bluuebunny/crossref_metadata_2025 huggingface dataset:
TINJAUAN HUKUM ISLAM TERHADAP PRAKTIK PENJUALAN IKAN HASIL PANEN MELALUI PERANTARA DI KECAMATAN GLAGAH KABUPATEN LAMONGAN
Authors: Qori Dani El
Published: January 2023

Buying and selling transactions are economic transactions that are mostly carried out by humans. This transaction continues to grow with the times. The development of buying and selling transactions necessitates the existence of appropriate and relevant legal instruments to regulate these transactions. Islamic law is believed to be a legal rule that is appropriate and relevant to be applied in all times and places. In its development, buying and selling not only confronts the seller and the buyer. Sometimes it takes a third party to act as an intermediary between the seller and the buyer. The practice of buying and selling in the presence of intermediaries is often carried out by fish pond owners in Glagah sub-district, Lamongan Regency. In this article, we will examine in depth the practice of selling fish through intermediaries from the perspective of Islamic law. The author uses the theory of buying and selling contracts, wakalah, ijarah, and samsarah in Islamic law.Kata Kunci : Buy and sell, intermediary, Islamic Law.
MAHAR UNIK DAN MAHAR BERNILAI FANTASTIS DALAM PERSPEKTIF FIKIH MUNAKAHAT
Authors: Nihayati Dini Arifah
Published: January 2023

The trend of unique dowry and fantastic dowry is mushrooming. Islam, does not specify the minimum and maximum dowry value. However, this trend seems to be a gap when it clashes with the public mindset that low dowry is identified with a lack of respect for women, while high dowries are considered difficult for men. Between the two, Indonesian people are used to following the dowry standards that apply in society to carry out the marriage contract. The mindset that collides with reality raises questions about the sharia and the law of giving dowry in various nominal or forms. Therefore, the authors need to examine this trend, especially its implications for the marriage contract. the author chooses fiqh munakahat as a knife of analysis. Because fiqh munakahat regulates the laws relating to marriage in Islam. This research is expected to be able to develop the application of fiqh munakahat to the unique and fantastic dowry trend. The author reaches the conclusion that in the perspective of munakahat fiqh, dowry can be given in any form and in unlimited value as long as the dowry meets the requirements. Unique or fantastic dowry does not affect the status of the marriage contract.
PRAKTIK JUAL BELI PADA AGROWISATA PETIK BUAH JERUK DI DESA WARU KECAMATAN PALANG KABUPATEN TUBAN PERSPEKTIF HUKUM ISLAM
Authors: Masyhudi Habib , Imroatus Shofiyah Zulfa
Published: January 2023

Tuban is one of the districts supporting the national food storage in East Java, where there are tourist attractions for citrus fruit picking gardens. Agriculture-based tourism will provide great opportunities for farmers and communities to expand the agricultural sector and increase income. The agro-tourism system for picking oranges in Waru Village, Palang District, Tuban Regency, is that every visitor who wants to enter an orange garden does not have an entry ticket, but is required to buy the fruit. Here the author is interested in researching this practice from the perspective of Islamic law. This study uses a qualitative method, data collection is done through interviews, observation, documentation, and meaning. The results of the analysis of buying and selling practices in citrus fruit picking agro-tourism concluded that buying and selling practices there did not meet the requirements in the specified buying and selling, namely the conditions of aqid (a person who has a contract), which should be the requirements of an aqid being baligh, intelligent, tamyyiz and without coercion, while on the other hand there is no opportunity for the buyer to cancel if he has agreed to the contract for granting permission to enter with these conditions. According to the Malikiyah and Hanafiyah scholars, a sale and purchase that has not fulfilled one of the terms and pillars means that the contract is classified as a vanity contract and the fiqh scholars state that a false contract is classified as an invalid contract..
Semilleros de Investigación Apuesta Curricular para la Formación Temprana en Investigación Científica.
Authors: Angulo Lerma Hernán
Published: January 2023

El contexto social y educativo presentan transformaciones sistémicas que irrumpen en el pensar, el ser y el devenir científico, este cambio, invade y confronta las fibras educativas que incitan a promover la investigación científica desde la formación temprana, asimismo, es evidente que el ser humanos es un ser pensante, analítico e inquieto por explorar y conocer el mundo.

Proponer semilleros de investigación como estrategia curricular para la formación temprana en investigación científica en estudiantes, de ahí que la investigación científica a través de la formación temprana de los estudiantes se constituye en una apuesta tentativa y enriquecedora para los planteles educativos, la sociedad y significativamente para la construcción del conocimiento y la creación de ciencia ciencia,  por consiguiente, visionar el ámbito investigativo con miras a fortalecer y promover la formación temprana en investigación científica fortalece todos los procesos educativos e investigativos de los estudiantes.

