bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive oxygen species as a double‐edged sword: The role of oxidative enzymes in antitumor therapy
Authors: Rosini Elena , Pollegioni Loredano 
Published: October 2021

AbstractA number of approaches have been developed over the years to manage cancer, such as chemotherapy using low‐molecular‐mass molecules and radiotherapy. Here, enzymes can also find useful applications. Among them, oxidases have attracted attention because of their ability to produce reactive oxygen species (ROS, especially hydrogen peroxide) in tumors and potentially modulate the production of this cytotoxic compound when enzymes active on substrates present in low amounts are used, such as the d‐amino acid oxidase and d‐amino acid couple system. These treatments have been also developed for additional cancer treatment approaches, such as phototherapy, nutrient starvation, and metal‐induced hydroxyl radical production. In addition, to improve tumor specificity and decrease undesired side effects, oxidases have been targeted by means of nanotechnologies and protein engineering (i.e., by designing chimeric proteins able to accumulate in the tumor). The most recent advances obtained by using six different oxidases (i.e., the FAD‐containing enzymes glucose oxidase, d‐ and l‐amino acid oxidases, cholesterol oxidase and xanthine oxidase, and the copper‐containing amine oxidase) have been reported. Anticancer therapy based on oxidase‐based ROS production has now reached maturity and can be applied in the clinic.
Online anatomy team‐based learning using blackboard collaborate platform during COVID‐19 pandemic
Authors: Al‐Neklawy Ahmed Farid , Ismail Amira Salem Alsagheer 
Published: October 2021

AbstractDuring the COVID‐19 pandemic, many educational institutions followed the blended learning system. Using the participants' opinions, we evaluated the Blackboard (Bb) collaborate platform for online team‐based learning (TBL) sessions for undergraduate students from different medical programs in the KSA. The participants were students on the MBBS Program (157 year two and 149 year three), together with 53 students in year one of the Nursing Program, 25 in year two of the Doctor of Pharmacy Program, and 11 in year two of the Medical Laboratory Sciences Program in Fakeeh College for Medical Sciences, (FCMS) KSA. To assess students' recall, engagement, and satisfaction with the sessions, an online TBL plan was designed and reviewed by the Medical Education Department. The students completed an online survey at the end of each session. All responses in this study showed a statistically significant positive difference from the neutral mid‐point response (p < 0.05), reflecting high satisfaction. In the MBBS Program, the survey was completed by 40 students in year two and 76 in year three. The mean responses were 4.1 ± 0.3 and 3.9 ± 0.2 respectively (mean ± SD). In the BSN Program, 19 students completed the survey. The mean response was 4.6 ± 0.2. In the Pharm D Program, 10 students completed the survey. The mean response was 4.9 ± 0.12. In the MLS Program, eight students completed the survey. The mean response was 4.8 ± 0.12. It was concluded that online TBL using Bb collaborate is a successful anatomy‐learning tool among FCMS students on different programs.
Model‐based automatic grading of object‐oriented programming assignments
Authors: Le Duc Minh 
Published: October 2021

AbstractAutomatic grading of object‐oriented programming (OOP) assignments is an important problem from practical, theoretical, and educational viewpoints. Apart from computing a specific grade, an effective grading method needs to provide systematic feedback comments to both the design and code elements. Existing works have proposed grading methods that make various assumptions about the design. However, none of these methods have considered using a design language for the program model. A challenge here is to use a language that eases learning and application in program design. In this paper, we propose a novel grading method, named OOPGRADER, which automatically grades OOP assignments constructed based on an essentially detailed program model. This model is defined in an embedded design language, which directly uses the annotation feature of OOP language to express the essential design rules. We explain how programming assignments can be designed with this language and propose a program checker and a grader for both student and teacher to use in working on the assignments and in grading them. We implement these components in a tool and develop an Eclipse plugin for this tool. We evaluate our method using a combination of qualitative and quantitative techniques. The main result is that our method helps students effectively learn to program through detailed feedback comments based on a program model. The tool is adaptable, has a good performance, and helps enhance the productivity of both students and teachers through IDE integration.
Identification of a glycolysis‐related gene signature for survival prediction of ovarian cancer patients
Authors: Zhang Dai , Li Yiche , Yang Si , Wang Meng , Yao Jia , Zheng Yi , Deng Yujiao , Li Na , Wei Bajin , Wu Ying , Zhai Zhen , Dai Zhijun , Kang Huafeng 
Published: October 2021

