bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of A166, an antibody‒drug conjugate in advanced HER2-expressing solid tumours
Authors: Zhang Jian , Liu Rujiao , Gao Shuiping , Li Wenhua , Chen Yang , Meng Yanchun , Liu Chang , Jin Wenyue , Wu Junyan , Wang Ying , Hao Yanrong , Yi Shuli , Qing Yan , Ge Junyou , Hu Xichun 
Published: April 2023

AbstractIn this phase I study, the safety, pharmacokinetics, and antitumour activity of the HER2-targeted antibody–drug conjugate A166 were evaluated in patients with HER2-expressing advanced solid tumours. Patients with advanced solid tumours refractory to standard therapies received A166 at doses of 0.1, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8 or 6.0 mg/kg Q3W in a standard “3 + 3” design. Dose cohorts were expanded at 4.8 and 6.0 mg/kg Q3W. Primary endpoints were assessment of the safety and tolerability of A166 and identification of the maximum tolerated dose or recommended phase II dose. In total, 81 patients were enroled and received A166 (n = 1 for 0.1 mg/kg;n = 3 for each of 0.3, 0.6, 1.2, 2.4 and 3.6 mg/kg doses;n = 27 for 4.8 mg/kg;n = 38 for 6.0 mg/kg). No dose-limiting toxicity or drug-related deaths occurred. The most common treatment-related adverse events at grade 3 or higher were corneal epitheliopathy (30.9%), blurred vision (18.5%), dry eyes (7.4%), and peripheral sensory neuropathy (6.2%). The Cmaxand area under the curve of Duo-5, its free payload, were approximately 0.1% and 0.2% of those of the ADC, respectively. For all assessable HER2-positive breast cancer patients enroled in the 4.8 mg/kg and 6.0 mg/kg cohorts, the corresponding ORRs were 73.9% (17/23) and 68.6% (24/35), respectively, and the median PFS was 12.3 and 9.4 months, respectively. A166 has a recommended phase II dose of 4.8 mg/kg Q3W, manageable toxicity, good stability in the circulation and promising antitumour activities in HER2-positive breast cancer patients.
Free-living bacteria stimulate sugarcane growth traits and edaphic factors along soil depth gradients under contrasting fertilization
Authors: Fallah Nyumah , Tayyab Muhammad , Yang Ziqi , Pang Ziqin , Zhang Caifang , Lin Zhaoli , Stewart Lahand James , Ntambo Mbuya Sylvain , Abubakar Ahmad Yusuf , Lin Wenxiong , Zhang Hua 
Published: April 2023

AbstractFree-living bacterial community and abundance have been investigated extensively under different soil management practices. However, little is known about their nitrogen (N) fixation abilities, and how their contributions to N budgets impact plant growth, yield, and carbon (C) and N cycling enzymes in a long-term consecutive sugarcane monoculture farming system, under contrasting amendments, along different soil horizons. Here, nifH gene amplicon was used to investigate diazotrophs bacterial community and abundance by leveraging high-throughput sequencing (HTS). Moreover, edaphic factors in three soil depths (0–20, 20–40, and 40–60 cm) under control (CK), organic matter (OM), biochar (BC), and filter mud (FM) amended soils were investigated. Our analysis revealed that β-glucosidase activity, acid phosphatase activity, ammonium (NH4+-N), nitrate (NO3–N), total carbon (TC), total nitrogen (TN), and available potassium (AK) were considerably high in 0–20 cm in all the treatments. We also detected a significantly high proportion of Proteobacteria and Geobacter in the entire sample, including Anabaena and Enterobacter in 0–20 cm soil depth under the BC and FM amended soils, which we believed were worthy of promoting edaphic factors and sugarcane traits. This phenomenon was further reinforced by network analysis, where diazotrophs bacteria belonging to Proteobacteria exhibited strong and positive associations soil electrical conductivity (EC), soil organic matter content (SOM) available phosphorus (AP), TN, followed by NH4+-N and NO3–N, a pattern that was further validated by Mantel test and Pearson’s correlation coefficients analyses. Furthermore, some potential N-fixing bacteria, including Burkholderia, Azotobacter, Anabaena, and Enterobacter exhibited a strong and positive association with sugarcane agronomic traits, namely, sugarcane stalk, ratoon weight, and chlorophyll content. Taken together, our findings are likely to broaden our understanding of free-living bacteria N-fixation abilities, and how their contributions to key soil nutrients such as N budgets impact plant growth and yield, including C and N cycling enzymes in a long-term consecutive sugarcane monoculture farming system, under contrasting amendments, along different soil horizons.
Association between adherence to the Dietary Approaches to Stop Hypertension diet and serum uric acid
Authors: Feng Jie , Huang Yuchai , Wang Haozhuo , Wang Chao , Xu Hongbin , Ke Pan , He Yan , Tian Qingfeng , Cao Shiyi , Lu Zuxun 
Published: April 2023

