bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Sam68 in Sunitinib induced renal cell carcinoma apoptosis
Authors: Wu Zeshen , Peng Yulu , Xiong Longbin , Wang Jun , Li Zhen , Ning Kang , Deng Minhua , Wang Ning , Wei Wensu , Li Zhiyong , Dong Pei , Yu Chunping , Zhou Fangjian , Zhang Zhiling 
Published: April 2022

AbstractSunitinib is one of the first‐line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src‐associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration‐dependent manner and inhibited the expression of total and phosphorylated Sam68 (p‐Sam68). Downregulation of Sam68 expression inhibited RCC cell apoptosis induced by sunitinib. While upregulation of Sam68 expression could enhance apoptosis induced by sunitinib. Xenograft models showed that tumors in the Sam68‐knockdown group did not shrink as much as those in the control group after treatment with sunitinib for 4 weeks. Together, our results suggest that Sam68 expression is associated with the sensitivity of ccRCC patients to sunitinib. Sam68 may promote cell apoptosis induced by sunitinib, and the Sam68 expression level may be a biomarker for predicting sunitinib sensitivity in ccRCC patients.
Efficacy and safety of PD‐1 inhibitor combined with antiangiogenic therapy for unresectable hepatocellular carcinoma: A multicenter retrospective study
Authors: Yao Junlin , Zhu Xudong , Wu Zhiheng , Wei Qing , Cai Yibo , Zheng Yu , Hu Xinyu , Hu Hong , Zhang Xiangyu , Pan Hongming , Zhong Xian , Han Weidong 
Published: April 2022

AbstractBackgroundImmunotherapy‐antiangiogenesis combination therapy has achieved excellent survival outcomes in hepatocellular carcinoma (HCC) in clinical trials. However, the combination therapy for HCC outside clinical trials is not well studied, and predictive factors are lacking. Here, we retrospectively analyzed the efficacy and safety of immunotherapy‐antiangiogenesis combination therapy in unresectable HCC patients in a real‐world setting.MethodsWe conducted a four‐center, retrospective study of unresectable HCC patients who received the combination of programmed death 1 (PD‐1) inhibitor and antiangiogenic agent between April 2018 and July 2021 in China.ResultsIn total, 136 patients were enrolled in the cohort. The objective response rate (ORR) and disease control rate (DCR) were 38.0% and 81.8%, respectively. The median time to progression (TTP), progression‐free survival (PFS), and overall survival (OS) were 7.2, 7.3, and 19.6 months, respectively. The multivariate analysis indicated that ECOG performance status score (PS) 2 was a significantly independent negative factor of ORR. Moreover, ECOG PS 2, peritoneum metastasis and previous immunotherapy were found to be independent negative predictors of PFS. A shorter OS was associated with ECOG PS 2, peritoneum metastasis, the presence of previous immunotherapy, Child‐Pugh stage B, and high alpha‐fetoprotein (AFP) concentration. One hundred and twenty‐five patients (91.9%) reported adverse events (AEs) with any grade.ConclusionWe elucidated the efficacy and safety of immunotherapy‐antiangiogenesis combination therapy and identified potential predictors for response and survival in a real‐world cohort of patients with unresectable HCC.
Sociopolitical development of female migrant domestic workers in Southern Spain: A qualitative study of a pathway against injustice
Authors: Duque Tatiana , Aceros Juan C. , Paloma Virginia 
Published: April 2022

AbstractDomestic work is a sector characterized by various forms of injustice, prompting some women to embark on a pathway towards activism. Based on the Sociopolitical Development (SPD) framework, this study aims to explore female Latin American migrants' experiences of injustice in the domestic work sector in Spain and how they challenge them, particularly when they become involved in organized collective action. To this end, in‐depth interviews were conducted with 11 women of Latin American origin who actively participate in the Association of Domestic Workers of Seville. The qualitative analysis found that being a domestic worker, having experiences of exploitation, discovering rights, receiving rights training, sharing stories of oppression, and engaging in sociopolitical actions are key experiences in guiding migrant women from the acritical and adaptive stages of SPD towards the pre‐critical, critical, and liberation ones. Knowledge about these significant life‐changing events may be useful for designing interventions aimed at fostering different ways in which oppressed groups can challenge injustice.
Religious counselors and LGBTQ+ clients: A Q‐sort of value navigation
Authors: Bayne Hannah B. , Harness Luke , Neuer Colburn Anita 
Published: April 2022

