Non-Fungible Tokens in Cardiovascular Medicine.

The integration of Non-Fungible Tokens (NFTs) in healthcare, particularly in cardiovascular medicine, represents a disruptive shift towards enhancing the security and interconnection of electronic health data around the patient. NFTs, unique digital certificates stored on a blockchain network, bind various sources of health data to their owner (the patient) and delineate the access rights for stakeholders (providers, researchers) using smart contracts. Data sources may include electronic medical records from different hospitals, clinics, pharmacies, test centers, and mHealth devices. Accordingly, patients and their providers benefit from seamless visibility of diagnoses, medications, electrocardiograms, imaging, home blood pressure logs, and artificial intelligence-enabled insights from these aggregated data. Rather than being stored on proprietary servers, data are encrypted and stored on decentralized networks with a unified point of access and immutable proof of ownership, making them more robust to theft or tampering. As custodians of their NFT, patients are incentivized to actively partake in their health monitoring and self-driven research that aligns with their needs using innovative marketplaces that allow them to browse studies, document their informed consent, and monetize their contributions. Furthermore, they are empowered to educate themselves and seek care across siloes in traditional settings or virtual platforms such as the metaverse, where NFTs serves as digital passports. Despite these exciting prospects, adoption within the healthcare sector remains in its infancy, with ethical and technical limitations still being addressed. This article explores the multifaceted applications and key players in the field, and outlines use-cases for patient-centered cardiovascular care featuring NFTs.

Unbalanced predatory communities and a lack of microbial degraders characterize the microbiota of a highly sewage-polluted Eastern-Mediterranean stream.

Wastewater pollution of water resources takes a heavy toll on humans and on the environment. In highly polluted water bodies, self-purification is impaired, as the capacity of the riverine microbes to regenerate the ecosystem is overwhelmed. To date, information on the composition, dynamics and functions of the microbial communities in highly sewage-impacted rivers is limited, in particular in arid and semi-arid environments. In this year-long study of the highly sewage-impacted Al-Nar/Kidron stream in the Barr al-Khalil/Judean Desert east of Jerusalem, we show, using 16S and 18S rRNA gene-based community analysis and targeted qPCR, that both the bacterial and micro-eukaryotic communities, while abundant, exhibited low stability and diversity. Hydrolyzers of organics compounds, as well as nitrogen and phosphorus recyclers were lacking, pointing at reduced potential for regeneration. Furthermore, facultative bacterial predators were almost absent, and the obligate predators Bdellovibrio and like organisms were found at very low abundance. Finally, the micro-eukaryotic predatory community differed from those of other freshwater environments. The lack of essential biochemical functions may explain the stream's inability to self-purify, while the very low levels of bacterial predators and the disturbed assemblages of micro-eukaryote predators present in Al-Nar/Kidron may contribute to community instability and disfunction.

An atlas of robust microbiome associations with phenotypic traits based on large-scale cohorts from two continents.

Numerous human conditions are associated with the microbiome, yet studies are inconsistent as to the magnitude of the associations and the bacteria involved, likely reflecting insufficiently employed sample sizes. Here, we collected diverse phenotypes and gut microbiota from 34,057 individuals from Israel and the U.S.. Analyzing these data using a much-expanded microbial genomes set, we derive an atlas of robust and numerous unreported associations between bacteria and physiological human traits, which we show to replicate in cohorts from both continents. Using machine learning models trained on microbiome data, we show prediction accuracy of human traits across two continents. Subsampling our cohort to smaller cohort sizes yielded highly variable models and thus sensitivity to the selected cohort, underscoring the utility of large cohorts and possibly explaining the source of discrepancies across studies. Finally, many of our prediction models saturate at these numbers of individuals, suggesting that similar analyses on larger cohorts may not further improve these predictions.

Community and single cell analyses reveal complex predatory interactions between bacteria in high diversity systems.

