bluuebunny/crossref_metadata_2025 huggingface dataset:
Achieving Nasal Septal Cartilage In Situ Regeneration: Focus on Cartilage Progenitor Cells
Authors: Zhang Chong , Wang Guanhuier , An Yang
Published: August 2023

The nasal septal cartilage plays an important role in preventing the collapse of the nasal bones and maintaining the appearance of the nose. In the context of inherent difficulties regarding septal cartilage repair and the shortage of cartilage graft resources for regeneration, tissue engineering, especially the in situ strategy based on scaffolds, has become a new prospect and become one of the most promising approaches. Given that it is difficult for chondrocytes to achieve directional migration and secrete matrix components to participate in tissue repair after cartilage injury, cartilage progenitor cells (CPCs), with great migratory ability and stem cell characteristics, have caught the attention of researchers and brought hope for nasal septal cartilage in situ regeneration. In this review, we first summarized the distribution, characteristics, isolation, and culture methods of nasal septal CPCs. Subsequently, we described the roles of migratory CPCs in cartilage regeneration. Finally, we reviewed the existing studies on CPCs-based cartilage tissue engineering and summarized the strategies for promoting the migration and chondrogenesis of CPCs so as to provide ideas for achieving nasal septal cartilage in situ regeneration.
The Avidity of Autoreactive Alpha-Synuclein Antibodies in Leucine-Rich Repeat Kinase 2 Mutation Carriers Is Not Altered Compared to Healthy Controls or Patients with Parkinson’s Disease
Authors: Albus Alexandra , Kronimus Yannick , Burg-Roderfeld Monika , van der Wurp Hendrik , Willbold Dieter , Ziehm Tamar , Dodel Richard , Ross Jean Alexander
Published: August 2023

The accumulation and aggregation of alpha-synuclein (α-Syn) are pathological processes associated with Parkinson’s disease, indicating that the regulation of protein is a crucial etiopathological mechanism. Interestingly, human serum and cerebrospinal fluid contain autoantibodies that recognize α-Syn. This potentially demonstrates an already existing, naturally decomposing, and protective system. Thus, quantitative or qualitative alterations, such as the modified antigen binding of so-called naturally occurring autoantibodies against α-Syn (nAbs-α-Syn), may induce disease onset and/or progression. We investigated the serum titers and binding characteristics of nAbs-α-Syn in patients suffering from sporadic Parkinson’s disease (n = 38), LRRK2 mutation carriers (n = 25), and healthy controls (n = 22). Methods: Titers of nAbs-α-Syn were assessed with ELISA and binding affinities and kinetics with SPR. Within the patient cohort, we discriminated between idiopathic and genetic (LRRK2-mutated) variants. Results: ELISA experiments revealed no significant differences in nAbs-α-Syn serum titers among the three cohorts. Moreover, the α-Syn avidity of nAbs-α-Syn was also unchanged. Conclusions: Our findings indicate that nAbs-α-Syn concentrations or affinities in healthy and diseased persons do not differ, independent of mutations in LRRK2.
Targeting Breast Cancer: The Familiar, the Emerging, and the Uncharted Territories
Authors: Montazeri Aliabadi Hamidreza , Manda Arthur , Sidgal Riya , Chung Co
Published: August 2023

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in clinics, the majority of these approaches seem to combine molecularly targeted drugs with chemotherapeutic agents. In this manuscript, we start by analyzing the list of FDA-approved molecularly targeted drugs for breast cancer to evaluate where molecular targeting stands in breast cancer treatment today. We will then provide an overview of other options currently under clinical trial or being investigated in pre-clinical studies.
Transition Mutations in the hTERT Promoter Are Unrelated to Potential i-motif Formation in the C-Rich Strand
Authors: Conrad James W. , Sowers Mark L. , Yap Dianne Y. , Cherryhomes Ellie , Pettitt B. Montgomery , Khanipov Kamil , Sowers Lawrence C.
Published: August 2023

Increased expression of the human telomere reverse transcriptase (hTERT) in tumors promotes tumor cell survival and diminishes the survival of patients. Cytosine-to-thymine (C-to-T) transition mutations (C250T or C228T) in the hTERT promoter create binding sites for transcription factors, which enhance transcription. The G-rich strand of the hTERT promoter can form G-quadruplex structures, whereas the C-rich strand can form an i-motif in which multiple cytosine residues are protonated. We considered the possibility that i-motif formation might promote cytosine deamination to uracil and C-to-T mutations. We computationally probed the accessibility of cytosine residues in an i-motif to attack by water. We experimentally examined regions of the C-rich strand to form i-motifs using pH-dependent UV and CD spectra. We then incubated the C-rich strand with and without the G-rich complementary strand DNA under various conditions, followed by deep sequencing. Surprisingly, deamination rates did not vary substantially across the 46 cytosines examined, and the two mutation hotspots were not deamination hotspots. The appearance of mutational hotspots in tumors is more likely the result of the selection of sequences with increased promoter binding affinity and hTERT expression.
Blood-Biomarkers for Glucose Metabolism in Preterm Infants
Authors: Bjerager Mia O. , Hansen Bo M. , Sørensen Frederik , Petersen Jes R. , Jensen Kristian V. , Hjelvang Brian R. , Hvelplund Anna C. , Olsen Dorte A. , Nielsen Aneta A. , Forman Julie L. , Brandslund Ivan , Greisen Gorm , Slidsborg Carina
Published: August 2023