AbstractIn this study, we explored variation in religious value conflict navigation through a Q‐sort procedure of strategies for reaching an affirming stance toward counseling lesbian, gay, bisexual, transgender, and queer (LGBTQ+) clients. Factor analysis of the correlation matrix revealed a five‐factor solution accounting for 63% of the variance. We consider implications for counselor training and research.
Cobalt Complexes Supported by Phosphinoquinoline Ligands for the Catalyzed Hydrosilylation of Carbonyl Compounds
Authors: Schiltz Pauline , Casaretto Nicolas , Auffrant Audrey , Gosmini Corinne 
Published: April 2022

AbstractP,N phosphinoquinoline based ligands differing by the nature of the phosphorus substituent (iPr, Ph) were employed to synthesize a series of cobalt(II) complexes ([LCoBr2], [L2CoBr](PF6) and [L’2CoBr](PF6)). The latter were obtained in high yield and characterized among others by X‐ray analysis and elemental analysis. Complex [L2CoBr](PF6) showed a very good catalytic activity for the hydrosilylation of various ketones. The catalysis proceeds at a low catalytic loading (1 mol %) with only 1 equivalent of Ph2SiH2 in mild conditions and was efficient with aliphatic or aromatic ketones giving moderate to excellent yields of the corresponding silylated ether.
GNPS‐Guided Discovery of Madurastatin Siderophores from the Termite‐Associated Actinomadura sp. RB99**
Authors: Lee Seoung Rak , Schalk Felix , Schwitalla Jan W. , Guo Huijuan , Yu Jae Sik , Song Moonyong , Jung Won Hee , de Beer Z. Wilhelm , Beemelmanns Christine , Kim Ki Hyun 
Published: April 2022

AbstractIn this study, we analyzed if Actinomadura sp. RB99 produces siderophores that that could be responsible for the antimicrobial activity observed in co‐cultivation studies. Dereplication of high‐resolution tandem mass spectrometry (HRMS/MS) and global natural product social molecular networking platform (GNPS) analysis of fungus‐bacterium co‐cultures resulted in the identification of five madurastatin derivatives (A1, A2, E1, F, and G1), of which were four new derivatives. Chemical structures were unambiguously confirmed by HR‐ESI‐MS, 1D and 2D NMR experiments, as well as MS/MS data and their absolute structures were elucidated based on Marfey's analysis, DP4+ probability calculation and total synthesis. Structure analysis revealed that madurastatin E1 (2) contained a rare 4‐imidazolidinone cyclic moiety and madurastatin A1 (5) was characterized as a Ga3+‐complex. The function of madurastatins as siderophores was evaluated using the fungal pathogen Cryptococcus neoformans as model organism. Based on homology models, we identified the putative NRPS‐based gene cluster region of the siderophores in Actinomadura sp. RB99.
Molecular Engineering of Star‐Shaped Indoline Hole Transport Materials: The Influence of Planarity on the Hole Extraction and Transport Processes
Authors: Lv Yang , Guo Huanxin , Ye Fangyuan , Yi Yanxin , Wu Yongzhen , Liu Bo 
Published: April 2022

AbstractAs the key properties of perovskite solar cells (PSCs), the hole extraction and transport capabilities of the hole transport material (HTM) affect the photovoltaic performance of PSCs to a considerable extent, while both capabilities can be adjusted by molecular planarity. Therefore, in this work, the molecular planarity of the HTM is systematically optimized to regulate the hole extraction and transport capabilities. Along with the improvement in planarity, the HTM′s HOMO level is increased, leading to the enhancement of hole extraction capability. Meanwhile, the hole transport capability can also be improved due to the intensification of molecular stacking during the film formation. As a result, the planar HTM achieves a relatively high efficiency of 18.48 %, which is higher than that of spiro‐OMeTAD. Accordingly, the molecular planarity presents an important impact on the photovoltaic performance of PSCs, providing us with a promising strategy for further optimization of efficient HTMs.
Identification of 4‐Anilinoquin(az)oline as a Cell‐Active Protein Kinase Novel 3 (PKN3) Inhibitor Chemotype**
Authors: Asquith Christopher R. M. , Temme Louisa , East Michael P. , Laitinen Tuomo , Pickett Julie , Kwarcinski Frank E. , Sinha Parvathi , Wells Carrow I. , Johnson Gary L. , Zutshi Reena , Drewry David H. 
Published: April 2022

