bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multimodal cortical network of sensory expectation violation revealed by fMRI
Authors: Grundei Miro , Schmidt Timo Torsten , Blankenburg Felix 
Published: September 2023

AbstractThe brain is subjected to multi‐modal sensory information in an environment governed by statistical dependencies. Mismatch responses (MMRs), classically recorded with EEG, have provided valuable insights into the brain's processing of regularities and the generation of corresponding sensory predictions. Only few studies allow for comparisons of MMRs across multiple modalities in a simultaneous sensory stream and their corresponding cross‐modal context sensitivity remains unknown. Here, we used a tri‐modal version of the roving stimulus paradigm in fMRI to elicit MMRs in the auditory, somatosensory and visual modality. Participants (N = 29) were simultaneously presented with sequences of low and high intensity stimuli in each of the three senses while actively observing the tri‐modal input stream and occasionally reporting the intensity of the previous stimulus in a prompted modality. The sequences were based on a probabilistic model, defining transition probabilities such that, for each modality, stimuli were more likely to repeat (p = .825) than change (p = .175) and stimulus intensities were equiprobable (p = .5). Moreover, each transition was conditional on the configuration of the other two modalities comprising global (cross‐modal) predictive properties of the sequences. We identified a shared mismatch network of modality general inferior frontal and temporo‐parietal areas as well as sensory areas, where the connectivity (psychophysiological interaction) between these regions was modulated during mismatch processing. Further, we found deviant responses within the network to be modulated by local stimulus repetition, which suggests highly comparable processing of expectation violation across modalities. Moreover, hierarchically higher regions of the mismatch network in the temporo‐parietal area around the intraparietal sulcus were identified to signal cross‐modal expectation violation. With the consistency of MMRs across audition, somatosensation and vision, our study provides insights into a shared cortical network of uni‐ and multi‐modal expectation violation in response to sequence regularities.
Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co‐mixture with recombinant human hyaluronidase: A phase 1 randomized trial
Authors: Bass Almasa , Plotka Anna , Mridha Khurshid , Sattler Catherine , Kim Albert M. , Plowchalk David R. 
Published: September 2023

AbstractAimPrior to the discontinuation of bococizumab's clinical development, it was considered advantageous to develop an infrequent dosing regimen (eg, monthly). Therefore, we conducted a phase 1 study to evaluate the pharmacokinetics, pharmacodynamics, and safety of bococizumab when administered in co‐mixture with recombinant human hyaluronidase (rHuPH20).MethodHealthy subjects (N = 60) were randomized equally among 4 groups that received a single subcutaneous dose of either bococizumab 150, 300, or 450 mg co‐mixed with rHuPH20 or bococizumab 300 mg alone. Bioavailability and lipid‐lowering effect of bococizumab were evaluated by using ANCOVA models.ResultsIn the groups administered bococizumab co‐mixed with rHuPH20, dose‐normalized Cmax and AUCinf were 26.6 to 39.1% and 18.3 to 36.6% greater, respectively, compared with bococizumab 300 mg alone. Despite these increases, mean percent reductions from baseline in low‐density lipoprotein cholesterol were smaller in the bococizumab 300 mg + rHuPH20 group than in the bococizumab 300‐mg group at Day 21 (52.2% and 59.5%, respectively) and were similar at Day 29 (51.7% and 49.6%, respectively). Compared with the group administered bococizumab 300 mg alone, the bococizumab 300 mg + rHuPH20 group did not show a significantly altered AUEC85 (ratio of adjusted means: 102.5%, 90% confidence interval: 96.1‐109.3%) but did show a higher MaxELDL‐C (ratio of adjusted means: 125.4%, 90% confidence interval: 103.3‐152.2%), indicating diminution of efficacy. The most frequent adverse events were injection‐site erythema, injection‐site bruising, and nasopharyngitis; all injection‐site adverse events were mild.ConclusionCo‐mixture with rHuPH20 increased the bioavailability of bococizumab without proportional increase in pharmacodynamic effect.Trial RegistrationClinicalTrials.gov, NCT02667223.
Molecular dynamics simulation on engine oil nanolubricant boundary lubrication conditions
Authors: Srivastava Isha , Kotia Ankit , Ghosh Subrata Kumar 
Published: September 2023

