Biomedical Study Research Articles

The BMS-LM ontology for biomedical data reporting throughout the lifecycle of a research study: From data model to ontology

Biomedical research data reuse and sharing is essential for fostering research progress. To this aim, data producers need to master data management and reporting through standard and rich metadata, as encouraged by open data initiatives such as the FAIR (Findable, Accessible, Interoperable, Reusable) guidelines. This helps data re-users to understand and reuse the shared data with confidence. Therefore, dedicated frameworks are required. The provenance reporting throughout a biomedical study lifecycle has been proposed as a way to increase confidence in data while reusing it. The Biomedical Study - Lifecycle Management (BMS-LM) data model has implemented provenance and lifecycle traceability for several multimodal-imaging techniques but this is not enough for data understanding while reusing it. Actually, in the large scope of biomedical research, a multitude of metadata sources, also called Knowledge Organization Systems (KOSs), are available for data annotation. In addition, data producers uses local terminologies or KOSs, containing vernacular terms for data reporting. The result is a set of heterogeneous KOSs (local and published) with different formats and levels of granularity. To manage the inherent heterogeneity, semantic interoperability is encouraged by the Research Data Management (RDM) community. Ontologies, and more specifically top ontologies such as BFO and DOLCE, make explicit the metadata semantics and enhance semantic interoperability. Based on the BMS-LM data model and the BFO top ontology, the BioMedical Study - Lifecycle Management (BMS-LM) core ontology is proposed together with an associated framework for semantic interoperability between heterogeneous KOSs. It is made of four ontological levels: top/core/domain/local and aims to build bridges between local and published KOSs. In this paper, the conversion of the BMS-LM data model to a core ontology is detailed. The implementation of its semantic interoperability in a specific domain context is explained and illustrated with examples from small animal preclinical research.

Overcoming epistemic injustices in the biomedical study of ayahuasca: Towards ethical and sustainable regulation.

After decades of biomedical research on ayahuasca's molecular compounds and their physiological effects, recent clinical trials show evidence of therapeutic potential for depression. However, indigenous peoples have been using ayahuasca therapeutically for a very long time, and thus we question the epistemic authority attributed to scientific studies, proposing that epistemic injustices were committed with practical, cultural, social, and legal consequences. We question epistemic authority based on the double-blind design, the molecularization discourse, and contextual issues about safety. We propose a new approach to foster epistemically fair research, outlining how to enforce indigenous rights, considering the Brazilian, Peruvian, and Colombian cases. Indigenous peoples have the right to maintain, control, protect, and develop their biocultural heritage, traditional knowledge, and cultural expressions, including traditional medicine practices. New regulations about ayahuasca must respect the free, prior, and informed consent of indigenous peoples according to the International Labor Organization Indigenous and Tribal Peoples Convention no. 169. The declaration of the ayahuasca complex as a national cultural heritage may prevent patenting from third parties, fostering the development of traditional medicine. When involving isolated compounds derived from traditional knowledge, benefit-sharing agreements are mandatory according to the United Nations' Convention on Biological Diversity. Considering the extremely high demand to treat millions of depressed patients, the medicalization of ayahuasca without adequate regulation respectful of indigenous rights can be detrimental to indigenous peoples and their management of local environments, potentially harming the sustainability of the plants and of the Amazon itself, which is approaching its dieback tipping point.

A simple energy efficient sol-gel combustion production of strontium orthosilicate and its biomedical study

Here we present a simple, effective, energy efficient method for the production of single phasic strontium orthosilicate (Sr2SiO4) powders at (1000 °C) low phase formation temperature using sol–gel combustion method. Detailed phase evaluation is investigated. The influence of different fuels on the synthesis of strontium orthosilicate also discussed. The prepared strontium orthosilicate powders were characterized using powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), Fourier transform Raman (FT-RAMAN), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) techniques. The strontium orthosilicate-polymer (chitin/chitosan) scaffold were prepared by solid state mixing. The strontium orthosilicate and strontium orthosilicate-polymer scaffold were found to have the ability to biomineralize as a bone substitute. The apatite formation ability was demonstrated by XRD studies after incubation up to 30 days. These preliminary in-vitro apatite formation abilities and hemocompatibility results show that strontium orthosilicate might possess properties that can serve as new biomedical material.

