MetaBIDx: a new computational approach to bacteria identification in microbiomes.

Objectives: This study introduces MetaBIDx, a computational method designed to enhance species prediction in metagenomic environments. The method addresses the challenge of accurate species identification in complex microbiomes, which is due to the large number of generated reads and the ever-expanding number of bacterial genomes. Bacterial identification is essential for disease diagnosis and tracing outbreaks associated with microbial infections. Methods: MetaBIDx utilizes a modified Bloom filter for efficient indexing of reference genomes and incorporates a novel strategy for reducing false positives by clustering species based on their genomic coverages by identified reads. The approach was evaluated and compared with several well-established tools across various datasets. Precision, recall, and F1-score were used to quantify the accuracy of species prediction. Results: MetaBIDx demonstrated superior performance compared to other tools, especially in terms of precision and F1-score. The application of clustering based on approximate coverages significantly improved precision in species identification, effectively minimizing false positives. We further demonstrated that other methods can also benefit from our approach to removing false positives by clustering species based on approximate coverages. Conclusion: With a novel approach to reducing false positives and the effective use of a modified Bloom filter to index species, MetaBIDx represents an advancement in metagenomic analysis. The findings suggest that the proposed approach could also benefit other metagenomic tools, indicating its potential for broader application in the field. The study lays the groundwork for future improvements in computational efficiency and the expansion of microbial databases.

Stromal Tumor-Infiltrating Lymphocytes Associated with Immunohistopathology and Molecular Subtypes of Breast Cancer in Vietnam.

OBJECTIVE: Breast cancer is a heterogeneous disease with varied symptoms and pathogenesis, as well as variable prognosis and therapeutic outcomes. Stromal tumor-infiltrating lymphocytes, one of the tumor microenvironment factors, has been recognized as an important immunological biomarker that reflected the antitumor immune response in breast cancer. METHODS: We analyzed 207 invasive breast cancer patients who had lumpectomy or mastectomy and have not received any pre-operative treatment. Clinicopathological characteristics, immunohistochemistry characteristics, molecular subtypes classification and stromal TILs evaluation were investigated. RESULT: Stromal TILs correlated with well-established prognostic markers. Tumor grade showed significantly higher sTILs percentages in high-grade tumors than in low-grade tumors (p<0.001). There was a statistically significant association between intermediate and high levels of sTILs and a high Ki-67 index (p< 0.001). ER/PR negative was significantly related to high sTILs. Mean sTILs score was significantly higher in TNBC (40.1±31.6%) compared to others, statistically significant (p<0.001). In HER2-negative breast cancer, sTILs were significantly associated with histologic grade, ER status, PR status, and Ki67 index. CONCLUSION: sTILs played an important role, associated with unfavorable factors in breast cancer. Our findings support the use of stromal sTILs to identify a more aggressive phenotype of tumors.

The Role of Bias in Clinical Decision-Making of People with Serious Mental Illness and Medical Co-morbidities: a Scoping Review.

The aim of this review was to examine the evidence for the impact of explicit and implicit biases against mental illness on the clinical decision-making of primary care physicians, medical students, and nurses when they are providing care to individuals with serious mental illness for cardiovascular disease, diabetes, and cancer. Studies were identified by searching MEDLINE, EBSCO host, and PsychINFO. A total of 18 studies published between 1996 and 2020 were reviewed and summarized. The studies were divided into two groups-studies that used a simulation or vignette methodology and those with a qualitative approach (interviews and focus groups). Of the simulation/vignette studies that allowed participants to report what they would have done in various clinical scenarios, there were roughly equal numbers of neutral or negative clinical decisions that represented 80% of the relevant behavioral results. Only 21% of the findings demonstrated a clinical decision that was favorable towards people with mental illness. Of the qualitative studies, all of the studies reported behaviors (either self-reported or observed) that were likely to be biased against people with mental illness, while 3 of the studies reported mixed results. Healthcare provider bias against individuals with mental illness does exist and impacts clinical decisions negatively. Much more empirical work needs to be done to determine the full extent and impact of the problem, including how these decisions affect the lives of individuals with mental illness.

Malignant Pigmented Epithelioid Angiomyolipoma of the Kidney in a Child with Tuberous Sclerosis Complex.

INTRODUCTION: Pigmented epithelioid angiomyolipoma is a variant of epithelioid angiomyolipoma (EAML) that has not previously been described in children with tuberous sclerosis. CASE PRESENTATION: A 15-year-old boy with tuberous sclerosis had a rapidly enlarging renal mass associated with a left lung nodule. Microscopically it was a pigmented EAML, confirmed by immunohistochemistry. DISCUSSION/CONCLUSION: The pigmented variant of EAML can arise and metastasize from the kidney of a teenager with tuberous sclerosis.

A Multicenter Study of Clinicopathology and Immunohistochemical Distinction between Adult and Pediatric Large B-Cell Lymphoma.

Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.

Representing bacteria with unique genomic signatures.

