Sparsity of higher-order landscape interactions enables learning and prediction for microbiomes.

Microbiome engineering offers the potential to leverage microbial communities to improve outcomes in human health, agriculture, and climate. To translate this potential into reality, it is crucial to reliably predict community composition and function. But a brute force approach to cataloging community function is hindered by the combinatorial explosion in the number of ways we can combine microbial species. An alternative is to parameterize microbial community outcomes using simplified, mechanistic models, and then extrapolate these models beyond where we have sampled. But these approaches remain data-hungry, as well as requiring an a priori specification of what kinds of mechanisms are included and which are omitted. Here, we resolve both issues by introducing a mechanism-agnostic approach to predicting microbial community compositions and functions using limited data. The critical step is the identification of a sparse representation of the community landscape. We then leverage this sparsity to predict community compositions and functions, drawing from techniques in compressive sensing. We validate this approach on in silico community data, generated from a theoretical model. By sampling just [Formula: see text]1% of all possible communities, we accurately predict community compositions out of sample. We then demonstrate the real-world application of our approach by applying it to four experimental datasets and showing that we can recover interpretable, accurate predictions on composition and community function from highly limited data.

Universal abundance fluctuations across microbial communities, tropical forests, and urban populations.

The growth of complex populations, such as microbial communities, forests, and cities, occurs over vastly different spatial and temporal scales. Although research in different fields has developed detailed, system-specific models to understand each individual system, a unified analysis of different complex populations is lacking; such an analysis could deepen our understanding of each system and facilitate cross-pollination of tools and insights across fields. Here, we use a shared framework to analyze time-series data of the human gut microbiome, tropical forest, and urban employment. We demonstrate that a single, three-parameter model of stochastic population dynamics can reproduce the empirical distributions of population abundances and fluctuations in all three datasets. The three parameters characterizing a species measure its mean abundance, deterministic stability, and stochasticity. Our analysis reveals that, despite the vast differences in scale, all three systems occupy a similar region of parameter space when time is measured in generations. In other words, although the fluctuations observed in these systems may appear different, this difference is primarily due to the different physical timescales associated with each system. Further, we show that the distribution of temporal abundance fluctuations is described by just two parameters and derive a two-parameter functional form for abundance fluctuations to improve risk estimation and forecasting.

Functional convergence in slow-growing microbial communities arises from thermodynamic constraints.

The dynamics of microbial communities is complex, determined by competition for metabolic substrates and cross-feeding of byproducts. Species in the community grow by harvesting energy from chemical reactions that transform substrates to products. In many anoxic environments, these reactions are close to thermodynamic equilibrium and growth is slow. To understand the community structure in these energy-limited environments, we developed a microbial community consumer-resource model incorporating energetic and thermodynamic constraints on an interconnected metabolic network. The central element of the model is product inhibition, meaning that microbial growth may be limited not only by depletion of metabolic substrates but also by accumulation of products. We demonstrate that these additional constraints on microbial growth cause a convergence in the structure and function of the community metabolic network-independent of species composition and biochemical details-providing a possible explanation for convergence of community function despite taxonomic variation observed in many natural and industrial environments. Furthermore, we discovered that the structure of community metabolic network is governed by the thermodynamic principle of maximum free energy dissipation. Our results predict the decrease of functional convergence in faster growing communities, which we validate by analyzing experimental data from anaerobic digesters. Overall, the work demonstrates how universal thermodynamic principles may constrain community metabolism and explain observed functional convergence in microbial communities.

Ecological landscapes guide the assembly of optimal microbial communities.

Assembling optimal microbial communities is key for various applications in biofuel production, agriculture, and human health. Finding the optimal community is challenging because the number of possible communities grows exponentially with the number of species, and so an exhaustive search cannot be performed even for a dozen species. A heuristic search that improves community function by adding or removing one species at a time is more practical, but it is unknown whether this strategy can discover an optimal or nearly optimal community. Using consumer-resource models with and without cross-feeding, we investigate how the efficacy of search depends on the distribution of resources, niche overlap, cross-feeding, and other aspects of community ecology. We show that search efficacy is determined by the ruggedness of the appropriately-defined ecological landscape. We identify specific ruggedness measures that are both predictive of search performance and robust to noise and low sampling density. The feasibility of our approach is demonstrated using experimental data from a soil microbial community. Overall, our results establish the conditions necessary for the success of the heuristic search and provide concrete design principles for building high-performing microbial consortia.

