bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in hippocampal β-amyloid accumulation in the triple-transgenic mouse model of Alzheimer’s disease and the potential role of local estrogens
Authors: Hu Yu-Ting , Chen Xin-Lu , Zhang Ya-Nan , McGurran Hugo , Stormmesand Jochem , Breeuwsma Nicole , Sluiter Arja , Zhao Juan , Swaab Dick , Bao Ai-Min 
Published: March 2023

IntroductionEpidemiological studies show that women have a higher prevalence of Alzheimer’s disease (AD) than men. Peripheral estrogen reduction during aging in women is proposed to play a key role in this sex-associated prevalence, however, the underlying mechanism remains elusive. We previously found that transcription factor early growth response-1 (EGR1) significantly regulates cholinergic function. EGR1 stimulates acetylcholinesterase (AChE) gene expression and is involved in AD pathogenesis. We aimed to investigate whether the triple-transgenic AD (3xTg-AD) mice harboring PS1M146V, APPSwe, and TauP301L show sex differences in β-amyloid (Aβ) and hyperphosphorylated tau (p-Tau), the two primary AD hallmarks, and how local 17β-estradiol (E2) may regulate the expression of EGR1 and AChE.MethodsWe first sacrificed male and female 3xTg-AD mice at 3–4, 7–8, and 11–12 months and measured the levels of Aβ, p-Tau, EGR1, and AChE in the hippocampal complex. Second, we infected SH-SY5Y cells with lentivirus containing the amyloid precursor protein construct C99, cultured with or without E2 administration we measured the levels of extracellular Aβ and intracellular EGR1 and AChE.ResultsFemale 3xTg-AD mice had higher levels of Aβ compared to males, while no p-Tau was found in either group. In SH-SY5Y cells infected with lentivirus containing the amyloid precursor protein construct C99, we observed significantly increased extracellular Aβ and decreased expression of intracellular EGR1 and AChE. By adding E2 to the culture medium, extracellular Aβ(1–42) was significantly decreased while intracellular EGR1 and AChE expression were elevated.DiscussionThis data shows that the 3xTg-AD mouse model can be useful for studying the human sex differences of AD, but only in regards to Aβ. Furthermore, in vitro data shows local E2 may be protective for EGR1 and cholinergic functions in AD while suppressing soluble Aβ(1–42) levels. Altogether, this study provides further in vivo and in vitro data supporting the human epidemiological data indicating a higher prevalence of AD in women is related to changes in brain estrogen levels.
Effects of television viewing on brain structures and risk of dementia in the elderly: Longitudinal analyses
Authors: Takeuchi Hikaru , Kawashima Ryuta 
Published: March 2023

IntroductionTV viewing in the elderly and in children is associated with subsequent greater decline of various cognitive functions including verbal working memory, but results of its association with subsequent risk of dementia were divided.MethodsIn this longitudinal cohort study of UK Biobank, we investigated the associations of TV viewing length with subsequent risk of dementia and longitudinal changes of brain structural measures after corrections of a wide range of potential confounders.ResultsOur results showed longer TV viewing was associated with increased risk of subsequent onset of dementia, as well as subsequent greater decline in intracellular volume fraction (ICVF) in the extensive areas of right lateral temporal cortex and the right medial temporal cortex, in the area around the left middle and inferior temporal cortex as well as the left fusiform gyrus, and the area adjacent to the left inferior frontal gyrus, and left insula.DiscussionThese results may suggest prolonged TV viewing was associated with decline in density of neurites (axon, dendrites) in areas particularly implicated in language, communication, and memory, which are altered in dementia.
Palmitoylation controls the stability of 190 kDa ankyrin-G in dendritic spines and is regulated by ZDHHC8 and lithium
Authors: Piguel Nicolas H. , Sanders Shaun S. , De Simone Francesca I. , Martin-de-Saavedra Maria D. , McCoig Emmarose , Dionisio Leonardo E. , Smith Katharine R. , Thomas Gareth M. , Penzes Peter 
Published: March 2023

