Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information into the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and issues of data volume that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct or analysis.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence, the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association (STREGA) studies initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.

The Sustainable Development Goal (SDG) target 3.2 is | to end preventable deaths of newborns and children | younger than 5 years by 2030. However, in 2020, more | than 5 million children younger than 5 years died, | mostly from preventable causes, and mainly in subSaharan Africa (54%) and southern Asia (26%).1 | As | increasing numbers of children with life-threatening | illnesses seek care from hospitals, the role of highquality facility-based care becomes increasingly crucial | for achieving this SDG target.2 | A growing body of | evidence points to a previously under-recognised | contributor to child mortality: deaths after hospital | discharge. Recent studies show that approximately | half of all deaths among children admitted to hospitals | in low-income and middle-income countries (LMICs) | occur within 6 months of discharge.3,4 That half of these | post-discharge deaths occur at home is of additional | concern. These findings indicate that children who are | discharged from hospital remain highly vulnerable in | the immediate post-discharge period. The reasons for | this vulnerability are undeniably complex and could | be related to multiple interacting factors such as | premature discharge, residual underlying conditions, | risky home environments, poor health-seeking | behaviours, and weak health systems.4–6 What is clear | is that achieving SDG target 3.2 on neonatal and child | mortality will be impossible without concerted efforts | to address post-discharge mortality and that hospitals | are additional points in the health system to identify | the most vulnerable

OBJECTIVE: Electronic cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) is a novel noncommunicable disease with an unknown cause. The objective of this analysis was to describe the Minnesota Department of Health's (MDH's) outbreak response to EVALI, including challenges, successes, and lessons learned. METHODS: MDH began investigating EVALI cases in August 2019 and quickly coordinated an agencywide response. This response included activating the incident command system; organizing multidisciplinary teams to perform the epidemiologic investigation; laboratory testing of e-cigarette, or vaping, products (EVPs) and clinical specimens; and collaborating with partners to gather information and develop recommendations. RESULTS: MDH faced numerous investigational challenges during the outbreak response of EVALI, including the need to gather information on unregulated and illicit substances and their use and collecting information from minors and critically ill people. MDH laboratorians faced methodologic challenges in characterizing EVPs. Despite these challenges, MDH epidemiologists successfully collaborated with the MDH public health laboratory, law enforcement, partners with clinical and toxicology expertise, and local and national public health partners. PRACTICE IMPLICATIONS: Lessons learned included ensuring the state public health agency has legal authority to conduct noncommunicable disease outbreak investigations and the necessity of cultivating and using internal and external partnerships, specifically with laboratories that can analyze clinical specimens and unknown substances. The lessons learned may be useful to public health agencies responding to similar public health emergencies. To improve preparedness for the next outbreak of EVALI or other noncommunicable diseases, we recommend building and maintaining partnerships with internal and external partners.

This report describes and contextualizes the high prevalence of mental health conditions (MHC) among Minnesota 2019 EVALI patients by examining the prevalence of MHC and associations between MHC and e-cigarette or vaping product (EVP) use in Minnesota population surveys. Investigators reviewed medical records for 140 EVALI patients to determine history of MHC. History of MHC and EVP use in the general population was estimated using self-reported measures and screening tools from two population-based surveys, the 2019 Minnesota Student Survey (MSS) and the 2018 Minnesota Behavioral Risk Factor Surveillance Survey (MN-BRFSS). Some 64.3% of EVALI patients had an MHC. In both Minnesota population surveys, MHCs were common among people who used EVP. The odds of MHC among youth aged <18 were higher among those who reported current EVP use compared with those did not report EVP use. Similarly, the odds of depression were higher among adults who reported current EVP use compared with those who did not. Clinicians treating patients with EVALI should consider evaluating the need for, and providing indicated referrals to, post-discharge mental health services for their patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shares common clinicopathologic features with other severe pulmonary illnesses. Hantavirus pulmonary syndrome was diagnosed in 2 patients in Arizona, USA, suspected of dying from infection with SARS-CoV-2. Differential diagnoses and possible co-infections should be considered for cases of respiratory distress during the SARS-CoV-2 pandemic.

Influenza virus non-structural protein 1 (NS1) counteracts host antiviral innate immune responses by inhibiting Retinoic acid inducible gene-I (RIG-I) activation. However, whether NS1 also specifically regulates RIG-I transcription is unknown. Here, we identify a CCAAT/Enhancer Binding Protein beta (C/EBPbeta) binding site in the RIG-I promoter as a repressor element, and show that NS1 promotes C/EBPbeta phosphorylation and its recruitment to the RIG-I promoter as a C/EBPbeta/NS1 complex. C/EBPbeta overexpression and siRNA knockdown in human lung epithelial cells resulted in suppression and activation of RIG-I expression respectively, implying a negative regulatory role of C/EBPbeta. Further, C/EBPbeta phosphorylation, its interaction with NS1 and occupancy at the RIG-I promoter was associated with RIG-I transcriptional inhibition. These findings provide an important insight into the molecular mechanism by which influenza NS1 commandeers RIG-I transcriptional regulation and suppresses host antiviral responses.

