bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway
Authors: Tanaka Masaru , Tóth Fanni , Polyák Helga , Szabó Ágnes , Mándi Yvette , Vécsei László
Published: June 2021

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases and psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses and chronic diseases. KYN, kynurenic acid, xanthurenic acid and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric disorders, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia and autism spectrum disorder.
Neural Basis of Anticipatory Multisensory Integration
Authors: Fiorini Linda , Berchicci Marika , Mussini Elena , Bianco Valentina , Lucia Stefania , Di Russo Francesco
Published: June 2021

The brain is able to gather different sensory information to enhance salient event perception, thus yielding a unified perceptual experience of multisensory events. Multisensory integration has been widely studied, and the literature supports the hypothesis that it can occur across various stages of stimulus processing, including both bottom-up and top-down control. However, evidence on anticipatory multisensory integration occurring in the fore period preceding the presentation of the expected stimulus in passive tasks, is missing. By means of event-related potentials (ERPs), it has been recently proposed that visual and auditory unimodal stimulations are preceded by sensory-specific readiness activities. Accordingly, in the present study, we tested the occurrence of multisensory integration in the endogenous anticipatory phase of sensory processing, combining visual and auditory stimuli during unimodal and multimodal passive ERP paradigms. Results showed that the modality-specific pre-stimulus ERP components (i.e., the auditory positivity -aP- and the visual negativity -vN-) started earlier and were larger in the multimodal stimulation compared with the sum of the ERPs elicited by the unimodal stimulations. The same amplitude effect was also present for the early auditory N1 and visual P1 components. This anticipatory multisensory effect seems to influence stimulus processing, boosting the magnitude of early stimulus processing. This paves the way for new perspectives on the neural basis of multisensory integration.
Effect of Auditory Maturation on the Encoding of a Speech Syllable in the First Days of Life
Authors: Ferreira Laís , Skarzynski Piotr Henryk , Skarzynska Magdalena Beata , Sanfins Milaine Dominici , Biaggio Eliara Pinto Vieira
Published: June 2021

(1) Background: In neonates and infants, the physiological modifications associated with language development are reflected in their Frequency Following Responses (FFRs) in the first few months of life. (2) Objective: This study aimed to test the FFRs of infants in the first 45 days of life in order to evaluate how auditory maturation affects the encoding of a speech syllable. (3) Method: In total, 80 healthy, normal-hearing infants, aged 3 to 45 days old, participated in this study. The sample was divided into three groups: GI, 38 neonates from 3 to 15 days; GII, 25 infants from 16 to 30 days; and GIII, 17 infants from 31 to 45 days. All participants underwent FFR testing. Results: With age, there was a decrease in the latency of all FFR waves, with statistically significant differences among the groups studied for waves V, A, E, F, and O. The mean amplitudes showed an increase, with a statistically significant difference only for wave V. The slope measure increased over the 45 days, with a statistically significant difference between GIII and GI and between GIII and GII. (4) Conclusions: The encoding of a speech sound changes with auditory maturation over the first 45 days of an infant’s life.
The Current Role of Dexmedetomidine as Neuroprotective Agent: An Updated Review
Authors: Liaquat Zaara , Xu Xiaoying , Zilundu Prince Last Mudenda , Fu Rao , Zhou Lihua
Published: June 2021

Dexmedetomidine, selective α2-adrenergic agonist dexmedetomidine, has been widely used clinically for sedation and anesthesia. The role of dexmedetomidine has been an interesting topic of neonatological and anesthetic research since a series of advantages of dexmedetomidine, such as enhancing recovery from surgery, reducing opioid prescription, decreasing sympathetic tone, inhibiting inflammatory reactions, and protecting organs, were reported. Particularly, an increasing number of animal studies have demonstrated that dexmedetomidine ameliorates the neurological outcomes associated with various brain and spinal cord injuries. In addition, a growing number of clinical trials have reported the efficacy of dexmedetomidine for decreasing the rates of postoperative neurological dysfunction, such as delirium and stroke, which strongly highlights the possibility of dexmedetomidine functioning as a neuroprotective agent for future clinical use. Mechanism studies have linked dexmedetomidine’s neuroprotective properties with its modulation of neuroinflammation, apoptosis, oxidative stress, and synaptic plasticity via the α2-adrenergic receptor, dependently or independently. By reviewing recent advances and preclinical and clinical evidence on the neuroprotective effects of dexmedetomidine, we hope to provide a complete understanding of the above mechanism and provide insights into the potential efficacy of this agent in clinical use for patients.
Predictors of Rehabilitation Service Utilisation among Children with Cerebral Palsy (CP) in Low- and Middle-Income Countries (LMIC): Findings from the Global LMIC CP Register
Authors: Al Imam Mahmudul Hassan , Jahan Israt , Muhit Mohammad , Hardianto Denny , Laryea Francis , Chhetri Amir Banjara , Smithers-Sheedy Hayley , McIntyre Sarah , Badawi Nadia , Khandaker Gulam
Published: June 2021