AbstractTo explore the relationship between Dietary Approaches to Stop Hypertension (DASH) diet and serum uric acid (SUA) levels among the Chinese adult population, and verify the mediating effect of BMI between DASH diet and SUA levels. A total of 1125 adults were investigated using a self-administered food frequency questionnaire. SUA levels were determined by uricase colorimetry. The total DASH score ranged from 9 to 72. The relationship between the DASH diet and SUA levels was examined by multiple adjusted regression analysis. Method of Bootstrap was used to test the mediation effect of BMI in the correlation of the DASH diet and SUA levels. After multivariable adjustment, there was a significant linear relationship between the DASH diet and SUA (P < 0.001). Compared with the lowest group, SUA of participants in group of highest DASH diet score decreased by 34.907 (95% CI − 52.227, − 17.588; P trend < 0.001) μmol/L. The association between the DASH diet scores and SUA levels was partly mediated by BMI (− 0.26, Bootstrap 95% CI − 0.49, − 0.07), with 10.53% of the total effect being mediated. Adopting the DASH diet might be helpful in reducing SUA level, and the effect might be partly mediated by BMI.
Single-particle properties of topological Wannier excitons in bismuth chalcogenide nanosheets
Authors: Maisel Licerán Lucas , García Flórez Francisco , Siebbeles Laurens D. A. , Stoof Henk T. C. 
Published: April 2023

AbstractWe analyze the topology, dispersion, and optical selection rules of bulk Wannier excitons in nanosheets of Bi2Se3, a topological insulator in the family of the bismuth chalcogenides. Our main finding is that excitons also inherit the topology of the electronic bands, quantified by the skyrmion winding numbers of the constituent electron and hole pseudospins as a function of the total exciton momentum. The excitonic bands are found to be strongly indirect due to the band inversion of the underlying single-particle model. At zero total momentum, we predict that the s-wave and d-wave states of two exciton families are selectively bright under left- or right-circularly polarized light. We furthermore show that every s-wave exciton state consists of a quartet with a degenerate and quadratically dispersing nonchiral doublet, and a chiral doublet with one linearly dispersing mode as in transition metal dichalcogenides. Finally, we discuss the potential existence of topological edge states of chiral excitons arising from the bulk-boundary correspondence.
Rational peptide design for inhibition of the KIX–MLL interaction
Authors: Sato Nao , Suetaka Shunji , Hayashi Yuuki , Arai Munehito 
Published: April 2023

AbstractThe kinase-inducible domain interacting (KIX) domain is an integral part of the general transcriptional coactivator CREB-binding protein, and has been associated with leukemia, cancer, and various viral diseases. Hence, the KIX domain has attracted considerable attention in drug discovery and development. Here, we rationally designed a KIX inhibitor using a peptide fragment corresponding to the transactivation domain (TAD) of the transcriptional activator, mixed-lineage leukemia protein (MLL). We performed theoretical saturation mutagenesis using the Rosetta software to search for mutants expected to bind KIX more tightly than the wild-type MLL TAD. Mutant peptides with higher helical propensities were selected for experimental characterization. We found that the T2857W mutant of the MLL TAD peptide had the highest binding affinity for KIX compared to the other 12 peptides designed in this study. Moreover, the peptide had a high inhibitory effect on the KIX–MLL interaction with a half-maximal inhibitory concentration close to the dissociation constant for this interaction. To our knowledge, this peptide has the highest affinity for KIX among all previously reported inhibitors that target the MLL site of KIX. Thus, our approach may be useful for rationally developing helical peptides that inhibit protein–protein interactions implicated in the progression of various diseases.
Factor-specific generative pattern from large-scale drug-induced gene expression profile
Authors: Ahn Se Hwan , Kim Ju Han 
Published: April 2023

