bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenecteplase vs. alteplase for acute ischemic stroke: a systematic review
Authors: Potla Neha , Ganti Latha 
Published: January 2022

Abstract
Introduction
Thrombolysis for acute ischemic stroke (AIS) with alteplase is the currently approved therapy for patients who present within 4.5 h of symptom onset and meet criteria. Recently, there has been interest in the thrombolytic tenecteplase, a modified version of alteplase, due to its lower cost, ease of administration, and studies reporting better outcomes when compared to alteplase.
This systematic review compares the efficacy of tenecteplase vs. alteplase with regard to three outcomes: (1) rate of symptomatic hemorrhage, (2) functional outcome at 90 days, and (3) reperfusion grade after thrombectomy to compare the efficacy of both thrombolytics in AIS

Methods
The search was conducted in August 2021 in PubMed, filtered for randomized controlled trials, and studies in English. The main search term was “tenecteplase for acute stroke.”

Results
A total of 6 randomized clinical trials including 1675 patients with AIS was included. No one’s study compared alteplase to tenecteplase with all three outcomes after acute ischemic stroke; however, by using a combination of the results, this systematic review summarizes whether tenecteplase outperforms alteplase.

Conclusions
The available evidence suggests that tenecteplase appears to be a better thrombolytic agent for acute ischemic stroke when compared to alteplase.
Targeted Deletion of the First Intron of the Wxb Allele via CRISPR/Cas9 Significantly Increases Grain Amylose Content in Rice
Authors: Liu Xingdan , Ding Qi , Wang Wenshu , Pan Yanling , Tan Chao , Qiu Yingbo , Chen Ya , Li Hongjing , Li Yinlong , Ye Naizhong , Xu Nian , Wu Xiao , Ye Rongjian , Liu Jianfeng , Ma Chonglie 
Published: January 2022

Abstract
Background
The rice Waxy (Wx) gene plays a major role in seed amylose synthesis and consequently controls grain amylose content. Wx gene expression is highly regulated at the post-transcriptional level. In particular, the GT/TT polymorphism at the 5′splicing site of its 1st intron greatly affects this intron’s splicing efficiency and defines two predominant Wx alleles, Wxa and Wxb. Wxa rice often harbours intermediate to high amylose contents, whereas Wxb rice exhibits low to intermediate amylose contents. By deleting the Wx 1st intron using CRISPR/Cas9 technology, we generate a completely novel Wx allele and further investigate how intron removal affects Wx gene expression and rice grain amylose content.

Results
CRISPR/Cas9-mediated targeted deletion of the Wx 1st intron was performed on 4 rice inbred lines: KY131 (Wxb), X32 (Wxb), X35 (Wxa) and X55 (Wxlv). Deletion of the 1st intron occurred in 8.6–11.8% of the primary transformants of these 4 inbred lines. Compared to wild-type plants, amylose content was significantly increased from 13.0% to approximately 24.0% in KY131 and X32 mutant lines, which both carried the Wxb allele. However, no significant difference in amylose content was observed between wild-type plants and X35 and X55 mutant lines, which carried the Wxa and Wxlv alleles, respectively. Wx gene expression analysis of wild-type plants and mutants yielded results that were highly consistent with amylose content results. KY131 and X32 mutants accumulated increased levels of steady mRNA transcripts compared with wild-type plants, whereas steady mRNA levels were not altered in X35 and X55 mutants compared with wild-type plants. Grain quality, including appearance quality and eating and cooking quality, which are tightly associated with amylose content, was also assessed in wild-type and mutant plants, and data were presented and analysed.