Background: We assessed the rehabilitation status and predictors of rehabilitation service utilisation among children with cerebral palsy (CP) in selected low- and middle-income countries (LMICs). Methods: Data from the Global LMIC CP Register (GLM-CPR), a multi-country register of children with CP aged <18 years in selected countries, were used. Descriptive and inferential statistics (e.g., adjusted odds ratios) were reported. Results: Between January 2015 and December 2019, 3441 children were registered from Bangladesh (n = 2852), Indonesia (n = 130), Nepal (n = 182), and Ghana (n = 277). The proportion of children who never received rehabilitation was 49.8% (n = 1411) in Bangladesh, 45.8% (n = 82) in Nepal, 66.2% (n = 86) in Indonesia, and 26.7% (n = 74) in Ghana. The mean (Standard Deviation) age of commencing rehabilitation services was relatively delayed in Nepal (3.9 (3.1) year). Lack of awareness was the most frequently reported reason for not receiving rehabilitation in all four countries. Common predictors of not receiving rehabilitation were older age at assessment (i.e., age of children at the time of the data collection), low parental education and family income, mild functional limitation, and associated impairments (i.e., hearing and/or intellectual impairments). Additionally, gender of the children significantly influenced rehabilitation service utilisation in Bangladesh. Conclusions: Child’s age, functional limitation and associated impairments, and parental education and economic status influenced the rehabilitation utilisation among children with CP in LMICs. Policymakers and service providers could use these findings to increase access to rehabilitation and improve equity in rehabilitation service utilisation for better functional outcome of children with CP.
Similarities and Differences in the Learning Profiles of Adolescents with SLD and SLI in Mathematics—A Preliminary Analysis
Authors: Bonti Eleni , Kamari Afroditi , Sofologi Maria , Giannoglou Sofia , Porfyri Georgia-Nektaria , Tatsiopoulou Paraskevi , Kougioumtzis Georgios , Efstratopoulou Maria , Diakogiannis Ioannis
Published: June 2021

SLI and SLD constitute two independent neurodevelopmental disorders, which frequently cause challenges in the diagnosis process, especially due to their nature. This has caused disagreement among clinicians regarding their recognition as separate or overlapping disorders. The objective of the study was to enlighten the path of valid diagnosis and intervention during adolescence when the two disorders change their manifestation and overlap. Two hundred Greek adolescents (140 boys and 60 girls), 124 already diagnosed with SLD and 76 diagnosed with SLI, 12–16 years old, participated in the study. All participants were assessed in reading, oral and written language and mathematics (mathematical operations and mathematical reasoning) along with IQ testing. In order to determine statistically significant differences, the chi-square test, independent samples t-test, odds ratios and their 95 per cent confidence intervals were implemented. The results revealed that the SLI group presented significantly greater difficulties than SLD in their overall cognitive-mental profile and in most language and mathematical measurements (number concept, executive-procedural part of solving operations and mathematical reasoning). The similarity of the two groups was mainly detected in their deficient metacognitive, metalinguistic and metamnemonic strategies. The research concludes that SLD adolescents managed to overcome their difficulties to a significant degree, while adolescents with SLI still struggle with many learning areas.
Integration of Modelling Approaches for the Seismic Assessment of Complex URM Buildings: The Podestà Palace in Mantua, Italy
Authors: Lagomarsino Sergio , Degli Abbati Stefania , Ottonelli Daria , Cattari Serena
Published: June 2021

This study investigated seismic assessments of the Podestà Palace in Mantua (Italy). This masonry palace has a complex geometrical configuration that resulted from the addition of various units stratified over centuries. This feature makes seismic assessment challenging from a modelling perspective due to the interaction among units. Here, an integrated use of three modelling strategies characterised by a different computational effort and degree of accuracy was employed: (i) the Structural Element Model, according to the Equivalent Frame Approach, to study the global response of the whole structure and to estimate the mutual dynamic interactions among units; (ii) the Macro-Block Model, to assess the out-of-plane response of facades prone to the activation of local mechanisms; and (iii) the Finite Element Model, to deepen the seismic response of some critical parts, highlighted by a global analysis but also roughly described by the Equivalent Frame Model. This integrated approach consists in the use of results achieved from one modelling approach as input for another. For example, the floor spectra estimated by (i) were used to define the seismic input in (ii); for assessing the most critical portions, more accurate models were addressed (as in case (iii)). The comprehensive interpretation of the seismic behaviour obtained by these models also allowed us to address more rationally possible strengthening solutions, such as the in-plane stiffening of vaults (particularly spread in the building), aimed to guarantee a better redistribution of seismic actions in such a complex building.
Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay
Authors: Chen Oleg , Michlíková Soňa , Eckhardt Lisa , Wondrak Marit , De Mendoza Adriana M. , Krause Mechthild , McLeod Damian D. , Kunz-Schughart Leoni A.
Published: June 2021