AbstractDrug discovery is a complex and interdisciplinary field that requires the identification of potential drug targets for specific diseases. In this study, we present FacPat, a novel approach that identifies the optimal factor-specific pattern explaining the drug-induced gene expression profile. FacPat uses a genetic algorithm based on pattern distance to mine the optimal factor-specific pattern for each gene in the LINCS L1000 dataset. We applied Benjamini–Hochberg correction to control the false discovery rate and identified significant and interpretable factor-specific patterns consisting of 480 genes, 7 chemical compounds, and 38 human cell lines. Using our approach, we identified genes that show context-specific effects related to chemical compounds and/or human cell lines. Furthermore, we performed functional enrichment analysis to characterize biological features. We demonstrate that FacPat can be used to reveal novel relationships among drugs, diseases, and genes.
Anaerobic co-digestion of grass and cow manure: kinetic and GHG calculations
Authors: Ulukardesler Ayse Hilal 
Published: April 2023

AbstractGrass is a highly desirable substrate for anaerobic digestion because of its higher biodegradability and biogas/methane yield. In this study, anaerobic co-digestion of grass, cow manure and sludge was studied under mesophilic conditions for 65 days. Experiments were performed on a feed ratio of grass/manure from 5 to 25%, respectively. The maximum cumulative biogas and methane yield was obtained as 331.75 mLbiogas/gVS and 206.64 mLCH4/gVS for 25% ratio. Also, the results of the experiments were tested on the three different kinetics model which are the first order kinetic model, modified Gompertz model and Logistics model. As a result of the study, it was found that by using grass nearly 480 × 106 kWh/year electricity may be produced and 0.5 × 106 tons/year CO2 greenhouse gas emission mitigation may be reached.
A pathogenicity locus of Streptococcus gallolyticus subspecies gallolyticus
Authors: Taylor John Culver , Kumar Ritesh , Xu Juan , Xu Yi 
Published: April 2023

AbstractStreptococcus gallolyticus subspecies gallolyticus (Sgg) is known to be strongly associated with colorectal cancer (CRC). Recent functional studies further demonstrated that Sgg actively stimulates CRC cell proliferation and promotes the development of colon tumors. However, the Sgg factors important for the pro-proliferative and pro-tumor activities of Sgg remain unclear. Here, we identified a chromosomal locus in Sgg strain TX20005. Deletion of this locus significantly reduced Sgg adherence to CRC cells and abrogated the ability of Sgg to stimulate CRC cell proliferation. Thus, we designate this locus as the Sgg pathogenicity-associated region (SPAR). More importantly, we found that SPAR is important for Sgg pathogenicity in vivo. In a gut colonization model, mice exposed to the SPAR deletion mutant showed significantly reduced Sgg load in the colonic tissues and fecal materials, suggesting that SPAR contributes to the colonization capacity of Sgg. In a mouse model of CRC, deletion of SPAR abolished the ability of Sgg to promote the development of colon tumors growth. Taken together, these results highlight SPAR as a critical pathogenicity determinant of Sgg.
Investigating mechanism of the effect of emotional facial expressions on attentional processing by data clustering approach
Authors: Li Yuezhi , Zhao Weifeng , Peng Xiaobo 
Published: April 2023

AbstractTo explore the mechanism of the effect of emotional facial expression on attentional process, time course and topographic map of Electroencephalographic activities affected by emotional stimuli were investigated. Emotional Stroop task was used to collect 64-channel event-related potentials (ERP) in nonclinical participants, and data clustering was applied to find significant effect of sad and happy facial expression on ERP. Several significant ERP clusters were found in the sad and happy conditions respectively. In the sad condition, the decreased N170 in the bilateral parietooccipital areas, the increased P3 in the right centroparietal region and the increased negative deflection between 600 and 650 ms in the prefrontal regions were observed, these alterations reflected inhibited perceptual processing of sad facial expression, and increased activations of the orienting network and the executive control network in attentional system, respectively. In the happy condition, increased negative slow wave was found in the left centroparietal region indicating strengthened awareness and readiness for successive trials. Importantly, nonpathological attentional bias to sad facial expression in nonclinical participants was associated with inhibited perceptual processing and increased activations of the orienting and executive control networks. It provides the basis for better understanding and application of attentional bias in psychiatric clinical utilization.
Characterization of aortic aging using 3D multi-parametric MRI-long-term follow-up in a population study
Authors: Loose Sophie , Solou Demetris , Strecker Christoph , Hennemuth Anja , Hüllebrand Markus , Grundmann Sebastian , Asmussen Alexander , Treppner Martin , Urbach Horst , Harloff Andreas 
Published: April 2023