Conclusions
This study presents a novel and rapid strategy to increase amylose content in inbred rice carrying a Wxb allele. Our data strongly suggest that the 1st intron of the Wx gene regulates Wx gene expression mainly at the post-transcriptional level in rice. This finding is in contrast to a previous hypothesis suggesting that it influences Wx gene transcription. In addition, removal of the first intron generates a completely novel Wx allele. Further studies on this new Wx allele will provide invaluable insights into the regulation of Wx gene expression, which will help researchers engineer new Wx alleles to facilitate the breeding of rice cultivars with better eating and cooking quality.
gGATLDA: lncRNA-disease association prediction based on graph-level graph attention network
Authors: Wang Li , Zhong Cheng 
Published: January 2022

Abstract
Background
Long non-coding RNAs (lncRNAs) are related to human diseases by regulating gene expression. Identifying lncRNA-disease associations (LDAs) will contribute to diagnose, treatment, and prognosis of diseases. However, the identification of LDAs by the biological experiments is time-consuming, costly and inefficient. Therefore, the development of efficient and high-accuracy computational methods for predicting LDAs is of great significance.

Results
In this paper, we propose a novel computational method (gGATLDA) to predict LDAs based on graph-level graph attention network. Firstly, we extract the enclosing subgraphs of each lncRNA-disease pair. Secondly, we construct the feature vectors by integrating lncRNA similarity and disease similarity as node attributes in subgraphs. Finally, we train a graph neural network (GNN) model by feeding the subgraphs and feature vectors to it, and use the trained GNN model to predict lncRNA-disease potential association scores. The experimental results show that our method can achieve higher area under the receiver operation characteristic curve (AUC), area under the precision recall curve (AUPR), accuracy and F1-Score than the state-of-the-art methods in five fold cross-validation. Case studies show that our method can effectively identify lncRNAs associated with breast cancer, gastric cancer, prostate cancer, and renal cancer.

Conclusion
The experimental results indicate that our method is a useful approach for predicting potential LDAs.
Hierarchical shared transfer learning for biomedical named entity recognition
Authors: Chai Zhaoying , Jin Han , Shi Shenghui , Zhan Siyan , Zhuo Lin , Yang Yu 
Published: January 2022

Abstract
Background
Biomedical named entity recognition (BioNER) is a basic and important medical information extraction task to extract medical entities with special meaning from medical texts. In recent years, deep learning has become the main research direction of BioNER due to its excellent data-driven context coding ability. However, in BioNER task, deep learning has the problem of poor generalization and instability.

Results
we propose the hierarchical shared transfer learning, which combines multi-task learning and fine-tuning, and realizes the multi-level information fusion between the underlying entity features and the upper data features. We select 14 datasets containing 4 types of entities for training and evaluate the model. The experimental results showed that the F1-scores of the five gold standard datasets BC5CDR-chemical, BC5CDR-disease, BC2GM, BC4CHEMD, NCBI-disease and LINNAEUS were increased by 0.57, 0.90, 0.42, 0.77, 0.98 and − 2.16 compared to the single-task XLNet-CRF model. BC5CDR-chemical, BC5CDR-disease and BC4CHEMD achieved state-of-the-art results.The reasons why LINNAEUS’s multi-task results are lower than single-task results are discussed at the dataset level.

Conclusion
Compared with using multi-task learning and fine-tuning alone, the model has more accurate recognition ability of medical entities, and has higher generalization and stability.
An effective drug-disease associations prediction model based on graphic representation learning over multi-biomolecular network
Authors: Jiang Hanjing , Huang Yabing 
Published: January 2022

AbstractBackgroundDrug-disease associations (DDAs) can provide important information for exploring the potential efficacy of drugs. However, up to now, there are still few DDAs verified by experiments. Previous evidence indicates that the combination of information would be conducive to the discovery of new DDAs. How to integrate different biological data sources and identify the most effective drugs for a certain disease based on drug-disease coupled mechanisms is still a challenging problem.ResultsIn this paper, we proposed a novel computation model for DDA predictions based on graph representation learning over multi-biomolecular network (GRLMN). More specifically, we firstly constructed a large-scale molecular association network (MAN) by integrating the associations among drugs, diseases, proteins, miRNAs, and lncRNAs. Then, a graph embedding model was used to learn vector representations for all drugs and diseases in MAN. Finally, the combined features were fed to a random forest (RF) model to predict new DDAs. The proposed model was evaluated on the SCMFDD-S data set using five-fold cross-validation. Experiment results showed that GRLMN model was very accurate with the area under the ROC curve (AUC) of 87.9%, which outperformed all previous works in terms of both accuracy and AUC in benchmark dataset. To further verify the high performance of GRLMN, we carried out two case studies for two common diseases. As a result, in the ranking of drugs that were predicted to be related to certain diseases (such as kidney disease and fever), 15 of the top 20 drugs have been experimentally confirmed.ConclusionsThe experimental results show that our model has good performance in the prediction of DDA. GRLMN is an effective prioritization tool for screening the reliable DDAs for follow-up studies concerning their participation in drug reposition.
An ontogenic study of receptor mechanisms by which acute administration of low-doses of methamphetamine suppresses DOI-induced 5-HT2A-receptor mediated head-twitch response in mice
Authors: Sun Yina , Chebolu Seetha , Henry Denise , Lankireddy Sandeep , Darmani Nissar A. 
Published: January 2022

