bluuebunny/crossref_metadata_2025 huggingface dataset:
Violin Ceramic Joist Slabs: Evaluation and Proposal for Intervention with Duplex-Type Stainless Steel
Authors: Salmerón Antonio , Climent Miguel-Ángel , Ivorra Salvador
Published: July 2022

Due to the present significant need to repair and maintain our buildings and the building repair sector’s minimal experience in special structural elements, we here describe a study on the repair of ceramic violin joist slabs in an actual intervention on a building erected in the 1950s that had been unsuccessfully repaired several times. Due to damp and being close to the sea, the main reinforcement elements had undergone considerable corrosion causing a significant risk to the building’s safety. The intervention necessarily involved replacing the affected steel rebars with appropriate elements with mechanical and corrosion resistance properties, as required by the latest building codes. An appropriate strengthening and repair system was developed with a stainless steel prosthesis fitted to the lower third of the joists that almost tripled their resistance, gave them 120 min of fire resistance, and increased their durability against corrosion at a cost of less than 50% of the current repair systems with minimum generation of construction waste. One of the most appealing characteristics of this new repair system is its avoidance of the full replacement of the joists, which can be considered as a relevant contribution to the sustainability of the construction industry.
Effect of Chemical Composition of Clay on Physical-Mechanical Properties of Clay Paving Blocks
Authors: Avizovas Rolandas , Baskutis Saulius , Navickas Valentinas , Tamándl László
Published: July 2022

Clay paving blocks made of natural, environmentally friendly materials have their own originality and colorful authenticity, but due to the complex technological production process, they are also relatively expensive products; therefore, their environmental resistance properties are strictly defined and controlled by the standards. The physical and mechanical properties of clay paving blocks are the key factors aiming to ensure the longevity of products and their long-term success in the market. Therefore, ensuring high physical and mechanical properties of clay paving blocks have become a most crucial challenge for the manufactures. This article considers the parameters of the technological production process of clay paving blocks manufacturing and evaluates the influence of the chemical composition of three different types of clay on the physical and mechanical properties of the paving blocks. Water absorption, linear shrinkage, freeze/thaw, acid resistance, and transverse breaking load of clay paving blocks are investigated. This study reveals the importance of raw material selection in the production process of clay paving blocks and provides the concept of main quality factors of clay.
Sex Differences in Neoplastic Progression in Barrett’s Esophagus: A Multicenter Prospective Cohort Study
Authors: Roumans Carlijn A. M. , Zellenrath Pauline A. , Steyerberg Ewout W. , Lansdorp-Vogelaar Iris , Doukas Michael , Biermann Katharina , Alderliesten Joyce , van Ingen Gert , Nagengast Wouter B. , Karrenbeld Arend , ter Borg Frank , Hage Mariska , ter Borg Pieter C. J. , den Bakker Michael A. , Alkhalaf Alaa , Moll Frank C. P. , Brouwer-Hol Lieke , van Baarlen Joop , Quispel Rutger , van Tilburg Arjan , Burger Jordy P. W. , van Tilburg Antonie J. P. , Ooms Ariadne H. A. G. , Tang Thjon J. , Romberg-Camps Mariëlle J. L. , Goudkade Danny , Bruno Marco J. , Rizopoulos Dimitris , Spaander Manon C. W.
Published: July 2022

Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models.
Reply to Serrano et al. Comment on “Colletti et al. Prevalence and Management of Cancer of the Rectal Stump after Total Colectomy and Rectal Sparing in Patients with Familial Polyposis: Results from a Registry-Based Study. Cancers 2022, 14, 298”
Authors: Colletti Gaia , Ciniselli Chiara Maura , Rausa Emanuele , Signoroni Stefano , Cocco Ivana Maria Francesca , Magarotto Andrea , Ricci Maria Teresa , Brignola Clorinda , Mancini Andrea , Cavalcoli Federica , Cattaneo Laura , Milione Massimo , Verderio Paolo , Vitellaro Marco
Published: July 2022

We carefully read the comment by Serrano et al. [...]
Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics
Authors: Bin Satter Khaled , Ramsey Zach , Tran Paul M. H. , Hopkins Diane , Bearden Gregory , Richardson Katherine P. , Terris Martha K. , Savage Natasha M. , Kavuri Sravan K. , Purohit Sharad
Published: July 2022

Malignant chromophobe renal cancer (chRCC) and benign oncocytoma (RO) are two renal tumor types difficult to differentiate using histology and immunohistochemistry-based methods because of their similarity in appearance. We previously developed a transcriptomics-based classification pipeline with “Chromophobe-Oncocytoma Gene Signature” (COGS) on a single-molecule counting platform. Renal cancer patients (n = 32, chRCC = 17, RO = 15) were recruited from Augusta University Medical Center (AUMC). Formalin-fixed paraffin-embedded (FFPE) blocks from their excised tumors were collected. We created a custom single-molecule counting code set for COGS to assay RNA from FFPE blocks. Utilizing hematoxylin-eosin stain, pathologists were able to correctly classify these tumor types (91.8%). Our unsupervised learning with UMAP (Uniform manifold approximation and projection, accuracy = 0.97) and hierarchical clustering (accuracy = 1.0) identified two clusters congruent with their histology. We next developed and compared four supervised models (random forest, support vector machine, generalized linear model with L2 regularization, and supervised UMAP). Supervised UMAP has shown to classify all the cases correctly (sensitivity = 1, specificity = 1, accuracy = 1) followed by random forest models (sensitivity = 0.84, specificity = 1, accuracy = 1). This pipeline can be used as a clinical tool by pathologists to differentiate chRCC from RO.
P3H4 Promotes Malignant Progression of Lung Adenocarcinoma via Interaction with EGFR
Authors: Fang Chen , Liang Yingkuan , Huang Yong , Jiang Dong , Li Jiaxi , Ma Haitao , Guo Lingchuan , Jiang Wei , Feng Yu
Published: July 2022

