bluuebunny/crossref_metadata_2025 huggingface dataset:
Resonance Energy Transfer to Track the Motion of Lanthanide Ions—What Drives the Intermixing in Core-Shell Upconverting Nanoparticles?
Authors: Bastian Philipp U. , Robel Nathalie , Schmidt Peter , Schrumpf Tim , Günter Christina , Roddatis Vladimir , Kumke Michael U.
Published: December 2021

The imagination of clearly separated core-shell structures is already outdated by the fact, that the nanoparticle core-shell structures remain in terms of efficiency behind their respective bulk material due to intermixing between core and shell dopant ions. In order to optimize the photoluminescence of core-shell UCNP the intermixing should be as small as possible and therefore, key parameters of this process need to be identified. In the present work the Ln(III) ion migration in the host lattices NaYF4 and NaGdF4 was monitored. These investigations have been performed by laser spectroscopy with help of lanthanide resonance energy transfer (LRET) between Eu(III) as donor and Pr(III) or Nd(III) as acceptor. The LRET is evaluated based on the Förster theory. The findings corroborate the literature and point out the migration of ions in the host lattices. Based on the introduced LRET model, the acceptor concentration in the surrounding of one donor depends clearly on the design of the applied core-shell-shell nanoparticles. In general, thinner intermediate insulating shells lead to higher acceptor concentration, stronger quenching of the Eu(III) donor and subsequently stronger sensitization of the Pr(III) or the Nd(III) acceptors. The choice of the host lattice as well as of the synthesis temperature are parameters to be considered for the intermixing process.
Unlike Brief Inhibition of Microglia Proliferation after Spinal Cord Injury, Long-Term Treatment Does Not Improve Motor Recovery
Authors: Poulen Gaëtan , Bartolami Sylvain , Noristani Harun N. , Perrin Florence E. , Gerber Yannick N.
Published: December 2021

Microglia are major players in scar formation after an injury to the spinal cord. Microglia proliferation, differentiation, and survival are regulated by the colony-stimulating factor 1 (CSF1). Complete microglia elimination using CSF1 receptor (CSF1R) inhibitors worsens motor function recovery after spinal injury (SCI). Conversely, a 1-week oral treatment with GW2580, a CSF1R inhibitor that only inhibits microglia proliferation, promotes motor recovery. Here, we investigate whether prolonged GW2580 treatment further increases beneficial effects on locomotion after SCI. We thus assessed the effect of a 6-week GW2580 oral treatment after lateral hemisection of the spinal cord on functional recovery and its outcome on tissue and cellular responses in adult mice. Long-term depletion of microglia proliferation after SCI failed to improve motor recovery and had no effect on tissue reorganization, as revealed by ex vivo diffusion-weighted magnetic resonance imaging. Six weeks after SCI, GW2580 treatment decreased microglial reactivity and increased astrocytic reactivity. We thus demonstrate that increasing the duration of GW2580 treatment is not beneficial for motor recovery after SCI.
An Integrated Safety, Health and Environmental Management Capability Maturity Model for Construction Organisations: A Case Study in Ghana
Authors: Asah-Kissiedu Millicent , Manu Patrick , Booth Colin Anthony , Mahamadu Abdul-Majeed , Agyekum Kofi
Published: December 2021

Safety, health and environmental (SHE) management is becoming a priority as construction companies (i.e., contractors) strive to reduce construction accidents and negative environmental impacts, conform to regulatory requirements, and sustain their competitiveness. Consequently, construction firms are expected to adopt and implement innovative SHE management systems to mitigate SHE risks effectively and efficiently. For construction firms to effectively do this, they need to have the adequate capability in respect of integrated SHE management. However, there is limited empirical insight regarding the integrated SHE management capabilities of construction companies. Furthermore, there is limited insight regarding the mechanisms for ascertaining the integrated SHE management capability of construction companies to guide such organisations towards SHE management excellence in their operations. Drawing on the capability maturity model integration (CMMI) concept, this study, by applying expert reviews (i.e., Delphi technique and the design methodology for capability maturity grids), developed an integrated Safety, Health and Environmental Management Maturity Model (iSHEM-CMM). The model offers capability maturity assessment on a five-level scale within five thematic categories and 20 integrated SHE management capability attributes. Based on an industrial validation by construction professionals, it is concluded that the maturity model is a useful assessment framework or tool for industry stakeholders, particularly construction firms, to evaluate the status of their current SHE management capabilities, identify strengths and improvement areas, and accordingly prioritise strategies/actions for improving their SHE management. Furthermore, clients who appoint construction companies could use the model as part of prequalification arrangements in selecting construction companies with an adequate SHE management capability.
Comprehensive Success Evaluation Framework for Socio-Natural Disaster Recovery Projects
Authors: Bahmani Homa , Zhang Wei
Published: December 2021

