Signet-Ring Cell/Histiocytoid Carcinoma: Report of Two Cases and Systematic Review of the Literature on the Epidemiology, Clinical Characteristics, and Pathological and Molecular Findings.

ABSTRACT: Signet-ring cell/histiocytoid carcinoma (SRCHC) is a rare appendageal tumor, mainly considering eyelids, more rarely axillae. This article describes 2 novel SRCHC cases of 71- and 66-year-old men and systematically reviews the literature on SRCHC. Of all cases reported in the literature, 73 (91.2%) were men and 7 (8.8%) were women. The median age at diagnosis was 71 years. Skin changes were located in the eyelids (68%) and axillae (32%). In all tested cases, SRCHC cells expressed CK7, CKAE1/AE3, EMA, CAM5.2, and AR and PIK3CA mutations. Future research should determine whether AR/PIK3CA-targeted therapies influence patients' survival.

Investigating the local structure of Ti based MXene materials by temperature dependent X-ray absorption spectroscopy.

The local structures of Ti based MXene-type electrode materials have been studied by Ti K-edge X-ray absorption fine structure measurements as a function of temperature to obtain direct information on the local bond lengths and their stiffness. In particular, the parent MAX phases Ti2AlC and Ti3AlC2 and their etched MXene systems are characterized and their properties compared. We find that selective etching has a substantial effect on the local structural properties of the Ti based MXene materials. It leads to an increase in the interatomic distances, i.e. a decrease in the covalency, and corresponding bond stiffness, that is a likely cause of higher achievable performances. The obtained results underline the importance of the local atomic correlations as limiting factors in the diffusion capacity of ion batteries.

Doped metal clusters as bimetallic AuCo nanocatalysts: insights into structural dynamics and correlation with catalytic activity by in situ spectroscopy.

Co-doped Au25 nanoclusters with different numbers of doping atoms were synthesized and supported on CeO2. The catalytic properties were studied in the CO oxidation reaction. In all cases, an enhancement in catalytic activity was observed compared to the pure Au25 nanocluster catalyst. Interestingly, a different catalytic performance was obtained depending on the number of Co atoms within the cluster. This was related to the mobility of atoms within the cluster's structure under pretreatment and reaction conditions, resulting in active CoAu nanoalloy sites. The evolution of the doped Au clusters into nanoalloys with well-distributed Co atoms within the Au cluster structure was revealed by combined XAFS, DRIFTS, and XPS studies. Overall, these studies contribute to a better understanding of the dynamics of doped nanoclusters on supports upon pretreatment and reaction, which is key information for the future development and application of bimetallic nanocluster (nanoalloy) catalysts.

Pathway-level mutation analysis in primary high-grade serous ovarian cancer and matched brain metastases.

Brain metastases (BMs) in ovarian cancer (OC) are a rare event. BMs occur most frequently in high-grade serous (HGS) OC. The molecular features of BMs in HGSOC are poorly understood. We performed a whole-exome sequencing analysis of ten matched pairs of formalin-fixed paraffin-embedded samples from primary HGSOC and corresponding BMs. Enrichment significance (p value; false discovery rate) was computed using the Reactome, the Kyoto Encyclopedia of Genes and Genomes pathway collections, and the Gene Ontology Biological Processes. Germline DNA damage repair variants were found in seven cases (70%) and involved the BRCA1, BRCA2, ATM, RAD50, ERCC4, RPA1, MLHI, and ATR genes. Somatic mutations of TP53 were found in nine cases (90%) and were the only stable mutations between the primary tumor and BMs. Disturbed pathways in BMs versus primary HGSOC constituted a complex network and included the cell cycle, the degradation of the extracellular matrix, cell junction organization, nucleotide metabolism, lipid metabolism, the immune system, G-protein-coupled receptors, intracellular vesicular transport, and reaction to chemical stimuli (Golgi vesicle transport and olfactory signaling). Pathway analysis approaches allow for a more intuitive interpretation of the data as compared to considering single-gene aberrations and provide an opportunity to identify clinically informative alterations in HGSOC BM.

PD-L1-Positive High-Grade Triple-Negative Breast Cancer Patients Respond Better to Standard Neoadjuvant Treatment-A Retrospective Study of PD-L1 Expression in Relation to Different Clinicopathological Parameters.

Triple negative breast cancer (TNBC) is typically a high-grade breast cancer with poorest clinical outcome despite available treatment modalities with chemo-, immuno- and radiotherapy. The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor closely related to programmed death ligand 1 (PD-L1) expressed on T lymphocytes modulating antitumor immunity. Immune-checkpoint inhibitors (ICI) are showing promising results in a subset of breast cancer patients in both neo- and adjuvant settings. Pathologic complete response (pCR) after neoadjuvant treatment was found to be associated with better prognosis. We analyzed the prognostic and predictive significance of PD-L1 (SP142 assay) immunohistochemical expression on TNBC patients' samples as illustrated by pCR with regard to its relation to treatment regimen, stage, BRCA mutational status and outcome. Furthermore, we analyzed a few other clinicopathological parameters such as age, TILs and proliferation index. The study highlighted a positive role of PD-L1 evaluation for personalized pCR probability assessment. Although considerable research was made on comparison of PD-L1 level in TNBC with different patient parameters, to our best knowledge, the relation of PD-L1 status to pCR while taking treatment regimen and stage into consideration was so far not investigated.

Toward h-BN/GaN Schottky Diodes: Spectroscopic Study on the Electronic Phenomena at the Interface.

Hexagonal boron nitride (h-BN), together with other members of the van der Waals crystal family, has been studied for over a decade, both in terms of fundamental and applied research. Up to now, the spectrum of h-BN-based devices has broadened significantly, and systems containing the h-BN/III-V junctions have gained substantial interest as building blocks in, inter alia, light emitters, photodetectors, or transistor structures. Therefore, the understanding of electronic phenomena at the h-BN/III-V interfaces becomes a question of high importance regarding device engineering. In this study, we present the investigation of electronic phenomena at the h-BN/GaN interface by means of contactless electroreflectance (CER) spectroscopy. This nondestructive method enables precise determination of the Fermi level position at the h-BN/GaN interface and the investigation of carrier transport across the interface. CER results showed that h-BN induces an enlargement of the surface barrier height at the GaN surface. Such an effect translates to Fermi level pinning deeper inside the GaN band gap. As an explanation, we propose a mechanism based on electron transfer from GaN surface states to the native acceptor states in h-BN. We reinforced our findings by thorough structural characterization and demonstration of the h-BN/GaN Schottky diode. The surface barriers obtained from CER (0.60 ± 0.09 eV for GaN and 0.91 ± 0.12 eV for h-BN/GaN) and electrical measurements are consistent within the experimental accuracy, proving that CER is an excellent tool for interfacial studies of 2D/III-V hybrids.

In Vivo Supportive Effects of Mesenchymal Stem Cells on Fat Graft Stabilization and Local Induction of Angiogenesis Are Not Dependent on the Cell Donor Age or In Vitro Cell Culture Duration.

Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of repair processes in situ by paracrine mechanisms. These unique capabilities make ASCs candidates for the regenerative medicine applications, including cell-assisted lipotransfer method. ASC aging processes have been extensively researched in vitro, there is however limited information about the impact of ASC aging on their biological role in tissue regeneration in vivo. The aim of our study was the research of the possible effects of aging processes of ASCs resulting from the donor age or from in vitro aging during long-term culture (ASC expansion in bioreactors) on their capability to support survival of adipose subcutaneous transplants in rats. The supportive in vivo effects of ASCs from young donors were compared with the effects of ASCs from old donors and ASCs "aged" in long-term in vitro cultures. Fat grafts enriched with ASCs (regardless of their age) retain their volume longer than fat grafts without ASCs supplementation. Vascular expansion in cell-enriched fat grafts was more intense when compared with the controls. It may be concluded that the aging of ASCs does not substantially reduce their ability for the support of the survival of adipose tissue grafts.

The role of stromal immune microenvironment in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer.

AIM: The first aim of the study was to compare the scores and types of stromal immune cells in 30 patients with primary DCIS and in the same patients after invasive breast recurrence in order to assess possible differences in both during tumor progression. The second aim was to evaluate possible differences in stromal cells of 30 patients with primary DCIS before progression and in the control group of 11 DCIS patients without recurrence during long-term follow-up. MATERIAL AND METHODS: Evaluation of tumor-infiltrating lymphocytes (TILs) and immunohistochemical stains for immune cell markers CD4, CD8, CD20, CD138, FOXP3, CD163 and TGF beta was performed on the stroma of primary DCIS before progression, invasive breast cancer of the same patients after progression and DCIS without progression. RESULTS: The comparison of stromal cells in 30 patients with initial DCIS and its invasive recurrence revealed an increased level of CD20 + immune cells (median score 5% vs. 17%, respectively, p < 0.001) and CD163 + cells (median score 1% vs. 5%, respectively, p < 0.001) in invasive breast cancer. The comparison of stromal cells in 30 patients with initial DCIS before recurrence and the control group of 11 patients with DCIS without recurrence showed statistically significant difference for CD138 + cells, which were more prevalent in patients with worse prognosis (median score 0 vs. 2%, respectively, p < 0.001). No similar relationship was found for the other tested cells as well as for TGF-beta. CONCLUSIONS: CD138 + immune cells that were more prevalent in patients with a worse prognosis should be explored in further studies to confirm or exclude their role as a potential biological marker of DCIS invasive recurrence.

