bluuebunny/crossref_metadata_2025 huggingface dataset:
In Situ Metrology for Pad Surface Monitoring in CMP Using a Common-Path Phase-Shifting Interferometry: A Feasibility Study
Authors: Kim Eun-Soo , Choi Woo-June
Published: July 2021

In the fabrication of semiconductors, chemical mechanical polishing (CMP) is an essential wafer-planarization process. For optimal CMP, it is crucial to monitor the texture of the polishing pad; this leads to homogenous planarization of wafers. Hence, we present a new interferometric approach for in situ evaluation of the CMP pad surface based on a common-path phase-shifting interferometry, with which a series of phase-modulated interference signals immune to external perturbation can be recorded. A nanoscopic surface topology can then be reconstructed to estimate surface roughness using the recorded interference images. The surface mapping performance of the proposed method was tested by retrieving a topology of a vibrating nanostructure in immersion, of which height profiles were consistent with the result from atomic force microscopy (AFM). The method was also validated by examining the surface of a used CMP pad in simulated conditions.
Effectiveness of Exercise and Manual Therapy as Treatment for Patients with Migraine, Tension-Type Headache or Cervicogenic Headache: An Umbrella and Mapping Review with Meta-Meta-Analysis
Authors: Herranz-Gómez Aida , García-Pascual Irene , Montero-Iniesta Pablo , Touche Roy La , Paris-Alemany Alba
Published: July 2021

The aim of the study was to perform a mapping and umbrella review with meta-meta-analysis (MMA) to synthesise and critically evaluate the effectiveness of manual therapy (MT) and aerobic exercise (AE) in relation to pain intensity, frequency, disability and quality of life in patients with migraines, tension-type headaches (TTH) and cervicogenic headaches (CGH). A systematic search was conducted in PubMed, PEDro, Scielo and Google Scholar up to December 2020. A total of 18 articles met the inclusion criteria, and only 8 were included in the quantitative analysis. The MMA showed results in favour of the interventions in terms of pain intensity and quality of life in migraine, TTH and CCH. Data were also in favour of the intervention in terms of pain frequency in migraine and in terms of disability in TTH. However, there were no significant effects on pain frequency in TTH and CGH. The results showed moderate evidence to suggest that AE reduces pain intensity in patients with migraine. In addition, the evidence in favour of MT or a mixed intervention (including therapeutic exercise) was also moderate in terms of reducing pain intensity in patients with TTH.
Assessment and Brain Training of Patients Experiencing Head and Facial Pain with a Distortion of Orofacial Somatorepresentation: A Narrative Review
Authors: von Piekartz Harry , Paris-Alemany Alba
Published: July 2021

The management of patients experiencing chronic orofacial pain is a great challenge, due to the complexity of chronic pain itself, combined with an increased peripheral sensitization in the craniofacial itself. Therefore, patients with orofacial pain may present a clear distortion of the somatorepresentation after some time. In this review, the authors develop a neurophysiological explanation of orofacial distortion, as well as propose assessment and treatment options, based on scarcely available scientific evidence and their own clinical experience. The assessments of facial somatosensory, cognitive-affective and motor dysfunctions are crucial to establish the most accurate treatment; the assessment tools are described in the article. Two-point discrimination, laterality recognition and emotion recognition are altered in patients with orofacial pain. Other sensorimotor assessment tools, such as motor acuity and auditory acuity, are also explained. Finally, the authors review their treatment proposals, based on the integration of brain training techniques and biobehavioral interventions. Somatosensory reintegration (tactile acuity training), facial emotion recognition, movement representation techniques, orofacial motor training and therapeutic patient education are explained in detail, and this may challenge new directions in rehabilitation and research.
Spanish Poplar Biomass as a Precursor for Nanocellulose Extraction
Authors: Mehanny Sherif , Magd Ehab E. Abu-El , Sorbara Simona , Navarro Jorge , Gil-San-Millan Rodrigo
Published: July 2021

The effect of acidic hydrolysis duration on nanocellulose size, morphology, and proper ties was investigated, which opens up a whole new horizon of versatility in poplar applications. This study aimed to examine Spanish poplar wastes as raw material to extract crystalline nanocellulose (CNC), which substantiates the importance of poplar wastes. Wastes were pulped using 1 L of 10% NaOH (wt./wt.) solution, and bleached several times by NaClO2; afterwards, white wastes were subjected to acidic hydrolysis by 60% H2SO4 for either 5, 10, or 15 min. Microcrystalline cellulose (MCC) underwent a similar hydrolysis protocol as poplar as control. TEM, IR, and XRD characterization techniques were performed. Poplar based nanocellulose sized 219 nm length and 69 nm width after 15 min acidic hydrolysis. MCC yielded 122 nm length and 12 nm width crystals after 10 min acidic hydrolysis. Hydrolysis resulted in a drastic change and intense peaks at 3500 and 2900 cm−1 for nanocellulose. Although pre-hydrolysis fiber treatment was not influencial on the crystallinity of poplar, acidic hydrolysis remarkably raised the crystallinity index (CI) by 7–8%. The more hydrolysis duration was prolonged, the size of the resulting crystal (whisker) decreased, and the aspect ratio increased. Hydrolysis was more impactful on MCC than poplar. However, for future work, it seems that longer duration of pulping and bleaching could have significantly removed unwanted components (hemicellulose and lignin), showcased in IR and XRD, and hence smoothened the following hydrolysis.
Climate Influence in Dendrochronological Series of Araucaria angustifolia from Campos do Jordão, Brazil
Authors: da Silva Daniela Oliveira , Prestes Alan , Klausner Virginia , de Souza Táyla Gabrielle Gonçalves
Published: July 2021