There is an ample amount of studies attempting to evaluate the success of recovery projects. However, they mostly focused on unilateral success indicators and ignored the continual lifespan and various stakeholders. This study has focused on addressing these obstacles by proposing a comprehensive success evaluation framework for recovery projects following socio-natural disasters through identifying the success dimensions and their effectual parameters. Triangulation of the results of quantitative and qualitative methods and the logic of qualitative comparative analysis were used to answer the research questions. System thinking and the concept of resiliency and sustainability, known as key performance indicators, structured the success measurements. The effectual elements on the success, critical success factors, were grouped according to the continuous life-cycle of these projects. Finally, the framework for success evaluation of socio-natural disaster recovery projects illustrates interactions among the deducted critical success factors and key performance indicators. The proposed framework may serve as more efficient guidelines to set and follow the recovery goals, comprehensively considering a wide range of stakeholders and long-term recovery. The results of this study can be subject to further research by using different methods to enhance the comprehensivity of the framework. The authors will conduct further research to verify the suggested framework by implementing case studies.
Experimental Study on Performance of Steel Fiber-Reinforced Concrete V-Shaped Columns
Authors: Hassan Rafea F. , Al-Salim Nabeel H. , Mohammed Nisreen S. , Hussein Husam H.
Published: December 2021

Structural engineers have used V-shaped columns based on technical requirements. The inclination of the V-shaped column underlines the individual purpose of the base floor. However, there is no any specification or guidance on the design of V-shaped columns to date. The aim of this study is to investigate the behavior of V-shaped reinforced concrete columns with three angles between columns (30°, 60°, and 90°) in order for the results to be used in the design and analysis of the V-shaped column. The impact of using a 1.5% dosage of micro-straight-steel fiber (MSSF) in the concrete mixture was also studied. The results showed that the V-shaped column with 30°, regardless of the concrete type (with and without MSSFs), exhibited crushing at legends when the sample reached the ultimate load, while no cracks occurred at the legends during the test for the other V-shaped columns. Upon increasing the angle of inclination of the V-shaped columns, the ultimate load capacity was decreased by 24%, 23%, and 20% for V-shaped columns with 30°, 60°, and 90° angles of inclination, respectively. The addition of MSSFs in the concrete significantly improved the ultimate axial load and the bending moment compared to the reference specimens with the normal reinforced concrete (NRC). The steel-fiber-reinforced concrete (SFRC) vertical column specimen demonstrated the highest increase in axial load, and the other SFRC V-shaped and flexural specimens showed a minor increase compared to the NRC specimens.
Identification of Morphologic Criteria Associated with Biochemical Recurrence in Intraductal Carcinoma of the Prostate
Authors: Diop Mame-Kany , Albadine Roula , Kougioumoutzakis André , Delvoye Nathalie , Hovington Hélène , Bergeron Alain , Fradet Yves , Saad Fred , Trudel Dominique
Published: December 2021

Intraductal carcinoma of the prostate (IDC-P) is an aggressive subtype of prostate cancer strongly associated with an increased risk of biochemical recurrence (BCR). However, approximately 40% of men with IDC-P remain BCR-free five years after radical prostatectomy. In this retrospective multicenter study, we aimed to identify histologic criteria associated with BCR for IDC-P lesions. A total of 108 first-line radical prostatectomy specimens were reviewed. In our test cohort (n = 39), presence of larger duct size (>573 µm in diameter), cells with irregular nuclear contours (CINC) (≥5 CINC in two distinct high-power fields), high mitotic score (>1.81 mitoses/mm2), blood vessels, and comedonecrosis were associated with early BCR (<18 months) (p < 0.05). In our validation cohort (n = 69), the presence of CINC or blood vessels was independently associated with an increased risk of BCR (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.09–4.96, p = 0.029). When combining the criteria, the presence of any CINC, blood vessels, high mitotic score, or comedonecrosis showed a stronger association with BCR (HR 2.74, 95% CI 1.21–6.19, p = 0.015). Our results suggest that IDC-P can be classified as low versus high-risk of BCR. The defined morphologic criteria can be easily assessed and should be integrated for clinical application following validation in larger cohorts.
Interstitial High-Dose-Rate Brachytherapy of Liver Metastases in Oligometastatic Patients
Authors: Walter Franziska , Rottler Maya , Nierer Lukas , Landry Guillaume , Well Justus , Rogowski Paul , Mohnike Konrad , Seidensticker Max , Ricke Jens , Belka Claus , Corradini Stefanie
Published: December 2021

Local ablative treatments have emerged as a promising treatment strategy for patients with oligometastatic disease. Among others, interstitial brachytherapy (iBT) is an upcoming treatment option for unresectable liver metastases. We report the feasibility and oncologic outcome of iBT of oligometastatic liver metastases performed in patients with limited tumor burdens in a high-volume center. Patients undergoing iBT between August 2017and March 2019 were included. A retrospective analysis of patient outcomes and treatment complications was performed. Patients treated for metastatic colorectal carcinoma (CRC) were compared to other histologies. A total of 141 iBT procedures were performed in 106 patients (male:52; female:54) and 244 liver metastases. Overall, 51% (54/106) of patients had a diagnosis of metastatic CRC. The median follow-up was 9 months, and overall survival (OS) was 92.3% at 6 months and 76.3% at 12 months. Local-relapse-free survival (LRFS) was 88.4% at 6 months and 71.5% at 12 months, with a significant difference between patients with CRC (84.1% and 50.6%) versus other histologies (92.4% and 92.4%, p < 0.001). A sub-group analysis showed a significant advantage in patients with CRC receiving a minimal dose (D100) of 20 Gy to the planning target volume. Treatments of smaller total liver-tumor volumes (<18 ccm) resulted in better LRFS rates. iBT is a safe and effective treatment approach for oligometastatic liver disease. A higher treatment dose is needed for patients with CRC. Moreover, lower metastatic burdens may be favorable for LRFS. Prospective studies are needed to assess the role of iBT in the oligometastatic setting as an alternative to other local ablative treatment approaches in patients with liver metastases.
miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells
Authors: Chang Wei-An , Tsai Ming-Ju , Hung Jen-Yu , Wu Kuan-Li , Tsai Ying-Ming , Huang Yung-Chi , Chang Chao-Yuan , Tsai Pei-Hsun , Hsu Ya-Ling
Published: December 2021

Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.
Genetic Literacy and Communication of Genetic Information in Families Concerned with Hereditary Breast and Ovarian Cancer: A Cross-Study Comparison in Two Countries and within a Timeframe of More Than 10 Years
Authors: Pedrazzani Carla , Ming Chang , Bürki Nicole , Caiata-Zufferey Maria , Chappuis Pierre O. , Duquette Debra , Heinimann Karl , Heinzelmann-Schwarz Viola , Graffeo-Galbiati Rossella , Merajver Sofia D. , Milliron Kara J. , Monnerat Christian , Pagani Olivia , Rabaglio Manuela , Katapodi Maria C.
Published: December 2021

Examining genetic literacy in families concerned with hereditary breast and ovarian cancer (HBOC) helps understand how genetic information is passed on from individuals who had genetic counseling to their at-risk relatives. This cross-study comparison explored genetic literacy both at the individual and the family level using data collected from three sequential studies conducted in the U.S. and Switzerland over ≥10 years. Participants were primarily females, at-risk or confirmed carriers of HBOC-associated pathogenic variants, who had genetic counselling, and ≥1 of their relatives who did not. Fifteen items assessed genetic literacy. Among 1933 individuals from 518 families, 38.5% had genetic counselling and 61.5% did not. Although genetic literacy was higher among participants who had counselling, some risk factors were poorly understood. At the individual level, genetic literacy was associated with having counselling, ≤5 years ago, higher education, and family history of cancer. At the family level, genetic literacy was associated with having counselling, higher education, and a cancer diagnosis. The findings suggest that specific genetic information should be emphasized during consultations, and that at-risk relatives feel less informed about inherited cancer risk, even if information is shared within families. There is a need to increase access to genetic information among at-risk individuals.
Postoperative Radiotherapy for Endometrial Cancer in Elderly (≥80 Years) Patients: Oncologic Outcomes, Toxicity, and Validation of Prognostic Scores
Authors: Meixner Eva , Lang Kristin , König Laila , Sandrini Elisabetta , Lischalk Jonathan W. , Debus Jürgen , Hörner-Rieber Juliane
Published: December 2021

Endometrial cancer is a common malignancy in elderly women that are more likely to suffer from limiting medical comorbidities. Given this narrower therapeutic ratio, we aimed to assess the oncologic outcomes and toxicity in the adjuvant setting. Out of a cohort of 975 women, seventy patients aged ≥ 80 years, treated with curative postoperative radiotherapy (RT) for endometrial cancer between 2005 and 2021, were identified. Outcomes were assessed using Kaplan–Meier-analysis and comorbidities using the Charlson Comorbidity Index and G8 geriatric score. The overall survival at 1-, 2- and 5-years was 94.4%, 82.6%, and 67.6%, respectively, with significant correlation to G8 score. At 1- and 5-years, the local control rates were 89.5% and 89.5% and distant control rates were 86.3% and 66.9%, respectively. Severe (≥grade 3) acute toxicity was rare with gastrointestinal (2.9%), genitourinary (1.4%), and vaginal disorders (1.4%). Univariate analysis significantly revealed inferior overall survival with lower RT dose, G8 score, hemoglobin levels and obesity, while higher grading, lymphangiosis, RT dose decrease and the omission of chemotherapy reduced distant control. Despite older age and additional comorbidities, elderly patients tolerated curative treatment well. The vast majority completed treatment as planned with very low rates of acute severe side-effects. RT offers durable local control; however, late distant failure remains an issue.
Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer
Authors: Al-Taie Zainab , Hannink Mark , Mitchem Jonathan , Papageorgiou Christos , Shyu Chi-Ren
Published: December 2021

Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.
NT1-Tau Is Increased in CSF and Plasma of CJD Patients, and Correlates with Disease Progression
Authors: Mengel David , Mok Tze How , Nihat Akin , Liu Wen , Rissman Robert A. , Galasko Douglas , Zetterberg Henrik , Mead Simon , Collinge John , Walsh Dominic M.
Published: December 2021

