bluuebunny/crossref_metadata_2025 huggingface dataset:
Purinergic Signaling in Spermatogenesis
Authors: Mundt Nadine , Kenzler Lina , Spehr Marc
Published: April 2022

Adenosine triphosphate (ATP) serves as the essential source of cellular energy. Over the last two decades, however, ATP has also attracted increasing interest as an extracellular signal that activates purinergic plasma membrane receptors of the P2 family. P2 receptors are divided into two types: ATP-gated nonselective cation channels (P2X) and G protein-coupled receptors (P2Y), the latter being activated by a broad range of purine and pyrimidine nucleotides (ATP, ADP, UTP, and UDP, among others). Purinergic signaling mechanisms are involved in numerous physiological events and pathophysiological conditions. Here, we address the growing body of evidence implicating purinergic signaling in male reproductive system functions. The life-long generation of fertile male germ cells is a highly complex, yet mechanistically poorly understood process. Given the relatively sparse innervation of the testis, spermatogenesis relies on both endocrine control and multi-directional paracrine communication. Therefore, a detailed understanding of such paracrine messengers, including ATP, is crucial to gain mechanistic insight into male reproduction.⁠
Acoustic-Electrical Joint Localization Method of Partial Discharge in Power Transformer Considering Multi-Path Propagation Impact
Authors: Jia Jun , Fu Hui , Wang Bo , Li Yong , Yu Yue , Cao Yuan , Jiang Di
Published: April 2022

Efficient and accurate localization of partial discharge (PD) is of paramount importance to ensure the safe operation of power transformers. However, the multi-path propagation effect introduced by the reflection, refraction and diffraction of the ultrasonic signal may add significant computational complexity to the localization process and degrade the localization accuracy. This paper proposes an acoustic- electrical joint method for partial discharge location in the power transformer with the full consideration of the multi-path propagation impact. Unlike the conventional error analysis methods, a partial discharge localization model is proposed for characterizing the multipath propagation impact without the prior knowledge of the transcendental error probability. Based on the matrix inequality transformation and relaxation, the high-dimensional nonlinear localization equations are transformed into a set of second-order convex optimization equations that can be solved using the convex second-order cone program (SOCP). The proposed solution can significantly reduce the computational complexity and improve the localization accuracy as well as avoid the local optimum and slow convergence. The solution is assessed through extensive experiments based on simulations, testbed and trial deployment in comparison with the existing solutions with the localization error of about 0.1 m.
Antecedents of Consumer’s Purchase Intention Towards Energy-Efficient Home Appliances: An Agenda of Energy Efficiency in the Post COVID-19 Era
Authors: Jamil Khalid , Dunnan Liu , Awan Fazal Hussain , Jabeen Gul , Gul Rana Faizan , Idrees Muhammad , Mingguang Liu
Published: April 2022

This study focuses on the energy efficiency in the past COVID-19 era and targeted the young population of Pakistan who are facing the critical situation of COVID-19 era and much aware that this situation will badly affect the energy situation when COVID-19 will end and they also aware that energy efficient appliances will be the most valuable products after the COVID-19 era. Data was collected from five major cities of Pakistan and analyzed by applying structure equation modelling through smart-PLS 3.3. Results show that knowledge of eco-labels has significant impact on perceived functional values, green trust and purchase intention of energy efficient home appliances. Results further indicate that consumers social responsibility has significant impact on personal norms and purchase intention of energy efficient home appliances. Moreover, functional value and green trust mediates the relationship of knowledge of eco-labels and purchase intention of energy efficient home appliances. Furthermore, attitude towards energy efficient appliances mediates the relationship between consumers social responsibility and purchase intention but surprisingly no mediating affect of attitude between consumer social responsibility and purchase intention of energy efficient home appliances. This study presents an antecedent model for predicting energy-efficient home appliances based on consumer awareness. This study will help companies for technology innovation and improvements in the efficiency of household appliances are among the key functional values that companies should emphasize, in order to attract consumers to value the surprising energy-saving effects of appliances.
Identification of Complex Fluid Properties in Condensate Gas Reservoirs Based on Gas–Oil Ratio Parameters Calculated by Optimization Mathematical Model
Authors: Zhao Bin , Li Zhaoping , Gao Chuqiao , Tang Yang
Published: April 2022

In the production development stages of volatile oil reservoirs and condensate gas reservoirs, especially in the early stages of production, the phenomenon of high gas–oil ratio often occurs. As a result, the prediction results of oil and gas are greatly deviated from the actual situation, which seriously affects the implementation of potential excavation and increases production operation for condensate gas reservoirs. Therefore, the accurate identification of condensate gas and volatile oil is the key to improve the development efficiency in condensate reservoirs. However, due to the similar geophysical logging response characteristics for condensate gas, volatile oil, and light oil reservoirs, the qualitative identification effect only based on conventional logging is not ideal. Therefore, we propose a method to calculate the gas–oil ratio by introducing gas logging information and use the gas–oil ratio quantitative calculation results to identify condensate gas and volatile oil layers. First, we establish a physical model of the formation components of the condensate gas reservoir. Based on this physical model, we establish the response equations of various logging tools and evaluate the correlation between the gas logging information and the production gas–oil ratio to establish the response equation of gas logging. Then, we comprehensively use the well logging and gas logging response equations to establish an optimization mathematical model, solve the optimization objective function, obtain the relative content of natural gas and movable oil in the formation to calculate the gas–oil ratio parameters, and finally use this calculation result of the gas–oil ratio to quantitatively identify the fluid type. The application results show that the gas–oil ratio quantitative calculation method that we proposed can calculate the gas–oil ratio parameter accurately, and the calculation results are consistent with the formation testing data, which provides technical support for the identification of complex fluid properties in condensate gas reservoirs.
Transdisciplinary, Co-Designed and Adaptive Management for the Sustainable Development of Rongcheng, a Coastal City in China in the Context of Human Activities and Climate Change
Authors: Tu Chen , Ma Haiqing , Li Yuan , Fu Chuancheng , You Zai-Jin , Newton Alice , Luo Yongming
Published: April 2022