Abstract
Background
Methamphetamine (MA) is a non-selective monoamine releaser and thus releases serotonin (5-HT), norepinephrine (NE) and dopamine (DA) from corresponding nerve terminals into synapses. DOI ((±)-2, 5-dimethoxy-4-iodoamphetamine) is a direct-acting serotonergic 5-HT2A/C receptor agonist and induces the head-twitch response (HTR) via stimulation of 5-HT2A receptor in mice. While more selective serotonin releasers such as d-fenfluramine evoke the HTR, monoamine reuptake blockers (e.g., cocaine) suppress the DOI-evoked HTR via indirect stimulation of serotonergic 5-HT1A- and adrenergic ɑ2-receptors. Since the induction of HTR by DOI is age-dependent, we investigated whether: (1) during development MA can evoke the HTR by itself, and (2) acute pretreatment with either the selective 5-HT2A receptor antagonist EMD 281014 or low-doses of MA can: (i) modulate the DOI-induced HTR in mice across postnatal days 20, 30 and 60, and (ii) alter the DOI-induced c-fos expression in mice prefrontal cortex (PFC). To further explore the possible modulatory effect of MA on DOI-induced HTR, we investigated whether blockade of inhibitory serotonergic 5-HT1A- or adrenergic ɑ2-receptors by corresponding selective antagonists (WAY 100635 or RS 79948, respectively), can prevent the effect of MA on DOI-induced HTR during aging.

Results
Although neither EMD 281014 nor MA by themselves could evoke the HTR, acute pretreatment with either EMD 281014 (0.01, 0.05 and 0.1 mg/kg, i.p.) or MA (1, 2.5, 5 mg/kg, i.p.), dose-dependently suppressed the DOI-induced HTR across ages. While WAY 100635 significantly reversed the inhibitory effect of MA in 20- and 30-day old mice, RS 79948 failed to significantly counter MA’s inhibitory effect. Moreover, DOI significantly increased c-fos expressions in several PFC regions. EMD 281014 prevented the DOI-induced increases in c-fos expression. Despite the inhibitory effect of MA on DOI-induced HTR, MA alone or in combination with DOI, significantly increased c-fos expression in several regions of the PFC.

Conclusion
The suppressive effect of MA on the DOI-evoked HTR appears to be mainly due to functional interactions between the HTR-inducing 5-HT2A receptor and the inhibitory 5-HT1A receptor. The MA-induced increase in c-fos expression in different PFC regions may be due to MA-evoked increases in synaptic concentrations of 5-HT, NE and/or DA.
Increased expression of pathological markers in Parkinson’s disease dementia post-mortem brains compared to dementia with Lewy bodies
Authors: Tu Haitao , Zhang Zhi Wei , Qiu Lifeng , Lin Yuning , Jiang Mei , Chia Sook-Yoong , Wei Yanfei , Ng Adeline S. L. , Reynolds Richard , Tan Eng-King , Zeng Li 
Published: January 2022

Abstract
Background
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are common age-related neurodegenerative diseases comprising Lewy body spectrum disorders associated with cortical and subcortical Lewy body pathology. Over 30% of PD patients develop PD dementia (PDD), which describes dementia arising in the context of established idiopathic PD. Furthermore, Lewy bodies frequently accompany the amyloid plaque and neurofibrillary tangle pathology of Alzheimer’s disease (AD), where they are observed in the amygdala of approximately 60% of sporadic and familial AD. While PDD and DLB share similar pathological substrates, they differ in the temporal onset of motor and cognitive symptoms; however, protein markers to distinguish them are still lacking.