This study investigates the diagnostic and prognostic potential of different forms of tau in biofluids from patients with Creutzfeldt-Jakob disease (CJD). Extracellular tau, which is molecularly heterogeneous, was measured using ultra-sensitive custom-made Simoa assays for N-terminal (NT1), mid-region, and full-length tau. We assessed cross-sectional CSF and plasma from healthy controls, patients with Alzheimer’s disease (AD) and CJD patients. Then, we evaluated the correlation of the best-performing tau assay (NT1-tau) with clinical severity and functional decline (using the MRC Prion Disease Rating Scale) in a longitudinal CJD cohort (n = 145). In a cross-sectional study, tau measured in CSF with the NT1 and mid-region Simoa assays, separated CJD (n = 15) from AD (n = 18) and controls (n = 21) with a diagnostic accuracy (AUCs: 0.98–1.00) comparable to or better than neurofilament light chain (NfL; AUCs: 0.96–0.99). In plasma, NT1-measured tau was elevated in CJD (n = 5) versus AD (n = 15) and controls (n = 15). Moreover, in CJD plasma (n = 145) NT1-tau levels correlated with stage and rate of disease progression, and the effect on clinical progression was modified by the PRNP codon 129. Our findings suggest that plasma NT1-tau shows promise as a minimally invasive diagnostic and prognostic biomarker of CJD, and should be further investigated for its potential to monitor disease progression and response to therapies.
Pleiotropic Effects of the Protease-Activated Receptor 1 (PAR1) Inhibitor, Vorapaxar, on Atherosclerosis and Vascular Inflammation
Authors: Friebel Julian , Moritz Eileen , Witkowski Marco , Jakobs Kai , Strässler Elisabeth , Dörner Andrea , Steffens Daniel , Puccini Marianna , Lammel Stella , Glauben Rainer , Nowak Franziska , Kränkel Nicolle , Haghikia Arash , Moos Verena , Schutheiss Heinz-Peter , Felix Stephan B. , Landmesser Ulf , Rauch Bernhard H. , Rauch Ursula
Published: December 2021

Background: Protease-activated receptor 1 (PAR1) and toll-like receptors (TLRs) are inflammatory mediators contributing to atherogenesis and atherothrombosis. Vorapaxar, which selectively antagonizes PAR1-signaling, is an approved, add-on antiplatelet therapy for secondary prevention. The non-hemostatic, platelet-independent, pleiotropic effects of vorapaxar have not yet been studied. Methods and Results: Cellular targets of PAR1 signaling in the vasculature were identified in three patient cohorts with atherosclerotic disease. Evaluation of plasma biomarkers (n = 190) and gene expression in endomyocardial biopsies (EMBs) (n = 12) revealed that PAR1 expression correlated with endothelial activation and vascular inflammation. PAR1 colocalized with TLR2/4 in human carotid plaques and was associated with TLR2/4 gene transcription in EMBs. In addition, vorapaxar reduced atherosclerotic lesion size in apolipoprotein E–knock out (ApoEko) mice. This reduction was associated with reduced expression of vascular adhesion molecules and TLR2/4 presence, both in isolated murine endothelial cells and the aorta. Thrombin-induced uptake of oxLDL was augmented by additional TLR2/4 stimulation and abrogated by vorapaxar. Plaque-infiltrating pro-inflammatory cells were reduced in vorapaxar-treated ApoEko mice. A shift toward M2 macrophages paralleled a decreased transcription of pro-inflammatory cytokines and chemokines. Conclusions: PAR1 inhibition with vorapaxar may be effective in reducing residual thrombo-inflammatory event risk in patients with atherosclerosis independent of its effect on platelets.
Lamin A/C-Dependent Translocation of Megakaryoblastic Leukemia-1 and β-Catenin in Cyclic Strain-Induced Osteogenesis
Authors: Khan Asmat Ullah , Qu Rongmei , Yang Yuchao , Fan Tingyu , Peng Yan , Sun Bing , Qiu Xianshuai , Wu Shutong , Wang Zetong , Zhou Zhitao , Khan Muhammad Akram , Dai Jingxing , Ouyang Jun
Published: December 2021

Lamins are intermediate filaments that play a crucial role in sensing mechanical strain in the nucleus of cells. β-catenin and megakaryoblastic leukemia-1 (MKL1) are critical signaling molecules that need to be translocated to the nucleus for their transcription in response to mechanical strain that induces osteogenesis. However, the exact molecular mechanism behind the translocation of these molecules has not been fully investigated. This study used 10% cyclic strain to induce osteogenesis in the murine osteoblast precursor cell line (MC3T3). The translocation of β-catenin and MKL1 was studied by performing knockdown and overexpression of lamin A/C (LMNA). Cyclic strain increased the expression of osteogenic markers such as alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and enhanced ALP staining after seven days of incubation. Resultantly, MKL1 and β-catenin were translocated in the nucleus from the cytoplasm during the stress-induced osteogenic process. Knockdown of LMNA decreased the accumulation of MKL1 and β-catenin in the nucleus, whereas overexpression of LMNA increased the translocation of these molecules. In conclusion, our study indicates that both MKL1 and β-catenin molecules are dependent on the expression of LMNA during strain-induced osteogenesis.
Glioblastoma: Relationship between Metabolism and Immunosuppressive Microenvironment
Authors: Hernández Ainhoa , Domènech Marta , Muñoz-Mármol Ana M. , Carrato Cristina , Balana Carmen
Published: December 2021

Glioblastoma (GBM) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping this tumor microenvironment (TME) regulate tumor initiation, progression, and treatment response. Genetic alterations and metabolism pathways are two main elements that influence tumor immune cells and TME. In this manuscript, we review how both factors can contribute to an immunosuppressive state and overview the strategies being tested.
Restoring Osteochondral Defects through the Differentiation Potential of Cartilage Stem/Progenitor Cells Cultivated on Porous Scaffolds
Authors: Wang Hsueh-Chun , Lin Tzu-Hsiang , Hsu Che-Chia , Yeh Ming-Long
Published: December 2021