Half the population of China live in coastal zones where 70% of large cities are also located. Intensive human activities pose significant environmental and ecological hazards to these cities that are already vulnerable to natural hazards and climate change. The sustainable development of coastal cities is thus both a national and international issue. Rongcheng is a typical coastal city in east China. It is a national marine ranch demonstration area that is subjected to multi-stressors from human activities and climate change. The dominant economic sectors include aquaculture and fisheries, agriculture, shipping and tourism. A multitude of resulting pressures come mainly from intensified human activities, such as intensive aquaculture, overfishing, industrial pollutants, agricultural runoff, land reclamation and port expansion. In addition, Rongcheng is also facing exogenic pressures from extreme climate events such as intensified storms, storm surges, droughts and sea ice. A growing awareness of these problems brought together a trans-disciplinary group from local government, research institutions, local practitioners and coastal representatives to jointly explore and co-design adaptive coastal management options. In this transdisciplinary study, a social-ecological analysis based on a combination of the Systems Approach Framework and the Drivers-Pressures-States-Impacts-Responses framework was used to analyze and formulate an adaptive management plan for the sustainability of Rongcheng. More than 40 stakeholders including government, companies, civil society and institutions participated in the study through questionnaires and on-site meetings. A statistical analysis of the results identified urgent issues impeding the sustainable development of Rongcheng. The issues identified were poorly regulated aquaculture, loss of shoreline, and the decline of seagrass and cultural heritage. The study identified management options and measures, some of which were adopted by the local government in a co-designed management plan. The measures included upgrading of aquaculture industry, habitat conservation and restoration, and the development of cultural tourism. Another outcome was the increased knowledge exchange between stakeholders to inform management, policy, and decision making, as well as raised awareness of vulnerability to natural hazards and climate change. The success of this case study provides a reference for the adaptive management of other coastal cities and their sustainable development in a changing climate.
Solar Drying as an Eco-Friendly Technology for Sewage Sludge Stabilization: Assessment of Micropollutant Behavior, Pathogen Removal, and Agronomic Value
Authors: An-nori Amal , Ezzariai Amine , El Mejahed Khalil , El Fels Loubna , El Gharous Mohamed , Hafidi Mohamed
Published: April 2022

Sewage sludge (SS) is a biosolid that includes nutrients, organic matter, and a mixture of micropollutants and pathogens. Regarding its final disposal, several criteria should be met to avoid the dissemination of the included micropollutants in the environment. Hence, an adequate treatment prior to SS disposal is highly required. Solar drying is being acknowledged as a sustainable process of SS treatment, yet it is still unclear to what extent this technique is efficient. This review aimed to assess the impact of solar drying on the composition of SS from environmental and agronomic standpoints. Herein, we present the state-of-the-art with regard to solar drying efficiency in terms of water content reduction, DM increase, agronomic parameters evolvement, and micropollutant stabilization including pathogens, heavy metals (HMs), and organic micropollutants. The reviewed literature is mostly focused on two drying cycles: summer and winter, thus addressing the extreme conditions met within a year with respect to temperature. Under different climatic conditions, more than 80% of dry matter is reached during summer. In winter, the efficiency decreases to an average of 50% of DM. Negatively correlated to DM content, pathogen concentration in SS significantly decreased, while DM increased. Thus, more efficiency in terms of pathogen abatement is reported in summer than in winter (e.g., 96% against 60% during summer and winter, respectively, under semi-arid climate). The high reliance of solar drying efficiency on weather has been deduced in terms of DM content increase and pathogen removal. Where climatic conditions are not favorable for solar drying, hybrid design and liming are the highly recommended methods to remove pathogens from SS. A few studies on the fate of HMs in SS during solar drying concluded that solar drying does not involve any removal mechanisms. Changes in HM speciation in solar-dried sludge were reported highlighting a decrease in their mobility. As for organic micropollutants (PAHs and antibiotics), only their occurrence in SS is reported in the literature, and their behavior during the solar drying process is still not addressed. This review allowed concluding the following: 1) solar drying is a sustainable, relevant process for SS handing in terms of volume reduction and pathogen removal, particularly in semi-arid regions; 2) solar drying does not lower the SS agronomic value and does not remove HMs, but under semi-arid climate, it changes HM speciation and reduces their mobility. The gap in research regarding organic micropollutant and heavy metal behavior during SS solar drying has been emphasized as a way forward for research within this topic. Hence, more research is required to help stakeholders decide on the feasibility of an agricultural disposal of solar-dried sludge.
Distribution Characteristics and Formula Revision of Lightning Current Amplitude and Cumulative Probability in Zhejiang Province
Authors: Xia Li , Nannan Song , Yanfeng Fan , Yinping Liu , Qing Liu , Xiaolin Guan , Pei Miao
Published: April 2022

