bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hit discovery of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5H‐cyclopenta[d]pyrimidines as potential anti‐glioblastoma therapeutics: Design, synthesis, biological evaluation, and computational screening
Authors: Khairnar Sanjay , Sonawane Anjali , Cheke Rameshwar S. , Kharkar Prashant S. , Gaikwad Vishwas , Patil Sambhaji , Aware Valmik 
Published: February 2023

AbstractGlioblastoma multiforme (GBM) is a highly‐aggressive, dreadful disease with poor prognosis and disappointing clinical success. There is an unmet medical need of molecularly‐targeted therapeutics for GBM treatment. In the present work, a series of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5H‐cyclopenta[d]pyrimidines was designed, synthesized, purified, characterized, and evaluated for cytotoxicity against glioblastoma cell line U87‐MG. The design process (virtual library enumeration around the core, physicochemical and molecular property prediction/calculation of the designs, filtering the undesirable ones, and the diversity analyses of the lead‐like designs), was carefully curated so as to obtain a set of structurally‐diverse, novel molecules (total 20), with a particular focus on the relatively unexplored core structure, 6,7‐dihydro‐5H‐cyclopenta[d]pyrimidine. The preliminary screening was done using MTT assay at 10 and 100 μM concentrations of the title compounds F1−F20 and positive c120cisplatin, which yielded six hits (% inhibition at 10 μM: ~50%)—F2, F3, F5, F7, F15, and F20, which were taken up for IC50 determination. The top hits F2 and F7 (IC50 < 10 μM) were further used for computational studies such as target prediction, followed by their molecular docking in the binding sites of the top‐3 predicted targets (epidermal growth factor receptor kinase domain, cyclin‐dependent kinase 2 [CDK2]) /cyclin E, and anaplastic lymphoma kinase [ALK]). The docking pose analyses revealed interesting trends. The relatively planar core structure, presence of favorable hinge‐binding substructures, basic groups, all added up, and culminated in appreciable cytotoxicity against GBM cell line.
Taxon‐dependent effects of dispersal limitation versus environmental filters on bryophyte assemblages―Multiple perspective studies in land‐bridge islands
Authors: Li Dandan , Zhang Feng , Luo Guangyu , Zhang Ting , Lv Jinqiao , Wang Wenchao , Yang Jun , You Dejun , Xu Nanlong , Guo Shuiliang , Yu Jing 
Published: February 2023

AbstractTo explore the taxon‐dependent contribution of dispersal limitation versus environmental filters to bryophyte assemblages. We investigated bryophytes and six environmental variables on 168 islands in the Thousand Island Lake,China. We compared the observed beta diversity with the expected values based on six null models (EE, EF, FE, FF, PE, and PF), detected the partial correlation of beta diversity with geographical distances. We quantified the contributions of spatial versus environmental variables and island isolation per se to species composition (SC) using variance partitioning. We modeled the species‐area relationships (SARs) for bryophytes and the other eight biotas. To explore the taxon‐dependent effects of spatial versus environmental filters on bryophytes, 16 taxa including five categories (total bryophytes, total mosses, liverworts, acrocarpous, and pleurocarpous mosses) and 11 species‐richest families were included in the analyses. The observed beta diversity values were significantly different from the predicted values for all 16 taxa. For all five categories, the observed partial correlations between beta diversity and geographical distance after controlling environmental effects were not only positive, but also significantly different from the predicted values based on the null models. Spatial eigenvectors are more important in shaping SC than environmental variables for all 16 taxa except Brachytheciaceae and Anomodontaceae. Spatial eigenvectors contributed more to SC variation in liverworts than in mosses and in pleurocarpous mosses than in acrocarpous mosses. The effects of island isolation on SC were significant for all five categories, highly varied at the family level. The z values of the SARs for the five bryophyte categories were all larger than those of the other eight biotas. In subtropical fragmented forests, dispersal limitation exerted significant, taxon‐dependent effects on bryophyte assemblages. It was dispersal limitation rather than environmental filtering that predominantly regulated the SC patterns of bryophytes.
High‐severity fire drives persistent floristic homogenization in human‐altered forests
Authors: Weeks JonahMaria , Miller Jesse E. D. , Steel Zachary L. , Batzer Evan E. , Safford Hugh D. 
Published: February 2023

