Parenteral Nutrition in Liver Resection

Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection

Bile duct injury after cholecystectomy: timing of surgical repair should be based on clinical presentation. The experience of a tertiary referral center with Hepp-Couinaud hepatico-jejunostomy

Impact of timing of repair on outcomes of patients repaired with Hepp-Couinaud hepatico-jejunostomy (HC-HJ) after bile duct injury (BDI) during cholecystectomy remains debated. This is an observational retrospective study at a tertiary referral hepato-biliary center. HC-HJ was always performed in patients without sepsis or bile leak and with dilated bile ducts. Timing of repair was classified as: early (≤ 2 weeks), intermediate (> 2 weeks, ≤ 6 weeks), and delayed (> 6 weeks). 114 patients underwent HC-HJ between 1994 and 2022: 42.1% underwent previous attempts of repair at referring institutions (Group A) and 57.9% were referred without any attempt of repair before referral (Group B). Overall, a delayed HC-HJ was performed in 78% of patients; intermediate and early repair were performed in 17% and 6%, respectively. In Group B, 10.6% of patients underwent an early, 27.3% an intermediate, and 62.1% a delayed repair. Postoperative mortality was nil. Median follow-up was 106.7 months. Overall primary patency (PP) attainment rate was 94.7%, with a 5- and 10-year actuarial primary patency (APP) of 84.6% and 84%, respectively. Post-repair bile leak was associated with PP loss in the entire population (odds ratio [OR] 9.75, 95% confidence interval [CI] 1.64–57.87, p = 0.012); no correlation of PP loss with timing of repair was noted. Treatment of anastomotic stricture (occurred in 15.3% of patients) was performed with percutaneous treatment, achieving absence of biliary symptoms in 93% and 91% of cases at 5 and 10 years, respectively. BDI can be successfully repaired by HC-HJ regardless of timing when surgery is performed in stable patients with dilated bile ducts and without bile leak

TGF-β signaling is an effective target to impair survival and induce apoptosis of human cholangiocarcinoma cells: a study on human primary cell cultures

Cholangiocarcinoma (CCA) and its subtypes (mucin-and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-beta signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin-and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i) CX-4945, a casein kinase-2 (CK2) inhibitor that blocks TGF-beta 1-induced EMT; and (ii) LY2157299, a TGF-beta receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin) but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive) in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay. Results: at a dose of 10 mu M, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30 mu M). At the same concentrations, CX4945 also induced apoptosis (3-fold increase vs controls) which correlated with the expression level of CK2 in the different CCA cell lines (mucin-and mixed-CCA). Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of gamma-H2ax (biomarker for DNA double-strand breaks) foci, suggesting the active role of CK2 as a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 mu M concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs) the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human CCA cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration. These results suggest that targeting the TGF-beta signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human CCA

{\mu}-Net: A Deep Learning-Based Architecture for {\mu}-CT Segmentation

X-ray computed microtomography ({\mu}-CT) is a non-destructive technique that can generate high-resolution 3D images of the internal anatomy of medical and biological samples. These images enable clinicians to examine internal anatomy and gain insights into the disease or anatomical morphology. However, extracting relevant information from 3D images requires semantic segmentation of the regions of interest, which is usually done manually and results time-consuming and tedious. In this work, we propose a novel framework that uses a convolutional neural network (CNN) to automatically segment the full morphology of the heart of Carassius auratus. The framework employs an optimized 2D CNN architecture that can infer a 3D segmentation of the sample, avoiding the high computational cost of a 3D CNN architecture. We tackle the challenges of handling large and high-resoluted image data (over a thousand pixels in each dimension) and a small training database (only three samples) by proposing a standard protocol for data normalization and processing. Moreover, we investigate how the noise, contrast, and spatial resolution of the sample and the training of the architecture are affected by the reconstruction technique, which depends on the number of input images. Experiments show that our framework significantly reduces the time required to segment new samples, allowing a faster microtomography analysis of the Carassius auratus heart shape. Furthermore, our framework can work with any bio-image (biological and medical) from {\mu}-CT with high-resolution and small dataset siz

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters