bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomics and metabolomics of engineered Synechococcus elongatus during photomixotrophic growth
Authors: Tan Lin-Rui , Cao Yi-Qi , Li Jian-Wei , Xia Peng-Fei , Wang Shu-Guang 
Published: March 2022

Abstract
Background
Converting carbon dioxide (CO2) into value-added chemicals using engineered cyanobacteria is a promising strategy to tackle the global warming and energy shortage issues. However, most cyanobacteria are autotrophic and use CO2 as a sole carbon source, which makes it hard to compete with heterotrophic hosts in either growth or productivity. One strategy to overcome this bottleneck is to introduce sugar utilization pathways to enable photomixotrophic growth with CO2 and sugar (e.g., glucose and xylose). Advances in engineering mixotrophic cyanobacteria have been obtained, while a systematic interrogation of these engineered strains is missing. This work aimed to fill the gap at omics level.

Results
We first constructed two engineered Synechococcus elongatus YQ2-gal and YQ3-xyl capable of utilizing glucose and xylose, respectively. To investigate the metabolic mechanism, transcriptomic and metabolomic analysis were then performed in the engineered photomixotrophic strains YQ2-gal and YQ3-xyl. Transcriptome and metabolome of wild-type S. elongatus were set as baselines. Increased abundance of metabolites in glycolysis or pentose phosphate pathway indicated that efficient sugar utilization significantly enhanced carbon flux in S. elongatus as expected. However, carbon flux was redirected in strain YQ2-gal as more flowed into fatty acids biosynthesis but less into amino acids. In strain YQ3-xyl, more carbon flux was directed into synthesis of sucrose, glucosamine and acetaldehyde, while less into fatty acids and amino acids. Moreover, photosynthesis and bicarbonate transport could be affected by upregulated genes, while nitrogen transport and assimilation were regulated by less transcript abundance of related genes in strain YQ3-xyl with utilization of xylose.

Conclusions
Our work identified metabolic mechanism in engineered S. elongatus during photomixotrophic growth, where regulations of fatty acids metabolism, photosynthesis, bicarbonate transport, nitrogen assimilation and transport are dependent on different sugar utilization. Since photomixotrophic cyanobacteria is regarded as a promising cell factory for bioproduction, this comprehensive understanding of metabolic mechanism of engineered S. elongatus during photomixotrophic growth would shed light on the engineering of more efficient and controllable bioproduction systems based on this potential chassis.
DFNA5 regulates immune cells infiltration and exhaustion
Authors: Hu Jian , Pei Wenceng , Jiang Minren , Huang Ying , Dong Fuyun , Jiang Zhenyou , Xu Ying , Li Zihuang 
Published: March 2022

Abstract
Background
DFNA5 (GSDME) belongs to Gasdermin familily that is involved in a variety of cancers and triggers cell pyroptosis after chemical treatment. However, the relationship in DFNA5 between prognosis and immune cells in diverse cancers has been receiving little attention. Tumor immune cells infiltration and exhaustion may associate with patients prognosis. The roles of DFNA5 in tumor immune cells infiltration and exhaustion have not been clarified.

Methods
The expression level of DFNA5 was determined by the Tumour Immune Estimation Resource and the Oncomine database. Then the impacts of DFNA5 in prognosis were assessed by Kaplan–Meier plotter and ULACAN. The correlations between DFNA5 and tumour-infiltrating lymphocytes were explored by TIMER. In addition, the relationships in the expression levels of DFNA5 and typical genes combination of tumour-infiltrating lymphocytes were analysed by GEPIA and TIMER. In this study, we screened the chemokine and immune related proteins interacted with DFNA5 using TurboID system to explore the instantaneous or weak interactions.

Results
DFNA5 significantly influences the prognosis in different cancers according to The Cancer Genome Atlas (TCGA). The expression levels of DFNA5 showed positive correlations to the infiltration of macrophages, CD8 + T cells, CD4 + T cells in liver hepatocellular carcinoma (LIHC), colon adenocarcinoma (COAD), and lung adenocarcinoma (LUAD). DFNA5 expression displayed obvious correlations with multiple lymphocytes gene makers in COAD, LIHC and LUAD. DFNA5 expression has effects on the prognosis of liver hepatocellular carcinoma and LUAD. DFNA5 upregulated the expression levels of PDCD1 and CD274 in a dose-dependent manner. Chemokine and immune related proteins interact with DFNA5.

