Abstract: Aging is a very complex process and it has been linked with Sirtuins. Sirtuin enzymes are a family of deacetylases that are related with caloric restriction and aging by modulating energy metabolism, genomic stability and stress resistance. Up to now, seven sirtuins have been recognized. Our purpose is to clarify the role of sirtuins in Chronic Kidney Disease (CKD). Moreover, as heart and kidney diseases are strictly interrelated, we’re going to explore their role in heart diseases and cardio-renal cross-talk. A reciprocal relationship between CKD and aging seems to exist, since CKD may contribute to premature biological aging of different organ systems. SIRTs are involved in pathophysiology of renal diseases; their activation can delay the progression of several renal diseases. Cardiovascular diseases (CVDs) are the leading cause of global mortality and a major contributor to disability. Notably, an increasing number of studies linked SIRTs with different CVDs. SIRTs affect the production of mitochondrial reactive oxygen species (ROS) by modulating mitochondrial function. The imbalance of SIRTs levels may increase the vulnerability to CVDs. SIRTs are involved in pathophysiological mechanisms of HFpEF (heart failure with preserved ejection fraction) through different signalling pathways. Fibrosis is the linkage mechanism between heart and kidney in the development of cardio-renal diseases. Different natural SIRT1 agonists showed renoprotective effects and among these Resveratrol (RSV) and other phenolic compounds have been widely investigated with interesting and positive results. Future research is obviously needed to clarify the role of these molecules and their potential therapeutical role in heart and kidney diseases.

Abstract: Prenatal hypoxia (PH) is a major cause of nervous system disorders in early childhood, leading to reduced learning and memory capabilities, increased anxiety, and a higher risk of developing mental and neurodegenerative diseases later in life. Compensatory-adaptive mechanisms of the mother-placenta-fetus system, which enhance the fetus’s CNS resilience, are known, including the activation of endogenous neuroprotection in response to hypoxic brain injury through pharmacological modulation of HSP70. To evaluate the effect of HSP70 modulators—Cerebrocurin, Angiolin, Tamoxifen, Glutaredoxin, Thiotriazoline, HSF-1 (heat shock factor 1 protein), as well as Mildronate and Mexidol—on motor, exploratory, psycho-emotional activity, learning, and memory of offspring after PH. Experimental PH was induced by daily intraperitoneal injections of sodium nitrite solution to pregnant female rats from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. Newborns received intraperitoneal injections of Angiolin (50 mg/kg), Thiotriazoline (50 mg/kg), Mexidol (100 mg/kg), Cerebrocurin (150 µL/kg), L-arginine (200 mg/kg), Glutaredoxin (200 µg/kg), HSF-1 (50 mg/kg), and Mildronate (50 mg/kg) for 30 days. At 1 month, rats were tested in the open field test, and at 2 months, they were trained and tested for working and spatial memory in the radial maze. Modeling PH led to persistent impairments in exploratory activity, psycho-emotional behavior, and a decrease in cognitive-mnestic functions of the CNS. It was found that Angiolin and Cerebrocurin had the most pronounced effects on the indicators of exploratory-activity and psycho-emotional status in 1-month-old animals after PH. They also exhibited the most significant cognitive-enhancing and memory-supporting effects during training and evaluation of skill retention in the maze in 2-month-old offspring after PH. The obtained results provide experimental justification for further research into Angiolin and Cerebrocurin as promising neuroprotective agents for use after PH. Obtained results will help to expand our understanding of the effect of beta-blockers of various generations used to treat cardiovascular diseases on energy metabolism, and are also an experimental justification for the practical choice of these drugs in the complex therapy of CHF.

Abstract:

The development of modern breakthroughs in drug solubility enhancement and targeted delivery rely on liposomal drug delivery systems. The study covers simple methods of liposomal encapsulation because these procedures increase exposure levels resulting in superior therapeutic outcomes. The article shows pharmaceutical science uses liposomal applications to treat cancer and antimicrobial diseases in its clinical pharmacological applications. Liposomal encapsulation enhances the composition of curcumin and Tribulus terrestris as well as other herbal medicine components by increasing their absorption rate in the human body.Scientists investigate regulatory control approaches for creating liposomal pharmacological agents as they study new developments of this modern therapeutic discipline. Liposomal delivery faces ongoing challenges but the author Kauffman expects this technology will develop through partnerships between nanotechnology and personalized medicine systems. Through research the authors emphasize that pharmaceutical advancement for future medicinal delivery platforms needs liposomal formulation technology development

