bluuebunny/crossref_metadata_2025 huggingface dataset:
A Prospective Feasibility Trial to Challenge Patient–Derived Pancreatic Cancer Organoids in Predicting Treatment Response
Authors: Beutel Alica K. , Schütte Lena , Scheible Jeanette , Roger Elodie , Müller Martin , Perkhofer Lukas , Kestler Annika M. T. U. , Kraus Johann M. , Kestler Hans A. , Barth Thomas F. E. , Lemke Johannes , Kornmann Marko , Ettrich Thomas J. , Gout Johann , Seufferlein Thomas , Kleger Alexander
Published: May 2021

Real-time isolation, propagation, and pharmacotyping of patient-derived pancreatic cancer organoids (PDOs) may enable treatment response prediction and personalization of pancreatic cancer (PC) therapy. In our methodology, PDOs are isolated from 54 patients with suspected or confirmed PC in the framework of a prospective feasibility trial. The drug response of single agents is determined by a viability assay. Areas under the curves (AUC) are clustered for each drug, and a prediction score is developed for combined regimens. Pharmacotyping profiles are obtained from 28 PDOs (efficacy 63.6%) after a median of 53 days (range 21–126 days). PDOs exhibit heterogeneous responses to the standard-of-care drugs, and are classified into high, intermediate, or low responder categories. Our developed prediction model allows a successful response prediction in treatment-naïve patients with an accuracy of 91.1% for first-line and 80.0% for second-line regimens, respectively. The power of prediction declines in pretreated patients (accuracy 40.0%), particularly with more than one prior line of chemotherapy. Progression-free survival (PFS) is significantly longer in previously treatment-naïve patients receiving a predicted tumor sensitive compared to a predicted tumor resistant regimen (mPFS 141 vs. 46 days; p = 0.0048). In conclusion, generation and pharmacotyping of PDOs is feasible in clinical routine and may provide substantial benefit.
Bifunctional Polymeric Carbon Nitride via Tuning Fabrication Conditions for Photocatalysis
Authors: Aleksandrzak Malgorzata , Baranowska Daria , Kukulka Wojciech , Onyszko Magdalena , Zielinska Beata , Mijowska Ewa
Published: May 2021

In this contribution, the hydrogen evolution reaction and photodegradation of Rhodamine B (RhB) dye were studied using urea-based polymeric carbon nitride (PCN) as photocatalyst. The effects of calcination temperature and heating rate of the PCN on structural, morphological, optical, photoelectrochemical, and photocatalytic properties were addressed. Different properties were found to be crucial in boosting photocatalytic performance dependending on the reaction type. The highest efficiency in hydrogen evolution was observed in the presence of PCN characterized by the superior charge transport and charge lifetime properties arising from higher degree of structural arrangement and lower defect content in comparison to that of other photocatalysts. However, photocatalytic degradation of RhB was the most powerful when the catalyst exhibited the highest specific surface area as a key parameter determining its efficiency, although it presented lower charge transport and charge carrier properties.
Kinetics of n-Hexane Cracking over Mesoporous HY Zeolites Based on Catalyst Descriptors
Authors: Chapellière Yann , Daniel Cécile , Tuel Alain , Farrusseng David , Schuurman Yves
Published: May 2021

A simple kinetic model based on the zeolite acid strength, the number of Brønsted acid sites, and the catalyst efficiency was developed for the cracking of n-hexane. A series of HY zeolites with a mesopore volume from 0.04 to 0.32 cm3/g was synthesized and characterized by various physical-chemical methods and tested for n-hexane cracking. The generation of mesoporosity influenced several other important parameters, such as acidity and extra-framework aluminum. Zero-length column diffusion measurements for mesitylene showed a large decrease in the characteristic diffusion time upon the introduction of mesoporosity, which changed only slightly with a further increase in mesoporosity. Similar n-hexane physisorption enthalpies were measured for all samples. The highest initial activity for n-hexane cracking per catalyst volume was observed for the sample with an intermediate mesopore volume of 0.15 cm3/g. The three mesoporous H-USY zeolites showed the same value of the intrinsic rate constant and the same activation energy. The difference in initial activity of the mesoporous zeolites was caused by the difference in the number of Brønsted acid sites. The increase in initial activity for the mesoporous zeolites compared to a microporous zeolite was caused by an increase in the acid strength.
Siglec Ligands
Authors: Gonzalez-Gil Anabel , Schnaar Ronald L.
Published: May 2021

A dense and diverse array of glycans on glycoproteins and glycolipids decorate all cell surfaces. In vertebrates, many of these carry sialic acid, in a variety of linkages and glycan contexts, as their outermost sugar moiety. Among their functions, glycans engage complementary glycan binding proteins (lectins) to regulate cell physiology. Among the glycan binding proteins are the Siglecs, sialic acid binding immunoglobulin-like lectins. In humans, there are 14 Siglecs, most of which are expressed on overlapping subsets of immune system cells. Each Siglec engages distinct, endogenous sialylated glycans that initiate signaling programs and regulate cellular responses. Here, we explore the emerging science of Siglec ligands, including endogenous sialoglycoproteins and glycolipids and synthetic sialomimetics. Knowledge in this field promises to reveal new molecular pathways controlling cell physiology and new opportunities for therapeutic intervention.
Structure and Immune Function of Afferent Lymphatics and Their Mechanistic Contribution to Dendritic Cell and T Cell Trafficking
Authors: Arasa Jorge , Collado-Diaz Victor , Halin Cornelia
Published: May 2021

