Progressive Evolution Research Articles

Multiple Pulmonary Involvement in the Rapidly Progressive Evolution of Rheumatoid Arthritis

A 66-year-old man, a 40-year smoker, was diagnosed with rheumatoid arthritis in 2018. He was treated for one year with methotrexate, and, later in 2020, he was diagnosed with interstitial pulmonary fibrosis. In 2022, treatment with nintedanib was initiated, with clinical improvement being indicated but without showing a functional or imaging benefit. The evolution of the disease was rapidly progressive and unfavorable, with death occurring due to pulmonary thromboembolism. Following the autopsy, triple lesions of the RA at the lung level were confirmed: interstitial, of the NSIP type with a fibrosing character at the level of the lower airways of the bilateral bronchiectasis type, and vascular damage due to pulmonary thromboembolism secondary to chronic inflammation.

Complex case of multiple sclerosis with multiple demyelinating locations

Multiple sclerosis (MS) is a chronic inflammatory disorder with an unpredictable progression that affects the central nervous system and has significant emotional, social, and professional implications. The therapeutic approach is multifactorial and requires complex management coordinated by a specialized, multidisciplinary team over the long term. Current non-pharmacological treatment strategies under study, which may improve the course of the disease, focus on the gut microbiome and include the administration of probiotics and fecal transplantation. This study presents a case of secondary progressive multiple sclerosis in a young patient, with rapidly progressive evolution despite ongoing background therapy. The study analyzed literature data regarding both medical rehabilitation programs used in secondary progressive multiple sclerosis and other therapeutic strategies that can improve the quality of life. Medical rehabilitation has no proven impact on disease progression but can enhance the quality of life for patients with multiple sclerosis through spasticity management, improved mental health, increased mobility, and muscle strength. These therapeutic strategies can improve involvement in professional activities and participation in social and family life for patients with multiple sclerosis.

DMF-ChIP-seq for Highly Sensitive and Integrated Epigenomic Profiling of Low-Input Cells.

Mapping genome-wide DNA-protein interactions (DPIs) provides insights into the epigenetic landscape of complex biological systems and elucidates the mechanisms of epigenetic regulation in biological progress. However, current technologies in DPI profiling still suffer from high cell demands, low detection sensitivity, and large reagent consumption. To address these problems, we developed DMF-ChIP-seq that builds on digital microfluidic (DMF) technology to profile genome-wide DPIs in a highly efficient, cost-effective, and user-friendly way. The entire workflow including cell pretreatment, antibody recognition, pA-Tn5 tagmentation, fragment enrichment, and PCR amplification is programmatically manipulated on a single chip. Leveraging closed submicroliter reaction volumes and a superhydrophobic interface, DMF-ChIP-seq presented higher sensitivity in peak enrichment than other current methods, with high accuracy (Pearson Correlation Coefficient (PCC) > 0.86) and high repeatability (PCC > 0.92). Furthermore, DMF-ChIP-seq was capable of processing the samples with as few as 8 cells while maintaining a high signal-to-noise ratio. By applying DMF-ChIP-seq, H3K27ac histone modification of early embryonic cells during differentiation was profiled for the investigation of epigenomic landscape dynamics. With the benefits of high efficiency and sensitivity in DPI analysis, the system provides great promise in studying epigenetic regulation during various biological processes.

Progressive hollow engineering induced raspberry-like magnetoelectric microspheres via synergistic etching-assembly strategy toward boosted microwave attenuation

Optimizing the electromagnetic (EM) properties of composites through elaborate tailoring of their microstructures has become an attractive research branch, but determining the correlations between morphology, composition, and performance remains challenging. Herein, a novel progressive hollow engineering strategy is proposed for the construction of hollow CuFe Prussian blue analog (CuFePBA, CF) precursors with asymptotic variations of cavities and PBA units based on a synergistic etching-assembly approach, subsequently combined with a polydopamine (PDA) coating and carbothermal process to acquire raspberry-like hollow Cu/Fe/Fe3C@NC (CFC) composites. The proposed approach addresses the drawbacks caused by organic ligand depletion or corrosive agent usage. We then present a systematic investigation of the mechanism by which the progressive hollow engineering-induced concurrent evolution of hollow cavities, phases, defects, and inhomogeneous interfaces contributes to the improvement of the dielectric properties of the CFC samples. An optimal reflection loss (RLmin) of − 65.17 dB at 3.29 mm was realized for the CFC-2 sample and the CFC-3 sample achieved an effective absorption bandwidth (EAB) of 4.4 GHz at an ultra-thin thickness of 1.29 mm. This work reveals the synergistic effects of compositional, interfacial, and defect variations on the EM wave attenuation properties of the composites, and will provide new design inspiration for novel absorbers with modulatable hollow architectures.

