Search Results (844)

Steel is an important product in many engineering sectors; however, steelmaking remains one of the largest ${\mathrm{CO}}_2$ emitters. Therefore, new governmental policies drive the steelmaking industry toward a cleaner and more sustainable operation such as the gas-based direct reduction–electric arc furnace process. To become carbon neutral, utilizing more scrap is one of the feasible solutions to achieve this goal. Addressing knowledge gaps regarding scrap heterogeneity (size, shape, and composition) is essential to evaluate the effects of increased scrap ratios in basic oxygen furnace (BOF) operations. This review systematically examines heat and mass transfer correlations relevant to scrap melting in BOF steelmaking, with a focus on low Prandtl number fluids (thick thermal boundary layer) and dense particulate systems. Notably, a majority of these correlations are designed for fluids with high Prandtl numbers. Even for the ones tailored for low Prandtl, they lack the introduction of the porosity effect which alters the melting behavior in such high temperature systems. The review is divided into two parts. First, it surveys heat transfer correlations for single elements (rods, spheres, and prisms) under natural and forced convection, emphasizing their role in predicting melting rates and estimating maximum shell size. Second, it introduces three numerical modeling approaches, highlighting that the computational fluid dynamics–discrete element method (CFD–DEM) offers flexibility in modeling diverse scrap geometries and contact interactions while being computationally less demanding than particle-resolved direct numerical simulation (PR-DNS). Nevertheless, the review identifies a critical gap: no current CFD–DEM framework simultaneously captures shell formation (particle growth) and non-isotropic scrap melting (particle shrinkage), underscoring the need for improved multiphase models to enhance BOF operation. Full article

Background: Polygenic risk scores (PRS) have emerged as promising tools for disease risk stratification. However, their validity across different populations remains unclear, particularly for autoimmune diseases, where environmental factors may play crucial roles. Methods: We calculated the population-level PRS for Sjögren’s syndrome using seven validated genetic variants (PGS001308) and allele frequency data from the 1000 Genomes Project Phase 3 for five European populations (CEU, TSI, FIN, GBR, and IBS). PRS values were correlated with published prevalence estimates from a systematic literature review. Statistical analyses included Pearson’s correlation and sensitivity analyses. Results: PRS values varied across European populations, ranging from 0.317 in the Spanish population to 0.370 in the Northern European population. A non-significant negative trend was observed between population PRS and Sjögren’s syndrome prevalence (r = −0.407, R² = 0.166). Italy showed the lowest genetic risk score (TSI: 0.349) but the highest disease prevalence (58.2 per 100,000), while Northern European populations demonstrated a higher PRS but lower prevalence. Conclusions: No significant correlation was found between genetic risk scores and disease prevalence in this limited sample of five European populations. Larger studies are needed to clarify the relationship between polygenic risk and disease prevalence. Full article

The aim of this study was to evaluate the relationship between visual functions and road traffic accidents (RTAs) by meta-analysis of observational studies. The analysis included all drivers of motor vehicles, regardless of age, and those using private or public transport. Self-reported visual outcomes were excluded. The risk of RTA in patients with reduced visual acuity was observed in commercial drivers in cross-sectional studies (PR 1.54, 95% CI 1.26–1.88), but not in private drivers in cohort (RR 1.04, 95% CI 0.74–1.46) or case–control studies (OR 1.04, 95% CI 0.78–1.40). A non-statistically significant association between colour vision defects and RTA was observed in cross-sectional studies (PR 1.50, 95% CI 0.91–2.45). No evidence was found for an increased risk of accidents in people with reduced stereopsis. In older adults with abnormal contrast sensitivity, a weak risk of RTA was observed in cohort studies. Evidence from low-quality cross-sectional studies suggests an increased risk of RTAs among commercial drivers with reduced visual acuity. The few case–control and cohort studies identified did not show an association between accident occurrence and visual function. Attention needs to be paid to this issue to facilitate the conduct of high-quality research that can support the development of road safety policies. Full article