AbstractDeep annotation of a library of 4‐anilinoquin(az)olines led to the identification of 7‐iodo‐N‐(3,4,5‐trimethoxyphenyl)quinolin‐4‐amine 16 as a potent inhibitor (IC50=14 nM) of Protein Kinase Novel 3 (PKN3) with micromolar activity in cells. Compound 16 is a potential tool compound to study the cell biology of PKN3 and its role in pancreatic and prostate cancer and T‐cell acute lymphoblastic leukemia. These 4‐anilinoquin(az)olines may also be useful tools to uncover the therapeutic potential of PKN3 inhibition in a broad range of diseases.
Racial disparities in frailty and geriatric assessment impairments in older adults with cancer in the Deep South: Results from the CARE Registry
Authors: Williams Grant R. , Al‐Obaidi Mustafa , Harmon Christian , Dai Chen , Outlaw Darryl , Gbolahan Olumide , Khushman Moh’d , Nyrop Kirsten A. , Gilmore Nikesha , Bhatia Smita , Giri Smith 
Published: April 2022

BackgroundDespite recent advances in cancer, racial disparities in treatment outcomes persist, and their mechanisms are still not fully understood. The objective of this study was to examine racial differences in frailty and geriatric assessment impairments in an unselected cohort of older adults with newly diagnosed gastrointestinal (GI) malignancies.MethodsThis study used data from the Cancer and Aging Resilience Evaluation Registry, a prospective cohort study that enrolled older adults (≥60 years) with GI malignancies who were presenting for their initial consultation. Participants who had a geriatric assessment completed before chemotherapy initiation and self‐reported as either White or Black were included. Frailty was defined with a frailty index based on the deficit accumulation method. The differences in the prevalence and adjusted odds ratios for frailty and geriatric assessment impairments between Black and White participants were examined.ResultsOf the 710 eligible patients who were seen, 553 consented with sufficient data for analyses. The mean age at enrollment was 70 ± 7.1 years, 58% were male, and 23% were Black. Primary cancer diagnoses included colorectal cancer (32%), pancreatic cancer (27%), and hepatobiliary cancer (18%). Black participants were more likely to be frail (50.0% vs 32.7%; P < .001) and report limitations in activities of daily living (27.3% vs 14.1%; P = .001), instrumental activities of daily living (64.8% vs 47.3%; P = .002), and walking 1 block (62.5% vs 48.2%; P = .004). These associations persisted even after adjustments for age, sex, education, cancer type, cancer stage, and comorbidity.ConclusionsBlack participants were frailer and reported more limitations in function in comparison with White participants. These findings may partially explain disparities in cancer outcomes and warrant further examination.
NCA‐GA‐SVM: A new two‐level feature selection method based on neighborhood component analysis and genetic algorithm in hepatocellular carcinoma fatality prognosis
Authors: Książek Wojciech , Turza Filip , Pławiak Paweł 
Published: April 2022

AbstractHepatocellular carcinoma (HCC) is one of the major challenges facing biomedical research. Despite the high lethality, methods to predict mortality for this type of aggressive malignant tumor are insufficient. Machine learning is recognized by many authors as a valuable, yet poorly studied tool in this field. Undoubtedly, searching for new feature selection methods is significant in building an effective machine‐learning model. In this study, we propose the novel hybrid model using neighborhood components analysis, genetic algorithm and support vector machine classifier (NCA‐GA‐SVM). Because SVM works with default parameters characterized by low classification results, we decided to use GA for the proper optimization and feature selection. As reported in the available literature, NCA and GA obtain high classification results. Here, we decided to combine these approaches, building a two‐level algorithm for HCC fatality prognosis. We used a well‐known dataset collected from 165 patients at Coimbra's Hospital and University Center, Portugal. Our results revealed 96.36% classification accuracy and 95.52% F1‐score. Additionally, we compared all data for these metrics published so far. We demonstrated that our algorithm achieved the highest accuracy and can be successfully applied for the assessment of hepatocellular carcinoma mortality in the future. Our findings bring methodological value for future HCC studies and emphasize the possibility of using machine‐learning techniques to improve the quality of medical decisions.
A Molten‐Salt Method to Synthesize Co9S8 Embedded, N, S Co‐Doped Mesoporous Carbons from Melamine Formaldehyde Resins for Electrocatalytic Hydrogen Evolution Reactions
Authors: Miao Sijia , Xu Jing , Cui Chengzhe , Tang Duihai , Zhang Wenting , Xin Shigang , Zhao Zhen 
Published: April 2022