Visible-Near Infrared Independent Modulation of Hexagonal WO3 Induced by Ionic Insertion Sequence and Cavity Characteristics.

Dual-band electrochromic materials have attracted significant attention due to their ability to independently control sunlight and solar heat. However, these materials generally exhibit notable limitations, and the mechanisms for their dual-band independent regulation remain poorly understood. Here, the visible-NIR-independent regulation capabilities of hexagonal WO3 (h-WO3) are introduced for the first time. A structure-activity relationship that perfectlylinks the microscopic ion insertion sequence and cavity characteristics to the macroscopic dual-band electrochromic properties is established. The progressive ion intercalation process and the distinctive optical activity of the cavities are keys for enabling h-WO3 to independently modulate "bright," "cool," and "dark" modes. Notably, h-WO3 demonstrates superior dual-band electrochromic performance with a broadband full shielding effect from 550 to 2000nm, achieving the widest full shielding band in dual-band electrochromic studies. Additionally, h-WO3 shows a high discharge capacity of 270.9 mAh m- 2 at 0.25 A m- 2, and requires only 49.1 and 209.7 mAh m- 2 to complete a full round-trip switch between "bright-cool" and "bright-dark" modes, respectively. The constructed device offers a dynamic temperature control range of up to 10.5°C and supports a maximum voltage of 2.86V, underscoring its considerable potential for practical applications and energy efficiency.

Converging Pathways between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Diabetes in Children.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM, where each condition influences and exacerbates the progression of the other. This review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment into the diagnostic arsenal for children showing insufficient glycemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

Developing an ensemble machine learning study: Insights from a multi-center proof-of-concept study.

To address the numerous unmeet clinical needs, in recent years several Machine Learning models applied to medical images and clinical data have been introduced and developed. Even when they achieve encouraging results, they lack evolutionary progression, thus perpetuating their status as autonomous entities. We postulated that different algorithms which have been proposed in the literature to address the same diagnostic task, can be aggregated to enhance classification performance. We suggested a proof of concept to define an ensemble approach useful for integrating different algorithms proposed to solve the same clinical task. The proposed approach was developed starting from a public database consisting of radiomic features extracted from CT images relating to 535 patients suffering from lung cancer. Seven algorithms were trained independently by participants in the AI4MP working group on Artificial Intelligence of the Italian Association of Physics in Medicine to discriminate metastatic from non-metastatic patients. The classification scores generated by these algorithms are used to train SVM classifier. The Explainable Artificial Intelligence approach is applied to the final model. The ensemble model was validated following an 80-20 hold-out and leave-one-out scheme on the training set. Compared to individual algorithms, a more accurate result was achieved. On the independent test the ensemble model achieved an accuracy of 0.78, a F1-score of 0.57 and a log-loss of 0.49. Shapley values representing the contribution of each algorithm to the final classification result of the ensemble model were calculated. This information represents an added value for the end user useful for evaluating the appropriateness of the classification result on a particular case. It also allows us to evaluate on a global level which methodological approaches of the individual algorithms are likely to have the most impact. Our proposal represents an innovative approach useful for integrating different algorithms that populate the literature and which lays the foundations for future evaluations in broader application scenarios.