Los semilleros de investigación son una apuesta importante, debido a que potencia el aprendizaje de los estudiantes con miras a desarrollar y generar nuevas habilidades que a su vez contribuyen al mejoramiento de las prácticas de enseñanza - aprendizaje, asimismo, incluirlos en el currículo visiona nuevas posibilidades a nivel institucional y social, permitiendo un enfoque significativo que involucra docentes, directivos docentes, estudiantes, padres de familia y entidades gubernamentales para la implementación y promoción de la investigación científica a temprana edad.
Relevance of HLA-DP/DQ and INF-λ4 Polymorphisms to COVID-19 Outcomes
Authors: Ghazy Amany A. , Alrasheedi Abdullah N. , Elashri Mohammed , Moussa Hany Hussein , Rashwan Eman K. , Amer Ibrahim , El Sharawy Shimaa , Elgamal Shimaa , Tawfik Salwa , Abdelnasser Mohamed , Elsheredy Amel
Published: January 2023

Background: Single nucleotide polymorphisms provide information on individuals’ potential reactions to environmental factors, infections, diseases, as well as various therapies. A study on SNPs that influence SARS-CoV-2 susceptibility and severity may provide a predictive tool for COVID-19 outcomes and improve the customized coronavirus treatment.

Aim: To evaluate the role of human leukocyte antigens DP/DQ and IFNλ4 polymorphisms on COVID-19 outcomes among Egyptian patients.

Participants and Methods: The study involved 80 patients with severe COVID-19, 80 patients with mild COVID-19, and 80 non-infected healthy volunteers. Genotyping and allelic discrimination of HLA-DPrs3077 (G/A), HLA-DQrs7453920 (A/G), and IFNλ4 rs73555604 (C/T) SNPs were performed using real-time PCR.

Results: Ages were 47.9 ± 8, 44.1 ± 12.1, and 45.8 ± 10 years in severe, mild and non-infected persons. There was a statistically significant association between severe COVID-19 and male gender (p = 0.002). A statistically significant increase in the frequency of HLA-DPrs3077G, HLA-DQrs7453920A, and IFNλ4rs73555604C alleles among severe COVID-19 patients when compared with other groups (p < 0.001). Coexistence of these alleles in the same individual increases the susceptibility to severe COVID-19 by many folds (p < 0.001). Univariate and multivariate logistic regression analysis for the studied parameters showed that old age, male gender, non-vaccination, HLA-DQ rs7453920AG+AA, HLA-DPrs3077GA+GG, and IFNλ4rs73555604CT+CC genotypes are independent risk factors for severe COVID-19 among Egyptian patients.

Conclusion: HLA-DQ rs7453920A, HLA-DPrs3077G, and IFNλ4rs73555604C alleles could be used as markers of COVID-19 severity.
Treatment of engineering waste slurries by microbially induced struvite precipitation mechanisms
Authors: He Yuhan , Liu Shiyu , Shen Gangqiang , Pan Muzhi , Cai Yanyan , Yu Jin
Published: January 2023

With societal development, the growing scale of engineering construction, and the increase in environmental protection requirements, the necessity of engineering waste mud disposal is becoming increasingly prominent. In this study, microbially induced struvite precipitation (MISP) was introduced to treat engineering waste mud. The study mainly focused on: i) the optimal mineralization scheme for microbially induced struvite precipitation, ii) the feasibility of the process and the effect of reaction parameters on treating engineering waste mud with microbially induced struvite precipitation, and iii) the mechanism of microbially induced struvite precipitation in treating engineering waste mud. The results showed that the waste mud could be well treated with 8.36×106 cell⋅mL−1 bacteria, 10 mM urea, 20 mM phosphate buffer, and 25 mM MgCl2 at pH 7. The kaolin suspension could be effectively flocculated. The flocculation rate reached approximately 87.2% under the optimum mineralization conditions. The flocculation effect was mainly affected by the concentrations of reactants and heavy metals and the suspension pH. The X-ray diffraction (XRD) patterns showed a strong struvite (MAP) diffraction peak. Scanning electron microscopy (SEM) images indicated that under the optimal mineralization conditions, the crystals were large and showed prismatic shapes tilted at both ends with adhered kaolin particles. In summary, this manuscript provides an effective way to treat engineering waste mud, and the findings should have a positive effect on enhancing soil fertility and preventing secondary pollution.
Data, discourse, and development: Building a sustainable world through education and science communication
Authors: Gibson Heidi , Short Mary E. , O'Donnell Carol
Published: January 2023

