Search Results (10,072)

Richter’s syndrome (RS) or transformation of chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma (e.g., diffuse large B cell lymphoma, DLBCL) is a distinct disease that portends an overall poor prognosis and remains a challenge for clinicians to identify and treat effectively. This review of the current literature focuses on the pathology, diagnosis, and management of Richter’s syndrome. Clonally related RS has been found to have a worse prognosis than unrelated disease and the genomic profile of DLBCL-RS differs from that of de novo DLBCL. The standard of care therapy for RS has historically been chemoimmunotherapy; consolidative stem cell transplants have a role in improving durability of disease response. Given generally poor response rates to chemotherapy, there have been recent investigations into combination treatments with immune checkpoint inhibitors and small molecule targeted therapies, which have had mixed results. Additional studies are evaluating the use of bispecific antibodies, chimeric antigen receptor T cell therapy, and antibody drug conjugates. RS remains difficult to manage; however, advancements in the understanding of the underlying pathology of transformation and continued investigations into new therapies demonstrate promise for the future. Full article

FKBP5 has been of special scientific interest in the behavioral sciences since it has been involved in the pathophysiology of several mental disorders. It is a gene with pleiotropic effects which encodes the protein FKBP5, a cochaperone that decreases glucocorticoid receptor (GR) affinity for glucocorticoids by competing with FKBP4, altering the GR chaperone complex, and impairing GR activation. As a key modulator of the stress response, FKBP5 plays a critical role in regulating cortisol levels in the organism. The FKBP5 gene is regulated through a combination of transcriptional, epigenetic, post-transcriptional, and environmental mechanisms, as well as genetic polymorphisms that influence its transcription and stress responsiveness. Notably, the rs1360780 T-allele in FKBP5 significantly affects FKBP5 regulation and has been linked to stress-related disorders by influencing transcription and stress responsiveness. In this narrative review, we aim to provide an overview of the role played by the single-nucleotide polymorphism rs1360780 in the FKBP5 locus in gene expression, its epigenetic regulation, and the impact of early stress in its functioning. We discuss some brain regions with differential expression of FKBP5 and some behavioral phenotypes linked to the locus. The T-allele of rs1360780 is considered a risk variant, as it leads to high FKBP5 induction, which delays negative feedback and increases GR resistance. This results in states of relative hypercortisolemia and brain morphofunctional alterations, particularly in regions sensitive to glucocorticoid activity during critical periods of neurodevelopment. Additionally, exposure to childhood maltreatment is associated with demethylation of the glucocorticoid response elements of FKBP5, further increasing its expression levels. Among the psychological dimensions analyzed in which FKBP5 is involved are neurocognition, aggression, suicidality, and social cognition. At the level of mental disorders, the gene may play a role in the pathogenesis of post-traumatic stress disorder, depression, and bipolar disorder. In psychotic disorders, its role is less clear. This knowledge enhances the understanding of disease mechanisms that operate through psychopathological dimensions, and highlights the need to design specific, person-centered psychopharmacological and environmental therapeutic interventions. Full article

Seedling cultivation is the foremost part of sweet potato (Ipomoea batatas L. Lam) production. It is of great significance to reveal the effects of different temperatures on the nutrients of sweet potato storage roots and their relationship with the sprouting quality and to explore the appropriate temperature management for seedlings. In this study, we simulated the temperature differences during the sprouting and seedling period in the summer growing area of sweet potato in the Yangtze River Basin and set three constant temperatures (17 °C, 22 °C and 27 °C) and corresponding three-day/night variable temperatures (21/13 °C, 26/18 °C and 31/23 °C). Thus, we investigated the nutrients, amylase activity, endogenous hormones, and sprouting characteristics of storage roots during the sprouting and seedling period of three sweet potato cultivars with different starch contents. The results showed that with the increase in temperature, the starch and soluble protein (SP) contents in sweet potato storage roots decreased, and the total soluble sugar (TSS), reducing sugar (RS), and sucrose contents increased during the sprouting and seedling period. The amylase activity enhanced; the hormone (IAA) content increased, and the abscisic acid (ABA) content decreased, which, in turn, led to an earlier time of sprouting time (ST), emergence stage (ES), and full stand of seedling stage (FSS). Comparing at the same average temperature, the physiological metabolism and sprouting time and quality of sweet potato were better at variable temperatures than at constant temperatures, in which 31/23 °C was more conducive to the advancement of the ST of sweet potato. At the same time, it was more conducive to the improvement of the seedling cutting amount (SCA), seedling weight (SDW), and seedling number (SDN). The sprouting time and quality of different sweet potato cultivars differed, and cultivars with higher starch content were superior to those with lower starch content. The sucrose and starch contents at different sprouting stages of storage roots can be used as important indicators of the quality of sweet potato seedlings. Full article

