Abstract: Background: Tapentadol is an atypical opioid with a dual mechanism as a mu agonist and norepinephrine reuptake inhibitor. This study characterized tapentadol use in the United States (US) using three databases. Methods: Drug distribution from 2010-2020 were extracted from the Drug Enforcement Administration’s (DEA) Automated Reports and Consolidated Orders System (ARCOS). Use per region (mg/person) and business activity (i.e., pharmacy). Tapentadol prescription claims from the Medicare and Medicaid programs for 2010-2020 were also examined. Results: The distributed amount of tapentadol was 3.5 tons in 2020. Distribution was over twice as high in southern (South Atlantic=29.0 mg/person, East South Central=28.8) relative to Pacific (12.9) or New England (12.8) states. Tapentadol use decreased nationally between 2012 and 2020 by -53.8%. Adult diabetes prevalence was significantly associated with tapentadol distribution in 2012 (r(50) = +.44, p < .01) and 2020 (r(50) = +.28, p < .05). Tapentadol prescribing to Medicaid patients declined -55.2% from the peak year, 2011, until 2020. Tapentadol prescribed by Nurse Practitioners accounted for over one-sixth (18.0%) of 2019 Medicare. Conclusions: There has been a substantial decline over the past decade in tapentadol distribution and prescribing. However, the substantial regional differences may warrant further attention by opioid stewardship programs.

Abstract: Background: Recent advances in aging research have enabled quantification of biological age through epigenetic clocks and the emergence of EpiScore, reshaping our understanding of aging and health. Methods: This review synthesizes key studies on biological clocks, evaluates the role of DNA methylation-based epigenetic clocks, EpiScores, and multi-omics integration, and explores their potential to reflect physiological and functional states. Results: Current tools, including epigenetic clocks and EpiScores, enable precise assessment of aging and disease risk. Integration with AI and exposome data supports the development of a comprehensive aging clock and well-being score, enabling health to be treated as a quantifiable asset. Conclusion: Epigenetics-centered evaluation offers opportunities for intervention, standardization, and ISO-based precision health management. This paradigm shift can transform anti-aging strategies and support longevity-focused public health policies.

Abstract: Background: The prevalence of preoperative anaemia in patients undergoing major surgery is approximately 30%, and is independently associated with higher mortality, a higher rate of postoperative complications, and a greater probability of receiving a transfusion. In a prehabilitation program, the evaluation and correction of anaemia in the preoperative period is essential, as it is a risk factor for transfusions and complications. The main objectives of this study were to analyse the need for blood transfusion, post-surgical complications, hospital length of stay, ICU length of stay, hospital readmissions, and surgical wound infection in patients treated with ferric carboxymaltose (FC) before surgery. Methods: A total of 152 patients were included, of whom 96 received FC before the intervention and 56 received no treatment (control group). Results: Preoperative treatment with FC significantly reduced the need for blood transfusion (p<0.001; OR 15.91 [4.44-57.01]), the incidence of complications (p<0.001; OR 7.36 [3, 35-16.16]) and the mean hospital length of stay (p<0.001). Conclusions: Preoperative anaemia is a common comorbidity in surgical patients and is associated with negative outcomes. The optimization of preoperative anaemia with FC is a blood-saving strategy that also reduces the incidence of surgical wound infection, post-surgical complications, and the length of hospital stay, among other results, and thereby improves patient quality of life.

Abstract: Background. The use of vasoconstricting agents is an important part of the armament used by modern medicine in the treatment of patients suffering from septic shock. Nevertheless, their administration is associated with different severities of limb ischemia. The aim of the current study was to quantify this adverse outcome of treatment. Methods. This retrospective study analyzed patients suffering from septic shock, who were hospitalized in a tertiary medical center. Results. Out of 7,160 patients suffering from septic shock that were hospitalized in our medical center over a period of 13 years, 4,468 were eligible for analysis. Among them 2,181 received vasopressor treatment, and 2,287 did not. While the rate of in-hospital mortality was higher in the vasopressor group (32.3% vs. 27.4%; p < 0.001), as was the incidence of acute kidney injury (28.1% vs. 18.4%; p < 0.001) and the portion of patients with in-hospital length of stay > 7 days (65.4% vs. 61.5%; p = 0.007), there was no significant difference between the rate of in-hospital amputations between the two study groups (0.8% vs. 1.1%; p = 0.44). Independent risk factors for amputations include older age and preexisting diagnosis of peripheral vascular disease.. Conclusion. The use of vasopressors as part of the treatment for patients suffering from septic shock does not appear to increase the risk of resultant amputations. Nevertheless, advanced age and pre-morbid peripheral vascular disease are associated with a higher likelihood of amputation.

Abstract: Objective: This study aims to investigate the correlation between the morphological and functional characteristics of the left atrial appendage (LAA) and the incidence of thromboembolic events by transesophageal echocardiography (TEE) in patients with acute ischemic stroke. Methods: This cross-sectional study included 171 patients with acute ischemic stroke from November 2022 to September 2024. Transesophageal echo-cardiography was performed to evaluate the presence of LAA thrombus. Multivariable logistic regression analysis was performed to identify risk factors for LAA thrombus. Results: Of the 171 patients, 19 (11.1%) were found to have LAA thrombus. Multivariable logistic regression identified two independent predictors of LAA thrombus formation: (1) left atrial spontaneous echo contrast (OR = 8, 95% CI: 3-19, p < 0.001) and (2) atrial fibrillation (OR = 8, 95% CI: 1.057-76.095, p = 0.044). Conclusion: Left atrial spontaneous echo contrast and atrial fibrillation are independent predictors of LAA thrombus in patients with acute ischemic stroke. The use of transesophageal echocardiography for early detection of LAA thrombus may help improve treatment strategies and prevent recur-rent strokes.

Abstract: Background: Bloodstream infections remain a critical global health concern due to their high morbidity and mortality, compounded by increasing antimicrobial resistance and delays in initiating targeted therapy. This study evaluates the effectiveness and timeliness of therapeutic recommendations generated by an artificial intelligence (AI)-driven clinical decision support system (CDSS), comparing outputs based solely on molecular diagnostics versus those integrating molecular and phenotypic data. Methods: In a prospective cross-sectional study conducted in Lima, Peru, 117 blood cultures were analyzed using FilmArray/GeneXpert for molecular identification and MALDI-TOF/VITEK 2.0 for phenotypic profiling. The AI-based CDSS provided treatment recommendations in two formats, which were assessed for concordance and turnaround time. Results: Therapeutic recommendations showed 80.3% consistency between data types, with 86.3% concordance in pathogen and resistance detection. Notably, molecular-only recommendations were delivered 29 hours earlier than those incorporating phenotypic data. Escherichia coli was the most frequently isolated pathogen, with a 95% concordance in suggested therapy. A substantial agreement was observed in treatment consistency (Kappa = 0.80). Conclusions: These findings highlight the potential of AI-powered molecular diagnostics to accelerate clinical decision-making in bacteremia, supporting more timely interventions and improved antimicrobial stewardship. Further research is warranted to assess scalability and impact across diverse clinical settings.

Abstract: Lung cancer is strongly associated with a hypercoagulable state, significantly increasing the risk of venous thromboembolism (VTE) and complicating clinical management. The mechanisms underlying cancer-associated coagulopathy are multifactorial, involving tumor-derived procoagulants, chronic inflammation, endothelial dysfunction, autoim-mune phenomena, and treatment-induced effects. These processes not only drive throm-bosis but also influence disease progression and therapeutic decisions. Moreover, the presence of antiphospholipid antibodies and acquired inhibitors of coagulation adds fur-ther complexity by simultaneously predisposing patients to both thrombosis and bleed-ing. This review provides a clinically oriented synthesis of the current evidence on coagu-lation abnormalities in lung cancer, highlighting diagnostic strategies—including mixing studies and biomarker evaluation—and exploring treatment approaches such as low-molecular-weight heparins, direct oral anticoagulants, and immunosuppressive regimens. Recognizing and managing coagulation disorders is essential for optimizing outcomes in lung cancer patients, and a multidisciplinary, personalized approach is in-creasingly warranted in oncologic practice.