Lung cancer is associated with the greatest number of cancer-related deaths worldwide. Lung adenocarcinoma (LUAD) accounts for 85% of all cases of lung cancer. Despite recent advances in treatment, the 5-year survival rate remains less than 15%. Thus, the diagnostic and therapeutic role of LUAD remain to be further studied. The prolyl 3-hydroxylase family member 4 (P3H4) is involved in various cancers, but little is known about its role in LUAD. Our study demonstrated that the P3H4 gene was upregulated in LUAD. Clinically, the expression of P3H4 was positively correlated with an advanced TNM stage and shorter survival. Functionally, P3H4 plays a significant role in the metastasis and proliferation of LUAD both in vitro and in vivo. Mechanistically, P3H4 might interact with EGFR to regulate the metabolic substances. Our study indicated that P3H4 is a critical gene in the malignant progression of LUAD and represents a potential biomarker and therapeutic target.
Effect of Pre-Existing Sarcopenia on Oncological Outcomes for Oral Cavity Squamous Cell Carcinoma Undergoing Curative Surgery: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study
Authors: Tsai Yu-Hsiang , Chen Wan-Ming , Chen Ming-Chih , Shia Ben-Chang , Wu Szu-Yuan , Huang Chun-Chi
Published: July 2022

Purpose: The effect of pre-existing sarcopenia on patients with oral cavity squamous cell carcinoma (OCSCC) remains unknown. Therefore, we designed a propensity score-matched population-based cohort study to compare the oncological outcomes of patients with OCSCC undergoing curative surgery with and without sarcopenia. Patients and Methods: We included patients with OCSCC undergoing curative surgery and categorized them into two groups according to the presence or absence of pre-existing sarcopenia. Patients in both the groups were matched at a ratio of 2:1. Results: The matching process yielded 16,294 patients (10,855 and 5439 without and with pre-existing sarcopenia, respectively). In multivariate Cox regression analyses, the adjusted hazard ratio (aHR, 95% confidence interval [CI]) of all-cause mortality for OCSCC with and without pre-existing sarcopenia was 1.15 (1.11–1.21, p < 0.0001). Furthermore, the aHRs (95% CIs) of locoregional recurrence and distant metastasis for OCSCC with and without pre-existing sarcopenia were 1.07 (1.03–1.18, p = 0.0020) and 1.07 (1.03–1.20, p = 0.0148), respectively. Conclusions: Pre-existing sarcopenia might be a significant poor prognostic factor for overall survival, locoregional recurrence, and distant metastasis for patients with OCSCC undergoing curative surgery. In susceptible patients at a risk of OCSCC, sarcopenia prevention measures should be encouraged, such as exercise and early nutrition intervention.
Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment
Authors: Asensi-Cantó Antonio , López-Abellán María Dolores , Castillo-Guardiola Verónica , Hurtado Ana María , Martínez-Penella Mónica , Luengo-Gil Ginés , Conesa-Zamora Pablo
Published: July 2022

Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs’ safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in the clinical setting. The current evidence points out that TCAs are safe and beneficial to treat neuropathic pain associated with cancer and chemotherapy, and they block different molecular pathways used by cancer cells from different locations for tumor growth and promotion. Likewise, ongoing clinical trials evaluating the antineoplastic effects of TCAs are discussed. TCAs are very biologically active compounds, and their repurposing as antitumoral drugs is a promising and straightforward approach to treat specific cancer subtypes and to further define their molecular targets, as well as an interesting starting point to design analogues with increased antitumoral activity.
Integrated MRI–Immune–Genomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma
Authors: Mazzaschi Giulia , Olivari Alessandro , Pavarani Antonio , Lagrasta Costanza Anna Maria , Frati Caterina , Madeddu Denise , Lorusso Bruno , Dallasta Silvia , Tommasi Chiara , Musolino Antonino , Tiseo Marcello , Michiara Maria , Quaini Federico , Crafa Pellegrino
Published: July 2022

