Diagnosis of Liver Fibrosis Using Artificial Intelligence: A Systematic Review.

Background and Objectives: The development of liver fibrosis as a consequence of continuous inflammation represents a turning point in the evolution of chronic liver diseases. The recent developments of artificial intelligence (AI) applications show a high potential for improving the accuracy of diagnosis, involving large sets of clinical data. For this reason, the aim of this systematic review is to provide a comprehensive overview of current AI applications and analyze the accuracy of these systems to perform an automated diagnosis of liver fibrosis. Materials and Methods: We searched PubMed, Cochrane Library, EMBASE, and WILEY databases using predefined keywords. Articles were screened for relevant publications about AI applications capable of diagnosing liver fibrosis. Exclusion criteria were animal studies, case reports, abstracts, letters to the editor, conference presentations, pediatric studies, studies written in languages other than English, and editorials. Results: Our search identified a total of 24 articles analyzing the automated imagistic diagnosis of liver fibrosis, out of which six studies analyze liver ultrasound images, seven studies analyze computer tomography images, five studies analyze magnetic resonance images, and six studies analyze liver biopsies. The studies included in our systematic review showed that AI-assisted non-invasive techniques performed as accurately as human experts in detecting and staging liver fibrosis. Nevertheless, the findings of these studies need to be confirmed through clinical trials to be implemented into clinical practice. Conclusions: The current systematic review provides a comprehensive analysis of the performance of AI systems in diagnosing liver fibrosis. Automatic diagnosis, staging, and risk stratification for liver fibrosis is currently possible considering the accuracy of the AI systems, which can overcome the limitations of non-invasive diagnosis methods.

Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.

Neurodegeneration is the pathological condition, in which the nervous system or neuron loses its structure, function, or both, leading to progressive degeneration or the death of neurons, and well-defined associations of tissue system, resulting in clinical manifestations. Neuroinflammation has been shown to precede neurodegeneration in several neurodegenerative diseases (NDs). No drug is yet known to delay or treat neurodegeneration. Although the etiology and potential causes of NDs remain widely indefinable, matrix metalloproteinases (MMPs) evidently have a crucial role in the progression of NDs. MMPs, a protein family of zinc (Zn2+)-containing endopeptidases, are pivotal agents that are involved in various biological and pathological processes in the central nervous system (CNS). The current review delineates the several emerging evidence demonstrating the effects of MMPs in the progression of NDs, wherein they regulate several processes, such as (neuro)inflammation, microglial activation, amyloid peptide degradation, blood brain barrier (BBB) disruption, dopaminergic apoptosis, and α-synuclein modulation, leading to neurotoxicity and neuron death. Published papers to date were searched via PubMed, MEDLINE, etc., while using selective keywords highlighted in our manuscript. We also aim to shed a light on pathophysiological effect of MMPs in the CNS and focus our attention on its detrimental and beneficial effects in NDs, with a special focus on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS), and Huntington's disease (HD), and discussed various therapeutic strategies targeting MMPs, which could serve as potential modulators in NDs. Over time, several agents have been developed in order to overcome challenges and open up the possibilities for making selective modulators of MMPs to decipher the multifaceted functions of MMPs in NDs. There is still a greater need to explore them in clinics.

Current Trends in Neurodegeneration: Cross Talks between Oxidative Stress, Cell Death, and Inflammation.

The human body is highly complex and comprises a variety of living cells and extracellular material, which forms tissues, organs, and organ systems. Human cells tend to turn over readily to maintain homeostasis in tissues. However, postmitotic nerve cells exceptionally have an ability to regenerate and be sustained for the entire life of an individual, to safeguard the physiological functioning of the central nervous system. For efficient functioning of the CNS, neuronal death is essential, but extreme loss of neurons diminishes the functioning of the nervous system and leads to the onset of neurodegenerative diseases. Neurodegenerative diseases range from acute to chronic severe life-altering conditions like Parkinson's disease and Alzheimer's disease. Millions of individuals worldwide are suffering from neurodegenerative disorders with little or negligible treatment available, thereby leading to a decline in their quality of life. Neuropathological studies have identified a series of factors that explain the etiology of neuronal degradation and its progression in neurodegenerative disease. The onset of neurological diseases depends on a combination of factors that causes a disruption of neurons, such as environmental, biological, physiological, and genetic factors. The current review highlights some of the major pathological factors responsible for neuronal degradation, such as oxidative stress, cell death, and neuroinflammation. All these factors have been described in detail to enhance the understanding of their mechanisms and target them for disease management.

Elucidating the Multi-Targeted Role of Nutraceuticals: A Complementary Therapy to Starve Neurodegenerative Diseases.

The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs.