Methods
Here, we systematically studied a series of AD and PD pathogenesis markers, as well as mitochondria, mitophagy, and neuroinflammation-related indicators, in the substantia nigra (SN), temporal cortex (TC), and caudate and putamen (CP) regions of human post-mortem brain samples from individuals with PDD and DLB and condition-matched controls.

Results
We found that p-APPT668 (TC), α-synuclein (CP), and LC3II (CP) are all increased while the tyrosine hydroxylase (TH) (CP) is decreased in both PDD and DLB compared to control. Also, the levels of Aβ42 and DD2R, IBA1, and p-LRRK2S935 are all elevated in PDD compared to control. Interestingly, protein levels of p-TauS199/202 in CP and DD2R, DRP1, and VPS35 in TC are all increased in PDD compared to DLB.

Conclusions
Together, our comprehensive and systematic study identified a set of signature proteins that will help to understand the pathology and etiology of PDD and DLB at the molecular level.
Melatonin increases growth and salt tolerance of Limonium bicolor by improving photosynthetic and antioxidant capacity
Authors: Li Junpeng , Liu Yun , Zhang Mingjing , Xu Hualing , Ning Kai , Wang Baoshan , Chen Min 
Published: January 2022

Abstract
Background
Soil salinization is becoming an increasingly serious problem worldwide, resulting in cultivated land loss and desertification, as well as having a serious impact on agriculture and the economy. The indoleamine melatonin (N-acetyl-5-methoxytryptamine) has a wide array of biological roles in plants, including acting as an auxin analog and an antioxidant. Previous studies have shown that exogenous melatonin application alleviates the salt-induced growth inhibition in non-halophyte plants; however, to our knowledge, melatonin effects have not been examined on halophytes, and it is unclear whether melatonin provides similar protection to salt-exposed halophytic plants.

Results
We exposed the halophyte Limonium bicolor to salt stress (300 mM) and concomitantly treated the plants with 5 μM melatonin to examine the effect of melatonin on salt tolerance. Exogenous melatonin treatment promoted the growth of L. bicolor under salt stress, as reflected by increasing its fresh weight and leaf area. This increased growth was caused by an increase in net photosynthetic rate and water use efficiency. Treatment of salt-stressed L. bicolor seedlings with 5 μM melatonin also enhanced the activities of antioxidants (superoxide dismutase [SOD], peroxidase [POD], catalase [CAT], and ascorbate peroxidase [APX]), while significantly decreasing the contents of hydrogen peroxide (H2O2), superoxide anion (O2•−), and malondialdehyde (MDA). To screen for L. bicolor genes involved in the above physiological processes, high-throughput RNA sequencing was conducted. A gene ontology enrichment analysis indicated that genes related to photosynthesis, reactive oxygen species scavenging, the auxin-dependent signaling pathway and mitogen-activated protein kinase (MAPK) were highly expressed under melatonin treatment. These data indicated that melatonin improved photosynthesis, decreased reactive oxygen species (ROS) and activated MAPK-mediated antioxidant responses, triggering a downstream MAPK cascade that upregulated the expression of antioxidant-related genes. Thus, melatonin improves the salt tolerance of L. bicolor by increasing photosynthesis and improving cellular redox homeostasis under salt stress.

Conclusions
Our results showed that melatonin can upregulate the expression of genes related to photosynthesis, reactive oxygen species scavenging and mitogen-activated protein kinase (MAPK) of L. bicolor under salt stress, which can improve photosynthesis and antioxidant enzyme activities. Thus melatonin can promote the growth of the species and maintain the homeostasis of reactive oxygen species to alleviate salt stress.
Trend of geographical distribution of stomach cancer in Iran from 2004 to 2014
Authors: Moradian Farid , Fararouei Mohammad , Karami Maryam , Ghelichi-Ghojogh Mousa , Gheibi Zahra , Nikeghbalian Zahra , Akbari Atieh , Akbari Mohammad-Esmaeil 
Published: January 2022

Abstract
Background
Among different common types of cancer, gastric cancer (GC) is a worldwide health priority in both developing and developed countries. The aim of this study was to map the distribution of incident cases of GC in Iran to provide a geographical presentation of the incidence of the disease.

