bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamic change of propagation from meteorological drought to hydrological drought at the basin scale: A case study from the Weihe River Basin, China
Authors: Zhao Panpan , Xie Bingbo , Huang Xudong , Qu Bo
Published: November 2022

Current climate change has led to frequent drought events in the Weihe River Basin, and the risks and impacts of drought are becoming increasingly severe. In order to study meteorological drought and hydrological drought at different scales and the propagation of drought between them, in this study, meteorological and hydrological drought conditions were calculated for 3-, 6-, 9-, and 12-month timescales based on 56 years of monthly precipitation and monthly runoff data of the Weihe River Basin using the Standardized Precipitation Index (SPI) and the Streamflow Drought Index (SDI), respectively. We explore analyzing the differences between them and their relationship and establishing regression equations based on the relationship and the dynamic propagation time of meteorological and hydrological droughts at different timescales. The results demonstrate that 1) the frequencies of both meteorological and hydrological droughts have shown an increasing trend in the last 56 years; 2) the relationship between meteorological drought and hydrological drought varied over time; 3) according to dynamic change analysis, propagation time tends to be shorter on the 3-month timescale and longer on the 6-month, 9-month, and 12-month timescales; and 4) the accelerated propagation time between meteorological drought and hydrological drought may be related to the increase in precipitation and temperature. The findings not only provide scientific support for the formulation of drought prevention and disaster reduction strategies in this basin but also have important scientific and practical application value.
Effectiveness and characteristics of atmospheric CO2 removal in croplands via enhanced weathering of industrial Ca-rich silicate byproducts
Authors: Yoshioka Rina , Nakamura Kengo , Sekiai Ryota , Wang Jiajie , Watanabe Noriaki
Published: November 2022

Enhanced weathering of industrial Ca-rich silicate byproducts in croplands is potentially profitable for large-scale atmospheric CO2 removal; during the weathering process, CO2 dissolves to form HCO3− and CO32− in alkaline soil pore water, which eventually flows into the ocean. However, the effectiveness of such systems is still in doubt, owing to the unrealistic models used for prediction and the insufficient consideration of the dynamic influences of soils on fluid chemistry. We determined the effectiveness of such systems for atmospheric CO2 removal, along with their characteristics, through a set of batch- and flow-through-type laboratory experiments, using andosol and decomposed granite soil as agricultural and non-agricultural soils, respectively, and Portland cement, steelmaking slag, and coal fly ash as industrial byproducts. The results of the batch-type experiments demonstrated that agricultural soils were suitable for CO2 removal, owing to their moderately high pH and Ca concentrations in pore water that prevented intensive calcium carbonate precipitation. The flow-through experiments demonstrated that a higher Ca-content byproduct can have a large atmospheric CO2 removal capacity. However, the magnitude of CO2 removal and its time-dependent behavior were difficult to predict because they were not in conjunction with the changes in the average pH value. This indicated that the diffusive transport of CO2 from the atmosphere-soil interface to deeper soils was more complex than expected. Maximizing CO2 removal requires a better understanding of the diffusive transport of CO2 through gas-filled pore spaces, created by unsteady-state air–water two-phase flow, due to intermittent rainfall.
Water pollution, industrial agglomeration and economic growth: Evidence from China
Authors: Huang Can , Wang Chien-Ming
Published: November 2022

This paper investigates the causal relationship between water pollution, industrial agglomeration, and economic growth in 11 Chinese provinces in China. Using a bootstrap autoregressive distributed lag (ARDL) analysis, we examine the estimated models’ stability and investigate the Granger causality relationships between system variables. The results indicate that our estimation provides evidence of a long-run relationship between water pollution, industrial agglomeration, and economic growth in China. The bidirectional running from other water pollution variables is confirmed from the casualty tests in Shanghai and Yunnan. Specifically, the unidirectional causality relationship running from industrial agglomeration and economic growth to water pollution provide statistical evidence of the important role that industrial agglomeration and economic growth play in increasing water pollution.
Isotopic (δ2H and δ13C) tracing the provenance and fate of individual fatty acids fueling migrating animals: A case study of the monarch butterfly (Danaus plexippus)
Authors: Pilecky Matthias , Wassenaar Leonard I. , Kainz Martin J. , Anparasan Libesha , Ramirez M. Isabel , McNeil Jeremy N. , Hobson Keith A.
Published: November 2022

Introduction

Among long-distance migratory insects, the monarch butterfly (Danaus plexippus) is one of the most iconic, whose journey is fueled by nectar from flowering plants along the migratory route which may involve up to 3,500 km. Understanding how and where monarchs obtain their dietary resources to fuel migratory flight and ensure overwintering stores would provide new insights into the migratory strategy of this species and subsequently help focus conservation efforts.

Methods

This pilot study was designed as a first attempt to assess the composition, dynamics, and isotopic (δ2H, δ13C) composition of essential and non-essential fatty acids (FA) acquired or manufactured de novo from larval host milkweed (Asclepias spp.) by monarch butterflies and from adult emergence to overwintering.