Background: The aim of the present study was to dissect the clinical outcome of GB patients through the integration of molecular, immunophenotypic and MR imaging features. Methods: We enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant). Two-Dimensional Free ROI on the Biggest Enhancing Tumoral Diameter (TDFRBETD) acquired by MRI sequences were used to perform a manual evaluation of multiple quantitative variables, among which we selected: SD Fluid Attenuated Inversion Recovery (FLAIR), SD and mean Apparent Diffusion Coefficient (ADC). Characterization of the Tumor Immune Microenvironment (TIME) involved the immunohistochemical analysis of PD-L1, and number and distribution of CD3+, CD4+, CD8+ Tumor Infiltrating Lymphocytes (TILs) and CD163+ Tumor Associated Macrophages (TAMs), focusing on immune-vascular localization. Genetic, MR imaging and TIME descriptors were correlated with overall survival (OS). Results: MGMT methylation was associated with a significantly prolonged OS (median OS = 20 months), while no impact of p53 and EGFR status was apparent. GB cases with high mean ADC at MRI, indicative of low cellularity and soft consistency, exhibited increased OS (median OS = 24 months). PD-L1 and the overall number of TILs and CD163+TAMs had a marginal impact on patient outcome. Conversely, the density of vascular-associated (V) CD4+ lymphocytes emerged as the most significant prognostic factor (median OS = 23 months in V-CD4high vs. 13 months in V-CD4low, p = 0.015). High V-CD4+TILs also characterized TIME of MGMTmeth GB, while p53mut appeared to condition a desert immune background. When individual genetic (MGMTunmeth), MR imaging (mean ADClow) and TIME (V-CD4+TILslow) negative predictors were combined, median OS was 21 months (95% CI, 0–47.37) in patients displaying 0–1 risk factor and 13 months (95% CI 7.22–19.22) in the presence of 2–3 risk factors (p = 0.010, HR = 3.39, 95% CI 1.26–9.09). Conclusion: Interlacing MRI–immune–genetic features may provide highly significant risk-stratification models in GB patients.
Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy
Authors: Lindgaard Sidsel C. , Maag Emil , Sztupinszki Zsófia , Chen Inna M. , Johansen Astrid Z. , Jensen Benny V. , Bojesen Stig E. , Nielsen Dorte L. , Szallasi Zoltan , Johansen Julia S.
Published: July 2022

Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a dismal prognosis. We aimed to find a prognostic protein signature for overall survival (OS) in patients with advanced PDAC, and to explore whether early changes in circulating-protein levels could predict survival. We investigated 92 proteins using the Olink Immuno-Oncology panel in serum samples from 363 patients with advanced PDAC. Protein panels for several survival cut-offs were developed independently by two bioinformaticians using LASSO and Ridge regression models. Two panels of proteins discriminated patients with OS < 90 days from those with OS > 2 years. Index I (CSF-1, IL-6, PDCD1, TNFRSF12A, TRAIL, TWEAK, and CA19-9) had AUCs of 0.99 (95% CI: 0.98–1) (discovery cohort) and 0.89 (0.74–1) (replication cohort). For Index II (CXCL13, IL-6, PDCD1, and TNFRSF12A), the corresponding AUCs were 0.97 (0.93–1) and 0.82 (0.68–0.96). Four proteins (ANGPT2, IL-6, IL-10, and TNFRSF12A) were associated with survival across all treatment groups. Longitudinal samples revealed several changes, including four proteins that were also part of the prognostic signatures (CSF-1, CXCL13, IL-6, TNFRSF12A). This study identified two circulating-protein indices with the potential to identify patients with advanced PDAC with very short OS and with long OS.
Identifying Lethal Dependencies with HUGE Predictive Power
Authors: Gimeno Marian , San José-Enériz Edurne , Rubio Angel , Garate Leire , Miranda Estíbaliz , Castilla Carlos , Agirre Xabier , Prosper Felipe , Carazo Fernando
Published: July 2022

Recent functional genomic screens—such as CRISPR-Cas9 or RNAi screening—have fostered a new wave of targeted treatments based on the concept of synthetic lethality. These approaches identified LEthal Dependencies (LEDs) by estimating the effect of genetic events on cell viability. The multiple-hypothesis problem is related to a large number of gene knockouts limiting the statistical power of these studies. Here, we show that predictions of LEDs from functional screens can be dramatically improved by incorporating the “HUb effect in Genetic Essentiality” (HUGE) of gene alterations. We analyze three recent genome-wide loss-of-function screens—Project Score, CERES score and DEMETER score—identifying LEDs with 75 times larger statistical power than using state-of-the-art methods. Using acute myeloid leukemia, breast cancer, lung adenocarcinoma and colon adenocarcinoma as disease models, we validate that our predictions are enriched in a recent harmonized knowledge base of clinical interpretations of somatic genomic variants in cancer (AUROC > 0.87). Our approach is effective even in tumors with large genetic heterogeneity such as acute myeloid leukemia, where we identified LEDs not recalled by previous pipelines, including FLT3-mutant genotypes sensitive to FLT3 inhibitors. Interestingly, in-vitro validations confirm lethal dependencies of either NRAS or PTPN11 depending on the NRAS mutational status. HUGE will hopefully help discover novel genetic dependencies amenable for precision-targeted therapies in cancer. All the graphs showing lethal dependencies for the 19 tumor types analyzed can be visualized in an interactive tool.
A RAS-Independent Biomarker Panel to Reliably Predict Response to MEK Inhibition in Colorectal Cancer
Authors: Pfohl Ulrike , Loskutov Jürgen , Bashir Sanum , Kühn Ralf , Herter Patrick , Templin Markus , Mamlouk Soulafa , Belanov Sergei , Linnebacher Michael , Bürtin Florian , Vetter Marcus , Reinhard Christoph , Wedeken Lena , Regenbrecht Christian R. A.
Published: July 2022

