bluuebunny/crossref_metadata_2025 huggingface dataset:
COBLL1 and IRS1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes
Authors: Ustianowski Przemyslaw , Malinowski Damian , Czerewaty Michał , Safranow Krzysztof , Tarnowski Maciej , Dziedziejko Violetta , Pawlik Andrzej
Published: August 2022

Gestational diabetes mellitus (GDM) is carbohydrate intolerance in pregnant women leading to various complications. Currently, there is a search for factors predisposing to GDM. Among them are genetic polymorphisms of genes involved in insulin secretion as well as carbohydrate metabolism. Due to the similar pathogenesis of GDM to type 2 diabetes (T2DM), genetic polymorphisms associated with T2DM are considered. The aim of this study was to examine the associations between the COBLL1 rs7607980 T > C and IRS1 rs2943641 T > C gene polymorphisms and the risk of GDM as well as selected clinical parameters in women with GDM. Additionally, we examined the expression of these genes in the placenta of women with and without GDM in correlation with selected clinical parameters. This study included 328 pregnant women with normal glucose tolerance (NGT) and 251 pregnant women with GDM diagnosed on the basis of a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation. There were no statistically significant differences in the distribution of IRS1 rs2943641 gene polymorphisms between women with GDM and pregnant women with NGT. In the GDM group, we observed a decreased frequency of COBLL1 rs7607980 CC homozygous women (CC vs. TC+TT, p = 0.048); however, there was no statistically significant difference in the frequency of alleles between women with GDM and the control group. There were no statistically significant associations between COBLL1 rs7607980 gene polymorphism and clinical parameters in women with GDM. In GDM women with the IRS1 rs2943641 TT genotype, fasting glucose levels were significantly higher than in women with CC and TC genotypes. There was no statistically significant difference in the expression of COBLL1 and IRS1 genes in the placenta between women with GDM and healthy women. There were no statistically significant correlations between COBLL1 gene expression in the placenta and clinical parameters. The expression of IRS1 correlated significantly with an increase in BMI during pregnancy. The results of this study suggest that COBLL1 rs7607980 and IRS1 rs2943641 gene polymorphisms are not significant risk factors for GDM in our population. The IRS1 TT genotype may be associated with higher fasting glucose levels in women with GDM. Expression of the IRS1 gene in the placenta positively correlates with an increase in BMI during pregnancy in women with GDM.
Contribution of the Environment, Epigenetic Mechanisms and Non-Coding RNAs in Psoriasis
Authors: Antonatos Charalabos , Grafanaki Katerina , Asmenoudi Paschalia , Xiropotamos Panagiotis , Nani Paraskevi , Georgakilas Georgios K. , Georgiou Sophia , Vasilopoulos Yiannis
Published: August 2022

Despite the increasing research and clinical interest in the predisposition of psoriasis, a chronic inflammatory skin disease, the multitude of genetic and environmental factors involved in its pathogenesis remain unclear. This complexity is further exacerbated by the several cell types that are implicated in Psoriasis’s progression, including keratinocytes, melanocytes and various immune cell types. The observed interactions between the genetic substrate and the environment lead to epigenetic alterations that directly or indirectly affect gene expression. Changes in DNA methylation and histone modifications that alter DNA-binding site accessibility, as well as non-coding RNAs implicated in the post-transcriptional regulation, are mechanisms of gene transcriptional activity modification and therefore affect the pathways involved in the pathogenesis of Psoriasis. In this review, we summarize the research conducted on the environmental factors contributing to the disease onset, epigenetic modifications and non-coding RNAs exhibiting deregulation in Psoriasis, and we further categorize them based on the under-study cell types. We also assess the recent literature considering therapeutic applications targeting molecules that compromise the epigenome, as a way to suppress the inflammatory cutaneous cascade.
Acute Kidney Injury (AKI) in Young Synthetic Cannabinoids Abusers
Authors: D’Errico Stefano , Zanon Martina , Radaelli Davide , Concato Monica , Padovano Martina , Scopetti Matteo , Frati Paola , Fineschi Vittorio
Published: August 2022

Background. Synthetic cannabinoid-related acute kidney injury represents an increasingly important public health issue due to the diagnostic challenges given by low clinical suspicion of the disease and the frequent undetectability in routine drug tests. Methods. A systematic literature search on PubMed was carried out until 31 January 2022. Case reports, case series, retrospective and prospective studies, as well as reviews on acute kidney injury related to the consumption of synthetic cannabinoid were searched. Results. The systematic review process selected 21 studies for a total of 55 subjects with synthetic cannabinoid-induced acute kidney injury. Renal damage was demonstrated by elevated serum creatinine levels in 49 patients (89%). On renal ultrasound, the most frequent finding was an increase in cortical echogenicity. Renal biopsy, performed in 33% of cases, revealed acute tubular damage, acute tubulointerstitial nephritis, and acute interstitial nephritis, in decreasing order of frequency. Conclusion. Prompt identification and treatment of synthetic cannabinoid-related acute kidney injury represent a sensitive public health goal both for the acute management of damage from synthetic cannabinoids and for the prevention of chronic kidney disease.
The Hypoxia-Adenosine Link during Myocardial Ischemia—Reperfusion Injury
Authors: Ruan Wei , Ma Xinxin , Bang In Hyuk , Liang Yafen , Muehlschlegel Jochen Daniel , Tsai Kuang-Lei , Mills Tingting W. , Yuan Xiaoyi , Eltzschig Holger K.
Published: August 2022

Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery.
The Role of Rab Proteins in Parkinson’s Disease Synaptopathy
Authors: Bellucci Arianna , Longhena Francesca , Spillantini Maria Grazia
Published: August 2022

In patients affected by Parkinson’s disease (PD), the most common neurodegenerative movement disorder, the brain is characterized by the loss of dopaminergic neurons in the nigrostriatal system, leading to dyshomeostasis of the basal ganglia network activity that is linked to motility dysfunction. PD mostly arises as an age-associated sporadic disease, but several genetic forms also exist. Compelling evidence supports that synaptic damage and dysfunction characterize the very early phases of either sporadic or genetic forms of PD and that this early PD synaptopathy drives retrograde terminal-to-cell body degeneration, culminating in neuronal loss. The Ras-associated binding protein (Rab) family of small GTPases, which is involved in the maintenance of neuronal vesicular trafficking, synaptic architecture and function in the central nervous system, has recently emerged among the major players in PD synaptopathy. In this manuscript, we provide an overview of the main findings supporting the involvement of Rabs in either sporadic or genetic PD pathophysiology, and we highlight how Rab alterations participate in the onset of early synaptic damage and dysfunction.
An Immunocolorimetric Sensing System for Highly Sensitive and High-Throughput Detection of BNP with Carbon-Gold Nanocomposites Amplification
Authors: Liu Xin , Gan Ying , Li Fengheng , Qiu Yong , Pan Yuxiang , Wan Hao , Wang Ping
Published: August 2022

Conventional immunocolorimetric sensing of biomolecules continues to be challenged with low sensitivity although its wide application as a diagnostic tool in medicine and biotechnology. Herein, we present a multifunctional immunocolorimetric sensing system for sensitive and high-throughput detection of B-type natriuretic peptide (BNP) with carbon-gold nanocomposite (CGNs) amplification. Using a “green” strategy, monodisperse carbon nanospheres (CNs) were successfully synthesized by glucose carbonization. A simple and efficient hydrothermal method was developed to assemble abundant gold nanoparticles (AuNPs) onto the surfaces of CNs. The resulting CGNs were characterized and utilized for biomarker detection with superior properties of easy manufacturing, good biocompatibility, satisfactory chemical stability, and high loading capacity for biomolecules. As a proof of concept, the as-prepared CGNs were conjugated with horseradish peroxidase-labeled antibody against BNP (CGNs@AntiBNP-HRP) functioning as the carrier, signal amplifier, and detector for the sensitive detection of BNP. Under optimal conditions, the established CGNs@AntiBNP-HRP immunoprobe remarkably enhanced the detection performance of BNP, achieving signal amplification of more than 9 times compared to the conventional method. Based on our self-developed bionic electronic eye (e-Eye) and CGNs@AntiBNP-HRP immunoprobe, the multifunctional sensing system displayed a wide dynamic linear range of 3.9–500 ng/mL and a LOD of 0.640 ng/mL for BNP detection with high specificity, good accuracy and reproducibility. This portable sensing system with enhanced performance demonstrates great potential for BNP detection in point of care applications, and offers a universal and reliable platform for in vitro biomarker detection.
A Wearable Flexible Acceleration Sensor for Monitoring Human Motion
Authors: He Zeqing , Wang Kuan , Zhao Zhao , Zhang Taihua , Li Yuhang , Wang Liu
Published: August 2022

Skin-inspired flexible wearable acceleration sensors attract much attention due to their advantages of portability, personalized and comfortable experience, and potential application in healthcare monitoring, human–machine interfaces, artificial intelligence, and physical sports performance evaluation. This paper presents a flexible wearable acceleration sensor for monitoring human motion by introducing the island–bridge configuration and serpentine interconnects. Compared with traditional wearable accelerometers, the flexible accelerometer proposed in this paper improves the wearing comfort while reducing the cost of the device. Simulation and experiments under bending, stretching, and torsion conditions demonstrate that the flexible performance of the flexible acceleration sensor can meet the needs of monitoring the daily movement of the human body, and it can work normally under various conditions. The measurement accuracy of the flexible acceleration sensor is verified by comparing it with the data of the commercial acceleration sensor. The flexible acceleration sensor can measure the acceleration and the angular velocity of the human body with six degrees of freedom and recognize the gesture and motion features according to the acceleration characteristics. The presented flexible accelerometers provide great potential in recognizing the motion features that are critical for healthcare monitoring and physical sports performance evaluation.
Biomechanical Sensing Using Gas Bubbles Oscillations in Liquids and Adjacent Technologies: Theory and Practical Applications
Authors: Maksymov Ivan S. , Huy Nguyen Bui Quoc , Suslov Sergey A.
Published: August 2022