Results

Data from controlled laboratory isotopic tracer tests suggested that adult monarchs convert their dietary energy mainly into 16:0 and 18:1 fatty acids and store them as neutral lipids in their abdomen. FA isotopic composition reflects not only dietary sources but also subsequent isotopic fractionation from metabolism. On the other hand, δ2H values of essential omega-3 fatty acid alpha-linolenic acid (ALA) correlated with δ2HWing, as markers of an individual’s geographic origin and indicated the importance of larval diet. Additionally, in wild-type females, high isotopic fractionation in δ13CALA between neutral and polar lipids might indicate increased bioconversion activity during gravidity. Finally, δ2HLIN showed positive H isotope fractionation from larval dietary sources, indicating that catabolic processes were involved in their manufacture. Furthermore, δ2HLIN showed a negative correlation with δ2HWing values, which could potentially be useful when investigating individual life-history traits, such as migratory catabolic efforts or periods of fasting.

Discussion

This interpretation was supported by significant larger variations in δ2HLIN and δ2HLIN overwintering monarchs compared to other FA. Altogether, our results provide the first evidence that the H isotopic analysis of individual fatty acids in migrating and overwintering monarchs can be used to infer the nutritional history of individuals including the provenance of nectaring sites used to fuel key life history events.
Heat wave induces oxidative damage in the Chinese pond turtle (Mauremys reevesii) from low latitudes
Authors: Tao Weijie , Ou Junwei , Wu Danyang , Zhang Qiong , Han Xingzhi , Xie Lei , Li Shuran , Zhang Yongpu
Published: November 2022

Introduction

Global warming has led to frequent heat waves, causing global organisms to face severe survival challenges. However, the way in which heat waves threaten the fitness and survival of animals remains largely unclear. Oxidative damage and immunity are widely considered the link between heat waves and threats to animals.

Methods

To evaluate the oxidative damage caused by heat waves and to reveal the physiological resistance to heat waves by the antioxidant defense of animals from different latitudes, we exposed both high-latitude (Zhejiang) and low-latitude (Hainan) populations of Chinese pond turtle (Mauremys reevesii) to simulate heat waves and a moderate thermal environment for 1 week, respectively. Next, we compared the oxidative damage by malondialdehyde (MDA) and antioxidant capacity by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity (T-AOC) in the liver tissues and evaluated the innate immunity by serum complement protein levels (C3, C4) and lysozyme activity in plasma of turtles.

Results and discussion

We found that heat waves significantly increased the content of MDA and the activity of CAT, whereas it decreased the activity of SOD, T-AOC, and GSH/GSSG in turtles from low latitudes. Furthermore, heat waves increased CAT activity but decreased GSH/GSSG in turtles from high latitudes. Although the turtles from high latitudes had higher levels of innate immunity, the heat waves did not affect the innate immunity of C3, C4, or lysozyme in either population. These results indicate that the low-latitude population suffered higher oxidative damage with lower antioxidant capacities. Therefore, we predict that Chinese pond turtles from low latitudes may be more vulnerable to heat waves caused by climate warming. This study reveals the physiological and biochemical resistance to heat waves in Chinese pond turtles from different latitudes and highlights the importance of integrative determination of fitness-related responses in evaluating the vulnerability of ectotherms from different latitudes to climate warming.
What makes a good phorophyte? Predicting occupancy, species richness and abundance of vascular epiphytes in a lowland seasonal tropical forest
Authors: Shen Ting , Song Liang , Collart Flavien , Guisan Antoine , Su Yang , Hu Hai-Xia , Wu Yi , Dong Jin-Long , Vanderpoorten Alain
Published: November 2022

Epiphytes typically exhibit clustered distribution patterns, but predicting the spatial variation of their distribution at fine scales has long been a challenge. Taking advantage of a canopy crane giving access to 1.1 ha of lowland seasonal rainforest in Yunnan (China), we assess here which factors promote the probability that a given tree hosts epiphytes, and the variation of species richness and abundance of epiphytic spermatophytes and ferns among trees. Variation in epiphyte species richness as a function of host tree size, characteristics of its surrounding environment, topography and microclimatic conditions, were analyzed by Random Forest. Epiphytic spermatophytes and ferns occupied 2.3 and 10.8% of the available host trees, respectively. Significant models predicting which trees are more likely to host epiphytes than others were obtained, indicating that host tree characteristics and their local environment play a significant role in determining which host tree is most likely to be colonized. These models, as well as models for species richness and abundance, however, exhibited a moderate to low accuracy (r2 0.28 and 0.24 and of 0.12 and 0.14 for spermatophyte and fern richness and abundance, respectively). The best predictor of the presence of epiphytes on a tree, of its epiphytic species richness and abundance, was its DBH. In ferns, however, two peaks of species richness were observed, representing shade-loving ferns on small trees and sun-loving ferns on large trees. Microclimatic conditions and light intensity were the second best factor accounting for variation in species richness and abundance among trees. The contribution of liana infestation, host tree identity, and characteristics of neighboring trees were marginal. Our inclusion of a large number of host-tree characteristics and their local environment did not allow for an apparent improvement of model accuracy over studies with a more limited number of predictors, pointing to the role of chance upon tree colonization. Our results confirm the utmost importance of large trees with emergent canopies for the conservation of the epiphytic flora, but also indicate that epiphytic diversity assessments in tropical forests must also include small understorey trees, which should be further considered for conservation. The importance of the micro-climatic conditions that prevail at the level of each individual host tree further points to the necessity of maintaining a buffer zone around large host trees targeted for conservation.
Comprehensive bioinformatics analysis reveals biomarkers of DNA methylation-related genes in varicose veins
Authors: Li Shengyu , Liu Yuehan , Liu Mingming , Wang Lizhao , Li Xiaofeng
Published: November 2022

Background: Patients with Varicose veins (VV) show no obvious symptoms in the early stages, and it is a common and frequent clinical condition. DNA methylation plays a key role in VV by regulating gene expression. However, the molecular mechanism underlying methylation regulation in VV remains unclear.

