bluuebunny/crossref_metadata_2025_split huggingface dataset:
m6A modification–mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability
Authors: Fang Deliang , Ou Xinde , Sun Kaiyu , Zhou Xingyu , Li Youpei , Shi Peng , Zhao Zirui , He Yulong , Peng Jianjun , Xu Jianbo 
Published: September 2022

AbstractLong noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination‐mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.
Genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue
Authors: Minnai Francesca , Noci Sara , Chierici Marco , Cotroneo Chiara Elisabetta , Bartolini Barbara , Incarbone Matteo , Tosi Davide , Mattioni Giovanni , Jurman Giuseppe , Dragani Tommaso A. , Colombo Francesca 
Published: September 2022

AbstractEmerging evidence suggests that the prognosis of patients with lung adenocarcinoma can be determined from germline variants and transcript levels in nontumoral lung tissue. Gene expression data from noninvolved lung tissue of 483 lung adenocarcinoma patients were tested for correlation with overall survival using multivariable Cox proportional hazard and multivariate machine learning models. For genes whose transcript levels are associated with survival, we used genotype data from 414 patients to identify germline variants acting as cis‐expression quantitative trait loci (eQTLs). Associations of eQTL variant genotypes with gene expression and survival were tested. Levels of four transcripts were inversely associated with survival by Cox analysis (CLCF1, hazard ratio [HR] = 1.53; CNTNAP1, HR = 2.17; DUSP14, HR = 1.78; and MT1F: HR = 1.40). Machine learning analysis identified a signature of transcripts associated with lung adenocarcinoma outcome that was largely overlapping with the transcripts identified by Cox analysis, including the three most significant genes (CLCF1, CNTNAP1, and DUSP14). Pathway analysis indicated that the signature is enriched for ECM components. We identified 32 cis‐eQTLs for CNTNAP1, including 6 with an inverse correlation and 26 with a direct correlation between the number of minor alleles and transcript levels. Of these, all but one were prognostic: the six with an inverse correlation were associated with better prognosis (HR < 1) while the others were associated with worse prognosis. Our findings provide supportive evidence that genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients' noninvolved lung tissue.
Survival prediction of stomach cancer using expression data and deep learning models with histopathological images
Authors: Wei Ting , Yuan Xin , Gao Ruitian , Johnston Luke , Zhou Jie , Wang Yifan , Kong Weiming , Xie Yujing , Zhang Yue , Xu Dakang , Yu Zhangsheng 
Published: September 2022

AbstractAccurately predicting patient survival is essential for cancer treatment decision. However, the prognostic prediction model based on histopathological images of stomach cancer patients is still yet to be developed. We propose a deep learning‐based model (MultiDeepCox‐SC) that predicts overall survival in patients with stomach cancer by integrating histopathological images, clinical data, and gene expression data. The MultiDeepCox‐SC not only automatedly selects patches with more information for survival prediction, without manual labeling for histopathological images, but also identifies genetic and clinical risk factors associated with survival in stomach cancer. The prognostic accuracy of the MultiDeepCox‐SC (C‐index = 0.744) surpasses the result only based on histopathological image (C‐index = 0.660). The risk score of our model was still an independent predictor of survival outcome after adjustment for potential confounders, including pathologic stage, grade, age, race, and gender on The Cancer Genome Atlas dataset (hazard ratio 1.555, p = 3.53e‐08) and the external test set (hazard ratio 2.912, p = 9.42e‐4). Our fully automated online prognostic tool based on histopathological images, clinical data, and gene expression data could be utilized to improve pathologists' efficiency and accuracy (https://yu.life.sjtu.edu.cn/DeepCoxSC).
Novel hKDR mouse model depicts the antiangiogenesis and apoptosis‐promoting effects of neutralizing antibodies targeting vascular endothelial growth factor receptor 2
Authors: Cao Yuan , Sun Chunyun , Huo Guitao , Wang Huiyu , Wu Yong , Wang Fei , Liu Susu , Zhai Shijie , Zhang Xiao , Zhao Haoyang , Hu Meiling , Gu Wenda , Yang Yanwei , Wang Sanlong , Liang Chunnan , Lyu Jianjun , Lu Tiangong , Wang Youchun , Xie Liangzhi , Fan Changfa 
Published: September 2022

