Search Results (143)

Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status. Materials and Methods: This study analyzed patients with grade 3 recurrent or metastatic NEC treated with first-line etoposide plus cisplatin at Samsung Medical Center between January 2019 and September 2023. All patients underwent next-generation sequencing to determine DDR mutation status, defined by pathogenic alterations in major DNA repair pathways. Clinical outcomes were assessed per RECIST v1.1. Survival analyses were conducted using Kaplan–Meier methods and Cox regression models, with significance set at p ≤ 0.05. Results: A total of 40 patients with NEC were included in this study. There were 16 patients with DDR wild-type (WT) and 24 patients with DDR mutant type (MT). The most common primary tumor sites were the pancreas (25.0%), stomach (20.0%), and gallbladder/duct (12.5%). Among 40 patients, those with DDR mutations (n = 24) showed significantly higher objective response (58.3% vs. 12.5%) and disease control rates (91.7% vs. 50.0%) compared to patients with DDR WT (n = 16). The median progression-free survival (PFS) showed the favorable trend in the DDR mutant group (8.0 vs. 4.3 months; p = 0.15), with similar trends observed across homologous recombination repair (HRR), Fanconi anemia (FA), and mismatch repair (MMR) subgroups. Conclusions: This study revealed that patients with DDR mutations had significantly higher response to first-line etoposide–cisplatin, suggesting DDR mutation status as a potential predictive marker to guide treatment and improve outcomes in recurrent or metastatic NEC. Full article

Accurate seismic performance assessment of flexure-shear critical reinforced concrete (RC) columns necessitates precise hysteresis modeling that captures their distinct cyclic characteristics—particularly pronounced strength degradation, stiffness deterioration, and pinching effects. However, existing hysteresis models for such circular RC columns fail to comprehensively characterize these coupled cyclic degradation mechanisms under repeated loading. This study develops a novel hysteresis model explicitly incorporating three key mechanisms: (1) directionally asymmetric strength degradation weighted by hysteretic energy, (2) cycle-dependent pinching governed by damage accumulation paths, and (3) amplitude-driven stiffness degradation decoupled from cycle count, calibrated and validated using 14 column tests from the Pacific Earthquake Engineering Research Center (PEER) structural performance database. Key findings reveal that significant strength degradation primarily manifests during initial loading cycles but subsequently stabilizes. Unloading stiffness degradation demonstrates negligible dependency on cycle number. Pinching effects progressively intensify with cyclic advancement. The model provides a physically rigorous framework for simulating seismic deterioration, significantly improving flexure-shear failure prediction accuracy, while parametric analysis confirms its potential adaptability beyond tested scenarios. However, applicability remains confined to specific parameter ranges with reliability decreasing near boundaries due to sparse data. Deliberate database expansion for edge cases is essential for broader generalization. Full article