Afferent lymphatic vessels (LVs) mediate the transport of antigen and leukocytes to draining lymph nodes (dLNs), thereby serving as immunologic communication highways between peripheral tissues and LNs. The main cell types migrating via this route are antigen-presenting dendritic cells (DCs) and antigen-experienced T cells. While DC migration is important for maintenance of tolerance and for induction of protective immunity, T cell migration through afferent LVs contributes to immune surveillance. In recent years, great progress has been made in elucidating the mechanisms of lymphatic migration. Specifically, time-lapse imaging has revealed that, upon entry into capillaries, both DCs and T cells are not simply flushed away with the lymph flow, but actively crawl and patrol and even interact with each other in this compartment. Detachment and passive transport to the dLN only takes place once the cells have reached the downstream, contracting collecting vessel segments. In this review, we describe how the anatomy of the lymphatic network supports leukocyte trafficking and provide updated knowledge regarding the cellular and molecular mechanisms responsible for lymphatic migration of DCs and T cells. In addition, we discuss the relevance of DC and T cell migration through afferent LVs and its presumed implications on immunity.
Tissue-Specific Microparticles Improve Organoid Microenvironment for Efficient Maturation of Pluripotent Stem-Cell-Derived Hepatocytes
Authors: Zahmatkesh Ensieh , Ghanian Mohammad Hossein , Zarkesh Ibrahim , Farzaneh Zahra , Halvaei Majid , Heydari Zahra , Moeinvaziri Farideh , Othman Amnah , Ruoß Marc , Piryaei Abbas , Gramignoli Roberto , Yakhkeshi Saeed , Nüssler Andreas , Najimi Mustapha , Baharvand Hossein , Vosough Massoud
Published: May 2021

Liver organoids (LOs) are receiving considerable attention for their potential use in drug screening, disease modeling, and transplantable constructs. Hepatocytes, as the key component of LOs, are isolated from the liver or differentiated from pluripotent stem cells (PSCs). PSC-derived hepatocytes are preferable because of their availability and scalability. However, efficient maturation of the PSC-derived hepatocytes towards functional units in LOs remains a challenging subject. The incorporation of cell-sized microparticles (MPs) derived from liver extracellular matrix (ECM), could provide an enriched tissue-specific microenvironment for further maturation of hepatocytes inside the LOs. In the present study, the MPs were fabricated by chemical cross-linking of a water-in-oil dispersion of digested decellularized sheep liver. These MPs were mixed with human PSC-derived hepatic endoderm, human umbilical vein endothelial cells, and mesenchymal stromal cells to produce homogenous bioengineered LOs (BLOs). This approach led to the improvement of hepatocyte-like cells in terms of gene expression and function, CYP activities, albumin secretion, and metabolism of xenobiotics. The intraperitoneal transplantation of BLOs in an acute liver injury mouse model led to an enhancement in survival rate. Furthermore, efficient hepatic maturation was demonstrated after ex ovo transplantation. In conclusion, the incorporation of cell-sized tissue-specific MPs in BLOs improved the maturation of human PSC-derived hepatocyte-like cells compared to LOs. This approach provides a versatile strategy to produce functional organoids from different tissues and offers a novel tool for biomedical applications.
Proteoglycan 4 Modulates Osteogenic Smooth Muscle Cell Differentiation during Vascular Remodeling and Intimal Calcification
Authors: Seime Till , Akbulut Asim Cengiz , Liljeqvist Moritz Lindquist , Siika Antti , Jin Hong , Winski Greg , van Gorp Rick H. , Karlöf Eva , Lengquist Mariette , Buckler Andrew J. , Kronqvist Malin , Waring Olivia J. , Lindeman Jan H. N. , Biessen Erik A. L. , Maegdefessel Lars , Razuvaev Anton , Schurgers Leon J. , Hedin Ulf , Matic Ljubica
Published: May 2021

Calcification is a prominent feature of late-stage atherosclerosis, but the mechanisms driving this process are unclear. Using a biobank of carotid endarterectomies, we recently showed that Proteoglycan 4 (PRG4) is a key molecular signature of calcified plaques, expressed in smooth muscle cell (SMC) rich regions. Here, we aimed to unravel the PRG4 role in vascular remodeling and intimal calcification. PRG4 expression in human carotid endarterectomies correlated with calcification assessed by preoperative computed tomographies. PRG4 localized to SMCs in early intimal thickening, while in advanced lesions it was found in the extracellular matrix, surrounding macro-calcifications. In experimental models, Prg4 was upregulated in SMCs from partially ligated ApoE−/− mice and rat carotid intimal hyperplasia, correlating with osteogenic markers and TGFb1. Furthermore, PRG4 was enriched in cells positive for chondrogenic marker SOX9 and around plaque calcifications in ApoE−/− mice on warfarin. In vitro, PRG4 was induced in SMCs by IFNg, TGFb1 and calcifying medium, while SMC markers were repressed under calcifying conditions. Silencing experiments showed that PRG4 expression was driven by transcription factors SMAD3 and SOX9. Functionally, the addition of recombinant human PRG4 increased ectopic SMC calcification, while arresting cell migration and proliferation. Mechanistically, it suppressed endogenous PRG4, SMAD3 and SOX9, and restored SMC markers’ expression. PRG4 modulates SMC function and osteogenic phenotype during intimal remodeling and macro-calcification in response to TGFb1 signaling, SMAD3 and SOX9 activation. The effects of PRG4 on SMC phenotype and calcification suggest its role in atherosclerotic plaque stability, warranting further investigations.
Role of the Endocannabinoid System in the Adipose Tissue with Focus on Energy Metabolism
Authors: Rakotoarivelo Volatiana , Sihag Jyoti , Flamand Nicolas
Published: May 2021

