Nightingale: web components for protein feature visualization.

Motivation: The visualization of biological data is a fundamental technique that enables researchers to understand and explain biology. Some of these visualizations have become iconic, for instance: tree views for taxonomy, cartoon rendering of 3D protein structures or tracks to represent features in a gene or protein, for instance in a genome browser. Nightingale provides visualizations in the context of proteins and protein features. Results: Nightingale is a library of re-usable data visualization web components that are currently used by UniProt and InterPro, among other projects. The components can be used to display protein sequence features, variants, interaction data, 3D structure, etc. These components are flexible, allowing users to easily view multiple data sources within the same context, as well as compose these components to create a customized view. Availability and implementation: Nightingale examples and documentation are freely available at https://ebi-webcomponents.github.io/nightingale/. It is distributed under the MIT license, and its source code can be found at https://github.com/ebi-webcomponents/nightingale.

Tyroviruses are a new group of temperate phages that infect Bacillus species in soil environments worldwide.

BACKGROUND: Bacteriophages are widely considered to be highly abundant and genetically diverse, with their role in the evolution and virulence of many pathogens becoming increasingly clear. Less attention has been paid on phages preying on Bacillus, despite the potential for some of its members, such as Bacillus anthracis, to cause serious human disease. RESULTS: We have isolated five phages infecting the causative agent of anthrax, Bacillus anthracis. Using modern phylogenetic approaches we place these five new Bacillus phages, as well as 21 similar phage genomes retrieved from publicly available databases and metagenomic datasets into the Tyrovirus group, a newly proposed group named so due to the conservation of three distinct tyrosine recombinases. Genomic analysis of these large phages (~ 160-170 kb) reveals their DNA packaging mechanism and genomic features contributing to virion morphogenesis, host cell lysis and phage DNA replication processes. Analysis of the three tyrosine recombinases suggest Tyroviruses undergo a prophage lifecycle that may involve both host integration and plasmid stages. Further we show that Tyroviruses rely on divergent invasion mechanisms, with a subset requiring host S-layer for infection. CONCLUSIONS: Ultimately, we expand upon our understanding on the classification, phylogeny, and genomic organisation of a new and substantial phage group that prey on critically relevant Bacillus species. In an era characterised by a rapidly evolving landscape of phage genomics the deposition of future Tyroviruses will allow the further unravelling of the global spread and evolutionary history of these Bacillus phages.

Telehealth Utilization Among Surgical Oncology Patients at a Large Academic Cancer Center.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic increased the use of telehealth within medicine. Data on sociodemographic and clinical characteristics associated with telehealth utilization among cancer surgical patients have not been well-defined. METHODS: Cancer patients who had a surgical oncology visit at the James Cancer Hospital in March 2020-May 2021 were included. Patient demographic and clinical characteristics were recorded; access to modern information technology was measured using the Digital Divide Index (DDI). A logistic regression model was used to assess odds of receiving a telehealth. RESULTS: Among 2942 patients, median DDI was 18.2 (interquartile range 17.4-22.1). Patients were most often insured through managed care (n = 1459, 49.6%), followed by Medicare (n = 1109, 37.7%) and Medicaid (n = 267, 9.1%). Overall, 722 patients (24.5%) received at least one telehealth visit over the study period. On multivariable analysis, age (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-0.98 per 10-year increase), sex (male vs. female: OR 1.83, 95% CI 1.45-2.32), cancer type (pancreatic vs. breast: OR 9.19, 95% CI 6.38-13.23; colorectal vs. breast: OR 5.31, 95% CI 3.71-7.58), insurance type (Medicare vs. Medicaid: OR 1.58, 95% CI 1.04-2.41) and county of residence (distant vs. neighboring: OR 1.33, 95% CI 1.06-1.66) were associated with increased odds of receiving a telehealth visit. Patients from high DDI counties were not less likely to receive telehealth visits versus patients from low DDI counties (OR 1.15, 95% CI 0.85-1.57). CONCLUSIONS: Several patient sociodemographic and clinical characteristics had an impact on the likelihood of receiving a telehealth visit versus an in-person visit, suggesting that telehealth may not be equally accessible to all surgical oncology patients.

Polygenic score accuracy in ancient samples: Quantifying the effects of allelic turnover.