AbstractWe developed a molten salts process to prepare Co9S8 nanoparticles (NPs) entrapped, S, N co‐doped carbons. Cobalt chloride was used as the cobalt source. The melamine‐formaldehyde (MF) resin provided the carbon source and nitrogen source, and thiourea provided sulfur source. In addition, common inorganic salts were added as templates to generate pores. The characterization results showed that the prepared materials contained high contents of N, S and Co, and were mesoporous composites. At the same time, the porosity of electrocatalyst depended on the type of salt and the mass ratio of precursor to salt, which further affected the electrocatalytic activity of hydrogen evolution reaction (HER). The best prepared catalyst showed excellent HER performance. The onset overpotential of the catalyst was low (33 mV) and had a small Tafel slope (61.1 mV dec−1), in addition to good stability in alkaline media.
Beyond compliance – Voluntary climate mitigation by New Zealand firms
Authors: Nikula Pii‐Tuulia 
Published: April 2022

AbstractThis article explores voluntary climate mitigation by New Zealand firms. To meet global emission reduction targets, rapid decarbonisation is required. Hence, it is important to understand how and why firms engage in climate change mitigation, what results these mitigation efforts yield and the related tensions. This article explores the practices and perspectives of climate‐proactive New Zealand firms. The firms in this study had engaged in a range of climate mitigation efforts associated with emission management and influencing. Emission management showed mixed results: most of the firms had succeeded in improving their emission intensity, but many had struggled to reduce their gross emissions. The key drivers behind climate engagement were found to be value‐based. Furthermore, multiple tensions and paradoxes, such as the nexus between business growth and gross emissions, were present. Understanding these challenges and firm perspectives is important when considering the feasibility of new measures to enhance organisational climate mitigation.
Coordinated patterning of zebrafish caudal fin symmetry by a central and two peripheral organizers
Authors: Desvignes Thomas , Robbins Amy E. , Carey Andrew Z. , Bailon‐Zambrano Raisa , Nichols James T. , Postlethwait John H. , Stankunas Kryn 
Published: April 2022

AbstractBackgroundCaudal fin symmetry characterizes teleosts and likely contributes to their evolutionary success. However, the coordinated development and patterning of skeletal elements establishing external symmetry remains incompletely understood. We explore the spatiotemporal emergence of caudal skeletal elements in zebrafish to consider evolutionary and developmental origins of caudal fin symmetry.ResultsTransgenic reporters and skeletal staining reveal that the hypural diastema‐defining gap between hypurals 2 and 3 forms early and separates progenitors of two plates of connective tissue. Two sets of central principal rays (CPRs) synchronously, sequentially, and symmetrically emerge around the diastema. The two dorsal‐ and ventral‐most rays (peripheral principal rays, PPRs) arise independently and earlier than adjacent CPRs. Muscle and tendon markers reveal that different muscles attach to CPR and PPR sets.ConclusionsWe propose that caudal fin symmetry originates from a central organizer that establishes the hypural diastema and bidirectionally patterns surrounding tissue into two plates of connective tissue and two mirrored sets of CPRs. Further, two peripheral organizers unidirectionally specify PPRs, forming a symmetric “composite” fin derived from three fields. Distinct CPR and PPR ontogenies may represent developmental modules conferring ray identities, muscle connections, and biomechanical properties. Our model contextualizes mechanistic studies of teleost fin morphological variation.
A hierarchical N‐mixture model to estimate behavioral variation and a case study of Neotropical birds
Authors: Ke Alison , Sollmann Rahel , Frishkoff Luke O. , Karp Daniel S. 
Published: April 2022