AbstractBackgroundOvarian cancer (OV) is deemed the most lethal gynecological cancer in women. The aim of this study was to construct an effective gene prognostic model for predicting overall survival (OS) in patients with OV.MethodsThe expression profiles of glycolysis‐related genes (GRGs) and clinical data of patients with OV were extracted from The Cancer Genome Atlas (TCGA) database. Univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analyses were conducted, and a prognostic signature based on GRGs was constructed. The predictive ability of the signature was analyzed using training and test sets.ResultsA gene risk signature based on nine GRGs (ISG20, CITED2, PYGB, IRS2, ANGPTL4, TGFBI, LHX9, PC, and DDIT4) was identified to predict the survival outcome of patients with OV. The signature showed a good prognostic ability for OV, particularly high‐grade OV, in the TCGA dataset, with areas under the curve (AUC) of 0.709 and 0.762 for 3‐ and 5‐year survival, respectively. Similar results were found in the test sets, and the AUCs of 3‐, 5‐year OS were 0.714 and 0.772 in the combined test set. And our signature was an independent prognostic factor. Moreover, a nomogram combining the prediction model and clinical factors was developed.ConclusionOur study established a nine‐GRG risk model and nomogram to better predict OS in patients with OV. The risk model represents a promising and independent prognostic predictor for patients with OV. Moreover, our study on GRGs could offer guidance for the elucidation of underlying mechanisms in future studies.
Evaluation of Antioxidant, Antibacterial and Enhancement of Antibiotic Action by Punica granatum Leaves Crude Extract and Enriched Fraction against Multidrug‐Resistant Bacteria
Authors: de Lima Liliane Bezerra , da Silva Wliana Alves Viturino , dos Santos Ewelyn Cintya Felipe , Machado Janaína Carla Barbosa , Procópio Thamara Figueiredo , de Moura Maiara Celine , Napoleão Thiago Henrique , Ferreira Magda Rhayanny Assunção , Soares Luiz Alberto Lira 
Published: October 2021

AbstractThe aim of this study was to evaluate the phytochemical composition, antioxidant, and antimicrobial potential of crude extract and fractions of Punica granatum leaves. The extract was produced by turbo extraction, after which hexanic, ethyl acetate, and aqueous fractions were obtained by partitioning. The chemical analyses were performed by thin layer chromatography and high‐performance liquid chromatography, and the antioxidant activities were assayed by DPPH. and ABTS.+. Minimal inhibitory and bactericidal concentrations (MIC/MBC) were applied to twenty‐two bacteria. Most strains susceptible to extract/fractions and resistant to antibiotics were selected, and ampicillin, azithromycin, ciprofloxacin, and gentamicin were associated with the ethyl acetate fraction (EAF) against multidrug‐resistant strains in modulatory and checkboard models. The data from chromatographic analyses showed flavonoids and tannins in the extract, as well as the enrichment of EAF in phenols, mainly flavonoids. The flavonoids were connected to the electron transfer activity demonstrated in the DPPH. and ABTS.+ assays. Gram‐positive strains are more susceptible to EAF. The subinhibitory concentrations of P. granatum enhanced the antimicrobial activity of the agents and reduced the EAF individual MIC, and the combination of EAF and antibiotics demonstrated a synergistic effect. These results present a promising approach for developing a therapy in which antioxidant extracts and fractions can be used in combination with antibiotics.
Plasmon Coupling Enhanced Micro‐Spectroscopy and Imaging for Sensitive Discrimination of Membrane Domains of a Single Cell
Authors: Pan Xiao‐Hui , Chen Min , Cao Shuo‐Hui , Xu Zi‐Qian , Li Zhao , Li Yao‐Qun 
Published: October 2021

AbstractDifferent cell membrane domains play different roles in many cell processes, and the discrimination of these domains is of considerable importance for the elucidation of cellular functions. However, the strategies available for distinguishing these cell membrane domains are limited. A novel technique called plasmon coupling enhanced micro‐spectroscopy and imaging to discriminate basal and lateral membrane domains of a single cell combines the application of an additional plasmonic silver film for surface plasmon (SP) excitation to selectively excite and enhance the basal membranes in the near‐field with directional enhanced microscopic imaging and spectroscopy. The SP and critical evanescent fields are induced upon excitation through a silver‐coated semitransparent coverslip at the surface plasmon resonance and critical angles, respectively. The basal and lateral membrane domains located within the SP and critical evanescent fields can be selectively excited and distinguished by adjusting the incident angle of laser irradiation. Moreover, the brighter images and more intense spectra of membrane‐targeting fluorescence‐Raman probes under directional excitation than in conventional EPI mode allow clear identification of the membrane domains.
Emerging Yttrium Phosphides with Tetrahedron Phosphorus and Superconductivity under High Pressures
Authors: Zhao Kaixuan , Yu Hong , Yang Qiuping , Li Wenjing , Han Fanjunjie , Liu Hanyu , Zhang Shoutao 
Published: October 2021