Classifying or identifying bacteria in metagenomic samples is an important problem in the analysis of metagenomic data. This task can be computationally expensive since microbial communities usually consist of hundreds to thousands of environmental microbial species. We proposed a new method for representing bacteria in a microbial community using genomic signatures of those bacteria. With respect to the microbial community, the genomic signatures of each bacterium are unique to that bacterium; they do not exist in other bacteria in the community. Further, since the genomic signatures of a bacterium are much smaller than its genome size, the approach allows for a compressed representation of the microbial community. This approach uses a modified Bloom filter to store short k-mers with hash values that are unique to each bacterium. We show that most bacteria in many microbiomes can be represented uniquely using the proposed genomic signatures. This approach paves the way toward new methods for classifying bacteria in metagenomic samples.

Cheminformatic quantum mechanical enzyme model design: A catechol-O-methyltransferase case study.

To accurately simulate the inner workings of an enzyme active site with quantum mechanics (QM), not only must the reactive species be included in the model but also important surrounding residues, solvent, or coenzymes involved in crafting the microenvironment. Our lab has been developing the Residue Interaction Network Residue Selector (RINRUS) toolkit to utilize interatomic contact network information for automated, rational residue selection and QM-cluster model generation. Starting from an x-ray crystal structure of catechol-O-methyltransferase, RINRUS was used to construct a series of QM-cluster models. The reactant, product, and transition state of the methyl transfer reaction were computed for a total of 550 models, and the resulting free energies of activation and reaction were used to evaluate model convergence. RINRUS-designed models with only 200-300 atoms are shown to converge. RINRUS will serve as a cornerstone for improved and automated cheminformatics-based enzyme model design.

Abatacept-Induced Panniculitis With Necrobiosis Lipoidica-Like Features in a Patient With Rheumatoid Arthritis.

We present a 57-year-old female with a past medical history of rheumatoid arthritis, hypertension, and hypothyroidism who presented with poorly demarcated, nonblanching, painful, erythematous nodules on the bilateral lower legs for two weeks. The patient recently switched from infliximab to abatacept infusions, and skin eruptions presented 53 days from her initial abatacept infusion. A 5 mm punch biopsy of the left anterior upper leg in the zone of involvement showed a deep dermal granulomatous infiltrate with associated eosinophils and a vaguely horizontally palisaded pattern with necrobiosis. The granulomatous inflammation extended into the subcutaneous septae with a widening of the septae, edema, and lipomembranous fat necrosis. The patient was started on naproxen 500 mg PO BID and halobetasol propionate 0.05% lotion BID. Concomitantly, she was started on a four-day course of oral prednisone 10 mg PO daily and restarted infliximab infusions on the third day of prednisone treatment. At her initial infliximab infusions, she received one dose of solumedrol 40 mg and diphenhydramine 50 mg. The eruption resolved 21 days after the initial presentation. The present case is unique from the nine other cutaneous eruptions described after initiating abatacept therapy. Less than 10 cases of cutaneous panniculitides have been reported as adverse reactions to abatacept, with the most common reactions associated with oral contraceptives, nonsteroidal anti-inflammatory drugs, antibiotics, and leukotriene modifying agents. This case underscores the variety of histological findings in drug-induced panniculitis, highlighting the possibility of a drug reaction in a patient with rheumatological disease presenting with panniculitis.

Is lactate lower in septic patients who are prescribed beta blockers? Retrospective cohort study of an intensive care population.

OBJECTIVE: Elevated serum lactate has long been considered an important marker of sepsis severity. Increasing evidence supports catecholamine-stimulated aerobic glycolysis being a major contributor to the hyperlactataemia seen in sepsis. Beta-blockade may blunt such catecholamine mediated rise in lactate analogous to the way it can mask tachycardia. This could impact the way we evaluate sepsis severity and adequacy of initial treatment. The objective of this study is to investigate whether septic patients who were on beta-blocker treatment at presentation have lower serum lactate level. METHODS: Using a retrospective cohort design we gathered data on patients admitted to our base hospital intensive care unit with APACHE III diagnosis of sepsis and septic shock during the 2017 calendar year. Serum lactate, current medications, presenting vital signs, illness severity scores, laboratory data and mortality outcome were extracted from patients' medical record and the unit's clinical database. RESULTS: Of 189 records analysed, 49 patients were concurrently prescribed beta-blockers. More beta-blocked patients were male, beta-blocked patients were older, and a greater proportion of beta blocked patients had their first lactate measured as an inpatient. After regression to correct for identified significant covariates mean serum lactate was 0.87 (95% confidence interval 0.05-1.69) mmol/L lower in those prescribed beta blockers. CONCLUSIONS: In our cohort pre-existing beta blocker treatment was associated with lower serum lactate measurements in patients presenting with sepsis. Pre-existing beta blocker treatment may reduce serum lactate at presentation in patients with sepsis.

icHET: interactive visualization of cytoplasmic heteroplasmy.