Background: Gastric cancer (GC) is a highly heterogeneous disease and remains one of the major causes of cancer-related mortality worldwide. The vast majority of GC cases are adenocarcinomas including diffuse and intestinal GC that may differ in their incidence between Asian and non-Asian cohorts. The intestinal-subtype GC has declined over the past 50 years. In contrast to the intestinal-subtype adenocarcinoma, the incidence of diffuse-subtype GC, often associated with poor overall survival, has constantly increased in the USA and Europe. The aim of this study was to analyze the expression and clinical significance of steroid hormone receptors, two membrane-bound receptors (ERRγ and GPER), and several genes involved in epigenetic alterations. The findings may contribute to revealing events driving tumorigenesis and may aid prognosis. Methods: Using mRNA from diffuse and intestinal GC tumor samples, the expression level of 11 genes, including those coding for sex hormone receptors (estrogen receptors ERα and ERβ), progesterone receptor (PR) and androgen receptor (AR), and the putative relevant ERRγ and GPER receptor were determined by RT-qPCR. Results: In diffuse GC, the expression of ERα, ERβ, PR and AR differed from their expression in the intestinal subtype. The expression of ERα and ERβ was strongly increased in the diffuse subtype compared to the intestinal subtype (×1.90, p = 0.001 and ×2.68, p = 0.002, respectively). Overexpression of ERα and ERβ was observed in diffuse GC (15 and 42%, respectively). The expression levels of PR and AR were strongly decreased in the intestinal subtype as compared to diffuse GC (×0.48, p = 0.005 and ×0.25, p = 0.003, respectively; 37.5% and 56% underexpression). ERα, ERβ, PR and AR showed notable differences for clinicopathological correlation in the diffuse and intestinal GC. A significant decrease of ERα, ERβ, PR and AR in intestinal GC correlated with the absence of lymphatic invasion and lower TNM (I-II). In diffuse GC, among the hormone receptors, increases of ERs and PR mainly correlated with expression of growth factors and receptors (IGF1, FGF7 and FGFR1), and with genes involved in epithelial-mesenchymal transition (VIM and ZEB2) or cell migration (MMP2). Our results also report the strong decreased expression of ERRγ and GPER (two receptors that bind estrogen or xenoestrogens) in diffuse and intestinal subtypes. Conclusions: Our study identified new target genes, namely hormone receptors and membrane receptors (ERRγ and GPER), whose expression is associated with an aggressive phenotype of diffuse GC, and revealed the importance of epigenetic factors (EZH2, HOTAIR, H19 and DNMT1) in gastric cancers. Full article

Pregnancy rhinitis (PR) is a transient, non-infectious nasal condition affecting a significant number of pregnant women, yet often remains underdiagnosed or misclassified. It can substantially impact maternal quality of life, sleep, and even fetal oxygenation. This narrative review explores the current understanding of PR, including hormonal and vascular mechanisms, clinical criteria, and therapeutic approaches considered safe during pregnancy. Despite increasing recognition, the differentiation between PR and other rhinitis forms remains challenging. Limited therapeutic options and the absence of standard diagnostic guidelines further complicate management. Evidence supports a multifactorial etiology involving estrogen, progesterone, and placental growth factors. Non-pharmacologic strategies are first-line, while pharmacological interventions are cautiously employed. PR is a distinct and clinically relevant condition requiring increased awareness among ENT and obstetric professionals. Future research should focus on standardized diagnostic criteria and evidence-based treatment protocols to improve maternal–fetal outcomes. Full article

Adult entertainment work may be associated with increased vulnerability to sexually transmitted infections, particularly HIV. In Brazil, pre-exposure prophylaxis (PrEP) for HIV infection has been available through the Brazilian Unified Health System (SUS) since November 2017, representing a significant advancement in public sexual health policy. The objective of this study was to understand the individual and social determinants that promote PrEP use among adult entertainment workers. This was a cross-sectional, analytical, and quantitative study. A multivariate modeling approach was employed to identify factors independently associated with PrEP use. The study included 254 adult entertainment workers using oral PrEP through the SUS, predominantly young adults (141; 55.5%), SUS users (248; 97.6%), single (213; 83.9%), non-white (142; 55.9%), cisgender (148; 58.3%), and heterosexual (152; 59.8%). Factors independently associated with greater PrEP use included having adult entertainment as the main source of income (aPR: 2.69; 95% CI: 1.86–3.95), prior use of PEP (aPR: 2.49; 95% CI: 1.63–3.81), undergoing any type of health treatment (aPR: 1.56; 95% CI: 1.15–2.12), and having a history of STIs (aPR: 1.51; 95% CI: 1.10–2.08). Conclusion: PrEP use in this population was strongly influenced by structural and contextual factors, indicating that the availability of the technology alone does not ensure its effectiveness. Full article

Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article

The evolution of 5G technology has led to significant advancements in high-accuracy positioning. However, the actual performance of 5G signals for user equipment (UE) positioning has not been thoroughly examined, especially under varying propagation conditions. This research presents a comprehensive evaluation of 5G positioning using both uplink sounding reference signals (UL-SRS) and downlink positioning reference signals (DL-PRS) under line-of-sight (LOS) and non-line-of-sight (NLOS) conditions. In the uplink scenario, the UE transmits SRS signals to the gNBs, enabling precise localization. In the downlink scenario, the gNBs transmit PRS signals to the UE for accurate position estimation. Expanding beyond LOS environments, this study explores the challenges posed by NLOS conditions and analyzes their impact on positioning accuracy. Through a comparative analysis of UL-SRS and DL-PRS signals, this study enhances the current understanding of 5G positioning performance, offering empirical insights and quantitative benchmarks that serve as a guide for the development of more precise localization methods. The simulation results show that DL-PRS achieves high accuracy in LOS conditions, while UL-SRS performs well for UE positioning under NLOS conditions in urban environments. Full article