Abstract: Background/Objectives: Recent studies brought evidence that the Long-Covid / post-COVID-19 Syndrome (PCS) and the related Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have an autoimmune pathomechanism[1]. It could be triggered by various infectious pathogens, like SARS-CoV-2, which may be one of the most common triggering factors of the disease. The identification of increased levels of autoantibodies alleged with the typical symptom-constellation of post-exertional malaise, sleeping disorders, cognitive malfunction, postural orthostatic tachycardia syndrome (POTS), etc. and several subjective health problems can lead to the correct diagnosis. ME/CFS patients have a high suffering level. Making a correct diagnosis is challenging, as well as the therapy of the complex and individual constellation of physical and psychical symptoms. Methods: Our aim was to identify the ME/CFS patients correctly, including an initial rule-in screening by investigating other possible causes (pulmonal/cardial/endocrine, etc.). In 7 cases we applied plasmapheresis (PE) with repetitive autoantibody-measurements. Additionally, according to references from literature, for monitoring the clinical outcomes psychometric follow-up assessments had been conducted: with the ISI (insomnia), FSS (fatigue), HADS (depression and anxiety) and EQ-5D-5L (quality of life) questionnaires. Patients who met the inclusion criteria received 4 PE sessions on day 1, 5, 30 and 60 and a low-dose intravenous immunoglobulin (IVIG) therapy after each treatment. The psychometric evaluation had been conducted before the first PE, 2 weeks after the second and two weeks after the last PE-therapy. All 4 antibodies were measured two times per patient over the course of the study at standardized sampling time points: baseline before starting PE and 2 weeks after the last PE. Results: It could be found a negative correlation between the ꞵ-Adrenergic and M3-muscarinic receptor antibodies concentration and the quality of life measurements assessed with the EQ-5D-5L questionnaire. Conclusions: In this pilot study a correlation could be shown between the autoantibody-concentration and the physical and psychical wellbeing of the treated ME/CFS patients. These first results should be seen as a hypothesis-building assessment, further investigation is needed to validate these promising pilot-study results of therapeutic PE and IVIG in ME/CFS cases.

Abstract: Objectives: We identified cell counts and proportions reported in, or calculated from, a complete blood count (CBC) that independently predicted mortality in hospitalized COVID-19 patients. The primary objective was to characterize a CBC signature at presentation that might provide insights for tracking immune response and disease management.Methods/Study design: This was a retrospective longitudinal observational study. The primary outcome was in-hospital mortality. Secondary outcomes included the need for mechanical ventilation, development of sepsis, and ICU admission. Electronic medical records underwent IRB exempted extraction of clinical data. Univariate logistic regression was used to identify CBC parameters and putative inflammatory markers independently predictive of hospital mortality. Bootstrap Forest (BF) modeling was employed to aggregate predictive CBC parameters that optimized generalized coefficient of variation (R2) concurrently computing their proportion of explained variance in mortality. BF modeling was replicated with inflammatory markers and subsequently with pooled features from both models.Results: CBC parameters including segmented neutrophils, bands, ANC, and RDW-CV were significantly elevated in non-survivors compared to survivors. In addition, patients with decreased platelets, lymphocytes and monocytes were more likely to be in the non-survivor group. Incorporating these CBC parameters amplified R2 for mortality in a presentation prognostic model with only inflammatory markers including C-reactive protein, lactate dehydrogenase and ferritin.Conclusion: Routinely obtained CBC parameters improve predictive power of putative COVID-19 severity markers and enhance accuracy of mortality risk assessment at presentation. We recommend that these CBC parameters be considered for presentation risk stratification, level of care triaging decisions and longitudinal tracking of disease management.

