Search Results (322)

Suicidality is a complex multifactorial phenomenon strongly associated with major depression and other psychiatric disorders. Building on evidence implicating the Major Histocompatibility Complex (MHC) in modulating the immune and inflammatory processes characterizing psychiatric disorders, we hypothesized that specific HLA-DQB1 and HLA-DRB1 variants may contribute to an increased genetic susceptibility to suicidal behavior. Human Leucocyte Antigen (HLA) typing by sequence-specific primers (PCR-SSP) was performed on a sample of 196 individuals, including 70 non-lethal suicide attempters, 28 cases of completed suicide, and matched controls. The *HLA-DQB1 02/06 (RR 1.60, CI95% 1.22–2.09, p = 0.03 *) and *HLA-DRB1 11/15 (RR 1.70, CI95% 1.3–2.24, p = 0.04 *) genotypes and the HLA-DRB115~DQB103 haplotype (RR 1.58, CI95% 1.22–2.04, p = 0.03 *) were found to favor suicidal behavior. Psychosocial determinants associated with an increased suicidal risk were bereavement of close relatives (linked with HLA-DQB1*02), memory dysfunction (HLA-DQB1*06), disillusionment (HLA-DRB1*07 and HLA-DRB1*15), and self-harm (HLA-DRB1*15). Our findings support the contributory role of HLA polymorphisms in shaping susceptibility to suicidal behavior. Full article

Background: Traditional parameters such as bone-to-implant contact percentage (BIC%) provide only static insights into implant integration and do not reflect the temporal dynamics of bone regeneration. The concept of Dynamic Regenerative Balance (DRB) was introduced to represent the biological equilibrium between bone formation and graft resorption. The break-even point serves as a measurable approximation of this equilibrium. This study aimed to illustrate the usefulness of the break-even point in expressing the balance between graft resorption and new bone formation, rather than to define definitive values for specific biomaterials. Methods: Four preclinical studies on sinus floor elevation in rabbits were selected. Each reported histomorphometric data on new bone formation and graft resorption at two or more time points. Six biomaterials were analyzed: autogenous bone, Bio-Oss^®, Bio-Oss Collagen^®, Gen-Os^®, Maxresorb^®, and Maxresorb^® Inject. The break-even point was calculated by linear extrapolation as the time at which new bone equals residual graft percentage. Results: The break-even point varied significantly among biomaterials (expressed in days/area %): autogenous bone reached equilibrium fastest (18.4 days/13.5%), followed by Gen-Os^® (40.4 d/19.1%). Bio-Oss Collagen^® (62.3 d/28.3%), Maxresorb^® (73.9 d/36.4%), and Maxresorb^® Inject (96.1 d/34.1%). For Bio-Oss^®, it occurred at 81.8 days (33.6%) in one study, while in another, it was not reached within 6 months. These differences reflect distinct regenerative kinetics and resorption profiles among materials. Conclusions: The break-even point offers a simple and informative parameter to describe the balance between graft resorption and new bone formation, providing a useful complement to conventional histomorphometric measures and a framework for future studies. Full article

Mesenchymal stromal cells (MSCs) exert their immunoregulatory properties after licensing by inflammatory signaling cues, e.g., interferon (IFN)-γ. However, MSCs licensing by IFN-γ may result in increased expression of human leukocyte antigen (HLA) class II, which is related to rapid cell elimination, impairment of their immunosuppressive properties, and patient sensitization. The aim of this study was to evaluate the impact of IFN-γ on mediated immunoregulation and HLA class II expression. In this study, Wharton’s jelly (WJ) MSCs were isolated from human umbilical cords. Well-defined WJ-MSCs were submitted to IFN-γ exposure, and after 96 h, evaluation of biomolecule secretion and HLA class II expression was performed. Typing of HLA alleles using a next-generation sequencing (NGS) platform was performed. IFN-γ-primed WJ-MSCs secreted a high amount of immunoregulatory biomolecules, while elevated expression of HLA-DRB1 was observed. Analyses the NGS results showed the possibility of WJ-MSCs cluster formation based on their frequency of detected HLA alleles and immunoregulatory potential. Taking into consideration that IFN-γ-primed WJ-MSCs express HLA class II alleles, it is suggested that the HLA histocompatibility between allogeneic donor and recipient should be strongly considered to acquire the most beneficial outcome for the MSCs therapeutic strategy. Full article

