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Background: Spinal cord injury (SCI) is a devastating problem for modern society, whether it affects young people in the most productive period of their lives or the elderly. The spinal cord injury is currently without curative treatment and the therapeutic intervention aims to minimize secondary complications and maximize residual function through rehabilitation medicine. The main objective of this scientific paper is to determine whether there is evidence in the literature regarding the importance and/or use of hydrotherapy, as part of the therapeutic management of the SCI patient, in order to decrease the degree of spasticity, of pain symptoms, increase or maintain range of motion, improve respiratory, cardiovascular, and metabolic status, as well as improve function and psychological benefits. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures, the following databases were analyzed between 2000 and 2021: Pub Med, Pub Med Central, Science Direct, Scopus, and SpringerLink. Initial keywords: rehabilitation treatment, spinal cord injury. Additional keywords: hydrotherapy, aqua therapy, spasticity, human. For the scientific quality of the included articles, risk of bias was assessed using the Downs and Black Appraisal Modified Scale. Results: Our research used only four publications as per PRISMA protocol, assessed with Downs and Black Scale. The study models used in the individual studies included in the research are the following: two systematic reviews, one experimental non-randomized control, and one individual semi-structured interview. Due to the low number of studies, despite two of them being reviews, there is the necessity for a more standardized methodology to prove the benefits hydrotherapy for SCI patients for the improvement of lower limb functioning. Conclusion: Hydrotherapy is an important component of the treatment of an SCI patient, despite the limited number of scientific studies that support this aspect. Clinical trials in the future are required. [ABSTRACT FROM AUTHOR]

In the case of pandemics such as COVID-19, the rapid development of medicines addressing the symptoms is necessary to alleviate the pressure on the medical system. One of the key steps in medicine evaluation is the determination of p I C 50 factor, which is a negative logarithmic expression of the half maximal inhibitory concentration ( I C 50 ). Determining this value can be a lengthy and complicated process. A tool allowing for a quick approximation of p I C 50 based on the molecular makeup of medicine could be valuable. In this paper, the creation of the artificial intelligence (AI)-based model is performed using a publicly available dataset of molecules and their p I C 50 values. The modeling algorithms used are artificial and convolutional neural networks (ANN and CNN). Three approaches are tested—modeling using just molecular properties (MP), encoded SMILES representation of the molecule, and the combination of both input types. Models are evaluated using the coefficient of determination ( R 2 ) and mean absolute percentage error (MAPE) in a five-fold cross-validation scheme to assure the validity of the results. The obtained models show that the highest quality regression ( R 2 ¯ = 0.99 ,   σ R 2 ¯ = 0.001 ;   M A P E ¯ = 0.009 % ,   σ M A P E ¯ = 0.009 ), by a large margin, is obtained when using a hybrid neural network trained with both MP and SMILES. [ABSTRACT FROM AUTHOR]

I Biomedicines i was able to uphold its high standards for published papers due to the outstanding efforts of our reviewers. [Extracted from the article]

Zinc phosphate cement is used in dentistry to lute crowns and bridges. So far, its biocompatibility for other applications has not been studied. This paper reports the biocompatibility of zinc phosphate towards MG63 cells, testing both the material (discs; 3 mm diameter × 1 mm thick) and leachate from the cement. Cell viability was determined using an MTT assay, and cytotoxicity from the effects of leachate, studied in triplicate. Microscopy (optical and scanning electron) determined the morphology and proliferation of cells attached to zinc phosphate. ICP-OES measured element release into leachate, and anti-microbial behaviour was determined against Streptococcus pyrogenes cultured on a Brain Heart Infusion agar using cement discs (3 mm diameter × 1 mm thick). Zones of inhibition were measured after 72 h. MG63 cells proliferated on zinc phosphate surfaces and retained their morphology. The cells were healthy and viable as shown by an MTT assay, both on cement and in leachate. High levels of phosphorus but low levels of zinc were released into leachate. The cement showed minimal antimicrobial activity against S. pyogenes, probably due to the long maturation times used. Zinc phosphate cement was found to be biocompatible towards MG63 cells, which indicates that it may be capable of use in bone contact applications. [ABSTRACT FROM AUTHOR]

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. MJD is characterized by late-onset progressive cerebellar ataxia associated with variable clinical findings, including pyramidal signs and a dystonic-rigid extrapyramidal syndrome. In the Portuguese archipelago of the Azores, the worldwide population cluster for this disorder (prevalence of 39 in 100,000 inhabitants), a cohort of MJD mutation carriers belonging to extensively studied pedigrees has been followed since the late 1990s. Studies of the homogeneous Azorean MJD cohort have been contributing crucial information to the natural history of this disease as well as allowing the identification of novel molecular biomarkers. Moreover, as interventional studies for this globally rare and yet untreatable disease are emerging, this cohort should be even more important for the recruitment of trial participants. In this paper, we profile the Azorean cohort of MJD carriers, constituted at baseline by 20 pre-ataxic carriers and 52 patients, which currently integrates the European spinocerebellar ataxia type 3/Machado-Joseph disease Initiative (ESMI), a large European longitudinal MJD cohort. Moreover, we summarize the main studies based on this cohort and highlight the contributions made to advances in MJD research. Knowledge of the profile of the Azorean MJD cohort is not only important in the context of emergent interventional trials but is also pertinent for the implementation of adequate interventional measures, constituting relevant information for Lay Associations and providing data to guide healthcare decision makers. [ABSTRACT FROM AUTHOR]

Ulrich "Uli" Siebenlist, our cherished colleague, passed away on 4 August 2020 after a long struggle with pancreatic cancer. In his latest papers, which were published posthumously inPLoSPathogens andImmunologyand CellBiology, Uli further delineated cell intrinsic and cell autonomous roles of Bcl-3 in the differentiation of regulatory T cells and LCMV-specific CD8 + memory T cells. Ulrich "Uli" Siebenlist, our cherished colleague, passed away on 4 August 2020 after a long struggle with pancreatic cancer. [Extracted from the article]

