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This manuscript critically examines existing research on cyber battle management systems (CBMS) and underscores the importance of advancing complex structure thinking, cybernetics, wicked problem-solving, and emerging behavior analysis. It advocates for a systems-thinking approach to solving complex problems by identifying and understanding associated systems, predicting their behavior, and managing changes. The manuscript explores the integration of cybernetics meta-methodology and the viable system model with metasystems reductionism to address negative emergent behavior in complex systems. The study highlights the roles of individual systems, systems of systems, and metasystems, emphasizing the deterministic nature of single systems and the stochastic characteristics of systems of systems. By integrating cybernetics, viable system models, and meta-metasystems, the manuscript explores key parameters for building intelligent systems, revealing that meta-metasystems offer superior capabilities for coordinating and integrating multiple systems. The research results demonstrate the successful development of a meta-metasystem tailored for CBMS, providing a strategic framework for the future of cyber battle management.

Similar to their counterparts in K-12 education, novice university instructors often confront a unique set of challenges when teaching at the post-secondary level for the first time. This article narrates the formative experiences of a novice university instructor who also teaches English as an Additional Language (EAL). By sharing insights from my experience as an undergraduate education student, my work with EAL adults, and my first term as a university sessional instructor, this paper provides valuable lessons and reflections that emerging university educators can resonate with and learn from.

While research on the sourdough microbiome has primarily focused on lactic acid bacteria (LAB) and yeast, recent studies have found that acetic acid bacteria (AAB) are also common members. However, the ecology, genomic diversity, and functional contributions of AAB in sourdough remain unknown. To address this gap, we sequenced 29 AAB genomes, including three that represent putatively novel species, from a collection of over 500 sourdough starters surveyed globally from community scientists. We found variations in metabolic traits related to carbohydrate utilization, nitrogen metabolism, and alcohol production, as well as in genes related to mobile elements and defense mechanisms. Sourdough AAB genomes did not cluster when compared to AAB isolated from other environments, although a subset of gene functions was enriched in sourdough isolates. The lack of a sourdough-specific genomic cluster may reflect the nomadic lifestyle of AAB. To assess the consequences of AAB on the emergent function of sourdough starter microbiomes, we constructed synthetic starter microbiomes, varying only the AAB strain included. All AAB strains increased the acidification of synthetic sourdough starters relative to yeast and LAB by 18.5% on average. Different strains of AAB had distinct effects on the profile of synthetic starter volatiles. Taken together, our results begin to define the ways in which AAB shape emergent properties of sourdough and suggest that differences in gene content resulting from intraspecies diversification can have community-wide consequences on emergent function., Importance: This study is a comprehensive genomic and ecological survey of acetic acid bacteria (AAB) isolated from sourdough starters. By combining comparative genomics with manipulative experiments using synthetic microbiomes, we demonstrate that even strains with >97% average nucleotide identity can shift important microbiome functions, underscoring the importance of species and strain diversity in microbial systems. We also demonstrate the utility of sourdough starters as a model system to understand the consequences of genomic diversity at the strain and species level on multispecies communities. These results are also relevant to industrial and home-bakers as we uncover the importance of AAB in shaping properties of sourdough starters that have direct impacts on sensory notes and the quality of sourdough bread., Competing Interests: The authors declare no conflict of interest.

Organic acids (short chain fatty acids, amino acids, etc.) are common metabolic byproducts of commensal bacteria of the gut and oral cavity in addition to microbiota associated with chronic infections of the airways, skin, and soft tissues. A ubiquitous characteristic of these body sites in which mucus-rich secretions often accumulate in excess, is the presence of mucins; high molecular weight (HMW), glycosylated proteins that decorate the surfaces of non-keratinized epithelia. Owing to their size, mucins complicate quantification of microbial-derived metabolites as these large glycoproteins preclude use of 1D and 2D gel approaches and can obstruct analytical chromatography columns. Standard approaches for quantification of organic acids in mucin-rich samples typically rely on laborious extractions or outsourcing to laboratories specializing in targeted metabolomics. Here we report a high-throughput sample preparation process that reduces mucin abundance and an accompanying isocratic reverse phase high performance liquid chromatography (HPLC) method that enables quantification of microbial-derived organic acids. This approach allows for accurate quantification of compounds of interest (0.01 mM - 100 mM) with minimal sample preparation, a moderate HPLC method run time, and preservation of both guard and analytical column integrity. This approach paves the way for further analyses of microbial-derived metabolites in complex clinical samples.