Cartilage stem/progenitor cells (CSPCs) are cartilage-specific, multipotent progenitor cells residing in articular cartilage. In this study, we investigated the characteristics and potential of human CSPCs combined with poly(lactic-co-glycolic acid) (PLGA) scaffolds to induce osteochondral regeneration in rabbit knees. We isolated CSPCs from human adult articular cartilage undergoing total knee replacement (TKR) surgery. We characterized CSPCs and compared them with infrapatellar fat pad-derived stem cells (IFPs) in a colony formation assay and by multilineage differentiation analysis in vitro. We further evaluated the osteochondral regeneration of the CSPC-loaded PLGA scaffold during osteochondral defect repair in rabbits. The characteristics of CSPCs were similar to those of mesenchymal stem cells (MSCs) and exhibited chondrogenic and osteogenic phenotypes without chemical induction. For in vivo analysis, CSPC-loaded PLGA scaffolds produced a hyaline-like cartilaginous tissue, which showed good integration with the host tissue and subchondral bone. Furthermore, CSPCs migrated in response to injury to promote subchondral bone regeneration. Overall, we demonstrated that CSPCs can promote osteochondral regeneration. A monophasic approach of using diseased CSPCs combined with a PLGA scaffold may be beneficial for repairing complex tissues, such as osteochondral tissue.
Ion Channels and Pumps in Autophagy: A Reciprocal Relationship
Authors: Abuammar Hussein , Bhattacharjee Arindam , Simon-Vecsei Zsófia , Blastyák András , Csordás Gábor , Páli Tibor , Juhász Gábor
Published: December 2021

Autophagy, the process of cellular self-degradation, is intrinsically tied to the degradative function of the lysosome. Several diseases have been linked to lysosomal degradative defects, including rare lysosomal storage disorders and neurodegenerative diseases. Ion channels and pumps play a major regulatory role in autophagy. Importantly, calcium signaling produced by TRPML1 (transient receptor potential cation channel, mucolipin subfamily) has been shown to regulate autophagic progression through biogenesis of autophagic-lysosomal organelles, activation of mTORC1 (mechanistic target of rapamycin complex 1) and degradation of autophagic cargo. ER calcium channels such as IP3Rs supply calcium for the lysosome, and lysosomal function is severely disrupted in the absence of lysosomal calcium replenishment by the ER. TRPML1 function is also regulated by LC3 (microtubule-associated protein light chain 3) and mTORC1, two critical components of the autophagic network. Here we provide an overview of the current knowledge about ion channels and pumps—including lysosomal V-ATPase (vacuolar proton-ATPase), which is required for acidification and hence proper enzymatic activity of lysosomal hydrolases—in the regulation of autophagy, and discuss how functional impairment of some of these leads to diseases.
Potential Mechanisms Underlying Hypoxia-Induced Diabetes in a Rodent Model: Implications for COVID-19
Authors: Pae Eung-Kwon , Harper Ronald M.
Published: December 2021

Previous studies reported that repetitive hypoxia in rat pups reduces insulin secretion and elevates fasting blood glucose levels; these sequelae persisted for several months. This report describes how episodic hypoxic events elevate a chloride ion exporter, K+-Cl− cotransporter-2 (KCC2), in the plasma membrane of insulin-secreting pancreatic β-cells. We assume that acute diabetic symptoms observed in rat pups with periodic oxygen desaturation could result from a lack of blood insulin levels due to disturbed β-cell function. This acute hypo-insulinemia may result from a disruption in chloride balance in β-cells arising from an imbalanced KCC2-NKCC1 (chloride exporter-importer) density as a consequence of periodic oxygen desaturation. Mechanistically, we postulate that a reduced insulin secretion due to the KCC2-NKCC1 imbalance subsequent to acute oxygen desaturation could result in hyperglycemia in rat pups, paralleling symptoms shown in patients with COVID-19 who experienced acute respiratory distress.
Standards of Nutritional Care for Patients with Cystic Fibrosis: A Methodological Primer and AGREE II Analysis of Guidelines
Authors: Grammatikopoulou Maria G. , Vassilakou Tonia , Goulis Dimitrios G. , Theodoridis Xenophon , Nigdelis Meletios P. , Petalidou Arianna , Gkiouras Konstantinos , Poulimeneas Dimitrios , Alexatou Olga , Tsiroukidou Kyriaki , Marakis Georgios , Daniil Zoe , Bogdanos Dimitrios P.
Published: December 2021

