bluuebunny/crossref_metadata_2025 huggingface dataset:
Biopolimer Peptide Batteries—A New Concept for Environmentally Friendly and Safer Energy Storage
Authors: Moklyak Volodymyr , Hrubiak Andrii , Gogitidze Zurab , Yavorskyi Yurii
Published: July 2021

The work shows a new approach to improving the performance of lithium power sources by using polypeptides as an active component of the cathode composition. Specifically, the experimental results of testing prototypes of lithium current sources with cathodes based on polypeptides, which demonstrate the value of the specific discharge capacity at the level of 2000–2700 mAh/g, depending on the content of the organic component, are presented. The use of the intermittent galvanostatic titration mode during the discharge showed an increase in the specific indicators of the current sources in comparison with the continuous discharge at different specific load currents. Based on this, the effect of “relaxation recovery” of the cathode material based on polypeptides was discovered, the essence of which is a significant increase (recovery) of the open-circuit voltage when the load of the lithium current source is disconnected, which leads to an increase of the discharge capacity without external energy influences. The functionalization of the surface of thermally expanded graphite with polypeptide components made it possible to create a cathode material, the use of which in lithium current source models increased the specific discharge capacity to 19,000 mA h/g at a discharge current of 10 mA/h.
MYOC Promotes the Differentiation of C2C12 Cells by Regulation of the TGF-β Signaling Pathways via CAV1
Authors: Zhang Yuhan , Li Shuang , Wen Xin , Tong Huili , Li Shufeng , Yan Yunqin
Published: July 2021

Myocilin (MYOC) is a glycoprotein encoded by a gene associated with glaucoma pathology. In addition to the eyes, it also expresses at high transcription levels in the heart and skeletal muscle. MYOC affects the formation of the murine gastrocnemius muscle and is associated with the differentiation of mouse osteoblasts, but its role in the differentiation of C2C12 cells has not yet been reported. Here, MYOC expression was found to increase gradually during the differentiation of C2C12 cells. Overexpression of MYOC resulted in enhanced differentiation of C2C12 cells while its inhibition caused reduced differentiation. Furthermore, immunoprecipitation indicated that MYOC binds to Caveolin-1 (CAV1), a protein that influences the TGF-β pathway. Laser confocal microscopy also revealed the common sites of action of the two during the differentiation of C2C12 cells. Additionally, CAV1 was upregulated significantly as C2C12 cells differentiated, with CAV1 able to influence the differentiation of the cells. Furthermore, the Western blotting analysis demonstrated that the expression of MYOC affected the TGF-β pathway. Finally, MYOC was overexpressed while CAV1 was inhibited. The results indicate that reduced CAV1 expression blocked the promotion of C2C12 cell differentiation by MYOC. In conclusion, the results demonstrated that MYOC regulates TGF-β by influencing CAV1 to promote the differentiation of C2C12 cells.
Ovarian Telomerase and Female Fertility
Authors: Toupance Simon , Fattet Anne-Julie , Thornton Simon N. , Benetos Athanase , Guéant Jean-Louis , Koscinski Isabelle
Published: July 2021

Women’s fertility is characterized both quantitatively and qualitatively mainly by the pool of ovarian follicles. Monthly, gonadotropins cause an intense multiplication of granulosa cells surrounding the oocyte. This step of follicular development requires a high proliferation ability for these cells. Telomere length plays a crucial role in the mitotic index of human cells. Hence, disrupting telomere homeostasis could directly affect women’s fertility. Strongly expressed in ovaries, telomerase is the most effective factor to limit telomeric attrition and preserve ovarian reserve. Considering these facts, two situations of infertility could be correlated with the length of telomeres and ovarian telomerase activity: PolyCystic Ovary Syndrome (PCOS), which is associated with a high density of small antral follicles, and Premature Ovarian Failure (POF), which is associated with a premature decrease in ovarian reserve. Several authors have studied this topic, expecting to find long telomeres and strong telomerase activity in PCOS and short telomeres and low telomerase activity in POF patients. Although the results of these studies are contradictory, telomere length and the ovarian telomerase impact in women’s fertility disorders appear obvious. In this context, our research perspectives aimed to explore the stimulation of ovarian telomerase to limit the decrease in the follicular pool while avoiding an increase in cancer risk.
Clinical Phenotype Classification of Atrial Fibrillation Patients Using Cluster Analysis and Associations with Trial-Adjudicated Outcomes
Authors: Vitolo Marco , Proietti Marco , Shantsila Alena , Boriani Giuseppe , Lip Gregory Y. H.
Published: July 2021

