bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Air Temperature Increase on Changes in Thermal Regime of the Oder and Neman Rivers Flowing into the Baltic Sea
Authors: Choiński Adam , Ptak Mariusz , Volchak Alexander , Kirvel Ivan , Valiuškevičius Gintaras , Parfomuk Sergey , Kirvel Pavel , Sidak Svetlana
Published: April 2021

The paper presents long-term changes in water temperature in two rivers, Oder and Neman, with catchments showing different climatic conditions (with dominance of marine climate in the case of the Oder and continental climate in the case of the Neman River). A statistically significant increase in mean annual water temperature was recorded for four observation stations, ranging from 0.17 to 0.39 °C dec−1. At the seasonal scale, for the winter half-year, water temperature increase varied from 0.17 to 0.26 °C dec−1, and for the summer half-year from 0.17 to 0.50 °C dec−1. In three cases (Odra-Brzeg, Odra-Słubice, Niemen-Grodno), the recorded changes referred to the scale of changes in air temperature. For the fourth station on Neman (Smalininkai), an increase in water temperature in the river was considerably slower than air temperature increase. It should be associated with the substantial role of local conditions (non-climatic) affecting the thermal regime in that profile. Short-term forecast of changes in water temperature showed its further successive increase, a situation unfavorable for the functioning of these ecosystems.
Chemical Composition, Bioactive Compounds, and Antioxidant Activity of Two Wild Edible Mushrooms Armillaria mellea and Macrolepiota procera from Two Countries (Morocco and Portugal)
Authors: Erbiai El Hadi , da Silva Luís Pinto , Saidi Rabah , Lamrani Zouhaire , Esteves da Silva Joaquim C. G. , Maouni Abdelfettah
Published: April 2021

The present study aimed to investigate the chemical composition, bioactive compounds, and antioxidant activity of two wild edible mushrooms, the honey fungus (Armillaria mellea) and the parasol mushroom (Macrolepiota procera), collected from Northern Morocco (MA) and Portugal (PT). Those species were chosen due to their edibility, nutraceutical, and medicinal properties. Bioactive compounds (ascorbic acid, tannin, total phenolic, total flavonoid, β-carotene, and lycopene) and their antioxidant activity were determined by spectrophotometric methods. Herein, the fruiting body of the samples revealed a significantly higher amount of bioactive compounds, and values varied between the Moroccan and the Portuguese ones. Methanolic extracts shown a strong antioxidant capacity: Using DPPH free radical-scavenging activity radicals (IC50 1.06–1.32 mg/mL); inhibition of β-carotene bleaching radicals (IC50 0.09–0.53 mg/mL); and, reducing power radicals (IC50 0.52–1.11 mg/mL). The mushroom species with the highest antioxidant capacity was A. mellea from MA. Chemical composition was analyzed by GC-MS and LC-MS methodologies. GC-MS analysis showed that the most abundant biomolecules group was sugar compositions in the four samples (62.90%, 48.93%, 59.00%, and 53.71%) and the main components were galactitol 16.74%, petroselinic acid 19.83%, d-galactose 38.43%, and glycerol 24.43% in A. mellea (MA), A. mellea (PT), M. procera (MA), and M. procera (PT), respectively. LC-MS analysis of individual phenolic compounds revealed that vanillic acid (198.40 ± 2.82 µg/g dry weight (dw) and cinnamic acid (155.20 ± 0.97 µg/g dw) were the main compounds detected in A. mellea, while protocatechuic acid (92.52 ± 0.45 and 125.50 ± 0.89 µg/g dw) was predominated in M. procera for MA and PT samples, respectively. In general, the results of this comparative study demonstrate that the geographic and climatic conditions of the collection site can influence biomolecule compounds and antioxidant properties of wild mushrooms. This study contributes to the elaboration of nutritional, nutraceutical, and pharmaceutical databases of the worldwide consumed mushrooms.
Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies
Authors: Wang Fei , Multhoff Gabriele
Published: April 2021

In recent years, evidence has accumulated that cannabinoids—especially the non-psychoactive compound, cannabidiol (CBD)—possess promising medical and pharmacological activities that might qualify them as potential anti-tumor drugs. This review is based on multiple studies summarizing different mechanisms for how CBD can target tumor cells including cannabinoid receptors or other constituents of the endocannabinoid system, and their complex activation of biological systems that results in the inhibition of tumor growth. CBD also participates in anti-inflammatory activities which are related to tumor progression, as demonstrated in preclinical models. Although the numbers of clinical trials and tested tumor entities are limited, there is clear evidence that CBD has anti-tumor efficacy and is well tolerated in human cancer patients. In summary, it appears that CBD has potential as a neoadjuvant and/or adjuvant drug in therapy for cancer.
Organotrialkoxysilane-Functionalized Noble Metal Monometallic, Bimetallic, and Trimetallic Nanoparticle Mediated Non-Enzymatic Sensing of Glucose by Resonance Rayleigh Scattering
Authors: Pandey Prem C. , Mitra Murli Dhar , Shukla Shubhangi , Narayan Roger J
Published: April 2021