Hyperthermia (HT) combined with irradiation is a well-known concept to improve the curative potential of radiotherapy. Technological progress has opened new avenues for thermoradiotherapy, even for recurrent head and neck squamous cell carcinomas (HNSCC). Preclinical evaluation of the curative radiosensitizing potential of various HT regimens remains ethically, economically, and technically challenging. One key objective of our study was to refine an advanced 3-D assay setup for HT + RT research and treatment testing. For the first time, HT-induced radiosensitization was systematically examined in two differently radioresponsive HNSCC spheroid models using the unique in vitro “curative” analytical endpoint of spheroid control probability. We further investigated the cellular stress response mechanisms underlying the HT-related radiosensitization process with the aim to unravel the impact of HT-induced proteotoxic stress on the overall radioresponse. HT disrupted the proteome’s thermal stability, causing severe proteotoxic stress. It strongly enhanced radiation efficacy and affected paramount survival and stress response signaling networks. Transcriptomics, q-PCR, and western blotting data revealed that HT + RT co-treatment critically triggers the heat shock response (HSR). Pre-treatment with chemical chaperones intensified the radiosensitizing effect, thereby suppressing HT-induced Hsp27 expression. Our data suggest that HT-induced radiosensitization is adversely affected by the proteotoxic stress response. Hence, we propose the inhibition of particular heat shock proteins as a targeting strategy to improve the outcome of combinatorial HT + RT.
A Real-World, Observational, Prospective Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon Progression on or after First-Line Therapy with a First- or Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: The ‘LUNGFUL’ Study
Authors: Mountzios Giannis , Koumarianou Anna , Bokas Alexandros , Mavroudis Dimitrios , Samantas Epaminondas , Fergadis Evangelos Georgios , Linardou Helena , Katsaounis Panagiotis , Athanasiadis Elias , Karamouzis Michalis V. , Pentheroudakis George , Lampaki Sofia , Froudarakis Marios E. , Perdikouri Eleni-Isidora A. , Somarakis Alvertos , Papageorgiou Foteini , Paparepa Zoe , Nikolaou Aristeidis , Syrigos Konstantinos N.
Published: June 2021

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas®EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.
Re-Irradiation for Head and Neck Cancer: Cumulative Dose to Organs at Risk and Late Side Effects
Authors: Embring Anna , Onjukka Eva , Mercke Claes , Lax Ingmar , Berglund Anders , Bornedal Sara , Wennberg Berit , Dalqvist Emmy , Friesland Signe
Published: June 2021

Re-irradiation in head and neck cancer is challenging, and cumulative dose constraints and dose/volume data are scarce. In this study, we present dose/volume data for patients re-irradiated for head and neck cancer and explore the correlations of cumulative dose to organs at risk and severe side effects. We analyzed 54 patients re-irradiated for head and neck cancer between 2011 and 2017. Organs at risk were delineated and dose/volume data were collected from cumulative treatment plans of all included patients. Receiver–operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. The ROC-curve for a logistic model of carotid blowout vs. maximum doses to the carotid arteries showed AUC = 0.92 (95% CI 0.83 to 1.00) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.89). The near-maximum dose to bones showed an association with the risk of osteoradionecrosis: AUC = 0.74 (95% CI 0.52 to 0.95) and a cut-off value of 119 Gy (sensitivity 1.00/specificity 0.52). Our analysis showed an association between cumulative dose to organs at risk and the risk of developing osteoradionecrosis and carotid blowout, and our results support the existing dose constraint for the carotid arteries of 120 Gy. The confirmation of these dose–response relationships will contribute to further improvements of re-irradiation strategies.
Immunity Depletion, Telomere Imbalance, and Cancer-Associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Short-Term Caloric Restriction
Authors: Maestri Evan , Duszka Kalina , Kuznetsov Vladimir A.
Published: June 2021

Systems cancer biology analysis of calorie restriction (CR) mechanisms and pathways has not been carried out, leaving therapeutic benefits unclear. Using metadata analysis, we studied gene expression changes in normal mouse duodenum mucosa (DM) response to short-term (2-weeks) 25% CR as a biological model. Our results indicate cancer-associated genes consist of 26% of 467 CR responding differential expressed genes (DEGs). The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest telomeric maintenance misbalance and metabolic pathway activation playing dual (anti-cancer and pro-oncogenic) roles. The aberrant DEG profile of DM epithelial cells is found within CR-induced overexpression of Paneth cells and is coordinated significantly across GI tract tissues mucosa. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor-immune surveillance. CR induces metabolic reprogramming, suppressing immune mechanics and activating oncogenic pathways. We introduce and argue for our network pro-oncogenic model of the mucosa multicellular tissue response to CR leading to aberrant transcription and pre-malignant states. These findings change the paradigm regarding CR’s anti-cancer role, initiating specific treatment target development. This will aid future work to define critical oncogenic pathways preceding intestinal lesion development and biomarkers for earlier adenoma and colorectal cancer detection.
Deciphering the Nature of Trp73 Isoforms in Mouse Embryonic Stem Cell Models: Generation of Isoform-Specific Deficient Cell Lines Using the CRISPR/Cas9 Gene Editing System
Authors: López-Ferreras Lorena , Martínez-García Nicole , Maeso-Alonso Laura , Martín-López Marta , Díez-Matilla Ángela , Villoch-Fernandez Javier , Alonso-Olivares Hugo , Marques Margarita M. , Marin Maria C.
Published: June 2021

