Search Results (678)

Background/Objectives: The management of patients with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL) is a real challenge. Studying endometrial proliferation and vascularization by ultrasound during the embryo implantation window is an option for investigating these failures. This approach involves measuring the endometrial volume, the uterine arteries pulsatility index (PI), and the sub-endometrial flow index (VFI). Methods: The aim of our single-center retrospective study was to evaluate the benefit of treatment with pentoxifylline (400 mg twice daily) and alpha-tocopherol (500 IU twice daily), which was administered for at least 3 months. This study included 52 patients presenting abnormal ultrasound criteria, i.e., endometrial volume less than 2 cm³ and/or PI greater than 2.8 and/or VFI less than 0.25. Results: After treatment, we observed a significant increase in endometrial volume of 0.32 cm³ (p = 0.0054), as well as a significant increase in VFI of 0.49 (p = 0.041) in comparison to the control group. After treatment, the PI of the right uterine artery decreased significantly by 0.25 (p = 0.029) and the PI of the left uterine artery decreased by 0.27, but not significantly. In addition, our study showed that the clinical pregnancy rate (CPR) was more improved in the treated group compared to controls. Conclusions: Our study showed a promising benefit of pentoxifylline and alpha-tocopherol on endometrial properties; this needs to be corroborated by a larger prospective study. Full article

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population. Full article

Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has become an intermittent yet economically significant disease of wheat in the Upper Midwest during the last decade. Because chemical and cultural controls remain ineffective, breeders rely on developing resistant varieties, yet visual ratings in inoculated nurseries are labor-intensive, subjective, and time-consuming. To accelerate this process, we combined unmanned-aerial-vehicle hyperspectral imaging (UAV-HSI) with a carefully tuned chemometric workflow that delivers rapid, objective estimates of disease severity. Principal component analysis cleanly separated BLS, leaf rust, and Fusarium head blight, with the first component explaining 97.76% of the spectral variance, demonstrating in-field pathogen discrimination. Pre-processing of the hyperspectral cubes, followed by robust Partial Least Squares (RPLS) regression, improved model reliability by managing outliers and heteroscedastic noise. Four variable-selection strategies—Variable Importance in Projection (VIP), Interval PLS (iPLS), Recursive Weighted PLS (rPLS), and Genetic Algorithm (GA)—were evaluated; rPLS provided the best balance between parsimony and accuracy, trimming the predictor set from 244 to 29 bands. Informative wavelengths clustered in the near-infrared and red-edge regions, which are linked to chlorophyll loss and canopy water stress. The best model, RPLS with optimal preprocessing and variable selection based on the rPLS method, showed high predictive accuracy, achieving a cross-validated R² of 0.823 and cross-validated RMSE of 7.452, demonstrating its effectiveness for detecting and quantifying BLS. We also explored the spectral overlap with Sentinel-2 bands, showing how UAV-derived maps can nest within satellite mosaics to link plot-level scouting to landscape-scale surveillance. Together, these results lay a practical foundation for breeders to speed the selection of resistant lines and for agronomists to monitor BLS dynamics across multiple spatial scales. Full article

Modern cloud-based Internet of Things (IoT) infrastructures face increasingly sophisticated and diverse cyber threats that challenge traditional detection systems in terms of scalability, adaptability, and explainability. In this paper, we present (H-DIR)², a hybrid entropy-based framework designed to detect and mitigate anomalies in large-scale heterogeneous networks. The framework combines Shannon entropy analysis with Associated Random Neural Networks (ARNNs) and integrates semantic reasoning through RDF/SPARQL, all embedded within a distributed Apache Spark 3.5.0 pipeline. We validate (H-DIR)² across three critical attack scenarios—SYN Flood (TCP), DAO-DIO (RPL), and NTP amplification (UDP)—using real-world datasets. The system achieves a mean detection latency of 247 ms and an AUC of 0.978 for SYN floods. For DAO-DIO manipulations, it increases the packet delivery ratio from 81.2% to 96.4% (p < 0.01), and for NTP amplification, it reduces the peak load by 88%. The framework achieves vertical scalability across millions of endpoints and horizontal scalability on datasets exceeding 10 TB. All code, datasets, and Docker images are provided to ensure full reproducibility. By coupling adaptive neural inference with semantic explainability, (H-DIR)² offers a transparent and scalable solution for cloud–IoT cybersecurity, establishing a robust baseline for future developments in edge-aware and zero-day threat detection. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is the seventh most prevalent cancer worldwide. Despite intensive treatments, the prognosis is unfavorable. Recently, immunotherapy has emerged as a novel therapeutic strategy, and several immune-checkpoint blockade blockers provide clinical benefits to patients. However, the response rates of these antibodies are limited, and there is a pressing need to increase the efficacy of immunotherapy for HNSCC patients. Epigenetic treatment is emerging as a promising combination approach able to change immune-related gene signatures in tumors and potentially increase the efficacy of immunotherapy. In this study, we sought to elucidate further immune-related gene signatures altered through epigenetic treatment and explored whether epigenetic drugs can increase the efficacy of anti PD-L1 treatment in HNSCC. Methods: At first, we treated six HNSCC cell lines with 5-azacytidine and romidepsin and analyzed gene expression patterns by microarray and TaqMan arrays analysis. We then explored the therapeutic efficacy of epigenetic treatment with an anti PD-L1 antibody in a syngeneic mouse model. Results: Our microarray analysis revealed the differential expression of immune-related genes in cell lines treated with epigenetic drugs, as compared to untreated controls. Most importantly, these array analyses showed a significant change in the transcription of some immune related-and biologically relevant genes, such as HLA-DRA, HMOX1, IFI6, IL12A, IRF7, NFKB2, RPL3L, STAT1, STAT3, CSF1, CSF2, FAS, OASL, and PD-L1, after epigenetic treatment. Furthermore, the combination of epigenetic treatment with an anti PD-L1 antibody significantly suppressed tumor growth in a syngeneic mouse model. In vivo tumors treated with epigenetic drugs expressed higher STAT1, STAT3, and PD-L1 compared to untreated tumors. Increased PD-L1 expression is postulated to increase the efficacy of anti PD-L1 treatment. Conclusions: Our results highlight the importance of a combinational strategy employing both epigenetic and immunotherapy in HNSCC. Full article

Background: Rosa L. is an economically significant genus with species that are notable for their rich content of phenolic compounds. Despite its importance, the taxonomy of Rosa remains complex and unresolved. Methods: We sequenced, assembled, and performed comparative analyses of the complete plastomes of four Rosa species: R. acicularis, R. iliensis, R. laxa, and R. spinosissima. In addition to the plastome, we sequenced the nuclear ribosomal internal transcribed spacer (ITS). Results: Plastomes ranged in size from 157,148 bp (R. iliensis) to 157,346 bp (R. laxa). In each plastome, 136 genes were annotated, comprising 90 protein-coding, 38 tRNA, and eight rRNA genes. A total of 905 SSRs were identified, ranging from 224 (R. acicularis) to 229 in R. spinosissima. Nine highly variable regions were detected, including two coding genes (rps16 and ycf1) and seven intergenic spacers (ycf3-trnS(GGA), trnT(UGU)-trnL(UAA), rpl14-rpl16, trnR(UCU)-atpA, trnD(GUC), trnG(UCC)-trnfM(CAU), and psbE-petL). Maximum Likelihood (ML) phylogenetic analyses based on the complete plastome and ycf1 gene datasets consistently resolved the Rosa species into three major clades, with strong bootstrap support. In contrast, the ML tree based on ITS resolved species into four clades but showed lower bootstrap values, indicating reduced resolution compared to plastid datasets. Conclusions: Our findings underscore the value of plastome data in resolving phylogenetic relationships within the genus Rosa. Full article