Superior damage tolerance observed in interpenetrating phase composites composed of aperiodic lattice structures

Interpenetrating Phase Composite (IPC) metamaterials, based on lattice topologies, have garnered significant attention as advanced materials for structural applications. However, conventional IPCs, which rely on periodic lattice unit cells, are prone to catastrophic failure due to their global deformation modes. To overcome this limitation, we present a novel IPC design utilizing aperiodic truss unit cells, inspired by the elusive “Einstein” monotile pattern. Our concept is demonstrated through IPC 3D printed via polymer jetting, using a hard polymer as the lattice filler and a soft polymer as the matrix. The distinctive mechanical properties of IPCs are characterized through single and cyclic quasi-static compression testing. Our findings demonstrate that aperiodic IPCs enable progressive deformation with gradual compression stress plateaus. Additionally, aperiodic IPCs exhibit remarkable damage tolerance, retaining 67.59 % of residual energy absorption and 73.83 % of ultimate strength after multiple cyclic compressions up to 30 % strain. These mechanisms are attributed to the synergistic deformation of interconnected unit cells, which lead to self-adjusting plastic collapse, progressive displacement evolution and delocalized deformation. This aperiodic concept paves the way for developing high-performance cushioning protection materials.

SeqImprove: Machine-Learning-Assisted Curation of Genetic Circuit Sequence Information.

The progress and utility of synthetic biology is currently hindered by the lengthy process of studying literature and replicating poorly documented work. Reconstruction of crucial design information through post hoc curation is highly noisy and error-prone. To combat this, author participation during the curation process is crucial. To encourage author participation without overburdening them, an ML-assisted curation tool called SeqImprove has been developed. Using named entity recognition, called entity normalization, and sequence matching, SeqImprove creates machine-accessible sequence data and metadata annotations, which authors can then review and edit before submitting a final sequence file. SeqImprove makes it easier for authors to submit sequence data that is FAIR (findable, accessible, interoperable, and reusable).

A Novel Multiobjective Genetic Programming Approach to High-Dimensional Data Classification.

The development of data sensing technology has generated a vast amount of high-dimensional data, posing great challenges for machine learning models. Over the past decades, despite demonstrating its effectiveness in data classification, genetic programming (GP) has still encountered three major challenges when dealing with high-dimensional data: 1) solution diversity; 2) multiclass imbalance; and 3) large feature space. In this article, we have developed a problem-specific multiobjective GP framework (PS-MOGP) for handling classification tasks with high-dimensional data. To reduce the large solution space caused by high dimensionality, we incorporate the recursive feature elimination strategy based on mining the archive of evolved GP solutions. A progressive domination Pareto archive evolution strategy (PD-PAES), which optimizes the objectives in a specific order according to their objectives, is proposed to evaluate the GP individuals and maintain a better diversity of solutions. Besides, to address the seriously imbalanced class issue caused by traditional binary decomposition (BD) one versus rest (OVR) for multiclass classification problems, we design a method named BD with a similar positive and negative class size (BD-SPNCS) to generate a set of auxiliary classifiers. Experimental results on benchmark and real-world datasets demonstrate that our proposed PS-MOGP outperforms state-of-the-art traditional and evolutionary classification methods in the context of high-dimensional data classification.

918P Deciphering the molecular drivers behind locoregional progression, intratumoral heterogeneity, and clonal evolution in locally advanced head and neck cancer

918P Deciphering the molecular drivers behind locoregional progression, intratumoral heterogeneity, and clonal evolution in locally advanced head and neck cancer

Unveiling the Uncanny: A Study of Gothic Elements in Jinnistan by Ayesha Muzaffar

This research explores the gothic elements in Jinnistan by Ayesha Muzaffar. This study utilizes the theory of uncanny by Sigmund Freud as a theoretical framework. Freud explores the word play between the concept of "homely" and its opposite, leading some to associate the unheimlich with the notion of the "unfamiliar." The study also uses Catherine Belsey’s textual analysis as an analytical framework. Gothic literature is a worldwide recognized genre. Gothic stories included symbols that symbolically conveyed the inner suffering of their tortured protagonists, such as supernatural phenomenon, unsettling environments, and ruined architectural settings. In Pakistan, gothic fiction is in its emerging phase with only a few writers exploring this genre in their noteworthy writings. Ayesha Muzaffar is a notable author in realm of horror fiction. The analysis of this study focuses on how the cultural elements have influenced the elements of uncanny in Jinnistan. This study aims to get better understanding of the evolutionary progression of gothic elements within Pakistani literature.

Quantitative ultrashort echo time MR imaging of knee osteochondral junction: An ex vivo feasibility study.

