bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of the diameter of simulated human capillaries using shifted position‐diffuse reflectance imaging
Authors: Späth Moritz , Hohmann Martin , Rohde Maximilian , Lengenfelder Benjamin , Stelzle Florian , Klämpfl Florian 
Published: January 2021

AbstractMultiple diseases are associated with a wide spectrum of microvascular dysfunctions, microangiopathies and microcirculation disorders. Monitoring the microcirculation could thus be useful to diagnose many local and systemic circulatory disorders and to supervise critically ill patients. Many of the scores currently available to help identify the condition of a microcirculation disorder are invasive or leave scope for interpretation. Thus, the present study aims to investigate with Monte‐Carlo simulations (as numerical solutions of the radiative transfer equation) whether shifted position‐diffuse reflectance imaging (SP‐DRI), a non‐invasive diagnostic technique, reveals information on the capillary diameter to assess the state of the microcirculation. To quantify the SP‐DRI signal, the modulation parameter K is introduced. It proves to correlate almost perfectly with the capillary diameter (), making it a valid parameter for reliably assessing microcirculation. SP‐DRI is emerging as an important milestone on the way to early and conveniently diagnosing microcirculation associated diseases.
Room temperature ionic liquid promoted improved and rapid synthesis of highly functionalized imidazole and evaluation of their inhibitory activity against human cancer cells
Authors: Jadhav Chetan K. , Nipate Amol S. , Chate Asha V. , Kamble Pratiksha M. , Kadam Ganesh A. , Dofe Vidya S. , Khedkar Vijay M. , Gill Charansingh H. 
Published: January 2021

AbstractIn this study, we report the use of a 1,8‐diazabicyclo [5.4.0]‐undec‐7‐en‐8‐ium imidazolate ionic liquid as a catalyst as well as a green solvent for the expeditious multicomponent transformation of tetra‐ and trisubstituted imidazole scaffolds via four‐ and pseudo‐four‐component reactions with short reaction time, excellent yield, and purity of products. The ionic liquid is cheap, biodegradable, and can be recovered and reused for more than five consecutive cycles. The advantage of this protocol for gram‐scale synthesis adds to its practical applicability. Selected synthesized tetra‐ and trisubstituted imidazole scaffolds were screened for their in vitro antiproliferative properties against the human cancer cell lines EC‐109, MCF‐7, HGC‐27, and PC‐3. Compounds 4m, 5e, and 5v showed potent cytotoxic activity against the human breast cancer cell line PC‐3, MCF‐7, and HGC‐27, respectively.
Antioxidant Sirt1/Akt axis expression in resveratrol pretreated adipose‐derived stem cells increases regenerative capability in a rat model with cardiomyopathy induced by diabetes mellitus
Authors: Chen Tung‐Sheng , Chuang Shou‐Ying , Shen Chia‐Yao , Ho Tsung‐Jung , Chang Ruey‐Lin , Yeh Yu‐Lan , Kuo Chia‐Hua , Mahalakshmi B. , Kuo Wei‐Wen , Huang Chih‐Yang 
Published: January 2021

AbstractHigh‐glucose (HG) suppresses mesenchymal stem cell (MSC) functions, resulting in a decrease in cardiac regenerative capability for MSC in diabetes mellitus (DM). Resveratrol enhances MSC functions under stress. This study explores if cardiac regenerative capability can be enhanced in MSCs pretreated with resveratrol in DM rats receiving MSCs. In vitro evidence confirms that HG decreases MSCs capability through suppression of survival markers, AMP‐activated protein kinase (AMPK)/Sirtuin 1 (Sirt1) axis, and expression of apoptotic markers. All of these markers are improved when MSCs are cocultured with resveratrol. Wistar male rats were randomly divided into Sham, DM (DM rats), DM rats with autologous transplantation of adipose‐derived stem cells (DM + ADSC), and DM rats with resveratrol pretreated ADSC (DM + RSVL‐ADSC). Compared to the Sham, DM induces pathological pathways (including fibrosis, hypertrophy, and apoptosis) and suppresses survival as well as the AMPK/Sirt1 axis in the DM group. DM + ADSC slightly improves the above pathways whereas DM + RSVL‐ADSC significantly improves the above pathways when compared to the DM group. These results illustrate that resveratrol pretreated with MSCs may show clinical potential in the treatment of heart failure in patients with DM.
Synergistic effect of three‐dimensional coculture and photobiomodulation therapy on vascularized liver spheroid formation by stem cells
Authors: Park In‐Su 
Published: January 2021

