Pass-through of unfair trading practices in EU food supply chains

This report presents the results of the research project “Pass-Through of Unfair Trading Practices in EU Food Supply Chains: Methodology and Empirical Application”. The purpose of the project is to design and test a monitoring system of unfair trading practices (UTP) along the agri-food supply chain. The investigation has special focus on assessment of the “pass-through effect”, defined as the consequences for the entire supply chain of UTPs adopted in a specific transaction. The report includes: (i) a review of the economic literature for a better understanding of the economic principles of UTPs; (ii) a review of available data sources and past experiences in UTP monitoring; (iii) the illustration of two alternative approaches for UTP monitoring: B-SEA (broad-scope empirical analysis) and IDEA (in-depth analysis); (iv) a test application of the two approaches to the EU fresh fruit sector; (v) a comparative analysis of the IDEA and B-SEA results and (vi) a discussion of the implications of our research.JRC.D.4-Economics of Agricultur

New Horizons in Metastatic Colorectal Cancer: Prognostic Role of CD44 Expression

Background: The transmembrane glycoprotein CD44, the major hyaluronan (HA) receptor, has been proven to regulate cell growth, survival, differentiation, and migration. It is therefore widely considered to be involved in carcinogenesis. Its role as a new therapeutic target in solid tumors is under evaluation in clinical trials. The prognostic value remains controversial. Here, we aimed to investigate the correlation between CD44 expression and the clinicopathological features and survival in metastatic colorectal cancer (mCRC) patients. Methods: Data from 65 mCRC patients of the Medical Oncology Unit, University Hospital and University of Cagliari were retrospectively collected from 2008 to 2021. Immunohistochemical analysis was performed at the Pathology Division, University Hospital of Cagliari on 3 μm thick sections obtained from paraffin blocks. The intensity of immunohistochemical staining was subclassified into four groups: score 0 if negative or weak membrane staining in less than 10% of tumor cells; score 1+ if weak membrane staining in at least 10% of tumor cells or moderate membrane staining in less than 10% of tumor cells; score 2+ if moderate membrane staining in at least 10% of tumor cells or intensive membrane staining in less than 10% of tumor cells; score 3+ if intense membrane staining in at least 10% of tumor cells. Based on this score, we distinguished patients into low CD44 expression (score 0, 1+, 2+) and high CD44 expression (score 3+). Statistical analysis was performed with MedCalc (survival distribution: Kaplan-Meier; survival comparison: log-rank test; association between categorical variables: Fisher's exact test). Results: Patients' median age was 66 years (range 49-85). Regarding CD44 expression, score was 0 in 18 patients, 1+ in 15 patients, 2+ in 18 patients, and 3+ in 14 patients. Median overall survival (mOS) was 28.1 months (95%CI: 21.3-101). CD44 overexpression (3+) was correlated with poor prognosis (p = 0.0011; HR = 0.2), with a mOS of 14.5 months (95%CI 11.7 to 35.9) versus 30.7 months (95%CI 27.8 to 101) in lower CD44 expression. Higher CD44 expression was associated with clinically poor prognostic features: age ≥ 70 years (p = 0.0166); inoperable disease (p = 0.0008); stage IV at diagnosis (p = 0.0241); BRAF mutated (p = 0.0111), high-grade tumor (p = 0.0084). Conclusions: CD44 markedly correlated with aggressive tumor behavior and contributed to the earlier progression of disease, thus suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients

Performance of the LHCb muon system

The performance of the LHCb Muon system and its stability across the full 2010 data taking with LHC running at ps = 7 TeV energy is studied. The optimization of the detector setting and the time calibration performed with the first collisions delivered by LHC is described. Particle rates, measured for the wide range of luminosities and beam operation conditions experienced during the run, are compared with the values expected from simulation. The space and time alignment of the detectors, chamber efficiency, time resolution and cluster size are evaluated. The detector performance is found to be as expected from specifications or better. Notably the overall efficiency is well above the design requirementsComment: JINST_015P_1112 201

CDX-2 expression correlates with clinical outcomes in MSI-H metastatic colorectal cancer patients receiving immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) showed efficacy in metastatic colorectal cancer (mCRC) with mismatch-repair deficiency or high microsatellite instability (dMMR-MSI-H). Unfortunately, a patient's subgroup did not benefit from immunotherapy. Caudal-related homeobox transcription factor 2 (CDX-2) would seem to influence immunotherapy's sensitivity, promoting the chemokine (C-X-C motif) ligand 14 (CXCL14) expression. Therefore, we investigated CDX-2 role as a prognostic-predictive marker in patients with mCRC MSI-H. We retrospectively collected data from 14 MSI-H mCRC patients treated with ICIs between 2019 and 2021. The primary endpoint was the 12-month progression-free-survival (PFS) rate. The secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and disease control rate (DCR). The PFS rate at 12 months was 81% in CDX-2 positive patients vs 0% in CDX-2 negative patients (p = 0.0011). The median PFS was not reached (NR) in the CDX-2 positive group versus 2.07 months (95%CI 2.07-10.8) in CDX-2 negative patients (p = 0.0011). Median OS was NR in CDX-2-positive patients versus 2.17 months (95% Confidence Interval [CI] 2.17-18.7) in CDX2-negative patients (p = 0.026). All CDX-2-positive patients achieved a disease response, one of them a complete response. Among CDX-2-negative patients, one achieved stable disease, while the other progressed rapidly (ORR: 100% vs 0%, p = 0.0005; DCR: 100% vs 50%, p = 0.02). Twelve patients received 1st-line pembrolizumab (11 CDX-2 positive and 1 CDX-2 negative) not reaching median PFS, while two patients (1 CDX-2 positive and 1 CDX-2 negative) received 3rd-line pembrolizumab reaching a median PFS of 10.8 months (95% CI, 10.8-12.1; p = 0.036). Although our study reports results on a small population, the prognostic role of CDX-2 in CRC seems confirmed and could drive a promising predictive role in defining the population more sensitive to immunotherapy treatment. Modulating the CDX-2/CXCL14 axis in CDX-2-negative patients could help overcome primary resistance to immunotherapy

Report from the American Society of Transplantation on frailty in solid organ transplantation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/1/ajt15198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148387/2/ajt15198.pd

Characterization of Voltage-Gated Ca2+ Conductances in Layer 5 Neocortical Pyramidal Neurons from Rats

Neuronal voltage-gated Ca2+ channels are involved in electrical signalling and in converting these signals into cytoplasmic calcium changes. One important function of voltage-gated Ca2+ channels is generating regenerative dendritic Ca2+ spikes. However, the Ca2+ dependent mechanisms used to create these spikes are only partially understood. To start investigating this mechanism, we set out to kinetically and pharmacologically identify the sub-types of somatic voltage-gated Ca2+ channels in pyramidal neurons from layer 5 of rat somatosensory cortex, using the nucleated configuration of the patch-clamp technique. The activation kinetics of the total Ba2+ current revealed conductance activation only at medium and high voltages suggesting that T-type calcium channels were not present in the patches. Steady-state inactivation protocols in combination with pharmacology revealed the expression of R-type channels. Furthermore, pharmacological experiments identified 5 voltage-gated Ca2+ channel sub-types – L-, N-, R- and P/Q-type. Finally, the activation of the Ca2+ conductances was examined using physiologically derived voltage-clamp protocols including a calcium spike protocol and a mock back-propagating action potential (mBPAP) protocol. These experiments enable us to suggest the possible contribution of the five Ca2+ channel sub-types to Ca2+ current flow during activation under physiological conditions

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine