dynamics, and DNA repair.

Diazaquinomycins E-G, novel diaza-anthracene analogs from a marine-derived Streptomyces sp.

As part of our program to identify novel secondary metabolites that target drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC50 values against OVCAR5 of 9.0 and 8.8 µM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites.

Interspecialty Opioid Prescribing Patterns in Ophthalmology Following Declaration of a Public Health Emergency.

Purpose: Previous literature has investigated opioid prescription trends in ophthalmology at large, however, little has been done looking at differences between subspecialties. We evaluate if significant trends exist among subspecialties in opioid prescribing patterns. This study aims to illuminate potential over-usage of opioids in ophthalmology that could compromise patient quality of life. Methods: Medicare data and "National Plan and Provider Enumeration System (NPPES) Downloadable File" were queried for cases of ophthalmologists with nonsuppressed opioid prescription data from 2014 to 2019. Ophthalmologists with no subspecialty code or missing regional, gender, degree, or graduation information were excluded. Chi-squared analysis, analysis of variance, t-tests, and multivariate logistic regression were utilized. Results: Five thousand one hundred forty-three physician records were included in analysis, 450 of which were by cornea subspecialists. Most cornea cases were male, graduated before 2005, and practiced in the South. All subspecialties had a significantly increased likelihood of making opioid claims and higher prescription rates compared with cornea (P < 0.050) besides glaucoma (P = 0.357). Only oculoplastics had significantly increased likelihood of greater total supply of opioids compared with cornea (odds ratio [OR] = 22.195, 95% confidence interval [CI] = 12.209-40.350, P < 0.001), while pediatrics (OR = 4.036, 95% CI = 1.377-11.831, P = 0.011) and neuro-ophthalmology (OR = 4.158, 95% CI = 1.237-13.975, P = 0.021) in addition to oculoplastics (OR = 64.380, 95% CI = 26.306-157.560, P < 0.001) were predicted to have significantly greater opioid beneficiaries. Males, the South/Midwest, and graduating before 2005, all were generally associated with increased likelihood of greater total opioid claims, supply, beneficiaries, and prescription rate (P < 0.050). Conclusion: Subspecialty, demographic, chronological, and regional trends exist for opioid prescribing patterns in ophthalmology.

Neonatal Fc Receptor Inhibitor Therapeutics in Neuromuscular Disease.

ABSTRACT: The Neonatal Fc Receptor (FcRn) is integral to a wide variety of processes including IgG recycling, serum albumin turnover, and bacterial opsonization. Thus, targeting FcRn will increase antibody degradation including pathogenic IgGs. FcRn inhibition provides a novel therapeutic mechanism by which autoantibody titers are reduced resulting in clinical improvement and disease abatement. The FcRn targeting mechanism is similar to that of intravenous immunoglobulin (IVIg) in which saturated FcRn facilitates accelerated pathogenic IgG degradation. Recently, the FcRn inhibitor efgartigimod was approved for the treatment of myasthenia gravis. Subsequently, clinical trials of this agent have been conducted for numerous inflammatory conditions involving pathogenic autoantibodies. These disorders include the Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and inflammatory myositis. Other disorders traditionally treated with IVIg may also benefit from FcRn inhibition in certain contexts. This manuscript discusses the mechanism of FcRn inhibition, preclinical data, and the results of clinical trials of this agent for a wide range of neuromuscular diseases.

Acetyl transferase EP300 deficiency leads to chronic replication stress mediated by defective fork protection at stalled replication forks.

Mutations in the epigenetic regulator and global transcriptional activator, E1A binding protein (EP300), is being increasingly reported in aggressive hematological malignancies including adult T-cell leukemia/lymphoma (ATLL). However, the mechanistic contribution of EP300 dysregulation to cancer initiation and progression are currently unknown. Independent inhibition of EP300 in human cells results in the differential expression of genes involved in regulating the cell cycle, DNA replication and DNA damage response. Nevertheless, specific function played by EP300 in DNA replication initiation, progression and replication fork integrity has not been studied. Here, using ATLL cells as a model to study EP300 deficiency and an p300-selective PROTAC degrader, degrader as a pharmacologic tool, we reveal that EP300-mutated cells display prolonged cell cycle kinetics, due to pronounced dysregulations in DNA replication dynamics leading to persistent genomic instability. Aberrant DNA replication in EP300-mutated cells is characterized by elevated replication origin firing due to increased replisome pausing genome-wide. We demonstrate that EP300 deficiency results in nucleolytic degradation of nascently synthesized DNA at stalled forks due to a prominent defect in fork stabilization and protection. This in turn results in the accumulation of single stranded DNA gaps at collapsed replication forks, in EP300-deficient cells. Inhibition of Mre11 nuclease rescues the ssDNA accumulation indicating a dysregulation in downstream mechanisms that restrain nuclease activity at stalled forks. Importantly, we find that the absence of EP300 results in decreased expression of BRCA2 protein expression and a dependency on POLD3-mediated error-prone replication restart mechanisms. The overall S-phase abnormalities observed lead to under-replicated DNA in G2/M that instigates mitotic DNA synthesis. This in turn is associated with mitotic segregation defects characterized by elevated micronuclei formation, accumulation of cytosolic DNA and transmission of unrepaired inherited DNA lesions in the subsequent G1-phase in EP300-deficient cells. We demonstrate that the DNA replication dynamics of EP300-mutated cells ATLL cells recapitulate features of BRCA-deficient cancers. Altogether these results suggest that mutations in EP300 cause chronic DNA replication stress and defective replication fork restart results in persistent genomic instability that underlie aggressive chemo-resistant tumorigenesis in humans.