The p53 family has been widely studied for its role in various physiological and pathological processes. Imbalance of p53 family proteins may contribute to developmental abnormalities and pathologies in humans. This family exerts its functions through a profusion of isoforms that are generated by different promoter usage and alternative splicing in a cell type dependent manner. In particular, the Trp73 gene gives rise to TA and DN-p73 isoforms that confer p73 a dual nature. The biological relevance of p73 does not only rely on its tumor suppression effects, but on its pivotal role in several developmental processes. Therefore, the generation of cellular models that allow the study of the individual isoforms in a physiological context is of great biomedical relevance. We generated specific TA and DN-p73-deficient mouse embryonic stem cell lines using the CRISPR/Cas9 gene editing system and validated them as physiological bona fide p73-isoform knockout models. Global gene expression analysis revealed isoform-specific alterations of distinctive transcriptional networks. Elimination of TA or DN-p73 is compatible with pluripotency but prompts naïve pluripotent stem cell transition into the primed state, compromising adequate lineage differentiation, thus suggesting that differential expression of p73 isoforms acts as a rheostat during early cell fate determination.
Deactivation and Regeneration of Zeolite Catalysts Used in Pyrolysis of Plastic Wastes—A Process and Analytical Review
Authors: Daligaux Vivien , Richard Romain , Manero Marie-Hélène
Published: June 2021

In catalytic industrial processes, coke deposition remains a major drawback for solid catalysts use as it causes catalyst deactivation. Extensive study of this phenomenon over the last decades has provided a better understanding of coke behavior in a great number of processes. Among them, catalytic pyrolysis of plastics, which has been identified as a promising process for waste revalorization, is given particular attention in this paper. Combined economic and environmental concerns rose the necessity to restore catalytic activity by recovering deactivated catalysts. Consequently, various regeneration processes have been investigated over the years and development of an efficient and sustainable process remains an industrial challenge. Coke removal can be achieved via several chemical processes, such as oxidation, gasification, and hydrogenation. This review focuses on oxidative treatments for catalyst regeneration, covering the current progress of oxidation treatments and presenting advantages and drawbacks for each method. Molecular oxidation with oxygen and ozone, as well as advanced oxidation processes with the formation of OH radicals, are detailed to provide a deep understanding of the mechanisms and kinetics involved (direct and indirect oxidation, reaction rates and selectivity, diffusion, and mass transfer). Finally, this paper summarizes all relevant analytical techniques that can be used to characterize deactivated and regenerated solid catalysts: XRD, N2 adsorption-desorption, SEM, NH3-TPD, elemental analysis, IR. Analytical techniques are classified according to the type of information they provide, such as structural characteristics, elemental composition, or chemical properties. In function of the investigated property, this overall tool is useful and easy-to-use to determine the adequate analysis.
The ‘Green’ Ni-UGSO Catalyst for Hydrogen Production under Various Reforming Regimes
Authors: Chamoumi Mostafa , Abatzoglou Nicolas
Published: June 2021

A new spinelized Ni catalyst (Ni-UGSO) using Ni(NO3)2·6H2O as the Ni precursor was prepared according to a less material intensive protocol. The support of this catalyst is a negative-value mining residue, UpGraded Slag Oxide (UGSO), produced from a TiO2 slag production unit. Applied to dry reforming of methane (DRM) at atmospheric pressure, T = 810 °C, space velocity of 3400 mL/(h·g) and molar CO2/CH4 = 1.2, Ni-UGSO gives a stable over 168 h time-on-stream methane conversion of 92%. In this DRM reaction optimization study: (1) the best performance is obtained with the 10–13 wt% Ni load; (2) the Ni-UGSO catalysts obtained from two different batches of UGSO demonstrated equivalent performances despite their slight differences in composition; (3) the sulfur-poisoning resistance study shows that at up to 5.5 ppm no Ni-UGSO deactivation is observed. In steam reforming of methane (SRM), Ni-UGSO was tested at 900 °C and a molar ratio of H2O/CH4 = 1.7. In this experimental range, CH4 conversion rapidly reached 98% and remained stable over 168 h time-on-stream (TOS). The same stability is observed for H2 and CO yields, at around 92% and 91%, respectively, while H2/CO was close to 3. In mixed (dry and steam) methane reforming using a ratio of H2O/CH4 = 0.15 and CO2/CH4 = 0.97 for 74 h and three reaction temperature levels (828 °C, 847 °C and 896 °C), CH4 conversion remains stable; 80% at 828 °C (26 h), 85% at 847 °C (24 h) and 95% at 896 °C (24 h). All gaseous streams have been analyzed by gas chromatography. Both fresh and used catalysts are analyzed by scanning electron microscopy-electron dispersive X-ray spectroscopy (SEM-EDXS), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) coupled with mass spectroscopy (MS) and BET Specific surface. In the reducing environment of reforming, such catalytic activity is mainly attributed to (a) alloys such as FeNi, FeNi3 and Fe3Ni2 (reduction of NiFe2O4, FeNiAlO4) and (b) to the solid solution NiO-MgO. The latter is characterized by a molecular distribution of the catalytically active Ni phase while offering an environment that prevents C deposition due to its alkalinity.
Novel Mutations in X-Linked, USP26-Induced Asthenoteratozoospermia and Male Infertility
Authors: Liu Chunyu , Shen Ying , Shen Qunshan , Zhang Wen , Wang Jiaxiong , Tang Shuyan , Wu Huan , Tian Shixiong , Cong Jiangshan , He Xiaojin , Jin Li , Zhang Feng , Jiang Xiaohui , Cao Yunxia
Published: June 2021