Background/Objectives: Human leukocyte antigens (HLAs) are major determinants of successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). Their alleles are closely linked to outcomes, even in HLA-identical sibling donor (ISD) HSCT. This retrospective study analyzed the impact of HLA alleles on HLA-ISD HSCT outcomes in Omani patients. Methods: Data were collected for a heterogenous cohort of patients registered at the Sultan Qaboos University Hospital (SQUH), who underwent HLA-ISD HSCT from 2012 to 2022 (n = 153). HSCT outcomes, namely acute GVHD (aGVHD), chronic GVHD (cGVHD), chimerism status (complete or mixed) at 6 to 12 months after HSCT, neutrophil and platelet engraftment time, and patient five-year overall survival, were included. Low-resolution HLA-typing records were collected for five HLA loci: HLA-A, B, C, DRB1 and DQB1. GVHD and chimerism were analyzed by logistic regression analysis. Platelet and neutrophil engraftment times were assessed by Mann–Whitney tests. Patient overall survival was evaluated by the Kaplan–Meier model and Log-rank testing. At a 95% confidence interval, the p-value threshold was corrected using Bonferroni correction. Results: The incidence rates of aGVHD and cGVHD from all grades were 16% and 15%, respectively. Although no association between HLA alleles or any of the investigated outcomes was identified, survival curve analyses indicated a significant protective effect of HLA-DQB1*05 (p = 0.01). Patients carrying this allele had a better-estimated 5-year overall survival (90%) than did DQB1*05 negative patients (68%). Conclusions: This study suggests that HLA-DQB1*05 in the Omani population could have an impact on overall survival and might be a predictive biomarker. Further studies on a larger scale in other regional populations are needed to validate our findings and explore the underlying mechanism. Full article

To address the limitations in the accuracy of current cerebral cortex structure segmentation methods, this study proposes an automatic segmentation network based on dynamic recalibration and region awareness. The network is an improved version of the classic U-shaped architecture, incorporating a Dynamic Recalibration Block (DRB) and a Region-Aware Block (RAB). The DRB enhances important feature channels by extracting global feature information across channels, computing the significance weights via a two-layer fully connected network, and applying these weights to the original feature maps for dynamic feature reweighting. Meanwhile, the RAB integrates spatial positional information and captures both global and local context across multiple dimensions. It recalibrates features using dimension-specific weights, enabling region-aware feature association and complementing the DRB’s function. Together, these components enable efficient and accurate segmentation of brain structures. The proposed DRA-Net model effectively overcomes the accuracy–efficiency trade-off in cortical segmentation through multi-scale feature fusion, dual attention mechanisms, and deep feature extraction strategies. Experimental results demonstrate that DRA-Net achieves an average Dice score of 91.35% across multiple datasets, outperforming segmentation atlases based on methods such as U-Net, QuickNAT, and FastSurfer. Full article

This study investigated the role of molecular mimicry in the context of autoimmunity associated with viral infection, using SARS-CoV-2 as a model system. A bioinformatic analysis was performed to identify sequence homologies between the SARS-CoV-2 Spike (S) protein and the human proteome, with a specific focus on immunogenic regions to assess potential cross-reactivity. The analysis revealed homologous regions between the viral S protein and several human proteins, including DAAM2, CHL1, HAVR2/TIM3, FSTL1, FHOD3, MYO18A, EMILIN3, LAMP1, and αENaC, which are predicted to be recognizable by B-cell receptors. Such recognition could potentially lead to the production of autoreactive antibodies, which can contribute to the development of autoimmune diseases. Furthermore, the study examined potential autoreactive CD4+ T-cell responses to human protein autoepitopes that could be presented by HLA class II molecules. Several HLA class II genetic variants were computationally associated with a higher likelihood of cross-reactive immune reactions following COVID-19, including HLA-DPA1*01:03/DPB1*02:01, HLA-DPA1*02:01/DPB1*01:01, HLA-DPA1*02:01/DPB1*05:01, HLA-DPA1*02:01/DPB1*14:01, HLA-DQA1*01:02/DQB1*06:02, HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*07:01, and HLA-DRB1*15:01. Additionally, seven T helper cell autoepitopes (YSEILDKYFKNFDNG, ERTRFQTLLNELDRS, AERTRFQTLLNELDR, RERKVEAEVQAIQEQ, NAINIGLTVLPPPRT, PQSAVYSTGSNGILL, TIRIGIYIGAGICAG) were identified that could be implicated in autoimmune T-cell responses through presentation by class II HLA molecules. These findings highlight the utility of viral B- and T-cell epitope prediction for investigating molecular mimicry as a possible mechanism in virus-associated autoimmunity. Full article

