bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-level jets and their implications on air pollution: A review
Authors: Wei Wei , Zhang Hongsheng , Zhang Xiaoye , Che Huizheng
Published: January 2023

Low-level jets (LLJ) are a common phenomenon in the atmospheric boundary layer and have been reported worldwide. Additionally, they have considerable relevance in a series of fields. This review aimed to document their implications on air quality, specifically particulate matter, mineral dust, and ozone in recent literature focus on i) generalizing long-range advection of pollutants by the low-level jets; ii) analysing vertical transport due to low-level jets-enhanced turbulence mixing and the corresponding mechanisms for different pollutants; and iii) introducing the performance of state-of-the-art numerical models. Finally, we suggest that high-resolution spatiotemporal observations of the pollutants and turbulence must be conducted, and current parameterization schemes should be improved to better represent the low-level jets and nocturnal boundary layer structures for reproducing the complicated interactions between the low-level jets and pollutants.
Influencing factors of air-quality perception in China: What is constructed? What is hidden?
Authors: Zeng Xiangming , Yang Gengjiao
Published: January 2023

China is known to be widely concerned about the air quality of its major cities. Nevertheless, the factors that influence air-quality perception (AQP) are still a matter of discussion. On the basis of one idea that AQP is constructed by media contact, this study assesses the effects of quantitative approach to compare the effect of constructionism and realism on AQP, that is media contact, individualism, and health condition on AQP. Based on data of the Chinese General Social Survey (CGSS) in 2010, we build an ordered logistic regression model and introduce urban/rural dual structure and urbanization as control variables. The results show that media contact, health condition, and individualization affect AQP. The effect of media contact, however, varies depending on the media type, and the relationships between media contact and AQP change according to region when adding control variables. Health condition is significant only when it affects work and activities as well as when mental health (MH) occurs. Additionally, the function of health effect (HE) and MH on AQP only becomes obvious in some areas after adding control variables. Moreover, in most places, the effect of some individualization variables on AQP disappear after adding control variables, whereas they continue to be obvious in others. Therefore, the effect of control variables, which are urbanization level and urban/rural dual structure, is hidden. Furthermore, there is a need to pursue economic and environmental justice between developed and undeveloped areas. The study replies with the effect of constructionism and realism on AQP. And it also sheds light on both the constructed and hidden functions of media contact.
The roles for branch shelters and sheep manure to accelerate the restoration of degraded grasslands in northern China
Authors: Liu Jing , Schneider Rebecca L. , Morreale Stephen J. , Wang Hongmei , Wang Ruixia , Wang Fang , Li Zhigang
Published: January 2023

New strategies are desperately needed for restoring the millions of hectares of degraded grasslands in arid and semiarid areas of northern China. This study evaluated using different combinations of manure amendments and shrub branch shelters for their impacts on soil moisture, nutrient availability, and plant growth over two growing seasons in a degraded grassland in Ningxia, China. A two-factor experiment was conducted, with three concentrations of 1.2 g m−2, 442 g m−2, and 884 g m−2 native Tan sheep manure as the main plots. Cut caragana (Caragana intermedia) branches were used to create branch shelters covering 0%, 20%, 40%, and 60% of ground area, and these acted as sub-main plots. Soil water storage, soil temperature, manure decomposition, branch decomposition, soil nutrients, and plant growth were monitored for 2 years. Results indicated that soil water storage was significantly increased, and soil temperature decreased, under the 40% and 60% branch shelters. Decomposition rate of manure and shrub branches also increased with increasing soil water availability associated with the higher branch sheltering effects, although soil carbon and nitrogen concentrations were primarily driven by the decomposing manure. The combination of high levels of shrub branch shelter and manure application significantly enhanced plant production, although the bulk of the biomass was concentrated in one species, Artemisia scoparia. In conclusion, our study successfully demonstrated feasible and inexpensive solution for the restoration of degraded grasslands, which takes advantage of resources associated with overgrazing Tan sheep and Caragana shrub encroachment in arid and semiarid areas.
Socioeconomic adaptation to geomorphological change: An empirical study in Cigu Lagoon, southwestern coast of Taiwan
Authors: Phuah Tony Leong-Keat , Chang Yang-Chi
Published: January 2023

Coastal erosion in the lagoon systems is concerned as they are dynamic landscapes, often highly productive and beneficial to humankind. Cigu Lagoon contains rich and diverse ecosystems ranging from mangroves to salt fields, and from fish to birds (e.g., endangered black-faced spoonbill). As well as forming part of the country’s natural defenses against typhoons and storm surges, it is also economically important for oyster farming, fish-pond aquaculture and ecotourism. However, with the construction of reservoir, fishery harbors and breakwaters, sediment transport decreases and sand barrier islands have eroded, narrowed, lowered and moved landwards. Cigu is a rural area with decreasing, aging population, becoming a “super-aged society” as defined by World Health Organization. Therefore, it is imperative to study the socioeconomic impacts of these changes, and then to explore critical adaptation factors and potential adaptation strategies. In this research, we conducted interviews and a fuzzy analytic hierarchy process survey. Diverse stakeholders were identified and mapped using a stakeholder rainbow diagram and a power–interest grid. The results show that stakeholders consider the economy to be the most important adaptation factor, especially in relation to the employment opportunities. There are some forms of livelihood diversification in Cigu. Collaboration among young entrepreneurs is the key to socioeconomic adaptation. These factors and strategies may foster socioeconomic adaptation to coastal erosion or geomorphological change, to be aggravated by climate change and other stressors.
Sensitivity of WRF multiple parameterization schemes to extreme precipitation event over the Poyang Lake Basin of China
Authors: Deng Chao , Chi Yongxiang , Huang Yuansen , Jiang Caiying , Su Lingjun , Lin Hui , Jiang Lizhi , Guan Xiaojun , Gao Lu
Published: January 2023