Some of the most intense thunderstorms and extreme weather events on Earth occur in the Hindu Kush Himalaya (HKH) region of Southern Asia. The need to provide end users, stakeholders, and decision makers with accurate forecasts and alerts of extreme weather is critical. To that end, a cutting edge weather modeling framework coined the High Impact Weather Assessment Toolkit (HIWAT) was created through the National Aeronautics and Space Administration (NASA) SERVIR Applied Sciences Team (AST) effort, which consists of a suite of varied numerical weather prediction (NWP) model runs to provide probabilities of straight-line damaging winds, hail, frequent lightning, and intense rainfall as part of a daily 54 h forecast tool. The HIWAT system was first deployed in 2018, and the recently released model archive hosted by the Global Hydrometeorology Resource Center (GHRC) Distributed Active Archive Center (DAAC) provides daily model outputs for the years of 2018–2022. With a nested modeling domain covering Nepal, Bangladesh, Bhutan, and Northeast India, the HIWAT archive spans the critical pre-monsoon and monsoon months of March–October when severe weather and flooding are most frequent. As part of NASA’s Transformation To Open Science (TOPS), this data archive is freely available to practitioners and researchers. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease characterized by chronic hyperglycemia and progressive microvascular complications, including retinopathy, nephropathy, and neuropathy. While traditional markers like HbA1c capture average glycemic control, they often fail to predict microvascular damage risk. Glycated CD59 (GCD59), a complement regulatory protein modified under hyperglycemic conditions, has emerged as a promising biomarker reflecting complement dysregulation and endothelial injury. This study aimed to examine the relationship between plasma GCD59 levels and the presence of microvascular complications in patients with type 2 diabetes mellitus and to evaluate whether GCD59 shows potential for future use as a predictive biomarker, pending prospective validation. Methods: In this single-center, prospective case–control study, 246 participants were enrolled: 82 healthy controls, 82 T2DM patients without microvascular complications (DM − MC), and 82 T2DM patients with microvascular complications (DM + MC). Microvascular complications were defined based on standardized criteria for retinopathy, nephropathy, and neuropathy. Plasma GCD59 levels were measured using validated ELISA methods. Receiver operating characteristic (ROC) analyses, forest plots, and odds ratio calculations were employed to assess the discriminatory performance of GCD59. Statistical significance was set at p < 0.05. Results: Plasma GCD59 levels were significantly elevated across all diabetic groups compared to healthy controls (p < 0.001), with the highest levels in the DM + MC group (median 4.5 ng/mL) versus DM − MC (median 1.9 ng/mL) and controls (median 1.2 ng/mL). ROC analysis demonstrated excellent diagnostic performance for distinguishing DM + MC from healthy controls (AUC = 0.946, sensitivity 89%, specificity 97.6%) and good performance for distinguishing DM + MC from DM − MC (AUC = 0.849, sensitivity 72%, specificity 87.8%). Forest plot analyses confirmed significantly elevated odds ratios for GCD59 across all microvascular subgroups. Importantly, GCD59 levels correlated positively with inflammatory markers (CRP, ESR, leukocyte count), suggesting a combined role of complement dysregulation and chronic inflammation in diabetic microangiopathy. Conclusions: Plasma GCD59 may be a promising biomarker for identifying T2DM patients who may be at increased risk for microvascular complications, independent of conventional glycemic markers. Given the cross-sectional design of this study, causal inference is not possible; prospective validation is required. The observed strong discriminatory performance highlights potential future clinical utility, pending further validation of diagnostic thresholds, assay standardization, and feasibility in routine care settings. Full article

Urban water supply pipelines play a critical role in ensuring the continuous delivery of water, and their failure during earthquakes can result in significant societal disruptions. This study proposes a seismic damage prediction method for urban buried water supply pipelines affected by seismic wave propagation, grounded in empirical data from past earthquake events. The method integrates key influencing factors, including pipeline material, diameter, joint type, age, and soil corrosivity. To enhance its practical applicability and address the challenge of quantifying soil corrosivity, a simplified classification approach is introduced. The proposed model is validated using observed pipeline damage data from the 2008 Wenchuan earthquake, with predicted results showing relatively good agreement with actual failure patterns, thereby demonstrating the model’s reliability for seismic risk assessment. Furthermore, the model is applied to assess potential earthquake-induced damage to buried pipelines in the city center of Ganzhou, and the corresponding results are presented. The findings support earthquake risk mitigation and the protection of urban infrastructure, while also providing valuable guidance for the replacement of aging pipelines and the enhancement of urban disaster resilience. Full article