A fundamental question in community ecology is the role of predator-prey interactions in food-web stability and species coexistence. Although microbial microcosms offer powerful systems to investigate it, interrogating the environment is much more arduous. Here, we show in a 1-year survey that the obligate predators Bdellovibrio and like organisms (BALOs) can regulate prey populations, possibly in a density-dependent manner, in the naturally complex, species-rich environments of wastewater treatment plants. Abundant as well as rarer prey populations are affected, leading to an oscillating predatory landscape shifting at various temporal scales in which the total population remains stable. Shifts, along with differential prey range, explain co-existence of the numerous predators through niche partitioning. We validate these sequence-based findings using single-cell sorting combined with fluorescent hybridization and community sequencing. Our approach should be applicable for deciphering community interactions in other systems.

Model of personalized postprandial glycemic response to food developed for an Israeli cohort predicts responses in Midwestern American individuals.

BACKGROUND: Controlled glycemic concentrations are associated with a lower risk of conditions such as cardiovascular disease and diabetes. Models commonly used to guide interventions to control the glycemic response to food have low efficacy, with recent clinical guidelines arguing for the use of personalized approaches. OBJECTIVE: We tested the efficacy of a predictive model of personalized postprandial glycemic response to foods that was developed with an Israeli cohort and that takes into consideration food components and specific features, including the microbiome, when applied to individuals from the Midwestern US. DESIGN: We recruited 327 individuals for this study. Participants provided information regarding lifestyle, dietary habits, and health, as well as a stool sample for characterization of their gut microbiome. Participants were connected to continuous glucose monitors for 6 d, and the glycemic response to meals logged during this time was computed. The ability of a model trained using meals logged by the Israeli cohort to correctly predict glycemic responses in the Midwestern cohort was assessed and compared with that of a model trained using meals logged by both cohorts. RESULTS: When trained on the Israeli cohort meals only, model performance for predicting responses of individuals in the Midwestern cohort was better (R = 0.596) than that observed for models taking into consideration the carbohydrate (R = 0.395) or calorie content of the meals alone (R = 0.336). Performance increased (R = 0.618) when the model was trained on meals from both cohorts, likely because of the observed differences in age distribution, diet, and microbiome. CONCLUSIONS: We show that the modeling framework described in Zeevi et al. for an Israeli cohort is applicable to a Midwestern population, and outperforms commonly used approaches for the control of blood glucose responses. The adaptation of the model to the Midwestern cohort further enhances performance and is a promising means for designing effective nutritional interventions to control glycemic responses to foods. This trial was registered at clinicaltrials.gov as NCT02945514.

Assessment of a Personalized Approach to Predicting Postprandial Glycemic Responses to Food Among Individuals Without Diabetes.

Importance: Emerging evidence suggests that postprandial glycemic responses (PPGRs) to food may be influenced by and predicted according to characteristics unique to each individual, including anthropometric and microbiome variables. Interindividual diversity in PPGRs to food requires a personalized approach for the maintenance of healthy glycemic levels. Objectives: To describe and predict the glycemic responses of individuals to a diverse array of foods using a model that considers the physiology and microbiome of the individual in addition to the characteristics of the foods consumed. Design, Setting, and Participants: This cohort study using a personalized predictive model enrolled 327 individuals without diabetes from October 11, 2016, to December 13, 2017, in Minnesota and Florida to be part of a study lasting 6 days. The study measured anthropometric variables, described the gut microbial composition, and assessed blood glucose levels every 5 minutes using a continuous glucose monitor. Participants logged their food and activity information for the duration of the study. A predictive model of individualized PPGRs to a diverse array of foods was trained and applied. Main Outcomes and Measures: Glycemic responses to food consumed over 6 days for each participant. The predictive model of personalized PPGRs considered individual features, including the microbiome, in addition to the features of the foods consumed. Results: Postprandial response to the same foods varied across 327 individuals (mean [SD] age, 45 [12] years; 78.0% female). A model predicting each individual's responses to food that considers several individual factors in addition to food features had better overall performance (R = 0.62) than current standard-of-care approaches using nutritional content alone (R = 0.34 for calories and R = 0.40 for carbohydrates) to control postprandial glycemic levels. Conclusions and Relevance: Across the cohort of adults without diabetes who were examined, a personalized predictive model that considers unique features of the individual, such as clinical characteristics, physiological variables, and the microbiome, in addition to nutrient content was more predictive than current dietary approaches that focus only on the calorie or carbohydrate content of foods. Providing individuals with tools to manage their glycemic responses to food based on personalized predictions of their PPGRs may allow them to maintain their blood glucose levels within limits associated with good health.

Bacteria and microeukaryotes are differentially segregated in sympatric wastewater microhabitats.

Wastewater purification is mostly performed in activated sludge reactors by bacterial and microeukaryotic communities, populating organic flocs and a watery liquor. While there are numerous molecular community studies of the bacterial fraction, those on microeukaryotes are rare. We performed a year-long parallel 16S rRNA gene and 18S rRNA-gene based analysis of the bacterial and of the microeukaryote communities, respectively, of physically separated flocs and particle-free liquor samples from three WWTPs. This uncovered a hitherto unknown large diversity of microeukaryotes largely composed of potential phagotrophs preferentially feeding on either bacteria or other microeukaryotes. We further explored whether colonization of the microhabitats was selective, showing that for both microbial communities, different but often closely taxonomically and functionally related populations exhibiting different dynamic patterns populated the microhabitats. An analysis of their between plants-shared core populations showed the microeukaryotes to be dispersal limited in comparison to bacteria. Finally, a detailed analysis of a weather-caused operational disruption in one of the plants suggested that the absence of populations common to the floc and liquor habitat may negatively affect resilience and stability.

Primary plasma cell leukemia in the era of novel agents for myeloma - a multicenter retrospective analysis of outcome.

Primary plasma cell leukemia (PPCL) is a rare form of multiple myeloma with a dismal prognosis. This retrospective multi-center study examines the national experience of PPCL in the era of novel agents. During 2002-2016, thirty-nine patients with PPCL were identified in 11 Israeli centers. One-fifth of them died in the first 2 months after diagnosis. The overall survival (OS) of those who survived the first 3 months was 22.5 months. About 70% of patients received at least one type of immunomodulatory drug (IMiD) and similarly proteasome inhibitor (PI) during treatment. There was a survival advantage for those who received IMiD but not for those who received PI or other type of standard dose chemotherapy. In multivariate analysis, low performance status and increased uric acid were also associated with shorter OS. In conclusion, this study demonstrates favorable impact of treatment with IMiDs and hematopoietic cell transplantation on the survival of PPCL patients.

Symmetric rearrangement of groundwater-fed streams.

Streams shape landscapes through headward growth and lateral migration. When these streams are primarily fed by groundwater, recent work suggests that their tips advance to maximize the symmetry of the local Laplacian field associated with groundwater flow. We explore the extent to which such forcing is responsible for the lateral migration of streams by studying two features of groundwater-fed streams in Bristol, Florida: their confluence angle near junctions and their curvature. First, we find that, while streams asymptotically form a 72° angle near their tips, they simultaneously exhibit a wide 120° confluence angle within approximately 10 m of their junctions. We show that this wide angle maximizes the symmetry of the groundwater field near the junction. Second, we argue that streams migrate laterally within valleys and present a new spectral analysis method to relate planform curvature to the surrounding groundwater field. Our results suggest that streams migrate laterally in response to fluxes from the surrounding groundwater table, providing evidence of a new mechanism that complements Laplacian growth at their tips.

Effect of counterface roughness on the friction of bionic wall-shaped microstructures for gecko-like attachments.

Hairy adhesive systems involved in gecko locomotion have drawn the interest of many researchers regarding the development of bionic solutions for fast and reversible adhesive technologies. To date, despite extensive efforts to design gecko-inspired adhesive surfaces, adhesion and friction capacities are often evaluated using smooth and rigid counterfaces, in general glass, whereas most natural and artificial surfaces inevitably have a certain level of roughness. For that reason, in this study experiments tested the effects of the substrate roughness on the friction of bionic wale-shaped microstructures for gecko-like attachments. To this end, 12 substrates with different isotropic roughness were prepared using the same Epoxy material. Friction force was measured under various normal loads. It was concluded that classical roughness parameters, considered separately, are not appropriate to explain roughness-related variations in friction force. This has led us to develop a new integrative roughness parameter that combines characteristics of the surface. The parameter is capable of classifying the obtained experimental results in a readable way. An analytical model based on the experimental results has been developed to predict the variation of the friction force as a function of counterface roughness and applied normal load.

