Search Results (112)

The growth of aquaculture poses significant challenges for disease management, impacting economic sustainability and global food security. Traditional diagnostics are slow and require expertise, while current deep learning models, including CNNs and Transformers, face a trade-off between capturing global symptom context and maintaining computational efficiency. This paper introduces FishMambaNet, a novel framework that integrates selective state space models (SSMs) with convolutional networks for accurate and efficient fish disease diagnosis. FishMambaNet features two core components: the Fish Disease Detection State Space block (FSBlock), which models long-range symptom dependencies via SSMs while preserving local details with gated convolutions, and the Multi-Scale Convolutional Attention (MSCA) mechanism, which enriches multi-scale feature representation with low computational cost. Experiments demonstrate state-of-the-art performance, with FishMambaNet achieving a mean Average Precision at 50% Intersection over Union (mAP@50) of 86.7% using only 4.3 M parameters and 10.7 GFLOPs, significantly surpassing models like YOLOv8-m and RT-DETR. This work establishes a new paradigm for lightweight, powerful disease detection in aquaculture, offering a practical solution for real-time deployment in resource-constrained environments. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) often presents at an advanced stage; therefore, the early detection of precursor lesions is crucial. However, the risk assessment of precursor lesions such as oral epithelial dysplasia (OED) remains challenging because of the subjectivity of histopathological grading. We aimed to identify molecular markers that enhance the diagnostic accuracy and prognostic stratification of OSCC and explore the differences in the molecular characterization of OED and OSCC using a few selected markers. Methods: A two-step diagnostic workflow was applied: (1) FISH evaluation of EGFR amplification and CDKN2A deletion to distinguish OED from OSCC and identify EGFR-dependent tumors, and (2) HRAS immunohistochemistry performed exclusively in EGFR-negative OSCCs to stratify EGFR-independent cases. Fluorescence in situ hybridization (FISH) was used to assess seven EGFR/cell cycle-related genes (CCND1, CDKN2A, EGFR, PIK3CA, PTEN, TP53, and 1p36 locus) in 117 formalin-fixed paraffin-embedded samples (66 OED and 51 OSCC) and 10 normal mucosa samples. HRAS expression was evaluated using immunohistochemistry (IHC) in 36 EGFR amplification-negative OSCCs samples. Results:EGFR amplification was frequent in OSCC, whereas CDKN2A deletion was common in OED. The EGFR-amplified/ CDKN2A-intact profile showed high specificity for OSCC and improved diagnostic performance (area under the curve = 0.77) when combined with the Ki-67 labeling index. It also predicted poor disease-free survival (hazard ratio [HR] = 5.08, p = 0.016) and overall survival (HR = 6.10, p = 0.047). Among EGFR-negative OSCCs, HRAS overexpression was associated with advanced-stage disease and a poor prognosis (HR = 6.15, p = 0.043). Conclusions:EGFR amplification was frequent in OSCC, and CDKN2A deletion was prevalent in OED, supporting their use as molecular markers for differential diagnoses. FISH for EGFR/CDKN2A and HRAS IHC can stratify OSCC by diagnosis and prognosis, enabling practical molecular subclassification, including EGFR-negative cases. Full article

Spring viremia of carp (SVC) is a highly contagious disease that affects cyprinids, resulting in systemic hemorrhage, abdominal distension, exophthalmia, and high mortality in juveniles. This can lead to significant losses in the aquaculture industry. The World Organization for Animal Health (WOAH) recommends a two-step semi-nested reverse transcription polymerase chain reaction (RT-PCR) method for diagnosis. However, this method is labor-intensive, requires large reagent volumes, and is prone to carry-over contamination. Here, we evaluated the detection sensitivity of one-step semi-nested RT-PCR (combining RT and primary amplification in a single tube, followed by a second nested PCR step) against conventional two-step semi-nested RT-PCR. SVC virus (SVCV) subgroup Ia was tested using cell culture, RT-quantitative PCR, and one-step RT-PCR. The two-step semi-nested PCR method detected viral RNA up to a 10⁻² dilution, whereas one-step semi-nested RT-PCR detected it up to a 10⁻⁵ dilution, showing a 1000-fold improvement in sensitivity. Moreover, detection rates increased from 84.2% with two-step semi-nested RT-PCR to 91.7% with one-step semi-nested RT-PCR in fish tissue samples. One-step semi-nested RT-PCR reduces processing time, minimizes handling steps, and contamination risk, and enhances analytical sensitivity. This supports its adoption as a practical, high-throughput diagnostic tool for SVCV and consideration for future WOAH guidelines. Full article