There are few studies on dementia and schizophrenia in older patients looking for structural differences. This paper aims to describe relation between cognitive performance and brain volumes in older schizophrenia patients. Twenty schizophrenic outpatients —10 without-dementia (SND), 10 with dementia (SD)— and fifteen healthy individuals —as the control group (CG)—, older than 50, were selected. Neuropsychological tests were used to examine cognitive domains. Brain volumes were calculated with magnetic resonance images. Cognitive performance was significantly better in CG than in schizophrenics. Cognitive performance was worst in SD than SND, except in semantic memory and visual attention. Hippocampal volumes showed significant differences between SD and CG, with predominance on the right side. Left thalamic volume was smaller in SD group than in SND. Structural differences were found in the hippocampus, amygdala, and thalamus; more evident in the amygdala and thalamus, which were mainly related to dementia. In conclusion, cognitive performance and structural changes allowed us to differentiate between schizophrenia patients and CG, with changes being more pronounced in SD than in SND. When comparing SND with SD, the functional alterations largely coincide, although sometimes in the opposite direction. Moreover, volume lost in the hippocampus, amygdala, and thalamus may be related to the possibility to develop dementia in schizophrenic patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Saphenous vein graft (SVG) is a cardiac surgical practice used to create a cardiac bypass in cases of coronary artery obstruction. It consists of a surgical procedure that involves the creation of an aorto-coronary communication by a venous conduit (saphenous vein) to bypass coronary stenosis and allow cardiac revascularization. This practice can be affected by early and late complications. The most feared complication is graft aneurysm or pseudoaneurysm degeneration and rupture which are considered late complications. This paper presents a rare case of SVG aneurysmal rupture that occurred 24 h after surgery and a review of the literature to provide a general look at the state of knowledge. Materials and Methods: The systematic review was carried out using the guidelines according to the PRISMA method. Results: Cases of aneurysmal rupture have never been described prior to one month after surgery. The male sex and subjects under 45 are the most affected by this complication. Death occurs in less than half of the cases, being more frequent in young people. Performing a CT or angio-CT examination led to the diagnosis. Conclusions: It is impossible to estimate the implanted vessel's quality, so postoperative follow-up is fundamental. Transesophageal ultrasound can be useful, and hematochemical tests are valuable early diagnostic tools, whrease CT and angio-CT can be useful even months after surgery. Forensic analysis should always perform an autopsy and graft histological examination. [ABSTRACT FROM AUTHOR]

Brain tumors affect the normal functioning of the brain and if not treated in time these cancerous cells may affect the other tissues, blood vessels, and nerves surrounding these cells. Today, a large population worldwide is affected by the precarious disease of the brain tumor. Healthy tissues of the brain are suspected to be damaged because of tumors that become the most significant reason for a large number of deaths nowadays. Therefore, their early detection is necessary to prevent patients from unfortunate mishaps resulting in loss of lives. The manual detection of brain tumors is a challenging task due to discrepancies in appearance in terms of shape, size, nucleus, etc. As a result, an automatic system is required for the early detection of brain tumors. In this paper, the detection of tumors in brain cells is carried out using a deep convolutional neural network with stochastic gradient descent (SGD) optimization algorithm. The multi-classification of brain tumors is performed using the ResNet-50 model and evaluated on the public Kaggle brain-tumor dataset. The method achieved 99.82% and 99.5% training and testing accuracy, respectively. The experimental result indicates that the proposed model outperformed baseline methods, and provides a compelling reason to be applied to other diseases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is mainly a neurodegenerative sickness. The primary characteristics are neuronal atrophy, amyloid deposition, and cognitive, behavioral, and psychiatric disorders. Numerous machine learning (ML) algorithms have been investigated and applied to AD identification over the past decades, emphasizing the subtle prodromal stage of mild cognitive impairment (MCI) to assess critical features that distinguish the disease's early manifestation and instruction for early detection and treatment. Identifying early MCI (EMCI) remains challenging due to the difficulty in distinguishing patients with cognitive normality from those with MCI. As a result, most classification algorithms for these two groups perform poorly. This paper proposes a hybrid Deep Learning Approach for the early detection of Alzheimer's disease. A method for early AD detection using multimodal imaging and Convolutional Neural Network with the Long Short-term memory algorithm combines magnetic resonance imaging (MRI), positron emission tomography (PET), and standard neuropsychological test scores. The proposed methodology updates the learning weights, and Adam's optimization is used to increase accuracy. The system has an unparalleled accuracy of 98.5% in classifying cognitively normal controls from EMCI. These results imply that deep neural networks may be trained to automatically discover imaging biomarkers indicative of AD and use them to identify the illness accurately. [ABSTRACT FROM AUTHOR]

Viral respiratory infections (VRI) are the most prevalent type of infectious diseases and constitute one of the most common causes of contact with medical care. Regarding the pathophysiology of the cardiovascular system, VRI can not only exacerbate already existing chronic cardiovascular disease (such as coronary artery disease or heart failure) but also trigger new adverse events or complications (e.g., venous thromboembolism), the latter particularly in subjects with multimorbidity or disease-related immobilization. In the current paper, we provide a narrative review of diverse cardiovascular complications of VRI as well as summarize available data on the pathology of the circulatory system in the course of coronavirus disease 2019 (COVID-19). [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are common diseases that strongly impact the quality and length of life. Their coexistence is determined by overlap syndrome (OS). This systematic review aims to define the significance of these comorbidities according to the current state of knowledge. For this systematic review, we searched PubMed, Scopus, and Cochrane for studies published between 2018 and 26 October 2022, to find original, observational, human studies published in English, where the diagnosis of COPD was according to the Global Initiative for Obstructive Lung Disease guidelines and the diagnosis of OSA was based on polysomnography. The quality of studies was assessed using the Newcastle–Ottawa quality assessment tool for cohort and case–control studies, as well as its modification for cross-sectional studies. Of the 1548 records identified, 38 were eligible and included in this systematic review. The included studies covered a total population of 27,064 participants. This paper summarizes the most important, up-to-date information regarding OS, including the prevalence, meaning of age/gender/body mass index, polysomnography findings, pulmonary function, comorbidities, predicting OSA among COPD patients, and treatment of this syndrome. [ABSTRACT FROM AUTHOR]

The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique has great potential in the diagnosis, therapy, and follow-up of patients with chronic kidney disease (CKD). Towards that end, precise kidney segmentation from DCE-MRI data becomes a prerequisite processing step. Exploiting the useful information about the kidney's shape in this step mandates a registration operation beforehand to relate the shape model coordinates to those of the image to be segmented. Imprecise alignment of the shape model induces errors in the segmentation results. In this paper, we propose a new variational formulation to jointly segment and register DCE-MRI kidney images based on fuzzy c-means clustering embedded within a level-set (LSet) method. The image pixels' fuzzy memberships and the spatial registration parameters are simultaneously updated in each evolution step to direct the LSet contour toward the target kidney. Results on real medical datasets of 45 subjects demonstrate the superior performance of the proposed approach, reporting a Dice similarity coefficient of 0.94 ± 0.03, Intersection-over-Union of 0.89 ± 0.05, and 2.2 ± 2.3 in 95-percentile of Hausdorff distance. Extensive experiments show that our approach outperforms several state-of-the-art LSet-based methods as well as two UNet-based deep neural models trained for the same task in terms of accuracy and consistency. [ABSTRACT FROM AUTHOR]

Gut health is crucial in many ways, such as in improving human health in general and enhancing production in agricultural animals. To maximize the effect of a healthy gastrointestinal tract (GIT), an understanding of the regulation of intestinal functions is needed. Proper intestinal functions depend on the activity, composition, and behavior of intestinal epithelial cells (IECs). There are various types of IECs, including enterocytes, Paneth cells, enteroendocrine cells (EECs), goblet cells, tuft cells, M cells, and intestinal epithelial stem cells (IESCs), each with unique 3D structures and IEC distributions. Although the communication between IECs and other cell types, such as immune cells and neurons, has been intensively reviewed, communication between different IECs has rarely been addressed. The present paper overviews the networks among IECs that influence intestinal functions. Intestinal absorption is regulated by incretins derived from EECs that induce nutrient transporter activity in enterocytes. EECs, Paneth cells, tuft cells, and enterocytes release signals to activate Notch signaling, which modulates IESC activity and intestinal homeostasis, including proliferation and differentiation. Intestinal immunity can be altered via EECs, goblet cells, tuft cells, and cytokines derived from IECs. Finally, tools for investigating IEC communication have been discussed, including the novel 3D intestinal cell model utilizing enteroids that can be considered a powerful tool for IEC communication research. Overall, the importance of IEC communication, especially EECs and Paneth cells, which cover most intestinal functional regulating pathways, are overviewed in this paper. Such a compilation will be helpful in developing strategies for maintaining gut health.