Compositional changes can occur in the osteochondral junction (OCJ) during the early stages and progressive disease evolution of knee osteoarthritis (OA). However, conventional magnetic resonance imaging (MRI) sequences are not able to image these regions efficiently because of the OCJ region's rapid signal decay. The development of new sequences able to image and quantify OCJ region is therefore highly desirable. We developed a comprehensive ultrashort echo time (UTE) MRI protocol for quantitative assessment of OCJ region in the knee joint, including UTE variable flip angle technique for T1 mapping, UTE magnetization transfer (UTE-MT) modeling for macromolecular proton fraction (MMF) mapping, UTE adiabatic T1ρ (UTE-AdiabT1ρ) sequence for T1ρ mapping, and multi-echo UTE sequence for T2* mapping. B1 mapping based on the UTE actual flip angle technique was utilized for B1 correction in T1, MMF, and T1ρ measurements. Ten normal and one abnormal cadaveric human knee joints were scanned on a 3T clinical MRI scanner to investigate the feasibility of OCJ imaging using the proposed protocol. Volumetric T1, MMF, T1ρ, and T2* maps of the OCJ, as well as the superficial and full-thickness cartilage regions, were successfully produced using the quantitative UTE imaging protocol. Significantly lower T1, T1ρ, and T2* relaxation times were observed in the OCJ region compared with those observed in both the superficial and full-thickness cartilage regions, whereas MMF showed significantly higher values in the OCJ region. In addition, all four UTE biomarkers showed substantial differences in the OCJ region between normal and abnormal knees. These results indicate that the newly developed 3D quantitative UTE imaging techniques are feasible for T1, MMF, T1ρ, and T2* mapping of knee OCJ, representative of a promising approach for the evaluation of compositional changes in early knee OA.

Navigating the personal carbon inclusion scheme: An evolutionary game theory approach to low-carbon behaviors among socio-economic groups

In response to the challenges posed by climate change, China has launched the Personal Carbon Inclusion (PCI) scheme to encourage individuals to transition towards low-carbon lifestyles. This study investigates the behaviors of participants within the PCI scheme using a tripartite evolutionary game model, encompassing high-income and low-income individuals, as well as the PCI platform itself. The research analyzes participants' strategies, examines the evolutionary stability of different strategies, and assesses the robustness of equilibrium points within the game dynamics. Key findings reveal: (1) High-income participants tend to be less willing to adopt low-carbon behaviors compared to low-income participants. (2) The PCI platform displays limited proactive engagement in promoting low-carbon policies. (3) Factors, particularly the cost and pricing mechanisms of low-carbon actions, significantly impact the evolutionary progression of the system. Moreover, practical recommendations are provided to enhance the effectiveness of PCI schemes.

A novel dual-stage failure criterion based on forming limit curve for uncured GLARE

Forming limit curve (FLC) is an essential criterion for evaluating the formability of fiber metal laminates (FMLs) in mass fabrication. However, conventional methodologies are unable to predict inner fiber failure, very sensitive to wrinkling defects, resulting in low measurement accuracy and stability. Hence, a novel dual-stage failure criterion considering the progressive failure of fiber and metal layers has been developed and validated by utilizing a notch-pattern sample and forming of typical thin-walled structure, with four typical categories of glass laminate aluminum reinforced epoxy (GLARE). The Nakajima tests of a series of notch-pattern and conventional pattern specimens with different widths were conducted in this study, demonstrating the superiority of wrinkling and delamination prevention of the notch-pattern by enhancing 22.84 % stress triaxiality and reducing 39.51 % compress strain in the edge area. Notably, punch reaction force and strain field analyses unveiled a mutation phenomenon indicative of premature fiber failure while the aluminum remained intact, which was also verified by numerical and interrupted methods. Furthermore, the acoustic emission in-situ method was adopted to monitor the progressive damage evolution of uncured GLARE in the Nakajima test, providing solid support for the occurrence of fiber failure at the mutation site. Leveraging these mutations, a list of dual-stage forming limit curves was devised to quantify the progressive damage behavior of uncured GLARE under biaxial tensile conditions. Finally, the practical application of this novel dual-stage forming limit curve methodology was demonstrated in the manufacturing process of a box-shaped part, serving as a proof of concept for its effectiveness. This study offers a foundational guideline for characterizing the intrinsic failure mechanisms of fiber metal laminates, particularly internal fiber failure under various strain conditions, thereby enhancing predictive accuracy.