Impact of Living Donor Liver Transplantation on COVID-19 Clinical Outcomes from a Quaternary Care Centre in Delhi.

Background and Aims: The anticipated fear of serious outcomes in coronavirus infected liver transplant recipients led to disruption of transplant services globally. The aim of our study was to analyze COVID-19 severity in transplant recipients and to compare the difference of COVID-19 clinical outcomes in early (<1 year) vs. late (>1 year) post-transplant period. Methods: 41 post-living donor liver transplant recipients with COVID-19 infection were studied retrospectively from 1st April 2020 to 28th February 2021. Results: The median age was 49.00 years with a male preponderance (80.49%). Fifteen patients had infection within 1 year of transplant and 26 were infected after 1 year of transplant. The overall median interval between transplantation and COVID-19 diagnosis was 816.00 days. Fever and malaise were the common presenting symptoms. The most common associated comorbidities were diabetes mellitus (65.85%) and hypertension (46.34%). The severity of illness was mild in 28 (68.29%), moderate in 4 (9.76%), severe in 6 (14.63%) and critical in 3 (7.32%). To identify associated risk factors, we divided our patients into less severe and more severe groups. Except for lymphopenia, there was no worsening of total bilirubin, transaminases, alkaline phosphatase, and gamma-glutamyl transferase in the more severe group. Eight (19.51%) patients required intensive care unit admission and three (7.32%) died, while none suffered graft rejection. In recipients with early vs. late post-transplant COVID-19 infection, there were similar outcomes in terms of severity of COVID-19 illness, intensive care unit care need, requirement of respiratory support, and death. Conclusion: Living donor liver transplantation can be performed during the COVID-19 pandemic without the fear of poor recipient outcome in cases of unfortunate contraction of severe acute respiratory syndrome coronavirus-2.

Protein cost minimization promotes the emergence of coenzyme redundancy.

SignificanceMetabolism relies on a small class of molecules (coenzymes) that serve as universal donors and acceptors of key chemical groups and electrons. Although metabolic networks crucially depend on structurally redundant coenzymes [e.g., NAD(H) and NADP(H)] associated with different enzymes, the criteria that led to the emergence of this redundancy remain poorly understood. Our combination of modeling and structural and sequence analysis indicates that coenzyme redundancy may not be essential for metabolism but could rather constitute an evolved strategy promoting efficient usage of enzymes when biochemical reactions are near equilibrium. Our work suggests that early metabolism may have operated with fewer coenzymes and that adaptation for metabolic efficiency may have driven the rise of coenzyme diversity in living systems.

A case of recurrent pneumothoraces in a newborn.

Pneumothoraces are not an uncommon finding in the newborn period. Recurrent pneumothoraces can be associated with complications of prematurity or use of ventilators but can be seen in rapidly progressive cystic lung disease. We report a case of recurrent pneumothoraces in an infant with the rapidly progressive cystic disease in the setting of an absent right pulmonary artery. The patient ultimately underwent pneumonectomy for definitive management of the recurrent unilateral pneumothoraces.

Complementary resource preferences spontaneously emerge in diauxic microbial communities.

Many microbes grow diauxically, utilizing the available resources one at a time rather than simultaneously. The properties of communities of microbes growing diauxically remain poorly understood, largely due to a lack of theory and models of such communities. Here, we develop and study a minimal model of diauxic microbial communities assembling in a serially diluted culture. We find that unlike co-utilizing communities, diauxic community assembly repeatably and spontaneously leads to communities with complementary resource preferences, namely communities where species prefer different resources as their top choice. Simulations and theory explain that the emergence of complementarity is driven by the disproportionate contribution of the top choice resource to the growth of a diauxic species. Additionally, we develop a geometric approach for analyzing serially diluted communities, with or without diauxie, which intuitively explains several additional emergent community properties, such as the apparent lack of species which grow fastest on a resource other than their most preferred resource. Overall, our work provides testable predictions for the assembly of natural as well as synthetic communities of diauxically shifting microbes.