Organotrialkoxysilanes like 3-aminopropyltrimethoxysilane (3-APTMS)-treated noble metal cations were rapidly converted into their respective nanoparticles in the presence of 3-glycidoxypropylytrimethoxysilane (3-GPTMS). The micellar activity of 3-APTMS also allowed us to replace 3-GPTMS with other suitable organic reagents (e.g., formaldehyde); this approach has significant advantages for preparing bimetallic and trimetallic analogs of noble metal nanoparticles that display efficient activity in many practical applications. The formation of monometallic gold, silver, and palladium nanoparticles, bimetallic Ag-Pd, and Au-Pd nanoparticles at various ratios of noble metal cations, and trimetallic Ag-Au-Pd nanoparticles were studied; their biocatalytic activity in non-enzymatic sensing of glucose based on monitoring synchronous fluorescence spectroscopy (SFS) was assessed. Of these nanoparticles, Au-Pd made with an 80:20 Au:Pd ratio displayed excellent catalytic activity for glucose sensing. These nanoparticles could also be homogenized with Nafion to enhance the resonance Rayleigh scattering (RRS) signal. In this study, the structural characterization of noble metal nanoparticles as well as bi- and tri-metallic nanoparticles in addition to their use in non-enzymatic sensing of glucose are reported.
Plasmonic Biosensors for Single-Molecule Biomedical Analysis
Authors: Mauriz Elba , Lechuga Laura
Published: April 2021

The rapid spread of epidemic diseases (i.e., coronavirus disease 2019 (COVID-19)) has contributed to focus global attention on the diagnosis of medical conditions by ultrasensitive detection methods. To overcome this challenge, increasing efforts have been driven towards the development of single-molecule analytical platforms. In this context, recent progress in plasmonic biosensing has enabled the design of novel detection strategies capable of targeting individual molecules while evaluating their binding affinity and biological interactions. This review compiles the latest advances in plasmonic technologies for monitoring clinically relevant biomarkers at the single-molecule level. Functional applications are discussed according to plasmonic sensing modes based on either nanoapertures or nanoparticle approaches. A special focus was devoted to new analytical developments involving a wide variety of analytes (e.g., proteins, living cells, nucleic acids and viruses). The utility of plasmonic-based single-molecule analysis for personalized medicine, considering technological limitations and future prospects, is also overviewed.
Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinson’s Disease
Authors: Gera Geetanjali , Guduru Zain , Yamasaki Tritia , Gurwell Julie A. , Chau Monica J. , Krotinger Anna , Schmitt Frederick A. , Slevin John T. , Gerhardt Greg A. , van Horne Craig , Quintero Jorge E.
Published: April 2021

Background: The efficacy of deep brain stimulation (DBS) and dopaminergic therapy is known to decrease over time. Hence, a new investigational approach combines implanting autologous injury-activated peripheral nerve grafts (APNG) at the time of bilateral DBS surgery to the globus pallidus interna. Objectives: In a study where APNG was unilaterally implanted into the substantia nigra, we explored the effects on clinical gait and balance assessments over two years in 14 individuals with Parkinson’s disease. Methods: Computerized gait and balance evaluations were performed without medication, and stimulation was in the off state for at least 12 h to best assess the role of APNG implantation alone. We hypothesized that APNG might improve gait and balance deficits associated with PD. Results: While people with a degenerative movement disorder typically worsen with time, none of the gait parameters significantly changed across visits in this 24 month study. The postural stability item in the UPDRS did not worsen from baseline to the 24-month follow-up. However, we measured gait and balance improvements in the two most affected individuals, who had moderate PD. In these two individuals, we observed an increase in gait velocity and step length that persisted over 6 and 24 months. Conclusions: Participants did not show worsening of gait and balance performance in the off therapy state two years after surgery, while the two most severely affected participants showed improved performance. Further studies may better address the long-term maintanenace of these results.
Fractal Dimension Calculation and Visual Attention Simulation: Assessing the Visual Character of an Architectural Façade
Authors: Lee Ju Hyun , Ostwald Michael J.
Published: April 2021

The design of a building façade has a significant impact on the way people respond to it physiologically and behaviourally. Few methods are available to assist an architect to understand such impacts during the design process. Thus, this paper examines the viability of using two computational methods to examine potential visual stimulus-sensation relationships in facade design. The first method, fractal analysis, is used to holistically measure the visual stimuli of a design. This paper describes both the box counting (density) and differential box counting (intensity) approaches to determining fractal dimension (D) in architecture. The second method, visual attention simulation, is used to explore pre-attentive processing and sensation in vision. Four measures—D-density (Dd), D-intensity (Di), heat map and gaze sequence—are used to provide quantitative and qualitative indicators of the ways people read different design options. Using two façade designs as examples, the results of this application reveal that the D values of a façade image have a relationship with the pre-attentive processing shown in heat map and gaze sequence simulations. The findings are framed as a methodological contribution to the field, but also to the disciplinary knowledge gap about the stimulus-sensation relationship and visual reasoning in design.
Modeling Deep Neural Networks to Learn Maintenance and Repair Costs of Educational Facilities
Authors: Kim Jimyong , Yum Sangguk , Son Seunghyun , Son Kiyoung , Bae Junseo
Published: April 2021