AbstractEcological disturbance regimes across the globe are being altered via direct and indirect human influences. Biodiversity loss at multiple scales can be a direct outcome of these shifts. Fire, especially in dry forests, is an ecological disturbance that is experiencing dramatic changes due to climate change, fire suppression, increased human population in fire‐prone areas, and alterations to vegetation composition and structure. Dry western conifer forests that historically experienced frequent, low‐severity fires are now increasingly burning at high severity. Relatively little work has been done looking at the effects of this novel disturbance type on affected plant communities, and little is known about how these impacts change over time. To fill in these knowledge gaps, we examined a fire that burned in a yellow pine and mixed conifer forest in the central Sierra Nevada in California, USA. We sampled at five time steps across the nine years following the fire (1, 3, 5, 8, and 9 years postfire). We found a generally unimodal relationship between fire severity and plant alpha and gamma diversity, but found that areas that burned at high severity supported progressively lower plant diversity as time since fire increased. Similarly, beta diversity decreased drastically through time for the high‐severity areas, while remaining more static in the other severity classes. The combination of these findings indicates that significant floristic homogenization can result from high‐severity fire in this ecosystem type. We also saw consistently lower diversity in unburned areas in comparison to area burned at low and moderate severity, underlining that both lack of fire and high‐severity fire can have negative impacts on postfire plant diversity. Unburned areas that experienced forest thinning after the first sample year saw an increase in plant diversity over time, suggesting that some—but not all—of the effects of fire on plant diversity can be approximated through forest management.
Bumble bee banquet: Genus‐ and species‐level floral selection by Midwestern Bombus
Authors: Lanterman Novotny Jessie , Lybbert Andrew , Reeher Paige , Mitchell Randall J. , Goodell Karen 
Published: February 2023

AbstractRegionally specific flower preference data are needed to optimize conservation habitat plantings for at‐risk pollinators such as bumble bees (Bombus spp.). Current tools for selecting flowers for plantings rely on raw bee flower visits, which can be biased toward abundant flowers. To assist in planning habitat enhancements for bumble bees, we quantified genus‐ and species‐level floral preferences using a selection index that accounts for floral availability. Through 477 h of observation in Ohio, USA during the summers of 2017 and 2018, we recorded 22,999 observations of eight Bombus species visiting 96 flowering plant taxa. As a genus, Bombus selected flowers nonrandomly; the most strongly preferred plants included Asclepias spp., Cirsium spp., Convolvulaceae, Dipsacus spp., Echinacea purpurea, Monarda fistulosa, Penstemon digitalis, and Silphium spp. Only a few Fabaceae were highly selected (Baptisia spp., Trifolium pratense, and Vicia spp.), while some were preferred only during their peak bloom (Securigera varia), and others were not preferred by bumble bees (T. hybridum and Melilotus spp.). Diets differed among habitats, and in restored meadows, bumble bees selected for native planted species such as Monarda fistulosa, Asclepias syriaca, Echinacea purpurea, Penstemon digitalis, and Silphium spp. Diets and preferences shifted over the season, largely driven by changes in plant phenologies (e.g., in June, Penstemon was strongly selected, in July, Asclepias, and in August, Verbena). For the three most common Bombus (B. impatiens, B. griseocollis, and B. bimaculatus), rarefaction analysis indicates that we were able to detect almost all plants in their summer diets. However, for five less common species, even our extensive sampling was insufficient to fully characterize their diets. The common Bombus species differed in their feeding niches, perhaps reducing interspecific competition. In contrast, we found high diet overlap between three rarer species—B. vagans, B. fervidus, and B. pensylvanicus, suggesting that these at‐risk species might benefit from different floral communities than would the common species. Five of eight species (including one that is currently under review for federal listing) most strongly preferred one or another non‐native plant, presenting managers with a conservation conundrum concerning how to balance the needs of bees with the preservation of native plants.
Personalized care of patients with heart failure: are we ready for a REWOLUTION? Insights from two international surveys on healthcare professionals' needs and patients' perceptions
Authors: Jankowska Ewa A. , Liu Peter P. , Cowie Martin R. , Groenhart Max , Cobey Kelly D. , Howlett Jonathan , Komajda Michel , Lund Lars H. , Magaña Serrano Jose Antonio , Mourilhe‐Rocha Ricardo , Rosano Giuseppe M.C. , Saldarriaga Clara , Schwartzmann Pedro V. , Zannad Faiez , Zhang Jian , Zhang Yuhui , Coats Andrew J.S. 
Published: February 2023

AbstractAimsGuidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient‐centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF.Methods and resultsAnonymous online questionnaires co‐developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline‐mandated medications over up‐titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline‐recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses.ConclusionsThese surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient‐centred, needs‐driven quality improvement programmes.
Potential role of FKBP5 single‐nucleotide polymorphisms in functional seizures
Authors: Asadi‐Pooya Ali A. , Simani Leila , Asadollahi Marjan , Rashidi Fatemeh Sadat , Ahmadipour Ehsan , Alavi Afagh , Roozbeh Mehrdad , Akbari Nayyereh , Firouzabadi Negar 
Published: February 2023

AbstractObjectiveWe investigated the associations between FKBP5 single‐nucleotide polymorphisms (SNPs) and functional seizures (FS).MethodsSeventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3′ region and rs9470080 in the 5′ region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used.ResultsPatients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis.SignificancePatients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group.
Upregulated microRNA‐450b‐5p represses the development of acute liver failure via modulation of liver function, inflammatory response, and hepatocyte apoptosis
Authors: Fang Jun , Kuang Jing , Hu Shuli , Yang Xiuhong , Wan Weibo , Li Jing , Fan Xuepeng 
Published: February 2023

AbstractObjectiveIt has been evidenced that microRNAs (miRs) exert crucial effects on acute liver failure (ALF), while the detailed function of miR‐450b‐5p in ALF progression remained obscure. The purpose of this research was to unravel the regulatory mechanism of miR‐450b‐5p in ALF via modulating Mouse Double Minute 2 protein (MDM2).MethodsALF was induced in mice by intraperitoneal injection of d‐galactosamine (
d‐GalN) and lipopolysaccharide (LPS). Adenoviruses containing overexpressed miR‐450b‐5p, MDM2 shRNA, and overexpressed MDM2 sequences were utilized to manipulate miR‐450b‐5p and MDM2 expression in the liver before the mice were treated with
d‐GalN/LPS‐induced ALF. Subsequently, miR‐450b‐5p and MDM2 expression levels in liver tissues of ALF mice were examined. Serum biochemical parameters of liver function were tested, serum inflammatory factors were assessed, and the histopathological changes and hepatocyte apoptosis in liver tissues were observed. The relation between miR‐450b‐5p and MDM2 was verified.ResultsIn ALF mice, miR‐450b‐5p was low‐expressed while MDM2 was high‐expressed. The upregulation of miR‐450b‐5p or downregulation of MDM2 could alleviate liver function, mitigate the serum inflammatory response and pathological changes in liver tissues, as well as inhibit the apoptosis of hepatocytes. MiR‐450b‐5p targeted MDM2. MDM2 overexpression reversed the repressive effects of elevated miR‐450b‐5p on ALF.ConclusionThe upregulated miR‐450b‐5p blocks the progression of ALF via targeting MDM2. This study contributes to affording novel therapeutic targets for ALF treatment.
Syringin exerts anti‐inflammatory and antioxidant effects by regulating SIRT1 signaling in rat and cell models of acute myocardial infarction
Authors: Zhao Di , Liu Ketong , Wang Jian , Shao Haifeng 
Published: February 2023