Staphylococcus aureus is associated with the development of persistent and severe inflammatory diseases of the upper airways. Yet, S. aureus is also carried asymptomatically in the sinonasal cavity of ∼50% of healthy adults. The causes of this duality and host and microbial factors that tip the balance between S. aureus pathogenesis and commensalism are poorly understood. We have shown that by degrading mucins, anaerobic microbiota support the growth of airway pathogens by liberating metabolites that are otherwise unavailable. Given the widely reported culture-based detection of anaerobes from individuals with chronic rhinosinusitis (CRS), here we tested our hypothesis that CRS microbiota is characterized by a mucin-degrading phenotype that alters S. aureus physiology. Using 16S rRNA gene sequencing, we indeed observed an increased prevalence and abundance of anaerobes in CRS relative to non-CRS controls. PICRUSt2-based functional predictions suggested increased mucin degradation potential among CRS microbiota that was confirmed by direct enrichment culture. Prevotella , Fusobacterium , and Streptococcus comprised a core mucin-degrading community across CRS subjects that generated a nutrient pool that augmented S. aureus growth on mucin as a carbon source. Finally, using transcriptome sequencing (RNA-seq), we observed that S. aureus transcription is profoundly altered in the presence of mucin-derived metabolites, though expression of several key metabolism- and virulence-associated pathways varied between CRS-derived bacterial communities. Together, these data support a model in which S. aureus metabolism and virulence in the upper airways are dependent upon the composition of cocolonizing microbiota and the metabolites they exchange.

Chronic rhinosinusitis (CRS) affects nearly all individuals with cystic fibrosis (CF) and is thought to serve as a reservoir for microbiota that subsequently colonize the lung. To better understand the microbial ecology of CRS, we generated a 16S rRNA gene sequencing profile of sinus mucus from CF-CRS patients. We show that CF-CRS sinuses harbor bacterial diversity not entirely captured by clinical culture. Culture data consistently identified the dominant organism in most patients, though lower abundance bacteria were not always identified. We also demonstrate that bacterial communities dominated by Staphylococcus spp. were significantly more diverse compared to those dominated by Pseudomonas spp. Diversity was not significantly associated with clinical factors or patient age, however, younger subjects yielded a much wider range of bacterial diversity. These data mirror bacterial community dynamics in the lung and provide additional insight into the role of sinus microbiota in chronic airway disease progression., Competing Interests: Declaration of Competing Interest The authors declare no conflicts., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Culture-independent studies of cystic fibrosis lung microbiota have provided few mechanistic insights into the polymicrobial basis of disease. Deciphering the specific contributions of individual taxa to CF pathogenesis requires comprehensive understanding of their ecophysiology at the site of infection. We hypothesize that only a subset of CF microbiota are translationally active and that these activities vary between subjects. Here, we apply bioorthogonal non-canonical amino acid tagging (BONCAT) to visualize and quantify bacterial translational activity in expectorated sputum. We report that the percentage of BONCAT-labeled (i.e. active) bacterial cells varies substantially between subjects (6-56%). We use fluorescence-activated cell sorting (FACS) and genomic sequencing to assign taxonomy to BONCAT-labeled cells. While many abundant taxa are indeed active, most bacterial species detected by conventional molecular profiling show a mixed population of both BONCAT-labeled and unlabeled cells, suggesting heterogeneous growth rates in sputum. Differentiating translationally active subpopulations adds to our evolving understanding of CF lung disease and may help guide antibiotic therapies targeting bacteria most likely to be susceptible.

Many US immigrant populations develop metabolic diseases post immigration, but the causes are not well understood. Although the microbiome plays a role in metabolic disease, there have been no studies measuring the effects of US immigration on the gut microbiome. We collected stool, dietary recalls, and anthropometrics from 514 Hmong and Karen individuals living in Thailand and the United States, including first- and second-generation immigrants and 19 Karen individuals sampled before and after immigration, as well as from 36 US-born European American individuals. Using 16S and deep shotgun metagenomic DNA sequencing, we found that migration from a non-Western country to the United States is associated with immediate loss of gut microbiome diversity and function in which US-associated strains and functions displace native strains and functions. These effects increase with duration of US residence and are compounded by obesity and across generations., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Metastasis of upper airway microbiota may have significant implications in the development of chronic lung disease. Here, we compare bacterial communities of matched sinus and lung mucus samples from cystic fibrosis (CF) subjects undergoing endoscopic surgery for treatment of chronic sinusitis., Methods: Mucus from one maxillary sinus and expectorated sputum were collected from twelve patients. 16S rRNA gene sequencing was then performed on sample pairs to compare the structure and function of CF airway microbiota., Results: Bacterial diversity was comparable between airway sites, though sinuses harbored a higher prevalence of dominant microorganisms. Ordination analyses revealed that samples clustered more consistently by airway niche rather than by individual. Finally, predicted metagenomes suggested that anaerobiosis was enriched in the lung., Conclusions: Our findings indicate that while the lung may be seeded by individual sinus pathogens, airway microenvironments harbor distinct bacterial communities that should be considered in selecting antimicrobial therapies., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics., Methods: A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample., Results: A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated., Conclusions: Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of Lactobacillales in women and Corynebacterium in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.