Educational facilities hold a higher degree of uncertainty in predicting maintenance and repair costs than other types of facilities. Moreover, achieving accurate and reliable maintenance and repair costs is essential, yet very little is known about a holistic approach to learning them by incorporating multi-contextual factors that affect maintenance and repair costs. This study fills this knowledge gap by modeling and validating deep neural networks to efficiently and accurately learn maintenance and repair costs, drawing on 1213 high-confidence data points. The developed model learns and generalizes claim payout records on the maintenance and repair costs from sets of facility asset information, geographic profiles, natural hazard records, and other causes of financial losses. The robustness of the developed model was tested and validated by measuring the root mean square error and mean absolute error values. This study attempted to propose an analytical modeling framework that can accurately learn various factors, significantly affecting the maintenance and repair costs of educational facilities. The proposed approach can contribute to the existing body of knowledge, serving as a reference for the facilities management of other functional types of facilities.
KEAP1 Is Required for Artesunate Anticancer Activity in Non-Small-Cell Lung Cancer
Authors: Hill Kristen S. , McDowell Anthony , McCorkle J. Robert , Schuler Erin , Ellingson Sally R. , Plattner Rina , Kolesar Jill M.
Published: April 2021

Artesunate is the most common treatment for malaria throughout the world. Artesunate has anticancer activity likely through the induction of reactive oxygen species, the same mechanism of action utilized in Plasmodium falciparum infections. Components of the kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway, which regulates cellular response to oxidative stress, are mutated in approximately 30% of non-small-cell lung cancers (NSCLC); therefore, we tested the hypothesis that KEAP1 is required for artesunate sensitivity in NSCLC. Dose response assays identified A549 cells, which have a G333C-inactivating mutation in KEAP1, as resistant to artesunate, with an IC50 of 23.6 µM, while H1299 and H1563 cells were sensitive to artesunate, with a 10-fold lower IC50. Knockdown of KEAP1 through siRNA caused increased resistance to artesunate in H1299 cells. Alternatively, the pharmacological inhibition of NRF2, which is activated downstream of KEAP1 loss, by ML385 partially restored sensitivity of A549 cells to artesunate, and the combination of artesunate and ML385 was synergistic in both A549 and H1299 cells. These findings demonstrate that KEAP1 is required for the anticancer activity of artesunate and support the further development of NRF2 inhibitors to target patients with mutations in the KEAP1/NRF2 pathway.
Morphological and Molecular Characterization of Proliferative Inflammatory Atrophy in Canine Prostatic Samples
Authors: de Godoy Fernandes Giovana , Pedrina Bruna , de Faria Lainetti Patrícia , Kobayashi Priscila Emiko , Govoni Verônica Mollica , Palmieri Chiara , de Moura Veridiana Maria Brianezi Dignani , Laufer-Amorim Renée , Fonseca-Alves Carlos Eduardo
Published: April 2021

Proliferative inflammatory atrophy (PIA) is an atrophic lesion of the prostate gland that occurs in men and dogs and is associated with a chronic inflammatory infiltrate. In this study, we retrospectively reviewed canine prostatic samples from intact dogs, identifying 50 normal prostates, 140 cases of prostatic hyperplasia, 171 cases of PIA, 84 with prostate cancer (PC), 14 with prostatic intraepithelial neoplasia (PIN) and 10 with bacterial prostatitis. PIA samples were then selected and classified according to the human classification. The presence of PIA lesions surrounding neoplastic areas was then evaluated to establish a morphological transition from normal to preneoplastic and neoplastic tissue. In addition, the expression of PTEN, P53, MDM2 and nuclear androgen receptor (AR) were analyzed in 20 normal samples and 20 PIA lesions by immunohistochemistry and qPCR. All PIA lesions showed variable degrees of mononuclear cell infiltration around the glands and simple atrophy was the most common histopathological feature. PIA was identified between normal glands and PC in 51 (61%) out of the 84 PC samples. PIA lesions were diffusely positive for molecular weight cytokeratin (HMWC). Decreased PTEN and AR gene and protein expression was found in PIA compared to normal samples. Overall, our results strongly suggest that PIA is a frequent lesion associated with PC. Additionally, this finding corroborates the hypothesis that in dogs, as is the case in humans, PIA is a pre neoplastic lesion that has the potential to progress into PC, indicating an alternative mechanism of prostate cancer development in dogs.
Total Psoas Area and Total Muscular Parietal Area Affect Long-Term Survival of Patients Undergoing Pneumonectomy for Non-Small Cell Lung Cancer
Authors: Daffrè Elisa , Prieto Mathilde , Martini Katharina , Hoang-Thi Trieu-Nghi , Halm Nara , Dermine Hervè , Bobbio Antonio , Chassagnon Guillaume , Revel Marie Pierre , Alifano Marco
Published: April 2021

