Search Results (2,209)

Background/Objectives: Breast cancer is the most common cancer in women. The neutrophil/lymphocyte ratio (NLR) is an emerging biomarker from peripheral blood that has been associated with breast cancer prognosis in some studies; however, some studies fail to demonstrate an association. We stratified breast cancer patients into invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) cohorts to evaluate if any meaningful association could be found in either cohort between NLR and mortality. Additionally, no prior studies have examined the relationship between NLR and background parenchymal enhancement (BPE) on breast MRI, an imaging feature linked to increased breast cancer risk and a potential imaging prognostic biomarker, so we examined the relationship between BPE and NLR in the two cohorts. Methods: This retrospective study included 794 breast cancer patients who had either IDC or ILC. Radiologists’ MRI reports and their BI-RADS categorization of BPE (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) were extracted and recorded. The NLR was calculated from blood counts obtained prior to treatment. Tumor characteristics were also recorded. Results: For patients with ILC, NLR was found to be associated with mortality. Additionally, patients with ILC and a high BPE had a significantly higher mean NLR compared to all other groups, including low BPE groups and all IDC groups. Conclusions: There is potential value in using NLR, a readily available blood biomarker, in models predicting prognosis in ILC patients. Full article

Langer–Giedion syndrome (LGS), also known as trichorhinophalangeal syndrome type II (TRPS II; OMIM #150230), is a contiguous-gene deletion disorder caused by haploinsufficiency of TRPS1 and EXT1. Cornelia de Lange syndrome (CdLS) is genetically heterogeneous; heterozygous variants in RAD21 cause the milder CdLS type 4 phenotype (OMIM #614701). Because RAD21 lies between TRPS1 and EXT1, overlapping phenotypes may arise when all three genes are deleted. We report a unique case of a 4-year-old female presenting with a blended phenotype of Langer–Giedion Syndrome (LGS) and Cornelia de Lange Syndrome (CdLS) type 4. This case is distinct from previously reported 8q deletions in three key aspects: (1) Complex Genomic Architecture: Chromosomal microarray revealed a novel complex rearrangement consisting of a 13.01 Mb mosaic interstitial deletion at 8q23.1–q24.12, flanked by two large duplications (21.5 Mb at 8q11.23–q23.1 and 25.78 Mb at 8q24.12–q24.3). (2) Rare Mosaicism: This represents only the second reported case of mosaicism affecting this contiguous gene region. Notably, the patient demonstrates a “mosaic rescue” effect, where the mosaicism appears to have mitigated the neurodevelopmental phenotype (the patient is bilingual and ambulatory) while failing to protect the skeleton. (3) First Bone-Specific Therapy: The patient suffered from severe, recurrent fractures due to a synergistic “double hit” of TRPS1-related osteopenia and EXT1-related exostoses. We report the first successful use of bisphosphonate therapy (pamidronate) in this specific mosaic profile, which resulted in a complete cessation of fractures during a 12-month follow-up. This case underscores the utility of detailed microarray analysis in complex phenotypes and suggests bisphosphonates as a viable rescue therapy for refractory syndromic osteoporosis. Full article

Primula beesiana is a perennial herbaceous plant predominantly distributed in the alpine wetland regions of Yunnan Province, China. This species faces dual threats from habitat fragmentation and climate change, but research into its genetic background is severely lacking. Consequently, systematic analysis of the genetic diversity and population structure of Primula beesiana is crucial in formulating scientific conservation strategies. In this study, 86 individuals from six natural populations in Lijiang City, Yunnan Province, were collected and genotyped using double-digest restriction site-associated DNA sequencing (ddRAD-seq). A total of 1537 high-quality SNP loci were identified and used for genetic diversity, principal component (PCA), population structure (STRUCTURE), and gene flow analyses. Analysis of base substitutions revealed twelve mutation types, with transversions accounting for 67.9% and a transition/transversion ratio (Ti/Tv) of 0.47, potentially indicating strong environmental selection pressure. Although high overall genetic diversity was observed, significant genetic differentiation may exist among populations (Fst = 0.0056-0.0407), with heterozygote deficiency detected across all populations. Genetic structure analyses consistently grouped the six populations into four distinct clusters. Populations MDJ, WH, and HS each formed independent clusters, exhibiting clear genetic isolation, whereas XHC2, XHC1, and NX clustered together, showing high genetic similarity and frequent gene flow. Mantel tests demonstrated a significant positive correlation between genetic and geographical distances (r = 0.854, p < 0.01), supporting an isolation-by-distance model. Gene flow estimates varied considerably among populations (5.90-44.69) and decreased with increasing geographical distance. This study provides the first genomic-level evidence of significant genetic differentiation and isolation based on distance in Primula beesiana populations, offering crucial scientific support in identifying evolutionarily significant units and developing zoned conservation management strategies for this species. Full article

