bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Experimental Toolbox for Structure‐Based Hit Discovery for P. aeruginosa FabF, a Promising Target for Antibiotics
Authors: Espeland Ludvik Olai , Georgiou Charis , Klein Raphael , Bhukya Hemalatha , Haug Bengt Erik , Underhaug Jarl , Mainkar Prathama S. , Brenk Ruth 
Published: June 2021

AbstractFabF (3‐oxoacyl‐[acyl‐carrier‐protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target for new antibiotics. Here, we focus on FabF from P. aeruginosa (PaFabF) as antibiotics against this pathogen are urgently needed. To facilitate exploration of this target we have set up an experimental toolbox consisting of binding assays using bio‐layer interferometry (BLI) as well as saturation transfer difference (STD) and WaterLOGSY NMR in addition to robust conditions for structure determination. The suitability of the toolbox to support structure‐based design of FabF inhibitors was demonstrated through the validation of hits obtained from virtual screening. Screening a library of almost 5 million compounds resulted in 6 compounds for which binding into the malonyl‐binding site of FabF was shown. For one of the hits, the crystal structure in complex with PaFabF was determined. Based on the obtained binding mode, analogues were designed and synthesised, but affinity could not be improved. This work has laid the foundation for structure‐based exploration of PaFabF.
Real‐world emetic risk of chemotherapy and the corresponding antiemetic therapy in Japan: A study based on a nationwide database
Authors: Okuyama Ayako , Boku Narikazu , Higashi Takahiro 
Published: June 2021

AbstractBackgroundChemotherapy‐induced nausea and vomiting (CINV) is a major concern of patients with cancer, leading to suboptimal treatment.AimThis study assessed the emetic risk associated with intravenous and oral chemotherapy and the prophylactic antiemetic drugs by cancer type in a real‐world setting.Methods and ResultsWe used the health services utilisation data for patients with cancer diagnosed in 2016. Patients aged at least 20 years at the time of diagnosis and who started their first course of chemotherapy were included. The emetic risk of chemotherapy was determined according to the cancer type and was classified based on clinical practice guidelines. The prescription of antiemetic drugs was assessed. Overall, 172 133 patients were evaluated, of whom 121 103 (70.4%) received intravenous chemotherapy. High‐emetic‐risk chemotherapy (HEC) was prescribed in 46 458 (27.0%) patients. HEC was prescribed most for patients with oesophageal cancer (80.3%), followed by malignant lymphoma (60.2%) and breast cancer (53.8%). Moderate‐emetic‐risk chemotherapy (MEC) was prescribed in 60 528 (35.2%) patients and was mostly prescribed for small cell lung cancer (59.9%). Meanwhile, more than 50% of the chemotherapy prescribed for patients with gastric, colorectal, and pancreatic cancer was low‐emetic‐risk chemotherapy. HEC was accompanied by three‐drug antiemetic prophylaxis in more than 90% of patients with small cell lung, non‐small cell lung, breast, and oesophageal cancer, whereas only 13.5% of patients with malignant lymphoma were administered CHOP (cyclophosphamide, doxorubicin, vincristine sulphate, and prednisolone) with prophylaxis.ConclusionThe risk of CINV differs with cancer type. HEC was less prescribed compared with MEC. Most patients received the recommended anti‐emetic prophylaxis.
Oncogenetic network estimation with disjunctive Bayesian networks
Authors: Nicol Phillip B. , Coombes Kevin R. , Deaver Courtney , Chkrebtii Oksana , Paul Subhadeep , Toland Amanda E. , Asiaee Amir 
Published: June 2021

