Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermolysis of N‐tetramethylpiperidinyl triphenylacetate: homolytic fragmentation of a TEMPO ester

Thermolysis of N-tetramethylpiperidinyl triphenylacetate (7, Ph3CCO2T, T=2,2,6,6-tetramethylpiperidinyl) in benzene at 146°C leads to the formation of triphenylmethane (Ph3CH, 80%), tetramethylpiperidine (TH, 91%), and tetraphenylmethane (Ph4C, 9%). First-order rate constants for the decomposition at 132.8 and 150.0°C were 2.20 × 10−6 and 2.88 × 10−5 s−1, respectively. In benzene-d6 solvent the triphenylmethane was formed as Ph3CD to the extent of 20%, as determined by 1H NMR and mass spectrometry. The results are interpreted as showing that Ph3CCO2T undergoes thermolysis by concerted two-bond scission with formation of Ph3C⋅, tetramethylpiperidinyl radicals and CO2. The formation of Ph4C occurs by addition of Ph3C⋅ to benzene, followed by hydrogen atom abstraction from the resulting adduct. Calculations using DFT methods at the B3LYP/6–311++G** level were used to elucidate the bond fission of HCO2T (2), and indicate that cleavage to HCO2⋅ and T⋅ is favored by 7.8 kcal mol−1 relative to cleavage to HC(•)O and TO⋅, in agreement with the experimental results. Copyright © 2003 John Wiley & Sons, Ltd.
Water-gas shift reaction kinetics over μ-structured Pt/CeO2/Al2O3 catalysts

Platinum/ceria/alumina catalysts have been prepared in the microchannels of stainless steel platelets. These catalysts are very active for the water-gas shift reaction between 250–400°C. The use of microreactors as kinetic devices has a clear advantage that the thin catalyst film allows the determination of the intrinsic kinetics even in the case of fast reactions. However, the channel design should be such that plug flow conditions are favored. The kinetics of the water-gas shift reaction, free from internal diffusion limitations, have been studied over thin catalyst layers over a large range of operation conditions. The reaction rate is almost zero-order in carbon monoxide and strongly inhibited by the partial pressure of hydrogen and to a lesser extent to that of carbon dioxide. An overall activation energy of 76.8 ± 2 kJ/mol has been measured. The data are best described by a dual-site mechanism, where platinum provides an adsorption site for carbon monoxide and ceria an adsorption site for water. The rate-determining step involves the formation of a complex between a carboxyl species and a hydroxyl group that decomposes over a free platinum site into carbon dioxide and hydrogen. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Structured Reporting Using CEUS LI-RADS for the Diagnosis of Hepatocellular Carcinoma (HCC)—Impact and Advantages on Report Integrity, Quality and Interdisciplinary Communication

Simple Summary Contrast-enhanced ultrasound (CEUS) is an increasingly accepted imaging modality for visualizing hepatocellular carcinoma (HCC) and is recommended as a secondary imaging option by most leading hepatology societies. In recent years, the use of structured reporting (SR) has been recommended by several societies to standardize report content and improve report quality of various diagnostic modalities when compared to conventional free-text reports (FTR). Our single-center study aimed to evaluate the use of SR using a CEUS LI-RADS software template in CEUS examinations of 50 HCC patients. SR significantly increased report integrity, satisfaction of the referring physicians, linguistic quality and overall report quality compared to FTR. Therefore, the use of SR in CEUS examinations of HCC patients may represent a valuable tool to facilitate clinical decision-making and improve interdisciplinary communication in the future. Abstract Background: Our retrospective single-center study aims to evaluate the impact of structured reporting (SR) using a CEUS LI-RADS template on report quality compared to conventional free-text reporting (FTR) in contrast-enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma (HCC). Methods: We included 50 patients who underwent CEUS for HCC staging. FTR created after these examinations were compared to SR retrospectively generated by using template-based online software with clickable decision trees. The reports were evaluated regarding report completeness, information extraction, linguistic quality and overall report quality by two readers specialized in internal medicine and visceral surgery. Results: SR significantly increased report completeness with at least one key feature missing in 31% of FTR vs. 2% of SR (p < 0.001). Information extraction was considered easy in 98% of SR vs. 86% of FTR (p = 0.004). The trust of referring physicians in the report was significantly increased by SR with a mean of 5.68 for SR vs. 4.96 for FTR (p < 0.001). SR received significantly higher ratings regarding linguistic quality (5.79 for SR vs. 4.83 for FTR (p < 0.001)) and overall report quality (5.75 for SR vs. 5.01 for FTR (p < 0.001)). Conclusions: Using SR instead of conventional FTR increases the overall quality of reports in CEUS examinations of HCC patients and may represent a valuable tool to facilitate clinical decision-making and improve interdisciplinary communication in the future.
Brain Metastases from Uterine Cervical and Endometrial Cancer

