Clinical Biomedical Research Research Articles

Light‐Driven Multi‐Core/Shell Microdroplets as a Targeted Drug Delivery System

AbstractTargeted drug delivery system (DDS) holds exciting prospects in biomedical clinical research and drug development. However, it faces a significant challenge in achieving stable and safe targeted transportation without drug leakage while obtaining precise and controllable drug dosing with a high drug utilization rate and low side effects. Herein, an optical tweezers‐based light‐driven technique is proposed to transport and construct multi‐core/shell microdroplets enveloping drug carriers and target cells as a novel, safe, and efficient targeted DDS. Drug‐loaded microdroplets with core/shell structures are first fabricated by a new and simple injection extrusion method and then it is transported to a target cell by a dynamic optical trap with a low optical power, which ensures no drug leakage, exogenous materials, and biothermal damage are introduced during the drug delivery process. Next, precise drug dosing is realized by pushing the target cell into the drug‐loaded microdroplet under the actions of optical forces, which constructs a multi‐core/shell microdroplet structure with a pure drug environment to improve the drug action efficiency. Moreover, quantitative drug dosing with a high drug utilization rate can also achieved by controlling the sizes/number of drug droplets inside the microdroplets. This light‐driven DDS is of great interest to frontier medical research and disease treatment fields.

Mueller matrix-based characterization of cervical tissue sections: a quantitative comparison of polar and differential decomposition methods.

Quantitative optical polarimetry has received considerable recent attention owing to its potential for being an efficient diagnosis and characterizing tool with potential applications in biomedical research and various other disciplines. In this regard, it is crucial to validate various Mueller matrix (MM) decomposition methods, which are utilized to extract and quantify the intrinsic individual polarization anisotropy properties of various complex optical media. To quantitatively compare the performance of both polar and differential MM decomposition methods for probing the structural and morphological changes in complex optical media through analyzing their intrinsic individual polarization parameters, which are extracted using the respective decomposition algorithms. We also intend to utilize the decomposition-derived anisotropy parameters to distinguish among the cervical tissues with different grades of cervical intraepithelial neoplasia (CIN) and to characterize the healing efficiency of an organic crystal. Polarization MM of the cervical tissues with different grades of CIN and the different stages of the self-healing crystal are recorded with a home-built MM imaging setup in the transmission detection geometry with a spatial resolution of . The measured MMs are then processed with both the polar and differential MM decomposition methods to extract the individual polarization parameters of the respective samples. The derived polarization parameters are further analyzed to validate and compare the performance of both the MM decomposition methods for probing and characterizing the structural changes in the respective investigated optical media through their decomposition-derived intrinsic individual polarization properties. Pronounced differences in the decomposed-derived polarization anisotropy parameters are observed for cervical tissue sections with different grades of CIN. While a significant increase in the depolarization parameter is obtained with the increment of CIN stages for both the polar [ for CIN grade one (CIN-I) and for CIN grade two (CIN-II))] and differential ( for CIN-I and for CIN-II) decomposition methods, a trend reversal is seen for the linear diattenuation parameter , indicating the structural distortion in the cervical morphology due to the CIN disease. More importantly, with the differential decomposition algorithm, the magnitude of the derived parameter decreases from 0.26 to 0.19 with the progression of CIN, which was not being probed by the polar decomposition method. Our results demonstrate that the differential decomposition of MM holds certain advantages over the polar decomposition method to characterize and probe the structural changes in the cervical tissues with different grades of CIN. Although the quantified individual polarization parameters obtained through both the MM decomposition methods can be used as useful metrics to characterize various optical media, in case of complex turbid media such as biological tissues, incorporation of the differential decomposition technique may yield more efficient information. Also, the study highlights the utilization of MM polarimetry with an appropriate decomposition technique as an efficient diagnostic and characterizing tool in the realm of biomedical clinical research, and various other disciplines.

How to Peer Review a Neurology Education Manuscript.

Peer review is an essential process in scientific research, ensuring the comprehensiveness, accuracy, and suitability of manuscripts for publication. Neurology education research differs from biomedical clinical research in several ways. These differences encompass specific paradigms, the use of theoretical frameworks, and different methodological approaches. Despite the high number of studies and journal publications on neurology education, there is a dearth of resources and guidance on how to perform a formal review on this specific literature. This article aims to review the distinctive features of neurology education from clinical research while proposing an organizational framework and model for performing peer reviews of papers focused on neurology education.

MTM: a multi-task learning framework to predict individualized tissue gene expression profiles.