Multiscale modeling of diffuse damage and localized cracking in quasi-brittle materials under compression with a quadratic friction law

The diffuse damage and localized cracking of quasi-brittle materials (i.e., rocks and concretes) under compression can be delineated by a matrix-microcrack system, wherein a solid matrix phase is weakened by a large number of randomly oriented and distributed microcracks, and the macroscopic cracking is formed by a progressive evolution of microcracks. Several homogenization-based multiscale models have been proposed to describe this matrix-microcrack system, but most of them are based on a linear friction law on the microcrack surface, rendering a linear strength criterion. In this paper, we propose a new quadratic friction law within the local multiscale friction-damage (LMFD) model to capture the plastic distortion due to frictional sliding along the rough microcrack surface. Following that, a macroscopic Ottosen-type nonlinear strength criterion is rationally derived with up-scaling friction-damage coupling analysis. An enhanced semi-implicit return mapping (ESRM) algorithm with a substepping scheme is then developed to integrate the complex nonlinear constitutive model. The performance of LMFD model is evaluated compared to a wide range of experimental data on plain concretes, and the robustness of ESRM algorithm is assessed through a series of numerical tests. Subsequently, to effectively describe the localized cracking process, a regularization scheme is proposed by combining the phase-field model with the established LMFD model, and the discretization independent crack localization is numerically verified.

Characterization of damage behavior and failure mechanisms of the bonded‐bolted hybrid three‐bolt joint in composite laminates

AbstractIn this paper, the mechanical properties, damage modes, and bolt load distribution of the bonded‐bolted hybrid three‐bolt joint were investigated by a combination of experiments and numerical simulations. Acoustic emission (AE) was used to monitor the tensile process of the connection in real time, and the K‐means clustering algorithm was used to realize the cluster analysis of the damage modes. A numerical simulation model of the tensile process of the joint was established using ABAQUS simulation software. The progressive damage evolution of composite laminates, and adhesive layer was characterized by using the VUMAT subroutine, the B‐K failure criterion, and cohesive element with zero thickness, respectively. The results show that four main damage modes occur in composite laminates during tension: matrix cracking, delamination, fiber pull‐out, and fiber breakage, with corresponding peak frequency ranges of (0–80 kHz), (80–210 kHz), (210–330 kHz), and (330–375 kHz), respectively. The adhesive layer between the laminates mainly exhibits peeling failure because of the secondary bending effect. In the load‐bearing process, the adhesive layer was loaded first and failed, and the bolt loading was delayed. Meanwhile, the results of bolt load distribution showed that the bolts and the adhesive layer at both ends carried greater loads.Highlights Damage modes and damage evolution of the bonded‐bolted hybrid joint in tension were analyzed by combining acoustic emission technology and numerical simulation. The simulation of delamination damage in composite laminates was carried out by inserting zero‐thickness cohesive elements into the laminates, and the delamination damage between the carbon fiber layup and the adjacent glass fiber layup was analyzed. The effect of the inclusion of the adhesive layer on the mechanical properties of the joint and the distribution of the bolt load was analyzed.

Pyridazine Derivatives: Molecular Docking, ADMET Prediction, and Synthesis for Antihypertensive Activity.

The drug discovery and development domain has witnessed remarkable advancements due to the integration of computational methods, particularly Computer-Aided Drug Design (CADD). Discovering and creating new drugs involves structural modifications to enhance their effectiveness and physical attributes. This frequently includes employing semisynthetic techniques to investigate structure-activity relationships thoroughly. Noticeable progress in molecular biology, computational chemistry, combinatorial chemistry, and highthroughput screening is steering transformative changes in the pharmaceutical industry. High blood pressure or hypertension, a significant health issue, elevates the chances of heart, kidney, and brain complications, among other health concerns. It's a leading cause of untimely mortality globally. Therefore, it is important to search for new antihypertensive compounds that have fewer side effects and higher therapeutic activity. Following molecular docking of the pyridazine derivatives, compounds were subjected to In-silico ADMET analysis. Subsequently, a low molecular weight compound was synthesized. Among the synthesized compounds characterization procedures include TLC, FT-IR, 1HNMR, and LC-MS techniques. Compound 8 exhibited the most favorable molecular docking results with alpha A1 and beta 1 adrenergic receptors. Compounds 3, 5, and 6 fulfilled the essential ADMET criteria. Subsequently, Compounds 3, 4, and 5 underwent additional synthesis and characterization procedures, including TLC, FT-IR, 1H-NMR, and LC-MS techniques. Similar behavior was observed in compounds 6, 8, 10, and 11, all violating Pfizer's 3/75 rules in terms of TPAS. Hydrazinolysis of these b-benzoyl propionic acids produced pyridazine, which was utilized in synthesizing pyridazine derivatives. TLC, FT-IR, 1HNMR, and LCMS have characterized the compounds.