Dramatic expansion of distance learning during COVID-19 widened the digital divide and highlighted the importance of students' digital and data literacy skills. Simultaneously, science was playing out in front of the public as information and communication about the importance of COVID-19 protective behaviors and vaccines evolved. Yet within the global discourse, misinformation was rampant. The public questioned the validity of COVID-19 data. They did not know who or what to trust. Their concerns about the impacts of COVID-19 protective behaviors and the need for vaccinations rose. Some science educators were asked to avoid discussing the topic with their students. All of this is emblematic of an even larger problem—the inability of many people to understand and use data to make informed decisions to develop their communities. This article will use one example from the Smithsonian Science for Global Goals project: Vaccines! How can we use science to help our community make decisions about vaccines?, which invites students ages 8–17 to use data to change discourse and develop their own communities using inspiration from the United Nations Sustainable Development Goals (SDGs). This project encourages students to: (1) use investigations to gather and analyze data from their communities as they build data literacy skills (data); (2) communicate this information to others as a way of catalyzing and changing community conversations to make informed decisions (discourse); and (3) become active partners in creating more sustainable and equitable communities (development). These competencies of data, discourse, and development—integrated into science, technology, engineering, and math education for sustainable development (STEM4SD)—are aligned with a “data for learning” conversation that emerged during the pandemic. To expand students' data skills, educators must be grounded in a framework that holistically considers ethics, community impact, and science. Data must be contextualized to the problems that students face locally. Students must be given the tools to communicate scientific understanding to others in service of sustainable development. As such, an SDG-aligned approach to data for learning that promotes discourse drives learners to act to protect themselves, our societies, and our planet, while educating students on the underlying science and social science of sustainable development.
Development and validation of nomogram models to discriminate between acute aortic syndromes and non-ST-elevation myocardial infarction during troponin-blind period
Authors: Tong Fei , Wang Yue , Sun Zhijun
Published: January 2023

Background

Blood-test-based methods of distinguishing between acute aortic syndromes (AASs) and non-ST-elevation myocardial infarction (NSTEMI) during the troponin-blind period of <2–3 h of symptom onset have not been studied previously. We aimed to explore whether routine biomarkers might facilitate differential diagnosis.

Methods

Data were retrospectively collected from 178 patients with AASs and 460 patients with NSTEMI within 3 h of onset. Differential risk factors related to AASs were identified by univariate and multivariate logistic regression analyses for patients with onset <2 h and onset ≥2 h, respectively, in the cardiac troponin (cTn) cohort. Nomograms were established in the cTn cohort as a training set and validated in the high-sensitivity cTn cohort. To assess the utility of the models in clinical practice, decision curve analyses were performed.

Results

D-dimer, fibrinogen, and age were identified as differential risk factors for AASs with the onset of <2 h. D-dimer at an optimal cutoff level of 281 ng/mL for AASs had a sensitivity of 86.4% and a specificity of 91.3%. A nomogram was developed and validated with areas under the curve (AUC) of 0.934 (95% CI: 0.880–0.988) and 0.952 (95% CI: 0.874–1.000), respectively. D-dimer, neutrophil, bilirubin, and platelet were the differential risk factors for AASs with the onset of ≥2 h. D-dimer at an optimal cutoff level of 385 ng/mL has a sensitivity of 91.8% and a specificity of 91.3%. The AUC of the second nomogram in the training set and the validation set were 0.965 (95% CI: 0.942–0.988) and 0.974 (95% CI: 0.944–1.000), respectively.

Conclusion

Time-dependent quality of D-dimer should be considered for discriminating AASs from NSTEMI. Both nomogram models may have a clinical utility for evaluating the probability of AASs.
Fault2SeisGAN: A method for the expansion of fault datasets based on generative adversarial networks
Authors: Zhao Shuo , Ding Renwei , Han Tianjiao , Liu YiLin , Zhang Jinwei , Zhao Lihong
Published: January 2023

The development of supervised deep learning technology in seismology and related fields has been restricted due to the lack of training sets. A large amount of unlabeled data is recorded in seismic exploration, and their application to network training is difficult, e.g., fault identification. To solve this problem, herein, we propose an end-to-end training data set generative adversarial network Fault2SeisGAN. This network can expand limited labeled datasets to improve the performance of other neural networks. In the proposed method, the Seis-Loss is used to constrain horizon and amplitude information, Fault-Loss is used to constrain fault location information, and the Wasserstein distance is added to stabilize the network training to generate seismic amplitude data with fault location labels. A new fault identification network model was trained with a combination of expansion and original data, and the model was tested using actual seismic data. The results show that the use of the expanded dataset generated in this study improves the performance of the deep neural network with respect to seismic data prediction. Our method solves the shortage of training data set problem caused by the application of deep learning technology in seismology to a certain extent, improves the performance of neural networks, and promotes the development of deep learning technology in seismology.
Maximizing frequency security margin via conventional generation dispatch and battery energy injection
Authors: Zhao Xiaohui , Wei Hua , Qi Junjian , Li Peijie , Bai Xiaoqing
Published: January 2023

To quantitatively evaluate the frequency stability margin during primary frequency control period following an under-frequency event, this paper presents a dynamic frequency response constrained optimal power flow (OPF) model. In this model, frequency security margin is defined and maximized by adjusting pre-disturbance generation outputs of conventional units and injections of battery energy storage system (BESS) immediately after a disturbance. Two nonlinear characteristics in speed-governing systems are considered and described as smooth and differentiable formulations to facilitate their incorporations into the proposed optimization model. A graphical tool is also provided to enable region-wise frequency security assessment based on the obtained maximum frequency security margin. Simulation results on WSCC 3-machine 9-bus system and New England 10-machine 39-bus system validate the suggested margin metric and the effectiveness of the proposed method.
A mixed integer linear programming model for minimum backbone grid
Authors: Mei Wenwen , Sun Zhiyuan , He Yuanjian , Liu Mosi , Gong Xianfu , Li Peijie
Published: January 2023

