bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital research on the resilience control of water ecological space under the concept of urban-water coupling
Authors: Yang Hua , Ning Qimeng , Zhou Hui , Lai Nan , Song Qidi , Ji Qianfu , Zeng Zhiwei 
Published: October 2023

Introduction: The construction of digital governance of national land space depends greatly on the development of a digital model for robust control of water and ecological space. However, how changes to the urban-water coupling relationships affect the resilience control of water ecological space is rarely reported.Methods: The evolution characteristics of urban and water space in the study area from 2000 to 2020 and the correlation between them are analyzed based on the grid analysis using InVEST and Moran’I methods. Based on the theory of human-environment interaction territorial system to provide a theoretical framework to explain the urban and water space. We used digital to construct an resilience control framework in the Dongting Lake area based on the correlation between the urban and water space.Results: The results show that: 1) From 2000 to 2020, the geographical evolution of towns and cities in the research area displayed obvious spatial variation in intensity, indicating a process of expansion and change. The regional and temporal fluctuations of the water conservation function are significant. The mountainous areas in the east, south, and northwest are where the high values of the water conservation function are primarily found. These regions have more vegetation, which increases the water conservation function. 2) According to the results of local binary spatial autocorrelation analysis, it can be seen that from 2000 to 2020, the high-high agglomeration of town space and water-related is mainly distributed in Linxiang City, Yueyang County, Miluo City, Li County, and Yiyang City, and the low-low agglomeration is mainly distributed in Dongting Lake, Datong Lake, and along the Yangtze River. 3) Based on how urban spatial evolution affects water ecological space, we construct a theoretical framework of urban-water coupling and establish a digital model of water ecological space resilience control in the Dongting Lake area from four perspectives: threshold, visualization, dynamics, and intelligence.
Pharmacokinetic–pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses
Authors: Lallemand Elodie A. , Bousquet-Mélou Alain , Chapuis Laura , Davis Jennifer , Ferran Aude A. , Kukanich Butch , Kuroda Taisuke , Lacroix Marlène Z. , Minamijima Yohei , Olsén Lena , Pelligand Ludovic , Portugal Felipe Ramon , Roques Béatrice B. , Santschi Elizabeth M. , Wilson Katherine E. , Toutain Pierre-Louis 
Published: October 2023

IntroductionThe aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses.MethodsA population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations.ResultsA 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. ThefAUC/MIC orfT&gt;MIC were calculated with a free BP fraction set at 0.4. ForfAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. ForfT&gt;MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, afT&gt;MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L.DiscussionThe PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.
Association between the risk and severity of Parkinson’s disease and plasma homocysteine, vitamin B12 and folate levels: a systematic review and meta-analysis
Authors: Quan Yuxin , Xu Jisen , Xu Qing , Guo Zhiqing , Ou Ruwei , Shang Huifang , Wei Qianqian 
Published: October 2023

BackgroundParkinson’s disease (PD) is recognized as the second most prevalent progressive neurodegenerative disease among the elderly. However, the relationship between PD and plasma homocysteine (Hcy), vitamin B12, and folate has yielded inconsistent results in previous studies. Hence, in order to address this ambiguity, we conducted a meta-analysis to summarize the existing evidence.MethodsSuitable studies published prior to May 2023 were identified by searching PubMed, EMBASE, Medline, Ovid, and Web of Science. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Meta-analysis and publication bias were then performed using R version 4.3.1.ResultsThe results of our meta-analysis, consisting of case–control and cross-sectional studies, showed that PD patients had lower folate and vitamin B12 levels (SMD [95%CI]: −0.30[−0.39, −0.22], p &lt; 0.001 for Vitamin B12; SMD [95%CI]: −0.20 [−0.28, −0.13], p &lt; 0.001 for folate), but a significant higher Hcy level (SMD [95%CI]: 0.86 [0.59, 1.14], p &lt; 0.001) than healthy people. Meanwhile, PD was significantly related to hyperhomocysteinemia (SMD [95%]: 2.02 [1.26, 2.78], p &lt; 0.001) rather than plasma Hcy below 15 μmol/L (SMD [95%]: −0.31 [−0.62, 0.00], p = 0.05). Subgroup analysis revealed associations between the Hcy level of PD patients and region (p = 0.03), age (p = 0.03), levodopa therapy (p = 0.03), Hoehn and Yahr stage (p &lt; 0.001), and cognitive impairment (p &lt; 0.001). However, gender (p = 0.38) and sample size (p = 0.49) were not associated.ConclusionHcy, vitamin B12, and folic acid potentially predict the onset and development of PD. Additionally, multiple factors were linked to Hcy levels in PD patients. Further studies are needed to comprehend their roles in PD.
The auditory function in migraine model rats induced by postauricular nitroglycerin injection
Authors: Qi Rongxiang , Zhang Jilei , Diao Tongxiang , Yu Lisheng 
Published: October 2023

