Search Results (681)

Background: Patients diagnosed with melanoma are at increased risk of developing multiple primary melanomas (MPMs). Identifying clinical and genetic factors associated with MPM is critical for implementing personalized surveillance strategies. This study aims to describe the clinical, histopathological, and genetic characteristics of patients with MPM managed in a tertiary hospital and to contextualize findings within the current literature. Methods: We conducted a retrospective review of patients diagnosed with two or more primary melanomas between 2010 and 2023 at a tertiary dermatology unit. Demographic data, personal and family cancer history, phototype, melanoma characteristics, genetic testing, staging, treatments, and outcomes were collected. These data were compared with findings from the recent literature. Results: Thirteen patients (ten males, three females; median age: 59 years) were found to have a total of 33 melanomas. Most patients had Fitzpatrick phototype II and no immunosuppression. The number of melanomas per patient ranged from two to five. Synchronous lesions were observed in two patients. Common locations included the trunk and extremities. Histologically, 57% were in situ melanomas, and subsequent melanomas were generally thinner than the index lesion. Two patients showed progression to advanced disease. One patient was positive for MC1R mutation; the rest were negative or inconclusive. Additional phenotypic and environmental risk factors were extracted from patient records and are summarized as follows: Ten patients (76.9%) had Fitzpatrick skin phototype II, and three (23.1%) had phototype III. Chronic occupational sun exposure was reported in four patients (30.8%), while five (38.5%) recalled having suffered multiple sunburns during childhood or adolescence. Eight patients (61.5%) presented with a total nevus count exceeding 50, and five (38.5%) exhibited clinically atypical nevi. None of the patients reported use of tanning beds. Conclusions: Our findings are consistent with the existing literature indicating that patients with MPM often present with thinner subsequent melanomas and require long-term dermatologic follow-up. The inclusion of genetic testing and phenotypic risk factors enables stratified surveillance and supports the application of personalized medicine in melanoma management. Full article

Background: Obese women have a significantly higher risk of bearing breast tumors that are resistant to therapies and are associated with poorer prognoses/treatment outcomes. Breast cancer-promoting action of obesity is often attributed to elevated levels of insulin, glucose, inflammatory mediators, and misbalanced estrogen production in adipose tissue under obese conditions. Metabolic endotoxemia, characterized by chronic presence of extremely low levels of bacterial endotoxin (lipopolysaccharide [LPS]) in the circulation, is a less explored obesity-associated factor. Results: Here, utilizing in vitro and in vivo models of breast carcinoma (BC), we report that subclinical levels of LPS typical for metabolic endotoxemia enhance the malignant phenotype of breast cancer cells and accelerate breast tumor progression. Conclusions: Our study, while focusing primarily on the direct effects of metabolic endotoxemia on breast tumor progression, also suggests that metabolic endotoxemia can contribute to obesity–breast cancer link. Thus, our findings add novel mechanistic insights into how obesity-associated metabolic changes, particularly metabolic endotoxemia, modulate the biological and clinical behavior of breast carcinoma. In turn, understanding of the mechanistic aspects underlying the association between obesity and breast cancer could help inform better strategies to reduce BC risk in an increasingly obese population and to suppress the breast cancer-promoting consequences of excess adiposity. Full article

Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article

The Gliomas account for 81% of all malignant central nervous system tumors and are classified by WHO into four grades of malignancy. Glioblastoma multiforme (GBM), the most common grade IV glioma, exhibits an extremely aggressive phenotype and a dismal five-year survival rate of only 6%, underscoring the urgent need for novel therapeutic approaches. Immunotherapy has emerged as a promising strategy, and photodynamic therapy (PDT) in particular has attracted attention for its dual cytotoxic and immunostimulatory effects. In GBM models, PDT induces immunogenic cell death characterized by the release of damage-associated molecular patterns (DAMPs), which promote antigen presentation and activate T cell responses. Additionally, PDT transiently increases blood–brain barrier permeability, facilitating immune cell infiltration into the tumor microenvironment, and enhances clearance of waste products via stimulation of meningeal lymphatic vessels. Importantly, PDT can reprogram or inactivate immunosuppressive tumor-associated macrophages, thereby counteracting the pro-tumoral microenvironment. Despite these encouraging findings, further preclinical and clinical studies are required to elucidate PDT’s underlying immunological mechanisms fully and to optimize treatment regimens that maximize its efficacy as part of integrated immunotherapeutic strategies against GBM. Full article

