Automated identification of aquatic insects: A case study using deep learning and computer vision techniques.

Deep learning techniques have recently found application in biodiversity research. Mayflies (Ephemeroptera), stoneflies (Plecoptera) and caddisflies (Trichoptera), often abbreviated as EPT, are frequently used for freshwater biomonitoring due to their large numbers and sensitivity to environmental changes. However, the morphological identification of EPT species is a challenging but fundamental task. Morphological identification of these freshwater insects is therefore not only extremely time-consuming and costly, but also often leads to misjudgments or generates datasets with low taxonomic resolution. Here, we investigated the application of deep learning to increase the efficiency and taxonomic resolution of biomonitoring programs. Our database contains 90 EPT taxa (genus or species level), with the number of images per category ranging from 21 to 300 (16,650 in total). Upon completion of training, a CNN (Convolutional Neural Network) model was created, capable of automatically classifying these taxa into their appropriate taxonomic categories with an accuracy of 98.7 %. Our model achieved a perfect classification rate of 100 % for 68 of the taxa in our dataset. We achieved noteworthy classification accuracy with morphologically closely related taxa within the training data (e.g., species of the genus Baetis, Hydropsyche, Perla). Gradient-weighted Class Activation Mapping (Grad-CAM) visualized the morphological features responsible for the classification of the treated species in the CNN models. Within Ephemeroptera, the head was the most important feature, while the thorax and abdomen were equally important for the classification of Plecoptera taxa. For the order Trichoptera, the head and thorax were almost equally important. Our database is recognized as the most extensive aquatic insect database, notably distinguished by its wealth of included categories (taxa). Our approach can help solve long-standing challenges in biodiversity research and address pressing issues in monitoring programs by saving time in sample identification.

The Association of Death Receptors and TGF-ß1 Expression in Urothelial Bladder Cancer and Their Prognostic Significance.

Death receptor signalization that triggers the extrinsic apoptotic pathway and TGF-ß1 have important roles in urothelial carcinogenesis, with a complex interplay between them. The aim of this research was to assess the association of death receptors DR4, DR5, and FAS as well as TGF-ß1 immunohistochemical expression with the clinicopathological characteristics of urothelial bladder cancer (UBC) and to evaluate their prognostic significance. The decrease or loss of death receptors' expression was significantly associated with muscle-invasive tumors, while non-invasive UBC often retains the expression of death receptors, which are mutually strongly linked. High DR4 expression is a marker of low-grade tumors and UBC associated with exposition to known carcinogens. Conversely, TGF-ß1 was significantly associated with high tumor grade and advanced stage. High expression of DR4 and FAS indicates longer overall survival. High TGF-ß1 signifies an inferior outcome and is an independent predictor of adverse prognosis in UBC patients. This study reveals the expression profile of death receptors in UBC and their possible interconnection with TGF-ß1 and indicates independent prognostic significance of high FAS and TGF-ß1 expression in UBC, which may contribute to deciphering the enigma of UBC heterogeneity in light of the rapid development of novel and effective therapeutic approaches, including targeting of the TRAIL-induced apoptotic pathway.

Changes in Dickkopf-1, but Not Sclerostin, in Gingival Crevicular Fluid Are Associated with Peroral Statin Treatment in Patients with Periodontitis.

Background and Objectives: Periodontitis is marked by the destruction of alveolar bone. Sclerostin (SOST) and dickkopf-1 (DKK-1) act as inhibitors of the Wingless-type (Wnt) signaling pathway, a key regulator of bone metabolism. Recent studies have suggested that statins play a role in bone resorption and formation by influencing Wnt signaling. The aim of this study was to determine the levels of SOST and DKK-1 in periodontal patients with and without peroral statins treatment in their therapy. Materials and Methods: A total of 79 patients with diagnosed periodontitis were divided into two groups: 39 patients on statin therapy (SP group) and 40 patients without statin therapy as a control group (P group). The periodontal clinical examination probing (pocket) depth (PD) and gingival recession (GR) were measured, and approximal plaque was detected, while vertical and horizontal bone resorption was measured using a panoramic radiograph image. Clinical attachment loss (CAL) values were calculated using PD and GR values. Gingival crevicular fluid (GCF) was collected and used for measuring SOST and DKK-1 levels. A questionnaire was used to assess lifestyle habits and statin intake. Patients' medical records were used to obtain biochemical parameters. Results: There was no significant difference in sclerostin concentration between the SP and P group. DKK-1 values were significantly higher in the SP group compared to the control group (p = 0.04). Also, PD (p = 0.001) and GR (p = 0.03) were significantly higher in the SP group. The level of DKK-1 had a positive relationship with the PD, the greater the PD, the higher the level of DKK-1 (Rho = 0.350), while there was no significant association with other parameters. Conclusions: Peroral statins in periodontal patients are associated with GCF levels of DKK-1 but not with sclerostin levels.

