bluuebunny/crossref_metadata_2025 huggingface dataset:
Precision Medicine Approach Based on Molecular Alterations for Patients with Relapsed or Refractory Multiple Myeloma: Results from the MM-EP1 Study
Authors: Andreozzi Fabio , Dragani Matteo , Quivoron Cyril , Le Bras Fabien , Assi Tarek , Danu Alina , Belhadj Karim , Lazarovici Julien , Cotteret Sophie , Bernard Olivier A. , Ribrag Vincent , Michot Jean-Marie
Published: March 2023

Background: Despite that cytogenetic and molecular analysis of tumor cells can rapidly identify recurring molecular abnormalities, no personalized therapy is currently available in the setting of relapsed/refractory multiple myeloma (r/r MM). Methods: MM-EP1 is a retrospective study aimed at comparing a personalized molecular-oriented (MO) versus a non-molecular-oriented (no-MO) approach in r/r MM. Actionable molecular targets and their associated therapies were the BRAF V600E mutation and BRAF inhibitors; t(11;14)(q13;q32) and BCL2 inhibitors; and t(4;14)(p16;q32) with FGFR3 fusion/rearrangements and FGFR3 inhibitors. Results: One hundred three highly pretreated r/r MM patients with a median age of 67 years (range 44–85) were included. Seventeen (17%) patients were treated using an MO approach with BRAF inhibitors (vemurafenib or dabrafenib, n = 6), BCL2 inhibitor (venetoclax, n = 9), or FGFR3 inhibitor (erdafitinib, n = 2). Eighty-six (86%) patients received non-MO therapies. Overall response rate was 65% in MO patients versus 58% in the non-MO group (p = 0.053). Median PFS and OS were 9 and 6 months (HR = 0.96; CI95 = 0.51–1.78; p = 0.88) and 26 and 28 months (HR = 0.98; CI95 = 0.46–2.12; p = 0.98), respectively, in MO and no-MO patients. Conclusion: Despite the low number of patients treated with an MO approach, this study highlights the strengths and weakness of a molecular-targeted approach for the treatment of multiple myeloma. Widespread biomolecular techniques and improvement of precision medicine treatment algorithms could improve selection for precision medicine in myeloma.
Salivary Interleukin Levels in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia: Findings from a Sri Lankan Study
Authors: Piyarathne Nadisha S. , Weerasekera Manjula M. , Fonseka Pasquel Fonsekalage Damith , Karunatilleke Appu Hennedi Thotahewage Sunil , Liyanage Rubasinha Liyanage Pemith Ranura , Jayasinghe Ruwan Duminda , De Silva Kanishka , Yasawardene Surangi , Gupta Ekta , Jayasinghe Jayasinghe Arachchilage Premasiri , Abu-Eid Rasha
Published: March 2023

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is paramount to improve patient outcome, and saliva testing is a promising non-invasive tool. The aim of this study was to assess salivary interleukins (lL1β, IL6, and IL8) in OSCC, OED and disease-free controls in a Sri Lankan study cohort. A case-control study with OSCC (n = 37), OED (n = 30) patients and disease-free controls (n = 30) was conducted. Salivary lL1β, IL6, and IL8 were quantified using enzyme-linked immuno-sorbent assay. Comparisons between different diagnostic groups and potential correlations to risk factors were assessed. Salivary levels for the three tested interleukins increased from disease-free controls through OED, and were highest in OSCC samples. Furthermore, the levels of IL1β, IL6, and IL8 increased progressively with OED grade. The discrimination between patients (OSCC and OED) and controls, as assessed by AUC of receiver operating characteristic curves, was 0.9 for IL8 (p = 0.0001) and 0.8 for IL6 (p = 0.0001), while IL1β differentiated OSCC from controls (AUC 0.7, p = 0.006). No significant associations were found between salivary interleukin levels and smoking, alcohol, and betel quid risk factors. Our findings suggest that salivary IL1β, IL6, and IL8 are associated with disease severity of OED, and are potential biomarkers for predicting disease progression in OED, and the screening of OSCC.
Discovering Synergistic Compounds with BYL-719 in PI3K Overactivated Basal-like PDXs
Authors: Boyd David C. , Zboril Emily K. , Olex Amy L. , Leftwich Tess J. , Hairr Nicole S. , Byers Holly A. , Valentine Aaron D. , Altman Julia E. , Alzubi Mohammad A. , Grible Jacqueline M. , Turner Scott A. , Ferreira-Gonzalez Andrea , Dozmorov Mikhail G. , Harrell J. Chuck
Published: March 2023