This paper investigates the degradation characteristics of a DC/DC converter operating under cold redundancy conditions when subjected to total ionizing dose (TID) effects. An optimized RCC isolated auxiliary power supply circuit was evaluated through ⁶⁰Co γ-ray irradiation up to 100 krad(Si) at dose rates of 3.89, 8.89, and 13.89 rad (Si)/s, with electrical characterizations performed at both the system level and the device level, focusing on the critical VDMOS transistors. The results indicate that the main output voltage and conversion efficiency remain essentially stable after irradiation, whereas the auxiliary supply voltage and efficiency degrade significantly, leading to a pronounced reduction in the controller supply margin. Device-level measurements reveal a negative threshold voltage shift of approximately 0.5–1.0 V with clear dose-rate dependence, while the subthreshold swing shows no obvious variation, suggesting that the degradation is primarily dominated by oxide-trapped charge effects. In addition, a substantial increase in drain current at low gate voltages is observed, which may further exacerbate restart risks under cold redundancy conditions. These findings demonstrate that the auxiliary power supply and startup margin constitute critical vulnerability points of cold-redundant DC/DC converters under TID stress and should therefore be primary targets for radiation-hardened design. Full article

In order to identify promising radioprotector candidates, a series of benzyl sulfoxide/sulfone coumarin derivatives were designed and synthesized based on the reported activity of Ex-Rad. Most of the target compounds demonstrated significant radioprotective effects at concentrations of 40 μmol/L and 20 μmol/L in HUVECs. Among them, compounds 5q and 5u displayed superior activity in mitigating DNA damage compared with Ex-RAD. Notably, compound 5u significantly enhanced the viability of mice exposed to a lethal dose of ionizing radiation. In summary, the above findings suggested that compound 5u might be a promising radioprotective agent deserving further investigation. Full article