There is no standardization in methods to assess sarcopenia; in particular the prognostic significance of muscular fatty infiltration in lung cancer patients undergoing surgery has not been evaluated so far. We thus performed several computed tomography (CT)-based morphometric measurements of sarcopenia in 238 consecutive non-small cell lung-cancer patients undergoing pneumonectomy from 1 January 2007 to 31 December 2015. Sarcopenia was assessed by the following CT-based parameters: cross-sectional total psoas area (TPA), cross-sectional total muscle area (TMA), and total parietal muscle area (TPMA), defined as TMA without TPA. Measures were performed at the level of the third lumbar vertebra and were obtained for the entire muscle surface, as well as by excluding fatty infiltration based on CT attenuation. Findings were stratified for gender, and a threshold of the 33rd percentile was set to define sarcopenia. Furthermore, we assessed the possibility of being sarcopenic at both the TPA and TPMA level, or not, by taking into account of not fatty infiltration. Five-year survival was 39.1% for the whole population. Lower TPA, TMA, and TPA were associated with lower survival at univariate analysis; taking into account muscular fatty infiltration did not result in more powerful discrimination. Being sarcopenic at both psoas and parietal muscle level had the optimum discriminating power. At the multivariable analysis, being sarcopenic at both psoas and parietal muscles (considering the whole muscle areas, including muscular fat), male sex, increasing age, and tumor stage, as well as Charlson Comorbidity Index (CCI), were independently associated with worse long-term outcomes. We conclude that sarcopenia is a powerful negative prognostic factor in patients with lung cancer treated by pneumonectomy.
Management of Synchronous Extrathoracic Oligometastatic Non-Small Cell Lung Cancer
Authors: Jones Gregory D. , Lengel Harry B. , Hsu Meier , Tan Kay See , Caso Raul , Ghanie Amanda , Connolly James G. , Bains Manjit S. , Rusch Valerie W. , Huang James , Park Bernard J. , Gomez Daniel R. , Jones David R. , Rocco Gaetano
Published: April 2021

Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state—≤5 extrathoracic metastatic lesions in ≤3 organs—is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12–29%), and the five-year OS was 36% (95% CI, 27–50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03–1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06–2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24–0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02–1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05–3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10–3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.
3D Whole-Brain Imaging Approaches to Study Brain Tumors
Authors: Taranda Julian , Turcan Sevin
Published: April 2021

Although our understanding of the two-dimensional state of brain tumors has greatly expanded, relatively little is known about their spatial structures. The interactions between tumor cells and the tumor microenvironment (TME) occur in a three-dimensional (3D) space. This volumetric distribution is important for elucidating tumor biology and predicting and monitoring response to therapy. While static 2D imaging modalities have been critical to our understanding of these tumors, studies using 3D imaging modalities are needed to understand how malignant cells co-opt the host brain. Here we summarize the preclinical utility of in vivo imaging using two-photon microscopy in brain tumors and present ex vivo approaches (light-sheet fluorescence microscopy and serial two-photon tomography) and highlight their current and potential utility in neuro-oncology using data from solid tumors or pathological brain as examples.
IDO1-Targeted Therapy Does Not Control Disease Development in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia
Authors: Öztürk Selcen , Kalter Verena , Roessner Philipp M. , Sunbul Murat , Seiffert Martina
Published: April 2021

Indoleamine-2,3-dioxygenase 1 (IDO1), a tryptophan (Trp)-catabolizing enzyme producing metabolites such as kynurenine (Kyn), is expressed by myeloid-derived suppressor cells (MDSCs) and associated with cancer immune escape. IDO1-expressing monocytic MDSCs were shown to accumulate in patients with chronic lymphocytic leukemia (CLL) and to suppress T cell activity and induce suppressive regulatory T cells (Tregs) in vitro. In the Eµ-TCL1 mouse model of CLL, we observed a strong upregulation of IDO1 in monocytic and granulocytic MDSCs, and a significantly increased Kyn to Trp serum ratio. To explore the potential of IDO1 as a therapeutic target for CLL, we treated mice after adoptive transfer of Eµ-TCL1 leukemia cells with the IDO1 modulator 1-methyl-D-tryptophan (1-MT) which resulted in a minor reduction in leukemia development which disappeared over time. 1-MT treatment further led to a partial rescue of the immune cell changes that are induced with CLL development. Similarly, treatment of leukemic mice with the clinically investigated IDO1 inhibitor epacadostat reduced the frequency of Tregs and initially delayed CLL development slightly, an effect that was, however, lost at later time points. In sum, despite the observed upregulation of IDO1 in CLL, its inhibition is not sufficient to control leukemia development in the Eµ-TCL1 adoptive transfer model.
Contemporary Neoadjuvant Therapies for High-Risk Melanoma: A Systematic Review
Authors: Boulva Kerianne , Apte Sameer , Yu Ashley , Tran Alexandre , Shorr Risa , Song Xinni , Ong Michael , Nessim Carolyn
Published: April 2021