Cell-free biosynthesis meets dynamic optimization and control: a fed-batch framework

Cell-free biosynthesis uses the machinery of cells, such as the metabolic reactions, to carry out conversion processes in vitro. This can be more beneficial than in vivo approaches like fermentations. Some advantages of these synthetic biology processes include higher product yields, rates and titers, and more flexibility in pathway design. Cell-free biosynthesis is still in early stages and, unlike in vivo production, there are very few examples of model-based optimization. Moreover, we encounter static optimizations in most cases, neglecting the dynamic nature of the processes. We present an optimal control framework to maximize the efficiency of cell-free biosynthesis. We focus on fed-batch setups as they allow enhancing the reaction rates via the feeding, extending production processes for longer times, and minimizing the potential negative effects of enzyme kinetics with substrate inhibition. Our framework can in principle handle several cost functions and exploit both static and dynamic degrees of freedom. An aspect that can hinder model-based optimization is model uncertainty, which can arise due to uncertain parameters, oversimplified model assumptions or unknown reaction mechanisms. To counteract this, we propose the use of model predictive control during the process operation. In addition, we outline the use of moving horizon estimation as an observer in the case of unmeasured states. We consider the de novo cell-free synthesis of uridine diphosphate-N-acetylglucosamine as a biomedical relevant case study, where we were able to maximize the volumetric productivity in simulations, and indirectly also the titer and enzyme efficiency use.

The effect of cryopreservation media on the quality of β-thalassemia mouse spermatozoa.

The mouse model of human diseases is commonly used for biomedical study, including β-thalassemia (β-thal), an inherited hemoglobin disorder. Maintaining the mice strain by natural mating systems is costly and seems impractical, especially during the COVID-19 pandemic. Sperm-freezing is a cost-effective solution for β-thal mouse colony management. To determine appropriate cryopreservation media for β-thal mouse spermatozoa to establish a β-thal mouse sperm bank. The epididymal spermatozoa of C57BL/6 wild-type (WT) and β-globin gene knockout thalassemia (BKO) mice were frozen in four freezing media: I) raffinose-skim milk-monothioglycerol (MTG), II) raffinose-skim milk-glutamine, III) raffinose-egg yolk-glycerol, and IV) egg yolk-TES-Tris. The sperm quality was assessed prior to and following freeze-thawing. Compared with WT counterparts, the viable spermatozoa before freezing exhibiting elevated levels of oxidative stress were significantly greater in BKO (p = 0.01). After thawing, the membrane integrity of BKO spermatozoa preserved in I was significantly lower (p = 0.001). The sperm viability and membrane integrity of BKO males were also inferior when media III and IV were used (p = 0.008-0.027). The amount of oxidative stress in the spermatozoon of BKO mice was significantly greater when preserved in I, III, and IV (p = 0.002-0.044). Comparing freezing media, the motility and acrosome integrity of WT and BKO spermatozoa preserved in IV were significantly higher than those in other media (p < 0.001 to p = 0.01). Spermatozoa with the highest mitochondrial membrane potential were observed in I in both genotypes (p = 0.012 to p > 0.05). The viability, membrane integrity, and oxidative stress of post-thaw BKO spermatozoa did not significantly differ among freezing solutions. Irrespective of freezing media, spermatozoa of BKO males are rather more sensitive to cryopreservation than those of WT. Raffinose-skim milk-MTG/glutamine, raffinose-egg yolk-glycerol, and egg yolk-TES-Tris can all be used to preserve BKO mouse spermatozoa. However, with slightly better sperm characteristics, egg yolk-TES-Tris may be a diluent of choice for BKO mouse sperm cryopreservation. The addition of a reducing agent to thawing media is also strongly recommended to efficiently prevent oxidative stress and therefore improve frozen-thawed sperm survival.

Advances in biomedical study of the myopia-related signaling pathways and mechanisms.