Chemo-Preventive Action of Resveratrol: Suppression of p53-A Molecular Targeting Approach.

Extensive experimental, clinical, and epidemiological evidence has explained and proven that products of natural origin are significantly important in preventing and/or ameliorating various disorders, including different types of cancer that researchers are extremely focused on. Among these studies on natural active substances, one can distinguish the emphasis on resveratrol and its properties, especially the potential anticancer role. Resveratrol is a natural product proven for its therapeutic activity, with remarkable anti-inflammatory properties. Various other benefits/actions have also been reported, such as cardioprotective, anti-ageing, antioxidant, etc. and its rapid digestion/absorption as well. This review aims to collect and present the latest published studies on resveratrol and its impact on cancer prevention, molecular signals (especially p53 protein participation), and its therapeutic prospects. The most recent information regarding the healing action of resveratrol is presented and concentrated to create an updated database focused on this topic presented above.

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients.

While the most common manifestations associated with rheumatoid arthritis (RA) are synovial damage and inflammation, the systemic effects of this autoimmune disorder are life-threatening, and are prevalent in 0.5-1% of the population, mainly associated with cardiovascular disorders (CVDs). Such effects have been instigated by an altered lipid profile in RA patients, which has been reported to correlate with CV risks. Altered lipid paradox is related to inflammatory burden in RA patients. The review highlights general lipid pathways (exogenous and endogenous), along with the changes in different forms of lipids and lipoproteins in RA conditions, which further contribute to elevated risks of CVDs like ischemic heart disease, atherosclerosis, myocardial infarction etc. The authors provide a deep insight on altered levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in RA patients and their consequence on the cardiovascular health of the patient. This is followed by a detailed description of the impact of anti-rheumatoid therapy on the lipid profile in RA patients, comprising DMARDs, corticosteroids, anti-TNF agents, anti-IL-6 agents, JAK inhibitors and statins. Furthermore, this review elaborates on the prospects to be considered to optimize future investigation on management of RA and treatment therapies targeting altered lipid paradigms in patients.

Promising Roles of Alternative Medicine and Plant-Based Nanotechnology as Remedies for Urinary Tract Infections.

Urinary tract infections (UTIs) are considered to be the most common infections worldwide, having an incidence rate of 40-60% in women. Moreover, the prevalence of this disorder in adult women is 30 times more than in men. UTIs are usually found in many hospitals and clinical practice; as disorders, they are complicated and uncomplicated; in uncomplicated cases, there is no structural or functional abnormality in the urogenital tract. However, obstruction, retention of urine flow and use of catheters increase the complexity. There are several bacteria (e.g., E. coli, Klebsiella pneumoniae, Proteus vulgaris, etc.) successfully residing in the tract. The diagnosis must not only be accurate but rapid, so early detection is an important step in the control of UTIs caused by uropathogens. The treatment of UTIs includes appropriate antimicrobial therapy to control the infection and kill the causal microbes inside the body. A long-time usage of antibiotics has resulted in multidrug resistance causing an impediment in treatment. Thus, alternative, combinatorial medication approaches have given some hope. Available treatments considered Homeopathic, Ayurvedic, Unani, and other herbal-based drugs. There are new upcoming roles of nanoparticles in combating UTIs which needs further validation. The role of medicinal plant-based nanotechnology approaches has shown promising results. Therefore, there must be active research in phyto-based therapies of UTIs, such as Ayurvedic Biology.

Enteroscopy versus Video Capsule Endoscopy for Automatic Diagnosis of Small Bowel Disorders-A Comparative Analysis of Artificial Intelligence Applications.

BACKGROUND: Small bowel disorders present a diagnostic challenge due to the limited accessibility of the small intestine. Accurate diagnosis is made with the aid of specific procedures, like capsule endoscopy or double-ballon enteroscopy, but they are not usually solicited and not widely accessible. This study aims to assess and compare the diagnostic effectiveness of enteroscopy and video capsule endoscopy (VCE) when combined with artificial intelligence (AI) algorithms for the automatic detection of small bowel diseases. MATERIALS AND METHODS: We performed an extensive literature search for relevant studies about AI applications capable of identifying small bowel disorders using enteroscopy and VCE, published between 2012 and 2023, employing PubMed, Cochrane Library, Google Scholar, Embase, Scopus, and ClinicalTrials.gov databases. RESULTS: Our investigation discovered a total of 27 publications, out of which 21 studies assessed the application of VCE, while the remaining 6 articles analyzed the enteroscopy procedure. The included studies portrayed that both investigations, enhanced by AI, exhibited a high level of diagnostic accuracy. Enteroscopy demonstrated superior diagnostic capability, providing precise identification of small bowel pathologies with the added advantage of enabling immediate therapeutic intervention. The choice between these modalities should be guided by clinical context, patient preference, and resource availability. Studies with larger sample sizes and prospective designs are warranted to validate these results and optimize the integration of AI in small bowel diagnostics. CONCLUSIONS: The current analysis demonstrates that both enteroscopy and VCE with AI augmentation exhibit comparable diagnostic performance for the automatic detection of small bowel disorders.