Despite advances in adjuvant immuno- and targeted therapies, the risk of relapse for stage III melanoma remains high. With 43 active entries on clinicaltrials.gov (8 July 2020), there is a surge of interest in the role of contemporary therapies in the neoadjuvant setting. We conducted a systematic review of trials performed in the last decade evaluating neoadjuvant targeted, immuno- or intralesional therapy for resectable stage III or IV melanoma. Database searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials were conducted from inception to 13 February 2020. Two reviewers assessed titles, abstracts, and full texts. Trials investigating contemporary neoadjuvant therapies in high-risk melanoma were included. Eight phase II trials (4 randomized and 4 single-arm) involving 450 patients reported on neoadjuvant anti-BRAF/MEK targeted therapy (3), anti-PD-1/CTLA-4 immunotherapy (3), and intralesional therapy (2). The safest and most efficacious regimens were dabrafenib/trametinib and combination ipilimumab (1 mg/kg) + nivolumab (3 mg/kg). Pathologic complete response (pCR) and adverse events were comparable. Ipilimumab + nivolumab exhibited longer RFS. Contemporary neoadjuvant therapies are not only safe, but also demonstrate remarkable pCR and RFS—outcomes which are regarded as meaningful surrogates for long-term survival. Studies defining predictors of pCR, its correlation with oncologic outcomes, and phase III trials comparing neoadjuvant therapy to standard of care will be crucial.
Minimal Disease Monitoring in Pediatric Non-Hodgkin’s Lymphoma: Current Clinical Application and Future Challenges
Authors: Mussolin Lara , Damm-Welk Christine , Pillon Marta , Woessmann Wilhelm
Published: April 2021

Minimal residual disease (MRD) detection is established routine practice for treatment stratification in leukemia and used for treatment optimization in adult lymphomas. Minimal disease studies in childhood non-Hodgkin lymphomas are challenged by stratified treatment in different subtypes, high cure rates, low patient numbers, limited initial tumor material, and early progression. Current clinical applications differ between the subtypes. A prognostic value of minimal disseminated disease (MDD) could not yet be clearly established for lymphoblastic lymphoma using flow cytometry and PCR-based methods for T-cell receptor (TCR) or immunoglobulin (IG) rearrangements. MYC–IGH fusion sequences or IG rearrangements enable minimal disease detection in Burkitt lymphoma and -leukemia. An additional prognostic value of MDD in Burkitt lymphoma and early MRD in Burkitt leukemia is implicated by single studies with risk-adapted therapy. MDD and MRD determined by PCR for ALK-fusion transcripts are independent prognostic parameters for patients with ALK-positive anaplastic large cell lymphoma (ALCL). They are introduced in routine clinical practice and used for patient stratification in clinical studies. Early MRD might serve as an endpoint for clinical trials and for guiding individual therapy. Validation of MDD and MRD as prognostic parameters is required for all subtypes but ALCL. Next-generation sequencing-based methods may provide new options and applications for minimal disease evaluation in childhood lymphomas.
Loss of RET Promotes Mesenchymal Identity in Neuroblastoma Cells
Authors: Siaw Joachim T. , Gabre Jonatan L. , Uçkun Ezgi , Vigny Marc , Zhang Wancun , Van den Eynden Jimmy , Hallberg Bengt , Palmer Ruth H. , Guan Jikui
Published: April 2021

Aberrant activation of anaplastic lymphoma kinase (ALK) drives neuroblastoma (NB). Previous work identified the RET receptor tyrosine kinase (RTK) as a downstream target of ALK activity in NB models. We show here that ALK activation in response to ALKAL2 ligand results in the rapid phosphorylation of RET in NB cells, providing additional insight into the contribution of RET to the ALK-driven gene signature in NB. To further address the role of RET in NB, RET knockout (KO) SK-N-AS cells were generated by CRISPR/Cas9 genome engineering. Gene expression analysis of RET KO NB cells identified a reprogramming of NB cells to a mesenchymal (MES) phenotype that was characterized by increased migration and upregulation of the AXL and MNNG HOS transforming gene (MET) RTKs, as well as integrins and extracellular matrix components. Strikingly, the upregulation of AXL in the absence of RET reflects the development timeline observed in the neural crest as progenitor cells undergo differentiation during embryonic development. Together, these findings suggest that a MES phenotype is promoted in mesenchymal NB cells in the absence of RET, reflective of a less differentiated developmental status.
NiCo Nanoneedles on 3D Carbon Nanotubes/Carbon Foam Electrode as an Efficient Bi-Functional Catalyst for Electro-Oxidation of Water and Methanol
Authors: Pham Tung Ngoc , Samikannu Ajaikumar , Tesfalidet Solomon , Wågberg Thomas , Mikkola Jyri-Pekka
Published: April 2021

In this study, we report a 3D structured carbon foam electrode assembled from a bi-functional NiCo catalyst, carbon nanotubes (CNT), and a monolith 3D structured carbon foam (CF) as a highly active and stable electrode for oxygen evolution reaction (OER) and methanol oxidation reaction (MOR). When the NiCo@CNTs/CF electrode was used as an anode in OER, after the anodization step, the electrode required a small overpotential of 320 mV to reach the current density of 10 mA cm−2 and demonstrated excellent stability over a long testing time (total 30 h) in 1 M KOH. The as-prepared NiCo@CNTs/CF electrode also exhibited a good performance towards methanol oxidation reaction (MOR) with high current density, 100 mA cm−2 at 0.6 V vs. Ag/AgCl, and good stability in 1 M KOH plus 0.5 M CH3OH electrolyte. The NiCo@CNTs/CF catalyst/electrode provides a potential for application as an anode in water electrolysis and direct methanol fuel cells.
The Transcriptional Adaptor Protein ADA3a Modulates Flowering of Arabidopsis thaliana
Authors: Poulios Stylianos , Dadarou Despoina , Gavriilidis Maxim , Mougiou Niki , Kargios Nestoras , Maliori Vasileia , Hark Amy T. , Doonan John H. , Vlachonasios Konstantinos E.
Published: April 2021

Histone acetylation is directly related to gene expression. In yeast, the acetyltransferase general control nonderepressible-5 (GCN5) targets histone H3 and associates with transcriptional co-activators alteration/deficiency in activation-2 (ADA2) and alteration/deficiency in activation-3 (ADA3) in complexes like SAGA. Arabidopsis thaliana has two genes encoding proteins, designated ADA3a and ADA3b, that correspond to yeast ADA3. We investigated the role of ADA3a and ADA3b in regulating gene expression during flowering time. Specifically, we found that knock out mutants ada3a-2 and the double mutant ada3a-2 ada3b-2 lead to early flowering compared to the wild type plants under long day (LD) conditions and after moving plants from short days to LD. Consistent with ADA3a being a repressor of floral initiation, FLOWERING LOCUS T (FT) expression was increased in ada3a mutants. In contrast, other genes involved in multiple pathways leading to floral transition, including FT repressors, players in GA signaling, and members of the SPL transcriptional factors, displayed reduced expression. Chromatin immunoprecipitation analysis revealed that ADA3a affects the histone H3K14 acetylation levels in SPL3, SPL5, RGA, GAI, and SMZ loci. In conclusion, ADA3a is involved in floral induction through a GCN5-containing complex that acetylates histone H3 in the chromatin of flowering related genes.
Recurrent Implication of Striatal Cholinergic Interneurons in a Range of Neurodevelopmental, Neurodegenerative, and Neuropsychiatric Disorders
Authors: Poppi Lauren A. , Ho-Nguyen Khue Tu , Shi Anna , Daut Cynthia T. , Tischfield Max A.
Published: April 2021

Cholinergic interneurons are “gatekeepers” for striatal circuitry and play pivotal roles in attention, goal-directed actions, habit formation, and behavioral flexibility. Accordingly, perturbations to striatal cholinergic interneurons have been associated with many neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The role of acetylcholine in many of these disorders is well known, but the use of drugs targeting cholinergic systems fell out of favor due to adverse side effects and the introduction of other broadly acting compounds. However, in response to recent findings, re-examining the mechanisms of cholinergic interneuron dysfunction may reveal key insights into underlying pathogeneses. Here, we provide an update on striatal cholinergic interneuron function, connectivity, and their putative involvement in several disorders. In doing so, we aim to spotlight recurring physiological themes, circuits, and mechanisms that can be investigated in future studies using new tools and approaches.
Transcriptional Regulation of Thrombin-Induced Endothelial VEGF Induction and Proangiogenic Response
Authors: Catar Rusan , Moll Guido , Hosp Isa , Simon Michele , Luecht Christian , Zhao Hongfan , Wu Dashan , Chen Lei , Kamhieh-Milz Julian , Korybalska Katarzyna , Zickler Daniel , Witowski Janusz
Published: April 2021

Thrombin, the ligand of the protease-activated receptor 1 (PAR1), is a well-known stimulator of proangiogenic responses in vascular endothelial cells (ECs), which are mediated through the induction of vascular endothelial growth factor (VEGF). However, the transcriptional events underlying this thrombin-induced VEGF induction and angiogenic response are less well understood at present. As reported here, we conducted detailed promotor activation and signal transduction pathway studies in human microvascular ECs, to decipher the transcription factors and the intracellular signaling events underlying the thrombin and PAR-1-induced endothelial VEGF induction. We found that c-FOS is a key transcription factor controlling thrombin-induced EC VEGF synthesis and angiogenesis. Upon the binding and internalization of its G-protein-coupled PAR-1 receptor, thrombin triggers ERK1/2 signaling and activation of the nuclear AP-1/c-FOS transcription factor complex, which then leads to VEGF transcription, extracellular secretion, and concomitant proangiogenic responses of ECs. In conclusion, exposure of human microvascular ECs to thrombin triggers signaling through the PAR-1–ERK1/2–AP-1/c-FOS axis to control VEGF gene transcription and VEGF-induced angiogenesis. These observations offer a greater understanding of endothelial responses to thromboinflammation, which may help to interpret the results of clinical trials tackling the conditions associated with endothelial injury and thrombosis.
Histone Epigenetic Signatures in Embryonic Limb Interdigital Cells Fated to Die
Authors: Sanchez-Fernandez Cristina , Lorda-Diez Carlos I. , Duarte-Olivenza Cristina , Hurle Juan M. , Montero Juan A.
Published: April 2021

During limb formation in vertebrates with free digits, the interdigital mesoderm is eliminated by a massive degeneration process that involves apoptosis and cell senescence. The degradation process is preceded by intense DNA damage in zones located close to methylated DNA, accompanied by the activation of the DNA repair response. In this study, we show that trimethylated histone 3 (H3K4me3, H3K9me3, and H3K27me3) overlaps with zones positive for 5mC in the nuclei of interdigital cells. This pattern contrasts with the widespread distribution of acetylated histones (H3K9ac and H4ac) and the histone variant H3.3 throughout the nucleoplasm. Consistent with the intense labeling of acetylated histones, the histone deacetylase genes Hdac1, Hdac2, Hdac3, and Hdac8, and at a more reduced level, Hdac10, are expressed in the interdigits. Furthermore, local treatments with the histone deacetylase inhibitor trichostatin A, which promotes an open chromatin state, induces massive cell death and transcriptional changes reminiscent of, but preceding, the physiological process of interdigit remodeling. Together, these findings suggest that the epigenetic profile of the interdigital mesoderm contributes to the sensitivity to DNA damage that precedes apoptosis during tissue regression.
Enhancing Lithium Manganese Oxide Electrochemical Behavior by Doping and Surface Modifications
Authors: Marincaş Alexandru-Horaţiu , Ilea Petru
Published: April 2021

Lithium manganese oxide is regarded as a capable cathode material for lithium-ion batteries, but it suffers from relative low conductivity, manganese dissolution in electrolyte and structural distortion from cubic to tetragonal during elevated temperature tests. This review covers a comprehensive study about the main directions taken into consideration to supress the drawbacks of lithium manganese oxide: structure doping and surface modification by coating. Regarding the doping of LiMn2O4, several perspectives are studied, which include doping with single or multiple cations, only anions and combined doping with cations and anions. Surface modification approach consists in coating with different materials like carbonaceous compounds, oxides, phosphates and solid electrolyte solutions. The modified lithium manganese oxide performs better than pristine samples, showing improved cyclability, better behaviour at high discharge c-rates and elevated temperate and improves lithium ions diffusion coefficient.
Comparative Study of High-Performance Concrete Characteristics and Loading Test of Pretensioned Experimental Beams
Authors: Mateckova Pavlina , Bilek Vlastimil , Sucharda Oldrich
Published: April 2021

High-performance concrete (HPC) is subjected to wide attention in current research. Many research tasks are focused on laboratory testing of concrete mechanical properties with specific raw materials, where a mixture is prepared in a relatively small amount in ideal conditions. The wider utilization of HPC is connected, among other things, with its utilization in the construction industry. The paper presents two variants of HPC which were developed by modification of ordinary concrete used by a precast company for pretensioned bridge beams. The presented variants were produced in industrial conditions using common raw materials. Testing and comparison of basic mechanical properties are complemented with specialized tests of the resistance to chloride penetration. Tentative expenses for normal strength concrete (NSC) and HPC are compared. The research program was accomplished with a loading test of model experimental pretensioned beams with a length of 7 m made of ordinarily used concrete and one variant of HPC. The aim of the loading test was to determine the load–deformation diagrams and verify the design code load capacity calculation method. Overall, the article summarizes the possible benefits of using HPC compared to conventional concrete.
Comparison of [18F]FDG PET/CT and MRI for Treatment Response Assessment in Multiple Myeloma: A Meta-Analysis
Authors: Yokoyama Kota , Tsuchiya Junichi , Tateishi Ukihide
Published: April 2021

The present study was designed to assess the additional value of 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) to magnetic resonance imaging (MRI) in the treatment response assessment of multiple myeloma (MM). We performed a meta-analysis of all available studies to compare the detectability of treatment response of [18F]FDG PET/CT and MRI in treated MM. We defined detecting a good therapeutic effect as positive, and residual disease as negative. We determined the sensitivities and specificities across studies, calculated the positive and negative likelihood ratios (LR), and made summary receiver operating characteristic curves (SROC) using hierarchical regression models. The pooled analysis included six studies that comprised 278 patients. The respective performance characteristics (95% confidence interval (CI)) of [18F]FDG PET/CT and MRI were as follows: sensitivity of 80% (56% to 94%) and 25% (19% to 31%); specificity of 58% (44% to 71%) and 83% (71% to 91%); diagnostic odds ratio (DOR) of 6.0 (3.0–12.0) and 1.7 (0.7–2.7); positive LR of 1.8 (1.3–2.4) and 1.4 (0.7–2.7); and negative LR of 0.33 (0.21–0.53) and 0.81 (0.62–1.1). In the respective SROC curves, the area under the curve was 0.77 (SE, 0.038) and 0.59 (SE, 0.079) and the Q* index was 0.71 and 0.57. Compared with MRI, [18F]FDG PET/CT had higher sensitivity and better DOR and SROC curves. Compared with MRI, [18F]FDG PET/CT had greater ability to detect the treatment assessment of MM.
Pneumomediastinum, Pneumoretroperitoneum, Pneumoperitoneum and Subcutaneous Emphysema Secondary to a Penetrating Anal Injury
Authors: Hsiao Yu-Ting , Lin Shyh-Wen , Chuang Pei Wen , Tsai Ming-Jen
Published: April 2021

Simultaneous occurrence of pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema is rare. The most reported mechanisms are barotrauma, thermal injury and instrument puncture caused by colonoscopy. Ectopic air may travel into different body compartments through distinct anatomical fascial planes. Definite curative treatment involves surgical repair of the bowel wall defect. Conservative treatment is available in selected patients. Here, we present a case of traumatic penetrating rectal injury leading to developing air in the peritoneum, retroperitoneum, mediastinum, and subcutaneous space with good recovery under conservative treatment.
The Trend and Status of Energy Resources and Greenhouse Gas Emissions in the Malaysia Power Generation Mix
Authors: Abdul Latif Siti Norasyiqin , Chiong Meng Soon , Rajoo Srithar , Takada Asako , Chun Yoon-Young , Tahara Kiyotaka , Ikegami Yasuyuki
Published: April 2021