This was an exploratory, prospective, longitudinal, cohort study that aimed to establish “healthy” reference levels related to growth parameters and glucose metabolites in preterm infants. This was conducted to further investigate growth and metabolic disturbances potentially related to neonatal illness. The study sample consisted of 108 preterm infants born before 32 weeks in 2018–2019 in the Capital Region of Denmark. Repetitive blood samples were acquired at the neonatal wards, while clinical data were obtained from the regional hospital medical record system. Thirty-four “healthy” preterm infants (31%) were identified. The “ill” infants were divided into four subgroups dependent on gestational age and small for gestational age. Reference levels for the growth parameters and metabolic biomarkers glucose, albumin, and adiponectin, and two glucose control indicators, glycated albumin and fructosamine, were determined for the “healthy” and “ill” subgroups. The “ill” extremely preterm infants had increased glucose levels (mean difference 0.71 mmol/L, 95% CI 0.23; 1.18 mmol/L) and glycated albumin (corrected; %) (mean difference 0.92 mmol/L, 95% CI 0.38 mmol/L;1.47 mmol/L) compared to the “healthy” infants. In “ill” extremely preterm infants and “ill” very preterm infants born small for gestational age, levels of biomarkers containing proteins were decreased. In the “Ill” extremely preterm infants and infants born small for gestational age, postnatal growth was continuously decreased throughout the postconceptional period. The short-term glucose-control indicator, glycated albumin (corrected; %), reflected well the high glucose levels due to its correction for the depleted plasma-protein pool.
The Role of Polymorphism in the Endothelial Homeostasis and Vitamin D Metabolism Genes in the Severity of Coronary Artery Disease
Authors: Ponasenko Anastasia , Sinitskaya Anna , Sinitsky Maxim , Khutornaya Maria , Barbarash Olga
Published: August 2023

Coronary artery disease (CAD) remains one of the leading causes of cardiovascular morbidity and mortality worldwide. The maintenance of endothelial homeostasis and vitamin D metabolism play an important role in CAD pathogenesis. This study aimed to determine the association of endothelial homeostasis and vitamin D metabolism gene polymorphism with CAD severity. A total of 224 low-risk patients (SYNTAX score ≤ 31) and 36 high-risk patients (SYNTAX score > 31) were recruited for this study. The serum level of E-, L- and P-selectins; endothelin; eNOS; 25OH; and 1.25-dihydroxy vitamin D was measured using an enzyme-linked immunosorbent assay (ELISA). Polymorphic variants in SELE, SELP, SELPLG, END1, NOS3, VDR and GC were analyzed using a polymerase chain reaction (PCR). We found no differences in the serum levels of the studied markers between high- and low-risk patients. Three polymorphic variants associated with CAD severity were discovered: END1 rs3087459, END1 rs5370 and GC rs2298849 in the log-additive model. Moreover, we discovered a significantly decreased serum level of 1.25-dihydroxy vitamin D in high-risk CAD patients with the A/A–A/G genotypes of the rs2228570 polymorphism of the VDR gene, the A/A genotype of the rs7041 polymorphism of the GC gene and the A/A genotype of the rs2298849 polymorphism of the GC gene.
Selective Inhibition of Cardiac Late Na+ Current Is Based on Fast Offset Kinetics of the Inhibitor
Authors: Naveed Muhammad , Mohammed Aiman Saleh A. , Topal Leila , Kovács Zsigmond Máté , Dienes Csaba , Ovári József , Szentandrássy Norbert , Magyar János , Bányász Tamás , Prorok János , Jost Norbert , Virág László , Baczkó István , Varró András , Nánási Péter P. , Horváth Balázs
Published: August 2023

The present study was designed to test the hypothesis that the selectivity of blocking the late Na+ current (INaL) over the peak Na+ current (INaP) is related to the fast offset kinetics of the Na+ channel inhibitor. Therefore, the effects of 1 µM GS967 (INaL inhibitor), 20 µM mexiletine (I/B antiarrhythmic) and 10 µM quinidine (I/A antiarrhythmic) on INaL and INaP were compared in canine ventricular myocardium. INaP was estimated as the maximum velocity of action potential upstroke (V+max). Equal amounts of INaL were dissected by the applied drug concentrations under APVC conditions. The inhibition of INaL by mexiletine and quinidine was comparable under a conventional voltage clamp, while both were smaller than the inhibitory effect of GS967. Under steady-state conditions, the V+max block at the physiological cycle length of 700 ms was 2.3% for GS967, 11.4% for mexiletine and 26.2% for quinidine. The respective offset time constants were 110 ± 6 ms, 456 ± 284 ms and 7.2 ± 0.9 s. These results reveal an inverse relationship between the offset time constant and the selectivity of INaL over INaP inhibition without any influence of the onset rate constant. It is concluded that the selective inhibition of INaL over INaP is related to the fast offset kinetics of the Na+ channel inhibitor.
Interplay of Chemokines Receptors, Toll-like Receptors, and Host Immunological Pathways
Authors: Chu Yuan-Tung , Liao Min-Tser , Tsai Kuo-Wang , Lu Kuo-Cheng , Hu Wan-Chung
Published: August 2023