Expression of Basal Compartment and Superficial Markers in Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy, a Worldwide Disease.

The aim of this study was to determine the association of basal compartment and superficial markers, comprising CK5/6, CD44, CK20, and the pathological characteristics of upper tract urothelial carcinoma (UTUC) associated with Balkan endemic nephropathy (BEN). Comparing the expression of the investigated markers in 54 tumors from the BEN region and 73 control UTUC, no significant difference between them was detected. In regression analysis, CK20 expression was not determined with expression of CK5/6, CD44, and the phenotypic characteristics of BEN and control UTUC. Parameters with predictive influence on the expression of CD44 in BEN UTUC included growth pattern (p = 0.010), necrosis (p = 0.019); differentiation (p = 0.001), and lymphovascular invasion (p = 0.021) in control UTUC. Divergent squamous differentiation in BEN tumors (p = 0.026) and stage in control tumors (p = 0.049) had a predictive influence on the expression of CK5/6. This investigation detected a predictive influence of the phenotypic characteristics of UTUC on the expression of basal compartment and superficial markers, with a significant influence of necrosis in BEN tumors (p = 0.006) and differentiation in control UTUC (p = 0.036).

Occupational Therapy and Public Safety Personnel: Return to Work Practices and Experiences.

Background. Public safety personnel (PSP) are frequently exposed to psychological trauma through their work. Evidence shows that worker's compensation claims for work-related psychological injuries are on the rise for PSP. Occupational therapists increasingly provide return to work (RTW) services for this population. Purpose. To explore the therapeutic practices and personal experiences of occupational therapists working with PSP who have work-related psychological injuries. Method. This mixed methods descriptive study included a chart review of available occupational therapy client records from 2016 to 2020 for PSP with work-related psychological injuries from two Ontario companies. Additionally, a web-based self-report survey for Ontario occupational therapists providing RTW services to this same population was available from November 1, 2021 to June 1, 2022. Findings. The chart review included 31 client records and the online survey was completed by 49 Ontario occupational therapists. Therapists commonly provided services in clients' homes, workplaces, and communities, and focused on functional activities. The evidence base drawn on by therapists was not always occupation-based. Barriers to RTW included challenges with interprofessional collaboration, stigma, and the COVID-19 pandemic. Implications. Occupational therapists are commonly working with PSP with work-related psychological injuries and have the opportunity to contribute to the evidence base for occupational approaches to RTW.

Biomarkers for Assessing Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus on Sodium-Glucose Cotransporter 2 Inhibitor Therapy.

In the current modern era of unhealthy lifestyles, non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and has become a serious global health problem. To date, there is no approved pharmacotherapy for the treatment of NAFLD, and necessary lifestyle changes such as weight loss, diet, and exercise are usually not sufficient to manage this disease. Patients with type 2 diabetes mellitus (T2DM) have a significantly higher risk of developing NAFLD and vice versa. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that have recently been approved for two other indications: chronic kidney disease and heart failure in diabetics and non-diabetics. They are also emerging as promising new agents for NAFLD treatment, as they have shown beneficial effects on hepatic inflammation, steatosis, and fibrosis. Studies in animals have reported favorable effects of SGLT2 inhibitors, and studies in patients also found positive effects on body mass index (BMI), insulin resistance, glucose levels, liver enzymes, apoptosis, and transcription factors. There are some theories regarding how SGLT2 inhibitors affect the liver, but the exact mechanism is not yet fully understood. Therefore, biomarkers to evaluate underlying mechanisms of action of SGLT2 inhibitors on the liver have now been scrutinized to assess their potential as a future in-label therapy for NAFLD. In addition, finding suitable non-invasive biomarkers could be helpful in clinical practice for the early detection of NAFLD in patients. This is crucial for a positive disease outcome. The aim of this review is to provide an overview of the most recent findings on the effects of SGLT2 inhibitors on NAFLD biomarkers and the potential of SGLT2 inhibitors to successfully treat NAFLD.