Male infertility is a multifactorial disease with a strong genetic background. Abnormal sperm morphologies have been found to be closely related to male infertility. Here, we conducted whole-exome sequencing in a cohort of 150 Han Chinese men with asthenoteratozoospermia. Two novel hemizygous mutations were identified in USP26, an X-linked gene preferentially expressed in the testis and encoding a deubiquitinating enzyme. These USP26 variants are extremely rare in human population genome databases and have been predicted to be deleterious by multiple bioinformatics tools. Hematoxylin-eosin staining and electron microscopy analyses of the spermatozoa from men harboring hemizygous USP26 variants showed a highly aberrant morphology and ultrastructure of the sperm heads and flagella. Real-time quantitative PCR and immunoblotting assays revealed obviously reduced levels of USP26 mRNA and protein in the spermatozoa from men harboring hemizygous deleterious variants of USP26. Furthermore, intracytoplasmic sperm injections performed on infertile men harboring hemizygous USP26 variants achieved satisfactory outcomes. Overall, our study demonstrates that USP26 is essential for normal sperm morphogenesis, and hemizygous USP26 mutations can induce X-linked asthenoteratozoospermia. These findings will provide effective guidance for the genetic and reproductive counseling of infertile men with asthenoteratozoospermia.
Distinctive Properties and Powerful Neuromodulation of Nav1.6 Sodium Channels Regulates Neuronal Excitability
Authors: Zybura Agnes , Hudmon Andy , Cummins Theodore R.
Published: June 2021

Voltage-gated sodium channels (Navs) are critical determinants of cellular excitability. These ion channels exist as large heteromultimeric structures and their activity is tightly controlled. In neurons, the isoform Nav1.6 is highly enriched at the axon initial segment and nodes, making it critical for the initiation and propagation of neuronal impulses. Changes in Nav1.6 expression and function profoundly impact the input-output properties of neurons in normal and pathological conditions. While mutations in Nav1.6 may cause channel dysfunction, aberrant changes may also be the result of complex modes of regulation, including various protein-protein interactions and post-translational modifications, which can alter membrane excitability and neuronal firing properties. Despite decades of research, the complexities of Nav1.6 modulation in health and disease are still being determined. While some modulatory mechanisms have similar effects on other Nav isoforms, others are isoform-specific. Additionally, considerable progress has been made toward understanding how individual protein interactions and/or modifications affect Nav1.6 function. However, there is still more to be learned about how these different modes of modulation interact. Here, we examine the role of Nav1.6 in neuronal function and provide a thorough review of this channel’s complex regulatory mechanisms and how they may contribute to neuromodulation.
Impact of Progerin Expression on Adipogenesis in Hutchinson—Gilford Progeria Skin-Derived Precursor Cells
Authors: Najdi Farah , Krüger Peter , Djabali Karima
Published: June 2021

Hutchinson–Gilford progeria syndrome (HGPS) is a segmental premature aging disease caused by a mutation in LMNA. The mutation generates a truncated and farnesylated form of prelamin A, called progerin. Affected individuals develop several features of normal aging, including lipodystrophy caused by the loss of general subcutaneous fat. To determine whether premature cellular senescence is responsible for the altered adipogenesis in patients with HGPS, we evaluated the differentiation of HGPS skin-derived precursor stem cells (SKPs) into adipocytes. The SKPs were isolated from primary human HGPS and normal fibroblast cultures, with senescence of 5 and 30%. We observed that the presence of high numbers of senescent cells reduced SKPs’ adipogenic differentiation potential. Treatment with baricitinib, a JAK–STAT inhibitor, ameliorated the ability of HGPS SKPs to differentiate into adipocytes. Our findings suggest that the development of lipodystrophy in patients with HGPS may be associated with an increased rate of cellular senescence and chronic inflammation.
Fe65: A Scaffolding Protein of Actin Regulators
Authors: Augustin Vanessa , Kins Stefan
Published: June 2021