Gas bubbles present in liquids underpin many natural phenomena and human-developed technologies that improve the quality of life. Since all living organisms are predominantly made of water, they may also contain bubbles—introduced both naturally and artificially—that can serve as biomechanical sensors operating in hard-to-reach places inside a living body and emitting signals that can be detected by common equipment used in ultrasound and photoacoustic imaging procedures. This kind of biosensor is the focus of the present article, where we critically review the emergent sensing technologies based on acoustically driven oscillations of bubbles in liquids and bodily fluids. This review is intended for a broad biosensing community and transdisciplinary researchers translating novel ideas from theory to experiment and then to practice. To this end, all discussions in this review are written in a language that is accessible to non-experts in specific fields of acoustics, fluid dynamics and acousto-optics.
Framework for BIM-Based Simulation of Construction Operations Implemented in a Game Engine
Authors: Osorio-Sandoval Carlos A. , Tizani Walid , Pereira Estacio , Ninić Jelena , Koch Christian
Published: August 2022

Construction simulation has been widely used in academia for research purposes. However, it has been neglected by the industry for various reasons, including the amount of data, skills, effort, and time required to develop complex simulation models, the difficulty of model reuse, and the abstract and confusing way in which simulation results are usually presented. This article demonstrates how BIM can be employed to facilitate the development of a construction simulation model that considers constraints related to resource allocation and task interdependencies. Furthermore, it shows how a game engine can be used as a platform to implement the proposed framework for the integration of BIM and construction simulation and to produce animations from simulation results. The feasibility of the framework is demonstrated through a case study on masonry construction. Results of implementing the framework reveal that BIM-based simulations can reduce the skills, effort, and time required to develop simulation models and enable model reuse. The integration of simulation-based animations provides a model verification and validation mechanism and a means to communicate model results to stakeholders unfamiliar with simulation.
Life Cycle Assessment of Embodied Carbon and Strategies for Decarbonization of a High-Rise Residential Building
Authors: Alotaibi Badr Saad , Khan Sahil Ali , Abuhussain Mohammed Awad , Al-Tamimi Nedhal , Elnaklah Rana , Kamal Mohammad Arif
Published: August 2022

The construction sector is responsible for the 40% of consumed resources, 40% of CO2 emissions, and approximately 40% of construction and demolition waste. For the assessment of the building, there exists a standardized method, life cycle assessment (LCA), however, the process requires time, cost, and most importantly expertise. In this paper, a method is proposed and analyzed for the life cycle assessment of the building for the embodied carbon in the three stages, construction, operation, and demolition. Moreover, the result of the analysis is considered as the base result, and de-carbonization strategies identified through literature study for the three stages of construction, operation, and demolition are assessed with the same method to know how much each strategy will be effective in minimizing the embodied carbon. For the base case, a high-rise residential building in an urban region of India is analyzed, based on existing conditions through the building information modeling (BIM) method. The carbon emission of the selected building comes out to be 414 kg CO2e/m2/year, and assessing different decarbonization strategies, considering the first analysis as the baseline, it can be minimized to 135 kg CO2e/m2/year.
Evaluation of a Community Center Based on Retrofit Strategies and Re-Design through Python Tools and Local Standards, Case Study in Al Ain, Abu Dhabi, United Arab Emirates
Authors: Bande Lindita , Alqahtani Deema , Hamad Hiba
Published: August 2022

Over the last 50 years the cities in the United Arab Emirates (UAE) developed rapidly. Building stock is very diverse in the country and varies from one city to another. While Dubai has a large stock of skyscrapers, Abu Dhabi has more of a mix of high-rise and mid-rise buildings, and AL Ain—mainly mid-rise and low-rise buildings. The aim of this study is to evaluate the energy consumption of a retrofitted building versus a new building designed based on advanced tools of calculation. The new design is based on sustainability principles of design as well as the advanced parametric design where the analysis considers several parameters. This evaluation is a comparison between the current building, a retrofitted building, and a new design of the same build-up area. This analysis will be conducted considering local sustainability standards such as Estidama and Abu Dhabi Realm Manual. The methodology starts with the building selection process which consists of the selected building as part of a villa compound done in the city of AL Ain. The site measurements are the following step. This file is used for the boundary conditions of the models. The following step involves energy simulations. The models were prepared with several scenarios as per the predefined analysis and run for simulation. Grasshopper throughthrough rhino were the softwares used for energy simulations and applied design. Therefore, energy saving was calculated based on the selected matrix. The results show that the selection of the shape of the building and application of sustainable measures in the early stages of design can save 32% of energy, and a retrofit of the current building would save 9% of the electricity used.
Experimental Study on the Flexural Performance of Timber–Steel Composite (TSC) I-Beams
Authors: Liu Jiatong , Liu Ruiyue , Li Wei , Wang Jiejun , Chen Ling
Published: August 2022