The cumulative probability distribution of the lightning current amplitude can reflect the lightning activity and is important for the lightning protection engineering technology. Based on the lightning location data from 2009 to 2019, the distribution characteristics of the lightning current amplitude and cumulative probability are studied. The results show that a total of 8,634,858 lightning flashes occurred in Zhejiang province in last 11 years. Negative flashes are much more common than positive ones, accounting for 87.44% of the total. The percentage of the lightning current amplitude between 2 and 100 kA is 94.3%. The average amplitude of positive flashes is significantly higher than that of negative flashes. For the current amplitude of positive flashes, the peak occurs in March and gradually decreases with the increase of the month, reaching its lowest in December. But the monthly distribution of negative flashes is relatively concentrated, especially from February to October. When lightning current amplitude is higher than 25.5 kA, the cumulative probability of positive flashes is significantly higher than that of negative flashes and vice versa. The cumulative probability distribution of negative flashes is closer to that of total flashes and is significantly different from that of positive flashes. In order to get a more suitable cumulative probability formula of lightning current amplitude and corresponding parameters in Zhejiang province, the Levenberg–Marquardt method is used. By fitting the measured data with the formulas recommended by the Institute of Electrical and Electronics Engineers (IEEE) and Electric Power Industry Standard of China (Code for design of overvoltage protection and insulation coordination for AC electrical installations GB/T 50064-2014), respectively, the correlation coefficients of different polarities are obtained. By comparing the aforementioned two fitting results, it is found that the formula recommended by the IEEE can more objectively reflect the probability distribution characteristics in Zhejiang province, and the accuracy of the derived formula is verified by using the lightning current data in 2020. It shows that the curve based on the measured values is consistent with that fitted by the IEEE formula but quite different from that fitted by the GB/T 50064-2014 formula.
Distinct Colony Types Caused by Diploid Male Production in the Buff-Tailed Bumblebee Bombus terrestris
Authors: Di Pietro Viviana , Ferreira Helena Mendes , Van Oystaeyen Annette , Wäckers Felix , Wenseleers Tom , Oliveira Ricardo Caliari
Published: April 2022

The buff-tailed bumblebee Bombus terrestris presents two distinct colony phenotypes in which some colonies already start producing males very early in the season, while others switch to producing sexuals much later in the season, and specialize mainly in the production of virgin queens. Despite having been extensively investigated in the past, the mechanisms underlying these two distinct phenotypes remain poorly understood. Here we use a combination of behavioral and genetic data to demonstrate that early switchers are in fact diploid male producing colonies, while late switchers produced normal, haploid males. Hence, at a proximate level, early switching to male production was caused by queens mating with males that by chance carried the same sex allele. These patterns were not the result of strong inbreeding within the study population, as the average inbreeding coefficient was very low and in fact slightly negative (−0.11). Moreover, an effect of inbreeding was further excluded because hybrids produced by crossing two distinct outbred populations also produced diploid males in early switching colonies. Finally, we found that diploid males only emerged after a first cohort of workers was produced, while we would have expected diploid males to be produced simultaneously with workers in a 50:50 ratio. We demonstrate that adult diploid males had a distinct cuticular hydrocarbon profile and propose that queens likely cull diploid males during early colony development to reduce the cost of diploid male production.
Bioactive Volatiles From Push-Pull Companion Crops Repel Fall Armyworm and Attract Its Parasitoids
Authors: Sobhy Islam S. , Tamiru Amanuel , Chiriboga Morales Xavier , Nyagol Dickens , Cheruiyot Duncan , Chidawanyika Frank , Subramanian Sevgan , Midega Charles A. O. , Bruce Toby J. A. , Khan Zeyaur R.
Published: April 2022

Fall armyworm,Spodoptera frugiperda, is a serious invasive pest in Africa but “Push-Pull” companion cropping can substantially reduce infestation. Here, we elucidate the underpinning chemical ecology mechanisms. We hypothesized that companion crop volatiles repel herbivores (push) while attracting natural enemies (pull). Headspace volatiles collected from companion plants (Desmodium intortum, Desmodium uncinatum,BrachiariaMulato II) were used in bioassays and electrophysiological recordings withS. frugiperdaand parasitoid wasps. Insect populations, plant damage and herbivore parasitism were assessed in field plots. Coupled GC-electroantennogram (GC-EAG) recordings showed robust responses to certain aromatic and terpenoid volatile compounds. In wind tunnel bioassays, maize volatiles mixed withDesmodiumvolatiles were less attractive to moths than maize alone. In oviposition bioassays,S. frugiperdalaid significantly fewer eggs on maize whenDesmodiumvolatiles were present. Conversely, in an olfactometer bioassay, parasitoid wasps were attracted to the scent of bothDesmodiumspp. (intercrop) and theBrachiariaborder crop. Our data provide evidence of the mechanisms underpinning reducedS. frugiperdainfestation in the Push-Pull companion cropping system, i.e., volatiles from companion crops repelS. frugiperdawhile attracting its parasitoid natural enemies. These findings explain why Push-Pull field plots had fewerS. frugiperdalarvae and lower crop damage than monocropped maize.
Canadian Consumer Preferences Regarding Gene-Edited Food Products
Authors: Vasquez Oswaldo , Hesseln Hayley , Smyth Stuart J.
Published: April 2022