Simple Summary This review investigated the prevalence, clinical characteristics, clinical presentation, diagnosis, treatment, and prognosis of patients with brain metastases from uterine cervical carcinoma (CC) and uterine endometrial carcinoma (EC). The findings of this review indicate the factors that can facilitate better treatment selection and, consequently, better outcomes in patients with CC and EC. Abstract Reports on brain metastases (BMs) from uterine cervical carcinoma (CC) and uterine endometrial carcinoma (EC) have recently increased due to the development of massive databases and improvements in diagnostic procedures. This review separately investigates the prevalence, clinical characteristics, clinical presentation, diagnosis, treatment, and prognosis of BMs from CC and uterine endometrial carcinoma EC. For patients with CC, early-stage disease and poorly differentiated carcinoma lead to BMs, and elderly age, poor performance status, and multiple BMs are listed as poor prognostic factors. Advanced-stage disease and high-grade carcinoma are high-risk factors for BMs from EC, and multiple metastases and extracranial metastases, or unimodal therapies, are possibly factors indicating poor prognosis. There is no “most effective” therapy that has gained consensus for the treatment of BMs. Treatment decisions are based on clinical status, number of the metastases, tumor size, and metastases at distant organs. Surgical resection followed by adjuvant radiotherapy appears to be the best treatment approach to date. Stereotactic ablative radiation therapy has been increasingly associated with good outcomes in preserving cognitive functions. Despite treatment, patients died within 1 year after the BM diagnosis. BMs from uterine cancer remain quite rare, and the current evidence is limited; thus, further studies are needed.
The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) during development and altered expression can cause developmental defects and/or disease. Indeed, aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has been linked to many cancers. Mounting evidence also indicates a role for miRNAs in the development of the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current research on miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentially expressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genes to influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications and isomiRs that are predicted to target the ALDH1, CD166, BMI1, LRIG1, and LGR5 SC genes. miR-23b and miR-92A are of particular interest because our previously reported studies on miRNA expression in isolated normal versus malignant human colonic SCs showed that miR-23b and miR-92a are regulators of the LGR5 and LRIG1 SC genes, respectively. We also identify additional miRNAs whose expression inversely correlated with mRNA levels of their target genes and associated with CRC patient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulation of SC genes could provide insight into how dysregulation of miRNAs leads to the emergence of different CSC populations and SC overpopulation in CRC.
Electrochemical chloride removal from reinforced concrete structures and its ability to repassivate prerusted steel surfaces