AbstractVascular endothelial growth factor receptor 2 (VEGFR2)/KDR plays a critical role in tumor growth, diffusion, and invasion. The amino acid sequence homology of KDR between mouse and human in the VEGF ligand‐binding domain was low, thus the WT mice could not be used to evaluate Abs against human KDR, and the lack of a suitable mouse model hindered both basic research and drug developments. Using the CRISPR/Cas9 technique, we successfully inserted different fragments of the human KDR coding sequence into the chromosomal mouse Kdr exon 4 locus to obtain an hKDR humanized mouse that can be used to evaluate the marketed Ab ramucirumab. In addition, the humanized mAb VEGFR‐HK19 was developed, and a series of comparative assays with ramucirumab as the benchmark revealed that VEGFR‐HK19 has higher affinity and superior antiproliferation activity. Moreover, VEGFR‐HK19 selectively inhibited tumor growth in the hKDR mouse model but not in WT mice. The most important binding epitopes of VEGFR2‐HK19 are D257, L313, and T315, located in the VEGF binding region. Therefore, the VEGFR2‐HK19 Ab inhibits tumor growth by blocking VEGF‐induced angiogenesis, inflammation, and promoting apoptosis. To our best knowledge, this novel humanized KDR mouse fills the gaps both in an animal model and the suitable in vivo evaluation method for developing antiangiogenesis therapies in the future, and the newly established humanized Ab is expected to be a drug candidate possibly benefitting tumor patients.
ROS inhibits RORα degradation by decreasing its arginine methylation in liver cancer
Authors: Im Hyuntae , Baek Hee‐ji , Yang Eunbi , Kim Kyeongkyu , Oh Se Kyu , Lee Jung‐Shin , Kim Hyunkyung , Lee Ji Min 
Published: September 2022

AbstractRetinoic acid receptor–related orphan receptor α (RORα) is a transcription factor involved in nuclear gene expression and a known tumor suppressor. RORα was the first identified substrate of lysine methylation–dependent degradation. However, the mechanisms of other post‐translational modifications (PTMs) that occur in RORα remain largely unknown, especially in liver cancer. Arginine methylation is a common PTM in arginine residues of nonhistone and histone proteins and affects substrate protein function and fate. We found an analogous amino acid disposition containing R37 at the ROR N‐terminus compared to histone H3 residue, which is arginine methylated. Here, we provide evidence that R37 methylation–dependent degradation is carried out by protein arginine methyltransferase 5 (PRMT5). Further, we discovered that PRMT5 regulated the interaction between the E3 ubiquitin ligase ITCH and RORα through RORα arginine methylation. Arginine methylation–dependent ubiquitination‐mediated RORα degradation reduced downstream target gene activation. H2O2‐induced reactive oxygen species (ROS) decreased PRMT5 protein levels, consequently increasing RORα protein levels in HepG2 liver cancer cells. In addition, ROS inhibited liver cancer progression by inducing apoptosis via PRMT5‐mediated RORα methylation and the ITCH axis. Our results potentiate PRMT5 as an elimination target in cancer therapy, and this additional regulatory level within ROS signaling may help identify new targets for therapeutic intervention in liver cancer.
Tau antibody 77G7 targeting microtubule binding domain suppresses proteopathic tau to seed tau aggregation
Authors: Li Longfei , Miao Jin , Chu Dandan , Jin Nana , Tung Yunn Chyn , Dai Chun‐Ling , Hu Wen , Gong Cheng‐Xin , Iqbal Khalid , Liu Fei 
Published: September 2022

AbstractIntroductionNeurofibrillary tangle (NFT) of hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and related tauopathies. Tau lesion starts in the trans‐entorhinal cortex, from where it spreads to limbic regions, followed by neocortical areas. The regional distribution of NFTs associates with the progression of AD. Accumulating evidence suggests that proteopathic tau can seed tau aggregation in a prion‐like fashion in vitro and in vivo. Inhibition of tau seeding activity could provide a potential therapeutic opportunity to block the propagation of tau pathology in AD and related tauopathies.AimsIn the present study, we investigated the role of 77G7, a monoclonal tau antibody to the microtubule‐binding repeats, in repressing the seeding activity of proteopathic tau.ResultsWe found that 77G7 had a higher affinity toward aggregated pathological tau fractions than un‐aggregated tau derived from AD brain. 77G7 inhibited the internalization of tau aggregates by cells, blocked AD O‐tau to capture normal tau, and to seed tau aggregation in vitro and in cultured cells. Tau pathology induced by hippocampal injection of AD O‐tau in 3xTg‐AD mice was suppressed by mixing 77G7 with AD O‐tau. Intravenous administration of 77G7 ameliorated site‐specific hyperphosphorylation of tau induced by AD O‐tau in the hippocampi of Tg/hTau mice.ConclusionThese findings indicate that 77G7 can effectively suppress the seeding activity of AD O‐tau and thus could be developed as a potential immunotherapeutic drug to inhibit the propagation of tau pathology in AD and related tauopathies.
A privacy‐preserving recommendation method with clustering and locality‐sensitive hashing
Authors: Zhang Hanrui , Li Qianmu , Xu Jiangmin , Meng Shunmei , Hou Jun 
Published: September 2022

AbstractNowadays, there is a significant increase in information, resulting in information overload. Recommendation systems have been widely adopted, and they can help users find information relevant to their interests. However, a malicious attacker can infer users' private information via recommendations. To solve problems of data sparseness, enormous high‐dimensional data, the cold start problem and privacy protection in an intelligent recommender system, this study proposes a privacy‐preserving collaborative filtering recommendation method with clustering and locality‐sensitive hashing. First, we cluster users according to their characteristic information to obtain sub‐rating matrices. We use the latent factor model to predict and fill in the missing ratings in those matrices. Second, we combine the sub‐rating matrices into a complete rating matrix, subsequently, we obtained the neighbors of the target user by analyzing the similarity of the users. We use a locality‐sensitive hashing algorithm to reduce the dimensionality of the user rating data and build an index that could quickly obtain the neighbors of the target user. Finally, we predict the target user's ratings and provide recommendations to the target user. Through experiments, our study shows that our method can deal with the problems of data sparseness and cold start problems well and the accuracy of the intelligent recommendation system has been improved. In addition, we use hash techniques to search for the neighbors, which effectively protects the privacy of the user.
Cardiovascular autonomic regulation in fighter pilots: Lessons from active standing tests
Authors: de Sá Grace Barros , Rodrigues Gabriel Dias , Soares Pedro Paulo da Silva 
Published: September 2022

AbstractFighter pilots (FP) are exposed to flight accelerations and stressful situations that defy cardiovascular control during and after flight. FP presents a smaller adjustment in sympatho‐vagal balance during tilt test after flight compared to baseline, suggesting a huge impact of flight on autonomic modulation to the heart. We undertake to test the hypothesis that FP will have a smaller vagal reentrance and lower sympathetic withdrawal during the recovery at the supine position after a prolonged active standing test that mimics flight hemodynamic demands. Twenty‐one military personnel (20–34 years old), composed of 9 FP and 12 non‐pilots (NP) matched by age, V̉O2max and body mass index were enroled in the experimental protocol. R‐R intervals were continuously recorded in the supine position for 15 min (SUPbaseline), during the prolonged active standing test (45 min) windowed in six 5 min time frames (from ORT1 to ORT6), and a recovery period in the supine position for 15 min (SUPrecovery). Heart rate variability was performed by spectral analysis to obtain the normalized low (LFn) and high (HFn) frequency components. The variation (Δ) from baseline (Δ = ORT6 − SUPbaseline) and from recovery (Δ = SUPrecovery–ORT6) periods were calculated. FP had a smaller ΔLFn (sympathetic mediated) and ΔHFn (vagal meditated) during recovery after active standing as compared to NP. Both groups showed similar changes in ΔLFn and ΔHFn during orthostatic stress compared to baseline, with no differences over time. Therefore, FP show a smaller vagal reentrance and a lower sympathetic reduction during recovery at supine following active standing compared to NP.
Over a decade of failure to implement UNEP/EUROBATS guidelines in wind energy planning: A call for action
Authors: Barré Kévin , Froidevaux Jérémy S. P. , Leroux Camille , Mariton Léa , Fritze Marcus , Kerbiriou Christian , Le Viol Isabelle , Bas Yves , Roemer Charlotte 
Published: September 2022