Abstract: The C1858T PTPN22 variant is strongly associated with Type 1 diabetes and autoimmune thyroid disease. Current treatment is the substitutive hormonal administration which does not target the disease pathogenetic mechanism. Background/Objectives: We previously implemented a novel immunotherapy, employing siRNA directed against the C1858T variant of PTPN22 delivered via functionalized lipoplexes in order to halt autoimmune disease progression. The objective of this study was to optimize lipoplexes formulations functionalized with F9-PEG (a Siglec-10's ligand) to facilitate targeted delivery, by testing their physical and chemical properties to warrant best performance in in vivo studies. Methods: The effectiveness of siRNA-liposome binding was evaluated by varying the relative lipid/siRNA charge ratio and analyzing the stability of the different formulations with respect to methods of F9-PEG addition and ATTO740 fluorescent labelling by electrophoresis, dynamic and dielectrophoretic light scattering (DLS, DELS), and high-performance liquid chromatography (HPLC). A preliminar investigation of lipoplexes biodistribution was conducted by fluorescent tagging in C57BL/6 mice. Results: The optimal charge ratio of +2 /-1 (lipid/siRNA) ensured greater stability of lipoplexes. Stability was improved by functionalization with F9-PEG further by the addition of ATTO740-dye. HPLC confirmed the integrity of siRNA after preparation. Injection of PKH26-labelled lipoplexes in mice showed selective accumulation in target tissues within 48 hours. Conclusions: The results of this study lead to formulations of F9-PEG lipoplexes with optimal properties that could be used for biodistribution and safety/efficacy studies in mice. Lipoplexes functionalized with F9-PEG could therefore represent a promising personalized nanotherapeutic platform for targeted siRNA delivery in endocrine C1858T patients.

Abstract:

Introduction: Post-surgical laboratory testing is commonly performed in patients after hip arthroplasty. Considering recent trends towards reduced transfusion rates, is it still necessary? Materials and Methods: We conducted clinical-laboratory follow-up on patients undergoing primary hip arthroplasty. We collected demographic data (sex, age, comorbidities, and risk factors for postoperative laboratory abnormalities), laboratory tests (hemoglobin (Hb), creatinine (Cr), sodium (Na)), pre-anesthetic assessment (ASA), surgical details (side, surgical approach, operative time, use tranexamic acid, intraoperative complications), laboratory results at 24 and 48 hours post-surgery, and changes in medical therapy based on laboratory findings. Results: 125 patients (73 women, 52 men), mean age 66.9 years. Preoperative laboratory: Hb 14.12 g/dL, Cr 0.84 mg/dL, Na 140.8 mEq/L. ASA classification: I (n=3), II (n=79), III (n=36), IV (n=2). Surgical approaches: posterior (n=74), anterolateral (n=51). Mean operative time: 76 minutes. Postoperative laboratory at 24 hours: Hb 11.69 g/dL (no differences between approaches, age, sex, IBM and operative time), Cr 0.94 mg/dL, Na 138.86 mEq/L. At 48 hours: Hb 11.07 g/dL. Tranexamic acid (TXA) was not used in 11.5% of patients, which was associated with a 13.9% transfusion rate, 0% in those who received TXA (p=0.046, Fisher’s test). Medical complications in 16% of patients. The most frequent therapy adjustment was transfusion, in 7% of patients (2.5% ASA II, 17% ASA III), though not statistically significant (Chi-square). No statistically significant associations with analyzed parameters were observed. Conclusions: Routine laboratory tests do not provide clinical benefit for most patients. Postoperative Hb testing should be reserved for those with additional indications, ASA III or higher patients in whom blood-saving strategies cannot be fully implemented.

Abstract:

This study aimed to investigate the impact of cisplatin-based chemoradiotherapy dos-age per cycle on prognosis for elderly patients. This retrospective study included 90 patients with head and neck squamous cell carcinoma who received cisplatin - based chemoradiotherapy. Those who received triweekly cisplatin (100) regimen for defini-tive chemoradiotherapy and triweekly cisplatin (80) regimen for postoperative chemoradiotherapy were allocated to the high-dose group. Meanwhile, those who re-ceived tri-weekly cisplatin (80) regimen for definitive chemoradiotherapy and weekly cisplatin (40) regimen for postoperative chemoradiotherapy were allocated to the low-dose group. The outcomes in elderly and non-elderly patients following chemora-diotherapy were compared between the groups. As a result, the patients in the high-dose group had a significantly higher incidence of severe toxicity than that in low-the groups (P < 0.05), and the elderly patients in the high-dose group demonstrat-ed the highest rate of severe toxicity (34.8%) compared to the other groups. Further-more, only in the elderly patients, overall survival became significantly shorter in the high-dose group than that in the low-dose group (P < 0.05). In elderly patients, the total dosage of cisplatin administered to those who developed severe toxicity was signifi-cantly lower than that for patients who did not experience toxicity (P < 0.01). Fur-thermore, these patients demonstrated significantly short overall survival (P < 1.0×10-5). In conclusion, current cisplatin dosage per cycle may exhibit excessive for el-derly patients.