Type 1 diabetes mellitus is an autoimmune condition characterized by the destruction of pancreatic β-cells, necessitating insulin therapy to prevent life-threatening complications such as diabetic ketoacidosis. Despite advancements in glucose monitoring and pharmacological treatments, managing this disease remains challenging, often leading to long-term complications and psychological burdens, including diabetes distress. Advanced treatment options, such as whole-pancreas transplantation and islet transplantation, aim to restore insulin production and improve glucose control in selected patients with diabetes. The risk of transplant rejection necessitates immunosuppressive therapy, which increases susceptibility to infections and other adverse effects. Additionally, surgical complications, including infection and bleeding, are significant concerns, particularly for whole-pancreas transplantation. Recently, stem cell-derived therapies for type 1 diabetes have emerged as a promising alternative, offering potential solutions to overcome the limitations of formerly established transplantation methods. The purpose of this scoping review was to: (1) summarize the current evidence on achieved insulin independence following various transplantation methods of insulin-producing cells in patients with type 1 diabetes; (2) compare insulin independence rates among whole-pancreas transplantation, islet cell transplantation, and stem cell transplantation; and (3) identify limitations, challenges and potential future directions associated with these techniques. We systematically searched three databases (PubMed, Scopus, and Web of Science) from inception to November 2024, focusing on English-language, peer-reviewed clinical studies. The search terms used were ‘transplantation’ AND ‘type 1 diabetes’ AND ‘insulin independence’. Studies were included if they reported on achieved insulin independence, involved more than 10 patients with type 1 diabetes, and had a mean follow-up period of at least one year. Reviewers screened citations and extracted data on transplant type, study population size, follow-up duration, and insulin independence rates. We identified 1380 papers, and after removing duplicates, 705 papers remained for title and abstract screening. A total of 139 English-language papers were retrieved for full-text review, of which 48 studies were included in this review. The findings of this scoping review indicate a growing body of literature on transplantation therapy for type 1 diabetes. However, significant limitations and challenges, like insufficient rates of achieved insulin independence, risks related to immunosuppression, malignant diseases, and ethical issues remain with each of the established techniques, highlighting the need for innovative approaches such as stem cell-derived islet transplantation to promote β-cell regeneration and protection.

A healthy diet has been highly associated with a decreased risk for mental health problems such as major depression. Evidence from human studies shows that diet can influence mood but there is a poor understanding of the molecular mechanisms behind these effects, especially the role of epigenetic alterations in the brain. Our objective was to use the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) format to gather all recent studies using animal models that investigate direct or indirect (on the offspring) effects of diet on depressive symptoms, including studies that assess epigenetic mechanisms in the brain. In this format, two authors conducted independent database searches of PubMed, Web of Science, and Academic search premier using one search block "diet epigenetics depression" to find papers published between 2000 and 2022. Relevant studies were selected using pre-defined inclusion/exclusion criteria that were performed independently by the two authors before a subset of studies were selected for qualitative analysis. A total of 11 studies met the inclusion criteria for this systematic scoping review. We found that the literature focuses primarily on the effects of individual nutrients, instead of a specific diet, on despair-like behaviour and anxiety. Studies are heterogenous with the techniques used to asses epigenetic changes in the brain and therefore making it hard to reach common mechanistic explanations. However, all studies report diet-induced changes in the epigenome mainly by the action of DNA methylation, histone acetylation and microRNAs that are parallelel with changes in behaviour. Moreover studies show that inadequate maternal diets can make the offspring more susceptible to develop anxiety and depressive-like behaviour later in life, which is paralleled with changes in the epigenome. Overall, this systematic review shows that there is some literature suggesting a role of brain epigenetics on the diet-induced protective or detrimental effects, specifically on anxiety and depressive-like behaviour. However, studies are limited, lacking the study of some types of diets, behavioural tasks or epigenetic mechanisms. Nevertherless, it shows the importance of genome-environment interactions, bringing new insights towards mechanisms that could be involved in the pathophysiology of mood disorders as well as putative therapeutic targets. [ABSTRACT FROM AUTHOR]

Over past years, the fabrication of Ti-based permanent implants for fracture fixation, joint replacement and bone or tooth substitution, has become a routine task. However, it has been found that some degradation phenomena occurring on the Ti surface limits the life or the efficiency of the artificial constructs. The task of avoiding such adverse effects, to prevent microbial colonization and to accelerate osteointegration, is being faced by a variety of approaches in order to adapt Ti surfaces to the needs of osseous tissues. Among the large set of biocompatible materials proposed as an interface between Ti and the hosting tissue, diamond has been proven to offer bioactive and mechanical properties able to match the specific requirements of osteoblasts. Advances in material science and implant engineering are now enabling us to produce micro- or nano-crystalline diamond coatings on a variety of differently shaped Ti constructs. The aim of this paper is to provide an overview of the research currently ongoing in the field of diamond-coated orthopedic Ti implants and to examine the evolution of the concepts that are accelerating the full transition of such technology from the laboratory to clinical applications. [ABSTRACT FROM AUTHOR]

Background: A variety of autoimmune diseases, including MS, amplify sex-based physiological differences in immunological responsiveness. Female MS patients experience pathophysiological changes during reproductive phases (pregnancy and menopause). Sex hormones can act on immune cells, potentially enabling them to modify MS risk, activity, and progression, and to play a role in treatment. Methods: Scientific papers (published between 1998 and 2021) were selected through PubMed, Google Scholar, and Web of Science literature repositories. The search was limited to publications analyzing the hormonal profile of male and female MS patients during different life phases, in particular focusing on sex hormone treatment. Results: Both men and women with MS have lower testosterone levels compared to healthy controls. The levels of estrogens and progesterone increase during pregnancy and then rapidly decrease after delivery, possibly mediating an immune-stabilizing process. The literature examined herein evidences the neuroprotective effect of testosterone and estrogens in MS, supporting further examinations of their potential therapeutic uses. Conclusions: A correlation has been identified between sex hormones and MS clinical activity. The combination of disease-modifying therapies with estrogen or estrogen plus a progestin receptor modulator promoting myelin repair might represent an important strategy for MS treatment in the future. [ABSTRACT FROM AUTHOR]