Background and purpose: Given the great clinical heterogeneity of atrial fibrillation (AF) patients, conventional classification only based on disease subtype or arrhythmia patterns may not adequately characterize this population. We aimed to identify different groups of AF patients who shared common clinical phenotypes using cluster analysis and evaluate the association between identified clusters and clinical outcomes. Methods: We performed a hierarchical cluster analysis in AF patients from AMADEUS and BOREALIS trials. The primary outcome was a composite of stroke/thromboembolism (TE), cardiovascular (CV) death, myocardial infarction, and/or all-cause death. Individual components of the primary outcome and major bleeding were also assessed. Results: We included 3980 AF patients treated with the Vitamin-K Antagonist from the AMADEUS and BOREALIS studies. The analysis identified four clusters in which patients varied significantly among clinical characteristics. Cluster 1 was characterized by patients with low rates of CV risk factors and comorbidities; Cluster 2 was characterized by patients with a high burden of CV risk factors; Cluster 3 consisted of patients with a high burden of CV comorbidities; Cluster 4 was characterized by the highest rates of non-CV comorbidities. After a mean follow-up of 365 (standard deviation 187) days, Cluster 4 had the highest cumulative risk of outcomes. Compared with Cluster 1, Cluster 4 was independently associated with an increased risk for the composite outcome (hazard ratio (HR) 2.43, 95% confidence interval (CI) 1.70–3.46), all-cause death (HR 2.35, 95% CI 1.58–3.49) and major bleeding (HR 2.18, 95% CI 1.19–3.96). Conclusions: Cluster analysis identified four different clinically relevant phenotypes of AF patients that had unique clinical characteristics and different outcomes. Cluster analysis highlights the high degree of heterogeneity in patients with AF, suggesting the need for a phenotype-driven approach to comorbidities, which could provide a more holistic approach to management aimed to improve patients’ outcomes.
Microbiota Depletion Promotes Human Rotavirus Replication in an Adult Mouse Model
Authors: Gozalbo-Rovira Roberto , Santiso-Bellón Cristina , Buesa Javier , Rubio-del-Campo Antonio , Vila-Vicent Susana , Muñoz Carlos , Yebra María J. , Monedero Vicente , Rodríguez-Díaz Jesús
Published: July 2021

Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice.
Endothelial Progenitor Cells: Relevant Players in the Vasculopathy and Lung Fibrosis Associated with the Presence of Interstitial Lung Disease in Systemic Sclerosis Patients
Authors: Pulito-Cueto Verónica , Remuzgo-Martínez Sara , Genre Fernanda , Atienza-Mateo Belén , Mora-Cuesta Víctor M. , Iturbe-Fernández David , Lera-Gómez Leticia , Pérez-Fernández Raquel , Prieto-Peña Diana , Portilla Virginia , Blanco Ricardo , Corrales Alfonso , Gualillo Oreste , Cifrián José M. , López-Mejías Raquel , González-Gay Miguel A.
Published: July 2021

Endothelial progenitor cells (EPC), which are key effectors in the physiologic vascular network, have been described as relevant players in autoimmune diseases. We previously showed that EPC frequency may help to identify the presence of interstitial lung disease (ILD) in rheumatoid arthritis patients. Given that ILD constitutes the main cause of mortality in systemic sclerosis (SSc) patients, we aimed to determine the EPC contribution to the pathogenic processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC quantification was performed by flow cytometry on blood from 83 individuals: 21 SSc-ILD+ patients and subjects from comparative groups (20 SSc-ILD− and 21 idiopathic pulmonary fibrosis (IPF) patients and 21 healthy controls (HC)). EPC were considered as CD34+, CD45low, CD309+, and CD133+. A significant increase in EPC frequency was found in SSc-ILD+ patients when compared to HC (p < 0.001). SSc-ILD+ patients exhibited a higher EPC frequency than SSc-ILD− patients (p = 0.012), whereas it was markedly reduced compared to IPF patients (p < 0.001). EPC frequency was higher in males (p = 0.04) and negatively correlated to SSc duration (p = 0.04) in SSc-ILD+ patients. Our results indicate a role of EPC in the processes of vasculopathy and lung fibrosis in SSc-ILD+. EPC frequency may be considered as a biomarker of ILD in SSc patients.
Ageing and Olfactory Dysfunction in Trisomy 21: A Systematic Review
Authors: Manan Hanani Abdul , Yahya Noorazrul
Published: July 2021

Purpose: The olfactory system is particularly vulnerable in an ageing brain, both anatomically and functionally, and these brain changes are more pronounced among individuals with trisomy 21. Furthermore, the age of the system starts to deteriorate, and the mechanism involved is unclear in an individual with trisomy 21. Therefore, the present review aims to summarise the available information related to this topic and to suggest questions still unanswered which can be a subject of further research. Methods: A systematic literature search of trisomy 21 and olfactory dysfunction was conducted using PubMed/MEDLINE and Scopus electronic database following PRISMA guidelines. References and citations were checked in the Google Scholar database. Reports were extracted for information on demographics and psychophysical evaluation. Then, the reports were systematically reviewed based on the effects of ageing on the three olfactory domains: threshold, discrimination, and identification. Results: Participants with trisomy 21 show an early onset of olfactory impairment, and the age effect of the olfactory deficit is fully expressed at age > 30 years old. The three olfactory domains, threshold, discrimination, and identification, are suggested to be impaired in trisomy 21 participants with age > 30 years old. Conclusions: Olfactory dysfunction in an individual with trisomy 21 commences at a relatively young age and affects the three olfactory domains. A challenge for the future is to quantitatively establish the olfactory function of an individual with trisomy 21 at all ages with more detailed measurements to further understand the pathophysiology of this brain deterioration.
Quality of Life and Psychological Distress in Portuguese Older Individuals with Tinnitus
Authors: Haider Haúla F. , Ribeiro Sara F. , Hoare Derek J. , Fialho Graça , Hall Deborah A. , Antunes Marília , Caria Helena , Paço João
Published: July 2021