Abstract: The COVID-19 pandemic has led to persistent complications beyond the respiratory system, with emerging evidence highlighting the role of gut dysbiosis in long COVID. Given the established gut-skin axis, alterations in gut microbiota post-COVID-19 may contribute to persistent dermatologic conditions such as eczema, acne, and rosacea. This review explores the mechanisms by which SARS-CoV-2 disrupts the gut microbiome, leading to systemic inflammation and skin disease. Furthermore, it examines potential interventions, including probiotics, prebiotics, and dietary modifications, as microbiome-targeted therapeutic strategies for post-COVID dermatologic recovery. Understanding this link may open new avenues for treating chronic inflammatory skin conditions in long COVID patients.

Abstract: The intraosseous environment is a dynamic and intricate system integral to bone health, encompassing vascular, cellular, and biochemical interactions that drive key processes such as hematopoiesis, bone remodeling, and systemic mineral regulation. This review examines the structural composition of the bone matrix, the diverse cellular landscape, and the interconnected vascular and nervous networks, highlighting their roles in preserving bone function and responding to pathological changes. Recent studies reveal regulatory mechanisms involving oxygen tension, ionic balance, signaling molecules, and mechanotransduction pathways that shape bone metabolism and its adaptation to mechanical forces. Insights into the bone microenvironment’s metabolic shifts in cancer and its interaction with inflammation underscore its pivotal role in disease progression and therapeutic innovation. Additionally, advances in imaging techniques and biomaterials fuel progress in bone regeneration and understanding its microenvironment. Exploring the intricate physiochemical dynamics and regulatory networks within the intraosseous system unlocks potential clinical applications in bone diseases, tissue engineering, and systemic metabolic disorders. This comprehensive review bridges fundamental science with translational research, offering insights into the complex yet essential intraosseous environment.

Abstract: Circumferential full-thickness burns present a significant risk for Burn-Induced Compartment Syndrome (BICS), often necessitating escharotomy to restore circulation. Traditional surgical approaches carry inherent risks, prompting the exploration of enzymatic debridement with NexoBrid® (EDNX) for swift and selective eschar removal. However, concerns persist regarding its efficacy in preventing BICS and its impact on elevated compartment pressures. This case series evaluates the use of early enzymatic debridement with NexoBrid® in patients with circumferential burns affecting the upper and lower extremities and the abdominal region. Our findings suggest that EDNX has the potential to serve as an alternative to traditional escharotomy by reducing the need for surgical intervention while maintaining vital functions. However, given the limited sample size, further controlled studies are necessary to confirm these preliminary observations.

Abstract: Tumor-educated platelets (TEPs) are emerging as powerful minimally invasive liquid bi-opsy modalities for cancer diagnosis and prognosis. Through crosstalk with tumor cells, platelets sequester tumor-derived molecules and exhibit altered RNA splicing, protein content, and activation status, all of which reflect tumor biology. Numerous studies have reported that TEP-based assays can distinguish cancer patients from controls, with sensi-tivities and specificities often exceeding 80%. Furthermore, platelet RNA signatures can identify cancer types and stages, and elevated platelet counts (thrombocytosis) and spe-cific platelet RNA/protein biomarkers are correlated with adverse prognoses in multiple malignancies, including ovarian and lung cancers. Recent large-scale investigations have validated these findings, reinforcing that TEPs are promising diagnostic and prognostic indicators. Despite this potential, some challenges remain. Ensuring sufficient platelet purity, standardizing sample processing, and accounting for non-cancerous conditions that influence platelet profiles remain critical hurdles. Moreover, tumor heterogeneity and dynamic platelet “education” can complicate assay interpretation. Ongoing efforts are focused on refining biomarker panels, improving computational models for classification, and integrating TEP data with other liquid biopsy analytes (e.g., circulating tumor DNA) for enhanced accuracy. Overall, TEP-based liquid biopsy could transform clinical deci-sion-making by enabling the earlier detection of malignancies and more precise prognos-tic assessments. With further validation in large prospective trials, TEP assays may soon provide a routine and cost-effective approach for guiding individualized cancer care.