To promote the development of timber–steel composite (TSC) structures, this paper proposes a TSC I-beam with an I-beam as the webs, covered with a timber board on its upper and lower surfaces and bolted together; the effect of varying the ratio of the timber board thickness to I-beam on the bending performance of the TSC I-beam was investigated. Considering the same total height of the beam cross-section and the variation of timber board thickness and I-beam height, three groups of six TSC beam specimens were designed and fabricated to carry out bending load failure tests, and the effects of the variation of timber board thickness with respect to I-beam height on the failure mode, flexural load capacity, ductility, and composite degree of TSC beams were analyzed. In addition, a model for predicting the elastic ultimate bending capacity and mid-span deflection of TSC I-beams was proposed on the basis of the composite coefficient method, which avoids the need to test the joints, and the theoretical calculation results were in good agreement with the test results, which can provide a reference for the design of TSC I-beams.
The Kinetics of FMS-Related Tyrosine Kinase 3 Ligand (Flt-3L) during Chemoradiotherapy Suggests a Potential Gain from the Earlier Initiation of Immunotherapy
Authors: Kuncman Łukasz , Orzechowska Magdalena , Stawiski Konrad , Masłowski Michał , Ciążyńska Magdalena , Gottwald Leszek , Milecki Tomasz , Fijuth Jacek
Published: August 2022

The optimal sequence of chemoradiotherapy with immunotherapy is still not established. The patient’s immune status may play a role in determining this order. We aim to determine the kinetics of a multi-potential haemopoietic factor FMS-related tyrosine kinase 3 ligand (Flt-3L) during chemoradiotherapy. Our pilot, a single arm prospective study, enrolled patients with rectal cancer who qualified for neoadjuvant chemoradiotherapy. Blood samples for Flt-3L were collected before and every second week of chemoradiotherapy for a complete blood count every week. The kinetics of Flt-3L were assessed using Friedman’s ANOVA. A multiple factor analysis (MFA) was performed to find relevant factors affecting levels of serum Flt-3L during chemoradiotherapy. FactoMineR and factoextra R packages were used for analysis. In the 33 patients enrolled, the level of Flt-3L increased from the second week and remained elevated until the end of treatment (p < 0.01). All patients experienced Grade ≥2 lymphopenia with a nadir detected mostly in the 5/6th week. MFA revealed the spatial partitioning of patients among the first and second dimensions (explained by 38.49% and 23.14% variance). The distribution along these dimensions represents the magnitude of early changes of Flt-3L. Patients with the lowest values of Flt-3L change showed the highest lymphocyte nadirs and lowest dose/volume parameters of active bone marrow. Our hypothesis-generating study supports the concept of early initiation of immuno-therapy when the concentration of Flt-3L is high and no lymphopenia has yet occurred.
Visceral Surgery Profoundly Affects the Cellular and Humoral Components of the Anti-Tumour Immune Response in a Murine Pancreatic Adenocarcinoma Model
Authors: Loening Friederike , Kleinwort Annabel , Partecke Lars Ivo , Schulze Tobias , Menges Pia
Published: August 2022

(1) Background: Surgery is the most important element of multimodal treatment concepts in oncological patients, especially in the early stages of pancreatic tumours. While the influence of primary tumour resection on the immune status was analysed in several studies, the impact of tumour-unrelated visceral surgery on the tumour-bearing organism and on the primary tumour itself is not yet fully understood. (2) Methods: We combined a murine model of orthotopically implanted adenocarcinoma of the pancreas with the model of surgically-induced immune dysfunction (SID). Mortality and general condition including body weight were observed over a period of 28 days. Tumour growth was analysed by MRI scans on days 8 and 27 following tumour implantation. On day 28, the immune cell populations in the blood and spleen as well as the serum cytokines were quantified. (3) Results: SID results in a significant deterioration of the general condition and a reduced increase in the body weight of tumour-bearing mice compared to the control groups, while mortality and tumour growth rate were not influenced. The numbers of spleen macrophages and neutrophils were increased in tumour-bearing animals following SID. Furthermore, both macrophage and neutrophil levels were increased in the peripheral blood. (4) Conclusions: The presented results might contribute to the basic understanding of the interaction of tumour and immune system and could contribute to new approaches to immunotherapeutic strategies.
Modern Immunotherapy in the Treatment of Triple-Negative Breast Cancer
Authors: Wesolowski Jakub , Tankiewicz-Kwedlo Anna , Pawlak Dariusz
Published: August 2022

Triple-Negative Breast Cancer is a subtype of breast cancer characterized by the lack of expression of estrogen receptors, progesterone receptors, as well as human epidermal growth factor receptor 2. This cancer accounts for 15–20% of all breast cancers and is especially common in patients under 40 years of age, as well as with the occurring BRCA1 mutation. Its poor prognosis is reflected in the statistical life expectancy of 8–15 months after diagnosis of metastatic TNBC. So far, the lack of targeted therapy has narrowed therapeutic possibilities to classic chemotherapy. The idea behind the use of humanized monoclonal antibodies, as inhibitors of immunosuppressive checkpoints used by the tumor to escape from immune system control, is to reduce immunotolerance and direct an intensified anti-tumor immune response. An abundance of recent studies has provided numerous pieces of evidence about the safety and clinical benefits of immunotherapy using humanized monoclonal antibodies in the fight against many types of cancer, including TNBC. In particular, phase three clinical trials, such as the IMpassion 130, the KEYNOTE-355 and the KEYNOTE-522 resulted in the approval of immunotherapeutic agents, such as atezolizumab and pembrolizumab by the US Food and Drug Administration in TNBC therapy. This review aims to present the huge potential of immunotherapy using monoclonal antibodies directed against immunosuppressive checkpoints—such as atezolizumab, avelumab, durvalumab, pembrolizumab, nivolumab, cemiplimab, tremelimumab, ipilimumab—in the fight against difficult to treat TNBCs as monotherapy as well as in more advanced combination strategies.
Vanadium Nitride Supported on N-Doped Carbon as High-Performance ORR Catalysts for Zn–Air Batteries
Authors: Fu Yidan , Han Lina , Zheng Pengfei , Peng Xianhui , Xian Xianglan , Liu Jinglin , Zeng Xiaoyuan , Dong Peng , Xiao Jie , Zhang Yingjie
Published: August 2022