Tinnitus is the perception of a sound without an external source, often associated with adverse psychological and emotional effects leading to impaired quality of life (QoL). The present study investigated QoL and psychological distress in tinnitus patients and analysed the effects of associated comorbidities. Tonal and speech audiometry, tinnitus assessment, and clinical interviews were obtained from 122 Portuguese individuals (aged from 55 to 75). Portuguese versions of the Brief Symptoms Inventory (BSI), the Medical Outcomes Study Short Form Health Survey (MOS SF-36) and Tinnitus Handicap Inventory (THI) were used to evaluate psychological distress, health-related QoL, social difficulties and tinnitus severity. The presence of tinnitus was significantly associated with hearing loss. The increases in tinnitus severity were associated with decreases in QoL, particularly regarding MOS SF-36 subscales “perception of health”, “social functioning”, and “mental health”. Regarding BSI, patients with greater tinnitus severity had more severe psychopathology symptoms, measured with scales “Obsessive–compulsive”, “Depression”, “Anxiety”, “Hostility” and “Phobic Anxiety”. Our study supports the notion of the negative impact of increased tinnitus severity on QoL and psychological distress in older adults. Presented data strengthen the importance of a multidisciplinary approach to tinnitus assessment and treatment.
Cofilin and Neurodegeneration: New Functions for an Old but Gold Protein
Authors: Lapeña-Luzón Tamara , Rodríguez Laura R. , Beltran-Beltran Vicent , Benetó Noelia , Pallardó Federico V. , Gonzalez-Cabo Pilar
Published: July 2021

Cofilin is an actin-binding protein that plays a major role in the regulation of actin dynamics, an essential cellular process. This protein has emerged as a crucial molecule for functions of the nervous system including motility and guidance of the neuronal growth cone, dendritic spine organization, axonal branching, and synaptic signalling. Recently, other important functions in cell biology such as apoptosis or the control of mitochondrial function have been attributed to cofilin. Moreover, novel mechanisms of cofilin function regulation have also been described. The activity of cofilin is controlled by complex regulatory mechanisms, with phosphorylation being the most important, since the addition of a phosphate group to cofilin renders it inactive. Due to its participation in a wide variety of key processes in the cell, cofilin has been related to a great variety of pathologies, among which neurodegenerative diseases have attracted great interest. In this review, we summarized the functions of cofilin and its regulation, emphasizing how defects in these processes have been related to different neurodegenerative diseases.
Stereotactic Body Radiotherapy for Patients with Lung Oligometastatic Disease: A Five-Year Systematic Review
Authors: Virbel Guillaume , Le Fèvre Clara , Noël Georges , Antoni Delphine
Published: July 2021

For several years, oligometastatic disease has represented an intermediate state between localized disease accessible to local treatment and multimetastatic disease requiring systemic therapy. The lung represents one of the most common metastatic locations. Stereotactic body radiation therapy (SBRT) appears to be the treatment of choice for these patients. There are few data defining the place of radiotherapy and reporting outcome after SBRT in lung metastases. This 5-year review aimed to determine areas of SBRT usefulness and methods for the management of pulmonary metastasis in oligometastatic patients. A search for articles on PubMed allowed selection of the most relevant studies. Eighteen articles were selected according to pre-established criteria for this purpose. The analysis concludes that SBRT is an effective and safe treatment in selected patients when the disease remains localized from one to three organs.
Immunotherapies in Non-Hodgkin’s Lymphoma
Authors: Bezombes Christine , Pérez-Galán Patricia
Published: July 2021

Immune-based therapies mobilize the immune system to promote or restore an effective antitumor immune response [...]
Rapid Response to the Combination of Lenvatinib and Pembrolizumab in Patients with Advanced Carcinomas (Lung Adenocarcinoma and Malignant Pleural Mesothelioma)
Authors: Shalata Walid , Iraqi Muhammed , Bhattacharya Baisali , Fuchs Vered , Roisman Laila C. , Cohen Ahron Yehonatan , Massalha Ismaell , Yakobson Alexander , Prasad Manu , Elkabets Moshe , Porgador Angel , Peled Nir
Published: July 2021

The new era of cancer treatments has made immune checkpoint inhibitors (ICIs) and emerging multikinase inhibitors (TKIs) the standards of care, thus drastically improving patient prognoses. Pembrolizumab is an anti-programmed cell death-1 antibody drug, and lenvatinib is a TKI with preferential antiangiogenic activity. We present, to our knowledge, the first reported series of cases consisting of patients with metastatic non–small cell lung cancer and malignant pleural mesothelioma who were treated with several types of chemotherapy combinations and ICIs followed by disease progression. They were subsequently treated with combined immunotherapy and TKI treatment, resulting in a near complete response within a very short time. Clinical responses were supported by in vitro testing of each patient’s lymphocytic response to pembrolizumab after pre-exposure of target cancer cells to lenvatinib.
Circadian Clock and Liver Cancer
Authors: Crespo María , Leiva Magdalena , Sabio Guadalupe
Published: July 2021

