bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Mysteries of Dyslexia—Lessons Learned from the Prospective Jyväskylä Longitudinal Study of Dyslexia
Authors: Lohvansuu Kaisa , Torppa Minna , Ahonen Timo , Eklund Kenneth , Hämäläinen Jarmo A. , Leppänen Paavo H. T. , Lyytinen Heikki
Published: March 2021

This paper reviews the observations of the Jyväskylä Longitudinal Study of Dyslexia (JLD). The JLD is a prospective family risk study in which the development of children with familial risk for dyslexia (N = 108) due to parental dyslexia and controls without dyslexia risk (N = 92) were followed from birth to adulthood. The JLD revealed that the likelihood of at-risk children performing poorly in reading and spelling tasks was fourfold compared to the controls. Auditory insensitivity of newborns observed during the first week of life using brain event-related potentials (ERPs) was shown to be the first precursor of dyslexia. ERPs measured at six months of age related to phoneme length identification differentiated the family risk group from the control group and predicted reading speed until the age of 14 years. Early oral language skills, phonological processing skills, rapid automatized naming, and letter knowledge differentiated the groups from ages 2.5–3.5 years onwards and predicted dyslexia and reading development, including reading comprehension, until adolescence. The home environment, a child’s interest in reading, and task avoidance were not different in the risk group but were found to be additional predictors of reading development. Based on the JLD findings, preventive and intervention methods utilizing the association learning approach have been developed.
Phonic and Motor Stereotypies in Autism Spectrum Disorder: Video Analysis and Neurological Characterization
Authors: Lanzarini Evamaria , Pruccoli Jacopo , Grimandi Irene , Spadoni Chiara , Angotti Marida , Pignataro Veronica , Sacrato Leonardo , Franzoni Emilio , Parmeggiani Antonia
Published: March 2021

Stereotypies are among the core symptoms of Autism spectrum disorder (ASD) and can cause significant clinical impairment. At present, phonic stereotypies in ASD have been scarcely explored. This study investigates the frequency, variability, and typologies of phonic and motor stereotypies in children with ASD and their association with clinical neurological variables. We examined 35 patients by recording standardized video sessions and administering the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). Phonic stereotypies were present in 83.0% of the patients. The most prevalent subtypes were noncommunicative vocalizations (60.0%), single syllables (37.1%), and echolalic stereotypies (22.9%). Noncommunicative vocalizations were more frequent in nonverbal patients (OR = 4.629, p = 0.008), while echolalic stereotypies were more represented in verbal patients (OR = 0.279, p = 0.028). Patients with intellectual disability (ID) showed a higher number (F(1,26) = 9.406, p = 0.005) and variability (F(1,25) = 7.174, p = 0.013) of motor stereotypies, with a higher number (F(1,26) = 13.268, p = 0.005) and variability (F(1,26) = 9.490, p = 0.005) of stereotypies involving the head/trunk/shoulders category. Patients with guttural stereotypies showed a higher variability of total motor stereotypies (OR = 1.487, p = 0.032) and self-directed motor stereotypies (OR = 4.389, p = 0.042). These results, combined with a standardized video-analysis, document the frequency and variability of phonic stereotypies among children with ASD. Correlations between specific phonic stereotypies and verbal abilities should be investigated further.
Brain Molecular Connectivity in Neurodegenerative Conditions
Authors: Carli Giulia , Tondo Giacomo , Boccalini Cecilia , Perani Daniela
Published: March 2021

Positron emission tomography (PET) allows for the in vivo assessment of early brain functional and molecular changes in neurodegenerative conditions, representing a unique tool in the diagnostic workup. The increased use of multivariate PET imaging analysis approaches has provided the chance to investigate regional molecular processes and long-distance brain circuit functional interactions in the last decade. PET metabolic and neurotransmission connectome can reveal brain region interactions. This review is an overview of concepts and methods for PET molecular and metabolic covariance assessment with evidence in neurodegenerative conditions, including Alzheimer’s disease and Lewy bodies disease spectrum. We highlight the effects of environmental and biological factors on brain network organization. All of the above might contribute to innovative diagnostic tools and potential disease-modifying interventions.
Prognostic Evidence of the miRNA-Based Ovarian Cancer Signature MiROvaR in Independent Datasets
Authors: De Cecco Loris , Bagnoli Marina , Chiodini Paolo , Pignata Sandro , Mezzanzanica Delia
Published: March 2021