AbstractWe comprehensively studied morphological and functional aortic aging in a population study using modern three-dimensional MR imaging to allow future comparison in patients with diseases of the aortic valve or aorta. We followed 80 of 126 subjects of a population study (20 to 80 years of age at baseline) using the identical methodology 6.0 ± 0.5 years later. All underwent 3 T MRI of the thoracic aorta including 3D T1 weighted MRI (spatial resolution 1 mm3) for measuring aortic diameter and plaque thickness and 4D flow MRI (spatial/temporal resolution = 2 mm3/20 ms) for calculating global and regional aortic pulse wave velocity (PWV) and helicity of aortic blood flow. Mean diameter of the ascending aorta (AAo) decreased and plaque thickness increased significantly in the aortic arch (AA) and descending aorta (DAo) in females. PWV of the thoracic aorta increased (6.4 ± 1.5 to 7.0 ± 1.7 m/s and 6.8 ± 1.5 to 7.3 ± 1.8 m/s in females and males, respectively) over time. Local normalized helicity volumes (LNHV) decreased significantly in the AAo and AA (0.33 to 0.31 and 0.34 to 0.32 in females and 0.34 to 0.32 and 0.32 to 0.28 in males). By contrast, helicity increased significantly in the DAo in both genders (0.28 to 0.29 and 0.29 to 0.30, respectively). 3D MRI was able to characterize changes in aortic diameter, plaque thickness, PWV and helicity during six years in our population. Aortic aging determined by 3D multi-parametric MRI is now available for future comparisons in patients with diseases of the aortic valve or aorta.
Genomic-regions associated with cold stress tolerance in Asia-adapted tropical maize germplasm
Authors: Shikha Kumari , Madhumal Thayil Vinayan , Shahi J. P. , Zaidi P. H. , Seetharam Kaliyamoorthy , Nair Sudha K , Singh Raju , Tosh Garg , Singamsetti Ashok , Singh Saurabh , Sinha B. 
Published: April 2023

AbstractMaize is gaining impetus in non-traditional and non-conventional seasons such as off-season, primarily due to higher demand and economic returns. Maize varieties directed for growing in the winter season of South Asia must have cold resilience as an important trait due to the low prevailing temperatures and frequent cold snaps observed during this season in most parts of the lowland tropics of Asia. The current study involved screening of a panel of advanced tropically adapted maize lines to cold stress during vegetative and flowering stage under field conditions. A suite of significant genomic loci (28) associated with grain yield along and agronomic traits such as flowering (15) and plant height (6) under cold stress environments. The haplotype regression revealed 6 significant haplotype blocks for grain yield under cold stress across the test environments. Haplotype blocks particularly on chromosomes 5 (bin5.07), 6 (bin6.02), and 9 (9.03) co-located to regions/bins that have been identified to contain candidate genes involved in membrane transport system that would provide essential tolerance to the plant. The regions on chromosome 1 (bin1.04), 2 (bin 2.07), 3 (bin 3.05–3.06), 5 (bin5.03), 8 (bin8.05–8.06) also harboured significant SNPs for the other agronomic traits. In addition, the study also looked at the plausibility of identifying tropically adapted maize lines from the working germplasm with cold resilience across growth stages and identified four lines that could be used as breeding starts in the tropical maize breeding pipelines.
Echo chamber effects on short video platforms
Authors: Gao Yichang , Liu Fengming , Gao Lei 
Published: April 2023