Global warming leads to more frequent and more violent extreme weather events, which cause severe natural disasters. The sensitivity of physical schemes in numerical weather prediction models for extreme precipitation is a significant challenge. To simulate a heavy precipitation process from 1 July 2020 to 10 July 2020 over the Poyang Lake Basin, where floods occur frequently, the Weather Research and Forecast model (WRF) was employed. The observation (OBS) from 92 meteorological stations was applied to evaluate WRF performance. To assess the optimal parameter, 27 combinations of multiphysics schemes based on three cumulus schemes (CUs), three microphysical schemes (MPs) and three land surface schemes (LSMs) were employed in WRF simulation. The Euclid distance (ED) was derived to evaluate the performance of the modelled total cumulative precipitation (TCP). The results showed that the simulation generally reproduced the spatial distribution of precipitation and captured the storm centre. In general, WRF underestimated the observation for most areas but overestimated the observation in the northeastern part of the basin. For total cumulative precipitation (TCP), the spatial correlation coefficients ranged from 0.6 to 0.8. M11 had the highest value of 0.796. The scores (TS, POD, FAR) of M15 were 0.66, 0.79, and 0.21, respectively. With the maximum similarity of 0.518, M7 (BMJ-WDM6-Noah) showed the best performance in ED based on six evaluation metrics. The mean values of OBS and M19 were 259.34 and 218.33 mm, respectively. M19 (NT-Thompson-Noah) was closest to the OBS for the range of the TCP. In terms of daily precipitation, the CC of M3 was maximum (0.96), and the RMSE of M24 was minimum (11.9 mm. day-1). The minimum error between the simulation and OBS was found for M3 (NT-Thompson-Noah). Therefore, with a comprehensive evaluation, five optimal combinations of physical schemes (M22, M19, M9, M3, M21) were found for the PLB, which is of great significance for extreme precipitation simulation and flood forecasting.
A configuration study on rural residents’ willingness to participate in improving the rural living environment in less-developed areas—Evidence from six provinces of western China
Authors: Su Yiqing , Qiu Yabiao , Xuan Yuan , Shu Quanfeng , Li Zhengxiao
Published: January 2023

Maintaining the sustained improvement of human living environments in rural areas while improving habitats poses a substantial challenge. While promoting participation by rural residents is key to achieving the improvement of rural living environments, existing studies have mostly focused on the “net effect” single factors have on their participation. However, few studies have considered the combined effects of multiple characteristics in complex contexts. In this study, a revised model of planned behavior is constructed, based on configuration theory; the histories of pathways that influence rural households’ willingness to participate in improving rural living environments are also explored. The perspective of concurrent causality is adopted, and this study examines whether a “mutual substitution effect” exists between the antecedent conditions in different paths. A questionnaire survey was conducted in six provinces (including autonomous regions) in less-developed areas of China. Six configuration paths of rural residents’ higher willingness to participate in the improvement of rural living environments were obtained using fuzzy-set qualitative comparative analysis. The results show that: 1) In the path of high willingness to participate, the behavioral attitudes characterized by the “trustworthiness of village leaders” and “group identity” play the central role. “Social capital” and the “trustworthiness of village leaders” have a mutual substitution effect. 2) When using positive behavioral attitude evaluation as a core condition, “educational level” and “environmental awareness” have a mutual substitution effect. “Household income level”, as the marginal condition, has a mutual substitution effect with “environmentally friendly habits”. Therefore, to increase rural residents’ willingness to participate in improving rural living environments in less-developed areas, the level of the “trustworthiness of village leaders” and “group identity” should be raised. In addition, depending on the “mutual substitution effect” between different conditions, to achieve the same improvement in rural areas with a low level of “social capital”, the focus should be on improving the “trustworthiness of village leaders”. For rural areas with a slight difference in “household income level”, the focus should be on promoting the formation of “environmentally friendly habits” among rural residents.
A low-carbon and hunger-free future for Bangladesh: An ex- ante assessment of synergies and trade-offs in different transition pathways
Authors: Moghayer Saeed , Zurek Monika , Muzammil Maliha , Mason-D’Croz Daniel , Magrath John , Tabeau Andrzej , Vervoort Joost Mattheus , Achterbosch Thom
Published: January 2023