AbstractUnderstanding how and why animals use the environments where they occur is both foundational to behavioral ecology and essential to identify critical habitats for species conservation. However, some behaviors are more difficult to observe than others, which can bias analyses of raw observational data. To our knowledge, no method currently exists to model how animals use different environments while accounting for imperfect behavior‐specific detection probability. We developed an extension of a binomial N‐mixture model (hereafter the behavior N‐mixture model) to estimate the probability of a given behavior occurring in a particular environment while accounting for imperfect detection. We then conducted a simulation to validate the model's ability to estimate the effects of environmental covariates on the probabilities of individuals performing different behaviors. We compared our model to a naïve model that does not account for imperfect detection, as well as a traditional N‐mixture model. Finally, we applied the model to a bird observation data set in northwest Costa Rica to quantify how three species behave in forests and farms. Simulations and sensitivity analyses demonstrated that the behavior N‐mixture model produced unbiased estimates of behaviors and their relationships with predictor variables (e.g., forest cover, habitat type). Importantly, the behavior N‐mixture model accurately characterized uncertainty, unlike the naïve model, which often suggested erroneous effects of covariates on behaviors. When applied to field data, the behavior N‐mixture model suggested that Hoffmann's woodpecker (Melanerpes hoffmanii) and Inca dove (Columbina inca) behaved differently in forested versus agricultural habitats, while turquoise‐browed motmot (Eumomota superciliosa) did not. Thus, the behavior N‐mixture model can help identify habitats that are essential to a species' life cycle (e.g., where individuals nest, forage) that nonbehavioral models would miss. Our model can greatly improve the appropriate use of behavioral survey data and conclusions drawn from them. In doing so, it provides a valuable path forward for assessing the conservation value of alternative habitat types.
Dual Photocatalysis for the Straightforward Coupling of Thiosugars and Arylsulfoximines: Towards Unprecedented Cyclic Heteroatomic Structures
Authors: Duhail Thibaut , Zhu Mingxiang , Rombault Coralie , Dagousset Guillaume , Messaoudi Samir , Magnier Emmanuel , Anselmi Elsa 
Published: April 2022

AbstractA general, scalable and easy to implement protocol is described for the coupling of thiosugars and various ortho‐functionalized S‐aryl S‐perfluoroalkyl sulfoximines. This dual photocatalysis methodology was developed with a commercial hydrogen atom transfer reagent and produced key structures that were transformed into original cyclic skeletons bearing previously undescribed chemical functions.
Screening prolyl hydroxylase domain 2 inhibitory activity of traditional Chinese medicine by CZE‐UV
Authors: Zhang Ying , Zhao Ming , Wang Cheng‐Bo , Wang Yu , Nsanzamahoro Stanislas , Zhu Ling‐Ling , Wang Wei‐Feng , Yang Jun‐Li 
Published: April 2022

AbstractProlyl hydroxylase domain 2 (PHD2) is a key enzyme regulating the expression of hypoxia inducible factor (HIF). Its inhibitors can improve the expression of HIF and downstream genes, which can treat hypoxia‐related diseases. Therefore, the establishment of a reliable PHD2 inhibitors screening method is of great significance for the drug development of hypoxia‐related diseases. In this work, an accurate, rapid, and simple screening method for PHD2 inhibitors was introduced by capillary zone electrophoresis (CZE). In order to improve the detection sensitivity, the derivative reaction of α‐ketoglutaric acid (α‐OG) and 1,2‐diaminobenzene (OPD) was used to enhance the UV absorption of α‐OG (the substrate in the enzymatic reaction). The CZE method selected 20 mM Na2B4O7 buffer (pH 9.0) as the separation buffer, +25 kV as the separation voltage, 25°C as the cartridge temperature, and 210 nm as the detection wavelength. Under this condition, the analysis of a single sample can be realized within 9 min. Compared with the existing reported methods, the present work can directly screen the PHD2 inhibitory activity of traditional Chinese medicine (TCM) extracts, which is of significance for the target‐purification of bioactive individual compounds from TCMs. Under the optimal conditions, the PHD2 inhibitor screening platform was successfully established, and it was found that 70% methanol/water extracts of Astragali Radix and Codonopsis pilosula had good PHD2 inhibitory activity. Furthermore, the present work provides a novel approach for screening the PHD2 inhibitory activity of TCM extracts and the discovery of anti‐hypoxia bioactive compounds.