Spondyloepimetaphyseal dysplasia type Isidor-Toutain (RPL13-SEMD) is an autosomal dominant skeletal dysplasia caused by heterozygous pathogenic variants in the RPL13 gene, encoding the ribosomal protein eL13. To date, 13 pathogenic variants in RPL13 have been reported, all clustering within intron 5 and exon 6, suggesting this hotspot region is critical for the function of ribosomes in skeletal tissues. Here, we present clinical and radiological characteristics of seven individuals, five children and two adults, from four unrelated families with RPL13-SEMD caused by two novel variants (c.477+5G>C and c.539_541del) and two previously reported variants (c.477+1G>C and c.548G>A) in RPL13. RNA analysis demonstrated that c.477+5G>C leads to a 54-nucleotide extension of exon 5, resulting in an 18-amino acid insertion. The phenotypic spectrum ranged from mild manifestations, such as Blount-like tibial deformity without significant short stature or Perthes-like femoral epiphyseal changes, to severe skeletal deformities with disproportionate short stature, accompanied by extraskeletal features (e.g., penoscrotal hypospadias, coccygeal abnormalities). For the first time, we describe Blount-like tibial deformity as a feature of this dysplasia, which resolves with age. Our study provides additional insights into the clinical, radiological, and genotypic features of RPL13-SEMD through detailed analysis of patients and their affected relatives. Full article

The molecular identification of valuable genotypes is an important problem of germplasm management. In this study, we evaluated the potential of 11 universal primer pairs for the DNA barcoding of locally derived cultivars of subtropical crops (actinidia, feijoa, citrus, and tea). A total of 47 accessions (elite cultivars, forms, and breeding lines) of these four genera were included in the study. The efficiency of the following universal primers was assessed using Sanger sequencing: ITS-p5/ITS-u4, ITS-p5/ITS-u2, ITS-p3/ITS-u4, 23S,4.5S&5S, 16S, petB/petD, rpl23/rpl2.l, rpl2 intron, rpoC1 intron, trnK intron, and trnE-UUC/trnT-GUU. Among these primers, trnE-UUC/trnT-GUU showed greater intraspecific polymorphisms, while rpl2 intron and 16S displayed the lowest polymorphism levels in all crops. In addition, the 23S,4.5S & 5S, and rpoC1 intron were efficient for intraspecific analysis of tea and actinidia species. Using five efficient chloroplast primers, a total of 22/6 SNPs/InDels were observed in tea accessions, 45/17 SNPs/InDels in actinidia, 23/3 SNPs/InDels in mandarins, and 5/4 SNPs/InDels in feijoa. These results will be useful for the further development of DNA barcodes of related accessions. Full article

Immunological factors have gained growing recognition as key contributors to recurrent pregnancy loss (RPL) after in vitro fertilization (IVF), representing a major challenge in reproductive medicine. RPL affects approximately 1–2% of women trying to conceive naturally and up to 10–15% of those undergoing IVF, where overall success rates remain around 30–40% per cycle. An imbalance in maternal immunological tolerance toward the semi-allogeneic fetus during pregnancy may lead to miscarriage and implantation failure. IVF-related ovarian stimulation and embryo modification offer additional immunological complications that can exacerbate existing immune dysregulation. Recent advances in reproductive immunology have significantly deepened our understanding of the immune mechanisms underlying RPL following IVF, particularly highlighting the roles of regulatory T cells (T regs), natural killer cells, cytokine dysregulation, and disruptions in maternal–fetal immune tolerance. In order to better customize therapies, this evaluation incorporates recently discovered immunological biomarkers and groups patients according to unique immune profiles. Beyond conventional treatments like intralipid therapy and intravenous immunoglobulin, it also examines new immunomodulatory medications that target certain immune pathways, such as precision immunotherapies and novel cytokine modulators. We also discuss the debates over immunological diagnostics and therapies, such as intralipid therapy, intravenous immunoglobulin, corticosteroids, and anticoagulants. The heterogeneity of patient immune profiles combined with a lack of strong evidence highlights the imperative for precision medicine to improve therapeutic consistency. Novel indicators for tailored immunotherapy and emerging treatments that target particular immune pathways have encouraging opportunities to increase pregnancy success rates. Improving management approaches requires that future research prioritize large-scale clinical trials and the development of standardized immunological assessments. This review addresses the immunological factors in RPL during IVF, emphasizing underlying mechanisms, ongoing controversies, and novel therapeutic approaches to inform researchers and clinicians. Full article