Delusions of a Magic Man Shared by Codependent Twin Sisters.

Folie à deux has been called double insanity or shared psychotic disorder. In this report, we describe the case of twin sisters who presented with identical delusions. Both sisters reported a "magic man" lived in their bodies and made them weak. Both underwent treatment with similar medications: the primary case with risperidone and the secondary case with paliperidone. The delusions of the primary case slowly abated with antipsychotics, whereas those of the secondary case completely resolved within a short duration after admission when the twins were separated in different hospital units.

A Rare Case of Intravascular Large B-cell Lymphoma Presenting With Bilateral Ophthalmoplegia, Along With a Literature Review.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of extranodal lymphoma that characteristically contains malignant lymphocytes within blood vessels. The clinical presentation of IVLBCL has high variability. In our case, the patient's initial presentation involved bilateral ptosis, restricted extraocular movements, periorbital pain, and bitemporal headache. The patient denied the classic "B symptoms" such as fever, night sweats, or weight loss. The patient also denied a family history of malignancy. Initial imaging studies were unremarkable, making diagnosis particularly challenging. Ultimately, functional endoscopic sinus surgery was performed. Pathological examination of the intraoperative specimen revealed a CD5+ large B-cell lymphoma within the vessels involving the left ethmoid sinus, respiratory mucosa, and nasal septum. The patient underwent steroid therapy prior to diagnosis, which led to rapid improvement in headache and mild improvement in extraocular function and ptosis. Following diagnosis, the patient underwent chemotherapy with supportive medications. Our case report may be considered a reference for cases presenting with extensive bilateral extraocular muscle deficits and levator palpebrae dysfunction in the absence of notable initial imaging findings, "B symptoms," or positive family history. The teaching point from this case is to demonstrate the difficulty of diagnosis and our train of thought in investigating an abnormal presentation with no clearly identifiable etiology following initial diagnostic workup and treatment.

Clinical impact of panel-based error-corrected next generation sequencing versus flow cytometry to detect measurable residual disease (MRD) in acute myeloid leukemia (AML).

We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD+ and 40.9% PC NGS-MRD+ (median VAF 0.76%). NGS-MRD+ patients had a significantly higher cumulative incidence of relapse (p = 0.003), inferior overall survival (p = 0.001) and relapse free survival (p < 0.001) as compared to NGS-MRD- patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD- patients had a significantly improved survival as compared to patients who became NGS-MRD- subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD- but FCM-MRD+. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.

Impact of COVID-19 on the Mental Health of Healthcare Professionals in Pakistan.

Introduction As a result of the ongoing COVID-19 pandemic, health care professionals (HDPs) are facing immense strain due to the heavy load of cases. In many cases, they work increasingly long hours, often with limited resources and a dubious infrastructure. Thus, it is important to check on the mental health of caregivers. Methods and materials This cross-sectional study was conducted in May 2020, at various hospitals in Karachi, Pakistan. All HCPs posted in the COVID-19 isolation wards were invited to participate and a total of 112 completed this study. A carefully structured form was created, which included the Depression Anxiety Stress Scale-21 (DASS-21). Results The overall mean score of anxiety was 19.01 ± 9.2, depression was 18.12 ± 10, and stress was 20.12 ± 12.0. There were 81 (72.3%) participants who suffered from moderate to extremely severe depression, 96 ( 85.7%) participants who suffered from moderate to extremely severe anxiety, and 101 (90.1%) participants who reported moderate to extreme stress levels Conclusions It is evident that there are a high number of healthcare workers affected by various psychological ailments such as anxiety, stress, and depression. It is important that the government take steps to ensure that HCPs' mental health is regularly checked and that efforts are made to reduce their burdens.

Comparision of Efficacy and Safety of Orlistat vs Placebo in Obese Patients in Pakistan.

Introduction Obesity has become a rising health concern in Pakistan. Several primary measures, such as dietary restrictions and regular exercise, are taken to limit the severe consequences of obesity. Still, such measures alone have been proven to be often short term and therefore, inadequate. In this study, we will evaluate the role of pharmacological management via orlistat in obesity. Methods and Materials A total of 120 patients were enrolled in this study and were divided randomly into two groups (drug arm and placebo arm) of 60 patients each. A standard dose of 120 mg capsules of orlistat given three times a day was administered to the participants of the drug arm group. A placebo was given to the participants in the second group. Baseline investigations were conducted on day 0 of the study, and follow-up visits were planned to take place in week 24 for all participants. Any side effects or adverse events were inquired about and documented in these visits. Results In the orlistat arm, we noted a significant reduction in both body mass index (BMI) (0.04) and waist circumference (0.04). Reduction in weight was more in the orlistat arm than in the placebo arm. However, it is non-significant when compared between day 0 and week 24. Adverse events, such as oily spotting (31.91%), flatus with discharge (27.65%), faecal urgency (25.53%) and fatty stool (35.553%), were significantly higher in the orlistat arm. Conclusion Orlistat has shown positive results in reducing weight, BMI and waist circumference; however, patients should be counselled about potential side effects caused by the mechanism of action of Orlistat.

Maternal and Fetal Outcome of Pregnant Patients Having Preexisting Cardiovascular Disease.

Introduction Cardiovascular disease is common in woman of all age, including child bearing age. In this study, we aim to compare maternal and fetal outcome in pregnant woman with and without preexisting cardiovascular disease. Methods This case control single center study was conducted by Obstetrics & Gynecology department and Cardiology department Shaikh Zayed Medical College/Hospital Rahimyar Khan from 1st March 2020 to 30th June 2020. Results Pregnant woman with preexisting cardiovascular disease had more preterm births and newborn with lower birth weight. Maternal and fetal deaths were numerical higher in pregnant women with preexisting cardiovascular disease but statistically non-significant compared to woman without preexisting cardiovascular disease. Conclusion It is important to identify underlying cardiovascular disease in pregnant woman. Proper counselling throughout pregnancy is needed and efforts should be made to minimize risk of maternal and fetal complications.

Correlation of Leptin With Acute Myocardial Infarction: A Case Control Study.

INTRODUCTION: Leptin, a satiety hormone, has the ability to inhibit hunger and is thus, a regulator of body weight. Leptin is also elevated in cardiovascular events such as acute myocardial infarction (AMI) and hence is considered as modifiable risk factors for AMI. The purpose of this study is therefore to investigate the correlation of leptin with AMI. METHODOLOGY: In this retrospective study, data of patients were taken from the database between January 2017 to December 2019 from a cardiovascular unit of tertiary care hospital in Pakistan. Patients were divided into two groups, based on participants who had suffered from AMI and other groups who had not suffered an AMI. Leptin levels were compared for both groups. Age, body mass index (BMI), and smoking history were noted in a self-structured questionnaire. In addition, mean blood pressure and cholesterol levels were also noted for both groups. RESULTS: Leptin was significantly higher in patients with first time AMI (29.21 ± 9.21 ng/mL vs. 11.23 ± 3.12 ng/mL: p-value, <0.0001). BMI (27.2 ± 3.2 kg/m2 vs. 24.9 ± 2.8 kg/m2: p-value, <0.0001) and percentage of smokers (40.9% vs. 22.9%: p-value, 0.032) were also significantly higher in patients with AMI. CONCLUSION: A positive correlation was found between AMI and serum leptin levels in smokers and obese patients. Hence, we suggest that cardiologists should stress upon controlling these modifiable risk factors to reduce the incidence of AMI in the future.

Machine learning derived genomics driven prognostication for acute myeloid leukemia with RUNX1-RUNX1T1.

Panel based next generation sequencing was performed on a discovery cohort of AML with RUNX1-RUNX1T1. Supervised machine learning identified NRAS mutation and absence of mutations in ASXL2, RAD21, KIT and FLT3 genes as well as a low mutation to be associated with favorable outcome. Based on this data patients were classified into favorable and poor genetic risk classes. Patients classified as poor genetic risk had a significantly lower overall survival (OS) and relapse free survival (RFS). We could validate these findings independently on a validation cohort (n = 61). Patients in the poor genetic risk group were more likely to harbor measurable residual disease. Poor genetic risk emerged as an independent risk factor predictive of inferior outcome. Using an unbiased computational approach based we provide evidence for gene panel-based testing in AML with RUNX1-RUNX1T1 and a framework for integration of genomic markers toward clinical decision making in this heterogeneous disease entity.

