Computational host range prediction-The good, the bad, and the ugly.

The rapid emergence and spread of antimicrobial resistance across the globe have prompted the usage of bacteriophages (i.e. viruses that infect bacteria) in a variety of applications ranging from agriculture to biotechnology and medicine. In order to effectively guide the application of bacteriophages in these multifaceted areas, information about their host ranges-that is the bacterial strains or species that a bacteriophage can successfully infect and kill-is essential. Utilizing sixteen broad-spectrum (polyvalent) bacteriophages with experimentally validated host ranges, we here benchmark the performance of eleven recently developed computational host range prediction tools that provide a promising and highly scalable supplement to traditional, but laborious, experimental procedures. We show that machine- and deep-learning approaches offer the highest levels of accuracy and precision-however, their predominant predictions at the species- or genus-level render them ill-suited for applications outside of an ecosystems metagenomics framework. In contrast, only moderate sensitivity (<80 per cent) could be reached at the strain-level, albeit at low levels of precision (<40 per cent). Taken together, these limitations demonstrate that there remains room for improvement in the active scientific field of in silico host prediction to combat the challenge of guiding experimental designs to identify the most promising bacteriophage candidates for any given application.

Developing an Appropriate Evolutionary Baseline Model for the Study of Human Cytomegalovirus.

Human cytomegalovirus (HCMV) represents a major threat to human health, contributing to both birth defects in neonates as well as organ transplant failure and opportunistic infections in immunocompromised individuals. HCMV exhibits considerable interhost and intrahost diversity, which likely influences the pathogenicity of the virus. Therefore, understanding the relative contributions of various evolutionary forces in shaping patterns of variation is of critical importance both mechanistically and clinically. Herein, we present the individual components of an evolutionary baseline model for HCMV, with a particular focus on congenital infections for the sake of illustration-including mutation and recombination rates, the distribution of fitness effects, infection dynamics, and compartmentalization-and describe the current state of knowledge of each. By building this baseline model, researchers will be able to better describe the range of possible evolutionary scenarios contributing to observed variation as well as improve power and reduce false-positive rates when scanning for adaptive mutations in the HCMV genome.

Phylogenomic analyses and host range prediction of cluster P mycobacteriophages.

Bacteriophages, infecting bacterial hosts in every environment on our planet, are a driver of adaptive evolution in bacterial communities. At the same time, the host range of many bacteriophages-and thus one of the selective pressures acting on complex microbial systems in nature-remains poorly characterized. Here, we computationally inferred the putative host ranges of 40 cluster P mycobacteriophages, including members from 6 subclusters (P1-P6). A series of comparative genomic analyses revealed that mycobacteriophages of subcluster P1 are restricted to the Mycobacterium genus, whereas mycobacteriophages of subclusters P2-P6 are likely also able to infect other genera, several of which are commonly associated with human disease. Further genomic analysis highlighted that the majority of cluster P mycobacteriophages harbor a conserved integration-dependent immunity system, hypothesized to be the ancestral state of a genetic switch that controls the shift between lytic and lysogenic life cycles-a temperate characteristic that impedes their usage in antibacterial applications.

Comparative Genomics of Closely-Related Gordonia Cluster DR Bacteriophages.

Bacteriophages infecting bacteria of the genus Gordonia have increasingly gained interest in the scientific community for their diverse applications in agriculture, biotechnology, and medicine, ranging from biocontrol agents in wastewater management to the treatment of opportunistic pathogens in pulmonary disease patients. However, due to the time and costs associated with experimental isolation and cultivation, host ranges for many bacteriophages remain poorly characterized, hindering a more efficient usage of bacteriophages in these areas. Here, we perform a series of computational genomic inferences to predict the putative host ranges of all Gordonia cluster DR bacteriophages known to date. Our analyses suggest that BiggityBass (as well as several of its close relatives) is likely able to infect host bacteria from a wide range of genera-from Gordonia to Nocardia to Rhodococcus, making it a suitable candidate for future phage therapy and wastewater treatment strategies.

Complete Genome Sequence of the Cluster P Mycobacteriophage Phegasus.

We characterized the complete genome of the cluster P mycobacteriophage Phegasus. Its 47.5-kb genome contains 81 protein-coding genes, 36 of which could be assigned a putative function. Phegasus is most closely related to two subcluster P1 bacteriophages, Mangethe and Majeke, with an average nucleotide identity of 99.63% each.