A free-boundary model of diffusive valley growth: theory and observation.

Valleys that form around a stream head often develop characteristic finger-like elevation contours. We study the processes involved in the formation of these valleys and introduce a theoretical model that indicates how shape may inform the underlying processes. We consider valley growth as the advance of a moving boundary travelling forward purely through linearly diffusive erosion, and we obtain a solution for the valley shape in three dimensions. Our solution compares well to the shape of slowly growing groundwater-fed valleys found in Bristol, Florida. Our results identify a new feature in the formation of groundwater-fed valleys: a spatially variable diffusivity that can be modelled by a fixed-height moving boundary.

Exact solution for the Poisson field in a semi-infinite strip.

The Poisson equation is associated with many physical processes. Yet exact analytic solutions for the two-dimensional Poisson field are scarce. Here we derive an analytic solution for the Poisson equation with constant forcing in a semi-infinite strip. We provide a method that can be used to solve the field in other intricate geometries. We show that the Poisson flux reveals an inverse square-root singularity at a tip of a slit, and identify a characteristic length scale in which a small perturbation, in a form of a new slit, is screened by the field. We suggest that this length scale expresses itself as a characteristic spacing between tips in real Poisson networks that grow in response to fluxes at tips.

Translocation t(11;14) in newly diagnosed patients with multiple myeloma: Is it always favorable?

The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32). According to several studies, this translocation represents a unique subset of patients with relatively favorable outcomes. Using combined analyses of morphology and fluorescence in situ hybridization (I-FISH), we examined the co-occurrence rates of t(11;14) with seven chromosomal aberrations (CAs), del(13q), del(17p), del(1p), gain(1q), multiple gains(1q), del(16q), and del(IGH), and assessed the effect of the different combinations on patient outcomes, with overall survival (OS) as the main outcome measure. Bone marrow samples and clinical data from 212 patients with MM with t(11;14) were analyzed. At least two additional CAs were found in 35% (75/205) of patients and a strong correlation between specific CAs. The occurrence of three CAs [multiple gains of (1q) (HR = 6.94, P = 0.001), del(1p) (HR = 4.47, P = 0.008), and del(IGH) (HR = 2.38, P = 0.002)] exerted a profoundly deleterious effect on median OS when compared with patients with t(11;14) only. Del(17p) and del(13q) have also exerted a deleterious effect albeit to a lesser extent (HR = 2.05, P = 0.07 and HR = 1.81, P = 0.03, respectively). When compared with t(11;14) alone, the addition of certain CAs lead to worse outcomes. These findings may have important clinical and biological implications. Patients with coexisting adverse lesions and t(11;14) may be considered at high risk and managed accordingly. © 2016 Wiley Periodicals, Inc.

Path selection in the growth of rivers.

River networks exhibit a complex ramified structure that has inspired decades of studies. However, an understanding of the propagation of a single stream remains elusive. Here we invoke a criterion for path selection from fracture mechanics and apply it to the growth of streams in a diffusion field. We show that, as it cuts through the landscape, a stream maintains a symmetric groundwater flow around its tip. The local flow conditions therefore determine the growth of the drainage network. We use this principle to reconstruct the history of a network and to find a growth law associated with it. Our results show that the deterministic growth of a single channel based on its local environment can be used to characterize the structure of river networks.

A New Comparative-Genomics Approach for Defining Phenotype-Specific Indicators Reveals Specific Genetic Markers in Predatory Bacteria.