ObjectiveThe mechanism by which migraines produce inner ear-related symptoms is not well understood. Previous studies have found that the latency of auditory brainstem response (ABR) in animal models of migraine has changed, but the threshold has not changed significantly. Therefore, it is necessary to establish a better animal model with both migraine and hearing loss to explore the relationship between migraine and auditory function deeply.MethodsIn this study, the rat model of migraine was induced by postauricular injection of nitroglycerin (NTG), and the effect on the auditory function of the inner ear was explored by comparing with intraperitoneal injection of nitroglycerin. The rats were given the drug repeatedly on alternate days, a total of 5 dosing, with the body weight monitored during the drug administration. The tactile threshold of the rats' forepaw was measured using von-Frey filaments and auditory function was assessed by ABR.ResultsThe results showed that the baseline tactile threshold of rats gradually decreased during the modeling process, and hyperalgesia appeared. Postauricular injection of NTG did not affect the weight gain of rats, while intraperitoneal injection of NTG showed slow or even negative weight gain. The ABR threshold of Click, 4 and 8 kHz of postauricular NTG injection rats increased, the latency was prolonged, and the ABR threshold in the right ear was higher than that in the left ear.ConclusionsWe demonstrated that postauricular injection of nitroglycerin may be safer and more effective than intraperitoneal injection of nitroglycerin in the process of creating rat migraine model without affecting the weight gain. Postauricular injection of nitroglycerin has more damage to the auditory function of rats. Therefore, the migraine model rat induced by postauricular injection of nitroglycerin may be a new model of cochlear migraine.
Frequency dependent whole-brain coactivation patterns analysis in Alzheimer’s disease
Authors: Zhang Si-Ping , Mao Bi , Zhou Tianlin , Su Chun-Wang , Li Chenxi , Jiang Junjie , An Simeng , Yao Nan , Li Youjun , Huang Zi-Gang ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2023

BackgroundThe brain in resting state has complex dynamic properties and shows frequency dependent characteristics. The frequency-dependent whole-brain dynamic changes of resting state across the scans have been ignored in Alzheimer’s disease (AD).ObjectiveCoactivation pattern (CAP) analysis can identify different brain states. This paper aimed to investigate the dynamic characteristics of frequency dependent whole-brain CAPs in AD.MethodsWe utilized a multiband CAP approach to model the state space and study brain dynamics in both AD and NC. The correlation between the dynamic characteristics and the subjects’ clinical index was further analyzed.ResultsThe results showed similar CAP patterns at different frequency bands, but the occurrence of patterns was different. In addition, CAPs associated with the default mode network (DMN) and the ventral/dorsal visual network (dorsal/ventral VN) were altered significantly between the AD and NC groups. This study also found the correlation between the altered dynamic characteristics of frequency dependent CAPs and the patients’ clinical Mini-Mental State Examination assessment scale scores.ConclusionThis study revealed that while similar CAP spatial patterns appear in different frequency bands, their dynamic characteristics in subbands vary. In addition, delineating subbands was more helpful in distinguishing AD from NC in terms of CAP.
Evaluation of subjective visual vertical and horizontal in patients with acoustic neuroma based on virtual reality
Authors: Zhang Lin , Ouyang Shunlin , Chen Ling , Huang Hemei , Ou Yongkang , Tang Xiaowu 
Published: October 2023

ObjectiveTo investigate potential differences in absolute deviation values of subjective visual vertical and horizontal between unilateral acoustic neuroma patients and healthy young adults under varying degrees of static head tilt, as well as the impact of proprioception on these values, with the aim of determining the effect of acoustic neuroma on gravity sensory pathway function in patients.MethodsWe recruited 22 patients diagnosed with unilateral acoustic neuroma and 25 healthy young adults and employed virtual reality technology to assess the absolute deviation values of subjective visual vertical (SVV) and subjective visual horizontal (SVH) under eight different static tilted head positions (Head centered (0° tilt), PdP, Head tilt 15°, 30°, 45° to the left and right), then compare and analyze intergroup differences.ResultsIn the Head-centered position, both SVV and SVH absolute deviated values were significantly higher in the AN group compared to healthy young adults. The AN group exhibited significantly higher absolute deviation values of SVV compared to the healthy group when tilting their head 30° left and right. Additionally, when tilting their heads to the right at 15° and 45° the AN group showed significant increases in SVH absolute deviated values compared to healthy adults. The SVV and SVH absolute deviation values of LAN and SAN groups did not reach statistical significance. The results of the SVV test for PDP position did not show any significant differences among all groups. However, the SVH test revealed that the absolute deviation values of the LAN group was significantly higher than that of healthy individuals.ConclusionOur study shows that the gravity sensing function of patients with unilateral acoustic neuroma is affected to different degrees, however, the degree of gravity sensing function damage of patients has little relationship with tumor size. When acoustic neuroma is larger than 2 cm, the effect of proprioception on patients’ SVH outcome is noteworthy. So, we should pay attention to the postoperative follow-up of patients with acoustic neuroma and the evaluation of vestibular rehabilitation effect. Meanwhile, for patients opting for conservative treatment, it is imperative to monitor the dynamic changes in vestibular function and seize timely opportunities for intervention.
Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation
Authors: Chen Ziyuan , Wang Pengfei , Cheng Hao , Wang Ning , Wu Mingzhe , Wang Ziwei , Wang Zhi , Dong Wenwen , Guan Dawei , Wang Linlin , Zhao Rui 
Published: October 2023

BackgroundTraumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI.MethodsA total of 160 male mice aged 8 weeks were used to mimic moderate TBI by controlled cortical impact. At 1, 3, 6 and 12 months post-injury (mpi), different neurological functions were evaluated by elevated plus maze, forced swimming test, sucrose preference test and Morris water maze. The levels of oxidative stress, antioxidant response, reactive astrocytes and microglia, and expression of inflammatory cytokines were subsequently assessed in the ipsilateral hippocampus, followed by neuronal apoptosis detection. Additionally, the morphological complexity of hippocampal astrocytes was evaluated by Sholl analysis.ResultsThe adolescent mice exhibited persistent and incremental deficits in memory and anxiety-like behavior after TBI, which were sharply exacerbated at 12 mpi. Depression-like behaviors were observed in TBI mice at 6 mpi and 12 mpi. Compared with the age-matched control mice, apoptotic neurons were observed in the ipsilateral hippocampus during the chronic phase of TBI, which were accompanied by enhanced oxidative stress, and expression of inflammatory cytokines (IL-1β and TNF-α). Moreover, the reactive astrogliosis and microgliosis in the ipsilateral hippocampus were observed in the late phase of TBI, especially at 12 mpi.ConclusionAdolescent TBI leads to incremental cognitive dysfunction, and depression- and anxiety-like behaviors in middle-aged mice. The chronic persistent neuroinflammation and oxidative stress account for the neuronal loss and neural dysfunction in the ipsilateral hippocampus. Our results provide evidence for the pathogenesis of chronic neural damage following TBI and shed new light on the treatment of TBI-induced late-phase neurological dysfunction.
The causal association between obesity and gastric cancer and shared molecular signatures: a large-scale Mendelian randomization and multi-omics analysis
Authors: Xing Abao , Tong Henry H. Y. , Liu Songyan , Zhai Xiaobing , Yu Li , Li Kefeng 
Published: October 2023

PurposeWhile observational studies have identified obesity as a potential risk factor for gastric cancer, the causality remains uncertain. This study aimed to evaluate the causal relationship between obesity and gastric cancer and identify the shared molecular signatures linking obesity to gastric cancer.MethodsA two-sample Mendelian randomization (MR) analysis was conducted using the GWAS data of body fat percentage (exposure, n = 331,117) and gastric cancer (outcome, n = 202,308). Bioinformatics and meta-analysis of multi-omics data were performed to identify key molecules mediating the causality. The meta-analysis of the plasma/serum proteome included 1,662 obese and 3,153 gastric cancer patients. Obesity and gastric cancer-associated genes were identified using seven common gene ontology databases. The transcriptomic data were obtained from TCGA and GEO databases. The Bioinformatic findings were clinically validated in plasma from 220 obese and 400 gastric cancer patients across two hospitals. Finally, structural-based virtual screening (SBVS) was performed to explore the potential FDA-approved drugs targeting the identified mediating molecules.ResultsThe MR analysis revealed a significant causal association between obesity and gastric cancer (IVW, OR = 1.37, 95% CI:1.12-1.69, P = 0.0028), without pleiotropy or heterogeneity. Bioinformatic and meta-analysis of multi-omics data revealed shared TNF, PI3K-AKT, and cytokine signaling dysregulation, with significant upregulation of AKT1, IL-6, and TNF. The clinical study confirmed widespread upregulation of systemic inflammatory markers in the plasma of both diseases. SBVS identified six novel potent AKT1 inhibitors, including the dietary supplement adenosine, representing a potentially preventive drug with low toxicity.ConclusionObesity causally increases gastric cancer, likely mediated by persistent AKT1/IL-6/TNF upregulation. As a potential AKT1 inhibitor, adenosine may mitigate the obesity-to-gastric cancer transition. These findings could inform preventive drug development to reduce gastric cancer risk in obesity.
Identification and characterization of interferon-γ signaling-based personalized heterogeneity and therapeutic strategies in patients with pancreatic cancer
Authors: Chen Xu , Yuan Qihang , Guan Hewen , Shi Xueying , Sun Jiaao , Wu Zhiqiang , Ren Jie , Xia Shilin , Shang Dong 
Published: October 2023