Tapentadol Immediate Release (IR) versus Morphine Hydrochloride for Postoperative Analgesia of Patients Undergoing Total Abdominal Hysterectomy-A Prospective Cohort Study.

Background and Objectives: This study aimed to examine the efficacy of tapentadol immediate release (IR) and morphine hydrochloride in the treatment of acute postoperative pain after total abdominal hysterectomy, as well as to examine the frequency of opioid-related side effects in observed patients. Materials and Methods: The prospective observational study was conducted over five months, and it included a total number of 100 patients. The two cohorts had different types of postoperative analgesia, and the effects were observed for 24 h postoperatively, by following the pain scores on NRS (Numerical Pain Scale), contentment with analgesia, and opioid-related side effects. Results: Statistical significance was found when assessing pain 24 h after surgery while coughing, where patients in the tapentadol IR group had significantly higher mean pain scores (p < 0.01). The subjective feeling of satisfaction with postoperative analgesia was statistically significant in the tapentadol IR group (p = 0.005). Vertigo appeared significantly more in patients from the morphine group (p = 0.03). Conclusions: Tapentadol IR (immediate release) and morphine hydrochloride are both effective analgesics used in the first 24 h after total transabdominal hysterectomy. Overall satisfaction of patients with analgesia was good. The frequency of side effects was higher in the morphine group, with statistical significance regarding the vertigo.

Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis.

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

The Role of GLP1-RAs in Direct Modulation of Lipid Metabolism in Hepatic Tissue as Determined Using In Vitro Models of NAFLD.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to improve glucose and lipid homeostasis, promote weight loss, and reduce cardiovascular risk factors. They are a promising therapeutic option for non-alcoholic fatty liver disease (NAFLD), the most common liver disease, associated with T2DM, obesity, and metabolic syndrome. GLP-1RAs have been approved for the treatment of T2DM and obesity, but not for NAFLD. Most recent clinical trials have suggested the importance of early pharmacologic intervention with GLP-1RAs in alleviating and limiting NAFLD, as well as highlighting the relative scarcity of in vitro studies on semaglutide, indicating the need for further research. However, extra-hepatic factors contribute to the GLP-1RA results of in vivo studies. Cell culture models of NAFLD can be helpful in eliminating extrahepatic effects on the alleviation of hepatic steatosis, modulation of lipid metabolism pathways, reduction of inflammation, and prevention of the progression of NAFLD to severe hepatic conditions. In this review article, we discuss the role of GLP-1 and GLP-1RA in the treatment of NAFLD using human hepatocyte models.

Preclinical Models and Promising Pharmacotherapeutic Strategies in Liver Fibrosis: An Update.

Liver fibrosis represents one of the greatest challenges in medicine. The fact that it develops with the progression of numerous diseases with high prevalence (NAFLD, viral hepatitis, etc.) makes liver fibrosis an even greater global health problem. Accordingly, it has received much attention from numerous researchers who have developed various in vitro and in vivo models to better understand the mechanisms underlying fibrosis development. All these efforts led to the discovery of numerous agents with antifibrotic properties, with hepatic stellate cells and the extracellular matrix at the center of these pharmacotherapeutic strategies. This review focuses on the current data on numerous in vivo and in vitro models of liver fibrosis and on various pharmacotherapeutic targets in the treatment of liver fibrosis.

MicroRNAs: Small Molecules with Significant Functions, Particularly in the Context of Viral Hepatitis B and C Infection.

A MicroRNA (miRNA) is defined as a small molecule of non-coding RNA (ncRNA). Its molecular size is about 20 nucleotides (nt), and it acts on gene expression's regulation at the post-transcription level through binding to the 3'untranslated regions (UTR), coding sequences, or 5'UTR of the target messenger RNAs (mRNAs), which leads to the suppression or degradation of the mRNA. In recent years, a huge evolution has identified the origin and function of miRNAs, focusing on their important effects in research and clinical applications. For example, microRNAs are key players in HCV infection and have important host cellular factors required for HCV replication and cell growth. Altered expression of miRNAs affects the pathogenicity associated with HCV infection through regulating different signaling pathways that control HCV/immunity interactions, proliferation, and cell death. On the other hand, circulating miRNAs can be used as novel biomarkers and diagnostic tools for HCV pathogenesis and early therapeutic response. Moreover, microRNAs (miRNA) have been involved in hepatitis B virus (HBV) gene expression and advanced antiviral discovery. They regulate HBV/HCV replication and pathogenesis with different pathways involving facilitation, inhibition, activation of the immune system (innate and adaptive), and epigenetic modifications. In this short review, we will discuss how microRNAs can be used as prognostic, diagnostic, and therapeutic tools, especially for chronic hepatitis viruses (HBV and HCV), as well as how they could be used as new biomarkers during infection and advanced treatment.