Basal-like triple-negative breast cancer (TNBC) tumor cells are difficult to eliminate due to resistance mechanisms that promote survival. While this breast cancer subtype has low PIK3CA mutation rates when compared to estrogen receptor-positive (ER+) breast cancers, most basal-like TNBCs have an overactive PI3K pathway due to gene amplification or high gene expression. BYL-719 is a PIK3CA inhibitor that has been found to have low drug-drug interactions, which increases the likelihood that it could be useful for combinatorial therapy. Alpelisib (BYL-719) with fulvestrant was recently approved for treating ER+ breast cancer patients whose cancer had developed resistance to ER-targeting therapy. In these studies, a set of basal-like patient-derived xenograft (PDX) models was transcriptionally defined with bulk and single-cell RNA-sequencing and clinically actionable mutation profiles defined with Oncomine mutational profiling. This information was overlaid onto therapeutic drug screening results. BYL-719-based, synergistic two-drug combinations were identified with 20 different compounds, including everolimus, afatinib, and dronedarone, which were also found to be effective at minimizing tumor growth. These data support the use of these drug combinations towards cancers with activating PIK3CA mutations/gene amplifications or PTEN deficient/PI3K overactive pathways.
The Clinical Spectrum, Diagnosis, and Management of GATA2 Deficiency
Authors: Santiago Marta , Liquori Alessandro , Such Esperanza , Zúñiga Ángel , Cervera José
Published: March 2023

Hereditary myeloid malignancy syndromes (HMMSs) are rare but are becoming increasingly significant in clinical practice. One of the most well-known syndromes within this group is GATA2 deficiency. The GATA2 gene encodes a zinc finger transcription factor essential for normal hematopoiesis. Insufficient expression and function of this gene as a result of germinal mutations underlie distinct clinical presentations, including childhood myelodysplastic syndrome and acute myeloid leukemia, in which the acquisition of additional molecular somatic abnormalities can lead to variable outcomes. The only curative treatment for this syndrome is allogeneic hematopoietic stem cell transplantation, which should be performed before irreversible organ damage happens. In this review, we will examine the structural characteristics of the GATA2 gene, its physiological and pathological functions, how GATA2 genetic mutations contribute to myeloid neoplasms, and other potential clinical manifestations. Finally, we will provide an overview of current therapeutic options, including recent transplantation strategies.
A Dual Biomarker TK1 Protein and CA125 or HE4-Based Algorithm as a Better Diagnostic Tool than ROMA Index in Early Detection of Ovarian Cancer
Authors: Cviič Diana , Jagarlamudi Kiran , Meglič Leon , Škof Erik , Zore Andrej , Lukanović David , Eriksson Staffan , Osredkar Joško
Published: March 2023

Background: The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients. Materials and methods: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA. Results: A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (p < 0.0001). Conclusions: The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages.
Tissue vs. Fecal-Derived Bacterial Dysbiosis in Precancerous Colorectal Lesions: A Systematic Review
Authors: Valciukiene Jurate , Strupas Kestutis , Poskus Tomas
Published: March 2023

Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota’s pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies.
A Propensity-Matched Retrospective Comparative Study with Historical Control to Determine the Real-World Effectiveness of Durvalumab after Concurrent Chemoradiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer
Authors: Park Cheol-Kyu , Jeon Nakyung , Park Hwa-Kyung , Oh Hyung-Joo , Kim Young-Chul , Jeon Ha-Lim , Kim Yong-Hyub , Ahn Sung-Ja , Oh In-Jae
Published: March 2023

This study aimed to add real-world evidence to the literature regarding the effectiveness and safety of durvalumab consolidation (DC) after concurrent chemoradiotherapy (CCRT) in the treatment of unresectable stage III non-small cell lung cancer (NSCLC). Using a hospital-based NSCLC patient registry and propensity score matching in a 2:1 ratio, we conducted a retrospective cohort study of patients with unresectable stage III NSCLC who completed CCRT with and without DC. The co-primary endpoints were 2-year progression-free survival and overall survival. For the safety evaluation, we evaluated the risk of any adverse events requiring systemic antibiotics or steroids. Of 386 eligible patients, 222 patients—including 74 in the DC group—were included in the analysis after propensity score matching. Compared with CCRT alone, CCRT with DC was associated with increased progression-free survival (median: 13.3 vs. 7.6 months, hazard ratio[HR]: 0.63, 95% confidence interval[CI]: 0.42–0.96) and overall survival (HR: 0.47, 95% CI: 0.27–0.82) without an increased risk of adverse events requiring systemic antibiotics or steroids. While there were differences in patient characteristics between the present real-world study and the pivotal randomized controlled trial, we demonstrated significant survival benefits and tolerable safety with DC after the completion of CCRT.
Independent Validation of a Deep Learning nnU-Net Tool for Neuroblastoma Detection and Segmentation in MR Images
Authors: Veiga-Canuto Diana , Cerdà-Alberich Leonor , Jiménez-Pastor Ana , Carot Sierra José Miguel , Gomis-Maya Armando , Sangüesa-Nebot Cinta , Fernández-Patón Matías , Martínez de las Heras Blanca , Taschner-Mandl Sabine , Düster Vanessa , Pötschger Ulrike , Simon Thorsten , Neri Emanuele , Alberich-Bayarri Ángel , Cañete Adela , Hero Barbara , Ladenstein Ruth , Martí-Bonmatí Luis
Published: March 2023