Soil erosion and wildfires are frequent natural disasters that threaten the environment. Identifying and zoning susceptible areas are crucial for the implementation of preventive measures. The Šar Mountains are a national park with rich biodiversity and various climate zones. Therefore, in addition to protecting the local population from natural disasters, special attention must be given to preserving plant and animal species and their habitats. The first step in this study involved collecting and organizing the data. The second step applied geographic information systems (GIS) and remote sensing (RS) to evaluate the intensity of erosion using the erosion potential model (EPM) and the wildfire susceptibility index (WSI). The EPM involved the analysis of four thematic maps, and a new index for wildfires was developed, incorporating nine natural and anthropogenic factors. This study introduces a novel approach by integrating the newly developed WSI with the EPM, offering a comprehensive framework for assessing dual natural hazards in a single region using advanced geospatial tools. The third step involved obtaining synthetic maps and comparing the final results with satellite images and field research. For the Šar Mountains (Serbia), high and very high susceptibility to wildfires was identified in 21.3% of the total area. Regarding soil erosion intensity, about 8.2% of the area is affected by intensive erosion, while excessive erosion is present in 2.2% of the study area. The synthetic hazard maps provide valuable insights into the dynamics of the erosive process and areas susceptible to wildfires. The final results can be useful for decision-makers, spatial planners, and emergency management services in implementing anti-erosion measures and improving forest management in the study area. Full article

Endometrial cancer is the most common gynecologic malignancy in developed countries, and its incidence is rising globally. Genetic predisposition plays a significant role in modulating risk, particularly in Asian populations. In Taiwan, the burden of endometrial cancer has increased, highlighting the need to gain a better understanding of the genetic loci associated with this disease. This retrospective case–control study included 373 endometrial cancer patients and 3730 controls from the Taiwan Precision Medicine Initiative. Genotype data were obtained using the TWB 2.0 SNP chip. Statistical analyses were conducted using PLINK and SPSS, with logistic regression models assessing the associations between genetic variants and endometrial cancer risk. In this study, we identified two SNPs, rs17601876 in CYP19A1 and rs2900478 in SLCO1B1, that were associated with endometrial cancer. The AG/GG genotypes of rs17601876 showed a protective effect (OR = 0.743, p = 0.006), while the TA/AA genotypes of rs2900478 exhibited a nonsignificant trend toward an increased risk. Higher BMI, LDL, triglyceride, total cholesterol, and HbA1c, as well as lower HDL, were strongly associated with greater risk. Our findings demonstrated a protective role of rs17601876 in CYP19A1 and further showed its potential impact on estrogen biosynthesis. Genetic factors involved in endometrial cancer risk are an important issue. Further functional studies are needed to validate the present findings. Full article

The COVID-19 pandemic has had a devastating impact, with more than 7 million deaths worldwide. Advanced age and comorbidities partially explain severe cases of the disease, but genetic factors also play a significant role. Genome-wide association studies (GWASs) have been instrumental in identifying loci associated with SARS-CoV-2 infection. Here, we report the results from a >820 K variant GWAS in a COVID-19 patient cohort from the hospitals associated with IIS Biobizkaia. We compared intensive care unit (ICU)-hospitalized patients with non-ICU-hospitalized patients. The GWAS was complemented with an integrated phenotype and genetic modeling analysis using HLA genotypes, a previously identified COVID-19 polygenic risk score (PRS) and clinical data. We identified four variants associated with COVID-19 severity with genome-wide significance (rs58027632 in KIF19; rs736962 in HTRA1; rs77927946 in DMBT1; and rs115020813 in LINC01283). In addition, we designed a multivariate predictive model including HLA, PRS and clinical data which displayed an area under the curve (AUC) value of 0.79. Our results combining human genetic information with clinical data may help to improve risk assessment for the development of a severe outcome of COVID-19. Full article