Horizontal gene transfer (HGT), the non-Mendelian transfer of genetic material between organisms, is relatively frequent in prokaryotes, whereas its extent among eukaryotes remains unclear. Here, we raise the hypothesis of a possible cross-phylum HGT event involving 5S ribosomal DNA (rDNA). A specific type of 5S rDNA sequence from the anuran Xenopus laevis was highly similar to a 5S rDNA sequence of the genome of its flatworm parasite Protopolystoma xenopodis. A maximum likelihood analysis revealed phylogenetic incongruence between the gene tree and the species trees, as the 5S rDNA sequence from Pr. xenopodis was grouped along with the sequences from the anurans. Sequence divergence analyses of the gene region and non-transcribed spacer also agree with an HGT event from Xenopus to Pr. xenopodis. Additionally, we examined whether contamination of the Pr. xenopodis genome assembly with frog DNA could explain our findings but found no evidence to support this hypothesis. These findings highlight the possible contribution of HGT to the high diversity observed in the 5S rDNA family. Full article

Strawberry post-harvest losses are estimated at 50%, due to improper handling and harvest timing, necessitating the use of non-invasive methods. This study develops a non-invasive in situ bioelectrical spectroscopy for strawberry peduncles. Based on traditional assessments and invasive metrics, 100 physiologically ripe (PR) and 100 commercially mature (CM) strawberries were distinguished. Spectra from their peduncles were measured from 1 kHz to 1 MHz, collecting four parameters (magnitude (Z(f)), phase angle (θ(f)), resistance (R(f)), and reactance (X(f))), resulting in 80,000 raw data points. Through systematic spectral preprocessing, Bode and Cole–Cole plots revealed a distinction between PR and CM strawberries. Frequency selection identified seven key frequencies (1, 5, 50, 75, 100, 250, 500 kHz) for deriving 37 engineered features from spectral, extrema, and derivative parameters. Feature selection reduced these to 6 parameters: phase angle at 50 kHz (θ (50 kHz)); relaxation time (τ); impedance ratio (|Z_1k/Z_250k|); dispersion coefficient (α); membrane capacitance (Cm); and intracellular resistivity (ρi). Four algorithms (TabPFN, CatBoost, GPC, EBM) were evaluated with Monte Carlo cross-validation with five iterations, ensuring robust evaluation. CatBoost achieved the highest accuracy at 93.3% ± 2.4%. Invasive reference metrics showed strong correlations with bioelectrical parameters (r = 0.74 for firmness, r = −0.71 for soluble solids). These results demonstrate a solution for precise harvest classification, reducing post-harvest losses without compromising marketability. Full article

Prion diseases such as chronic wasting disease involve the conformational conversion of the cellular prion protein (PrP^C) into its misfolded, β-rich isoform (PrP^Sc). While chemical denaturants such as guanidine hydrochloride (GdnHCl) and urea are commonly used to study this process in vitro, their distinct molecular effects on native and misfolded PrP conformers remain incompletely understood. In this study, we employed 500 ns all-atom molecular dynamics simulations and essential collective dynamics analysis to investigate the differential effects of GdnHCl and urea on a composite PrP^C/PrP^Sc system, where white-tailed deer PrP^C interfaces with a corresponding PrP^Sc conformer. GdnHCl was found to preserve interfacial alignment and enhance β-sheet retention in PrP^Sc, while urea promoted partial β-strand dissolution and interfacial destabilization. Both denaturants formed transient contacts with PrP, but urea displaced water hydrogen bonds more extensively. Remarkably, we also observed long-range dynamical coupling across the PrP^C/PrP^Sc interface and between transiently bound solutes and distal protein regions. These findings highlight distinct, denaturant-specific mechanisms of protein destabilization and suggest that localized interactions may propagate non-locally via mechanical or steric pathways. Our results provide molecular-scale insights relevant to prion conversion mechanisms and inform experimental strategies using GdnHCl and urea to modulate misfolding processes in vitro. Full article