Background: In colorectal cancer (CRC), mutations of genes associated with the TGF-β/BMP signaling pathway, particularly affecting SMAD4, are known to correlate with decreased overall survival and it is assumed that this signaling axis plays a key role in chemoresistance. Methods: Using CRISPR technology on syngeneic patient-derived organoids (PDOs), we investigated the role of a loss-of-function of SMAD4 in sensitivity to MEK-inhibitors. CRISPR-engineered SMAD4R361H PDOs were subjected to drug screening, RNA-Sequencing, and multiplex protein profiling (DigiWest®). Initial observations were validated on an additional set of 62 PDOs with known mutational status. Results: We show that loss-of-function of SMAD4 renders PDOs sensitive to MEK-inhibitors. Multiomics analyses indicate that disruption of the BMP branch within the TGF-β/BMP pathway is the pivotal mechanism of increased drug sensitivity. Further investigation led to the identification of the SFAB-signature (SMAD4, FBXW7, ARID1A, or BMPR2), coherently predicting sensitivity towards MEK-inhibitors, independent of both RAS and BRAF status. Conclusion: We identified a novel mutational signature that reliably predicts sensitivity towards MEK-inhibitors, regardless of the RAS and BRAF status. This finding poses a significant step towards better-tailored cancer therapies guided by the use of molecular biomarkers.
Intratumoral Switch of Molecular Phenotype and Overall Survival in Muscle Invasive Bladder Cancer
Authors: De Carlo Camilla , Valeri Marina , Rudini Noemi , Zucali Paolo , Cieri Miriam , Elefante Grazia , D’antonio Federica , Hurle Rodolfo , Giordano Laura , Bressan Alessandra , Lazzeri Massimo , Perrino Matteo , Guazzoni Giorgio , Terracciano Luigi , Colombo Piergiuseppe
Published: July 2022

In recent years, immunohistochemical protein expression was studied as a surrogate to the molecular classification of bladder cancer, although no tissue biomarkers are available for clinical use to predict survival or the response to neoadjuvant chemotherapy (CT) in UC, as the literature produced conflicting results. This retrospective study included TURB specimens harboring foci of HG pT2 muscle-invasive bladder carcinoma (MIBC) from 251 patients who subsequently underwent radical cystectomy. We performed immunohistochemical analysis on tumor samples, for relevant gene-expression-based markers for basal type (CD44, CK5/6) and luminal type (CK20 and pPARγ). Piescore, investigated in both non-muscle-invasive (NMI) and muscle-invasive (MI) components of the tumor, divided basal and luminal UC-types when at least three of the four markers were consistent with a specific phenotype, mixed types if one/two luminal and basal markers were present simultaneously, and neu-like types when all four markers investigated were negative. Eighteen selected cases were also investigated with RT-PCR to validate, and to increase the specificity of, the immunohistochemical results. We observe an immunophenotypical difference in the NMI and MI components in 96/251 UC patients (38.25%): half of tumors (44/96 cases) have a transition to basal, 36.46% (35/96 cases) to neu-like, 12.5% (12/96 cases) to mixed, and 5.2% (5/96 cases) to luminal phenotypes. Mixed tumors in the NMI component are more likely to change phenotype than other groups, particularly compared with basal tumors, which demonstrate greater stability (only 8/96 cases, p < 0.00001). The transition of luminal tumors to basal display a better OS compared with the transition toward neu-like tumors (p = 0.027). Overall, the phenotypical switch does not affect lymphovascular invasion, pT, DFS, or OS compared with non-switched cases. In the MI component, the presence of CD44 expression, irrespective of score-related phenotype, shows a protective effect in papillary-type UC (OS p = 0.008, HR 0.453, PFS p = 0.07, HR 0.599), and in UC naïve for CT (p = 0.0479). Piescore immunophenotyping reveals an intratumoral phenotypical transition between the NMI and MI components of the same tumor. The molecular change is a common event in the mixed and luminal categories, but not in basal tumors, which show better phenotypical stability. This phenomenon could partially explain the sensitivity of a subset of luminal UC to chemotherapy: good responders could be “non-real” luminal UC, which acquire nasal markers, such as CD44.
Prediction Models and Decision Aids for Women with Ductal Carcinoma In Situ: A Systematic Literature Review
Authors: Schmitz Renée , Wilthagen Erica , van Duijnhoven Frederieke , van Oirsouw Marja , Verschuur Ellen , Lynch Thomas , Punglia Rinaa , Hwang E. , Wesseling Jelle , Schmidt Marjanka , Bleiker Eveline , Engelhardt Ellen , Grand Challenge PRECISION Consortium
Published: July 2022