A dendrochronological series of Araucaria angustifolia was analyzed for a better understanding of the climatic factors that operate in Campos do Jordão city, São Paulo state, Brazil. The dendroclimatic analysis was carried out using 45 samples from 16 Araucaria angustifolia trees to reconstruct the precipitation and the temperature over the 1803–2012 yearly interval. To this end, Pearson’s correlation was calculated between mean chronology and the climatic time series using a monthly temporal resolution to calibrate our models. We obtained correlations as high as r=0.22(α=0.1) for precipitation (February), and r=0.21(α=0.1) for temperature (March), both corresponding to the end of the summer season. Our results show evidence of temporal instabilities because the correlations for the halves of 1963–2012 were very different, as well as for the full period. To overcome this problem, the dendrochronological series and the climatic data were investigated using the wavelet techniques searching for time-dependent cause–effect relationships. From these analyses, we find a strong influence of the region’s precipitation and temperature on the growth of tree ring widths.
CRISPR/Cas12a-Based Ultrasensitive and Rapid Detection of JAK2 V617F Somatic Mutation in Myeloproliferative Neoplasms
Authors: Chen Miaomiao , Zhang Chunhua , Hu Zhiqing , Li Zhuo , Li Menglin , Wu Lingqian , Zhou Miaojin , Liang Desheng
Published: July 2021

The JAK2 V617F mutation is a major diagnostic, therapeutic, and monitoring molecular target of Philadelphia-negative myeloproliferative neoplasms (MPNs). To date, numerous methods of detecting the JAK2 V617F mutation have been reported, but there is no gold-standard diagnostic method for clinical applications. Here, we developed and validated an efficient Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 12a (Cas12a)-based assay to detect the JAK2 V617F mutation. Our results showed that the sensitivity of the JAK2 V617F/Cas12a fluorescence detection system was as high as 0.01%, and the JAK2 V617F/Cas12a lateral flow strip assay could unambiguously detect as low as 0.5% of the JAK2 V617F mutation, which was much higher than the sensitivity required for clinical application. The minimum detectable concentration of genomic DNA achieved was 0.01 ng/μL (~5 aM, ~3 copies/μL). In addition, the whole process only took about 1.5 h, and the cost of an individual test was much lower than that of the current assays. Thus, our methods can be applied to detect the JAK2 V617F mutation, and they are highly sensitive, rapid, cost-effective, and convenient.
Non-Suicidal Self-Injury: An Observational Study in a Sample of Adolescents and Young Adults
Authors: Matera Emilia , Margari Mariella , Serra Maria , Petruzzelli Maria Giuseppina , Gabellone Alessandra , Piarulli Francesco Maria , Pugliese Assunta , Tassiello Anna Rita , Croce Federica , Renna Caterina , Margari Anna
Published: July 2021

Non-Suicidal Self-Injury (NSSI) is the self-inflicted destruction of body tissues without suicidal intent with a prevalence of 1.5% to 6.7% in the youth population. At present, it is not clear which emotional and behavioral components are specifically associated with it. Therefore, we studied NSSI in a clinical sample of youth using the Ottawa Self-injury Inventory and the Barratt Impulsiveness Scale 11. The Mann–Whitney test was used to compare the numerical responses provided to the tests. We found 54 patients with NSSI, with a mean age of 17 years. Scores were analyzed in the total sample and in four subgroups. In the total sample, Internal Emotion and External Emotion Regulation, Craving, Non-Planning and Total Impulsivity were significantly associated with NSSI. There were statistically significant differences in Craving between patients with multiple NSSI episodes, suicide attempts and multiple injury modes and patients of other corresponding subgroups, in Internal Emotion Regulation, Sensation Seeking and Motor Impulsivity between NSSI patients with suicide attempts and no suicide attempts, and in Cognitive Impulsivity between NSSI patients with multiple injury modes and one injury mode. It is necessary to carefully evaluate the components underlying NSSI in order to activate personalized treatment options.
Restrained Eating Is Associated with Lower Cortical Thickness in the Inferior Frontal Gyrus in Adolescents
Authors: García-García Isabel , Garolera Maite , Ottino-González Jonatan , Prats-Soteras Xavier , Prunell-Castañé Anna , Jurado María Ángeles
Published: July 2021

Some eating patterns, such as restrained eating and uncontrolled eating, are risk factors for eating disorders. However, it is not yet clear whether they are associated with neurocognitive differences. In the current study, we analyzed whether eating patterns can be used to classify participants into meaningful clusters, and we examined whether there are neurocognitive differences between the clusters. Adolescents (n = 108; 12 to 17 years old) and adults (n = 175, 18 to 40 years old) completed the Three Factor Eating Questionnaire, which was used to classify participants according to their eating profile using k means clustering. Participants also completed personality questionnaires and a neuropsychological examination. A subsample of participants underwent a brain MRI acquisition. In both samples, we obtained a cluster characterized by high uncontrolled eating patterns, a cluster with high scores in restrictive eating, and a cluster with low scores in problematic eating behaviors. The clusters were equivalent with regards to personality and performance in executive functions. In adolescents, the cluster with high restrictive eating showed lower cortical thickness in the inferior frontal gyrus compared to the other two clusters. We hypothesize that this difference in cortical thickness represents an adaptive neural mechanism that facilitates inhibition processes.
Renal Involvement in Hereditary Transthyretin Amyloidosis: An Italian Single-Centre Experience
Authors: Ferraro Pietro Manuel , D’Ambrosio Viola , Di Paolantonio Andrea , Guglielmino Valeria , Calabresi Paolo , Sabatelli Mario , Luigetti Marco
Published: July 2021

Objective: Hereditary transthyretin amyloidosis (ATTRv) represents a diagnostic challenge considering the great variability of clinical presentation and multiorgan involvement. In the present study, we report the prevalence of kidney involvement and kidney function over time in a cohort of ATTRv patients with different transthyretin gene mutations. Patients and Methods: For this study, we systematically collected data from all patients with a diagnosis of ATTRv followed at the Neurology Unit of Fondazione Policlinico Universitario A. Gemelli IRCCS. Kidney involvement was defined as presence of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 obtained with CKD-EPI equation, abnormal urinary protein excretion (UPE) (>150 mg/24 h) and/or albuminuria > 30 mg/24 h (or mg/g creatinine). The analysis included data from 46 patients with 122 measurements of serum creatinine. Results: Among the 46 patients included in the analysis, kidney involvement was present in 37%, with 15% showing reduced eGFR and 22% abnormal UPE (63% of patients with available UPE data). No single predictor was associated with either eGFR values or its slope over time. Conclusions: Kidney involvement is quite common in patients with ATTRv regardless of the underlying genetic variant. In particular, abnormal UPE appears to be a common feature of the disease.
Characterizing Positive Energy District (PED) through a Preliminary Review of 60 Existing Projects in Europe
Authors: Zhang Xingxing , Penaka Santhan , Giriraj Samhita , Sánchez Maria , Civiero Paolo , Vandevyvere Han
Published: July 2021

Positive Energy District (PED) is recently proposed to be an integral part of a district/urban energy system with a corresponding positive influence. Thus, the PED concept could become the key solution to energy system transition towards carbon neutrality. This paper intends to report and visualize the initial analytical results of 60 existing PED projects in Europe about their main characteristics, including geographical information, spatial-temporal scale, energy concepts, building archetypes, finance source, keywords, finance model and challenges/barriers. As a result, a dedicated date base is developed and it could be further expanded/interoperated through an interactive dashboard. It is found that Norway and Italy have the most PED projects so far. Many PED projects state a ‘yearly’ time scale while nearly 1/3 projects have less than 0.2 km2 area in terms of spatial scale. The private investment together with regional/national grants is commonly observed. A mixture of residential, commercial and office/social buildings are found. The most common renewable energy systems include solar energy, district heating/cooling, wind and geothermal energy. Challenges and barriers for PED related projects vary from the planning stage to the implementation stage. Furthermore, the text mining approach is applied to examine the keywords or concentrations of PED-related projects at different stages. These preliminary results are expected to give useful guidance for future PED definitions and proposals of ‘reference PED’.
Immunotherapy in Glioblastoma: A Clinical Perspective
Authors: Desbaillets Nicolas , Hottinger Andreas Felix
Published: July 2021

Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. In this review, the rationale underlying immune targeting of glioblastoma, as well as the challenges faced when targeting these highly immunosuppressive tumors, are discussed. Innovative immune-targeting strategies including cancer vaccines, oncolytic viruses, checkpoint blockade inhibitors, adoptive cell transfer, and CAR T cells that have been investigated in glioblastoma are reviewed. From a clinical perspective, key clinical trial findings and ongoing trials are discussed for each approach. Finally, limitations, either biological or arising from trial designs are analyzed, and strategies to overcome them are presented. Proof of efficacy for immunotherapy approaches remains to be demonstrated in glioblastoma, but our rapidly expanding understanding of its biology, its immune microenvironment, and the emergence of novel promising combinatorial approaches might allow researchers to finally fulfill the medical need for GBM patients.
Characterization of a Solvent-Tolerant Amidohydrolase Involved in Natural Product Heterocycle Formation
Authors: Winand Lea , Vollmann Dustin Joshua , Hentschel Jacqueline , Nett Markus
Published: July 2021

Heterocycles are important building blocks in pharmaceutical drugs and their enzymatic synthesis is attracting increasing interest. In recent years, various enzymes of the amidohydrolase superfamily were reported to catalyze heterocycle-forming condensation reactions. One of these enzymes, MxcM, is biochemically and kinetically characterized in this study. MxcM generates an imidazoline moiety in the biosynthesis of the natural product pseudochelin A, which features potent anti-inflammatory properties. The enzyme shows maximal activity at 50 °C and pH 10 as well as a kcat/Km value of 22,932 s−1 M−1 at its temperature optimum. Experimental data suggest that the activity of MxcM does not depend on a catalytic metal ion, which is uncommon among amidohydrolases. MxcM is highly active in diverse organic solvents and concentrated salt solutions. Furthermore, we show that MxcM is also capable to introduce imidazoline rings into derivatives of its natural substrate myxochelin B. Overall, MxcM is a solvent-stable, halotolerant enzyme with promising biochemical and kinetic properties and, in future, might become a valuable biocatalyst for the manufacturing of pharmaceutical drugs.
Turbidity Changes during Carbamazepine Oxidation by Photo-Fenton
Authors: Villota Natalia , Ferreiro Cristian , Qulatein Hussein A. , Lomas Jose M. , Lombraña Jose Ignacio
Published: July 2021