It is desirable to prepare low-cost non-noble metal catalysts using a simple and efficient method. Herein, we display for the first time that nitrogen-doped hierarchical porous carbon-supported vanadium nitride (VN/NC/C-x) catalysts can be regulated by dicyandiamide (DCDA). The introduction of DCDA not only effectively controls the pore structure, but also plays an important role in adjusting oxygen vacancies and d-electrons. In addition, DCDA is not only a significant raw material for the N-doped carbon, but also a nitrogen source for the preparation of vanadium nitride. The VN/NC/C-3 catalyst was prepared after optimization of the preparation parameters, and the macro/micro structure demonstrates a superior ORR performance in alkaline media with a positive onset potential of 0.85 V and a half-wave potential of 0.75 V, the limiting current density is as high as 4.52 mA·cm−2, and the Tafel slope is only 75.54 mV·dec−1. The VN/NC/C-3-based Zn–air battery exhibits a highest peak power density (161.82 mW∙cm−2) and an excellent energy density (702.28 mAh·kgZn−1 and 861.51 Wh·kgZn−1). This work provides a valuable synthetic approach for the preparation of other transition metal nitride catalysts with a relative economic value and high performance.
PARA: A New Platform for the Rapid Assembly of gRNA Arrays for Multiplexed CRISPR Technologies
Authors: Yuan Guoliang , Martin Stanton , Hassan Md Mahmudul , Tuskan Gerald A. , Yang Xiaohan
Published: August 2022

Multiplexed CRISPR technologies have great potential for pathway engineering and genome editing. However, their applications are constrained by complex, laborious and time-consuming cloning steps. In this research, we developed a novel method, PARA, which allows for the one-step assembly of multiple guide RNAs (gRNAs) into a CRISPR vector with up to 18 gRNAs. Here, we demonstrate that PARA is capable of the efficient assembly of transfer RNA/Csy4/ribozyme-based gRNA arrays. To aid in this process and to streamline vector construction, we developed a user-friendly PARAweb tool for designing PCR primers and component DNA parts and simulating assembled gRNA arrays and vector sequences.
Membrane Properties of Human Induced Pluripotent Stem Cell-Derived Cultured Red Blood Cells
Authors: Bernecker Claudia , Matzhold Eva Maria , Kolb Dagmar , Avdili Afrim , Rohrhofer Lisa , Lampl Annika , Trötzmüller Martin , Singer Heike , Oldenburg Johannes , Schlenke Peter , Dorn Isabel
Published: August 2022

Cultured red blood cells from human induced pluripotent stem cells (cRBC_iPSCs) are a promising source for future concepts in transfusion medicine. Before cRBC_iPSCs will have entrance into clinical or laboratory use, their functional properties and safety have to be carefully validated. Due to the limitations of established culture systems, such studies are still missing. Improved erythropoiesis in a recently established culture system, closer simulating the physiological niche, enabled us to conduct functional characterization of enucleated cRBC_iPSCs with a focus on membrane properties. Morphology and maturation stage of cRBC_iPSCs were closer to native reticulocytes (nRETs) than to native red blood cells (nRBCs). Whereas osmotic resistance of cRBC_iPSCs was similar to nRETs, their deformability was slightly impaired. Since no obvious alterations in membrane morphology, lipid composition, and major membrane associated protein patterns were observed, reduced deformability might be caused by a more primitive nature of cRBC_iPSCs comparable to human embryonic- or fetal liver erythropoiesis. Blood group phenotyping of cRBC_iPSCs further confirmed the potency of cRBC_iPSCs as a prospective device in pre-transfusional routine diagnostics. Therefore, RBC membrane analyses obtained in this study underscore the overall prospects of cRBC_iPSCs for their future application in the field of transfusion medicine.
Modulation of Neuroendocrine and Immunological Biomarkers Following Rehabilitation in Sarcopenic Patients
Authors: Piancone Federica , La Rosa Francesca , Marventano Ivana , Hernis Ambra , Miglioli Rossella , Trecate Fabio , Saresella Marina , Clerici Mario
Published: August 2022