Unexpected decline in pediatric asthma morbidity during the coronavirus pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic profoundly impacted health care utilization. We evaluated asthma-related emergency department (ED) and inpatient health care utilization by a county-specific Medicaid population, ages 2-18, during the COVID-19 pandemic and compared it to utilization from a 3-year average including 2017-2019. All-cause ED utilization and asthma medication fill rates were evaluated during the same timeframes. Relative to the 2017-2019 3-year average, cumulative asthma-related ED visits from January through June decreased by 45.8% (p = .03) and inpatient admission rates decreased by 50.5% (p = .03). The decline in asthma-related ED utilization was greater than the reduction of overall ED use during the same time period, suggesting that the decline involved factors specific to asthma and was not due solely to avoidance of health care facilities. Fill rates for asthma controller medications decreased during this time (p = .03) and quick relief medication fill rates had no significant change (p = .31). Multiple factors may have contributed to the decrease in acute asthma health care visits. Locally, decreased air pollution and viral exposures coincided with the "Stay-at-home" order in Ohio, and increased utilization of telehealth for assessment during exacerbations may have impacted outcomes. Identification of the cause of the decline in visit rates could spur new interventions to limit the need for ED and inpatient visits for asthma patients, leading to both economic and health-associated benefits.

Survey of patients with cystic fibrosis and caregivers decisions regarding CFTR modulators.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are a novel approach to CF management that has become more readily available chronic CF therapies for certain populations of patients with CF. A cross-sectional survey of adults with CF and caregivers of pediatric patients with CF was done in two CF Centers to better understand the decision-making process including the potential influence of social media, CF care-teams, and family members on their decision whether to begin a CFTR modulator. For the 90 participants, the most common influences in the decision to start modulator therapy were the CF providers/care teams (n = 63), parents (n = 49), and individuals with CF (n = 27). The most impactful influence in the decision-making process were providers/care team (n = 47) and parents (n = 18). Social media was an influence for only 12 respondents, with an overall positive impact. Information from the CF Foundation was an influence for 12 participants and the main influence for six participants. The most common reasons for stopping lumacaftor-ivacaftor were having tezacaftor-ivacaftor as an option (n = 25) and side-effects (n = 15). Family and CF clinicians were the two main influences on the decision to initiate modulator therapy. CF clinicians were seen to be the most influential source. Social media had less influence on the decision-making process than expected despite the wide presence of the CF community online.

A comprehensive review on chemical properties and applications of biopolymers and their composites.

In a world that canopies numerous opportunities to advance towards a green sustainable life, biopolymer development offers a platform that fits into the paradigm of achieving an eco-friendly environment whilst reducing reliance on the scarce fossil fuel elements for the fabrication of day-to-day products. Today's technological improvements have aided biopolymer end-products to escalate to higher purposes and soon may have their performance level in par with the petroleum-based synthetic polymers. The motive of this paper is to shimmer light on some aspects of biopolymers that include its classes, properties, composites and applications. Depending on the type of class on the basis of various categories, many enthralling chemistries of polymer composition can be substantiated. Essential properties can imparted to the ensuing biopolymer by altering its chemical configuration and method of synthesis while also focusing on its functional purpose. Nowadays, biopolymer composites blend qualities of one biopolymer with another to acquire an enhanced component that showcases unique explicit attributes. There are several techniques to process biopolymer composites, of which in-situ, infiltration and electrospinning methods have captured considerable limelight. Biopolymers and its composites have embarked captivating impressions in regions of biomedical, packaging, agricultural and automotive applications. Although their efficacy is yet to reach their fossil fuel counterparts, biopolymers have laid a distinguishing mark that will continue to inspire creation of novel substances for many years to come.

Ex situ liver resection and autotransplantation for advanced cholangiocarcinoma.