Circadian clocks control several homeostatic processes in mammals through internal molecular mechanisms. Chronic perturbation of circadian rhythms is associated with metabolic diseases and increased cancer risk, including liver cancer. The hepatic physiology follows a daily rhythm, driven by clock genes that control the expression of several proteins involved in distinct metabolic pathways. Alteration of the liver clock results in metabolic disorders, such as non-alcoholic fatty liver diseases (NAFLD) and impaired glucose metabolism, that can trigger the activation of oncogenic pathways, inducing spontaneous hepatocarcinoma (HCC). In this review, we provide an overview of the role of the liver clock in the metabolic and oncogenic changes that lead to HCC and discuss new potentially useful targets for prevention and management of HCC.
Targeted Next-Generation Sequencing Analysis Predicts the Recurrence in Resected Lung Adenocarcinoma Harboring EGFR Mutations
Authors: Kim In Ae , Hur Jae Young , Kim Hee Joung , Lee Song Am , Hwang Jae Joon , Kim Wan Seop , Lee Kye Young
Published: July 2021

Targeted NGS, widely applied to identify driver oncogenes in advanced lung adenocarcinoma, may also be applied to resected early stage cancers. We investigated resected EGFR-mutated lung adenocarcinoma mutation profiles to evaluate prognostic impacts. Tissues from 131 patients who had complete resection of stage I–IIIA EGFR-mutated lung adenocarcinoma were analyzed by targeted NGS for 207 cancer-related genes. Recurrence free survival (RFS) was estimated according to genetic alterations using the Kaplan–Meier method and Cox proportional regression analysis. The relapse rate was 25.2% (33/131). Five-year RFS of stages IA, IB, II, and IIIA were 82%, 75%, 35%, and 0%, respectively (p < 0.001). RFS decreased with the number of co-mutations (p = 0.025). Among co-mutations, the CTNNB1 mutation was associated with short RFS in a multivariate analysis (hazard ratio: 5.4, 95% confidence interval: 2.1–14.4; p = 0.001). TP53 mutations were associated with short RFS in stage IB–IIIA (p = 0.01). RFS was shorter with EGFR exon 19 deletion (19-del) than with mutation 21-L858R in stage IB–IIIA tumors (p = 0.008). Among 19-del subtypes, pL747_P753delinS (6/56, 8.9%) had shorter RFS than pE746_A750del (39/56, 69.6%), the most frequent subtype (p = 0.004).
Immune Microenvironment Features and Dynamics in Hodgkin Lymphoma
Authors: Bertuzzi Clara , Sabattini Elena , Agostinelli Claudio
Published: July 2021

Classical Hodgkin’s lymphoma (cHL) accounts for 10% of all lymphoma diagnosis. The peculiar feature of the disease is the presence of large multinucleated Reed–Sternberg and mononuclear Hodgkin cells interspersed with a reactive microenvironment (ME). Due to the production of a large number of cytokines, Hodgkin cells (HCs) and Hodgkin Reed–Sternberg cells (HRSCs) attract and favour the expansion of different immune cell populations, modifying their functional status in order to receive prosurvival stimuli and to turn off the antitumour immune response. To this purpose HRSCs shape a biological niche by organizing the spatial distribution of cells in the ME. This review will highlight the contribution of the ME in the pathogenesis and prognosis of cHL and its role as a possible therapeutic target.
PXR Modulates the Prostate Cancer Cell Response to Afatinib by Regulating the Expression of the Monocarboxylate Transporter SLC16A1
Authors: Matheux Alice , Gassiot Matthieu , Fromont Gaëlle , Leenhardt Fanny , Boulahtouf Abdelhay , Fabbrizio Eric , Marchive Candice , Garcin Aurélie , Agherbi Hanane , Combès Eve , Evrard Alexandre , Houédé Nadine , Balaguer Patrick , Gongora Céline , Mbatchi Litaty C. , Pourquier Philippe
Published: July 2021

Resistance to castration is a crucial issue in the treatment of metastatic prostate cancer. Kinase inhibitors (KIs) have been tested as potential alternatives, but none of them are approved yet. KIs are subject of extensive metabolism at both the hepatic and the tumor level. Here, we studied the role of PXR (Pregnane X Receptor), a master regulator of metabolism, in the resistance to KIs in a prostate cancer setting. We confirmed that PXR is expressed in prostate tumors and is more frequently detected in advanced forms of the disease. We showed that stable expression of PXR in 22Rv1 prostate cancer cells conferred a resistance to dasatinib and a higher sensitivity to erlotinib, dabrafenib, and afatinib. Higher sensitivity to afatinib was due to a ~ 2-fold increase in its intracellular accumulation and involved the SLC16A1 transporter as its pharmacological inhibition by BAY-8002 suppressed sensitization of 22Rv1 cells to afatinib and was accompanied with reduced intracellular concentration of the drug. We found that PXR could bind to the SLC16A1 promoter and induced its transcription in the presence of PXR agonists. Together, our results suggest that PXR could be a biomarker of response to kinase inhibitors in castration-resistant prostate cancers.
SPTAN1 Expression Predicts Treatment and Survival Outcomes in Colorectal Cancer
Authors: Schrecker Christopher , Behrens Sophia , Schönherr Rebecca , Ackermann Anne , Pauli Daniel , Plotz Guido , Zeuzem Stefan , Brieger Angela
Published: July 2021