AbstractThe employment of nanoparticle additives in engine oil provides an effective technique for improvement in engine performance and emission. In this study, graphene, graphene–MWCNT, and graphene–SiO2 hybrid nanoparticles have been dispersed in engine oil (n‐decane) to measure the effects of microscopic characteristics of interfacial layer between the carbon–carbon, carbon–hydrogen, carbon–oxygen, and hydrogen–oxygen molecules under fixed shear rate 600 s−1. The boundary lubrication conditions are depicted with nanoindentation operation, in which interaction between the atoms generates the molecular forces under indentation and scratching operation that provide the nucleation and propagation of dislocation in the planes. The result shows that in an early stage of nanoindentation, plastic deformation occurs in the lubricant substrate around the indenter. Furthermore, forces generated in the z‐direction have a significant effect as compared with the forces x‐ and y‐directions. Nanoindentation results concluded that for graphene–MWCNT/engine oil (n‐decane) nanoparticles, at a volume fraction of 1.8%, the nanoparticles outperformed all other nanolubricants. At a volume fraction of 0.3%, the adhesion between the solid and liquid interface was increased by 2.5% graphene nanolubricant, 4% graphene–MWCNT nanolubricant, and 8% graphene–SiO2 nanolubricant. At 1.8% volume fraction, 240% increase in graphene–MWCNT nanolubricant, 72% increase in graphene nanolubricant, and 20% increase in graphene–SiO2 nanolubricant. This trend indicates that the performance of graphene SiO2 nanolubricants is superior at low‐volume fractions, whereas the performance of graphene nanolubricants and graphene–MWCNT nanolubricants is superior at high‐volume fractions. Also we observed the scratching effect of indenter on nanolubricants.
Different adverse childhood experiences and adolescents' altruism: The mediating role of life history strategy
Authors: Gao Hanjing , Liu Qianwen , Wang Zhenhong 
Published: September 2023

AbstractIntroductionThe present study sought to investigate whether the relationship between childhood trauma, childhood socioeconomic (SES), and adolescents' altruism were mediated by their life history strategies and different adverse childhood experiences may function diversely on altruism, with two waves of data collected 6 months apart in a longitudinal design among Chinese adolescents.MethodsA total of 658 adolescents (Mage = 13.51, SD = 0.73 at T1) were recruited and completed the online survey; their life history strategies were measured by the Mini‐K, the Delayed of Gratification Questionnaire (DOG), and the Chinese version of the Adolescent Risk‐Taking Questionnaire (ARQ‐RB) together, and their altruism was collected again after six months.ResultsAfter controlling for gender and their altruism at T1, the results showed that childhood trauma (i.e., emotional maltreatment, physical maltreatment), as well as low SES and fast life history strategy, were significantly negatively correlated with adolescents' altruism at T2. Importantly, life history strategy at T1 mediated the relationship between T1 emotional maltreatment, T1 low SES, and adolescents' altruism at T2. However, the effect of physical maltreatment on altruism was not mediated by life history strategy.ConclusionsThis study indicated that emotional maltreatment and low SES can affect adolescents' altruism by influencing the formation of adolescents' life history strategies. The findings revealed the different influences of adverse childhood experiences on adolescents' altruism, which supplied new empirical evidence for the life history theory and provided certain reference values for cultivating adolescents' altruism.
Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS
Authors: Komaba Hirotaka , Zhao Junhui , Karaboyas Angelo , Yamamoto Suguru , Dasgupta Indranil , Hassan Mohamed , Zuo Li , Christensson Anders , Combe Christian , Robinson Bruce M. , Fukagawa Masafumi 
Published: September 2023

ABSTRACT
Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).
Stem cell factor modulates HIF‐1α levels and diminishes 5‐FU sensitivity in 5‐FU resistant pancreatic cells by altering the anabolic glucose metabolism
Authors: Xiang Fu , Luo Fuwen 
Published: September 2023

