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Discrimination between axonotmesis and neurotmesis is crucial in traumatic nerve injury. We present the case of a 43-year-old woman which presented hypoesthesia in the fourth and fifth right fingers, started after surgery for Dupuytren syndrome. At ultrasound study, the ulnar digital sensory branch was identified. Before the division into the two terminal branches, a neuroma was observed, while neurotmesis was excluded. This case shows the utility of ultrasonography in peripheral nervous system examination and the possibility of visualization of very small nerves and their terminal branches. [ABSTRACT FROM AUTHOR]

Undifferentiated pleomorphic sarcomas (UPS) represent a prevalent and aggressive subtype of soft tissue sarcomas (STS) in adults. Despite advancements in loco regional treatments, many patients with high grade STS, including UPS, develop metastatic disease. Neoadjuvant chemotherapy is a standard approach to mitigate this risk, but response variability necessitates refined patient selection strategies. This study investigated the correlation between UPS microenvironment and neoadjuvant chemotherapy response in resectable UPS. The NEOSARCOMICS study (NCT02789384) enrolled patients with resectable STS from six sarcoma centers in France. Patients received anthracycline based chemotherapy, followed by surgery. Histological response, gene expression profiling, and multiplex immunohistofluorescence were performed on baseline and post treatment tumor samples. Plasma proteomics was analyzed to identify biomarkers. Good responders to neoadjuvant chemotherapy showed enrichment in genes related to stemness and cell cycle regulation, while poor responders exhibited immune related gene enrichment. Proteomic profiling revealed immune pathway activation and downregulation of cell cycle pathways in non responders. Despite being associated with a good prognosis, high immune infiltration, particularly of CD8 + T cells and CD20 + B cells, predicts a poor response to neoadjuvant chemotherapy in UPS, suggesting the need for alternative therapeutic strategies for patients with inflamed UPS.Ongoing clinical trials are exploring the efficacy of combining chemotherapy with immune checkpoint inhibitors to improve outcomes., (© 2024. The Author(s).)

Social engagement is fundamental to successful aging and linked to better emotional, physical, and cognitive health. Maintaining social engagement is challenging for many older adults but especially for those with a cognitive impairment (CI). Information and communication technologies (ICT) can provide enhanced opportunities for social and cognitive engagement for older adults with a CI via increased information, education, and social connectivity access. This study used a pre-test post-test design to evaluate the feasibility, acceptability, and preliminary efficacy of the PRISM-CI software system, a tablet-based application designed to enhance access to resources, information, and social engagement, in 52 individuals with a CI between the ages of 65-88 years who had access to PRISM-CI for five months. Findings show that social isolation, loneliness, and depressive symptoms significantly decreased, and mobile device proficiency significantly increased, from baseline to follow-up. Results highlight ICTs potential to foster social engagement among older adults with a CI., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Real-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC)., Patients and Methods: In this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI-CPI or tyrosine kinase inhibitor (TKI)-CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS)., Results: Data from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI-CPI therapy (n = 171) and 5.0 months for TKI-CPI therapy (n = 58). After 1L CPI-CPI or TKI-CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies., Conclusion: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI-CPI or TKI-CPI therapy is used., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn't shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-β and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease's biological underpinnings and a commitment to innovative research approaches., (© 2024. The Author(s).)

Our objective was to capture subgroups of soft-tissue sarcoma (STS) using handcraft and deep radiomics approaches to understand their relationship with histopathology, gene-expression profiles, and metastatic relapse-free survival (MFS). We included all consecutive adults with newly diagnosed locally advanced STS (N = 225, 120 men, median age: 62 years) managed at our sarcoma reference center between 2008 and 2020, with contrast-enhanced baseline MRI. After MRI postprocessing, segmentation, and reproducibility assessment, 175 handcrafted radiomics features (h-RFs) were calculated. Convolutional autoencoder neural network (CAE) and half-supervised CAE (HSCAE) were trained in repeated cross-validation on representative contrast-enhanced slices to extract 1024 deep radiomics features (d-RFs). Gene-expression levels were calculated following RNA sequencing (RNAseq) of 110 untreated samples from the same cohort. Unsupervised classifications based on h-RFs, CAE, HSCAE, and RNAseq were built. The h-RFs, CAE, and HSCAE grouping were not associated with the transcriptomics groups but with prognostic radiological features known to correlate with lower survivals and higher grade and SARCULATOR groups (a validated prognostic clinical-histological nomogram). HSCAE and h-RF groups were also associated with MFS in multivariable Cox regressions. Combining HSCAE and transcriptomics groups significantly improved the prognostic performances compared to each group alone, according to the concordance index. The combined radiomic-transcriptomic group with worse MFS was characterized by the up-regulation of 707 genes and 292 genesets related to inflammation, hypoxia, apoptosis, and cell differentiation. Overall, subgroups of STS identified on pre-treatment MRI using handcrafted and deep radiomics were associated with meaningful clinical, histological, and radiological characteristics, and could strengthen the prognostic value of transcriptomics signatures., (© 2024. The Author(s).)

Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin's antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas. 50 patients participated: 20 in phase I and 30 in phase II. Changes in the TME were assessed in 28 patients using sequential tumor samples at baseline and day two of the cycle. Treatment notably decreased CD68 + CD163 + macrophages in biopsies from tumor lesions compared to pre-treatment samples in 9 of the 28 patients after 4 weeks. Baseline CD8 + T cell presence increased in 11 of these patients. In summary, up to 57% of patients exhibited a positive immunological response marked by reduced M2 macrophages or increased CD8 + T cells post-treatment. This positive shift in the TME correlated with improved clinical benefit and progression-free survival. This study offers the first prospective evidence of trabectedin's immunological effect in advanced STS patients, highlighting a relationship between TME modulation and patient outcomes.This study was registered with ClinicalTrial.gov, number NCT02406781., (© 2024. The Author(s).)

<b><br>Introduction:</b> The results of some studies show that predictors of less favourable outcomes of surgery for carpal tunnel syndrome might include the presence of comorbidities, such as diabetes and thyroid gland diseases. The role of these factors has not been clearly determined, but in most trials the patients burdened with comorbidities conducive to CTS are excluded from the analysis.</br> <b><br>Aim:</b> The aim of this study was to investigate the effect of concomitant diseases on the clinical profile and outcomes of surgery for carpal tunnel syndrome.</br> <b><br>Material and methods:</b> The study group consisted of 1117 patients - 909 women (81%) and 208 men (19%) - at a mean age of 63 years. A total of 972 patients (87%) declared having at least one comorbidity, whereas 145 patients (13%) declared no comorbidities. The measurements were performed preoperatively and at 6 months postoperatively; they included pain intensity, total grip and key-pinch strength, digital sensibility and hand function with Levine's questionnaire.</br> <b><br>Results:</b> At baseline, the patients with comorbidities had significantly worse digital sensiblility, weaker total grip strength and greater functional impairment of the hand, but only grip strength reached the minimal important difference (3.5 kg). Carpal tunnel release resulted in significant improvement in the tested variables for all patients, although the outcomes at 6 months were less favourable for those with comorbidities with regard to digital sensiblility, total grip and pinch strength and function of the hand. All these differences were statistically significant, but only grip strength reached the minimal important difference (2.9 kg).</br> <b><br>Conclusion:</b> The results of this study show that comorbidities in patients suffering from CTS had a statistically and clinically significant negative effect only on the total grip strength pre- and postoperatively, and no significant effect on the outcome of surgery, which was satisfactory in all patients.</br&gt.

Dentex gibbosus (Pink dentex) is a fish species of increasing economic interest in the Mediterranean Sea that is consumed both whole and processed. The growing value of this sparid in European markets is responsible for its substitution with fraudulent species. The distinctive morphologic feature of D. gibbosus is the conspicuous hump on the forehead in the older and larger specimens. However, the head is regularly convex in young individuals, requiring high skills and competencies for correct identification. Authentication becomes even more challenging in the case of prepared and processed products. Therefore, the molecular characterization of Pink dentex plays a crucial role in preventing commercial fraud with species substitution. This paper proposes a comparative mitogenome analysis between 19 sparid species of commercial interest as a tool to accurately design species-specific primers targeting a fragment of the NAD2 gene for the identification of D. gibbosus . We successfully detected Pink dentex DNA both using endpoint and real-time PCR. The findings showed the high specificity of the designed primers, demonstrating this a suitable, fast, and cost-effective method that could be used for the unambiguous identification of Pink dentex. This innovative approach for sparid authentication is expected to contribute to seafood traceability, public health assurance, integrity, and the credibility of the seafood industry.