The endocannabinoid system is involved in a wide range of processes including the control of energy acquisition and expenditure. Endocannabinoids and their receptors are present in the central nervous system but also in peripheral tissues, notably the adipose tissues. The endocannabinoid system interacts with two main hormones regulating appetite, namely leptin and ghrelin. The inhibitory effect of the cannabinoid receptor 1 (CB1) antagonist rimonabant on fat mass suggested that the endocannabinoid system can also have a peripheral action in addition to its effect on appetite reduction. Thus, several investigations have focused on the peripheral role of the endocannabinoid system in the regulation of metabolism. The white adipose tissue stores energy as triglycerides while the brown adipose tissue helps to dissipate energy as heat. The endocannabinoid system regulates several functions of the adipose tissues to favor energy accumulation. In this review we will describe the presence of the endocannabinoid system in the adipose tissue. We will survey the role of the endocannabinoid system in the regulation of white and brown adipose tissue metabolism and how the eCB system participates in obesity and metabolic diseases.
Oxidative Stress-Induced Unscheduled CDK1–Cyclin B1 Activity Impairs ER–Mitochondria-Mediated Bioenergetic Metabolism
Authors: Chang Jan-Gowth , Tien Ni , Chang Yi-Chih , Lin Meng-Liang , Chen Shih-Shun
Published: May 2021

Targeting the activities of endoplasmic reticulum (ER)–mitochondrial-dependent metabolic reprogramming is considered one of the most promising strategies for cancer treatment. Here, we present biochemical subcellular fractionation, coimmunoprecipitation, gene manipulation, and pharmacologic evidence that induction of mitochondria-localized phospho (p)-cyclin dependent kinase 1 (CDK1) (Thr 161)–cyclin B1 complexes by apigenin in nasopharyngeal carcinoma (NPC) cells impairs the ER–mitochondrial bioenergetics and redox regulation of calcium (Ca++) homeostasis through suppressing the B cell lymphoma 2 (BCL-2)/BCL-2/B-cell lymphoma-extra large (BCL-xL)-modulated anti-apoptotic and metabolic functions. Using a specific inducer, inhibitor, or short hairpin RNA for acid sphingomyelinase (ASM) demonstrated that enhanced lipid raft-associated ASM activity confers alteration of the lipid composition of lipid raft membranes, which leads to perturbation of protein trafficking, and induces formation of p110α free p85α–unphosphorylated phosphatase and tensin homolog deleted from chromosome 10 complexes in the lipid raft membranes, causing disruption of phosphatidylinositol 3-kinase (PI3K)−protein kinase B (Akt)−GTP-ras-related C3 botulinum toxin substrate 1 (Rac1)-mediated signaling, thus triggering the p-CDK1 (Thr 161))–cyclin B1-mediated BCL-2 (Thr 69/Ser 87)/BCL-xL (Ser 62) phosphorylation and accompanying impairment of ER–mitochondria-regulated bioenergetic, redox, and Ca++ homeostasis. Inhibition of apigenin-induced reactive oxygen species (ROS) generation by a ROS scavenger N-acetyl-L-cysteine blocked the lipid raft membrane localization and activation of ASM and formation of ceramide-enriched lipid raft membranes, returned PI3K−Akt−GTP-Rac1-modulated CDK1–cyclin B1 activity, and subsequently restored the BCL-2/BCL-xL-regulated ER–mitochondrial bioenergetic activity. Thus, this study reveals a novel molecular mechanism of the pro-apoptotic activity of ASM controlled by oxidative stress to modulate the ER–mitochondrial bioenergetic metabolism, as well as suggests the disruption of CDK1–cyclin B1-mediated BCL-2/BCL-xL oncogenic activity by triggering oxidative stress−ASM-induced PI3K−Akt−GTP-Rac1 inactivation as a therapeutic approach for NPC.
Testicular Torsion in the Absence of Severe Pain: Considerations for the Pediatric Surgeon
Authors: Kapp Alexander , Troxler David , Prüfer Friederike , Holland-Cunz Stefan , Frech Martina , Gros Stephanie J.
Published: May 2021

Testicular torsion is a surgical emergency. Early diagnosis and surgical treatment are vital in order to preserve the affected gonad. Current surgical teaching emphasizes sudden, severe, persistent, unilateral scrotal pain as a cardinal symptom of testicular torsion. We present the case of unilateral testicular torsion in a 14-year-old patient who presented with the absence of severe pain. Despite a delayed presentation to the emergency department, the gonad could be salvaged successfully. Literature on the topic of testicular torsion presenting with minimal pain is limited. Nevertheless, pediatric surgeons might be faced with cases similar to the one we describe. Underestimating this phenomenon might lead to a delay of treatment. In such cases, ultrasound can be a beneficial addition in the diagnosis and accelerate definitive operative treatment. The presented case clearly demonstrates that, although we do not include testicular torsion without severe pain in our surgical teaching algorithms, we might encounter it in our clinical practice.
The Influence of Archaeometallurgical Copper Alloy Castings Microstructure towards Corrosion Evolution in Various Corrosive Media
Authors: Papadopoulou Olga , Vassiliou Panayota
Published: May 2021