Epithelial ovarian cancer (EOC) remains the second most common cause of gynecological cancer deaths. To improve patients’ outcomes, we still need reliable biomarkers of early relapse, of which external independent validation is a crucial process. Our previously established prognostic signature, MiROvaR, including 35 microRNAs (miRNA) able to stratify EOC patients for their risk of relapse, was challenged on a new independent cohort of 197 EOC patients included in the Pelvic Mass Study whose miRNA profile was made publically available, thus resulting in the only accessible database aside from the EOC TCGA collection. Following accurate data matrix adjustment to account for the use of different miRNA platforms, MiROvaR confirmed its ability to discriminate early relapsing patients. The model’s original cutoff separated 156 (79.2%) high- and 41 (20.8%) low-risk patients with median progression free survival (PFS) of 16.3 months and not yet reached (NYR), respectively (hazard ratio (HR): 2.42–95% Confidence Interval (CI) 1.49–3.93; Log-rank p = 0.00024). The MiROvaR predictive accuracy (area under the curve (AUC) = 0.68; 95% Cl 0.57–0.79) confirms its prognostic value. This external validation in a totally independently collected, handled and profiled EOC cohort suggests that MiROvaR is a strong and reliable biomarker of EOC early relapse, warranting prospective validation.
Impact of Goal Directed Therapy in Head and Neck Oncological Surgery with Microsurgical Reconstruction: Free Flap Viability and Complications
Authors: Tapia Blanca , Garrido Elena , Cebrian Jose Luis , Del Castillo Jose Luis , Gonzalez Javier , Losantos Itsaso , Gilsanz Fernando
Published: March 2021

(1) Background: Surgical outcomes in free flap reconstruction of head and neck defects in cancer patients have improved steadily in recent years; however, correct anaesthesia management is also important. The aim of this study has been to show whether goal directed therapy can improve flap viability and morbidity and mortality in surgical patients. (2) Methods: we performed an observational case control study to analyse the impact of introducing a semi invasive device (Flo Trac®) during anaesthesia management to optimize fluid management. Patients were divided into two groups: one received goal directed therapy (GDT group) and the other conventional fluid management (CFM group). Our objective was to compare surgical outcomes, complications, fluid management, and length of stay between groups. (3) Results: We recruited 140 patients. There were no differences between groups in terms of demographic data. Statistically significant differences were observed in colloid infusion (GDT 53.1% vs. CFM 74.1%, p = 0.023) and also in intraoperative and postoperative infusion of crystalloids (CFM 5.72 (4.2, 6.98) vs. GDT 3.04 (2.29, 4.11), p < 0.001), which reached statistical significance. Vasopressor infusion in the operating room (CFM 25.5% vs. GDT 74.5%, p < 0.001) and during the first postoperative 24h (CFM 40.6% vs. GDT 75%, p > 0.001) also differed. Differences were also found in length of stay in the intensive care unit (hours: CFM 58.5 (40, 110) vs. GDT 40.5 (36, 64.5), p = 0.005) and in the hospital (days: CFM 15.5 (12, 26) vs. GDT 12 (10, 19), p = 0.009). We found differences in free flap necrosis rate (CMF 37.1% vs. GDT 13.6%, p = 0.003). One-year survival did not differ between groups (CFM 95.6% vs. GDT 86.8%, p = 0.08). (4) Conclusions: Goal directed therapy in oncological head and neck surgery improves outcomes in free flap reconstruction and also reduces length of stay in the hospital and intensive care unit, with their corresponding costs. It also appears to reduce morbidity, although these differences were not significant. Our results have shown that optimizing intraoperative fluid therapy improves postoperative morbidity and mortality.
Early Clinical Outcomes of Intensity Modulated Radiation Therapy/Intensity Modulated Proton Therapy Combination in Comparison with Intensity Modulated Radiation Therapy Alone in Oropharynx Cancer Patients
Authors: Yoon Han Gyul , Ahn Yong Chan , Oh Dongryul , Noh Jae Myoung , Park Seung Gyu , Nam Heerim , Ju Sang Gyu , Kwon Dongyeol , Park Seyjoon
Published: March 2021

Purpose: To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.
Combing MRI Perfusion and 18F-FDG PET/CT Metabolic Biomarkers Helps Predict Survival in Advanced Nasopharyngeal Carcinoma: A Prospective Multimodal Imaging Study
Authors: Chan Sheng-Chieh , Yeh Chih-Hua , Chang Joseph Tung-Chieh , Chang Kai-Ping , Wang Jen-Hung , Ng Shu-Hang
Published: March 2021

We prospectively investigated the prognostic value of imaging parameters for nasopharyngeal carcinoma (NPC) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography (18F-FDG PET)/computed tomography (CT). Patients with stage III–IVb NPC underwent F-FDG PET/CT, DCE-MRI, and DWI before treatment. Kaplan-Meier and Cox-regression analyses were used to assess associations of PET and MRI imaging biomarkers with overall survival (OS) and recurrence-free survival (RFS). We used independent prognosticators to establish prognostic models; model performance was examined using Harrell’s concordance index (c-index). Sixty-one patients were available for analysis, as 13 patients died and 20 experienced recurrence. Total lesion glycolysis (TLG) (p = 0.002) from PET/CT and the initial area under the curve (iAUC) (p = 0.036) from DCE-MRI were identified as independent prognosticators of OS; Epstein-Barr virus (EBV) DNA (p = 0.027), the extracellular volume fraction (Ve) (p = 0.027) from DCE-MRI, and TLG/iAUC (p = 0.025) were significant predictors of RFS. The c-indices of the prognostic models incorporating TLG + iAUC in predicting OS and incorporating EBV DNA + Ve + TLG/iAUC in predicting RFS were 0.79 and 0.76, respectively. These were significantly higher than the corresponding c-indices of the TNM staging system (p = 0.047 and 0.025, respectively); they were also higher than those of models with only MRI or PET biomarkers. In conclusion, the combination of pretreatment DCE-MRI and 18F-FDG PET/CT imaging biomarkers helps survival prediction in advanced NPC. Integrating MRI perfusion with PET metabolism and plasma EBV information may aid clinicians in planning the optimal personalized management strategy.
Risk Prediction and New Prophylaxis Strategies for Thromboembolism in Cancer
Authors: Ferroni Patrizia , Guadagni Fiorella , Roselli Mario
Published: March 2021