A comprehensive framework has been established for understanding immunological pathways, which can be categorized into eradicated and tolerable immune responses. Toll-like receptors (TLRs) are associated with specific immune responses. TH1 immunity is related to TLR7, TLR8, and TLR9, while TH2 immunity is associated with TLR1, TLR2, and TLR6. TH22 immunity is linked to TLR2, TLR4, and TLR5, and THαβ (Tr1) immunity is related to TLR3, TLR7, and TLR9. The chemokine receptor CXCR5 is a marker of follicular helper T cells, and other chemokine receptors can also be classified within a framework based on host immunological pathways. On the basis of a literature review on chemokines and immunological pathways, the following associations were identified: CCR5 with TH1 responses, CCR1 with TH1-like responses, CCR4 (basophils) and CCR3 (eosinophils) with TH2 and TH9 responses, CCR10 with TH22 responses, CCR6 with TH17 responses, CXCR3 with THαβ responses, CCR8 with regulatory T cells (Treg), and CCR2 with TH3 responses. These findings contribute to the identification of biomarkers for immune cells and provide insights into host immunological pathways. Understanding the chemokine and Toll-like receptor system is crucial for comprehending the function of the innate immune system, as well as adaptive immune responses.
Toward Continuous Molecular Testing Using Gold-Coated Threads as Multi-Target Electrochemical Biosensors
Authors: Hanze Martin , Khaliliazar Shirin , Réu Pedro , Toldrà Anna , Hamedi Mahiar M.
Published: August 2023

Analytical systems based on isothermal nucleic acid amplification tests (NAATs) paired with electroanalytical detection enable cost-effective, sensitive, and specific digital pathogen detection for various in situ applications such as point-of-care medical diagnostics, food safety monitoring, and environmental surveillance. Self-assembled monolayers (SAMs) on gold surfaces are reliable platforms for electroanalytical DNA biosensors. However, the lack of automation and scalability often limits traditional chip-based systems. To address these challenges, we propose a continuous thread-based device that enables multiple electrochemical readings on a functionalized working electrode Au thread with a single connection point. We demonstrate the possibility of rolling the thread on a spool, which enables easy manipulation in a roll-to-roll architecture for high-throughput applications. As a proof of concept, we have demonstrated the detection of recombinase polymerase amplification (RPA) isothermally amplified DNA from the two toxic microalgae species Ostreopsis cf. ovata and Ostreopsis cf. siamensis by performing a sandwich hybridization assay (SHA) with electrochemical readout.
The Impact of Shared Information Presentation Time on Users’ Privacy-Regulation Behavior in the Context of Vertical Privacy: A Moderated Mediation Model
Authors: Zhuang Lei , Sun Rui , Chen Lijun , Tang Wenlong
Published: August 2023

Combining data-sharing models and algorithm technologies has led to new data flow structures and usage patterns. In this context, the presentation time of shared low-sensitivity information across platforms has become a crucial factor that affects user perception and privacy-regulation behavior. However, previous studies have not conducted an in-depth exploration of this issue. Based on privacy process theory, this study discusses the impact and potential mechanism of the presentation time (immediate or delayed) of shared low-sensitivity information across platforms on privacy-regulation behavior. Through a pre-study and two online survey experimental studies, which included 379 participants in total, we verified that the immediate information presentation time has a significantly higher impact on online vigilance and privacy-regulation behavior than the delayed condition, βdirect = 0.5960, 95% CI 0.2402 to 0.9518; βindirect = 0.1765, 95% CI 0.0326 to 0.3397, and users’ perceived control as the moderating role influences online vigilance and privacy-regulation behaviors (preventive or corrective), βpreventive = −0.0562, 95% CI −0.1435 to −0.0063; βcorrective = −0.0581, 95% CI −0.1402 to −0.0065. Based on these results, we suggest that the presentation time of using shared low-sensitivity information across platforms should be concerned by companies’ recommendation algorithms to reduce users’ negative perceptions and privacy behaviors and improve user experience.
Experimental and Theoretical Analysis of Flexural Properties of Mortar Beam Reinforced with Coated Carbon-Fiber Textile
Authors: Hong Geuntae , Park Jangsoon , Lee Seong-Cheol , Cha Soo Won , Ryu Jaewoo , Choi Seongcheol
Published: August 2023

The flexural behavior of mortar beams reinforced with coated carbon-fiber textile was experimentally analyzed in this study. Accordingly, pull-out and bending tests were performed on textile-reinforced mortar (TRM) beam specimens. The experimental results demonstrated the superior bond performance of the coated carbon-fiber textile. The TRM beam exhibited sufficient ductility even after the occurrence of flexural cracks. In addition, a theoretical analysis method for predicting the flexural behavior of a TRM beam was established based on the experimentally determined bond behaviors of the textile reinforcement in cementitious materials. The analysis demonstrated that the bending behavior of the TRM beam was reasonably predicted. The results of this study can serve as basic data for the structural application of textile-reinforced cementitious composites.
Outcomes of Liver Cancer Patients Undergoing Elective Surgery after Recovering from Mild SARS-CoV-2 Omicron Infection: A Retrospective Cohort Study
Authors: Wang Yizhou , Ma Junyong , Wu Yali , Zhang Shichao , Li Xifeng , Xia Yong , Yan Zhenlin , Liu Jian , Shen Feng , Zhang Xiaofeng
Published: August 2023