IntroductionAnkG, encoded by the ANK3 gene, is a multifunctional scaffold protein with complex isoform expression: the 480 and 270 kDa isoforms have roles at the axon initial segment and node of Ranvier, whereas the 190 kDa isoform (AnkG-190) has an emerging role in the dendritic shaft and spine heads. All isoforms of AnkG undergo palmitoylation, a post-translational modification regulating protein attachment to lipid membranes. However, palmitoylation of AnkG-190 has not been investigated in dendritic spines. The ANK3 gene and altered expression of AnkG proteins are associated with a variety of neuropsychiatric and neurodevelopmental disorders including bipolar disorder and are implicated in the lithium response, a commonly used mood stabilizer for bipolar disorder patients, although the precise mechanisms involved are unknown.ResultHere, we showed that Cys70 palmitoylation stabilizes the localization of AnkG-190 in spine heads and at dendritic plasma membrane nanodomains. Mutation of Cys70 impairs AnkG-190 function in dendritic spines and alters PSD-95 scaffolding. Interestingly, we find that lithium reduces AnkG-190 palmitoylation thereby increasing its mobility in dendritic spines. Finally, we demonstrate that the palmitoyl acyl transferase ZDHHC8, but not ZDHHC5, increases AnkG-190 stability in spine heads and is inhibited by lithium.DiscussionTogether, our data reveal that palmitoylation is critical for AnkG-190 localization and function and a potential ZDHHC8/AnkG-190 mechanism linking AnkG-190 mobility to the neuronal effects of lithium.
Anti-cancer potential of synergistic phytochemical combinations is influenced by the genetic profile of prostate cancer cell lines
Authors: Gano Carol A. , Fatima Shadma , Failes Timothy W. , Arndt Gregory M. , Sajinovic Mila , Mahns David , Saedisomeolia Ahmad , Coorssen Jens R. , Bucci Joseph , de Souza Paul , Vafaee Fatemeh , Scott Kieran F. 
Published: March 2023

IntroductionDespite strong epidemiological evidence that dietary factors modulate cancer risk, cancer control through dietary intervention has been a largely intractable goal for over sixty years. The effect of tumour genotype on synergy is largely unexplored.MethodsThe effect of seven dietary phytochemicals, quercetin (0–100 μM), curcumin (0–80 μM), genistein, indole-3-carbinol (I3C), equol, resveratrol and epigallocatechin gallate (EGCG) (each 0–200 μM), alone and in all paired combinations om cell viability of the androgen-responsive, pTEN-null (LNCaP), androgen-independent, pTEN-null (PC-3) or androgen-independent, pTEN-positive (DU145) prostate cancer (PCa) cell lines was determined using a high throughput alamarBlue® assay. Synergy, additivity and antagonism were modelled using Bliss additivism and highest single agent equations. Patterns of maximum synergy were identified by polygonogram analysis. Network pharmacology approaches were used to identify interactions with known PCa protein targets.ResultsSynergy was observed with all combinations. In LNCaP and PC-3 cells, I3C mediated maximum synergy with five phytochemicals, while genistein was maximally synergistic with EGCG. In contrast, DU145 cells showed resveratrol-mediated maximum synergy with equol, EGCG and genistein, with I3C mediating maximum synergy with only quercetin and curcumin. Knockdown of pTEN expression in DU145 cells abrogated the synergistic effect of resveratrol without affecting the synergy profile of I3C and quercetin.DiscussionOur study identifies patterns of synergy that are dependent on tumour cell genotype and are independent of androgen signaling but are dependent on pTEN. Despite evident cell-type specificity in both maximally-synergistic combinations and the pathways that phytochemicals modulate, these combinations interact with similar prostate cancer protein targets. Here, we identify an approach that, when coupled with advanced data analysis methods, may suggest optimal dietary phytochemical combinations for individual consumption based on tumour molecular profile.
A novel risk score model based on gamma-aminobutyric acid signature predicts the survival prognosis of patients with breast cancer
Authors: Yang Liping , Zhu Jin , Wang Lieliang , He Longbo , Gong Yi , Luo Qingfeng 
Published: March 2023