AbstractMotivation: Cancer is the process of accumulating genetic alterations that confer selective advantages to tumor cells. The order in which aberrations occur is not arbitrary, and inferring the order of events is challenging due to the lack of longitudinal samples from tumors. Moreover, a network model of oncogenesis should capture biological facts such as distinct progression trajectories of cancer subtypes and patterns of mutual exclusivity of alterations in the same pathways.In this paper, we present the disjunctive Bayesian network (DBN), a novel oncogenetic model with a phylogenetic interpretation. DBN is expressive enough to capture cancer subtypes' trajectories and mutually exclusive relations between alterations from unstratified data.Results: In cases where the number of studied alterations is small (), we provide an efficient dynamic programming implementation of an exact structure learning method that finds a best DBN in the superexponential search space of networks. In rare cases that the number of alterations is large, we provided an efficient genetic algorithm in our software package, OncoBN. Through numerous synthetic and real data experiments, we show OncoBN's ability in inferring ground truth networks and recovering biologically meaningful progression networks.Availability: OncoBN is implemented in R and is available at https://github.com/phillipnicol/OncoBN.
Integrative multiomics analysis of human atherosclerosis reveals a serum response factor‐driven network associated with intraplaque hemorrhage
Authors: Jin Han , Goossens Pieter , Juhasz Peter , Eijgelaar Wouter , Manca Marco , Karel Joël M. H. , Smirnov Evgueni , Sikkink Cornelis J. J. M. , Mees Barend M. E. , Waring Olivia , van Kuijk Kim , Fazzi Gregorio E. , Gijbels Marion J. J. , Kutmon Martina , Evelo Chris T. A. , Hedin Ulf , Daemen Mat J. A. P. , Sluimer Judith C. , Matic Ljubica , Biessen Erik A. L. 
Published: June 2021

AbstractBackgroundWhile single‐omics analyses on human atherosclerotic plaque have been very useful to map stage‐ or disease‐related differences in expression, they only partly capture the array of changes in this tissue and suffer from scale‐intrinsic limitations. In order to better identify processes associated with intraplaque hemorrhage and plaque instability, we therefore combined multiple omics into an integrated model.MethodsIn this study, we compared protein and gene makeup of low‐ versus high‐risk atherosclerotic lesion segments from carotid endarterectomy patients, as judged from the absence or presence of intraplaque hemorrhage, respectively. Transcriptomic, proteomic, and peptidomic data of this plaque cohort were aggregated and analyzed by DIABLO, an integrative multivariate classification and feature selection method.ResultsWe identified a protein‐gene associated multiomics model able to segregate stable, nonhemorrhaged from vulnerable, hemorrhaged lesions at high predictive performance (AUC >0.95). The dominant component of this model correlated with αSMA−PDGFRα+fibroblast‐like cell content (p = 2.4E‐05) and Arg1+macrophage content (p = 2.2E‐04) and was driven by serum response factor (SRF), possibly in a megakaryoblastic leukemia‐1/2 (MKL1/2) dependent manner. Gene set overrepresentation analysis on the selected key features of this model pointed to a clear cardiovascular disease signature, with overrepresentation of extracellular matrix synthesis and organization, focal adhesion, and cholesterol metabolism terms, suggestive of the model's relevance for the plaque vulnerability. Finally, we were able to corroborate the predictive power of the selected features in several independent mRNA and proteomic plaque cohorts.ConclusionsIn conclusion, our integrative omics study has identified an intraplaque hemorrhage‐associated cardiovascular signature that provides excellent stratification of low‐ from high‐risk carotid artery plaques in several independent cohorts. Further study revealed suppression of an SRF‐regulated disease network, controlling lesion stability, in vulnerable plaque, which can serve as a scaffold for the design of targeted intervention in plaque destabilization.
Diversity and intratumoral heterogeneity in human gallbladder cancer progression revealed by single‐cell RNA sequencing
Authors: Chen Peizhan , Wang Yueqi , Li Jingquan , Bo Xiaobo , Wang Jie , Nan Lingxi , Wang Changcheng , Ba Qian , Liu Houbao , Wang Hui 
Published: June 2021