AbstractIntroductionThis study aimed to investigate the role of syringin in improving heart function during myocardial ischemia/reperfusion (I/R) and to determine whether the sirtuin 1/peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (SIRT1/PGC‐1α) pathway contributes to this cardioprotective effect in vivo and in vitro.MethodsH9c2 cells were incubated with H2O2 for 12 h. The effect of syringin was assessed by measuring cell viability; the apoptotic rate; Keap1/NRF2/HO‐1 activation; and the levels of proinflammatory cytokines, oxidative products, and antioxidative enzymes. In addition, SIRT1 was silenced via short hairpin RNA (shRNA)‐SIRT1 transfection to evaluate its involvement in syringin‐mediated protection. Syringin rescued cells from H2O2‐induced reductions in viability, antioxidative enzyme levels, and NRF2/HO‐1 activation; likewise, syringin inhibited apoptosis, inflammation, and oxidative stress. We also created a rat model of I/R by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 12 min. Syringin was then intraperitoneally injected, and the effect on infarct size and cardiac function was examined after 7 days. NRF2/HO‐1 activity and the levels of myocardial proinflammatory cytokines, oxidative products, and antioxidative enzymes were measured.ResultsIn comparison to the untreated I/R group, the syringin treatment group exhibited improved cardiac function and reduced cardiac lesion and infarct size. Syringin administration also markedly reduced the levels of proinflammatory cytokines and reactive oxygen species and promoted antioxidative enzyme expression and NRF2/HO‐1 pathway activation.ConclusionsSyringin may serve a protective role in animal and cell models of I/R by improving cardiac function, inhibiting the inflammatory response, and activating the antioxidative response.
Retracted: METTL3 enhances the effect of YTHDF1 on NEDD1 mRNA stability by m6A modification in diffuse large B‐cell lymphoma cells
Authors: Feng Lili , Yan Qinying , Pan Hui , Shi Wodong 
Published: February 2023

AbstractAimDiffuse large B‐cell lymphoma (DLBCL) remains the most frequent subpopulation of lymphoma, and N6‐methyladenosine (m6A) was implicated in the DLBCL progression. Herein, we sought to decipher the m6A‐asociated mechanism of NEDD1 in DLBCL development.MethodsThe NEDD1 expression profile in DLBCL was assessed by quantitative real‐time polymerase chain reaction (RT‐qPCR) and Western blot. NEDD1 was artificially downregulated or upregulated in DLBCL cells, followed by EdU, Transwell assays and flow cytometry. The Hedgehog pathway activity was assayed by a dual‐luciferase assay. The m6A methylation of NEDD1 in DLBCL was assessed by meRIP‐qPCR, and the regulatory mechanism of METTL3 on NEDD1 was validated. The LDH assay was conducted to examine the impact of CD8+ T cells on DLBCL cells. The DLBCL cells were administrated into mice to evaluate the tumorigenic activity and ki‐67 activity in tumor tissues.ResultsNEDD1 was overexpressed in DLBCL. Depletion of NEDD1 inhibited the aggressiveness of SU‐DHL‐8 and OCI‐LY1 cells, whereas overexpression of NEDD1 expedited the aggressiveness of SU‐DHL‐8 and OCI‐LY1 cells. METTL3 promoted NEDD1 translation in an m6A‐dependent manner via YTHDF1. Depletion of METTL3 inhibited SU‐DHL‐8 and OCI‐LY1 cell activity through regulation of NEDD1. NEDD1 reversed the repressive effect of METTL3 loss on the aggressiveness of SU‐DHL‐8 and OCI‐LY1 cells. NEDD1 activated the Hedgehog signaling to promote immune escape of DLBCL.ConclusionsMETTL3 promotes translation of NEDD1 via YTHDF1‐depedndent m6A modification, thereby activating the Hedgehog signaling pathway to promote immune escape of DLBCL cells.
Oncologic and obstetric outcomes of early‐stage epithelial ovarian cancer patients who underwent fertility‐sparing surgery: A retrospective study
Authors: Ayhan Ali , Tunç Mehmet , Atasoy Karakaş Latife , Tekelioğlu Tuğba , Haberal Reyhan Asuman Nihan , Önalan Göğşen , Kuşçu Esra 
Published: February 2023