Developing a minimum backbone grid in the power system planning is beneficial to improve the power system’s resilience. To obtain a minimum backbone grid, a mixed integer linear programming (MILP) model with network connectivity constraints for a minimum backbone grid is proposed. In the model, some constraints are presented to consider the practical application requirements. Especially, to avoid islands in the minimum backbone grid, a set of linear constraints based on single-commodity flow formulations is proposed to ensure connectivity of the backbone grid. The simulations on the IEEE-39 bus system and the French 1888 bus system show that the proposed model can be solved with higher computational efficiency in only about 30 min for such a large system and the minimum backbone grid has a small scale only 52% of the original grid. Compared with the improved fireworks method, the minimum backbone grid from the proposed method has fewer lines and generators.
Exploring the impact of the digital economy on green total factor productivity in China: A spatial econometric perspective
Authors: Sun Xin , Jiang Ke , Cui Zhikun , Xu Jilan , Zhao Xin
Published: January 2023

The digital economy is considered a driving force of green economic development. However, only a few studies have examined the relationship between the digital economy and green total factor productivity (GTFP). According to the principal component method and super-efficient Slacks-based measure model, the digital economy level and green total factor productivity GTFP were measured for China’s provinces based on panel data from 2013 to 2019. The spatial econometric model was then used to analyze the effects of the digital economy level on green total factor productivity GTFP. Results showed that the overall level of green total factor productivity GTFP maintained a steady growth trend, with an average yearly growth of 4.19%. Significant regional differences reflecting the development characteristics of eastern, central, and western regions were also observed. Most provinces showed either high or low values of both green total factor productivity GTFP and digital economic development thereby revealing spatial heterogeneity for the different provinces and cities. The spatial Durbin model showed that the digital economy had a significant direct effect (0.1498) and spatial spillover effect (0.3438) on green total factor productivity GTFP, the latter being greater than the former, with this conclusion supported by the robustness test. Technological innovation positively regulates the contribution of the region’s digital economy to green total factor productivity GTFP and negatively regulates the spatial spillover of the digital economy to green total factor productivity GTFP in neighboring regions.
Pakistan’s water resource management: Ensuring water security for sustainable development
Authors: Ishaque Waseem , Mukhtar Mudassir , Tanvir Rida
Published: January 2023

Pakistan is blessed with abundant water resources but facing a critical water shortage due to a lack of storage facilities, poor water governance, and the adverse impacts of climate change. The burgeoning population at present 225 million, which is expected to cross 250 million by 2025 is creating an additional burden on water resources, as per capita availability is depleting sharply from 5,000 m3 in 1951 to 1,100 m3 in 2005, which is expected to fall to 800 m3 by 2025. Pakistan’s water demand is increasing at an average yearly rate of 10% which in terms of the area will increase to 338 km3 by 2025, against the availability of 240–258 km3. Out of the available surface water, approximately 74% is extracted, while 83% of the groundwater is used for agricultural and other uses, which is an exceptionally high ratio for a water-scarce country like Pakistan. The adverse impacts of climate change are also causing extreme weather conditions, resulting in drought and floods almost every year. Inadequate water reservoirs, water wastage in agriculture and households, negligible wastewater recycling, and contamination of drinking water are causing health risks that have turned serious national security challenges for Pakistan. This research article argues that surface and subsurface water in Pakistan is depleting sharply, and if not addressed in time, has the potential of becoming the biggest national security problem. The article investigates the available water status in Pakistan covering surface and subsurface resources in detail, including reservoirs for storage, and sectoral utilization, to draw conclusions on water availability and usage requirement. The policy recommendations highlight the effective integration of smart technology in addressing multidimensional water issues and efficient water governance for ensuring water security for the sustainable development of Pakistan.
Screening potential lncRNA biomarkers for breast cancer and colorectal cancer combining random walk and logistic matrix factorization
Authors: Li Shijun , Chang Miaomiao , Tong Ling , Wang Yuehua , Wang Meng , Wang Fang
Published: January 2023

Breast cancer and colorectal cancer are two of the most common malignant tumors worldwide. They cause the leading causes of cancer mortality. Many researches have demonstrated that long noncoding RNAs (lncRNAs) have close linkages with the occurrence and development of the two cancers. Therefore, it is essential to design an effective way to identify potential lncRNA biomarkers for them. In this study, we developed a computational method (LDA-RWLMF) by integrating random walk with restart and Logistic Matrix Factorization to investigate the roles of lncRNA biomarkers in the prognosis and diagnosis of the two cancers. We first fuse disease semantic and Gaussian association profile similarities and lncRNA functional and Gaussian association profile similarities. Second, we design a negative selection algorithm to extract negative LncRNA-Disease Associations (LDA) based on random walk. Third, we develop a logistic matrix factorization model to predict possible LDAs. We compare our proposed LDA-RWLMF method with four classical LDA prediction methods, that is, LNCSIM1, LNCSIM2, ILNCSIM, and IDSSIM. The results from 5-fold cross validation on the MNDR dataset show that LDA-RWLMF computes the best AUC value of 0.9312, outperforming the above four LDA prediction methods. Finally, we rank all lncRNA biomarkers for the two cancers after determining the performance of LDA-RWLMF, respectively. We find that 48 and 50 lncRNAs have the highest association scores with breast cancer and colorectal cancer among all lncRNAs known to associate with them on the MNDR dataset, respectively. We predict that lncRNAs HULC and HAR1A could be separately potential biomarkers for breast cancer and colorectal cancer and need to biomedical experimental validation.
Inversion of shallow seabed structure and geoacoustic parameters with waveguide characteristic impedance based on Bayesian approach
Authors: Zhu Hanhao , Xue Yangyang , Ren Qunyan , Liu Xu , Wang Jiahui , Cui Zhiqiang , Zhang Shu , Fan Huili
Published: January 2023