Future Prospects, Approaches, and the Government's Role in the Development of a Hepatitis C Virus Vaccine.

Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal.

Principal Component Analysis (PCA) of Molecular Descriptors for Improving Permeation through the Blood-Brain Barrier of Quercetin Analogues.

Despite its beneficial pharmacological effects in the brain, partly by modulating inositol phosphate multikinase (IPMK) activity, the therapeutic use of quercetin is limited due to its poor solubility, low oral bioavailability, and low permeability through the blood-brain barrier (BBB). We aimed to identify quercetin analogues with improved BBB permeability and preserved binding affinities towards IPMK and to identify the molecular characteristics required for them to permeate the BBB. Binding affinities of quercetin analogues towards IPMK were determined by molecular docking. Principal component analysis (PCA) was applied to identify the molecular descriptors contributing to efficient permeation through the BBB. Among 34 quercetin analogues, 19 compounds were found to form more stable complexes with IPMK, and the vast majority were found to be more lipophilic than quercetin. Using two distinct in silico techniques, insufficient BBB permeation was determined for all quercetin analogues. However, using the PCA method, the descriptors related to intrinsic solubility and lipophilicity (logP) were identified as mainly responsible for clustering four quercetin analogues (trihydroxyflavones) with the highest BBB permeability. The application of PCA revealed that quercetin analogues could be classified with respect to their structural characteristics, which may be utilized in further analogue syntheses and lead optimization of BBB-penetrating IPMK modulators as neuroprotective agents.

Glycosylation Alterations in Cancer Cells, Prognostic Value of Glycan Biomarkers and Their Potential as Novel Therapeutic Targets in Breast Cancer.

Although we are lately witnessing major improvements in breast cancer treatment and patient outcomes, there is still a significant proportion of patients not receiving efficient therapy. More precisely, patients with triple-negative breast cancer or any type of metastatic disease. Currently available prognostic and therapeutic biomarkers are not always applicable and oftentimes lack precision. The science of glycans is a relatively new scientific approach to better characterize malignant transformation and tumor progression. In this review, we summarize the most important information about glycosylation characteristics in breast cancer cells and how different glycoproteins and enzymes involved in glycosylation could serve as more precise biomarkers, as well as new therapeutic targets.

Therapeutic Perspectives of IL1 Family Members in Liver Diseases: An Update.

Interleukin (IL) 1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the liver. Progression of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage, the release of inflammatory cytokines and disturbances in gut microbiota. IL1 cytokines and receptors can have pro- or anti-inflammatory roles, even dual functionalities conditioned by the microenvironment. Developing novel therapeutic strategies to block the IL1/IL1R signaling pathways seems like a reasonable option. This mode of action is now exploited by anakinra and canakinumab, which are used to treat different inflammatory illnesses, and studies in liver diseases are on the way. In this mini review, we have focused on the IL1 superfamily members, given their crucial role in liver inflammation diseases, specifically discussing their potential role in developing new treatment strategies.

Anabolic androgenic steroid-induced liver injury: An update.

Anabolic androgenic steroids (AASs) are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects. These properties make them therapeutically beneficial in medical conditions such as hypogonadism. However, they are commonly bought illegally and misused for their anabolic, skeletal muscle building, and performance-enhancing effects. Supraphysiologic and long-term use of AASs affects all organs, leading to cardiovascular, neurological, endocrine, gastrointestinal, renal, and hematologic disorders. Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse. Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis, peliosis hepatis, and hepatic benign and malignant tumors. It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors, upregulation of bile acid synthesis, and induction of hepatocyte hyperplasia. Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS. However, some long-term consequences are irreversible. AAS-induced liver injury should be taken in consideration in patients with liver disorders, especially with the increasing unintentional ingestion of supplements containing AAS. In this paper, we review the most current knowledge about AAS-associated adverse effects on the liver, and their clinical presentations, prevalence, and pathophysiological mechanisms.