Structural and stratigraphic history of the southern domain of the Indian Mountain Deformed Zone, southeastern New Brunswick, Canada: Tournaisian (Lower Carboniferous) tectonic ‘pop-up’ and collapse

The southern domain of the Indian Mountain Deformed Zone (IMDZ) in southeastern New Brunswick marks a major right-lateral strike-slip fault belt active during late Tournaisian (Lower Carboniferous) sedimentation. The rocks of the Sussex Group, representing a depositional cycle from subsidence to basin inversion, occupy this zone and lie unconformable on crystalline basement, the latter representing a partially exhumed portion of the adjacent (to the south) buried Westmorland uplift. Deformation is related to early reverse faults/thrusts, later strike-slip faults. and latest normal faults. The Gorge Fault zone in the southern domain of the IMDZ demonstrates many essential features of the entire zone. The offset of The Gorge Fault zone increases to the east. In the west it forms a blind thrust and asymmetric anticline whereas in the east it expands into a reverse fault/thrust complex. A progressive evolution from reverse faults/thrusts to strike-slip fault movement resulted in a tectonic pop-up, culminating in gravitational collapse along normal faults with listric profiles that flatten out within 100–200 metres of the present erosion surface. Megabreccias formed during deposition of the Sussex Group are contemporary with reverse fault/thrusts. The geometry of the various faults is best explained by progressive deformation within an overall right-lateral strike-slip regime under general shear, with early formed features rotating both congruently and incongruently to the main IMDZ boundaries. Further complexity is a consequence of many reverse faults/thrusts and normal faults occurring close to a free surface and the latter a response to gravitational instability of the pop-up structure controlled by topography. A revised stratigraphy for the Sussex Group in the Indian Mountain Deformed Zone and its interpretation is integral to constructing the structural history. Two units, Stilesville Formation and Briggs Cross Formation, are formally defined here.

Cell as a reference point in medicine (185 years of cell theory)

the cellular theory, formulated by T. Schwann in 1839, defines the cell as the elementary unit of living things, and has retained its relevance even now as a basic concept of medicine. Aim is to substantiate the definition of the concept of a cell as a reference point for the use of ideas about its organization and properties as a tool for the study of vital processes/pathology in the human body and in experiments. The progress of biology and medicine over the past century and a half has led to numerous attempts to revise the formulation and content of the cell theory. In fact, attempts were made to expand the interpretation/definition of the semantic parts of the initial content of its definition, namely: what is a cell (structure, composition, and properties); what is an elementary unit (taking into account the existence of proto- and eukaryotes, unicellular and multicellular organisms); what is this living thing? Systemic analysis of the organization of the cell allows, as an option, to consider it as a system for the vital activity of which such subsystems are necessary and sufficient as: the carrier of hereditary information (genome), the system of implementation of hereditary information, the plastic support system, the energy supply system, the regulatory system, the reproduction system. Ideas about these functional life support systems can be extrapolated to a multicellular organism. T. Schwann 's idea that a cell is the elementary unit of a living thing, and R. Virchow’s idea that a pathological process is a manifestation of cell changes are generally accepted today. Accordingly, cellular acts as a reference point for analyzing the development of the pathological process and methods of its correction. From these positions, the disease begins with a change in a some pattern of cells associated with changes in their genetic landscape or life support systems. Cells dysfunction of a certain differentiation leads to a lesion of the tissue specific function and the corresponding organ, and ultimately to a lesion of the organism vital activity as a whole. Accordingly, the systematization of facts and the clear definition of certain ideas about the composition, properties of the cell, the nature of its differentiation and the formation of tissue in the composition of the organs of the body is an effective tool for solving many applied questions of medicine.