Underwater acoustic technology is essential for ocean observation, exploration and exploitation, and its development is based on an accurate predication of underwater acoustic wave propagation. In shallow sea environments, the geoacoustic parameters, such as the seabed structure, the sound speeds, the densities, and the sound speed attenuations in seabed layers, would significantly affect the acoustic wave propagation characteristics. To obtain more accurate inversion results for these parameters, this study presents an inversion method using the waveguide characteristic impedance based on the Bayesian approach. In the inversion, the vertical waveguide characteristic impedance, which is the ratio of the pressure over the vertical particle velocity, is set as the matching object. The nonlinear Bayesian theory is used to invert the above geoacoustic parameters and analysis the uncertainty of the inversion results. The numerical studies and the sea experiment processing haven shown the validity of this inversion method. The numerical studies also proved that the vertical waveguide characteristic impedance is more sensitive to the geoacoustic parameters than that of single acoustic pressure or single vertical particle velocity, and the error of simulation inversion is within 3%. The sea experiment processing showed that the seabed layered structure and geoacoustic parameters can be accurately determined by this method. The root mean square between the vertical waveguide characteristic impedance and the measured impedance is 0.38dB, and the inversion results accurately represent the seabed characteristics in the experimental sea area.
Avian strains of emerging pathogen Escherichia fergusonii are phylogenetically diverse and harbor the greatest AMR dissemination potential among different sources: Comparative genomic evidence
Authors: Srinivas Kandhan , Ghatak Sandeep , Pyngrope Daniel Aibor , Angappan Madesh , Milton Arockiasamy Arun Prince , Das Samir , Lyngdoh Vanita , Lamare John Pynhun , Prasad Mosuri Chendu Bharat , Sen Arnab
Published: January 2023

Introduction

Escherichia fergusonii is regarded as an emerging pathogen with zoonotic potential. In the current study, we undertook source-wise comparative genomic analyses (resistome, virulome, mobilome and pangenome) to understand the antimicrobial resistance, virulence, mobile genetic elements and phylogenetic diversity of E. fergusonii.

Methods

Six E. fergusonii strains (5 multidrug resistant strains and 1 biofilm former) were isolated from poultry (duck faeces and retail chicken samples). Following confirmation by phenotypic and molecular methods, the isolates were further characterized and their genomes were sequenced. Comparative resisto-virulo-mobilome analyses and pangenomics were performed for E. fergusonii genomes, while including 125 other E. fergusonii genomes available from NCBI database.

Results and discussion

Avian and porcine strains of E. fergusonii were found to carry significantly higher number of antimicrobial resistance genes (p < 0.05) and mobile genetic elements (plasmids, transposons and integrons) (p < 0.05), while the pathogenic potential of bovine strains was significantly higher compared to other strains (p < 0.05). Pan-genome development trends indicated open pan-genome for all strains (0 < γ < 1). Genomic diversity of avian strains was found to be greater than that from other sources. Phylogenetic analysis revealed close clustering among isolates of similar isolation source and geographical location. Indian isolates of E. fergusonii clustered closely with those from Chinese and a singleton Australian isolate. Overall, being the first pangenomic study on E. fergusonii, our analysis provided important cues on genomic features of the emerging pathogen E. fergusonii while highlighting the potential role of avian strains in dissemination of AMR.
The SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways mediated by microRNA-25-3p are altered in the schizophrenic rat brain
Authors: Pan Bo , Zhu Xiaoli , Han Bing , Weng Jianjun , Wang Yuting , Liu Yanqing
Published: January 2023