Abstract: Background/Objectives: The global burden caused by high body mass index (BMI) particularly in postmenopausal (PMP) women is increasing significantly and is expected to be increasing in geographical and socioeconomic perspectives. Serum vitamin D (vitD) and pro-inflammatory factors influence the development and progression of T2DM particularly in overweight (OW)/obese PMP women. However, since there are controversies about the impact and interactive association of vitD with some of the pro-inflammatory biomarkers (interleukin-6 (IL-6), homocysteine (Hcy) and others) and therapeutic significance of vitD in OW women in PMP with T2DM, we planned to carry out study in NW and OW women with/ without T2DM in PMP. Methods: The normal weight (NW, BMI: 18.5 to 24.9 kg/m2) and OW (n: BMI: 25.0 to29.9 kg/m2) nondiabetic (ND, n: 199) and T2DM (n: 197) women in PMP (age range: 51-60 years) were consulted. The women subjects (n: 396) were categorized into NW-ND (n: 101), OW-ND (n:98), NW-DM (n:101) and OW-DM (n:96). Fasting blood samples were collected for the determination of serum levels of vitD, IL-6, Hcy, hemoglobin (HB) and hepcidin (Hp). Results: The present report in PMP women with and without T2DM showed significant difference of serum vitD for NW-ND vs. OW-ND, NW-DM vs. OW-DM, and NW-ND vs. NW-DM, Hcy for OW-ND vs. OW-DM and NW-DM vs. OW-DM and IL-6 for OW-ND vs. OW-DM and NW-DM vs. OW-DM. Among-groups comparison showed significant variation of serum vitD, Hcy and IL-6. A significant negative linear correlation of BMI was obtained against vitD for OW-ND and OW-DM. A significant positive linear correlation of BMI was found against Hcy as well as IL-6 for OW-ND and OW-DM. A significant inverse linear correlation of vitD was obtained against Hcy for OW-DM, and against IL-6 for NW-ND, NW-DM and OW-DM. Hcy plot with IL-6 levels showed significant positive linear correlation for NW-DM, OW-ND and OW-DM. Conclusions: The results obtained for the alterations noted for serum vitD, proinflammatory biomarkers (Hcy and IL-6) and other variables in the present investigation in PMP women (NW and OW) with T2DM, and associations among these factors are quite convincing to introduce a novel therapeutic approach based on vitD and proinflammatory markers for T2DM patients of high BMI levels.

Abstract:

Lactic acidosis is a serious metabolic disorder characterized by an accumulation of lactate in the body, which can lead to a severe acid-base imbalance. Metfor-min-associated lactic acidosis is a rare but life-threatening complication of metformin therapy, particularly in the setting of acute kidney injury or other conditions that im-pair lactate clearance. In this case report, we present the remarkable survival of a patient who experienced severe metformin-associated lactic acidosis with a blood pH of 6.8 and a lactate level of 29 mmol/L, which are typically considered incompatible with life.

Abstract: Ventilator-associated pneumonia (VAP) remains a significant concern in intensive care units (ICUs), contributing to increased morbidity, mortality, and healthcare costs. Probiotics and synbiotics have been explored as potential preventive measures due to their ability to modulate gut microbiota, reduce pathogenic colonization, enhance immune responses, and maintain intestinal barrier integrity. While some randomized controlled trials (RCTs) suggest that specific strains, such as Lactobacillus rhamnosus GG and Bifidobacterium breve, may reduce VAP incidence, larger trials have not confirmed significant benefits. Systematic reviews and meta-analyses indicate a potential 28–38% relative risk reduction in VAP, but evidence quality remains low due to methodological limitations and study heterogeneity. Economic evaluations also question the cost-effectiveness of probiotic use in ICU settings. Future research should focus on large-scale, multicenter RCTs to determine the optimal strains, dosages, and administration methods, along with standardized diagnostic criteria. Until stronger evidence emerges, probiotics should be considered an adjunctive rather than a primary VAP prevention strategy.