Gravimetric and electrochemical measurements were used to expose the relationship between the degree of prerusting of reinforcements embedded in chloride-contaminated mortar or concrete and the efficiency with which they are repassivated once depassivating ions are removed. The results show that, above a certain, ill-defined rusting threshold, the electrochemical chloride removal does not ensure effective repassivation of reinforcements in the steel/concrete system. Once the passivity of reinforcements embedded in reinforced concrete structures (RCS) is overcome, the typical corrosion rates of the active state seemingly suffice to maintain an acid pH at the metal/rust interface in the bulk of such a strongly alkaline material as concrete. After this local acidification, the metal inside pits probably behaves similarly as it would in an acid solution. As a result, it does not suffice to remove the rusting agent in RCS in order to stop corrosion; rather, the agent must be removed before the first visible signs of deterioration appear. Elektrochemische Chloridentfernung an Stahlbetonbauwerken und Moglichkeiten der Repassivierung vorgerosteter Stahloberflachen Gravimetrische und elektrochemische Messungen wurden durchgefuhrt, um die Beziehung zwischen dem Grad der Vorrostung von Bewehrungsstahl, der in chloridhaltigem Mortel oder Beton eingebettet war, und der Wirksamkeit einer Repassivierung, nachdem die depassivierenden Ionen entfernt wurden, zu untersuchen. Die Ergebnisse zeigen, dass oberhalb eines bestimmten, schlecht zu definierenden Rostgrades die elektrochemische Chloridentfernung eine wirksame Repassivierung der Bewehrung in dem Stahl/Beton-System nicht sicherstellt. Sobald die Passivitat der Bewehrungen, die in Stahlbetonbauwerken eingebettet sind, verloren gegangen ist, scheinen die typischen Korrosionsgeschwindigkeiten des aktiven Zustandes auszureichen, um einen sauren pH-Wert an der Metall/Rost-Grenze selbst in einem so stark alkalischen Material wie Beton aufrechtzuerhalten. Nach dieser ortlichen Ansauerung verhalt sich das Metall im Loch wahrscheinlich ahnlich wie in einer sauren Losung. Als Ergebnis ergibt sich, dass es nicht ausreicht das Korrosionsreaktionsmittel zu entfernen, um die Korrosion zu stoppen; vielmehr muss das Reaktionsmittel, d.h. das Chlorid entfernt werden, bevor die ersten Anzeichen einer Schadigung auftauchen.
Analysis of Italian BRCA1/2 Pathogenic Variants Identifies a Private Spectrum in the Population from the Bergamo Province in Northern Italy

Simple Summary The Italian population is characterized by a high genetic heterogeneity mostly due to its long history of migration and colonization and to its geographical conformation. Consistently, several BRCA1/2 pathogenic variants (PVs) have been reported to be recurrent or even founder in defined geographical areas including the Bergamo province in Northern Italy. In this study, we retrospectively analyzed the data from 1019 women affected with breast cancer with BRCA1/2 PVs. We compared the BRCA1/2 PVs spectrum found in the carrier individuals from the Bergamo province (BGP) with that of the general Italian population. We found that the majority of the BGP PVs had a local origin and remained confined to the BGP or to the surrounding Lombardy region. We also observed that the BGP BRCA1/2 PV spectrum is private and conserved comprising a smaller number of variants with an average higher frequency with respect to that of carrier individuals from the rest of Italy. Abstract Germline pathogenic variants (PVs) in the BRCA1 or BRCA2 genes cause high breast cancer risk. Recurrent or founder PVs have been described worldwide including some in the Bergamo province in Northern Italy. The aim of this study was to compare the BRCA1/2 PV spectra of the Bergamo and of the general Italian populations. We retrospectively identified at five Italian centers 1019 BRCA1/2 PVs carrier individuals affected with breast cancer and representative of the heterogeneous national population. Each individual was assigned to the Bergamo or non-Bergamo cohort based on self-reported birthplace. Our data indicate that the Bergamo BRCA1/2 PV spectrum shows less heterogeneity with fewer different variants and an average higher frequency compared to that of the rest of Italy. Consistently, four PVs explained about 60% of all carriers. The majority of the Bergamo PVs originated locally with only two PVs clearly imported. The Bergamo BRCA1/2 PV spectrum appears to be private. Hence, the Bergamo population would be ideal to study the disease risk associated with local PVs in breast cancer and other disease-causing genes. Finally, our data suggest that the Bergamo population is a genetic isolate and further analyses are warranted to prove this notion.
Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.
How to Get Them off?—Assessment of Innovative Techniques for Generation and Detachment of Mature Osteoclasts for Biomaterial Resorption Studies