To resolve the conflict between global structure modeling and local detail preservation in image super-resolution, we propose SwinT-SRGAN, a novel framework integrating Swin Transformer with GAN. Key innovations include: (1) A dual-path generator where Transformer captures long-range dependencies via window attention while CNN extracts high-frequency textures; (2) An end-to-end Detail Recovery Block (DRB) suppressing artifacts through dual-path attention; (3) A triple-branch discriminator enabling hierarchical adversarial supervision; (4) A dynamic loss scheduler adaptively balancing six loss components (pixel/perceptual/high-frequency constraints). Experiments on CelebA-HQ and Flickr2K demonstrate: (1) Very good performance (max gains: 0.71 dB PSNR, 0.83% SSIM, 4.67 LPIPS reduction vs. Swin-IR); (2) Ablation studies validate critical roles of DRB. This work offers a robust solution for high-frequency-sensitive applications. Full article

The global impact of COVID-19 was staggering, with millions of cases and related mortality reported worldwide. Genetic variations play a significant role in determining an individual’s susceptibility to SARS-CoV-2 infection and progress to severe disease. This pilot study provides an experimental approach using WES to identify certain rare and novel genetic variants that might affect an individual’s susceptibility to the risk of SARS-CoV-2 infection, offering an initial exploration of these genetic variants. In the study cohort with 16 patients, the mortality rate was higher in male patients due to severe disease. There was a substantial burden of comorbidity, including hypertension, ischemic heart disease, and T2DM, conditions which independently increase the risk of adverse outcomes in COVID-19 patients. A total of 4478 variants were identified, distributed across 322 genes within the cohort. The majority of these variants were missense substitutions along with frameshift variants, inframe insertions/deletions (indels), and nonsense variants. The variants were further categorized by types to include single-nucleotide polymorphisms (SNPs), deletions (DEL), and insertions (INS). The gene with the highest number of variants was HLA-DRB1, followed by HLA-B, ABO, HPS4, and SP110 displaying both common polymorphisms and rare variants. Moreover, the HLA-B gene exhibited the highest number of rare candidate variants, followed by AK2, IRF7, KMT2D, TAP1, and HLA-DRB1. Several genes harbored multiple novel variants, including TAP1, AK2, G6PC3, HLA-B, IL12RB2, and ITGB2. The frequencies of the identified variants were found to be either zero or extremely low (below 1% threshold) in the Middle Eastern or in the overall combined population, suggesting that these are indeed rare and do not represent common indigenous polymorphisms. Functional enrichment analysis of the constructed protein–protein interaction network in our preliminary findings revealed that the identified genes are primarily enriched in pathways associated with immune deficiency and DNA repair. This initial exploration of genetic variants in COVID-19 susceptibility provides a foundation for future large-scale studies. Full article

Background: It has been shown that human leucocyte antigen (HLA) alleles are related to certain diseases. Some alleles were associated with alloimmunization in individuals with thalassemia. In this study, we studied the distribution of HLA alleles among beta thalassemia (BT) patients compared to healthy controls. Material and Methods: The HLA results of 100 patients with BT and 100 healthy controls were obtained for the study. The HLA-A, -B and -DRB1 tissue typing were performed at the laboratory. The low-resolution sequence-specific primer (SSP)–polymerase chain reaction (PCR-SSP) (Olerup HLA-A,B,DR typing kit, USA) and sequence-specific oligonucleotide (SSO)–PCR (LABType HLA-A,B,DR kit, ABD) methods were performed using the Luminex genotyping kits. All related data were retrospectively analyzed. Results: One in five patients (21%) underwent hematopoietic stem cell transplantation (HSCT). Patients with HSCT had significantly lower frequency of HLA-B *14, HLA-DRB1 *11 and HLA-DRB1 *16 alleles and had a higher frequency of HLA-A *66, HLA-B *41, HLA-B *55, HLA-DRB1 *3 alleles compared to patients without HSCT (p < 0.05). The HLA-A *3, HLA-B *41 and HLA-B *55 alleles were more commonly seen in HSCT patients compared to the healthy group (p = 0.04). Female patients showed a higher frequency of HLA-B *58 and HLA-DRB1 *4 alleles (p = 0.04). Conclusions: This study demonstrated that HLA-B *41 and -B *55 alleles were closely related to HSCT among BT patients. It might be considered that the variance in certain HLA-B alleles in BT patients might cause difficulty in finding a matched donor in this limited population. Full article

Aero-engines, as complex systems integrating numerous rotating components and accessory equipment, operate under harsh and demanding conditions. Prolonged use often leads to frequent mechanical wear and surface defects on accessory parts, which significantly compromise the engine’s normal and stable performance. Therefore, accurately and rigorously identifying failure modes is of critical importance. In this study, failure modes are categorized into notches, scuffs, and scratches based on original bearing structure images. The YOLOv8 architecture is adopted as the base framework, and a Dilated Reparameterization Block (DRB) is introduced to enhance the Dilation-Wise Residual (DWR) module. This structure uses a large convolutional kernel to capture fragmented and sparse features in wear images, ensuring a wide receptive field. The concept of structural reparameterization is incorporated into DWR to improve its ability to capture detailed target information. Additionally, the standard convolutional layer in the head of the improved DWR-DRB structure is replaced by Spatial-Depth Convolution (SPD-Conv) to reduce the loss of wear morphology and enhance the accuracy of fault feature extraction. Finally, a fusion structure combining Focaler and MPDIoU is integrated into the loss function to leverage their strengths in handling imbalanced classification and bounding box geometric regression. The proposed method achieves effective recognition and diagnosis of mechanical wear fault patterns. The experimental results demonstrate that, compared to the baseline YOLOv8, the proposed method improves the mAP50 for fault diagnosis and recognition from 85.4% to 91%. Full article

Bovine leukemia virus (BLV) is widespread globally and causes economic losses in the cattle industry. BoLA-DRB3 is a polymorphic gene associated with the BLV proviral load (PVL), which correlates with disease progression and transmission risk. However, the distribution of BoLA-DRB3 alleles in semen and their potential impact on the PVL of progeny remain unclear. Here, we investigated whether BLV susceptibility linked to BoLA-DRB3 alleles in semen is inherited by progeny. We analyzed 178 commercial semen samples from Japanese Black sires and identified 20 BoLA-DRB3 alleles and 70 genotypes. The susceptible allele DRB3*016:01 was the most frequent (26.4%), whereas resistant alleles DRB3*011:01 (5.3%) and DRB3*009:02 (0.6%) were rare. Subsequently, we collected blood samples from 200 progeny produced by artificial insemination using 36 of the 178 semen samples. Progeny derived from semen carrying at least one susceptible allele and no resistant alleles had significantly higher PVL in the blood than those derived from semen containing at least one resistant allele. These findings demonstrate that BLV susceptibility is inherited via BoLA-DRB3 alleles in semen and highlight the potential of BoLA-DRB3 alleles as valuable markers in breeding strategies aimed at mitigating BLV infection and transmission. Full article

The endangered Bengal slow loris (Nycticebus bengalensis) relies heavily on captive/rescue populations for conservation. This study investigated the critical link between Major Histocompatibility Complex (MHC) class II DRB1 exon 2 (DRB1e2) genetic variation and gut microbiota in 46 captive individuals, aiming to improve ex situ management. Using standardized conditions across three enclosure types, we characterized DRB1e2 polymorphism via targeted sequencing and analyzed fecal microbiota using 16S rRNA gene amplicon sequencing. Results demonstrated that high DRB1e2 polymorphism significantly reduced microbial community evenness. Specific genotypes showed distinct microbial associations: G9 strongly correlated with beneficial short-chain fatty acid producers like Fructobacillus, and G2 positively correlated with Bifidobacterium spp., while G2, G3, and G4 correlated negatively with Buchnera (a nutrient-provisioning symbiont). Genotypes and polymorphism collectively explained 9.77% of microbiota variation, exceeding the weaker (5.15%), though significant, influence of enclosure type on β-diversity. These findings reveal that host DRB1e2 variation is a primary driver shaping gut microbiota structure and taxon abundance in captive slow lorises, providing evidence for MHC-mediated host–microbe co-adaptation. This offers a genetically informed framework for optimizing conservation strategies, such as tailoring diets or probiotics to specific genotypes, to enhance gut health and population viability. Full article