Objectives. To externally validate and assess the accuracy of a previously trained fully automatic nnU-Net CNN algorithm to identify and segment primary neuroblastoma tumors in MR images in a large children cohort. Methods. An international multicenter, multivendor imaging repository of patients with neuroblastic tumors was used to validate the performance of a trained Machine Learning (ML) tool to identify and delineate primary neuroblastoma tumors. The dataset was heterogeneous and completely independent from the one used to train and tune the model, consisting of 300 children with neuroblastic tumors having 535 MR T2-weighted sequences (486 sequences at diagnosis and 49 after finalization of the first phase of chemotherapy). The automatic segmentation algorithm was based on a nnU-Net architecture developed within the PRIMAGE project. For comparison, the segmentation masks were manually edited by an expert radiologist, and the time for the manual editing was recorded. Different overlaps and spatial metrics were calculated to compare both masks. Results. The median Dice Similarity Coefficient (DSC) was high 0.997; 0.944–1.000 (median; Q1–Q3). In 18 MR sequences (6%), the net was not able neither to identify nor segment the tumor. No differences were found regarding the MR magnetic field, type of T2 sequence, or tumor location. No significant differences in the performance of the net were found in patients with an MR performed after chemotherapy. The time for visual inspection of the generated masks was 7.9 ± 7.5 (mean ± Standard Deviation (SD)) seconds. Those cases where manual editing was needed (136 masks) required 124 ± 120 s. Conclusions. The automatic CNN was able to locate and segment the primary tumor on the T2-weighted images in 94% of cases. There was an extremely high agreement between the automatic tool and the manually edited masks. This is the first study to validate an automatic segmentation model for neuroblastic tumor identification and segmentation with body MR images. The semi-automatic approach with minor manual editing of the deep learning segmentation increases the radiologist’s confidence in the solution with a minor workload for the radiologist.
Improving Effects of Laccase-Mediated Pectin–Ferulic Acid Conjugate and Transglutaminase on Active Peptide Production in Bovine Lactoferrin Digests
Authors: Xing Mingxia , Ji Ying , Ai Lianzhong , Xie Fan , Wu Yan , Lai Phoency F. H.
Published: March 2023

Bovine lactoferrin (bLf) is a multifunctional glycoprotein and a good candidate for producing diverse bioactive peptides, which are easily lost during over-digestion. Accordingly, the effects of laccase-mediated pectin–ferulic acid conjugate (PF) and transglutaminase (TG) on improving the production of bLf active peptides by in vitro gastrointestinal digestion were investigated. Using ultra-high-performance liquid chromatography tandem mass spectroscopy (UPLC-MS-MS), the digests of bLf alone, PF-encapsulated bLf complex (LfPF), and TG-treated LfPF complex (LfPFTG) produced by conditioned in vitro gastric digestion (2000 U/mL pepsin, pH 3.0, 37 °C, 2 h) were identified with seven groups of active peptide-related fragments, including three common peptides (VFEAGRDPYKLRPVAAE, FENLPEKADRDQYEL, and VLRPTEGYL) and four differential peptides (GILRPYLSWTE, ARSVDGKEDLIWKL, YLGSRYLT, and FKSETKNLL). The gastric digest of LfPF contained more diverse and abundant detectable peptides of longer lengths than those of bLf and LfPFTG. After further in vitro intestinal digestion, two active peptide-related fragments (FEAGRDPYK and FENLPEKADRDQYE) remained in the final digest of LfPFTG; one (EAGRDPYKLRPVA) remained in that of bLf alone, but none remained in that of LfPF. Conclusively, PF encapsulation enhanced the production of bLf active peptide fragments under the in vitro gastric digestion applied. TG treatment facilitated active peptide FENLPEKADRDQYE being kept in the final gastrointestinal digest.
Preparation of Mn-Doped Co3O4 Catalysts by an Eco-Friendly Solid-State Method for Catalytic Combustion of Low-Concentration Methane
Authors: Xue Linshuang , Yuan Chenyi , Wu Shipeng , Huang Zhen , Yan Zhen , Streiff Stéphane , Xu Hualong , Shen Wei
Published: March 2023

Coalbed methane is a significant source of methane in the atmosphere, which is a potent greenhouse gas with a considerable contribution to global warming, thus it is of great importance to remove methane in coalbed gas before the emission. Exploring the economical non-noble metal catalysts for catalytic methane combustion (CMC) has been a wide concern to mitigate the greenhouse effect caused by the emitted low-concentration methane. Herein, a series of Mn-doped Co3O4 catalysts have been synthesized by the environmentally friendly solid-state method. As a result, the Mn0.05Co1 catalyst performed the best CMC activity (T90 = 370 °C) and good moisture tolerance (3 vol% steam). The introduction of an appropriate amount of manganese conduced Co3O4 lattice distortion and transformed Co3+ to Co2+, thus producing more active oxygen vacancies. Mn0.05Co1 exhibited better reducibility and oxygen mobility. In situ studies revealed that methane was adsorbed and oxidized much easier on Mn0.05Co1, which is the crucial reason for its superior catalytic performance.
Maternal and Intrauterine Influences on Feto-Placental Growth Are Accompanied by Sexually Dimorphic Changes in Placental Mitochondrial Respiration, and Metabolic Signalling Pathways
Authors: Salazar-Petres Esteban , Pereira-Carvalho Daniela , Lopez-Tello Jorge , Sferruzzi-Perri Amanda N.
Published: March 2023