Myopia has become one of the most critical health problems in the world with the increasing time spent indoors and increasing close work. Pathological myopia may have multiple complications, such as myopic macular degeneration, retinal detachment, cataracts, open-angle glaucoma, and severe cases that can cause blindness. Mounting evidence suggests that the cause of myopia can be attributed to the complex interaction of environmental exposure and genetic susceptibility. An increasing number of researchers have focused on the genetic pathogenesis of myopia in recent years. Scleral remodeling and excessive axial elongating induced retina thinning and even retinal detachment are myopia's most important pathological manifestations. The related signaling pathways are indispensable in myopia occurrence and development, such as dopamine, nitric oxide, TGF-β, HIF-1α, etc. We review the current major and recent progress of biomedicine on myopia-related signaling pathways and mechanisms.

Synergetic dual-toehold mediated controllable transcription amplification for detecting lung cancer-related circulating miRNAs in blood

Circulating microRNAs (miRNAs) in blood are recognized as key biomarkers of cancers. Herein, taking advantage of the dynamic DNA nanotechnology, we report an assay to detect lung cancer-related circulating miRNAs in blood based on a synergetic dual-toehold mediated controllable transcription amplification (SMART). Unlike traditional single-toehold overhanging system with limited design flexibility, the synergetic dual-toehold exchange was employed to not only inhibit background signal, but also facilitate the downstream introducing of target-responsive isothermal amplification. This feature allows the SMART platform combines synergetic dual-toehold mediated strand displacement with transcription amplification. The SMART, acting as an effective signal transducer and amplifier, is thus able to ultrasensitively output the let-7a recognition event via significantly accumulating Broccoli RNA aptamers responsible for the binding with DFHBI-1 T. Moreover, the Broccoli/DFHBI-1 T reporter increases the signal-to-background ratio compared to that using non-specific nucleic acid dyes and eliminates the use of chemically labeled oligonucleotide probes. The experimental demonstration shows the SMART method realized the detection of let-7a lower into 10 fM, identification of let-7a from homologous and heterologous analogues, and profiling let-7a from clinical blood samples. This work improves the rational design of dynamic DNA devices-based signal isothermal in the fields of disease diagnosis and biomedical study.

Glucohealth: The potential of porang (Amorphophallus muelleri) acid hydrolysed glucomannan as an inhibitor of SARS-CoV-2 interaction with ACE2

The novel SARS-CoV-2 that causing global pandemic COVID-19 known to enter the host cell using the hACE2 as cell receptor. SARS-CoV S1 protein cleaves the ACE2 receptor, then the S2 subunits facilitates the cell membrane fusion, the inhibition of S1-ACE2 interaction can help develop anti SARS-CoV-2 medication. Porang glucomannan is a polysaccharide known as immunomodulator but never reported as anti-virus by direct inhibition of viral entry. Glucohealth was developed to investigate its potential. Method: Glucohealth is a glucomannan hydrolysate (HGM) that made from porang (Amorphophallus muelleri). Hydrolysis was carried using HCl in different concentration (0.25N, 0.5N, 1N) then analyzed its inhibitor activity using ELISA kit. Result: Higher HCl concentration produced HGM with smaller average particle size and lower glucomannan content. However, ELISA studies showed that glucomannan, including its hydrolysates, have the potency to bind with S1 protein and inhibit the binding activity of S1-ACE2. Degraded glucomannan proven to have better bioactivity and able to interact with pathogen to inhibit its cell entry. This project should be a gateway for further biomedical study of glucomannan from Indonesia’s local tuber and new approach to produce more natural therapy against COVID-19.

Vitamin B12 Hydrophobic Derivative Exhibits Bioactivity: Biomedical and Photophysical Study

Vitamin B12 Hydrophobic Derivative Exhibits Bioactivity: Biomedical and Photophysical Study

Insight into the adhesion propensities of extracellular polymeric substances (EPS) on the abiotic surface using XDLVO theory