Concomitant sensitisation to non-specific lipid transfer proteins (nsLTPs) from olive pollen (Ole e 7) and peach (Pru p 3) has been observed in the south of Spain. In the search for reasons to explain this observation, we studied a potential causal relationship between Human Leukocyte Antigen (HLA) molecules and nsLTP sensitisation. For this purpose, eighteen Ole e 7-monosensitised (MONOLE) patients, 22 Pru p 3-monosensitised (MONPRU) patients, and 22 bisensitised (BI) patients were genotyped for HLA class II alleles. Complementarily, T-cell epitopes were predicted with the Immune Epitope Database analysis tool to test HLA epitope presentation. Our results showed a significant increase in DRB1*11 and DQB1*03 frequencies in MONPRU patients and DRB1*04 frequency in MONOLE patients. Additionally, T-cell epitope analysis revealed high binding affinity between the predicted Pru p 3 epitopes and DRB1*11 and between the predicted Ole e 7 epitopes and DRB1*04, suggesting that presentation of these epitopes may be favoured and predisposing individuals to sensitisation. Conversely, low DQB1*05 frequency and poor binding ability of predicted epitopes from both nsLTPs postulated this allele as a possible protective factor to sensitisation. Variations in the binding affinity between nsLTP epitopes and HLA molecules may underlie individual susceptibility to nsLTP allergy. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by the immune system attacking the central nervous system, leading to demyelination and neurodegeneration. This work investigates the relationship between specific human leukocyte antigen (HLA) polymorphisms and MS, aiming to reveal the immunogenetic background of this disease for more individualized management approaches. This study employed a case–control design, analyzing HLA allele frequencies in 179 MS patients and 200 control subjects using next-generation sequencing, The key findings indicate significant associations between several HLA Class I and II alleles and MS, including HLA-B*35:03:01:03, HLA-C*04:01:01:14, HLA-DRB1*15:01:01:26, and HLA-DQA1*05:05:01:02. These findings emphasize the critical role of HLA molecules in MS Romanian patients. Full article

Rapid socio-economic development and the impact of human activities have exerted tremendous pressure on the groundwater system of the Dawen River Basin (DRB), the largest tributary in the middle and lower reaches of the Yellow River. Hydrochemical studies on the DRB have largely centered on the upstream Muwen River catchment and downstream Dongping Lake, with some focusing solely on karst groundwater. Basin-wide evaluations suggest good overall groundwater quality, but moderate to severe contamination is confined to the lower Dongping Lake area. The hydrogeologically complex mid-reach, where the Muwen and Chaiwen rivers merge, warrants specific focus. This region, adjacent to populous areas and industrial/agricultural zones, features diverse aquifer systems, necessitating a thorough analysis of its hydrochemistry and origins. This study presents an integrated hydrochemical, isotopic investigation and EWQI evaluation of groundwater quality and formation mechanisms within the multiple groundwater types of the central DRB. Central DRB groundwater has a pH of 7.5–8.2 (avg. 7.8) and TDSs at 450–2420 mg/L (avg. 1075.4 mg/L) and is mainly brackish, with Ca²⁺ as the primary cation (68.3% of total cations) and SO₄²⁻ (33.6%) and NO₃⁻ (28.4%) as key anions. The Piper diagram reveals complex hydrochemical types, primarily HCO₃·SO₄-Ca and SO₄·Cl-Ca. Isotopic analysis (δ²H, δ¹⁸O) confirms atmospheric precipitation as the principal recharge source, with pore water showing evaporative enrichment due to shallow depths. The Gibbs diagram and ion ratios demonstrate that hydrochemistry is primarily controlled by silicate and carbonate weathering (especially calcite dissolution), active cation exchange, and anthropogenic influences. EWQI assessment (avg. 156.2) indicates generally “good” overall quality but significant spatial variability. Pore water exhibits the highest exceedance rates (50% > Class III), driven by nitrate pollution from intensive vegetable cultivation in eastern areas (Xiyangzhuang–Liangzhuang) and sulfate contamination from gypsum mining (Guojialou–Nanxiyao). Karst water (26.7% > Class III) shows localized pollution belts (Huafeng–Dongzhuang) linked to coal mining and industrial discharges. Compared to basin-wide studies suggesting good quality in mid-upper reaches, this intensive mid-reach sampling identifies critical localized pollution zones within an overall low-EWQI background. The findings highlight the necessity for aquifer-specific and land-use-targeted groundwater protection strategies in this hydrogeologically complex region. Full article