Extended reality (XR) and collaborative robots are reshaping human–robot interaction (HRI) by introducing novel control methods that enhance user experience (UX). However, human factors such as cognitive workload, usability, trust, and task performance are often underexplored. This study evaluated UX during robotic manipulation tasks under three interaction modalities: manual control, XR-based control at real-time speed (RS), and XR-based control at reduced safety speed (SS). Twenty-one participants performed a series of tasks across three scenarios, where we measured usability, workload, flow state, trust, and agency using a subjective questionnaire adapted from SUS, NASA-TLX, FSS, SoAS, and Trust in Industrial Human–Robot Collaboration Questionnaire, and objective task metrics (completion time, errors, and attempts). Our results reveal that RS-based control modes significantly reduced physical workload and improved usability compared to manual control. RS control at real-time speed enhanced task efficiency but increased error rates during complex tasks, while SS mode mitigated errors at the cost of prolonged completion times. Trust and agency remained stable across all modalities, indicating extended reality technologies do not undermine user confidence. These findings contribute to the field of human–robot collaboration by offering insights regarding efficiency, accuracy, and UX. The results are particularly relevant for industries seeking to optimize safety, productivity, and human-centric robotic systems. Full article

High-precision three-dimensional geological modeling of mining faces is crucial for intelligent coal mining and disaster prevention. Accurate spatial interpolation is essential for building high-quality models. This study focuses on the 25214 workface of the Hongliulin coal mine, addressing challenges in interpolating terrain elevation, stratum thickness, and coal seam thickness data. We evaluate eight interpolation methods (four kriging methods, an inverse distance weighting method, and three radial basis function methods) for terrain and stratum thickness, and nine methods (including the Bayesian Maximum Entropy method) for coal seam thickness, using cross-validation to assess their accuracy. Research results indicate that for terrain elevation data with dense and evenly distributed sampling points, linear kriging achieves the highest accuracy (MAE = 1.01 m, RMSE = 1.20 m). For the optimal interpolation methods of five layers of thickness data with sparse sampling points, the results are as follows: Q₄, spherical kriging (MAE = 2.13 m, RMSE = 2.83 m); N₂b, IDW (p = 2), MAE = 2.08 m, RMSE = 2.44 m; J₂y³, RS-RBF (MAE = 0.89 m, RMSE = 1.05 m); J₂y², TPS-RBF (MAE = 1.96 m, RMSE = 2.25 m); J₂y¹, HS-RBF (MAE = 2.36 m, RMSE = 2.71 m). A method for accurately delineating the zero line of strata thickness by assigning negative values to virtual thickness in areas of missing strata has been proposed. For coal seam thickness data with uncertain data (from channel wave exploration), a soft-hard data fusion interpolation method based on Bayesian Maximum Entropy has been introduced, and its interpolation results (MAE = 0.64 m, RMSE = 0.66 m) significantly outperform those of eight other interpolation algorithms. Using the optimal interpolation methods for terrain, strata, and coal seams, we construct a high-precision three-dimensional geological model of the workface, which provides reliable support for intelligent coal mining. Full article

Background/Objectives: A vitamin D deficiency is prevalent in post-stroke patients and may impair neurological recovery. While observational studies highlight the neuroprotective role of vitamin D, there is limited evidence from interventional studies evaluating its impact on functional recovery during stroke rehabilitation. This study aimed to assess whether daily vitamin D3 supplementation enhances functional recovery. Methods: This prospective, randomized, placebo-controlled, single-blind study included 159 patients (mean age: 62.5 ± 8.4 years) with a first ischemic stroke that were admitted for early rehabilitation. The participants were randomly allocated to receive 2000 IU of vitamin D3 daily (n = 79) or a placebo (n = 80) for six weeks. The functional outcomes were measured using the Barthel index (BI) and modified Rankin scale (mRS) at baseline and after 42 days. The serum 25-hydroxyvitamin D [25(OH)D] and insulin-like growth factor 1 (IGF-1) levels were analyzed. Results: Vitamin D3 supplementation significantly increased the serum 25(OH)D levels (p < 0.001). Supplementation was associated with improved BI scores (β = 0.07, p = 0.006). A higher BMI (β = −0.06, p = 0.033), higher NIHSS scores (β = −0.18, p = 0.036), hypertension, and statin use negatively impacted functional recovery. Anticoagulant use was correlated with higher mRS scores, indicating greater disability (p = 0.04). Conclusions: Vitamin D3 supplementation positively influences the functional outcomes during post-stroke rehabilitation, supporting its potential role in enhancing neuroplasticity and recovery. Larger multi-center trials are needed to confirm these findings and optimize vitamin D supplementation strategies. Full article