Innovations in food production and processing have largely remained “behind the scenes” for decades. The current nature of social media and calls for increased transparency regarding food results in a new landscape where consumer product demands are more important than ever, but are increasingly based on limited, or incorrect, information. One area where consumer awareness is rapidly emerging is the area of gene-edited food products. This article uses a consumer survey to gather perceptions regarding food safety, gene editing and willingness to consume for three gene-edited food products. Four factors were found to strongly influence consumer perceptions: trust in the Canadian food safety system; food technology neophobia scores; knowledge of genetics; and self-knowledge of gene editing. The survey of 497 Canadians found that 15% identified as neophobics and 12% as neophilics. The majority of participants identified as neutral. When presented with various food values, participants indicated that nutrition, price, and taste were the three most important values. A participants’ willingness to consume gene-edited food products strongly correlated with neophobic and neophilic preferences, with neophobics unwilling to consume and neophilics being uncertain. The only food value that strongly affects consumer willingness to consume is the environmental impact of a products’ production. Canadian consumers have a moderate to high level of trust in Canada’s food safety system, but this level of trust fails to carry over to food products produced through innovative technologies; however, consumers express a higher level of trust in gene-edited technology than genetically modified technology.
Whole-Genome-Based Web Genomic Resource for Water Buffalo (Bubalus bubalis)
Authors: Khan Aamir , Singh Kalpana , Jaiswal Sarika , Raza Mustafa , Jasrotia Rahul Singh , Kumar Animesh , Gurjar Anoop Kishor Singh , Kumari Juli , Nayan Varij , Iquebal Mir Asif , Angadi U. B. , Rai Anil , Datta Tirtha Kumar , Kumar Dinesh
Published: April 2022

Water buffalo (Bubalus bubalis), belonging to the Bovidae family, is an economically important animal as it is the major source of milk, meat, and drought in numerous countries. It is mainly distributed in tropical and subtropical regions with a global population of approximately 202 million. The advent of low cost and rapid sequencing technologies has opened a new vista for global buffalo researchers. In this study, we utilized the genomic data of five commercially important buffalo breeds, distributed globally, namely, Mediterranean, Egyptian, Bangladesh, Jaffrarabadi, and Murrah. Since there is no whole-genome sequence analysis of these five distinct buffalo breeds, which represent a highly diverse ecosystem, we made an attempt for the same. We report the first comprehensive, holistic, and user-friendly web genomic resource of buffalo (BuffGR) accessible at http://backlin.cabgrid.res.in/buffgr/, that catalogues 6028881 SNPs and 613403 InDels extracted from a set of 31 buffalo tissues. We found a total of 7727122 SNPs and 634124 InDels distributed in four breeds of buffalo (Murrah, Bangladesh, Jaffarabadi, and Egyptian) with reference to the Mediterranean breed. It also houses 4504691 SSR markers from all the breeds along with 1458 unique circRNAs, 37712 lncRNAs, and 938 miRNAs. This comprehensive web resource can be widely used by buffalo researchers across the globe for use of markers in marker trait association, genetic diversity among the different breeds of buffalo, use of ncRNAs as regulatory molecules, post-transcriptional regulations, and role in various diseases/stresses. These SNPs and InDelscan also be used as biomarkers to address adulteration and traceability. This resource can also be useful in buffalo improvement programs and disease/breed management.
Genetic Variation in the ZNF208 Gene at rs8103163 and rs7248488 Is Associated With Laryngeal Cancer in the Northwestern Chinese Han Male
Authors: Wang Shiyang , Wen Xiulin , Zhao Ruimin , Bai Yanxia
Published: April 2022

Background: Laryngeal cancer is more common in middle-aged and older men. We conducted an association analysis between ZNF208 polymorphisms and laryngeal cancer (LC) risk in the Northwestern Chinese Han male.

Methods: A total of 352 subjects (172 LC patients and 180 controls) were involved in this study. Agena MassARRAY was used to determine the genotypes. Unconditional logistic regression analysis was performed to explore the relevance.

Results: Two SNPs were associated with the risk of LC: rs8103163, OR = 1.41, p = 0.043; rs7248488, OR = 1.45, p = 0.025. Furthermore, rs8103163 was associated with an increased risk of LC under a log-additive model (OR = 1.40, p = 0.042), and rs7248488 was related to a higher risk of LC under a recessive model (OR = 2.33, p = 0.025) and a log-additive model (OR = 1.44, p = 0.026).