AbstractResistance to chemotherapy in cancer leads to poor therapeutic outcomes and also leads to challenges in treatment. The present work evaluated the mechanism involved in the resistance of 5‐flurouracil (5‐FU) in pancreatic cancer. At least 14 different pancreatic cancer (PC) cell lines were used for the study. For in vivo study female nude mice were selected. Patient‐derived tumor xenograft samples were obtained from patients. The study involved, study for glucose uptake, fluorescence‐activated cell sorting for glucose transporter, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide for cell survival, Picto‐micrography for clonogenic assay, glutamine uptake assay, extracellular acidification and oxygen consumption rate, carbon dioxide release assay and lactate assay were also done. In addition to this, quantitative real‐time polymerase chain reaction analysis for expression of genes, chromatin immunoprecipitation assay, western blot for protein expression, and immunohistochemical analysis in tumor sections, the tumors were studied by imaging for hypoxia and localization of TKT and CTPS‐2. Also, patient‐derived xenograft tumors were engrafted in nude mice, followed by a glucose uptake assay. We reported that elevated glycolytic flux causes dependence on glucose in cancer cells and, at the same time, increases pyrimidine biosynthesis. It was also found that stem cell factor‐mediated stabilization of hypoxia‐inducible factor‐1a (HIF‐1α) modulates the resistance in PC. Targeting HIF‐1α in combination with 5‐FU, strongly reduced the tumor burden. The study concludes that stem cell factor modulates HIF‐1α and decreases the sensitivity in 5‐FU resistant pancreatic cancer cells by targeting glucose metabolism. Deceased expression levels of CTPS‐2 and TKT, which are regulators of pyrimidine biosynthesis could better the chance of survival in patients of pancreatic cancer receiving treatment of 5‐FU.
Synthesis of 2‐amino‐4‐aryl‐6‐styrylpyrimidines through aza‐Michael addition/nucleophilic addition/dehydrogenation cascade reactions
Authors: Wang Yue , Li Zheng 
Published: September 2023

AbstractAn efficient method for the synthesis of 2‐amino‐4‐aryl‐6‐styrylpyrimidines by the reactions of various distyryl ketones with guanidine hydrochloride through aza‐Michael addition/nucleophilic addition/dehydrogenation cascade processes is described. The salient features of this protocol are the use of easy‐to‐obtain substrates, transition‐metal‐free system, mild reaction conditions, high atom economy, wide substrate scope, satisfactory yield, and simple work‐up procedures.
Understanding citizens' perception of channels for participating in administration based on their motivation in an authoritarian regime: The case of Gaza Province, Mozambique
Authors: Sitoe Artur José , Lim Seunghoo 
Published: September 2023

AbstractStudies aiming to evaluate the effectiveness of channels for participating in administration have been conducted mainly in democratic, developed countries. However, outcomes from those settings may not apply to developing or less developed countries where democracy has yet to be consolidated. In Mozambique, which has an authoritarian regime, the effectiveness of participatory channels from the public point of view remains unexplored. Therefore, based on participants' motives for participation, this study empirically examines citizens' perception of channels for participating in administration with specific reference to Gaza Province and suggests that policy makers and administrators design participation channels for local governments to ensure and protect citizens' authentic participation in administration.
CRISPR/Cas9‐based functional genomics strategy to decipher the pathogenicity of genetic variants in inherited metabolic disorders
Authors: Muñoz‐Pujol Gerard , Ugarteburu Olatz , Segur‐Bailach Eulàlia , Moliner Sonia , Jurado Susana , Garrabou Glòria , Guitart‐Mampel Mariona , García‐Villoria Judit , Artuch Rafael , Fons Carme , Ribes Antonia , Tort Frederic 
Published: September 2023