The human genome is composed of unique DNA sequences that encode proteins and unique sequence noncoding RNAs that are essential for normal development and cellular differentiation. The human genome also contains over 50% of genome sequences that are repeat in nature (tandem and interspersed repeats) that are now known to contribute dynamically to genetic diversity in populations, to be transcriptionally active under certain physiological conditions, and to be aberrantly active in disease states including cancer, where consequences are pleiotropic with impact on cancer cell phenotypes and on the tumor immune microenvironment. Repeat element-derived RNAs play unique roles in exogenous and endogenous cell signaling under normal and disease conditions. A key component of repeat element-derived transcript-dependent signaling occurs via triggering of innate immune receptor signaling that then feeds forward to inflammatory responses through interferon and NFκB signaling. It has recently been shown that cancer cells display abnormal transcriptional activity of repeat elements and that this is linked to either aggressive disease and treatment failure or to improved prognosis/treatment response, depending on cell context and the amplitude of the so-called 'viral mimicry' response that is engaged. 'Viral mimicry' refers to a cellular state of active antiviral response triggered by endogenous nucleic acids often derived from aberrantly transcribed endogenous retrotransposons and other repeat elements. In this paper, the literature regarding transcriptional activation of repeat elements and engagement of inflammatory signaling in normal (focusing on hematopoiesis) and cancer is reviewed with an emphasis on the role of innate immune receptor signaling, in particular by dsRNA receptors of the RIG-1 like receptor family and interferons/NFκB. How repeat element-derived RNA reprograms cell identity through RNA-guided chromatin state modulation is also discussed. [ABSTRACT FROM AUTHOR]

Researchers have revealed that Rhus verniciflua heartwood, which contains fustin as an important component, possesses antioxidant-mediated, anti-mutagenic, and anti-rheumatoid arthritis characteristics. Additionally, out of the numerous plant-derived secondary metabolites, there are various research papers concentrating on flavonoids for potential advantages in neurological illnesses. The current study aims to assess the neuroprotective potential of fustin in rodents over 3-nitropropionic acid (3-NPA)-induced Huntington's disease (HD)-like consequences. The efficacy of fustin 50 and 100 mg/kg was studied with multiple-dose administrations of 3-NPA, which experimentally induced HD-like symptoms in rats for 22 days. At the end of the study, several behavioral tests were performed including a beam walk, rotarod, and grip strength tests. Similarly, some biochemical parameters were assessed to support oxidative stress (reduced glutathione—GSH, superoxide dismutase—SOD, catalase—CAT, and malondialdehyde—MDA), alteration in neurotransmitters (gamma-aminobutyric acid—GABA—and glutamate), alteration in brain-derived neurotrophic factor activity, and nitrite levels. Additionally, pro-inflammatory parameters were carried out to evaluate the neuroinflammatory responses associated with streptozotocin such as TNF-α, IL-1β, and COX in the perfused brain. The fustin-treated group exhibited a significant restoration of memory function via modulation in behavioral activities. Moreover, 3-NPA altered biochemical, neurotransmitters, brain protein levels, and neuroinflammatory measures, which fustin efficiently restored. This is the first report demonstrating the efficacy of novel phytoconstituent fustin as a potential future candidate for the treatment of HD via offering neuroprotection by subsiding the oxidative and enzymatic activity in the 3-NPA experimental animal paradigm. [ABSTRACT FROM AUTHOR]

In this study, generative adversarial networks named SleepGAN are proposed to expand the training set for automatic sleep stage classification tasks by generating both electroencephalogram (EEG) epochs and sequence relationships of sleep stages. In order to reach high accuracy, most existing classification methods require substantial amounts of training data, but obtaining such quantities of real EEG epochs is expensive and time-consuming. We introduce few-shot learning, which is a method of training a GAN using a very small set of training data. This paper presents progressive Wasserstein divergence generative adversarial networks (GANs) and a relational memory generator to generate EEG epochs and stage transition sequences, respectively. For the evaluation of our generated data, we use single-channel EEGs from the public dataset Sleep-EDF. The addition of our augmented data and sequence to the training set was shown to improve the performance of the classification model. The accuracy of the model increased by approximately 1% after incorporating generated EEG epochs. Adding both the augmented data and sequence to the training set resulted in a further increase of 3%, from the original accuracy of 79.40% to 83.06%. The result proves that SleepGAN is a set of GANs capable of generating realistic EEG epochs and transition sequences under the condition of insufficient training data and can be used to enlarge the training dataset and improve the performance of sleep stage classification models in clinical practice. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, inflammatory skin disease that may occur at any age, with a bimodal peak of incidence around the age of 16–20 years of age (early onset) and 57–60 years (late-onset). It is estimated that roughly 70% of patients develop the disease before the age of 40, which coincides with the reproductive years. Moreover, psoriasis is a chronic disease, meaning that, with increased life-duration expectancy, the number of patients affected with psoriasis aged over 65 years is going to increase and represent a big therapeutic challenge. Actually, no specific drug recommendation is available, based only on the age of the patients, while therapeutic prescription should take into account that elderly patients have more comorbidities than younger patients, with polypharmacy and an increased risk of drug interactions. Women with psoriasis are more likely to report a worse influence of the disease on their quality of life, and they are more susceptible to the development of depression. Furthermore, pregnancy and lactation represent a major contraindication to several systemic agents, and only a few studies exist providing the safety of certain drugs during these periods of life of a woman, such as certolizumab pegol. In this paper, we discuss systemic therapeutic strategies, including conventional and biological therapies, in a special subset of patients affected with moderate-to-severe psoriasis focusing on elderly patients and on female patients in fertile age, pregnancy, and lactation. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major public health problem with a developing incidence and prevalence. As a consequence of the growing number of patients diagnosed with renal dysfunction leading to the development of CKD, it is particularly important to explain the mechanisms of its underlying causes. In our paper, we discuss the molecular mechanisms of the development and progression of CKD, focusing on oxidative stress, the role of the immune system, neutrophil gelatinase-associated lipocalin, and matrix metalloproteinases. Moreover, growing evidence shows the importance of the role of the gut–kidney axis in the maintenance of normal homeostasis and of the dysregulation of this axis in CKD. Further, we discuss the therapeutic potential and highlight the future research directions for the therapeutic targeting of CKD. However, additional investigation is crucial to improve our knowledge of CKD progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology. [ABSTRACT FROM AUTHOR]

This paper provides an assessment of molecular and functional changes in blood vessels, and a description of vascular patterns during preeclampsia (PE). Patients with normal pregnancy, and pregnancy complicated by PE at earlier (20–34 weeks) and later terms (≥34 weeks) underwent a 24 h monitoring of blood pressure, central hemodynamics, arterial stiffness, and myocardial function. The blood levels of the structural components of endothelial glycocalyx (eGC): syndecan-1 (SDC 1), heparan sulfate proteoglycan 2 (HSPG2), and hyaluronic acid (HA) were determined. In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes, probably leading to more severe course of PE and the formation of morphological grounds for cardiovascular disorders. The vascular pattern in late-onset PE, including changes in HA levels, central hemodynamics, and myocardial function, may be a signal of potential cardiovascular disorder. PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium, with its subsequent hypertrophy and decompensation, leading to a delayed development of cardiovascular disorders after PE. Further clinical studies of these indicators will possibly identify predictors of PE and long-term consequences of the disease. [ABSTRACT FROM AUTHOR]