During August 9-October 31, 2019, 96 patients were classified as having e-cigarette, or vaping, product use-associated lung injury (EVALI) by the Minnesota Department of Health (MDH); other patients are being investigated for case classification and exposures. Among 58 patients interviewed, 53 (91%) reported obtaining tetrahydrocannabinol (THC)-containing products from informal sources such as friends, family members, or in-person or online dealers. Using gas chromatography-mass spectrometry (GCMS), the MDH Public Health Laboratory (PHL) analyzed 46 THC-containing e-cigarette, or vaping, products obtained from 12 EVALI patients for various potential toxicants, including vitamin E acetate, which has recently been detected in some THC-containing products and in samples of lung fluid from EVALI patients (1-4). To explore whether vitamin E acetate is a recently added component in THC-containing products, MDH tested ten products seized by law enforcement in 2018, before the EVALI outbreak, and 20 products seized in 2019, during the outbreak. Twenty-four products obtained from 11 EVALI patients from 2019 contained vitamin E acetate. Among the seized products tested by MDH, none seized in 2018 contained vitamin E acetate, although all tested THC-containing products seized in 2019 tested positive for vitamin E acetate. These chemical analyses of products obtained from EVALI patients and of products intended for the illicit market both before and during the outbreak support a potential role for vitamin E acetate in the EVALI outbreak; however, the number of products tested was small, and further research is needed to establish a causal link between exposure to inhaled vitamin E acetate and EVALI. Collaboration between public health jurisdictions and law enforcement to characterize THC-containing products circulating before the recognition of the EVALI outbreak and during the outbreak might provide valuable information about a dynamic market. These Minnesota findings highlight concerns about e-cigarette, or vaping, products that contain THC acquired from informal sources. Because local supply chains and policy environments vary, CDC continues to recommend not using e-cigarette, or vaping, products that contain THC or any e-cigarette, or vaping, products obtained from informal sources. E-cigarette, or vaping, products should never be used by youths, young adults, or pregnant women.* Until the relationship between inhaled vitamin E acetate and lung health is better characterized, vitamin E acetate should not be added to e-cigarette, or vaping, products.

Retinoic acid inducible gene-I (RIG-I) is a key regulator of antiviral immunity. RIG-I is generally thought to be activated by ssRNA species containing a 5'-triphosphate (PPP) group or by unphosphorylated dsRNA up to approximately 300 bp in length. However, it is not yet clear how changes in the length, nucleotide sequence, secondary structure, and 5' end modification affect the abilities of these ligands to bind and activate RIG-I. To further investigate these parameters in the context of naturally occurring ligands, we examined RNA sequences derived from the 5' and 3' untranslated regions (UTR) of the influenza virus NS1 gene segment. As expected, RIG-I-dependent interferon-beta (IFN-beta) induction by sequences from the 5' UTR of the influenza cRNA or its complement (26 nt in length) required the presence of a 5'PPP group. In contrast, activation of RIG-I by the 3' UTR cRNA sequence or its complement (172 nt) exhibited only a partial 5'PPP-dependence, as capping the 5' end or treatment with CIP showed a modest reduction in RIG-I activation. Furthermore, induction of IFN-beta by a smaller, U/A-rich region within the 3' UTR was completely 5'PPP-independent. Our findings demonstrated that RNA sequence, length, and secondary structure all contributed to whether or not the 5'PPP moiety is needed for interferon induction by RIG-I.

BACKGROUND: Emergence of drug-resistant strains of influenza viruses, including avian H5N1 with pandemic potential, 1918 and 2009 A/H1N1 pandemic viruses to currently used antiviral agents, neuraminidase inhibitors and M2 Ion channel blockers, underscores the importance of developing novel antiviral strategies. Activation of innate immune pathogen sensor Retinoic Acid Inducible Gene-I (RIG-I) has recently been shown to induce antiviral state. RESULTS: In the present investigation, using real time RT-PCR, immunofluorescence, immunoblot, and plaque assay we show that 5'PPP-containing single stranded RNA (5PPP-RNA), a ligand for the intracytoplasmic RNA sensor, RIG-I can be used as a prophylactic agent against known drug-resistant avian H5N1 and pandemic influenza viruses. 5'PPP-RNA treatment of human lung epithelial cells inhibited replication of drug-resistant avian H5N1 as well as 1918 and 2009 pandemic influenza viruses in a RIG-I and type 1 interferon dependant manner. Additionally, 5'PPP-RNA treatment also inhibited 2009 H1N1 viral replication in vivo in mice. CONCLUSIONS: Our findings suggest that 5PPP-RNA mediated activation of RIG-I can suppress replication of influenza viruses irrespective of their genetic make-up, pathogenicity, and drug-sensitivity status.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.