Advanced cholangiocarcinoma especially those involving the vasculature have extremely limited options of cure. Ex situ liver resection entails performing a total hepatectomy, resecting the tumour on the back-table followed by reimplantation (autotransplantation) of the liver. Application of this technique for these tumours has rarely been done due to complexity of the procedure and the dismal prognosis of the lesions. We present our experience of two cases of advanced intrahepatic cholangiocarcinoma with limited extrahepatic disease who underwent ex situ resection with autotransplantation. They underwent preoperative therapy with a waiting period to assess the tumour biology. Both patients underwent ex situ resection with extended hepatectomy on the back table. Both patients remain well on follow-up 24 months and 20 months, respectively, with excellent quality of life. Despite its technical complexity, ex situ liver resection may offer prolonged overall survival in selected patients with advanced cholangiocarcinoma and limited extrahepatic disease.

Pinned, locked, pushed, and pulled traveling waves in structured environments.

Traveling fronts describe the transition between two alternative states in a great number of physical and biological systems. Examples include the spread of beneficial mutations, chemical reactions, and the invasions by foreign species. In homogeneous environments, the alternative states are separated by a smooth front moving at a constant velocity. This simple picture can break down in structured environments such as tissues, patchy landscapes, and microfluidic devices. Habitat fragmentation can pin the front at a particular location or lock invasion velocities into specific values. Locked velocities are not sensitive to moderate changes in dispersal or growth and are determined by the spatial and temporal periodicity of the environment. The synchronization with the environment results in discontinuous fronts that propagate as periodic pulses. We characterize the transition from continuous to locked invasions and show that it is controlled by positive density-dependence in dispersal or growth. We also demonstrate that velocity locking is robust to demographic and environmental fluctuations and examine stochastic dynamics and evolution in locked invasions.

Chirality provides a direct fitness advantage and facilitates intermixing in cellular aggregates.

Chirality in shape and motility can evolve rapidly in microbes and cancer cells. To determine how chirality affects cell fitness, we developed a model of chiral growth in compact aggregates such as microbial colonies and solid tumors. Our model recapitulates previous experimental findings and shows that mutant cells can invade by increasing their chirality or switching their handedness. The invasion results either in a takeover or stable coexistence between the mutant and the ancestor depending on their relative chirality. For large chiralities, the coexistence is accompanied by strong intermixing between the cells, while spatial segregation occurs otherwise. We show that the competition within the aggregate is mediated by bulges in regions where the cells with different chiralities meet. The two-way coupling between aggregate shape and natural selection is described by the chiral Kardar-Parisi-Zhang equation coupled to the Burgers' equation with multiplicative noise. We solve for the key features of this theory to explain the origin of selection on chirality. Overall, our work suggests that chirality could be an important ecological trait that mediates competition, invasion, and spatial structure in cellular populations.

Surgical Management of Life Threatening Bleeding after Endoscopic Cystogastrostomy.

Postprocedural bleeding is a rare but life threatening complication of endoscopic cystogastrostomy which may require surgical management in some patients. The presence of adhesions and inflammation due to antecedent acute pancreatitis, difficult location of the bleeding site and breach in the posterior wall of stomach pose significant challenges during the surgical management. Here we have described the surgical approach and technique that we used to manage three patients who required surgery for life threatening bleeding after endoscopic cystogastrostomy.

Higher prevalence of coagulase-negative staphylococci carriage among reclaimed water spray irrigators.

Coagulase negative staphylococci (CoNS) are leading causes of nosocomial infections and community-acquired methicillin-resistant CoNS (MRCoNS) infections are increasing. CoNS have been previously detected in reclaimed water. To date, no studies have evaluated the prevalence of CoNS carriage among humans exposed to reclaimed water in the U.S. We examined the prevalence and odds of CoNS and antibiotic-resistant CoNS carriage in spray irrigators exposed to reclaimed water compared to controls. We collected nasal and dermal swab samples from 19 reclaimed water spray irrigation workers (n=96 total samples) and 24 controls (n=92 total samples). Samples were analyzed for CoNS using culture-based assays. Isolates were confirmed using biochemical tests and PCR. Antimicrobial susceptibility testing was performed using disk diffusion. Data were analyzed by two-sample proportion tests, logistic regression, and generalized linear mixed effects models. The prevalence of CoNS, antibiotic-resistant CoNS, and MRCoNS carriage among spray irrigation workers was 79% (15/19), 32% (6/19), and 16% (3/19), compared to 13% (3/24), 4% (1/24), and 0% (0/24) of controls. Spray irrigators were more likely to be carriers of CoNS (p<0.01), antibiotic-resistant CoNS (p<0.01), and MRCoNS (p=0.02) compared to controls. The odds of CoNS carriage significantly increased with exposure to reclaimed water (p=0.04) even accounting for changes over time (p=0.05). Our data highlight the need to further examine the potential dissemination of CoNS and antibiotic-resistant CoNS from reclaimed water into the environment and human communities and related public health implications.