SUMMARY: Although heteroplasmy has been studied extensively in animal systems, there is a lack of tools for analyzing, exploring and visualizing heteroplasmy at the genome-wide level in other taxonomic systems. We introduce icHET, which is a computational workflow that produces an interactive visualization that facilitates the exploration, analysis and discovery of heteroplasmy across multiple genomic samples. icHET works on short reads from multiple samples from any organism with an organellar reference genome (mitochondrial or plastid) and a nuclear reference genome. AVAILABILITY AND IMPLEMENTATION: The software is available at https://github.com/vtphan/HeteroplasmyWorkflow. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

An accurate and fast alignment-free method for profiling microbial communities.

Determining abundances of microbial genomes in metagenomic samples is an important problem in analyzing metagenomic data. Although homology-based methods are popular, they have shown to be computationally expensive due to the alignment of tens of millions of reads from metagenomic samples to reference genomes of hundreds to thousands of environmental microbial species. We introduce an efficient alignment-free approach to estimate abundances of microbial genomes in metagenomic samples. The approach is based on solving linear and quadratic programs, which are represented by genome-specific markers (GSM). We compared our method against popular alignment-free and homology-based methods. Without contamination, our method was more accurate than other alignment-free methods while being much faster than a homology-based method. In more realistic settings where samples were contaminated with human DNA, our method was the most accurate method in predicting abundance at varying levels of contamination. We achieve higher accuracy than both alignment-free and homology-based methods.

Using 16S rRNA gene as marker to detect unknown bacteria in microbial communities.

BACKGROUND: Quantification and identification of microbial genomes based on next-generation sequencing data is a challenging problem in metagenomics. Although current methods have mostly focused on analyzing bacteria whose genomes have been sequenced, such analyses are, however, complicated by the presence of unknown bacteria or bacteria whose genomes have not been sequence. RESULTS: We propose a method for detecting unknown bacteria in environmental samples. Our approach is unique in its utilization of short reads only from 16S rRNA genes, not from entire genomes. We show that short reads from 16S rRNA genes retain sufficient information for detecting unknown bacteria in oral microbial communities. CONCLUSION: In our experimentation with bacterial genomes from the Human Oral Microbiome Database, we found that this method made accurate and robust predictions at different read coverages and percentages of unknown bacteria. Advantages of this approach include not only a reduction in experimental and computational costs but also a potentially high accuracy across environmental samples due to the strong conservation of the 16S rRNA gene.

Predictors for dioxin accumulation in residents living in Da Nang and Bien Hoa, Vietnam, many years after Agent Orange use.

Agent Orange (AO) was the main defoliant used by the US in Vietnam from 1961 to 1971; AO was contaminated with dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD). Three major dioxin "hot spots" remain from previous AO storage and use at former US bases at Bien Hoa, Da Nang, and Phu Cat, posing potential health risks for Vietnamese living on or near these hot spots. We evaluated potential risk factors contributing to serum TCDD levels in Vietnamese residents at and near contaminated sites in Da Nang and Bien Hoa, Vietnam. We used multiple linear regression to analyze possible associations of blood dioxin concentrations with demographic, socioeconomic, lifestyle, and dietary risk factors for residents living on or near these hot spots. For the Da Nang study, fish farming on the site, living on property flooded from monsoon rains, and age were among the factors showing significant positive associations with serum TCDD concentrations. For the Bien Hoa study, fish farmers working at this site and their immediate family members had significantly higher serum TCDD concentrations. Our results suggest that water-related activities, especially fish-farming, at the hot spots increased the risk of exposure to dioxin.

Exposure to extremely low frequency magnetic fields induces fos-related antigen-immunoreactivity via activation of dopaminergic d1 receptor.

We previously demonstrated that repeated exposure to extremely low frequency magnetic fields (ELF-MF) increases locomotor activity via stimulation of dopaminergic D1 receptor (J. Pharmacol. Sci., 2007;105:367-371). Since it has been demonstrated that activator protein-1 (AP-1) transcription factors, especially 35-kDa fos-related antigen (FRA), play a key role in the neuronal and behavioral adaptation in response to various stimuli, we examined whether repeated ELF-MF exposure induces FRA-immunoreactivity (FRA-IR) in the striatum and nucleus accumbens (striatal complex) of the mice. Repeated exposure to ELF-MF (0.3 or 2.4 mT, 1 h/day, for consecutive fourteen days) significantly induced hyperlocomotor activity and FRA-IR in the striatal complex in a field intensity-dependent manner. ELF-MF-induced FRA-IR lasted for at least 1 year, while locomotor activity returned near control level 3 months after the final exposure to ELF-MF. Pretreatment with SCH23390, a dopaminergic D1 receptor antagonist, but not with sulpiride, a dopaminergic D2 receptor antagonist, significantly attenuated hyperlocomotor activity and FRA-IR induced by ELF-MF. Our results suggest that repeated exposure to ELF-MF leads to prolonged locomotor stimulation and long-term expression of FRA in the striatal complex of the mice via stimulation of dopaminergic D1 receptor.