The scaffolding protein family Fe65, composed of Fe65, Fe65L1, and Fe65L2, was identified as an interaction partner of the amyloid precursor protein (APP), which plays a key function in Alzheimer’s disease. All three Fe65 family members possess three highly conserved interaction domains, forming complexes with diverse binding partners that can be assigned to different cellular functions, such as transactivation of genes in the nucleus, modulation of calcium homeostasis and lipid metabolism, and regulation of the actin cytoskeleton. In this article, we rule out putative new intracellular signaling mechanisms of the APP-interacting protein Fe65 in the regulation of actin cytoskeleton dynamics in the context of various neuronal functions, such as cell migration, neurite outgrowth, and synaptic plasticity.
A Gas Sensor Based on Network Nanowire for H2S Monitor in Construction Waste Landfill
Authors: Ren Pengyu , Shi Qingwei , Qi Lingling
Published: June 2021

As an extremely harmful gas, H2S gas is the major pollutant in construction waste landfill. Herein, a one-dimensional oxide nanomaterial was produced from a simple wet chemical method to serve as a H2S gas sensing material. The SEM observation indicates that the nanomaterial with network structure is constructed by a lot of nanowires with an approximate diameter from 24 nm to 40 nm. The sensing film was formed on a ceramic substrate using a slurry composed of the as-prepared network nanowires. Furthermore, a gas sensing measurement was carried out to determine the gas sensing performances towards the H2S gas. The detection results at different working temperature towards various gas concentrations demonstrate that the network nanowires-based sensor exhibits a higher gas response to H2S as compared to that of the rod-like one. The optimum working temperature of the network and rod-like nanomaterials is both 300 °C, and the corresponding maximum gas response is 24.4 and 13.6, respectively. Namely, the gas response of the network-based gas sensor is almost larger than that of the rod-like oxide. Moreover, the network nanowires-based gas sensor display a faster gas response and recovery speed. In addition, the fabricated gas sensors all exhibit excellent repeatability. Such improved sensing properties may offer a promising potential to realize an efficient detection of harmful H2S gas released from construction waste landfill.
Electrochemical Determination of Lead & Copper Ions Using Thiolated Calix[4]arene-Modified Screen-Printed Carbon Electrode
Authors: Mei Chong Jin , Yusof Nor Azah , Alang Ahmad Shahrul Ainliah
Published: June 2021

This study used a thiolated calix[4]arene derivative modified on gold nanoparticles and a screen-printed carbon electrode (TC4/AuNPs/SPCE) for Pb2+ and Cu2+ determination. The surface of the modified electrode was characterised via Fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Differential pulse voltammetry (DPV) was used for the detection of Pb2+ and Cu2+ under optimum conditions. The limit of detection (LOD) for detecting Pb2+ and Cu2+ was 0.7982 × 10−2 ppm and 1.3358 × 10−2 ppm, respectively. Except for Zn2+ and Hg2+, the presence of competitive ions caused little effect on the current response when detecting Pb2+. However, all competitive ions caused a significant drop in the current response when detecting Cu2+, except Ca2+ and Mg2+, suggesting the sensing platform is more selective toward Pb2+ ions rather than copper (Cu2+) ions. The electrochemical sensor demonstrated good reproducibility and excellent stability with a low relative standard deviation (RSD) value in detecting lead and copper ions. Most importantly, the result obtained in the analysis of Pb2+ and Cu2+ had good recovery in river water, demonstrating the applicability of the developed sensor for real samples.
Flexible Wearable Sensors Based in Carbon Nanotubes Reinforced Poly(Ethylene Glycol) Diglycidyl Ether (PEGDGE): Analysis of Strain Sensitivity and Proof of Concept
Authors: del Bosque Antonio , Sánchez-Romate Xoan F. , Sánchez María , Ureña Alejandro
Published: June 2021

The electromechanical capabilities of carbon nanotube (CNT) doped poly(ethylene glycol) diglycidyl ether (PEGDGE) have been explored. In this regard, the effect of both CNT content and curing conditions were analyzed. The electrical conductivity increased both with CNT content and curing temperature due to the lower gel time that leads to a lower reaggregation during curing. More specifically, the percolation threshold at 160 and 180 °C curing temperatures is below 0.01 wt.%, and this limit increases up to 0.1 wt.% at 140 °C for an 8 h curing cycle. Moreover, the strain monitoring capabilities were investigated, and the effect of contact resistance was also analyzed. The electrical contacts made with silver ink led to higher values of gauge factor (GF) but presented some issues at very high strains due to their possible detachment during testing. In every case, GF values were far above conventional metallic gauges with a very significant exponential behavior, especially at low CNT content due to a prevalence of tunneling mechanisms. Finally, a proof of concept of fingers and knee motion monitoring was carried out, showing a high sensitivity for human motion sensing.
Redefining the Relationship: Palliative Care in Critical Perinatal and Neonatal Cardiac Patients
Authors: Afonso Natasha S. , Ninemire Margaret R. , Gowda Sharada H. , Jump Jaime L. , Lantin-Hermoso Regina L. , Johnson Karen E. , Puri Kriti , Hope Kyle D. , Kritz Erin , Achuff Barbara-Jo , Gurganious Lindsey , Bhat Priya N.
Published: June 2021