Background/Objectives: Accurate detection of all classes of genomic structural variants (SVs), including chromosomal rearrangements and copy number alterations (CNAs), is essential for the diagnosis and classification of hematologic neoplasms. Conventional cytogenetic methods currently serve as routine clinical tools for detecting SVs. However, each commonly used cytogenetic test has specific limitations, and sequential application of these different tests may delay timely diagnosis and treatment. Methods: In this study, we evaluated the feasibility and utility of genomic proximity mapping (GPM), a novel high-throughput chromosome conformation capture (Hi-C)-based next-generation sequencing (NGS) method, to identify chromosomal and genetic aberrations in hematologic neoplasms in the clinical setting. GPM was performed on 18 cases of hematologic neoplasms (fresh/frozen cells or formalin-fixed paraffin-embedded tissue), and concordance with other methodologies was assessed, including karyotyping, FISH, RT-PCR, chromosomal microarray analysis (CMA), and/or RNA sequencing. Results: GPM reliably detected balanced and unbalanced chromosomal rearrangements, including chimeric gene fusions and gene juxtapositions, with 95.2% concordance with previously applied methods in cases with >10% tumor burden. Additionally, GPM can detect CNAs and copy-neutral loss of heterozygosity (cnLOH) simultaneously in a single assay. Furthermore, detection of genomic rearrangements not identified by other methods improved the accuracy of disease classification. Conclusions: These findings demonstrate that GPM is a powerful method for identifying clinically actionable variants in hematologic neoplasms, overcoming some limitations of current cytogenetic technologies and improving the diagnostic accuracy and classification in challenging cases Full article

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, typically presenting with systemic symptoms and mediastinal involvement. Leukemia cutis (LC) and renal infiltration are rare, especially at disease onset. A 27-year-old man presented with a solitary scalp lesion without systemic symptoms or hematologic abnormalities. Histopathology revealed a blastoid lymphoid infiltrate with a T-ALL immunophenotype. Two weeks later, laboratory tests showed leukocytosis, lymphocytosis, and renal dysfunction. Imaging revealed a large mediastinal mass, scalp soft tissue involvement, and bilateral renal infiltration. Bone marrow biopsy confirmed T-ALL with a mature phenotype. FISH identified TRAD:NKX2 rearrangement and CDKN2AB deletion. The patient received three cycles of pediatric-inspired chemotherapy, achieving complete molecular remission and resolution of extramedullary disease. He subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-matched sibling. Post-transplant complications included febrile neutropenia and mucositis. On day +100, he remained in minimal residual disease (MRD)-negative remission. This case illustrates a rare presentation of T-ALL with isolated skin involvement and renal infiltration at diagnosis, highlighting the importance of early biopsy and immunophenotyping of atypical skin lesions. Intensive chemotherapy followed by HSCT represents a viable strategy for young adults with high-risk T-ALL and extramedullary disease. Full article