Feeding and nourishing a growing global population in Bangladesh is a major challenge in a changing climate. A multi-level participatory scenario approach with corresponding modeling and decision support tools is developed and applied to support decision-makers in developing scenario-guided enabling policy for food security in the future under climate change. The results presented in this paper show how, under different scenarios, the agri-food system may transform in the next decade as a result of the interaction of intertwined institutional, technological, and market drivers in Bangladesh. For scenario building, the food and agriculture community was brought together with the climate and energy community. We also experimented with different ways to bring voices that are often less included in policymaking, such as poor rural communities and youth. The scenario quantification is performed by MAGNET, a GTAP-based multi-sector and multi-region computable general equilibrium model. The simulation results depict a comprehensive picture of corresponding and varied pressures on agricultural resources and opportunities for economic development and trade in Bangladesh. Finally, we did an ex-ante assessment of the trade-offs and synergies between zero-hunger- and zero-emission-related targets within the Bangladesh Sustainable Development Goals (SDGs) under the developed scenarios.
Impact of atrazine on the dynamic response of Daphnia pulex populations to fish predation risk
Authors: Qin Shanshan , Xia Tian , Li Gongzheng , Gu Lei , Sun Yunfei , Yang Zhou
Published: January 2023

Herbicide pollution is persistent, which not only has a negative impact on individual organisms, but also may alter population dynamics and stability of interspecific relationships. Cladocerans, an important part of zooplankton, are often simultaneously exposed to environmental pollutants and predation risk in the aquatic environment. To evaluate the combined effects of atrazine and fish predation risk on the population traits of cladocerans, we exposed Daphnia pulex to different concentrations of atrazine (0, 0.05, 0.10, and 1.0 mg L−1) with or without fish (Rhodeus ocellatus) kairomone, recorded the key population traits, and fitted Gaussian model to population dynamics. Results showed that fish kairomone increased the population density at the end of the experiment and resting eggs production, and tended to decrease the total biomass and the average dry weight per individual of D. pulex. Atrazine reduced the total biomass, the average dry weight per individual, and resting eggs production of D. pulex populations. Atrazine also decreased the population density at the end of the experiment of D. pulex in fish kairomone treatment, and attenuated the promoting effect of fish kairomone on resting eggs production and the reduction of the total biomass. The findings highlighted the importance of considering the combined impact of environmental pollutants and predation risks on zooplankton populations.
Modelling autonomous vehicle interactions with bicycles in traffic simulation
Authors: Rampf Felix , Grigoropoulos Georgios , Malcolm Patrick , Keler Andreas , Bogenberger Klaus
Published: January 2023

With the undeniable advance of automated vehicles and their gradual integration in day-today urban traffic, many new technologies have been developed that offer great potential for this emerging field of research. However, testing automated vehicle technologies in real road traffic with vulnerable road users (VRUs) is still a complicated and time consuming procedure. The virtual development and evaluation of automated vehicles using simulation tools offers a good opportunity to test new functions efficiently. However, existing models prove to be insufficient in modeling the interaction between autonomous vehicles and vulnerable road users such as bicyclists and pedestrians. In this paper, an automated vehicle model for microscopic traffic simulation tools is developed with the open-source traffic simulation software Simulation of Urban Mobility (SUMO) and evaluated in common traffic interaction scenarios with bicyclists. A controller model is proposed using different path-finding algorithms from the field of robotic and automated vehicle research, which covers all important control levels of a self-driving vehicle. Finally, its performance is compared to existing car-following and lane-changing models. Results showcase that the autonomous vehicle model achieves either comparable results or has a much steadier and more realistic driving behavior when compared to existing driving models while interacting with bicyclists. The whole source code developed over the course of this work is freely accessible at: https://github.com/FlixFix/Kimarite.
The impact of violating the independence assumption in meta-analysis on biomarker discovery
Authors: Abbas-Aghababazadeh Farnoosh , Xu Wei , Haibe-Kains Benjamin
Published: January 2023

With rapid advancements in high-throughput sequencing technologies, massive amounts of “-omics” data are now available in almost every biomedical field. Due to variance in biological models and analytic methods, findings from clinical and biological studies are often not generalizable when tested in independent cohorts. Meta-analysis, a set of statistical tools to integrate independent studies addressing similar research questions, has been proposed to improve the accuracy and robustness of new biological insights. However, it is common practice among biomarker discovery studies using preclinical pharmacogenomic data to borrow molecular profiles of cancer cell lines from one study to another, creating dependence across studies. The impact of violating the independence assumption in meta-analyses is largely unknown. In this study, we review and compare different meta-analyses to estimate variations across studies along with biomarker discoveries using preclinical pharmacogenomics data. We further evaluate the performance of conventional meta-analysis where the dependence of the effects was ignored via simulation studies. Results show that, as the number of non-independent effects increased, relative mean squared error and lower coverage probability increased. Additionally, we also assess potential bias in the estimation of effects for established meta-analysis approaches when data are duplicated and the assumption of independence is violated. Using pharmacogenomics biomarker discovery, we find that treating dependent studies as independent can substantially increase the bias of meta-analyses. Importantly, we show that violating the independence assumption decreases the generalizability of the biomarker discovery process and increases false positive results, a key challenge in precision oncology.
Development of a novel pyroptosis-related LncRNA signature with multiple significance in acute myeloid leukemia
Authors: Zhong Guangcai , Guo Chong , Shang Yangli , Cui Zelong , Zhou Minran , Sun Mingshan , Fu Yue , Zhang Lu , Feng Huimin , Chen Chunyan
Published: January 2023

Background: Pyroptosis, a programmed cell death (PCD) with highly inflammatory form, has been recently found to be associated with the origin of hematopoietic malignancies. Long noncoding RNA (lncRNA) had emerged as an essential mediator to regulate gene expression and been involved in oncogenesis. However, the roles of pyroptosis-related lncRNA (PRlncRNA) in acute myeloid leukemia (AML) have not yet been completely clarified.