Assessment of Burnout and its Factors Among Doctors Using the Abbreviated Maslach Burnout Inventory.

Background Occupational burnout is an unwanted outcome of chronic workplace stressors which may be emotional or interpersonal. Chronic exposure to human suffering and long working hours have contributed to greater job stress and early burnout among healthcare providers. This study utilized the abbreviated Maslach Burnout Inventory (aMBI) to gauge the extent of overall burnout and on three subscales - perspective taking, compassionate care, and walking in patients' shoes - among interns, postgraduate trainees, and physicians of internal medicine. Materials and methods In this cross-sectional study, 71 internal medicine doctors - 40 interns, 22 postgraduate trainees, and nine physicians - completed aMBI with informed consent. It is a nine-item scale with three subscales - emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA). Each subscale has three items that are marked on a seven-point Likert scale. Higher scores of EE and DP indicate higher burnout, and a higher score of PA indicates lower burnout. Overall burnout was taken as the sum of EE and DP. Data were entered and analyzed using SPSS v. 22. Results  There were 23 (32.4%) male and 48 (67.5%) female doctors with a mean age of 24.25 ± 13.17 years. The mean score of overall burnout was 22.51 ± 6.07 (range: 0-36) and PA was 15.35 ± 1.82 (range: 0-18). Overall moderate to high burnout was seen in 33.8% of doctors. On an individual subscale, 47.8% had high EE, 24% had high DP, and 25.4% reported high burnout on PA. Overall burnout had a statistically significant correlation with the marital status of the doctors, their working hours per week, their average on-call days per week, and their level of expertise. Conclusion There is a high degree of burnout among internal medicine physicians. Working hours and the number of on-call days per week were significant predicting factors. Interns reported the highest frequency of burnout.

Comparison of the Efficacy of Duloxetine and Pregabalin in Pain Relief Associated with Diabetic Neuropathy.

Introduction Painful diabetic peripheral neuropathy (PDPN) complicates 25% of type II diabetes mellitus. It has a profound impact on diabetes-related morbidity and worsens the quality of life. Both pregabalin and duloxetine may be indicated for PDPN. In this study, the efficacy of duloxetine and pregabalin was compared in patients with PDPN. Methods It was a single-centre open-label study conducted with patients of diabetes mellitus type II diagnosed with PDPN. Patients were randomized to receive 60 mg/daily duloxetine or 300 mg/daily pregabalin. Pain scores were recorded using visual analogue scale (VAS) on day 0, week 4, and week 12. Data was entered and analysed using SPSS version 22.0 (IBM Corp., Armonk, NY). Results In the duloxetine group, the mean VAS score decreased from 6.81 ± 0.91 to 4.01 ± 1.12 with 12 weeks of therapy (p <0.0001). In the pregabalin group, the mean VAS score decreased from 6.99 ± 1.12 to 4.91 ± 0.82 with 12 weeks of therapy (p <0.0001). At 12 weeks, duloxetine showed lower VAS scores than pregabalin (p <0.0001). In the duloxetine group, the mean change in VAS score over time was - 2.80 and in the pregabalin group, the mean change was - 2.80. Adverse events were reported in 17.9% of the participants. Lethargy/somnolence (8.1%) and peripheral edema (3.4%) were commonly reported in the pregabalin group and constipation (6.9%) and orthostatic hypotension (4.6%) were commonly reported in the duloxetine group. Conclusions Duloxetine at a daily fixed dose of 60 mg is efficacious in the relief of neuropathic pain. Pregabalin also showed a comparable outcome. Both duloxetine and pregabalin have a promising safety profile and are well-tolerated.

A Genome-wide Functional Signature Ontology Map and Applications to Natural Product Mechanism of Action Discovery.

Gene expression signature-based inference of functional connectivity within and between genetic perturbations, chemical perturbations, and disease status can lead to the development of actionable hypotheses for gene function, chemical modes of action, and disease treatment strategies. Here, we report a FuSiOn-based genome-wide integration of hypomorphic cellular phenotypes that enables functional annotation of gene network topology, assignment of mechanistic hypotheses to genes of unknown function, and detection of cooperativity among cell regulatory systems. Dovetailing genetic perturbation data with chemical perturbation phenotypes allowed simultaneous generation of mechanism of action hypotheses for thousands of uncharacterized natural products fractions (NPFs). The predicted mechanism of actions span a broad spectrum of cellular mechanisms, many of which are not currently recognized as "druggable." To enable use of FuSiOn as a hypothesis generation resource, all associations and analyses are available within an open source web-based GUI (http://fusion.yuhs.ac).

The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery.

Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries.