Priority Challenge Research Articles

Proteomic analysis of plasma exosomes in patients with metastatic colorectal cancer

BackgroundThe diagnosis and treatment of colorectal cancer (CRC), especially metastatic colorectal cancer (mCRC), is a major priority and research challenge. We screened for expression differences in the plasma exosomal proteomes of patients with mCRC, those with CRC, and healthy controls (HCs) to discover potential biomarkers for mCRC.MethodsPlasma samples from five patients with mCRC, five patients with CRC, and five HCs were collected and processed to isolate exosomes by ultracentrifugation. Exosomal protein concentrations were determined using the BCA kit, and liquid chromatography-mass spectrometry was utilized to identify and analyze the proteins.ResultsFrom the exosomes isolated from plasma samples, a total of 994 quantifiable proteins were detected, including 287 differentially expressed proteins identified by quantitative proteomics analyses. Totals of 965, 963 and 968 proteins were identified in mCRC patients, CRC patients, and HCs, respectively. The study identified 83 proteins with differential expression in the plasma exosomes of mCRC patients. The top 10 upregulated proteins in the mCRC group and CRC groups were ITGA4, GNAI1, SFTPA2, UGGT1, GRN, LBP, SMIM1, BMP1, HMGN5, and MFAP4, while the top 10 downregulated proteins were PSMB8, LCK, RAB35, PSMB4, CD81, CD63, GLIPR2, RAP1B, RAB30, and CES1. Western Blot validation data confirmed that ITGA4 and GNAI1 were unequivocally enriched in plasma-derived exosomes from mCRC patients.ConclusionsThese differential proteins offer potential new candidate molecules for further research on the pathogenesis of mCRC and the identification of therapeutic targets. This study sheds light on the potential significance of plasma exosome proteomics studies in our understanding and treatment of mCRC.

Comparison of different intervention methods to reduce the incidence of venous thromboembolism: study protocol for a cluster-randomized, crossover trial

BackgroundVenous thromboembolism (VTE) remains a priority challenge among orthopedic trauma patients. It is crucial to further improve the prophylaxis against VTE in routine orthopedic treatment. This study aims to compare the efficacy of two low molecular weight heparin (LMWH) regimens and additional intermittent pneumatic compression in preventing VTE among orthopedic trauma patients.Methods and analysisThis is a cluster-randomized crossover clinical study conducted in four hospitals in Shanghai from December 2019 to December 2023. The unit of randomization is orthopedic wards, and each ward will define a cluster. All clusters will implement four diverse intervention measures and one control measure in a given random sequence. Perioperative orthopedic trauma patients aged ≥ 18 years with stable vital signs, Caprini score > 2, and no contraindication of anticoagulation or intermittent pneumatic compression (IPC) devices will be eligible. The sample size will be determined to be 2590, considering cluster effect, period effect, and interactions. We will generally use the intention-to-treat (ITT) at the subject level for each outcome. For the primary outcome of the study, the incidence of VTE will be presented as risk ratio and 95% CIs. Generalized estimating equation (GEE) will be deployed to compare differences and adjust cluster effect, period effect, and interaction among interventions and periods if applicable.DiscussionVTE is a complication that cannot be underestimated after major orthopedic surgery. Early identification, early assessment, and early prevention can significantly reduce the incidence of VTE. Most guidelines recommend both medical and physical prevention, and we hope to demonstrate how they would affect the incidence among perioperative orthopedic patients. We want to explore if there is a difference between the two types of LWMH with or without an IPC device to provide more evidence for future guidelines and prevent more patients from the threat of VTE.Ethics and disseminationThe study received approval from the IRB of the coordinating center and all participating hospitals. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registrationChiCTR1900027659. Registered on 17 November 2019

The Impact ofthe COVID-19 Pandemic onthe Military Health System's Care ofMilitary Sexual Assault.

Sexual assault remains a high priority challenge for leaders in the U.S. military. The COVID-19 pandemic further complicated the issue by disrupting work and lifestyles, potentially affecting reporting and care-seeking by victims. To date, there are no studies addressing the impact of changes in access to health services and reporting of sexual assault by active duty service members to inform medical and public health interventions in a post-COVID-19 era and during future public health emergencies. Using the Military Health System Data Repository (MDR), we identified a retrospective open cohort of active duty servicemembers receiving care in the Military Health System (MHS) from fiscal years 2018 to 2021. Through the use of ICD-10 diagnostic codes, all corresponding sexual assault care was identified for the cohort before (October 1, 2017-February 28, 2020; pre-pandemic period) and after (March 1, 2020-September 30, 2021; pandemic period) the institution of COVID-19 pandemic protective measures. Pre-pandemic and pandemic period rates of sexual assault associated encounters per 10,000 total health encounters were calculated by geographic location and compared using Wilcoxon's sign rank test. Multivariate log binomial regression models were performed to estimate associated risk of sexual assault among active duty servicemembers and compared across both periods. The study identified 47,067,073 encounters for servicemembers in the pre-pandemic period, of which 7,813 (0.016%) were associated with sexual assault. During the pandemic period, 4,377 (0.015%) of 28,926,480 encounters were associated with sexual assault, indicating a 44% reduction in total encounters and a 9% reduction in the proportion of encounters associated with sexual assault. Eighteen installations within the MHS had statistically significant increases in rates of encounters. Most sexual assault encounters occurred in the 20-24 year age, Female, White, Junior Enlisted, Army, and Unmarried categories. During both time-frames, younger age and being female were associated with an increased risk of sexual assault encounters. Race, service branch, and marital status were also associated with the risk of encounters. Contrary to reports indicating a modest increase in the number of sexual assaults reported within the DoD, we found a reduction in the frequency of healthcare encounters associated with sexual assault during the pandemic which may be related to reduced access to care. Men comprised approximately 22% of sexual assault encounters delivered through the MHS although the racial distribution of encounters approximates the estimates of the DoD-published demographic statistics. This study illustrates that COVID-19 measures appear to have reduced access to care for sexual assault within the MHS but did not demonstrably alter the demographics of servicemembers seeking care. These findings suggest that the MHS may require contingency plans for future disruptions to care and public health emergencies.

Mainstreaming nature-based solutions through five forms of scaling: Case of the Kiiminkijoki River basin, Finland.

Nature-based solutions (NBS) are considered as means to tackle climate change and biodiversity loss while simultaneously enhancing human well-being. Yet, it is still poorly understood how NBS could be mainstreamed. We address this gap by proposing a framework on NBS and employing it in Finland's Kiiminkijoki River basin through participatory workshops and a questionnaire. We examine socio-environmental challenges and visions, existing and emerging NBS to reach the visions, and ways to scale-up NBS to a river basin level. In the river basin, water quality is the priority challenge, due to its relationships with local culture, climate change, and biodiversity. Our results consider how (1) to ensure the relevance of NBS for local actors, (2) instrumental, intrinsic, and relational value perspectives can be enhanced simultaneously by NBS, and (3) site specific NBS can be mainstreamed (i.e., by scaling up, down, out, in, deep) to the river basin level and beyond.

Beyond medication: Exploring social prescribing for mental ill health in Portugal

Abstract Mental ill health represents a priority challenge in public health due to its considerable burden on people's health and well-being, as well as economic consequences. Individuals with mental health problems have been presented with limited alternatives for improving their mental well-being, with medication being the most widely adopted solution. It is imperative that the focus shifts to prevention and the promotion of positive mental health. This can be achieved through non-medical alternatives, such as social prescribing (SP), a person-centered and intersectoral intervention. Some studies reveal that mental ill health is one of the most common reasons for referral to a SP service, with encouraging results about SP's benefits in mental health. SP has been implemented in Portugal since 2018, a country that had one of the highest prevalence of mental health disorders in the European Union. The aim of this study was to establish the prevalence of mental health-related referrals in Portugal and to describe the type of community services patients were referred to. Sociodemographic, health, and referral-related data was collected for 714 patients at primary healthcare units in Lisbon between 2018-2021. Results show that 53.6% of participants were aged between 26-65 and 66.9% were female. Approximately 20% were referred for mental health reasons and 65.5% had been diagnosed with a mental health disorder. Patients were referred to a range of third-sector organizations (associations, ONGs, municipalities) and activities (swimming, music classes, volunteering, pregnancy club), but no specific mental health services were identified among them. This could suggest that there is a lack of available mental health responses in the community or that they are not yet accessible to SP team. Further efforts are needed to map out these resources and reinforce the intersectoral work to create and promote mental well-being responses, to ensure access to mental health support for all. Key messages • There is a need to shift the focus towards prevention and promoting positive mental health through non-medical alternatives, such as social prescribing. • In SP in Portugal, there is a lack of available mental health resources in the community, suggesting the need for further efforts to create and promote mental well-being responses for all individuals.

Анализ канцерогенного риска и динамики заболеваемости и смертности населения Иркутской области от злокачественных новообразований

Morbidity and mortality caused by malignant neoplasms (MNs) is a priority challenge for health care. We analyzed some rough and standardized levels (oncological morbidity and mortality) over 2009–2018 based on official statistics. We ranked the RF regions as per the standardized morbidity level and established that the Irkutsk region took the 1st rank place among 85 RF regions as per it; it took the 16th rank place as per the ‘rough’ level. Morbidity and mortality levels that were higher in the Irkutsk region than the national average were established for such localizations as trachea, bronchi and lung cancer; prostate cancer; cervical cancer. The mortality to morbidity ratios were on average equal to 0.45 in the Irkutsk region and 0.49 in the RF as a whole; we identified a certain decrease in them, by 19.3 % and 20.0 % accordingly. We provided evidence of unacceptable individual carcinogenic chemical risk for people in cities with developed chemical industry and non-ferrous metallurgy. High carcinogenic radiation risks were caused by natural radon levels in soils. We calculated some prognostic morbidity and mortality levels: in 2021, the standardized morbidity level would be between 270.9 and 329.8 cases per 100 thousand people; the ‘rough’ level, between 372.7 and 532.4. The ‘rough’ mortality level would be between 220 and 230 cases per 100 thousand people.

Analysis of carcinogenic risk and dynamics of population morbidity and mortality in the Irkutsk region due to malignant neoplasms

Morbidity and mortality caused by malignant neoplasms (MNs) is a priority challenge for health care. We analyzed some rough and standardized levels (oncological morbidity and mortality) over 2009–2018 based on official statistics. We ranked the RF regions as per the standardized morbidity level and established that the Irkutsk region took the 1st rank place among 85 RF regions as per it; it took the 16th rank place as per the ‘rough’ level. Morbidity and mortality levels that were higher in the Irkutsk region than the national average were established for such localizations as trachea, bronchi and lung cancer; prostate cancer; cervical cancer. The mortality to morbidity ratios were on average equal to 0.45 in the Irkutsk region and 0.49 in the RF as a whole; we identified a certain decrease in them, by 19.3 % and 20.0 % accordingly. We provided evidence of unacceptable individual carcinogenic chemical risk for people in cities with developed chemical industry and non-ferrous metallurgy. High carcinogenic radiation risks were caused by natural radon levels in soils. We calculated some prognostic morbidity and mortality levels: in 2021, the standardized morbidity level would be between 270.9 and 329.8 cases per 100 thousand people; the ‘rough’ level, between 372.7 and 532.4. The ‘rough’ mortality level would be between 220 and 230 cases per 100 thousand people. We determined some priority tasks for future research aimed at identifying adverse effects produced by environmental factors and lifestyle-related factors as well as some tasks related to developing relevant targeted activities aimed at eliminating and mitigating cancer-inducing exposures.

European Union Trade Measures and Highest Priority Challenge Related to Climate Change in EU-Americas Relations

European Union Trade Measures and Highest Priority Challenge Related to Climate Change in EU-Americas Relations

FROG: A PORTABLE UNDERWATER MOBILE MAPPING SYSTEM

Abstract. Browsing the scientific and professional literature it appears that the concept of mobile mapping underwater is not as common as in ‘terrestrial’ applications. Nevertheless, exploring and mapping the ocean’s depths is a priority challenge for humankind, today more than ever. Radio waves, such as the GNSS or UWB signal, have a very limited transmission underwater, resulting in the absence of an underwater global positioning system. Consequently, the main sounding methods (i.e., depth measuring systems) are based on the fusion of inertial and acoustic sensors, which allow for systematic mapping of vast seafloor areas. However, photogrammetric surveying methods are preferred when high resolution and reliable colour information are essential aspects in the project economy. This class of approaches include visual odometry and visual SLAM (vSLAM), which represent a valid tool for navigation and positioning in GNSS-denied environments, such as underwater. In this paper, we present a portable underwater mobile mapping system, named FROG, which implements a vSLAM based solution to guide the survey according to photogrammetric principles. FROG is built upon the Guided Photogrammetry - GuPho concept and, thanks to its modular design, can be used by a diver or installed on a micro ROV and controlled remotely from a support vessel. In the paper, FROG characteristics will be detailed, and its potentialities demonstrated in real case applications at sea and in lakes.

Optimizing solar-assisted industrial heating and cooling system for cost-effective installation

Integrating solar thermal collectors into industrial processes could be a viable way to replace the use of conventional fuels and achieve economic and environmental goals. However, there is a need to consider the detailed dynamic operation of a system with storage on a systematic control scale to fully optimize realistic system performance under variable conditions by minimizing excess energy production and maximizing annual life-cycle cost savings. In this study, we developed a TRNSYS-based dynamic statistical optimization model and evaluated FPC-based solar-assisted heating systems to develop a cost-effective system design for two industries: MOHA soft drinks and Sheba leather factories in the Tigray region, Ethiopia. Three operating loads were compared: process heat, utility heat, and utility heat and chilled water. The optimized designs resulted in significant annual life-cycle cost savings, high solar fractions, and a good margin on temperature trends where solar collector size has a greater impact. Annual cost savings per unit area of solar collector for process and utility heat were in the range of $51–90/m2 for a collector mass flow rate and storage volume of 0.01–0.02 m3/h-m2 and 0.04–0.08 m3/m2, respectively. For the utility heat and chilled water loads, the values were $49/m2 for a mass flow rate of 0.04 m3/h-m2 and a storage volume of 0.07 m3/m2. Thus, the study supports the transient analysis of solar-assisted industrial heat. The case studies have shown that the method provides optimal solutions for the use of solar thermal energy. As investment and financial sourcing remain a priority challenge, the model and case study results could help in decision-making for similar and other production capacities, regions, industries, and solar technologies.

Calcium looping in the steel industry: GHG emissions and energy demand

The development of innovative solutions to decarbonize hard-to-abate sectors is a priority challenge in the quest to mitigate climate change. The GHG emission mitigation potential of the carbon capture Calcium Looping process (CaL) is investigated in this work. Two steelmaking routes are modeled: a blast furnace and a basic oxygen furnace (BF-BOF), and a direct reduction process and an electric arc furnace (DR-EAF), both of which are coupled with CaL technology. The carbon footprints of the two systems were evaluated, through an eco-design approach, with the aim of quantifying the GHG emissions and identifying the hotspots of the emissions. DR-EAF was found to be characterized by lower GHG emissions than BF-BOF (0.9 t vs 2.1 t CO2eq per tonne of liquid steel produced), as it is intrinsically more efficient and less carbon intensive. For this reason, the adoption of the CaL technology resulted to be more effective when applied to the BF-BOF, as it led to a reduction in GHG emissions of up to 66%, with respect to baseline plant configuration without the CaL system. The primary energy demand increased considerably by the integration of CaL in BF-BOF and this would be amplified in a future scenario dominated by renewable energy resources. We also remarked the importance of the CaL technology being circular to reduce and reuse the spent material deployed for CO2 sequestration. This work ends with a parametric analysis that points out the importance of the timescale of climate change metrics on the evaluation of the carbon footprint.

Efficient cell death mediated by bioengineered killer extracellular vesicles

Extracellular vesicles (EVs) are biological vehicles that are thought to mediate cell–cell communication via the transfer of biomolecules from donor to acceptor cells. Repurposing those natural vesicles into therapeutics delivery vectors is a high priority challenge for translational science. Here we engineer donor cells to produce copious amount of fusogenic EVs loaded with the catalytic domain of the Diphteria Toxin, known to trigger cell death through protein synthesis inhibition. We show that, when incubated with cancer acceptor cells, these Killer EVs block protein synthesis and lead to cell death. This proof of concept establishes the efficacy of Killer EVs in vitro, and suggests that further development may lead to tumor ablation in vivo, expanding the existing cancer therapeutics arsenal.

МЕТОДИКА ОПРЕДЕЛЕНИЯ ХАРАКТЕРИСТИК ВИБРОПРОЧНОСТИ КОНСТРУКЦИИ ПРИ ВЫСОКОСКОРОСТНЫХ ТРЕКОВЫХ ИСПЫТАНИЯХ АВИАЦИОННОЙ ТЕХНИКИ

Achieving the speed limits by ballistic aircraft is a priority, relevant and new technical challenge for the present. Track tests of such products are one of the final stages, confirming their practical performance and efficiency. Testing of products of aviation and rocket technology at the "Rocket Rail Track 3500" FKP "GkNIPAS" named after L.K. Safronov allow to accurately simulate the real conditions in which they are operated. The experimental setup includes a two-rail track, made on a special base, which excludes the unacceptable deflection of the R65 rail, with its fixing every 0.5 m by a special embedment design. The rail track has an acceleration section with an angle of attack of 2º and a length of 2500 m and a deceleration section. The test object is placed on the missile track carriage in such a way as to exclude the impact on it of shock waves reflected from the elements of the carriage and relief. Solid propellant rocket engines are installed on the carriage, which provide the necessary thrust. The sliding bearings of the rocket carriage cover the head of the rails. The thrust of the starting rocket engines provides the necessary acceleration to achieve the maximum values of the required test speed. Track high-speed tests of special equipment objects are accompanied by intense vibration and shock loading of the structure. As the speed of products increases above 600 m/s, as tests have shown, the amplitude of elastic oscillations of the structure can reach the maximum values permissible from the strength conditions. Experimental and theoretical study of vibration and shock effects on the structure of a track carriage with test objects under the conditions of an existing rail track is an urgent task for practice.

Biofabrication of nanovesicles for brain diseases.

Biofabrication of nanovesicles for brain diseases.

Cyberbullying research — Alignment to sustainable development and impact of COVID-19: Bibliometrics and science mapping analysis

The explosive growth and online media usage have transformed the communication landscape globally. Social media platforms have become a thriving ground for online exploitation and Cyberbullying, a high priority challenge in many countries (Gottschalk, 2022). Our study aims to provide a bibliometric overview of Cyberbullying research between 2010 and 2021, including a new analysis through the lens of sustainable development and the impact of COVID-19. We introduce altmetrics to assess the social media attention of publications. Analysis of 7045 publications, of which 1149 publications are directly aligned to the Sustainable Development Goals (SDG) and 123 publications related to COVID-19 are presented. Science mapping of countries and journals, prolific authors, and institutions, along with gender-related contributions, are captured in this study. Computers in Human Behavior is the most prolific journal in terms of publications and citations. The top three SDG are SDG16 peace, justice, and strong institutions, SDG4 Quality education, and SDG3 Good health and well-being. Within each SDG, we find focussed studies on the themes relating to psychological impact, prior exposure to violence, inequality and gender biases, lack of awareness and need for education, and social support and their implications for sustainable development. Further, studies on COVID-19 impact revealed a definitive increase in occurrences of Cyberbullying stemming from concurrent infodemics and confinement-induced digital addiction. Asian countries contributed to over 20% of the studies during the pandemic. We offer suggestions for future studies on shifting focus on populous developing economies, longitudinal studies of interventions, and a critical need to enhance technologies for auto-detection in multilingual contexts.

Two-photon responsive porphyrinic metal-organic framework involving Fenton-like reaction for enhanced photodynamic and sonodynamic therapy.

Designing new oxygenation nanomaterials by oxygen-generating or oxygen-carrying strategies in hypoxia-associated anti-tumor therapy is a high priority target yet challenge. In this work, we fabricated a nanoplatform involving Fenton-like reaction, Pd@MOF-525@HA, to relieve tumor hypoxia via oxygen-generating strategy for enhanced oxygen-dependent anti-tumor therapy. Thereinto, the porphyrinic MOF-525 can produce singlet oxygen (1O2) via light or ultrasonic irradiation for photodynamic and sonodynamic therapy. Notably, the well-dispersed Pd nanocubes within MOF-525 can convert H2O2 into O2 to mitigate the hypoxic environment for enhanced therapy outcome. Moreover, the two-photon activity and cancer cell specific targeting capability of Pd@MOF-525@HA gave rise to deeper tissue penetration and near-infrared light-induced fluorescence imaging to achieve precise guidance for cancer therapy. This work provides a feasible way in designing new oxygenation nanomaterials to relieve tumor hypoxia for enhanced cancer treatment.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s12951-022-01436-3.

Influence of rotational speed on the electrical and mechanical properties of the friction stir spot welded aluminium alloy sheets

AbstractAn efficient and productive joining technique to weld aluminium has become a priority challenge for promoting the use of aluminium in the electrical industry. One of the challenges is to obtain welds with superior mechanical properties with the consistent quality of weld surface as well as low electrical resistance. In this paper, the influence of rotational speed during the friction stir spot welding of AA 5754-H111 was studied to analyse the mechanical and electrical properties of the welds. The results from two rotational speeds (1000 rpm and 4500 rpm) are presented and compared to the base material. It was observed that the samples welded at 1000 rpm showed a higher average shear failure load (~ 1.1 kN) compared to the samples welded at 4500 rpm (~ 0.94 kN). The microhardness of the samples welded at 1000 rpm was higher than that of the base material, while the microhardness of samples welded at 4500 rpm was lower. It was also found that the friction welded sheets, regardless of the rotational speed used, showed increased electrical resistance compared to the base material, albeit this increase for the samples welded at 1000 rpm was about 42%, compared to samples welded at 4500 rpm where this increase was just 14%.

Optimizing renewable-based energy supply options for power generation in Ethiopia.

Ethiopia unveiled homegrown economic reform agenda aimed to achieve a lower-middle status by 2030 and sustain its economic growth to achieve medium-middle and higher-middle status by 2040 and 2050 respectively. In this study, we evaluated the optimal renewable energy mix for power generation and associated investment costs for the country to progressively achieve upper-middle-income countries by 2050. Two economic scenarios: business as usual and Ethiopia’s homegrown reform agenda scenario were considered. The study used an Open Source energy Modeling System. The model results suggest: if projected power demand increases as anticipated in the homegrown reform agenda scenario, Ethiopia requires to expand the installed power capacity to 31.22GW, 112.45GW and 334.27GW to cover the current unmet and achieve lower, medium and higher middle-income status by 2030, 2040 and 2050 respectively. The Ethiopian energy mix continues to be dominated by hydropower and starts gradually shifting to solar and wind energy development towards 2050 as a least-cost energy supply option. The results also indicate Ethiopia needs to invest about 70 billion US$ on power plant investments for the period 2021–2030 to achieve the lower-middle-income electricity per capita consumption target by 2030 and staggering cumulative investment in the order of 750 billion US$ from 2031 to 2050 inclusive to achieve upper-middle-income electricity consumption rates by 2050. Ethiopia has enough renewable energy potential to achieve its economic target. Investment and financial sourcing remain a priority challenge. The findings could be useful in supporting decision-making concerning socio-economic development and investment pathways in the country.