Although many Clinical Practice Guidelines (CPGs) have been published for the care of patients with Cystic Fibrosis (CF), including a variety of nutrition recommendations, the quality of these CPGs has never been evaluated. The aim of this study was to compare, review, and critically appraise CPGs for the nutritional management of CF, throughout the lifespan. We searched PubMed, Guidelines International Network (GIN), ECRI Institute, and Guidelines Central for CPGs, with information on the nutritional management of CF. Retrieved CPGs were appraised by three independent reviewers, using the Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument and checklist. A total of 22 CPGs (seven solely nutrition oriented), by 14 different publishers, were retrieved. The Thoracic Society of Australia and New Zealand CPGs scored the highest overall quality (94.4%), while the Paediatric Gastroenterology Society/Dietitians Association of Australia CPGs had the lowest score (27.8%). Great variation in AGREE II domain-specific scores was observed in all CPGs, suggesting the existence of different strengths and weaknesses. Despite the availability of several CPGs, many appear outdated, lacking rigor, transparency, applicability, and efficiency, while incorporating bias. Considering that CPGs adherence is associated with better outcomes and the need for improving life expectancy in patients with CF, the development of CPGs of better quality is deemed necessary.
Numerical Analysis of High-Velocity Oxygen Fuel Thermal-Spray Process for Fe-Based Amorphous Coatings
Authors: Yu Jianxing , Liu Xin , Yu Yang , Li Haoda , Liu Pengfei , Sun Ruoke , Wang Limin , Li Pengfei
Published: December 2021

High-velocity oxygen fuel (HVOF)-sprayed amorphous alloy coatings usually have advantages of a dense structure that improve their resistance to corrosion, wear, and fatigue in the substrate. The flame flow characteristics and particle behaviors during the spray process have a significant influence on the amorphous coating structure and properties. In this study, a computational fluid dynamics model is enforced to analyze the flame flow and Fe-based amorphous alloy particle behavior in an HVOF spray process. The flame flow temperature, velocity characteristics, and the Fe48Cr15Mo14C15B6Y2 Fe-based amorphous alloy particles’ velocities, temperatures, flight trajectories, and mass concentration distribution characteristics are simulated. Moreover, the effects of the oxygen/fuel ratio, particle morphology parameter, particle-injection rate, and angle on the particle behavior are also investigated. Judging from the simulation results, the optimum amorphous alloy particle size varies between 20 and 30 μm, the shape factor is within the range of 0.9–1, the optimum O/F ratio is 3.4, the optimum injection angle is 45°, and the optimum injection rate is 10 m/s. With these conditions, most of the particles settled toward the centerline of the spray gun and are in a semisolid or solid state before affecting the substrate, giving the materials optimal coating structure and performance.
Evaluation of a Moisture Diffusion Model for Analyzing the Convective Drying Kinetics of Lavandula x allardii Leaves
Authors: Chasiotis Vasileios , Tzempelikos Dimitrios , Filios Andronikos
Published: December 2021

In the present case study, a moisture diffusion model is developed to simulate the drying kinetics of Lavandula x allardii leaves for non-stationary convective drying regimes. Increasing temperature profiles are applied over the drying duration and the influence of temperature advancing rates on the moisture removal and the drying rate is investigated. The model assumes a one-dimensional moisture transfer under transient conditions, which occurs from the leaf center to the surface by liquid diffusion due to the concentration gradient developed by the surface water evaporation caused by the difference of water vapor partial pressure between the drying medium and the leaf surface. A numerical solution of Fick’s 2nd law is obtained by an in-house code using the finite volume method, including shrinkage and a variable temperature-dependent effective moisture diffusion coefficient. The numerical results have been validated against experimental data for selected cases using statistical indices and the predicted dehydration curves presented a good agreement for the higher temperature advancing rates. The examined modeling approach was found stable and can output, in a computationally efficient way, the temporal changes of moisture and drying rate. Thus, the present model could be used for engineering applications involving the design, optimization and development of drying equipment and drying schedules for the examined type of non-stationary drying patterns.
Evaluation of Pseudo-Random Number Generation on GPU Cards
Authors: Askar Tair , Shukirgaliyev Bekdaulet , Lukac Martin , Abdikamalov Ernazar
Published: December 2021

Monte Carlo methods rely on sequences of random numbers to obtain solutions to many problems in science and engineering. In this work, we evaluate the performance of different pseudo-random number generators (PRNGs) of the Curand library on a number of modern Nvidia GPU cards. As a numerical test, we generate pseudo-random number (PRN) sequences and obtain non-uniform distributions using the acceptance-rejection method. We consider GPU, CPU, and hybrid CPU/GPU implementations. For the GPU, we additionally consider two different implementations using the host and device application programming interfaces (API). We study how the performance depends on implementation parameters, including the number of threads per block and the number of blocks per streaming multiprocessor. To achieve the fastest performance, one has to minimize the time consumed by PRNG seed setup and state update. The duration of seed setup time increases with the number of threads, while PRNG state update decreases. Hence, the fastest performance is achieved by the optimal balance of these opposing effects.
X-ray Micro-Tomography as a Method to Distinguish and Characterize Natural and Cultivated Pearls
Authors: Vigorelli Luisa , Croce Elisabetta , Angelici Debora , Navone Raffaella , Grassini Sabrina , Guidorzi Laura , Re Alessandro , Lo Giudice Alessandro
Published: December 2021