Background/Objectives: The bidirectional selection of the Roman low- (RLA) and Roman high-avoidance (RHA) rat strains for extremely slow vs. very rapid acquisition of the two-way (shuttle-box) avoidance response has generated two divergent phenotypic profiles: RHA rats exhibit a behavioural pattern and gene expression profile in the frontal cortex and hippocampus (HPC) that are relevant to social and attentional/cognitive schizophrenia-linked symptoms; on the other hand, RLA rats display phenotypic traits linked to increased anxiety and sensitivity to stress-induced depression-like behaviours. The present studies aimed to evaluate the enduring and potentially positive effects of neonatal handling-stimulation (NH) on the traits differentiating these two strains of rats. Methods: We evaluated the effects of NH on anxious behaviour, prepulse inhibition of startle (PPI), spatial working memory, and hormone responses to stress in adult rats of both strains. Furthermore, given the proposed involvement of neuronal/synaptic plasticity and neurotrophic factors in the development of anxiety, stress, depression, and schizophrenia-related symptoms, using Western blot (WB) we assessed the effects of NH on the content of brain-derived neurotrophic factor (BDNF), its trkB receptor and Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the prefrontal cortex (PFC), anterior cingulate cortex (ACg), ventral (vHPC), and dorsal (dHPC) hippocampus of adult rats from both strains. Results: NH increased novelty-induced exploration and reduced anxiety, particularly in RLA rats, attenuated the stress-induced increment in corticosterone and prolactin plasma levels, and improved PPI and spatial working memory in RHA rats. These effects correlated to long-lasting increases of BDNF and PSA-NCAM content in PFC, ACg, and vHPC. Conclusions: Collectively, these findings show enduring and distinct NH effects on neuroendocrine and behavioural and cognitive processes in both rat strains, which may be linked to neuroplastic and synaptic changes in the frontal cortex and/or hippocampus. Full article

Background/Objetives: Sea lice (Caligus rogercresseyi) pose a major threat to Atlantic salmon (Salmo salar) aquaculture by compromising fish health and reducing production efficiency. While genetic variation in parasite load has been reported, the molecular mechanisms underlying this variation remain unclear. Methods: two sea lice challenge trials were conducted, achieving high infestation rates (47.5% and 43.5%). A total of 85 fish, selected based on extreme phenotypes for lice burden (42 low, 43 high), were subjected to transcriptomic analysis. Differential gene expression was integrated with allele-specific expression (ASE) analysis to uncover cis-regulatory variation influencing host response. Results: Sixty genes showed significant ASE (p < 0.05), including 33 overexpressed and 27 underexpressed. Overexpressed ASE genes included Keratin 15, Collagen IV/V, TRIM16, and Angiopoietin-1-like, which are associated with epithelial integrity, immune response, and tissue remodeling. Underexpressed ASE genes such as SOCS3, CSF3R, and Neutrophil cytosolic factor suggest individual variation in cytokine signaling and oxidative stress pathways. Conclusions: several ASE genes co-localized with previously identified QTLs for sea lice resistance, indicating that cis-regulatory variants contribute to phenotypic differences in parasite susceptibility. These results highlight ASE analysis as a powerful tool to identify functional regulatory elements and provide valuable candidates for selective breeding and genomic improvement strategies in aquaculture. Full article

The wheat planted at the end of the rainy season in the Cerrado suffers from a strong water deficit. A selection of genetic material with drought tolerance is necessary. In improvement programs that evaluate a large number of materials, efficient, automated, and non-destructive phenotyping is essential, which requires the use of sensors. The experiment was conducted in 2016 using a phenotyping platform, where irrigation gradients ranging from 184 (WR4) to 601 mm (WR1) were created, allowing for the comparison of four genotypes. In addition to productivity, we evaluated plant height, hectoliter weight, the number of spikes per square meter, ear length, photosynthesis, and the indices calculated by the sensors. For most morphophysiological parameters, extreme stress makes it difficult to discriminate materials. WR1 (601 mm) and WR2 (501 mm) showed similar trends in almost all variables. The data validated the phenotyping platform, which creates an irrigation gradient, considering that the results obtained, in general, were proportional to the water levels. The similar trend between sensors (NDVI, PRI, and LIFT) and morphophysiological, plant growth, and crop yield evaluations validated the use of sensors as a tool in selecting drought-tolerant wheat genotypes using a non-invasive methodology. Considering that only four genotypes were used, none showed absolute and unequivocal tolerance to drought; however, each genotype exhibited some desirable characteristics related to drought tolerance mechanisms. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Drought stress has a significant impact on cotton growth, development, and productivity. This study conducted drought stress treatment and normal water treatment (control group) on 502 cotton accessions and analyzed data on eight phenotypic traits closely related to drought stress tolerance. The results showed that all indicators changed significantly under drought stress conditions compared to the control group, with varying degrees of response among different indicators. To comprehensively evaluate the drought resistance of cotton during the germination period, the values of drought resistance comprehensive evaluation (D-value), weight drought resistance coefficient (WDC-value), and comprehensive drought resistance coefficient (CDC-value) were calculated based on membership function analysis and principal component analysis. Cluster analysis based on the D-value divided the germplasm into five drought-resistant grades, followed by the selection of one extreme material, each from the strongly drought-resistant and strongly drought-sensitive groups. An evaluation model was established using stepwise regression analysis, including the following effective indicators: Relative Fresh Weight (RFW), Relative Hypocotyl Length (RHL), Relative Seeds Water Absorption Rate (RAR), Relative Germination Rate (RGR), Relative Germination Potential (RGP), and Relative Drought Tolerance Index (RDT). The validation of the D-value prediction model based on the Best Linear Unbiased Prediction (BLUP) showed that the results obtained from two independent biological replicates were highly consistent. The comprehensive evaluation system and screening indicators established in this study provide a reliable method for identifying drought tolerance during the germination period. Full article

Background/Objectives: Lung cancer remains a major cause of cancer-related mortality, with regional differences in incidence and patient characteristics. This study aimed to verify and quantify a perceived dramatic increase in lung cancer cases at a Romanian center, identify distinct patient phenotypes using unsupervised machine learning, and characterize contributing factors, including demographic shifts, changes in the healthcare system, and geographic patterns. Methods: A comprehensive retrospective analysis of 4206 lung cancer patients admitted between 2013 and 2024 was conducted, with detailed molecular characterization of 398 patients from 2023 to 2024. Temporal trends were analyzed using statistical methods, while k-means clustering on 761 clinical features identified patient phenotypes. The geographic distribution, smoking patterns, respiratory comorbidities, and demographic factors were systematically characterized across the identified clusters. Results: We confirmed an 80.5% increase in lung cancer admissions between pre-pandemic (2013–2020) and post-pandemic (2022–2024) periods, exceeding the 51.1% increase in total hospital admissions and aligning with national Romanian trends. Five distinct patient clusters emerged: elderly never-smokers (28.9%) with the highest metastatic rates (44.3%), heavy-smoking males (27.4%), active smokers with comprehensive molecular testing (31.7%), young mixed-gender cohort (7.3%) with balanced demographics, and extreme heavy smokers (4.8%) concentrated in rural areas (52.6%) with severe comorbidity burden. Clusters demonstrated significant differences in age (p < 0.001), smoking intensity (p < 0.001), geographic distribution (p < 0.001), as well as molecular characteristics. COPD prevalence was exceptionally high (44.8–78.9%) across clusters, while COVID-19 history remained low (3.4–8.3%), suggesting a limited direct association between the pandemic and cancer. Conclusions: This study presents the first comprehensive machine learning-based stratification of lung cancer patients in Romania, confirming genuine epidemiological increases beyond healthcare system artifacts. The identification of five clinically meaningful phenotypes—particularly rural extreme smokers and age-stratified never-smokers—demonstrates the value of unsupervised clustering for regional healthcare planning. These findings establish frameworks for targeted screening programs, personalized treatment approaches, and resource allocation strategies tailored to specific high-risk populations while highlighting the potential of artificial intelligence in identifying actionable clinical patterns for the implementation of precision medicine. Full article

Climate change poses significant challenges to temperate rice production, particularly affecting grain quality and market acceptance. This review synthesizes current knowledge of climate-induced quality changes, with a focus on the Australian rice industry as a case study with comparisons to other temperate regions. Environmental stressors such as extreme temperatures, variable rainfall, elevated CO₂, and salinity disrupt biochemical pathways during grain development, altering physicochemical, textural, and aromatic traits. Different rice classes exhibit distinct vulnerabilities: medium-grain japonica varieties show reduced amylose under heat stress, aromatic varieties experience disrupted aroma synthesis under drought, and long-grain types suffer kernel damage under combined stresses. Temperature is a key driver, with quality deterioration occurring above 35 °C and below 15 °C. Systems biology analyses reveal complex signalling networks underpinning these stress responses, although experimental validation remains limited. The Australian industry has responded by developing cold-tolerant cultivars, precision agriculture, and water-saving practices, yet projected climate variability demands more integrated strategies. Priorities include breeding for stress-resilient quality traits, refining water management, and deploying advanced phenotyping tools. Emerging technologies like hyperspectral imaging and machine learning offer promise for rapid quality assessment and adaptive management. Sustaining high-quality rice in temperate zones requires innovation linking physiology with practical adaptation. Full article

The increasing concentration of greenhouse gases is amplifying the global risk of drought on crop productivity. This study sought to investigate the effects of drought on the growth of maize (Zea mays L.) seedlings. A total of 78 maize hybrids were employed in this study to replicate drought conditions through the potting method. The maize seedlings were subjected to a 10-day period of water breakage following a standard watering cycle until they reached the third leaf collar (V3) stage. Parameters including plant height, stem diameter, chlorophyll content, and root number were assessed. The eight phenotypic traits include the fresh and dry weights of both the aboveground and underground parts. Three machine learning methods—random forest (RF), K-nearest neighbor (KNN), and extreme gradient boosting (XGBoost)—were employed to systematically analyze the relevant traits of maize seedlings’ drought tolerance and to assess their predictive performance in this regard. The findings indicated that plant height, aboveground weight, and chlorophyll content constituted the primary indices for phenotyping maize seedlings under drought conditions. The XGBoost model demonstrated optimal performance in the classification (AUC = 0.993) and regression (R² = 0.863) tasks, establishing itself as the most effective prediction model. This study provides a foundation for the feasibility and reliability of screening drought-tolerant maize varieties and refining precision breeding strategies. Full article

Global climate change is leading to more frequent extreme cold events, underscoring the need to study citrus cold tolerance to support breeding and enable potential northward expansion of citrus cultivation. In this study, the ‘Miyagawa’ wild type and its cold-tolerant mutant were selected for systematic comparison across cold-resistant phenotypes, leaf tissue structure, physiological and biochemical characteristics, and Cor8 gene expression. The mutant exhibited 50% lower relative conductivity and malondialdehyde (MDA) content under −6 °C stress compared to the wild type, indicating reduced membrane damage. Antioxidant enzyme activities were significantly higher in the mutant: superoxide dismutase (SOD) activity increased by 10–30%, peroxidase (POD) by 28%, and catalase (CAT) by up to 2-fold. Proline content was 57% higher in the mutant at peak levels, supporting stronger osmotic regulation. Moreover, Cor8 gene expression in the mutant was up to 2.98 times higher than in the wild type during natural overwintering. These findings confirm that the ‘Miyagawa’ mutant possesses distinct physiological, anatomical, and molecular advantages for low-temperature adaptation and provides valuable germplasm for breeding cold-tolerant citrus varieties. Full article

