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Glioblastoma (GBM) cancer stem cells (GSCs) contribute to GBM's origin, recurrence, and resistance to treatment. However, the understanding of how mRNA expression patterns of GBM subtypes are reflected at global proteome level in GSCs is limited. To characterize protein expression in GSCs, we performed in‐depth proteogenomic analysis of patient‐derived GSCs by RNA‐sequencing and mass‐spectrometry. We quantified > 10 000 proteins in two independent GSC panels and propose a GSC‐associated proteomic signature characterizing two distinct phenotypic conditions; one defined by proteins upregulated in proneural and classical GSCs (GPC‐like), and another by proteins upregulated in mesenchymal GSCs (GM‐like). The GM‐like protein set in GBM tissue was associated with necrosis, recurrence, and worse overall survival. Through proteogenomics, we discovered 252 non‐canonical peptides in the GSCs, i.e., protein sequences that are variant or derive from genome regions previously considered non‐protein‐coding, including variants of the heterogeneous ribonucleoproteins implicated in RNA splicing. In summary, GSCs express two protein sets that have an inverse association with clinical outcomes in GBM. The discovery of non‐canonical protein sequences questions existing gene models and pinpoints new protein targets for research in GBM. Cancer stem cells (GSCs) drive malignancy in glioblastoma. However, their molecular phenotype is not well understood. Here, we report proteomic profiling of GSCs and protein sets that separate two GSC types, which are differentially associated with overall survival in glioblastoma. Through proteogenomics, we detect matching mRNA and protein sequences mapping to gene regions previously considered non‐coding for proteins, including variants of HNRNPs.

The clinical and biological significance of clonal hematopoiesis (CH) has not been investigated in the myeloid compartment of chronic lymphocytic leukemia (CLL). By studying 488 newly diagnosed CLL through CAPP‐seq using a 28‐gene panel on granulocyte genomic DNA (gDNA), CH occurred in 231 (47.3%) patients. Cell sorting of cases that never developed Richter transformation (RT) confirmed that CH mutations, including CH‐related TP53 mutations, were restricted to the myelomonocytic compartment and absent in CLL cells, as also documented by single‐cell DNA sequencing. CH associated with shorter overall survival (OS) (hazard ratio [HR] 1.36, 95% CI 1.04–1.77, P = 0.023); specifically, TET2 mutations independently predicted inferior OS (HR 1.62, 95% CI 1.15–2.28, P = 0.01) after adjusting for age and for CLL‐related prognostic biomarkers, namely IGHV and TP53 status. Regarding therapy‐related toxicities, CH correlated with a higher incidence of Grade ≥ 3 neutropenia (P = 0.004) after venetoclax‐based regimens. Sequential samples ( n = 57) analysis showed that Bruton tyrosine kinase (BTK) and BCL2 inhibitors do not induce CH expansion, which was instead driven by chemotherapy. CH is significantly associated with a higher risk of second hematological malignancies only in chemo‐exposed patients. Single‐cell RNA sequencing of seven CH+ and six CH− CLL revealed that the T‐cell compartment of CH+ patients exhibits a less exhausted phenotype, documented by lower expression of TOX, the master regulator of T‐cell exhaustion, and a higher pro‐inflammatory profile. CH also influenced RT, since CH ASXL1 mutations independently associated with higher RT risk (HR 11.19, 95% CI 4.09–30.62, P < 0.001). Overall, CH in CLL impacts survival, therapeutic toxicity, and transformation risk while also influencing the T‐cell immune compartment.

Minimal/measurable residual disease (MRD) evaluation has resulted in a fundamental instrument to guide patient management in acute lymphoblastic leukemia (ALL). From a methodological standpoint, MRD is defined as any approach aimed at detecting and possibly quantifying residual neoplastic cells beyond the sensitivity level of cytomorphology. The molecular methods to study MRD in ALL are polymerase chain reaction (PCR) amplification-based approaches and are the most standardized techniques. However, there are some limitations, and emerging technologies, such as digital droplet PCR (ddPCR) and next-generation sequencing (NGS), seem to have advantages that could improve MRD analysis in ALL patients. Furthermore, other blood components, namely cell-free DNA (cfDNA), appear promising and are also being investigated for their potential role in monitoring tumor burden and response to treatment in hematologic malignancies. Based on the review of the literature and on our own data, we hereby discuss how emerging molecular technologies are helping to refine the molecular monitoring of MRD in ALL and may help to overcome some of the limitations of standard approaches, providing a benefit for the care of patients.

Glioblastoma’s (GBM) origin, recurrence and resistance to treatment are driven by GBM cancer stem cells (GSCs). Existing transcriptomic characterisations of GBM classify the tumours to three subtypes: classical, proneural, and mesenchymal. The comprehension of how expression patterns of the GBM subtypes are reflected at global proteome level in GSCs is limited. To characterise protein expression in GSCs, we performed in-depth proteogenomic analysis of patient-derived GSCs by RNA-sequencing and mass-spectrometry proteomics. We identified and quantified over 10,000 proteins in two independent GSCs panels, and propose a GSC-associated proteomic signature (GSAPS) that defines two distinct morphological conditions; one defined by a set of proteins expressed in non-mesenchymal - proneural and classical - GSCs (GPC-like), and another expressed in mesenchymal GSCs (GM-like). The expression of GM-like protein set in GBM tissue was associated with hypoxia, necrosis, recurrence, and worse overall survival in GBM patients. In a proof-of-concept proteogenomic approach, we discovered 252 non-canonical peptides expressed in GSCs, i.e., protein sequences that are variant or derive from genome regions previously considered protein-non-coding. We report new variants of the heterogeneous ribonucleoproteins (HNRNPs), which are implicated in mRNA splicing. Furthermore, we show that per-gene mRNA-protein correlations in GSCs are moderate and vary compared to GBM tissue. Competing Interest Statement The authors have declared no competing interest.

Sea fennel (Crithmum maritimum L.) is an emerging crop valued for its nutritional and sensory properties and has been reported to exert health-promoting effects, including antioxidant, anti-inflammatory, antimicrobial, and cardioprotective activities, as well as potential benefits for gut health and metabolic regulation. Building on these features, the present study aimed to unlock the potential of sea fennel to produce novel pickles. Two independent batches were prepared using young leaves and stems of sea fennel fermented in brine. After fermentation, salt concentration was standardized in all prototypes, and two types of vinegar (apple and wine) were added at four acetic acid levels (0.05%, 0.2%, 0.5%, and 0.7%). All prototypes were subsequently subjected to mild pasteurization. During fermentation, physicochemical and microbiological parameters were monitored, while after pasteurization additional physicochemical, microbiological, volatile organic compound (VOCs), and sensory analyses were performed during storage. In both batches and across all prototypes, fermentation resulted in a significant pH decrease, dominance of lactic acid bacteria, inhibition of Enterobacteriaceae, and a gradual increase in yeasts. Following vinegar addition and pasteurization, pH, titratable acidity, and salt content remained stable over six months of storage in most prototypes, particularly those with 0.2% acetic acid. Pasteurization effectively inactivated lactic acid bacteria and Enterobacteriaceae in all prototypes, whereas yeasts and mesophilic bacteria persisted in low-acidity samples (0.05%). Therefore, the 0.05% acidity samples were later excluded due to mid-stage microbial spoilage. Batch-dependent differences were observed in color and sensory attributes, with batch 2 showing higher overall stability mainly in acidic flavor and aroma, particularly in prototypes with 0.2% acidity. VOCs analysis revealed profiles primarily driven by batch variation, with secondary modulation by vinegar type: sesquiterpenes remained stable, while γ-terpinene, limonene, and p-cymene were the dominant compounds, with greater stability observed in batch 2. Overall, the combined use of lactic acid fermentation, vinegar pickling, and mild pasteurization represents a promising strategy for preserving sea fennel and supports its potential as a vegetable crop.

BackgroundInguinal hernia repair via multi-trocar laparoscopy (MTL) has gained an increasing popularity worldwide. Single-incision laparoscopy (SIL) has been introduced to reduce the port-related complications and to improve the cosmetic results. The authors report a prospective randomized study comparing SIL versus MTL totally extraperitoneal (TEP) inguinal hernia repair.MethodsBetween January 2013 and May 2015, 113 versus 97 patients were prospectively randomized between SILTEP and MTLTEP. Perioperative, short-term, and mid-term outcomes have been assessed. The primary endpoint was the mid-term outcomes (late postoperative complications, late inguinal hernia recurrence, surgical and cosmetic satisfactions). Secondary endpoints were perioperative outcomes (operative time, mesh fixation, operative complications, postoperative pain, and hospital stay) and short-term outcomes (early postoperative complications, early inguinal hernia recurrence, and days to return to normal activities).ResultsAfter a mean follow-up of 27 ± 8 months, a statistically significant difference was found between the two groups in terms of mean operative time for both unilateral and bilateral inguinal hernia repair (p = 0.016; p = 0.039) and cosmetic satisfaction (p = 0.003).ConclusionPerioperative, short-term, and mid-term outcomes were comparable between the two groups. At 2-year follow-up, a significant shorter operative time after MTLTEP and a greater cosmetic satisfaction after SILTEP have been found.

The effect of dietary supplementation with vitamin E, oregano, and prebiotic on fatty acids and oxidative profiles of rabbit meat (loin and hind leg) was evaluated. New Zealand white rabbits weaned at 30 days of age were fed with one of six diets until 80 days of age: standard diet including ω3 polyunsaturated fatty and conjugated linolenic acids sources (S) and five diets adding vitamin E (150 ppm, E), oregano water extract (2 g/kg feed diet, O), prebiotic (THEPAX® 1.5 g/kg feed diet, T), vitamin E plus prebiotic (TE), and oregano water extract plus prebiotic (TO), respectively. The lipid oxidative status (TBARS) showed lower values with respect to S, mainly when vitamin E was administered. In particular, all the experimental diets decreased TBARS values with respect to the control group in the loin, but no effect was found in the hind leg. In all feed samples, the amounts of fatty acid classes increased in the following order: polyunsaturated fatty acids > monounsaturated fatty acid > saturated fatty acid. The dietary supplementations did not affect the fatty acid composition of meat. The experimented diets compared to the control were not able to provide a selective increase of bioactive fatty acid in meat samples; however, the six nutritional strategies led to highly nutritional rabbit meat with an interesting value of the ω6/ω3 ratio.