AbstractBackgroundGallbladder cancer (GC) is a malignant disease characterized with highly cellular heterogeneity and poor prognosis. Determining the intratumoral heterogeneity and microenvironment (TME) can provide novel therapeutic strategies for GC.MethodsWe performed the single‐cell RNA sequencing on the primary and lymph node metastatic gallbladder tumors and the adjacent normal tissues of five patients. The transcriptomic atlas and ligand–receptor‐based intercellular communication networks of the single cells were characterized.ResultsThe transcriptomic landscape of 24,887 single cells was obtained and characterized as 10 cellular clusters, including epithelial, neuroendocrine tumor cells, T&NK cells, B cells, RGS5+ fibroblasts, POSTN+ fibroblasts, PDGFRA+ fibroblasts, endothelial, myeloid cells, and mast cells. Different types of GC harbored distinct epithelial tumor subpopulations, and squamous cell carcinoma could be differentiated from adenocarcinoma cells. Abundant immune cells infiltrated into adenocarcinoma and squamous cell carcinoma, rather than neuroendocrine neoplasms, which showed significant enrichment of stromal cells. CD4+/FOXP3+ T‐reg and CD4+/CXCL13+ T helper cells with higher exhausting biomarkers, as well as a dynamic lineage transition of tumor‐associated macrophages from CCL20hi/CD163lo, CCL20lo/CD163hi to APOE+, were identified in GC tissues, suggesting the immunosuppressive and tumor‐promoting status of immune cells in TME. Two distinct endothelial cells (KDR+ and ACKR1+), which were involved in angiogenesis and lymphangiogenesis, showed remarkable ligand–receptor interactions with primary GC cells and macrophages in gallbladder tumors.ConclusionsThis study reveals a widespread reprogramming across multiple cell populations in GC progression, dissects the cellular heterogeneity and interactions in gallbladder TME, and provides potential therapeutic targets for GC.
Activated neutrophils polarize protumorigenic interleukin‐17A‐producing T helper subsets through TNF‐α‐B7‐H2‐dependent pathway in human gastric cancer
Authors: Shan Zhi‐guo , Chen Jun , Liu Jin‐shan , Zhang Jin‐yu , Wang Ting‐ting , Teng Yong‐sheng , Mao Fang‐yuan , Cheng Ping , Zou Quan‐ming , Zhou Wei‐ying , Peng Liu‐sheng , Zhao Yong‐liang , Zhuang Yuan 
Published: June 2021

AbstractRationaleNeutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown.MethodsFlow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan‐Meier plots and Multivariate analysis for the survival of patients were used by log‐rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays.ResultsGC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8‐CXCR1‐mediated chemotaxis, and expressed activated molecule CD54 and co‐signaling molecule B7‐H2. Neutrophils induced by tumors strongly expressed CD54 and B7‐H2 in both dose‐ and time‐dependent manners, and a close correlation was obtained between the expressions of CD54 and B7‐H2 on intratumoral neutrophils. Tumor‐derived tumor necrosis factor‐α (TNF‐α) promoted neutrophil activation and neutrophil B7‐H2 expression through ERK‐NF‐κB pathway, and a significant correlation was found between the levels of TNF‐α and CD54+ or B7‐H2+ neutrophils in tumor tissues. Tumor‐infiltrating and tumor‐conditioned neutrophils effectively induced IL‐17A‐producing Th subset polarization through a B7‐H2‐dependent manner ex vivo and these polarized IL‐17A‐producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL‐17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL‐17A is blocked. Moreover, increased B7‐H2+ neutrophils and IL‐17A in tumors were closely related to advanced GC progression and predicted poor patient survival.ConclusionWe illuminate novel underlying mechanisms that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC.
Impact of beta‐blocker use on the long‐term outcomes of heart failure patients with chronic obstructive pulmonary disease
Authors: Kubota Yoshiaki , Tay Wan Ting , Teng Tiew‐Hwa Katherine , Asai Kuniya , Noda Takashi , Kusano Kengo , Suzuki Atsushi , Hagiwara Nobuhisa , Hisatake Shinji , Ikeda Takanori , Yasuoka Ryobun , Kurita Takashi , Shimizu Wataru ,   ASIAN‐HF Executive Committee
Published: June 2021

AbstractAimsThe number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta‐blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio‐selective beta‐blocker use on the long‐term outcomes of patients with HF and COPD.Methods and resultsAmong the 5232 patients with HFrEF (left ventricular ejection fraction of <40%) prospectively enrolled from 11 Asian regions in the ASIAN‐HF registry, 412 (7.9%) had a history of COPD. We compared the clinical characteristics and long‐term outcomes of the patients with HF and COPD according to the use and type of beta‐blockers used: cardio‐selective beta‐blockers (n = 149) vs. non‐cardio‐selective beta‐blockers (n = 124) vs. no beta‐blockers (n = 139). The heart rate was higher, and the outcome was poorer in the no beta‐blocker group than in the beta‐blocker groups. The 2 year all‐cause mortality was significantly lower in the non‐cardio‐selective beta‐blocker group than in the no beta‐blocker group. Further, the cardiovascular mortality significantly decreased in the non‐cardio‐selective beta‐blocker group before (hazard ratio: 0.36; 95% confidence interval: 0.18–0.73; P = 0.004) and after adjustments (hazard ratio: 0.37; 95% confidence interval: 0.19–0.73; P = 0.005), but not in the cardio‐selective beta‐blocker group.ConclusionsBeta‐blockers reduced the all‐cause mortality of patients with HFrEF and COPD after adjusting for age and heart rate, although the possibility of selection bias could not be completely excluded due to multinational prospective registry.
Synthesis of Emulsion by Using Vegetable Oil Modified by Titanium Dioxide (TiO2) Nanoparticles: A Peculiar Source for Synthesis of Bio‐Based Lubricant and Novel Approach to Enhance the Efficiency of Emulsion
Authors: Ajmal Muhammad , Ali Syed Abid , Tahir Hajira , Shah Muhammad Raza , Saad Muhammad 
Published: June 2021