Venous thromboembolism (VTE) is a compelling challenge across all phases of cancer care as it may result in treatment delays, impaired quality of life (QoL), and increased mortality [...]
Erratum: Hindi, N., et al. Trabectedin Plus Radiotherapy for Advanced Soft-Tissue Sarcoma: Experience in Forty Patients Treated at a Sarcoma Reference Center. Cancers 2020, 12, 3740
Authors: Hindi Nadia , García Irene , Sánchez-Camacho Alberto , Gutierrez Antonio , Peinado Javier , Rincón Inmaculada , Benedetti Johanna , Sancho Pilar , Santos Paloma , Sánchez-Bustos Paloma , Marcilla David , Encinas Victor , Chacon Sara , Muñoz-Casares Cristobal , Moura David , Martin-Broto Javier
Published: March 2021

The authors noticed that content of “Conflicts of Interest” in the original version [...]
NF2 and Canonical Hippo-YAP Pathway Define Distinct Tumor Subsets Characterized by Different Immune Deficiency and Treatment Implications in Human Pleural Mesothelioma
Authors: Yang Haitang , Hall Sean R. R. , Sun Beibei , Zhao Liang , Gao Yanyun , Schmid Ralph A. , Tan Swee T. , Peng Ren-Wang , Yao Feng
Published: March 2021

(1) Inactivation of the tumor suppressor NF2 is believed to play a major role in the pathogenesis of malignant pleural mesothelioma (MPM) by deregulating the Hippo-YAP signaling pathway. However, NF2 has functions beyond regulation of the Hippo pathway, raising the possibility that NF2 contributes to MPM via Hippo-independent mechanisms. (2) We performed weighted gene co-expression analysis (WGCNA) in transcriptomic and proteomic datasets obtained from The Cancer Gene Atlas (TCGA) MPM cohort to identify clusters of co-expressed genes highly correlated with NF2 and phospho (p)-YAP protein, surrogate markers of active Hippo signaling and YAP inactivation. The potential targets are experimentally validated using a cell viability assay. (3) MPM tumors with NF2 loss-of-function are not associated with changes in p-YAP level nor YAP/TAZ activity score, but are characterized by a deficient B-cell receptor (BCR) signaling pathway. Conversely, MPM tumors with YAP activation display exhausted CD8 T-cell-mediated immunity together with significantly upregulated PD-L1, which is validated in an independent MPM cohort, suggesting a potential benefit of immune-checkpoint inhibitors (ICI) in this patient subset. In support of this, mutations in core Hippo signaling components including LATS2, but not NF2, are independently associated with better overall survival in response to ICI in patients. Additionally, based on cancer cell line models, we show that MPM cells with a high Hippo-YAP activity are particularly sensitive to inhibitors of BCR-ABL/SRC, stratifying a unique MPM patient subset that may benefit from BCR-ABL/SRC therapies. Furthermore, we observe that NF2 physically interacts with a considerable number of proteins that are not involved in the canonical Hippo-YAP pathway, providing a possible explanation for its Hippo-independent role in MPM. Finally, survival analyses show that YAP/TAZ scores together with p-YAP protein level, but not NF2, predict the prognosis of MPM patients. (4) NF2 loss-of-function and dysregulated Hippo-YAP pathway define distinct MPM subsets that differ in their molecular features and prognosis, which has important clinical implications for precision oncology in MPM patients.
ADAM and ADAMTS Proteins, New Players in the Regulation of Hepatocellular Carcinoma Microenvironment
Authors: Théret Nathalie , Bouezzeddine Fidaa , Azar Fida , Diab-Assaf Mona , Legagneux Vincent
Published: March 2021