AbstractMetal phosphides have triggered growing interest for their exotic structures and striking properties. Hence, within advanced structure search and first‐principle calculations, several unprecedented Y−P compounds (e. g., Y3P, Y2P, Y3P2, Y2P3, YP2, and YP3) were identified under compression. Interestingly, as phosphorus content increases, P atoms exhibit diverse behaviors corresponding to standalone anion, dumbbell, zigzag chain, planar sheet, crossing chain‐like network, buckled layer, three‐dimensional framework, and wrinkled layer. Particularly, Fd‐3m YP2 can be viewed as assemblage of diamond‐like Y structure and rare vertex‐sharing tetrahedral P4 units. Impressively, electron‐phonon coupling (EPC) calculations elucidate that Pm‐3m Y3P possesses the highest superconducting critical temperature Tc of 10.2 K among binary transition metal phosphides. Remarkably, the EPC of Pm‐3m Y3P mainly arises from the contribution of low‐frequency soft phonon modes, whereas mid‐frequency phonon modes of Fd‐3m YP2 dominate. These results strengthen knowledge of metal phosphides and pave a way for seeking superconductive transition metal phosphides.
Synthesis of Isocryptolepine‐Triazole Adducts and Evaluation of Their Cytotoxic Activity
Authors: Rodphon Warabhorn , Laohapaisan Pavitra , Supantanapong Nantamon , Reamtong Onrapak , Ngiwsara Lukana , Lirdprapamongkol Kriengsak , Thongsornkleeb Charnsak , Khunnawutmanotham Nisachon , Tummatorn Jumreang , Svasti Jisnuson , Ruchirawat Somsak 
Published: October 2021

AbstractEighteen hybrid compounds between 8‐bromo‐2‐fluoro‐isocryptolepine (4) and 1,2,3‐triazole were synthesized via azide rearrangement‐annulation reaction. Compound 4 underwent regioselective N‐propargylation and click reaction to form 8‐bromo‐2‐fluoro‐isocryptolepine‐triazole hybrids 11 which were evaluated for cytotoxic activity. Compound 11 c containing 1‐anisyltriazole was the most effective in inhibiting HepG2, HuCCA‐1 and A549 cell lines (IC50 values of 1.65–3.07 μM) while compounds 11 a (1‐phenyltriazole), 11 j (1‐para‐CF3‐benzyltriazole) and 11 l (1‐meta‐Cl‐benzyltriazole) were potent inhibitors of HuCCA‐1, HepG2 and A549 cell lines, respectively. Moreover, 11 l showed the lowest cytotoxicity to normal human kidney cell line. Compounds 11 c and 11 l provided improvement of cytotoxic activity over 4. Compounds 4, 11 c and 11 l were selected to investigate their mechanisms of action. The results showed that 4 could induce G2/M cell cycle arrest and was involved in the upregulation of p53 and p21 proteins. However, the mechanisms of growth inhibition by 11 c and 11 l were associated with G0/G1 cell cycle arrest and mediated by induction of oxidative stress.
Surgical palliation in poorly differentiated neuroendocrine carcinoma of the hypopharynx: Case report
Authors: Fiorini Francesca Romana , Abbas Yasmin , Mukhopadhyay Suchana , Tatla Taran 
Published: October 2021

AbstractBackgroundPrimary neuroendocrine carcinomas (NECs) are very rare entities accounting for 0.49% of all malignancies. Within the head and neck, the most common sites are the larynx and paranasal sinuses, while the hypopharynx is seldom described.CaseWe present a patient with a poorly differentiated metastatic NEC of the hypopharynx treated palliatively with organ‐preserving surgery and post‐operative chemotherapy, and literature review for well‐documented pure hypopharyngeal NECs. Our patient died of chest infection during chemotherapy, 4 months after surgery.ConclusionChemotherapy remains the mainstay of treatment in the presence of metastases with 2‐year overall survival of 15.7%. Due to the aggressive nature of poorly differentiated metastatic NECs, surgical management is seldom considered. We report and advocate the successful palliative role of organ‐preserving, minimally invasive trans‐oral LASER micro‐surgery and neck dissection to control loco‐regional head and neck disease, safe‐guarding better quality of home life, despite limited life expectancy for this condition.
Excogitating marine predators algorithm based on random opposition‐based learning for feature selection
Authors: Balakrishnan Kulanthaivel , Dhanalakshmi Ramasamy , Mahadeo Khaire Utkarsh 
Published: October 2021