Even though Ductal Carcinoma in Situ (DCIS) can potentially be an invasive breast cancer (IBC) precursor, most DCIS lesions never will progress to IBC if left untreated. Because we cannot predict yet which DCIS lesions will and which will not progress, almost all women with DCIS are treated by breast-conserving surgery +/− radiotherapy, or even mastectomy. As a consequence, many women with non-progressive DCIS carry the burden of intensive treatment without any benefit. Multiple decision support tools have been developed to optimize DCIS management, aiming to find the balance between over- and undertreatment. In this systematic review, we evaluated the quality and added value of such tools. A systematic literature search was performed in Medline(ovid), Embase(ovid), Scopus and TRIP. Following the PRISMA guidelines, publications were selected. The CHARMS (prediction models) or IPDAS (decision aids) checklist were used to evaluate the tools’ methodological quality. Thirty-three publications describing four decision aids and six prediction models were included. The decision aids met at least 50% of the IPDAS criteria. However, most lacked tools to facilitate discussion of the information with healthcare providers. Five prediction models quantify the risk of an ipsilateral breast event after a primary DCIS, one estimates the risk of contralateral breast cancer, and none included active surveillance. Good quality and external validations were lacking for all prediction models. There remains an unmet clinical need for well-validated, good-quality DCIS risk prediction models and decision aids in which active surveillance is included as a management option for low-risk DCIS.
Physicochemical Features and NH3-SCR Catalytic Performance of Natural Zeolite Modified with Iron—The Effect of Fe Loading
Authors: Saramok Magdalena , Inger Marek , Antoniak-Jurak Katarzyna , Szymaszek-Wawryca Agnieszka , Samojeden Bogdan , Motak Monika
Published: July 2022

In modern dual-pressure nitric acid plants, the tail gas temperature usually exceeds 300 °C. The NH3-SCR catalyst used in this temperature range must be resistant to thermal deactivation, so commercial vanadium-based systems, such as V2O5-WO3 (MoO3)-TiO2, are most commonly used. However, selectivity of this material significantly decreases above 350 °C due to the increase in the rate of side reactions, such as oxidation of ammonia to NO and formation of N2O. Moreover, vanadium compounds are toxic for the environment. Thus, management of the used catalyst is complicated. One of the alternatives to commercial V2O5-TiO2 catalysts are natural zeolites. These materials are abundant in the environment and are thus relatively cheap and easily accessible. Therefore, the aim of the study was to design a novel iron-modified zeolite catalyst for the reduction of NOx emission from dual-pressure nitric acid plants via NH3-SCR. The aim of the study was to determine the influence of iron loading in the natural zeolite-supported catalyst on its catalytic performance in NOx conversion. The investigated support was firstly formed into pellets and then impregnated with various contents of Fe precursor. Physicochemical characteristics of the catalyst were determined by XRF, XRD, low-temperature N2 sorption, FT-IR, and UV–Vis. The catalytic performance of the catalyst formed into pellets was tested on a laboratory scale within the range of 250–450 °C using tail gases from a pilot nitric acid plant. The results of this study indicated that the presence of various iron species, including natural isolated Fe3+ and the introduced FexOy oligomers, contributed to efficient NOx reduction, especially in the high-temperature range, where the NOx conversion rate exceeded 90%.
Copper-Catalyzed Diastereo- and Enantioselective Borylative Cyclization
Authors: Manna Srimanta
Published: July 2022

Copper-catalyzed enantioselective borylative cyclization with various electrophiles via difunctionalization of unsaturated hydrocarbons is a powerful tool for the generation of interesting boron-containing carbocycles and heterocycles processes involving a chiral organocopper intermediate. Alkenes, allenes, and alkynes are versatile and easily accessible substrates that can be subjected to a wide range of reactions to produce densely functionalized, enantioenriched products. In this chapter, I discuss copper-catalyzed alkenes, allenes, and alkynes borofunctionalization and enantioselective cyclization via chiral organocopper intermediate. Copper-catalyzed enantioselective borylative cyclization and regiodivergent functionalization of alkenes, allenes, and alkynes, as well as the current mechanistic understanding of such processes, are given special attention in this review.
Elucidating Evidence for the In Situ Reduction of Graphene Oxide by Magnesium Hydride and the Consequence of Reduction on Hydrogen Storage
Authors: Pukazhselvan D , Shaula Aliaksandr L. , Mikhalev Sergey M. , Bdikin Igor , Fagg Duncan P.
Published: July 2022

The current study highlights important information regarding how graphene oxide (GO) additive interacts with magnesium hydride (MgH2) and transforms to reduced graphene oxide (rGO). A mild reduction occurs during mechanical milling itself, whereas a strong reduction of GO happens concurrently with the oxidation of Mg formed during the dehydrogenation of MgH2. Owing to the in situ transformation of GO to rGO, the dehydrogenation temperature of MgH2 reduces by about 60 °C, whereas the hydrogen ab/desorption reaction kinetics of MgH2 increases by two orders of magnitude and the dehydrogenation activation energy decreases by about 20 kJ/mol. We have thoroughly scrutinized the transformation of GO to rGO by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) techniques. Interestingly, the GO to rGO transformation triggered by magnesium hydride in the current study further paves the way for the facile preparation of rGO- and MgO-decked rGO composites, which are important materials for energy storage applications.
Mechanisms of Sperm–Egg Interactions: What Ascidian Fertilization Research Has Taught Us
Authors: Sawada Hitoshi , Saito Takako
Published: July 2022

Fertilization is an essential process in terrestrial organisms for creating a new organism with genetic diversity. Before gamete fusion, several steps are required to achieve successful fertilization. Animal spermatozoa are first activated and attracted to the eggs by egg-derived chemoattractants. During the sperm passage of the egg’s extracellular matrix or upon the sperm binding to the proteinaceous egg coat, the sperm undergoes an acrosome reaction, an exocytosis of acrosome. In hermaphrodites such as ascidians, the self/nonself recognition process occurs when the sperm binds to the egg coat. The activated or acrosome-reacted spermatozoa penetrate through the proteinaceous egg coat. The extracellular ubiquitin–proteasome system, the astacin-like metalloproteases, and the trypsin-like proteases play key roles in this process in ascidians. In the present review, we summarize our current understanding and perspectives on gamete recognition and egg coat lysins in ascidians and consider the general mechanisms of fertilization in animals and plants.
Hallmarks and Molecular Tools for the Study of Mitophagy in Parkinson’s Disease
Authors: Goiran Thomas , Eldeeb Mohamed A. , Zorca Cornelia E. , Fon Edward A.
Published: July 2022