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk. Full article

Background: Chronic kidney disease (CKD) and its advanced stage, end-stage renal disease (ESRD), affect millions worldwide and are associated with a paradoxical hemostatic imbalance—marked by both increased thrombotic and bleeding risks—which complicates anticoagulant use and demands clearer, evidence-based clinical guidance. Design: This study is a critical review synthesizing the current literature on anticoagulant therapy in CKD and ESRD, with emphasis on altered pharmacokinetics, clinical complications, and therapeutic adjustments. Data Sources: PubMed, Scopus, and Google Scholar were searched for articles discussing anticoagulation in CKD/ESRD, focusing on pharmacokinetics, clinical outcomes, and dosing recommendations. Study Selection: Studies examining the safety, efficacy, and pharmacokinetics of anticoagulants—including heparin, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs)—in CKD and ESRD populations were included. Data Extraction and Synthesis: Key findings were summarized to highlight the dose modifications, therapeutic considerations, and clinical challenges in managing anticoagulation in CKD/patients with ESRD. Emphasis was placed on balancing thrombotic and bleeding risks and identifying gaps in existing guidelines. Results: Patients with CKD and ESRD exhibit a paradoxical hypercoagulable state marked by platelet dysfunction, altered coagulation factors, and vascular endothelial damage. This condition increases the risk of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), while simultaneously elevating bleeding risks. Hemodialysis and CKD-associated variables further complicate the management of coagulation. Among anticoagulants, unfractionated heparin (UFH) is preferred due to its short half-life and adjustability based on activated partial thromboplastin time (aPTT). Low-molecular-weight heparins (LMWHs) offer predictable pharmacokinetics but require dose adjustments in CKD stages 4 and 5 due to reduced clearance. Warfarin necessitates careful dosing based on the estimated glomerular filtration rate (eGFR) to maintain an international normalized ratio (INR) ≤ 4, minimizing bleeding risks. Direct oral anticoagulants (DOACs), particularly Apixaban, are recommended for patients with eGFR < 15 mL/min or those on dialysis, although data on other DOACs in CKD remain limited. The lack of comprehensive guidelines for anticoagulant use in CKD and ESRD highlights the need for individualized, patient-centered approaches that account for comorbidities, genetics, and clinical context. Conclusions: Managing anticoagulation in CKD/ESRD is challenging due to complex coagulation profiles and altered pharmacokinetics. Judicious dosing, close monitoring, and patient-centered care are critical. High-quality randomized controlled trials are needed to establish clear guidelines and optimize therapy for this vulnerable population. Full article

In earthquake-prone regions, predicting the impact of seismic events on highway bridges is crucial for post-earthquake effective emergency response and recovery planning. This paper presents a methodology for a simplified seismic risk assessment of bridges using fragility curves that integrates updated ductility ratios of reinforced concrete bridge columns from literature based on experimental results on cyclic tests of reinforced concrete circular columns. The methodology considers two damage states (cover spalling and bar buckling) for bridge columns with seismic and non-seismic design considerations and then estimates displacement thresholds for each damage state. The Damage Margin Ratio (DMR) is introduced as an index defined by the ratio of the median Peak Ground Acceleration (PGA) for a specific damage state to the PGA that corresponds to the target seismic hazard probability of exceedance in 50 years that is typically defined in bridge design and evaluation codes and standards. The DMR is then compared to a user-specified Threshold Damage Margin Ratio (TDMR) to evaluate the level of risk at a specific threshold probability of exceedance of the damage state (5% and 10%). Comparative assessment is conducted for the relative seismic risk and performance of non-seismic and seismic bridges corresponding to the seismic hazard values at 10% and 2% probability of exceedance in 50 years for 7 urban centers in the province of Quebec as a case study demonstration of the methodology. The proposed methodology offers a rapid tool for screening and prioritizing bridges for detailed seismic evaluation. Full article

Exhaust manifolds accumulate creep and fatigue damage under cyclic thermal loading, leading to localized failure. Understanding a material’s mechanical behavior is crucial for accurate life assessment. This study systematically investigated the low-cycle fatigue (LCF) and creep–fatigue interaction behaviors of medium-silicon molybdenum ductile iron. It was found that QTRSi4Mo exhibited cyclic hardening at room temperature and 400 °C, whereas it exhibited cyclic softening at 600 °C and 700 °C for low-cycle stress–strain responses. During creep–fatigue tests with hold time, variations in the strain amplitude did not alter the hysteresis loop shape or the hardening/softening characteristics of the material. They only induced a slight upward shift in the yield center. Additionally, stress relaxation primarily occurred in the initial phase of the hold period, so the hold duration had little effect on the final stress value. The investigation of creep–fatigue life models highlighted that accurately characterizing the damage induced by stress relaxation during the hold stage is critical for creep damage evaluation. The calculated creep damage results differed greatly from the experimental results of the time fraction model (TF). A combined approach using the strain energy density dissipation model (T-SEDE) and the Ostergren method demonstrated excellent predictive capability for creep–fatigue life. Full article