Abstract: Background and Objectives: Group A Streptococcus (GAS) is a leading cause of acute pharyngitis with seasonal outbreaks in Japan. The coronavirus disease 2019 (COVID-19) pandemic significantly altered respiratory infection trends; however, its impact on GAS pharyngitis (GAS-P) remains unclear. Additionally, data on co-infections of GAS and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. This study examined temporal trends in GAS-P incidence and characteristics of GAS–SARS-CoV-2 co-infections. Materials and Methods: We conducted this retrospective observational study at Tokyo Shinagawa Hospital between January 2019 and December 2024. Data on GAS and SARS-CoV-2 test results and patient demographics were extracted from medical records. The study period was categorized into three phases based on major public health policy changes: the pre-COVID social period (January 2019–April 2020), restricted social period (May 2020–April 2023), and post-restriction period (May 2023–December 2024). GAS positivity rates, age distributions, and case proportions were compared across these periods. Clinical characteristics of patients with concurrent GAS and SARS-CoV-2 infections were analyzed. Results: Among 4,837 GAS tests, 463 (9.6%) were positive. GAS positivity rates varied significantly: 11.4% (pre-COVID), 7.1% (restricted social period), and 12.6% (post-restriction period, p &lt; 0.001). The proportion of pediatric cases decreased significantly during the restricted social period (24.8%–5.3%) before rising sharply in the post-restriction period (47.1%, p &lt; 0.001). Among 151 patients tested for both GAS and SARS-CoV-2, 14 (9.3%) had co-infections, which were identified exclusively after July 2022. Most patients exhibited mild symptoms, primarily fever and sore throat, with decreased lymphocyte counts despite normal white blood cell levels. Conclusions: COVID-19-related infection control measures affected GAS-P incidence and age distribution, particularly the increase in pediatric cases post-restrictions. Limited testing may contribute to the underdiagnosis of GAS–SARS-CoV-2 co-infections. Further large-scale studies are warranted to assess microbial interactions, disease severity, and long-term outcomes.

Abstract: Pain is a fundamental yet highly complex biological and psychosocial phenomenon. While acute pain functions as a defence mechanism, alerting the body to tissue damage or injury, chronic pain loses this protective role and becomes a persistent, independent problem. Chronic pain in the elderly is of significant clinical importance, as it impacts not only physical health but also severely affects mental well-being, quality of life, and social participation. Diagnosing pain in older adults is particularly challenging due to its subjective nature, which is influenced by cognitive decline, comorbidities, and diminished communication abilities. As such, both objective scales and subjective self-assessment tools are essential in pain evaluation. Managing chronic pain in the elderly requires a multidisciplinary approach combining pharmacological and non-pharmacological therapies. Analgesic use, including non-steroid-antiinflammatory drugs (NSAIDs) and opioids, should match pain type and intensity. Age-related pharmacokinetic and pharmacodynamic changes, like reduced renal function and slower metabolism, impact drug efficacy and side effects, raising complication risks. Non-pharmacological therapies, such as physiotherapy, psychological interventions and complementary techniques (e.g., acupuncture), can also be effective, particularly for long-term pain relief. These methods aim to reduce pain perception and contribute to maintaining physical activity, psychological well-being, and social engagement. Developing and continuously revising personalized pain management plans are essential for preserving patients' quality of life. Nurses are crucial in alleviating chronic pain in the elderly, extending beyond patient monitoring to emotional support and multidisciplinary care coordination. Adequate training and access to essential tools are vital for effective pain management.