The best-known hallmarks of Parkinson’s disease (PD) are the motor deficits that result from the degeneration of dopaminergic neurons in the substantia nigra. Dopaminergic neurons are thought to be particularly susceptible to mitochondrial dysfunction. As such, for their survival, they rely on the elaborate quality control mechanisms that have evolved in mammalian cells to monitor mitochondrial function and eliminate dysfunctional mitochondria. Mitophagy is a specialized type of autophagy that mediates the selective removal of damaged mitochondria from cells, with the net effect of dampening the toxicity arising from these dysfunctional organelles. Despite an increasing understanding of the molecular mechanisms that regulate the removal of damaged mitochondria, the detailed molecular link to PD pathophysiology is still not entirely clear. Herein, we review the fundamental molecular pathways involved in PINK1/Parkin-mediated and receptor-mediated mitophagy, the evidence for the dysfunction of these pathways in PD, and recently-developed state-of-the art assays for measuring mitophagy in vitro and in vivo.
Prevention of Cell Death by Activation of Hydroxycarboxylic Acid Receptor 1 (GPR81) in Retinal Explants
Authors: Vohra Rupali , Sanz-Morello Berta , Tams Anna Luna Mølgaard , Mouhammad Zaynab Ahmad , Freude Kristine Karla , Hannibal Jens , Aldana Blanca Irene , Bergersen Linda Hildegaard , Kolko Miriam
Published: July 2022

Background: Progressive retinal ganglion cell (RGC) dysfunction and death are common characteristics of retinal neurodegenerative diseases. Recently, hydroxycarboxylic acid receptor 1 (HCA1R, GPR81) was identified as a key modulator of mitochondrial function and cell survival. Thus, we aimed to test whether activation of HCA1R with 3,5-Dihydroxybenzoic acid (DHBA) also promotes RGC survival and improves energy metabolism in mouse retinas. Methods: Retinal explants were treated with 5 mM of the HCA1R agonist, 3,5-DHBA, for 2, 4, 24, and 72 h. Additionally, explants were also treated with 15 mM of L-glutamate to induce toxicity. Tissue survival was assessed through lactate dehydrogenase (LDH) viability assays. RGC survival was measured through immunohistochemical (IHC) staining. Total ATP levels were quantified through bioluminescence assays. Energy metabolism was investigated through stable isotope labeling and gas chromatography-mass spectrometry (GC-MS). Lactate and nitric oxide levels were measured through colorimetric assays. Results: HCA1R activation with 3,5-DHBAincreased retinal explant survival. During glutamate-induced death, 3,5-DHBA treatment also increased survival. IHC analysis revealed that 3,5-DHBA treatment promoted RGC survival in retinal wholemounts. 3,5-DHBA treatment also enhanced ATP levels in retinal explants, whereas lactate levels decreased. No effects on glucose metabolism were observed, but small changes in lactate metabolism were found. Nitric oxide levels remained unaltered in response to 3,5-DHBA treatment. Conclusion: The present study reveals that activation of HCA1R with 3,5-DHBA treatment has a neuroprotective effect specifically on RGCs and on glutamate-induced retinal degeneration. Hence, HCA1R agonist administration may be a potential new strategy for rescuing RGCs, ultimately preventing visual disability.
Increased Resection at DSBs in G2-Phase Is a Unique Phenotype Associated with DNA-PKcs Defects That Is Not Shared by Other Factors of c-NHEJ
Authors: Xiao Huaping , Li Fanghua , Mladenov Emil , Soni Aashish , Mladenova Veronika , Pan Bing , Dueva Rositsa , Stuschke Martin , Timmermann Beate , Iliakis George
Published: July 2022

The load of DNA double-strand breaks (DSBs) induced in the genome of higher eukaryotes by different doses of ionizing radiation (IR) is a key determinant of DSB repair pathway choice, with homologous recombination (HR) and ATR substantially gaining ground at doses below 0.5 Gy. Increased resection and HR engagement with decreasing DSB-load generate a conundrum in a classical non-homologous end-joining (c-NHEJ)-dominated cell and suggest a mechanism adaptively facilitating resection. We report that ablation of DNA-PKcs causes hyper-resection, implicating DNA-PK in the underpinning mechanism. However, hyper-resection in DNA-PKcs-deficient cells can also be an indirect consequence of their c-NHEJ defect. Here, we report that all tested DNA-PKcs mutants show hyper-resection, while mutants with defects in all other factors of c-NHEJ fail to do so. This result rules out the model of c-NHEJ versus HR competition and the passive shift from c-NHEJ to HR as the causes of the increased resection and suggests the integration of DNA-PKcs into resection regulation. We develop a model, compatible with the results of others, which integrates DNA-PKcs into resection regulation and HR for a subset of DSBs. For these DSBs, we propose that the kinase remains at the break site, rather than the commonly assumed autophosphorylation-mediated removal from DNA ends.
Endogenous Neural Stem Cell Mediated Oligodendrogenesis in the Adult Mammalian Brain
Authors: Radecki Daniel Z. , Samanta Jayshree
Published: July 2022