Polygenic scores link the genotypes of ancient individuals to their phenotypes, which are often unobservable, offering a tantalizing opportunity to reconstruct complex trait evolution. In practice, however, interpretation of ancient polygenic scores is subject to numerous assumptions. For one, the genome-wide association (GWA) studies from which polygenic scores are derived, can only estimate effect sizes for loci segregating in contemporary populations. Therefore, a GWA study may not correctly identify all loci relevant to trait variation in the ancient population. In addition, the frequencies of trait-associated loci may have changed in the intervening years. Here, we devise a theoretical framework to quantify the effect of this allelic turnover on the statistical properties of polygenic scores as functions of population genetic dynamics, trait architecture, power to detect significant loci, and the age of the ancient sample. We model the allele frequencies of loci underlying trait variation using the Wright-Fisher diffusion, and employ the spectral representation of its transition density to find analytical expressions for several error metrics, including the expected sample correlation between the polygenic scores of ancient individuals and their true phenotypes, referred to as polygenic score accuracy. Our theory also applies to a two-population scenario and demonstrates that allelic turnover alone may explain a substantial percentage of the reduced accuracy observed in cross-population predictions, akin to those performed in human genetics. Finally, we use simulations to explore the effects of recent directional selection, a bias-inducing process, on the statistics of interest. We find that even in the presence of bias, weak selection induces minimal deviations from our neutral expectations for the decay of polygenic score accuracy. By quantifying the limitations of polygenic scores in an explicit evolutionary context, our work lays the foundation for the development of more sophisticated statistical procedures to analyze both temporally and geographically resolved polygenic scores.

Implications of intensive care unit admissions among medicare beneficiaries following resection of pancreatic cancer.

BACKGROUND: Intensive care unit (ICU) use has increased among patients with cancer. We sought to define factors associated with ICU admissions among patients with pancreatic cancer and characterize trends in mortality among hospital survivors. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database was used to identify patients with pancreatic cancer who underwent resection. Multivariable analyses were conducted to identify factors associated with ICU admission and mortality among hospital survivors. RESULTS: Among 6422 Medicare beneficiaries who underwent resection of pancreatic cancer, 2386 (37.1%) had an ICU admission. Patients with ICU admissions were more likely to be younger (10-year increase odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.77-0.89), male (OR: 1.17, 95% CI 1.05-1.30) and undergo resection at a teaching hospital (OR: 1.19, 95% CI: 1.05-1.36). While the majority of patients survived to hospital discharge (n = 2106; 88.3%), a majority of patients (n = 1296; 54.3%) died within 6 months. Among patients who had subsequent ICU admissions, 1- and 5-year survival was only 31.8% and 11.0%, respectively. CONCLUSIONS: Over one-third of patients with pancreatic cancer had an ICU admission. While most patients survived hospitalization, more than one-half of patients died within 6 months of discharge and two-thirds died within 1 year. These data should serve to guide patient-provider discussions around prognosis relative to ICU utilization.

Isolation and Characterisation of the Bundooravirus Genus and Phylogenetic Investigation of the Salasmaviridae Bacteriophages.

Bacillus is a highly diverse genus containing over 200 species that can be problematic in both industrial and medical settings. This is mainly attributed to Bacillus sp. being intrinsically resistant to an array of antimicrobial compounds, hence alternative treatment options are needed. In this study, two bacteriophages, PumA1 and PumA2 were isolated and characterized. Genome nucleotide analysis identified the two phages as novel at the DNA sequence level but contained proteins similar to phi29 and other related phages. Whole genome phylogenetic investigation of 34 phi29-like phages resulted in the formation of seven clusters that aligned with recent ICTV classifications. PumA1 and PumA2 share high genetic mosaicism and form a genus with another phage named WhyPhy, more recently isolated from the United States of America. The three phages within this cluster are the only candidates to infect B. pumilus. Sequence analysis of B. pumilus phage resistant mutants revealed that PumA1 and PumA2 require polymerized and peptidoglycan bound wall teichoic acid (WTA) for their infection. Bacteriophage classification is continuously evolving with the increasing phages' sequences in public databases. Understanding phage evolution by utilizing a combination of phylogenetic approaches provides invaluable information as phages become legitimate alternatives in both human health and industrial processes.

End-of-Life Hospice Use and Medicare Expenditures Among Patients Dying of Hepatocellular Carcinoma.

