Colorectal cancer screening: The value of early detection and modern challenges.

The screening of colorectal cancer (CRC) is pivotal for both the prevention and treatment of this disease, significantly improving early-stage tumor detection rates. This advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with treatment. However, the adoption of CRC screening methods faces numerous challenges, including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and specificity. Moreover, socioeconomic factors such as regional disparities, economic conditions, and varying levels of awareness affect screening uptake. The coronavirus disease 2019 pandemic further intensified these cha-llenges, leading to reduced screening participation and increased waiting periods. Additionally, the growing prevalence of early-onset CRC necessitates innovative screening approaches. In response, research into new methodologies, including artificial intelligence-based systems, aims to improve the precision and accessibility of screening. Proactive measures by governments and health organizations to enhance CRC screening efforts are underway, including increased advocacy, improved service delivery, and international cooperation. The role of technological innovation and global health collaboration in advancing CRC screening is undeniable. Technologies such as artificial intelligence and gene sequencing are set to revolutionize CRC screening, making a significant impact on the fight against this disease. Given the rise in early-onset CRC, it is crucial for screening strategies to continually evolve, ensuring their effectiveness and applicability.

A holistic overview of the in-situ and ex-situ carbon mineralization: Methods, mechanisms, and technical challenges.

To mitigate anthropogenic CO2 emissions and address the climate change effects, carbon capture and storage by mineralization (CCSM) and industrial mineral carbonation are gaining attraction. Specifically, in-situ carbon mineralization in the subsurface geological formations occurs due to the transformation of silicate minerals into carbonates (e.g., CaCO3, MgCO3) while ex-situ carbon mineralization at the surface undergoes chemical reactions with metal cations - thus leading to permanent storage. However, both processes are complex and require a rigorous investigation to enable large-scale mineralization. This paper, therefore, aims to provide an overreaching review of the in-situ and ex-situ methods for carbon mineralization for different rock types, various engineered processes, and associated mechanisms pertinent to mineralization. Furthermore, the factors influencing in-situ and ex-situ processes, e.g., suitable minerals, optimal operating conditions, and technical challenges, have also been inclusively reviewed. Our findings suggest that in-situ carbon mineralization, i.e., subsurface permanent storage of CO2 by mineralization, arguably is more promising than ex-situ mineralization due to energy efficiency and large-scale storage potential. Furthermore, the effect of rock type can be ranked as igneous (basalt) > carbonates (sedimentary) > sandstone (sedimentary) to consider for rapid and large-scale CCSM. The findings of this review will, therefore, help towards a better understanding of carbon mineralization, which contributes towards large-scale CO2 storage to meet the global net-zero targets.

Endovascular balloon usage in endoscopic third ventriculostomy for hydrocephalus during a national shortage: case series and technical note.

Endoscopic third ventriculostomy (ETV) is a well-established surgical technique for treating hydrocephalus. Many providers have transitioned to utilizing the specialized Neuroballoon for the stoma dilation in ETV; however, these devices are intermittently unavailable during supply chain shortages. We present the experience of employing cardiac angioplasty and neurovascular balloons as substitutes for the Neuroballoon in 3 patients. The scepter balloon (Microvention), priced at $1800 compared to the standard $300 Neuroballoon (Integra), proved effective, but its pliability presented technical challenges. The substantial cost differential compared to a Neuroballoon ($300) raises economic considerations. The Cardiac TREK balloon (Abbott) was similarly effective, while also being easier to manage endoscopically and cheaper at $158. These experiences support the viability of non-neuroendoscopic specialized balloons as alternatives for ETV dilation of the floor of tuber cinereum.

Unraveling germline predisposition in hematological neoplasms: Navigating complexity in the genomic era.

Genomic advancements have yielded pivotal insights into hematological neoplasms, particularly concerning germline predisposition mutations. Following the WHO 2016 revisions, dedicated segments were proposed to address these aspects. Current WHO 2022, ICC 2022, and ELN 2022 classifications recognize their significance, introducing more mutations and prompting integration into clinical practice. Approximately 5-10% of hematological neoplasm patients show germline predisposition gene mutations, rising with risk factors such as personal cancer history and familial antecedents, even in older adults. Nevertheless, technical challenges persist. Optimal DNA samples are skin fibroblast-extracted, although not universally applicable. Alternatives such as hair follicle use are explored. Moreover, the scrutiny of germline genomics mandates judicious test selection to ensure precise and accurate interpretation. Given the significant influence of genetic counseling on patient care and post-assessment procedures, there arises a demand for dedicated centers offering specialized services.

An integrative literature review of the potential technical challenges in Forensic Odontology practice ­ an exploratory study / Uma revisão integrativa da literatura sobre os potenciais desafios técnicos na prática da Odontologia Forense ­ um estudo exploratório

Forensic Odontology deals with the presentation of dental evidence in a court of law. An academic exploration revealed instances of technical challenges within the field. This study endeavours to delve into the spheres where these challenges occur, with the core objective of enhancing the quality of practice. An integrative literature review was conducted using the online platforms SCOPUS and Web of Science. Based on the selection criteria, 29 pertinent papers dated 2000-2023 were included. Quantitative analysis of the categories of selected articles was performed using Microsoft Excel 2019 (Microsoft Corp., Redmond, WA, USA). Technical concerns were reported in all facets of Forensic Odontology with the general role of expert witnesses being reported the most (n=8; 27.58%). Within the different facets of the field, age estimation was the most prominent area of concern (n=8; 27.58%) and child abuse and neglect (n=1; 3.57%) represented the least reported category. Findings indicate that there is a need to prioritize avenues to enhance the quality of practice in the general role of expert witnesses and the specific area of dental age estimation. To this end, increased support for researchers must be provided to help validate methodologies. It is advisable to institute mandatory formal training and proficiency testing within the field. Inadequate knowledge of dentists regarding child abuse and neglect has been noted, demonstrating the need for more dedicated quality training. Recommendations for Forensic Odontologists have been curated combining this study's results and the codes of ethics of various forensic organisations

A Odontologia Legal trata da apresentação de provas odontológicas em juízo. Uma exploração acadêmica revelou exemplos de desafios técnicos na área. Este estudo procura aprofundar as esferas onde estes desafios ocorrem, com o objetivo central de melhorar a qualidade da prática. Foi realizada uma revisão integrativa da literatura utilizando as plataformas online SCOPUS e Web of Science. Com base nos critérios de seleção, foram incluídos 29 artigos pertinentes datados de 2000-2023. A análise quantitativa das categorias dos artigos selecionados foi realizada no Microsoft Excel 2019 (Microsoft Corp., Redmond, WA, EUA). Preocupações técnicas foram relatadas em todas as áreas da Odontologia Legal, sendo o papel geral dos peritos o mais relatado (n=8; 27,58%). Dentro das diferentes áreas de atuação, a estimativa da idade foi a área de preocupação mais proeminente (n=8; 27,58%), e o abuso infantil e a negligência (n=1; 3,57%) representaram a categoria menos relatada. Os resultados indicam que há uma necessidade de priorizar caminhos para melhorar a qualidade da prática no papel geral dos peritos e na área específica da estimativa da idade dental. Para este efeito, deve ser prestado maior apoio aos investigadores para ajudar a validar metodologias. É aconselhável instituir treinamento formal obrigatório e testes de proficiência na área. Foi observado um conhecimento inadequado dos dentistas sobre abuso e negligência infantil, demonstrando a necessidade de uma formação mais dedicada e de qualidade. As recomendações para Dentistas Forenses foram selecionadas combinando os resultados deste estudo e os códigos de ética de várias organizações forenses.

A review of the challenges, learnings and future directions of home handheld spirometry in interstitial lung disease.