Conclusions
These results indicate that DFNA5 is related to patient prognosis and immune cells, consisting of macrophages, CD4 + T cells, and CD8 + T cells, in diverse cancers. In addition, DFNA5 expression might contribute to the regulation of T cell exhaustion, tumour-associated macrophages (TAMs), and Tregs in COAD, LIHC and LUAD. DFNA5 may regulate immune infiltration via EIF2AK2. IFNGR1 was related to the functions of PD-L1 expression and PD-1 checkpoint pathway. These results indicate that DFNA5 levels may be act as a prognostic factor and predict the degrees of immune cells infiltration in LIHC and LUAD.
Factors associated with knowledge about malaria prevention among women of reproductive age, Tete Province, Mozambique, 2019–2020
Authors: Afai Gerson , Rossetto Erika Valeska , Baltazar Cynthia Semá , Candrinho Baltazar , Saifodine Abuchahama , Zulliger Rose 
Published: March 2022

Abstract
Background
Mozambique is a malaria endemic country with an estimated prevalence of malaria in children 6–59 months old that is twice as high in rural areas (46.0%) as in urban areas (18.0%). However, only 46.0% of women aged 15–49 years had complete knowledge about malaria in 2018. This study aimed to identify the factors associated with malaria knowledge among women of reproductive age in a high malaria burden district.

Methods
Data from a cross-sectional study, using a population-based malaria research study in Mágoe District, 2019, were analysed. This analysis included women aged 15–49 years. A multivariate logistic regression model was developed to determine factors associated with complete knowledge of malaria that calculated adjusted odds ratio (aOR) and 95% confidence interval (CI) at a p < 0.05 significance level. Complete malaria knowledge was defined as when a woman correctly identified: fever as a malaria symptom, mosquito bites as the means of malaria transmission, mosquito nets as a tool for malaria prevention, malaria as curable, and were able to name an anti-malarial.

Results
A total of 1899 women were included in this analysis. There was complete malaria knowledge among 49% of the respondents. Seventy one percent mentioned fever as one of malaria symptoms, 92% mentioned mosquito bite as the cause of malaria infection, 94% identified that mosquito nets prevent malaria, 92% agreed that malaria has cure, and 76% were able to name at least one anti-malarial medicine. In the multivariate analysis, the following characteristics were associated with significantly higher odds of having complete malaria knowledge: having a secondary school or above education level (adjusted Odds Ratio, aOR = 2.5 CI [1.3–4.6] p = 0.005), being from the middle socioeconomic status group (aOR = 1.5 CI [1.1–2.1] p = 0.005), being from older age group of 35–39 (aOR = 1.9; CI [1.1–3.1] p < 0.001), having 1–2 children (aOR = 1.8; CI [1.2–2.6] p = 0.003), and having interviews completed in Portuguese or Cinyungwe (aOR = 2.3; CI [1.3–4.1] p = 0.004 and aOR = 2.1; CI [1.5–2.8] p < 0.001, respectively).

Conclusion
Most women in this study had some malaria knowledge, but gaps in complete knowledge remained. In order to broaden knowledge, educational messages about malaria prevention should be more effectively targeted to reach younger, less-educated women and in non-dominant languages.
Multi-functional self-assembly nanoparticles originating from small molecule natural product for oral insulin delivery through modulating tight junctions
Authors: Jia Xiaohui , Yuan Zhihua , Yang Yuqin , Huang Xuemei , Han Nana , Liu Xiaojing , Lin Xiaoyu , Ma Tao , Xu Bing , Wang Penglong , Lei Haimin 
Published: March 2022

Abstract
Background
Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers.

Result
In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl3 through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model.

Conclusion
This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy.

Graphical Abstract
Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances
Authors: Mahmoud Khaled , Swidan Shady , El-Nabarawi Mohamed , Teaima Mahmoud 
Published: March 2022

AbstractLiver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive nanoparticles. In this review, the effect of utilizing lipidic nanoparticles is being discussed as well as the different tumor uptake enhancement techniques used.Graphical Abstract
Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA
Authors: Chen Xutao , Wan Zhuo , Yang Liu , Song Shuang , Fu Zhaoyue , Tang Kang , Chen Lihua , Song Yingliang 
Published: March 2022

Abstract
Background
Periodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive.

Results
Exosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway.

Conclusion
In conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos.