The local patterns at the interfaces of corrosion stratification, developed on two archaeometallurgical bronzes (a Cu-Sn-Pb and a Cu-Zn-Sn-Pb alloy), in the as-cast condition, were assessed by OM and SEM-EDS systematic elemental chemical analyses. Previously, the alloys—whose metallurgical features and electrochemical behaviour were already well studied—have been subjected to laboratory corrosion experiments. The corrosion procedures involved electrochemical anodic polarization experiments in various chloride media: 0.1 mol/L NaCl, 0.6 mol/L NaCl and two other synthetic chloride-containing solutions, representing electrolytes present in marine urban atmosphere and in the soil of coastal sites. The characterization of the Cu-Sn-Pb alloy electrochemical patinas after anodic sweep (OCP+ 0.6 V) revealed that the metal in all electrolytes undergoes extensive chloride attack and selective dissolution of copper which initiates from the dendritic areas acting as anodic sites. The most abundant corrosion products identified by FTIR in all electrochemical patinas were Cu2(OH)3Cl), Cu2(OH)2CO3 and amorphous Cu and Sn oxides. The characterization of the Cu-Sn-Pb alloy electrochemical patina after slow anodic sweep (OCP+ 1.5 V) in 0.1 mol/L NaCl reveals selective oxidation of dendrites and higher decuprification rate in these areas. Corrosion products of Sn-rich interdendritic areas are dominated by oxygen species (oxides, hydroxides, hydroxyoxides) and Cu-rich dendrites by chlorides. In the case of Cu-Zn-Sn-Pb, Zn in dendritic areas is preferentially attacked. The alloy undergoes simultaneous dezincification and decuprification, with the former progressing faster, especially in dendritic areas. The two processes at the alloy/patina interface leave behind a metal surface where α-dendrites are enriched in Sn compared to the alloy matrix. The results of this study highlight the dynamic profile of corrosion layer build-up in bronze and brass. Moreover, the perception of the dealloying mechanisms progression on casting features, at mid-term corrosion stages, is extended.
Iron Oxide-Coupled Graphite/Fe–Si Steel Structure for Analog Computing from Recycling Principle
Authors: Baca-Arroyo Roberto
Published: May 2021

Analog computing from recycling principle for next circular economy scenario has been studied with an iron oxide-coupled graphite/Fe–Si steel structure which was built using recycled waste materials, such as lead pencil and 3% Si steel (Fe–Si steel) foils. Proximity phenomena, such as disordered structure of iron oxide and magnetostriction-induced conduction, inside graphite lattice resulted in functional properties to advance analog architectures. Thermal oxidation was the synthesis route to produce iron oxide as coating film on Fe–Si steel foil, whose structure properties were validated by Raman spectroscopy where phase formation of hematite, α-Fe2O3, resulted as iron oxide thin-film. Three graphite layers with different compositions were also analyzed by Raman spectroscopy and used for studying electrical conduction in Fe–Si steel/α-Fe2O3/graphite structure from current–voltage plots at room temperature.
Synthesis of 1-[(Aryl)(3-amino-5-oxopyrazolidin-4-ylidene) methyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic Acid Derivatives and Their Breast Anticancer Activity
Authors: Gaber Ahmed , Alsanie Walaa F. , Alhomrani Majid , Alamri Abdulhakeem S. , El-Deen Ibrahim M. , Refat Moamen S.
Published: May 2021

This research aimed to produce new 1-[(aryl)(3-amino-5-oxopyrazolidin-4-ylidene) methyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic acid derivatives and check their anticancer effect against the breast cancer MCF-7 cell line. The 2-oxo-1,2-dihydroquinoline-3-carboxylic acid (4) compound was obtained by hydrolyzing ethyl 2-oxo-1,2-dihydroquinoline-3-carboxylate (2) with thiourea and anhydrous potassium carbonate ethanol, which was then treated with ethyl 3-substituted 2-cyanoacrylates (6) in the presence of triethylamine in diethyl formamide to give 1-[2-(ethoxy)carbonyl-2-cyano-1-arylvinyl]-2-oxo-1,2-dihydroquinoline-3-carboxylic (7a,d). Cyclization of compound 7 with hydrazine hydrate ethanol inferred the association of 1-[(aryl)(3 amino-5-oxopyrazolidin-4-ylidene)methyl-2-oxo-1,2-dihydroquinol-3-carboxylates (8a,d). Spectroscopic and micro-analytical techniques such as IR, NMR, and elemental analysis were used to validate the structure of the synthesized organic compounds. The anticancer effects of the synthesized compounds 7a–d and 8a–d were tested by using the MTT assay on the MCF-7 cell line. When compared to the reference compound Dox, the compounds 7b,c and 8a–c demonstrated strong anticancer activity against the MCF-7 cell line. The anticancer effects of the synthesized compounds 7a–d and 8a–d were tested against the MCF-7 cell line, using MTT assay. The compounds 7b,c and 8a–c showed significant anticancer activity compared to the reference compound Dox against the MCF-7 cell line.
Cytoreductive Nephrectomy Following Immunotherapy-Base Treatment in Metastatic Renal Cell Carcinoma: A Case Series and Review of Current Literature
Authors: Dawsey Scott J. , Campbell Steven C. , Ornstein Moshe C.
Published: May 2021