Conclusions: We first demonstrated that the rs8103163 A allele and the rs7248488 A allele in ZNF208 create susceptibility to laryngeal cancer in the Northwestern Chinese Han male.
Genetic Evaluations of Stillbirth for Five United States Dairy Breeds: A Data-Resource Feasibility Study
Authors: Sigdel Anil , Wu Xiao-Lin , Parker Gaddis Kristen L. , Norman H. Duane , Carrillo José A. , Burchard Javier , Peñagaricano Francisco , Dürr João
Published: April 2022

Genetic selection has been an effective strategy to improve calving traits including stillbirth in dairy cattle. The primary objectives of the present study were to characterize stillbirth data and determine the feasibility of implementing routine genetic evaluations of stillbirth in five non-Holstein dairy breeds, namely Ayrshire, Guernsey, Milking Shorthorn, Brown Swiss, and Jersey. An updated sire-maternal grandsire threshold model was used to estimate genetic parameters and genetic values for stillbirth. Stillbirth data with the birth years of dams from 1995 to 2018 were extracted from the United States national calving ease database maintained by the Council on Dairy Cattle Breeding. The extracted stillbirth records varied drastically among the five dairy breeds. There were approximately 486K stillbirth records for Jersey and more than 80K stillbirth records for Brown Swiss. The direct and maternal heritability estimates of stillbirth were 6.0% (4.5–7.6%) and 4.7% (3.3–6.1%) in Jersey and 6.8% (3.2–10.5%) and 1.1% (0.6–2.9%) in Brown Swiss. The estimated genetic correlations between direct and maternal genetic effects for stillbirth were −0.15 (−0.38 to −0.08) in Jersey and −0.35 (−0.47 to −0.12) in Brown Swiss. The estimated genetic parameters for stillbirth in these two breeds were within close ranges of previous studies. The reliabilities of predicted transmitting abilities in Jersey and Brown Swiss increased substantially, thanks to the substantial increase in available stillbirth data in the past 10 years. The stillbirth records for Ayrshire, Guernsey, and Milking Shorthorn, which ranged approximately between 3K and 12K, are insufficient to implement reliable routine genetic evaluations of stillbirth in these three dairy breeds. Estimated genetic (co)variances and genetic values deviated considerably from the reported ranges of previous studies, and the reliabilities of predicted transmitting abilities were low in these three breeds. In conclusion, routine genetic evaluations of stillbirth are feasible in Brown Swiss and Jersey. However, reliable genetic evaluations of stillbirth in Ayrshire, Guernsey, and Milking Shorthorn require further data collection on stillbirth.
Association of DNA Methylation Patterns in 7 Novel Genes With Ischemic Stroke in the Northern Chinese Population
Authors: Sun Hongwei , Xu Jia , Hu Bifeng , Liu Yue , Zhai Yun , Sun Yanyan , Sun Hongwei , Li Fang , Wang Jiamin , Feng Anqi , Tang Ying , Zhao Jingbo
Published: April 2022

Background: Ischemic stroke is a highly complex disorder. This study aims to identify novel methylation changes in ischemic stroke.

Methods: We carried out an epigenome-wide study of ischemic stroke using an Infinium HumanMethylation 850K array (cases:controls = 4:4). 10 CpG sites in 8 candidate genes from gene ontology analytics top-ranked pathway were selected to validate 850K BeadChip results (cases:controls = 20:20). We further qualified the methylation level of promoter regions in 8 candidate genes (cases:controls = 188:188). Besides, we performed subgroup analysis, dose-response relationship and diagnostic prediction polygenic model of candidate genes.

Results: In the discovery stage, we found 462 functional DNA methylation positions to be associated with ischemic stroke. Gene ontology analysis highlighted the “calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules” item, including 8 candidate genes (CDH2/PCDHB10/PCDHB11/PCDHB14/PCDHB16/PCDHB3/PCDHB6/PCDHB9). In the replication stage, we identified 5 differentially methylated loci in 20 paired samples and 7 differentially methylated genes (CDH2/PCDHB10/PCDHB11/PCDHB14/PCDHB16/PCDHB3/PCDHB9) in 188 paired samples. Subgroup analysis showed that the methylation level of above 7 genes remained significantly different in the male subgroup, large-artery atherosclerosis subgroup and right hemisphere subgroup. The methylation level of each gene was grouped into quartiles, and Q4 groups of the 7 genes were associated with higher risk of ischemic stroke than Q1 groups (p < 0.05). Besides, the polygenic model showed high diagnostic specificity (0.8723), sensitivity (0.883), and accuracy (0.8777).

Conclusion: Our results demonstrate that DNA methylation plays a crucial part in ischemic stroke. The methylation of these 7 genes may be potential diagnostic biomarker for ischemic stroke.
miR-107 Inhibits the Proliferation of Gastric Cancer Cells In vivo and In vitro by Targeting TRIAP1
Authors: Yan Jiexin , Dai Lu , Yuan Jun , Pang Min , Wang Yueqiu , Lin Lang , Shi Yawei , Wu Fuli , Nie Rongping , Chen Qiuling , Wang Lei
Published: April 2022