AbstractThe determination of the functional impact of variants of uncertain significance (VUS) is one of the major bottlenecks in the diagnostic workflow of inherited genetic diseases. To face this problem, we set up a CRISPR/Cas9‐based strategy for knock‐in cellular model generation, focusing on inherited metabolic disorders (IMDs). We selected variants in seven IMD‐associated genes, including seven reported disease‐causing variants and four benign/likely benign variants. Overall, 11 knock‐in cell models were generated via homology‐directed repair in HAP1 haploid cells using CRISPR/Cas9. The functional impact of the variants was determined by analyzing the characteristic biochemical alterations of each disorder. Functional studies performed in knock‐in cell models showed that our approach accurately distinguished the functional effect of pathogenic from non‐pathogenic variants in a reliable manner in a wide range of IMDs. Our study provides a generic approach to assess the functional impact of genetic variants to improve IMD diagnosis and this tool could emerge as a promising alternative to invasive tests, such as muscular or skin biopsies. Although the study has been performed only in IMDs, this strategy is generic and could be applied to other genetic disorders.
LncRNA‐associated competing endogenous RNA network analysis uncovered key lncRNAs involved in temozolomide resistance and tumor recurrence of glioblastoma
Authors: Nayak Rojalin , Mallick Bibekanand 
Published: September 2023

AbstractTemozolomide (TMZ) is a common alkylating chemotherapeutic agent used to treat brain tumors such as glioblastoma multiforme (GBM) and anaplastic astrocytoma. GBM patients develop resistance to this drug, which has an unclear and complicated molecular mechanism. The competing endogenous RNAs (ceRNAs) play critical roles in tumorigenesis, drug resistance, and tumor recurrence in cancers. This study aims to predict ceRNAs, their possible involvement, and underlying molecular mechanisms in TMZ resistance. Therefore, we analyzed coding and non‐coding RNA expression levels in TMZ‐resistant GBM samples compared to sensitive GBM samples and performed pathway analysis of mRNAs differentially expressed (DE) in TMZ‐resistant samples. We next applied a mathematical model on 950 DE long non‐coding RNAs (lncRNAs), 116 microRNAs (miRNAs), and 7977 mRNAs and obtained 10 lncRNA‐associated ceRNAs that may be regulating potential target genes involved in cancer‐related pathways by sponging 25 miRNAs in TMZ‐resistant GBM. Among these, two lncRNAs named ARFRP1 and RUSC2 regulate five target genes (IRS1, FOXG1, GNG2, RUNX2, and CACNA1E) involved in AMPK, AKT, mTOR, and TGF‐β signaling pathways that activate or inhibit autophagy causing TMZ resistance. The novel lncRNA‐associated ceRNA network predicted in GBM offers a fresh viewpoint on TMZ resistance, which might contribute to treating this malignancy.
Investigation of α‐glucosidase and α‐amylase inhibitory effects of phenoxy chalcones and molecular modeling studies
Authors: Kurşun‐Aktar Bedriye Seda , Adem Şevki , Tatar‐Yilmaz Gizem , Hameed Zeyad Adıl Hameed , Oruç‐Emre Emine Elçin 
Published: September 2023

AbstractDiabetes mellitus is one of the most critical health problems affecting the quality of life of people worldwide, especially in developing countries. According to the World Health Organization reports, the number of patients with diabetes is approximately 420 million, and this number is estimated to be 642 million in 2040. There are 2 main types of diabetes: Type 1 (T1DM), where the body cannot produce enough insulin, and Type 2 (T2DM), where the body cannot use insulin properly. Patients with T1DM are treated with insulin injections while oral glucose‐lowering drugs are used for patients with T2DM. Oral antihyperglycemic drugs used in the treatment of type 2 diabetes mellitus have different mechanisms. Among these, α‐Glucosidase and α‐amylase inhibitors are one of the most important inhibitors. The antidiabetic effect of the chalcones, which show rich activity, draws attention. This research aims to synthesize chalcone derivatives that could show potential antidiabetic activity. In this study, the inhibitory activity of the chalcone compounds (4a‐4g, 5a‐5g) was tested against α‐glucosidase and α‐amylase enzymes. Besides, molecular modeling was utilized to predict potential interactions of the synthesized compounds that exhibit inhibitory effects. In both in vitro and in silico studies, the analyses revealed that compound 5e exhibits strong inhibitory effects against α‐glucosidase enzymes (Binding energy: −7.75 kcal/mol, IC50: 28.88 μM). Additionally, compound 4f demonstrates encouraging inhibitory effects against α‐Amylase (Binding energy: −11.08 kcal/mol, IC50: 46. 21 μM).
Effects of three different plant‐derived polysaccharides on growth performance, immunity, antioxidant function, and cecal microbiota of broilers
Authors: Zhao Guiling , Niu Yu , Wang Huixian , Qin Songke , Zhang Ruiqiang , Wu Yanping , Xiao Xiao , Xu Yinglei , Yang Caimei 
Published: September 2023