The tumor microenvironment plays a major role in tumor growth, invasion and resistance to chemotherapy, however understanding how all actors from microenvironment interact together remains a complex issue. The tumor microenvironment is classically represented as three closely connected components including the stromal cells such as immune cells, fibroblasts, adipocytes and endothelial cells, the extracellular matrix (ECM) and the cytokine/growth factors. Within this space, proteins of the adamalysin family (ADAM for a disintegrin and metalloproteinase; ADAMTS for ADAM with thrombospondin motifs; ADAMTSL for ADAMTS-like) play critical roles by modulating cell–cell and cell–ECM communication. During last decade, the implication of adamalysins in the development of hepatocellular carcinoma (HCC) has been supported by numerous studies however the functional characterization of most of them remain unsettled. In the present review we propose both an overview of the literature and a meta-analysis of adamalysins expression in HCC using data generated by The Cancer Genome Atlas (TCGA) Research Network.
Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study
Authors: Banys-Paluchowski Maggie , Gasparri Maria , de Boniface Jana , Gentilini Oreste , Stickeler Elmar , Hartmann Steffi , Thill Marc , Rubio Isabel , Di Micco Rosa , Bonci Eduard-Alexandru , Niinikoski Laura , Kontos Michalis , Karadeniz Cakmak Guldeniz , Hauptmann Michael , Peintinger Florentia , Pinto David , Matrai Zoltan , Murawa Dawid , Kadayaprath Geeta , Dostalek Lukas , Nina Helidon , Krivorotko Petr , Classe Jean-Marc , Schlichting Ellen , Appelgren Matilda , Paluchowski Peter , Solbach Christine , Blohmer Jens-Uwe , Kühn Thorsten ,   the AXSANA Study Group
Published: March 2021

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).
MR Image Changes of Normal-Appearing Brain Tissue after Radiotherapy
Authors: Witzmann Katharina , Raschke Felix , Troost Esther G. C.
Published: March 2021

Radiotherapy is part of the standard treatment of most primary brain tumors. Large clinical target volumes and physical characteristics of photon beams inevitably lead to irradiation of surrounding normal brain tissue. This can cause radiation-induced brain injury. In particular, late brain injury, such as cognitive dysfunction, is often irreversible and progressive over time, resulting in a significant reduction in quality of life. Since 50% of patients have survival times greater than six months, radiation-induced side effects become more relevant and need to be balanced against radiation treatment given with curative intent. To develop adequate treatment and prevention strategies, the underlying cause of radiation-induced side-effects needs to be understood. This paper provides an overview of radiation-induced changes observed in normal-appearing brains measured with conventional and advanced MRI techniques and summarizes the current findings and conclusions. Brain atrophy was observed with anatomical MRI. Changes in tissue microstructure were seen on diffusion imaging. Vascular changes were examined with perfusion-weighted imaging and susceptibility-weighted imaging. MR spectroscopy revealed decreasing N-acetyl aspartate, indicating decreased neuronal health or neuronal loss. Based on these findings, multicenter prospective studies incorporating advanced MR techniques as well as neurocognitive function tests should be designed in order to gain more evidence on radiation-induced sequelae.
The Role of [18F]Fluciclovine PET/CT in the Characterization of High-Risk Primary Prostate Cancer: Comparison with [11C]Choline PET/CT and Histopathological Analysis
Authors: Zanoni Lucia , Mei Riccardo , Bianchi Lorenzo , Giunchi Francesca , Maltoni Lorenzo , Pultrone Cristian Vincenzo , Nanni Cristina , Bossert Irene , Matti Antonella , Schiavina Riccardo , Fiorentino Michelangelo , Fonti Cristina , Lodi Filippo , D’Errico Antonietta , Brunocilla Eugenio , Fanti Stefano
Published: March 2021

The primary aim of the study was to evaluate the role of [18F]Fluciclovine PET/CT in the characterization of intra-prostatic lesions in high-risk primary PCa patients eligible for radical prostatectomy, in comparison with conventional [11C]Choline PET/CT and validated by prostatectomy pathologic examination. Secondary aims were to determine the performance of PET semi-quantitative parameters (SUVmax; target-to-background ratios [TBRs], using abdominal aorta, bone marrow and liver as backgrounds) for malignant lesion detection (and best cut-off values) and to search predictive factors of malignancy. A six sextants prostate template was created and used by PET readers and pathologists for data comparison and validation. PET visual and semi-quantitative analyses were performed: for instance, patient-based, blinded to histopathology; subsequently lesion-based, un-blinded, according to the pathology reference template. Among 19 patients included (mean age 63 years, 89% high and 11% very-high-risk, mean PSA 9.15 ng/mL), 45 malignant and 31 benign lesions were found and 19 healthy areas were selected (n = 95). For both tracers, the location of the “blinded” prostate SUVmax matched with the lobe of the lesion with the highest pGS in 17/19 cases (89%). There was direct correlation between [18F]Fluciclovine uptake values and pISUP. Overall, lesion-based (n = 95), the performance of PET semiquantitative parameters, with either [18F]Fluciclovine or [11C]Choline, in detecting either malignant/ISUP2-5/ISUP4-5 PCa lesions, was moderate and similar (AUCs ≥ 0.70) but still inadequate (AUCs ≤ 0.81) as a standalone staging procedure. A [18F]Fluciclovine TBR-L3 ≥ 1.5 would depict a clinical significant lesion with a sensitivity and specificity of 85% and 68% respectively; whereas a SUVmax cut-off value of 4 would be able to identify a ISUP 4-5 lesion in all cases (sensitivity 100%), although with low specificity (52%). TBRs (especially with threshold significantly higher than aorta and slightly higher than bone marrow), may be complementary to implement malignancy targeting.
Degradation Kinetics of Methyl Orange Dye in Water Using Trimetallic Fe/Cu/Ag Nanoparticles
Authors: Kgatle Masaku , Sikhwivhilu Keneiloe , Ndlovu Gebhu , Moloto Nosipho
Published: March 2021