The need for measurement science in digital pathology

BackgroundPathology services experienced a surge in demand during the COVID-19 pandemic. Digitalisation of pathology workflows can help to increase throughput, yet many existing digitalisation solutions use non-standardised workflows captured in proprietary data formats and processed by black-box software, yielding data of varying quality. This study presents the views of a UK-led expert group on the barriers to adoption and the required input of measurement science to improve current practices in digital pathology. MethodsWith an aim to support the UK’s efforts in digitalisation of pathology services, this study comprised: (1) a review of existing evidence, (2) an online survey of domain experts, and (3) a workshop with 42 representatives from healthcare, regulatory bodies, pharmaceutical industry, academia, equipment, and software manufacturers. The discussion topics included sample processing, data interoperability, image analysis, equipment calibration, and use of novel imaging modalities. FindingsThe lack of data interoperability within the digital pathology workflows hinders data lookup and navigation, according to 80% of attendees. All participants stressed the importance of integrating imaging and non-imaging data for diagnosis, while 80% saw data integration as a priority challenge. 90% identified the benefits of artificial intelligence and machine learning, but identified the need for training and sound performance metrics.Methods for calibration and providing traceability were seen as essential to establish harmonised, reproducible sample processing, and image acquisition pipelines. Vendor-neutral data standards were seen as a “must-have” for providing meaningful data for downstream analysis. Users and vendors need good practice guidance on evaluation of uncertainty, fitness-for-purpose, and reproducibility of artificial intelligence/machine learning tools. All of the above needs to be accompanied by an upskilling of the pathology workforce. ConclusionsDigital pathology requires interoperable data formats, reproducible and comparable laboratory workflows, and trustworthy computer analysis software. Despite high interest in the use of novel imaging techniques and artificial intelligence tools, their adoption is slowed down by the lack of guidance and evaluation tools to assess the suitability of these techniques for specific clinical question. Measurement science expertise in uncertainty estimation, standardisation, reference materials, and calibration can help establishing reproducibility and comparability between laboratory procedures, yielding high quality data and providing higher confidence in diagnosis.

Identification of bacterial antibiotic resistance genes in next-generation sequencing data (review of literature).

The spread of antibiotic-resistant human bacterial pathogens is a serious threat to modern medicine. Antibiotic susceptibility testing is essential for treatment regimens optimization and preventing dissemination of antibiotic resistance. Therefore, development of antibiotic susceptibility testing methods is a priority challenge of laboratory medicine. The aim of this review is to analyze the capabilities of the bioinformatics tools for bacterial whole genome sequence data processing. The PubMed database, Russian scientific electronic library eLIBRARY, information networks of World health organization and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) were used during the analysis. In this review, the platforms for whole genome sequencing, which are suitable for detection of bacterial genetic resistance determinants, are described. The classic step of genetic resistance determinants searching is an alignment between the query nucleotide/protein sequence and the subject (database) nucleotide/protein sequence, which is performed using the nucleotide and protein sequence databases. The most commonly used databases are Resfinder, CARD, Bacterial Antimicrobial Resistance Reference Gene Database. The results of the resistance determinants searching in genome assemblies is more correct in comparison to results of the searching in contigs. The new resistance genes searching bioinformatics tools, such as neural networks and machine learning, are discussed in the review. After critical appraisal of the current antibiotic resistance databases we designed a protocol for predicting antibiotic resistance using whole genome sequence data. The designed protocol can be used as a basis of the algorithm for qualitative and quantitative antimicrobial susceptibility testing based on whole genome sequence data.