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality. In a cohort of 189 patients with CRC, we recently showed that expression of the cytoskeletal scaffolding protein non-erythroid spectrin αII (SPTAN1) was lower in advanced metastatic tumours. The aim of the present study was to clarify the association of intratumoural SPTAN1 expression levels with treatment and survival outcomes in patients with CRC. The analysis was based on histologic assessment of SPTAN1 protein levels in our own CRC cohort, and transcriptome data of 573 CRC cases from The Cancer Genome Atlas (TCGA). We first establish that high intratumoural levels of SPTAN1 protein and mRNA associate with favourable survival outcomes in patients with CRC. Next, a response prediction signature applied to the TCGA data reveals a possible link between high SPTAN1 transcript levels and improved patient responses to FOLFOX chemotherapy. Complementary in vitro experiments confirm that SPTAN1 knockdown strains of the colon cancer cell lines HT-29, HCT116 mlh1-2 and Caco-2 are less responsive to FOLFOX chemotherapy compared with SPTAN1-proficient control strains. Taken together, we identify SPTAN1 as a novel prognostic biomarker in CRC and show that SPTAN1 expression levels may predict patient responses to chemotherapy. These investigations illustrate how an affordable, histology-based diagnostic test could directly impact therapeutic decision-making at the bedside.
FORGE: A Novel Scoring System to Predict the MIB-1 Labeling Index in Intracranial Meningiomas
Authors: Wach Johannes , Lampmann Tim , Güresir Ági , Schuss Patrick , Vatter Hartmut , Herrlinger Ulrich , Becker Albert , Hölzel Michael , Toma Marieta , Güresir Erdem
Published: July 2021

The MIB-1 index is an essential predictor of progression-free-survival (PFS) in meningioma. To date, the MIB-1 index is not available in preoperative treatment planning. A preoperative score estimating the MIB-1 index in patients with intracranial meningiomas has not been investigated so far. Between 2013 and 2019, 208 patients with tumor morphology data, MIB-1 index data, and plasma fibrinogen and serum C-reactive protein (CRP) data underwent surgery for intracranial WHO grade I and II meningioma. An optimal MIB-1 index cut-off value (≥6/<6) in the prediction of recurrence was determined by ROC curve analysis (AUC: 0.71; 95% CI: 0.55–0.87). A high MIB-1 index (≥6%) was present in 50 cases (24.0%) and was significantly associated with male sex, peritumoral edema, low baseline CRP, and low fibrinogen level in the multivariate analysis. A scoring system (“FORGE”) based on sex, peritumoral edema, preoperative CRP value, and plasma fibrinogen level supports prediction of the MIB-1 index (sensitivity 62%, specificity 79%). The MIB-1 labeling index and the FORGE score are significantly associated with an increased risk of poor PFS time. We suggest a novel score (“FORGE”) to preoperatively estimate the risk of an increased MIB-1 index (≥6%), which might help in surgical decision making and follow-up interval determination and inform future trials investigating inflammatory burden and proliferative activity.
Encapsulation of Combi-CLEAs of Glycosidases in Alginate Beads and Polyvinyl Alcohol for Wine Aroma Enhancement
Authors: Tavernini Luigi , Aburto Carla , Romero Oscar , Illanes Andrés , Wilson Lorena
Published: July 2021

The aromatic expression of wines can be enhanced by the addition of specific glycosidases, although their poor stability remains a limitation. Coimmobilization of glycosidases as cross-linked enzyme aggregates (combi-CLEAs) offers a simple solution yielding highly stable biocatalysts. Nevertheless, the small particle size of combi-CLEAs hinders their recovery, preventing their industrial application. Encapsulation of combi-CLEAs of glycosidases in alginate beads and in polyvinyl alcohol is proposed as a solution. Combi-CLEAS of β-d-glucosidase and α-l-arabinofuranosidase were prepared and encapsulated. The effects of combi-CLEA loading and particle size on the expressed specific activity (IU/gbiocatalyst) of the biocatalysts were evaluated. Best results were obtained with 2.6 mm diameter polyvinyl alcohol particles at a loading of 60 mgcombi-CLEA/gpolyvinyl alcohol, exhibiting activities of 1.9 and 1.0 IU/gbiocatalyst for β-d-glucosidase and α-l-arabinofuranosidase, respectively. Afterwards, the stability of the biocatalysts was tested in white wine. All the encapsulated biocatalysts retained full activity after 140 incubation days, outperforming both free enzymes and nonencapsulated combi-CLEAs. Nevertheless, the alginate-encapsulated biocatalysts showed a brittle consistency, making recovery unfeasible. Conversely, the polyvinyl-encapsulated biocatalyst remained intact throughout the assay. The encapsulation of combi-CLEAs in polyvinyl alcohol proved to be a simple methodology that allows their recovery and reuse to harness their full catalytic potential.
Sex-Specific Differences in Autophagic Responses to Experimental Ischemic Stroke
Authors: Patrizz Anthony N. , Moruno-Manchon Jose F. , O’Keefe Lena M. , Doran Sarah J. , Patel Anita R. , Venna Venugopal R. , Tsvetkov Andrey S. , Li Jun , McCullough Louise D.
Published: July 2021