Finasteride (Fin) causes androgen imbalance by inhibiting the conversion of testosterone (T) to its more active metabolite, dihydrotestosterone (DHT). Androgen receptors (AR) are present (e.g., in hepatocytes), which have well-developed endoplasmic reticulum (ERet). Cellular protein quality control is carried out by ERet in two paths: (i) unfolded protein response (UPR) and/or (ii) endoplasmic reticulum associated degradation (ERAD). ERet under continuous stress can generate changes in the UPR and can direct the cell on the pathway of life or death. It has been demonstrated that genes involved in ERet stress are among the genes controlled by androgens in some tissues. Oxidative stress is also one of the factors affecting the functions of ERet and androgens are one of the regulators of antioxidant enzyme activity. In this paper, we discuss/analyze a possible relationship between androgen imbalance in paternal generation with ERet stress and liver disorders in both paternal and filial generation. In our rat model, hyperglycemia and subsequent higher accumulation of hepatic glycogen were observed in all filial generation obtained from females fertilized by Fin-treated males (F1:Fin). Importantly, genes encoding enzymes involved in glucose and glycogen metabolism have been previously recognized among UPR targets. [ABSTRACT FROM AUTHOR]

This document is an editorial from the journal Biomedicines titled "miRNAs: From Master Regulators of Gene Expression to Biomarkers Involved in Intercellular Communication." It discusses the role of microRNAs (miRNAs) in gene expression regulation and their involvement in various physiological processes and diseases. The editorial highlights three main aspects: the role of miRNAs in human disease, the use of extracellular miRNAs (ex-miRNAs) as biomarkers for disease diagnosis and monitoring, and the discovery of novel players in the miRNA regulatory network. It also explores the challenges and advancements in using ex-miRNAs as biomarkers and the potential of ex-miRNAs in intercellular communication. The editorial concludes by emphasizing the importance of miRNA research and its potential for further advancements in the field. [Extracted from the article]

This document, published in the journal Biomedicines, discusses advances in the treatment of kidney and upper urinary tract cancers. The authors highlight the heterogeneity of patients with renal cell cancer and the need for predicting treatment response. The document includes several studies on topics such as the effects of anticancer drugs on renal cell cancer cells, the relevance of circulating soluble levels of programmed death ligand-1 in upper tract urothelial carcinoma, and the response of renal carcinoma subtypes to immune checkpoint inhibitors. Other studies explore the association of biomarkers with the prognosis of renal cell carcinoma and the occurrence of systemic inflammatory reaction syndrome in patients undergoing kidney tumor surgery. The document concludes by emphasizing the ongoing research and the hope for improved survival rates and quality of life for those affected by these cancers. [Extracted from the article]

Among soluble actors that have emerged as druggable factors, the chemokine interleukin-8 (IL-8) has emerged as a possible determinant of response to immunotherapy and targeted treatment in several cancer types; however, its prognostic/predictive role in colorectal cancer (CRC) remains to be established. We: (i) conducted a systematic review of published literature on IL-8 expression in CRC; (ii) searched public transcriptomics databases; (iii) investigated IL-8 expression, by tumor and infiltrating cells, in a series of CRC samples; and (iv) carried out a meta-analysis of published literature correlating IL-8 expression and CRC prognosis. IL-8 possesses an important role as a mediator of the bidirectional crosstalk between tumor/stromal cells. Transcriptomic analysis indicated that specific IL-8 transcripts were significantly overexpressed in CRC compared to normal colon mucosa. Moreover, in our series we observed a statistically significant correlation between PTEN-loss and IL-8 expression by infiltrating mononuclear and tumor cells. In total, 12 papers met our meta-analysis inclusion criteria, demonstrating that high IL-8 levels significantly correlated with shorter overall survival and progression-free survival. Sensitivity analysis demonstrated a highly significant correlation with outcome for circulating, but not for tissue-detected, IL-8. IL-8 is overexpressed in CRC tissues and differentially produced by tumor or stromal components depending on CRC genetic background. Moreover, circulating IL-8 represents a strong prognostic factor in CRC, suggesting its use in the refining of prognostic CRC assessment and potentially the tailoring of therapeutic strategies in individual CRC patients. [ABSTRACT FROM AUTHOR]

This paper presents an investigation of the temperature dependence of the oligomeric state of the horseradish peroxidase (HRP) enzyme on the temperature of its solution, and on the solution storage time, at the single-molecule level. Atomic force microscopy has been employed to determine how the temperature and the storage time of the HRP solution influence its aggregation upon direct adsorption of the enzyme from the solution onto bare mica substrates. In parallel, spectrophotometric measurements have been performed in order to estimate whether the HRP enzymatic activity changes over time upon the storage of the enzyme solution. The temperature dependence of the HRP oligomeric state has been studied within a broad (15–40 °C) temperature range. It has been demonstrated that the storage of the HRP solution for 14 days does not have any considerable effect on the oligomeric state of the enzyme, neither does it affect its activity. At longer storage times, AFM has allowed us to reveal a tendency of HRP to oligomerization during the storage of its buffered solution, while the enzymatic activity remains virtually unchanged even after a 1-month-long storage. By AFM, it has been revealed that after the incubation of a mica substrate in the HRP solution at various temperatures, the content of the mica-adsorbed oligomers increases insignificantly owing to a high-temperature stability of the enzyme. [ABSTRACT FROM AUTHOR]

Atherosclerosis manifests by the thickening of artery walls and their narrowed channels through the accumulation of plaque. It is one of the most important indicators of cardiovascular disease. It can be caused by various factors, such as smoking, a high cholesterol diet, hypertension, hyperglycemia, and genetic factors. However, atherosclerosis can also develop due to infection. It has been reported that some bacteria and viruses can cause the development of atherosclerosis. Examples of these viruses are influenza viruses, herpes viruses, hepatitis viruses, or papillomaviruses, which are all prevalent and eminent globally for infecting the population worldwide. Moreover, many patients with coronavirus disease 2019 (COVID-19) showed symptoms of cardiovascular disease. In this review paper, the viruses linked to the development of atherosclerosis are introduced, and their viral characteristics, the mechanisms of the development of atherosclerosis, and the current vaccines and antiviral treatment methods are summarized. [ABSTRACT FROM AUTHOR]