Background: Resection or damage of the supplementary motor area (SMA) is associated with the development of a transient negative motor response defined as SMA syndrome. The risk of neurological deficits after resection in the SMA has been reported to vary widely from 23% to 100%. Various influencing factors can be involved. However, since tumors in the SMA are relatively infrequent, most of the evidence for surgical treatment of these lesions is based on small, retrospective, single-center case series. Furthermore, previous studies focused only on a few variables, and our knowledge regarding the outcome of these patients is still limited. Objective: To better define the risk of neurological deficits after brain tumor resection in the SMA. Methods: We retrospectively reviewed 66 surgeries that involved the SMA for gliomas and metastasis in 53 patients from two separate centers. Out of those, 13 cases were recurrence of the disease. We carefully evaluated various clinical factors, preoperative neuroimaging, intraoperative neurophysiology monitoring, and anatomical factors. By using Fisher’s exact probability test, we examined the relationship between these factors and the occurrence of postoperative neurological deficits. Statistical significance was considered at a p-value of less than 0.05. Results: In 28 cases, patients experienced neurological deficits after surgery. Among those cases, 26 experienced partial SMA syndrome, one experienced complete SMA syndrome, and one experienced a permanent neurological deficit. The research found that the patient’s past medical history (p = 0.005), lack of intraoperative language mapping (p = 0.044), and extent of resection (p = 0.040) significantly influenced the occurrence of language deficits. Additionally, the proximity between the corticospinal tract and the tumor (p = 0.005) and fMRI activation of the SMA in response to motor tasks (p = 0.044) were found to correlate with the development of motor deficits. However, there was no correlation found between the lack of intraoperative monitoring of motor-evoked potentials (MEPs) and the development of motor deficits (p > 0.05). Conclusions: Certain pre-existing medical conditions may increase the risk of postoperative language deficits. Intraoperative language mapping can help prevent these deficits. The extent of resection, along with the anatomical characteristics of the resection cavity, correlates with postoperative outcomes. Tractography and fMRI can assist in predicting the risk of motor deficits. Although intraoperative MEP monitoring can help prevent permanent motor deficits, it does not appear to prevent the transient deficits characteristic of SMA syndrome. Further intraoperative studies are needed to refine mapping and monitoring strategies for tumors involving the SMA and pre-SMA. Full article

Cardiovascular diseases represent one of the major problems faced by modern society. In addition to reducing people’s quality of life, bringing high costs to the health system, and causing losses in economic productivity, they are the leading cause of death in the world. Early diagnosis and treatment are the best actions to minimize the damage and costs caused by these diseases. For this, developing techniques and technologies that have higher accuracy in the analysis of electrocardiogram (ECG) signals is necessary. Early diagnosis benefits from relevant ECG interpretation. Then, it can contribute to reducing healthcare costs by replacing interventionist responses with preventive actions. This work presents a method and system for heart rate estimation using Linear Prediction Coefficients (LPCs) centered on an ESP32 microprocessor module and an AD8232 ECG signal conditioning module. The proposal was validated with a Tektronix AFG1022 function generator that produces ECG signals and obtained measurements with accuracy above 98.87%, showing performance similar to studies presented in the literature. Also, the LPC algorithm showed good performance in rejecting low-frequency noise caused by some common artifacts, such as body movement and electrode displacement. Full article