DNA barcoding of intraspecific diversity of agricultural crops is important to develop the genetic passports of valuable genotypes and cultivars. The advantage of DNA-barcoding as compared to traditional genotyping of cultivars is that the procedure can be unified and applied for the broad range of accessions. This not only makes it cost efficient, but also allows to develop open access genetic databases to accumulate information of the world’s germplasm collections of different crops. In this regard, the aim of the review was to analyze the latest research in this field, including the selection of loci, universal primers, strategies of amplicons analysis, bioinformatic tools, and the development of databases. We reviewed the advantages and disadvantages of each strategy with the focus of cultivars identification. The data indicates that following chloroplast loci are the most prominent for the intraspecific diversity analysis: (trnE-UUC/trnT-GUU, rpl23/rpl2.l, psbA-trnH, trnL-trnF, trnK, rpoC1, ycf1-a, rpl32-trnL, trnH-psbA and matK). We suggest that the combination of three or four of these loci can be a sufficient DNA barcode for cultivar-level identification. This combination has to be selected for each crop. Advantages and disadvantages of different approaches of amplicons analysis are discussed. The bioinformatic tools and databases for the plant barcoding are reviewed. This review will be useful for selecting appropriate strategies for barcoding of intraspecific diversity of agricultural crops to develop genetic passports of valuable cultivars in germplasm collections worldwide. Full article

Immunotherapy has emerged as a key modality in cancer treatment, yet its effectiveness varies significantly among patients, often due to the metabolic stress imposed by the tumor microenvironment. Hypoxia, a major factor in the tumor microenvironment, results from the high metabolic rate of tumor cells and inadequate vascularization, impairing immune cells’ function and potentially influencing gene expression profiles. Despite the widespread use of quantitative real-time PCR in immunological studies, to the best of our knowledge, data on reference gene stability in human peripheral blood mononuclear cells under hypoxic conditions is limited. In our study, we assessed the expression stability of commonly used reference genes (S18, HPRT, IPO8, RPL13A, SDHA, PPIA, and UBE2D2) in both non-stimulated and CD3/CD28-activated peripheral blood mononuclear cells cultured under normoxic, hypoxic (1% O₂), and chemically induced hypoxic conditions for 24 h. Analysis using four different algorithms—delta Ct, geNorm, NormFinder, and BestKeeper—identified RPL13A, S18, and SDHA as the most suitable reference genes for human peripheral blood mononuclear cells under hypoxic conditions. In contrast, IPO8 and PPIA were found to be the least suitable housekeeping genes. The study provides essential insights into the stability of reference genes in peripheral blood mononuclear cells under hypoxic conditions, a critical but understudied aspect of immunological research. Given the significant impact of hypoxia on T cell metabolism and function in the tumor microenvironment, selecting reliable reference genes is crucial for accurate gene expression analysis. Our findings will be valuable for future studies investigating hypoxia-driven metabolic reprogramming in immune cells, ultimately contributing to a better understanding of T cell responses in cancer immunotherapy. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more consecutive pregnancy losses before 20 weeks of gestation, encompassing both embryonic and fetal losses. Although previous studies have provided substantial insights into RPL, the causes in many cases remain unexplained. This lack of information has prompted continued investigation into various risk factors, including those identified through next-generation sequencing (NGS). In the present study, whole-exome sequencing (WES) was used to identify genes potentially associated with RPL and infertility, which may serve as novel biomarkers. Confirmation of the association between these genetic variants and RPL may help to develop functional biomarkers for early diagnosis. The findings revealed that the PCSK5 rs1110222 G > A polymorphism was significantly associated with a reduced risk of RPL. In contrast, the MUC2 rs10902088 C > T polymorphism was associated with an increased risk of RPL among women with more than four pregnancy losses. Notably, the A-T allele combination of PCSK5 rs1110222 G > A and MUC2 rs10902088 C > T showed a significant association with a decreased risk of RPL relative to the G-C combination. In conclusion, this study confirms that the PCSK5 rs1110222 G > A and MUC2 rs10902088 C > T polymorphisms are genetically associated with the prevalence of RPL in Korean women. Full article