Methods: The mRNA and methylation data of VV and normal samples were obtained from the Gene Expression Omnibus (GEO) database. Methylation-Regulated Genes (MRGs) between VV and normal samples were crossed with VV-associated genes (VVGs) obtained by weighted gene co-expression network analysis (WGCNA) to obtain VV-associated MRGs (VV-MRGs). Their ability to predict disease was assessed using receiver operating characteristic (ROC) curves. Biomarkers were then screened using a random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM). Next, gene set enrichment analysis (GSEA) was performed to explore the functions of biomarkers. Furthermore, we also predicted their drug targets, and constructed a competing endogenous RNAs (ceRNA) network and a drug target network. Finally, we verified their mRNA expression using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Total three VV-MRGs, namely Wnt1-inducible signaling pathway protein 2 (WISP2), Cysteine-rich intestinal protein 1 (CRIP1), and Odd-skipped related 1 (OSR1) were identified by VVGs and MRGs overlapping. The area under the curves (AUCs) of the ROC curves for these three VV-MRGs were greater than 0.8. RF was confirmed as the optimal diagnostic model, and WISP2, CRIP1, and OSR1 were regarded as biomarkers. GSEA showed that WISP2, CRIP1, and OSR1 were associated with oxidative phosphorylation, extracellular matrix (ECM), and respiratory system functions. Furthermore, we found that lncRNA MIR17HG can regulate OSR1 by binding to hsa-miR-21-5p and that PAX2 might treat VV by targeting OSR1. Finally, qRT-PCR results showed that the mRNA expression of the three genes was consistent with the results of the datasets.

Conclusion: This study identified WISP2, CRIP1, and OSR1 as biomarkers of VV through comprehensive bioinformatics analysis, and preliminary explored the DNA methylation-related molecular mechanism in VV, which might be important for VV diagnosis and exploration of potential molecular mechanisms.
Network pharmacology- and molecular docking-based approaches to unveil the pharmacological mechanisms of dihydroartemisinin against esophageal carcinoma
Authors: Wang Haixia
Published: November 2022

Objective: Dihydroartemisinin (DHA) is an active metabolite of artemisinin and its derivatives, which is a potent drug extensively applied in clinical treatment of malaria. The antitumor properties of DHA have received increasing attention. However, there is no systematic summary on the pharmacological mechanisms of DHA against esophageal carcinoma (ESCA). The present study implemented network pharmacology- and molecular docking-based approaches to unveil the pharmacological mechanisms of DHA against ESCA.

Methods: DHA targets were accessed through integrating the SwissTargetPrediction, HERB, as well as BATMAN-TCM platforms. In TCGA-ESCA dataset, genes with differential expression were screened between 161 ESCA and 11 normal tissue specimens. DHA targets against ESCA were obtained through intersection. Their biological significance was evaluated with functional enrichment analysis. A prognostic signature was established via uni- and multivariate cox regression analyses. DHA-target interactions were predicted via molecular docking. Molecular dynamics simulation was implemented to examine the stability of DHA binding to potential targets. Results: The study predicted 160 DHA targets as well as 821 genes with differential expression in ESCA. Afterwards, 16 DHA targets against ESCA were obtained, which remarkably correlated to cell cycle progression. The ADORA2B- and AURKA-based prognostic signature exhibited the reliability and independency in survival prediction. The stable docking of DHA-ADORA2B and DHA-AURKA was confirmed.

Conclusion: Collectively, this study systematically revealed the basis and mechanism of DHA against ESCA through targeting multi-target and multi-pathway mechanisms, and thus offered theoretical and scientific basis for the clinical application of DHA.
Immunogenomic correlates of immune-related adverse events for anti–programmed cell death 1 therapy
Authors: Zhang Lei , Shi Yuankai , Han Xiaohong
Published: November 2022