The role and timing of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based regimens is unclear. However, the ability to achieve a complete response for metastatic renal cell carcinoma likely requires a nephrectomy at some point during treatment. Here we present a case series of three patients with metastatic clear-cell renal-cell carcinoma who received front-line immunotherapy-based treatment and subsequently underwent a cytoreductive nephrectomy. All three patients had a complete response to therapy and have subsequently remained off systemic therapy for a median of 531 days (range, 476–602). We also review the limited literature in this setting and highlight ongoing clinical trials. Although the role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma receiving immunotherapy-based treatment is uncertain, a subset of patients will benefit from either an immediate or deferred cytoreductive nephrectomy. Ongoing trials are underway to further determine how to incorporate cytoreductive nephrectomy into the treatment paradigm for patients with metastatic renal cell carcinoma.
Histovariability and Palaeobiological Implications of the Bone Histology of the Dromornithid, Genyornis newtoni
Authors: Chinsamy Anusuya , Worthy Trevor H.
Published: May 2021

The bone microstructure of extinct animals provides a host of information about their biology. Although the giant flightless dromornithid, Genyornis newtoni, is reasonably well known from the Pleistocene of Australia (until its extinction about 50–40 Ka), aside from various aspects of its skeletal anatomy and taxonomy, not much is known about its biology. The current study investigated the histology of fifteen long bones of Genyornis (tibiotarsi, tarsometatarsi and femora) to deduce information about its growth dynamics and life history. Thin sections of the bones were prepared using standard methods, and the histology of the bones was studied under normal and polarised light microscopy. Our histological analyses showed that Genyornis took more than a single year to reach sexual maturity, and that it continued to deposit bone within the OCL for several years thereafter until skeletal maturity was attained. Thus, sexual maturity and skeletal maturity were asynchronous, with the former preceding the latter. Our results further indicated that Genyornis responded to prevailing environmental conditions, which suggests that it retained a plesiomorphic, flexible growth strategy. Additionally, our analyses of the three long bones showed that the tibiotarsus preserved the best record of growth for Genyornis.
Morphological Characteristics of the Nasopalatine Canal and the Relationship with the Anterior Maxillary Bone—A Cone Beam Computed Tomography Study
Authors: Milanovic Pavle , Selakovic Dragica , Vasiljevic Milica , Jovicic Nemanja U. , Milovanović Dragan , Vasovic Miroslav , Rosic Gvozden
Published: May 2021

The aim of this study was to evaluate the interconnection between the type of nasopalatine canal (NPC) and morphometric characteristics of the anterior maxilla. The investigation involved 113 subjects, and the morphometric parameters were obtained using cone beam computed tomography (CBCT). NPC shapes were classified into four types: banana-, hourglass-, cylindrical-, and funnel-shaped (distribution of approximately 9, 25, 31, and 35%, respectively). The analysis revealed that the NPC shape was significantly connected with the morphometric properties of anterior maxilla horizontal dimensions. In general, a banana-shaped NPC was accompanied with an overall reduction in anterior maxilla diameters when compared to other NPC shapes, with no significant difference between the other three NPC shapes. Furthermore, the morphometric characteristics that depend on NPC shape at the sagittal cross-section were significantly correlated with diameters of the incisive foramen, nasal foramen, and NPC length. According to the results of our study, it seems that the presented analyses of morphometric data may allow useful insight into the algorithms of various interconnections between the measures obtained in the region of the anterior maxilla, which could be of interest for a time rationale approach when planning some surgical procedures, such as immediate dental implant placement planning.
Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence
Authors: Repetto Ombretta , Lovisa Federica , Elia Caterina , Enderle Daniel , Romanato Filippo , Buffardi Salvatore , Sala Alessandra , Pillon Marta , Steffan Agostino , Burnelli Roberta , Mussolin Lara , Mascarin Maurizio , De Re Valli
Published: May 2021

Exosomes and other small extracellular vesicles (EVs) are potential sources of cancer biomarkers. Plasma-derived EVs have not yet been studied in pediatric Hodgkin lymphoma (HL), for which predictive biomarkers of relapse are greatly needed. In this two-part proteomic study, we used two-dimensional difference gel electrophoresis (2D-DIGE) followed by liquid chromatography–tandem mass spectrometry (LC–MS/MS) to analyze EV proteins of plasma collected at diagnosis from children with nodular sclerosis HL, relapsed or not. EVs isolated using membrane affinity had radii ranging from 20 to 130 nm and contained the programmed cell death 6-interacting (ALIX) and the tumor susceptibility gene 101 (TSG101) proteins, whereas calnexin (CANX) was not detected. 2D-DIGE identified 16 spots as differentially abundant between non-relapsed and relapsed HL (|fold change| ≥ 1.5, p < 0.05). LC–MS/MS identified these spots as 11 unique proteins, including five more abundant in non-relapsed HL (e.g., complement C4b, C4B; fibrinogen γ chain, FGG) and six more abundant in relapsed HL (e.g., transthyretin, TTR). Shotgun LC–MS/MS on pooled EV proteins from non-relapsed HL identified 161 proteins, including 127 already identified in human exosomes (ExoCarta data). This EV cargo included 89 proteins not yet identified in exosomes from healthy plasma. Functional interrogation by the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that the EV proteins participate in platelet degranulation and serine-type endopeptidase activity as the most significant Gene Ontology (GO) biological process and molecular function (p < 0.01).
How to Differentiate Gout, Calcium Pyrophosphate Deposition Disease, and Osteoarthritis Using Just Four Clinical Parameters
Authors: Kravchenko Dmitrij , Behning Charlotte , Bergner Raoul , Schäfer Valentin
Published: May 2021