One of the key challenges in financial distress data is class imbalance, where the data are characterized by a highly imbalanced ratio between the number of distressed and non-distressed samples. This study examines eight resampling techniques for improving distress prediction using the XGBoost algorithm. The study was performed on a dataset acquired from the CSMAR database, containing 26,383 firm-quarter samples from 639 Chinese A-share listed companies (2007–2024), with only 12.1% of the cases being distressed. Results show that standard Synthetic Minority Oversampling Technique (SMOTE) enhanced F1-score (up to 0.73) and Matthews Correlation Coefficient (MCC, up to 0.70), while SMOTE-Tomek and Borderline-SMOTE further boosted recall, slightly sacrificing precision. These oversampling and hybrid methods also maintained reasonable computational efficiency. However, Random Undersampling (RUS), though yielding high recall (0.85), suffered from low precision (0.46) and weaker generalization, but was the fastest method. Among all techniques, Bagging-SMOTE achieved balanced performance (AUC 0.96, F1 0.72, PR-AUC 0.80, MCC 0.68) using a minority-to-majority ratio of 0.15, demonstrating that ensemble-based resampling can improve robustness with minimal impact on the original class distribution, albeit with higher computational cost. The compared findings highlight that no single approach fits all use cases, and technique selection should align with specific goals. Techniques favoring recall (e.g., Bagging-SMOTE, SMOTE-Tomek) are suited for early warning, while conservative techniques (e.g., Tomek Links) help reduce false positives in risk-sensitive applications, and efficient methods such as RUS are preferable when computational speed is a priority. Full article

Background: Facial trauma is one of the few surgical conditions that is routinely managed by three distinct disciplines, including Oral and Maxillofacial Surgery (OMS), Plastic and Reconstructive Surgery (PRS), and Otolaryngology (ENT). This study aims to evaluate mandibular trauma management strategies and clinical outcomes among three operating services. Methods: An IRB-approved, retrospective chart review was performed over a ten-year period (2007–2016) at a major, urban, Level I trauma center for all patients treated for an isolated mandibular injury determined by ICD-9 codes. Of the 2299 patients evaluated for traumatic facial injuries, 191 met the inclusion criteria and 137 had longitudinal data. Patient, fracture, and management characteristics and clinical outcomes were compared among three surgical services. Results: Most patients were male (95.3%), and assaults were the most common etiology of injury (79.1%). The angle/ramus was the most common single location (31.4%), and 47.6% of patients had multiple fractures. There was a statistically significant difference between specialties when assessing the use of operative versus non-operative approaches to fracture management (p < 0.001), and within operative management, for the use of open reduction-internal fixation (ORIF) alone versus ORIF with maxillomandibular fixation (MMF) (p = 0.002). There was no significant difference in the overall complications between specialties (p = 0.227). Conclusions: Services differ in their decision to pursue operative versus non-operative management, as well as the decision for postoperative MMF, though these differences in decision-making were not associated with a significant difference in the overall complications. Full article

Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitative polymerase chain reaction (qPCR) using a ViiA7^® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming to uncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity. Full article

Prion diseases are classically attributed to the accumulation of protease-resistant prion protein (PrP^Sc); however, recent evidence suggests that alternative misfolded prion conformers and systemic inflammatory factors may also contribute to neurodegeneration. This study investigated whether recombinant moPrP^Res, generated by incubating wild-type mouse PrP^C with bacterial lipopolysaccharide (LPS), can induce prion-like disease in FVB/N female mice, whether LPS alone causes neurodegeneration, and how LPS modulates disease progression in mice inoculated with the Rocky Mountain Laboratory (RML) strain of prions. Wild-type female FVB/N mice were randomized into six subcutaneous treatment groups: saline, LPS, moPrP^Res, moPrP^Res + LPS, RML, and RML + LPS. Animals were monitored longitudinally for survival, body weight, and clinical signs. Brain tissues were analyzed histologically and immunohistochemically for vacuolar degeneration, PrP^Sc accumulation, reactive astrogliosis, and amyloid-β plaque deposition. Recombinant moPrP^Res induced a progressive spongiform encephalopathy characterized by widespread vacuolation and astrogliosis, yet with no detectable PrP^Sc by Western blot or immunohistochemistry. LPS alone triggered a distinct neurodegenerative phenotype, including cerebellar amyloid-β plaque accumulation and terminal-stage spongiosis, with approximately 40% mortality by the end of the study. Co-administration of moPrP^Res and LPS resulted in variable regional pathology and intermediate survival (50% at 750 days post-inoculation). Interestingly, RML + LPS co-treatment led to earlier clinical onset and mortality compared to RML alone; however, vacuolation levels were not significantly elevated and, in some brain regions, were reduced. These results demonstrate that chronic endotoxemia and non-infectious misfolded PrP conformers can independently or synergistically induce key neuropathological hallmarks of prion disease, even in the absence of classical PrP^Sc. Targeting inflammatory signaling and toxic prion intermediates may offer novel therapeutic strategies for prion and prion-like disorders. Full article