The history of medical records is thousand-year-long, with earlier roots in ancient civilizations. Until the 19th century, medical records mainly served educational purposes, later assuming other roles such as in insurance or legal procedures. This article comprehensively describes and reviews the development of medical records from ancient to modern times in Europe and North America, reflecting alterations and adaptations compliant with the mental and technological capabilities of a given period. We searched PubMed and Google Scholar databases to collect pertinent articles. English articles or those having English abstracts were considered. The search terms included "Medical Records," "Health Records," "History of Medicine," and "eHealth" and covered the last hundred years. References were also picked out from the identified articles. Overall, 600 articles were identified, 158 of which were judged thematically relevant. The general conclusion is that medical records undergo a revolutionary change from paper-based to electronic format, which reflects the development of eHealth systems. The migration process to eHealth records involves the use of artificial intelligence (AI) algorithms that streamline medical services by using faster and simpler working methods. AI benefits both patients and providers as it improves patient management and communication among medical centers, spares resources, identifies contamination or infections, and limits health costs. These advantages have become pointedly apparent during the recent COVID-19 scourge. [ABSTRACT FROM AUTHOR]

Tuberculosis is a chronic and lethal infectious disease caused by Mycobacterium tuberculosis. In previous decades, most studies in this area focused on the pathogenesis and drug targets for disease treatments. However, the emergence of drug-resistant strains has increased the difficulty of clinical trials over time. Now, more post-translational modified proteins in Mycobacterium tuberculosis have been discovered. Evidence suggests that these proteins have the ability to influence tuberculosis drug resistance. Hence, this paper systematically summarizes updated research on the impacts of protein acylation and phosphorylation on the acquisition of drug resistance in Mycobacterium tuberculosis through acylation and phosphorylation protein regulating processes. This provides us with a better understanding of the mechanism of antituberculosis drugs and may contribute to a reduction the harm that tuberculosis brings to society, as well as aiding in the discovery of new drug targets and therapeutic regimen adjustments in the future. [ABSTRACT FROM AUTHOR]

Neurological and psychiatric patients have increased dramatically in number in the past few decades. However, effective treatments for these diseases and disorders are limited due to heterogeneous and unclear pathogenic mechanisms. Therefore, further exploration of the biological aspects of the disease, and the identification of novel targets to develop alternative treatment strategies, is urgently required. Systems-level investigations have indicated the potential involvement of the brain–gut axis and intestinal microbiota in the pathogenesis and regulation of neurological and psychiatric disorders. While intestinal microbiota is crucial for maintaining host physiology, some important sensory and regulatory cells in the host should not be overlooked. Intestinal epithelial enteroendocrine cells (EECs) residing in the epithelium throughout intestine are the key regulators orchestrating the communication along the brain-gut-microbiota axis. On one hand, EECs sense changes in luminal microorganisms via microbial metabolites; on the other hand, they communicate with host body systems via neuroendocrine molecules. Therefore, EECs are believed to play important roles in neurological and psychiatric disorders. This review highlights the involvement of EECs and subtype cells, via secretion of endocrine molecules, in the development and regulation of neurological and psychiatric disorders, including Parkinson's disease (PD), schizophrenia, visceral pain, neuropathic pain, and depression. Moreover, the current paper summarizes the potential mechanism of EECs in contributing to disease pathogenesis. Examination of these mechanisms may inspire and lead to the development of new aspects of treatment strategies for neurological and psychiatric disorders in the future. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO), a signaling molecule, regulates multiple biological functions, including a variety of physiological and pathological processes. In this regard, NO participates in cutaneous inflammations, modulation of mitochondrial functions, vascular diseases, COVID-19, neurologic diseases, and obesity. It also mediates changes in the skeletal muscle function. Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by the malfunction of phagocytes caused by mutations in some of the genes encoding subunits of the superoxide-generating phagocyte NADPH (NOX). The literature consulted shows that there is a relationship between the production of NO and the NADPH oxidase system, which regulates the persistence of NO in the medium. Nevertheless, the underlying mechanisms of the effects of NO on CGD remain unknown. In this paper, we briefly review the regulatory role of NO in CGD and its potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

In the past years, deep neural networks (DNNs) have become popular in many disciplines such as computer vision (CV). One of the most important challenges in the CV area is Medical Image Analysis (MIA). However, adversarial attacks (AdAs) have proven to be an important threat to vision systems by significantly reducing the performance of the models. This paper proposes a new black-box adversarial attack, which is based οn orthogonal image moments named Mb-AdA. Additionally, a corresponding defensive method of adversarial training using Mb-AdA adversarial examples is also investigated, with encouraging results. The proposed attack was applied in classification and segmentation tasks with six state-of-the-art Deep Learning (DL) models in X-ray, histopathology and nuclei cell images. The main advantage of Mb-AdA is that it does not destroy the structure of images like other attacks, as instead of adding noise it removes specific image information, which is critical for medical models' decisions. The proposed attack is more effective than compared ones and achieved degradation up to 65% and 18% in terms of accuracy and IoU for classification and segmentation tasks, respectively, by also presenting relatively high SSIM. At the same time, it was proved that Mb-AdA adversarial examples can enhance the robustness of the model. [ABSTRACT FROM AUTHOR]

The endocannabinoid system (ECS) dynamically regulates many aspects of mammalian physiology. ECS has gained substantial interest since growing evidence suggests that it also plays a major role in several pathophysiological conditions due to its ability to modulate various underlying mechanisms. Furthermore, cannabinoids, as components of the cannabinoid system (CS), have proven beneficial effects such as anti-inflammatory, immunomodulatory, neuromodulatory, antioxidative, and cardioprotective effects. In this comprehensive review, we aimed to describe the complex interaction between CS and most common age-related diseases such as neuro-degenerative, oncological, skeletal, and cardiovascular disorders, together with the potential of various cannabinoids to ameliorate the progression of these disorders. Since chronic inflammation is postulated as the pillar of all the above-mentioned medical conditions, we also discuss in this paper the potential of CS to ameliorate aging-associated immune system dysregulation. [ABSTRACT FROM AUTHOR]

Despite recent advances in heart failure (HF) management, the risk of death and hospitalizations remains high in the long term. HF is characterized by endothelial dysfunction, inflammation and increased oxidative stress, due to a reduction in the activity of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway. All these factors contribute to direct damage at the myocardial, vascular and renal level. Vericiguat restores the deficiency in this signaling pathway, through stimulation and activation of sGC, aiming to increase cGMP levels, with a reduction in HF-related oxidative stress and endothelial dysfunction. Two main clinical trials were developed in this setting: the SOCRATES-REDUCED phase II study and the VICTORIA phase III study. They found that vericiguat is safe, well tolerated and effective with an absolute event-rate reduction in patients affected by HF with reduced ejection fraction (HFrEF) and recent cardiac decompensation. In patients with HF with preserved ejection fraction (HfpEF), the SOCRATES-PRESERVED trial demonstrated an improvement in quality of life and health status, but the proven beneficial effects with vericiguat are still limited. Further studies are needed to correctly define the role of this drug in heart failure syndromes. Our paper reviews the potential applications and pharmacological characteristics of vericiguat in HFrEF and HFpEF. [ABSTRACT FROM AUTHOR]