The adhesion of microorganisms is ubiquitous and plays a central role in a wide spectrum of problems, including biomedical study, industrial application and environmental microbiology. To know more about mechanisms underlying microalgal early-stage adhesion, the soluble EPS (sEPS) and the bound EPS (bEPS) of Chlorella vulgaris were extracted and characterized for their adhesion behaviors on the hydrophilic polymethyl methacrylate (PMMA) and the hydrophobic polytetrafluoroethylene (PTFE) surfaces in this work. It was found that the sEPS and the bEPS were dominated by hydrophilic fractions (57.6%) and hydrophobic fractions (49.6%) respectively. As a result, the bEPS always showed a higher adhesion propensity than the sEPS, and its adhesion on PTFE was more significant than that on PMMA. According to the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, the adhesion behavior was dominated by the Lewis acid-base interfacial free energy (∆GmwfAB) of algal EPS. The bEPS could promote adhesive propensity of both two materials, whereas the sEPS would repulse the hydrophilic surfaces. Additionally, the dissolved organic carbon (DOC) was shown to be a more suitable index for the description of EPS adhesion. This work presents evidence on the mechanisms of the EPS-mediated adhesion process in algal biofilm formation.

Seven-day Oral Intake of Orthosiphon stamineus Leaves Infusion Exerts Antiadhesive Ex Vivo Activity Against Uropathogenic E. coli in Urine Samples.

Orthosiphon stamineus leaves (Java tea) extract is traditionally used for the treatment of urinary tract infections. According to recent in vitro data, animal infection studies, and transcriptomic investigations, polymethoxylated flavones from Java tea exert antiadhesive activity against uropathogenic Escherichia coli (UPEC). This antiadhesive activity has been shown to reduce bladder and kidney lesion in a mice infection model. As no data on the antivirulent activity of Java tea intake on humans are available, a biomedical study was performed on 20 healthy volunteers who self-administered Orthosiphon infusion (4 × 3 g per day, orally) for 7 days. The herbal material used for the study conformed to the specification of the European Pharmacopoeia, and ultra high-performance liquid chromatography (UHPLC) of the infusion showed rosmarinic acid, caffeic acid, and cichoric acid to be the main compounds aside from polymethoxylated flavones. Rosmarinic acid was quantified in the tea preparations with 243 ± 22 µg/mL, indicating sufficient reproducibility of the preparation of the infusion. Urine samples were obtained during the biomedical study on day 1 (control urine, prior to Java tea intake), 3, 6 and 8. Antiadhesive activity of the urine samples was quantified by flowcytometric assay using pre-treated UPEC NU14 and human T24 bladder cells. Pooled urine samples indicated significant inhibition of bacterial adhesion on day 3, 6 and 8. The urine samples had no influence on the invasion of UPEC into host cells. Bacterial proliferation was slightly reduced after 24 h incubation with the urine samples. Gene expression analysis (qPCR) revealed strong induction of fitness and motility gene fliC and downregulation of hemin uptake system chuT. These data correlate with previously reported datasets from in vitro transcriptomic analysis. Increased bacterial motility was monitored using a motility assay in soft agar with UPEC UTI89. The intake of Java tea had no effect on the concentration of Tamm-Horsfall Protein in the urine samples. The present study explains the antiadhesive and anti-infective effect of the plant extract by triggering UPEC from a sessile lifestyle into a motile bacterial form, with reduced adhesive capacity.

Biomedical Courses Should Also Be Designed for Dental Students: The Perceptions of Dental Students.

Introduction: It can be challenging integrating biomedical sciences into dentistry programs. The aim was to examine students’ perceptions of how joint biomedical courses with medical students and courses tailored for dental students supported their clinical studies. Materials and methods: The target group was clinical phase dental students. Cross-sectional survey data were collected using a questionnaire, which consisted of questions covering biomedical and clinical study content and learning methods. Results: A total of 110 (82%) students completed the survey. Students had difficulty recognising the relevance of joint biomedical courses for clinical work, but when the link was clear, their interest in the content increased. The closer the respondents were to graduation, the less relevance they expressed the biomedical sciences had. Almost all students (95%) wanted more dental content for the early study years. Discussion: The student perspective provides valuable information for the development of biomedical courses. Students should be offered customised courses that include dental content and perspectives on clinical work, whenever suitable to the didactic content of the basic science course. Our study shows that the dental perspective needs greater integration with the biomedical content. This also supports interprofessional learning and appreciation for the other field’s contribution to human health.

High-dynamic-range blood flow rate measurement in a large-diameter vessel.