SummaryObtaining precise information from a high‐dimensional dataset is one of the most difficult tasks as datasets contain more features and fewer samples. The high‐dimensionality of the dataset reduces predictive capability and increases the computational complexity of the analytical model. The widespread employment of meta‐heuristic methods to handle the challenge of high‐dimensional datasets has been exceptional in recent years. The marine predators algorithm (MPA) is a recently developed meta‐heuristic algorithm based on the “survival‐of‐the‐fittest” notion. This research critique overcomes the drawbacks of the existing MPA and proposes a feature selection model using random opposition‐based learning (ROBL). The searching for the optimum solution in a single direction of the traditional MPA reduces its performance. The incorporation of ROBL in the MPA enhances its ability to reconnoiter bigger search space. The proposed algorithm generates a new population based on the initial and random opposite population. The performance of ROBL‐MPA is inspected on six high‐dimensional microarray datasets. The results of the proposed ROBL‐MPA are compared to traditional MPA and opposition based MPA (OBL‐MPA). The proposed ROBL‐MPA outperforms traditional MPA based on several benchmark performance analysis tests.
Intravital Imaging of Hepatic Blood Biliary Barrier in Live Mice
Authors: Vats Ravi , Kaminski Tomasz W. , Pradhan‐Sundd Tirthadipa 
Published: October 2021

AbstractUnderstanding the kinetics and spatiotemporal interactions of living cells within the tissue environment requires real‐time imaging. The introduction of two‐photon microscopy has substantially boosted the power of live intravital imaging, making it possible to obtain information of individual cells in near‐physiologic conditions within intact tissues nondestructively. Intravital imaging of the liver has proved useful in understanding its 3D structure, function, and dynamic cellular interactions. Recently we have shown that integrity of the blood‒bile barrier in different physiologic and pathophysiologic conditions can be imaged in real time using intravital microscopy. Here we discuss the real‐time intravital imaging method to visualize blood‒bile barrier integrity in the murine liver. © 2021 Wiley Periodicals LLC.Basic Protocol 1: Live imaging in the mouse liverSupport Protocol: Monitoring vital signs of the mouse during live liver imagingBasic Protocol 2: Visualizing blood and bile transport using intravital microscopy
LIR‐1 educates expanded human NK cells and defines a unique antitumor NK cell subset with potent antibody‐dependent cellular cytotoxicity
Authors: Leijonhufvud Caroline , Reger Robert , Segerberg Filip , Theorell Jakob , Schlums Heinrich , Bryceson Yenan T , Childs Richard W , Carlsten Mattias 
Published: October 2021

AbstractObjectiveKIR and NKG2A receptors educate human NK cells to stay responsive to cells with diminished HLA class I. Here, we addressed whether the HLA class I‐binding receptor LIR‐1 (LILRB1/ILT2/CD85j), which is widely expressed on human NK cells, can mediate education and contribute to antitumor functions of NK cells.MethodsHealthy donor NK cells either unstimulated, overnight cytokine‐activated or ex vivo‐expanded were used to target human cell lines. Phenotype and function were analysed using flow cytometry and 51Cr‐release assays.ResultsWe found that the inhibitory receptor LIR‐1 can mediate NK cell education under specific conditions. This novel finding was exclusive to expanded NK cells and further characterisation of the cells revealed high expression of granzyme B and DNAM‐1, which both previously have been linked to NK cell education. Corroborating the rheostat education model, LIR‐1 co‐expression with an educating KIR further increased the responsiveness of expanded NK cells. Inversely, antibody masking of LIR‐1 decreased the responsiveness. LIR‐1+ expanded NK cells displayed high intrinsic ADCC that, in contrast to KIR and NKG2A, was not inhibited by HLA class I.ConclusionThese findings identify a unique NK cell subset attractive for adoptive cell therapy to treat cancer. Given that LIR‐1 binds most HLA class I molecules, this subset may be explored in both autologous and allogeneic settings to innately reject HLA class I‐ tumor cells as well as HLA class I+ target cells when combined with antitumor antibodies. Further studies are warranted to address the potential of this subset in vivo.
Comprehensive metabolic study of IOX4 in equine urine and plasma using liquid chromatography/electrospray ionization Q Exactive high‐resolution mass spectrometer for the purpose of doping control
Authors: Ishii Hideaki , Shibuya Mariko , So Yat‐Ming , Wong Jenny K. Y. , Ho Emmie N. M. , Kusano Kanichi , Sone Yu , Kamiya Takahiro , Wakuno Ai , Ito Hideki , Miyata Kenji , Yamada Masayuki , Leung Gary Ngai‐Wa 
Published: October 2021