This study aimed to investigate if rehabilitation could down-regulated sarcopenia-associated inflammation by modulating the crosstalk between the neuroendocrine and immune systems, with the aim of ameliorating quality of life of sarcopenic subjects. A total of 60 sarcopenic patients (49 females and 11 males; median age 74.5, interquartile range 71–79), undergoing a personalized rehabilitation program, have been recruited and subjected to: (1) functional and physical evaluation (Short Physical Performance Battery (SPPB), Barthel Index and Tinetti Test); (2) pro-inflammatory IL-1β, TNF-α, IL-6, IL-18, and anti-inflammatory IL-10 cytokines plasmatic level measures; and (3) norepinephrine, epinephrine, dopamine, and serotonin neurotransmitter level evaluation at time of enrollment (T0) and once rehabilitation was concluded (1 month, T1). Rehabilitation combined a balance and strength training program with two daily sessions that were fine-tuned and personalized according to the ability of the patient. The results showed a significant increase at T1 in the plasmatic levels of IL-10 (p = 0.018) and of norepinephrine (p = 0.016)), whereas the concentration of IL-18 was significantly reduced (p = 0.012). Notably, changes in norepinephrine were positively correlated with clinical improvements (Tinetti and Barthel scores, p ≤ 0.0001; SPPB scores, p = 0.0002). These results show that efficient rehabilitation induces a reduction of inflammation, suggesting that this effect could be mediated by a modulation of the neuro-immune axis that results in an increase of norepinephrine.
Combination of dl922-947 Oncolytic Adenovirus and G-Quadruplex Binders Uncovers Improved Antitumor Activity in Breast Cancer
Authors: Napolitano Fabiana , Di Somma Sarah , Castellano Giuliano , Amato Jussara , Pagano Bruno , Randazzo Antonio , Portella Giuseppe , Malfitano Anna Maria
Published: August 2022

G-quadruplexes (G4s) are nucleic secondary structures characterized by G-tetrads. G4 motif stabilization induces DNA damage and cancer cell death; therefore, G4-targeting small molecules are the focus of clinical investigation. DNA destabilization induced by G4 ligands might potentiate the anticancer activity of agents targeting DNA or inhibiting its repair such as oncolytic viruses. This study represents the first approach combining G4 ligands, BRACO-19 (B19), pyridostatin (PDS), and the adenovirus dl922-947 in breast cancer cells. We demonstrated that G4 binders and dl922-947 induce cytotoxicity in breast cancer cells (MDA-MB-231 and MCF-7) and at higher doses in other neoplastic cell lines of thyroid (BHT-101 cells) and prostate (PC3 cells). G4 binders induce G4 motifs distributed in the S and G2/M phases in MCF-7 cells. G4 binder/dl922-947 combination increases cell cytotoxicity and the accumulation in subG0/G1. Indeed, G4 binders favor viral entry and replication with no effect on coxsackie and adenovirus receptor. Notably, dl922-947 induces G4 motifs and its combination with PDS potentiates this effect in MCF-7 cells. The agents alone or in combination similarly enhanced cell senescence. Additionally, PDS/dl922-947 combination inactivates STING signaling in MDA-MB-231 cells. Our results suggest that G4 binder/virotherapy combination may represent a novel therapeutic anticancer approach.
Contrasting Roles of Ethylene Response Factors in Pathogen Response and Ripening in Fleshy Fruit
Authors: Li Shan , Wu Pan , Yu Xiaofen , Cao Jinping , Chen Xia , Gao Lei , Chen Kunsong , Grierson Donald
Published: August 2022

Fleshy fruits are generally hard and unpalatable when unripe; however, as they mature, their quality is transformed by the complex and dynamic genetic and biochemical process of ripening, which affects all cell compartments. Ripening fruits are enriched with nutrients such as acids, sugars, vitamins, attractive volatiles and pigments and develop a pleasant taste and texture and become attractive to eat. Ripening also increases sensitivity to pathogens, and this presents a crucial problem for fruit postharvest transport and storage: how to enhance pathogen resistance while maintaining ripening quality. Fruit development and ripening involve many changes in gene expression regulated by transcription factors (TFs), some of which respond to hormones such as auxin, abscisic acid (ABA) and ethylene. Ethylene response factor (ERF) TFs regulate both fruit ripening and resistance to pathogen stresses. Different ERFs regulate fruit ripening and/or pathogen responses in both fleshy climacteric and non-climacteric fruits and function cooperatively or independently of other TFs. In this review, we summarize the current status of studies on ERFs that regulate fruit ripening and responses to infection by several fungal pathogens, including a systematic ERF transcriptome analysis of fungal grey mould infection of tomato caused by Botrytis cinerea. This deepening understanding of the function of ERFs in fruit ripening and pathogen responses may identify novel approaches for engineering transcriptional regulation to improve fruit quality and pathogen resistance.
Fast Initiating Furan-Containing Hoveyda-Type Complexes: Synthesis and Applications in Metathesis Reactions
Authors: Nadirova Maryana , Zieliński Adam , Malinska Maura , Kajetanowicz Anna
Published: August 2022

Two new ruthenium complexes with chelating-ether benzylidene ligands bearing a furan moiety were synthesized and characterized, including X-ray crystallography. They initiated fast, also at 0 °C, and were found to be highly active in a variety of ring-closing, ene-yne, and cross-metathesis reactions, including an active pharmaceutical ingredient (API) model, which makes them good candidates for the transformation of complex polyfunctional compounds that require mild reaction conditions.
Polygraphic EEG Can Identify Asphyxiated Infants for Therapeutic Hypothermia and Predict Neurodevelopmental Outcomes
Authors: Lugli Licia , Guidotti Isotta , Pugliese Marisa , Roversi Maria Federica , Bedetti Luca , Della Casa Muttini Elisa , Cavalleri Francesca , Todeschini Alessandra , Genovese Maurilio , Ori Luca , Amato Maria , Miselli Francesca , Lucaccioni Laura , Bertoncelli Natascia , Candia Francesco , Maura Tommaso , Iughetti Lorenzo , Ferrari Fabrizio , Berardi Alberto
Published: August 2022