The objective of this study is to evaluate the turbidity generated during the Fenton photo-reaction applied to the oxidation of waters containing carbamazepine as a function of factors such as pH, H2O2 concentration and catalyst dosage. The results let establish the degradation pathways and the main decomposition byproducts. It is found that the pH affects the turbidity of the water. Working between pH = 2.0 and 2.5, the turbidity is under 1 NTU due to the fact that iron, added as a catalyst, is in the form of a ferrous ion. Operating at pH values above 3.0, the iron species in their oxidized state (mainly ferric hydroxide in suspension) would cause turbidity. The contribution of these ferric species is a function of the concentration of iron added to the process, verifying that the turbidity increases linearly according to a ratio of 0.616 NTU L/mg Fe. Performing with oxidant concentrations at (H2O2) = 2.0 mM, the turbidity undergoes a strong increase until reaching values around 98 NTU in the steady state. High turbidity levels can be originated by the formation of coordination complexes, consisting of the union of three molecules containing substituted carboxylic groups (BaQD), which act as ligands towards an iron atom with Fe3+ oxidation state.
The Parkinson’s Disease-Associated Protein DJ-1 Protects Dictyostelium Cells from AMPK-Dependent Outcomes of Oxidative Stress
Authors: Chen Suwei , Annesley Sarah J. , Jasim Rasha A. F. , Fisher Paul R.
Published: July 2021

Mitochondrial dysfunction has been implicated in the pathology of Parkinson’s disease (PD). In Dictyostelium discoideum, strains with mitochondrial dysfunction present consistent, AMPK-dependent phenotypes. This provides an opportunity to investigate if the loss of function of specific PD-associated genes produces cellular pathology by causing mitochondrial dysfunction with AMPK-mediated consequences. DJ-1 is a PD-associated, cytosolic protein with a conserved oxidizable cysteine residue that is important for the protein’s ability to protect cells from the pathological consequences of oxidative stress. Dictyostelium DJ-1 (encoded by the gene deeJ) is located in the cytosol from where it indirectly inhibits mitochondrial respiration and also exerts a positive, nonmitochondrial role in endocytosis (particularly phagocytosis). Its loss in unstressed cells impairs endocytosis and causes correspondingly slower growth, while also stimulating mitochondrial respiration. We report here that oxidative stress in Dictyostelium cells inhibits mitochondrial respiration and impairs phagocytosis in an AMPK-dependent manner. This adds to the separate impairment of phagocytosis caused by DJ-1 knockdown. Oxidative stress also combines with DJ-1 loss in an AMPK-dependent manner to impair or exacerbate defects in phototaxis, morphogenesis and growth. It thereby phenocopies mitochondrial dysfunction. These results support a model in which the oxidized but not the reduced form of DJ-1 inhibits AMPK in the cytosol, thereby protecting cells from the adverse consequences of oxidative stress, mitochondrial dysfunction and the resulting AMPK hyperactivity.
The Combined Treatment with Chemotherapeutic Agents and the Dualsteric Muscarinic Agonist Iper-8-Naphthalimide Affects Drug Resistance in Glioblastoma Stem Cells
Authors: Guerriero Claudia , Matera Carlo , Del Bufalo Donatella , De Amici Marco , Conti Luciano , Dallanoce Clelia , Tata Ada Maria
Published: July 2021

Background: Glioblastoma multiforme (GBM) is characterized by heterogeneous cell populations. Among these, the Glioblastoma Stem Cells (GSCs) fraction shares some similarities with Neural Stem Cells. GSCs exhibit enhanced resistance to conventional chemotherapy drugs. Our previous studies demonstrated that the activation of M2 muscarinic acetylcholine receptors (mAChRs) negatively modulates GSCs proliferation and survival. The aim of the present study was to analyze the ability of the M2 dualsteric agonist Iper-8-naphthalimide (N-8-Iper) to counteract GSCs drug resistance. Methods: Chemosensitivity to M2 dualsteric agonist N-8-Iper and chemotherapy drugs such as temozolomide, doxorubicin, or cisplatin was evaluated in vitro by MTT assay in two different GSC lines. Drug efflux pumps expression was evaluated by RT-PCR and qRT-PCR. Results: By using sub-toxic concentrations of N-8-Iper combined with the individual chemotherapeutic agents, we found that only low doses of the M2 agonist combined with doxorubicin or cisplatin or temozolomide were significantly able to counteract cell growth in both GSC lines. Moreover, we evaluated as the exposure to high and low doses of N-8-Iper downregulated the ATP-binding cassette (ABC) drug efflux pumps expression levels. Conclusions: Our results revealed the ability of the investigated M2 agonist to counteract drug resistance in two GSC lines, at least partially by downregulating the ABC drug efflux pumps expression. The combined effects of low doses of conventional chemotherapy and M2 agonists may thus represent a novel promising pharmacological approach to impair the GSC-drug resistance in the GBM therapy.
Role of NRF2 in Lung Cancer
Authors: Sánchez-Ortega Miriam , Carrera Ana Clara , Garrido Antonio
Published: July 2021

The gene expression program induced by NRF2 transcription factor plays a critical role in cell defense responses against a broad variety of cellular stresses, most importantly oxidative stress. NRF2 stability is fine-tuned regulated by KEAP1, which drives its degradation in the absence of oxidative stress. In the context of cancer, NRF2 cytoprotective functions were initially linked to anti-oncogenic properties. However, in the last few decades, growing evidence indicates that NRF2 acts as a tumor driver, inducing metastasis and resistance to chemotherapy. Constitutive activation of NRF2 has been found to be frequent in several tumors, including some lung cancer sub-types and it has been associated to the maintenance of a malignant cell phenotype. This apparently contradictory effect of the NRF2/KEAP1 signaling pathway in cancer (cell protection against cancer versus pro-tumoral properties) has generated a great controversy about its functions in this disease. In this review, we will describe the molecular mechanism regulating this signaling pathway in physiological conditions and summarize the most important findings related to the role of NRF2/KEAP1 in lung cancer. The focus will be placed on NRF2 activation mechanisms, the implication of those in lung cancer progression and current therapeutic strategies directed at blocking NRF2 action.
Macrophage as a Peripheral Pain Regulator
Authors: Domoto Risa , Sekiguchi Fumiko , Tsubota Maho , Kawabata Atsufumi
Published: July 2021

A neuroimmune crosstalk is involved in somatic and visceral pathological pain including inflammatory and neuropathic components. Apart from microglia essential for spinal and supraspinal pain processing, the interaction of bone marrow-derived infiltrating macrophages and/or tissue-resident macrophages with the primary afferent neurons regulates pain signals in the peripheral tissue. Recent studies have uncovered previously unknown characteristics of tissue-resident macrophages, such as their origins and association with regulation of pain signals. Peripheral nerve macrophages and intestinal resident macrophages, in addition to adult monocyte-derived infiltrating macrophages, secrete a variety of mediators, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, high mobility group box 1 and bone morphogenic protein 2 (BMP2), that regulate the excitability of the primary afferents. Neuron-derived mediators including neuropeptides, ATP and macrophage-colony stimulating factor regulate the activity or polarization of diverse macrophages. Thus, macrophages have multitasks in homeostatic conditions and participate in somatic and visceral pathological pain by interacting with neurons.
Tissue-Resident T Cells in Chronic Relapsing–Remitting Intestinal Disorders
Authors: Barreto de Albuquerque Juliana , Mueller Christoph , Gungor Bilgi
Published: July 2021

Tissue-resident memory T (TRM) cells critically contribute to the rapid immunoprotection and efficient immunosurveillance against pathogens, particularly in barrier tissues, but also during anti-tumor responses. However, the involvement of TRM cells also in the induction and exacerbation of immunopathologies, notably in chronically relapsing auto-inflammatory disorders, is becoming increasingly recognized as a critical factor. Thus, TRM cells may also represent an attractive target in the management of chronic (auto-) inflammatory disorders, including multiple sclerosis, rheumatoid arthritis, celiac disease and inflammatory bowel diseases. In this review, we focus on current concepts of TRM cell biology, particularly in the intestine, and discuss recent findings on their involvement in chronic relapsing–remitting inflammatory disorders. Potential therapeutic strategies to interfere with these TRM cell-mediated immunopathologies are discussed.
Long Non-Coding RNAs Involved in Progression of Non-Alcoholic Fatty Liver Disease to Steatohepatitis
Authors: Atanasovska Biljana , Rensen Sander S. , Marsman Glenn , Shiri-Sverdlov Ronit , Withoff Sebo , Kuipers Folkert , Wijmenga Cisca , van de Sluis Bart , Fu Jingyuan
Published: July 2021

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease and is characterized by different stages varying from benign fat accumulation to non-alcoholic steatohepatitis (NASH) that may progress to cirrhosis and liver cancer. In recent years, a regulatory role of long non-coding RNAs (lncRNAs) in NAFLD has emerged. Therefore, we aimed to characterize the still poorly understood lncRNA contribution to disease progression. Transcriptome analysis in 60 human liver samples with various degrees of NAFLD/NASH was combined with a functional genomics experiment in an in vitro model where we exposed HepG2 cells to free fatty acids (FFA) to induce steatosis, then stimulated them with tumor necrosis factor alpha (TNFα) to mimic inflammation. Bioinformatics analyses provided a functional prediction of novel lncRNAs. We further functionally characterized the involvement of one novel lncRNA in the nuclear-factor-kappa B (NF-κB) signaling pathway by its silencing in Hepatoma G2 (HepG2) cells. We identified 730 protein-coding genes and 18 lncRNAs that responded to FFA/TNFα and associated with human NASH phenotypes with consistent effect direction, with most being linked to inflammation. One novel intergenic lncRNA, designated lncTNF, was 20-fold up-regulated upon TNFα stimulation in HepG2 cells and positively correlated with lobular inflammation in human liver samples. Silencing lncTNF in HepG2 cells reduced NF-κB activity and suppressed expression of the NF-κB target genes A20 and NFKBIA. The lncTNF we identified in the NF-κB signaling pathway may represent a novel target for controlling liver inflammation.
Ciliary Dyneins and Dynein Related Ciliopathies
Authors: Antony Dinu , Brunner Han G. , Schmidts Miriam
Published: July 2021

Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel developments in the field.
Germ Cell Derivation from Pluripotent Stem Cells for Understanding In Vitro Gametogenesis
Authors: Hong Tae-Kyung , Song Jae-Hoon , Lee So-Been , Do Jeong-Tae
Published: July 2021

Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising technology to overcome infertility, particularly germ cell aplasia. Early germ cells, such as primordial germ cells, can be relatively easily derived from pluripotent stem cells (PSCs); however, further progression to post-meiotic germ cells usually requires a gonadal niche and signals from gonadal somatic cells. Here, we review the recent advances in in vitro male and female germ cell derivation from PSCs and discuss how this technique is used to understand the biological mechanism of gamete development and gain insight into its application in infertility.
Prognostic Value of a Glycolytic Signature and Its Regulation by Y-Box-Binding Protein 1 in Triple-Negative Breast Cancer
Authors: Lai Yi-Wen , Hsu Wen-Jing , Lee Wen-Ying , Chen Cheng-Hsun , Tsai Ying-Huei , Dai Jia-Zih , Yang Ching-Chieh , Lin Cheng-Wei
Published: July 2021

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer as it shows a high capacity for metastasis and poor prognoses. Metabolic reprogramming is one of the hallmarks of cancer, and aberrant glycolysis was reported to be upregulated in TNBC. Thus, identifying metabolic biomarkers for diagnoses and investigating cross-talk between glycolysis and invasiveness could potentially enable the development of therapeutics for patients with TNBC. In order to determine novel and reliable metabolic biomarkers for predicting clinical outcomes of TNBC, we analyzed transcriptome levels of glycolysis-related genes in various subtypes of breast cancer from public databases and identified a distinct glycolysis gene signature, which included ENO1, SLC2A6, LDHA, PFKP, PGAM1, and GPI, that was elevated and associated with poorer prognoses of TNBC patients. Notably, we found a transcription factor named Y-box-binding protein 1 (YBX1) to be strongly associated with this glycolysis gene signature, and it was overexpressed in TNBC. A mechanistic study further validated that YBX1 was upregulated in TNBC cell lines, and knockdown of YBX1 suppressed expression of those glycolytic genes. Moreover, YBX1 expression was positively associated with epithelial-to-mesenchymal transition (EMT) genes in breast cancer patients, and suppression of YBX1 downregulated expressions of EMT-related genes and tumor migration and invasion in MDA-MB-231 and BT549 TNBC cells. Our data revealed an YBX1-glycolysis-EMT network as an attractive diagnostic marker and metabolic target in TNBC patients.
Role of Long Non-Coding RNAs in Pulmonary Arterial Hypertension
Authors: Han Yun , Ali Md Khadem , Dua Kamal , Spiekerkoetter Edda , Mao Yuqiang
Published: July 2021

Pulmonary arterial hypertension (PAH) is a debilitating condition of the pulmonary circulatory system that occurs in patients of all ages and if untreated, eventually leads to right heart failure and death. Despite existing medical treatment options that improve survival and quality of life, the disease remains incurable. Thus, there is an urgent need to develop novel therapies to treat this disease. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in pulmonary vascular remodeling and PAH. LncRNAs are implicated in pulmonary arterial endothelial dysfunction by modulating endothelial cell proliferation, angiogenesis, endothelial mesenchymal transition, and metabolism. LncRNAs are also involved in inducing different pulmonary arterial vascular smooth muscle cell phenotypes, such as cell proliferation, apoptosis, migration, regulation of the phenotypic switching, and cell cycle. LncRNAs are essential regulators of gene expression that affect various diseases at the chromatin, transcriptional, post-translational, and even post-translational levels. Here, we focus on the role of LncRNAs and their molecular mechanisms in the pathogenesis of PAH. We also discuss the current research challenge and potential biomarker and therapeutic potentials of lncRNAs in PAH.
PEO Infiltration of Porous Garnet-Type Lithium-Conducting Solid Electrolyte Thin Films
Authors: Waidha Aamir Iqbal , Vanita Vanita , Clemens Oliver
Published: July 2021

Composite electrolytes containing lithium ion conducting polymer matrix and ceramic filler are promising solid-state electrolytes for all solid-state lithium ion batteries due to their wide electrochemical stability window, high lithium ion conductivity and low electrode/electrolyte interfacial resistance. In this study, we report on the polymer infiltration of porous thin films of aluminum-doped cubic garnet fabricated via a combination of nebulized spray pyrolysis and spin coating with subsequent post annealing at 1173 K. This method offers a simple and easy route for the fabrication of a three-dimensional porous garnet network with a thickness in the range of 50 to 100 µm, which could be used as the ceramic backbone providing a continuous pathway for lithium ion transport in composite electrolytes. The porous microstructure of the fabricated thin films is confirmed via scanning electron microscopy. Ionic conductivity of the pristine films is determined via electrochemical impedance spectroscopy. We show that annealing times have a significant impact on the ionic conductivity of the films. The subsequent polymer infiltration of the porous garnet films shows a maximum ionic conductivity of 5.3 × 10−7 S cm−1 at 298 K, which is six orders of magnitude higher than the pristine porous garnet film.
Rear Earth Oxide Multilayer Deposited by Plasma Spray-Physical Vapor Deposition for Envisaged Application as Thermal/Environmental Barrier Coating
Authors: Zhong Jie , Yang Dongling , Guo Shuangquan , Zhang Xiaofeng , Liang Xinghua , Wu Xi
Published: July 2021