Methods: We collected AML datasets from public databases to obtain PRlncRNA associated with survival and constructed a PRlncRNA signature using Lasso-Cox regression analysis. Subsequently, we employed RT-PCR to confirm its expression difference and internal training to further verify its reliability. Next, AML patients were classified into two subgroups by the median risk score. Finally, the differences between two groups in immune infiltration, enrichment analysis and drug sensitivity were further explored.

Results: A PRlncRNA signature and an effective nomogram combined with clinicopathological variables to predict the prognosis of AML were constructed. The internal validations showed that the PRlncRNA risk score model was an accurate and productive indicator to predict the outcome of AML. Furthermore, this study indicated that higher inflammatory cell and immunosuppressive cells, and less sensitive to conventional chemotherapy drugs were highlighted in the high-risk group.

Conclusion: Through comprehensive analysis of PRlncRNA model, our study may offer a valuable basis for future researches in targeting pyroptosis and tumor microenvironment (TME) and provide new measures for prevention and treatment in AML.
SADLN: Self-attention based deep learning network of integrating multi-omics data for cancer subtype recognition
Authors: Sun Qiuwen , Cheng Lei , Meng Ao , Ge Shuguang , Chen Jie , Zhang Longzhen , Gong Ping
Published: January 2023

Integrating multi-omics data for cancer subtype recognition is an important task in bioinformatics. Recently, deep learning has been applied to recognize the subtype of cancers. However, existing studies almost integrate the multi-omics data simply by concatenation as the single data and then learn a latent low-dimensional representation through a deep learning model, which did not consider the distribution differently of omics data. Moreover, these methods ignore the relationship of samples. To tackle these problems, we proposed SADLN: A self-attention based deep learning network of integrating multi-omics data for cancer subtype recognition. SADLN combined encoder, self-attention, decoder, and discriminator into a unified framework, which can not only integrate multi-omics data but also adaptively model the sample’s relationship for learning an accurately latent low-dimensional representation. With the integrated representation learned from the network, SADLN used Gaussian Mixture Model to identify cancer subtypes. Experiments on ten cancer datasets of TCGA demonstrated the advantages of SADLN compared to ten methods. The Self-Attention Based Deep Learning Network (SADLN) is an effective method of integrating multi-omics data for cancer subtype recognition.
siMS score- method for quantification of metabolic syndrome, confirms co-founding factors of metabolic syndrome
Authors: Dimitrijevic-Sreckovic V. , Petrovic H. , Dobrosavljevic D. , Colak E. , Ivanovic N. , Gostiljac D. , Ilic S. , Nikolic D. , Gacic J. , Soldatovic I.
Published: January 2023

Background: Adipose tissue is a dynamic endocrine organ, a highly active metabolic tissue, and an important source of cytokines. Inflammatory factors play an important role in visceral obesity associated with insulin resistance (IR), metabolic syndrome (MS), hypertension, non-alcoholic fatty liver disease (NAFLD), diabetes mellitus type 2 (DM2), endothelial dysfunction (ED) and atherosclerosis.

Objectives: To examine corelation of siMS score, as a quantification method for metabolic syndrome (MS), with insulin resistance, glucoregulation parameters, as with other co-founding factors of MS, inflammation and thrombosis factors, microalbuminuria, uric acid, fatty liver index (FLI) and homocysteine.

Methods: The study included 451 obese individuals with pre–metabolic syndrome (pre-MS) and MS (age 16–75, body mass index (BMI) > 25kg/m2) classified into two groups: I-age 10–30 (167 patients); II-age 31–75 (284 patients). International Diabetes Federation (IDF) classification was applied for diagnosing metabolic syndrome. Patients with less than three criteria indicated below were considered pre-metabolic syndrome. siMS risk score was used.

Results: siMS score increased with age: I-3.03 ± 0.87, II-3.27 ± 0.90. siMS score correlated with associated factors of MS: hyperinsulinemia and IR, ALT, gama-GT, FLI, uric acid in both groups and CRP (p < 0.01) in group I. Correlations in II group: siMS score with PAI-1 (p = 0.01), microalbuminuria (p = 0.006), homocysteine ​​(p = 0.076).

Conclusion: Correlation of siMS score with HOMA-IR confirmed that hyperinsulinism and insulin resistance are in the basis of MS. Correlation of siMS score with parameters of NAFLD, CRP, PAI-1, uric acid, microalbuminuria and homocysteine indicates that they are significant co-founding factors of MS. Correlation of siMS score with PAI-1, microalbuminuria, homocysteine, indicates higher risk for progression of endothelial dysfunction and atherosclerosis with age.
Non-coding RNA and autophagy: Finding novel ways to improve the diagnostic management of bladder cancer
Authors: Tantray Ishaq , Ojha Rani , Sharma Aditya P.
Published: January 2023