Wechsler Memory Scale-Third edition (WMS-III) performance in 25 mild traumatic brain injury (TBI) litigants who met the criteria for probable malingered neurocognitive dysfunction (MND) was compared with 50 nonmalingering subjects. The base rate for probable MND in the population studied was 27%. Overall, malingerers showed globally depressed memory function. They returned significantly poorer scores than nonmalingerers on all WMS-III indexes and subtests, and on selected WMS-III index difference scores and intelligence-memory difference scores. Using the minimum score returned in the nonmalingerers as the cut-off for malingering, the delayed auditory recognition memory tasks were highly effective in detecting malingering. Raw scores below 43 on the auditory recognition-delayed (AR-D) subtest or below 18 on word list II-recognition, identified around 80% of the malingerers. In a group of 50 severe TBI litigants, only a very small proportion (i.e., <10%) returned scores below the cut-offs for malingering for the mild TBI subjects.

To evaluate the role of left ventricular distention in the pathophysiology of myocardial injury during cardiac surgery, 40 isolated, perfused feline hearts were subjected to 1 hour of either hypothermic potassium arrest (groups 1, 2 and 3) or 1 hour of hypothermic ventricular fibrilation (groups 4 and 5). During this period, intracavitary left ventricular pressure was maintained at 0 mm Hg in groups 1 and 4, at 30 mm Hg in groups 2 and 5 and 45 mm Hg in group 3. After either reperfusion of defibrillation, myocardial gas tensions, left ventricular function, coronary blood flow, the ration of endocardial to epicardial blood flow, and myocardial water content were measured to evaluate the degree of myocardial injury incurred. In addition, structural changes in the myocardium were assessed using light and electron microscopy. No differences in these parameters were seen in hearts that underwent ischemic arrest, regardless of the presence or absence of significant left ventricular distention. In fibrillating hearts, however, dilatation decreased ventricular performance, impaired subendocaridal blood flow and elevated myocardial CO2 tensions. These results suggest that left ventricular distention per se is not harmful during periods of ischemia. During periods of ventricular fibrillation, howevr, distention produces impaired subendocardial blood flow, resulting increased ischemia and decreased recovery of ventricular performance.

Between April, 1965, and August, 1982, 17 children ranging in age from 2 days to 4 years were identified as having interruption of the aortic arch and operated on at our institution. There were eight type A interruptions, eight type B interruptions, and one type C interruption. Associated intracardiac anomalies were present in all but 3 patients. These 3 children, who all had type A interruption, underwent repair by mobilization of the aorta and end-to-end reconstruction. The other 14 children had initial palliative operations. The 2 patients in Group 1 had type A interruption with associated ventricular septal defect (VSD), and underwent subclavian artery-aorta anastomosis. In Group 2, the palliative procedure consisted of placement of a Dacron tube graft in 1 patient with type A interruption and associated VSD, and placement of a polytetrafluoroethylene (PTFE) graft, division of the patent ductus arteriosus, and banding of the pulmonary arteries in 11 patients--2 with type A, 8 with type B, and 1 with type C interruption. Ten children (71%) survived initial palliation, 1 of the 2 in Group 1 and 9 of the 12 in Group 2. In Group 2, 5 children had interruption of the aortic arch (4, type B; 1, type C) with associated VSD; among the 4 who survived palliation, 3 subsequently have had successful closure of the VSD and 1 is awaiting closure. Among the patients who had palliative procedures, there are 6 long-term survivors (43%). In the total series, there are 9 long-term survivors (53%).(ABSTRACT TRUNCATED AT 250 WORDS)