AbstractWind power generation has grown exponentially over the past 20 years to meet international goals of increasing the share of renewables in energy production. Yet, this process has too often been conducted at the cost of airborne biodiversity such as birds and bats. The latter are severely threatened due to deaths by collision at wind turbine. The UNEP/EUROBATS agreement that came into force in 1994 is now ratified by 37 countries; since 2008, it recommends to site wind turbines at least 200 m away from woody edges to decrease bat fatality risks. However, 14 years later we still do not know to what extent this international recommendation has been applied in Europe. We assessed siting distances between woody edges and wind turbines for the largest wind energy producers among the UNEP/EUROBATS parties: the UK, Germany, and France. We show that 61%, 78%, and 56%, respectively, of the installed wind turbines did not comply with UNEP/EUROBATS guidelines, without improvement over time. We identified probable causes of these findings and provided key policy recommendations to achieve compliance to UNEP/EUROBATS guidelines such as better: (i) inclusion in regulatory texts, (ii) notification of the environmental authorities, and (iii) strategic, well‐informed, forward planning of areas suitable for wind turbine development.
Unveiling the Relationship between Economic Growth and Equality for Developing Countries
Authors: Cheong Tsun Se , Wan Guanghua , Chui David Kam Hung 
Published: September 2022

AbstractThis study investigates the relationship between economic growth and inequality by employing the artificial neural network approach. There are many important findings. First, this work reveals the underlying functional form of economic growth and inequality by using three‐dimensional diagrams. Second, the findings show that there was an inverted‐U relationship between economic growth and inequality. This explains apparent contradictions in research findings in the literature. Third, the optimal level of inequality, which corresponds to the highest level of economic growth, is computed for different economies. Our findings were confirmed by the development processes in many developing countries and also in China in recent years, thereby highlighting the importance of inequality alleviation in promoting further economic growth. These findings enable us to derive pragmatic policy implications for other developing countries at different stages of economic development in achieving sustainable growth with equity.
Financial Literacy: The Case of China
Authors: He Yanna , Ahunov Muzaffarjon 
Published: September 2022

AbstractWe scrutinized determinants of financial literacy in China – the largest developing economy, and one with a rapidly expanding financial landscape. We used the China Household Finance Survey's 2013 and 2015 waves, which included the so‐called “Big Three” financial literacy questions that test individuals' understanding of compound interest rates, inflation, and risk. We found that financial literacy in the country was low. Our results showed that, unlike in developed countries, risk literacy in China was high and financially illiterate people's awareness of their own lack of financial skills was high. Importantly, we showed that female, old, less educated, and low‐income people were increasingly lagging in gaining financial skills. This was especially true for the western and central regions of China. Our study complements a limited number of studies on the financial literacy of the middle class in developing economies.
Early detection of developmental delay in infants born very preterm or with very low birthweight
Authors: Caesar Rebecca A. , Boyd Roslyn N. , Cioni Giovanni , Ware Robert S. , Doherty Julie , Jackson Maxine P. , Salthouse Kaye L. , Colditz Paul B. ,   PREMTiME Study Group
Published: September 2022