Rhododendron purdomii Rehder & E. H. Wilson (Ericaceae) is a threatened ornamental and medicinal shrub or small tree species primarily distributed in the Qinling-Daba Mountains of Central China. To facilitate its conservation and utilization, the complete chloroplast genome of Rh. purdomii was sequenced, assembled, and characterized. The cp genome exhibited a typical quadripartite structure with a total length of 208,062 bp, comprising a large single copy (LSC) region of 110,618 bp, a small single copy (SSC) region of 2606 bp, and two inverted repeat (IR) regions of 47,419 bp each. The overall GC content was 35.81%. The genome contained 146 genes, including 96 protein-coding genes, 42 transfer RNA genes, and 8 ribosomal RNA genes. Structure analysis identified 67,354 codons, 96 long repetitive sequences, and 171 simple sequence repeats. Comparative genomic analysis across Rhododendron species revealed hypervariable coding regions (accD, rps9) and non-coding regions (trnK-UUU-ycf3, trnI-CAU-rpoB, trnT-GGU-accD, rpoA-psbL, rpl20-trnC-GCA, trnI-CAU-rrn16, and trnI-CAU-rps16), which may serve as potential molecular markers for genetic identification. Phylogenetic reconstruction confirmed the monophyly of Rhododendron species and highlighted a close relationship between Rh. purdomii and Rh. henanense subsp. lingbaoense. These results provide essential genomic resources for advancing taxonomic, evolutionary, conservation, and breeding studies of Rh. purdomii and other species within the genus Rhododendron. Full article

Recurrent pregnancy loss (RPL) is a multifactorial condition affecting 1–5% of couples, often with unclear etiology. Idiopathic pregnancy losses (iPLs) are particularly challenging due to unknown molecular mechanisms. This study investigates the transcriptomic profiles of first-trimester products of conception (POC) from iPLs to uncover underlying molecular pathways. We performed RNA-sequencing on nine POC samples, identifying two distinct clusters enriched in trophoblast and decidual cells. Deconvolution analysis revealed reduced syncytiotrophoblast (STB) cells, with increased cytotrophoblast (CTB) and extravillous trophoblast (EVT) cells in iPLs. Gene Set Enrichment Analysis highlighted immune pathways enrichment in both villous trophoblasts and decidua. Gene ontology (GO) analysis of downregulated genes implicated hormonal and endocrine processes, consistent with STB reduction, while upregulated genes were associated with MHC protein complex and immune system processes, aligning with EVT increases. Histological analysis showed chronic histiocytic intervillositis (CHI) in iPL samples, supporting maternal immune dysregulation in unexplained RPL. Together, transcriptomic and histological analyses indicate that immune signaling dysregulation and impaired trophoblast differentiation may underlie unexplained iPLs. These findings bridge molecular and histopathological evidence, underscoring the interplay between trophoblast dysfunction and immune imbalance. Our results provide insights into iPL pathogenesis, highlighting potential biomarkers that may contribute to improved diagnosis and future research. Full article