Ischemic stroke triggers a series of complex pathophysiological processes including autophagy. Differential activation of autophagy occurs in neurons derived from males versus females after stressors such as nutrient deprivation. Whether autophagy displays sexual dimorphism after ischemic stroke is unknown. We used a cerebral ischemia mouse model (middle cerebral artery occlusion, MCAO) to evaluate the effects of inhibiting autophagy in ischemic brain pathology. We observed that inhibiting autophagy reduced infarct volume in males and ovariectomized females. However, autophagy inhibition enhanced infarct size in females and in ovariectomized females supplemented with estrogen compared to control mice. We also observed that males had increased levels of Beclin1 and LC3 and decreased levels of pULK1 and p62 at 24 h, while females had decreased levels of Beclin1 and increased levels of ATG7. Furthermore, the levels of autophagy markers were increased under basal conditions and after oxygen and glucose deprivation in male neurons compared with female neurons in vitro. E2 supplementation significantly inhibited autophagy only in male neurons, and was beneficial for cell survival only in female neurons. This study shows that autophagy in the ischemic brain differs between the sexes, and that autophagy regulators have different effects in a sex-dependent manner in neurons.
Transcriptomic Hallmarks of Ischemia-Reperfusion Injury
Authors: Movahed Mandana , Brockie Sydney , Hong James , Fehlings Michael G.
Published: July 2021

Ischemia reperfusion injury (IRI) is associated with a broad array of life-threatening medical conditions including myocardial infarct, cerebral stroke, and organ transplant. Although the pathobiology and clinical manifestations of IRI are well reviewed by previous publications, IRI-related transcriptomic alterations are less studied. This study aimed to reveal a transcriptomic hallmark for IRI by using the RNA-sequencing data provided by several studies on non-human preclinical experimental models. In this regard, we focused on the transcriptional responses of IRI in an acute time-point up to 48 h. We compiled a list of highly reported genes in the current literature that are affected in the context of IRI. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and found many of the up-regulated genes to be involved in cell survival, cell surface signaling, response to oxidative stress, and inflammatory response, while down-regulated genes were predominantly involved in ion transport. Furthermore, by GO analysis, we found that multiple inflammatory and stress response processes were affected after IRI. Tumor necrosis factor alpha (TNF) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways were also highlighted in the Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In the last section, we discuss the treatment approaches and their efficacy for IRI by comparing RNA sequencing data from therapeutic interventions with the results of our cross-comparison of differentially expressed genes and pathways across IRI.
Tetracycline Antibiotics: Elucidating the Electrochemical Fingerprint and Oxidation Pathway
Authors: Cánovas Rocío , Sleegers Nick , van Nuijs Alexander L.N. , De Wael Karolien
Published: July 2021

Herein, a complete study of the electrochemical behavior of the most commonly used tetracycline antibiotics (TCs) on unmodified carbon screen-printed electrodes (SPEs) is presented. In addition, the oxidation pathway of TCs on SPE is elucidated, for the first time, with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Square wave voltammetry (SWV) was used to study the electrochemical fingerprint (EF) of the antibiotics shaping the different oxidation processes of the TCs in a pH range from 2 to 12. Their characteristic structure and subsequent EF offer the possibility of distinguishing this class of antibiotics from other types. Under the optimized parameters, calibration curves of tetracycline (TET), doxycycline (DOXY), oxytetracycline (OXY), and chlortetracycline (CHL) in a Britton Robinson buffer solution (pH 9) exhibited a linear range between 5 and 100 µM with excellent reproducibilities (RSDTET = 3.01%, RSDDOXY = 3.29%, RSDOXY = 9.78% and RSDCHL = 6.88% at 10 µM, N = 3) and limits of detection (LOD) of LODTET = 4.15 µM, LODDOXY = 2.14 µM, LODOXY = 3.07 µM and LODCHL = 4.15 µM. Furthermore, binary, tertiary, and complex mixtures of all TCs were analyzed with SWV to investigate the corresponding EF. A dual pH screening (pH 4 and pH 9), together with the use of a custom-made Matlab script for data treatment, allowed for the successful confirmation of a single presence of TCs in the unknown samples. Overall, this work presents a straightforward study of the electrochemical behavior of TCs in SPE, allowing for the future on-site identification of residues of tetracycline antibiotics in real samples.
Self-Assembly of an Equimolar Mixture of Liquid Crystals and Magnetic Nanoparticles
Authors: Shrivastav Gaurav P.
Published: July 2021