AbstractObjectiveThis study aimed to assess the long‐term oncologic and obstetric outcomes of women with epithelial ovarian cancer who underwent fertility‐sparing surgery.MethodsA total of 68 patients observed between March 2007 and July 2021 were included in this retrospective study. Unilateral salpingo‐oophorectomy and uterine preservation with staging surgery were the main procedures for fertility‐sparing surgery. Disease‐free, overall survival, and obstetric outcomes were measured as primary outcomes.ResultsThe median age of the patients was 30.5 years. The median follow‐up time was 60.5 months. Disease recurrence occurred in 15 (22.1%) of the patients. Five‐year disease‐free survival and overall survival (OS) percentages were 75.6% and 83.3%, respectively, for all stages. The FIGO (International Federation of Gynecology & Obstetrics) stage was the only significant factor that affected OS (P = 0.001). Twenty‐three patients tried to conceive, and 15 (65.2%) patients became pregnant. Twelve (80%) pregnancies reached term and resulted in 15 live births. Chemotherapy administration and surgical intervention (cystectomy or unilateral salpingo‐oophorectomy) showed no difference in pregnancy results (P = 0.806 and P = 0.066, respectively).ConclusionFertility preservation is safe for invasive epithelial ovarian cancer at early stages for women in the reproductive era. Disease recurrence and OS results are similar to standard treatment at early stages with decent obstetric outcomes.
Feature selection and classification using bio‐inspired algorithms for the diagnosis of pulmonary emphysema subtypes
Authors: Isaac Anisha , Nehemiah H. Khanna , Dunston Snofy D , Kannan A. 
Published: February 2023

AbstractA computer‐assisted diagnosis framework to examine computed tomography (CT) slices for diagnosing pulmonary emphysema is designed. Partitioning of lung tissues and regions of Interest (ROIs) from the CT slices is achieved using Spatial Intuitionistic Fuzzy C‐Means (SIFCM) clustering algorithm. Shape features, texture features, and run‐length features are extracted from each ROI. Feature selection is performed as a wrapper technique by employing manta ray foraging optimization (MRFO) algorithm and random forest (RF) classifier. A backpropagation neural network (BPNN) using gradient descent is used to train the selected features. Adaptive butterfly optimization algorithm (ABOA) is used to fix the optimal topology and parameters, namely weights and biases of the neural network. The BPNN classifier is initialized with the optimized topology and parameters obtained by the ABOA. The developed framework attained an accuracy of 87.52% when tested on an emphysema dataset, which outperforms the BPNN classifier in terms of accuracy, specificity, precision, and recall.
Impact of biochar‐based slow‐release N‐fertilizers on maize growth and nitrogen recovery efficiency
Authors: Banik Chumki , Bakshi Santanu , Laird David A. , Smith Ryan G. , Brown Robert C. 
Published: February 2023

AbstractBiochar has been used to address several environmental problems and may be efficacious as a carrier of N‐fertilizer in slow‐release N‐fertilizer (SRF) formulations. Our objective was to compare the efficacy of SRF pellets formulated with different mass ratios of biochar and urea with traditional N‐fertilizers for improving N use efficiency by maize (Zea mays L.) grown under greenhouse conditions. Two different soil types, four SRF formulations with different biochar‐to‐urea (BCN) ratios (1:2 BCN, 1:3 BCN, 1:4 BCN, and 1:6 BCN), three traditional N‐fertilizers (urea, urea ammonium nitrate, and S‐coated urea), and unfertilized controls for each soil were tested. The accelerated urea release test showed significantly less loss of urea for the SRF over time than the traditional N‐fertilizers. The biochar‐based SRF formulations significantly (p < 0.05) decreased nitrate leaching loss for both soils relative to the traditional fertilizers. All the SRF formulations increased maize shoot (1%–34%) and root (0%–23%) biomass, N‐recovery efficiency (17%–50%), and soil potential mineralizable‐N relative to urea and S‐coated urea. The results also indicate that the BCN ratio in the SRF formulation can be used to influence the timing of N release and plant N uptake. The results of the greenhouse study suggest that biochar‐based SRFs have potential agronomic and environmental benefits; however, more research is needed to assess their agronomic value under field conditions.