Search Results (567)

Regulatory T cells (Tregs), particularly their phenotypically distinct subpopulations, are critical for the establishment of maternal immune tolerance during embryo implantation. Despite advances in assisted reproductive technologies, implantation failure remains a frequent and often unexplained clinical challenge. Variations in Treg frequency and phenotype have been proposed to influence implantation success, particularly under differing hormonal conditions. This study aimed to investigate peripheral blood Treg levels and their subpopulations on the day of blastocyst transfer in both stimulated in vitro fertilization (IVF/ICSI) cycles involving controlled ovarian hyperstimulation (COH) and true natural cycles with frozen embryo transfer (FET), and to examine their associations with systemic hormone levels and anti-Müllerian hormone (AMH). A prospective observational study was conducted including women undergoing IVF/ICSI with fresh embryo transfer (ET) and women undergoing natural cycle FET. Peripheral blood samples were collected on the day of ET and analyzed using 13-colour flow cytometry, enabling detailed subdivision of Tregs into multiple subpopulations based on the expression of differentiation and chemokine markers, including CXCR5. In addition, because common $\gamma$-chain cytokines may influence pregnancy success by modulating the balance between suppressive Treg and non-Treg subsets, intracellular STAT5 signaling was assessed using phospho-specific flow cytometry. Serum estradiol, progesterone, FSH, LH, and AMH levels were measured in parallel. Significant differences were observed in Treg subpopulation distributions between women who conceived and those who did not. Higher frequencies of naïve CXCR5⁻ Tregs were associated with clinical pregnancy, independent of age, and correlated with serum progesterone levels. Moreover, both naïve Treg frequency and enhanced IL-7-dependent STAT5 signaling in naïve Tregs from women undergoing COH were associated with AMH levels, suggesting a link between ovarian reserve and Treg homeostasis mediated by signal transducer and activator of transcription 5 (STAT5) signaling. In conclusion, Treg subpopulations, particularly CXCR5⁻ naïve Tregs, appear to play a central role in implantation success following ET. Their distribution differs between stimulated and natural cycles and is influenced by systemic progesterone levels and STAT5 signaling. These findings suggest that peripheral Treg profiling may represent a potential biomarker of implantation competence and could inform personalized approaches in assisted reproduction. Full article

Heart failure (HF) remains a major cause of morbidity and mortality worldwide, with its prevalence continuing to rise due to an aging population and the increasing burden of cardiometabolic diseases. Advances in understanding HF pathophysiology—neurohormonal, inflammatory, and metabolic mechanisms—have led to significant improvements in diagnosis and management, emphasizing earlier detection and patient-centered approaches. Novel biomarkers have the potential to enhance risk assessment beyond traditional natriuretic peptides. Imaging advances can enhance structural and functional assessment, enabling more accurate phenotyping, disease characterization, and risk stratification. Recent advances and real-world data have been used to implement and optimize guideline-directed medical therapy (GDMT) for HF to reduce HF hospitalizations and cardiovascular mortality across the spectrum of HF etiologies. Adjunctive therapies are reserved for select patients with persistent symptoms or high-risk features despite optimal GDMT. Device- and transcatheter-based interventions include established and emerging technologies that address persistent symptoms, structural abnormalities, and hemodynamic abnormalities despite optimal GDMT, thereby expanding treatment options for high-risk patients. Collectively, these advancements highlight a paradigm shift toward precise, personalized approaches to HF management, thereby improving long-term outcomes across the spectrum of HF etiologies. Full article

The Transforming Growth Factor-β (TGF-β) superfamily comprises highly conserved cytokines that orchestrate key cellular functions, including proliferation, differentiation, and apoptosis. Within the ovary, TGF-β family members serve as pivotal regulators of folliculogenesis, exerting stage-specific actions from embryonic germ cell development to advanced follicular maturation. During fetal development, activins and SMAD-dependent signaling pathways are essential for primordial germ cell proliferation, survival, and the breakdown of germ cell cysts, enabling the establishment of the primordial follicle pool. Throughout folliculogenesis, TGF-β supports follicle activation, promotes the transition from dormant to growing follicles, stimulates granulosa cell proliferation, sustains follicular viability, and modulates steroidogenesis through theca cell regulation. Notably, anti-müllerian hormone, a TGF-β family member, plays a central role in inhibiting premature follicle recruitment and serves as a key biomarker of ovarian reserve. Dysregulation of TGF-β signaling contributes to various ovarian disorders, including polycystic ovary syndrome and premature ovarian insufficiency. A deeper understanding of these complex signaling networks is critical for identifying novel therapeutic targets and advancing clinical interventions in female reproductive pathologies. This review provides an integrated overview of the roles of the TGF-β superfamily in ovarian physiology and its contributions to disease development. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