A case of sulfhemoglobinemia in a child with chronic constipation.

Sulfhemoglobinemia is a rare condition in which a sulfur atom oxidizes the heme moiety in hemoglobin, making the hemoglobin incapable of carrying oxygen and leading to hypoxia and cyanosis. This condition has been described in patients taking sulfur medications or who have cultured hydrogen sulfide producing intestinal bacteria such as Morganella morganii. This case describes a pediatric patient who was found to have cyanosis on two occasions of urinary tract infection in the setting of chronic constipation, with confirmed sulfhemoglobinemia during the second admission. Sulfhemoglobinemia due to increases in sulfur producing intestinal bacteria led to cyanosis and low oxygen saturations. The patient had an incidental finding of a pulmonary arteriovenous malformation (AVM) but had a normal PAO2 so was not hypoxemic though she was cyanotic. Low oxygen saturations by pulse oximetry may be explained by dyshemoglobinemia as opposed to true arterial hypoxemia; the importance of measuring an arterial blood gas in cases of cyanosis is paramount.

Resilience and receptivity worked in tandem to sustain a geothermal mat community amidst erratic environmental conditions.

To elucidate how geothermal irregularities affect the sustainability of high-temperature microbiomes we studied the synecological dynamics of a geothermal microbial mat community (GMMC) vis-à-vis fluctuations in its environment. Spatiotemporally-discrete editions of a photosynthetic GMMC colonizing the travertine mound of a circum-neutral hot spring cluster served as the model-system. In 2010 a strong geyser atop the mound discharged mineral-rich hot water, which nourished a GMMC continuum from the proximal channels (PC) upto the slope environment (SE) along the mound's western face. In 2011 that geyser extinguished and consequently the erstwhile mats disappeared. Nevertheless, two relatively-weaker vents erupted in the southern slope and their mineral-poor outflow supported a small GMMC patch in the SE. Comparative metagenomics showed that this mat was a relic of the 2010 community, conserved via population dispersal from erstwhile PC as well as SE niches. Subsequently in 2012, as hydrothermal activity augmented in the southern slope, ecological niches widened and the physiologically-heterogeneous components of the 2011 "seed-community" split into PC and SE meta-communities, thereby reclaiming either end of the thermal gradient. Resilience of incumbent populations, and the community's receptiveness towards immigrants, were the key qualities that ensured the GMMC's sustenance amidst habitat degradation and dispersal to discrete environments.

Occupational exposure to Staphylococcus aureus and Enterococcus spp. among spray irrigation workers using reclaimed water.

As reclaimed water use expands, it is important to evaluate potential occupational health risks from exposure to this alternative water source. We compared odds of colonization with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), vancomycin-resistant enterococci (VRE), and vancomycin-susceptible enterococci (VSE) between spray irrigation workers using reclaimed water and office worker controls. Nasal and dermal swabs from 19 spray irrigation workers and 24 office worker controls were collected and analyzed for MRSA, MSSA, VRE, and VSE. Isolates were confirmed using standard biochemical tests and polymerase chain reaction assays. Antimicrobial susceptibility testing was performed by Sensititre® microbroth dilution. Data were analyzed by two-sample proportion, chi-square, Fisher's exact tests, and logistic regression. No MRSA or VRE were detected in any samples. MSSA was detected in 26% and 29% of spray irrigators and controls, respectively. VSE was detected in 11% and 0% of spray irrigation workers and controls, respectively. The adjusted odds of MSSA, multidrug-resistant MSSA, and either MSSA or VSE colonization were greater among spray irrigation workers, however results were not statistically significant. Future studies with larger sample sizes are needed to further evaluate this relationship.