BackgroundGamma-aminobutyric acid (GABA) participates in the migration, differentiation, and proliferation of tumor cells. However, the GABA-related risk signature has never been investigated. Hence, we aimed to develop a reliable gene signature based on GABA pathways-related genes (GRGs) to predict the survival prognosis of breast cancer patients.MethodsGABA-related gene sets were acquired from the MSigDB database, while mRNA gene expression profiles and corresponding clinical data of breast cancer patients were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate Cox regression analysis was used to identify prognostic-associated GRGs. Subsequently, LASSO analysis was applied to establish a risk score model. We also constructed a clinical nomogram to perform the survival evaluation. Besides, ESTIMATE and ssGSEA algorithms were used to assess the immune cell infiltration among the risk score subgroups.ResultsA GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort. The risk score was significantly related to the overall survival of breast cancer patients, which could predict the survival prognosis of breast cancer patients independently of other clinical features. Breast cancer patients in the low-risk score group exhibited higher immune cell infiltration levels.ConclusionA novel prognostic model containing five GRGs could accurately predict the survival prognosis and immune infiltration of breast cancer patients. Our findings provided a novel insight into investigating the immunoregulation roles of GRGs.
American college of radiology ovarian-adnexal reporting and data system ultrasound (O-RADS): Diagnostic performance and inter-reviewer agreement for ovarian masses in children
Authors: Wang Huimin , Wang Limin , An Siwei , Ma Qiuping , Tu Yanping , Shang Ning , Pan Yunxiang 
Published: March 2023

ObjectiveTo evaluate the diagnostic performance and inter-observer agreement of the American College of Radiology Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS) in the diagnosis of ovarian masses in children.MethodsFrom June 2012 to December 2021, 163 ovarian masses in 159 patients with pathologic results were retrospectively analyzed. Each mass was classified into an O-RADS category according to the criteria. The diagnostic performance of O-RADS for detecting malignant ovarian masses was assessed using histopathology as the reference standard. Kappa (k) statistic was used to assess inter-observer agreement between a less-experienced and a well-experienced radiologist.ResultsOut of 163 ovarian masses, 18 (11.0%) were malignant and 145 (89.0%) were benign. The malignancy rates of O-RADS 5, O-RADS 4, and O-RADS 3 masses were 72.7%, 34.6%, and 4.8%, respectively. The area under the receiver operating characteristic curve was 0.944 (95% CI, 0.908–0.981). The optimal cutoff value for predicting malignant ovarian masses was  &gt; O-RADS 3 with a sensitivity, specificity, and accuracy of 94.4%, 86.2% and 86.2% respectively. The inter-observer agreement of the O-RADS category was good (k = 0.777).ConclusionsO-RADS has a high diagnostic performance for children with ovarian masses. It provides an effective malignant risk classification for ovarian masses in children, which shows high consistency between radiologists with different levels of experience.
Eating order and childhood obesity among preschoolers in China: A cross-sectional study
Authors: Dai Jin , Yang Jingyun , Fan Hailing , Wu Yixin , Wu Huilan , Wang Yun , Tung Tao-Hsin , Wang Lizhen , Zhang Meixian 
Published: March 2023

BackgroundEarly childhood is a critical period for dietary education and development of good eating habits. However, few studies have investigated the effect of eating order in children and childhood obesity in real-world settings.ObjectiveTo examine whether the order in which meats/fish or vegetables are consumed affects the risk of obesity in preschoolers.MethodsWe conducted a population-based cross-sectional study using a self-administered online survey on the lifestyle and health behaviors of preschoolers in Taizhou, China. A total of 3,200 parents were invited to take part in the survey, and 2,049 of them completed the questionnaire. Children were classified as having a normal weight, overweight, or obesity using the definitions provided by the International Obesity Task Force, and z-scores for body mass index were calculated. We divided the children's eating order at the beginning of the meal into two groups: “vegetables before meats/fish” or “meats/fish before vegetables”. We analyzed the relationship between what was consumed first at a meal and the overweight status of each child.ResultsNo difference in body mass index was observed between the children eating meats/fish-first and the children eating vegetables-first during a meal. Children with parents who were affected by obesity were more likely to eat vegetables first. Among children of mothers with obesity, body mass index was significantly higher in the meats/fish-first group than that in the vegetable-first group (2.891 vs. 0.845, P = 0.007). In children whose mothers were affected by obesity, those that ate meats/fish first had a 12.21 times higher risk of being overweight compared with those that ate vegetables first (95% CI:1.22–121.74, P = 0.033).ConclusionOur findings suggest eating vegetables or meats/fish at the start of a meal does not affect weight status in preschoolers.
Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway
Authors: Chen Tingting , Hu Yingying , Lu Liying , Zhao Qianlei , Tao Xiaoyue , Ding Bingqing , Chen Shangqin , Zhu Jianghu , Guo Xiaoling , Lin Zhenlang 
Published: March 2023