The Calakmul Biosphere Reserve, in southeastern Mexico, is a major conservation area known for its tropical forests, emblematic wildlife species, and long history of Maya occupation. Established in 1989 as a federal Natural Protected Area, it was incorporated into UNESCO’s Man and the Biosphere Program in 1993 and designated a mixed World Heritage Site in 2014. Its socioecological trajectory is distinctive: conservation efforts advanced alongside the contemporary rural settlement resulting from agrarian reform and subsequent development and welfare policies. This article examines the persistent imbalance between ecological conservation and socioeconomic development surrounding the Calakmul Biosphere Reserve, focusing on water vulnerability in adjacent communities. The study integrates environmental history with household-level survey data on water access and vulnerability among 200 households in eight communities in the Biosphere Reserve’s transition zone, complemented by interviews with key water-management stakeholders. We document the consolidation of conservation through management plans, advisory councils, payments for ecosystem services, scientific research, and expanding voluntary conservation areas. Yet these advances contrast sharply with everyday socioeconomic realities: 68% of households face prolonged water scarcity, with an average of more than 30 days annually without water. Calakmul’s case highlights structural mismatch between conservation and local human well-being in Natural Protected Areas contexts. Full article

The automation of logistics processes in companies is an essential part of the modernization and advancement of companies around the world. This article deals with the issue of deploying a selected type of automated guided vehicle (AGV) in very specific conditions. AGV is suitable for optimizing the circular supply chain in specific conditions of a manufacturing company. The deployment of AGVs is governed by the production needs of the section in question. The selection criterion was therefore the quantity of products that needed to be transported on the selected route. The article uses a new calculation of AGV requirements based on the saturation of individual components from the picking location to the assembly line. The ratio indicator was considered: driving time per shift, depending on the length of working time. Based on this calculation, the most effective option was applied from the individual solutions. Based on our calculation, we arrived at a requirement for three AGVs, plus a reserve, i.e., four. Our selected calculations were applied to the FRONT and TOP positions, where a decision was made between the option of using under-run AGVs or a truck. The decision was made based on the saturation level, and the result is described at the end of the discussion. The AGV is one of the tools for sustainable supply chain management in a company. However, it is important to evaluate the total cost of ownership, including lower labour costs, less risk of damage to goods, higher productivity, and long service life of the trucks. Thanks to these factors, AGVs often prove to be economically advantageous. Full article

Background/Objectives: The diagnosis and risk stratification of valvular heart disease have traditionally relied on resting echocardiography. However, in a significant portion of patients, resting findings do not fully reflect the hemodynamic severity of the condition, particularly in asymptomatic individuals with severe valvular disease or those with nonspecific symptoms. In this context, stress echocardiography emerges as a vital imaging modality, providing a dynamic assessment of valvular, ventricular, and pulmonary function under hemodynamic load (from physical exercise or pharmacological agents). Methods: We conducted a comprehensive synthesis and critical evaluation of the current landscape, recent advancements, and future directions regarding the application of stress echocardiography in valvular heart disease. Results: This comprehensive review explores the incremental role of stress echocardiography in valvular heart disease, analyzing the evolution of its clinical applications, from low-flow, low-gradient aortic stenosis to the evaluation of contractile reserve and exercise-induced pulmonary hypertension in mitral stenosis and regurgitation. We discuss standardized protocols, key parameters to monitor, and the diagnostic and prognostic outcomes from major clinical trials and current guidelines. Attention is given to stress echocardiography’s ability to unmask the true severity of the disease and to identify patients at high risk for adverse events, thereby guiding crucial clinical decisions, such as the optimal timing for surgical or transcatheter intervention. Conclusions: The review evaluates the limitations of modality and outlines future research directions, including its integration with new technologies like 3D echocardiography and speckle tracking techniques, to further optimize the role of stress echocardiography as a decision-making tool in the multidisciplinary management of valvular heart disease. Full article