SiC fiber-reinforced SiC ceramic matrix composites (SiCf/SiC CMCs) are being increasingly used in the hot sections of gas turbines because of their light weight and mechanical properties at high temperatures. The objective of this investigation was the development of a thermal/environmental barrier coating (T/EBC) composite coating system consisting of an environmental barrier coating (EBC) to protect the ceramic matrix composites from chemical attack and a thermal barrier coating (TBC) that insulates and reduces the ceramic matrix composites substrate temperature for increased lifetime. In this paper, a plasma spray-physical vapor deposition (PS-PVD) method was used to prepare multilayer Si–HfO2/Yb2Si2O7/Yb2SiO5/Gd2Zr2O7 composite coatings on the surface of SiCf/SiC ceramic matrix composites. The purpose of this study is to develop a coating with resistance to high temperatures and chemical attack. Different process parameters are adopted, and their influence on the microstructure characteristics of the coating is discussed. The water quenching thermal cycle of the coating at high temperatures was tested. The results show that the structure of the thermal/environmental barrier composite coating changes after water quenching because point defects and dislocations appear in the Gd2Zr2O7 and Yb2SiO5 coatings. A phase transition was found to occur in the Yb2SiO5 and Yb2Si2O7 coatings. The failure mechanism of the T/EBC composite coating is mainly spalling when the top layer penetrates cracks and cracking occurs in the interface of the Si–HfO2/Yb2Si2O7 coating.
A Narrative Review of the Complex Relationship between Pregnancy and Eye Changes
Authors: Anton Nicoleta , Doroftei Bogdan , Ilie Ovidiu-Dumitru , Ciuntu Roxana-Elena , Bogdănici Camelia Margareta , Nechita-Dumitriu Ionela
Published: July 2021

Pregnancy is a condition often characterized by changes that occur in different parts of the body. Generally, the eyes suffer several changes during pregnancy that are usually transient but may become permanent at times. This may occur due to the release of placental hormones and those of maternal endocrine glands and fetal adrenal glands. Due to hormonal influences, physiological ocular changes during pregnancy have been shown in Caucasian women, so corneal sensitivity, refractive status, intraocular pressure, and visual acuity may change during pregnancy. Within this review, all studies that referred to physiological aspects and to changes of ocular pathology of pregnancy, the effect of the pregnancy on pre-existing (diabetic retinopathy, neuro-ophthalmic disorders) eye disorders, postpartum ocular changes, the intraocular pressure and the effect of hypotensive ophthalmic medicine during pregnancy, the connection between pregnancy and the neuro-ophthalmic pathology, as well as the role of anesthesia were analyzed.
Spectrum of Causative Pathogens and Resistance Rates to Antibacterial Agents in Bacterial Prostatitis
Authors: Trinchieri Alberto , Abdelrahman Khalid Mohammed , Bhatti Kamran Hassan , Bello Jibril O. , Das Krishanu , Gatsev Ognyan , Gergova Ivanka , Magri Vittorio , Mourmouras Nikos , Mourmouris Panagiotis , Murdeshwar Soni , Perletti Gianpaolo , Saltirov Iliya , Sissoko Idrissa , Stamatiou Konstantinos , Buchholz Noor
Published: July 2021

Objective: To evaluate spectrum and resistance rates to antibacterial agents in causative pathogens of bacterial prostatitis in patients from Southern Europe, the Middle East, and Africa. Materials: 1027 isolates from cultures of urine or expressed prostatic secretion, post-massage urine or seminal fluid, or urethral samples were considered. Results: Escherichia coli (32%) and Enterococcus spp. (21%) were the most common isolates. Other Gram-negative, Gram-positive, and atypical pathogens accounted for 22%, 20%, and 5%, respectively. Resistance was <15% for piperacillin/tazobactam and carbapenems (both Gram-negative and -positive pathogens); <5% for glycopeptides against Gram-positive; 7%, 14%, and 20% for aminoglycosides, fosfomycin, and macrolides against Gram-negative pathogens, respectively; 10% for amoxicillin/clavulanate against Gram-positive pathogens; <20% for cephalosporins and fluoroquinolones against to Gram-negative pathogens (higher against Gram-positive pathogens); none for macrolides against atypical pathogens, but 20% and 27% for fluoroquinolones and tetracyclines. In West Africa, the resistance rates were generally higher, although the highest rates for ampicillin, cephalosporins, and fluoroquinolones were observed in the Gulf area. Lower rates were observed in Southeastern Europe. Conclusions: Resistance to antibiotics is a health problem requiring local health authorities to combat this phenomenon. Knowledge of the spectrum of pathogens and antibiotic resistance rates is crucial to assess local guidelines for the treatment of prostatitis.
Lorenz-63 Model as a Metaphor for Transient Complexity in Climate
Authors: Kravtsov Sergey , Tsonis Anastasios A.
Published: July 2021