Adverse maternal environments such as small size, malnutrition, and metabolic conditions are known to influence fetal growth outcomes. Similarly, fetal growth and metabolic alterations may alter the intrauterine environment and affect all fetuses in multiple gestation/litter-bearing species. The placenta is the site of convergence between signals derived from the mother and the developing fetus/es. Its functions are fuelled by energy generated by mitochondrial oxidative phosphorylation (OXPHOS). The aim of this study was to delineate the role of an altered maternal and/or fetal/intrauterine environment in feto-placental growth and placental mitochondrial energetic capacity. To address this, in mice, we used disruptions of the gene encoding phosphoinositol 3-kinase (PI3K) p110α, a growth and metabolic regulator to perturb the maternal and/or fetal/intrauterine environment and study the impact on wildtype conceptuses. We found that feto-placental growth was modified by a perturbed maternal and intrauterine environment, and effects were most evident for wildtype males compared to females. However, placental mitochondrial complex I+II OXPHOS and total electron transport system (ETS) capacity were similarly reduced for both fetal sexes, yet reserve capacity was additionally decreased in males in response to the maternal and intrauterine perturbations. These were also sex-dependent differences in the placental abundance of mitochondrial-related proteins (e.g., citrate synthase and ETS complexes), and activity of growth/metabolic signalling pathways (AKT and MAPK) with maternal and intrauterine alterations. Our findings thus identify that the mother and the intrauterine environment provided by littermates modulate feto-placental growth, placental bioenergetics, and metabolic signalling in a manner dependent on fetal sex. This may have relevance for understanding the pathways leading to reduced fetal growth, particularly in the context of suboptimal maternal environments and multiple gestation/litter-bearing species.
Estrogen Mediates the Sexual Dimorphism of GT1b-Induced Central Pain Sensitization
Authors: Lee Jaesung , Chung Seohyun , Hwang Minkyu , Kwon Yeongkag , Han Seung Hyun , Lee Sung Joong
Published: March 2023

We have previously reported that the intrathecal (i.t.) administration of GT1b, a ganglioside, induces spinal cord microglia activation and central pain sensitization as an endogenous agonist of Toll-like receptor 2 on microglia. In this study, we investigated the sexual dimorphism of GT1b-induced central pain sensitization and the underlying mechanisms. GT1b administration induced central pain sensitization only in male but not in female mice. Spinal tissue transcriptomic comparison between male and female mice after GT1b injection suggested the putative involvement of estrogen (E2)-mediated signaling in the sexual dimorphism of GT1b-induced pain sensitization. Upon ovariectomy-reducing systemic E2, female mice became susceptible to GT1b-induced central pain sensitization, which was completely reversed by systemic E2 supplementation. Meanwhile, orchiectomy of male mice did not affect pain sensitization. As an underlying mechanism, we present evidence that E2 inhibits GT1b-induced inflammasome activation and subsequent IL-1β production. Our findings demonstrate that E2 is responsible for sexual dimorphism in GT1b-induced central pain sensitization.
Functional Deficiency of Interneurons and Negative BOLD fMRI Response
Authors: Aksenov Daniil P. , Li Limin , Serdyukova Natalya A. , Gascoigne David A. , Doubovikov Evan D. , Drobyshevsky Alexander
Published: March 2023

The functional deficiency of the inhibitory system typically appears during development and can progress to psychiatric disorders or epilepsy, depending on its severity, in later years. It is known that interneurons, the major source of GABAergic inhibition in the cerebral cortex, can make direct connections with arterioles and participate in the regulation of vasomotion. The goal of this study was to mimic the functional deficiency of interneurons through the use of localized microinjections of the GABA antagonist, picrotoxin, in such a concentration that it did not elicit epileptiform neuronal activity. First, we recorded the dynamics of resting-state neuronal activity in response to picrotoxin injections in the somatosensory cortex of an awake rabbit; second, we assessed the altered neuronal and hemodynamic responses to whisker stimulation using BOLD fMRI and electrophysiology recordings; third, we evaluated brain tissue oxygen levels before and after picrotoxin injection. Our results showed that neuronal activity typically increased after picrotoxin administration, the BOLD responses to stimulation became negative, and the oxygen response was nearly abolished. Vasoconstriction during the resting baseline was not observed. These results indicate that picrotoxin provoked imbalanced hemodynamics either due to increased neuronal activity, decreased vascular response, or a combination of both.
Degradation Studies of Air-Exposed Black Phosphorous and Black Arsenic Phosphorous
Authors: Abu Usman O. , Vithanage Dinushika , Vitharana Ashan , Jasinski Jacek B. , Sumanasekera Gamini
Published: March 2023

This work investigates the effects of oxygen and humidity on black phosphorous (BP) and black arsenic phosphorous (AsxP1−x ) flakes using Raman spectroscopy and in situ electric transport measurements (four-probe resistance and thermoelectric power, TEP). The results show that the incorporation of arsenic into the lattice of BP renders it more stable, with the degradation times for BP, As0.2P0.8, and As0.4P0.6 being 4, 5, and 11 days, respectively. The P-P Raman peak intensities were determined to decrease with exposure to oxygen and moisture. The TEP measurements confirmed that both BP and AsxP1−x are p-type semiconductors with the TEP of As0.4P0.6 stabilizing more slowly than that of BP. In addition, the four-probe resistance of BP and AsxP1−x stabilized significantly faster when exposed to air after being degassed in a vacuum. This was attributed to the charge transfer between the oxygen redox potential of air and the Fermi energy (EF) of the semiconductors.
Conversion of Sugar Di-Ketals to Bio-Hydrocarbons through Catalytic Cracking over Beta Catalysts in Fixed and Fluidized Catalytic Beds
Authors: Cardoso Cristiane , Lam Yiu L. , de Almeida Marlon B. B. , Pereira Marcelo Maciel
Published: March 2023

