Fisheries Inspection in Portuguese Waters from 2015 to 2023.

As a coastal state, Portugal must ensure active surveillance over its maritime area, ensuring its proper control and inspection. One of the most critical inspection activities is the fishery inspection. To protect biodiversity, we must ensure that all the ships comply with the existing safety regulations and respect the current fishing quotas. This georeferenced dataset describes the fisheries inspections done in Portuguese waters between 2015 and 2023. Since we are dealing with occurrences that may have originated some legal process to the ship's owner, we have ensured data anonymization by pre-processing the dataset to maintain its accuracy while guaranteeing no unique identifiers exist. All the pre-processing performed to ensure data consistency and accuracy is described in detail to allow a quick analysis and implementation of new algorithms. The data containing the results of these inspections can be easily analyzed to implement data mining algorithms that can efficiently retrieve more knowledge and, e.g., suggest new areas of actuation or new strategies.

Side-scan sonar imaging data of underwater vehicles for mine detection.

Unmanned vehicles have become increasingly popular in the underwater domain in the last decade, as they provide better operation reliability by minimizing human involvement in most tasks. Perception of the environment is crucial for safety and other tasks, such as guidance and trajectory control, mainly when operating underwater. Mine detection is one of the riskiest operations since it involves systems that can easily damage vehicles and endanger human lives if manned. Automating mine detection from side-scan sonar images enhances safety while reducing false negatives. The collected dataset contains 1170 real sonar images taken between 2010 and 2021 using a Teledyne Marine Gavia Autonomous Underwater Vehicle (AUV), which includes enough information to classify its content objects as NOn-Mine-like BOttom Objects (NOMBO) and MIne-Like COntacts (MILCO). The dataset is annotated and can be quickly deployed for object detection, classification, or image segmentation tasks. Collecting a dataset of this type requires a significant amount of time and cost, which increases its rarity and relevance to research and industrial development.

Georeferenced dataset of maritime piracy in the Gulf of Guinea from 2010 to 2021.

Piracy has been a global concern and a threat to the safety of people performing maritime trade around the globe. Since ancient times maritime piracy has been a common practice that, unfortunately, has not ended in the current days. A georeferenced dataset providing the position, meteorologic conditions, and a description of the occurrence can provide essential information for analyzing this global phenomenon. The dataset focuses on the Gulf of Guinea (GoG) as an area dominated by corruption and weak supervision capacity by the local authorities. The time interval considered in this paper is between 2010 and 2021. Using this simple dataset, it is possible to analyze attributes such as when the piracy occurred or if the illegal activity involved deaths or kidnapping. The accuracy of the data was guaranteed by cross-referencing data sources, so we have 595 pirate attacks accurately described. This dataset can easily be used for data mining, allowing further analysis of the patterns and trends of pirate attacks in the GoG over time.

pTERT C250T mutation: A potential biomarker of poor prognosis in metastatic melanoma.

Melanoma is the most aggressive form of skin cancer and the leading cause of death from cutaneous tumors. Several studies have associated alterations in the TERT promoter region (pTERT) with gene overexpression, aggressiveness and poor prognosis of the disease. The aim of this study was to clarify the role of pTERT molecular status in paired samples of primary melanoma and metastasis using tissue and plasma to establish a correlation with disease progression and survival. A total of 88 FFPE tissue samples from 53 patients with advanced melanoma were analyzed. Of these, 35 had paired samples. We also examined cfDNA samples from plasma of 25 patients. We detected a good correlation between primary tumors and metastases in pTERT mutation and methylation status. We were also able to identify pTERT mutations in plasma samples that correlated with mutational status in tissue samples. Interestingly, the C250T mutation was associated with worse survival and higher TERT mRNA expression, compared to the other most common mutation: C228T. In addition, hyper-methylation of the promoter region seems to be related to the progression of pTERT wild type (WT) patients. These results suggest that TERT gene alterations plays an important role during tumor progression, with the detection of the C250T mutation in tissue and plasma as a potential biomarker of poor prognosis in patients with advanced melanoma.