Survey of the Knowledge, Attitudes and Practice towards Antibiotic Use among Prospective Antibiotic Prescribers in Serbia.

The complex issue of antibacterial resistance (ABR) requires actions taken with the One Health approach, involving both human and veterinarian medicine. It can spread from animals to humans through the food chain or through direct contact. Health profession students, as the future antibiotic providers, can greatly impact antibiotic-related issues in the future. The study was conducted to evaluate knowledge, attitudes and practice of future antibiotic prescribers in relation to judicious use of antibiotics. This cross-sectional, questionnaire-based study was performed on 400 students of health professions who were allowed to prescribe antibiotics of the University of Novi Sad, Serbia. Students of medicine and students of dentistry showed a significantly higher knowledge score compared to students of veterinary medicine (p = 0.001). Multivariate regression identified predictors of adequate antibiotic knowledge: being a female student (B = 0.571; p = 0.020), higher grade average (B = 1.204; p = 0.001), students of medicine (B = 0.802; p = 0.006) and dentistry (B = 0.769; p = 0.026), and students who used a complete package of antibiotics during the last infection (B = 0.974; p = 0.001) or for the period recommended by the doctor (B = 1.964; p = 0.001). Out of the total sample, self-medication was reported among 42.8% of students. The identified predictors of self-medication were: more frequent (B = 0.587; p = 0.001) and irregular (B = 0.719; p = 0.007) antibiotic use, taking antibiotics until symptoms disappeared (B = 2.142; p = 0.001) or until the bottle was finished (B = 1.010; p = 0.001) during the last infection. It seems prudent to reevaluate the educational curricula regarding antibiotic use and ABR of prospective prescribers in Serbia.

Multiscale Contextual Poverty in the Netherlands: Within and Between-Municipality Inequality.

Contextual poverty refers to high proportions of people with a low income in a certain (residential) space, and it can affect individual socioeconomic outcomes as well as decisions to move into or out of the neighbourhood. Contextual poverty is a multiscale phenomenon: Poverty levels at the regional scale reflect regional economic development, while meso-scale concentrations of poverty within cities are related to city-specific social, economic and housing characteristics. Within cities, poverty can also concentrate at micro spatial scales, which are often neglected, largely due to a lack of data. Exposure to poverty at lower spatial scales, such as housing blocks and streets, is important because it can influence individuals through social mechanisms such as role models or social networks. This paper is based on the premise that sociospatial context is necessarily multiscalar, and therefore contextual poverty is a multiscale problem which can be better understood through the inequality within and between places at different spatial scales. The question is how to compare different spatial contexts if we know that they include various spatial scales. Our measure of contextual poverty embraces 101 spatial scales and compares different locations within and between municipalities in the Netherlands. We found that the national inequality primarily came from the concentrations of poverty in areas of a few kilometres, located in cities, which have different spatial patterns of contextual poverty, such as multicentre, core-periphery and east-west. In addition to the inequality between municipalities, there are considerable within-municipality inequalities, particularly among micro-areas of a few hundred metres.

Self-Medication Perceptions and Practice of Medical and Pharmacy Students in Serbia.

BACKGROUND: Attitudes towards conventional and complementary medicine among future healthcare professionals can impact their future pharmacotherapy practice. This study aimed to determine the prevalence and predisposing factors related to self-medication among medical and pharmacy students. METHODS: This cross-sectional questionnaire-based study was performed at the Faculty of Medicine, University of Novi Sad, Serbia, on first- and final-year students of medicine and pharmacy. The multivariate Poisson regression model with robust variance was used to identify the main predictors of self-medication. RESULTS: The overall self-medication prevalence in the past year was 81.3%. Independent risk factors for self-medication identified in the regression analysis were the final study year, housing condition, i.e., living in a leased apartment or in a student dormitory in comparison to living with parents, and cigarette consumption. The conventional drugs were the most frequently used, mostly for the symptoms of cold and pain. Final-year students had more confidence in conventional medicines than in herbal drugs and were more aware of the risks of their concomitant use. CONCLUSION: Self-medication is highly prevalent among students of medical sciences, especially among final-year students. Increased medical knowledge led to the higher awareness of the drug interaction risks.