Transcriptional profiles of diverse tissues provide significant insights in both fundamental and translational researches, while transcriptome information is not always available for tissues that require invasive biopsies. Alternatively, predicting tissue expression profiles from more accessible "surrogate" samples, especially blood transcriptome, has become a promising strategy when invasive procedures are not practical. However, existing approaches ignore tissue-shared intrinsic relevance, inevitably limiting predictive performance. We propose a unified deep learning-based multi-task learning framework, multi-tissue transcriptome mapping (MTM), enabling the prediction of individualized expression profiles from any available tissue of an individual. By jointly leveraging individualized cross-tissue information from reference samples through multi-task learning, MTM achieves superior sample-level and gene-level performance on unseen individuals. With the high prediction accuracy and the ability to preserve individualized biological variations, MTM could facilitate both fundamental and clinical biomedical research. MTM's code and documentation are available upon publication on GitHub (https://github.com/yangence/MTM).

Applications of Body Imaging Techniques in Clinical Practice and Biomedical Research: An Overview

Background: Applications of imaging technology modalities have accumulated evidence that individual components of body composition (BC) have significant influences on chronic disease onset, disease progression, treatment responses and health outcomes. Objective: To analyse the currently available body imaging techniques and their applications in clinical practice and medical research. Methods: To review the various body imaging techniques and their applications in clinical practice and medical research, Medline, PubMed, Google scholar, ResearchGate and other databases were searched. Furthermore, references of selected studies and documents available in different libraries were also searched. Findings: Imaging modalities have provided a systematic method for differentiating phenotypes of BC that diverge from normal, i.e. having low bone mass (osteopenia/osteoporosis), low muscle mass (sarcopenia), high fat mass (obesity), or high fat with low muscle mass (sarcopenic obesity). Tremendous advances were made over the past decades in the sensitivity and quality of imaging techniques such as Duel-Energy X-Ray Absorptiometry (DXA), Computed Axial Tomography (CT), Ultrasound (US), Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), Positron Emission Tomography (PET), Bioelectrical Impedance Analysis (BIA) etc. These imaging techniques have been useful to differentiate layers or depots within tissues and cells enhancing our understanding of distinct mechanistic, metabolic and functional roles of BC within human phenotypes. Conclusion: In the present overview, we focused on DXA, CT and US for the use in clinical practice and biomedical research relevant to future investigation of human BC and how they may be applied to remedy the pandemic of obesity, diabetes and metabolic syndrome. Bangladesh Med Res Counc Bull 2021; 47(2): 103-109

SemClinBr - a multi-institutional and multi-specialty semantically annotated corpus for Portuguese clinical NLP tasks

BackgroundThe high volume of research focusing on extracting patient information from electronic health records (EHRs) has led to an increase in the demand for annotated corpora, which are a precious resource for both the development and evaluation of natural language processing (NLP) algorithms. The absence of a multipurpose clinical corpus outside the scope of the English language, especially in Brazilian Portuguese, is glaring and severely impacts scientific progress in the biomedical NLP field.MethodsIn this study, a semantically annotated corpus was developed using clinical text from multiple medical specialties, document types, and institutions. In addition, we present, (1) a survey listing common aspects, differences, and lessons learned from previous research, (2) a fine-grained annotation schema that can be replicated to guide other annotation initiatives, (3) a web-based annotation tool focusing on an annotation suggestion feature, and (4) both intrinsic and extrinsic evaluation of the annotations.ResultsThis study resulted in SemClinBr, a corpus that has 1000 clinical notes, labeled with 65,117 entities and 11,263 relations. In addition, both negation cues and medical abbreviation dictionaries were generated from the annotations. The average annotator agreement score varied from 0.71 (applying strict match) to 0.92 (considering a relaxed match) while accepting partial overlaps and hierarchically related semantic types. The extrinsic evaluation, when applying the corpus to two downstream NLP tasks, demonstrated the reliability and usefulness of annotations, with the systems achieving results that were consistent with the agreement scores.ConclusionThe SemClinBr corpus and other resources produced in this work can support clinical NLP studies, providing a common development and evaluation resource for the research community, boosting the utilization of EHRs in both clinical practice and biomedical research. To the best of our knowledge, SemClinBr is the first available Portuguese clinical corpus.

Combining multiple biomarkers to linearly maximize the diagnostic accuracy under ordered multi-class setting.

Either in clinical study or biomedical research, it is a common practice to combine multiple biomarkers to improve the overall diagnostic performance. Despite the fact there exist a large number of statistical methods for biomarker combination under binary classification, research on this topic under multi-class setting is sparse. The overall diagnostic accuracy, i.e. the sum of correct classification rates, directly measures the classification accuracy of the combined biomarkers. Hence the overall accuracy can serve as an important objective function for biomarker combination, especially when the combined biomarkers are used for the purpose of making medical diagnosis. In this paper, we address the problem of combining multiple biomarkers to directly maximize the overall diagnostic accuracy by presenting several grid search methods and derivation-based methods. A comprehensive simulation study was conducted to compare the performances of these methods. An ovarian cancer data set is analyzed in the end.

Sensitive Detection of Argonaute2 by Triple-Helix Molecular Switch Reaction and Pyrene Excimer Switching

RNA interference (RNAi) is a powerful tool for silencing target genes in a variety of cells and has great therapeutic potential. It is triggered by small interfering RNAs (siRNAs) and by an RNA-binding protein (argonaute, Ago). In this manuscript, we designed a simple fluorescence sensor strategy for sensitive detection of argonaute2 (Ago2) based on the base pairing principle of Watson–Crick and Hoogsteen and the pyrene excimer switch. The sensing platform has extremely high sensitivity and a detection limit of 0.1nM. It can be used to detect endogenous Ago2 in cancer cells and has great potential in clinical diagnosis and biomedical research.

A new database of the references on international clinical practice guidelines: a facility for the evaluation of clinical research

Although there are now several bibliographic databases of research publications, such as Google Scholar, Pubmed, Scopus, and the Web of Science (WoS), and some also include counts of citations, there is at present no similarly comprehensive database of the rapidly growing number of clinical practice guidelines (CPGs), with their references, which sometimes number in the hundreds. CPGs have been shown to be useful for the evaluation of clinical (as opposed to basic) biomedical research, which often suffers from relatively low counts of citations in the serial literature. The objectives were to introduce a new citation database, clinical impact®, and demonstrate how it can be used to evaluate research impact of clinical research publications by exploring the characteristics of CPG citations of two sets of papers, as well as show temporal variation of clinical impact® and the WoS. The paper includes the methodology used to retain the data and also the rationale adopted to achieve data quality. The analysis showed that although CPGs tend preferentially to cite papers from their own country, this is not always the case. It also showed that cited papers tend to have a more clinical research level than uncited papers. An analysis of diachronous citations in both clinical impact® and the WoS showed that although the WoS citations showed a decreasing trend after a peak at 2–3 years after publication, this was less clear for CPG citations and a longer timescale would be needed to evaluate their impact on these documents.

Ending the Human Immunodeficiency Virus Pandemic: Optimizing the Prevention and Treatment Toolkits.

Unprecedented basic and clinical biomedical research advances over the past 4 decades have led to the development of "toolkits" of highly effective interventions for preventing and treating human immunodeficiency virus (HIV). Despite many successes in decreasing the incidence and mortality of HIV, major challenges remain in the goal of ending the HIV pandemic in the United States and globally. Overcoming these challenges will require optimization of the implementation of existing interventions for HIV prevention and treatment together with the continued development of new and innovative approaches that can be readily utilized by individuals with HIV and those at risk of infection.

An efficient forward model based on the Lattice Boltzmann method for optical tomography

Optical tomography is a powerful tool for preclinical and clinical biomedical research, which enables quantitative observation and precise localization of regions of interest within biological tissues. However, the excessive time caused by the forward model of optical tomography is the main limitation of its application in many fields, such as the dynamic imaging. In this paper, we present an efficient forward model based on the Lattice Boltzmann method (LBM), which is realized by radiation transfer equation discretization to simplify the mathematical structures and apply it for optical tomography. To demonstrate the feasibility of the proposed model for optical tomography, we carried out numerical cylinder simulation to validate the simulated light source distribution. To evaluate the performance of the proposed model for optical tomography, we performed a numerical phantom and a physical phantom experiments on a hybrid fluorescence diffuse optical tomography/X-CT imaging system to observe the tomographic reconstruction, by using the simulated phantom data and the experimental phantom data, respectively. The results showed that our proposed forward model obtained similar light source distribution comparing with the standard Monte Carlo method and the cosine similarity was about 96%. Further, our proposed forward model greatly improves the efficiency of optical tomography without a degradation of quality. The LBM provided about 5 times speed enhancement for phantom experiment and 2 times contrast-to-noise ratio boost for physical phantom experiment. Experimental results showed that our proposed model has large potential for performance improvement in optical tomography.