AbstractDespite studies reporting functional differentiation of liver cells, a three‐dimensional, vascularized liver organ has yet to be developed from mesenchymal stem cells. We investigated whether treatment with photobiomodulation (PBM) before three‐dimensional liver spheroid transplantation improved the recovery of liver function via stimulation of angiogenesis and hepatocyte differentiation. Liver spheroids composed of hepatic, endothelial, and mesenchymal cells were subjected to PBM therapy. To evaluate the in vivo therapeutic effect of the liver spheroids treated with PBM, phosphate‐buffered saline, liver spheroid, and PBM‐treated liver spheroid were transplanted into a damaged host liver using conventional chimeric mouse models. To further characterize the maturation of transplanted PBM‐liver spheroid compared with the newly generated non‐PBM‐liver spheroid or human liver tissues, the expression profiles of mature liver signature genes were analyzed. Liver spheroids expressed hepatocyte growth factors, including vascular endothelial growth factor and angiogenic factors. The cells in liver spheroid compensated for the low viability and improved the function of hepatocytes. Here, we demonstrate the formation of vascularized and functional human liver spheroid from human adipose‐derived stem cells by transplantation of liver tissue created in vitro. Albumin secretion by PBM‐treated liver spheroid was higher on Day 28 compared with liver spheroid‐seeded transplant group. PBM‐liver spheroids serve as individual vascularization units, promoting the simultaneous development of new microvascular networks at different locations inside the implanted tissue constructs. The vasculature in the liver spheroid transplants became functional by connecting to the host vessels within 48 h. These PBM‐liver spheroids may be useful in designing artificial three‐dimensional hepatic tissue constructs and in cell therapy with limited numbers of human hepatocytes.
Effect of Hepatic Impairment on the Pharmacokinetics of Itacitinib
Authors: Barbour April M. , Rockich Kevin , Cimino Evan , Zhou Gongfu , Leonetti‐Whalen Caterina , Chen Xuejun , Yeleswaram Swamy , Epstein Noam , Punwani Naresh 
Published: January 2021

AbstractItacitinib is a potent, selective JAK‐1 inhibitor currently in development for the treatment of chronic graft‐vs‐host‐disease in combination with corticosteroids. Itacitinib is primarily eliminated via cytochrome P450 3A metabolism with minimal renal elimination. The purpose of this open‐label study was to investigate the effect of hepatic impairment, as determined by Child‐Pugh grade, on itacitinib pharmacokinetics. All participants received a single 300‐mg dose of itacitinib orally in the fasted state. Blood samples were collected serially through 96 hours after dosing; 4 hours after dosing, an additional sample was collected for protein binding determination. Participants with moderate hepatic impairment (N = 8) had an approximate 2.5‐fold increase in total exposure (area under the plasma concentration–time curve from time 0 to infinity [AUC0‐∞]) and an approximate 2‐fold increase in maximal exposure (Cmax) compared to those with normal hepatic function (N = 8) (geometric mean ratio, 2.51 [90% confidence interval (CI), 1.54‐4.08] for AUC0‐∞ and 1.95 [90%CI, 1.14‐3.35] for Cmax). Participants with severe hepatic impairment (N = 6) had an approximate 4‐fold increase in total exposure (AUC0‐∞) and an approximate 3.5‐fold increase in maximal exposure compared to participants with normal hepatic function (geometric mean ratio, 4.08 [90%CI, 2.41‐6.89] for AUC0‐∞ and 3.48 [90%CI, 1.94‐6.23] for Cmax). Protein binding was similar between participants with moderate or severe hepatic impairment and participants with normal hepatic function, with average unbound fractions (percent free) of 25.7%, 31.5%, and 25.6%, respectively. There were no serious or fatal treatment‐related adverse events. The results of this study combined with exposure, efficacy, and safety data from the pivotal study in the relevant patient population will inform final dosing recommendations.
Novel ceric dioxide nanospheres as sulfur hosts for advanced electrochemical performance of lithium‐sulfur batteries
Authors: Zhou Dawei 
Published: January 2021

