Search Results (5,031)

The objective of this study is to mitigate the bottom-out failure and improve the energy absorption of conventional helmet liners during high-energy impacts, thereby reducing the risk of head injuries. To this end, a locally reinforced Primitive-type triply periodic minimal surface (P-TPMS) energy-absorbing liner is proposed for the helmet forehead region, which facilitates progressive energy dissipation through layer-by-layer buckling deformation. A finite element model of a helmet–head coupling was created based on a previously verified high-fidelity head model and subsequently validated against the ECE 22.06 standard drop-test methodology. Three critical design parameters—outer protective layer thickness, triply periodic minimal surface (TPMS) unit cell size, and wall thickness—were optimized employing the Box–Behnken Design (BBD) response surface methodology, resulting in quadratic regression models for the head injury criteria (HIC) and peak linear acceleration (PLA) with good fit ($R^2$ > 0.97). Optimal parameter combinations were established using multi-objective optimization, with protective efficacy carefully assessed from both head dynamic response and biomechanical response perspectives. The ideal P-TPMS liner possesses an outer protective layer thickness of 14.95 mm, a TPMS unit cell size of 12.23 mm, and a wall thickness of 3.93 mm. Compared to the traditional expanded polystyrene (EPS) liner, the optimized P-TPMS liner significantly reduces HIC (by ∼16%) and PLA (by ∼14%) while extending the impact duration. More critically, it transitions both intracranial pressure and brain tissue strain below their respective clinical injury thresholds, substantially lowering the risks of skull fracture and mild traumatic brain injury (mTBI). The P-TPMS construction facilitates continuous energy dissipation during impacts via incremental layer-by-layer buckling deformation, hence extending impact duration and markedly improving helmet protective efficacy. These findings offer theoretical foundations and technical direction for the creation of localized heterogeneous liner designs in advanced high-performance helmets, although the results are limited to frontal flat-anvil impact conditions. Full article

In reliability and survival studies, lifetime data are frequently subject to progressive Type-II censoring, leading to incomplete failure-time information and challenging statistical inference problems. In this study, statistical inference for the Rayleigh–Logarithmic (RL) distribution is developed under progressive Type-II censoring. The RL distribution provides a flexible lifetime model by combining a Rayleigh lifetime component with a logarithmically distributed number of latent failure causes. A competing-risk interpretation of the model is presented, and parameter estimation is carried out using both maximum likelihood estimation (MLE) and maximum product spacing (MPS) methods. The performance of the proposed inference procedures is investigated through extensive Monte Carlo simulations under different parameter settings and censoring schemes. The results indicate that both MLE and MPS provide reliable estimates, with estimation accuracy improving as the sample size increases. The methodology is further illustrated using simulated and real lifetime data sets and compared with classical lifetime distributions. The findings show that the RL distribution offers a flexible and effective framework for modeling progressively censored lifetime data, particularly in the presence of heterogeneous and latent failure mechanisms. Full article

A trend toward comorbid conditions is seen in around 50% of gynecological patients, with a significant contribution made by endometriosis as a common and incurable gynecological condition. Over the last decades, the global burdens of different forms of endometriosis have shown a progressive increase, while their diagnosis and management present persistent and significant challenges. Currently, endometriosis is divided into two primary types: genital (adenomyosis and external genital endometriosis, including ovarian endometriosis) and extragenital endometriosis. Regardless of the location of endometriosis, lesions or ectopic endometrium follow a consistent pathological process characterized by active proliferation, local inflammation, neoangiogenesis, and extracellular matrix remodeling. These pathogenetic patterns are associated not only with process progression, but also with the impact on the eutopic endometrium. External genital or extragenital endometriosis and adenomyosis (an internal genital endometriosis) are currently considered as a major cause of infertility and implantation failures due to the negative impact on the eutopic endometrium. However, it has been proven that the pathogenetic pathways for the development of eutopic endometrium dysfunction in these endometriosis phenotypes (despite the common pathophysiology of the ectopic endometrium) differ significantly. This narrative review is focused on highlighting the relevance and pathogenetic patterns of the two most frequently diagnosed forms of endometriosis—adenomyosis and ovarian endometrioid cysts—as key areas of research interest relating to their relevance, specific pathophysiology and impacts on the eutopic endometrium. Full article