Setting and motivation in the decision to participate: An approach to the engagement of diverse samples in mobile research

Internet and mobile based research are powerful tools in the creation of large, cohort studies (eCohort). However, recent analysis indicates that an underrepresentation of minority and low income groups in these studies might exceed that found in traditional research [1–5]. In this report, we present findings from an experiment in research engagement using the Eureka Research Platform developed to enroll diverse populations in support of biomedical clinical research. This experiment involved the recruitment of African American and Latino participants in a smartphone based survey at a temporary, charitable, dental event sponsored, in part, by the research team, in order to explore the impact of setting and approach on recruitment outcomes. 211 participants enrolled including a significant representation of African Americans (51%) and Latinos (31%) and those with education levels at high school or less (37%). Interviews conducted after the study confirmed that our recruitment efforts within the context of a service event affected the decision to participate. While further research is necessary, this experiment holds promise for the engagement of underrepresented groups in research.

TRENDS: Toward a Separate Ethics of Political Field Experiments

In this article, I develop a critical view of the development and state of research ethics in political science. The central problem is that political scientists have inappropriately followed the lead of clinical biomedical research ethics in thinking about their own designs. Specifically I argue that the focus on institutional and group decision-making contexts distinctive to political research presents normative problems not well-addressed by clinical biomedical approaches. First, I make the case that research ethics as it has been conceived won’t capture all that might be wrong in political research designs because some of the potential harms/wrongs will be to political norms and institutions and thus will violate political (although not individual ethical) rights/values/and so on. Second, I rebut the challenge that principles of justice and equipoise standard to biomedical research ethics might be suitable for political research. And third, I argue that political theorists and philosophers must involve themselves in empirical political science research ethics if we are to effectively communicate the stakes of these research designs to practitioners, consumers, funders, and editors who remain steeped in the norms of biomedical research ethics.

Gross osteology and radiology of the pelvic limb of the adult small East African goat.

The aim of this study was to provide the detailed normal gross osteology and radiographic anatomy of the pelvic limb in adult small East African goats as a reference for clinical use, biomedical research and teaching. Radiography of the pelvic limb was performed in five adult small East African goats. Bone specimens of four skeletally mature small East African goats were used for gross osteological study. The ilial wing was wide. The ischiatic tuberosity was prominent and well developed. The acetabulum was rounded. The minor trochanter was located caudomedially, and the femoral trochlea was deep and narrow. The lateral and medial condyles of the femur were approximately of the same size. The tibial tuberosity was prominent, and the cochlea grooves were deep with a pronounced intermediate ridge. The trochlea of the talus was deep. The patella presented a prominent tuberosity on the cranial surface. The metatarsal sesamoid bone was seen in all animals. The observed gross osteology and radiographic anatomy of the pelvic limb of small East African goats was consistent with the presence of strong extensor muscles of the hip, stifle and tarsus for propulsion during terrestrial walking and trotting.

Biotechnical System for Recording Phonocardiography

The Phonocardiography is a graphical method of recording of the tones and noise generated by the heart with the help of the phonocardiogram machine. Cardiovascular disease (CVD) and heart failure (HF) are considered life-threatening and mostly cause death. The phonocardiograph signal (PCG) considers an indicator of abnormalities in the cardiovascular system. It provides the ability to carry out qualitative information and quantitative analysis of different tones and heart murmurs. PCG plays a major role in treatment, diagnosis and decision making of the clinical examination and biomedical research fields. The use of simple stethoscope for diagnosis the heart problem requires an experienced physician or doctors. Many people with CVD and HF are dying every day because of the lack of facilities that analysis the heart defects. Most of the low come countries suffer from a severe shortage in the Electrocardiogram (ECG) and PCG devices and trained physicians and doctors. The Poor healthcare system in these countries needs to be improved especially the problem of heart disease diagnostics. The PCG is a technique for recording and monitoring the cardiac acoustics by using a transducer and microphone. This paper attempts to design a cheap and simple biotechnical system for recording and monitoring PCG signal. The hardware was designed and implemented using the stethoscope, electret microphone, amplifiers, DC source, and jack for transmitting the PCG signal to the computer. The software was codded for monitoring and processing the PCG signal.

The ethics of uninsured participants accessing healthcare in biomedical research: A literature review.