Graphical Abstract
Self-esteem in patients with venous thromboembolism predicts time trade-off values for own health
Authors: Stalmeier Peep F. M. , Volmeijer Eva E. 
Published: March 2022

Abstract
Background
The time trade-off (TTO) is a commonly used preference based method to assess health related values used in health economic analyses. Surprisingly little is known about the factors influencing the TTO. Since self-esteem is a predictor for health status measurements, and health status affects the TTO, we studied the relation between self-esteem and TTO values.

Methods
Data of 128 patients treated with vitamin K antagonists for venous thromboembolism on Short Form-36 (SF-36), Rosenberg self-esteem and patient characteristics were collected. TTO values were obtained for ‘current health’ and three chronic health states related to thrombosis, in face-to-face interviews with patients. Regression analyses were performed with the TTO as dependent variable. Analyses were performed in two groups; the complete sample, and traders only. Selected predictors were entered in four blocks: socio-demographic factors, medical-clinical factors, health status, and self-esteem.

Results
In the complete sample (N = 128), bivariate regression analysis showed that self-esteem explained 14% of the variance in TTO values for current health (p < .000, N = 117). In traders, multivariate regression analysis showed a significant relationship between self-esteem and TTO values for current health. Self-esteem increased the variance explained (R2) by 8.8%, from 28.1 to 36.9%, (p = 0.01; N = 57). For hypothetical health states, the effect of self-esteem was weaker and mostly absent after controlling for selected variables.

Conclusions
In patients willing to trade-off time, higher self-esteem was associated with higher TTO values for own current health. Self-esteem explained an appreciable proportion of the variance in TTO values in traders. For hypothetical health states such associations were weak or absent.
Coagulation dysfunction events associated with tigecycline: a real-world study from FDA adverse event reporting system (FAERS) database
Authors: Guo Mingxing , Liang Jinwei , Li Dandan , Zhao Ying , Xu Wanyi , Wang Lei , Cui Xiangli 
Published: March 2022

Abstract
Background
Tigecycline has broad-spectrum anti-bacterial activity and often used for critically ill patients with complicated infections. Only a few clinical studies have reported the coagulation disorder induced by tigecycline. The aim of this study was to investigate the association between tigecycline and coagulation dysfunction using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Method
Data from January 2005 to December 2020 in FAERS were retrieved. We investigated the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare tigecycline with the full database and other antibiotics.

Results
The total number of reports of coagulation dysfunction related to tigecycline as the primary suspect drug was 223. The median time to event of the coagulation dysfunction events was 10 (interquartile range [IQR] 6.75–13) days. 80.72% coagulation-related adverse events appeared within the first 14 days since the initiation of tigecycline administration. The overall ROR (95% CI) for coagulation-related adverse events was 3.55 (3.08, 4.09). The RORs (95% CI) for thrombocytopenia, hypofibrinogenaemia, coagulopathy, activated partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time prolonged were 8.21 (6.34, 10.62), 705.41 (526.81, 944.54), 30.67 (21.92, 42.92), 42.98 (24.85, 74.31), 4.67 (2.51, 8.71), and 27.99 (15.01, 52.19), respectively. In analyses stratified on comparing tigecycline to vancomycin and daptomycin, significant coagulation dysfunction signals were found with the RORs (95% CI) 2.74 (2.34, 3.22) and 3.08 (2.57, 3.70).

Conclusions
We found a strong signal of high frequency of reporting coagulation dysfunction in tigecycline. Health professionals should be aware of the potential coagulation disorders risk and monitor coagulation parameters during anti-bacterial therapy with tigecycline, particularly the need to monitor fibrinogen levels.
Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19
Authors: Jing Xixi , Xu Min , Song Deye , Yue Tingting , Wang Yali , Zhang Pan , Zhong Yanjun , Zhang Min , Lam Tommy Tsan-Yuk , Faria Nuno Rodrigues , De Clercq Erik , Li Guangdi 
Published: March 2022

Abstract
Background
COVID-19 patients may experience “cytokine storm” when human immune system produces excessive cytokines/chemokines. However, it remains unclear whether early responses of inflammatory cytokines would lead to high or low titers of anti-SARS-CoV-2 antibodies.

Methods
This retrospective study enrolled a cohort of 272 hospitalized patients with laboratory-confirmed SARS-CoV-2. Laboratory assessments of serum cytokines (IL-2R, IL-6, IL-8, IL-10, TNF-α), anti-SARS-CoV-2 IgG/IgM antibodies, and peripheral blood biomarkers were conducted during hospitalization.