We propose a new, to the best of our knowledge, compound technique to measure high-dynamic-range blood flow rate in a large-diameter vessel, which combines the dynamic scattering light (DLS) and the laser speckle contrast imaging (LSCI) methods, possessing the advantages of the high temporal resolution of DLS and the robust property of LSCI. By controlling the second-order spatial correlations of the laser speckle through two imaging systems, the speckle temporal intensity autocorrelation function g2(t) and the decorrelation time τc are directly measured using a high-speed camera. It turns out the enhanced spatial second-order correlation helps to measure the blood flow with higher dynamic range and that the measured parameter β and the blood flow dynamics n were accurately determined. For further improvement the dynamic range, the modified LSCI method was adopted, and the decorrelation time as a function of blood flow rate was constructed. It reveals the feasibility of measuring the high flow rate in large-diameter vessels and provides significant guidance for the future biomedical study of the myocardial perfusion in coronary artery bypass grafting, ghost imaging, and ghost cytometry.

Auto-focusing and quantitative phase imaging using deep learning for the incoherent illumination microscopy system.

It is well known that the quantitative phase information which is vital in the biomedical study is hard to be directly obtained with bright-field microscopy under incoherent illumination. In addition, it is impossible to maintain the living sample in focus over long-term observation. Therefore, both the autofocusing and quantitative phase imaging techniques have to be solved in microscopy simultaneously. Here, we propose a lightweight deep learning-based framework, which is constructed by residual structure and is constrained by a novel loss function model, to realize both autofocusing and quantitative phase imaging. It outputs the corresponding in-focus amplitude and phase information at high speed (10fps) from a single-shot out-of-focus bright-field image. The training data were captured with a designed system under a hybrid incoherent and coherent illumination system. The experimental results verify that the focused and quantitative phase images of non-biological samples and biological samples can be reconstructed by using the framework. It provides a versatile quantitative technique for continuous monitoring of living cells in long-term and label-free imaging by using a traditional incoherent illumination microscopy system.

Correlates of attendance at community engagement meetings held in advance of bio-behavioral research studies: A longitudinal, sociocentric social network study in rural Uganda.

Community engagement is central to the conduct of health-related research studies as a way to determine priorities, inform study design and implementation, increase recruitment and retention, build relationships, and ensure that research meets the goals of the community. Community sensitization meetings, a form of community engagement, are often held prior to the initiation of research studies to provide information about upcoming study activities and resolve concerns in consultation with potential participants. This study estimated demographic, health, economic, and social network correlates of attendance at community sensitization meetings held in advance of a whole-population, combined behavioral, and biomedical research study in rural Uganda. Research assistants collected survey data from 1,630 adults participating in an ongoing sociocentric social network cohort study conducted in a rural region of southwestern Uganda. These community survey data, collected between 2016 and 2018, were linked to attendance logs from community sensitization meetings held in 2018 and 2019 before the subsequent community survey and community health fair. Of all participants, 264 (16%) attended a community sensitization meeting before the community survey, 464 (28%) attended a meeting before the community health fair, 558 (34%) attended a meeting before either study activity (survey or health fair), and 170 (10%) attended a meeting before both study activities (survey and health fair). Using multivariable Poisson regression models, we estimated correlates of attendance at community sensitization meetings. Attendance was more likely among study participants who were women (adjusted relative risk [ARR]health fair = 1.71, 95% confidence interval [CI], 1.32 to 2.21, p < 0.001), older age (ARRsurvey = 1.02 per year, 95% CI, 1.01 to 1.02, p < 0.001; ARRhealth fair = 1.02 per year, 95% CI, 1.01 to 1.02, p < 0.001), married (ARRsurvey = 1.74, 95% CI, 1.29 to 2.35, p < 0.001; ARRhealth fair = 1.41, 95% CI, 1.13 to 1.76, p = 0.002), and members of more community groups (ARRsurvey = 1.26 per group, 95% CI, 1.10 to 1.44, p = 0.001; ARRhealth fair = 1.26 per group, 95% CI, 1.12 to 1.43, p < 0.001). Attendance was less likely among study participants who lived farther from meeting locations (ARRsurvey = 0.54 per kilometer, 95% CI, 0.30 to 0.97, p = 0.041; ARRhealth fair = 0.57 per kilometer, 95% CI, 0.38 to 0.86, p = 0.007). Leveraging the cohort's sociocentric design, social network analyses suggested that information conveyed during community sensitization meetings could reach a broader group of potential study participants through attendees' social network and household connections. Study limitations include lack of detailed data on reasons for attendance/nonattendance at community sensitization meetings; achieving a representative sample of community members was not an explicit aim of the study; and generalizability may not extend beyond this study setting. In this longitudinal, sociocentric social network study conducted in rural Uganda, we observed that older age, female sex, being married, membership in more community groups, and geographical proximity to meeting locations were correlated with attendance at community sensitization meetings held in advance of bio-behavioral research activities. Information conveyed during meetings could have reached a broader portion of the population through attendees' social network and household connections. To ensure broader input and potentially increase participation in health-related research studies, the dissemination of research-related information through community sensitization meetings may need to target members of underrepresented groups.