AbstractMany advanced methods are developed for the synthesis of emulsions in the literature, but the effect of imperative parameters of emulsion like oil concentration, pH, temperature, and time on the emulsion stability index (ESI) by design of experiments have not been studied previously. The ESI is an important parameter of emulsion to run the industrial process extensively and reflects the emulsion efficiency to sustain against instability like creaming, coalescence, and flocculation. In the present study, the research plan consists of three phases. In the first phase, the synthesis of an eco‐friendly and cost‐effective mustard oil‐based nanoemulsion with a suitable selection of the surfactant on the bases of the polydispersity index (PDI) is developed. In the next phase emulsions, characteristic properties are scanned by employing various techniques and antirust property compared with reference emulsion. Finally, the impact of emulsion's parameters on ESI is studied by factorial design. The findings that depict the impact of parameters of oil concentration and time on ESI are found influential, whereas the effect of pH and temperature is insignificant. Therefore, good characteristic results, stability, and the inhibition against rust of newly developed emulsion can be adapted to run the cold rolling process smoothly.Practical Application: In the present era, metal processing industries are forced to explore the environmentally friendly oil‐in‐water emulsions (that used as an interface, lubricant, cooling, and antifrictional agents in cold rolling industries) to overcome increasing environmental pollution. Mustard oil‐based emulsion modified by nanoparticles (Nps) offers a good source of eco‐friendly, cost‐effective, and economic booster for metal processing industries. The antimicrobial properties of mustard oil are well defined in previous research articles. Such oil is a magnificent source for the synthesis of the emulsion and modification of mustard oil‐based emulsion with titanium dioxide. Nps provide significant protection against rust. Such applications can encourage the use of mustard oil‐based nanoemulsion for metal processing industries.
Bad mood food? Increased versus decreased food cue reactivity in anorexia nervosa and bulimia nervosa during negative emotions
Authors: Schnepper Rebekka , Richard Anna , Georgii Claudio , Arend Ann‐Kathrin , Naab Silke , Voderholzer Ulrich , Wilhelm Frank H. , Blechert Jens 
Published: June 2021

AbstractObjectiveEmotion regulation difficulties in anorexia nervosa (AN) and bulimia nervosa (BN) might underlie bingeing and purging in BN, extreme fasting in AN, or combinations of these symptoms in binge‐purge type AN. In this study, we tested for decreased food cue reactivity in response to negative emotions in AN, and the opposite pattern for BN. Furthermore, we explored subgroup differences (restrictive vs. binge‐purging AN; history of AN in BN).MethodPatients with AN (n = 41), BN (n = 39), and matched controls (n = 70) completed an emotional eating questionnaire. In a laboratory experiment, we induced negative emotions and measured food cue reactivity (pleasantness, desire to eat (DTE), and corrugator muscle activity).ResultsAN reported emotional undereating, while BN reported emotional overeating. In the laboratory task, BN showed increased DTE and an appetitive corrugator response during negative emotions, selectively towards high‐calorie foods. AN showed generalized reduced cue reactivity to high‐calorie food regardless of emotional state. This pattern appears to be characteristic of restrictive AN, while cue reactivity of both BN subgroups pointed towards emotional overeating.ConclusionsThe emotional over‐ versus undereating framework might help to explain bingeing and restricting along the anorectic‐bulimic disorder spectrum, which calls for novel transdiagnostic theories and subgroup‐specific treatments.
Heat‐induced compounds development in processed tomato and their influence on corrosion initiation in metal food cans
Authors: Dhuey Elliot , Castada Hardy Z. , Barringer Sheryl , Joseph Jojo , Hadad Christopher M. , Ruffley Ken , Pascall Melvin A. 
Published: June 2021