Gastric cancer is a kind of gastrointestinal tumor with high morbidity and mortality. Finding effective methods for early diagnosis and treatment of gastric cancer has important significance and application prospects. MicroRNAs without protein coding potential affect the occurrence and development of gastric cancer. This study aims to explore the biological function and mechanism of microRNA-107 (miR-107) in gastric cancer. The results show that miR-107 is low expressed in gastric cancer, while TRIAP1 is highly expressed; the overexpression of miR-107 can inhibit the progression of gastric cancer in vivo and in vitro, while the overexpression plasmid of TRIAP1 can restore the miR-107 mimic-induced cell proliferation and metastasis inhibition, and the small interfering RNA of TRIAP1 can inhibit the cell proliferation and invasion induced by miR-107 inhibitor. In conclusion, the results of this study show that miR-107 can inhibit the proliferation of gastric cancer in vivo and in vitro by targeting TRIAP1.
DeepLION: Deep Multi-Instance Learning Improves the Prediction of Cancer-Associated T Cell Receptors for Accurate Cancer Detection
Authors: Xu Ying , Qian Xinyang , Zhang Xuanping , Lai Xin , Liu Yuqian , Wang Jiayin
Published: April 2022

Recent studies highlight the potential of T cell receptor (TCR) repertoires in accurately detecting cancers via noninvasive sampling. Unfortunately, due to the complicated associations among cancer antigens and the possible induced T cell responses, currently, the practical strategy for identifying cancer-associated TCRs is the computational prediction based on TCR repertoire data. Several state-of-the-art methods were proposed in recent year or two; however, the prediction algorithms were still weakened by two major issues. To facilitate the computational processes, the algorithms prefer to decompose the original TCR sequences into length-fixed amino acid fragments, while the first dilemma comes as the lengths of cancer-associated motifs are suggested to be various. Moreover, the correlations among TCRs in the same repertoire should be further considered, which are often ignored by the existing methods. We here developed a deep multi-instance learning method, named DeepLION, to improve the prediction of cancer-associated TCRs by considering these issues. First, DeepLION introduced a deep learning framework with alternative convolution filters and 1-max pooling operations to handle the amino acid fragments with different lengths. Then, the multi-instance learning framework modeled the TCR correlations and assigned adjusted weights for each TCR sequence during the predicting process. To validate the performance of DeepLION, we conducted a series of experiments on several cohorts of patients from nine cancer types. Compared to the existing methods, DeepLION achieved, on most of the cohorts, higher prediction accuracies, sensitivities, specificities, and areas under the curve (AUCs), where the AUC reached notably 0.97 and 0.90 for thyroid and lung cancer cohorts, respectively. Thus, DeepLION may further support the detection of cancers from TCR repertoire data. DeepLION is publicly available on GitHub, at https://github.com/Bioinformatics7181/DeepLION, for academic usage only.
Neural Networks for Classification and Image Generation of Aging in Genetic Syndromes
Authors: Duong Dat , Hu Ping , Tekendo-Ngongang Cedrik , Hanchard Suzanna E. Ledgister , Liu Simon , Solomon Benjamin D. , Waikel Rebekah L.
Published: April 2022

Background: In medical genetics, one application of neural networks is the diagnosis of genetic diseases based on images of patient faces. While these applications have been validated in the literature with primarily pediatric subjects, it is not known whether these applications can accurately diagnose patients across a lifespan. We aimed to extend previous works to determine whether age plays a factor in facial diagnosis as well as to explore other factors that may contribute to the overall diagnostic accuracy.

Methods: To investigate this, we chose two relatively common conditions, Williams syndrome and 22q11.2 deletion syndrome. We built a neural network classifier trained on images of affected and unaffected individuals of different ages and compared classifier accuracy to clinical geneticists. We analyzed the results of saliency maps and the use of generative adversarial networks to boost accuracy.

Results: Our classifier outperformed clinical geneticists at recognizing face images of these two conditions within each of the age groups (the performance varied between the age groups): 1) under 2 years old, 2) 2–9 years old, 3) 10–19 years old, 4) 20–34 years old, and 5) ≥35 years old. The overall accuracy improvement by our classifier over the clinical geneticists was 15.5 and 22.7% for Williams syndrome and 22q11.2 deletion syndrome, respectively. Additionally, comparison of saliency maps revealed that key facial features learned by the neural network differed with respect to age. Finally, joint training real images with multiple different types of fake images created by a generative adversarial network showed up to 3.25% accuracy gain in classification accuracy.

Conclusion: The ability of clinical geneticists to diagnose these conditions is influenced by the age of the patient. Deep learning technologies such as our classifier can more accurately identify patients across the lifespan based on facial features. Saliency maps of computer vision reveal that the syndromic facial feature attributes change with the age of the patient. Modest improvements in the classifier accuracy were observed when joint training was carried out with both real and fake images. Our findings highlight the need for a greater focus on age as a confounder in facial diagnosis.
MAPPER: An Open-Source, High-Dimensional Image Analysis Pipeline Unmasks Differential Regulation of Drosophila Wing Features
Authors: Kumar Nilay , Huizar Francisco J. , Farfán-Pira Keity J. , Brodskiy Pavel A. , Soundarrajan Dharsan K. , Nahmad Marcos , Zartman Jeremiah J.
Published: April 2022