Digital radiography and computed tomography are two fundamental diagnostic techniques in different fields of research, including cultural heritage studies and gemmology. The application of these physical methods of investigation has gained considerable importance as they are non-invasive techniques. The presented work has been mainly focused on micro-tomographic analysis. The project is concerned with the study of natural and cultivated pearls in order to develop an investigation methodology for the analysis, distinction and characterization of different types of pearls, some of them belonging to different precious jewels from private collections. The investigations, carried out on a total of 22 heterogeneous types of pearls, allowed us to establish their origin (natural or cultivated) or to confirm/deny if a hypothesis was already expressed, and as well to highlight the cultivation methodology used case by case. Furthermore, it was possible to ascertain how large and varied the market for cultured pearls is nowadays and how difficult is, in some particular cases, to ascertain their attribution to a certain origin.
Beyond Bitcoin: Recent Trends and Perspectives in Distributed Ledger Technology
Authors: Romano Diego , Schmid Giovanni
Published: December 2021

In the last four years, the evolution and adoption of blockchain and, more generally, distributed ledger systems have shown the affirmation of many concepts and models with significant differences in system governance and suitable applications. This work aims to analyze distributed ledger technology (DLT) critically. Starting from the topical idea of decentralization, we introduce concepts and building blocks currently adopted in the available systems centering on their functional aspects and impact on possible applications. We present some conceptual framing tools helpful in the application context: a DLT reference architecture, off-chain and on-chain governance models, and classification of consensus protocols. Finally, we introduce the concept of process authenticity, reviewing tools and strategies for integrating DLT with the physical world and proposing a constructive scheme for the authentication of a physical resource through alphanumeric data.
Simultaneous Detection of Relative Humidity and Temperature Based on Silicon On-Chip Cascaded Photonic Crystal Nanobeam Cavities
Authors: Ye Lun , Liu Xiao , Pei Danyang , Peng Jing , Liu Shuchang , Guo Kai , Li Xiaogang , Chen Xuanyu , Zhang Xuan , Yang Daquan
Published: December 2021

In this paper, we propose and numerically demonstrate a novel cascaded silicon-on-insulator (SOI) photonic crystal nanobeam cavity (PCNC) dual-parameter sensor for the simultaneous detection of relative humidity (RH) and temperature. The structure consists of two independent PCNCs supporting two different resonant modes: a dielectric-mode and an air-mode, respectively. The dielectric-mode nanobeam cavities (cav1) are covered with SU-8 cladding to increase the sensitivity ratio contrast between RH sensing and temperature sensing. The air-mode nanobeam cavities (cav2) are coated with a water-absorbing polyvinyl-alcohol (PVA) layer that converts the change in RH into a change in refractive index (RI) under different ambient RH levels, thereby inducing a wavelength shift. Due to the positive thermo-optic (TO) coefficient of silicon and the negative TO coefficient of SU-8 cladding, the wavelength responses take the form of a red shift for cav2 and a blue shift for cav1 as the ambient temperature increases. By using 3D finite-difference time-domain (3D-FDTD) simulations, we prove the feasibility of simultaneous sensing by monitoring a single output transmission spectrum and applying the sensor matrix. For cav1, the RH and temperature sensitivities are 0 pm/%RH and −37.9 pm/K, while those of cav2 are −389.2 pm/%RH and 58.6 pm/K. The sensitivity ratios of temperature and RH are −1.5 and 0, respectively, which is the reason for designing two different resonant modes and also implies great potential for realizing dual-parameter sensing detection. In particular, it is also noteworthy that we demonstrate the ability of the dual-parameter sensor to resist external interference by using the dual wavelength matrix method. The maximum RH and temperature detection errors caused by the deviation of resonance wavelength 1 pm are only 0.006% RH and 0.026 K, which indicates that it achieves an excellent anti-interference ability. Furthermore, the structure is very compact, occupying only 32 μm × 4 μm (length × width). Hence, the proposed sensor shows promising prospects for compact lab-on-chip integrated sensor arrays and sensing with multiple parameters.
Clinical Usefulness of Red Cell Distribution Width/Albumin Ratio to Discriminate 28-Day Mortality in Critically Ill Patients with Pneumonia Receiving Invasive Mechanical Ventilation, Compared with Lacate/Albumin Ratio: A Retrospective Cohort Study
Authors: Jeong Jong Hwan , Heo Manbong , Lee Seung Jun , Jeong Yi Yeong , Lee Jong Deog , Yoo Jung-Wan
Published: December 2021

The value of the red cell distribution width (RDW) is associated with prognosis in critically ill patients. A simplex combined index—the RDW/albumin ratio—has been proposed for the prediction of mortality, as has the lactate/albumin ratio. The aim of this study was to evaluate the clinical utility of the RDW/albumin ratio regarding 28-day mortality in critically ill patients with pneumonia. Clinical data of critically ill patients with pneumonia who were hospitalized in the medical intensive care unit from May 2018 to December 2020, and received invasive mechanical ventilation (IMV), were reviewed retrospectively. The values of RDW, lactate, and albumin measured at the time of IMV, were used for the index calculations. Of the 234 patients, the median age was 76 years, and 74.2% were male. The 28-day mortality rate was 47.3%. The median RDW/albumin ratio was significantly higher in non-survivors than survivors at 28 days (5.8 vs. 4.9, p < 0.001). A higher RDW/albumin ratio was significantly associated with increased 28-day mortality (odds ratio [OR] 1.338, 95% confidence interval [CI] 1.094–1.637, p = 0.005). The area under the receiver operating curve (AUROC) was 0.694 (95% CI: 0.630–758, p < 0.005) to discern 28-day mortality without significant difference, compared with that of the lactate/albumin ratio. Our data suggest that high RDW/albumin ratio has a similar predictability to the lactate/albumin ratio in critically ill patients with pneumonia receiving IMV.
Uterine Artery Embolization Combined with Subsequent Suction Evacuation as Low-Risk Treatment for Cesarean Scar Pregnancy
Authors: Bohiltea Roxana , Ducu Ionita , Mihai Bianca , Iordache Ana-Maria , Dorobat Bogdan , Vladareanu Emilia Maria , Iordache Stefan-Marian , Bohiltea Alexia-Teodora , Bacalbasa Nicolae , Grigorescu Cristiana Eugenia Ana , Varlas Valentin
Published: December 2021