Major fraction of the human genome is transcribed in to the RNA but is not translated in to any specific functional protein. These transcribed but not translated RNA molecules are called as non-coding RNA (ncRNA). There are thousands of different non-coding RNAs present inside the cells, each regulating different cellular pathway/pathways. Over the last few decades non-coding RNAs have been found to be involved in various diseases including cancer. Non-coding RNAs are reported to function both as tumor enhancer and/or tumor suppressor in almost each type of cancer. Urothelial carcinoma of the urinary bladder is the second most common urogenital malignancy in the world. Over the last few decades, non-coding RNAs were demonstrated to be linked with bladder cancer progression by modulating different signalling pathways and cellular processes such as autophagy, metastasis, drug resistance and tumor proliferation. Due to the heterogeneity of bladder cancer cells more in-depth molecular characterization is needed to identify new diagnostic and treatment options. This review emphasizes the current findings on non-coding RNAs and their relationship with various oncological processes such as autophagy, and their applicability to the pathophysiology of bladder cancer. This may offer an understanding of evolving non-coding RNA-targeted diagnostic tools and new therapeutic approaches for bladder cancer management in the future.
Two novel variants in CEP152 caused Seckel syndrome 5 in a Chinese family
Authors: Zhang Li , Teng Yanling , Hu Haoran , Zhu Huimin , Wen Juan , Liang Desheng , Li Zhuo , Wu Lingqian
Published: January 2023

Background:Seckel syndrome (SCKL) is a rare autosomal recessive inherited disorder, which is mainly characterized by intrauterine and postnatal growth restrictions, microcephaly, intellectual disability, and a typical “bird-head” facial appearance. Here, we aimed to identify the genetic etiology of a family with suspected SCKL.

Methods:This study enrolled a Chinese family suspected of SCKL with their detailed family history and clinical data. We performed karyotype analysis, copy number variation sequencing (CNV-seq), and trio whole-exome sequencing (WES) to explore the genetic etiology in the proband. Furthermore, the quantitative real-time polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) were conducted to confirm the pathogenicity of novel variants.

Results:The karyotype analysis and CNV-seq were normal in the proband. Two novel variants inCEP152, c.1060C>T (p.Arg354*) and c.1414-14A>G, were identified in the proband through trio-WES. The qPCR results showed that the totalCEP152mRNA expression levels were significantly reduced in c.1060C>T (p.Arg354*) and c.1414-14A>G compared with healthy control individuals. Moreover, aberrant skipping of exon 12 due to the non-canonical splice-site variant was revealed by RT-PCR and Sanger sequencing.

Conclusion:Our findings expanded pathogenic variant spectra in SCKL and offered new insights into the pathogenicity of a non-classical splice-site variant inCEP152, which provided additional information for helping the family improve pregnancy plans in the future.
Mesoangioblasts at 20: From the embryonic aorta to the patient bed
Authors: Cossu Giulio , Tonlorenzi Rossana , Brunelli Silvia , Sampaolesi Maurilio , Messina Graziella , Azzoni Emanuele , Benedetti Sara , Biressi Stefano , Bonfanti Chiara , Bragg Laricia , Camps Jordi , Cappellari Ornella , Cassano Marco , Ciceri Fabio , Coletta Marcello , Covarello Diego , Crippa Stefania , Cusella-De Angelis M. Gabriella , De Angelis Luciana , Dellavalle Arianna , Diaz-Manera Jordi , Galli Daniela , Galli Francesco , Gargioli Cesare , Gerli Mattia F. M. , Giacomazzi Giorgia , Galvez Beatriz G. , Hoshiya Hidetoshi , Guttinger Maria , Innocenzi Anna , Minasi M. Giulia , Perani Laura , Previtali Stefano C , Quattrocelli Mattia , Ragazzi Martina , Roostalu Urmas , Rossi Giuliana , Scardigli Raffaella , Sirabella Dario , Tedesco Francesco Saverio , Torrente Yvan , Ugarte Gonzalo
Published: January 2023

In 2002 we published an article describing a population of vessel-associated progenitors that we termed mesoangioblasts (MABs). During the past decade evidence had accumulated that during muscle development and regeneration things may be more complex than a simple sequence of binary choices (e.g., dorsal vs. ventral somite). LacZ expressing fibroblasts could fuse with unlabelled myoblasts but not among themselves or with other cell types. Bone marrow derived, circulating progenitors were able to participate in muscle regeneration, though in very small percentage. Searching for the embryonic origin of these progenitors, we identified them as originating at least in part from the embryonic aorta and, at later stages, from the microvasculature of skeletal muscle. While continuing to investigate origin and fate of MABs, the fact that they could be expanded in vitro (also from human muscle) and cross the vessel wall, suggested a protocol for the cell therapy of muscular dystrophies. We tested this protocol in mice and dogs before proceeding to the first clinical trial on Duchenne Muscular Dystrophy patients that showed safety but minimal efficacy. In the last years, we have worked to overcome the problem of low engraftment and tried to understand their role as auxiliary myogenic progenitors during development and regeneration.
How many missed abortions are caused by embryonic chromosomal abnormalities and what are their risk factors?
Authors: Li Xin , Kang Han , Yin Huifeng , Liu Tianjiao , Hou Qiannan , Yu Xiaolan , Guo Yuanlin , Shen Wei , Ge Huisheng , Zeng Xiaoyan , Lu Kangmu , Xiong Ying
Published: January 2023

Introduction: Though embryonic chromosome abnormalities have been reported to be the most common cause of missed abortions, previous studies have mainly focused on embryonic chromosome abnormalities of missed abortions, with very few studies reporting that of non-missed abortion. Without chromosome studies of normal abortion samples, it is impossible to determine the risk factors of embryo chromosome abnormalities and missed abortion. This study aimed to investigate the maternal and embryonic chromosome characteristics of missed and non-missed abortion, to clarify the questions that how many missed abortions are caused by embryonic chromosomal abnormalities and what are their risk factors.