Environmental issues in energy policy, especially global warming, have received more attention lately than ever before. Excessive dependence on fossil fuels, deforestation, and land degradation are the three main factors that lead to increased carbon dioxide (CO2) emissions. Consequently, the global average temperature has doubled compared to anticipation. Various international protocols and agendas have been established, pledged to restore the global average temperature to the 1990 level. As a result, energy policies worldwide have also undergone various transformations to align with these protocols since then. As a developing nation, Malaysian’s electricity demand has continuously grown in the past two decades. To date, the electricity sector is still dominated by fossil fuels. Government incentives have been the most influential factor in the nation’s energy mix trend. Several energy policies implemented throughout the past 22 years have seen the shift from natural gas to coal power in power plants, and in more recent years, renewable energy resources. Numerous studies in the past have independently outlined the status of various energy source in Malaysia. However, they all fell short in providing the greenhouse gas (GHG) emissions in the Malaysian energy sector. Notably, the question that remains to be answered is how GHG emissions have changed in response to the amendment in the energy mix; hence, the effectiveness of policy change in this aspect remains unknown. This paper analysed the past and present trend of Malaysia electricity generation mix and the resultant GHG emissions. In particular, this paper focused on investigating the variation of combined specific GHG emissions in the Malaysian electricity sector, in response to the policy change within the past 22 years. This provides the insight for Malaysian policymakers to evaluate the effectiveness of past policies in GHG emissions and the measures to be taken in future. The finding of this paper shows the attention on the nation’s GHG emissions has evolved over the years, following the diversification in energy mix driven by the policy change. It was also found that, on average, it took a decade for a significant reduction in specific GHG emission to be visible since the government’s energy policy implementation.
Model-Predictive-Control-Based Reference Governor for Fuel Cells in Automotive Application Compared with Performance from a Real Vehicle
Authors: Vrlić Martin , Ritzberger Daniel , Jakubek Stefan
Published: April 2021

In this paper, a real-time capable reference governor superordinate model predictive controller (RG-MPC) is developed for fuel cell (FC) control suitable for automotive application. The RG-MPC provides reference trajectories for the subordinate proportional-integral (PI) controllers, which act directly on the FC system. Antiwindup and decoupling schemes, which are common problems in multivariable PI control, are unnecessary, given that the RG-MPC can inherently consider constraints and multivariable systems. The PI dynamics are incorporated into the prediction model used for control, ensuring the feasibility of the provided references for the PI controllers. The successive linearization technique is used in the RG-MPC to cope with the model’s nonlinear nature in real-time. The concept has been illustrated in a simulation scenario featuring efficient and safe power control of an FC stack in automotive application using real driving data obtained from an in-house-built FC vehicle. This work is the first step towards upgrading an existing, PI-based control scheme without the necessity of completely rebuilding the interface.
Contribution of Wind Farms to the Stability of Power Systems with High Penetration of Renewables
Authors: Castro Martinez Jesus , Arnaltes Santiago , Alonso-Martinez Jaime , Rodriguez Amenedo Jose Luis
Published: April 2021

Power system inertia is being reduced because of the increasing penetration of renewable energies, most of which use power electronic interfaces with the grid. This paper analyses the contribution of inertia emulation and droop control to the power system stability. Although inertia emulation may appear the best option to mitigate frequency disturbances, a thorough analysis of the shortcomings that face real-time implementations shows the opposite. Measurement noise and response delay for inertia emulation hinder controller performance, while the inherently fast droop response of electronic converters provides better frequency support. System stability, expressed in terms of rate of change of frequency (ROCOF) and frequency nadir, is therefore improved with droop control, compared to inertia emulation.
Stability Analysis of Shunt Active Power Filter with Predictive Closed-Loop Control of Supply Current
Authors: Bielecka Agata , Wojciechowski Daniel
Published: April 2021

This paper presents a shunt active power filter connected to the grid via an LCL coupling circuit with implemented closed-loop control. The proposed control system allows selective harmonic currents compensation up to the 50th harmonic with the utilization of a model-based predictive current controller. As the system is fully predictive, it provides high effectiveness of the harmonic reduction, which is proved by waveforms achieved in performed tests. On the other hand, the control system is prone to loss of stability. Therefore, the paper is focused on the stability analysis of the discussed control system with the additional outer control loop of the supply current with predictive control of this current. The conducted stability analysis encompasses the assessment of system stability as a function of the coupling circuit parameter identification accuracy, whose values are implemented in the current controller, as well as parameters such as the sampling frequency and proportional-integral (PI) controller coefficients. The obtained results show that the ranges of the LCL circuit parameter identification accuracy for which the system remains stable are relatively wide. However, the most effective compensation of the supply current distortion is achieved for the parameters identified correctly, and the greatest impact on the compensation quality has the value of L1 inductance.