Diagnostic Reliability of Plain Radiography in Osteonecrosis of the Femoral Head: General Radiological Features Revised.

BACKGROUND AND OBJECTIVES: Osteonecrosis of the femoral head (ONFH) is an incapacitating disease that frequently results in the collapse of the femoral head and secondary osteoarthritis. The diagnosis and staging of this pathology, which usually rely on imaging studies, are challenging. Currently, conventional radiography is the basis of the initial diagnostic assessment. In recent decades, however, radiographs have been considered insensitive to early changes in ONFH and thus, a suboptimal diagnostic tool. Paradoxically, the imaging features of radiographs are often profuse, substantial, and characteristic. This study aimed to elucidate the real limitations of this radiologic tool by assessing the diagnostic reliability of the key radiologic features and staging. METHODS: This was a retrospective study in which radiographs from 28 idiopathic ONFH confirmed cases who underwent hip arthroplasty were analyzed by eight observers who were asked to identify the presence or absence of ONFH universally reported imaging features in AP hip radiographs. RESULTS: Concordance analysis revealed a poor agreement between observers for most of the assessed imaging features. Only the identification of femoral head flattening and osteoarthritis signs exhibited moderate agreement with statistical significance. In contrast, the detection of radiological osteoporosis and the loss of trabeculation showed the lowest reliability, with negative kappa coefficients. CONCLUSION: There is a lack of agreement between qualified observers, even for the identification of the most characteristic ONFH radiographic feature. The reliability of plain radiography for the detection of basic radiological elements is even weaker in the early stages of the disease.

Tumour microenvironment and heterotypic interactions in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDA) is a disease with a survival rate of 9%; this is due to its chemoresistance and the large tumour stroma that occupies most of the tumour mass. It is composed of a large number of cells of the immune system, such as Treg cells, tumour-associated macrophages (TAMs), myeloid suppressor cells (MDCs) and tumour-associated neutrophiles (TANs) that generate an immunosuppressive environment by the release of inflammatory cytokines. Moreover, cancer-associated fibroblast (CAFs) provide a protective coverage that would difficult the access of chemotherapy to the tumour. According to this, new therapies that could remodel this heterogeneous tumour microenvironment, such as adoptive T cell therapies (ACT), immune checkpoint inhibitors (ICI), and CD40 agonists, should be developed for targeting PDA. This review organizes the different cell populations found in the tumour stroma involved in tumour progression in addition to the different therapies that are being studied to counteract the tumour. (AU)

Tumour microenvironment and heterotypic interactions in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is a disease with a survival rate of 9%; this is due to its chemoresistance and the large tumour stroma that occupies most of the tumour mass. It is composed of a large number of cells of the immune system, such as Treg cells, tumour-associated macrophages (TAMs), myeloid suppressor cells (MDCs) and tumour-associated neutrophiles (TANs) that generate an immunosuppressive environment by the release of inflammatory cytokines. Moreover, cancer-associated fibroblast (CAFs) provide a protective coverage that would difficult the access of chemotherapy to the tumour. According to this, new therapies that could remodel this heterogeneous tumour microenvironment, such as adoptive T cell therapies (ACT), immune checkpoint inhibitors (ICI), and CD40 agonists, should be developed for targeting PDA. This review organizes the different cell populations found in the tumour stroma involved in tumour progression in addition to the different therapies that are being studied to counteract the tumour.

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.

Targeting BPTF Sensitizes Pancreatic Ductal Adenocarcinoma to Chemotherapy by Repressing ABC-Transporters and Impairing Multidrug Resistance (MDR).

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.

Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic.

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia-PanIN) and the molecular alterations associated with them. Mutations in KRAS and inactivation of CDKN2A, SMAD4 and TP53 are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.

Otras causas de dolor abdominal: síndrome de la arteria mesentérica superior / Other causes of abdominal pain: superior mesenteric artery syndrome

La clínica del síndrome de la arteria mesentérica superior se basa en los siguientes síntomas: dolor epigástrico postpandrial, saciedad temprana, náuseas o vómitos biliosos, sobre todo en pacientes con una pérdida significativa de peso reciente o con una intervención quirúrgica previa, en la mayoría de ocasiones por escoliosis. En nuestro trabajo presentamos el caso de un varón de 83 años con antecedentes de fibrilación auricular y EPOC e intervenido por colecistitis litiásica crónica y ulcus péptico, que acude al servicio de urgencias con dolor abdominal intenso junto con vómitos y ausencia de ventoseo y deposición. Debemos pensar en este síndrome una vez descartadas las causas más frecuentes de dolor abdominal. Mediante la sospecha clínica y la realización del TC conseguimos un diagnóstico temprano, y evitamos complicaciones posteriores como alteraciones electrolíticas, perforación gástrica o gas venoso portal

The symptoms of superior mesenteric artery syndrome are: postprandial epigastric pain, early satiety, nausea or bilious vomiting, particularly in patients with significant recent weight loss or with previous surgery, most often scoliosis. We present the case of an 83-year-old man with a history of atrial fibrillation and COPD and previous surgeries due to peptic ulcer and chronic calculous cholecystitis, who arrives in the Emergency Department with severe abdominal pain, vomiting, not passing gas and constipation. We must think about this syndrome once the most frequent causes of abdominal pain have been ruled out. Thanks to clinical suspicion and CT scan we can obtain an early diagnosis and avoid later complications such as electrolyte imbalance, gastric perforation or portal venous gas

Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas.

Chronic inflammation increases the risk of developing one of several types of cancer. Inflammatory responses are currently thought to be controlled by mechanisms that rely on transcriptional networks that are distinct from those involved in cell differentiation. The orphan nuclear receptor NR5A2 participates in a wide variety of processes, including cholesterol and glucose metabolism in the liver, resolution of endoplasmic reticulum stress, intestinal glucocorticoid production, pancreatic development and acinar differentiation. In genome-wide association studies, single nucleotide polymorphisms in the vicinity of NR5A2 have previously been associated with the risk of pancreatic adenocarcinoma. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration and cooperates with mutant Kras in tumour progression. Here, using a global transcriptomic analysis, we describe an epithelial-cell-autonomous basal pre-inflammatory state in the pancreas of Nr5a2+/- mice that is reminiscent of the early stages of pancreatitis-induced inflammation and is conserved in histologically normal human pancreases with reduced expression of NR5A2 mRNA. In Nr5a2+/-mice, NR5A2 undergoes a marked transcriptional switch, relocating from differentiation-specific to inflammatory genes and thereby promoting gene transcription that is dependent on the AP-1 transcription factor. Pancreatic deletion of Jun rescues the pre-inflammatory phenotype, as well as binding of NR5A2 to inflammatory gene promoters and the defective regenerative response to damage. These findings support the notion that, in the pancreas, the transcriptional networks involved in differentiation-specific functions also suppress inflammatory programmes. Under conditions of genetic or environmental constraint, these networks can be subverted to foster inflammation.

c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis.