Despite impressive antitumor efficacy of programmed cell death 1 (PD-1) inhibitors, this inhibition can induce mild to severe autoimmune toxicities, termed immune-related adverse events (irAEs). Yet, predictive pretreatment biomarkers for irAEs development across cancer types remain elusive. We first assessed cellular and molecular factors. To determine factors predicting the risk of irAEs for anti–PD-1 immunotherapy across multiple cancer types, an integrative analysis of cellular and molecular factors from 9104 patients across 21 cancer types and 4865522 postmarketing adverse event reports retrieved from adverse event reporting system was then performed. Accuracy of predictions was quantified as Pearson correlation coefficient determined using leave-one-out cross-validation. Independent validation sets included small cell lung cancer and melanoma cohorts. Out of 4865522 eligible adverse events reports, 10412 cases received anti–PD-1 monotherapy, of which, 2997 (28.78%) exhibited at least one irAE. Among established immunogenomic factors, dendritic cells (DC) abundance showed the strongest correlation with irAEs risk, followed by tumor mutational burden (TMB). Further predictive accuracy was achieved by DC and TMB in combination with CD4+ naive T-cells abundance, and then validated in the small cell lung cancer cohort. Additionally, global screening of multiomics data identified 11 novel predictors of irAEs. Of these, IRF4 showed the highest correlation. Best predictive performance was observed in the IRF4 – TCL1A – SHC-pY317 trivariate model. Associations of IRF4 and TCL1A expression with irAEs development were verified in the melanoma cohort receiving immune checkpoint inhibitors. Collectively, pretreatment cellular and molecular irAEs-associated features as well as their combinations are identified regardless of cancer types. These findings may deepen our knowledge of irAEs pathogenesis and, ultimately, aid in early detection of high-risk patients and management of irAEs.
Identification of two robust subclasses of sepsis with both prognostic and therapeutic values based on machine learning analysis
Authors: Zhou Wei , Zhang Chunyu , Zhuang Zhongwei , Zhang Jing , Zhong Chunlong
Published: November 2022

Background

Sepsis is a heterogeneous syndrome with high morbidity and mortality. Optimal and effective classifications are in urgent need and to be developed.

Methods and results

A total of 1,936 patients (sepsis samples, n=1,692; normal samples, n=244) in 7 discovery datasets were included to conduct weighted gene co-expression network analysis (WGCNA) to filter out candidate genes related to sepsis. Then, two subtypes of sepsis were classified in the training sepsis set (n=1,692), the Adaptive and Inflammatory, using K-means clustering analysis on 90 sepsis-related features. We validated these subtypes using 617 samples in 5 independent datasets and the merged 5 sets. Cibersort method revealed the Adaptive subtype was related to high infiltration levels of T cells and natural killer (NK) cells and a better clinical outcome. Immune features were validated by single-cell RNA sequencing (scRNA-seq) analysis. The Inflammatory subtype was associated with high infiltration of macrophages and a disadvantageous prognosis. Based on functional analysis, upregulation of the Toll-like receptor signaling pathway was obtained in Inflammatory subtype and NK cell-mediated cytotoxicity and T cell receptor signaling pathway were upregulated in Adaptive group. To quantify the cluster findings, a scoring system, called, risk score, was established using four datasets (n=980) in the discovery cohorts based on least absolute shrinkage and selection operator (LASSO) and logistic regression and validated in external sets (n=760). Multivariate logistic regression analysis revealed the risk score was an independent predictor of outcomes of sepsis patients (OR [odds ratio], 2.752, 95% confidence interval [CI], 2.234-3.389, P<0.001), when adjusted by age and gender. In addition, the validation sets confirmed the performance (OR, 1.638, 95% CI, 1.309-2.048, P<0.001). Finally, nomograms demonstrated great discriminatory potential than that of risk score, age and gender (training set: AUC=0.682, 95% CI, 0.643-0.719; validation set: AUC=0.624, 95% CI, 0.576-0.664). Decision curve analysis (DCA) demonstrated that the nomograms were clinically useful and had better discriminative performance to recognize patients at high risk than the age, gender and risk score, respectively.

Conclusions

In-depth analysis of a comprehensive landscape of the transcriptome characteristics of sepsis might contribute to personalized treatments and prediction of clinical outcomes.
Natural and oil surface slicks as microbial habitats in marine systems: A mini review
Authors: Voskuhl Lisa , Rahlff Janina
Published: November 2022

Natural and oil surface slicks are widespread phenomena at the air-water interface and represent visible surface films with distinct physicochemical and biological properties compared to non-slick surface films and underlying marine water. Both types of slicks have major functions in nourishing and dispersing surface-dwelling micro- and macroorganisms, contribute to particle generation and carbon cycling, and are known to accumulate pollutants. Despite these functions and the high frequency of slicks in the marine environment, slicks are little understood considering their microbial inhabitants and contributions of these organisms for natural and oil slick establishment, function, and ecology. Our mini review summarizes the current knowledge of microbial life in natural slicks, natural and anthropogenic oil slicks, including the major knowledge gaps and perspectives for future research. Overall, we aim for an increased awareness about the existence of natural slicks, the differentiation between natural and anthropogenic oil slicks and an improved reporting of slick events during sampling of surface film and seawater from the epipelagic zone.
Low high-density lipoprotein cholesterol levels predicting poor outcomes in patients with hepatitis B virus-related acute-on-chronic liver failure
Authors: Zhang Yue , Chen Peng , Zhang Yun , Nie Yuan , Zhu Xuan
Published: November 2022

Background

Lipid profile disorders frequently occur in patients with advanced liver diseases. High-density lipoprotein cholesterol (HDL-C) levels decrease rapidly during acute conditions of some diseases, and HDL-C levels may be related to mortality in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).