Second-generation biomass (BM) can be produced in amounts that meet worldwide fuel demands. However, BM favors parallel and undesirable reactions in its transformation chain. We circumvent this problem by first modifying BM by ketalization, giving a user-friendly liquid we named BP (bio-petroleum). This study converted a representative compound of BP, DX (1,2:3,5-di-O-isopropylidene-α-D-xylofuranose), mixed with n-hexane by beta zeolites and catalysts containing beta zeolite. Beta zeolite showed low coke and high liquid product yields in converting this mixture (having 30 wt. % DX) into hydrocarbons in a fixed-bed reactor at 500 °C with a space velocity of 16 h−1 (0.3 catalyst/feed). Its performance was further improved by steam treatment (lowering the coke yield by lowering the acid site density) or incorporation into a catalyst (improving DX participation due to the active sites in the matrix). Further, by changing the conversion process from a fixed bed to a fluidized cracking unit, a much larger amount of the deactivated catalyst could be used (catalyst/feed = 3), remarkably reducing oxygenates and fully converting DX. Additionally, the green hydrocarbon efficiency (olefin, aromatics, furans, and cyclo-alkanes) of DX was approximately 77%. Hence, beta catalysts were shown to have a great potential to provide green fuels for future bio-refineries.
Design of a Boron-Doped Diamond Microcell Grafted with HRP for the Sensitive and Selective Detection of Ochratoxin A
Authors: Chrouda Amani , Ayed Dhekra , Elamin Manahil Babiker , Ali Shazalia Mahmoud Ahmed , Alhaidari Laila M. , Bessueille Francois , Jaffrezic-Renault Nicole
Published: March 2023

Ochratoxin A (OTA) is considered the most toxic member of the ochratoxin group. Herein, a novel label-free electrochemical sensor based on the horseradish peroxidase (HRP) enzyme is developed for OTA detection. The HRP enzyme was covalently immobilized on the working electrode of a planar boron-doped diamond (BDD) electrochemical microcell previously covered with diazonium film and grafted with single-walled carbon nanotubes (SWCNTs). Each surface modification step was evaluated by cyclic voltammetry and scanning electron microscopy. Square wave voltammetry was used for the detection of OTA. The linear working range of the biosensors ranged between 10−14 and 0.1 M, with a limit of detection (LOD) of 10 fM, an RSD equal to 5%, and a sensitivity of 0.8 µA per decade. In addition, the sensor showed good selectivity in the presence of OTA analogs; it was validated in samples such as corn, feed, and wheat. The metrological performance of the present sensor makes it a good alternative for OTA detection.
The Effect of SSRI Exposure in Pregnancy on Early Respiratory and Metabolic Adaptation in Infants Born Preterm
Authors: Gover Ayala , Endrawes Kareen , Molad Michal , Lavie-Nevo Karen , Riskin Arieh
Published: March 2023

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used for maternal depression during pregnancy; however, their use has been linked to adverse effects in newborns. Respiratory and feeding problems, jaundice, metabolic and temperature dysregulation and hypoglycemia have been described in term infants. However, scarce data exists on early neonatal adaptation in exposed infants born prematurely. We aimed to assess the effects of SSRI exposure on early neonatal adaptation measures in infants born prematurely. Data from preterm infants exposed to maternal SSRIs during pregnancy and from matched controls were retrospectively collected. Forty-two infants comprised the final cohort: 21 infants with SSRI exposure and 21 matched controls. 1 min Apgar score was significantly lower in the exposed group compared to the non-exposed group (p = 0.043). No differences were found in 5 min Apgar scores, cord pH, need for delivery room resuscitation, rate of hypoglycemia, hyponatremia, hyperbilirubinemia, need for phototherapy, temperature stability and maximal oxygen requirements. No differences were found in the total time of respiratory support, time to reaching full enteral feeds, length of stay and complications of prematurity. Unlike studies in term infants, no significant differences were found in adaptation and short-term outcomes between preterm infants with and without SSRI exposure in pregnancy.
Basic Activity of Daily Living Evaluation of Children with Autism Spectrum Disorder: Do-Eat Washy Adaption Preliminary Psychometric Characteristics
Authors: Levy-Dayan Hana , Josman Naomi , Rosenblum Sara
Published: March 2023