Results
At hospital admission, 36.4% patients were severely ill, 51.5% patients were ≥ 65 years, and 60.3% patients had comorbidities. Higher levels of IL-2R and IL-6 were observed in older patients (≥65 years). Significant differences of IL-2R (week 2 to week ≥5 from symptom onset), IL-6 (week 1 to week ≥5), IL-8 (week 2 to week ≥5), and IL-10 (week 1 to week 3) were observed between moderately-ill and severely ill patients. Anti-SARS-CoV-2 IgG titers were significantly higher in severely ill patients than in moderately ill patients, but such difference was not observed for IgM. High titers of early-stage IL-6, IL-8, and TNF-α (≤2 weeks after symptom onset) were positively correlated with high titers of late-stage IgG (≥5 weeks after symptom onset). Deaths were mostly observed in severely ill older patients (45.9%). Survival analyses revealed risk factors of patient age, baseline COVID-19 severity, and baseline IL-6 that affected survival time, especially in severely ill older patients.

Conclusion
Early responses of elevated cytokines such as IL-6 reflect the active immune responses, leading to high titers of IgG antibodies against COVID-19.
A survey of few-shot learning in smart agriculture: developments, applications, and challenges
Authors: Yang Jiachen , Guo Xiaolan , Li Yang , Marinello Francesco , Ercisli Sezai , Zhang Zhuo 
Published: March 2022

AbstractWith the rise of artificial intelligence, deep learning is gradually applied to the field of agriculture and plant science. However, the excellent performance of deep learning needs to be established on massive numbers of samples. In the field of plant science and biology, it is not easy to obtain a large amount of labeled data. The emergence of few-shot learning solves this problem. It imitates the ability of humans’ rapid learning and can learn a new task with only a small number of labeled samples, which greatly reduces the time cost and financial resources. At present, the advanced few-shot learning methods are mainly divided into four categories based on: data augmentation, metric learning, external memory, and parameter optimization, solving the over-fitting problem from different viewpoints. This review comprehensively expounds on few-shot learning in smart agriculture, introduces the definition of few-shot learning, four kinds of learning methods, the publicly available datasets for few-shot learning, various applications in smart agriculture, and the challenges in smart agriculture in future development.
Concerns among people who use opioids during the COVID-19 pandemic: a natural language processing analysis of social media posts
Authors: Sarker Abeed , Nataraj Nisha , Siu Wesley , Li Sabrina , Jones Christopher M. , Sumner Steven A. 
Published: March 2022

Abstract
Background
Timely data from official sources regarding the impact of the COVID-19 pandemic on people who use prescription and illegal opioids is lacking. We conducted a large-scale, natural language processing (NLP) analysis of conversations on opioid-related drug forums to better understand concerns among people who use opioids.

Methods
In this retrospective observational study, we analyzed posts from 14 opioid-related forums on the social network Reddit. We applied NLP to identify frequently mentioned substances and phrases, and grouped the phrases manually based on their contents into three broad key themes: (i) prescription and/or illegal opioid use; (ii) substance use disorder treatment access and care; and (iii) withdrawal. Phrases that were unmappable to any particular theme were discarded. We computed the frequencies of substance and theme mentions, and quantified their volumes over time. We compared changes in post volumes by key themes and substances between pre-COVID-19 (1/1/2019—2/29/2020) and COVID-19 (3/1/2020—11/30/2020) periods.

Results
Seventy-seven thousand six hundred fifty-two and 119,168 posts were collected for the pre-COVID-19 and COVID-19 periods, respectively. By theme, posts about treatment and access to care increased by 300%, from 0.631 to 2.526 per 1000 posts between the pre-COVID-19 and COVID-19 periods. Conversations about withdrawal increased by 812% between the same periods (0.026 to 0.235 per 1,000 posts). Posts about drug use did not increase (0.219 to 0.218 per 1,000 posts). By substance, among medications for opioid use disorder, methadone had the largest increase in conversations (20.751 to 56.313 per 1,000 posts; 171.4% increase). Among other medications, posts about diphenhydramine exhibited the largest increase (0.341 to 0.927 per 1,000 posts; 171.8% increase).

Conclusions
Conversations on opioid-related forums among people who use opioids revealed increased concerns about treatment and access to care along with withdrawal following the emergence of COVID-19. Greater attention to social media data may help inform timely responses to the needs of people who use opioids during COVID-19.