Complete Genome Sequence of the Gordonia Bacteriophage BiggityBass.

Here, we characterized the complete genome of the Siphoviridae BiggityBass, a lytic subcluster DR bacteriophage infecting Gordonia terrae CAG3. Its 63.2-kb genome contains 84 protein-coding genes, of which 40 could be assigned a putative function. BiggityBass is related most closely to AnClar and Yago84 with 90.61% and 90.52% nucleotide identity, respectively.

Nontraditional Small House Nursing Homes Have Fewer COVID-19 Cases and Deaths.

OBJECTIVES: Green House and other small nursing home (NH) models are considered "nontraditional" due to their size (10-12 beds), universal caregivers, and other home-like features. They have garnered great interest regarding their potential benefit to limit Coronavirus Disease 2019 (COVID-19) infections due to fewer people living, working, visiting, and being admitted to Green House/small NHs, and private rooms and bathrooms, but this assumption has not been tested. If they prove advantageous compared with other NHs, they may constitute an especially promising model as policy makers and providers reinvent NHs post-COVID. DESIGN: This cohort study compared rates of COVID-19 infections, COVID-19 admissions/readmissions, and COVID-19 mortality, among Green House/small NHs with rates in other NHs between January 20, 2020 and July 31, 2020. SETTING AND PARTICIPANTS: All Green House homes that held a skilled nursing license and received Medicaid or Medicare payment were invited to participate; other small NHs that replicate Green House physical design and operational practices were eligible if they had the same licensure and payer sources. Of 57 organizations, 43 (75%) provided complete data, which included 219 NHs. Comparison NHs (referred to as "traditional NHs") were up to 5 most geographically proximate NHs within 100 miles that had <50 beds and ≥50 beds for which data were available from the Centers for Medicare and Medicaid Services (CMS). Because Department of Veterans Affairs organizations are not required to report to CMS, they were not included. METHODS: Rates per 1000 resident days were derived for COVID-19 cases and admissions, and per 100 COVID-19 positive cases for mortality. A log-rank test compared rates between Green House/small NHs and traditional NHs with <50 beds and ≥50 beds. RESULTS: Rates of all outcomes were significantly lower in Green House/small NHs than in traditional NHs that had <50 beds and ≥50 beds (log-rank test P < .025 for all comparisons). The median (middle value) rates of COVID-19 cases per 1000 resident days were 0 in both Green House/small NHs and NHs <50 beds, while they were 0.06 in NHs ≥50 beds; in terms of COVID-19 mortality, the median rates per 100 positive residents were 0 (Green House/small NHs), 10 (<50 beds), and 12.5 (≥50 beds). Differences were most marked in the highest quartile: 25% of Green House/small NHs had COVID-19 case rates per 1000 resident days higher than 0.08, with the corresponding figures for other NHs being 0.15 (<50 beds) and 0.74 (≥50 beds). CONCLUSIONS AND IMPLICATIONS: COVID-19 incidence and mortality rates are less in Green House/small NHs than rates in traditional NHs with <50 and ≥50 beds, especially among the higher and extreme values. Green House/small NHs are a promising model of care as NHs are reinvented post-COVID.

A Randomized Trial Comparing Brief Advice and Motivational Interviewing for Persons with HIV-HCV Co-infection Who Drink Alcohol.

Alcohol use contributes to the progression of liver disease in HIV-HCV co-infected persons, but alcohol interventions have never addressed low levels of alcohol use in this population. We enrolled 110 persons consuming at least 4 alcoholic drinks weekly in a clinical trial comparing two active 18-month long interventions, delivered every 3 months by phone, brief advice about drinking versus a motivational intervention. Final assessment was at 24 months. MI had larger reductions in alcohol use days than the BA arm at all follow-up assessments. The treatment by time effect was not significant for days of drinking (p = 0.470), mean drinks per day (p = 0.155), or for the continuous FIB-4 index (p = 0.175). Drinking declined in both conditions from baseline, but given the small sample, we do not have sufficient data to make any conclusion that one treatment is superior to the other.Trial Registry Trial registered at clinicaltrials.gov; Clinical Trial NCT02316184.

Sustained Sobriety: A Qualitative Study of Persons with HIV and Chronic Hepatitis C Coinfection and a History of Problematic Drinking.