AbstractBACKGROUNDMetal oxides are promising sulfur host materials because of their superior adsorption ability. Based on this theme, ceric dioxide (CeO2) nanospheres with mesoporous structure were synthesized and designed as host materials to form CeO2 nanospheres/sulfur (CO‐NSs/S) composites.RESULTSThe as‐prepared CO‐NSs/S composites with sulfur content of 71% exhibited an initial high discharge capacity of 1396 mAh g−1 at the current density of 0.1 C. In addition, an excellent cycling stability with a reversible capacity of 678 mAh g−1 was obtained at 2 C after 500 discharge/charge cycles.CONCLUSIONThe advanced improvements of electrochemical performance are ascribed to the presence of metal oxide ceric dioxide nanospheres with mesoporous structure, which could not only inhibit the dissolution and migration of soluble polysulfide during the electrochemical cycles, but also improve the electronic conductivity of the element sulfur. © 2021 Society of Chemical Industry
Age‐related ultrastructural characterizations of the teeth of the white grouper (Epinephelus aeneus) in the different three age‐stages
Authors: Alsafy Mohamed , Madkour Naglaa F. , El‐Bakary Raafat , Karkoura Ashraf , El‐Gendy Samir , Zaki Mohamed A. , Tanekhy Mahmoud , Abumandour Mohamed M. A. 
Published: January 2021

AbstractThis study represents the first attempt to describe ultrastructural features of teeth in different three ages of white grouper (Epinephelus aeneus) grossly and by the aid of the electron microscope. The current study depends on 18 oropharyngeal cavity of E. aeneus from each age‐stages. There are common and special characterization between each age. Five teeth bands in the roof (incisive, canine, upper molar, palatine, and vomer), while two bands in the floor (incisive, molar). The apical teeth part resembles the arrowhead that bordered by groove distally. In 5 cm age, small upper incisive teeth had two appearance (straight and curved), and vomer teeth arranged in triangular in only one row (while, in 12 cm fish arranged in two rows and in 15 cm fish arranged in more than two rows), the palatine teeth began rostrally as one row then two rows and terminated by one row, while in other two ages began by two, then three and ended by two rows. There is no canine teeth in lower jaw in all age. In 12 cm fish, the rostral row of lower incisive teeth usually contain small straight teeth, while the posterior row mainly contain large with some medium upper incisive teeth. In 18 cm fish, upper incisive teeth located within two incisive fossa that separated from each other by longitudinal part of T‐shaped upper incisive ridge and small incisive teeth had two appearance (straight and curved), and each canined teeth group contain four teeth (while in other two ages each group contain only two canine teeth).
Single‐vesicle imaging and co‐localization analysis for tetraspanin profiling of individual extracellular vesicles
Authors: Han Chungmin , Kang Hyejin , Yi Johan , Kang Minsu , Lee Hyunjin , Kwon Yongmin , Jung Jaehun , Lee Jingeol , Park Jaesung 
Published: January 2021

AbstractExtracellular vesicles (EVs) are secreted nano‐sized vesicles that contain cellular proteins, lipids, and nucleic acids. Although EVs are expected to be biologically diverse, current analyses cannot adequately characterize this diversity because most are ensemble methods that inevitably average out information from diverse EVs. Here we describe a single vesicle analysis, which directly visualizes marker expressions of individual EVs using a total internal‐reflection microscopy and analyzes their co‐localization to investigate EV subpopulations. The single‐vesicle imaging and co‐localization analysis successfully illustrated the diversity of EVs and revealed distinct patterns of tetraspanin expressions. Application of the analysis demonstrated similarities and dissimilarities between the EV fractions that had been acquired from different conventional EV isolation methods. The analysis method developed in this study will provide a new and reliable tool for investigating characteristics of single EVs, and the findings of the analysis might increase understanding of the characteristics of EVs.
The ClpP activator ONC‐212 (TR‐31) inhibits BCL2 and B‐cell receptor signaling in CLL
Authors: Fatima Narjis , Shen Yandong , Crassini Kyle , Iwanowicz Edwin J. , Lang Henk , Karanewsky Donald S. , Christopherson Richard I. , Mulligan Stephen P. , Best Oliver G. 
Published: January 2021