BACKGROUND AND AIMS: c-Myc is highly expressed in pancreatic multipotent progenitor cells (MPC) and in pancreatic cancer. The transition from MPC to unipotent acinar progenitors is associated with c-Myc downregulation; a role for c-Myc in this process, and its possible relationship to a role in cancer, has not been established. DESIGN: Using coimmunoprecipitation assays, we demonstrate that c-Myc and Ptf1a interact. Using reverse transcriptase qPCR, western blot and immunofluorescence, we show the erosion of the acinar programme. To analyse the genomic distribution of c-Myc and Ptf1a and the global transcriptomic profile, we used ChIP-seq and RNA-seq, respectively; validation was performed with ChIP-qPCR and RT-qPCR. Lineage-tracing experiments were used to follow the effect of c-Myc overexpression in preacinar cells on acinar differentiation. RESULTS: c-Myc binds and represses the transcriptional activity of Ptf1a. c-Myc overexpression in preacinar cells leads to a massive erosion of differentiation. In adult Ela1-Myc mice: (1) c-Myc binds to Ptf1a, and Tcf3 is downregulated; (2) Ptf1a and c-Myc display partially overlapping chromatin occupancy but do not bind the same E-boxes; (3) at the proximal promoter of genes coding for digestive enzymes, we find reduced PTF1 binding and increased levels of repressive chromatin marks and PRC2 complex components. Lineage tracing of committed acinar precursors reveals that c-Myc overexpression does not restore multipotency but allows the persistence of a preacinar-like cell population. In addition, mutant KRas can lead to c-Myc overexpression and acinar dysregulation. CONCLUSIONS: c-Myc repression during development is crucial for the maturation of preacinar cells, and c-Myc overexpression can contribute to pancreatic carcinogenesis through the induction of a dedifferentiated state.

c-MYC partners with BPTF in human cancer.

The c-MYC oncogene is deregulated in virtually all human tumors and therefore constitutes an attractive therapeutic target. We found that the chromatin remodeler BPTF is a c-MYC interactor required for c-MYC chromatin recruitment and transcriptional activity. Moreover, inhibition of BPTF delays tumor development both in vitro and in vivo and its levels positively correlate with c-MYC signatures in human tumors. We propose BPTF as a therapeutic target in c-MYC-addicted tumors.

BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis.

c-MYC oncogene is deregulated in most human tumours. Histone marks associated with transcriptionally active genes define high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are unknown. Here we report that c-MYC interacts with BPTF, a core subunit of the NURF chromatin-remodelling complex. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to decreased c-MYC recruitment to DNA and changes in chromatin accessibility. In Bptf-null MEFs, BPTF is necessary for c-MYC-driven proliferation, G1-S progression and replication stress, but not for c-MYC-driven apoptosis. Bioinformatics analyses unveil that BPTF levels correlate positively with c-MYC-driven transcriptional signatures. In vivo, Bptf inactivation in pre-neoplastic pancreatic acinar cells significantly delays tumour development and extends survival. Our findings uncover BPTF as a crucial c-MYC co-factor required for its biological activity and suggest that the BPTF-c-MYC axis is a potential therapeutic target in cancer.

Choline Kinase Alpha (CHKα) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors.

Choline kinase α (CHKα) plays a crucial role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. We have analyzed the expression of CHKα in cell lines derived from pancreatic ductal adenocarcinoma (PDAC) and have found increased CHKα expression, associated with differentiation. CHKα protein expression was directly correlated with sensitivity to MN58b, a CHKα inhibitor that reduced cell growth through the induction of apoptosis. Accordingly, CHKα knockdown led to reduced drug sensitivity. In addition, we found that gemcitabine-resistant PDAC cells displayed enhanced sensitivity to CHKα inhibition and, in vitro, MN58b had additive or synergistic effects with gemcitabine, 5-fluorouracil, and oxaliplatin, three active drugs in the treatment of PDAC. Using tissue microarrays, CHKα was found to be overexpressed in 90% of pancreatic tumors. While cytoplasmic CHKα did not relate to survival, nuclear CHKα distribution was observed in 43% of samples and was associated with longer survival, especially among patients with well/moderately differentiated tumors. To identify the mechanisms involved in resistance to CHKα inhibitors, we cultured IMIM-PC-2 cells with increasingly higher concentrations of MN58b and isolated a subline with a 30-fold higher IC50. RNA-Seq analysis identified upregulation of ABCB1 and ABCB4 multidrug resistance transporters, and functional studies confirmed that their upregulation is the main mechanism involved in resistance. Overall, our findings support the notion that CHKα inhibition merits further attention as a therapeutic option in patients with PDAC and that expression levels may predict response.

Mnk1 is a novel acinar cell-specific kinase required for exocrine pancreatic secretion and response to pancreatitis in mice.

OBJECTIVE: Pancreatic acinar cell maturation is dependent on the activity of the pancreas transcription factor 1 (PTF1) complex. Induction of pancreatitis leads to MAP kinase activation and transient suppression of the acinar differentiation programme. We investigated the role of MAP kinase-interacting kinase 1 (Mnk1) in mouse exocrine pancreas development and in the response to secretagogue-induced pancreatitis. DESIGN: Mnk1 expression was analysed using immunohistochemistry, RT-qPCR and western blotting. Ptf1a binding to Mnk1 was assessed by chromatin immunoprecipitation and qPCR. Acute pancreatitis was induced in wild type and Mnk1(-/-) mice by 7 h intraperitoneal injections of caerulein. In vitro amylase secretion and trypsinogen activation were assessed using freshly isolated acinar cells. In vivo secretion was quantified by secretin-stimulated MRI. RESULTS: Mnk1 is expressed at the highest levels in pancreatic acinar cells and is a direct PTF1 target. Mnk1 is activated upon induction of pancreatitis and is indispensable for eIF4E phosphorylation. The pancreas of Mnk1(-/-) mice is histologically normal. Digestive enzyme content is significantly increased and c-Myc and Ccnd1 levels are reduced in Mnk1(-/-) mice. Upon induction of acute pancreatitis, Mnk1(-/-) mice show impaired eIF4E phosphorylation, activation of c-Myc and downregulation of zymogen content. Acinar cells show defective relocalisation of digestive enzymes, polarity defects and impaired secretory response in vitro and in vivo. CONCLUSIONS: Mnk1 is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and eIF4E phosphorylation. It is required for the physiological secretory response of acinar cells and for the homeostatic response to caerulein administration during acute pancreatitis.

Ribonucleoprotein HNRNPA2B1 interacts with and regulates oncogenic KRAS in pancreatic ductal adenocarcinoma cells.

BACKGROUND & AIMS: Development of pancreatic ductal adenocarcinoma (PDAC) involves activation of c-Ki-ras2 Kirsten rat sarcoma oncogene homolog (KRAS) signaling, but little is known about the roles of proteins that regulate the activity of oncogenic KRAS. We investigated the activities of proteins that interact with KRAS in PDAC cells. METHODS: We used mass spectrometry to demonstrate that heterogeneous nuclear ribonucleoproteins (HNRNP) A2 and B1 (encoded by the gene HNRNPA2B1) interact with KRAS G12V. We used co-immunoprecipitation analyses to study interactions between HNRNPA2B1 and KRAS in KRAS-dependent and KRAS-independent PDAC cell lines. We knocked down HNRNPA2B1 using small hairpin RNAs and measured viability, anchorage-independent proliferation, and growth of xenograft tumors in mice. We studied KRAS phosphorylation using the Phos-tag system. RESULTS: We found that interactions between HRNPA2B1 and KRAS correlated with KRAS-dependency of some human PDAC cell lines. Knock down of HNRNPA2B1 significantly reduced viability, anchorage-independent proliferation, and formation of xenograft tumors by KRAS-dependent PDAC cells. HNRNPA2B1 knock down also increased apoptosis of KRAS-dependent PDAC cells, inactivated c-akt murine thymoma oncogene homolog 1 signaling via mammalian target of rapamycin, and reduced interaction between KRAS and phosphatidylinositide 3-kinase. Interaction between HNRNPA2B1 and KRAS required KRAS phosphorylation at serine 181. CONCLUSIONS: In KRAS-dependent PDAC cell lines, HNRNPA2B1 interacts with and regulates the activity of KRAS G12V and G12D. HNRNPA2B1 is required for KRAS activation of c-akt murine thymoma oncogene homolog 1-mammalian target of rapamycin signaling, interaction with phosphatidylinositide 3-kinase, and PDAC cell survival and tumor formation in mice. HNRNPA2B1 might be a target for treatment of pancreatic cancer.