Data of postoperative complications related to fibrinogen-to-albumin ratio in pancreatic resections

Pancreatic surgery is one of the surgeries burdened with the highest mortality and morbidity rate. This is due both to the aggressive biological nature of the pathology affecting the organ and to the technical difficulties associated with surgery. A further aspect on which research is focusing is represented by inflammation related to oncological pathology. Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival (OS) in malignant tumors. Inflammatory markers had demonstrated also a role in the prediction of postoperative complication after pancreatic surgery. We speculate that FAR, as an easily available, cost-effective, and non-invasive prognostic indicator for pancreatic cancer patients, could help to identify patients at increased risk of postoperative pancreatic fistula (POPF). We therefore retrospectively analyzed the data relating to 117 pancreatic resections relating direct and indirect markers of inflammation with the incidence of post-operative complications. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/

Magnetic Core Loss of Ultrahigh Strength FeCo Alloys

Hiperco® 50 alloy heat treated between 450 and 650 °C exhibits superior mechanical properties. We report the measurements of the ac core loss at various frequencies up to 4500 Hz of the Hiperco® 50 alloy samples annealed at 450 and 650 °C. The 650 °C annealed specimens have lower ac core loss than the 450 °C annealed ones. The total core loss, consisting of contributions from hysteresis core loss and eddy-current core loss, depends on the frequency f as af+bf2. The eddy current loss of a single laminate is minor compared to the hysteresis loss

Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response

Cancer cells, which use more glucose than normal cells and accumulate extracellular lactate even under normoxic conditions (Warburg effect), have been reported to undergo cell death under glucose deprivation, whereas normal cells remain viable. As it may be relevant to exploit the molecular mechanisms underlying this biological response to achieve new cancer therapies, in this paper we sought to identify them by using transcriptome and proteome analysis applied to an established glucoseaddicted cellular model of transformation, namely, murine NIH-3T3 fibroblasts harboring an oncogenic K-RAS gene, compared with parental cells. Noteworthy is that the analyses performed in high-and low-glucose cultures indicate that reduction of glucose availability induces, especially in transformed cells, a significant increase in the expression of several unfolded protein response (UPR) hallmark genes. We show that this response is strictly associated with transformed cell death, given that its attenuation, by reducing protein translation or by increasing cell protein folding capacity, preserves the survival of transformed cells. Such an effect is also observed by inhibiting c-Jun NH2-terminal kinase, a pro-apoptotic signaling mediator set downstream of UPR. Strikingly, addition of N-acetyl-D-glucosamine, a specific substrate for the hexosamine biosynthesis pathway (HBP), to glucose-depleted cells completely prevents transformed cell death, stressing the important role of glucose in HBP fuelling to ensure UPR attenuation and increased cell survival. Interestingly, these results have been fully recognized in a human model of breast cancer, MDA-MB-231 cells. In conclusion, we show that glucose deprivation, leading to harmful accumulation of unfolded proteins in consequence of a reduction of protein glycosylation, induces a UPR-dependent cell death mechanism. These findings may open the way for new therapeutic strategies to specifically kill glycolytic cancer cells

The triad hsp60-mirnas-extracellular vesicles in brain tumors: Assessing its components for understanding tumorigenesis and monitoring patients

Brain tumors have a poor prognosis and progress must be made for developing efficacious treatments, but for this to occur their biology and interaction with the host must be elucidated beyond current knowledge. What has been learned from other tumors may be applied to study brain tumors, for example, the role of Hsp60, miRNAs, and extracellular vesicles (EVs) in the mechanisms of cell proliferation and dissemination, and resistance to immune attack and anticancer drugs. It has been established that Hsp60 increases in cancer cells, in which it occurs not only in the mitochondria but also in the cytosol and plasma-cell membrane and it is released in EVs into the extracellular space and in circulation. There is evidence suggesting that these EVs interact with cells near and far from their original cell and that this interaction has an impact on the functions of the target cell. It is assumed that this crosstalk between cancer and host cells favors carcinogenesis in various ways. We, therefore, propose to study the triad Hsp60-related miRNAs-EVs in brain tumors and have standardized methods for the purpose. These revealed that EVs with Hsp60 and related miRNAs increase in patients’ blood in a manner that reflects disease status. The means are now available to monitor brain tumor patients by measuring the triad and to dissect its effects on target cells in vitro, and in experimental models in vivo

Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were measured in FD patients and healthy subjects divided into age classes, in vitro, in human umbilical vein endothelial cells (HUVECs) "young" and undergoing replicative senescence, through a quantitative polymerase chain reaction (qPCR) approach. We confirmed that, in vivo, circulating miR-126 levels physiologically increase with age. In vitro, miR-126 augments in HUVECs underwent replicative senescence. We observed that FD patients are characterized by higher miR-126-3p levels in sEVs, compared to age-matched healthy subjects. We also explored, in vitro, the effect on ECs of glycosphingolipids that are typically accumulated in FD patients. We observed that FD storage substances induced in HUVECs premature senescence and increased of miR-126-3p levels. This study reinforces the hypothesis that FD may aggravate the normal aging process

Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens

Grimaldi and Cammarata et al. develop a proteomics-based, target discovery platform to identify immunogenic proteins specific to apoptotic tumor cells. This study highlights the importance of protein modifications in apoptotic tumor cells as a mechanism of generating immunogenic neoantigens that can be targeted for T cell-based immunotherapy.Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4(+) and CD8(+) T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients' survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients

Influence of pump laser fluence on ultrafast structural changes in myoglobin

High-intensity femtosecond pulses from an X-ray free-electron laser enable pump probe experiments for investigating electronic and nuclear changes during light-induced reactions. On time scales ranging from femtoseconds to milliseconds and for a variety of biological systems, time-resolved serial femtosecond crystallography (TR-SFX) has provided detailed structural data for light-induced isomerization, breakage or formation of chemical bonds and electron transfer. However, all ultra-fast TR-SFX studies to date have employed such high pump laser energies that several photons were nominally absorbed per chromophore. As multiphoton absorption may force the protein response into nonphysiological pathways, it is of great concern whether this experimental approach allows valid inferences to be drawn vis-a-vis biologically relevant single-photon-induced reactions. Here we describe ultrafast pump-probe SFX experiments on photodissociation of carboxymyoglobin, showing that different pump laser fluences yield markedly different results. In particular, the dynamics of structural changes and observed indicators of the mechanistically important coherent oscillations of the Fe-CO bond distance (predicted by recent quantum wavepacket dynamics) are seen to depend strongly on pump laser energy. Our results confirm both the feasibility and necessity of performing TR-SFX pump probe experiments in the linear photoexcitation regime. We consider this to be a starting point for reassessing design and interpretation of ultrafast TR-SFX pump probe experiments such that biologically relevant insight emerges

Polarization Control in Integrated Graphene-Silicon Quantum Photonics Waveguides

We numerically investigated the use of graphene nanoribbons placed on top of silicon-on-insulator (SOI) strip waveguides for light polarization control in silicon photonic-integrated waveguides. We found that two factors mainly affected the polarization control: the graphene chemical potential and the geometrical parameters of the waveguide, such as the waveguide and nanoribbon widths and distance. We show that the graphene chemical potential influences both TE and TM polarizations almost in the same way, while the waveguide width tapering enables both TE-pass and TM-pass polarizing functionalities. Overall, by increasing the oxide spacer thickness between the silicon waveguide and the top graphene layer, the device insertion losses can be reduced, while preserving a high polarization extinction ratio

Modeling and simulation in tribology across scales: An overview

This review summarizes recent advances in the area of tribology based on the outcome of a Lorentz Center workshop surveying various physical, chemical and mechanical phenomena across scales. Among the main themes discussed were those of rough surface representations, the breakdown of continuum theories at the nano- and micro-scales, as well as multiscale and multiphysics aspects for analytical and computational models relevant to applications spanning a variety of sectors, from automotive to biotribology and nanotechnology. Significant effort is still required to account for complementary nonlinear effects of plasticity, adhesion, friction, wear, lubrication and surface chemistry in tribological models. For each topic, we propose some research directions