Potato common scab is one of the major diseases posing a threat to potato production on a global scale. No chemical agents have been found to effectively control the occurrence of this disease, and research on the identification of resistance genes and the development of molecular markers remains relatively limited. In this study, a diploid potato variety H535, which exhibits resistance to the predominant pathogen Streptomyces scabies, was utilized as the male parent, whereas the susceptible diploid potato variety H012 served as the female parent. Building upon the resistance QTL intervals pinpointed through a genome-wide association study, two potential resistance loci were localized on chromosome 2 of the potato genome, spanning the regions between 38–38.6 Mb and 41.3–42.7 Mb. These intervals accounted for 18.03% of the total phenotypic variance and are presumed to be the primary QTLs underlying scab resistance. Building upon this foundation, we expanded the hybrid progeny population, conducted resistance assessments, selected individuals with extreme phenotypes, developed molecular markers, and conducted fine mapping of the resistance gene. A phenotypic evaluation of scab resistance was carried out using a pot-based inoculation test on 175 potato hybrid progenies to characterize the F1 generation population. Twenty lines exhibiting high resistance and thirty lines displaying high susceptibility were selected for investigations. Within the preliminary mapping interval on potato chromosome 2 (spanning 38–43 Mb), a total of 214 SSR (Simple Sequence Repeat) and 133 InDel (Insertion/Deletion) primer pairs were designed. Initial screening with parental lines identified 18 polymorphic markers (8 SSR and 10 InDel) that demonstrated stable segregation patterns. Validation using bulked segregant analysis revealed that 3 SSR markers (with 70–90% linkage) and 6 InDel markers (with 70–90% linkage) exhibited significant co-segregation with the resistance trait. A high-density genetic linkage map spanning 104.59 cm was constructed using 18 polymorphic markers, with an average marker spacing of 5.81 cm. Through linkage analysis, the resistance locus was precisely mapped to a 767 kb interval (41.33–42.09 Mb) on potato chromosome 2, flanked by SSR-2-9 and InDel-3-9. Within this refined interval, four candidate disease resistance genes were identified: RHC02H2G2507, RHC02H2G2515, PGSC0003DMG400030643, and PGSC0003DMG400030661. This study offers novel insights into the genetic architecture underlying scab resistance in potato. The high-resolution mapping results and characterized markers will facilitate marker-assisted selection (MAS) in disease resistance breeding programs, providing an efficient strategy for developing cultivars with enhanced resistance to Streptomyces scabies. Full article

Background/Objectives: Desert plants exhibit remarkable resilience to extreme environments, and their capacity for population establishment is noteworthy. However, the adaptation process mechanisms of those plants to harsh habitats, particularly concerning intraspecific differentiation and genetic diversity, remain poorly understood, and a comprehensive framework is lacking. Zygophyllum loczyi Kanitz, an annual or biennial desert herb, demonstrates significant phenotypic plasticity across diverse habitats. Methods: Using mixed-effects models, this study examined 20 populations from four deserts to assess phenotypic variation and predict trait_environment relationships. Results: The findings indicated substantial inter-population phenotypic differentiation in Z. loczyi, with greater variation observed between deserts than within them. Traits such as blade length, petal length, sepal length, and stamen length were influenced by environmental conditions. Mixed-effects model prediction showed that the growth location of Z. loczyi significantly impacted its phenotypic traits. The characteristics of the four desert populations displayed varying responses to temperature and moisture changes, with the most pronounced response noted in the Gurbantunggut desert (Gt) population, indicating that survival stress has an important influence on the performance of plants. The single nucleotide polymorphisms result further confirmed that the differentiation and genetic diversity of the Gt population displayed the highest selection pressure, resulting the small effective size of the population. Conclusions: This study uncovers the adaptive mechanism of Z. loczyi to habitat through investigating the inter-population phenotypic differentiation and genetic diversity and provides new insight into local adaptation and evolutionary processes in the desert environment. Full article