AbstractDespite advances in therapy, a significant proportion of patients with chronic lymphocytic leukemia (CLL) relapse with drug resistant disease. Novel treatment approaches are required, particularly for high risk disease.The imipridones represent a new class of cancer therapy that has been investigated in pre‐clinical and clinical trials against a range of different cancers. We investigated the effects of the imipridone, ONC‐212, against CLL cells cultured under conditions that mimic aspects of the tumour microenvironment and a TP53ko CLL cell line (OSU‐CLL‐TP53ko). ONC‐212 induced dose‐dependent apoptosis, cell cycle arrest and reduced the migration of CLL cells in vitro, including cells from patients with TP53 lesions and OSU‐CLL‐TP53ko cells. The effects of ONC‐212 were associated with protein changes consistent with activation of the mitochondrial protease, CIpP, and the integrated stress response. We also observed inhibition of pathways downstream of the B‐cell receptor (BCR) (AKT and MAPK‐ERK1/2) and a pro‐apoptotic shift in the balance of proteins of the BCL2 family of proteins (BCL2, MCL1, BCLxL, BAX and NOXA).In conclusion, the study suggests ONC‐212 may represent an effective treatment for high risk CLL disease by inhibiting multiple facets of the BCR signaling pathway and the pro‐survival effects of the BCL2‐family proteins.
A structured approach to analyse logistics risks in the blood transfusion process
Authors: Cagliano Anna Corinna , Grimaldi Sabrina , Rafele Carlo 
Published: January 2021

AbstractBlood transfusion is a critical health care process due to the nature of the products handled and the complexity driven by the strong interdependence among the sub‐processes involved. Most of the errors causing adverse events originate during the blood logistics activities. Several literature contributions apply risk management to the transfusion process but often in a fragmented and reactive way. Moreover, few of them focus on logistics risks and assess the effectiveness of risk responses through operational key performance indicators (KPIs). The present paper applies a comprehensive and structured approach to proactively identify and analyse logistics risks as well as define responses to improve blood bag traceability, focusing on hospital wards. The implementation of such actions is monitored by specific KPIs whose measurement enables an improved communication flow among actors allowing to uncover residual risks. Future research will extend the application to further blood transfusion settings and supply chain echelons. The outcomes of this work might assist practitioners in improving policy making about blood supply chains. As a matter of fact, they allow a better understanding of the associated material and informational flows and the related risks, which supports setting effective strategies to either prevent adverse events or mitigate their effects.
Frontline Science: The expression of integrin αDβ2 (CD11d/CD18) on neutrophils orchestrates the defense mechanism against endotoxemia and sepsis
Authors: Bailey William P , Cui Kui , Ardell Christopher L , Keever Kasey R , Singh Sanjay , Rodriguez-Gil Diego J , Ozment Tammy R , Williams David L , Yakubenko Valentin P 
Published: January 2021

Abstract
Neutrophil-macrophage interplay is a fine-tuning mechanism that regulates the innate immune response during infection and inflammation. Cell surface receptors play an essential role in neutrophil and macrophage functions. The same receptor can provide different outcomes within diverse leukocyte subsets in different inflammatory conditions. Understanding the variety of responses mediated by one receptor is critical for the development of anti-inflammatory treatments. In this study, we evaluated the role of a leukocyte adhesive receptor, integrin αDβ2, in the development of acute inflammation. αDβ2 is mostly expressed on macrophages and contributes to the development of chronic inflammation. In contrast, we found that αD-knockout dramatically increases mortality in the cecal ligation and puncture sepsis model and LPS-induced endotoxemia. This pathologic outcome of αD-deficient mice is associated with a reduced number of monocyte-derived macrophages and an increased number of neutrophils in their lungs. However, the tracking of adoptively transferred fluorescently labeled wild-type (WT) and αD−/− monocytes in WT mice during endotoxemia demonstrated only a moderate difference between the recruitment of these two subsets. Moreover, the rescue experiment, using i.v. injection of WT monocytes to αD-deficient mice followed by LPS challenge, showed only slightly reduced mortality. Surprisingly, the injection of WT neutrophils to the bloodstream of αD−/− mice markedly increased migration of monocyte-derived macrophage to lungs and dramatically improves survival. αD-deficient neutrophils demonstrate increased necrosis/pyroptosis. αDβ2-mediated macrophage accumulation in the lungs promotes efferocytosis that reduced mortality. Hence, integrin αDβ2 implements a complex defense mechanism during endotoxemia, which is mediated by macrophages via a neutrophil-dependent pathway.
A critical comparison of three MS‐based approaches for quantitative proteomics analysis
Authors: Taverna Domenico , Gaspari Marco 
Published: January 2021