Drug-coated balloons (DCBs) have emerged as an alternative to drug-eluting stents (DESs) in percutaneous coronary intervention, delivering antiproliferative drugs without leaving a permanent implant. This review provides a comparative analysis of sirolimus-coated DCBs (DCB-S), paclitaxel-coated DCBs (DCB-P), and DESs across key scenarios: de novo coronary lesions in chronic coronary syndrome (CCS), acute coronary syndromes (ACS), and in-stent restenosis (ISR). We discuss late lumen loss (LLL), target lesion/vessel revascularization (TLR/TVR), vessel patency, and major adverse cardiac events (MACE) outcomes, along with current guidelines and emerging indications for DCB-S. We also examine pharmacological differences between sirolimus and paclitaxel (mechanisms of action, tissue uptake, and healing profiles), trial methodologies, and recent innovations in DCB technology. Across stable de novo lesions (especially small vessels and high bleeding-risk patients), multiple trials show DCB-P can achieve non-inferior clinical outcomes to DES. Early data suggest newer DCB-S may likewise match DES outcomes in broader populations. In ACS, DCB-only strategies have demonstrated feasibility and safety in carefully selected lesions without heavy thrombus, with randomized studies like REVELATION (STEMI) showing non-inferior fractional flow reserve and low revascularization rates compared to DES. For ISR, DCB-P is an established Class I treatment in both BMS-ISR and DES-ISR, yielding similar or lower TLR rates than repeat stenting. DCB-S are now being evaluated as an alternative in ISR, aiming to avoid additional stent layers. Contemporary guidelines endorse DCB use in ISR and small vessels, and experts anticipate expanding indications as evidence grows. Sirolimus and paclitaxel differ in antiproliferative mechanisms and pharmacokinetics—sirolimus (cytostatic, mTOR inhibition) may offer faster endothelial recovery, whereas paclitaxel’s high lipophilicity ensures sustained arterial wall retention. Technological advances (e.g., phospholipid micro-reservoirs for sirolimus) are enhancing drug transfer and addressing prior limitations. In summary, DCB-P and DCB-S now represent viable alternatives to DES in specific scenarios, especially where “leaving nothing behind” could reduce long-term complications. Ongoing large randomized trials, such as SELUTION DeNovo, currently available as conference-presented data, together with longer-term follow-up will further clarify the optimal niches for DCB-S versus DCB-P and DES. Full article

Maintaining the stability of the mine roadway is of paramount importance, as it is critical in ensuring the daily operational continuity, personnel safety, long-term economic viability, and sustainability of the entire mining operation. Significant instability can trigger serious disruptions—such as production stoppages, equipment damage, and severe safety incidents—which ultimately compromise the project’s financial returns and future prospects. Therefore, the proactive assessment and rigorous control of roadway stability constitute a foundational element of successful and sustainable resource extraction. In China, thick and extra-thick coal seams constitute over 44% of the total recoverable coal reserves. Consequently, their safe and efficient extraction is considered vital in guaranteeing energy security and enhancing the efficiency of resource utilization. The surrounding rock of gob-side roadways in typical coal seams is often fractured due to high ground stress, intensive mining disturbances, and overhanging goaf roofs. Consequently, asymmetric failure patterns such as bolt failure, steel belt tearing, anchor cable fracture, and shoulder corner convergence are common in these entries, which pose a serious threat to mine safety and sustainable mining operations. This deformation and failure process is associated with several parameters, including the coal seam thickness, mining technology, and surrounding rock properties, and can lead to engineering hazards such as roof subsidence, rib spalling, and floor heave. This study proposes countermeasures against asymmetric deformation affecting gob-side entries under intensive mining pressure during the fully mechanized caving of extra-thick coal seams. This research selects the 8110 working face of a representative coal mine as the case study. Through integrated field investigation and engineering analysis, the principal factors governing entry stability are identified, and effective control strategies are subsequently proposed. An elastic foundation beam model is developed, and the corresponding deflection differential equation is formulated. The deflection and stress distributions of the immediate roof beam are thereby determined. A systematic analysis of the asymmetric deformation mechanism and its principal influencing factors is conducted using the control variable method. A support approach employing a mechanical constant-resistance single prop (MCRSP) has been developed and validated through practical application. The findings demonstrate that the frequently observed asymmetric deformation in gob-side entries is primarily induced by the combined effect of the working face’s front abutment pressure and the lateral pressure originating from the neighboring goaf area. It is found that parameters including the immediate roof thickness, roadway span, and its peak stress have a significant influence on entry convergence. Under both primary and secondary mining conditions, the maximum subsidence shows an inverse relationship with the immediate roof thickness, while exhibiting a positive correlation with both the roadway span and the peak stress. Based on the theoretical analysis, an advanced support scheme, which centers on the application of an MCRSP, is designed. Field monitoring data confirm that the peak roof subsidence and two-side closure are successfully limited to 663 mm and 428 mm, respectively. This support method leads to a notable reduction in roof separation and surrounding rock deformation, thereby establishing a theoretical and technical foundation for the green and safe mining of deep extra-thick coal seams. Full article