The Alberta Stroke Program Early CT score (ASPECTS): A predictor of mortality in acute ischemic stroke.

Stroke is one of the leading causes of mortality globally and a main cause of disability. The objective of this study was to evaluate the importance and utility of the Alberta Stroke Program Early CT Score (ASPECTS) as a mortality predictor factor in diabetic vs. non-diabetic patients with acute ischemic stroke (AIS), correlated with age, monocyte values, and high-sensitivity cardiac troponin I (hs-cTnI). The prospective longitudinal observational study included 340 patients with AIS divided into two groups: diabetics and non-diabetics. ASPECTS was evaluated within the first 24 h after admission to the center. The ASPECTS was lower in the group of diabetic patients on average 4.9 vs. 6.05 (P<0.0001). As the age of the patients increased, the lower the ASPECTS and the higher infarct size, indicating a statistically significant (P<0.0001) result. The optimal correlation was observed between infarct size (ASPECTS) and hs-cTnI serum level [95% confidence interval (CI): -0.3216 to -0.1193; P<0.0001]. Almost 94% of patients who had an ASPECTS higher than 3 points on admission survived, resulting in a favorable outcome and a very good predictability of the score (95% CI: 0.85 to 0.926, P<0.0001). The ASPECTS is a mortality predictor, its value correlating inversely with the severity and evolution of patients, confirming a good predictability with good specificity, sensitivity and area under the curve.

Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium.

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are diseases that can be influenced by the structure of gut microbiota, whose improvement is often neglected in metabolic pathology. This review highlights the following main aspects: the relationship between probiotics/gut microbes with the pathogenesis of MetS, the particular positive roles of Akkermansia muciniphila supplementation in the onset of MetS, and the interaction between dietary polyphenols (prebiotics) with gut microbiota. Therefore, an extensive and in-depth analysis of the often-neglected correlation between gut microbiota and chronic metabolic diseases was conducted, considering that this topic continues to fascinate and stimulate researchers through the discovery of novel strains and their beneficial properties.

Value of Hematological and Coagulation Parameters as Prognostic Factors in Acute Coronary Syndromes.

The values of hematological and coagulation biomarkers were evaluated as predictors of in hospital mortality and complications, in patients with acute coronary syndromes (ACS). This retrospective observational study enrolled 936 ACS subjects admitted to the Clinical Emergency Hospital of Oradea, Romania, between January-December 2019. Hematological and coagulation parameters were obtained at admission. During hospitalization, the following adverse events were recorded: death, ventricular rhythm disturbances, atrial fibrillation, heart failure, re-infarction, and stroke. Accuracy of hematological and coagulation parameters as predictors of adverse outcome were also evaluated. The diagnosis was unstable angina in 442 patients (47.22%), non-ST-elevation myocardial infarction (NSTEMI) in 113 patients (12.1%) and ST-elevation myocardial infarction (STEMI) in 381 patients (40.70%); 87 patients (9.29%) died during hospitalization and 193 (20.7%) developed complications. Predictors for in hospital mortality were as follows: red cell distribution width (RDW) (AUC 0.691, p < 0.0001), white blood cells (WBC) (AUC 0.684, p < 0.0001), neutrophils (NEU) (AUC 0.684, p < 0.0001), and prothrombin time (PT) (AUC 0.765, p < 0.0001). WBC (AUC 0.659, p < 0.0001), NEU (AUC 0.664, p < 0.0001), RDW (AUC 0.669, p < 0.0001), and PT (AUC 0.669, 95% CI 0.622-0.714, p < 0.0001) also had accuracy for complications prediction. RDW had a good ability to predict heart failure in NSTEMI patients (AUC 0.832, p < 0.0001). An acceptable ability to predict ventricular rhythm disturbances occurrence had WBC (AUC 0.758, p < 0.0001) and NEU (AUC 0.772, p < 0.0001). Hematological and coagulation parameters can help in risk stratification of ACS patients. RDW, WBC, NEU, and PT were able to predict mortality and in-hospital complications in ACS patients. RDW has a good accuracy in predicting complications and heart failure in NSTEMI patients. WBC and NEU are good predictors for ventricular rhythm disturbances.

A morphological and immunohistochemical study of the endoscopic ultrasound-fine-needle biopsy samples from solid pancreatic masses: a single center study.