With the emergence of new virus variants, limited data are available on the impact of SARS-CoV-2 Omicron infection on surgery outcomes in cancer patients who have been widely vaccinated. This study aimed to determine whether undergoing hepatectomy poses a higher risk of postoperative complications for liver cancer patients who have had mild Omicron infection before surgery. A propensity-matched cohort study was conducted at a tertiary liver center from 8 October 2022 to 13 January 2023. In total, 238 liver cancer patients who underwent hepatectomy were included, with 57 (23.9%) recovering from preoperative SARS-CoV-2 Omicron infection and 190 (79.8%) receiving COVID-19 vaccination. Pre- and post-matching, there was no significant difference in the occurrence of postoperative outcomes between preoperative COVID-19 recovered patients and COVID-19 negative patients. Multivariate logistic regression showed that the COVID-19 status was not associated with postoperative major pulmonary and cardiac complications. However, preexisting comorbidities (odds ratio [OR], 4.645; 95% confidence interval [CI], 1.295–16.667), laparotomy (OR, 10.572; 95% CI, 1.220–91.585), and COVID-19 unvaccinated (OR, 5.408; 95% CI, 1.489–19.633) had increased odds of major complications related to SARS-CoV-2 infection. In conclusion, liver cancer patients who have recovered from preoperative COVID-19 do not face an increased risk of postoperative complications.
Immune Checkpoint Inhibitors after Radiation Therapy Improve Overall Survival Rates in Patients with Stage IV Lung Cancer
Authors: Tanaka Hidekazu , Ueda Kazushi , Karita Masako , Ono Taiki , Manabe Yuki , Kajima Miki , Fujimoto Koya , Yuasa Yuki , Shiinoki Takehiro
Published: August 2023

This exploratory and retrospective study aimed to evaluate whether there is a difference in the overall survival (OS) rates of patients with stage IV lung cancer who underwent radiation therapy (RT) depending on the presence or absence of immune checkpoint inhibitors (ICIs) and the timing of their use. Eighty patients with histologically confirmed stage IV lung cancer were enrolled, and ICIs were administered to thirty (37.5%). ICIs were administered before RT and after RT in 11 and 20 patients, respectively. The median follow-up period was 6 (range: 1–37) months. Patients treated with ICIs had significantly better OS rates than those not treated with ICIs (p < 0.001). The 6-month OS rates in patients treated with and without ICIs were 76.3% and 34.5%, respectively. The group that received ICI therapy after RT had a significantly better OS rate than the group that received ICI therapy prior to RT (6-month OS: 94.7% vs. 40.0%, p < 0.001). In the multivariate analysis, performance status (0–1 vs. 2–4) and ICI use after RT were significant factors for OS (p = 0.032 and p < 0.001, respectively). Our results suggest that ICI administration after RT may prolong the OS of patients with stage IV lung cancer.
Failure of a Multi-Centric Clinical Trial Investigating Neoadjuvant Radio-Chemotherapy in Resectable Pancreatic Carcinoma (NEOPA-NCT01900327)—Which Lessons Are Learnt?
Authors: Tachezy Michael , Gebauer Florian , Yekebas Emre , Izbicki Jakob Robert
Published: August 2023

Background: A significant number of clinical trials must be prematurely discontinued due to recruitment failure, and only a small fraction publish results and a failure analysis. Based on our experience on conducting the NEOPA trial on neoadjuvant radiochemotherapy for resectable and borderline resectable pancreatic carcinoma (NCT01900327—funded by the German Federal Ministry of Education and Research—BMBF), we performed an analysis of potential reasons for recruitment failure and general problems in conducting clinical trials in Germany. Methods: Systematic analysis of environmental factors, trial history, conducting and funding in the background of the published literature. Results: The recruitment failure was based on various study-specific conceptional and local environmental aspects and in peculiarities of the German surgical study culture. General reservations against a neo-adjuvant study concept combined with game changing scientific progresses during the long-lasting planning and funding phase have led to a reduced interest in the trial design and recruitment. Conclusions: Trial planning and conducting should be focused, professionalized and financed on a national basis. Individual interests must be subordinated to reach the goal to perform more relevant and successful clinical trials in Germany. Bureaucratic processes must be further fastened between a trial idea and the start of a study.
PCR-Based Strategy for Introducing CRISPR/Cas9 Machinery into Hematopoietic Cell Lines
Authors: González-Romero Elisa , Martínez-Valiente Cristina , García-García Gema , Rosal-Vela Antonio , Millán José María , Sanz Miguel Ángel , Sanz Guillermo , Liquori Alessandro , Cervera José Vicente , Vázquez-Manrique Rafael P.
Published: August 2023

Acute myeloid leukemia is a complex heterogeneous disease characterized by the clonal expansion of undifferentiated myeloid precursors. Due to the difficulty in the transfection of blood cells, several hematological models have recently been developed with CRISPR/Cas9, using viral vectors. In this study, we developed an alternative strategy in order to generate CRISPR constructs by fusion PCR, which any lab equipped with basic equipment can implement. Our PCR-generated constructs were easily introduced into hard-to-transfect leukemic cells, and their function was dually validated with the addition of MYBL2 and IDH2 genes into HEK293 cells. We then successfully modified the MYBL2 gene and introduced the R172 mutation into the IDH2 gene within NB4 and HL60 cells that constitutively expressed the Cas9 nuclease. The efficiency of mutation introduction with our methodology was similar to that of ribonucleoprotein strategies, and no off-target events were detected. Overall, our strategy represents a valid and intuitive alternative for introducing desired mutations into hard-to-transfect leukemic cells without viral transduction.
The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment
Authors: Dalir Abdolahinia Elaheh , Han Xiaozhe
Published: August 2023

The onset and progression of oral cancer are accompanied by a dynamic interaction with the host immune system, and the immune cells within the tumor microenvironment play a pivotal role in the development of the tumor. By exploring the cellular immunity of oral cancer, we can gain insight into the contribution of both tumor cells and immune cells to tumorigenesis. This understanding is crucial for developing effective immunotherapeutic strategies to combat oral cancer. Studies of cancer immunology present unique challenges in terms of modeling due to the extraordinary complexity of the immune system. With its multitude of cellular components, each with distinct subtypes and various activation states, the immune system interacts with cancer cells and other components of the tumor, ultimately shaping the course of the disease. Conventional two-dimensional (2D) culture methods fall short of capturing these intricate cellular interactions. Mouse models enable us to learn about tumor biology in complicated and dynamic physiological systems but have limitations as the murine immune system differs significantly from that of humans. In light of these challenges, three-dimensional (3D) culture systems offer an alternative approach to studying cancer immunology and filling the existing gaps in available models. These 3D culture models provide a means to investigate complex cellular interactions that are difficult to replicate in 2D cultures. The direct study of the interaction between immune cells and cancer cells of human origin offers a more relevant and representative platform compared to mouse models, enabling advancements in our understanding of cancer immunology. This review explores commonly used 3D culture models and highlights their significant contributions to expanding our knowledge of cancer immunology. By harnessing the power of 3D culture systems, we can unlock new insights that pave the way for improved strategies in the battle against oral cancer.
Role of YY1 in the Regulation of Anti-Apoptotic Gene Products in Drug-Resistant Cancer Cells
Authors: Jung Megan , Bui Indy , Bonavida Benjamin
Published: August 2023

Cancer is a leading cause of death among the various diseases encountered in humans. Cancer is not a single entity and consists of numerous different types and subtypes that require various treatment regimens. In the last decade, several milestones in cancer treatments were accomplished, such as specific targeting agents or revitalizing the dormant anti-tumor immune response. These milestones have resulted in significant positive clinical responses as well as tumor regression and the prolongation of survival in subsets of cancer patients. Hence, in non-responding patients and non-responding relapsed patients, cancers develop intrinsic mechanisms of resistance to cell death via the overexpression of anti-apoptotic gene products. In parallel, the majority of resistant cancers have been reported to overexpress a transcription factor, Yin Yang 1 (YY1), which regulates the chemo-immuno-resistance of cancer cells to therapeutic anticancer cytotoxic agents. The relationship between the overexpression of YY1 and several anti-apoptotic gene products, such as B-cell lymphoma 2 protein (Bcl-2), B-cell lymphoma extra-large (Bcl-xL), myeloid cell leukemia 1 (Mcl-1) and survivin, is investigated in this paper. The findings demonstrate that these anti-apoptotic gene products are regulated, in part, by YY1 at the transcriptional, epigenetic, post-transcriptional and translational levels. While targeting each of the anti-apoptotic gene products individually has been examined and clinically tested for some, this targeting strategy is not effective due to compensation by other overexpressed anti-apoptotic gene products. In contrast, targeting YY1 directly, through small interfering RNAs (siRNAs), gene editing or small molecule inhibitors, can be therapeutically more effective and generalized in YY1-overexpressed resistant cancers.
Two Cascade Reactions with Oleate Hydratases for the Sustainable Biosynthesis of Fatty Acid-Derived Fine Chemicals
Authors: Prem Sophia A. , Haack Martina , Melcher Felix , Ringel Marion , Garbe Daniel , Brück Thomas
Published: August 2023

Oleate hydratases (OHs) are of significant industrial interest for the sustainable generation of valuable fine chemicals. When combined with other enzymes in multi-step cascades, the direct formation of fatty acid congeners can be accomplished with minimal processing steps. In this study, two cascade reactions are presented, which can be applied in one-pot approaches. The first cascade was placed “upstream” of an OH derived from Rhodococcus erythropolis (OhyRe), where a lipase from Candida rugosa was applied to hydrolyze triglycerides into free fatty acids, a crucial step for OH conversion. Further, we tested the lipase–OhyRe cascade with various types of renewable triglycerides of plant and microbial origin. In this context, the most efficient conversion was observed for microbial oil from Cutaneotrichosporon oleaginosus leading the way toward its industrial application. In contrast, the second cascade was placed “downstream” of OhyRe, where a novel secondary alcohol dehydrogenase (secADH) was applied to oxidize the hydroxylated fatty acid into a fatty acid ketone. Optimal reaction parameters for the cascade with the secADH were established, which allows this to be applied to high-throughput screens. Moreover, we describe a light-dependent route, thereby extending the catalytic efficiency of the OH enzyme system.
Z-Scheme Photocatalytic Degradation of Potassium Butyl Xanthate by a 2D/2D Heterojunction of Bi2WO6 Using MoS2 as a Co-Catalyst
Authors: Tamtam Mohan Rao , Koutavarapu Ravindranadh , Choi Gyu Sang , Shim Jaesool
Published: August 2023