Material and methods: This study was conducted on 131 women with missed or non-missed abortion from the Longitudinal Missed Abortion Study (LoMAS). Logistic regression analysis was used to identify the association between maternal covariates and embryonic chromosomal abnormalities and missed abortions. Data on the characteristics of women with abortions were collected.

Results: The embryonic chromosome abnormality rate was only 3.9% in non-missed abortion embryos, while it was 64.8% in missed-abortion embryos. Assisted reproductive technology and prior missed abortions increased the risk of embryonic chromosome abnormalities by 1.637 (95% CI: 1.573, 4.346. p = 0.010) and 3.111 (95% CI: 1.809, 7.439. (p < 0.001) times, respectively. In addition, as the age increased by 1 year, the risk of embryonic chromosome abnormality increased by 14.4% (OR: 1.144, 95% CI: 1.030, 1.272. p = 0.012). Moreover, advanced age may lead to different distributions of chromosomal abnormality types.

Conclusion: Nearly two-thirds of missed abortions are caused by embryonic chromosomal abnormalities. Moreover, advanced age, assisted reproductive technology, and prior missed abortions increase the risk of embryonic chromosomal abnormalities.
Identification of extremely GC-rich micro RNAs for RT-qPCR data normalization in human plasma
Authors: Baumann Volker , Athanasiou Angelos-Theodoros , Faridani Omid R. , Schwerdtfeger Andreas R. , Wallner Bernard , Steinborn Ralf
Published: January 2023

We aimed at extending the repertoire of high-quality miRNA normalizers for reverse transcription-quantitative PCR (RT-qPCR) of human plasma with special emphasis on the extremely guanine-cytosine-rich portion of the miRNome. For high-throughput selection of stable candidates, microarray technology was preferred over small-RNA sequencing (sRNA-seq) since the latter underrepresented miRNAs with a guanine-cytosine (GC) content of at least 75% (p = 0.0002, n = 2). miRNA abundances measured on the microarray were ranked for consistency and uniformity using nine normalization approaches. The eleven most stable sequences included miRNAs of moderate, but also extreme GC content (45%–65%: miR-320d, miR-425-5p, miR-185-5p, miR-486-5p; 80%–95%: miR-1915-3p, miR-3656-5p, miR-3665-5p, miR-3960-5p, miR-4488-5p, miR-4497 and miR-4787-5p). In contrast, the seven extremely GC-rich miRNAs were not found in the two plasma miRNomes screened by sRNA-seq. Stem-loop RT-qPCR was employed for stability verification in 32 plasma samples of healthy male Caucasians (age range: 18–55 years). The lowest inter-individual variance of miRNA abundance was determined for miR-3665 and miR-1915-3p [coefficient of variation (CV) values: 0.08 and 0.50, respectively]. The eight most stable sequences included four extremely GC-rich miRNAs (miR-1915-3p, miR-3665, miR-4787-5p and miR-4497). The best-performing duo normalization factor (NF) for the condition of human plasma, miR-320d and miR-4787-5p, also included a GC-extreme miRNA. In summary, the identification of extremely guanine-cytosine-rich plasma normalizers will help to increase accuracy of PCR-based miRNA quantification, thus raise the potential that miRNAs become markers for psychological stress reactions or early and precise diagnosis of clinical phenotypes. The novel miRNAs might also be useful for orthologous contexts considering their conservation in related animal genomes.
Genome-wide exploration of a pyroptosis-related gene module along with immune cell infiltration patterns in bronchopulmonary dysplasia
Authors: Chen Leiming , Shi Chaofan , Zhou Guoping , Yang Xiaofeng , Xiong Zhenqin , Ma Xiaoxue , Zhu Lan , Ma Xuejiao , Mao Yan , Hu Yifang , Wang Jimei , Tang Xinfang , Bao Yunlei , Ma Yunxia , Luo Fei , Wu Chuyan , Jiang Feng
Published: January 2023

Pyroptosis plays a crucial role in bronchopulmonary dysplasia (BPD) and is associated with various lung injury illnesses. However, the function of pyroptosis-related genes (PRGs) in BPD remains poorly understood. The gene expression omnibus (GEO) database was searched for information on genes associated with BPD. Twenty-five BPD-related DE-PRGs were identified, all of which were closely associated with pyroptosis regulation and immunological response. LASSO and SVM-RFE algorithms identified CHMP7, NLRC4, NLRP2, NLRP6, and NLRP9 among the 25 differentially expressed PRGs as marker genes with acceptable diagnostic capabilities. Using these five genes, we also generated a nomogram with excellent predictive power. Annotation enrichment analyses revealed that these five genes may be implicated in BPD and numerous BPD-related pathways. In addition, the ceRNA network showed an intricate regulatory link based on the marker genes. In addition, CIBERSORT-based studies revealed that alterations in the immunological microenvironment of BPD patients may be associated with the marker genes. We constructed a diagnostic nomogram and gave insight into the mechanism of BPD. Its diagnostic value for BPD must be evaluated in further research before it can be used in clinical practice.
An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma
Authors: Zheng Xiwang , Zhang Chunming , Zheng Defei , Guo Qingbo , Maierhaba Mijiti , Xue Lingbin , Zeng Xianhai , Wu Yongyan , Gao Wei
Published: January 2023

Background: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma (HNSC) are among the most common malignant tumors, with a 5-year relative survival rate ranging between 40% and 50%. The underlying mechanisms and clinical significance of cuproptosis-related genes (CRGs) in HNSC progression have not been clarified.