This preliminary study aims to demonstrate the reliability and validity of the adapted Do-Eat Basic activities of daily living (BADL) assessment for children with autism spectrum disorder (ASD). Participants were 53 children ages 6–10 years: 17 diagnosed with high-severity ASD (HS-ASD) and 16 with low-severity ASD according to the DSM-5 and based on the CARS-2, and 20 controls with typical development. Measurement tools were the adapted Do-Eat Washy (Washy), Participation in Childhood Occupations Questionnaire (PICO-Q), and Pediatric Evaluation of Disability Inventory (PEDI). The Washy domains exhibited high internal consistency (α = 0.841–0.856). Significant differences were found between the HS-ASD and other groups in the Washy domains, exhibiting discriminant validity. The Washy convergent and concurrent validity indicated good results. A highly substantial negative correlation was shown between the Washy and three PICO-Q ADL difficulty-in-performance items (p < 0.001): bathing (−0.550), hygiene (−0.571), and handwashing (−0.733). The Washy performance scores and the PEDI total score demonstrated a strong correlation. (r = 0.799, p < 0.001). Primary results indicate that, following further research on larger representative samples, the Washy may be a reliable and valid tool for assessing BADL among children with ASD.
Epigenetic Modification of Mesenchymal Stromal Cells Derived from Bone Marrow and Embryonal Tumors to Facilitate Immunotherapeutic Approaches in Pediatric Malignancies
Authors: Kruchen Anne , Johann Pascal-David , Rekowski Laura , Müller Ingo
Published: March 2023

Mesenchymal stromal cells (MSC) are part of the bone marrow architecture and contribute to the homeostasis of hematopoietic stem cells. Moreover, they are known to regulate immune effector cells. These properties of MSC are pivotal under physiologic conditions, and they may aberrantly also protect malignant cells. MSCs are also found in the leukemic stem cell niche of the bone marrow and as part of the tumor microenvironment. Here, they protect malignant cells from chemotherapeutic drugs and from immune effector cells in immunotherapeutic approaches. Modulation of these mechanisms may improve the efficacy of therapeutic regimens. We investigated the effect of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA, Vorinostat™) on the immunomodulatory effect and cytokine profile of MSC derived from bone marrow and pediatric tumors. The immune phenotype of MSC was not markedly affected. SAHA-treated MSC showed reduced immunomodulatory effects on T cell proliferation and NK cell cytotoxicity. This effect was accompanied by an altered cytokine profile of MSC. While untreated MSC inhibited the production of certain pro-inflammatory cytokines, SAHA treatment led to a partial increase in IFNγ and TNFα secretion. These alterations of the immunosuppressive milieu might be beneficial for immunotherapeutic approaches.
Site-Specific Seismic Analysis of Buildings Supported by Lightly Reinforced Precast Concrete Walls
Authors: Weng Xiangzhe , Hoult Ryan D. , Lumantarna Elisa
Published: March 2023

This paper aims to show the application of site-specific response spectra in the analysis of buildings that are supported by lightly reinforced precast concrete walls. Previous surveys on load-bearing precast reinforced concrete walls in multi-storey buildings in low-to-moderate seismic regions have found that many existing precast walls are lightly reinforced with a connection reinforcement ratio less than the wall reinforcement ratio. When these precast walls are subjected to reversed cyclic loads, the lateral response is typically controlled by rocking and the ultimate performance is governed by the ruptures of connection dowels. This paper uses moment–curvature analyses in combination with plastic hinge analyses to evaluate the force–displacement capacity of planar lightly reinforced load-bearing precast walls. The seismic performance of a building supported by these lightly reinforced precast walls can then be assessed by superimposing the capacity curve and the inelastic site-specific response spectra developed for the building site. The proposed analytical approach is illustrated through a case study building. By comparing a lightly reinforced precast wall with a comparable limited ductile reinforced concrete wall, it is also found that, although these two walls exhibit similar force capacities, the ultimate displacement capacity of the lightly reinforced precast wall is significantly lower. This finding highlights the potential seismic vulnerability of lightly reinforced precast walls in some existing buildings.
Phase Composition, Hardness, and Thermal Shock Properties of AlCrTiN Hard Films with High Aluminum Content
Authors: Peng Lijing , Zhang Jun , Wang Xiaoyang
Published: March 2023

TiCrAlN hard films based on TiN or CrN show superior properties in terms of hardness, wear resistance, and thermal stability due to the addition of alloying elements. AlCrTiN films based on AlN may have higher thermal shock properties, but the knowledge of AlCrTiN films with high Al content has been insufficient until now. In this study, two sets of AlCrTiN hard films with different Al contents of 48 at.% and 58 at.% among metal components were prepared via multi-arc ion plating so as to investigate the effect of Al content on the phase composition, hardness, and thermal shock resistance of the films. The same microstructures, morphologies, and thicknesses of the fabricated film samples were achieved by changing the combination of cathode alloy targets and adjusting the arc source current during deposition. The surface chemical composition, cross-sectional elemental distribution, microstructure, morphology, phase composition, surface hardness, film/substrate adhesion strength, and thermal shock performance of the AlCrTiN films were examined. The obtained results reveal that the two sets of AlTiCrN hard films are face-centered cubic solid solutions with a columnar fine grain structure and a preferred growth orientation of (200) crystal plane. The hardness of the AlCrTiN films can be improved up to HV2850 by properly reducing the Al content from 58 at.% to 48 at.%. Meanwhile, the film/substrate adhesion performance is strong enough in terms of critical loads greater than 200 N. Furthermore, the AlCrTiN films maintain high thermal shock resistance at 600 °C when the Al content decreases from 58 at.% to 48 at.%. The optimal composition of the AlCrTiN hard films is 25:13:15:47 (at.%), based on the consideration of hardness, adhesion, and thermal shock cycling resistance. This optimal AlCrTiN hard film can be suggested as an option for protective coatings of hot process die tools.
Polymer Waveguide-Based Optical Sensors—Interest in Bio, Gas, Temperature, and Mechanical Sensing Applications
Authors: Khonina Svetlana N. , Voronkov Grigory S. , Grakhova Elizaveta P. , Kazanskiy Nikolay L. , Kutluyarov Ruslan V. , Butt Muhammad A.
Published: March 2023