The release of azo dye contaminants from textile industries into the environment is an issue of major concern. Nanoscale zerovalent iron (nZVI) has been extensively studied in the degradation of azo dye pollutants such as methyl orange (MO). In this study, iron was coupled with copper and silver to make trimetallic Fe/Cu/Ag nanoparticles, in order to enhance the degradation of MO and increase reactivity of the catalyst by delaying the rate of oxidation of iron. The synthesis of the trimetallic nanoparticles (Fe/Cu/Ag) was carried out using the sodium borohydride reduction method. The characterization of the particles was performed using XRD, XPS, EDX, and TEM. The analyses confirmed the successful synthesis of the nanoparticles; the TEM images also showed the desired structures and geometry of the nanoscale zerovalent iron particles. The assessment of the nanoparticles in the degradation of methyl orange showed a notable degradation within few minutes into the reaction. The effect of parameters such as nanoparticle dosage, initial MO concentration, and the solution pH on the degradation of MO using the nanoparticles was investigated. Methyl orange degradation efficiency reached 100% within 1 min into the reaction at a low pH, with lower initial MO concentration and higher nanoparticle dosage. The degradation rate of MO using the nanoparticles followed pseudo first-order kinetics and was greatly influenced by the studied parameters. Additionally, LC-MS technique confirmed the degradation of MO within 1 min and that the degradation occurs through the splitting of the azo bond. The Fe/Cu/Ag trimetallic nanoparticles have proven to be an appropriate and efficient alternative for the treatment of dye wastewater.
Temporal Quantitative Proteomics Analysis of Neuroblastoma Cells Treated with Bovine Milk-Derived Extracellular Vesicles Highlights the Anti-Proliferative Properties of Milk-Derived Extracellular Vesicles
Authors: Fonseka Pamali , Kang Taeyoung , Chee Sing , Chitti Sai V. , Sanwlani Rahul , Ang Ching-Seng , Mathivanan Suresh
Published: March 2021

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.
DiseaseLinc: Disease Enrichment Analysis of Sets of Differentially Expressed LincRNAs
Authors: More Piyush , Talyan Sweta , Fontaine Jean-Fred , Muro Enrique M. , Andrade-Navarro Miguel A.
Published: March 2021

Long intergenic non-coding RNAs (LincRNAs) are long RNAs that do not encode proteins. Functional evidence is lacking for most of them. Their biogenesis is not well-known, but it is thought that many lincRNAs originate from genomic duplication of coding material, resulting in pseudogenes, gene copies that lose their original function and can accumulate mutations. While most pseudogenes eventually stop producing a transcript and become erased by mutations, many of these pseudogene-based lincRNAs keep similarity to the parental gene from which they originated, possibly for functional reasons. For example, they can act as decoys for miRNAs targeting the parental gene. Enrichment analysis of function is a powerful tool to discover the functional effects of a treatment producing differential expression of transcripts. However, in the case of lincRNAs, since their function is not easy to define experimentally, such a tool is lacking. To address this problem, we have developed an enrichment analysis tool that focuses on lincRNAs exploiting their functional association, using as a proxy function that of the parental genes and has a focus on human diseases.
The Modified Random Network (MRN) Model within the Configuron Percolation Theory (CPT) of Glass Transition
Authors: Ojovan Michael I.
Published: March 2021

A brief overview is presented of the modified random network (MRN) model in glass science emphasizing the practical outcome of its use. Then, the configuron percolation theory (CPT) of glass–liquid transition is concisely outlined, emphasizing the role of the actual percolation thresholds observed in a complex system. The MRN model is shown as an important tool enabling to understand within CPT the reduced percolation threshold in complex oxide systems.
Laboratory and Statistical Analysis of the Fatigue Response of Self-Healing Asphalt Mixtures Containing Metal By-Products
Authors: Vila-Cortavitarte Marta , Jato-Espino Daniel , Castro-Fresno Daniel , Calzada-Pérez Miguel Á.
Published: March 2021