We studied the equilibrium self-assembly of an equimolar mixture of uniaxial liquid crystals (LCs) and magnetic nanoparticles (MNPs) using molecular dynamics simulations. The LCs are modeled by ellipsoids interacting via Gay–Berne potential, and MNPs are represented by dipolar soft spheres (DSS). We found that the LCs show isotropic, nematic, and smectic phases when the mixture is compressed at a fixed temperature. The DSS form chain-like structures, which remain randomly oriented at low densities where the LCs are in the isotropic phase. At intermediate and high densities, the DSS chains align along the nematic and smectic directors of LCs. We found that the DSS inside a chain follow a ferromagnetic ordering. However, the mixture does not show a significant macroscopic magnetization. The extent of nematic order in the DSS remains very similar to the LCs in intermediate densities. At high densities, the DSS have a lower extent of nematic order than the LCs. The structure of the LC–DSS mixture was further analyzed via projected pair correlation functions for distances parallel and perpendicular to directors in the nematic and smectic phases.
Carbonation of Sodium Aluminate/Sodium Carbonate Solutions for Precipitation of Alumina Hydrates—Avoiding Dawsonite Formation
Authors: Marinos Danai , Kotsanis Dimitrios , Alexandri Alexandra , Balomenos Efthymios , Panias Dimitrios
Published: July 2021

Experimental work has been performed to investigate the precipitation mechanism of aluminum hydroxide phases from sodium aluminate/sodium carbonate pregnant solutions by carbon dioxide gas purging. Such solutions result from leaching calcium aluminate slags with sodium carbonate solutions, in accordance with the Pedersen process, which is an alternative process for alumina production. The concentration of carbonate ions in the pregnant solution is revealed as a key factor in controlling the nature of the precipitating phase. Synthetic aluminate solutions of varying sodium carbonate concentrations, ranging from 20 to 160 g/L, were carbonated, and the resulting precipitating phases were characterized by X-ray diffraction analysis. Based on the results of the previous carbonation tests, a series of experiments were performed in which the duration of carbonation and the aging period of the precipitates varied. For this work, a synthetic aluminate solution containing 20 g/L free Na2CO3 was used. The precipitates were characterized with X-ray diffraction analysis and Fourier-transform infrared spectroscopy.
Modern History of Organic Conductors: An Overview
Authors: Naito Toshio
Published: July 2021

This short review article provides the reader with a summary of the history of organic conductors. To retain a neutral and objective point of view regarding the history, background, novelty, and details of each research subject within this field, a thousand references have been cited with full titles and arranged in chronological order. Among the research conducted over ~70 years, topics from the last two decades are discussed in more detail than the rest. Unlike other papers in this issue, this review will help readers to understand the origin of each topic within the field of organic conductors and how they have evolved. Due to the advancements achieved over these 70 years, the field is nearing new horizons. As history is often a reflection of the future, this review is expected to show the future directions of this research field.
Petrographic-Mineralogical Characterization of Archaeological Materials from “Casa di Diana” Mithraeum Sited in the Open Museum of Ostia Antica
Authors: Scatigno Claudia , Preite Martinez Maria , Prieto-Taboada Nagore , Madariaga Juan Manual , Conte Aida Maria
Published: July 2021

Mithraea, religious Roman buildings, are very common in Italian archeological sites. There are sixteen in Ostia Antica (Rome, Italy)The poor state of conservation, due to the intrinsic environmental conditions, characterized them: they consist of open-air museums and caves simultaneously. These places of worship are characterized by the presence of heterogeneous materials, such as wall building materials (bricks and mortars) and others used for furnishings and fittings. This increases the risk of accelerated damage because the materials ‘rheology is different. Here, a full petrographic-mineralogical characterization with polarized light microscopy (PLM), X-ray diffraction (XRD), scanning electron microscope with energy dispersive X-ray (SEM-EDS) and isotopic analysis (δ13C, δ18O) is carried out on materials like travertine, marble, pumice, ceramic, and wall-building materials in “Casa di Diana” Mithraeum (Ostia Antica). Their characterization gives provenance information as well as conservation and restoration purposes. The prevalence of siliciclastic or carbonate components discriminates between red and yellow bricks, as well as different textures and minerals in the aggregate of the red ones. The mortars are typically pozzolanic, and the aggregate is mostly made up of black and red pozzolanic clasts. In the altar, apse, and aedicule, which constitute the principal place of the Mithraeum, a variety of materials used for the ornamental purpose are represented by pumices, travertine, marble, and limestone. The altar material, catalogued as marble, resulted in being a limestone coated with a white pigment.
Statistical Methods to Support Difficult Diagnoses
Authors: Pilz Guenter F. , Weber Frank , Mueller Werner G. , Schaefer Juergen R.
Published: July 2021

Far too often, one meets patients who went for years or even decades from doctor to doctor without obtaining a valid diagnosis. This brings pain to millions of patients and their families, not to speak of the enormous costs. Often patients cannot tell precisely enough which factors (or combinations thereof) trigger their problems. If conventional methods fail, we propose the use of statistics and algebra to provide doctors much more useful inputs from patients. We use statistical regression for triggering factors of medical problems, and in particular, “balanced incomplete block designs” for factors detection. These methods can supply doctors with much more valuable inputs and can also find combinations of multiple factors through very few tests. In order to show that these methods do work, we briefly describe a case in which these methods helped to solve a 60-year-old problem in a patient and provide some more examples where these methods might be particularly useful. As a conclusion, while regression is used in clinical medicine, it seems to be widely unknown in diagnosing. Statistics and algebra can save the health systems much money, as well as the patients a lot of pain.
The Design of Preventive Automated Driving Systems Based on Convolutional Neural Network
Authors: Lee Wooseop , Kang Min-Hee , Song Jaein , Hwang Keeyeon
Published: July 2021