BACKGROUND: The increasing incidence of hepatocellular carcinoma (HCC) coupled with rising health care costs contributes to high end-of-life expenditures. The current study aimed to characterize health care expenditures and hospice use among patients with HCC using a large, national database. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database was used to identify patients with HCC. Logistic regression was used to identify factors associated with overall hospice use and end-of-life expenditures among individuals who died of HCC. RESULTS: Among 14,369 Medicare beneficiaries with HCC, 8069 (63.7 %) used hospice. Racial/ethnic minority patients were less likely to use hospice services during the last year of life than white patients (no hospice: n = 2034 [44.3 %] vs. hospice: n = 2513 [31.1 %]). Social vulnerability also had an impact on the likelihood of patients using hospice services; in particular, the probability of hospice use among patients declined as social vulnerability increased (P < 0.05). Hospice use was associated with an approximate $10,000 decrease in inpatient expenditures (hospice: US$7900 [IQR, US$0-26,600] vs. no hospice: US$18,000 [IQR $400-49,100]; P < 0.001) and $1300 decrease in outpatient expenditures (hospice: US$900 [IQR, US$0-4500] vs. non-hospice: US$2200 [IQR, US$200-7900; P < 0.001) compared with individuals who did not use hospice. CONCLUSIONS: Minority patients and individuals residing in high-vulnerability areas were less likely to use hospice. Patients who used hospice at the end of life had a reduction in inpatient and outpatient Medicare claims. Patients with HCC in need of hospice services should be ensured timely referral regardless of race/ethnicity or social vulnerability.

Do Religious/Spiritual Preferences and Needs of Cancer Patients Vary Based on Clinical- and Treatment-Level Factors?

BACKGROUND: The objective of this study is to characterize the religion and spiritual (R&S) needs of patients who undergo cancer-directed surgery. In addition, we seek to examine how R&S needs vary based on R&S identity and clinical and surgical treatment characteristics. PATIENTS AND METHODS: A cross-sectional survey was administered to potential participants who were recruited through outpatient clinics and online. Respondent desires for R&S resources and engagement with the healthcare team  around R&S topics were assessed. RESULTS: Among 383 potential participants who were identified, 236 respondents were included in the analytic cohort. Mean age was 58.8 (SD 12.10) years, and most participants were female (75.8%) and White/Caucasian (94.1%). The majority (78.4%) identified as currently cancer free. Commonly treated malignancies included breast (43.2%), male reproductive (8.9%), skin (8.5%), and gastrointestinal (GI) (7.2%). Two-thirds of the respondents indicated a desire to have R&S incorporated into their cancer treatment (63.3%). Patients who identified as highly/moderately religious reported wanting R&S more often (highly religious: 95.2% versus moderately religious: 71.4% vs. nonreligious but spiritual: 4.5%). On multivariable analysis, patients who believed their health would improve in the future were more likely to report wanting R&S service (OR 2.2, 95% CI 1.0-4.7) as well as wanting to engage their healthcare providers on R&S topics (OR 2.4, 95% CI 1.2-4.7). In contrast, perception of current or future health status was not associated with patient desire for the actual surgeon/doctor him/herself to be involved in R&S activities (OR 1.83, 95% CI 0.97-3.45). CONCLUSIONS: Two-thirds of patients undergoing cancer-directed surgery expressed a desire to have R&S incorporated into their cancer treatment. Incorporating R&S into cancer treatment can help a subset of patients throughout their cancer experience.

The religious/spiritual beliefs and needs of cancer survivors who underwent cancer-directed surgery.

OBJECTIVE: We sought to characterize patients' preferences for the role of religious and spiritual (R&S) beliefs and practices during cancer treatment and describe the R&S resources desired by patients during the perioperative period. METHOD: A cross-sectional survey was administered to individuals who underwent cancer-directed surgery. Data on demographics and R&S beliefs/preferences were collected and analyzed. RESULTS: Among 236 participants, average age was 58.8 (SD = 12.10) years; the majority were female (76.2%), white (94.1%), had a significant other or spouse (60.2%), and were breast cancer survivors (43.6%). Overall, more than one-half (55.9%) of individuals identified themselves as being religious, while others identified as only spiritual (27.9%) or neither (16.2%). Patients who identified as religious wanted R&S integrated into their care more often than patients who were only spiritual or neither (p < 0.001). Nearly half of participants (49.6%) wanted R&S resources when admitted to the hospital including the opportunity to speak with an R&S leader (e.g., rabbi; 72.1%), R&S texts (64.0%), and journaling materials (54.1%). Irrespective of R&S identification, 68.0% of patients did not want their physician to engage with them about R&S topics. SIGNIFICANCE OF RESULTS: Access to R&S resources is important during cancer treatment, and incorporating R&S into cancer care may be especially important to patients that identify as religious. R&S needs should be addressed as part of the cancer care plan.

A variant-centric perspective on geographic patterns of human allele frequency variation.

A key challenge in human genetics is to understand the geographic distribution of human genetic variation. Often genetic variation is described by showing relationships among populations or individuals, drawing inferences over many variants. Here, we introduce an alternative representation of genetic variation that reveals the relative abundance of different allele frequency patterns. This approach allows viewers to easily see several features of human genetic structure: (1) most variants are rare and geographically localized, (2) variants that are common in a single geographic region are more likely to be shared across the globe than to be private to that region, and (3) where two individuals differ, it is most often due to variants that are found globally, regardless of whether the individuals are from the same region or different regions. Our variant-centric visualization clarifies the geographic patterns of human variation and can help address misconceptions about genetic differentiation among populations.

A Rapid Method for the Detection of Diarrhetic Shellfish Toxins and Azaspiracid Shellfish Toxins in Washington State Shellfish by Liquid Chromatography Tandem Mass Spectrometry.

BACKGROUND: Diarrhetic shellfish toxins (DSTs) in domestic shellfish and azaspiracids (AZAs) in imported products are emerging seafood safety issues in the United States. In addition to causing gastrointestinal illnesses, some of these toxins are also carcinogenic and genotoxic. Efficient analytical strategies are needed for their monitoring in U.S. domestic and imported shellfish. OBJECTIVE: In the US, DSTs and AZAs are the only lipophilic shellfish toxins addressed in regulations. Streamlining of existing methods for several classes of lipophilic toxins, based on liquid chromatography coupled with triple quadrupole mass spectrometry, was pursued. METHOD: The resulting simplified LC-MS/MS method is focused on the separation and detection of just the AZAs and total DSTs using a C18 Hypersil gold column. Filter vials are used to expedite and simplify sample handling. RESULTS: The method has a run time of 7.25 min. LOQs for the AZAs and DSTs in shellfish were 0.3-0.4 µg/kg. Recoveries (AZAs and total DSTs) for three spiking levels in three matrixes ranged from 68 to 129%. Trueness was established using certified reference materials. Method equivalence was established using shellfish provided blind by the Washington State Department of Health Public Health Laboratory (WA DOH PHL). Data obtained from these samples agreed well with data from another LC-MS/MS method used in harvest control by WA DOH PHL (R = 0.999; P < 0.0001). CONCLUSIONS: The LC-MS/MS method described offers more rapid sample handling and has excellent sensitivity, linearity, and repeatability.

The community compositions of three nitrogen removal wastewater treatment plants of different configurations in Victoria, Australia, over a 12-month operational period.

Amplicon sequence fingerprinting of communities in activated sludge systems have provided data revealing the true level of their microbial biodiversity and led to suggestions of which intrinsic and extrinsic parameters might affect the dynamics of community assemblage. Most studies have been performed in China and Denmark, and comparatively little information is available for plants in other countries. This study looked at how the communities of three plants in Victoria, Australia, treating domestic sewage changed with season. All were designed to remove nitrogen microbiologically. They were all located close together to minimise any influence that climate and demographics might have on their operation, and samples were taken at weekly intervals for 12 months. 16S rRNA amplicon sequencing revealed that each plant community was distinctively different to the others and changed over the 12-month sampling period. Many of the factors suggested in other similar studies to be important in determining community composition in activated sludge systems could not explain the changes noted here. The most likely influential factors were considered to be temperature and influent composition reflecting changes in dietary intake by the populations served by each plant, since in all three, the most noticeable changes corresponded to seasonal shifts. KEY POINTS: • Monitoring microbial communities in 3 wastewater treatment plants removing nitrogen • Temperature is the most influential factor in dynamic changes in community composition.

Inside the courtroom: An analysis of malpractice litigation in gallbladder surgery.