Fatigue is one of the main forms of deterioration in asphalt mixtures, endangering their service life due to the progressive appearance and expansion of cracks. A sustainable approach to increase the lifetime of asphalt pavement has been found in self-healing technology, especially if boosted with metal by-products due to their economic and environmental interest. Under these circumstances, this research addressed the fatigue behavior of self-healing asphalt mixtures including industrial sand blasting by-products obtained from sieving and aspiration processes. Hence, a uniaxial fatigue test was carried out to determine whether these experimental mixtures can provide a similar response to that of a reference asphalt concrete (AC-16). This analysis was undertaken with the support of descriptive and inferential statistics, whose application proved the absence of significant differences in the fatigue performance of self-healing experimental mixtures with respect to conventional asphalt concrete. These results suggest that designing self-healing mixtures with metal by-products is a sustainable approach to increase the lifetime of asphalt pavements, while contributing to the circular economy through diverse economic and environmental benefits.
Tribological Behaviour and Lubricating Mechanism of Tire Pyrolysis Oil
Authors: Yaqoob Haseeb , Teoh Yew Heng , Sher Farooq , Jamil Muhammad Ahmad , Nuhanović Mirza , Razmkhah Omid , Erten Begum
Published: March 2021

The four-ball tester was used in this analysis to demonstrate the lubricity of tire pyrolysis oil (TPO). The tribological performance of the tire pyrolysis oil was compared with diesel fuel (DF) and their blends, DT10 (TPO 10%, Diesel 90%) and DT20 (TPO 20%, Diesel 80%). A scanning electron microscope (SEM) was used to investigate the wear scar. In contrast to diesel fuel, TPO demonstrated better antiwear behaviour in terms of higher load-carrying capacity. DT10, DT20, and TPO’s wear scar diameter (WSD) was 22.35%, 16.01%, and 31.99% smaller than that of diesel at 80 kg load, respectively. The scanning electron microscope micrographs showed that the TPO and DT10 had less wear than their counterparts.
Determination of Al-2.18Mg-1.92Li Alloy’s Microstructure Degradation in Corrosive Environment
Authors: Kozina Franjo , Brodarac Zdenka Zovko , Brajčinović Sandra , Petrič Mitja
Published: March 2021

The utilization of aluminum-lithium-magnesium (Al-Li-Mg) alloys in the transportation industry is enabled by excellent engineering properties. The mechanical properties and corrosion resistance are influenced by the microstructure development comprehending the solidification of coherent strengthening precipitates, precipitation of course and angular equilibrium phases as well as the formation and widening of the Precipitate-free zone. The research was performed to determine the microstructure degradation of Al-2.18Mg-1.92Li alloy in a corrosive environment using electrochemical measurements. The solidification sequence of the Al-2.18Mg-1.92Li alloy, obtained using Thermo–Calc software support, indicated the transformation of the αAl dendritic network and precipitation of AlLi (δ), Al2LiMg (T), and Al8Mg5 (β) phase. All of the phases are anodic with respect to the αAl enabling microstructure degradation. To achieve higher microstructure stability, the sample was solution hardened at 520 °C. However, the sample in as-cast condition showed a lower corrosion potential (−749.84 mV) and corrosion rate (17.01 mm/year) with respect to the solution-hardened sample (−752.52 mV, 51.24 mm/year). Higher microstructure degradation of the solution-hardened sample is a consequence of δ phase precipitation at the grain boundaries and inside the grain of αAl, leading to intergranular corrosion and cavity formation. The δ phase precipitates from the Li and Mg enriched the αAl solid solution at the solution-hardening temperature.
Crystal Structure of an Active Site Mutant Form of IRG1 from Bacillus subtilis
Authors: Park Hyun Ho
Published: March 2021

Immune-responsive gene1 (IRG1), an enzyme that is overexpressed during immune reactions, catalyzes the production of itaconate from cis-aconitate. Itaconate is a multifunctional immuno-metabolite that displays antibacterial and antiviral activities. The recent resolution of its structure has enabled the mechanism underlying IRG1 function to be speculated on. However, the precise mechanism underlying the enzymatic reaction of IRG1 remains vague owing to the absence of information regarding the structure of the IRG1/substrate or the product complex. In this study, we determined the high-resolution structure of the active site mutant form of IRG1 from Bacillus subtilis (bsIRG1_H102A). Structural analysis detected unidentified electron densities around the active site. Structural comparison with the wildtype revealed that H102 was critical for the precise location of the side chain of residues around active site of IRG1. Finally, the activity of bsIRG1 was extremely low compared with that of mammalian IRG1. The current structural study will expectedly help understand the working mechanism of IRG1.
Electrical Properties and Thermal Annealing Effects of Polycrystalline MoS2-MoSX Nanowalls Grown by Sputtering Deposition Method
Authors: Um Doo-Seung , Jin Mi-Jin , Woo Jong-Chang , Kim Dong-Pyo , Park Jungmin , Jo Younghun , Kim Gwan-Ha
Published: March 2021