Background: Neonatal encephalopathy due to perinatal asphyxia is one of the leading causes of neonatal death and morbidity worldwide. The neurodevelopmental outcomes of asphyxiated neonates have considerably improved after therapeutic hypothermia (TH). The current challenge is to identify all newborns with encephalopathy at risk of cerebral lesions and subsequent disability within 6 h of life and who may be within the window period for treatment with TH. This study evaluated the neurodevelopmental outcomes in surviving asphyxiated neonates who did and did not receive TH, based on clinical and polygraphic electroencephalographic (p-EEG) criteria. Methods: The study included 139 asphyxiated newborns divided into two groups: 82 who received TH and 57 who were not cooled. TH was administered to asphyxiated newborns (gestational age ≥ 35 weeks, birth weight ≥ 1800 g) with encephalopathy of any grade and moderate-to-severe p-EEG abnormalities or seizures. Neurodevelopmental outcomes between the groups at 24 months of life and the risk factors for severe outcomes were assessed. Results: Severe neurodevelopmental impairment occurred in 10 (7.2%) out of the 139 enrolled neonates. Nine out of the 82 cooled neonates (11.0%) had severe neurodevelopmental impairment. All but one neonate (98.2%) who did not receive TH had normal outcomes. The multivariate logistic regression analysis showed that abnormal p-EEG patterns (OR: 27.6; IC: 2.8–267.6) and general movements (OR: 3.2; IC: 1.0–10.0) were significantly associated with severe neurodevelopmental impairment (area under ROC curve: 92.7%). Conclusion: The combination of clinical and p-EEG evaluations in hypoxic–ischemic encephalopathy contributed to a more accurate selection of patients treated with therapeutic hypothermia. When administered to infants with moderate to severe p-EEG abnormalities, TH prevents approximately 90% of severe neurodevelopmental impairment after any grade of hypoxic–ischemic encephalopathy.
Decision-Making in the Pediatric Emergency Department—A Survey of Guidance Strategies among Residents
Authors: Gaus Sebastian , Schmidt Jeremy , Lüse Paul , Barthlen Winfried , Hamelmann Eckard , Vossschulte Hendrik
Published: August 2022

(1) Introduction: Working in an emergency department requires fast and straightforward decisions. Therefore, decision guidance represents an essential tool for successful patient-centered care. Beyond the residents’ own knowledge and experience, printed books have been the primary source of information in the past. The aim of this study was to discover which strategies current residents use the most and to identify alternative quick reference strategies in the digital age. (2) Materials and Methods: This study analyzed the responses of a short questionnaire directed at 41 residents in a single pediatric emergency department (32 pediatric and 9 pediatric surgery residents) over a period of one month. (3) Results: Thirty-three (80.5%) residents answered the entire questionnaire. Strikingly, responses indicated that printed books are still pivotal in guiding decision-making. In addition, the acquisition of information via computers or smartphones plays an increasing role. However, the opinion and council of the attending physician is still of great value to the residents and is not to be underestimated. Overall, most of the residents would prefer to have access to a specially designed smartphone application. (4) Conclusions: Certainty and validity are essential in decision-making in a pediatric emergency department. Although printed books and attending physicians are still considered as reliable sources of information, internet-based information plays an increasing role. In order to provide the best up-to-date and most recent information, a validated and consistently updated smartphone application could be a useful option.
Limb Length Discrepancy and Corticospinal Tract Disruption in Hemiplegic Cerebral Palsy
Authors: Kim Hyo , Son Su
Published: August 2022

This study aimed to investigate the relationship between the corticospinal tract (CST) and limb length discrepancy (LLD) in patients with hemiplegic cerebral palsy (CP). Using diffusion tensor tractography, a retrospective study on 92 pediatric patients with hemiplegic CP who visited our hospital from May 2017 to the end of 2020 was conducted. Limb length was measured by anthropometry to calculate LLD. The functional level of hemiplegia scale (FxL), modified Ashworth scale, and manual muscle test (MMT) were evaluated for clinical function. Patients were classified into two groups according to the presence or absence of disruption of the affected CST: disruption (A) and preservation (B) groups. Fractional anisotropy (FA) and mean diffusivity (MD) of the affected CSTs were measured and correlated with LLD. The results of the independent t-test and chi-square test did not show significant differences between the two groups, except in the FxL and finger extensor of MMT (p < 0.05). For the LLD, there were no significant differences in total upper, total lower, and foot limb lengths. A significant difference was observed only in hand LLD (p < 0.05) from ANCOVA. Hand LLD was significantly correlated with FA (r = −0.578), MD (r = 0.512), and degree of CST disruption (r = −0.946) from the Pearson correlation test. The results of this study suggested that patients with hemiplegic CP would likely have LLD especially in the hand, and that CST evaluation using diffusion tensor tractography might be helpful in assessing and predicting LLD in hemiplegic CP.
The Influence of Anion-Stripped MIL-101(Cr) Dispersed in Thin-Film Polyvinyl Alcohol Membrane Matrix on the Methylene Blue Dye Separation
Authors: Mehdipour Ghazi Mohsen , Bagherian Abbas
Published: August 2022