Abstract:

The faster rate in the advancement of drug delivery technology has transformed the practice of modern medicine with greater bioavailability, therapeutic effect, and patient compliance. Low solubility, high clearance, and non-targeted delivery have contributed extensively to conventional drug delivery modes. While overcoming these shortcomings, new drug delivery carriers like liposomes, nanoparticles, and polymer systems are at the forefront as delivery carriers of controlled and targeted therapy.The article addresses the promise, innovation in stimulus-sensitive and ligand-targeted platforms, and translation to industry and clinic for nanoparticle and liposomal drug delivery. Follow-on more recent FDA approvals of other nanomedicine therapeutics show promise and efficacy in infectious disease, management of chronic disease, and cancer. Continuing to revolutionize the era of personalized medicine are the advancement in AI-enabled drug design, nature-inspired delivery platforms, and gene therapy-based carriers.While such monumental leaps have already been made, safety, scale-up, and regulatory challenges must be overcome first before such treatments become the norm around the world. With the synergy of disruptive technologies and best-practice formulation approaches, second-generation drug delivery systems have a generation-defining task to revolutionize therapeutics with more efficient, safer, and patient-more-friendly therapeutics.

Abstract: Background: Drug discovery is an inherently complex, resource-intensive, and time-consuming process, often requiring more than a decade to progress from initial target identification to regulatory approval. Despite technological advancements, high attrition rates and escalating research costs remain significant barriers. Artificial intelligence (AI) has emerged as a transformative force in pharmaceutical research, integrating machine learning, deep learning, and computational biology to revolutionize drug discovery processes. AI-driven models enable faster target identification, molecular docking, lead optimization, and drug repurposing, offering unprecedented efficiency in discovering novel therapeutics. Objective: This systematic review aims to assess the integration of AI in drug discovery, focusing on its applications in target identification, structure-based drug design (SBDD), ligand-based drug design (LBDD), and predictive modeling for clinical trials. The review highlights AI-driven advancements in molecular simulations, de novo drug design, and biomarker identification, providing insights into how AI enhances pharmaceutical innovation. Methods: A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar, covering research published between 2015 and 2025. Studies evaluating AI applications in computational drug discovery, virtual screening, molecular dynamics, and predictive analytics were included. The methodologies analyzed include convolutional neural networks (CNNs), generative adversarial networks (GANs), reinforcement learning models, and graph neural networks (GNNs). Quality assessment was performed using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool to ensure the reliability of selected studies. Results: AI-powered approaches have significantly improved drug discovery by enhancing target identification, optimizing molecular docking simulations, and accelerating lead optimization. Notable achievements include DeepMind’s AlphaFold in protein structure prediction, Insilico Medicine’s AI-driven fibrosis drug (which entered clinical trials in under 18 months), and BenevolentAI’s identification of Janus kinase inhibitors (JAK) for COVID-19 treatment. AI has also been instrumental in drug repurposing efforts, uncovering new therapeutic potentials for existing FDA-approved drugs. Furthermore, AI-enhanced clinical trial modeling and patient stratification have improved trial efficiency and success rates. Challenges & Future Directions: Despite its potential, AI-driven drug discovery faces challenges, including data bias, lack of interpretability, regulatory barriers, and ethical concerns regarding AI-generated predictions. To maximize AI’s impact, future research should focus on standardizing biological datasets, integrating multi-omics data, and developing explainable AI (XAI) models. The emergence of quantum AI and hybrid AI-physics models presents promising avenues for further accelerating drug discovery. Conclusion: AI is reshaping the landscape of drug discovery, offering unparalleled efficiency in identifying novel drug candidates, optimizing molecular interactions, and predicting clinical outcomes. Its integration with biological data and computational simulations paves the way for the development of personalized and highly effective therapeutics. However, addressing AI-related challenges in transparency, validation, and regulatory compliance remains crucial for translating AI-generated discoveries into clinically viable treatments.

Abstract:

Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within one year if left untreated. The pathophysiology of POR is multifactorial, involving dysregulated immune responses, gut microbiota alterations, and mucosal healing impairment, highlighting the need for targeted therapeutic strategies. This review aims to explore the current landscape of POR management, focusing on biologic therapies and emerging advanced treatments. Conventional management relies on early prophylactic therapy with anti-TNF agents such as infliximab and adalimumab, which have demonstrated efficacy in reducing endoscopic and clinical recurrence. However, newer biologics, including IL-23 inhibitors (risankizumab) and Janus kinase (JAK) inhibitors (upadacitinib), have shown promise in CD management, though their role in POR remains underexplored. The lack of direct clinical evidence for advanced biologics in POR prevention, combined with inter-individual variability in treatment response, underscores the need for further research. Future directions should focus on optimizing therapeutic strategies through personalized medicine, identifying predictive biomarkers, and conducting robust trials to establish the efficacy of novel agents in POR prevention. A tailored, evidence-driven approach is essential to improving long-term outcomes and minimizing disease recurrence in post-operative CD patients.

Abstract: For patients suffering from actinic keratosis (AK) and clinical evidence of chronic sun damage, achieving both actinic keratosis eradication and treating field cancerization is essential. AKs should not be underestimated. While the majority does not progress to squamous cell carcinoma (SCC), most cases of SCC develop from pre-existing AKs and nobody can differentiate between AKs that will develop into SCC and those that will either resolve on their own or remain unchanged. Photodynamic therapy (PDT) ad-dresses AKs and also targets surrounding sun-damaged areas with precancerous cells. This dual action reduces the risk of new AK formation, making PDT a valuable ap-proach for comprehensive skin cancer prevention in chronically sun-exposed individ-uals. The conventional PDT (cPDT) has already been proven a safe and effective method to treat non hyperkeratotic actinic keratosis and field cancerization. However, in the real world, PDT has not reached its maximum potential use, possibly due to the need of an office-based light source equipment and the associated peri-procedural pain. The daylight variation of PDT, which uses natural sunlight to activate the pho-tosensitizer and eradicate the premalignant cells. Daylight PDT (dPDT) is an effective, well-tolerated, and convenient treatment for AKs and field cancerization, with high satisfaction rates reported by both patients and physicians. Although its efficacy may be reduced in hyperkeratotic lesions and areas with insufficient sunlight, combining daylight PDT with lesion-targeted treatments and using indoor alternatives can help overcome these limitations. Additionally, the reduced peri-procedural pain and fewer topical side effects provide a significant advantage over other field treatments, such as 5-FU, imiquimod, and cPDT, making dPDT a highly practical and accessible option in real-world clinical practice in Dermatology.

Abstract:

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein-Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as viral evasion of IFN-I effect via degradation of IFN-receptors; may be present in ME/CFS, which demands further studies.

Abstract: Background/Objectives: Artificial intelligence (AI) integration in colon polyp detection often exhibits high sensitivity but notably low specificity in real-world settings, primarily due to reliance on publicly available datasets alone. To address this limitation, we proposed a semi-automatic annotation method using real colonoscopy videos to enhance AI model performance and reduce manual labeling labor. Methods: An integrated AI model was trained and validated on 86,258 training images and 17,616 validation images. Model 1 utilized only publicly available datasets, while Model 2 additionally incorporated images obtained from real colonoscopy videos of patients through a semi-automatic annotation process, significantly reducing the labeling burden on expert endoscopists. Results: The integrated AI model (Model 2) significantly outperformed the public-dataset-only model (Model 1). At epoch 35, Model 2 achieved a sensitivity of 90.6%, specificity of 96.0%, overall accuracy of 94.5%, and an F1 score of 89.9%. All polyps in test videos were successfully detected, demonstrating considerable enhancement in detection performance compared to the public dataset-only model. Conclusions: Integrating real-world colonoscopy video data using semi-automatic annotation markedly improved diagnostic accuracy and significantly reduced manual annotation workload. However, the findings need validation through multicenter external datasets to ensure generalizability.

Abstract: Wearable devices are increasingly used for health monitoring, yet the impact of consistent wear on physiological and behavioral outcomes is unclear. Leveraging nearly a million days and nights of longitudinal data from 11,914 subscribers, we examined associations between the frequency of wearing a wrist-worn wearable device (WHOOP Inc., Boston, MA) and 12-week changes in biometric, sleep, and activity profiles, modeling both between and within-person effects. Higher average wear frequency, and week-to-week increases in wear, were associated with lower resting heart rate (RHR), higher heart rate variability (HRV), longer and more consistent sleep, and greater weekly and daily physical activity duration (Ps< 0.01). A within-person multiple mediation analysis indicated that increased sleep duration partially mediated the association between wear frequency and standardized (z-scored) RHR (indirect effect = -0.0387 [95% CI: -0.0464, -0.0326]), whereas physical activity minutes did not (indirect effect = 0.0003 [95% CI: -0.0036, 0.0040]). Granger causality analysis revealed a modest but notable association between prior wear frequency and future RHR in participants averaging ≤5 days of weekly wear (P< 0.05 in 10.92% of tests). While further research is needed, our findings provide real-world evidence that sustained wearable engagement may support healthier habits and improved physiological outcomes over time