Local Interactions Governing the Performances of Lithium- and Manganese-Rich Cathodes.

The local structural and electronical transformations occurring along the first charge and discharge cycle of Li- and Mn-rich Li[Li0.2Ni0.16Mn0.56Co0.08]O2 cathode material have been characterized by X-ray absorption spectroscopy at several complementary edges. The irreversible spinel formation, occurring at the expenses of the cycling layered phase during the first charge, is quantified (about 10%) and spatially localized. The local strains induced by the Ni oxidation have been evaluated. They induce the formation of a low spin Mn3+ in the layered structure in parallel to the irreversible formation of the spinel phase in the particles bulk. The charge balance has been quantified for all the elements along the first charging cycle, confirming a reversible oxygen oxidation along the charge. Overall, these quantitative results provide an experimental basis for modeling aimed to control the structure and its evolution, for instance, hindering the spinel formation for the benefit of the material cycle life.

Limited Practical Utility of Liquid Biopsy in the Treated Patients with Advanced Breast Cancer.

Recently, liquid biopsy has emerged as a tool to monitor oncologic disease progression and the effects of treatment. In this study we aimed to determine the clinical utility of liquid biopsy relative to conventional oncological post-treatment surveillance. Plasma cell-free (cf) DNA was collected from six healthy women and 37 patients with breast cancer (18 and 19 with stage III and IV tumors, respectively). CfDNA was assessed using the Oncomine Pan-Cancer Cell-Free Assay. In cfDNA samples from patients with BC, 1112 variants were identified, with only a few recurrent or hotspot mutations within specific regions of cancer genes. Of 65 potentially pathogenic variants detected in tumors, only 19 were also discovered in at least one blood sample. The allele frequencies of detected variants (VAFs) were <1% in cfDNA from all controls and patients with stage III BC, and 24/85 (28.2%) variants had VAFs > 1% in only 8 of 25 (32%) patients with stage IV BC. Copy number variations (CNVs) spanning CDK4, MET, FGFR1, FGFR2, ERBB2, MYC, and CCND3 were found in 1 of 12 (8%) and 8 of 25 (32%) patients with stage III and IV tumors, respectively. In healthy controls and patients without BC progression after treatment, VAFs were <1%, while in patients with metastatic disease and/or more advanced genomic alterations, VAFs > 1% and/or CNV were detected in approximately 30%. Therefore, most patients with stage IV BC could not be distinguished from those with stage III disease following therapy, based on liquid biopsy results.

The Dynamic Structure of Au38(SR)24 Nanoclusters Supported on CeO2 upon Pretreatment and CO Oxidation.

Atomically precise thiolate protected Au nanoclusters Au38(SC2H4Ph)24 on CeO2 were used for in-situ (operando) extended X-ray absorption fine structure/diffuse reflectance infrared fourier transform spectroscopy and ex situ scanning transmission electron microscopy-high-angle annular dark-field imaging/X-ray photoelectron spectroscopy studies monitoring cluster structure changes induced by activation (ligand removal) and CO oxidation. Oxidative pretreatment at 150 °C "collapsed" the clusters' ligand shell, oxidizing the hydrocarbon backbone, but the S remaining on Au acted as poison. Oxidation at 250 °C produced bare Au surfaces by removing S which migrated to the support (forming Au+-S), leading to highest activity. During reaction, structural changes occurred via CO-induced Au and O-induced S migration to the support. The results reveal the dynamics of nanocluster catalysts and the underlying cluster chemistry.

Combined micro X-ray absorption and fluorescence spectroscopy to map phases of complex systems: the case of sphalerite.