This paper investigates classical and Bayesian inferences for the parameters and reliability metrics of the Hjorth distribution using a new censoring mechanism called the adaptive progressive first-failure censoring scheme. This new strategy combines guaranteed observation of a fixed number of failures with adaptive control of test duration, providing a flexible and practically efficient framework for modern reliability experiments. The Hjorth distribution is considered due to its capability to model various hazard-rate shapes within a simple two-parameter structure. Maximum likelihood estimation is developed, and approximate confidence intervals are constructed using normal approximation and logarithmic transformation methods based on the observed Fisher information matrix and the delta method. A Bayesian framework is also established using independent gamma prior distributions, with posterior inference carried out through maximum a posteriori estimation and Markov chain Monte Carlo simulation. Bayes estimates and both equal-tail and highest-posterior-density credible intervals are obtained. The performance of the proposed methods is evaluated through simulation studies and illustrated using real lifetime data from an engineering domain consisting of the tensile strength of polyester fibers, demonstrating their effectiveness under adaptive censoring settings. Full article

Cardiac rehabilitation (CR) is strongly recommended in secondary cardiovascular prevention; indeed, in patients after cardiac surgery or with coronary artery disease or heart failure, this intervention is recommended to decrease mortality, morbidity, and disability, and to improve quality of life and cardiorespiratory fitness. Moreover, each step of the cardiovascular continuum denotes a potential risk factor for the progression of cognitive frailty; this interaction is highly prevalent, affecting approximately one-third of all patients in cardiology settings. For these reasons, CR should consider the patient’s cognitive domain; however, cognitive assessment is still rarely integrated into standard CR protocols. Therefore, this comprehensive review presents current evidence and recent updates on the interaction between CR and cognitive impairment, focusing on physiological mechanisms, core components, benefits, and strategies for implementing CR in patients with cognitive frailty to optimize recovery and prognosis. Full article

Background: Modern warfare has introduced novel mechanisms of injury, particularly drone-induced blast trauma, resulting in complex craniomaxillofacial injuries. These injuries differ substantially from typical ballistic wounds and require adapted surgical strategies. This study was conducted to evaluate the clinical characteristics, management approaches, and long-term outcomes of midfacial blast injuries. Methods: A retrospective analytical study was conducted on 41 patients with drone-induced midfacial blast injuries treated at a tertiary referral center in Armenia following the 2020 Nagorno-Karabakh War. All patients underwent surgical management after initial stabilization and were followed for 5 years. Clinical outcomes, complications, and reconstructive needs were assessed. Results: All patients presented with comminuted midfacial fractures, which were frequently associated with polytrauma (87.8%). Burns were observed in 82.9% of cases. Surgical management included radical debridement and early definitive osteosynthesis using titanium fixation systems. No cases of postoperative osteomyelitis, bone sequestration, or implant failure were observed during the 5-year follow-up period. Patients with extensive soft tissue defects, particularly nasal and lip amputations, required multiple reconstructive procedures. Long-term follow-up revealed progressive soft tissue thinning over titanium meshes, especially in the zygomatico-orbital region, necessitating secondary interventions such as lipofilling. Conclusions: Drone-induced midfacial blast injuries represent a distinct and severe form of trauma. Early definitive reconstruction following adequate debridement was associated with favorable outcomes. However, soft tissue reconstruction remains challenging and often requires staged procedures. Long-term follow-up is essential to manage delayed complications and optimize aesthetic outcomes. Full article

B-cell maturation antigen (BCMA)-directed therapies (BDTs) have transformed relapsed/refractory multiple myeloma treatment, but optimal post-failure sequencing remains undefined. We evaluated real-world outcomes from three retrospective, multicenter analyses. Study 1 compared BCMA CAR-T and BCMA T-cell engagers (TCEs) in BDT-exposed patients (n = 95). Study 2 evaluated teclistamab in BDT-exposed versus BDT-naïve patients (n = 164). Study 3 examined talquetamab (GPRC5D-targeting TCE) in heavily pretreated patients (n = 68). CAR-T therapy achieved superior outcomes versus TCE (overall response rate [ORR] 79% vs. 51%, p < 0.001; median overall survival [OS] 30 vs. 12 months, p = 0.008). Teclistamab-treated BDT-exposed patients had lower ORR (53% vs. 68%, p = 0.02) and shorter median progression-free survival (PFS; 2.5 vs. 9.7 months, p = 0.01) compared with BDT-naïve patients. Administration < 6 months post-BDT showed inferior outcomes (hazard ratio [HR] 2.5 for PFS; HR 2.9 for OS). Talquetamab achieved an ORR of 68.3% among BDT-exposed patients, with significantly lower response rates when administered < 6 months post-BDT or when BDT was the immediate preceding treatment (56.8% vs. 84.6% and 48% vs. 80.6%, respectively). Treatment-free intervals of ≥6 months between T-cell-redirecting therapies improved efficacy and survival. Post-BDT sequencing should prioritize CAR-T therapy when feasible, allow >6-month intervals before BDT re-challenge, and utilize non-BCMA targets for early relapse or BDT-refractory disease. Full article

Obesity is a major risk factor for colorectal cancer (CRC) and is increasingly recognized as a contributor to cancer-related cognitive impairment; however, the mechanistic pathways linking metabolic dysfunction, tumor progression, and brain dysfunction remain incompletely defined. Emerging evidence indicates that obesity-induced gut microbial dysbiosis and intestinal barrier disruption may serve as a biologically plausible mechanism connecting these processes via the gut–brain axis although direct clinical causality remains to be firmly established. In obesity, alterations in gut microbiota composition characterized by depletion of barrier-protective taxa and enrichment of pro-inflammatory and genotoxic pathobionts compromise epithelial tight-junction integrity and promote metabolic endotoxemia. The translocation of microbial products, including lipopolysaccharide, sustains chronic systemic inflammation, accelerates CRC progression, and remodels the tumor microenvironment. Notably, these peripheral inflammatory signals extend beyond the intestine and tumor, disrupting blood–brain barrier integrity, activating microglia and astrocytes, and impairing synaptic plasticity within hippocampal and frontal networks. Clinically, these processes manifest as cancer-related cognitive impairment (CRCI), with predominant deficits in attention, processing speed, and working memory, which are often detectable around the time of diagnosis and independent of chemotherapy exposure. This review synthesizes in vivo, in vitro, and human evidence into a proposed theoretical “two-barrier failure” model of obesity-associated CRC and cognitive dysfunction. In addition to mechanistic synthesis, we discuss barrier-centered therapeutic strategies, including targeted probiotics, postbiotics, SCFA supplementation, obesity management through dietary and weight-loss interventions, and potential pharmacological approaches to epithelial and neurovascular barrier protection. We also outline testable clinical trial designs for evaluating these interventions in obesity-associated CRC. Full article