The fusion process of mononuclear monocytes into multinuclear osteoclasts in vitro is an essential process for the study of osteoclastic resorption of biomaterials. Thereby biomaterials offer many influencing factors such as sample shape, material composition, and surface topography, which can have a decisive influence on the fusion and thus the entire investigation. For the specific investigation of resorption, it can therefore be advantageous to skip the fusion on samples and use mature, predifferentiated osteoclasts directly. However, most conventional detachment methods (cell scraper, accutase), lead to a poor survival rate of osteoclasts or to a loss of function of the cells after their reseeding. In the present study different conventional and novel methods of detachment in combination with different culture surfaces were investigated to obtain optimal osteoclast differentiation, yield, and vitality rates without loss of function. The innovative method—using thermoresponsive surfaces for cultivation and detachment—was found to be best suited. This is in particular due to its ability to maintain osteoclast activity, as proven by TRAP 5b-, CTSK-activity and resorption pits on dentin discs and decellularized osteoblast-derived matrix plates. In conclusion, it is shown, that osteoclasts can be predifferentiated on cell culture dishes and transferred to a reference biomaterial under preservation of osteoclastic resorption activity, providing biomaterial researchers with a novel tool for material characterization.
Peptidylarginine Deiminase Inhibitor Application, Using Cl-Amidine, PAD2, PAD3 and PAD4 Isozyme-Specific Inhibitors in Pancreatic Cancer Cells, Reveals Roles for PAD2 and PAD3 in Cancer Invasion and Modulation of Extracellular Vesicle Signatures

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with limited survival rate. Roles for peptidylarginine deiminases (PADs) have been studied in relation to a range of cancers with roles in epigenetic regulation (including histone modification and microRNA regulation), cancer invasion, and extracellular vesicle (EV) release. Hitherto though, knowledge on PADs in PDAC is limited. In the current study, two PDAC cell lines (Panc-1 and MiaPaCa-2) were treated with pan-PAD inhibitor Cl-amidine as well as PAD2, PAD3, and PAD4 isozyme-specific inhibitors. Effects were assessed on changes in EV signatures, including EV microRNA cargo (miR-21, miR-126, and miR-221), on changes in cellular protein expression relevant for pancreatic cancer progression and invasion (moesin), for mitochondrial housekeeping (prohibitin, PHB), and gene regulation (deiminated histone H3, citH3). The two pancreatic cancer cell lines were found to predominantly express PAD2 and PAD3, which were furthermore expressed at higher levels in Panc-1, compared with MiaPaCa-2 cells. PAD2 isozyme-specific inhibitor had the strongest effects on reducing Panc-1 cell invasion capability, which was accompanied by an increase in moesin expression, which in pancreatic cancer is found to be reduced and associated with pancreatic cancer aggressiveness. Some reduction, but not significant, was also found on PHB levels while effects on histone H3 deimination were variable. EV signatures were modulated in response to PAD inhibitor treatment, with the strongest effects observed for PAD2 inhibitor, followed by PAD3 inhibitor, showing significant reduction in pro-oncogenic EV microRNA cargo (miR-21, miR-221) and increase in anti-oncogenic microRNA cargo (miR-126). While PAD2 inhibitor, followed by PAD3 inhibitor, had most effects on reducing cancer cell invasion, elevating moesin expression, and modulating EV signatures, PAD4 inhibitor had negligible effects and pan-PAD inhibitor Cl-amidine was also less effective. Compared with MiaPaCa-2 cells, stronger modulatory effects for the PAD inhibitors were observed in Panc-1 cells, which importantly also showed strong response to PAD3 inhibitor, correlating with previous observations that Panc-1 cells display neuronal/stem-like properties. Our findings report novel PAD isozyme regulatory roles in PDAC, highlighting roles for PAD isozyme-specific treatment, depending on cancer type and cancer subtypes, including in PDAC.
BBS Proteins Affect Ciliogenesis and Are Essential for Hedgehog Signaling, but Not for Formation of iPSC-Derived RPE-65 Expressing RPE-Like Cells

Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal dystrophy, renal cysts, obesity and polydactyly. BBS genes have been implicated in ciliogenesis, hedgehog signaling and retinal pigment epithelium maturation. BBS1 and BBS5 are members of the BBSome, implicated in cilia transport of proteins, and BBS10 is a member of the chaperonin-complex, mediating BBSome assembly. In this study, involvement of BBS1, BBS5 and BBS10 in ciliogenesis and hedgehog signaling were investigated in BBS-defective patient fibroblasts as well as in RPE-hTERT cells following siRNA-mediated knockdown of the BBS genes. Furthermore, the ability of BBS1-defective induced pluripotent stem-cells (iPSCs) to differentiate into RPE cells was assessed. We report that cells lacking functional BBS5 or BBS10 have a reduced number of primary cilia, whereas cells lacking functional BBS1 display shorter primary cilia compared to wild-type cells. Hedgehog signaling was substantially impaired and Smoothened, a component of hedgehog signaling, was trapped inside the cilia of the BBS-defective cells, even in the absence of Smoothened agonist. Preliminary results demonstrated the ability of BBS1-defective iPSC to differentiate into RPE-65 expressing RPE-like cells. The BBS1−/−-defective RPE-like cells were less pigmented, compared to RPE-like cells differentiated from control iPSCs, indicating an impact of BBS1 on RPE maturation.
Auditory Cue Based on the Golden Ratio Can Improve Gait Patterns in People with Parkinson’s Disease

The harmonic structure of walking relies on an irrational number called the golden ratio (ϕ): in healthy subjects, it coincides with the stride-to-stance ratio, and it is associated with a smooth gait modality. This smoothness is lost in people with Parkinson’s disease (PD), due to deficiencies in the execution of movements. However, external auditory cues seem to facilitate movement, by enabling the timing of muscle activation, and helping in initiating and modulating motor output. Based on a harmonic fractal structure of gait, can the administration of an auditory cue based on individual’s ϕ-rhythm improve, in acute, gait patterns in people with PD? A total of 20 participants (16 males, age 70.9 ± 8.4 years, Hoehn and Yahr stage-II) were assessed through stereophotogrammetry: gait spatio-temporal parameters, and stride-to-stance ratio were computed before, during, and after the ϕ-rhythm administration. Results show improvements in terms of stride length (p = 0.018), walking speed (p = 0.014), and toe clearance (p = 0.013) when comparing gait patterns before and after the stimulus. Furthermore, the stride-to-stance ratio seems to correlate with almost all spatio-temporal parameters, but it shows the main changes in the before–during rhythm comparison. In conclusion, ϕ-rhythm seems an effective cue able to compensate for defective internal rhythm of the basal ganglia in PD.
Modeling Bainitic Transformations during Press Hardening

We revisit recent findings on experimental and modeling investigations of bainitic transformations under the influence of external stresses and pre-strain during the press hardening process. Experimentally, the transformation kinetics in 22MnB5 under various tensile stresses are studied both on the macroscopic and microstructural level. In the bainitic microstructure, the variant selection effect is analyzed with an optimized prior-austenite grain reconstruction technique. The resulting observations are expressed phenomenologically using a autocatalytic transformation model, which serves for further scale bridging descriptions of the underlying thermo-chemo-mechanical coupling processes during the bainitic transformation. Using analyses of orientation relationships, thermodynamically consistent and nondiagonal phase field models are developed, which are supported by ab initio generated mechanical parameters. Applications are related to the microstructure evolution on the sheaf, subunit, precipitate and grain boundary level.