BACKGROUND: Patients with interstitial lung disease (ILD) require regular physician visits and referral to specialist ILD clinics. Difficulties or delays in accessing care can limit opportunities to monitor disease trajectory and response to treatment, and the COVID-19 pandemic has added to these challenges. Therefore, home monitoring technologies, such as home handheld spirometry, have gained increased attention as they may help to improve access to care for patients with ILD. However, while several studies have shown that home handheld spirometry in ILD is acceptable for most patients, data from clinical trials are not sufficiently robust to support its use as a primary endpoint. This review discusses the challenges that were encountered with handheld spirometry across three recent ILD studies, which included home spirometry as a primary endpoint, and highlights where further optimisation and research into home handheld spirometry in ILD is required. Rate of decline in forced vital capacity (FVC) as measured by daily home handheld spirometry versus site spirometry was of primary interest in three recently completed studies: STARLINER (NCT03261037), STARMAP and a Phase II study of pirfenidone in progressive fibrosing unclassifiable ILD (NCT03099187). Unanticipated practical and technical issues led to problems with estimating FVC decline. In all three studies, cross-sectional correlations for home handheld versus site spirometry were strong/moderate at baseline and later timepoints, but longitudinal correlations were weak. Other issues observed with the home handheld spirometry data included: high within-patient variability in home handheld FVC measurements; implausible longitudinal patterns in the home handheld spirometry data that were not reflected in site spirometry; and extreme estimated rates of FVC change. CONCLUSIONS: Home handheld spirometry in ILD requires further optimisation and research to ensure accurate and reliable FVC measurements before it can be used as an endpoint in clinical trials. Refresher training, automated alerts of problems and FVC changes, and patient support could help to overcome some practical issues. Despite the challenges, there is value in incorporating home handheld spirometry into clinical practice, and the COVID-19 pandemic has highlighted the potential for home monitoring technologies to help improve access to care for patients with ILD.

Macrophage phagocytosis after spinal cord injury: when friends become foes.

After spinal cord injury, macrophages can exert either beneficial or detrimental effects depending on their phenotype. Aside from their critical role in inflammatory responses, macrophages are also specialized in the recognition, engulfment, and degradation of pathogens, apoptotic cells, and tissue debris. They promote remyelination and axonal regeneration by removing inhibitory myelin components and cellular debris. However, excessive intracellular presence of lipids and dysregulated intracellular lipid homeostasis result in the formation of foamy macrophages. These develop a pro-inflammatory phenotype that may contribute to further neurological decline. Additionally, myelin-activated macrophages play a crucial role in axonal dieback and retraction. Here, we review the opposing functional consequences of phagocytosis by macrophages in spinal cord injury, including remyelination and regeneration versus demyelination, degeneration, and axonal dieback. Furthermore, we discuss how targeting the phagocytic ability of macrophages may have therapeutic potential for the treatment of spinal cord injury.

The Epic of In Vitro Meat Production-A Fiction into Reality.

Due to a proportionally increasing population and food demands, the food industry has come up with wide innovations, opportunities, and possibilities to manufacture meat under in vitro conditions. The amalgamation of cell culture and tissue engineering has been the base idea for the development of the synthetic meat, and this has been proposed to be a pivotal study for a futuristic muscle development program in the medical field. With improved microbial and chemical advancements, in vitro meat matched the conventional meat and is proposed to be eco-friendly, healthy, nutrient rich, and ethical. Despite the success, there are several challenges associated with the utilization of materials in synthetic meat manufacture, which demands regulatory and safety assessment systems to manage the risks associated with the production of cultured meat. The role of 3D bioprinting meat analogues enables a better nutritional profile and sensorial values. The integration of nanosensors in the bioprocess of culture meat eased the quality assessment throughout the food supply chain and management. Multidisciplinary approaches such as mathematical modelling, computer fluid dynamics, and biophotonics coupled with tissue engineering will be promising aspects to envisage the future prospective of this technology and make it available to the public at economically feasible rates.

Acute and late side-effects after low dose-rate brachytherapy for prostate cancer; incidence, management and technical considerations.

PURPOSE: To review common reported side effects and complications after primary LDR-BT (monotherapy) and discuss some of the technical aspects that could impact the treatment outcomes. METHODS AND MATERIALS: A literature search was undertaken using medical subject headings (MeSH) complemented by the authors' personal and institutional expertise. RESULTS: The reported incidence of acute and late grade 2 or above urinary, bowel and sexual side effects is very variable across the literature. The learning curve and the implant quality have a clear impact on the toxicity outcomes. Being aware of some of the technical challenges encountered during the procedure and ways to mitigate them could decrease the incidence of side effects. Careful planning of seed placement and seed deposition allow sparing of the organs at risk and a lower incidence of urinary and gastro-intestinal toxicity. CONCLUSIONS: Low dose-rate brachytherapy remains a standard monotherapy treatment in the setting of favorable-risk prostate cancer. High disease control and low long-term toxicities are achievable in expert hands with a good technique.

Transcranial direct current stimulation with functional magnetic resonance imaging: a detailed validation and operational guide.

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate human brain and behavioural function in both research and clinical interventions. The combination of functional magnetic resonance imaging (fMRI) with tDCS enables researchers to directly test causal contributions of stimulated brain regions, answering questions about the physiology and neural mechanisms underlying behaviour. Despite the promise of the technique, advances have been hampered by technical challenges and methodological variability between studies, confounding comparability/replicability. Methods: Here tDCS-fMRI at 3T was developed for a series of experiments investigating language recovery after stroke. To validate the method, one healthy volunteer completed an fMRI paradigm with three conditions: (i) No-tDCS, (ii) Sham-tDCS, (iii) 2mA Anodal-tDCS. MR data were analysed in SPM12 with region-of-interest (ROI) analyses of the two electrodes and reference sites. Results: Quality assessment indicated no visible signal dropouts or distortions introduced by the tDCS equipment. After modelling scanner drift, motion-related variance, and temporal autocorrelation, we found no field inhomogeneity in functional sensitivity metrics across conditions in grey matter and in the three ROIs. Discussion: Key safety factors and risk mitigation strategies that must be taken into consideration when integrating tDCS into an fMRI environment are outlined. To obtain reliable results, we provide practical solutions to technical challenges and complications of the method. It is hoped that sharing these data and SOP will promote methodological replication in future studies, enhancing the quality of tDCS-fMRI application, and improve the reliability of scientific results in this field. Conclusions: The method and data provided here provide a technically safe, reliable tDCS-fMRI procedure to obtain high quality MR data. The detailed framework of the Standard Operation Procedure SOP ( https://doi.org/10.5281/zenodo.4606564) systematically reports the technical and procedural elements of our tDCS-fMRI approach, which we hope can be adopted and prove useful in future studies.

Tidal Volume in Pediatric Ventilation: Do You Get What You See?

Mechanical ventilators are increasingly evolving into computer-driven devices. These technical advancements have impact on clinical decisions in pediatric intensive care units (PICUs). A good understanding of the design of mechanical ventilators can improve clinical care. Tidal volume (TV) is one of the corner stones of ventilation: multiple technical factors influence the TV and, thus, influence clinical decision making. Ventilator manufacturers make various design choices regarding the phase, site and conditions of TV measurement as well as algorithmic processing choices. Such choice may impact the measurement and subsequent display of TV. A software change of the TV measuring algorithm of the SERVO-i® (Getinge, Solna, Sweden) at the PICU of the University Medical Centre Utrecht was studied in a prospective cohort. It showed, as example, a clinically significant impact of 8% difference in reported TV. Design choices in both the hardware and software of mechanical ventilators can have a clinically relevant impact on the measurement of tidal volume. In our search for the optimal TV for lung-protective ventilation, such choices should be taken into account.

Challenges for Therapeutic Applications of Opsin-Based Optogenetic Tools in Humans.

As the technological hurdles are overcome and optogenetic techniques advance to have more control over neurons, therapies based on these approaches will begin to emerge in the clinic. Here, we consider the technical challenges surrounding the transition of this breakthrough technology from an investigative tool to a true therapeutic avenue. The emerging strategies and remaining tasks surrounding genetically encoded molecules which respond to light as well as the vehicles required to deliver them are discussed.The use of optogenetics in humans would represent a completely new paradigm in medicine and would be associated with unprecedented technical considerations. To be applied for stimulation of neurons in humans, an ideal optogenetic tool would need to be non-immunogenic, highly sensitive, and activatable with red light or near-infrared light (to maximize light penetration while minimizing photodamage). To enable sophisticated levels of neuronal control, the combined use of optogenetic actuators and indicators could enable closed-loop all-optical neuromodulation. Such systems would introduce additional challenges related to spectral orthogonality between actuator and indicator, the need for decision making computational algorithms and requirements for large gene cassettes. As in any gene therapy, the therapeutic efficiency of optogenetics will rely on vector delivery and expression in the appropriate cell type. Although viral vectors such as those based on AAVs are showing great potential in human trials, barriers to their general use remain, including immune responses, delivery/transport, and liver clearance. Limitations associated with the gene cassette size which can be packaged in currently approved vectors also need to be addressed.

Adaptive Design: A Review of the Technical, Statistical, and Regulatory Aspects of Implementation in a Clinical Trial.

BACKGROUND: In an adaptive trial, the researcher may have the option of responding to interim safety and efficacy data in a number of ways, including narrowing the study focus or increasing the number of subjects, balancing treatment allocation or different forms of randomization based on responses of subjects prior to treatment. This research aims at compiling the technical, statistical, and regulatory implications of the employment of adaptive design in a clinical trial. METHODS: Review of adaptive design clinical trials in Medline, PubMed, EU Clinical Trials Register, and ClinicalTrials.gov. Phase I and seamless phase I/II trials were excluded. We selected variables extracted from trials that included basic study characteristics, adaptive design features, size and use of independent data-monitoring committees (DMCs), and blinded interim analysis. RESULTS: The research retrieved 336 results, from which 78 were selected for analysis. Sixty-seven were published articles, and 11 were guidelines, papers, and regulatory bills. The most prevalent type of adaptation was the seamless phase II/III design 23.1%, followed by adaptive dose progression 19.2%, pick the winner / drop the loser 16.7%, sample size re-estimation 10.3%, change in the study objective 9.0%, adaptive sequential design 9.0%, adaptive randomization 6.4%, biomarker adaptive design 3.8%, and endpoint adaptation 2.6%. Discussion DISCUSSION: It is possible to infer that the use of Adaptive Design is an ethical and scientific advantage when properly planned and applied, since it increases the flexibility of the trial, shortens the overall clinical investigation time of a drug, and reduces the risk of patient exposure to adverse effects related to the experimental drug. Its greater methodologic and analytic complexity requires an adequate statistical methodology. CONCLUSIONS: The application of "adaptive clinical designs" for phase II/III studies appear to have been limited to trials with a small number of study centers, with smaller extensions of time and to experimental drugs with more immediate clinical effects that are amenable to risk/benefit decisions based on interim analyses. According to the reviewed studies, simple adaptive trial designs-such as early study terminations due to futility and sample size re-estimation-are becoming widely adopted throughout the pharmaceutical industry, especially in phase II and III studies. The pharmaceutical industry and contract research organizations (CROs) are implementing simple adaptations more frequently and the more complex adaptations-biomarker adaptive design, endpoint adaptation-are more sporadic.

Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes.

Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.

Creating a foundation for implementing an electronic health records (EHR)-integrated Social Knowledge Networking (SKN) system on medication reconciliation.

Background: In fall 2016, Augusta University received a two-year grant from AHRQ, to implement a Social Knowledge Networking (SKN) system for enabling its health system, AU-Health, to progress from "limited use" of EHR Medication Reconciliation (MedRec) Technology, to "meaningful use." Phase 1 sought to identify a comprehensive set of issues related to EHR MedRec encountered by practitioners at AU-Health. These efforts helped develop a Reporting Tool, which, along with a Discussion Tool, was incorporated into the AU-Health EHR, at the end of Phase 1. Phase 2 (currently underway), comprises a 52-week pilot of the EHR-integrated SKN system in outpatient and inpatient medicine units. The purpose of this paper is to describe the methods and results of Phase 1. Methods: Phase 1 utilized an exploratory mixed-method approach, involving two rounds of data collection. This included 15 individual interviews followed by a survey of 200 practitioners, i.e., physicians, nurses, and pharmacists, based in the outpatient and inpatient medicine service at AU Health. Results: Thematic analysis of interviews identified 55 issue-items related to EHR MedRec under 9 issue-categories. The survey sought practitioners' importance-rating of all issue-items identified from interviews. A total of 127 (63%) survey responses were received. Factor analysis served to validate the following 6 of the 9 issue-categories, all of which, were rated "Important" or higher (on average), by over 70% of all respondents: 1) Care-Coordination (CCI); 2) Patient-Education (PEI); 3) Ownership-and-Accountability (OAI); 4) Processes-of-Care (PCI); 5) IT-Related (ITRI); and 6) Workforce-Training (WTI). Significance-testing of importance-rating by professional affiliation revealed no statistically significant differences for CCI and PEI; and some statistically significant differences for OAI, PCI, ITRI, and WTI. Conclusion: There were two key gleanings from the issues related to EHR MedRec unearthed by this study: 1) there was an absence of shared understanding among practitioners, of the value of EHR MedRec in promoting patient safety, which contributed to workarounds, and suboptimal use of the EHR MedRec system; and 2) there was a socio-technical dimension to many of the issues, creating an added layer of complexity. These gleanings in turn, provide insights into best practices for managing both clinical transitions-of-care in the EHR MedRec process; and socio-technical challenges encountered in EHR MedRec implementation.