The complete nucleotide sequence of the mitochondrial (mt) genome of the demersal zebra seabream Diplodus cervinus (Lowe, 1838) was determined for the first time. The double stranded circular molecule is 16,559 base pairs (bp) in length and encodes for the typical 37 metazoan mitochondrial genes, and 2 non-coding regions (D-loop and L-origin). The gene arrangement of the D. cervinus mt genome follows the usual one for fishes. The nucleotide sequences of the mt protein coding and ribosomal genes of D. cervinus mt genome were aligned with orthologous sequences from representatives of the Sparidae family and phylogenetic relationships were inferred. Maximum likelihood analyses placed D. cervinus as a sister species of Diplodus sargus (Linnaeus, 1758)., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

L. monocytogenes is a foodborne pathogen responsible for a serious disease with a high mortality rate, particularly in vulnerable consumers. Recently, the scientific community has shown increasing attention to the search for new natural molecules with antimicrobial activity, aimed at preventing the spread of foodborne diseases. Extremophilic microorganisms, typical of extreme temperature environments, are a valuable source of these molecules. The present work aimed to study the antibacterial activity of four pure compounds derived from a molecule, the pentadecanal, produced by the Antarctic bacterium Pseudoalteromonas haloplanktis , against two different pathotypes of L. monocytogenes . Growth assays were performed in 96-well polystyrene plates with serial dilutions of the tested compounds at different concentrations (0.6, 0.3, 0.15, 0.07 mg/mL). The plates were incubated at 37°C for 24 h, with a spectrophotometric reading at OD 600 nm. Preliminary results of this study showed that pentadecanal inhibits the growth of L. monocytogenes , with a MIC (Minimum Inhibitory Concentration) of 0.6 mg/mL. Acetal, carboxylic acid, and ester did not demonstrate antibacterial activity at the concentrations tested. These findings suggest the possibility of using pentadecanal as a natural antibacterial to improve safety standards along the food supply chain., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort., Experimental Design: Data from 185 patients were retrospectively collected in 23 European GIST reference centers. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Univariate and multivariate unweighted and weighted Cox proportional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival., Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79-2.28]. The variables consistently associated with worse survival outcomes were high mitotic index and nongastric tumor location., Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted., (©2021 The Authors; Published by the American Association for Cancer Research.)

This study focused on the characterization of salami produced with meat from different pig breeds. The aim consisted in evaluating the added value of the inclusion of Apulo-Calabrese meat in the production of salami, which was characterized by production until the end of maturation (1, 30, 60, and 120 days). The experimental design involved three types of salami, two of which were produced by partial inclusion of 50 and 75% of the Italian breed pork meat (S50 and S75, respectively). Physicochemical (pH, a w , fatty acid analysis, and malondialdehyde concentration), rheological parameters (texture analyses and color measurement), and bacterial biodiversity were evaluated. Results showed that the partial inclusion of Apulo-Calabrese meat influences the fatty acid profile of final products, which were characterized by a higher percentage of monounsaturated fatty acids compared to traditional salami; however, due to the high content of unsaturated fatty acids, S50 and S75 showed higher values of secondary lipid oxidation up to the 120th day. The linoleic and palmitic acid content significantly affected hardness and brightness. Overall, the ripening process was able to control the microbiological profile and the S50 formulation appeared as a suitable choice that could satisfy consumers for nutritional expectations and sensory profiles.