Clinical differentiation between gout, osteoarthritis (OA), and calcium pyrophosphate deposition disease (CPPD) remains a hurdle in daily practice without imaging or arthrocentesis. We performed a retrospective analysis of consecutive patients with gout, CPPD, and OA at a tertiary rheumatology center. A total of 277 patients were enrolled, with 164 suffering from gout, 76 from CPPD, and 37 from OA. We used ANOVA and conditional inference tree analysis (Ctrees) to find associations between clinical, laboratory, and imaging data and gout, OA, and CPPD. The sonographic double contour sign was unable to differentiate gout from CPPD. Ctrees were able to exclude OA and CPPD as possible differentials based on elevated uric acid, C-reactive protein (CRP), presence of arterial hypertension, and sex, diagnosing gout with a sensitivity and specificity of 95.1% and 41.6%, respectively. Elevated CRP was observed using simple linear regressions in patients with type II diabetes, higher cumulative joint scores, increased number of affected joints, as well as elevated uric acid, erythrocyte sedimentation rate, and leukocyte count. Ctrees were able to differentiate gout, OA, and CPPD based on just four characteristics. Inflammatory response correlated with type II diabetes, more or larger joint involvement, and elevated uric acid levels.
Parameter Estimation of a Single-Phase Boost PFC Converter with EMI Filter Based on an Optimization Algorithm
Authors: Rojas-Dueñas Gabriel , Riba Jordi-Roger , Moreno-Eguilaz Manuel
Published: May 2021

This paper proposes an approach to estimate the parameters of an AC–DC boost power factor corrector converter that includes an EMI filter. To this end, once the topology was known, the values of the passive elements were identified from measurements at the input and output terminals of the converter. The parameters of the converter were identified based on the trust region nonlinear least squares algorithm. The steady-state and the transient signals of the converter at the input/output terminals were acquired non-intrusively without any internal modification of the circuitry. The accuracy of the proposed parameter identification approach was determined by comparing the estimated values with those provided by the manufacturer, and by comparing the measured signals with those obtained with a simulation model that included the estimated values of the parameters. The results presented in this paper prove the accuracy of the proposed approach, which can be extended to other power converters and filters.
Development of a Flexible Framework Multi-Design Optimization Scheme for a Hand Launched Fuel Cell-Powered UAV
Authors: Alrayes Zaid O. , Gadalla Mohamed
Published: May 2021

This paper presents different methods for the design of a hand-launchable, fixed wing, fuel cell-powered unmanned aerial vehicle (UAV) to maximize flight endurance during steady level flight missions. The proposed design methods include the development of physical models for different propulsion system components. The performance characteristics of the aircraft are modeled through empirical contributing analyses in which each analysis corresponds to an aircraft subsystem. The contributing analyses are collected to form a design structure matrix which is included into a multi-disciplinary analysis to solve for the design variables over a defined design space. The optimal solution is found using a comprehensive optimization tool developed for long endurance flight missions. Optimization results showed a significant improvement in UAV flight endurance that reached up to 475 min with take-off ratio equals to 59 min/kg. Wind tunnel and bench-top tests and HiL simulation tests are performed to validate the results obtained from the optimization tools. Validated optimization results showed an increase of the overall UAV flight endurance by 19.4% compared to classical approaches in design methods.
Mass Transport Limitations of Water Evaporation in Polymer Electrolyte Fuel Cell Gas Diffusion Layers
Authors: Mularczyk Adrian , Michalski Andreas , Striednig Michael , Herrendörfer Robert , Schmidt Thomas J. , Büchi Felix N. , Eller Jens
Published: May 2021

Facilitating the proper handling of water is one of the main challenges to overcome when trying to improve fuel cell performance. Specifically, enhanced removal of liquid water from the porous gas diffusion layers (GDLs) holds a lot of potential, but has proven to be non-trivial. A main contributor to this removal process is the gaseous transport of water following evaporation inside the GDL or catalyst layer domain. Vapor transport is desired over liquid removal, as the liquid water takes up pore space otherwise available for reactant gas supply to the catalytically active sites and opens up the possibility to remove the waste heat of the cell by evaporative cooling concepts. To better understand evaporative water removal from fuel cells and facilitate the evaporative cooling concept developed at the Paul Scherrer Institute, the effect of gas speed (0.5–10 m/s), temperature (30–60 °C), and evaporation domain (0.8–10 mm) on the evaporation rate of water from a GDL (TGP-H-120, 10 wt% PTFE) has been investigated using an ex situ approach, combined with X-ray tomographic microscopy. An along-the-channel model showed good agreement with the measured values and was used to extrapolate the differential approach to larger domains and to investigate parameter variations that were not covered experimentally.
Comparative Transcriptome Analysis of Sophora japonica (L.) Roots Reveals Key Pathways and Genes in Response to PEG-Induced Drought Stress under Different Nitrogen Conditions
Authors: Tian Jing , Pang Yue , Zhao Zhong
Published: May 2021