Schizophrenia is a group of severe mental disorders. MiR-25-3p was shown to be involved in various neuropsychiatric diseases and can regulate SIK1 and TWIST1. The CRTC2/CREB1 and PI3K/Akt/GSK3β signaling pathways are downstream pathways of SIK1 and TWIST1, respectively. This study investigated whether miR-25-3p-mediated SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways are present in an animal model relevant to schizophrenia. A schizophrenic rat model was established by using sub-chronic MK-801 administration. An RNA-seq test was performed to examine the differentially expressed genes (DEGs) in the rat prefrontal cortex (PFC). The mRNA levels of miR-25-3p, SIK1, and TWIST in the PFC and caudate putamen (CPu) were assessed by qRT-PCR. Phosphorylation of the SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β pathways in the two brain regions was examined by Western blots. The RNA-seq data revealed down-regulated miR-25-3p expression and up-regulated SIK1 and TWIST1 mRNA expression induced by MK-801. Additionally, SIK1 and TWIST1 were shown to be possible downstream responders of miR-25-3p in previous studies. qRT-PCR confirmed the changes of miR-25-3p, SIK1, and TWIST1 induced by MK-801 in both brain regions, which, however, was reversed by risperidone. Furthermore, the phosphorylation of the SIK1/CRTC2/CREB1 pathway was repressed by MK-801, whereas the phosphorylation of the TWIST1/PI3K/Akt/GSK3β pathway was increased by MK-801 in either of the two brain regions. Moreover, the altered phosphorylation of these two signaling pathways induced by MK-801 can be restored by risperidone. In conclusion, this study suggests that altered SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways mediated by miR-25-3p is very likely to be associated with schizophrenia, revealing potential targets for the treatment and clinical diagnosis of schizophrenia.
The efficacy and mechanism of berberine in improving aging-related cognitive dysfunction: A study based on network pharmacology
Authors: Yao Jiuxiu , Wei Wei , Wen Jiayu , Cao Yu , Li Hao
Published: January 2023

Objective

To analyze the effects and mechanisms of berberine in the treatment of aging-related cognitive dysfunction based on network pharmacology methods, molecular docking techniques, and animal experiments.

Methods

A mouse model of cognitive dysfunction was constructed by subcutaneous injection of D-galactose (D-gal) for 10 weeks, and the neuroprotective effects of berberine on aging-related cognitive dysfunction mice were evaluated by the Morris water maze (MWM) and immunofluorescence staining. The targets of berberine were obtained by SwissTargetPrediction, GeneCards, and PharmMapper. Putative targets of cognitive dysfunction were obtained by GeneCards, TTD, and DrugBank database. The STRING database and Cytoscape software were applied for protein-protein interaction (PPI) analysis and further screening of core targets. The DAVID database was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analysis to clarify the biological processes and pathways involved in the intersection targets, and AutoDockTools was adopted for molecular docking verification of core targets. Finally, the core genes were validated using real-time quantitative PCR.

Results

The MWM results showed that treatment with berberine significantly improved spatial learning and memory in mice with cognitive decline induced by D-gal. Immunofluorescence staining indicated that berberine modified the levels of aging-related markers in the brain. A total of 386 berberine putative targets associated with cognitive dysfunction were identified based on the public database. The core targets of berberine for improving cognitive function, include Mapk1, Src, Ctnnb1, Akt1, Pik3ca, Tp53, Jun, and Hsp90aa1. GO enrichment and KEGG pathway enrichment analyses indicated that the mechanism of berberine in the treatment of aging-related cognitive dysfunction is attributed to pathways such as PI3K-AKT and MAPK pathways. In vivo experiments further confirmed that Akt1, Ctnnb1, Tp53, and Jun were involved in the neuroprotective actions of berberine.

Conclusion

This study reveals the multi-target and multi-pathway effects of berberine on regulating aging-related cognitive dysfunction, which provides preclinical evidence and may promote new drug development in mitigating cognitive dysfunction.
A novel food processing-based nutrition classification scheme for guiding policy actions applied to the Australian food supply
Authors: Dickie Sarah , Woods Julie , Machado Priscila , Lawrence Mark
Published: January 2023

Unhealthy diets are a leading risk factor for non-communicable diseases and negatively impact environmental sustainability. Policy actions recommended to address dietary risk factors, such as restrictions on marketing and front-of-pack labelling, are informed by nutrition classification schemes (NCSs). Ultra-processed foods are associated with adverse population and planetary health outcomes, yet the concept is rarely incorporated in nutrition classification schemes for policy actions. This study aims to develop a novel food processing-based nutrition classification scheme for guiding policy actions. A secondary aim is to validate the scheme by classifying food and beverage items in the Australian food supply (face validity) and comparing them to the classifications of existing NCSs (convergent validity). Two versions of a model were developed, classifying foods and beverages in two steps, first using the NOVA classification system and secondly by applying upper thresholds for added free sugars and sodium, producing a binary output of either healthy or unhealthy. All food and beverage items (n = 7,322) in a dataset combining the Australian Food Composition Database (AUSNUT 2011–2013) and Mintel’s Global New Product Database (2014–2019) were classified using the two models. The same dataset was also classified by the Health Star Rating system (HSR), The Australian Dietary Guidelines (ADGs), The Pan American Health Organization’s Nutrient Profile Model (PAHO NPM), and the NOVA classification scheme, and pairwise agreement between all NCSs and the two models was determined (using Cohen’s Kappa coefficient). A higher proportion of food categories consistent with dietary patterns that are associated with positive health outcomes, such and fruits, vegetables, and eggs were classified as healthy. And the clear majority of food categories consistent with dietary patterns associated with adverse health outcomes, such as confectionery, snack foods, and convenience foods were classified as unhealthy. The two versions of the model showed substantial agreement with NOVA and the PAHO NPM, fair agreement with the ADGs and slight to moderate agreement with the HSR system. A model NCS combining level of processing and nutrient criteria presents a valid alternative to existing methods to classify the health potential of individual foods for policy purposes.
Current status of and progress in the treatment of malignant pleural effusion of lung cancer
Authors: Zhao Yuhua , Yu Limeng , Wang Lili , Wu Yingxi , Chen Haiyang , Wang Qiming , Wu Yufeng
Published: January 2023