Patients with perinatal and neonatal congenital heart disease (CHD) represent a unique population with higher morbidity and mortality compared to other neonatal patient groups. Despite an overall improvement in long-term survival, they often require chronic care of complex medical illnesses after hospital discharge, placing a high burden of responsibility on their families. Emerging literature reflects high levels of depression and anxiety which plague parents, starting as early as the time of prenatal diagnosis. In the current era of the global COVID-19 pandemic, the additive nature of significant stressors for both medical providers and families can have catastrophic consequences on communication and coping. Due to the high prognostic uncertainty of CHD, data suggests that early pediatric palliative care (PC) consultation may improve shared decision-making, communication, and coping, while minimizing unnecessary medical interventions. However, barriers to pediatric PC persist largely due to the perception that PC consultation is indicative of “giving up.” This review serves to highlight the evolving landscape of perinatal and neonatal CHD and the need for earlier and longitudinal integration of pediatric PC in order to provide high-quality, interdisciplinary care to patients and families.
Electophoretically Deposition of Ti3C2 on Titanium Surface for Hard Tissue Implant Applications
Authors: Jang Jun-Hwee , Oh Jun-Sung , Lee Eun-Jung , Han Cheol-Min
Published: June 2021

As a metallic biomaterial, titanium (Ti) exhibits excellent biocompatibility, but its osteoinductivity is limited. Therefore, to improve this property, an electrophoretic deposition (EPD) technique was used to coat the Ti surface with Ti3C2 MXene (Ti3C2), a new class of two-dimensional nanomaterial. Ti3C2 is known to have good biocompatibility and better osteoinductivity than graphene oxide. The coating layer was characterized by a particulate microstructure and exhibited X-ray diffraction and Raman spectroscopy peaks corresponding to the Ti3C2 phase. In vitro cell tests using human mesenchymal stem cells confirmed that the cell attachment and proliferation on Ti3C2-coated Ti were similar to that of bare Ti, and that the osteoinductivity was significantly enhanced compared with bare Ti.
Curved-Mechanical Characteristic Measurements of Transparent Conductive Film-Coated Polymer Substrates Using Common-Path Optical Interferometry
Authors: Wen Bor-Jiunn , Hsu Jui-Jen
Published: June 2021

This study proposes a method for measuring curved-mechanical characteristics based on a whole-folding test for transparent conductive film-coated polymer substrates using common-path optical interferometry. Accordingly, 80-, 160-, and 230-nm indium tin oxide films coated on 40 × 40 mm 125-μm-thick polyethylene terephthalate (PET) substrates, and monolayer graphene films coated on 40 × 40 mm 250-μm-thick PET substrates are inspected and analyzed under the curving conditions of 50-, 30-, 20-, and 10-mm radii before and after an 11,000 whole-folding cycle test based on a 10-mm folding radius. This study utilizes the changes in the phase retardations of transparent conductive film-coated polymer substrates under different curving conditions before and after 11,000 whole-folding cycles to analyze the substrates’ residual stress characteristics that were the direct result of manufacturing process parameters. The results from this study of curved-mechanical characteristic measurements of flexible transparent conductive substrates can provide designers with improved product development and can assist manufacturers in improving the manufacturing design of enhanced coating processes.
B-Site Cation Ordering in Films, Superlattices, and Layer-by-Layer-Grown Double Perovskites
Authors: Ksoll Philipp , Meyer Christoph , Schüler Leonard , Roddatis Vladimir , Moshnyaga Vasily
Published: June 2021

The preparation of cation-ordered thin films of correlated oxides is of great interest for both fundamental and applied research. The scientific long-term vision is strongly motivated by the perspective of studying electronic correlations in condensed matter without the presence of chemical or quenched disorder. A promising material platform provides double perovskite A2BB’O6 bulk samples with different types of B/B’ ordering. However, the growth of A- and/or B-site-ordered correlated oxide thin films is known to be a challenging task. In this review, we evaluate the growth of double perovskite A2BB’O6 thin films by means of well-elaborated physical vacuum deposition techniques, such as pulsed laser deposition (PLD) and sputtering and compare them with a close-to-equilibrium growth with the metalorganic aerosol deposition (MAD) technique. The latter was further developed to grow an emergent interfacial double perovskite phase in LaNiO3/LaMnO3 superlattices, and finally, by way of a layer-by-layer route. The growth of La2CoMnO6 films on SrTiO3(111) substrates by sequential deposition of single perovskite layers of LaCoO3/LaMnO3/LaCoO3/… was demonstrated and the film properties were compared to those obtained within the state-of-the art growth mode.
Nanostructured Crystalline Semiconductors: Structure, Morphology and Functional Properties
Authors: Shifa Tofik Ahmed
Published: June 2021