Abstract: The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a process essential for the methylation of homocysteine to methionine. Polymorphisms in the MTHFR gene can reduce enzyme activity, disrupting the folate cycle and leading to hyperhomocysteinemia. The two most common polymorphisms associated with this gene are 667C&gt;T (rs1801133) and 1298A&gt;C (rs1801131). Background: This review provides a comprehensive summary of current knowledge regarding MTHFR polymorphisms, with a particular focus on their potential impact on disease susceptibility. We hope this review will serve as a valuable resource for understanding the significance of MTHFR polymorphisms and their complex relationships with various diseases. Methods: For this review, we prioritized recent evidence, focusing on reviews and meta-analyses published between 2015 and 2025, sourced from PubMed and Google Scholar. Results: We explore the connection between these polymorphisms and a broad spectrum of medical conditions, including: cardiovascular diseases and oxidative stress pathology, neurological and psychiatric disorders, such as Autism Spectrum Disorder, Alzheimer’s disease, Schizophrenia, and Major Depressive Disorder, fertility, pregnancy, and neonatal complications, including recurrent pregnancy loss, preeclampsia, preterm birth, low birth weight, and neural tube defects, metabolic disorders, such as diabetes mellitus, inflammatory bowel disease, and non-alcoholic fatty liver disease, oncological conditions, including breast, prostate, and ovarian cancers, as well as leukemia, autoimmune diseases, particularly rheumatoid arthritis. Conclusions: While some diseases have a well-established association with MTHFR polymorphisms, others require further investigation. Our analysis highlights the crucial role of environmental factors, such as ethnic background and dietary folate intake, in influencing study outcomes.

Abstract: Background/Objectives: Cardiovascular complications are the most common cause of mortality and morbidity in diabetic patients. Therefore, the aim of antidiabetic therapy should not only be to provide glucose regulation but also to protect patients from com-plications and related mortality. Brain natriuretic peptide (BNP) is a peptide secreted as a result of myocardial stress. BNP levels increase in conditions of increased myocar-dial stress, such as heart failure. It is important not only in diagnosis but also in fol-low-up. In our study, we aimed to evaluate BNP level and, thus, the factors affecting the risk of developing heart failure in the course of diabetes mellitus. Methods: This study was conducted at the University of Health Sciences, Haseki Training and Re-search Hospital diabetes outpatient clinic. Two hundred fifty-two patients met the in-clusion criteria and were enrolled in the study. Laboratory parameters, including BNP values, comorbidities, and anamnesis data, were recorded. Results: The mean BNP levels were significantly lower in patients using metformin and pioglitazone. Other antidiabetic medications were not associated with BNP levels. BNP levels were posi-tively correlated with age and diabetes duration and negatively correlated with hemo-globin. According to regression analysis, age, metformin use, and hemoglobin were found to independently affect BNP levels. Conclusions: Our findings suggest that metformin could potentially play a significant role in preventing the development of heart failure in diabetic patients without heart failure, owing to its favorable effects on myocardial stress. This suggests metformins potential in preventing heart failure in type 2 diabetic patients.

Abstract: Type 2 diabetes (T2D) and cardiovascular diseases (CVDs) are major public health challenges worldwide. Metabolomics, the exhaustive assessment of metabolites in biological systems, offers important understanding regarding metabolic disturbances related to these disorders. Recent advances towards integration of metabolomics into clinical practice to facilitate the discovery of novel biomarkers that can improve diagnosis, prognosis, and treatment of T2D and CVDs are discussed in this review. Metabolomics offers potential to characterize key metabolic alterations associated with disease pathophysiology and treatment. T2D is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms, and therefore disease-causing pathways of T2D have not been completely understood. Recent studies have identified several robust clusters of T2D variants representing biologically meaningful distinct pathways, beta cell and proinsulin cluster related to pancreatic insulin secretion, obesity, lipodystrophy, liver/lipid cluster, glycemia, blood pressure and metabolic syndrome clusters representing different pathways causing insulin resistance. For CVDs, recent studies have allowed the metabolomic profile to delineate pathways that contribute to atherosclerosis and heart failure, as well as to the development of targeted therapy. It also covers the role of metabolomics in integrated metabolic genomics and other omics platforms to better understand disease mechanisms, and the transition towards precision medicine. This review further investigates the use of metabolomics in multi-metabolite modelling to enhance risk prediction models for the first occurrence of major adverse cardiovascular events among the individuals with T2D highlighting the value of such approaches in optimizing preventive and therapeutic models in clinical practice.