Background: Disability and poor quality of life are frequently reported by patients with inflammatory bowel diseases (IBDs). There is an increased interest in the use and development of self-administered questionnaires of patient-reported outcomes including depression symptoms, potentially allowing easier and even remote monitoring of health status and permitting treatment adjustments. Aim: We noticed a significant overlap in some of the parameters evaluated by Beck’s Depression Inventory and the IBD Disk, which led to the idea that the IBD Disk might be a useful and easy-to-use tool to assess the mental state and quality of life of patients with IBD. Our objective was to validate the IBD Disk in measuring depression symptoms, as well as the correlation between IBD Disk scores and patient background and disease activity. Methods: Patients included in this study were asked to complete Beck’s Depression Inventory (BDI) and the IBD Disk. The resulting scores of BDI and IBD Disk were compared and both questionnaires were corelated with the patients’ background and disease activity. Results: Eighty-two patients with IBD, age 43.11 +/− 13.07, 63.4% male, 61.0% with Crohn’s disease and 39.0% with Ulcerative Colitis, were included. The total scores of BDI and IBD Disk significantly correlated (r_s(80) = 0.951, p < 0.001), as well as the overlapping questions. Disease remission was associated with lower total scores in both questionnaires (BDI and IBD Disk) (r_s(80) = 0.559, p < 0.016; r_s(80) = 0.951, p < 0.005, respectively). Conclusions: Our findings suggest that IBD Disk is a useful and easy-to-use tool for screening for depression symptoms and establishing the quality of life of IBD patients. We encourage its routine use in patients during IBD care and follow-up. Full article

Background/Objectives: Tumor necrosis factor alpha (TNF-α) is the key inflammatory cytokine involved in the pathogenesis of inflammatory bowel diseases (IBDs). Anti-TNF-α therapy has been successfully used for IBD treatment, although the therapeutic response differs among patients due to the genetic background. The aim of this study was to investigate whether the presence of single nucleotide polymorphisms (SNPs) on TNFA, TNFRSF1A, and TNFRSF1B genes could affect anti-TNF-α treatment effectiveness in IBD patients. Methods: In this prospective cohort study, 83 European IBD patients treated with infliximab or adalimumab (with or without steroid bridge therapy) as first-line therapy were enrolled. Genomic DNA was extracted from peripheral blood, and TNF-α (rs1800629, rs361525, rs1799724), TNFRSF1A (rs767455), and TNFRSF1B (rs1061622, rs1061624, rs3397, rs976881) SNPs were assessed. Steroid-free remission (SFR) (clinical remission together with steroid interruption) and anti-TNF-α therapy persistence after 12 months of follow-up were evaluated. Patients who stopped anti-TNF-α therapy before the end of follow-up, due to side effects or treatment failure, were defined as discontinuers. Results: A higher frequency of the G/G genotype in rs1800629 and the A/A genotype in rs1061624 was observed in the SFR group compared to non-SFR (97.7% vs. 82.8%; p = 0.025 and 32.6% vs. 10.3%; p = 0.029, respectively). Moreover, carriers of the A/A genotype in rs361525 and the C/C genotype in rs767455 had a lower probability of achieving SFR than wild-type patients (OR = 0.14; 95% CI= 0.03–0.69; p = 0.016 and OR = 0.10; 95% CI = 0.02–0.60; p = 0.012, respectively). Furthermore, an increased frequency of rs1800629 A allele was observed in patients who discontinued treatment compared to completers (27.3% vs. 6.9%; p = 0.033), as well as a high risk of interrupting therapy (HR = 6.47; 95% CI = 1.15–36.38). Conclusions: These results suggest that the evaluation of SNPs in TNF-α, TNFR1A, and TNFR1B genes could improve the management of IBD, leading to more effective, individualized treatment plans and a reduction in healthcare costs associated with ineffective therapies and disease complications. Full article

The regenerative properties of platelet-rich plasma (PRP) result from the high concentration of growth factors, including transforming growth factor beta 1 (TGF-β1). Nevertheless, this form of therapy may not always be effective due to the variability in genetic factors. In this study, the association of TGFB1 gene polymorphisms with the effectiveness of lateral elbow tendinopathy (LET) treatment with PRP was investigated. The effectiveness of therapy was assessed using minimal clinically important difference (MCID) and patient-reported outcome measures (PROM), specifically visual analog scale (VAS), quick version of disabilities of the arm, shoulder, and hand score (QDASH), and patient-rated tennis elbow evaluation (PRTEE) for two years (in weeks 2, 4, 8, 12, 24, 52, and 104). The most effective therapy was noticed in CC rs2278422 genotype carriers, whereas carriers of AA, CC, and CC genotypes (rs12461895, rs4803455, rs2241717) showed more severe pain before therapy. Moreover, the analyses revealed an association of studied polymorphisms with such parameters of blood morphology as eosinophils (EOS), neutrophils (NEU), and monocytes (MONO). In conclusion, genotyping of rs2278422 variant may be a valuable diagnostic method for patient selection for PRP therapy, while genotyping of rs12461895, rs4803455, and rs2241717 polymorphisms may be used for prediction of increased risk of pain sensation. Full article