As automated vehicles have been considered one of the important trends in intelligent transportation systems, various research is being conducted to enhance their safety. In particular, the importance of technologies for the design of preventive automated driving systems, such as detection of surrounding objects and estimation of distance between vehicles. Object detection is mainly performed through cameras and LiDAR, but due to the cost and limits of LiDAR’s recognition distance, the need to improve Camera recognition technique, which is relatively convenient for commercialization, is increasing. This study learned convolutional neural network (CNN)-based faster regions with CNN (Faster R-CNN) and You Only Look Once (YOLO) V2 to improve the recognition techniques of vehicle-mounted monocular cameras for the design of preventive automated driving systems, recognizing surrounding vehicles in black box highway driving videos and estimating distances from surrounding vehicles through more suitable models for automated driving systems. Moreover, we learned the PASCAL visual object classes (VOC) dataset for model comparison. Faster R-CNN showed similar accuracy, with a mean average precision (mAP) of 76.4 to YOLO with a mAP of 78.6, but with a Frame Per Second (FPS) of 5, showing slower processing speed than YOLO V2 with an FPS of 40, and a Faster R-CNN, which we had difficulty detecting. As a result, YOLO V2, which shows better performance in accuracy and processing speed, was determined to be a more suitable model for automated driving systems, further progressing in estimating the distance between vehicles. For distance estimation, we conducted coordinate value conversion through camera calibration and perspective transform, set the threshold to 0.7, and performed object detection and distance estimation, showing more than 80% accuracy for near-distance vehicles. Through this study, it is believed that it will be able to help prevent accidents in automated vehicles, and it is expected that additional research will provide various accident prevention alternatives such as calculating and securing appropriate safety distances, depending on the vehicle types.
Towards Hybrid Multimodal Manual and Non-Manual Arabic Sign Language Recognition: mArSL Database and Pilot Study
Authors: Luqman Hamzah , El-Alfy El-Sayed M.
Published: July 2021

Sign languages are the main visual communication medium between hard-hearing people and their societies. Similar to spoken languages, they are not universal and vary from region to region, but they are relatively under-resourced. Arabic sign language (ArSL) is one of these languages that has attracted increasing attention in the research community. However, most of the existing and available works on sign language recognition systems focus on manual gestures, ignoring other non-manual information needed for other language signals such as facial expressions. One of the main challenges of not considering these modalities is the lack of suitable datasets. In this paper, we propose a new multi-modality ArSL dataset that integrates various types of modalities. It consists of 6748 video samples of fifty signs performed by four signers and collected using Kinect V2 sensors. This dataset will be freely available for researchers to develop and benchmark their techniques for further advancement of the field. In addition, we evaluated the fusion of spatial and temporal features of different modalities, manual and non-manual, for sign language recognition using the state-of-the-art deep learning techniques. This fusion boosted the accuracy of the recognition system at the signer-independent mode by 3.6% compared with manual gestures.
A 33 MHz Fast-Locking PLL with Programmable VCO and Automatic Band Selection for Clock Generator Application
Authors: Agarwal Neeraj , Agarwal Neeru , Lu Chih-Wen , Oh-e Masahito
Published: July 2021

This paper presents a prototype of an auto-ranging phase-locked loop (PLL) with low jitter noise over a wide operating frequency range using the multiband programmable voltage-controlled oscillator (VCO) gain stage with automatic band selection. We successfully reduce the VCO gain (Kvco) and retain the desired frequency band. The proposed PLL comprises a prescaler, phase frequency detector (PFD), charge pump (CP), programmable VCO and automatic band selection circuit. The PLL prototype with all subblocks was implemented using the TSMC 0.18 μm 1P6M process. Contrary to conventional PLL architectures, the proposed architecture incorporates a real-time check and automatic band selection circuit in the secondary loop. A high-performance dual-loop PLL wide tuning range was realized using an ASIC digital control circuit. A suitable way to maintain the Kvco low is to use multiple discrete frequency bands to accommodate the required frequency range. To maintain a low Kvco and fast locking, the automatic frequency band selection circuit also has two indigenous, most probable voltage levels. The proposed architecture provides the flexibility of not only band hopping but also band twisting to obtain an optimized Kvco for the desired output range, with the minimum jitter and spurs. The proposed programmable VCO was designed using a voltage-to-current-converter circuit and current DAC followed by a four-stage differential ring oscillator with a cross-coupled pair. The VCO frequency output range is 150–400 MHz, while the input frequency is 25 MHz. A sequential phase detection loop with a negligible dead zone was designed to adjust fine phase errors between the reference and feedback clocks. All circuit blocks of the proposed PLL were simulated using the EDA tool HSPICE and layout generation by Laker. The simulation and measured results of the proposed PLL show high linearity, with a dead zone of less than 10 pV. The differential VCO was used to improve the linearity and phase noise of the PLL. The chip measured results show rms jitter of 19.10 ps. The PLL prototype also has an additional safety feature of a power down mode. The automatic band selection PLL has good immunity for possible frequency drifting due to temperature, process and supply voltage variations. The proposed PLL is designed for −40 to +85 °C, a wide temperature range.