Abstract: Background/Objectives: Influenza infection is associated with cardiovascular mor-bidity and mortality, but effect of influenza vaccination on cardiovascular outcomes is not fully understood. This clinical trial aimed to investigate correlation between car-diovascular outcomes and influenza vaccine (FluVac) in coronary artery diseases (CAD) subjects. Methods: This was a randomized single blinded placebo-controlled trial. Enrolled CAD subjects received 0.5 ml of 2007-2008 trivalent FluVac (15µg he-magglutinin of each of Solomon Islands/3/2006 (H1N1), Wisconsin/67/2005 (H3N2), and Malaysia/2506/2004 (B)). Subjects were followed up at 1 month (hemagglutinin (HA) antibody titers), and at 12 months post-vaccination for evaluation of outcomes (influenza-like episodes, acute coronary syndrome (ACS), myocardial infarction (MI), coronary revascularization, and death). Results: 278 eligible CAD subjects were ran-domized to receive either FluVac (n = 137) or placebo (n = 141) of which consequently 131 and 135 subejcts completed the study. Cardiovascular deaths (3/131 [2.29%] vs. 3/135 [2.22%]) and all-cause deaths (4/131 [3.05%] vs. 4/135 [2.96%]) were similar in both groups. Adverse cardiovascular events, including ACS, MI, and coronary revas-cularization were less frequent in the vaccine group, but did not reach statistical sig-nificance. Magnitude of antibody change and serologic response (≥4-fold HI titer rise) of all three antibodies were significantly higher in the vaccine group compared to the placebo but did not correlate with cardiovascular outcomes in the FluVac group. Con-clusions: Influenza vaccine may improve cardiovascular outcomes, though this im-provement is not correlated with post-vaccination antibody titers. Despite controver-sies, Influenza vaccination is recommended in CAD population. (ClinicalTrials.gov NCT00607178)

Abstract:

In this study, it was aimed to deterimine the in vitro antibacterial activity of Anatolian Sweetgum (Liquidambar orientalis Mill.) oil (ASO) against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Listeria monocytogenes, Salmonella typhimurium, Pseudomonas aeruginosa, Mannheimia haemolytica, Brucella melitensis, and Corynebacterium pseudotoberculosis strains. Methods: The volatile constituents of ASO were determined by gas chromatograph/mass selective detector (GC/MSD) system. The amount of α-pinene, camphene, benzaldehyde, sabinene, p-cymene, dl-limonene, benzyl alcohol, 3-phenyl-1-propanol, cinnamaldehyde, cinnamyl alcohol, ethyl cinnamate, geraniol acetate, torreyol, benzyl cinnamate, 3-methyl-3-phenyl-azetidin, 4-methylcoumarine-7-cinnamate, acetyl tributyl citrate, (1-methylcyclobutyl) benzene, cinnamyl cinnamate, squalene, and other compounds were determined. Disc diffusion and agar well diffusion tests were used to determine the in vitro antibacterial activity of ASO. Results: The volatile constituents of ASO were found in amounts ranging from 0.01% (camphene) to 62.56% (cinnamyl cinnamate). ASO showed in vitro antibacterial activity against tested bacterial strains as 58.3% and 62.5% by the disk diffusion test and agar well diffusion test, respectively. The antibacterial activity of ASO was determined to be slightly higher in Gram-positive bacteria (80.0%) than in Gram-negative bacteria (78.57%). The highest antibacterial activity was detected against S. aureus by the disk diffusion test and against B. melitensis by the agar well diffusion test. Conclusions: The results highlight the potential of ASO as an antibacterial activity against a broad spectrum of bacterial strains, with slightly higher efficacy against Gram-positive bacteria. To confirm these findings and explore practical applications, additional in vivo studies are required to evaluate its therapeutic applicability in combating bacterial infections in both human and veterinary medicine.

Abstract:

The management of prosthetic joint infections (PJIs) poses significant challenges, requiring a multidisciplinary approach involving surgical, microbiological, and pharmacological expertise. Suppressive antibiotic therapy (SAT) has emerged as a viable option in cases where curative interventions are deemed unfeasible. This review provides an updated synthesis of recent evidence on SAT, including its indications, efficacy, practical considerations, and associated challenges. We aim to highlight the nuances of this therapeutic approach, discuss the factors influencing its success, and propose future directions for research to optimize patient outcomes.