Materials and methods

A retrospective cohort study was conducted on 200 subjects with HBV-ACLF. The patients were separated into non-survivors and survivors according to their 28-day outcome. Univariate and multivariate Cox regression analyses were performed to identify predictors of mortality, and the performance of these predictors was evaluated by receiver operating characteristic (ROC) curve analysis. Kaplan–Meier analysis was performed to draw survival curves of HDL-C.

Results

The 28-day mortality in the cohort was 27.0%. HDL-C levels differed markedly between non-survivors and survivors. In the multivariate analysis, HDL-C, the Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH-ACLF II) scores were identified as independent predictors for mortality (HR = 0.806, 95% CI: 0.724–0.898; HR = 1.424, 95% CI: 1.143–1.775; HR = 1.006, 95% CI: 1.002–1.007; and HR = 1.609, 95% CI: 1.005–2.575, respectively). Patients with lower HDL-C levels had a worse prognosis than those with higher HDL-C levels. In ROC analysis, the prognostic accuracy for mortality was similar between HDL-C (AUROC: 0.733) and the CTP, MELD, and COSSH-ACLF II scores (AUROC: 0.753; 0.674 and 0.770, respectively).

Conclusion

The HDL-C level may serve as a potential indicator for the prognosis of HBV-ACLF and can be used as a simple marker for risk assessment and selection of therapeutic options.
Global excellence in rheumatology: Africa–The contribution of African women rheumatologists
Authors: Hmamouchi Ihsane , Adebajo Adewale
Published: November 2022

Over the last few decades, the development of Rheumatology on the African continent has made great strides. Alongside an increasing recognition of the prevalence and burden of disease from these conditions, has been a determination to raise awareness of these disorders in Africa together with an appreciation of the associated disease impact on individuals, families and society as a whole. Great improvements have also been made across the continent with regards to the education of medical students, trainee doctors and allied health professionals of these conditions. Furthermore, high quality rheumatological research is now emanating from Africa. Taken together, these actions mean that Africa is making a significant contribution to global excellence in Rheumatology. Although this achievement has been made possible by visionary, hardworking and inspirational men and women, we believe that it is vital to bring to light the extraordinary efforts of African female rheumatologists in this endeavor. Their contribution is all the more remarkable because of the barriers that women still face in medicine in general and in academia in particular. We showcase here, four women of distinction who in their own unique way, have exemplified the contribution of African female rheumatologists to global excellence in Africa. We pay tribute to them and to their ongoing efforts to act as beacons of excellence in rheumatology in Africa to men and especially to other women.
Genetic diversity of Bartonella infection in residential and field rodents in Hebei, China
Authors: Jian Rui , Ren Qing , Xue Jing , Xie Guang-Cheng , Wang Jiangli , Chen Guo-Qing , Du Luanying , Guo Wen-Ping
Published: November 2022

Rodents are the primary natural reservoirs of Bartonella spp., and some of which are zoonotic causative agents. Hence, surveillance of Bartonella sp. infection in rodents is very important for the prevention of human bartonellosis caused by them. In this study, rodents were captured, and their spleen samples were collected for Bartonella sp. DNA detection and identification by amplifying the 16S rRNA, gltA, and ftsz genes using semi-nested polymerase chain reaction (PCR). The results indicated that Bartonella sp. DNA was detected in seven Rattus norvegicus individuals with a detection rate of 6.7% in Chengde City and bacterial DNA in 31 Apodemus agrarius individuals with a detection rate of 28.4% in Handan City. The DNA detection rate across the genders and ages of rodents was not found to be statistically significant. Furthermore, sequence analysis of the above-mentioned three genes demonstrated that at least eight Bartonella species were circulating in Hebei Province, of which three, including Bartonella rattimassiliensis, Bartonella grahamii, and Bartonella tribocorum, are human pathogens, thus suggesting the existence of a major public health risk. Overall, these results revealed the detection rate and genetic diversity of Bartonella species infection in rodents in Hebei Province, which could be potentially helpful for the prevention of bartonellosis caused by rodent-associated Bartonella species. This study highlights the urgent need for the surveillance of Bartonella infections in rodents and ectoparasites that affect both rodents and humans and can cause fever of unknown origin or endocarditis.
Analysis of gut microbiome composition, function, and phenotype in patients with osteoarthritis
Authors: Liu Su , Li Guoqing , Zhu Yuanchao , Xu Chang , Yang Qi , Xiong Ao , Weng Jian , Yu Fei , Zeng Hui
Published: November 2022