Phenomics requires quantification of large volumes of image data, necessitating high throughput image processing approaches. Existing image processing pipelines for Drosophila wings, a powerful genetic model for studying the underlying genetics for a broad range of cellular and developmental processes, are limited in speed, precision, and functional versatility. To expand on the utility of the wing as a phenotypic screening system, we developed MAPPER, an automated machine learning-based pipeline that quantifies high-dimensional phenotypic signatures, with each dimension quantifying a unique morphological feature of the Drosophila wing. MAPPER magnifies the power of Drosophila phenomics by rapidly quantifying subtle phenotypic differences in sample populations. We benchmarked MAPPER’s accuracy and precision in replicating manual measurements to demonstrate its widespread utility. The morphological features extracted using MAPPER reveal variable sexual dimorphism across Drosophila species and unique underlying sex-specific differences in morphogen signaling in male and female wings. Moreover, the length of the proximal-distal axis across the species and sexes shows a conserved scaling relationship with respect to the wing size. In sum, MAPPER is an open-source tool for rapid, high-dimensional analysis of large imaging datasets. These high-content phenomic capabilities enable rigorous and systematic identification of genotype-to-phenotype relationships in a broad range of screening and drug testing applications and amplify the potential power of multimodal genomic approaches.
Novel Indel Variation of NPC1 Gene Associates With Risk of Sudden Cardiac Death
Authors: Zhao Wenfeng , Zhang Qing , Wang Jiawen , Yu Huan , Zhen Xiaoyuan , Li Lijuan , Qu Yan , He Yan , Zhang Jianhua , Li Chengtao , Zhang Suhua , Luo Bin , Huang Jiang , Gao Yuzhen
Published: April 2022

Background and Aims: Sudden cardiac death (SCD) was defined as an unexpected death from cardiac causes during a very short duration. It has been reported that Niemann-Pick type C1 (NPC1) gene mutations might be related to cardiovascular diseases. The purpose of the study is to investigate whether common genetic variants of NPC1 is involved in SCD susceptibility.

Methods: Based on a candidate-gene-based approach and systematic screening strategy, this study analyzed an 8-bp insertion/deletion polymorphism (rs150703258) within downstream of NPC1 for the association with SCD risk in Chinese populations using 158 SCD cases and 524 controls. The association of rs150703258 and SCD susceptibility was analyzed using logistic regression. Genotype-phenotype correlation analysis was performed using public database including 1000G, expression quantitative trait loci (eQTL), and further validated by human heart tissues using PCR. Dual-luciferase assay was used to explore the potential regulatory role of rs150703258. Gene expression profiling interactive analysis and transcription factors prediction were performed.

Results: Logistic regression analysis exhibited that the deletion allele of rs150703258 significantly increased the risk of SCD [odds ratio (OR) = 1.329; 95% confidence interval (95%CI):1.03–1.72; p = 0.0289]. Genotype-phenotype correlation analysis showed that the risk allele was significantly associated with higher expression of NPC1 at mRNA and protein expressions level in human heart tissues. eQTL analysis showed NPC1 and C18orf8 (an adjacent gene to NPC1) are both related to rs150703258 and have higher expression level in the samples with deletion allele. Dual-luciferase activity assays indicate a significant regulatory role for rs150703258. Gene expression profiling interactive analysis revealed that NPC1 and C18orf8 seemed to be co-regulated in human blood, arteries and heart tissues. In silico analysis showed that the rs150703258 deletion variant may create transcription factor binding sites. In addition, a rare 12-bp allele (4-bp longer than the insertion allele) of rs150703258 was discovered in the current cohort.

Conclusion: In summary, our study revealed that rs150703258 might contribute to SCD susceptibility by regulating NPC1 and C18orf8 expression. This indel may be a potential marker for risk stratification and molecular diagnosis of SCD. Validations in different ethnic groups with larger sample size and mechanism explorations are warranted to confirm our findings.
Effects of Different Types of Pathogenic Variants on Phenotypes of Familial Hypercholesterolemia
Authors: Tada Hayato , Kojima Nobuko , Yamagami Kan , Nomura Akihiro , Nohara Atsushi , Usui Soichiro , Sakata Kenji , Fujino Noboru , Takamura Masayuki , Kawashiri Masa-Aki
Published: April 2022

Objective: It has been shown that pathogenic variants are associated with poor clinical outcomes in patients with familial hypercholesterolemia (FH). However, data on the effect of different types of pathogenic variants on FH phenotype is limited.

Methods: We retrospectively investigated the associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of major adverse cardiac events (MACEs), defined as cardiovascular death, myocardial infarction, unstable angina, or coronary artery revascularization, in patients with FH (N = 1,050, male/female = 490/560). Based on genotype, the patients were divided into the following three groups: patients without pathogenic variants, patients with missense variants, and patients with protein-truncating variants (PTVs). Cox proportional hazard model was used to identify the factors associated with MACEs.

Results: The median follow-up duration was 12.6 years (interquartile range = 9.5–17.9 years). There were 665 patients with FH-mutation (277 patients with missense variants and 388 patients with PTVs) and 385 patients without FH-mutation. Over the follow-up duration, 175 MACEs were observed. We identified 89 different pathogenic variants in the 665 patients with FH. LDL cholesterol level was found to be significantly higher in patients with PTVs (256 mg/dl) than in patients with missense variants (236 mg/dl) and patients without pathogenic variants (216 mg/dl). It was also found that PTVs and missense variants are significantly associated with MACEs (hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.08–2.08, p = 0.0033 and HR = 3.24, 95% CI = 2.12–4.40, p = 3.9 × 10−6, respectively), independent of classical risk factors.