AbstractAimThis study aimed to identify early clinical biomarkers from birth to 16 weeks corrected age to predict typical outcome and developmental delay in infants born very preterm or with very low birthweight.MethodA prospective cohort of infants on the Sunshine Coast, Australia, was assessed using the Premie‐Neuro Examination, the General Movement Assessment (GMA), the Alberta Infant Motor Scale, and the Infant Sensory Profile 2. At 24 months corrected age, delay was identified using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley‐III) and Neurosensory Motor Developmental Assessment (NSMDA).ResultsOne hundred and four infants were recruited; 79 completed outcome assessments (43 females, 36 males; mean gestational age 30 weeks [SD 1 week 6 days], mean birthweight 1346 g [SD 323]). The incidence of developmental delay (motor or cognitive) was 6.3%. Suboptimal quality of fidgety general movements (temporal organization) at 16 weeks corrected age demonstrated the best predictive accuracy (Bayley‐III motor: sensitivity 100% [95% confidence interval {CI} 3–100], specificity 75% [95% CI 63–84], area under the curve [AUC] 0.87); Bayley‐III cognitive: sensitivity 100% [95% CI 3–100], specificity 75% [95% CI 64–84], AUC 0.88); NSMDA motor: sensitivity 100% [95% CI 40–100], specificity 81% [95% CI 70–90], AUC 0.91 [95% CI 0.86–0.95]). GMA trajectories that combined abnormal writhing general movements at 4 to 5 weeks corrected age with suboptimal quality of fidgety movement at 16 weeks corrected age were strongly predictive of developmental delay, superior to all other clinical tools, and perinatal and demographic variables investigated (p = 0.01, Akaike information criterion method 18.79 [score corrected for small sample size], accounting for 93% of the cumulative weight).InterpretationOnly the GMA had sufficient predictive validity to act as a biomarker for both conditions: typical outcome and developmental delay (motor or cognitive). GMA trajectories that assessed both writhing general movements at 4 to 5 weeks corrected age and quality of fidgety movement at 16 weeks corrected age predicted adverse neurodevelopmental outcome, accurately differentiating between infants with typical outcomes and those at increased risk for motor or cognitive delay.
Impact of case‐mix adjustment on observed variation in the healing of diabetic foot ulcers at 12 weeks using data from the National Diabetes Foot Care Audit of England and Wales: A cohort study
Authors: Yelland Arthur C. , Meace Claire , Knighton Peter , Holman Naomi , Wild Sarah H. , Michalowski Julie , Young Bob , Jeffcoate William J. 
Published: September 2022

AbstractAimThis cohort study investigates the extent to which variation in ulcer healing between services can be explained by demographic and clinical characteristics.MethodsThe National Diabetes Foot Care Audit collated data on people with diabetic foot ulcers presenting to specialist services in England and Wales between July 2014 and March 2018. Logistic regression models were created to describe associations between risk factors and a person being alive and ulcer‐free 12 weeks from presentation, and to investigate whether variation between 120 participating services persisted after risk factor adjustment.ResultsOf 27,030 people with valid outcome data, 12,925 (47.8%) were alive and ulcer‐free at 12 weeks, 13,745 (50.9%) had an unhealed ulcer and 360 had died (1.3%). Factors associated with worse outcome were male sex, more severe ulcers, history of cardiac or renal disease and a longer time between first presentation to a non‐specialist healthcare professional and first expert assessment. After adjustment for these factors, four services (3.3%) were more than 3SD above and seven services (5.8%) were more than 3SD below the national mean for proportions that were alive and ulcer‐free at follow‐up.Conclusions/InterpretationsVariation in the healing of diabetic foot ulcers between specialist services in England and Wales persisted after adjusting for demographic characteristics, ulcer severity, smoking, body mass index and co‐morbidities. We conclude that other factors contribute to variation in healing of diabetic foot ulcers and include the time to specialist assessment.