In the realization of photonic integrated devices, materials such as polymers are crucial. Polymers have shown compatibility with several patterning techniques, are generally affordable, and may be functionalized to obtain desired optical, electrical, or mechanical characteristics. Polymer waveguides are a viable platform for optical connectivity since they are easily adaptable to on-chip and on-board integration and promise low propagation losses <1 dB/cm. Furthermore, polymer waveguides can be made to be extremely flexible, able to withstand bending, twisting, and even stretching. Optical sensing is an interesting field of research that is gaining popularity in polymer photonics. Due to its huge potential for use in several industries, polymer waveguide-based sensors have attracted a lot of attention. Due to their resilience to electromagnetic fields, optical sensors operate better in difficult situations, such as those found in electrical power generating and conversion facilities. In this review, the most widely used polymer materials are discussed for integrated photonics. Moreover, four significant sensing applications of polymer-waveguide based sensors which include biosensing, gas sensing, temperature sensing and mechanical sensing have been debated.
The Influence of the Ion Implantation on the Degradation Level of the Coated Particles of Nuclear Fuel Samples
Authors: Krajewska Zuzanna M. , Buchwald Tomasz , Droździel Andrzej , Gudowski Wacław , Pyszniak Krzysztof , Tokarski Tomasz , Turek Marcin
Published: March 2023

TRIstructural ISOtropic (TRISO)-particle fuel is nuclear fuel used in high-temperature reactors. During reactor operation, partial damage may occur to the covering layers of this fuel. The authors of the publication propose an ion implantation method as a surrogate for neutron irradiation in the reactor core. This method makes it possible to reflect the damage that can be caused by irradiating samples in the reactor much faster and without having to deal with radioactive material. This paper presents an experiment on the p-TRISO samples, with a focus on the level of damage to the covering layers that could occur after 1, 3 and 5 years of neutron irradiation. The paper presents research conducted on both polished and unpolished p-TRISO fuel samples implanted with ions (Ne+, He+) of appropriate fluence and energy. It is necessary to determine whether the passage of time affects the occurrence of structural changes in p-TRISO fuel layers and, at the same time, whether it contributes to an increase in the probability of damage in the examined fuel material. The result of this work is confirmation that ion implantation is an efficient tool for reflecting irradiation-induced damage in the p-TRISO samples. In addition, the assumption that the sample does not need to be polished to obtain information about damage in the p-TRISO covering layers was confirmed.
Synthesis and Characterization of Co-Modified Polyurethane Nanocomposite Latexes by Terminal and Pendant Fluoroalkyl Segments
Authors: Jin Hua , Deng Fuquan , Xu Wei
Published: March 2023

To further improve the hydrophobic and thermal properties of fluorinated polyurethane (FPU), we initially prepared the fluorine- and silicon-containing pendant groups’ diols (DEFA and DESiA) by Michael addition reaction. Next, we synthesized a series of co-modified polyurethane nanocomposite (TPFPU-SiO2) latexes by terminal and pendant fluoroalkyl segments via varying the additive amount of silica sols. Structure and performance properties of the target materials were characterized by IR, TEM, TGA, DSC, XRD, XPS, SEM, AFM, and contact angle measurements. Results showed that with the increase in silica sols dosage, the mean particle size of the TPFPU-SiO2 latexes was increased and their emulsion stability gradually decreased. The thermal stability of the TPFPU-SiO2 films were gradually increased and hydrophobicity of the TPFPU-SiO2 films increased first and then slightly decreased. The maximum water contact angle on the TPFPU-SiO2 films was 119.8° and the lowest water absorptivity was 2.49%. Thus, these novel fluorinated polyurethane nanocomposite latexes can find valuable applications in heat-resistant and anti-fouling coatings.
In Situ Plasma Impedance Monitoring of the Oxide Layer PECVD Process
Authors: Park Hyun Keun , Song Wan Soo , Hong Sang Jeen
Published: March 2023

The use of plasma in semiconductor fabrication processes has been continuously increasing because of the miniaturization of semiconductor device structure, and plasma enhanced chemical vapor deposition (PECVD) has become a major process in thin film deposition. As a consequence, plasma diagnosis has become crucial during the deposition process, but the lack of in situ plasma monitoring sensors requires further development of existing in situ sensors, such as the Langmuir probe and optical emission spectroscopy (OES), for in situ plasma process monitoring. In this study, electrically equivalent circuit models of the PECVD chamber functioned as a plasma impedance model with respect to the deposited thin film thickness while plasma impedance was measured using a radio frequency voltage–current (VI) probe. We observed a significant correlation between the deposited film thickness of the chamber wall and the measured impedance of the PECVD chamber cleaning application in the semiconductor industry.
Preparation of Anticorrosive Epoxy Nanocomposite Coating Modified by Polyethyleneimine Nano-Alumina
Authors: Liang Xin , Hua Cheng , Zhang Mingrui , Zheng Yu , Song Shijie , Cai Meng , Huang Yu , He Can , Fan Xiaoqiang
Published: March 2023