Predatory bacteria seek and consume other live bacteria. Although belonging to taxonomically diverse groups, relatively few bacterial predator species are known. Consequently, it is difficult to assess the impact of predation within the bacterial realm. As no genetic signatures distinguishing them from non-predatory bacteria are known, genomic resources cannot be exploited to uncover novel predators. In order to identify genes specific to predatory bacteria, we developed a bioinformatic tool called DiffGene. This tool automatically identifies marker genes that are specific to phenotypic or taxonomic groups, by mapping the complete gene content of all available fully-sequenced genomes for the presence/absence of each gene in each genome. A putative 'predator region' of ~60 amino acids in the tryptophan 2,3-dioxygenase (TDO) protein was found to probably be a predator-specific marker. This region is found in all known obligate predator and a few facultative predator genomes, and is absent from most facultative predators and all non-predatory bacteria. We designed PCR primers that uniquely amplify a ~180bp-long sequence within the predators' TDO gene, and validated them in monocultures as well as in metagenetic analysis of environmental wastewater samples. This marker, in addition to its usage in predator identification and phylogenetics, may finally permit reliable enumeration and cataloguing of predatory bacteria from environmental samples, as well as uncovering novel predators.

Mechanisms for mechanical trapping of geologically sequestered carbon dioxide.

Carbon dioxide (CO2) sequestration in subsurface reservoirs is important for limiting atmospheric CO2 concentrations. However, a complete physical picture able to predict the structure developing within the porous medium is lacking. We investigate theoretically reactive transport in the long-time evolution of carbon in the brine-rock environment. As CO2 is injected into a brine-rock environment, a carbonate-rich region is created amid brine. Within the carbonate-rich region minerals dissolve and migrate from regions of high-to-low concentration, along with other dissolved carbonate species. This causes mineral precipitation at the interface between the two regions. We argue that precipitation in a small layer reduces diffusivity, and eventually causes mechanical trapping of the CO2. Consequently, only a small fraction of the CO2 is converted to solid mineral; the remainder either dissolves in water or is trapped in its original form. We also study the case of a pure CO2 bubble surrounded by brine and suggest a mechanism that may lead to a carbonate-encrusted bubble owing to structural diffusion.

The European Gaucher Alliance: a survey of member patient organisations' activities, healthcare environments and concerns.

BACKGROUND: The European Gaucher Alliance (EGA) was established in 1994 and constituted in 2008 as an umbrella group supporting patient organisations for Gaucher disease. Every two years, the EGA conducts a questionnaire survey of member associations to help develop its priorities and annual work programme. Results of the latest survey are presented. METHODS: Between June 2012 and April 2013, the 36 members and associate members of the EGA were asked to complete a questionnaire detailing membership numbers, disease specific treatments used by patients, means of access to treatment, availability of treatment centres and home infusions, sources of support for patients with Gaucher disease, patient organisations' activities, collaborations, funding sources and any issues of concern. Questionnaires completed in 2012 were revised in January 2013 and responses analysed between July and September 2013. RESULTS: Thirty three members returned data on one or more questions. Findings identified inequalities in access to treatment both within and between members' countries. Three of 27 countries, for which data were available, relied totally on humanitarian aid for treatment and 6% of untreated patients in 20 countries were untreated because of funding issues, a situation many feared would worsen with deteriorating economic climates. Access to treatment and reimbursement represented 45% of members' concerns, while 35% related to access to specialist treatment centres, home infusions and doctors with expertise in Gaucher disease. Member associations' main activities centred on patient support (59% of responses) and raising awareness of Gaucher disease and patients' needs amongst the medical community, government and healthcare decision makers and the general public (34% of responses). Twenty one (78% of respondents) indicated they were the only source of help for Gaucher disease patients in their country. For many, activities were constrained by funds; two members had no external funding source. Activities were maximised through collaboration with other patient organisations and umbrella organisations for rare diseases. CONCLUSION: The survey provided a 'snapshot' of the situation for patients and families affected by Gaucher disease, helping the EGA direct its activities into areas of greatest need.

Multiple micro-predators controlling bacterial communities in the environment.

Predator-prey interactions are a main issue in ecological theory, including multispecies predator-prey relationships and intraguild predation. This knowledge is mainly based on the study of plants and animals, while its relevance for microorganisms is not well understood. The three key groups of micro-predators include protists, predatory bacteria and bacteriophages. They greatly differ in size, in prey specificity, in hunting strategies and in the resulting population dynamics. Yet, their potential to jointly control bacterial populations and reducing biomass in complex environments such as wastewater treatment plants is vast. Here, we present relevant ecological concepts and recent findings on micropredators, and propose that an integrative approach to predation at the microscale should be developed enabling the exploitation of this potential.