Gut microbiome (GMB) disturbance can induce chronic low-grade inflammation, which is closely related to the occurrence and development of osteoarthritis (OA). However, the relationship between GMB and OA remains unclear. In this study, we collected stool samples from OA patients and healthy people, and performed Alpha diversity, Beta diversity, MetaStat, and LEfSe analysis by 16S rRNA sequencing to find out the species with significant difference between the two groups. Random forest analysis was performed to find out biomarkers that could distinguish between OA patients and healthy people. PICRUSt and Bugbase analysis were used to compare the difference in functions and phenotypes. Multivariate linear regression analysis (MaAsLin) was used to adjust for gender, age, and body mass index (BMI). The results showed that there was a significant difference in the overall composition of GMB between the two groups (p = 0.005). After adjusting for gender, age, and BMI, we found that p_Bacteroidota (Q = 0.039), c_Bacteroidia (Q = 0.039), and o_Bacteroidales (Q = 0.040) were enriched in the OA group, while s_Prevotella_copri (Q = 0.001) was enriched in the healthy control group. Prevotella could distinguish between OA patients and healthy people with a better diagnostic power (AUC = 77.5%, p < 0.001, 95% CI: 66.9–88.1%). The functions of DNA transcription, amino acid metabolism (including histidine, lysine, and isoleucine), ATP metabolism, and phospholipid metabolism significantly decreased, while glucose metabolism, protein acetylation, and aspartate kinase activity significantly increased in the OA group. In terms of phenotypes, we found that the relative abundance of aerobic (p = 0.003) and Gram-negative (p < 0.001) was higher in the OA group, while contains mobile elements (p = 0.001) and Gram-positive (p < 0.001) were higher in the healthy control group. Our study preliminarily demonstrated that there were differences in the composition, function, and phenotype of GMB in stool samples between OA patients and healthy people, which provided a novel perspective on further study in OA.
Identifying SM-miRNA associations based on layer attention graph convolutional network and matrix decomposition
Authors: Ni Jie , Cheng Xiaolong , Ni Tongguang , Liang Jiuzhen
Published: November 2022

The accurate prediction of potential associations between microRNAs (miRNAs) and small molecule (SM) drugs can enhance our knowledge of how SM cures endogenous miRNA-related diseases. Given that traditional methods for predicting SM-miRNA associations are time-consuming and arduous, a number of computational models have been proposed to anticipate the potential SM–miRNA associations. However, several of these strategies failed to eliminate noise from the known SM-miRNA association information or failed to prioritize the most significant known SM-miRNA associations. Therefore, we proposed a model of Graph Convolutional Network with Layer Attention mechanism for SM-MiRNA Association prediction (GCNLASMMA). Firstly, we obtained the new SM-miRNA associations by matrix decomposition. The new SM-miRNA associations, as well as the integrated SM similarity and miRNA similarity were subsequently incorporated into a heterogeneous network. Finally, a graph convolutional network with an attention mechanism was used to compute the reconstructed SM-miRNA association matrix. Furthermore, four types of cross validations and two types of case studies were performed to assess the performance of GCNLASMMA. In cross validation, global Leave-One-Out Cross Validation (LOOCV), miRNA-fixed LOOCV, SM-fixed LOOCV and 5-fold cross-validation achieved excellent performance. Numerous hypothesized associations in case studies were confirmed by experimental literatures. All of these results confirmed that GCNLASMMA is a trustworthy association inference method.
PCW-A1001, AI-assisted de novo design approach to design a selective inhibitor for FLT-3(D835Y) in acute myeloid leukemia
Authors: Jang Seong Hun , Sivakumar Dakshinamurthy , Mudedla Sathish Kumar , Choi Jaehan , Lee Sungmin , Jeon Minjun , Bvs Suneel Kumar , Hwang Jinha , Kang Minsung , Shin Eun Gyeong , Lee Kyu Myung , Jung Kwan-Young , Kim Jae-Sung , Wu Sangwook
Published: November 2022

Treating acute myeloid leukemia (AML) by targeting FMS-like tyrosine kinase 3 (FLT-3) is considered an effective treatment strategy. By using AI-assisted hit optimization, we discovered a novel and highly selective compound with desired drug-like properties with which to target the FLT-3 (D835Y) mutant. In the current study, we applied an AI-assisted de novo design approach to identify a novel inhibitor of FLT-3 (D835Y). A recurrent neural network containing long short-term memory cells (LSTM) was implemented to generate potential candidates related to our in-house hit compound (PCW-1001). Approximately 10,416 hits were generated from 20 epochs, and the generated hits were further filtered using various toxicity and synthetic feasibility filters. Based on the docking and free energy ranking, the top compound was selected for synthesis and screening. Of these three compounds, PCW-A1001 proved to be highly selective for the FLT-3 (D835Y) mutant, with an IC50 of 764 nM, whereas the IC50 of FLT-3 WT was 2.54 μM.
Reduced brain activity during a working memory task in middle-aged apolipoprotein E ε4 carriers with overweight/obesity
Authors: Drake Jermon A. , Jakicic John M. , Rogers Renee J. , Aghjayan Sarah L. , Stillman Chelsea M. , Donofry Shannon D. , Roecklein Kathryn A. , Lang Wei , Erickson Kirk I.
Published: November 2022

Objective

The apolipoprotein E ε4 (APOE ε4) allele and midlife obesity are independent risk factors for Alzheimer’s disease (AD). Both of these risk factors are also associated with differences in brain activation, as measured by blood oxygenation level-dependent (BOLD) responses, in the absence of detectable cognitive deficits. Although the presence of these risk factors may influence brain activity during working memory tasks, no study to date has examined whether the presence of the ε4 allele explains variation in working memory brain activity while matching for levels of overweight/obesity. The primary aim of this study was to determine whether the presence of the ε4 allele is associated with differences in task-functional magnetic resonance imaging (fMRI) brain activation in adults with overweight/obesity. We predicted that ε4 carriers would have greater brain activation in regions that support working memory.