AbstractBACKGROUNDThis study investigated the effects of dietary plant polysaccharides on growth performance, immune status and intestinal health in broilers. We randomly divided 960 one‐day‐old Arbor Acres broiler chicks into four groups. The control (CON) group was fed a basal diet, and the remaining groups were fed a basal diet supplemented with 1000 mg kg−1 Ginseng polysaccharide (GPS), Astragalus polysaccharide (APS), or Salvia miltiorrhiza polysaccharide (SMP) for 42 days.RESULTSDietary supplementation with SMP significantly increased body weight (BW) at 21 and 42 days of age, average daily gain (ADG) and average daily feed intake (ADFI) during the starter and whole experimental period, decreased the concentrations of interleukin‐1 beta (IL‐1β), tumor necrosis factor α (TNF‐α) and malondialdehyde (MDA), increased the levels of interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10) and catalase (CAT) activity in the serum (P < 0.05). GPS, APS, and SMP supplementation increased serum levels of immunoglobulins, activities of glutathione peroxidase (GSH‐Px), total superoxide dismutase (T‐SOD) and total antioxidant capacity (T‐AOC), and cecal concentrations of acetic acid and propionic acid of broilers (P < 0.05). Furthermore, high‐throughput sequencing results showed that the relative abundance of Firmicutes was decreased while the relative abundance of Bacteroidota, Alistipes, and Prevotellaceae_NK3B31_group were increased (P < 0.05) in the GPS, APS, and SMP groups compared with the CON group.CONCLUSIONDietary GPS, APS, and SMP supplementation could improve growth performance, enhance immune function by increasing serum immunoglobulin and regulating cytokines, improve antioxidant function by increasing serum antioxidant enzyme activity, increase volatile fatty acid levels and improve the microbial composition in the cecum of broilers. Dietary SMP supplementation had the optimal effect in this study. © 2023 Society of Chemical Industry.
Impacts of abiotic factors on the growth of three commercial biological control agents, on the growth and mycotoxinogenesis of Fusarium graminearum and on their interaction
Authors: Dieye Cheikh Ahmeth Tidiane , Durand Noël , Schorr‐Galindo Sabine , Strub Caroline , Fontana Angélique 
Published: September 2023

AbstractBACKGROUNDEvolving climatic conditions impact the behavior of microorganisms. The lack of efficiency of beneficial microorganisms against pathogens can be due to these evolving abiotic factors more favorable to the development and adaptation of pathogens. It is therefore of great interest to understand their impact (especially temperature increase and relative humidity (RH) variation) on pathogenic and non‐pathogenic microorganisms. This work aimed to examine the possible effects of increasing temperature (20, 25, 30 and 33 °C) and RH (40%, 50%, 60% and 80%) on the growth and mycotoxin production (deoxynivalenol (DON) and zearalenone (ZEN)) of Fusarium graminearum, on the growth of three commercial biocontrol agents (BCAs; Mycostop®, Xedavir® and Polyversum®) and on the pathogen–BCA interaction.RESULTSResults demonstrated that BCAs have contrasting impacts on the growth and mycotoxinogenesis of F. graminearum depending on abiotic factors. At 25 °C and regardless of RH, commercial BCAs limit DON production by F. graminearum, but at 30 °C and intermediate RH, Xedavir® is no longer effective. The ability of Xedavir® to control the production of ZEN production by F. graminearum is also affected by abiotic factors. However, increasing temperature has an opposite effect on its ability to control the accumulation of ZEN. Polyversum® oomycete is the BCA with the most resilient efficacy against F. graminearum toxinogenesis under the different abiotic factors.CONCLUSIONThis work provides new knowledge of the effect of these abiotic parameters on the interaction between BCA and F. graminearum, especially on the production of mycotoxins. It paves the way for the development of efficient and resilient mycotoxin biocontrol strategies using beneficial microorganisms against F. graminearum, thus contributing to global food security. © 2023 Society of Chemical Industry.