OBJECTIVE: The purpose of this study was to present the experience of a single center on endoscopic ultrasound-fine-needle biopsy (EUS-FNB) of pancreatic solid tumors amenable to immunohistochemistry (IHC) assay. PATIENTS, MATERIALS AND METHODS: Inclusion criterion for this prospective study was identifying patients with pancreatic solid tumors, by means of imaging methods, from January 2018 to February 2020, within the Department of Gastroenterology, Emergency Clinical Hospital, Bucharest, Romania. All patients underwent EUS-FNB and the harvested tissue was sent to the Department of Pathology for histopathological (HP) diagnosis and IHC assessment if tumoral origin remained undetermined. RESULTS: A total of 57 patients were ultimately selected to take part in our study. We performed immunohistochemical analysis based on the morphological diagnosis of the pancreatic tumors and assessed cytokeratin (CK)7, CK20, caudal type homeobox 2 (CDX2), MutL homolog 1 (MLH1), MutS homolog (MSH)2, MSH6, postmeiotic segregation 2 (PMS2) for all histopathologically uncertain pancreatic ductal adenocarcinoma (PDAC) and chromogranin A, synaptophysin, pan-CK AE1∕AE3 for pancreatic neuroendocrine tumors (pNETs). Cox hazard regression was performed to identify the factors influencing the survival rate. In univariate analysis, patient survival time was significantly associated with stage, location, surgical management and CK7 positivity. Our data show a statistically significant predictive relationship between stage (regional or metastatic) and hazard for survival (p=0.015). Tumoral location in the tail (p=0.015) and radicality surgery (p=0.015) significantly decrease the survival of pancreatic cancer (PAC) patients. The presence of CK7 (p=0.015) significantly increases the survival of pancreas cancer patients. CONCLUSIONS: EUS-FNB has opened up a new path for pancreatic tumor diagnosis providing enough tissue for HP examination and IHC. A panel of several immunomarkers might aid in providing new therapies for PAC patients.

Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease.

Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.

Rice bran, an off-shoot to newer therapeutics in neurological disorders.

Normal brain functioning involves the interaction of interconnected molecular and cellular activities, which appear to alter normal to abnormal brain functioning when worsened, contributing to the emergence of neurological disorders. There are currently millions of people who are living with brain disorders globally and this will rise if suitable prevention strategies are not explored. Nutraceutical intended to treat numerous health goals with little adverse effect possible together can be more beneficial than pharmaceutical monotherapy for fostering balanced brain functioning. Nutraceutical provides a specific composition of effective macronutrients and micronutrients that are difficult to synthesize in the laboratory. Numerous elements of rice fibers in rice bran are characterized as natural anti-oxidant and having potential anti-inflammatory activity. The rice bran captures interest among the researchers as it is widespread, affordable, and rich in nutrients including protein, fat, carbohydrates, bioactive components, and dietary fiber. This review covers the neuroprotective multiplicity of rice bran and its constituents to deter pathological conditions of the brain and to facilitate balanced brain functioning at the same time.

Current Management of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. It affects about 1 billion individuals worldwide. While people with simple steatosis have no higher risk of death than the general population, people with non-alcoholic steatohepatitis are at increased risk of death compared to general population. Current management for NAFLD includes diet and lifestyle changes, management of underlying metabolic risk factors and pharmacological therapies. The objective of therapy is to prevent the complications. The problem with dietary and lifestyle interventions is that they are hard to implement. Compliance is the key. Until now, there is still no approved drug for the treatment of NAFLD. Insulin resistance is the main target of pharmacological therapy, but the question that we ask ourselves as physicians is who should receive medical treatment among NAFLD patients and for how long.

From NAFLD to Cardiovascular Disease. Is it (Still) the Metabolic Syndrome?

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries. The incidence of NAFLD in the general population is 30-38% deppending on the geographical area and the diagnostic method used. NAFLD is considered to be the liver manifestation of the metabolic syndrome. A better understanding of the natural evolution would have practical consequences related mainly to the need of early and aggressive diagnosis, active monitoring and therapeutic solutions. Cardiovascular disease appears to be the main cause of death in these patients. The mechanisms linking NAFLD with cardiovascular disease are not fully understood yet, but attention was focused primarily on insulin resistance. The visceral adipose tissue, the epicardial adipose tissue, the systemic inflammatory response syndrome, the lipid profile, the procoagulants factors, the oxidative stress, and type 2 diabetes mellitus, they all might play a role in the link between NAFLD and cardiovascular disease. Currently, there isn't any medication specifically recommended for the treatment of NAFLD. Although the mechanisms underlying the association between NAFLD and cardiovascular disease are not fully known, attention must be paid to this association, given that these patients are more likely to die due to heart disease rather than liver disease.