Sophora japonica is a native leguminous tree species in China. The high stress tolerance contributes to its long lifespan of thousands of years. The lack of genomic resources greatly limits genetic studies on the stress responses of S. japonica. In this study, RNA-seq was conducted for S. japonica roots grown under short-term 20% polyethylene glycol (PEG) 6000-induced drought stress under normal N and N starvation conditions (1 and 0 mM NH4NO3, respectively). In each of the libraries, we generated more than 25 million clean reads, which were then de novo assembled to 46,852 unigenes with an average length of 1310.49 bp. In the differential expression analyses, more differentially expressed genes (DEGs) were found under drought with N starvation than under single stresses. The number of transcripts identified under N starvation and drought in S. japonica was nearly the same, but more upregulated genes were induced by drought, while more downregulated genes were induced by N starvation. Genes involved in “phenylpropanoid biosynthesis” and “biosynthesis of amino acids” pathways were upregulated according to KEGG enrichment analyses, irrespective of the stress treatments. Additionally, upregulated N metabolism genes were enriched upon drought, and downregulated photosynthesis genes were enriched under N starvation. We found 4,372 and 5,430 drought-responsive DEGs under normal N and N starvation conditions, respectively. N starvation may aggravate drought by downregulating transcripts in the “carbon metabolism”, “ribosome”, “arginine biosynthesis pathway”, “oxidative phosphorylation” and “aminoacyl-tRNA biosynthesis” pathways. We identified 78 genes related to N uptake and assimilation, 38 of which exhibited differential expression under stress. A total of 395 DEGs were categorized as transcription factors, of which AR2/ERF-ERF, WRKY, NAC, MYB, bHLH, C3H and C2C2-Dof families played key roles in drought and N starvation stresses. The transcriptome data obtained, and the genes identified facilitate our understanding of the mechanisms of S. japonica responses to drought and N starvation stresses and provide a molecular foundation for understanding the mechanisms of its long lifespan for breeding resistant varieties for greening.
On the Comparison of Flow Physics between Minimal and Extended Flow Units in Turbulent Channels
Authors: Davis Ethan A. , Mirfendereski Siamak , Park Jae Sung
Published: May 2021

Direct numerical simulations were performed to study the effects of the domain size of a minimal flow unit (MFU) and its inherent periodic boundary conditions on flow physics of a turbulent channel flow in a range of 200≤Reτ≤1000. This was accomplished by comparing turbulent statistics with those computed in sub-domains (SD) of extended domain simulations. The dimensions of the MFU and SD were matched, and SD dynamics were set to minimize artificial periodicities. Streamwise and spanwise dimensions of healthy MFUs were found to increase linearly with Reynolds number. It was also found that both MFU and SD statistics and dynamics were healthy and in good agreement. This suggests that healthy MFU dynamics represent extended-domain dynamics well up to Reτ=1000, indicating a nearly negligible effect of periodic conditions on MFUs. However, there was a small deviation within the buffer layer for the MFU at Reτ=200, which manifested in an increased mean velocity and a tail in the Q2 quadrant of the u′-v′ plane. Thus, it should be noted that when considering an MFU domain size, stricter criteria may need to be put in place to ensure healthy turbulent dynamics.
Low-Noise Synthetic Turbulence Tailored to Lateral Periodic Boundary Conditions
Authors: Rigall Tommy , Cotté Benjamin , Lafon Philippe
Published: May 2021

The present work is dedicated to turbulence synthesis tailored to lateral periodic boundary conditions for direct noise computations through compressible large eddy simulations. Synthetic turbulence can be essential for aeroacoustic applications when computing airfoil turbulent inflow noise or for accurately capturing the behavior of boundary layers. This behavior determines both trailing edge noise and complex flow structures such as laminar separation bubbles. For airfoil simulation purposes, spanwise periodic boundary conditions are usually considered. If synthetic perturbations are injected without observing the periodicity rule, strong spurious pressure waves are emitted and pollute the entire computational domain. In this work, the random Fourier modes method for turbulence generation is adapted in order to respect the spanwise periodicity constraint right at the computational domain inlet. This approach does not affect the turbulence properties such as the spectral shape and the turbulent kinetic energy decay. Since the emphasis is put on the generation and convection of the turbulence, only the turbulence convection region between the inlet and the airfoil is considered in this paper, without the airfoil. Two geometrical configurations are tested: the first one is a simple box with a constant mesh size, and the second one concentrates the fine cells on the area in front of the airfoil. In the second configuration, the computational cost is reduced by up to 25%, but more spurious noise is present because of interpolation areas between different grids using the Chimera method. Finally, the results’ reproducibility is assessed using different turbulence realizations.
Squeeze Flow of Stress Power Law Fluids
Authors: Fusi Lorenzo , Ballotti Andrea
Published: May 2021

In this paper, we studied the squeeze flow between circular disks of a new class of fluids defined by an implicit relation referred to as stress power law fluids. The constitutive response of these fluids was written expressing the symmetric part of the velocity gradient as a tensorial function of the Cauchy stress. We assumed that the aspect ratio between the gap separating the disks and the radius was small so that a lubrication expansion could be adopted. We wrote the general problem and looked for a solution that could be written in terms of the small aspect ratio parameter. We obtained a sequence of problems that could be solved iteratively at each order, and we focused on the leading and first order, deriving explicit expressions for the velocity field, stress, and pressure.
Macrophage Migration Inhibitory Factor—An Innovative Indicator for Free Flap Ischemia after Microsurgical Reconstruction
Authors: Megas Ioannis-Fivos , Simons David , Kim Bong-Sung , Stoppe Christian , Piatkowski Andrzej , Fikatas Panagiotis , Fuchs Paul Christian , Bastiaanse Jacqueline , Pallua Norbert , Bernhagen Jürgen , Grieb Gerrit
Published: May 2021