This study investigates the production and performance of a novel nanofiltration membrane for removal of cationic dye (Methylene blue) and multivalent cations. These positively charged membranes are made by dispersing a modified cationic metal–organic framework, Cl-MIL-101(Cr), into the polyvinyl alcohol matrix as a membrane skin layer. To this end, the mobile anion (Cl−) embedded in the MIL-101(Cr) structure plays a role to create a positive partial charge on the membrane. In this study, the effects of MOF content and their types on the membrane structure were considered by FTIR, XRD, FESEM, Zeta potential and water contact angle. The results have shown that membranes filled with Cl-MIL-101(Cr) attained higher permeate flux and rejection than those of MIL-101(Cr). Particularly, this study indicates that the low irreversible resistance (19.49%) and high flux return ratio (80.50%) have been related to the membrane containing 15% cationic Cl-MIL-101(Cr). However, this membrane rejected more than 30.41% of AlCl3 salt and 99.08% of methylene blue with approximate permeate flux of 20 L/m2·h. It is recommended that the fabricated membrane be placed in the flow path process of cationic dyes purification.
On Three “Anomalous” Measurements of Nonlinear QPC Conductance
Authors: Das Mukunda P. , Green Frederick
Published: August 2022

Practical mesoscopic devices based on quantum point contacts (QPCs) must function at operating point involving large internal driving fields. Experimental evidence has accumulated to display anomalous nonlinear features of QPC response beyond the capacities of accepted tunnelling-based models of nonlinear quantum transport. Here, we recall the physical setting of three anomalous QPC experiments and review how, for two of them, a microscopically based nonequilibrium quantum kinetic description—the correct physical boundary conditions being crucial—has already overcome the predictive limitations of standard nonequilibrium mesoscopic models. The third experiment remains a significant challenge to all theorists.
Increased Mobility in 4H-SiC MOSFETs by Means of Hydrogen Annealing
Authors: Idris Muhammad Idzdihar , Horsfall Alton
Published: August 2022

Enhancement-mode 4H-SiC MOSFETs utilising an aluminium oxide (Al2O3) dielectric without the requirement for an underlying silicon oxide (SiO2) layer have been shown to have a field effect mobility of 150 cm2V−1s−1 and a subthreshold swing of 160 mV/dec. The fabricated devices utilised a forming gas (3% H2 in N2) anneal immediately prior to the deposition of the Al2O3 by Atomic Layer Deposition (ALD). A comparison MOSFET using an identical Al2O3 deposition process with a 0.7 nm SiO2 layer had a field effect mobility of approximately 20 cm2V−1s−1. The hydrogen annealed device had a lower density of interface traps (Dit), a lower subthreshold swing, and a significantly reduced hysteresis in the transconductance data than the thin SiO2 sample. This finding solves the issue of inconsistency of device performance using thin film gate dielectric as an interfacial layer by offering a simple and controllable process.
Enhanced Ammonia Gas Adsorption through Site-Selective Fluorination of Graphene
Authors: Duan Tianbo , Li Hu , Daukiya Lakshya , Simon Laurent , Leifer Klaus
Published: August 2022

Graphene has been widely explored as an ideal platform for gas sensing owing to exceptional properties, such as its atom-thin two-dimensional conjugated structure and large specific surface area. Herein, we report that, by introducing covalent C-F bonds via site-selective ion-beam-induced fluorination, graphene sensing response to ammonia gas can be considerably improved due to the enhanced gas adsorption on the surface of fluorinated graphene. The response to the ammonia gas increased by a factor of eight together with the limit of detection approaching 65 ppb. The absorption kinetics between the ammonia gas and fluorinated graphene were analyzed by using the Langmuir isotherm model and the result shows that the enhanced sensitivity is mainly attributed to the strong binding energy of fluorinated graphene to ammonia gas molecules, which is consistent with previous theoretical predictions.
Misinformation and Facts about Breast Cancer Screening
Authors: Kopans Daniel B.
Published: August 2022

Quality medical practice is based on science and evidence. For over a half-century, the efficacy of breast cancer screening has been challenged, particularly for women aged 40–49. As each false claim has been raised, it has been addressed and refuted based on science and evidence. Nevertheless, misinformation continues to be promoted, resulting in confusion for women and their physicians. Early detection has been proven to save lives for women aged 40–74 in randomized controlled trials of mammography screening. Observational studies, failure analyses, and incidence of death studies have provided evidence that there is a major benefit when screening is introduced to the general population. In large part due to screening, there has been an over 40% decline in deaths from breast cancer since 1990. Nevertheless, misinformation about screening continues to be promoted, adding to the confusion. Despite claims to the contrary, a careful reading of the guidelines issued by major groups such as the U.S. Preventive Services Task Force and the American College of Physicians shows that they all agree that most lives are saved by screening starting at the age of 40. There is no scientific support for using the age of 50 as a threshold for screening. All women should be provided with the facts and not false information about breast cancer screening so that they can make “informed decisions” for themselves about whether to participate.