The increasing world market demand for seafood requires an expansion of product categories available to consumers. Inland fish are usually considered having unmarked taste and are less appreciated by consumers; thus, they have low commercial value. Therefore, the marketing of the lake's fresh and processed fish is limited to the local market and consumers are currently uninformed and mistrustful about these species. In this study, six different fish species were caught in the Fondi lake (Lazio, central Italy): Anguilla anguilla , Tinca tinca , Carassius gibelio , Cyprinus carpio , Micropterus salmoides , Chelon ramada . All the samples were subjected to nutritional and DNA barcoding analysis. Moisture, protein, fat, carbohydrates, ash, and sodium content were measured. As regards the fatty acids profile, the most abundant were MUFAs with the highest value in Anguilla anguilla (45.97%). Oleic acid (C18: 1 n9 cis) was particularly high in Cyprinus carpio (55.46%). The fraction of polyunsaturated fatty acids (PUFA) revealed a higher DHA content (C22: 6 n3) in Anguilla anguilla than the other species (>12 %) while Chelon ramada presented both higher EPA content (C 20: 5 n3) and total fraction of omega 3 PUFAs. Concerning molecular analysis, a 655 bp fragment of cytochrome C oxidase subunit I ( COI ) gene was successfully used for the identification at the species level using both BOLD and BLAST public databases. The present study gives the basis for improving the knowledge and promoting inland fish' market and traceability along the supply chain., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Purpose: Neoadjuvant chemotherapy (NAC) has been increasingly used in patients with locally advanced high-risk soft tissue sarcomas in the past decade, but definition and prognostic impact of a good histologic response (GHR) are lacking. Our aim was to investigate which histologic feature from the post-NAC surgical specimen independently correlated with metastatic relapse-free survival (MFS) in combination with clinical, radiologic, and pathologic features using a machine learning approach., Methods: This retrospective study included 175 consecutive patients (median age: 59 years, 75 women) with resectable disease, treated with anthracycline-based NAC between 1989 and 2015 in our sarcoma reference center, and with quantitative histopathologic analysis of the surgical specimen. The outcome of interest was the MFS. A multimodel, multivariate survival analysis was used to define GHR. The added prognostic value of GHR was investigated through the comparisons with the standard model (including histologic grade, size, and depth) and SARCULATOR nomogram using concordance indices (c-index) and Monte-Carlo cross-validation., Results: Seventy-two patients (72 of 175, 41.1%) had a metastatic relapse. Stepwise Cox regression, random survival forests, and least absolute shrinkage and selection operator-penalized Cox regression all converged toward the same definition for GHR, ie, < 5% stainable tumor cells. The five-year MFS probability was 1 (95% CI, 1 to 1) in patients with GHR versus 0.73 (95% CI, 0.65 to 0.81) in patients without GHR (log-rank P = .0122). The final prognostic model incorporating the GHR was significantly better than the standard model and SARCULATOR (average c-index in testing sets = 0.72 [95% CI, 0.61 to 0.82] v 0.57 [95% CI, 0.44 to 0.70] and 0.54 [95% CI, 0.45 to 0.64], respectively; P = .0414 and .0091)., Conclusion: Histologic response to NAC improves the prediction of MFS in patients with soft tissue sarcoma and represents a possible end point in future studies exploring innovative regimens in the neoadjuvant setting., Competing Interests: François Le LoarerSpeakers' Bureau: Blueprint MedicinesTravel, Accommodations, Expenses: PharmaMar Eberhard StoeckleHonoraria: Bayer, Daiichi Sankyo, Lilly, Epizyme, Novartis, Roche, IPSENConsulting or Advisory Role: Roche, Immune Design, Epizyme, Bayer, LillyResearch Funding: Roche, Bayer, AstraZeneca/MedImmune, PharmaMar, MSD Oncology, Merck SeronoPatents, Royalties, Other Intellectual Property: BMSNo other potential conflicts of interest were reported.

The white seabream Diplodus sargus (Linnaeus, 1758) is a species of interest for commercial fisheries throughout its range of distribution and it is also reared using aquaculture techniques. Herein, we present the first complete sequence and annotation of the mitochondrial genome of this species. The D. sargus mitogenome is 16,515 base pairs in length and contains 13 protein-coding genes, 2 rRNA, 22 tRNA, and 2 non-coding regions (D-loop and L-origin). The overall nucleotide composition is: 27.3% A, 28.9% C, 26.8% T, and 17.0% G. Maximum likelihood analyses placed D. sargus as a sister species of Diplodus puntazzo. This study provides valuable information for further studying identification methods and evolutionary relationships of Sparidae species., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Beef burgers are meat preparations with easy perishability. To ensure a longer shelflife, the Regulation EU 1129/11 allows the use of some additives. However, healthconscious consumers prefer products which do not contain synthetic substances. Aim of the present study was to evaluate the effect of Red Beetroot ( Beta vulgaris ) integration on Black Angus made burgers shelf life. Red beet was prepared as powder and added to meat mixture as the same or in water solution. The study was split into 2 trials to assess the extract activity also in burgers vacuum-packaged stored. Burgers were analysed (up to 9 days at 4°C) in terms of sensory properties, microbiological profile, pH, a w and lipid oxidation (TBARS). At the end of storage, treated samples showed the highest values of redness and the lowest content of malondialdehyde, probably due to antioxidant properties of red beet towards myoglobin and lipid oxidation processes. Moreover, results highlighted that Red Beetroot activities were dose-dependent and intensified if dissolved in water. The a w values did not appear to be conditioned by extract integrations, unlike the pH that was lower in treated samples than control ones. Microbiological analyses identified beetroot as a potential antimicrobial substance, especially in high concentration. In conclusion, Beta vulgaris extract could be proposed as natural compound exploitable in beef burgers to preserve qualities and extend their shelf-life., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