Background: Heart transplantation (HTx) is a well-established therapy for pediatric patients with end-stage heart failure. Over the past decades, the field has considerably evolved, with noticeable changes in surgical techniques and post-transplant outcomes. This study presents our center’s experience over the past three decades. Methods: Between 1988 and 2024, we performed 256 heart transplants in pediatric patients (<18 years) with congenital heart defects (CHD) or myopathy. We divided our cohort into three periode, eras: Era1 (1988–1999), Era2 (2000–2011), and Era3 (2012–2024). We analyzed and reported baseline patient data, postoperative outcomes, and survival analysis. Results: In the first era, most HTx recipients were infants (75%), with CHD accounting for 75% of cases. In the latest era, older children and adolescents were transplanted more frequently with infants representing only 22%, and myopathies became a more predominant indication, representing 57% of patients. The use of mechanical circulatory support increased significantly (<0.001), and a complete shift towards the bi-caval surgical technique was achieved in the recent era. In terms of post-HTx outcomes, 30-day mortality and allograft vasculopathy significantly decreased in the recent era compared with previous periods (<0.001). Conversely, operative time and post-HTx hemodialysis were more frequently observed in the recent era (<0.001). Long-term survival numerically improved in the middle and recent eras compared with the early era; however, no statistically significant difference in Kaplan–Meier survival across eras was observed (log-rank p = 0.19). Conclusions: Over the past three decades, HTx in pediatric patients has evolved, with improvements in early survival and reduced allograft vasculopathy. Changes in patient demographics, surgical technique, and use of MCS in the recent era highlight the ongoing progress as well as the remaining challenges in this complex population. Full article

To meet the increasing demands of aircraft engines for high thrust-to-weight ratios and elevated turbine inlet temperatures, turbine blades have been progressively designed with thin-walled structures. It has been demonstrated that the mechanical properties of Ni₃Al-based single-crystal alloys (SXs) are highly sensitive to specimen thickness. In this study, the high-cycle fatigue behavior of [111]-oriented Ni₃Al-based SXs with wall thicknesses of 0.3, 0.5, and 0.8 mm was systematically investigated under tensile–tensile loading conditions at 1000 °C. The results revealed that, as the wall thickness decreased, the fatigue life of the alloy significantly deteriorated, while the crack initiation site gradually shifted from the specimen interior toward the surface and near-surface regions. Furthermore, the fatigue failure mode transitioned from being dominated by internal defects to being controlled primarily by near-surface damage. Near-surface damage induced by high-temperature oxidation and geometric constraints was identified as the primary factor responsible for the degradation of the high-cycle fatigue performance of the SXs. In addition, the cyclic deformation behavior at 1000 °C was governed by the synergistic effects of dislocation climb, cross-slip, and γ′-phase shearing. This study provides both theoretical guidance and experimental evidence for the structural optimization of next-generation single-crystal turbine blades for advanced aircraft engines. Full article

Chronic kidney disease (CKD) affects approximately 700 million people worldwide and is a major contributor to end-stage renal disease (ESRD), cardiovascular morbidity, and premature mortality. Although oxidative stress has long been considered central to CKD progression, conventional antioxidant strategies have not consistently improved clinical outcomes, suggesting that excess reactive oxygen species (ROS) alone cannot fully account for the underlying disease pathophysiology. Emerging evidence supports a broader paradigm of redox network failure, characterized by the disruption of coordinated signaling among ROS, nitric oxide (NO), and reactive sulfur species (RSS). Within this framework, hydrogen sulfide (H₂S), a major endogenous RSS, functions as a key regulator of renal redox homeostasis. CKD is consistently associated with systemic and renal H₂S deficiency, accompanied by downregulation of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), as well as impaired transsulfuration and disrupted mitochondrial sulfide oxidation. Importantly, this deficiency cannot be explained solely by reduced renal function but instead reflects active suppression of H₂S biosynthesis. Uremic toxins, particularly indoxyl sulfate (IS), contribute to this process through activation of the aryl hydrocarbon receptor (AhR), which inhibits specificity protein 1 (Sp1)-dependent transcription of H₂S-producing enzymes. This IS–AhR–Sp1 axis provides a mechanistic link between toxin accumulation and disruption of the sulfur arm of the redox network, amplifying oxidative stress, endothelial dysfunction, mitochondrial impairment, ferroptotic vulnerability, and fibrotic remodeling. Beyond H₂S itself, downstream RSS, including persulfides, polysulfides, and thiosulfate, may represent the principal bioactive mediators of sulfur-dependent redox signaling, and their coordinated depletion in CKD may impair redox buffering capacity beyond what H₂S measurement alone reflects. This review integrates current evidence to propose a conceptual model in which CKD progression involves failure of coordinated redox signaling—characterized by feed-forward network collapse and threshold-dependent transition to a self-sustaining high-ROS state—with H₂S deficiency representing one mechanistically supported component of this broader network disruption. This framework highlights the therapeutic potential of targeting redox network restoration rather than isolated oxidative pathways in CKD. Full article

Background/Objectives: Perioperative chemo-immunotherapy (CHT-IO) has emerged as a standard treatment strategy for resectable stage II–IIIB NSCLC. However, data regarding surgical feasibility, mini-invasive surgery rates, perioperative outcomes, and postoperative complications in real-world single-center experiences remain limited. Methods: A retrospective single-center analysis was performed including consecutive patients with locally advanced NSCLC treated with perioperative chemo-immunotherapy between March 2024 and March 2026. Patients received platinum-based chemotherapy combined with pembrolizumab or durvalumab, followed by surgical resection with curative intent. Surgical, pathological, and postoperative outcomes were analyzed. Results: Thirty patients received neoadjuvant CHT-IO, of which 25 (83.3%) underwent surgical resection. Reasons for failure to proceed to surgery included treatment-related toxicity or deterioration in performance status (n = 3), disease progression (n = 1), and patient refusal (n = 1). Lobectomy was the most performed procedure (64%), while a minimally invasive approach (uniportal VATS) was adopted in 44% of cases. Moderate-to-severe pleural adhesions (64%) and hilar fibrosis (60%) were observed intraoperatively. Despite these technical challenges, conversion to thoracotomy was required in only one case (4%), no intraoperative complications occurred, and complete (R0) resection was achieved in 96% of patients. Pathological complete response and major pathological response were observed in 36% and 52% of cases, respectively. Postoperative complications occurred in 56% of patients, although most were Clavien–Dindo grade I–II. The presence of comorbidities was the only factor associated with an increased risk of postoperative complications (OR 10.00, 95% CI 0.99–100.46; p = 0.05). Median length of hospital stay was 5.65 ± 2.04 days. One postoperative death due to septic complications was recorded. Conclusions: In this real-world monocentric experience, the combination of perioperative CH-ICIs and surgical resection (including mini-invasive approach) was safe and feasible in patients with locally advanced NSCLC. High rates of complete (R0) resection and encouraging pathological responses were observed, consistent with outcomes reported in randomized trials. Although surgery was overall frequently technically demanding, these changes did not appear to compromise perioperative safety or oncological radicality, even when minimally invasive approaches were adopted. Larger studies with longer follow-up are needed to better define long-term oncological outcomes. Full article