Xanthate pollution during mineral processing is currently a major global challenge. Solar energy-induced photocatalysis is an effective and sustainable solution to this problem. The synthesis of specially designed photocatalysts is a critical step in this field of research. Even though a large number of structures have been developed in this regard, they are limited by low visible-light absorption and the fast recombination of photoinduced electron–hole pairs. To address these barriers, a novel nano-hybrid was developed with Bi2WO6 nanoflakes using MoS2 nanosheets as the co-catalyst. The as-prepared hybrid was critically examined to confirm its successful formation and determine its inherent exclusive characteristics. Finally, the photocatalytic ability for xanthate removal from wastewater was measured. The bandgap energy of Bi2WO6 and MoS2 was 2.85 eV and 1.87 eV, respectively, while that of the synthesized heterostructure was 2.54 eV. The photocatalytic ability of this novel structure is 6.65 and 9.65 times that of Bi2WO6 and MoS2, respectively.
Metabolomics Applied to Pediatric Asthma: What Have We Learnt in the Past 10 Years?
Authors: Ferraro Valentina Agnese , Zanconato Stefania , Carraro Silvia
Published: August 2023

Background: Asthma is the most common chronic condition in children. It is a complex non-communicable disease resulting from the interaction of genetic and environmental factors and characterized by heterogeneous underlying molecular mechanisms. Metabolomics, as with the other omic sciences, thanks to the joint use of high-throughput technologies and sophisticated multivariate statistical methods, provides an unbiased approach to study the biochemical–metabolic processes underlying asthma. The aim of this narrative review is the analysis of the metabolomic studies in pediatric asthma published in the past 10 years, focusing on the prediction of asthma development, endotype characterization and pharmaco-metabolomics. Methods: A total of 43 relevant published studies were identified searching the MEDLINE/Pubmed database, using the following terms: “asthma” AND “metabolomics”. The following filters were applied: language (English), age of study subjects (0–18 years), and publication date (last 10 years). Results and Conclusions: Several studies were identified within the three areas of interest described in the aim, and some of them likely have the potential to influence our clinical approach in the future. Nonetheless, further studies are needed to validate the findings and to assess the role of the proposed biomarkers as possible diagnostic or prognostic tools to be used in clinical practice.
Facile Preparation of Isocyanate-Modified Melamine Sponges as Efficient Absorbents for Oil and Organic Solvents
Authors: Chen Mingkang , Xie Fatu , Chen Yongping
Published: August 2023

Hydrophobic melamine sponges were prepared via a facile one-step reaction of three isocyanates (i.e., cyclohexyl isocyanate, octadecyl isocyanate, and butyl isocyanate) with hydroxymethyl groups located on the melamine sponge. The modified sponges were characterized by infrared spectroscopy, scanning electron microscope, X-ray photoelectron spectroscopy, and contact angle tester. The results showed that the water contact angle of the modified sponges reached around 140°, and the sponges had a three-dimensional network with high porosity, which can be used as efficient adsorbents to adsorb a variety of oils or organic solvents with different viscosities and densities. The experiments found that the modified sponges had good oil absorption performance, with 62–143 times their weight, for different oil and organic solvents. In addition, after being soaked in strong acid, strong alkali, and 3.5% sodium chloride aqueous solutions for 72 h, the modified sponges’ absorption capacity remained high.
Effect of Cu Addition on Properties of an Al-La Alloy
Authors: Wang Shuanqiang , Meng Guanghui , Song Menghua
Published: August 2023

The effect of copper content on the microstructure and properties of an aluminum copper alloy containing lanthanum was studied by adding 0.5 wt% lanthanum and different contents of copper to the 2A12 alloy. We used a universal testing machine, Brinell hardness tester, and friction and wear testing machine to test the mechanical properties of the alloy. The microstructure and phase composition of the alloy were analyzed using scanning electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. The results show that, after adding La and Cu, the alloy grain is refined, and the fracture mode changes from dissociation fracture to quasi dissociation fracture. A new phase containing La accumulates at the grain boundary. If the amount of Cu added is too large, the tendency for hot cracking increases, which can easily lead to the formation of voids or even cracks. The tensile strength and hardness of the cast alloy significantly increase with the increase in Cu addition. In the range of adding 2 wt% to 5 wt% Cu, the tensile strength and hardness of the cast alloy increases by approximately 12% and 17.84%, respectively, compared with the original alloy. With the increase in Cu addition, the elongation of the alloy first increases and then decreases, reaching its maximum value when Cu addition is 3 wt%. Adding Cu is beneficial for improving the wear resistance of the alloy. When the addition of Cu is 3 wt%, the alloy has the best wear resistance and minimum wear amount. This is due to the enrichment of La and Cu at the grain boundaries, forming new La phases or other phases with higher hardness, which changes the properties of the alloy. It shows that the content of Cu in the 2A12 alloy can be increased to 7-8% with the increasing of additional rare-earth elements, and a new Al-Cu (7 wt% to 8 wt%)-Mg (1.2 wt% to 1.8 wt%)-Mn (0.3 wt% to 0.9 wt%)-La (0.5 wt%) alloy, in which tensile strength, hardness, and elongation of the alloy are increased by 8.1%, 16%, and 79.1%, respectively, can be formed. In addition, the wear resistance of Al-La alloys also improves significantly with the addition of copper content. The coefficient of friction is reduced by 68% compared with no copper addition.
Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome
Authors: Nastasio Silvia , Mosca Antonella , Alterio Tommaso , Sciveres Marco , Maggiore Giuseppe
Published: August 2023

Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.
Plasma Glial Fibrillary Acidic Protein and N-Terminal Pro B-Type Natriuretic Peptide: Potential Biomarkers to Differentiate Ischemic and Hemorrhagic Stroke
Authors: Han Eunhee , Kim Hyejeong , Cho Bongrae , Lee Jeong-Joong , Shin Soyoung , Oh Eun-Jee , Chae Hyojin
Published: August 2023

Acute stroke management is critically time-sensitive and challenging. Blood-based biomarkers that can differentiate acute ischemic stroke (IS) from hemorrhagic stroke (HS) can greatly facilitate triage and early management. Admission blood samples obtained within 6 h of stroke symptom onset were analyzed in a derivation/validation design. GFAP, N-FL, NT-proBNP, copeptin, neutrophils (%), NLR, and platelet counts were assessed in the derivation cohort. The informative markers and the derived cutoff values were evaluated in the validation cohort. GFAP > 703 pg/mL showed a PPV of 76.9% and NPV of 95.8% for differentiating HS from IS. Multiple logistic regression analysis showed that GFAP and NT-proBNP were independent variables associated with IS and HS differentiation. Furthermore, applying a combined cutoff (GFAP > 703 pg/mL and NT-proBNP ≤ 125 pg/mL) for HS detection increased the PPV in both the derivation and validation cohorts (93.3% and 100%, respectively). GFAP and NT-proBNP levels were validated as informative blood biomarkers in the differentiation of IS and HS and using a combination of GFAP and NT-proBNP is suggested as a feasible strategy to differentiate stroke subtypes in the hyperacute phase of stroke.
Patient Blood Management in Microsurgical Procedures for Reconstructive Surgery
Authors: Rondinelli Maria Beatrice , Weltert Luca Paolo , Ruocco Giovanni , Ornelli Matteo , Delle Femmine Pietro Francesco , De Rosa Alessandro , Pierelli Luca , Felici Nicola
Published: August 2023

Introduction: The main purpose of reconstructive surgery (RS) is to restore the integrity of soft tissues damaged by trauma, surgery, congenital deformity, burns, or infection. Microsurgical techniques consist of harvesting tissues that are separated from the vascular sources of the donor site and anastomosed to the vessels of the recipient site. In these procedures, there are some preoperative modifiable factors that have the potential to influence the outcome of the flap transfer and its anastomosis. The management of anemia, which is always present in the postoperative period and plays a decisive role in the implantation of the flap, covers significant importance, and is associated with clinical and laboratory settings of chronic inflammation. Methods: Chronic inflammatory anemia (ACD) is a constant condition in patients who have undergone RS and correlates with the perfusion of the free flap. The aim of this treatment protocol is to reduce the transfusion rate by maintaining both a good organ perfusion and correction of the patient’s anemic state. From January 2017 to September 2019, we studied 16 patients (16 males, mean age 38 years) who underwent microsurgical procedures for RS. Their hemoglobin (Hb) levels, corpuscular indexes, transferrin saturation (TSAT) ferritin concentrations and creatinine clearance were measured the first day after surgery (T0), after the first week (T1), and after five weeks (T2). At T0, all the patients showed low hemoglobin levels (average 7.4 g/dL, STD 0.71 range 6.2–7.4 g dL−1), with an MCV of 72, MCH of 28, MCHC of 33, RDW of 16, serum iron of 35, ferritin of 28, Ret% of 1.36, TRF of 277, creatinine clearance of 119 and high ferritin levels (range 320–560 ng mL−1) with TSAT less than 20%. All the patients were assessed for their clinical status, medical history and comorbidities before the beginning of the therapy. Results: A collaboration between the two departments (Department of Transfusion Medicine and Department of Reconstructive Surgery) resulted in the application of a therapeutic protocol with erythropoietic stimulating agents (ESAs) (Binocrit 6000 UI/week) and intravenous iron every other day, starting the second day after surgery. Thirteen patients received ESAs and FCM (ferric carboxymaltose, 500–1000 mg per session), three patients received ESAs and iron gluconate (one vial every other day). No patients received blood transfusions. No side effects were observed, and most importantly, no limb or flap rejection occurred. Conclusions: Preliminary data from our protocol show an optimal therapeutic response, notwithstanding the very limited scientific literature and data available in this specific surgical field. The enrollment of further patients will allow us to validate this therapeutic protocol with statistically sound data.
“Who’s Better at Math, Boys or Girls?”: Changes in Adolescents’ Math Gender Stereotypes and Their Motivational Beliefs from Early to Late Adolescence
Authors: Starr Christine R. , Gao Yannan , Rubach Charlott , Lee Glona , Safavian Nayssan , Dicke Anna-Lena , Eccles Jacquelynne S. , Simpkins Sandra D.
Published: August 2023