Objective: The aim of this study is to propose a standardized management of care for patients diagnosed with cesarean scar pregnancy (CSP). There are two types of CSP: Type 1 (on the scar) vs. type 2 (in the niche). To date there is no international standard to predict the extent of invasion or the optimal management of CSP. Materials and methods: We used intramuscular methotrexate injection followed by uterine artery embolization combined with suction evacuation as a conservative approach for the treatment of seven patients diagnosed with CSP. Our inclusion criteria, to be satisfied simultaneously, were established as follows: (1) patients with CSP; (2) early gestational age ≤ 9 weeks, and (3) written consent of the proposed treatment of the patient. Results: This course of treatment produced a positive outcome in all cases. We did not have any complications (e.g., emergency hysterectomy, perforation of the uterine cavity, severe hemorrhage, or endometritis) during the procedures or in the follow-up. The most important predictors of successful management are early diagnosis of CSP and orientation of the invasive trophoblast opposite to the scar. Conclusions: The main finding from this series of cases is that associating systemic methotrexate and uterine artery embolization provides efficient and low-risk management of CSP. This treatment regime is adequate for both types of CSPs. We consider that early localization diagnosis of pregnancy following a cesarean delivery is mandatory for CSP morbidity prevention.
Semi-Quantitative and Quantitative [18F]FDG-PET/CT Indices for Diagnosing Large Vessel Vasculitis: A Critical Review
Authors: Gheysens Olivier , Jamar François , Glaudemans Andor W. J. M. , Yildiz Halil , van der Geest Kornelis S. M.
Published: December 2021

To confirm the diagnosis of large vessel vasculitis (LVV) with high accuracy, one of the recommended imaging techniques is [18F]Fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography ([18F]FDG-PET/CT). Visual assessment of [18F]FDG uptake in the arterial wall compared to liver uptake is the mainstay for diagnosing LVV in routine clinical practice. To date, there is no consensus on the preferred semi-quantitative or quantitative parameter for diagnosing LVV. The aim of this review is to critically update the knowledge on the available evidence of semi-quantitative and quantitative [18F]FDG uptake parameters for diagnosing LVV and to provide future directions for methodological standardization and research.
Regularization, Bayesian Inference, and Machine Learning Methods for Inverse Problems
Authors: Mohammad-Djafari Ali
Published: December 2021

Classical methods for inverse problems are mainly based on regularization theory, in particular those, that are based on optimization of a criterion with two parts: a data-model matching and a regularization term. Different choices for these two terms and a great number of optimization algorithms have been proposed. When these two terms are distance or divergence measures, they can have a Bayesian Maximum A Posteriori (MAP) interpretation where these two terms correspond to the likelihood and prior-probability models, respectively. The Bayesian approach gives more flexibility in choosing these terms and, in particular, the prior term via hierarchical models and hidden variables. However, the Bayesian computations can become very heavy computationally. The machine learning (ML) methods such as classification, clustering, segmentation, and regression, based on neural networks (NN) and particularly convolutional NN, deep NN, physics-informed neural networks, etc. can become helpful to obtain approximate practical solutions to inverse problems. In this tutorial article, particular examples of image denoising, image restoration, and computed-tomography (CT) image reconstruction will illustrate this cooperation between ML and inversion.
RF Signal-Based UAV Detection and Mode Classification: A Joint Feature Engineering Generator and Multi-Channel Deep Neural Network Approach
Authors: Yang Shubo , Luo Yang , Miao Wang , Ge Changhao , Sun Wenjian , Luo Chunbo
Published: December 2021

With the proliferation of Unmanned Aerial Vehicles (UAVs) to provide diverse critical services, such as surveillance, disaster management, and medicine delivery, the accurate detection of these small devices and the efficient classification of their flight modes are of paramount importance to guarantee their safe operation in our sky. Among the existing approaches, Radio Frequency (RF) based methods are less affected by complex environmental factors. The similarities between UAV RF signals and the diversity of frequency components make accurate detection and classification a particularly difficult task. To bridge this gap, we propose a joint Feature Engineering Generator (FEG) and Multi-Channel Deep Neural Network (MC-DNN) approach. Specifically, in FEG, data truncation and normalization separate different frequency components, the moving average filter reduces the outliers in the RF signal, and the concatenation fully exploits the details of the dataset. In addition, the multi-channel input in MC-DNN separates multiple frequency components and reduces the interference between them. A novel dataset that contains ten categories of RF signals from three types of UAVs is used to verify the effectiveness. Experiments show that the proposed method outperforms the state-of-the-art UAV detection and classification approaches in terms of 98.4% and F1 score of 98.3%.