Anticipating Emerging Biotechnology Threats: A case study of CRISPR.

This article discusses the contingencies and complexities of CRISPR. It outlines key problems regarding off-target effects and replication of experimental work that are important to consider in light of CRISPR's touted ease of use and diffusion. In light of literature on the sociotechnical dimensions of the life sciences and biotechnology and literature on former bioweapons programs, this article argues that we need more detailed empirical case studies of the social and technical factors shaping CRISPR and related gene-editing techniques in order to better understand how they may be different from other advances in biotechnology-or whether similar features remain. This information will be critical to better inform intelligence practitioners and policymakers about the security implications of new gene-editing techniques.

Technical challenges related to implementation of a formula one real time data acquisition and analysis system in a paediatric intensive care unit.

Most existing, expert monitoring systems do not provide the real time continuous analysis of the monitored physiological data that is necessary to detect transient or combined vital sign indicators nor do they provide long term storage of the data for retrospective analyses. In this paper we examine the feasibility of implementing a long term data storage system which has the ability to incorporate real-time data analytics, the system design, report the main technical issues encountered, the solutions implemented and the statistics of the data recorded. McLaren Electronic Systems expertise used to continually monitor and analyse the data from F1 racing cars in real time was utilised to implement a similar real-time data recording platform system adapted with real time analytics to suit the requirements of the intensive care environment. We encountered many technical (hardware and software) implementation challenges. However there were many advantages of the system once it was operational. They include: (1) The ability to store the data for long periods of time enabling access to historical physiological data. (2) The ability to alter the time axis to contract or expand periods of interest. (3) The ability to store and review ECG morphology retrospectively. (4) Detailed post event (cardiac/respiratory arrest or other clinically significant deteriorations in patients) data can be reviewed clinically as opposed to trend data providing valuable clinical insight. Informed mortality and morbidity reviews can be conducted. (5) Storage of waveform data capture to use for algorithm development for adaptive early warning systems. Recording data from bed-side monitors in intensive care/wards is feasible. It is possible to set up real time data recording and long term storage systems. These systems in future can be improved with additional patient specific metrics which predict the status of a patient thus paving the way for real time predictive monitoring.

Circulating endothelial cells and their subsets: novel biomarkers for cancer.

Angiogenesis contributes to the growth of solid tumors. Antiangiogenic agents are widely used in various cancers and considerable efforts have been made in the development of novel biomarkers that can predict the outcome of an anticancer treatment. Of those, circulating endothelial cells (CECs) and their subsets constitute a surrogate tool for monitoring disease activity. However, owing to the lack of standardization on the phenotypes and detection of CECs and their subsets, results have always been inconsistent and uninterpretable. In this review, we focus on the biological characteristics in terms of physiology, phenotypes and detection of CECs along with their subsets; review the current scenario of CEC enumeration as a surrogate biomarker in clinical oncology; and explore their future potential applications.

Advances in addressing technical challenges of point-of-care diagnostics in resource-limited settings.

The striking prevalence of HIV, TB and malaria, as well as outbreaks of emerging infectious diseases, such as influenza A (H7N9), Ebola and MERS, poses great challenges for patient care in resource-limited settings (RLS). However, advanced diagnostic technologies cannot be implemented in RLS largely due to economic constraints. Simple and inexpensive point-of-care (POC) diagnostics, which rely less on environmental context and operator training, have thus been extensively studied to achieve early diagnosis and treatment monitoring in non-laboratory settings. Despite great input from material science, biomedical engineering and nanotechnology for developing POC diagnostics, significant technical challenges are yet to be overcome. Summarized here are the technical challenges associated with POC diagnostics from a RLS perspective and the latest advances in addressing these challenges are reviewed.