Though adults tend to endorse the stereotype that boys are better than girls in math, children tend to favor their own gender or be gender egalitarian. When do individuals start endorsing the traditional stereotype that boys are better? Using two longitudinal U.S. datasets that span 1993 to 2011, we examined three questions: (1) What are the developmental changes in adolescents’ gender stereotypes about math abilities from early to late adolescence? (2) Do the developmental changes vary based on gender and race/ethnicity? (3) Are adolescents’ stereotypes related to their math motivational beliefs? Finally, (4) do these patterns replicate across two datasets that vary in historical time? Adolescents in grades 8/9 and 11 were asked whether girls or boys are better at math (n’s = 1186 and 23,340, 49–53% girls, 30–54% White, 13–60% Black, 1–22% Latinx, and 2% to 4% Asian). Early adolescents were more likely to be gender egalitarian or favor their own gender. By late adolescence, adolescents’ stereotypes typically shifted towards the traditional stereotype that boys are better. In terms of race/ethnicity, White and Asian adolescents significantly favored boys, whereas Black and Latinx adolescents were more likely to endorse gender egalitarian beliefs. Adolescents’ stereotypes were significantly related to their expectancy beliefs, negatively for girls and positively for boys.
Universal Design for Learning across Formal School Structures in Europe—A Systematic Review
Authors: Ewe Linda , Galvin Tracy
Published: August 2023

Over the past two decades, there has been a global movement towards creating more inclusive education systems and learning environments, which involves adopting transformative pedagogies, such as Universal Design for Learning (UDL). However, empirical research on UDL conducted across Europe has primarily focused on the higher education context, resulting in limited knowledge or publications on formal school settings. Therefore, the purpose of this article is to highlight empirical studies conducted across Europe that specifically focus on UDL in the formal school years. The study employed a systematic literature review, conducting an extensive search across three databases (Libsearch, Ebsco and Scopus). Empirical studies were selected based on predefined inclusion and exclusion criteria, and the results were analyzed using descriptive narrative synthesis. The results revealed that the included articles mainly explored students’ and/or teachers’ perceptions of various phenomena related to the learning process, predominantly employing a qualitative approach. The findings suggest a need for further research in this area, with a particular emphasis on explicit learning outcomes. Moreover, there appears to be a lack of research on UDL implementation in preschool and early years education.
Implications of the COVID-19 Pandemic on the Family Structural Dimensions: A Correlational Study
Authors: Silva Margarida , Ferreira Manuela , Loureiro Helena , Kraus Teresa , Santos Angelica , Figueiredo Maria Henriqueta
Published: August 2023

The COVID-19 pandemic caused changes in the families’ social support network, employment status, and family income, which are the focus of attention of family health nurses. This study aims to describe the pandemic’s repercussions in the areas of attention of the structural dimension of families according to the Dynamic Model of Family Assessment and Intervention, as perceived by Portuguese families, and to relate the changes in their employment status according to the variables of the structural dimension. A quantitative, descriptive, and correlational study was conducted using snowball sampling. A questionnaire of sociodemographic characterization and assessment of the family structural dimension according to the model’s operational matrix was applied to 235 family members. Changes were found in their employment status; family income; intensity and frequency of contact with family, friends, and coworkers; frequency of contact with educational/health/religious institutions and community groups; cultural activities; and housing comfort conditions such as the use of heating/air conditioning, gas, and water consumption. Changes in employment status were related to family income, interaction with friends, frequency of cultural activities, and use of air conditioning and heating. Knowing the implications of the pandemic on the family’s structural dimension results in a nursing intervention more focused on family needs.
Integration of Wearables and Wireless Technologies to Improve the Interaction between Disabled Vulnerable Road Users and Self-Driving Cars
Authors: Guerrero-Ibañez Antonio , Amezcua-Valdovinos Ismael , Contreras-Castillo Juan
Published: August 2023

The auto industry is accelerating, and self-driving cars are becoming a reality. However, the acceptance of such cars will depend on their social and environmental integration into a road traffic ecosystem comprising vehicles, motorcycles, bicycles, and pedestrians. One of the most vulnerable groups within the road ecosystem is pedestrians. Assistive technology focuses on ensuring functional independence for people with disabilities. However, little effort has been devoted to exploring possible interaction mechanisms between pedestrians with disabilities and self-driving cars. This paper analyzes how self-driving cars and disabled pedestrians should interact in a traffic ecosystem supported by wearable devices for pedestrians to feel safer and more comfortable. We define the concept of an Assistive Self-driving Car (ASC). We describe a set of procedures to identify people with disabilities using an IEEE 802.11p-based device and a group of messages to express the intentions of disabled pedestrians to self-driving cars. This interaction provides disabled pedestrians with increased safety and confidence in performing tasks such as crossing the street. Finally, we discuss strategies for alerting disabled pedestrians to potential hazards within the road ecosystem.