Methods: In this study, expression pattern, biological functions, Immunohistochemistry (IHC), gene variants and immune status were analyzed to investigate the effects of CRGs on HNSC progression. Moreover, a 12-CRGs signature and nomogram were also constructed for prognosis prediction of HNSC.

Results: The results revealed that some CRGs were dysregulated, had somatic mutations, and CNV in HNSC tissues. Among them, ISCA2 was found to be upregulated in HNSC and was strongly correlated with the overall survival (OS) of HNSC patients (HR = 1.13 [1.01–1.26], p-value = 0.0331). Functionally, CRGs was mainly associated with the TCA cycle, cell cycle, iron-sulfur cluster assembly, p53 signaling pathway, chemical carcinogenesis, and carbon metabolism in cancer. A 12-CRGs signature for predicting the OS was constructed which included, CAT, MTFR1L, OXA1L, POLE, NTHL1, DNA2, ATP7B, ISCA2, GLRX5, NDUFA1, and NDUFB2. This signature showed good prediction performance on the OS (HR = 5.3 [3.4–8.2], p-value = 3.4e-13) and disease-specific survival (HR = 6.4 [3.6–11], p-value = 2.4e-10). Furthermore, 12-CRGs signature significantly suppressed the activation of CD4+ T cells and antigen processing and presentation. Finally, a nomogram based on a 12-CRGs signature and clinical features was constructed which showed a significantly adverse effect on OS (HR = 1.061 [1.042–1.081], p-value = 1.6e-10) of HNSC patients.

Conclusion: This study reveals the association of CRGs with the progression of HNSC based on multi-omics analysis. The study of CRGs is expected to improve clinical diagnosis, immunotherapeutic responsiveness and prognosis prediction of HNSC.
Hybrid gMLP model for interaction prediction of MHC-peptide and TCR
Authors: Zhang Lichao , Li Haojin , Zhang Zhenjiu , Wang Jinjin , Chen Gang , Chen Dong , Shi Wentao , Jia Gaozhi , Liu Mingjun
Published: January 2023

Understanding the interaction of T-cell receptor (TCR) with major histocompatibility-peptide (MHC-peptide) complex is extremely important in human immunotherapy and vaccine development. However, due to the limited available data, the performance of existing models for predicting the interaction of T-cell receptors (TCR) with major histocompatibility-peptide complexes is still unsatisfactory. Deep learning models have been applied to prediction tasks in various fields and have achieved better results compared with other traditional models. In this study, we leverage the gMLP model combined with attention mechanism to predict the interaction of MHC-peptide and TCR. Experiments show that our model can predict TCR-peptide interactions accurately and can handle the problems caused by different TCR lengths. Moreover, we demonstrate that the models trained with paired CDR3β-chain and CDR3α-chain data are better than those trained with only CDR3β-chain or with CDR3α-chain data. We also demonstrate that the hybrid model has greater potential than the traditional convolutional neural network.
Genes related to N6-methyladenosine in the diagnosis and prognosis of idiopathic pulmonary fibrosis
Authors: Zhang Jingcheng , Zhang Ying , Wang Ziyuan , Zhao Jiachao , Li Zhenyu , Wang Keju , Tian Lin , Yao Baojin , Wu Qibiao , Wang Tan , Wang Jing
Published: January 2023

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive pulmonary fibrotic disease with unknown etiology and poor outcomes. It severely affects the quality of life. In this study, we comprehensively analyzed the expression of N6-methyladenosine (m6A) RNA methylation regulators using gene expression data from various tissue sources in IPF patients and healthy volunteers.

Methods: The gene expression matrix and clinical characteristics of IPF patients were retrieved from the Gene Expression Omnibus database. A random forest model was used to construct diagnosis signature m6A regulators. Regression analysis and correlation analysis were used to identify prognosis m6A regulators. Consensus cluster analysis was used to construct different m6A prognosis risk groups, then functional enrichment, immune infiltration and drug sensitivity analysis were performed.

Result: Five candidate m6A genes from lung tissue were used to predict the incidence, and the incidence was validated using datasets from bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells. Subsequently, the BALF dataset containing outcomes data was used for the prognosis analysis of m6A regulators. METTL14, G3BP2, and ZC3H13 were independent protective factors. Using correlation analysis with lung function in the lung tissue-derived dataset, METTL14 was a protective factor in IPF. Based on METTL14 and G3BP2, a consensus cluster analysis was applied to distinguish the prognostic m6A regulation patterns. The low-risk group’s prognosis was significantly better than the high-risk group. Biological processes regulated by various risk groups included fibrogenesis and cell adhesion. Analysis of immune cell infiltration showed upregulation of neutrophils in the m6A high-risk group. Subsequently, five m6A high-risk group sensitive drugs and one m6A low-risk group sensitive drug were identified.

Discussion: These findings suggest that m6A regulators are involved in the diagnosis and prognosis of IPF, and m6A patterns are a method to identify IPF outcomes.
A novel missense ALMS1 variant causes aberrant splicing identified in a cohort of patients with Alström syndrome
Authors: Shi Jie , Xu Ke , Zhang Xin , Xie Yue , Chang Haoyu , Li Yang
Published: January 2023

Purpose: Alström syndrome (AS) is a rare autosomal recessive disorder caused by variants of ALMS1. The objectives of this study were to describe the clinical and genetic characteristics of 19 Chinese patients with biallelic variants in ALMS1.

Methods: We recruited 19 probands with biallelic disease-causing ALMS1 variants. All patients underwent ophthalmic and systematic evaluations and comprehensive molecular genetic analysis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays were performed to observe the effect of a novel missense variant on ALMS1 pre-mRNA splicing.

Results: We identified 33 causative variants in ALMS1, including 15 frameshift small indels, 14 non-sense variants, two gross deletions, one splicing variant, and one missense variant. RT-PCR showed that the missense variant c.9542G>A (p.R3181Q) altered pre-mRNA splicing to generate a truncated protein p. (Ser3082Asnfs*6). Retinal dystrophy (RD) was noted in all the patients, followed by metabolism disturbance (obesity or acanthosis nigricans) in 66.7% and hearing impairment in 61.1% of the patients. Patient systemic symptom numbers and their age at evaluation showed a significant positive correlation, and BCVA and age at the last examination showed a moderate correlation. All patients exhibited early-onset RD and severe visual impairment. The exception was one patient carrying homozygous p. R3181Q, who showed a mild visual defect and atypical retinal phenotype.

Conclusion: Our findings expand the pathogenic variant spectrum of ALMS1 and provide the first verification of a novel missense variant caused AS by aberrant pre-mRNA splicing. Patients with AS might demonstrate varied clinical spectra; therefore, genetic analysis is vital for the early and accurate diagnosis of patients with atypical AS.
Doubly bi-allelic variants of MTHFR and MTHFD1 in a Chinese patient with hyperhomocysteinemia and failure of folic acid therapy
Authors: Liu Yu-Xing , Ding Man-Hua , Sheng Yue , Sun Meng-Fei , Liu Lv , Zhang Yang
Published: January 2023

Background: Hyperhomocysteinemia (HHcy) is a risk factor for thromboembolic disease. Defects in one-carbon metabolism (1-CM)-related genes, such as methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1), can cause HHcy and may also affect the efficacy of folic acid therapy. The details of mechanisms are yet to be further investigated.

Method: We described a Chinese family with hereditary HHcy. The proband suffered from severe thromboembolic disease and experienced failure of folic acid therapy. Two sons of the proband were also diagnosed with HHcy but were sensitive to folic acid therapy. Whole-exome sequencing (WES) was conducted to evaluate the genetic lesion of this family.

Results: Compound heterozygous variants (a common polymorphism, p. A222V, and a novel variant, p. C631*fs*1) of the MTHFR gene and a homozygous missense variant (p. K134R) of the MTHFD1 gene were identified in the proband. The two sons, with successful intervention, only harbored the homozygous p. A222V variant of the MTHFR gene.

Conclusion: The clinical manifestations and genetic research synergistically confirmed the diagnosis of HHcy and clarified the failure of folic acid therapy in the proband caused by doubly bi-allelic variants of the MTHFR and MTHFD1 genes. Our study increased our understanding of the molecular basis of 1-CM-related gene defects on folic acid therapy in HHcy.
GWAS of depression in 4,520 individuals from the Russian population highlights the role of MAGI2 (S-SCAM) in the gut-brain axis
Authors: Pinakhina Daria , Yermakovich Danat , Vergasova Ekaterina , Kasyanov Evgeny , Rukavishnikov Grigory , Rezapova Valeriia , Kolosov Nikita , Sergushichev Alexey , Popov Iaroslav , Kovalenko Elena , Ilinskaya Anna , Kim Anna , Plotnikov Nikolay , Ilinsky Valery , Neznanov Nikholay , Mazo Galina , Kibitov Alexander , Rakitko Alexander , Artomov Mykyta
Published: January 2023

We present the results of the depression Genome-wide association studies study performed on a cohort of Russian-descent individuals, which identified a novel association at chromosome 7q21 locus. Gene prioritization analysis based on already known depression risk genes indicated MAGI2 (S-SCAM) as the most probable gene from the locus and potential susceptibility gene for the disease. Brain and gut expression patterns were the main features highlighting functional relatedness of MAGI2 to the previously known depression risk genes. Local genetic covariance analysis, analysis of gene expression, provided initial suggestive evidence of hospital anxiety and depression scale and diagnostic and statistical manual of mental disorders scales having a different relationship with gut-brain axis disturbance. It should be noted, that while several independent methods successfully in silico validate the role of MAGI2, we were unable to replicate genetic association for the leading variant in the MAGI2 locus, therefore the role of rs521851 in depression should be interpreted with caution.