Aquaculture has rapidly become a vital sector for ensuring global food security by meeting the growing demand for animal protein. Bangladesh, one of the world’s leading aquaculture producers, recorded a production of 4.91 million MT in 2022–2023, largely driven by inland farming systems. Despite this remarkable growth, the sector is highly vulnerable to disease outbreaks, which are aggravated by different factors. Pathogens such as bacteria, viruses, fungi, and parasites cause significant losses, while conventional disease diagnosis in Bangladesh still depends mainly on visual assessment and basic laboratory techniques, limiting early detection. This narrative review highlights recent advances in diagnostics as molecular tools, immunodiagnostics, nanodiagnostics, machine learning, and next-generation sequencing (NGS) that are widely applied globally but remain limited in Bangladesh due to infrastructure gaps, lack of skilled manpower, and resource constraints. Current treatment strategies largely rely on antibiotics and aquaculture medicinal products (AMPs), often misused without proper diagnosis, contributing to antimicrobial resistance (AMR). Promising alternatives, including probiotics, immunostimulants, vaccines, and enhanced biosecurity, require greater adoption and farmer awareness. The near-term priorities for Bangladesh include standardized disease and AMR surveillance, prudent antibiotic stewardship, phased adoption of validated rapid diagnostics, and investment in diagnostic and human capacity. Policy-level actions, including a national aquatic animal health strategy, stricter antimicrobial regulation, strengthening diagnostic infrastructure in institution, are crucial to achieve sustainable disease management and ensure long-term resilience of aquaculture in Bangladesh. Full article

Background: Although telomere length maintenance is a common characteristic of hematological malignancies, the role of telomere length as a prognostic factor to stratify acute lymphoblastic leukemia (ALL) patients depending on their risk of relapse remains elusive. Methods: This knowledge gap motivated us to examine telomere length values in children with ALL at the time of diagnosis and after treatment using quantitative polymerase chain reaction (qPCR) (n = 35). To achieve high-resolution precision and cell specificity, a quantitative fluorescence in situ hybridization (qFISH) technique was developed (n = 5). Results: The results demonstrated statistically significant evidence of telomere shortening in the lymphoblasts of children with ALL but not in the lymphocytes of children after remission following treatment. Our findings also suggested a significant association between telomere shortening and a high risk of relapse disease. Last but not least, our preliminary results showed a trend that telomere shortening was more pronounced in children with B-ALL compared to those with T-ALL in a non-significant manner. Conclusions: Consequently, the current study provides preliminary insights into the potentially substantial prognostic value of telomere length in the progression of pediatric ALL, with the possibility of predicting treatment response. To clarify the application of telomere length as a possible biomarker for disease progression and treatment response in children with ALL, the telomere length values of additional participants need to be examined in further studies. Full article

Background and Clinical Significance: Ovarian ectopic pregnancy (OEP) is a rare occurrence, and molar degeneration is even more exceptional. Differential diagnosis between a partial and complete hydatidiform mole is paramount as the complete type carries a higher risk of post-molar gestational trophoblastic neoplasia. Herein, we describe a case of a partial mole in an OEP (OPHM) with thorough investigations. Case Presentation: A 39-year-old woman presented at 6 weeks of amenorrhea with abdominal pain and vaginal bleeding. Ultrasound showed no intrauterine pregnancy, but an ovarian cyst suspicious for OEP. The patient underwent surgical removal of the cyst. Histological diagnosis was suspicious for OPHM with only one abnormal villous. Immunohistochemistry for p57^kip2 and fluorescent in situ hybridization (FISH) were not conclusive. STR-based (Short Tandem Repeat) molecular technique demonstrated the chromosomal asset of 69,XXX, confirming the diagnosis of OPHM. The patient was fully monitored for 1 year with periodic measurements of beta-hCG levels. After that period, the patient was in good health and disease-free. Conclusions: Histologically, ancillary techniques might not be sufficient to confirm the diagnosis of a hydatidiform mole, especially if the tissue available is scarce. In this case, STR has been demonstrated an effective tool in defining the chromosomal asset, even in paraffin-embedded samples. Full article

Fish are a vital aquatic resource worldwide, and the sustainable development of aquaculture is essential for global food security and economic growth. However, the high incidence of fish diseases in complex aquaculture environments significantly hampers sustainability, and traditional manual diagnosis methods are inefficient and often inaccurate. To address the challenges of small-lesion detection, lesion area size and morphological variation, and background complexity, we propose YOLO-TPS, a high-precision fish-disease detection model based on an improved YOLOv11n architecture. The model integrates a multi-module synergy strategy and a triple-attention mechanism to enhance detection performance. Specifically, the SPPF_TSFA module is introduced into the backbone to fuse spatial, channel, and neuron-level attention for better multi-scale feature extraction of early-stage lesions. A PC_Shuffleblock module incorporating asymmetric pinwheel-shaped convolutions is embedded in the detection head to improve spatial awareness and texture modeling under complex visual conditions. Additionally, a scale-aware dynamic intersection over union (SDIoU) loss function was designed to accommodate changes in the scale and morphology of lesions at different stages of the disease. Experimental results on a dataset comprising 4596 images across six fish-disease categories demonstrate superior performance (mAP_0.5: 97.2%, Precision: 97.9%, Recall: 95.1%) compared to the baseline. This study offers a robust, scalable solution for intelligent fish-disease diagnosis and has promising implications for sustainable aquaculture and animal health monitoring. Full article

Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. Full article

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Apart from the traditional causes of NS, such as minimal change disease, focal segmental glomerulosclerosis, diabetes, infections, malignancies, autoimmune conditions, and nephrotoxic agents, there are also rare causes of NS, whose knowledge is of the utmost importance. The aim of this article was to highlight the less well-known causes that have a significant impact on diagnosis and treatment. Genetic syndromes such as Schimke immuno-osseous dysplasia, familial lecithin-cholesterol acyltransferase deficiency with two clinical variants (fish-eye Disease and the p.Leu364Pro mutation), lead to NS through mechanisms involving podocyte and lipid metabolism dysfunction. Congenital disorders of glycosylation and Nail–Patella Syndrome emphasize the role of deranged protein processing and transcriptional regulation in glomerular injury. The link of NS with type 1 diabetes, though rare, suggests an etiology on the basis of common HLA loci and immune dysregulation. Histopathological analysis, particularly electron microscopy, shows mainly podocyte damage, mesangial sclerosis, and alteration of the basement membrane, which aids in differentiating rare forms. Prompt recognition of these novel etiologies by genetic analysis, renal biopsy, and an interdisciplinary panel is essential to avoid delays in diagnosis and tailored treatment. Full article

Bycatch is the most common cause of death of small delphinids worldwide, including the Mediterranean Sea. The diagnosis of bycatch as cause of death in stranded cetaceans depends on the cumulative presence of multiple findings, termed bycatch criteria. In this study, we retrospectively evaluated the presence of bycatch criteria in 138 necropsied cetaceans, 136 stranded and 2 confirmed bycaught, in the Catalan Mediterranean Sea across a 13-year period. With the aim of identifying the most specific and reliable bycatch criteria, the animals’ cause of death was classified as either bycaught or other causes. Animals were necropsied according to standard procedures with complete histopathological examination and ancillary diagnostic techniques. We reviewed the necropsy reports and photographs of 138 cetaceans of seven species. Bycatch had been determined as the cause of death/stranding in 40 (29%) necropsied cetaceans. Both sexes were equally represented in the bycatch group. Bycatch was diagnosed in the Mediterranean common bottlenose dolphin (10/14; 71.4%), striped dolphin (29/108; 26.9%), and Risso’s dolphin (1/11; 9.1%). Sixty-seven out of 98 (68.3%) cetaceans that had been classified as non-bycatch had one or two bycatch criteria. Cetaceans with two and three major criteria had an overlap of causes of death, as some animals were diagnosed with bycatch and others with other causes of mortality. Animals with four criteria were invariably diagnosed as being bycaught. Recent feeding, absence of disease, good nutritional status, marks of fishing gear, multiorgan intravascular gas bubbles, hyphema and amputations or sharp incisions presumably inflicted by humans were significantly more likely to result in a diagnosis of bycatch, while loss of teeth and cranial fractures were not. None of the dolphins diagnosed as bycatch had ingested fishing gear. Our results highlight the relevance of bycatch as the cause of death of dolphins in the Mediterranean and suggest that some criteria traditionally linked to bycatch are not specific for bycatch in our region. Full article