For persons diagnosed with HIV and who are coinfected with hepatitis C virus (HCV), chronic liver disease is a leading cause of death and excessive consumption of alcohol can be a contributing factor. Little is known about the factors these individuals identify as key to achieving sustained sobriety. In this qualitative study, fourteen HIV/HCV coinfected persons who endorsed past problematic drinking were interviewed about their path to sustained sobriety. In open-ended interviews, participants often described their drinking in the context of polysubstance use and their decision to become sober as a singular response to a transcendent moment or a traumatic event. All articulated specific, concrete strategies for maintaining sobriety. The perceived effect of the HIV or HCV diagnosis on sobriety was inconsistent, and medical care as an influence on sobriety was rarely mentioned. Qualitative interviews may offer new insights on interventions and support strategies for heavy-drinking persons with HIV/HCV coinfection.

Perceptions of Alcohol Risk Among HIV/Hepatitis C Coinfected Patients.

OBJECTIVES: We examined how patient perceptions of alcohol risk, provider discussions about alcohol, and treatment of hepatitis C virus (HCV) differed among HIV-HCV coinfected patients in primary care. METHODS: Between April, 2016 and April, 2017, we conducted a screening survey with patients in an HIV primary care clinic in Seattle, Washington, who had chronic HCV coinfection or a history of chronic HCV infection who had successfully cleared their infection with treatment. RESULTS: Of 225 participants, 84 (37%) were active drinkers (drank ≥2-4 times/mo in past 3 months). Of those with little to no use for ≥3 months, 65 (29%) were former drinkers with a history of alcohol use and 76 were abstainers with no such history. Former drinkers and abstainers were more likely than active drinkers to perceive that any drinking was unsafe (69% vs 58% vs 31%; P < 0.001). Former drinkers were more likely to report a physician's recommendation to stop drinking than active drinkers (63% vs 47%; P = 0.05). The great majority (87%) of former drinkers decided to stop or reduce drinking on their own (most often in response to a nonhealth life event) and only 13% acknowledged doing so on their doctor's prompting. HCV treatment was not associated with former or active drinking status. CONCLUSIONS: Our findings underscore the importance of educating not only HIV-HCV patients about the effects of alcohol use but also HIV clinicians about delivering consistent counseling about alcohol avoidance. Understanding the reasons that HIV-HCV coinfected persons make changes in their alcohol use could drive novel interventions that reduce the negative consequences of drinking.

accuMUlate: a mutation caller designed for mutation accumulation experiments.

Summary: Mutation accumulation (MA) is the most widely used method for directly studying the effects of mutation. By sequencing whole genomes from MA lines, researchers can directly study the rate and molecular spectra of spontaneous mutations and use these results to understand how mutation contributes to biological processes. At present there is no software designed specifically for identifying mutations from MA lines. Here we describe accuMUlate, a probabilistic mutation caller that reflects the design of a typical MA experiment while being flexible enough to accommodate properties unique to any particular experiment. Availability and implementation accuMUlate is available from https://github.com/dwinter/accuMUlate. Supplementary information: Supplementary data are available at Bioinformatics online.

Clinicians' perceptions of the usefulness of a communication facilitator in the intensive care unit.

BACKGROUND: Despite its documented importance, communication between clinicians and patients' families in the intensive care unit often fails to meet families' needs, and interventions to improve communication are needed. Use of a communication facilitator-an additional staff member-to improve communication between clinicians and patients' families is the focus of an ongoing randomized trial. The clinical team's acceptance of the communication facilitator as an integral part of the team is important. OBJECTIVES: To explore clinicians' perceptions of the usefulness of a communication facilitator in the intensive care unit. METHODS: Fourteen semistructured qualitative interviews to assess perspectives of physicians, nurses, and social workers who had experience with the communication facilitator intervention on the intervention and the role of the facilitator. Methods based on grounded theory were used to analyze the data. RESULTS: Clinicians perceived facilitators as (1) facilitating communication between patients' families and clinicians, (2) providing practical and emotional support for patients' families, and (3) providing practical and emotional support for clinicians. Clinicians were enthusiastic about the communication facilitator but concerned about overlapping or conflicting roles. CONCLUSIONS: Clinicians in the intensive care unit saw the facilitator intervention as enhancing communication and supporting both patients' families and clinicians. They also identified the importance of the facilitator within the interdisciplinary team. Negative perceptions about the use of a facilitator should be addressed before the intervention is implemented, in order to ensure its effectiveness.