AbstractMS‐based proteomics is expanding its role as a routine tool for biological discovery. Nevertheless, the task of accurately and precisely quantifying thousands of analytes in a single experiment remains challenging. In this study, the diagnostic accuracy of three popular data‐dependent methods for protein relative quantification (label‐free [LF], dimethyl labelling [DML] and tandem mass tags [TMT]) has been assessed using a mixed species proteome (three species) and five experimental replicates per condition. Data were produced using a quadrupole‐Orbitrap mass spectrometer and analysed using a single platform (the MaxQuant/Perseus software suite). The whole comparative analysis was repeated three times over a period of 6 months, in order to assess the consistency of the reported findings. As expected, label‐based methods reproducibly provided a lower false positives rate, whereas TMT and LF performed similarly, and significantly better than DML, in terms of proteome coverage using the same instrument time. Although parameters like proteome coverage and precision were consistent in between replicates, other parameters like sensitivity, intended as the capacity of correctly classifying true positives (regulated proteins), were found to be less reproducible, especially at challenging fold‐changes (1.5). Collectively, data suggest that an increased interest in data reproducibility would be desirable in the quantitative proteomics field.
A matrix‐assisted laser desorption/ionization imaging mass spectrometric approach to study weight‐related changes within thyroid tissue
Authors: Alfadda Assim A. , Benabdelkamel Hicham , Fathaddin Amany A. , Alanazi Ibrahim O. , Lauzon Nidia , Chaurand Pierre , Masood Afshan 
Published: January 2021

AbstractObesity is associated with numerous comorbidities along with abnormalities of the endocrine system, more commonly manifesting as dysfunctions of the thyroid gland such as goiter. Changes in weight, especially an increase, could lead to an increase in the incidence of thyroid dysfunction; however, its pathophysiology remains to be elucidated. In the present study, we aimed to interrogate the changes in the protein distribution and abundance between the lean patients and patients with obesity thyroid tissue sections through utilizing this technique. The FFPE‐fixed thyroid tissue blocks from the selected cases and controls were identified and targeted for matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) analysis. Patients in the 30 to 75 years age group and undergoing total thyroidectomy for benign thyroid disease were recruited. Patients with thyroid cancers, autoimmune disorders, and other inflammatory conditions were excluded from the study. The selected patients were divided into two groups according to their BMIs: lean (BMI < 25) and obese (BMI > 35). An initial trial set was used as a pilot study for the optimization of the MALDI IMS protocol that was next applied to the selected thyroid tissues. MALDI IMS data from all the samples were aligned and statistical analysis carried out by k‐means and linear discriminant analysis (LDA) classification model using principle component analysis (PCA) results were evaluated between the two groups: controls (lean) and cases (obese). Receiver operator characteristic (ROC) curves were alternatively used to calculate the variability of the identified peptides. The discriminating peptides were also independently identified and related to their corresponding proteins by using liquid chromatography and tandem mass spectrometry (LC–MS/MS) analyses. Eight peptides mainly from thyroglobulin were found to be upregulated whereas 10 others were found to be downregulated in the lean compared to the obese group. Through this technique, we will be able to better understand the relationship between the disease entity and obesity.
Antibody response to SARS‐CoV‐2 in infected patients with different clinical outcome
Authors: Anichini Gabriele , Gandolfo Claudia , Terrosi Chiara , Fabrizi Simonetta , Miceli Giovanni Battista , Gori Savellini Gianni , Prathyumnan Shibily , Franchi Federico , Cusi Maria Grazia 
Published: January 2021

AbstractData regarding antibody responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) in patients infected with COVID‐19 are not yet available. In this study, we aimed to evaluate serum antibody responses in patients regardless of the outcome. We measured the circulating immunoglobulin G (IgG) antibody levels in 60 subjects with a certified history of SARS‐CoV‐2 infection by using immunoenzymatic, chemiluminescent, and Neutralization assays. Half patients had a severe infection, the other half were pauci‐symptomatic. We analyzed their antibody response to see the trend of the humoral response. Our results showed a significant difference in circulating IgG level among the two groups. The neutralizing antibody response against SARS‐CoV‐2 was significantly higher among those who had severe disease. Furthermore, ten subjects from each group were screened twice, and a declining antibody trend was observed in pauci‐symptomatic individuals. These findings provide evidence that humoral immunity against SARS‐CoV‐2 in pauci‐symptomatic people is weak and may not be long‐lasting. This may have implications for immunity strategy and prevention, since it is still not clear whether a time‐dependent decrease of both circulating and neutralizing antibodies to nonprotective levels could occur in a longer time span and whether potential vaccines are able to induce a herd immunity and a durable response.