Digital technologies are shifting the paradigm of medicine in a way that will transform the healthcare industry. Conventional medical approaches focus on treating symptoms and ailments for large groups of people. These approaches can elicit differences in treatment responses and adverse reactions based on population variations, and are often incapable of treating the inherent pathophysiology of the medical conditions. Advances in genetics and engineering are improving healthcare via individualized treatments that include gene and cell therapies, pharmacogenetics, disease detection, and diagnostics. This paper highlights ways that artificial intelligence can help usher in an age of personalized medicine. [ABSTRACT FROM AUTHOR]

Pharmacokinetic assessment of drug disposition processes in vivo is critical in predicting pharmacodynamics and toxicology to reduce the risk of inappropriate drug development. The blood–brain barrier (BBB), a special physiological structure in brain tissue, hinders the entry of targeted drugs into the central nervous system (CNS), making the drug concentrations in target tissue correlate poorly with the blood drug concentrations. Additionally, once non-CNS drugs act directly on the fragile and important brain tissue, they may produce extra-therapeutic effects that may impair CNS function. Thus, an intracerebral pharmacokinetic study was developed to reflect the disposition and course of action of drugs following intracerebral absorption. Through an increasing understanding of the fine structure in the brain and the rapid development of analytical techniques, cerebral pharmacokinetic techniques have developed into non-invasive imaging techniques. Through non-invasive imaging techniques, molecules can be tracked and visualized in the entire BBB, visualizing how they enter the BBB, allowing quantitative tools to be combined with the imaging system to derive reliable pharmacokinetic profiles. The advent of imaging-based pharmacokinetic techniques in the brain has made the field of intracerebral pharmacokinetics more complete and reliable, paving the way for elucidating the dynamics of drug action in the brain and predicting its course. The paper reviews the development and application of imaging technologies for cerebral pharmacokinetic study, represented by optical imaging, radiographic autoradiography, radionuclide imaging and mass spectrometry imaging, and objectively evaluates the advantages and limitations of these methods for predicting the pharmacodynamic and toxic effects of drugs in brain tissues. [ABSTRACT FROM AUTHOR]

Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA-Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. Despite the GSE113957 RNA-Seq dataset being well-known and frequently analyzed, the RNA-Seq data shared by Fleischer et al. is far from exhausted and reusing and repurposing the data still reveals new insights. By analyzing the literature citing the use of the dataset and subsequently conducting a comparative analysis comparing the RNA-Seq data analyses of different subsets of the dataset (healthy children, nonagenarians and progeria patients), we identified several genes involved in both natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved indicated their possible roles in aging, suggesting the need for further in vitro and in vivo research. In this paper, we (1) compare "normal aging" (nonagenarians vs. healthy children) and progeria (HGPS patients vs. healthy children), (2) enlist genes possibly involved in both the natural aging process and progeria, including the first mention of IGFBP2 in progeria, (3) predict miRNAs and interactomes for WNT16 (hsa-mir-181a-5p), UCP2 (hsa-mir-26a-5p and hsa-mir-124-3p), and IGFBP2 (hsa-mir-124-3p, hsa-mir-126-3p, and hsa-mir-27b-3p), (4) demonstrate the compatibility of well-established R packages for RNA-Seq analysis for researchers interested but not yet familiar with this kind of analysis, and (5) present comparative proteomics analyses to show an association between our RNA-Seq data analyses and corresponding changes in protein expression. [ABSTRACT FROM AUTHOR]

(1) Introduction: Inflammatory Bowel Disease (IBD) patients may benefit from cannabinoid administration supplementary therapy; currently no consensus on its effect has been reached. (2) Methods: a systematic review of RCTs on cannabinoid supplementation therapy in IBD has been conducted; data sources were MEDLINE, Scopus, ClinicalTrials. (3) Results: out of 974 papers found with electronic search, six studies have been included into the systematic review, and five of them, for a grand total of 208 patients, were included into the meta-analysis. (4) Conclusions: cannabinoid supplementation as adjuvant therapy may increase the chances of success for standard therapy of Crohn's Disease during the induction period; no statement on its potential usage during maintenance period can be derived from retrieved evidence. Its usage in Ulcerative Colitis is not to be recommended. If ever, low-dose treatment may be more effective than higher dosage. Mean CDAI reduction was found stronger in patients treated with cannabinoids (mean CDAI reduction = 36.63, CI 95% 12.27–61.19) than placebo. In future studies, it is advisable to include disease activity levels, as well as patient-level information such as genetic and behavioral patterns. [ABSTRACT FROM AUTHOR]

Medical records generated in hospitals are treasures for academic research and future references. Medical Image Retrieval (MIR) Systems contribute significantly to locating the relevant records required for a particular diagnosis, analysis, and treatment. An efficient classifier and effective indexing technique are required for the storage and retrieval of medical images. In this paper, a retrieval framework is formulated by adopting a modified Local Binary Pattern feature (AvN-LBP) for indexing and an optimized Fuzzy Art Map (FAM) for classifying and searching medical images. The proposed indexing method extracts LBP considering information from neighborhood pixels and is robust to background noise. The FAM network is optimized using the Differential Evaluation (DE) algorithm (DEFAMNet) with a modified mutation operation to minimize the size of the network without compromising the classification accuracy. The performance of the proposed DEFAMNet is compared with that of other classifiers and descriptors; the classification accuracy of the proposed AvN-LBP operator with DEFAMNet is higher. The experimental results on three benchmark medical image datasets provide evidence that the proposed framework classifies the medical images faster and more efficiently with lesser computational cost. [ABSTRACT FROM AUTHOR]

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response. [ABSTRACT FROM AUTHOR]

The present paper evaluates the effect of physical activity on the increase of the conditioned rewarding effects of cocaine induced by intermittent social stress and on the neuroinflammatory response that contributes to the enhancement of drug response. For that purpose, three studies were designed in which social stress was induced in different samples of mice through a social-defeat protocol; the mice underwent an increase of physical activity by different modalities of voluntary wheel running (continuous and intermittent access). The results showed that continuous access to running wheels prior to stress enhanced the establishment of cocaine place preference, whereas an intermittent access exerted a protective effect. Wheel running contingent to cocaine administration prevented the development of conditioned preference, and if applied during the extinction of drug memories, it exerted a dual effect depending on the stress background of the animal. Our biological analysis revealed that increased sensitivity to cocaine may be related to the fact that wheel running promotes inflammation though the increase of IL-6 and BDNF levels. Together, these results highlight that physical exercise deeply impacts the organism's response to stress and cocaine, and these effects should be taken into consideration in the design of a physical intervention. [ABSTRACT FROM AUTHOR]