Conclusion: Pathogenic variants, especially PTVs, are significantly associated with poor outcomes in patients with FH. Genetic testing is useful for the diagnosis and risk stratification of patients with FH.
The R93C Variant of PCSK9 Reduces the Risk of Premature MI in a Chinese Han Population
Authors: Yang Lincheng , Pu Tian , Zhang Yan , Yan Hua , Yu Haiyi , Gao Wei
Published: April 2022

Background: Dyslipidemia is a common risk factor for premature myocardial infarction (PMI). Our previous work has shown that single-nucleotide polymorphisms (SNPs) of LDLR, APOB, and PCSK9 are associated with dyslipidemia, but how these SNPs correlate with risk for PMI is unknown.

Objective: This study aims to evaluate the association between SNPs of LDLR, APOB, and PCSK9 and risk of PMI in Chinese Han population.

Methods: Two cohorts were established. In Cohort 1 (413 in the PMI group and 1,239 in the control group), SNPs of APOB, LDLR, and PCSK9 with minor allele frequency (MAF) > 1%, which has been shown to impact the risk of PMI in a Chinese Han population, were thoroughly examined, and gene–environment interactions were analyzed. A model for PMI risk prediction was developed in Cohort 1 and externally validated in Cohort 2 (577 in the PMI group and 270 in the control group).

Results: The distribution of the T allele at the PCSK9 R93C variant (rs151193009, C > T) was lower in the PMI group than that in the control group (PMI vs. Control in Cohort 1, 0.8% vs. 2.3%, Padjust < 0.05; in Cohort 2, 1.0% vs. 2.4%, Padjust < 0.05). The T allele at PCSK9 R93C variant (rs151193009, C > T) reduced the risk of PMI by ∼60% regardless of adjusting for confounding factors (in Cohort 1, adjusted odds ratio (OR) 0.354, 95% confidence interval (CI) 0.139–0.900, p = 0.029; in Cohort 2, adjusted OR 0.394, 95% CI 0.157–0.987, p = 0.047). No gene–environment interactions were observed between the R93C variant and diabetes/hypertension/smoking in PMI occurrence in this Chinese Han population. Our model showed good performance in predicting the risk of PMI in Cohort 1 (AUC 0.839, 95% CI 0.815–0.862, p < 0.001) and in an external cohort (AUC 0.840, 95% CI 0.810–0.871, p < 0.001).

Conclusions: The PCSK9 R93C variant was associated with significantly reduced risk of PMI in the Chinese Han population, and the model we developed performed well in predicting PMI risk in this Chinese Han population.
Asymptomatic SARS-CoV-2 Infection Is Associated With Higher Levels of Serum IL-17C, Matrix Metalloproteinase 10 and Fibroblast Growth Factors Than Mild Symptomatic COVID-19
Authors: Soares-Schanoski Alessandra , Sauerwald Natalie , Goforth Carl W. , Periasamy Sivakumar , Weir Dawn L. , Lizewski Stephen , Lizewski Rhonda , Ge Yongchao , Kuzmina Natalia A. , Nair Venugopalan D. , Vangeti Sindhu , Marjanovic Nada , Cappuccio Antonio , Cheng Wan Sze , Mofsowitz Sagie , Miller Clare M. , Yu Xuechen B. , George Mary-Catherine , Zaslavsky Elena , Bukreyev Alexander , Troyanskaya Olga G. , Sealfon Stuart C. , Letizia Andrew G. , Ramos Irene
Published: April 2022

Young adults infected with SARS-CoV-2 are frequently asymptomatic or develop only mild disease. Because capturing representative mild and asymptomatic cases require active surveillance, they are less characterized than moderate or severe cases of COVID-19. However, a better understanding of SARS-CoV-2 asymptomatic infections might shed light into the immune mechanisms associated with the control of symptoms and protection. To this aim, we have determined the temporal dynamics of the humoral immune response, as well as the serum inflammatory profile, of mild and asymptomatic SARS-CoV-2 infections in a cohort of 172 initially seronegative prospectively studied United States Marine recruits, 149 of whom were subsequently found to be SARS-CoV-2 infected. The participants had blood samples taken, symptoms surveyed and PCR tests for SARS-CoV-2 performed periodically for up to 105 days. We found similar dynamics in the profiles of viral load and in the generation of specific antibody responses in asymptomatic and mild symptomatic participants. A proteomic analysis using an inflammatory panel including 92 analytes revealed a pattern of three temporal waves of inflammatory and immunoregulatory mediators, and a return to baseline for most of the inflammatory markers by 35 days post-infection. We found that 23 analytes were significantly higher in those participants that reported symptoms at the time of the first positive SARS-CoV-2 PCR compared with asymptomatic participants, including mostly chemokines and cytokines associated with inflammatory response or immune activation (i.e., TNF-α, TNF-β, CXCL10, IL-8). Notably, we detected 7 analytes (IL-17C, MMP-10, FGF-19, FGF-21, FGF-23, CXCL5 and CCL23) that were higher in asymptomatic participants than in participants with symptoms; these are known to be involved in tissue repair and may be related to the control of symptoms. Overall, we found a serum proteomic signature that differentiates asymptomatic and mild symptomatic infections in young adults, including potential targets for developing new therapies and prognostic tests.