Straightforward growth of nanostructured low-bandgap materials is a key issue in mass production for electronic device applications. We report here facile nanowall growth of MoS2-MoSX using sputter deposition and investigate the electronic properties of the nanowalls. MoS2-MoSX nanowalls become gradually thicker and taller, with primarily (100)-plane growth directions, with increasing deposition time. Nanowalls combine with nearby walls when a rapid thermal annealing (RTA, 200 °C–500 °C) process is applied. All samples have conventional low-bandgap semiconductor behavior with exponential resistance increase as measurement temperature decreases. The 750 nm-thick MoS2-MoSX nanowalls have a sheet carrier mobility of up to 2 cm2·V−1·s−1 and bulk carrier concentration of ~1017–1019 cm−3 range depending on RTA temperature. Furthermore, perpendicular field-dependent magnetoresistance at 300 K shows negative magnetoresistance behavior, which displays resistance decay by applying a magnetic field (MR ratio in the −1 % range at 5 T). Interestingly, 400 °C RTA treated samples show a resistance upturn when applying an external magnetic field of more than 3 T. Our research suggests tuneability of MoS2 nanowall size and mesoscopic electronic transport properties.
The Impact of Radiotherapy Dose in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy
Authors: Lo Chien-Ming , Wang Yu-Ming , Chen Yen-Hao , Fang Fu-Min , Huang Shun-Chen , Lu Hung-I , Li Shau-Hsuan
Published: March 2021

Objective: For patients with esophageal squamous cell carcinoma, preoperative chemoradiotherapy followed by planned esophagectomy is used as a curative treatment modality. However, the impact of radiotherapy dose remains undefined. Method: A total of 141 patients with stage III esophageal squamous cell carcinoma (ESCC; as defined by the 7th American Joint Committee on Cancer), receiving preoperative chemoradiotherapy followed by esophagectomy between 2000 and 2015 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were retrospectively reviewed. The radiotherapy dose of preoperative chemoradiotherapy (36 Gy before 2009 and 50–50.4 Gy after 2009) and other clinicopathological parameters were collected and correlated with the response to chemoradiotherapy and treatment outcome. Result: Of these 141 patients, the radiotherapy dose was 36 Gy in 59 (42%) patients and 50 Gy in 82 (58%) patients. A complete pathological response was noted in 12 (20%) of 59 patients receiving 36 Gy radiotherapy, and 37 (45%) of 82 patients receiving 50 Gy radiotherapy (p = 0.002). The three-year overall survival and disease-free survival rates were 31% and 25% in patients receiving 36 Gy radiotherapy, and 54% and 46% in patients receiving 50–50.4 Gy radiotherapy, respectively (p = 0.023 for overall survival; p = 0.047 for disease-free survival). Multivariate analysis showed that a higher radiotherapy dose was associated with increased pathological complete response (p = 0.003, hazard ratio: 3.215), better overall survival (p = 0.024, hazard ratio: 1.585), and superior disease-free survival (p = 0.049, hazard ratio: 1.493). However, higher radiotherapy doses revealed more surgical complications, including acute respiratory distress syndrome (p = 0.048) and anastomosis leaks (p = 0.004). Conclusion: For patients with locally advanced ESCC, preoperative chemoradiotherapy with higher radiotherapy doses led to increased pathologic complete response rates and improved survival.
Genetic Diversity of Purple Passion Fruit, Passiflora edulis f. edulis, Based on Single-Nucleotide Polymorphism Markers Discovered through Genotyping by Sequencing
Authors: Rodriguez Castillo Nohra Cecilia , Wu Xingbo , Chacón María Isabel , Melgarejo Luz Marina , Blair Matthew Wohlgemuth
Published: March 2021

Orphan crops, which include many of the tropical fruit species used in the juice industry, lack genomic resources and breeding efforts. Typical of this dilemma is the lack of commercial cultivars of purple passion fruit, Passiflora edulis f. edulis, and of information on the genetic resources of its substantial semiwild gene pool. In this study, we develop single-nucleotide polymorphism (SNP) markers for the species and show that the genetic diversity of this fruit crop has been reduced because of selection for cultivated genotypes compared to the semiwild landraces in its center of diversity. A specific objective of the present study was to determine the genetic diversity of cultivars, genebank accession, and landraces through genotyping by sequencing (GBS) and to conduct molecular evaluation of a broad collection for the species P. edulis from a source country, Colombia. We included control genotypes of yellow passion fruit, P. edulis f. flavicarpa. The goal was to evaluate differences between fruit types and compare landraces and genebank accessions from in situ accessions collected from farmers. In total, 3820 SNPs were identified as informative for this diversity study. However, the majority distinguished yellow and purple passion fruit, with 966 SNPs useful in purple passion fruits alone. In the population structure analysis, purple passion fruits were very distinct from the yellow ones. The results for purple passion fruits alone showed reduced diversity for the commercial cultivars while highlighting the higher diversity found among landraces from wild or semi-wild conditions. These landraces had higher heterozygosity, polymorphism, and overall genetic diversity. The implications for genetics and breeding as well as evolution and ecology of purple passion fruits based on the extant landrace diversity are discussed with consideration of manual or pollinator-assisted hybridization of this species.
Dark Energy with Phantom Crossing and the H0 Tension
Authors: Di Valentino Eleonora , Mukherjee Ankan , Sen Anjan A.
Published: March 2021

We investigate the possibility of phantom crossing in the dark energy sector and the solution for the Hubble tension between early and late universe observations. We use robust combinations of different cosmological observations, namely the Cosmic Microwave Background (CMB), local measurement of Hubble constant (H0), Baryon Acoustic Oscillation (BAO) and SnIa for this purpose. For a combination of CMB+BAO data that is related to early universe physics, phantom crossing in the dark energy sector was confirmed at a 95% confidence level and we obtained the constraint H0=71.0−3.8+2.9 km/s/Mpc at a 68% confidence level, which is in perfect agreement with the local measurement by Riess et al. We show that constraints from different combinations of data are consistent with each other and all of them are consistent with phantom crossing in the dark energy sector. For the combination of all data considered, we obtained the constraint H0=70.25±0.78 km/s/Mpc at a 68% confidence level and the phantom crossing happening at the scale factor am=0.851−0.031+0.048 at a 68% confidence level.
Using Community of Inquiry (CoI) to Facilitate the Design of a Holistic E-Learning Experience for Students with Visual Impairments
Authors: Ngubane-Mokiwa Sindile A. , Khoza Simon Bheki
Published: March 2021

Information and Communication Technology (ICT) tools provide an ideal mechanism by which students can interact closely with their lecturers in an open distance learning (ODL) context. This is especially true for students with disabilities who require access through alternative formats. This paper demonstrates teaching and learning practices in an ODL institution in South Africa, with a focus on the indispensable role of lecturers and tutors in an online learning setting. The paper employs the Community of Inquiry, which sees the effective online learning environment through three elements: cognitive, social, and teaching presence. The findings shed light on the use of vision-based approaches in course design; limited implementation of open-access policies, and the academic faculty’s lack of knowledge on how to facilitate inclusive learning. The paper concludes by presenting a proposed student-centred framework that seeks to facilitate inclusive teaching and learning towards positive and inclusive learning experiences for students. The proposed framework could be beneficial during pandemic situations.
Intimate Partner Violence and Pregnancy Termination in Armenia: Evidence from Nationally-Representative Survey Data
Authors: Samad Nandeeta , Das Pranta , Ahinkorah Bright Opoku , Seidu Abdul-Aziz , Frimpong James Boadu , Okyere Joshua , Hagan John Elvis , Nabi Mohammad Hayatun , Hawlader Mohammad Delwer Hossain
Published: March 2021

Intimate partner violence has been associated with numerous consequences for women, including pregnancy termination. This study examined the association between predictive capacity of intimate partner violence and pregnancy termination among women in Armenia. The study analyzed the 2015–16 Armenia Demographic and Health Survey (ADHS) data on women aged 15–49 (Mean: 31.49; Standard Deviation, SD: 9.51). Marital control exercised by husbands, ever experienced physical violence, sexual violence, and emotional violence by husbands were the four indicators of intimate partner violence used in this study. To assess the association between intimate partner violence and pregnancy termination, a binary logistic regression model was fitted. After controlling for confounders, we found that women whose husbands exercised marital control were 26% more likely to experience pregnancy termination, compared to women whose husbands did not exercise marital control (adjusted odds ratio (aOR): 1.26, 95% Confidence interval (CI): 1.03–1.53). Women who ever experienced sexual violence were about 10 times likely to experience pregnancy termination than women who did not experience sexual violence (aOR: 9.76, 95% CI: 1.91–49.96). Both ever experienced physical violence and emotional violence did not have any significant associations with pregnancy termination. Forms of intimate partner violence are associated with pregnancy termination. The findings of this study provide evidence for government and policymakers to formulate, modify, and implement policies and program that target both men and women regarding the prevailing intimate partner violence and its consequences. Strengthening the policy implementation will ensure that women are empowered to make decisions about their reproductive health. Making husbands and their family members aware of the basics and consequences of intimate partner violence and focusing on child cognitive development which can be hampered due to the prevalence violence in families are recommended.
Structural Changes Induced by Heating in Sputtered NiO and Cr2O3 Thin Films as p-Type Transparent Conductive Electrodes
Authors: Guillén Cecilia , Herrero José
Published: March 2021

NiO and Cr2O3 are transition metal oxides with a partially filled d electron band that supports p-type conduction. Both are transparent to the visible light due to optical absorption beginning at wavelengths below 0.4 μm and the creation of holes by metal vacancy defects. The defect and strain effects on the electronic characteristics of these materials need to be established. For this purpose, NiO and Cr2O3 thin films were deposited on unheated glass substrates by reactive DC sputtering from metallic targets. Their structural, morphological, optical and electrical properties were analyzed comparatively in the as-grown conditions (25 °C) and after heating in air at 300 °C or 500 °C. The cubic NiO structure was identified with some tensile strain in the as-grown conditions and compressive strain after heating. Otherwise, the chromium oxide layers were amorphous as grown at 25 °C and crystallized into hexagonal Cr2O3 at 300 °C or above also with compressive strain after heating. Both materials achieved the highest visible transmittance (72%) and analogous electrical conductivity (~10−4 S/cm) by annealing at 500 °C. The as-grown NiO films showed a higher conductivity (2.5 × 10−2 S/cm) but lower transmittance (34%), which were related to more defects causing tensile strain in these samples.