AbstractIOX4 is a hypoxia‐inducible factor prolyl hydroxylase (HIF‐PHD) inhibitor, which was developed for the treatment of anemia by exerting hematopoietic effects. The administration of HIF‐PHD inhibitors such as IOX4 to horses is strictly prohibited by the International Federation of Horseracing Authorities and the Fédération Équestre Internationale. To the best of our knowledge, this is the first comprehensive metabolic study of IOX4 in horse plasma and urine after a nasoesophageal administration of IOX4 (500 mg/day, 3 days). A total of four metabolites (three mono‐hydroxylated IOX4 and one IOX4 glucuronide) were detected from the in vitro study using homogenized horse liver. As for the in vivo study, post‐administration plasma and urine samples were comprehensively analyzed with liquid chromatography/electrospray ionization high‐resolution mass spectrometry to identify potential metabolites and determine their corresponding detection times. A total of 10 metabolites (including IOX4 glucuronide, IOX4 glucoside, O‐desbutyl IOX4, O‐desbutyl IOX4 glucuronide, four mono‐hydroxylated IOX4, N‐oxidized IOX4, and N‐oxidized IOX4 glucoside) were found in urine and three metabolites (glucuronide, glucoside, and O‐desbutyl) in plasma. Thus, the respective quantification methods for the detection of free and conjugated IOX4 metabolites in urine and plasma with a biphase enzymatic hydrolysis were developed and applied to post‐administration samples for the establishment of elimination profiles of IOX4. The detection times of total IOX4 in urine and plasma could be successfully prolonged to at least 312 h.
The association of chronic, enhanced immunosuppression with outcomes of diabetic foot infections
Authors: Uçkay Ilker , Schöni Madlaina , Berli Martin C. , Niggli Fabian , Noschajew Emil , Lipsky Benjamin A. , Waibel Felix W. A. 
Published: October 2021

AbstractWe investigated if a chronic, enhanced immunosuppressed condition, beyond the immunodeficiency related to diabetes, is associated with clinical failures after combined surgical and medical treatment for diabetic foot infection (DFI). This is a case‐control cohort study in a tertiary centre for diabetic foot problems, using case‐mix adjustments with multivariate Cox regression models. Among 1013 DFI episodes in 586 patients (median age 67 years; 882 with osteomyelitis), we identified a chronic, enhanced immune‐suppression condition in 388 (38%) cases: dialysis (85), solid organ transplantation (25), immune‐suppressive medication (70), cirrhosis (9), cancer chemotherapy (15) and alcohol abuse (243). Overall, 255 treatment episodes failed (25%). By multivariate analysis, the presence (as compared with absence) of chronic, enhanced immune‐suppression was associated with a higher rate of clinical failures in DFI cases (hazard ratio 1.5, 95% confidence interval 1.1–2.0). We conclude that a chronic, enhanced immune‐suppressed state might be an independent risk factor for treatment failure in DFI. Validation of this hypothesis could be useful information for both affected patients and their treating clinicians.
Biomarkers in the management of acute heart failure: state of the art and role in COVID‐19 era
Authors: Aleksova Aneta , Sinagra Gianfranco , Beltrami Antonio P. , Pierri Alessandro , Ferro Federico , Janjusevic Milijana , Gagno Giulia 
Published: October 2021

AbstractAcute heart failure (AHF) affects millions of people worldwide, and it is a potentially life‐threatening condition for which the cardiologist is more often brought into play. It is crucial to rapidly identify, among patients presenting with dyspnoea, those with AHF and to accurately stratify their risk, in order to define the appropriate setting of care, especially nowadays due to the coronavirus disease 2019 (COVID‐19) outbreak. Furthermore, with physical examination being limited by personal protective equipment, the use of new alternative diagnostic and prognostic tools could be of extreme importance. In this regard, usage of biomarkers, especially when combined (a multimarker approach) is beneficial for establishment of an accurate diagnosis, risk stratification and post‐discharge monitoring. This review highlights the use of both traditional biomarkers such as natriuretic peptides (NP) and troponin, and emerging biomarkers such as soluble suppression of tumourigenicity (sST2) and galectin‐3 (Gal‐3), from patients' emergency admission to discharge and follow‐up, to improve risk stratification and outcomes in terms of mortality and rehospitalization.