Carbonyl stress, chronic inflammation, and progressive tissue injury accompany type 2 diabetes mellitus (T2DM) and obesity. Yet, the molecular systems that connect these processes with cardiac, vascular and neuronal complications are incompletely defined. This review examines the AGE–RAGE–DIAPH1 axis as a mechanistic link between metabolic dysfunction and diabetic myocardial and neuronal injury, with emphasis on vascular and myocardial remodeling and emerging implications for autonomic neuronal vulnerability. We summarize current evidence on the formation and accumulation of advanced glycation end-products and other RAGE ligands in metabolic disease, DIAPH1’s structural and signaling role as an intracellular effector of RAGE, and the cellular consequences of pathway activation in vascular, neural, and cardiac tissues. Across experimental models, this signaling axis promotes oxidative stress and inflammatory activation, leading to endothelial dysfunction and barrier failure. Subsequent fibrotic remodeling provides a biologically plausible route through which metabolic stress may be translated into persistent organ injury. In the heart, these mechanisms are linked to coronary microvascular dysfunction, altered cardiomyocyte phenotype, calcium handling abnormalities, and myocardial fibrosis. In the autonomic nervous system, limited but emerging data connect RAGE activation to oxidative injury and mitochondrial dysfunction, abnormal neuronal excitability, and structural vulnerability. Direct evidence linking DIAPH1 to autonomic neurons is lacking. We also review biomarker candidates related to this pathway, including circulating AGEs and soluble RAGE isoforms, skin AGE measurements, imaging markers of myocardial remodeling, and autonomic functional measures. Finally, we discuss pharmacological and natural compounds that target AGE formation, ligand accumulation, RAGE signaling, or intracellular protein interactions linked to this axis. Overall, the available evidence supports the AGE–RAGE–DIAPH1 axis as a credible mechanistic concept and a potentially informative translational hypothesis in T2DM. However, the AGE–RAGE component is supported more strongly than DIAPH1-specific involvement in human diabetic myocardial disorder or cardiovascular autonomic neuropathy. The value of DIAPH1 as a biomarker or therapeutic target in these neurocardiac complications remains to be established. Full article

Additively manufactured cellular architectures frequently exhibit brittle failure under impact due to layer-induced stress concentrations. Through the programming of architectural and material design, specifically combining Fused Deposition Modeling (FDM) lattice topology with hyperelastic polyurea infiltration, this study achieves active control over the macroscopic transition from catastrophic structural fragmentation to stable progressive collapse. To evaluate this, auxetic and honeycomb specimens printed with ABS and glass-fiber-reinforced polyamide (PA-GF) were evaluated in unreinforced and polyurea-infiltrated states under quasi-static compression, three-point bending, and Charpy impact loading. Results show that the compressive response depends primarily on cellular topology; the pure auxetic (A-A) configuration provided the highest stiffness and energy absorption. Polyurea infiltration did not significantly alter elastic stiffness but increased post-yield stability, leading to a 96.6% elastic recovery in PA-GF A-A structures. In flexure, the base polymer governed stiffness, with ABS structures measuring 68% stiffer than PA-GF. Unreinforced ABS achieved 34% higher specific energy absorption (SEA) than PA-GF under compression, with the A-H topology maximizing SEA. Under dynamic impact, PA-GF absorbed an average of 70% more energy than ABS, and the H-A configuration recorded the highest impact resistance. The addition of polyurea shifted the failure mode from brittle fragmentation to stable elastomeric deformation, increasing absorbed impact energy by 52% for ABS and over 30% for PA-GF, preventing catastrophic structural failure. Integrating topological sequencing with elastomeric confinement provides a direct method to control energy dissipation and damage tolerance in 3D-printed cellular composites. Full article

Chronic kidney disease (CKD) is associated with a high burden of cardiovascular morbidity and mortality, while lipid disorders in renal failure differ substantially from the LDL-C-centered pattern observed in the general population. This narrative review aimed to synthesize recent evidence on the mechanisms, clinical implications, and therapeutic management of dyslipidemia in patients with renal failure, with emphasis on cardiovascular events and CKD progression. A structured literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science for publications from January 2018 to April 2026. The review shows that CKD-related dyslipidemia is characterized by triglyceride-rich lipoprotein and remnant particle accumulation, small dense and modified LDL, and dysfunctional HDL within a uremic-inflammatory environment that promotes endothelial injury, vascular calcification, and residual cardiovascular risk. These abnormalities may also contribute to renal lipotoxicity, proteinuria, glomerulosclerosis, tubulointerstitial injury, and fibrosis, although direct causal and therapeutic implications remain incompletely established. Statin-based therapy remains central in non-dialysis CKD, whereas lipid management in dialysis, transplantation, frailty, and severe hypertriglyceridemia requires individualized interpretation. Future risk assessment should integrate lipid, inflammatory, vascular, nutritional, and renal-trajectory markers rather than relying on LDL-C alone. Full article