Introduction: Hypoxic-ischemic encephalopathy (HIE) is a crucial cause of neonatal death and neurological sequelae, but currently there is no effective therapy drug for HIE. Both oxidative stress and apoptosis play critical roles in the pathological development of HIE. Myricetin, a naturally extracted flavonol compound, exerts remarkable effects against oxidative stress, apoptosis, and inflammation. However, the role and underlying molecular mechanism of myricetin on HIE remain unclear.Methods: In this study, we established the neonatal rats hypoxic-ischemic (HI) brain damage model in vivo and CoCl2 induced PC12 cell model in vitro to explore the neuroprotective effects of myricetin on HI injury, and illuminate the potential mechanism.Results: Our results showed that myricetin intervention could significantly reduce brain infarction volume, glia activation, apoptosis, and oxidative stress marker levels through activating NRF2 (Nuclear factor-E2-related factor 2) and increase the expressions of NRF2 downstream proteins NQO-1 and HO-1. In addition, the NRF2 inhibitor ML385 could significantly reverse the effects of myricetin.Conclusion: This study found that myricetin might alleviate oxidative stress and apoptosis through NRF2 signaling pathway to exert the protective role for HI injury, which suggested that myricetin might be a promising therapeutic agent for HIE.
Long way to go: Progress of orphan drug accessibility in China from 2017 to 2022
Authors: Liu Jia , Yu Yue , Zhong Mingkang , Ma Chunlai , Shao Rong 
Published: March 2023

Introduction: Over 400 million patients worldwide suffer from rare diseases. Access to orphan drugs is, therefore, crucial for this population. China has been actively working on improving orphan drug accessibility in the past decades, especially since 2018 when the First National List of Rare Diseases was announced. This study aimed to evaluate the current status of orphan drug accessibility in China regarding availability, daily cost, and affordability.Methods: Market availability of orphan drugs in China was based on their approval status in China up to May 2022. Information on drug availability in hospitals and the cost of each drug from 2017 to 2021 was obtained from the database of the Science and Technology Development Center of the Chinese Pharmaceutical Association. Affordability was assessed by comparing the disposable daily income per capita to the cost of the defined daily dose of each drug.Results: Market availability rate was 44.3% by May 2022, and the average delay in drug approval in China compared to its orphan approval in the United States of America was 5.9 ± 6.07 years. Drug availability in hospitals showed an upward trend, with availability in tertiary hospitals significantly higher than in secondary hospitals (~20%, p &lt;0.0001). The eastern area was significantly higher in availability from 2019 onwards. Fifty-eight percent of the orphan drugs were still considered to have very low availability (&lt;30%). The national median cost of the defined daily dose across all available orphan drugs had increased to 254.97 RMB in 2021. Only 34.98% of the orphan drugs were considered affordable when compared with the national average disposable daily income in 2021, and drug affordability decreased during the past 5 years.Discussion: Changes in orphan drug regulations in China have enabled progress regarding the drugs’ market availability, but the current status of drug availability at hospitals, drug cost, and affordability were not optimal. Legislation for encouraging domestic drug development and novel payment schemes for high-value drugs are essential to further improve the availability and cost burden of orphan drugs in China
Rainfed assessment of foxtail millet (Setaria italica L. beauv) germplasms through genotyping and principal component analysis
Authors: Singh Divya , Lawrence Kapil , Marker Shailesh , Bhattacharjee Indranil , Lawrence Reena , Choudhary Ravish , Ercisli Sezai , Karunakaran Rohini 
Published: March 2023