Background/aims Sparse literature exists on the challenges and ethical considerations of including people with limited access to healthcare, such as the uninsured and low-income, in clinical research in high-income countries. However, many ethical issues should be considered with respect to working with uninsured and low-income participants in clinical research, including enrollment and retention, ancillary care, and post-trial responsibilities. Attention to the uninsured and low-income is particularly salient in the United States due to the high rates of uninsurance and underinsurance. Thus, we conducted a scoping review on the ethical considerations of biomedical clinical research with uninsured and low-income participants in high-income countries in order to describe what is known and to pinpoint areas of needed research on this issue. Methods MEDLINE/PubMed, Embase, and Scopus databases were searched using terms that described main concepts of interest (e.g., uninsured, underinsured, access to healthcare, poverty, ethics, compensation, clinical research). Articles were included if they met four inclusion criteria: (1) English, (2) high-income countries context, (3) about research participants who are uninsured or low-income, which limits their access to healthcare, and in biomedical clinical research that either had a prospect of direct medical benefit or was offered to them on the basis of their ill health, and (4) recognizes and/or addresses challenges or ethical considerations of uninsured or low-income participants in biomedical clinical research. Results The searches generated a total of 974 results. Ultimately, 23 papers were included in the scoping review. Of 23 articles, the majority (n = 19) discussed enrollment and retention of uninsured or low-income participants. Several barriers to enrolling uninsured and low-income groups were identified, including limited access to primary or preventive care; lack of access to institutions conducting trials or physicians with enough time or knowledge about trials; overall lack of trust in the government, research, or medical system; and logistical issues. Considerably fewer articles discussed treatment of these participants during the course of research (n = 5) or post-trial responsibilities owed to them (n = 4). Thus, we propose a research agenda that builds upon the existing literature by addressing three broad questions: (1) What is the current status of uninsured research participants in biomedical clinical research in high-income countries? (2) How should uninsured research participants be treated during and after clinical research? (3) How, if at all, should additional protections for uninsured research participants affect their enrollment? Conclusions This review reveals significant gaps in both data and thoughtful analysis on how to ethically involve uninsured research participants. To address these gaps, we propose a research agenda to gather needed data and theoretical analysis that addresses three broad research questions.

Theranostics with radiation-induced ultrasound emission (TRUE)

Two novel ultrasound imaging techniques with imaging contrast mechanisms are in the works: X-ray-induced acoustic computed tomography (XACT), and nanoscale photoacoustic tomography (nPAT). XACT has incredible potential in: (1) biomedical imaging, through which a 3D image can be generated using only a single X-ray projection, and (2) radiation dosimetry. nPAT as a new alternative of super-resolution microscopy can break through the optical diffraction limit and is capable of exploring sub-cellular structures without reliance on fluorescence labeling. We expect these new imaging techniques to find widespread applications in both pre-clinical and clinical biomedical research.

A Hospital-Based Committee of Moral Philosophy to Revive Ethics.

The Méditerranée Infection Foundation's primary goal is supporting a research hospital for the treatment of infectious diseases in Marseille. The main objective of this innovative center is to understand the mechanisms of contagion and face them. The Foundation will include a committee on moral philosophy that will accompany and supervise biomedical research. This is not a conventional ethics committee, frequently giving rise to a board's bureaucratic excesses, which might slow down creative biomedical clinical research without necessarily restricting abuses. Moral philosophy, however, can handle contemporary biomedical issues. In all its diversity, this discipline is able to enrich the debate on medical issues, thanks to many philosophical currents such as deontological ethics and consequentialism. The purpose of this committee is therefore to advance reflection on the bioethical issues encountered in biomedical research in infectious diseases, while respecting the precepts of moral philosophy.

La acreditación de los comités de ética de la investigación

ObjectiveAccording to Law 14/2007 and Royal Decree 1090/2015, biomedical research must be assessed by an Research Ethics Committee (REC), which must be accredited as an Research ethics committee for clinical trials involving medicinal products (RECm) if the opinion is issued for a clinical trial involving medicinal products or clinical research with medical devices. The aim of this study is to ascertain how IEC and IECm accreditation is regulated. MethodsNational and regional legislation governing biomedical research was analysed. ResultsNo clearly-defined IEC or IECm accreditation procedures exist in the national or regional legislation. DiscussionIndependent Ethics Committees are vital for the development of basic or clinical biomedical research, and they must be accredited by an external body in order to safeguard their independence, multidisciplinary composition and review procedures.

Attention to Individuals: Mixed Methods for N-of-1 Health Care Interventions.

In several ways, randomized controlled trials represent a high standard of rigor in clinical biomedical research. Randomized controlled trials fail, however, to yield knowledge applicable to specific individuals. This article presents a methodological rationale for a mixed methods approach to n-of-1 clinical studies that attends to the preferences and concerns of individuals while attaining high standards of qualitative and quantitative rigor. An illustrative research design involving a hypothetical music therapy intervention for a quality of life outcome is examined in some detail and a concluding argument is made that the proposed mixed methods approach is especially appropriate for early-stage research interventions intended to generate explanatory hypotheses.