(1) Background: Emergence of methods interrogating gene expression at high throughput gave birth to quantitative transcriptomics, but also posed a question of inter-comparison of expression profiles obtained using different equipment and protocols and/or in different series of experiments. Addressing this issue is challenging, because all of the above variables can dramatically influence gene expression signals and, therefore, cause a plethora of peculiar features in the transcriptomic profiles. Millions of transcriptomic profiles were obtained and deposited in public databases of which the usefulness is however strongly limited due to the inter-comparison issues; (2) Methods: Dozens of methods and software packages that can be generally classified as either flexible or predefined format harmonizers have been proposed, but none has become to the date the gold standard for unification of this type of Big Data; (3) Results: However, recent developments evidence that platform/protocol/batch bias can be efficiently reduced not only for the comparisons of limited transcriptomic datasets. Instead, instruments were proposed for transforming gene expression profiles into the universal, uniformly shaped format that can support multiple inter-comparisons for reasonable calculation costs. This forms a basement for universal indexing of all or most of all types of RNA sequencing and microarray hybridization profiles; (4) Conclusions: In this paper, we attempted to overview the landscape of modern approaches and methods in transcriptomic harmonization and focused on the practical aspects of their application. [ABSTRACT FROM AUTHOR]

Defining reliable tools for early prediction of outcome is the main target for physicians to guide care decisions in patients with brain injury. The application of machine learning (ML) is rapidly increasing in this field of study, but with a poor translation to clinical practice. This is basically dependent on the uncertainty about the advantages of this novel technique with respect to traditional approaches. In this review we address the main differences between ML techniques and traditional statistics (such as logistic regression, LR) applied for predicting outcome in patients with stroke and traumatic brain injury (TBI). Thirteen papers directly addressing the different performance among ML and LR methods were included in this review. Basically, ML algorithms do not outperform traditional regression approaches for outcome prediction in brain injury. Better performance of specific ML algorithms (such as Artificial neural networks) was mainly described in the stroke domain, but the high heterogeneity in features extracted from low-dimensional clinical data reduces the enthusiasm for applying this powerful method in clinical practice. To better capture and predict the dynamic changes in patients with brain injury during intensive care courses ML algorithms should be extended to high-dimensional data extracted from neuroimaging (structural and fMRI), EEG and genetics. [ABSTRACT FROM AUTHOR]

Cardiolipin (CL) plays a pivotal role in mitochondria-mediated apoptosis. Acyl-CoA: lysocardiolipin acyltransferase 1 (ALCAT1) can accelerate CL reactive oxygen production and cause mitochondrial damage. Although we have demonstrated that aerobic exercise significantly reduced ALCAT1 levels in MI mice, what is the temporal characteristic of ALCAT1 after MI? Little is known. Based on this, the effect of exercise on ALCAT1 in MI rats needs to be further verified. Therefore, this paper aimed to characterize ALCAT1 expression, and investigate the possible impact of exercise on ALCAT1 and its role in fibrosis, antioxidant capacity, and apoptosis in MI rats. Our results indicated that the potential utility of MI increased ALCAT1 expression within 1–6 h of MI, and serum CK and CKMB had significant effects in MI at 24 h, while LDH exerted an effect five days after MI. Furthermore, ALCAT1 expression was upregulated, oxidative capacity and excessive apoptosis were enhanced, and cardiac function was decreased after MI, and aerobic exercise can reverse these changes. These findings revealed a previously unknown endogenous cardiac injury factor, ALCAT1, and demonstrated that ALCAT1 damaged the heart of MI rats, and aerobic exercise reduced ALCAT1 expression, oxidative stress, and apoptosis after MI-induced cardiac injury in rats. [ABSTRACT FROM AUTHOR]

Although there are number of available therapies for ulcerative colitis (UC), many patients are unresponsive to these treatments or experience secondary failure during treatment. Thus, the development of new therapies or alternative strategies with minimal side effects is inevitable. Strategies targeting dysbiosis of gut microbiota have been tested in the management of UC due to the unquestionable role of gut microbiota in the etiology of UC. Advanced molecular analyses of gut microbiomes revealed evident dysbiosis in UC patients, characterized by a reduced biodiversity of commensal microbiota. Administration of conventional probiotic strains is a commonly applied approach in the management of the disease to modify the gut microbiome, improve intestinal barrier integrity and function, and maintain a balanced immune response. However, conventional probiotics do not always provide the expected health benefits to a patient. Their benefits vary significantly, depending on the type and stage of the disease and the strain and dose of the probiotics administered. Their mechanism of action is also strain-dependent. Recently, new candidates for potential next-generation probiotics have been discovered. This could bring to light new approaches in the restoration of microbiome homeostasis and in UC treatment in a targeted manner. The aim of this paper is to provide an updated review on the current options of probiotic-based therapies, highlight the effective conventional probiotic strains, and outline the future possibilities of next-generation probiotic and postbiotic supplementation and fecal microbiota transplantation in the management of UC. [ABSTRACT FROM AUTHOR]

This paper presents pioneering results on the evaluation of noble metal film hetero-structures to improve some functional characteristics of carbon-based implant materials: carbon-composite material (CCM) and carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). Metal-organic chemical vapor deposition (MOCVD) was successfully applied to the deposition of Ir, Pt, and PtIr films on these carriers. A noble metal layer as thin as 1 µm provided clear X-ray imaging of 1–2.5 mm thick CFR-PEEK samples. The coated and pristine CCM and CFR-PEEK samples were further surface-modified with Au and Ag nanoparticles (NPs) through MOCVD and physical vapor deposition (PVD) processes, respectively. The composition and microstructural features, the NPs sizes, and surface concentrations were determined. In vitro biological studies included tests for cytotoxicity and antibacterial properties. A series of samples were selected for subcutaneous implantation in rats (up to 3 months) and histological studies. The bimetallic PtIr-based heterostructures showed no cytotoxicity in vitro, but were less biocompatible due to a dense two-layered fibrous capsule. AuNP heterostructures on CFR-PEEK promoted cell proliferation in vitro and exhibited a strong inhibition of bacterial growth (p < 0.05) and high in vitro biocompatibility, especially Au/Ir structures. AgNP heterostructures showed a more pronounced antibacterial effect, while their in vivo biocompatibility was better than that of the pristine CFR-PEEK, but worse than that of AuNP heterostructures. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is one of the leading causes of mortality and hospitalization worldwide. The accurate prediction of mortality and readmission risk provides crucial information for guiding decision making. Unfortunately, traditional predictive models reached modest accuracy in HF populations. We therefore aimed to present predictive models based on machine learning (ML) techniques in HF patients that were externally validated. We searched four databases and the reference lists of the included papers to identify studies in which HF patient data were used to create a predictive model. Literature screening was conducted in Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition and MEDLINE. The protocol of the current systematic review was registered in the PROSPERO database with the registration number CRD42022344855. We considered all types of outcomes: mortality, rehospitalization, response to treatment and medication adherence. The area under the receiver operating characteristic curve (AUC) was used as the comparator parameter. The literature search yielded 1649 studies, of which 9 were included in the final analysis. The AUCs for the machine learning models ranged from 0.6494 to 0.913 in independent datasets, whereas the AUCs for statistical predictive scores ranged from 0.622 to 0.806. Our study showed an increasing number of ML predictive models concerning HF populations, although external validation remains infrequent. However, our findings revealed that ML approaches can outperform conventional risk scores and may play important role in HF management. [ABSTRACT FROM AUTHOR]