Background: CIC-rearranged sarcoma is a rare and aggressive type of undifferentiated round cell tumor characterized by CIC gene fusion, most commonly CIC::DUX4. This study presents a series of eleven cases, highlighting their clinicopathological features. Methods: Pathology records (2019 to 2024) were searched using “sarcoma with CIC”, identifying eleven cases, of which seven referred cases were initially misdiagnosed. Pathological and clinical analysis was conducted. Treatment was dictated upon multidisciplinary panel discussion based on tumor stage. Follow-up data (1–25 months) was available for all patients. Results: The cohort included six males and five females, with a median age of 43 years (range;14–53), with nine in soft tissue and two in bone. Tumor size ranged from 3.5 cm to 20.0 cm (mean: 9.8 cm). Most cases showed sheets of undifferentiated round- to oval-shaped cells. Two cases showed an Ewing-like pattern, and one case showed spindle cells in a fibrotic stroma transitioning to epithelioid cells. Necrosis was present in nine cases, and mitotic count ranged from 2 to 38/ 10HPFs (mean = 14.2). CD99 was positive in (10/11) cases and WT-1 in (6/9). NKX2.2, S100, and MDM2 were positive in rare cases. CIC::DUX4 fusion was detected in four cases. FISH for CIC gene rearrangement was positive in seven cases, two of them confirmed by methylation analysis. Metastasis at diagnosis was common (n = 8), primarily in the lungs, with later metastasis to the brain and bone. At time of final analysis, eight patients died within a median of 10 months (range: 1–19 months), while three were alive, two with stable disease (for a period of 6 and 25 months) and one with progression after 10 months. Significant correlation was seen between overall survival and the presence of metastasis at diagnosis (p value = 0.03). Conclusions: CIC-rearranged sarcomas are rare, high-grade tumors with predilection for soft tissue. Misdiagnosis is frequent, necessitating molecular confirmation. These tumors are treatment-resistant, often present with lung metastasis, and carry a poor prognosis, especially with initial metastasis. Full article

Background/Objectives: Genetic abnormalities play a pivotal role in patient risk stratification, therapeutic decision-making, and elucidating the disease pathogenesis in hematological malignancies. In multiple myeloma (MM) and acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), numerous recurring genetic aberrations are well documented. Fluorescence in situ hybridization (FISH) is a cornerstone of clinical diagnostics for detecting these abnormalities. Conventionally, FISH assesses up to two biomarkers, with one or two circles per slide, but this approach faces challenges when cancer cell yields are limited, particularly in post-treatment follow-up specimens. Methods: To overcome this limitation, we developed a multi-well method, enabling the simultaneous testing of multiple biomarkers on a single microscopic slide. This study included 53 MM and 129 AML/MDS cases. Results: With a cohort of 182 patients, 1016 FISH assays performed on multi-well slides accurately detected diagnostic genetic aberrations previously identified by karyotyping and/or FISH, achieving a sensitivity and specificity of 100%. The use of multi-well slides achieved up to a 2.5-fold increase in the number of wells per slide while achieving more than a 3-fold reduction in the reagent volume compared to traditional methods. This advancement leverages distinct FISH signal patterns to strategically combine biomarkers within multiple wells, suitable for specimens from diagnosis, follow-ups, and relapses, regardless of the cancer cell quantity. Conclusions: The multi-well approach enhances the accessibility to comprehensive biomarker analysis, reducing both the processing time and costs. Beyond MM and AML/MDS, this technique holds promise for use with other hematological malignancies with limited sample volumes, offering an efficient, cost-effective solution for precision diagnostics. Full article

Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies. This review seeks to enhance the comprehension of medical professionals regarding the risk factors and environmental influences that contribute to the development of the disease, as well as its underlying mechanisms. In addition, we aim to provide a schematic yet thorough overview of diagnostic techniques in PM, emphasizing the significance of the immunohistochemical markers BAP1 and MTAP, with the latter serving as an almost ideal surrogate for the gold-standard diagnostic approach, FISH p16/CDKN2A deletion. The scientific world is grappling with BAP1, MTAP, and the tumour inflammatory microenvironment, because they are the key for personalized treatments and palliative care in this disease. Considering that the survival rate for patients with PM seldom surpasses five years, every moment is significant. Therefore, our article also highlights recent advancements in clinical assessments related to prognostic scoring and treatment options. PM is a complex disease, with gradual progression over decades, which requires further investigation covering the prevention, mutations, diagnosis and treatment. Full article