Objective: We evaluate the performance and relevance of MRI to detect csPC in men with normal PSA. Methods: Out of our database of patients referred for prostate MRI, we selected men with PSA < 4 ng/mL for whom histopathology or at least 2 years of clinical follow-up data were available as standard of reference. Subgroup analyses were performed for the patients with PSA < 3 ng/mL, <2 ng/mL, and 2–3.9 ng/mL. The reasons for prostate MRI referral despite their normal PSA level were retrieved by exploring the patients’ files. The prostate MRIs were reported according to the Prostate Imaging and Reporting Data System (PI-RADS), and the overall assessment score was registered. For evaluation of the performance, PI-RADS ≥ 3 was set as a threshold for a positive exam. The patients without PC or only International Society of Urological Pathology (ISUP) grade group 1 PC (Gleason 3+3) were considered as one category having no csPC. The performance of prostate MRI was separately evaluated for detection of ISUP ≥ 2 and for ISUP ≥ 3 csPC. Results: A total of 148 men were included, with PSA ranging from 0.42 to 3.99 ng/mL (median 2.95, IQR 1.68–3.50) and age ranging from 36 to 84 years (median 58, IQR 52–66). A total of 74 men (50.0%) had a PSA level < 3 ng/mL, 42 (28.4%) had a PSA level < 2 ng/mL, and 106 (71.6%) had a PSA level of 2–3.9 ng/mL. They were referred for prostate MRI for a wide variety, and usually a combination of, reasons, such as younger age (<60 years in 55.4%, N = 82; <50 years in 17.6%, N = 26), abnormal digital rectal examination in 31.8% of cases (N = 47), suspicious PSA dynamics in 29.7% (N = 44), positive familial history in 27.0% (N = 40), clinical signs of prostatitis in 18.2% (N = 27), suspicious findings on Transrectal Ultrasound (TRUS) in 16.9% (N = 25), hematospermia in 7.4% (N = 11), hematuria in 4.1% (N = 6), incidental hot spot in the prostate on Fluoro-Deoxy-Glucose (FDG) Positron Emission Tomography (PET)–Computed Tomography (CT) in 4.1% (N = 6), lymphadenopathies on CT in 2.7% (N = 4), or severe patient anxiety in 3.4% (N = 5). Overall, ISUP ≥ 2 PC was present in 18.9% (N = 28) of cases, and MRI detected this with a sensitivity of 92.9%, a specificity of 66.7%, and a positive predictive value of 39.4%. ISUP ≥ 3 PC was present in 9.5% (N = 14) of cases, and prostate MRI detected this with a sensitivity of 100%, a specificity of 61.2%, and a positive predictive value of 21.2%. In patients with PSA < 2 ng/mL (N = 42), no csPC was found, but MRI generated false positives in 33.3%. Conclusions: Performing prostate MRI in men with normal PSA (<4 ng/mL) seems useful if there are other reasons that increase the clinical suspicion of csPC. In about one-fifth of these patients, csPC is present and MRI has high sensitivity for its detection. Prostate MRI has, however, low positive predictive value in this patient group, and clinicians should be aware of the risk of false-positive MRI. Below a PSA level of 2 ng/mL, no csPC was found and prostate MRI generated only false positives, suggesting limited value in this subgroup. Full article

The Cladia aggregata group of lichen-forming fungi comprises multiple species that are difficult to differentiate based on phenotypic characters. It has a wide distribution across several continents, but is most diverse in Australasia. We aimed to delimit the species complex further, investigate the relatedness of the lineages, and examine their distributional ranges and phenotypic traits. We used Restriction Site Associated DNA Sequencing (RAD-seq) to compare thousands of loci across 91 individuals from the Americas, Asia, and Australasia. All Asian samples formed a distinct, monophyletic clade in all phylogenetic trees, while the American samples divided into two clades, one comprising South American samples and another comprising Caribbean samples, with the latter representing C. aggregata sensu stricto, as the type specimen was collected in Jamaica. Further population-genomic analyses support the conclusion that the Asian samples are genetically distinct and are here described as a new species. The new species, Cladia asiatica, accommodates the Asian samples previously included in C. aggregata. Our analysis highlights the potential of next-generation sequencing to reveal hidden diversity and resolve the phylogeny of this species complex and lichen-forming fungi in general. Full article

Fruit size and pungency are key yield and quality traits in chili. This study combines high-throughput genotyping with bulk segregant analysis (BSA) to identify candidate SNPs and quantitative trait loci (QTLs) by analyzing extreme phenotypes from a Ghotki × Chakwal-4 F2 population. The traits were fruit length, diameter, length-to-diameter ratio, and weight, along with capsaicin content. Significant correlations were observed among length, diameter, and length-to-diameter ratio. A total of 534 single nucleotide polymorphisms (SNP) markers were used to develop genetic maps from 4315 to 6607 cM long. The SNP frequency data was pooled for the 25% of individuals showing extreme values for each measured trait, and bulk segregant analysis (BSA) was performed. BSA identified high-scoring SNPs associated with pungency (SNP 1_41308232; SNP 12_104377148), fruit length (SNP 1_92509300; SNP 6_218780813), and fruit weight (SNP 6_100989762 and SNP 6_138660974). Genetic mapping identified twelve pungency QTLs, three for fruit length, two for fruit diameter, two for the length-to-diameter ratio, and thirteen for fruit weight. Overlapping QTL regions on chromosome 6 influence fruit length, fruit width, and capsaicin content, indicating potential pleiotropy and offering promising targets for multi-trait selection in chili breeding. The study identifies key SNPs and QTLs that simultaneously influence chili fruit size and pungency, providing valuable targets for multi-trait breeding. Full article

