Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

Background

The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings.

Purpose

Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems.

Methods and Results

We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry.

Conclusion

This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries.     

The Pneumatron: An automated pneumatic apparatus for estimating xylem vulnerability to embolism at high temporal resolution

Xylem vulnerability to embolism represents an important trait to determine species distribution patterns and drought resistance. However, estimating embolism resistance frequently requires time-consuming and ambiguous hydraulic lab measurements. Based on a recently developed pneumatic method, we present and test the “Pneumatron”, a device that generates high time-resolution and fully automated vulnerability curves. Embolism resistance is estimated by applying a partial vacuum to extract air from an excised xylem sample, while monitoring the pressure change over time. Although the amount of gas extracted is strongly correlated with the percentage loss of xylem conductivity, validation of the Pneumatron was performed by comparison with the optical method for Eucalyptus camaldulensis leaves. The Pneumatron improved the precision of the pneumatic method considerably, facilitating the detection of small differences in the (percentage of air discharged [PAD] < 0.47%). Hence, the Pneumatron can directly measure the 50% PAD without any fitting of vulnerability curves. PAD and embolism frequency based on the optical method were strongly correlated (r² = 0.93) for E. camaldulensis. By providing an open source platform, the Pneumatron represents an easy, low-cost, and powerful tool for field measurements, which can significantly improve our understanding of plant–water relations and the mechanisms behind embolism.     

Biochemical characterization of ClpB3, a chloroplastic disaggregase from Arabidopsis thaliana

Plant Molecular Biology - The first biochemical characterization of a chloroplastic disaggregase is reported (Arabidopsis thaliana ClpB3). ClpB3 oligomerizes into active hexamers that resolubilize...     

High FUT3 expression is a marker of lower overall survival of breast cancer patients

Glycoconjugate Journal - The complex enzyme network responsible for glycan synthesis suffers significant changes during the first steps of tumor development, leading to the early formation of...     

Elevated atmospheric CO2 modifies responses to water-stress and flowering of Mediterranean desert truffle mycorrhizal shrubs

Predicted increases in atmospheric concentration of carbon dioxide (CO₂) coupled with increased temperatures and drought are expected to strongly influence the development of most of the plant species in the world, especially in areas with high risk of desertification like the Mediterranean basin. Helianthemum almeriense is an ecologically important Mediterranean shrub with an added interest because it serves as the host for the Terfezia claveryi mycorrhizal fungus, which is a desert truffle with increasingly commercial interest. Although both plant and fungi are known to be well adapted to dry conditions, it is still uncertain how the increase in atmospheric CO₂ will influence them. In this article we have addressed the physiological responses of H. almeriense × T. claveryi mycorrhizal plants to increases in atmospheric CO₂ coupled with drought and high vapor pressure deficit. This work reports one of the few estimations of mesophyll conductance in a drought deciduous Mediterranean shrub and evaluates its role in photosynthesis limitation. High atmospheric CO₂ concentrations help desert truffle mycorrhizal plants to cope with the adverse effects of progressive drought during Mediterranean springs by improving carbon net assimilation, intrinsic water use efficiency and dispersal of the species through increased flowering events.     

Silencing of OsCV (chloroplast vesiculation) maintained photorespiration and N assimilation in rice plants grown under elevated CO2

High CO₂ concentrations stimulate net photosynthesis by increasing CO₂ substrate availability for Rubisco, simultaneously suppressing photorespiration. Previously, we reported that silencing the chloroplast vesiculation (cv) gene in rice increased source fitness, through the maintenance of chloroplast stability and the expression of photorespiration-associated genes. Because high atmospheric CO₂ conditions diminished photorespiration, we tested whether CV silencing might be a viable strategy to improve the effects of high CO₂ on grain yield and N assimilation in rice. Under elevated CO₂, OsCV expression was induced, and OsCV was targeted to peroxisomes where it facilitated the removal of OsPEX11-1 from the peroxisome and delivered it to the vacuole for degradation. This process correlated well with the reduction in the number of peroxisomes, the decreased catalase activity and the increased H₂O₂ content in wild-type plants under elevated CO₂. At elevated CO₂, CV-silenced rice plants maintained peroxisome proliferation and photorespiration and displayed higher N assimilation than wild-type plants. This was supported by higher activity of enzymes involved in NO₃⁻ and NH₄⁺ assimilation and higher total and seed protein contents. Co-immunoprecipitation of OsCV-interacting proteins suggested that, similar to its role in chloroplast protein turnover, OsCV acted as a scaffold, binding peroxisomal proteins.     