Methods

This ancillary study included 48 (n = 24 APOE ε4 carriers; n = 24 APOE ε4 non-carriers), sedentary middle-aged adults (Mean age = 44.63 ± 8.36 years) with overweight/obesity (Mean BMI = 32.43 ± 4.12 kg/m2) who were matched on demographic characteristics. Participants were a subsample enrolled in 12-month randomized clinical trial examining the impact of energy-restricted diet and exercise on cardiovascular health outcomes. Participants completed a n-back working memory task with fMRI, which were completed within one month of the start of the intervention. Participants also underwent pseudo-continuous arterial spin labeling scans, a MRI measure of cerebral blood flow (CBF).

Results

Compared to non-ε4 carriers with overweight/obesity, ε4 carriers with overweight/obesity had lower fMRI brain activity in the middle frontal gyrus, pre and post central gyrus, supramarginal gyrus, superior temporal gyrus, lateral occipital cortex, and angular gyrus (z range = 2.52–3.56) during the n-back working memory task. Differences persisted even when controlling for CBF in these brain regions.

Conclusion

These results indicate that presence of the APOE ε4 allele in middle-aged adults with overweight/obesity is related to altered brain activity during a working memory paradigm, which may confer risk for accelerated neurocognitive decline in late adulthood. Future research is needed to clarify the clinical implications of these findings in the context of risk for AD.
Underlying reasons for post-mortem diagnosed lung cancer cases – A robust retrospective comparative study from Hungary (HULC study)
Authors: Kiss Zolta´n , Bogos Krisztina , Tamási Lilla , Ostoros Gyula , Müller Veronika , Bittner Nóra , Sárosi Veronika , Vastag Aladár , Knollmajer Kata , Várnai Máté , Kovács Krisztina , Berta Andrea , Köveskuti István , Karamousouli Eugenia , Rokszin György , Abonyi-Tóth Zsolt , Barcza Zsófia , Kenessey István , Weber András , Nagy Péter , Freyler-Fadgyas Petra , Szócska Miklós , Szegner Péter , Hilbert Lászlóné , Géczy Gabriella Branyiczkiné , Surján György , Moldvay Judit , Vokó Zoltán , Gálffy Gabriella , Polányi Zoltán
Published: November 2022

Objective

The Hungarian Undiagnosed Lung Cancer (HULC) study aimed to explore the potential reasons for missed LC (lung cancer) diagnosis by comparing healthcare and socio-economic data among patients with post-mortem diagnosed LC with those who were diagnosed with LC during their lives.

Methods

This nationwide, retrospective study used the databases of the Hungarian Central Statistical Office (HCSO) and National Health Insurance Fund (NHIF) to identify patients who died between January 1, 2019 and December 31, 2019 and were diagnosed with lung cancer post-mortem (population A) or during their lifetime (population B). Patient characteristics, socio-economic factors, and healthcare resource utilization (HCRU) data were compared between the diagnosed and undiagnosed patient population.

Results

During the study period, 8,435 patients were identified from the HCSO database with LC as the cause of death, of whom 1,203 (14.24%) had no LC-related ICD (International Classification of Diseases) code records in the NHIF database during their lives (post-mortem diagnosed LC population). Post-mortem diagnosed LC patients were significantly older than patients diagnosed while still alive (mean age 71.20 vs. 68.69 years, p<0.001), with a more pronounced age difference among female patients (difference: 4.57 years, p<0.001), and had significantly fewer GP (General Practitioner) and specialist visits, X-ray and CT scans within 7 to 24 months and 6 months before death, although the differences in GP and specialist visits within 7–24 months did not seem clinically relevant. Patients diagnosed with LC while still alive were more likely to be married (47.62% vs. 33.49%), had higher educational attainment, and had more children, than patients diagnosed with LC post-mortem.

Conclusions

Post-mortem diagnosed lung cancer accounts for 14.24% of total lung cancer mortality in Hungary. This study provides valuable insights into patient characteristics, socio-economic factors, and HCRU data potentially associated with a high risk of lung cancer misdiagnosis.
Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma
Authors: Peng Lu-Shan , Duan Sai-Li , Li Run-Qi , Wang Dan , Han Ying-Ying , Huang Tao , Yu Yu-Pei , Ou Chun-Lin , Wang Jun-Pu
Published: November 2022

Background

The GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood.

Methods

In this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape.

Results

The findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers.

Conclusions

GSDM family may be prognostic markers and novel strategies for the treatment of LUAD.
Bayesian state estimation in partially-observed dynamic multidisciplinary systems
Authors: Asadi Negar , Ghoreishi Seyede Fatemeh
Published: November 2022

Multidisciplinary systems comprise several disciplines that are connected to each other with feedback coupled interactions. These coupled multidisciplinary systems are often observed through sensors providing noisy and partial measurements from these systems. A large number of disciplines and their complex interactions pose a huge uncertainty in the behavior of multidisciplinary systems. The reliable analysis and monitoring of these partially-observed multidisciplinary systems require an accurate estimation of their underlying states, in particular the coupling variables which characterize their stability. In this paper, we present a probabilistic state-space formulation of coupled multidisciplinary systems and develop a particle filtering framework for state estimation of these systems through noisy time-series measurements. The performance of the proposed framework is demonstrated through comprehensive numerical experiments using a coupled aerostructural system and a fire detection satellite. We empirically analyze the impact of monitoring a single discipline on state estimation of the entire coupled system.
Valley and spin quantum Hall conductance of silicene coupled to a ferroelectric layer
Authors: Rafi-Ul-Islam S. M. , Siu Zhuo Bin , Sahin Haydar , Jalil Mansoor B. A.
Published: November 2022