Trichorhinophalangeal syndrome type II (TRPS II) is a rare disease caused by a contiguous gene deletion in the 8q23.3–q24.11 region. Three genes (TRPS1, RAD21, and EXT1) are considered responsible for the most common clinical features, which include facial dysmorphism, ectodermal and skeletal anomalies, osteochondromas, and cognitive impairment. To date, seven patients with 8q23–q24 deletions not involving TRPS1 have been reported, with phenotypes overlapping TRPS II. In this paper, we present clinical and genetic aspects from three non-related patients with 8q23–q24 deletions, and we review the available testing strategies for such patients and their families. The deletions harbored by these patients have been identified through microarray, with two of them also undergoing initial MLPA evaluation. The observed clinical and genetic features are heterogeneous, and generally in keeping with known associations between the three main genes from the deleted region and the clinical manifestations of TRPS II. Particularly, the deleted regions vary substantially in size, genomic coordinates, and gene content, with one not including TRPS1, and another, with a more distal loss, not including either TRPS1 nor RAD21. By describing three new patients, we hope to enlarge the genetic and clinical landscape of TRPS II and 8q23–q24 deletions, and help identify further genotype–phenotype correlations. Full article

Noncontact, high-fidelity data acquisition has enabled terrestrial laser scanning (TLS) to be widely adopted for bridge geometry measurement and condition monitoring. In TLS applications, point cloud registration directly affects data quality and the correctness of subsequent results. For long-span bridges in large-scale scenes, complex geometry and sparse sampling pose challenges to surface-based, data-driven registration methods, and may degrade registration accuracy. A data-driven approach for high-precision point cloud registration, referred to as the Iterative Closest-Surface (IC-Surface) method, is presented in this study. The method extracts neighboring surface patches via a bounding box and applies random sampling-based plane fitting to derive surface features for registration, effectively mitigating the impact of sparse points and outliers in long-span bridges. Regular points are generated on the source patch and projected onto the corresponding target patch to establish high precision correspondences, yielding a stable and accurate transformation. This method effectively overcomes the limitations of the Iterative Closest Point (ICP), which struggles with unreliable correspondences and outliers. Comparative experiments were conducted using synthetic data, large bridge segments, and full-bridge datasets against commonly used registration methods. The results show that the IC-Surface method maintains high accuracy and stability across varying levels of outliers and overlap ratios. In complex scenes, IC Surface achieves higher registration accuracy than both ICP and the sphere target method, with distance errors reduced from 3 mm to 1 mm and inter-plane angle errors reduced from 0.016 rad to 0.009 rad. These findings demonstrate the method’s broad applicability in digital construction and operation and maintenance assessments of long-span bridges. Full article

This pilot hypothesis-generating study evaluated whether lipid-related biomarkers (Lp(a), ApoB, and oxLDL), endothelial injury markers (endocan, vimentin), and extracellular matrix glycoproteins (TSP-1, TSP-2) reflect the severity of coronary artery disease (CAD) in patients with stable angina pectoris. 93 patients underwent invasive coronary angiography/coronary CT angiography. CAD severity was evaluated using Gensini, SIS, SSS, and CAD-RADS scores. CAD was confirmed in 76.3% (n = 71). OxLDL correlated with Gensini (r = 0.455; p = 0.006), atherosclerotic segments (r = 0.469; p = 0.005), arteries (r = 0.479; p = 0.004), revascularization indication (r = 0.318; p = 0.003), circumflex artery stenosis (r = 0.323; p = 0.005). OxLDL also correlated with vimentin (r = 0.459; p < 0.001). Vimentin correlated with Gensini (r = 0.480; p = 0.005), SIS (r = 0.349; p = 0.003), SSS (r = 0.320; p = 0.008), CAD-RADS (r = 0.331; p = 0.005), atherosclerotic segments (r = 0.515; p = 0.003), arteries (r = 0.384; p = 0.030), revascularization indication (r = 0.324; p = 0.003). Endocan, TSP-1, and TSP-2 showed no significant associations. These exploratory findings suggest that oxLDL and vimentin may be associated with CAD severity; however, confirmation in larger, prospective cohorts is required. Full article