Isolation of Arsenic Resistant and Arsenopyrite Oxidizing Acidithiobacillus Species from pH Neutral Colombian Mine Effluents

Abstract

Inactive mines provide a great source of bacterial diversity for studying acidophilic communities and their biotechnological applications, but prospecting of these anthropogenic environments in Colombia has been limited. Conventional microbiological methods were used to isolate acidophilic bacterial strains from effluents emanating from the Colombian gold mine ‘El Zancudo’ (Titiribí, Antioquia). Despite the drainage waters having circumneutral pH, all of the isolated strains were phylogenetically related to the extreme acidophile Acidithiobacillus genus. However, based upon 16S rRNA gene sequences the mesophilic sulfur-oxidizing indigenous strains could not be assigned to a species. Pure cultures were selected by screening in medium with soluble inorganic arsenic (III) and their mineral-oxidative activity was evaluated at 30?°C in Erlenmeyer flasks with arsenopyrite ore under rotary shaking conditions. The indigenous strains were able to catalyze arsenopyrite oxidation in a mixed culture with a pulp density of 10%, maintaining their growth in the presence of >80?mM leached arsenic. This research provides information regarding the isolation of arsenic resistant bacterial communities from neutral effluents from El Zancudo mine and the possibility of the isolated strains to be useful in the biooxidation pretreatment of refractory gold-bearing arsenopyrite ores and concentrates.     

Variation in carbon and nitrogen isotopic ratios of fin and muscle tissues of Longnose Gar (Lepisosteus osseus) and Smallmouth Buffalo (Ictiobus bubalus)

Fin clips have been proposed as a non-lethal and non-invasive alternative to dorsal muscle samples in stable isotope analysis. However, potential differences in elemental composition and turnover rates can bias inferences when different tissues are combined. Here, we tested the average difference and correlation of the isotopic signature of δ¹³C and δ¹⁵N between muscle and fin samples in two arge-bodied fishes: Longnose Gar (Lepisosteus osseus) and Smallmouth Buffalo (Ictiobus bubalus). We found that δ¹⁵N signatures of muscle and fin tissues were strongly and positively correlated for both species, although the muscle tissue for Smallmouth Buffalo was slightly more enriched in δ15N. δ¹³C signatures of both tissues were significatively different and not strongly correlated for Longnose Gar, but similar and strongly correlated for Smallmouth Buffalo. Our results suggest that fin and muscle tissue can be combined for analyses of δ¹⁵N, but correction for higher enrichment of muscle tissue may be necessary for Smallmouth Buffalo. Conversely, combining fin and muscle tissue for analysis of δ¹³C requires more caution due to their weaker correlation and dependence of species identity.     

Length-weight relationship of twelve mesopelagic fishes from the western Tropical Atlantic

Length-weight relationship parameters were calculated for twelve mesopelagic fish species from the western Tropical Atlantic: Diretmus argenteus, Melamphaes polylepis, Bolinichthys distofax, Diaphus lucidus, Diaphus splendidus, Electrona risso, Hygophum taaningi, Taaningichthys bathyphilus, Melanolagus bericoides, Winteria telescopa, Diplophos taenia, Astronesthes similus. Data was collected off northeastern Brazil from April 9th to May 6th, 2017. Hauls were conducted during day and night at 47 stations by using a micronekton trawl (body mesh: 40 mm, cod-end mesh: 10 mm) from 10 to 1,113 m depth. The material was fixed in a 4% formalin solution for 1 month and then preserved in a 70% alcohol solution for proximally 6 months before processing for length (nearest 0.1 cm of standard length) and weight (nearest 0.01 g of total weight). A new maximum standard length for Winteria telescopa is also provided.     

Structural and posttranslational analysis of human calcium-binding protein,spermatid-associated 1

Recently, we detected a novel biomarker in human saliva called calcium-binding protein, spermatid-associated 1 (CABS1). CABS1 protein had previously been described only in testis, and little was known of its characteristics other than it was considered a structurally disordered protein. Levels of human CABS1 (hCABS1) in saliva correlate with stress, whereas smaller sized forms of hCABS1 in saliva are associated with resilience to stress. Interestingly, hCABS1 also has an anti-inflammatory peptide sequence near its carboxyl terminus, similar to that of a rat prohormone, submandibular rat 1. We performed phylogenetic and sequence analysis of hCABS1. We found that from 72 CABS1 sequences currently annotated in the National Center for Biotechnology Information protein database, only 14 contain the anti-inflammatory domain “TxIFELL,” all of which are primates. We performed structural unfoldability analysis using PONDER and FoldIndex and discovered three domains that are highly disordered. Predictions of three-dimensional structure of hCABS1 using RaptorX, IonCom, and I-TASSER software agreed with these findings. Predicted neutrophil elastase cleavage density also correlated with hCABS1 regions of high structural disorder. Ligand binding prediction identified Ca²⁺, Mg²⁺, Zn²⁺, leucine, and thiamine pyrophosphate, a pattern observed in enzymes associated with energy metabolism and mitochondrial localization. These new observations on hCABS1 raise intriguing questions about the interconnection between the autonomic nervous system, stress, and the immune system. However, the precise molecular mechanisms involved in the complex biology of hCABS1 remain unclear. We provide a detailed in silico analysis of relevant aspects of the structure and function of hCABS1 and postulate extracellular and intracellular roles.