BACKGROUND: Cholecystectomy is one of the most commonly performed operations in the United States, yet it still carries up to a 6% risk of major morbidity. Lawsuits are a major source of emotional, financial, and personal stress for surgeons. We sought to characterize malpractice claims associated with gallbladder surgery as well as define contributing factors and costs with these claims. METHODS: The Westlaw database (Thomson Reuters Corporation, Toronto, Canada) was queried for jury verdicts and settlements related to cholecystectomy and malpractice between 2000 and 2018. Data were abstracted from the case files and details of the settlements, jury verdicts, and factors related to the claims were assessed. RESULTS: Among 231 cases, a plaintiff verdict was reached in 45 (19.5%) and a defendant verdict was reached in 122 (53%); other cases were either settled (n = 29, 12%), dismissed (n = 31, 13%), or denied (n = 4, 2%). Plaintiff cases often involved young (median age, 44 years [interquartile range: 35-57]) female (n = 146, 63%) patients. The attending surgeon accounted for 59% of defendants. Procedural error (49%), wrongful death (18%), or failure to treat in a timely manner (13%) were the most commonly cited reasons for litigation. Among the 134 cases where a second surgical procedure was performed, the most common types of procedures were biliary tract repair (n = 82, 61%) and bowel repair (n = 16, 12%). The total cost of the claims over the study period was $22 million with a median payout of $500,000; the median time from operative event to final disposition was over 5 years (interquartile range: 4-7). CONCLUSION: A plaintiff verdict or settlement was reached in 1 in 3 cases, and large payouts were common. Minimizing procedural error and improving care of patients after cholecystectomy complications should be emphasized.

Health expenditures and financial burden among patients with major gastrointestinal cancers relative to other common cancers in the United States.

BACKGROUND: Gastrointestinal cancers contribute substantially to the cost of health care. We sought to quantify and compare the financial burden associated with treatment of gastrointestinal cancers versus other common nongastrointestinal cancers. METHODS: The Medical Expenditure Panel Survey from 2006 to 2015 was used to identify individuals with gastrointestinal cancer, other nongastrointestinal cancer (breast/prostate or lung), or no history of malignancy. Total and out-of-pocket medical expenditures were compared. Among each cohort, risk of high and catastrophic financial burden was determined. RESULTS: A total of 90,344 individuals were identified, which was extrapolated to a national representative sample of 95,449,062 individuals. Overall, an estimated 365,367 (0.4%) individuals had a gastrointestinal cancer while 2,015,724 (2.1%) had lung, breast, or prostate cancer. Mean adjusted total health expenditures was greater among patients with gastrointestinal cancer ($13,716; 95% confidence interval, $9,805-$17,628) versus patients with nongastrointestinal cancer ($8,665; 95% confidence interval, $8,222-$9,108) or individuals without cancer ($5,807; 95% confidence interval $5,740-$5,874). An estimated 15.8% (n = 57,898) and 7.1% (n = 25,956) of patients with gastrointestinal cancer experienced a high and catastrophic financial burden, respectively. Patients with gastrointestinal cancer had a 64% increased odds of experiencing catastrophic financial burden compared with patients without a history of cancer (odds ratio 1.64, 95% confidence interval, 1.17-2.31). Furthermore, patients with a gastrointestinal cancer had nearly 40% increased odds of high financial burden associated with their care compared with patients without cancer (odds ratio 1.37; 95% confidence interval, 1.00-1.88). CONCLUSION: The risk of experiencing catastrophic financial burden among patients with gastrointestinal cancer was considerable, as roughly 1 in 7 patients experienced high financial burden, and 1 in 13 had a catastrophic financial burden.

Complete Genome Sequence of Moraxella osloensis Strain YV1, Isolated from an Australian Wastewater Treatment Plant.

We report the complete genome sequence of Moraxella osloensis strain YV1, which was isolated from a wastewater treatment plant in Australia. The YV1 genome comprises a 2,615,801-bp chromosome and four plasmids. Moraxella osloensis strain YV1 displays the distinctive morphology of Eikelboom morphotype 1863.

Exploring the operating factors controlling Kouleothrix (type 1851), the dominant filamentous bacterial population, in a full-scale A2O plant.

This study reveals that the abundance of the filament Kouleothrix (Eikelboom type 1851) correlated positively with poor settleability of activated sludge biomass in a Japanese full-scale nutrient removal wastewater treatment plant sampled over a one-year period. 16S rRNA amplicon sequence data confirmed that Kouleothrix was the dominant filament in the plant, with a relative abundance of 3.06% positively correlated with sludge volume index (SVI) (R = 0.691). Moreover, Kouleothrix (type 1851) appeared to form interfloc bridges, typical of bulking sludge, regardless of season. Together with earlier studies that indicated the responsibility of Kouleothrix (type 1851) on bulking events, these data suggest that their high relative abundances alone may be responsible for sludge bulking. 16S rRNA qPCR data for this filament showed changes in its relative abundance correlated with changes in several operational parameters, including mixed liquor temperature, sludge retention time, and suspended solids concentration, and it may be that manipulating these may help control Kouleothrix bulking.