Malignant pleural effusion (MPE) is a common complication in the late stage of malignant tumors. The appearance of MPE indicates that the primary tumor has spread to the pleura or progressed to an advanced stage. The survival time of the patients will be significantly shortened, with a median survival of only a few months. There are a variety of traditional treatments, and their advantages and disadvantages are relatively clear. There are still many problems that cannot be solved by traditional methods in clinical work. The most common one is intrapleural perfusion therapy with chemotherapy drugs, but it has a large side effect of chemotherapy. At present, with the development of medical technology, there are a variety of treatment methods, and many innovative, significant and valuable treatment methods have emerged, which also bring hope for the treatment of refractory and recurrent MPE patients. Several clinical trials had confirmed that drug-carrying microparticles has less adverse reactions and obvious curative effect. However, there is still a long way to go to completely control and cure MPE, and the organic combination of clinical work and scientific research results is needed to bring dawn to refractory MPE patients.
High risk-myelodysplastic syndrome following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma: A case report and literature review
Authors: Accorsi Buttini Eugenia , Farina Mirko , Lorenzi Luisa , Polverelli Nicola , Radici Vera , Morello Enrico , Colnaghi Federica , Almici Camillo , Ferrari Emilio , Bianchetti Andrea , Leoni Alessandro , Re Federica , Bosio Katia , Bernardi Simona , Malagola Michele , Re Alessandro , Russo Domenico
Published: January 2023

Background

Chimeric antigen receptor (CAR) T-cell therapy represents the most advanced immunotherapy against relapsed/refractory B cell malignancies. While cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are distinctive, known CAR T-cell acute adverse events, hematological toxicity has been increasingly reported. Cytopenia following CAR T-cell treatment is attributed in most cases to lymphodepletion regimens, bridging chemotherapy, or radiotherapy. However, when cytopenia becomes prolonged, the development of myelodysplastic syndrome (MDS) should be considered.

Case presentation

We report a case of high risk (HR)-MDS following CAR T-cell therapy in a patient with relapsed diffuse large B cell lymphoma. Eight months after CAR T-cell infusion, the blood count showed progressive, worsening cytopenia and the bone marrow biopsy revealed multilineage dysplasia without excess of blasts associated with chromosome 7 deletion and RUNX1 mutation. Next generation sequencing analysis, retrospectively performed on stored samples, showed a germ line CSF3R mutation, CEBPA clonal hematopoiesis, but no RUNX1 lesion.

Conclusion

We describe a case of HR-MDS, with deletion of chromosome 7 and acquisition of RUNX1 mutation, developing after CAR T-cell therapy in a patient with clonal hematopoiesis (CH). Previous chemotherapy favored MDS onset; however, we could not exclude the fact that the impairment of immunosurveillance related to either lymphodepletion or CAR T-cell infusion may play a role in MDS development. Thus, we designed a multicenter prospective study (ClonHema-CAR-T-Study) to investigate if cytopenia after CAR T-cell treatment may be due to underling CH as well as the presence of secondary myeloid malignancies.
Age independent survival benefit for patients with small hepatocellular carcinoma undergoing percutaneous cryoablation: A propensity scores matching study
Authors: Zhang Huixin , Xu Muoyan , Shao Jiashen , Kong Huifang , Gao Xudong , Zhang Wei , Chang Xiujuan , Yang Bin , Chen Yan , Dong Zheng , Huang Jiagan , Zeng Zhen , Yang Yongping
Published: January 2023

Background

Hepatocellular carcinoma (HCC) is the major cause of malignancy-related deaths worldwide, and its incidence is likely to increase in the future as life expectancy increases. Therefore, the management of elderly patients with HCC has become a global issue. Aim of this study was to assess whether elderly patients with small HCC could obtain survival benefit from cryoablation (CRYO) in a real-world.

Materials and methods

From July 2007 to June 2013, 185 patients with small HCC who underwent curative-intent percutaneous CRYO. All patients were divided into three groups according to age distribution. Overall survival (OS) and tumor-free survival (TFS) were compared between among of groups before and after the 1:1 propensity score matching, respectively. Univariate and multivariate Cox analyses were performed to determine the potential relationships between variables and prognostic outcomes.

Results

One hundred and eighty-five patients (144 men, 41 women) received CRYO for small HCC, including 59 patients with age <50 years, 105 patients with age between 50 and 65 years, and 21 patients with age >65 years. The three age groups showed significant differences in the terms of underlying chronic liver disease and the number of patients with minor postoperative complications. After propensity score matching, the younger and elderly groups showed significant differences in mean OS (P=0.008) and tumor progression (P=0.050). However, no significant differences were shown in mean progression-free survival (PFS) (P=0.303). The Cox multivariate analysis showed that the Child-Pugh grade (HR=3.1, P<0.001), albumin (HR=0.85, P=0.004) and total of bilirubin (HR=1, P=0.024) were the independent prognostic factor for mean OS.