The early warning of disasters such as ground pressure in deep hard rock mines has long constrained the safe and efficient development of mining activities. Based on fractal theory and fractal dimension interpretation, this study constructs a microseismic monitoring system for mining areas, extracting key elements, particularly time and energy elements. Using the box-counting method of fractal theory, the study investigates the fractal dimensions of microseismic time–energy elements, data interpretation, and disaster source early warning. Through parameter analysis, events related to local potential failure are identified and extracted, and disaster characteristics are revealed based on microseismic activity. A time–energy fractal dimension-based analysis method is developed for preliminary fractal analysis and prediction of regional damage. A time–energy-centered early warning model is constructed, narrowing the prediction range to a scale of 10 m. Based on the fractal interpretation of time–energy data, the prediction and early warning of rock mass failure in mining areas are achieved, with the reliability of nested energy warnings ranging between 91.7% and 96.2%. A comprehensive evaluation criterion for fractal dimension values is established, enabling accurate delineation of warning zones and providing scientific decision-making support for mine safety promotion. Full article

Background: Minimally invasive thoracic surgery has advanced since the introduction of multiportal video-assisted thoracoscopic surgery (mVATS) in 1991. Primary spontaneous pneumothorax (PSP) is an ideal condition for refining minimally invasive techniques owing to its straightforward procedures and predictable bullae distributions. Methods: Uniportal VATS (uVATS), which involves a single incision, is an alternative to mVATS, offering reduced postoperative pain, lower paresthesia rates, and comparable recurrence outcomes. This review explores two main uVATS approaches: intercostal and subxiphoid. Results: The intercostal approach is common to surgeons trained in mVATS, easier to adopt, and provides excellent cosmetic outcomes. Innovations such as the chest wall pulley method and anchoring sutures further enhance its operability and prevent recurrence. Subxiphoid uVATS minimizes intercostal nerve damage and postoperative pain, making it advantageous for bilateral PSP surgeries. However, it poses challenges such as longer operative times and limited dorsal visualization. Emerging strategies, including drainless postoperative management and two-lung ventilation with CO₂ insufflation, have reduced surgical invasiveness. Additionally, cosmetic techniques such as subaxillary incisions enhance patient satisfaction. Conclusions: uVATS continues to redefine PSP surgery, prioritize patient-centered outcomes, and integrate novel strategies to achieve superior results. Full article

Evaluating physical slope stability is essential to prevent landslides and damage to infrastructure located on sloping terrains. This study analyzes how static and pseudo-static conditions affect slope safety, considering the magnitude and location of the loads exerted. A total of 2394 simulations were carried out on 399 terrain profiles, using the Spencer method to calculate factors of safety (FSs). The results reveal that uniformly distributed loads placed at the center of the slope increase stability under static conditions. However, in pseudo-static scenarios, the action of dynamic forces, such as seismicity, drastically reduces the FS, especially on slopes greater than 15%. This analysis allowed the identification of critical zones of high susceptibility, promoting the implementation of reinforcement techniques, such as retaining walls and drainage systems. In addition, zoning maps were developed that prioritize safe areas for urban development, aligned with the international standards. The findings underscore the importance of integrating predictive models into design and planning processes, considering both static and dynamic factors. In conclusion, this study provides practical tools for risk mitigation and resilient infrastructure design in sloping terrains. Full article

To safeguard historic centers with masonry buildings in medium-high seismic areas, the local seismic response (LSR) should be used. These portions of the urban areas are commonly characterized by complex subsurface features (i.e., underground cavities, buried anthropic structures, and archeological remains) that could be responsible for unexpected amplifications at period intervals similar to the building’s ones. In this study, San Giustino’s Square (Chieti, Italy) was considered due to the differentiated damage caused by the 2009 L’Aquila earthquake mainshock (6 April 2009 at 3:32 CEST, 6.3 M_w). Out of the eight buildings overlooking the square, the structure that suffered the heaviest damage was the Justice Palace. Two-dimensional finite element analyses have been carried out in San Giustino’s square to predict the LSR induced by the seismic shear wave propagation. The influence of the Chieti hill, the anthropogenic shallow soil deposit, and the manmade cavity were investigated. The results outlined that the amplifications of the seismic shaking peaked between 0.2 and 0.4 s. The crest showed amplifications over a wide period range of 0.1–0.8 s with an amplification factor (FA) equal to 2. Throughout the square, FA = 2.0–2.4 was predicted due to the cavities and the filled soil thickness. The large amplified period range is considered responsible for the Justice Court damage. Full article