Groundwater is a critical resource in arid regions such as Khamis Mushayt, located in southwestern Saudi Arabia, where surface water availability is limited. This study integrates various geospatial and environmental datasets to delineate groundwater potential zones (GWPZs) using Geographic Information Systems (GISs) and remote sensing (RS) techniques. Key parameters considered include lithology, slope, drainage density, precipitation, soil type, and vegetation index (NDVI). The influence of each theme and subunit/class on groundwater recharge was evaluated by weighted overlay analysis, including previous studies and field data. The results reveal three distinct groundwater potential zones: poor, moderate, and good. Areas with good groundwater potential account for 8.2% of the study area (16.3 km²) and are predominantly located in the eastern and central parts of the study area, in valleys and low-lying regions with permeable geological formations such as alluvial deposits, supported by higher drainage density and favorable precipitation. Conversely, poor-potential zones represent 27.6% (54.50 km²), corresponding to areas with steep slopes and impermeable rock formations. Moderate-potential zones include places where infiltration is possible but limited, such as gently sloping terrain or regions with slightly broken rock structures, and account for 64.2% (127.0 km²). Validation using existing well data demonstrates strong agreement between the identified potential zones and actual groundwater availability. These findings provide a strong framework for sustainable water resource management, urban planning, and agricultural development in Khamis Mushayt and similar arid regions. Full article

The invasion of exotic plants threatens biodiversity, affecting ecosystem services and ecological processes in native ecosystems. Road construction creates new environments and contributes to the introduction and spread of exotic and invasive plants. This study aimed to evaluate the representation of different functional groups (annual/biannual herbs and grasses, perennial herbs and grasses, shrubs, trees) in the invasion of exotic species within the assemblage on roadside slopes in the Austrocedrus chilensis forest in northwest Andean Patagonia, Argentina. Roadside slopes (RS) and nearby reference areas (RA) were selected, and the cover of native, exotic, and invasive species from the functional groups was evaluated in 1 m² plots using the Braun-Blanquet method. It was found that invasive perennial herbs and grasses predominated on RS, with a cover (19.6 ± 3.0%) higher than that of RA (8.9 ± 1.5%). Agrostis capillaris and Rumex acetosella were the most abundant invasive species. Native shrubs and perennial herbs and grasses were predominant on RS, with Baccharis rhomboidalis and Acaena pinnatifida being the most abundant. This study demonstrates that the roadside slopes of the Austrocedrus chilensis forest harbor invasive exotic species that can invade nearby natural areas. Early detection of these species is important for proper management and control, thus promoting the conservation of biodiversity in forest environments. Full article

Background/Objectives: Lactoferrin, a protein involved in the immune response, plays a significant role in the etiopathogenesis of periodontitis in the general population. This cross-sectional study aims to determine the salivary concentration of lactoferrin in Down syndrome individuals with periodontitis. Methods: A convenience cohort of 76 Down syndrome individuals was established, including 34 with periodontitis, 29 with gingivitis, and 13 with healthy gums. Unstimulated saliva samples were collected and processed to quantify the lactoferrin concentration using the Human Lactoferrin ELISA kit, the total protein concentration (bicinchoninic acid assay [BCA]) using the BCA Protein Assay Kit (Pierce, Rockford, IL, USA), and the lactoferrin/BCA ratio. Additionally, the Lf rs1126478 (140A/G in exon 2, Lys/Arg) genotypes were determined via PCR with restriction fragment length polymorphism (RFLP) analysis using the Earl enzyme. Results: The lactoferrin levels were comparable across patients with periodontitis, gingivitis, and healthy gums (median = 8.20, 6.57, and 7.61 µg/mL, respectively). There were no differences in the BCA levels between the three groups (median = 2.21, 3.17, and 2.08 µg/µL, respectively) nor in the lactoferrin/BCA ratios. The distribution of the Lf 140A/G polymorphism did not show differences concerning periodontal health status. Conclusions: In Down syndrome individuals, salivary lactoferrin and BCA levels are not influenced by the periodontal health condition. Additionally, no significant genetic associations were found with the rs1126478 polymorphism in Down syndrome individuals with and without periodontitis. Lactoferrin production in Down syndrome may not be upregulated in response to periodontal pathogens, which could be indicative of an immune system dysregulation contributing to the early onset and severity of periodontitis in this population. Full article