Conclusion

Our propensity-score-matched study suggested that elderly patients with small HCC can achieve acceptable prognostic outcomes with PFS similar to those of younger patients with small HCC after treatment with CRYO, while Child-Pugh grade, bilirubin and serum albumin levels were associated with the prognosis of small HCCs.
A low phase noise high power Er-fiber frequency comb synchronized to the hydrogen maser clock by harmonic phase locking
Authors: Li Mingkun , Yang Xiguang , Rao Bingjie , Yan Lulu , Chen Xin , Yuan Ru , Zhang Pan , Zhang Yanyan , Liu Tao
Published: January 2023

We demonstrate a low phase noise all polarization-maintaining (PM) Er-fiber optical frequency comb (OFC) with low phase noise, which is synchronized to the hydrogen maser clock (HMC) using the 18th harmonic of the repetition rate for tight phase locking. The instability of the locked carrier envelope offset frequency is 1.24 × 10−18@1 s, the phase noise of the OFC is −96 dBc/Hz at 1 Hz offset, and the corresponding RMS timing jitter of the repetition rate is 62 fs (1 Hz–1 MHz). The residual frequency instability of the repetition rate (200 MHz) is 1.46 × 10−14@1 s, and the residual phase noise of the OFC normalized to 10 MHz is −138 dBc/Hz at 1 Hz offset and declines to about −160 dBc/Hz at the far-end, much lower than that of the HMC (−122 dBc/Hz at 1 Hz and −156 dBc/Hz at the far-end).
Conventional and new-breeding technologies for improving disease resistance in lentil (Lens culinaris Medik)
Authors: Roy Anirban , Sahu Parmeshwar K. , Das Camellia , Bhattacharyya Somnath , Raina Aamir , Mondal Suvendu
Published: January 2023

Lentil, an important cool season food legume, is a rich source of easily digestible protein, folic acid, bio-available iron, and zinc nutrients. Lentil grows mainly as a sole crop in the winter after harvesting rice in South Asia. However, the annual productivity is low due to its slow growth during the early phase, competitive weed infestation, and disease outbreaks during the crop growth period. Disease resistance breeding has been practiced for a long time to enhance resistance to various diseases. Often the sources of resistance are available in wild crop relatives. Thus, wide hybridization and the ovule rescue technique have helped to introgress the resistance trait into cultivated lentils. Besides hybridization, induced mutagenesis contributed immensely in creating variability for disease tolerance, and several disease-resistant mutant lines have been developed. However, to overcome the limitations of traditional breeding approaches, advancement in molecular marker technologies, and genomics has helped to develop disease-resistant and climate-resilient lentil varieties with more precision and efficiency. This review describes types of diseases, disease screening methods, the role of conventional and new breeding technologies in alleviating disease-incurred damage and progress toward making lentil varieties more resilient to disease outbreaks under the shadow of climate change.
Integrated GWAS and transcriptomic analysis reveal the candidate salt-responding genes regulating Na+/K+ balance in barley (Hordeum vulgare L.)
Authors: Xu Tingting , Meng Shan , Zhu Xiaopin , Di Jiachun , Zhu Yin , Yang Xin , Yan Wei
Published: January 2023

Salt stress is one of the main abiotic stresses affecting crop yield and quality. Barley has strong salt tolerance, however, the underlying genetic basis is not fully clear, especially in the seedling stage. This study examined the ionic changes in barley core germplasms under the control and salt conditions. Genome-wide association study (GWAS) analysis revealed 54 significant SNPs from a pool of 25,342 SNPs distributed in 7 chromosomes (Chr) of the Illumina Barley 50K SNP array. These SNPs are associated with ion homeostasis traits, sodium (Na+) and potassium (K+) content, and Na+/K+ ratio representing five genomic regions on Chr 2, 4, 5, 6, and 7 in the leaves of worldwide barley accessions. And there are 3 SNP peaks located on the Chr 4, 6, and 7, which could be the “hot spots” regions for mining and identifying candidate genes for salt tolerance. Furthermore, 616 unique candidate genes were screened surrounding the significant SNPs, which are associated with transport proteins, protein kinases, binding proteins, and other proteins of unknown function. Meanwhile, transcriptomic analysis (RNA-Seq) was carried out to compare the salt-tolerant (CM72) and salt-sensitive (Gairdner) genotypes subjected to salt stress. And there was a greater accumulation of differentially expressed genes(DEGs) in Gairdner compared to CM72, mainly enriched in metabolic pathway, biosynthesis of secondary metabolites, photosynthesis, signal transduction,emphasizing the different transcriptional response in both genotypes following salt exposure. Combined GWAS and RNA-Seq analysis revealed 5 promising salt-responding genes (PGK2, BASS3, SINAT2, AQP, and SYT3) from the hot spot regions, which were verified between the salt-tolerant and salt-sensitive varieties by qRT-PCR. In all, these results provide candidate SNPs and genes responsible for salinity responding in barley, and a new idea for studying such genetic basis in similar crops.