BackgroundInterferon-γ (IFN-γ) is a key cytokine with diverse biological functions, including antiviral defense, antitumor activity, immune regulation, and modulation of cellular processes. Nonetheless, its role in pancreatic cancer (PC) therapy remains debated. Therefore, it is worthwhile to explore the role of Interferon-γ related genes (IFN-γGs) in the progression of PC development.MethodologyTranscriptomic data from 930 PC were sourced from TCGA, GEO, ICGC, and ArrayExpress, and 93 IFN-γGs were obtained from the MSigDB. We researched the characteristics of IFN-γGs in pan-cancer. Subsequently, the cohort of 930 PC was stratified into two distinct subgroups using the NMF algorithm. We then examined disparities in the activation of cancer-associated pathways within these subpopulations through GSVA analysis. We scrutinized immune infiltration in both subsets and probed classical molecular target drug sensitivity variations. Finally, we devised and validated a novel IFN-γ related prediction model using LASSO and Cox regression analyses. Furthermore, we conducted RT-qPCR and immunohistochemistry assays to validate the expression of seven target genes included in the prediction model.ResultsWe demonstrated the CNV, SNV, methylation, expression levels, and prognostic characteristics of IFN-γGs in pan-cancers. Notably, Cluster 2 demonstrated superior prognostic outcomes and heightened immune cell infiltration compared to Clusters 1. We also assessed the IC50 values of classical molecular targeted drugs to establish links between IFN-γGs expression levels and drug responsiveness. Additionally, by applying our prediction model, we segregated PC patients into high-risk and low-risk groups, identifying potential benefits of cisplatin, docetaxel, pazopanib, midostaurin, epothilone.B, thapsigargin, bryostatin.1, and AICAR for high-risk PC patients, and metformin, roscovitine, salubrinal, and cyclopamine for those in the low-risk group. The expression levels of these model genes were further verified through HPA website data and qRT-PCR assays in PC cell lines and tissues.ConclusionThis study unveils IFN-γGs related molecular subsets in pancreatic cancer for the first time, shedding light on the pivotal role of IFN-γGs in the progression of PC. Furthermore, we establish an IFN-γGs related prognostic model for predicting the survival of PC, offering a theoretical foundation for exploring the precise mechanisms of IFN-γGs in PC.
Knowledge mapping and current trends of Warburg effect in the field of cancer
Authors: Zhao Quan , Wang Lina , Lv Zongwei , Wang Xia , Xu Zhenqun , Wang Kefeng 
Published: October 2023

BackgroundSince abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics.MethodsArticles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software.ResultsOver the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends.ConclusionThe study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.
Identification of a prognostic evaluator from glutamine metabolic heterogeneity studies within and between tissues in hepatocellular carcinoma
Authors: Bao Jie , Yu Yan 
Published: October 2023

Background: The liver is the major metabolic organ of the human body, and abnormal metabolism is the main factor influencing hepatocellular carcinoma (HCC). This study was designed to determine the effect of glutamine metabolism on HCC heterogeneity and to develop a prognostic evaluator based on the heterogeneity study of glutamine metabolism within HCC tumors and between tissues.Methods: Single-cell transcriptome data were extracted from the GSE149614 dataset and processed using the Seurat package in R for quality control of these data. HCC subtypes in the Cancer Genome Atlas and the GSE14520 dataset were identified via consensus clustering based on glutamine family amino acid metabolism (GFAAM) process genes. The machine learning algorithms gradient boosting machine, support vector machine, random forest, eXtreme gradient boosting, decision trees, and least absolute shrinkage and selection operator were utilized to develop the prognosis model of differentially expressed genes among the molecular gene subtypes.Results: The samples in the GSE149614 dataset included 10 cell types, and there was no significant difference in the GFAAM pathway. HCC was classified into three molecular subtypes according to GFAAM process genes, showing molecular heterogeneity in prognosis, clinicopathological features, and immune cell infiltration. C1 showed the worst survival rate and the highest immune score and immune cell infiltration. A six-gene model for prognostic and immunotherapy responses was constructed among subtypes, and the calculated high-risk score was significantly correlated with poor prognosis, high immune abundance, and a low response rate of immunotherapy in HCC.Conclusion: Our discovery of GFAAM-associated marker genes may help to further decipher the role in HCC occurrence and progression. In particular, this six-gene prognostic model may serve as a predictor of treatment and prognosis in HCC patients.