One of the most significant impacts of climate change is sea-level rise, which is increasingly threatening to the coastal setting, infrastructure, and socioeconomic systems. Since a change at the sea level is spatially non-uniform and highly modulated by local oceanographic and climatic events, local or regional-scale measurements are necessary—especially in semi-enclosed basins. This paper examines the long-term variability of sea levels throughout the Persian Gulf and illustrates a strong spatial variance of the trends over the past and the future. Using three decades of satellite-derived observations, regional sea-level trends were estimated from monthly sea-level anomaly (SLA) data, which were also used to generate future projections to 2100. The analysis shows that the rate of sea-level rise along the UAE–Oman stretch is 3.88 mm year⁻¹ and that of the Strait of Hormuz is 5.23 mm year⁻¹, with a mean of 4.44 mm year⁻¹ in the basin. Statistical forecasts of sea-level change were projected by a statistical forecasting scheme with high predictive ability with the optimal configuration of an average of 0.0391 m, an RMSE of 0.0492 m, and an R² of 0.80 when independent validation was conducted. It is estimated that by 2100, the average rise of the sea level in the Persian Gulf is about 0.30–0.40 m, and the peak rise in sea level is at the Strait of Hormuz. Since these projections are based on statistical extrapolation rather than physics-based climate models, they are interpreted within the uncertainty envelope defined by IPCC AR6 scenarios. This study presents a unique, regionally resolved viewpoint on sea-level rise that is relevant to coastal risk management and adaptation planning in semi-enclosed marine basins by connecting robust statistical performance with physically interpretable regional patterns. Full article

The article presents the current state of knowledge on genetic modifiers of ovarian cancer risk in women carrying pathogenic variants (PVs) in the BRCA1 and BRCA2 genes, which are major contributors to hereditary susceptibility to this malignancy. Although PV carriers have high disease penetrance (BRCA1: ~40% and BRCA2: 11–27%), substantial variability in individual risk is observed, suggesting the influence of additional genetic variants. Background: Ovarian cancer is characterized by late detection and high mortality, and a significant portion of risk among BRCA1/2 carriers is shaped by reproductive and environmental factors as well as genetic modifiers. The article emphasizes that carriers of the same BRCA PV can exhibit markedly different risk levels depending on additional variants that modulate key biological processes, such as DNA repair, cell cycle regulation, and apoptosis. Methods: A systematic literature search covering the years 1996–2025 was conducted in the PubMed database. Initially, 734 publications were identified; after removing duplicates, thematically irrelevant articles, non-full-text papers, and studies not meeting the inclusion criteria, 47 articles were included in the review. These studies covered candidate gene analyses, GWAS, and data from the CIMBA consortium, which enables the examination of large cohorts of PV carriers. Results: The review identified numerous variants associated with increased or decreased ovarian cancer risk in BRCA1 carriers, including the following: OGG1, DR4, MDM2, CYP2A7, CASP8, ITGB3, HRAS1, TRIM61, and MTHFR. The reviewed studies also identified both protective and risk-increasing variants among BRCA2 PV carriers: UNG, TDG, and PARP2, and haplotypes in ATM, BRIP1, BARD1, MRE11, RAD51, and 9p22.2. The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP. Protective variants include BNC2 and LINC00824. The only SNP reaching genome-wide significance (p < 5 × 10⁻⁸) was in BNC2. Conclusions: The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets. Full article

Prostate cancer (PCa) is the most common malignancy in men worldwide. Multiparametric MRI (mpMRI) improves the detection of clinically significant PCa (csPCa); however, it remains limited by false-positive findings and inter-observer variability. Time-dependent diffusion (TDD) MRI provides microstructural information that may enhance csPCa characterization beyond standard mpMRI. This prospective observational diagnostic accuracy study protocol describes the evaluation of PROS-TD-AI, an in-house developed AI workflow integrating TDD-derived metrics for zone-aware csPCa risk prediction. PROS-TD-AI will be compared with PI-RADS v2.1 in routine clinical imaging using MRI-targeted prostate biopsy as the reference standard. Full article