AbstractIn recent years, short videos have become an increasingly vital source of information. To compete for users’ attention, short video platforms have been overusing algorithmic technology, making the group polarization intensify, which is likely to push users into the homogeneous “echo chamber”. However, echo chambers can contribute to the spread of misleading information, false news, or rumors, which have negative social impacts. Therefore, it is necessary to explore echo chamber effects in short video platforms. Moreover, the communication paradigms between users and feed algorithms greatly vary across short video platforms. This paper investigated echo chamber effects of three popular short video platforms (Douyin, TikTok, and Bilibili) using social network analysis and explored how user features influenced the generation of echo chambers. We quantified echo chamber effects through two primary ingredients: selective exposure and homophily, in both platform and topic dimensions. Our analyses indicate that the gathering of users into homogeneous groups dominates online interactions on Douyin and Bilibili. We performed performance comparison of echo chamber effects and found that echo chamber members tend to display themselves to attract the attention of their peers and that cultural differences can prevent the development of echo chambers. Our findings are of great value in designing targeted management strategies to prevent the spread of misleading information, false news, or rumors.
Comparative study of Dapagliflozin versus Glimepiride effect on insulin regulated aminopeptidase (IRAP) and interleukin-34 (IL-34) in patient with type 2 diabetes mellitus
Authors: Zekry Rania , Omran Gamal A. , El-Gharbawy Nashwa M. , Werida Rehab H. 
Published: April 2023

AbstractType 2 diabetes mellitus (T2DM) is one of the most common diseases, that managed by several medications such as Glimepiride and Dapagliflozin. This study aims to compare the effects of Dapagliflozin versus Glimepiride on glycemic control, insulin resistance, and biomarkers as (extracellular domain of insulin regulated aminopeptidase) IRAPe, (interleukin-34) IL-34, and (N-terminal pro b-type natriuretic peptide) NT-proBNP. This study included 60 type 2 diabetic patients, who are randomized to receive either Glimepiride 4 mg/day (group 1) or Dapagliflozin 10 mg/day (group 2). Blood samples were collected at baseline and after 3 months of treatment for biochemical analysis. Additionally, HOMA-IR is calculated. After 3 months of receiving the intervention, there is no significant difference between the effects of Glimepiride and Dapagliflozin on FBG, PPBG, HbA1C%, fasting insulin, and HOMA-IR. The difference between both groups is significant for IL-34 (p = 0.002) and non-significant for IRAPe (p = 0.12) and NT-Pro BNP (p = 0.68). Both Glimepiride and Dapagliflozin significantly improve glycemic control, and HOMA-IR with no significant difference between them. Both drugs significantly improved the level of NT-proBNP. Dapagliflozin has a borderline significant effect on IRAPe but not IL-34, and Glimepiride has significant effect on IL-34 but not IRAPe.
Clinical Trial Registration: This trial was registered on clinicaltrial.gov (NCT04240171).
CBGA ameliorates inflammation and fibrosis in nephropathy
Authors: Suzuki Sayuri , Fleig Andrea , Penner Reinhold 
Published: April 2023

AbstractCannabidiol (CBD) is thought to have multiple biological effects, including the ability to attenuate inflammatory processes. Cannabigerols (CBGA and its decarboxylated CBG molecule) have pharmacological profiles similar to CBD. The endocannabinoid system has recently emerged to contribute to kidney disease, however, the therapeutic properties of cannabinoids in kidney disease remain largely unknown. In this study, we determined whether CBD and CBGA can attenuate kidney damage in an acute kidney disease model induced by the chemotherapeutic cisplatin. In addition, we evaluated the anti-fibrosis effects of these cannabinoids in a chronic kidney disease model induced by unilateral ureteral obstruction (UUO). We find that CBGA, but not CBD, protects the kidney from cisplatin-induced nephrotoxicity. CBGA also strongly suppressed mRNA of inflammatory cytokines in cisplatin-induced nephropathy, whereas CBD treatment was only partially effective. Furthermore, both CBGA and CBD treatment significantly reduced apoptosis through inhibition of caspase-3 activity. In UUO kidneys, both CBGA and CBD strongly reduced renal fibrosis. Finally, we find that CBGA, but not CBD, has a potent inhibitory effect on the channel-kinase TRPM7. We conclude that CBGA and CBD possess reno-protective properties, with CBGA having a higher efficacy, likely due to its dual anti-inflammatory and anti-fibrotic effects paired with TRPM7 inhibition.