AbstractSelected ion flow tube mass spectrometry (SIFT‐MS) and ion chromatography (IC) were used to investigate the presence of volatile and nonvolatile compounds in canned tomatoes and in the polymeric lining before and after retorting the cans. This allowed us to observe if these compounds contributed to corrosion and the migration of iron and tin compounds from the cans to the tomatoes. Diced Roma tomatoes and other simulant treatment groups were sealed in two‐piece tinplated cans (controls in glass jars), retorted at 121℃ for 30 min, then stored at 49℃ for 50 days. Results showed that thermal degradation of amino acids in the tomatoes gave rise to volatile methyl sulfides and nonvolatile nitrogenous compounds which were subsequently sorbed by the can lining. SIFT‐MS showed a 20‐fold increase in dimethyl sulfide concentration. Inductively coupled plasma (ICP‐MS) results showed fourfold and 16‐fold increases in iron and tin compounds, respectively, that migrated from the metal to the tomatoes as a result of acid and electrolyte interactions.
Association study of taste preference: Analysis in the Lithuanian population
Authors: Kavaliauskienė Ingrida , Domarkienė Ingrida , Ambrozaitytė Laima , Barauskienė Lina , Meškienė Raimonda , Arasimavičius Justas , Irnius Algimantas , Kučinskas Vaidutis 
Published: June 2021

AbstractTaste has strong evolutionary basis in the sense of survival by influencing our behavior to obtain food/medicine or avoid poisoning. It is a complex trait and varies among individuals and distinct populations. We aimed to investigate the association between known genetic factors (673 SNPs) and taste preference in the Lithuanian population, as well as to determine a reasonable method for qualitative evaluation of a specific taste phenotype for further genetic analysis. Study group included individuals representing six ethnolinguistic regions of Lithuania. Case and control groups for each taste were determined according to the answers selected to the taste‐specific and frequency of specific food consumption questions. Sample sizes (case/control) for each taste are as follows: sweetness (55/179), bitterness (82/208), sourness (32/259), saltiness (42/249), and umami (96/190). Genotypes were extracted from the Illumina HumanOmniExpress‐12v1.1 arrays’ genotyping data. Analysis was performed using PLINK v1.9. We found associations between the main known genetic factors and four taste preferences in the Lithuanian population: sweetness—genes TAS1R3, TAS1R2, and GNAT3 (three SNPs); bitterness—genes CA6 and TAS2R38 (six SNPs); sourness—genes PKD2L1, ACCN2, PKD1L3, and ACCN1 (48 SNPs); and saltiness—genes SCNN1B and TRPV1 (five SNPs). We found our questionnaire as a beneficial aid for qualitative evaluation of taste preference. This was the first initiative to analyze genetic factors related to taste preference in the Lithuanian population. Besides, this study reproduces, supports, and complements results of previous limited taste genetic studies or ones that lack comprehensive results concerning distinct (ethnic) human populations.
On trigonometric cosine, square, sawtooth, and triangular wave‐type rotational modulations on triple‐diffusive convection in salted water
Authors: Rudziva M. , Sibanda P. , Noreldin O. A. I. , Goqo S. 
Published: June 2021

AbstractThe effect of sinusoidal (trigonometric cosine) and nonsinusoidal (square, sawtooth, and triangular) rotational modulations on triple‐diffusive convection in a Newtonian fluid is studied in this paper. The derived Ginzburg–Landau equation for the stationary mode of convection is used to quantify heat and mass transport. The enhancement of heat and mass transport in water due to the addition of different salts is explained in terms of the thermophysical properties of the fluid and the aqueous solutes. The flow equations are reduced to a Lorenz‐type scheme of nonlinear evolution equations using a truncated Fourier series. The equations describing the growth of convection amplitudes are solved using the multidomain spectral collocation method. With the aid of thermophysical properties of the fluid, numerical computations are performed for different values of the revised Rayleigh number (), Taylor number (), the amplitude of modulation , and modulation frequency . A comparison of heat and mass transport in different combinations of aqueous solutions is made. The study reveals that all modes of rotational modulation can control the rate of heat and mass transport. It is noted that amongst all other modulations, the square wave modulation is the most destabilizing one.