We study the quantum valley and Hall conductances in silicene coupled to a ferroelectric (FE) layer. The spin orbit interaction in silicene couples the valley, pseudospin, and real spin degrees of freedom resulting in a topological Berry curvature in the system. The finite Berry curvature in turn induces a transverse Hall conductance. In particular, if the Fermi level Ef is within the bulk energy gap, the Hall conductance is quantized to integer multiples of π. We study the quantum spin and valley Hall conductivities (QSH and QVH) as functions of the applied out-of-plane electric field for different values of Ef and temperature. Both conductivities vary linearly as 1/|Ef| when Ef is within the conduction or valence bands but reach a quantized plateau value when Ef is within the bulk gap. Further, by coupling silicene to a FE layer, the QSH and QVH signals can be modulated by means of the coupling strength. This can potentially provide a robust topological memory read-out with distinct binary outputs over a wide temperature range.
Effects of hypomagnetic field on adult hippocampal neurogenic niche and neurogenesis in mice
Authors: Luo Yukai , Zhan Aisheng , Fan Yunchang , Tian Lanxiang
Published: November 2022

The elimination of geomagnetic field (GMF), also called hypomagnetic field (HMF), is one of the major environmental hazards faced by deep-space astronauts and the workers in magnetically shielded rooms on Earth. We previously reported that long-term HMF exposure impaired adult hippocampal neurogenesis (AHN) and cognition by reducing endogenous reactive oxygen species (ROS) levels in adult neural stem cells (aNSCs). In addition to the aNSCs themselves, adult neurogenesis is also regulated by the local environment, i.e., the neurogenic niche. Neurogenic niche is mainly composed of astrocyte, microglia, and vascular system. However, whether the HMF exposure affects the neurogenic niche in hippocampus remains unknown. In this study, we investigated the effects of the HMF exposure on the neurogenic niche and adult neurogenesis in hippocampus, as well as the cognitive function in mice. The HMF is simulated by using the newly upgraded double-wrapped coils, different with our previous coils, which are capable of providing a very low-strength static magnetic field and identical electromagnetic field background between the HMF group and the GMF group. Here, we for the first time clearly revealed that 8-week HMF exposure significantly induced microglia activation and increased the number of astrocytes in hippocampal dentate gyrus (DG), suggesting the abnormalities in the neurogenic niche. Meanwhile, 8-week HMF exposure also markedly reduced proliferation and differentiation of aNSCs in the DG, and impaired the cognitive behavior of mice, consistent with our previous findings. In addition, we also found that 8-week HMF exposure significantly induced anxiety-like behaviors of mice. In summary, this study indicates that 8-week HMF exposure induces the neurogenic niche abnormalities, contributing to the AHN impairments, thus leads to the cognitive dysfunction and anxiety-like behaviors in mice.
Optimizing maize yields using growth stimulants under the strategy of replacing chemicals with biological fertilizers
Authors: Abdo Ahmed I. , El-Sobky El-Sayed E. A. , Zhang Jiaen
Published: November 2022

Partial replacement of chemicals with biological fertilizers is a recommended strategy to reduce the adverse environmental effects of chemical fertilizer losses. Enhancing the reduced mineral with biological fertilizers strategy by foliar application of humic acid (HA) and amino acids (AA) can reduce environmental hazards, while improving maize (Zea mays L.) production under semiarid conditions. The recommended doses of N, P and K (e.g., 286 kg N ha-1, 75 kg P2O5 ha-1 and 67 kg K2O ha-1) were applied as the first fertilization level (100% NPK) and were replaced with biofertilizers by 100%, 75%, 50% and 25% as levels of reducing mineral fertilization. These treatments were applied under four foliar applications of tap water (TW), HA, AA and a mixture of HA and AA. Our results reported significant reductions in all parameters, including maize ear yield attributes and grain nutrient uptake, when replacing the mineral NPK with biofertilizers by 25-100% replacement. However, these reductions were mitigated significantly under the application of growth stimulants in the descending order: HA and AA mixture>AA>HA>TA. Applying a mixture of HA and AA with 75% NPK + biofertilizers increased ear length, grain yield, grain uptake of N and K, and crude protein yield by 37, 3, 4, 11 and 7%, respectively as compared with 100% mineral fertilizer only. Moreover, all investigated parameters were maximized under the application of 75% NPK + biofertilizers combined with AA or the mixture of HA and AA, which reveals the importance of growth stimulants in enhancing the reduced chemical NPK strategy. It could be concluded that the mineral NPK rate can be reduced by 25% with biofertilization without any yield losses when combined with HA and AA under arid and semi-arid conditions. That achieves the dual goals of sustainable agriculture by improving yield, while reducing environmental adverse effects.