Nanotechnology has contributed a lot to the development of the semiconductor industry [...]
Temperature Stable, High-Quality Factor Li2TiO3-Li4NbO4F Microwave Dielectric Ceramics
Authors: Xu Shangrui , Jiang Juan , Cheng Zelai , Chen Xiangyi , Sun Shikuan , Wang Dawei , Zhang Tianjin
Published: June 2021

In this work, (1-x)Li2TiO3-xLi4NbO4F ceramics were prepared by the conventional solid-state ceramic route. With the increase of Li4NbO4F content, the phase structure transformed from ordered monoclinic to disordered cubic. By increasing Li3NbO4F content, the temperature coefficient of resonant frequency (τf) was successfully adjusted closer to zero, while the dielectric constant (εr) and microwave quality factor (Qf) decreased to some degree. Outstanding microwave dielectric properties with a εr = 18.7, Qf = 61,388 GHz (6.264 GHz), and τf = 0.9 ppm/°C were obtained for 0.9Li2TiO3-0.1Li4NbO4F ceramics sintered at 1050 °C for 2 h, which indicated that these ceramics are suitable for practical applications in the field of microwave substrates and components.
A Numerical Study on Chloride Diffusion in Cracked Concrete
Authors: Wang Qiannan , Zhang Guoshuai , Tong Yunyun , Gu Chunping
Published: June 2021

The cracks in concrete are a fast transport path for chlorides and influence the service life of concrete structures in chloride environments. This study aimed to reveal the effect of crack geometry on chloride diffusion in cracked concrete. The chloride diffusion process in cracked concrete was simulated with the finite difference method by solving Fick’s law. The results showed that the apparent chloride diffusivity was lower in more tortuous cracks, and the cracks with more narrow points also showed lower apparent chloride diffusivity. For tortuous cracks, a higher crack width meant relatively more straight cracks, and consequently, higher apparent chloride diffusivity, while a lower crack width resulted in more tortuous cracks and lower apparent chloride diffusivity. The crack depth showed a more significant influence on the chloride penetration depth in cracked concrete than crack geometry did. Compared with rectangular and V-shaped cracks, the chloride diffusion process in cracked concrete with a tortuous crack was slower at the early immersion age. At the same crack depth, the crack geometry showed a marginal influence on the chloride penetration depth in cracked concrete during long-term immersion.
Bridging Nanowires for Enhanced Gas Sensing Properties
Authors: Alenezi Mohammad R , Almeshal Abdullah M.
Published: June 2021

It is crucial to develop new bottom-up fabrication methods with control over the physical properties of the active materials to produce high-performance devices. This article reports well-controlled, without seed layer and site-selective hydrothermal method to produce ZnO bridging nanowires sensors. By controlling the growth environment, the performance of the sensor became more efficient. The presented on-chip bridging nanowire sensor enhanced sensitivity toward acetone gas (200 ppm) around 63 and fast response time (420 ms) and recovery time (900 ms). The enhancement in the speed of response and recovery is ascribed to the exceptional NW-NW junction barrier that governs the sensor’s conductivity, and the excellent contact between ZnO nanowires and Au electrodes.
Recent Radiomics Advancements in Breast Cancer: Lessons and Pitfalls for the Next Future
Authors: Pesapane Filippo , Rotili Anna , Agazzi Giorgio Maria , Botta Francesca , Raimondi Sara , Penco Silvia , Dominelli Valeria , Cremonesi Marta , Jereczek-Fossa Barbara Alicja , Carrafiello Gianpaolo , Cassano Enrico
Published: June 2021

Radiomics is an emerging translational field of medicine based on the extraction of high-dimensional data from radiological images, with the purpose to reach reliable models to be applied into clinical practice for the purposes of diagnosis, prognosis and evaluation of disease response to treatment. We aim to provide the basic information on radiomics to radiologists and clinicians who are focused on breast cancer care, encouraging cooperation with scientists to mine data for a better application in clinical practice. We investigate the workflow and clinical application of radiomics in breast cancer care, as well as the outlook and challenges based on recent studies. Currently, radiomics has the potential ability to distinguish between benign and malignant breast lesions, to predict breast cancer’s molecular subtypes, the response to neoadjuvant chemotherapy and the lymph node metastases. Even though radiomics has been used in tumor diagnosis and prognosis, it is still in the research phase and some challenges need to be faced to obtain a clinical translation. In this review, we discuss the current limitations and promises of radiomics for improvement in further research.