Aluminum alloys with low density and high specific strength have been widely used in marine engineering. Epoxy coatings, a simple and economical protection strategy, have been applied on alloy surfaces to prolong service life. However, a pure epoxy coating cannot provide long-term protection for metals in the marine environment. Hence, in this work, nano-alumina (nano-Al2O3) modified by polyethyleneimine (PEI) were added into epoxy coatings to enhance anticorrosion properties. Using Fourier transform infrared spectroscopy (FTIR), we found that the molecular chain of PEI was successfully grafted on the surface of nano-Al2O3, and the cross profile of coatings indicated that the modified nano-Al2O3 uniformly dispersed in the epoxy coating. Electrochemical impedance spectroscopy (EIS) results demonstrate that the coating resistance of the modified epoxy nanocomposite coating was 10 times higher than that of the pure epoxy coating after 3 days of immersion in 3.5 wt.% NaCl solution. Meanwhile, the surface morphologies and EDS-mapping of substrates after EIS testing show that the substrate coated with modified epoxy nanocomposite coating had the smallest amount of corrosion products. These results show that this modified epoxy nanocomposite coating has excellent anticorrosion performance.
Preparation and Super-Hydrophobic Mechanism Analysis of FAS-17-Modified SiO2/PDMS Coatings for High-Voltage Composite Insulators
Authors: Li Chengqian , Dou Peng , Zhao Ruyi , Shi Yurou , Fu Gaojie , Shen Bin
Published: March 2023

Pollution flashover on insulators is one of the greatest challenges affecting the smooth operation of high-voltage transmission lines. Demonstrating super-hydrophobic coatings on insulators’ interfaces is an effective measure to prevent insulator flashovers. In the present investigation, a super-hydrophobic FAS-17-modified SiO2/PDMS coating on a composite insulator was demonstrated by spraying. The coating had a contact angle of 159.2° and a sliding angle of 1.3° with better insulation properties. The prepared FAS-17-modified nano-SiO2 nanoparticles were not easy to agglomerate; to illustrate this, the binding energy was calculated by the density functional theory. The super-hydrophobic mechanism of the coating was explained in terms of the adsorption energy between SiO2 molecules and water before and after modification. This paper provides a new method to solve the pollution flashover problem of insulators and a new angle to explain the super-hydrophobic mechanism.
How to Find Orchestrated Trolls? A Case Study on Identifying Polarized Twitter Echo Chambers
Authors: Kratzke Nane
Published: March 2023

Background: This study presents a graph-based, macro-scale, polarity-based, echo chamber detection approach for Twitter. Echo chambers are a concern as they can spread misinformation, and reinforce harmful stereotypes and biases in social networks. Methods: This study recorded the German-language Twitter stream over two months, recording about 6.7M accounts and their 75.5M interactions (33M retweets). This study focuses on retweet interaction patterns in the German-speaking Twitter stream and found that the greedy modularity maximization and HITS metric are the most effective methods for identifying echo chambers. Results: The purely structural detection approach identified an echo chamber (red community, 66K accounts) focused on a few topics with a triad of anti-Covid, right-wing populism and pro-Russian positions (very likely reinforced by Kremlin-orchestrated troll accounts). In contrast, a blue community (113K accounts) was much more heterogeneous and showed “normal” communication interaction patterns. Conclusions: The study highlights the effects of echo chambers as they can make political discourse dysfunctional and foster polarization in open societies. The presented results contribute to identifying problematic interaction patterns in social networks often involved in the spread of disinformation by problematic actors. It is important to note that not the content but only the interaction patterns would be used as a decision criterion, thus avoiding problematic content censorship.
A Scoping Review on COVID-19-Induced Cardiovascular Complications
Authors: Osoro Ian , Vohra Manisha , Amir Mohammad , Kumar Puneet , Sharma Amit
Published: March 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a type of human coronavirus that resulted in the 2019 coronavirus disease (COVID-19). Although it was generally categorized as a respiratory disease, its involvement in cardiovascular complications was identified from the onset. Elevated cardiac troponin levels (a myocardial injury marker) and echocardiograms, which showed the anomalous performance of the patients’ hearts, were noted in the early case reports obtained from Wuhan, China. A couple of mechanisms have been proposed to explain COVID-19-induced cardiovascular complications, with systemic inflammation being the major focus recently. Chest pain and palpitations are among the prevalent symptoms in moderate to severe COVID-19-recovering patients. Cardiac damage potentially occurs due to multifactorial factors, which include cytokine-induced inflammation, direct cardiotoxicity, and disseminated intravascular coagulation (DIC), among others. The cardiovascular manifestations include cardiac arrhythmia, cardiogenic shock, venous thromboembolism, and elevated cardiac biomarkers. Both the long- and short-term effects of these cardiovascular complications remain puzzling to researchers, as substantial evidence is yet to be gathered to reach a consensus on the severity of COVID-19 in the heart. The treatment considerations currently include antiarrhythmic management, ACEI or ARB use, anticoagulation, hemodynamic support, and immunosuppression. This review aimed to outline the pathogenesis of the various cardiac complications due to COVID-19 as well as the available treatment modalities of COVID-19 infection. Both the mechanisms and the treatments have been succinctly explained in a proper manner to ensure understanding.