The common dentex ( Dentex dentex (Linnaeus, 1758)) is an iconic fish in the Mediterranean diet. Due to its commercial and organoleptic importance, this sparid is highly appreciated in European markets and is often subjected to species substitution frauds. Comparative mitogenomics is a suitable approach for identifying new and effective barcode markers. This study aimed to find a molecular tag useful for unequivocally discriminating the sparid species D. dentex . The comparison of the complete mitochondrial DNA (mtDNA) sequences of 16 sparid species allowed us to highlight the potential of the NAD2 gene for direct identification purposes. Common dentex-specific primers were created and successfully evaluated by end-point and real-rime PCR (Polymerase Chain Reaction) for several fish species, achieving amplification only in the D. dentex . The method proposed in this study appears fast, simple, and inexpensive and requires affordable instrumentation. This approach provides unambiguous results for the common dentex authentication without the sequencing step. The presence/absence assay for D. dentex can be executed in a few hours of lab work. Therefore, national authorities responsible for food safety and traceability could apply and make full use of DNA-testing methods for deterring operators from false seafood declarations.

Sardina pilchardus and Engraulis encrasicolus are considered the principal target species for commercial fishing in Europe and are widely consumed as semipreserved products. Although they are considered shelf-stable products, if treatment is not correctly applied, their consumption may represent a public health risk in regard to anisakiasis and allergic reactions. Little is known about the prevalence of Anisakis spp. in ripened products. This study aimed to evaluate the presence of Anisakis spp. larvae in deboned, in-oil anchovy and sardine fillets marketed in the EU to assess the influence of processing techniques on the prevalence of larvae. Ninety semipreserved anchovy and sardine products deriving from the Mediterranean Sea or Atlantic Ocean were collected from different EU retailers and examined using chloropeptic digestion to evaluate the presence of larvae and identify them. Thirty nonviable Anisakid larvae- A. pegreffii (30%) and A. simplex (70%)-were found. The frequency of larvae was higher in anchovies (28.8%). The low frequency of parasites found proved that processing technologies can influence the presence of larvae in final products, but it is important that visual inspection is performed only by trained people. The sources of raw materials should be considered in the production flow chart.

The commercialization of porgies or seabreams of the family Sparidae has greatly increased in the last decade, and some valuable species have become subject to seafood substitution. DNA regions currently used for fish species identification in fresh and processed products belong to the mitochondrial (mt) genes cytochrome b ( Cytb ), cytochrome c oxidase I ( COI ), 16S and 12S . However, these markers amplify for fragments with lower divergence within and between some species, failing to provide informative barcodes. We adopted comparative mitogenomics, through the analysis of complete mtDNA sequences, as a compatible approach toward studying new barcoding markers. The intent is to develop a specific and rapid assay for the identification of the common pandora Pagellus erythrinus , a sparid species frequently subject to fraudulent replacement. The genetic diversity analysis (Hamming distance, p -genetic distance, gene-by-gene sequence variability) between 16 sparid mt DNA genomes highlighted the discriminating potential of a 291 bp NAD2 gene fragment. A pair of species-specific primers were successfully designed and tested by end-point and real-time PCR, achieving amplification only in P. erythrinus among several fish species. The use of the NAD2 barcoding marker provides a rapid presence/absence method for the identification of P. erythrinus .