IntroductionFoxtail millet (Setaria italica L. beauv) is an important crop in underdeveloped countries; however, yield levels are low. The use of varied germplasm in a breeding approach is critical for increasing productivity. Foxtail millet can be cultivated effectively in a wide range of environmental circumstances but it is best suited to hot and dry climates.MethodsIn the current study, multivariant traits were used to define 50 genotypes in the first year and 10 genotypes in the second year. The phenotypic correlations among all traits in the entire germplasm were assessed, and the data acquired for all quantitative characters were subjected to analysis of variance for augmented block design. Furthermore, WINDOWS STAT statistical software was used to carry out a principal component analysis (PCA). The presence of substantial variations in most symptoms was shown by analysis of variance.ResultsGenotypic coefficient of variation (GCV) projections for grain yields were the highest, followed by panicle lengths and biological yields. Plant height and leaf length had the highest PCV estimates, followed by leaf width. Low GCV and phenotypic coefficient of variation (PCV) were measured as leaf length and 50% flowering in days. According to the PCV study, direct selection based on characters, panicle weight, test weight, and straw weight had a high and positive effect on grain yield per plant in both the rainy and summer seasons, indicating the true relationship between these characters and grain yield per plant, which aids indirect selection for these traits and thus improves grain yield per plant. Variability in foxtail millet germplasm enables plant breeders to effectively select appropriate donor lines for foxtail millet genetic improvement.DiscussionBased on the average performance of genotypes considered superior in terms of grain yield components under Prayagraj agroclimatic conditions, the best five genotypes were: Kangni-7 (GS62), Kangni-1 (G5-14), Kangni-6 (GS-55), Kangni-5 (GS-389), and Kangni-4 (GS-368).
Fertilizer source and application method influence sugarcane production and nutritional status
Authors: Castro Sérgio Gustavo Quassi de , Coelho Anderson Prates , Castro Saulo Augusto Quassi de , Souza Chiachia Thais Regina de , Castro Rosilaine Araldi de , Lemos Leandro Borges 
Published: March 2023

IntroductionThe contrasting weather conditions throughout the sugarcane harvest period in south-central Brazil (April to November) influence fertilization management in sugarcane ratoon.MethodsThrough field studies carried out over two cropping seasons, we aimed to compare the performance of sugarcane at sites harvested in the early and late periods of the harvest season as a function of fertilizer sources associated with application methods. The design used in each site was a randomized block in a 2 x 3 factorial scheme; the first factor consisted of fertilizer sources (solid and liquid), and the second factor consisted of application methods (above the straw, under the straw, and incorporated into the middle of the sugarcane row).ResultsThe fertilizer source and application method interacted at the site harvested in the early period of the sugarcane harvest season. Overall, the highest sugarcane stalk and sugar yields at this site were obtained with the incorporated application applying liquid fertilizer and under straw applying solid fertilizer, with increments of up to 33%. For the site harvested in the late period of the sugarcane harvest season, the liquid fertilizer promoted a 25% higher sugarcane stalk yield compared to the solid fertilizer in the crop season with low rainfall in the spring, while in the crop season with normal rainfall, there were no differences between treatments.DiscussionThis demonstrates the importance of defining fertilization management in sugarcane as a function of harvest time, thereby promoting greater sustainability in the production system
Does brand community participation lead to early new product adoption? The roles of networking behavior and prior purchase experience
Authors: Jiang Ying , Liao Junyun , Pang Jiecong , Hu Hsin-Li 
Published: March 2023

IntroductionConsumers’ adoption behavior is critical to the success of new products, but the effects of brand communities on new product adoption have rarely been investigated. In this study, we draw on network theory to examine how consumer participation in brand communities (in terms of participation intensity and social networking behaviors) affects the adoption of new products.MethodsWe collected longitudinal data from 8,296 members of an online community of a well-known smartphone brand to assess the factors influencing new product adoption.ResultsThe results from applying a hazard model indicated that brand community participation increases the speed of adoption of new products. The positive effect of members’ out-degree centrality on new product adoption was found to be significant, but in-degree centrality only had an effect when users had previous purchasing experience.DiscussionThese findings extend the literature by revealing how new products are disseminated across brand communities. The study also makes theoretical and practical contributions to the literature on brand community management and product marketing.