Methods
This study used the Iranian National Cancer Registry (INCR) data from 2004 to 2014. We calculated the crude and age-standardized incidence rates of GC for each province and also defined the frequency distribution of different types and locations of GC by the provinces.

Results
According to the results of the present study, the patients were predominantly male 49,907 (70.0%) and the most prevalent type of tumour was A1 (almost 96.4%) and C3‌ (2.0%). Also, a significant difference was observed between males and females in the distribution of the types of tumour (P < 0.001). In addition, a comparison of the distribution of the types of GC in Iran suggested that a significant difference exists between the provinces (P < 0.001). A significant difference was observed when the distribution of the location of GC tumors was compared between males and females and provinces (P < 0.001). Accordingly, pylori and cardia are the most common location of GC cancer among the study population (28.1% and 31.3% respectively).

Conclusions
The results of the current study suggested a higher rate of GC incidence in Iran when compared to the global figure in both females and males. Our study also revealed significant disparities between provinces with regard to the distribution of types, and location of GC. This may suggest involving different factors in GC in different parts of Iran. Further studies are needed to better understand the epidemiology and etiology of the disease in Iran.
Dolutegravir plus lamivudine versus efavirenz plus tenofovir disoproxil fumarate and lamivudine in antiretroviral-naive adults with HIV-1 infection
Authors: Deng Lisi , Li Chunna , Chen Ping , Luo Xiaoqing , Zheng Xinchun , Zhou Lanlan , Zhou Yi , Xia Jinyu , Hong Zhongsi 
Published: January 2022

Abstract
Background
Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China.

Methods
This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm.

Results
Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05).

Conclusions
DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients.
Clinical Trial Registration ChiCTR1900027640 (22/November/2019).
Risk factors and prediction model of severe pertussis in infants < 12 months of age in Tianjin, China
Authors: Zhang Cui , Zong Yanmei , Wang Zhe , Wang Li , Li Ying , Yang Yuejie 
Published: January 2022

Abstract
Background
To identify risk factors associated with the prognosis of pertussis in infants (< 12 months).

Methods
A retrospective study on infants hospitalized with pertussis January 2017 to June 2019. The infants were divided into two groups according to the severity of disease: severe pertussis and non-severe pertussis groups. We collected all case data from medical records including socio-demographics, clinical manifestations, and auxiliary examinations. Univariate analysis and Logistic regression were used.

Results
Finally, a total of 84 infants with severe pertussis and 586 infants with non-severe pertussis were admitted. The data of 75% of the cases (severe pertussis group, n = 63; non-severe pertussis group, n = 189) were randomly selected for univariate and multivariate logistic regression analysis. The results showed rural area [P = 0.002, OR = 6.831, 95% CI (2.013–23.175)], hospital stay (days) [P = 0.002, OR = 1.304, 95% CI (1.107–1.536)], fever [P = 0.040, OR = 2.965, 95% CI (1.050–8.375)], cyanosis [P = 0.008, OR = 3.799, 95% CI (1.419–10.174)], pulmonary rales [P = 0.021, OR = 4.022, 95% CI (1.228–13.168)], breathing heavily [P = 0.001, OR = 58.811, 95% CI (5.503–628.507)] and abnormal liver function [P < 0.001, OR = 9.164, 95% CI (2.840–29.565)] were independent risk factors, and higher birth weight [P = 0.006, OR = 0.380, 95% CI (0.191–0.755)] was protective factor for severe pertussis in infants. The sensitivity and specificity of logistic regression model for remaining 25% data of severe group and common group were 76.2% and 81.0%, respectively, and the consistency rate was 79.8%.

Conclusions
The findings indicated risk factor prediction models may be useful for the early identification of severe pertussis in infants.