Abstract: Background: Neurological diseases contribute significantly to disability and mortality, necessitating improved diagnostic and prognostic tools. Advances in molecular biomarkers at genomic, transcriptomic, epigenomic, and proteomic levels have facilitated early disease detection. Notably, neurofilament light chain (NfL) serves as a key biomarker of neurodegeneration, while liquid biopsy techniques enable non-invasive monitoring through exosomal tau, α-synuclein, and inflammatory markers. Artificial intelligence (AI) and multi-omics integration further enhance biomarker discovery, promoting precision medicine. Methods: A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science to identify studies (2010–2024) on molecular biomarkers in neurodegenerative and neuroinflammatory disorders. Key findings on genomic mutations, transcriptomic signatures, epigenetic modifications, and protein-based biomarkers were analyzed. Results: Findings highlight the potential of liquid biopsy and multi-omics approaches in improving diagnostic accuracy and therapeutic stratification. Genomic, transcriptomic, and proteomic markers demonstrate utility in early detection and disease monitoring. AI-driven analysis enhances biomarker discovery and clinical application. Conclusion: Despite advancements, challenges remain in biomarker validation, standardization, and clinical implementation. Large-scale longitudinal studies are essential to ensure reliability. AI-powered multi-omics analysis may accelerate biomarker application, ultimately improving patient outcomes in neurological diseases.

Abstract: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is defined by hepatic fat accumulation unrelated to significant alcohol use and is strongly associated with metabolic disorders. It progresses from simple steatosis to inflammation and fibrosis, increasing the risk of cirrhosis and hepatocellular carcinoma. In contrast, acute cholangitis (AC) is a severe biliary infection usually caused by bile duct obstruction—often due to gallstones, strictures, or tumors—and presents with symptoms such as fever, jaundice, and abdominal pain. While both conditions affect liver health, their causes differ. There is pieces of evidence from clinical and experimental studies that shows there could be a relationship between MASLD and AC. It has been demonstrated that MASLD significantly increases AC risk, with worse clinical outcomes, including higher mortality, prolonged hospitalization, and severe complications such as sepsis and acute kidney injury. A piece of evidence has been provided mechanistic insights, showing that MASLD exacerbates cholangitis through chronic inflammation, ductular proliferation, and fibrosis, driven by bile acid (BA) dysregulation and gut-liver axis dysfunction. Studies highlighted BA metabolism disruptions in MASLD, while other studies emphasized the role of metabolic comorbidities and dysbiosis in amplifying biliary inflammation. Collectively, these studies underscore MASLD as a critical risk factor for AC, mediated by metabolic, inflammatory, and biliary pathways. This review aims to explain these connections, offering insights into preventive strategies and therapeutic targets to mitigate AC risk and improve outcomes in MASLD patients.

Abstract: Nephrin is an essential constituent of the slit-diaphragm of the kidney filtering unit. Loss of nephrin expression leads to protein leakage into the urine, one of the hallmarks of kidney damage. Autoantibodies against nephrin have been reported in patients with minimal change disease and recurrent focal segmental glomerulosclerosis. Understanding the mechanism of nephrin loss may help improve or lead to the development of a novel treatment strategies. In this study we demonstrated the important function of miR-204-5p expression on the protection of nephrin from anti-nephrin antibodies present in nephrotoxic serum (NTS). In addition, we identified that the aspartyl protease cathepsin D is one enzyme that may be involved in nephrin enzymatic degradation and that cathepsin D is a direct target of miR-204-5p gene regulation. The regulation of miR-204-5p expression was determined to be regulated by the long non-coding RNA Josd1-ps. In an NTS in vivo animal model, treatment with the pan aspartic proteases inhibitor Pepstatin A ameliorated the renal damage. Finally, we showed that the expression of miR-204-5p had a nephrin protecting function in vitro. Developing a method of delivery of miR-204-5p specifically to podocytes in vivo may provide a novel method of nephroprotection against nephrin autoantibodies.