Background/Objectives: Basal cell carcinoma (BCC) is the most common form of skin cancer, typically exhibiting slow growth and limited metastatic potential. However, in rare, long-standing cases, particularly in high-risk facial regions, deep infiltration into structures such as bone may occur. This study aimed to evaluate whether BCC with bone involvement remains a relevant clinical issue, based on three decades of clinical experience, supplemented by a review of the existing literature. Methods: Medical records of patients treated for facial BCC between 1994 and 2025 at a dermatologic surgery department in Lower Silesia were retrospectively reviewed. Among more than 10,000 cases, eight instances of histologically confirmed bone invasion were identified. Clinical and surgical parameters were analyzed, including patient age, tumor size and location, prior treatment and reconstruction method. Relevant literature was incorporated to provide broader clinical context. Results: Patients with bone-invasive BCC were elderly (mean age: 75.3 years, SD: 10.94 years) and lesions were typically large (mean diameter 38.9 mm), most frequently located on the nose and forehead. Many cases lacked previous treatment. Smaller nasal tumors were managed with local flaps, while larger lesions on the forehead and temple required skin grafts. Findings from the literature confirm that bone invasion is rare and usually associated with long-standing tumors in anatomically high-risk areas. Conclusions: Although rare, BCC with bone infiltration remains a clinically relevant phenomenon, particularly in elderly patients with advanced or recurrent tumors. Early diagnosis, complete excision with histologically clear margins, and individualized surgical planning are essential to prevent deep tissue involvement. Imaging should be reserved for cases in which advanced local invasion is clinically suspected. Full article

Background: Tumors of the pineal region account for less than 1% of supratentorial neoplasms in adults and represent a distinct neuro-oncological challenge. Their management requires a multidisciplinary and multimodal approach. Traditionally, direct surgical resection was considered the primary treatment modality. Recent advances in minimally invasive techniques and onco-radiotherapy have paved the way for safer and more personalized treatment strategies, in line with the principles of precision medicine. This study aims to present our institutional approach, which relies on a combination of endoscopic and radiotherapy-based techniques. Methods: A retrospective, single-center clinical study was conducted involving 28 adult patients who underwent endoscopic third ventriculostomy and biopsy of a pineal region tumor between January 2014 and March 2025. Descriptive statistics, permutation tests with bootstrap-derived confidence intervals, Fisher’s exact test, and Kaplan–Meier survival analysis were applied for data evaluation. Results: Endoscopic intervention resulted in clinical improvement in 78% of cases. A significant increase in performance status was observed in the postoperative period (<0.001) compared to preoperative results. Radiotherapy contributed to either tumor regression or disease stabilization. Conclusions: Based on our findings, the combination of endoscopic intervention and personalized radiotherapy represents a safe and effective treatment strategy, offering a compelling alternative to direct surgical resection, which is reserved as a second-line treatment. Full article

Background/Objectives: Alzheimer’s disease (AD) has a prolonged preclinical phase and marked heterogeneity. Brain age and the Brain Age Gap (BAG), derived from neuroimaging and machine learning (ML), offer a non-invasive, system-level indicator of brain integrity, with potential relevance for early detection, risk stratification, and intervention monitoring. This review summarizes the conceptual basis, imaging characteristics, biological relevance, and explores its potential clinical utility of BAG across the AD continuum. Methods: We conducted a narrative synthesis of evidence from morphometric structural magnetic resonance imaging (sMRI), connectivity-based functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and diffusion tensor imaging (DTI), alongside recent advances in deep learning architectures and multimodal fusion techniques. We further examined associations between BAG and the Amyloid/Tau/Neurodegeneration (A/T/N) framework, neuroinflammation, cognitive reserve, and lifestyle interventions. Results: BAG may reflect neurodegeneration associated with AD, showing greater deviations in individuals with mild cognitive impairment (MCI) and early AD, and is correlated with tau pathology, neuroinflammation, and metabolic or functional network dysregulation. Multimodal and deep learning approaches enhance the sensitivity of BAG to disease-related deviations. Longitudinal BAG changes outperform static BAG in forecasting cognitive decline, and lifestyle or exercise interventions can attenuate BAG acceleration. Conclusions: BAG emerges as a promising, dynamic, integrative, and modifiable complementary biomarker with the potential for assessing neurobiological resilience, disease staging, and personalized intervention monitoring in AD. While further standardization and large-scale validation are essential to support clinical translation, BAG provides a novel systems-level perspective on brain health across the AD continuum. Full article