(1) Background: Nowadays, the use of microsurgical free flaps is a standard operative procedure in reconstructive surgery. Still, thrombosis of the microanastomosis is one of the most fatal postoperative complications. Clinical evaluation, different technical devices and laboratory markers are used to monitor critical flap perfusion. Macrophage migration inhibitory factor (MIF), a structurally unique cytokine with chemokine-like characteristics, could play a role in predicting vascular problems and the failure of flap perfusion. (2) Methods: In this prospective observational study, 26 subjects that underwent microsurgical reconstruction were observed. Besides clinical data, the number of blood leukocytes, CRP and MIF were monitored. (3) Results: Blood levels of MIF, C-reactive protein (CRP) and leukocytes increased directly after surgery. Subjects that needed surgical revision due to thrombosis of the microanastomosis showed significantly higher blood levels of MIF than subjects without revision. (4) Conclusion: We conclude that MIF is a potential and innovative indicator for thrombosis of the microanastomosis after free flap surgery. Since it is easy to obtain diagnostically, MIF could be an additional tool to monitor flap perfusion besides clinical and technical assessments.
Right Ventricular Outflow Tract Stenting as Palliation of Critical Tetralogy of Fallot: Techniques and Results
Authors: Pizzuto Alessandra , Cuman Magdalena , Assanta Nadia , Franchi Eliana , Marrone Chiara , Pak Vitali , Santoro Giuseppe
Published: May 2021

Background. Despite current trends toward early primary repair, the surgical systemic-to-pulmonary shunt is still considered the first-choice palliation in patients with critical tetralogy of Fallot (TOF) and duct-dependent pulmonary circulation unsuitable for primary repair. However, stenting of the right ventricular outflow tract (RVOT) is nowadays emerging as an effective alternative to surgical palliation in selected patients. Methods and results. RVOT stenting is usually performed from a venous route, either femoral or, in selected cases, the right internal jugular vein. Less frequently, mostly in pulmonary infundibular/valvar atresia, this procedure can be performed using a hybrid surgical/interventional approach by surgical exposure of the RVOT, puncture of the atretic valve, and stent deployment under direct vision. The size and type of the most appropriate stent may be chosen, based on ultrasound measurements of the RVOT, to cover the right ventricular infundibulum completely and, at the same time, sparing the pulmonary valve, unless significant pulmonary valve annulus hypoplasia and/or supra-valvular stenosis is a significant component of the obstruction. In the large series so far published, early mortality of RVOT stenting is less than 2%, comparing favourably with either Blalock-Thomas-Taussig shunt or early primary repair. In addition, morbidity and clinical sequelae of this approach do not significantly differ from surgical palliation, even if RVOT stenting shows lesser durability and a higher rate of trans-catheter re-interventions over a mid-term follow-up. Finally, similar but more balanced pulmonary artery growth than surgical palliation following RVOT stenting is reported over a mid-term follow-up. Conclusions. RVOT stenting is a technically feasible, well-tolerated, and effective palliation in critical TOF. This approach is cost-effective with respect to surgical palliation either in high-risk neonates or whenever a short-term pulmonary blood flow source is anticipated due to the early surgical repair. It effectively increases pulmonary blood flow, improves arterial saturation, and promotes balanced pulmonary artery growth over a mid-term follow-up.
Modeling of the Geological Probability Procedure for the Prediction of High Flows in Small Streams, Case Study of Medvednica Mt., Croatia
Authors: Sudar Vedran , Malvić Tomislav , Vujnović Tatjana , Ivšinović Josip
Published: May 2021

Floods are defined by maximum water levels or flow of high-water waves. Here, we defined the deterministic method for the calculation of the probability of a high discharge event, named as the Probability Of Success (POS). The POS method previously developed for petroleum subsurface systems has been modified for the surface hydrological system with the purpose of flood prediction. The case study of this research is the small basin of Kašina Stream on Medvednica Mt. (NW Croatia). The data are obtained upstream from the hydrological station Gornja Kašina. The POS model is defined by four categories. Each geological category is described with accompanied events and probabilities. Floods are defined by four categories: total precipitation, total water flow, basement, and maximal water capacity in soil. The categories total precipitation and basement were divided into two sub-categories each: quantity and duration; porosity and soil depth. Data are collected for a hydrometeorological event, namely an intensive convective storm on 24–25 July 2020, when Zagreb was locally hit by heavy urban floods. The presented probability method yielded a probability of 1.76% that such an event could happen to the station. However, the flooding was not recorded. A comparison of the real event and the predicted probability supported the adequacy and applicability of the method, showing it has high reliability. The presented probability model could be easily applied, with small modifications, to the entire area of Northern Croatia for the prediction of small basin flooding events.
Transgender Person and Pre-Exposure Prophylaxis for HIV: A Renal Dilemma
Authors: Sheikh Abu , Javed Nismat , Dunn Angela
Published: May 2021

Sexual health care for transgender people is often inadequate and not addressed. Targeted prevention approaches that respond to the specific needs of transgender individuals are essential to reducing HIV infections. HIV prophylaxis is a proven intervention in the prevention of HIV among high-risk populations. However, creatinine clearance is one major determining factor in prescribing HIV pre-exposure prophylaxis. One of the variables used in the equation to calculate creatinine clearance is gender. Additionally, regarding transgender people, gender-affirming hormonal therapy also alters the clearance by modifying other variables, such as muscle mass. Here, we present the case of a 58-year-old designated female at birth, who transitioned to male 15 months ago, currently using testosterone, and had presented to the clinic requesting HIV pre-exposure prophylaxis, due to his anticipation of new sexual partners soon. He was initially denied HIV pre-exposure prophylaxis, due to lower estimated creatinine clearance when calculated per his natal assigned gender. The transgender population requires effective HIV pre-exposure prophylaxis, dependent on creatinine clearance, that is dictated by many factors, considering the high prevalence rate. Therefore, validation of eGFR equations in the transgender population is of utmost importance to ensure optimal decision-making and provision of health care.