Oligodendrogenesis is essential for replacing worn-out oligodendrocytes, promoting myelin plasticity, and for myelin repair following a demyelinating injury in the adult mammalian brain. Neural stem cells are an important source of oligodendrocytes in the adult brain; however, there are considerable differences in oligodendrogenesis from neural stem cells residing in different areas of the adult brain. Amongst the distinct niches containing neural stem cells, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are considered the principle areas of adult neurogenesis. In addition to these areas, radial glia-like cells, which are the precursors of neural stem cells, are found in the lining of the third ventricle, where they are called tanycytes, and in the cerebellum, where they are called Bergmann glia. In this review, we will describe the contribution and regulation of each of these niches in adult oligodendrogenesis.
Angiotensin 1–7 Stimulates Proliferation of Lung Bronchoalveolar Progenitors—Implications for SARS-CoV-2 Infection
Authors: Ciechanowicz Andrzej K. , Lay Wen Xin , Prado Paulino Jefte , Suchocki Erika , Leszczak Susanne , Leszczak Christian , Kucia Magdalena
Published: July 2022

SARS-CoV-2 infection leads to severe lung damage due to pneumonia and, in more severe cases, leads to acute respiratory distress syndrome, or ARDS. This affects the viability of bronchoalveolar cells. An important role in the pathogenesis of these complications is the hyperactivation of the renin-angiotensin-aldosterone (RAA) pathway and induction of cytokine storm that occurs in an Nlrp3 inflammasome-dependent manner. To shed more light on the susceptibility of lung tissue to SARS-CoV-2 infection, we evaluated murine bronchioalveolar stem cells (BASC), alveolar type II cells (AT2), and 3D-derived organoids expression of mRNA encoding genes involved in virus entry into cells, components of RAA, and genes that comprise elements of the Nlrp3 inflammasome pathway. We noticed that all these genes are expressed by lung alveolar stem cells and organoids-derived from these cells. Interestingly, all these cells express a high level of ACE2 that, on the one hand, serves as an entry receptor for SARS-CoV-2 and, on the other, converts angiotensin II into its physiological antagonist, angiotensin 1–7 (Ang 1–7), which has been reported to have a protective role in lung damage. To shed more light on the role of Ang 1–7 on lung tissue, we exposed lung-derived BASC and AT2 cells to this mediator of RAA and noticed that it increases the proliferation of these cells. Based on this, Ang 1–7 could be employed to alleviate the damage to lung alveolar stem/progenitor cells during SARS-CoV-2 infection.
Electrochemical Biosensor Based on Chitosan- and Thioctic-Acid-Modified Nanoporous Gold Co-Immobilization Enzyme for Glycerol Determination
Authors: Yan Caiyun , Jin Kaifeng , Luo Xiangyi , Piao Jinhua , Wang Fang
Published: July 2022

An electrochemical biosensor based on chitosan- and thioctic-acid-modified nanoporous gold (NPG) co-immobilization glycerol kinase (GK) and glycerol-3-phosphate oxidase (GPO) was constructed for glycerol determination in wine. The NPG, with the properties of porous microstructure, large specific surface area, and high conductivity, was beneficial for protecting the enzyme from inactivation and denaturation and enhancing electron transfer in the modified electrode. The co-immobilization of the enzyme by chitosan-embedding and thioctic-acid-modified NPG covalent bonding was beneficial for improving the catalytic performance and stability of the enzyme-modified electrode. Ferrocene methanol (Fm) was used as a redox mediator to accelerate the electron transfer rate of the enzyme-modified electrode. The fabricated biosensor exhibited a wide determination range of 0.1–5 mM, low determination limit of 77.08 μM, and high sensitivity of 9.17 μA mM−1. Furthermore, it possessed good selectivity, repeatability, and stability, and could be used for the determination of glycerol in real wine samples. This work provides a simple and novel method for the construction of biosensors, which may be helpful to the application of enzymatic biosensors in different determination scenarios.
The Attitudes of Children Undergoing Orthodontic Treatment toward Face Mask Wearing during the COVID-19 Pandemic: A Cross Sectional Study
Authors: Cherecheș Jessica Olivia , Ciavoi Gabriela , Moca Abel Emanuel , Iurcov Raluca , Dima Raluca , Bembea Marius , Vaida Luminița Ligia
Published: July 2022