Combining micro-X-ray absorption spectroscopy (µXAS) and micro-X-ray fluorescence spectroscopy (µXRF) is a promising approach for the investigation of complex multi-phase systems. In this work, we have employed this approach to investigate natural sphalerite, the most common form of Zinc Sulfide. Spatially resolved elemental distribution maps of common 3d metal atoms (Zn, Cu, Ni, Co, and Fe) are superimposed with chemical speciation and structural parameter maps in order to understand the sphaleriteore-formation process and metamorphosis. Chemical speciation and structural parameters have been obtained by analyzing the µXAS spectra collected in several representative points of the sample, after µXRF mapping. In the present case, this X-ray based approach has permitted to determine the spatial distribution of the Zn species in sphalerite. The presence of two main zincite and smithsonite inclusions has been established, with the latter located close to copper impurity center. Since copper is known to remarkably reduce the corrosion resistance of zinc, resulting in the formation of carbonate as the corrosion product, this implies a possible role of Cu in the growth of the carbonate inclusions. The results obtained highlight the efficiency of this method in univocally identifying the spatial distribution of phases in complex systems, thanks to the simultaneous access to complementary information.

An evaluation of the construction of the device along with the software for digital archiving, sending the data, and supporting the diagnosis of cervical cancer.

Cervical cancer is still an important cause of mortality among women in a number of countries. There are effective methods of prevention and early diagnosis, but they require well-trained medical professionals including cytologists. Within this project, we built a prototype of a new device together with implemented software using U-NET and CNN architectures of neural networks (ANN), to convert the currently used optical microscopes into fully independent scanning and evaluating systems for cytological samples. To evaluate the specificity and sensitivity of the system, 2058 (2000 normal and 58 abnormal samples) consecutive liquid-based cytology (LBC) samples were analysed. The observed sensitivity and specificity to distinguish normal and abnormal samples was 100%. We observed slight incompatibility in the evaluation of the type of abnormality. The use of ANN is promising for increasing the effectiveness of cervical screening. The low cost of neural network usage further increases the potential areas of application of the presented method. Further refinement of neural networks on a larger sample size is required to evaluate the software.

Influence of Showerhead-Sample Distance (GAP) in MOVPE Close Coupled Showerhead Reactor on GaN Growth.

The distance between the showerhead and the sample surface (GAP) is one of the main growth parameters of the commonly used research reactor, Close Coupled Showerhead. We examine its influence on the growth rate of GaN layers deposited under various conditions (growth temperature, carrier gas, V/III ratio and growth pressure). Regardless of other growth parameters, increasing the GAP value leads to a reduction in the growth rate.

Autologous Platelet-Rich Plasma Reduces Healing Time of Chronic Venous Leg Ulcers: A Prospective Observational Study.

The study investigated whether the application of dressings with autologous platelet-rich plasma (PRP) would reduce the healing time in patients with chronic venous leg ulcers. This is a prospective observational study that included 100 patients diagnosed with lower extremity venous insufficiency complicated by ulceration of a leg or foot, who had been after angioplasty of stenotic artery. Patients were divided into two groups of 50 each: treated with PRP (study group) and treated with conventional hydrocolloid dressings (control group). We followed the wound changes at Day 10, Day 20, and Day 30 of treatment and compared them with the baseline appearance at Day 0. We evaluated the appearance, area, and depths of wounds with ultrasound. The granulation process was examined histologically to document skin formation and wound tissue neovascularization. The findings were that treatment with PRP dressings resulted in a significant progressive reduction in ulcer size, irrespective of the ulcer's initial size, compared to treatment with conventional dressings. Further, the best effect of PRP was noticed in the category of largest wounds. After a month of treatment with PRP dressings, more than 50% of all ulcers were completely healed. The young epidermis appeared together with the granulation tissue, and the formation of dermis took shape after 20 days of treatment. We conclude that the use of PRP dressings is a safe, nonsurgical adjunctive procedure for treating chronic venous leg ulcers. The potential benefit of PRP dressings over conventional ulcer treatment requires further in-depth exploration.

Role of Manganese in Lithium- and Manganese-Rich Layered Oxides Cathodes.

Lithium-rich transition-metal-oxide cathodes are among the most promising materials for next generation lithium-ion-batteries because they operate at high voltages and deliver high capacities. However, their cycle-life remains limited, and individual roles of the transition-metals are still not fully understood. Using bulk-sensitive X-ray absorption and emission spectroscopy on Li[Li0.2Ni0.16Mn0.56Co0.08]O2, we inspect the behavior of Mn, generally considered inert upon the electrochemical process. During the first charge Mn appears to be redox-active showing a partial transformation from high-spin Mn4+ to Mn3+ in both high and low spin configurations, where the latter is expected to favor reversible cycling. The Mn redox-state with cycling continues changing in opposition to the expected charge compensation and is correlated with Ni oxidation/reduction, also spatially. The findings suggest that strain induced on the Mn-O sublattice by Ni oxidation triggers Mn reduction. These results unravel the Mn role in controlling the electrochemistry of Li-rich cathodes.

Effects of nanostructuring on the bond strength and disorder in V2O5 cathode material for rechargeable ion-batteries.

We have investigated the nanostructuring effects on the local structure of V2O5 cathode material by means of temperature dependent V K-edge X-ray absorption fine structure measurements. We have found that the nanostructuring largely affects V-O and V-V bond characteristics with a general softening of the local V-O and V-V bonds. The obtained bond strengths correlate with the specific capacity shown by the different systems, with higher capacity corresponding to softer atomic pairs. The present study suggests the key role of local atomic displacements in the diffusion and storage of ions in cathodes for batteries, providing important information for designing new functional materials.

Ligand Migration from Cluster to Support: A Crucial Factor for Catalysis by Thiolate-protected Gold Clusters.

Thiolate protected metal clusters are valuable precursors for the design of tailored nanosized catalysts. Their performance can be tuned precisely at atomic level, e. g. by the configuration/type of ligands or by partial/complete removal of the ligand shell through controlled pre-treatment steps. However, the interaction between the ligand shell and the oxide support, as well as ligand removal by oxidative pre-treatment, are still poorly understood. Typically, it was assumed that the thiolate ligands are simply converted into SO2, CO2 and H2O. Herein, we report the first detailed observation of sulfur ligand migration from Au to the oxide support upon deposition and oxidative pre-treatment, employing mainly S K-edge XANES. Consequently, thiolate ligand migration not only produces clean Au cluster surfaces but also the surrounding oxide support is modified by sulfur-containing species, with pronounced effects on catalytic properties.

Role of plasma growth factor in the healing of chronic ulcers of the lower legs and foot due to ischaemia in diabetic patients.

INTRODUCTION: It has been demonstrated that plasma growth factor (PGF) responsible for proliferation of smooth muscle cells and fibroblasts significantly shortens treatment duration. AIM: To determine the role of human growth factor in the healing of ulcers due to ischaemic diabetic foot syndrome (DFS) following previous angioplasty of the blood vessels of the lower leg and foot. MATERIAL AND METHODS: The study group included 50 patients with ischaemic diabetic foot complicated by lower leg ulcers in which angioplasty of the stenotic arteries in the distal lower leg and foot was performed. It has been assumed that the area of the ulcer cannot exceed 5 cm2. Following surgical debridement, each patient received platelet-rich plasma in the form of dressings applied on an ulcer, followed by hydrocolloid dressings. Each dressing was replaced after 10 days, and this procedure was repeated after 20 and 30 days of treatment. The control group included 50 patients with ischaemic diabetic foot complicated by an ulcer up to 5 cm2. Angioplasty of the lower leg arteries was also performed in this group. However, after surgical debridement, wounds were covered with hydrocolloid dressings. RESULTS: After 3 months of combined treatment, all wounds in the study group healed whereas in the control group, only wounds of the smallest size healed. CONCLUSIONS: Combined treatment of ulcers due to ischaemic DFS with endovascular procedures to re-establish blood flow to the vessels and dressings with autologous platelet-rich plasma significantly shortens the healing time.

Brain Metastasis Prediction by Transcriptomic Profiling in Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen receptor α and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of TNBC transcriptomic profiles associated with high risk of brain metastasis (BM) might identify patients requiring alternative, more aggressive, or specific preventive and therapeutic approaches. PATIENTS AND METHODS: Using a cDNA-mediated annealing, selection, extension, and ligation assay, we investigated expression of 29,369 gene transcripts in primary TNBC tumor samples from 119 patients-71 in discovery cohort A and 48 in independent cohort B-that included best discriminating genes. Expression of mRNA was correlated with the occurrence of symptomatic BM. RESULTS: In cohort A, the difference at the noncorrected P < .005 was found for 64 transcripts (P = .23 for global test), but none showed significant difference at a preset level of false-discovery rate of < 10%. Of the 30 transcripts with the largest differences between patients with and without BM in cohort A, none was significantly associated with BM in cohort B. CONCLUSION: Analysis based on the primary tumor gene transcripts alone is unlikely to predict BM development in advanced TNBC. Despite its negative findings, the study adds to the knowledge on the biology of TNBC and paves the way for future projects using more advanced molecular assays.