Cryotherapy involves flash freezing of tissue and removing unwanted tissue. Mechanism of injury is causing cell membrane rupture by rapid multiple freeze–thaw cycles, while reserving tissue architecture and the collagen matrix. This promotes favorable wound healing. In recent years, it has gained increasing attention as a treatment option for upper gastrointestinal diseases (Barrett’s Esophagus and early cancer). Currently, two FDA-approved delivery methods are available in the GI tract: Cryoballoon and spray cryotherapy, which will be discussed. In this review, we also propose to examine the expanding role of cryotherapy in gastrointestinal practice, drawing from both clinical studies and illustrative vignettes. In addition, we will highlight its established role in eradicating Barrett’s with low and high-grade dysplasia and compare its outcomes and safety profile with radiofrequency ablation (RFA). We will also discuss the application and safety of spray cryotherapy in the palliation of malignant esophageal strictures when compared with Esophageal stent placement. Cryotherapy may have immunological potential, and it may shrink both primary and metastatic diseases. Ongoing research in this field of Cryo-immunology will be highlighted. Beyond esophageal neoplasia, cryotherapy is increasingly utilized in other upper gastrointestinal precancerous conditions. Through this synthesis, our goal is to provide a timely and comprehensive overview of advancements in cryotherapy and its potential to reshape novel therapeutic approaches in upper gastrointestinal cancers. Finally, we highlight the evolution of a novel platform using nitrous oxide delivered by a handheld device, a contact balloon, and a small replaceable cartridge. This approach may make delivery of cryogen application favorable and a first-line approach in the management of Barrett’s esophagus and early cancer. In addition, Cryoballoon therapy for dysphagia palliation for malignant esophageal strictures may become a preferred approach as more data evolves. Full article

Paleogene lacustrine shale is a key source rock for large oil reserves in China and a major target for shale oil exploration. However, differences in the chemical characteristics of felsic and carbonate shales during burial and thermal evolution remain poorly understood. This study evaluates hydrocarbon generation and expulsion efficiency in these shale types using pyrolysis experiments on lower Paleocene Kongdian Formation samples (Type I) from the Eastern China Sedimentary Basin. Results show that felsic shale has higher hydrocarbon generation capacity than carbonate shale. During pyrolysis, carbonate shale retained ~119 mg/g more oil but expelled 184 mg/g less than felsic shale. Felsic shale reached peak oil generation and retention faster but with lower retention efficiency. The larger volume of residual hydrocarbons in felsic shale facilitated earlier expulsion onset, higher yields of gaseous hydrocarbons, and superior gas expulsion efficiency. While both shales exhibited similar thermal evolution trends for hydrocarbon gases, methane proportions and gas-oil ratios (GOR) differed significantly. Carbon loss was comparable during the oil window, but felsic shale lost more carbon overall. At higher temperatures, n-alkanes in residual oil decreased sharply, with lighter oil retained at advanced maturity, increasing GOR and reducing heavy hydrocarbons. These findings demonstrate the effective hydrocarbon potential of medium-high TOC felsic and carbonate shales. Full article

Background: Parkinson’s disease (PD) and frailty frequently co-occur and may interact bidirectionally through shared mechanisms of aging biology, mitochondrial dysfunction, inflammation, and reduced physiological reserve. Objective: We aimed to synthesize current evidence on prevalence, directionality, clinical overlap, adverse outcomes, and management implications of the PD–frailty nexus. Methods: A narrative review of epidemiologic, cohort, and interventional studies was performed, examining frailty in PD and PD risk in prefrail/frail populations, plus trials of multimodal interventions. Results: Frailty is common in PD, affecting approximately one-third of patients overall and becoming more prevalent as the disease advances. It independently predicts falls, cognitive decline, hospitalization, institutionalization, and mortality. Large cohorts suggest prefrailty/frailty is associated with incident PD risk, supporting a potential bidirectional association rather than direct causation. Diagnostic complexity arises because PD motor and non-motor features overlap with frailty constructs, risking misclassification. Management based on Comprehensive Geriatric Assessment (CGA) enhances personalized, multidisciplinary care. Exercise, particularly combined aerobic and resistance training reduces frailty and improves mobility, postural control, and quality of life. Complementary nutritional strategies, including muscle-targeted supplementation, can further strengthen rehabilitation outcomes, while careful attention to social determinants and polypharmacy remains essential to optimizing overall health and functional independence. Conclusions: Frailty is best understood as a clinical marker of vulnerability within PD and a correlate of more adverse trajectories rather than a proven causal determinant. Systematic frailty assessment integrated into PD care may help refine prognosis, individualize treatment, and support efforts to preserve independence. Priorities include PD-adapted frailty tools, CGA implementation, and rigorous trials of combined exercise–nutrition programs. Full article