During the COVID-19 pandemic, the protective face mask has proven to be essential. The protective face masks cover the lower part of the face, including teeth and, for orthodontic patients, the orthodontic appliances. The aim of this study was to assess the impact that the restrictive measures that were imposed during the COVID-19 pandemic and, especially, wearing a protective face mask had on a sample of Romanian children, and to compare the results previously obtained on a sample of Romanian teenagers with the results obtained after investigating children under the age of 12 years. The cross-sectional survey was conducted in two orthodontic offices from the city of Oradea, Romania. The study sample included children with ages between 8 and 11.9 years that were undergoing an orthodontic treatment with removable or fixed orthodontic appliances. After obtaining the results, comparisons were made with the answers provided by a group of adolescents previously investigated. The questionnaires consisted of 9 items that investigated children’ attitudes toward protective face mask wearing and other aspects related to the COVID-19 pandemic. Two hundred fifty-six children were included in the study (53.1% female patients, 46.9% male patients). Most of the children were not worried that face masks would hide their orthodontic appliances (Item 1—Never, 40.2%; Rarely, 28.9%) and did not consider that the necessity of face mask wearing negatively impacted their desire to undergo an orthodontic treatment, despite the fact that it covered the appliances (Item 2—Never, 37.1%; Rarely, 31.6%). However, 44.5% of children were not happy because they had to wear a face mask during the orthodontic treatment, considering the fact that it covered the orthodontic appliance (Item 6), and most patients (49.2%) did not want the face mask to continue to be mandatory (Item 7). Although children were not happy that they had to wear a face mask that covered the orthodontic appliances, protective face masks were generally well tolerated by Romanian children.
Validation of the WHO-5 Well-Being Scale among Adolescents in Ghana: Evidence-Based Assessment of the Internal and External Structure of the Measure
Authors: Quansah Frank , Hagan John Elvis , Ankomah Francis , Agormedah Edmond Kwesi , Nugba Regina Mawusi , Srem-Sai Medina , Schack Thomas
Published: July 2022

The WHO-5 well-being measure happens to be one of the most renowned measures of subjective well-being across the globe. Although the instrument has been calibrated in different countries, its psychometric properties and applicability in Africa, especially in Ghana, are not known. In this study, the WHO-5 well-being scale was validated among adolescents in Ghana by assessing the validity evidence of the measure based on the internal and external structure. In particular, the study examined the (1) dimensionality of the WHO-5 well-being scale, (2) quality of the items (including the scale functioning) for the measure, and (3) criterion validity of the well-being measure. Using a survey approach, 997 adolescents were recruited in secondary schools across the northern belt of Ghana. The study found a one-factor structure of the scale, which supports the factor solution of the original measure. The items were found to be of high quality, except for one item. The WHO-5 well-being measure was found to have sufficient evidence regarding convergent and divergent validity. The outcome of this validation study provides support for the validity and reliability of the WHO-5 well-being scale’s utility and use among adolescents in Ghana. The study encourages further validation studies to be conducted in Ghana to widen the reproducibility of the WHO-5 well-being measure.
Deep-Learning-Based Automated Classification of Chinese Speech Sound Disorders
Authors: Kuo Yao-Ming , Ruan Shanq-Jang , Chen Yu-Chin , Tu Ya-Wen
Published: July 2022

This article describes a system for analyzing acoustic data to assist in the diagnosis and classification of children’s speech sound disorders (SSDs) using a computer. The analysis concentrated on identifying and categorizing four distinct types of Chinese SSDs. The study collected and generated a speech corpus containing 2540 stopping, backing, final consonant deletion process (FCDP), and affrication samples from 90 children aged 3–6 years with normal or pathological articulatory features. Each recording was accompanied by a detailed diagnostic annotation by two speech–language pathologists (SLPs). Classification of the speech samples was accomplished using three well-established neural network models for image classification. The feature maps were created using three sets of MFCC (Mel-frequency cepstral coefficients) parameters extracted from speech sounds and aggregated into a three-dimensional data structure as model input. We employed six techniques for data augmentation to augment the available dataset while avoiding overfitting. The experiments examine the usability of four different categories of Chinese phrases and characters. Experiments with different data subsets demonstrate the system’s ability to accurately detect the analyzed pronunciation disorders. The best multi-class classification using a single Chinese phrase achieves an accuracy of 74.4 percent.
Biopsychosocial Contributors to Parent Behaviors during Child Venipuncture
Authors: Constantin Kaytlin L. , Moline Rachel L. , Pillai Riddell Rebecca , Spence Jeffrey R. , McMurtry C. Meghan
Published: July 2022

Children’s needle-related distress is strongly related to parental verbal behaviors. Yet, empirical data supporting theorized contributors to parent behaviors in this context remain limited. This is the first study to collectively measure biological (heart rate variability; HRV), psychological (catastrophizing, anxiety), and social (child behaviors) contributors to parent verbal behaviors throughout pediatric venipuncture. HRV was used as a measure of emotion regulation capacity and examined as a moderator in the associations between parent psychological factors and their behaviors, and between child and parent behaviors. Sixty-one children aged 7 to 12 years who presented at an outpatient blood lab for venipuncture and a parent participated. Parent baseline HRV, state catastrophizing, and anxiety were measured prior to venipuncture. The procedure was video-recorded for later coding of pairs’ verbal behaviors. Strong associations emerged between child behaviors and parent behaviors. Baseline HRV moderated the association between parent catastrophizing and behavior. Social factors remain a strong influence related to parent behaviors. Psychologically, parent negative cognitions differentially related to parent behaviors based on their emotion regulation capacity. Biologically, low baseline HRV may increase the risk that certain parents engage in a constellation of behaviors that simultaneously direct their child’s attention toward the procedure and inadvertently communicate parental worry, fear, or concern.
Looking for New Materials: The Molecular Clocks
Authors: Carotenuto Gianfranco
Published: July 2022

Frequently, new materials have been discovered by looking at the interface among some of the already existing material classes [...]