Implementing Personalized Genetic Medicine

Implementing Personalized Genetic Medicine

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction

Mitotic catastrophe (MC) is a form of programmed cell death induced by mitotic process disorders, which is very important in tumor prevention, development, and drug resistance. Because rapidly increased data for MC is vigorously promoting the tumor-related biomedical and clinical study, it is urgent for us to develop a professional and comprehensive database to curate MC-related data. Mitotic Catastrophe Database (MCDB) consists of 1214 genes/proteins and 5014 compounds collected and organized from more than 8000 research articles. Also, MCDB defines the confidence level, classification criteria, and uniform naming rules for MC-related data, which greatly improves data reliability and retrieval convenience. Moreover, MCDB develops protein sequence alignment and target prediction functions. The former can be used to predict new potential MC-related genes and proteins, and the latter can facilitate the identification of potential target proteins of unknown MC-related compounds. In short, MCDB is such a proprietary, standard, and comprehensive database for MC-relate data that will facilitate the exploration of MC from chemists to biologists in the fields of medicinal chemistry, molecular biology, bioinformatics, oncology and so on. The MCDB is distributed on http://www.combio-lezhang.online/MCDB/index_html/.

The impact of the ecological state of the region of birth on the functional state of health

The paper considers the problem of the impact of a complex of environmental factors and their impact on the health of young people. Young people aged 18 to 21 years old, who lived up to 18 years old in different environmental conditions, were examined in order to assess the general functional state of their body. The study used a developed non-invasive optical method for assessing the oxygen status of tissues and general functional state, as well as an independent biomedical study. The results of the experiment revealed the significance of the influence of the ecological factors of the region of birth on the functional state of health of the young generation.

Ultra-widefield photoacoustic microscopy with a dual-channel slider-crank laser-scanning apparatus for in vivo biomedical study

Photoacoustic microscopy (PAM) is an important imaging tool that can noninvasively visualize the anatomical structure of living animals. However, the limited scanning area restricts traditional PAM systems for scanning a large animal. Here, we firstly report a dual-channel PAM system based on a custom-made slider-crank scanner. This novel scanner allows us to stably capture an ultra-widefield scanning area of 24 mm at a high B-scan speed of 32 Hz while maintaining a high signal-to-noise ratio. Our system's spatial resolution is measured at ∼3.4 μm and ∼37 μm for lateral and axial resolution, respectively. Without any contrast agent, a dragonfly wing, a nude mouse ear, an entire rat ear, and a portion of mouse sagittal are successfully imaged. Furthermore, for hemodynamic monitoring, the mimicking circulating tumor cells using magnetic contrast agent is rapidly captured in vitro. The experimental results demonstrated that our device is a promising tool for biological applications.

Protocol for Anesthesia Animal Model in Biomedical Study

Recognition of pain depends upon intact pathways from pain receptors to thethalamus and cerebral cortex, as well as functional cerebral cortex and subcorticalstructures. Thus any means that renders the cerebral cortex nonfunctional, suchas hypoxia or drug depression, prevents pain. When this happens, stimuli thatevoke motor nerve reflexes that may be painful to the conscious animal are notpainful in the unconscious animal. Equally painful stimuli administered toanimals chemically paralyzed by curare or succinylcholine will not evoke a motorreflex simply because of paralysis, but will cause pain because of the consciousstate. Hence, it is possible that unconscious animals may feel no pain but respondto certain stimuli, and paralyzed animals may feel pain but cannot respond.