The desmoid tumor is a locally aggressive proliferative disease within the family of soft-tissue sarcomas. Despite its relatively good prognosis, the clinical management of desmoid tumors requires constant multidisciplinary evaluation due to its highly variable clinical behavior. Recently, active surveillance has being regarded as the appropriate strategy at diagnosis, as indolent persistence or spontaneous regressions are not uncommon. Here, we review the most recent advances in desmoid tumor therapy, including low-dose chemotherapy and treatment with tyrosine kinase inhibitors. We also explore the recent improvements in our knowledge of the molecular biology of this disease, which are leading to clinical trials with targeted agents.

Listeria monocytogenes is a foodborne pathogen responsible for about 1600 illnesses each year in the United States (US) and about 2500 confirmed invasive human cases in European Union (EU) countries. Several technologies and antimicrobials are applied to control the presence of L. monocytogenes in food. Among these, the use of natural antimicrobials is preferred by consumers. This is due to their ability to inhibit the growth of foodborne pathogens but not prompt negative safety concerns. Among natural antimicrobials, plant extracts are used to inactivate L. monocytogenes . However, there is a large amount of these types of extracts, and their active compounds remain unexplored. The aim of this study was to evaluate the antibacterial activity against L. monocytogenes of about 800 plant extracts derived from plants native to different countries worldwide. The minimal inhibitory concentrations (MICs) were determined, and scanning electron microscopy (SEM) was used to verify how the plant extracts affected L. monocytogenes at the microscopic level. Results showed that 12 of the plant extracts had inhibitory activity against L. monocytogenes . Future applications of this study could include the use of these plant extracts as new preservatives to reduce the risk of growth of pathogens and contamination in the food industry from L. monocytogenes .

The sharpsnout seabream Diplodus puntazzo Walbaum, 1792 is a target species of small-scale fishery activities and is cage-cultured for human consumption. Nonetheless, genetic information on this species is limited. We here first sequence its complete mitochondrial genome. The sequence is composed of 16,638 base pairs, accounting for 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non-coding regions (D-loop and L-origin). The overall nucleotide composition is: 27.4% A, 28.9% C, 26.9% T, and 16.8% G. Maximum likelihood analyses placed D. puntazzo close to Acanthopagrus and some Pagellus species., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Escherichia coli sequence type 131 (ST131) has recently emerged as a leading multidrug-resistant pathogen that causes urinary tract and bloodstream infections in humans. Here, we report the draft genomic sequences of three E. coli ST131 isolates, H45, H43ii, and H43iii, from urine samples of patients in Lagos, Nigeria.

A series of new 3-phenyl-5-aryl- N -(4-sulfamoylphenyl)-4,5-dihydro-1 H -pyrazole-1-carboxamide derivatives was designed here, synthesized, and studied for carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity against the human (h) isozymes I, II, and VII (cytosolic, off-target isoforms), and IX and XII (anticancer drug targets). Generally, CA I was not effectively inhibited, whereas effective inhibitors were identified against both CAs II (K I s in the range of 5.2-233 nM) and VII (K I s in the range of 2.3-350 nM). Nonetheless, CAs IX and XII were the most susceptible isoforms to this class of inhibitors. In particular, compounds bearing an unsubstituted phenyl ring at the pyrazoline 3 position showed 1.3-1.5 nM K I s against CA IX. In contrast, a subset of derivatives having a 4-halo-phenyl at the same position of the aromatic scaffold even reached subnanomolar K I s against CA XII (0.62-0.99 nM). Docking studies with CA IX and XII were used to shed light on the derivative binding mode driving the preferential inhibition of the tumor-associated CAs. The identified potent and selective CA IX/XII inhibitors are of interest as leads for the development of new anticancer strategies.

Introduction: Desmoid tumour (DT) is a locally aggressive fibroblastic proliferative disease representing the most common extraintestinal manifestation of familial adenomatosis polyposis (FAP). As data on the activity of chemotherapy in these patients are limited, we examined the outcomes of patients treated with low-dose methotrexate (MTX)+vinca alkaloids (vinorelbine or vinblastine)., Patients and Methods: We retrospectively reviewed clinical and outcome data from all patients with confirmed FAP-associated DTs treated with weekly MTX+vinca alkaloids in seven European sarcoma reference centres between January 2000 and December 2018. Radiological responses were assessed using RECIST V.1.0 and V.1.1. The Kaplan-Meier method associated to the log-rank test was used to estimate and compare survival curves., Results: We identified 37 patients (median age 29 years, range 7-44). According to RECIST, 20/37 (54.1%) patients achieved partial response (PR), 15/37 (40.5%) patients had stable disease and 2/37 (5.4%) had progressive disease as best response. Overall, the median progression-free survival (PFS) was 6.5 years (range, 0.3-12.1 years). In the subset of patients achieving PR as best response, the median PFS was not reached. In a subset of 11 patients with progressive disease offered MTX+vinca alkaloids rechallenge (after chemotherapy withdrawal following prolonged disease control), the disease control rate was 100%, resulting in a median PFS after rechallenge of 5.8 years., Conclusions: This is the largest series on the activity of low-dose chemotherapy in patients with FAP-related DT. In this population, MTX+vinca alkaloids is an active combination, as already reported in patients with sporadic DT., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Sparid fish species have different commercial values related to their organoleptic features. Mitochondrial (mt) DNA provides a potential tool to distinguish species, but the enrichment of high-quality mtDNA from total genomic DNA is critical to obtain entire mtDNA sequences. Conventional mtDNA isolation is relatively low-cost and proficient. However, high numbers of PCR cycles can lead to artefacts (10 -6 mutations/bp). We describe a rapid protocol for mtDNA extraction and enrichment from fish tissues, based on conventional miniprep columns and paramagnetic bead-based purification, without the need to employ PCR amplification. This newly described method generates a substrate for next-generation sequencing (NGS) analysis and is likely to have wider applications for mitochondrial studies in other fish families to help ensure traceability and differentiation of fish with high commercial values., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Sixteen 5-aryl-substituted isothiazol-3(2H)-one-1,(1)-(di)oxide analogs have been prepared from the corresponding 5-chloroisothiazol-3(2H)-one-1-oxide or -1,1-dioxide by a Suzuki-Miyaura cross-coupling reaction and screened for their inhibition potency against four human carbonic anhydrase isoenzymes: the transmembrane tumor-associated hCA IX and XII and the cytosolic off-target hCA I and II. Most of the synthesized derivatives inhibited hCA IX and XII isoforms in nanomolar range, whereas remained inactive or modestly active against both hCA I and II isoenzymes. In the N-tert-butylisothiazolone series, the 5-phenyl-substituted analog (1a) excelled in the inhibition of tumor-associated hCA IX and XII (K i  = 4.5 and K i  = 4.3 nM, respectively) with excellent selectivity against off target hCA I and II isoenzymes (S > 2222 and S > 2325, respectively). Since the highest inhibition activities were observed with N-tert-butyl derivatives, lacking a zinc-binding group, we suppose to have a new binding mode situated out of the active site. Additionally, three free-NH containing analogs (3a, 4a, 3i) have also been prepared in order to study the impact of free-NH containing N-acyl-sulfinamide- (-SO-NH-CO-) or N-acyl-sulfonamide-type (-SO 2 -NH-CO-) derivatives on the inhibitory potency and selectivity. Screening experiments evidenced 5-phenylisothiazol-3(2H)-one-1,1-dioxide (4a), the closest saccharin analog, to be the most active derivative with inhibition constants of K i  = 40.3 nM and K i  = 9.6 nM against hCA IX and hCA XII, respectively. The promising biological results support the high potential of 5-arylisothiazolinone-1,(1)-(di)oxides to be exploited for the design of potent and cancer-selective carbonic anhydrase inhibitors., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

In this case report, we describe an older adult man affected by advanced chordoma progressing after treatment with cisplatin and imatinib. The patient was symptomatic for uncontrolled pain. We decided to treat the patient with metronomic cyclophosphamide, unexpectedly achieving long-lasting clinical and radiological benefit., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The tyrosine kinase inhibitor (TKI) imatinib has radically changed the natural history of KIT-driven gastrointestinal stromal tumours (GISTs). Approved second-line and third-line medical therapies are represented by the TKIs sunitinib and regorafenib, respectively. While imatinib remains the cardinal drug for patients with GISTs, novel therapies are being developed and clinically tested to overcome the mechanisms of resistance after treatments with the approved TKI, or to treat subsets of GISTs driven by rarer molecular events. Here, we review the therapy of GISTs, with a particular focus on the newest drugs in advanced phases of clinical testing that might soon change the current therapeutic algorithm., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.