Dynamical systems like the one described by the three-variable Lorenz-63 model may serve as metaphors for complex natural systems such as climate systems. When these systems are perturbed by external forcing factors, they tend to relax back to their equilibrium conditions after the forcing has shut off. Here we investigate the behavior of such transients in the Lorenz-63 model by studying its trajectories initialized far away from the asymptotic attractor. Counterintuitively, these transient trajectories exhibit complex routes and, in particular, the sensitivity to initial conditions is akin to that of the asymptotic behavior on the attractor. Thus, similar extreme events may lead to widely different variations before the perturbed system returns back to its statistical equilibrium.
Burnout, Organizational Self-Efficacy and Self-Esteem among Brazilian Teachers during the COVID-19 Pandemic
Authors: Pereira Henrique , Gonçalves Vivianne Oliveira , Assis Renata Machado de
Published: July 2021

The purpose of this study was to assess the prevalence of, and the association between burnout, organizational self-efficacy and self-esteem, and to assess the predictive influence of burnout and organizational self-efficacy on self-esteem among Brazilian teachers during the COVID-19 pandemic. Brazilian teachers (n = 302) between 24 and 70 years old (Mage = 46.75, SD = 11.02) participated in this study. Measurement instruments included a sociodemographic questionnaire, the Burnout Assessment Tool, the Organizational Self-Efficacy Scale and the Rosenberg Self-Esteem Scale. The prevalence of burnout symptoms was 3.2%, the prevalence of low occupational self-efficacy was 21.5%, and the prevalence of low self-esteem was 2.7%. Significant correlations were found between all variables under study. Hierarchical linear regression analysis showed that overall levels of burnout explained 40% of the variance of self-esteem, while together with organizational self-efficacy, it explained 55%. This study presents evidence of the impact of overall levels of burnout and self-efficacy on teachers’ self-esteem and also contributes to the body of knowledge under construction about the scenario perceived by teachers in Brazil during the COVID-19 pandemic.
Factors Related with Underperformance in Reading Proficiency, the Case of the Programme for International Student Assessment 2018
Authors: Vazquez-Lopez Vianey , Huerta-Manzanilla Eric Leonardo
Published: July 2021

Almost 217 million secondary school students (60% of the world’s adolescents) do not reach minimum levels in reading proficiency at the end of secondary school, according to objective 4.1 of the UN’s Sustainable Development Goals. Therefore, the early and efficient identification of this disadvantage and implementation of remedial strategies is critical for economies. In 2018, the Programme for International Student Assessment (PISA) assessed the reading skills of 15-year-old students in 80 countries and economies. This work introduces a methodology that uses PISA’s data to build logistic regression models to identify the main factors contributing to students’ underperforming reading skills. Results showed that socioeconomic status (SES), metacognition strategies, Information and Communication Technology (ICT) skills, and student–teacher relationships are the most important contributors to low reading abilities.
Bloom Filter-Based Parallel Architecture for Accelerating Equi-Join Operation on FPGA
Authors: He Binhao , Xue Meiting , Liu Shubiao , Luo Wei
Published: July 2021

As one of the most important operations in relational databases, the join is data-intensive and time-consuming. Thus, offloading this operation using field-programmable gate arrays (FPGAs) has attracted much interest and has been broadly researched in recent years. However, the available SRAM-based join architectures are often resource-intensive, power-consuming, or low-throughput. Besides, a lower match rate does not lead to a shorter operation time. To address these issues, a Bloom filter (BF)-based parallel join architecture is presented in this paper. This architecture first leverages the BF to discard the tuples that are not in the join result and classifies the remaining tuples into different channels. Second, a binary search tree is used to reduce the number of comparisons. The proposed method was implemented on a Xilinx FPGA, and the experimental results show that under a match rate of 50%, our architecture achieved a high join throughput of 145.8 million tuples per second and a maximum acceleration factor of 2.3 compared to the existing SRAM-based join architectures.
Energy, Exergy, Exergoeconomic, and Exergoenvironmental Assessment of Flash-Binary Geothermal Combined Cooling, Heating and Power Cycle
Authors: Shamoushaki Moein , Aliehyaei Mehdi , Taghizadeh-Hesary Farhad
Published: July 2021

This research presents the energy, exergy, economic, and environmental assessment, and multi-objective optimization of a flash-binary geothermal CCHP cycle. A sensitivity analysis of production well inlet temperature and cooling to power flow ratio on exergetic, economic, and environmental parameters was conducted. Furthermore, the effects of the inflation rate and plant working hours on economic parameters were investigated. Results showed that increasing the production well inlet temperature harms exergy efficiency and exergetic performance criteria and results in a gain in exergo-environmental impact index and heating capacity. In addition, the total plant cost increased by raising the production well temperature. Furthermore, increasing the cooling to power flow ratio caused a reduction in exergy efficiency, exergetic performance criteria, and produced net power and an enhancement in exergy destruction, cooling capacity, and total plant cost. The exergy efficiency and total cost rate in the base case were 58% and 0.1764, respectively. Optimization results showed that at the selected optimum point, exergy efficiency was 4.5% higher, and the total cost rate was 10.3% lower than the base case. Levelized cost of energy and the pay-back period at the optimum point was obtained as 6.22 c$/kWh, 3.43 years, which were 5.14% and 6.7% lower than the base case.