bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arginine regulates inflammation response-induced by Fowl Adenovirus serotype 4 via JAK2/STAT3 pathway
Authors: Xiang Silin , Huang Ruiling , He Qing , Xu Lihui , Wang Changkang , Wang Quanxi 
Published: May 2022

Abstract
Background
Fowl Adenovirus serotype 4 (FAdV-4) infection causes severe inflammatory response leading to hepatitis-hydropericardium syndrome (HHS) in poultry. As an essential functional amino acid of poultry, arginine plays a critical role in anti-inflammatory and anti-oxidative stress.

Results
In this study, the differential expression genes (DEGs) were screened by transcriptomic techniques, and the DEGs in gene networks of inflammatory response-induced by FAdV-4 in broiler’s liver were analyzed by Kyoto encyclopedia of genes and genomes (KEGG) enrichment. The results showed that the cytokines pathway and JAK/STAT pathway were significantly enriched, in which the DEGs levels of IL-6, IL-1β, IFN-α, JAK and STAT were significantly up-regulated after FAdV-4 infection. It was further verified with real-time fluorescence quantitative polymerase chain reaction (Real-time qPCR) and Western blotting (WB) in vitro and in vivo. The findings demonstrated that FAdV-4 induced inflammatory response and activated JAK2/STAT3 pathway. Furthermore, we investigated whether arginine could alleviate the liver inflammation induced by FAdV-4. After treatment with 1.92% arginine level diet to broilers or 300 μg/mL arginine culture medium to LMH cell line with FAdV-4 infection at the same time, we found that the mRNA levels of IL-6, IL-1β, IFN-α and the protein levels of p-JAK2, p-STAT3 were down-regulated, compared with FAdV-4 infection group. Furthermore, we confirmed that the inflammation induced by FAdV-4 was ameliorated by pre-treatment with JAK inhibitor AG490 in LMH cells, and it was further alleviated in LMH cells treatment with AG490 and ARG.

Conclusions
These above results provide new insight that arginine protects hepatocytes against inflammation induced by FAdV-4 through JAK2/STAT3 signaling pathway.
A high-starch vs. high-fibre diet: effects on the gut environment of the different intestinal compartments of the horse digestive tract
Authors: Raspa Federica , Vervuert Ingrid , Capucchio Maria Teresa , Colombino Elena , Bergero Domenico , Forte Claudio , Greppi Martina , Cavallarin Laura , Giribaldi Marzia , Antoniazzi Sara , Cavallini Damiano , Valvassori Ermenegildo , Valle Emanuela 
Published: May 2022

AbstractBackgroundHorses are often fed high amounts of starch in their diets despite the well-established benefits of a fibre-based diet to promote gut health and animal welfare. The aim of the present study was to compare the effects of two different diets – one based on high amounts of starch (HS) vs. one base on high amounts of fibre (HF) – on specific parameters of the gut environment across different intestinal compartments of the horse digestive tract. To this end differences in the gastrointestinal environment between HS vs. HF fed horses were assessed in terms of dry matter, organic matter and ash content; the particle size distribution and volatile fatty acid composition were also investigated.ResultsNineteen Bardigiano horses of 14.3 ± 0.7 months of age and destined to slaughter were divided into two group pens – one fed with high amounts of starch (HS;n = 9; 43% hay plus 57% starch-rich pelleted feed); vs. fed with high amounts of fibre (HF;n = 10; 70% hay plus 30% fibre-rich pelleted feed). Horses fed HS diet presented a higher dry matter content in the right dorsal colon. Moreover, they showed a higher organic matter and ash content in the sternal flexure, pelvic flexure, right dorsal colon and rectum. In these latter intestinal compartments, horses fed a HS diet also showed a higher proportion of particles retained on an 8 mm sieve and a higher proportion of particles that washed through the finest sieve (< 1 mm). Moreover, the total amounts of volatile fatty acids as well as valeric acid were found to be significantly higher in horses fed the HS vs. HF diet.ConclusionsA high-starch diet causes significant changes in the horse gut environment. We observed an increase in the dry matter content in the right dorsal colon, as well as reduced particle sizes and an increase in the production of valeric acid in all the gut compartments studied. High-starch diets should be avoided in favour of fibre-based diets with the goal of safeguarding gut health in horses.
G-CSF upregulates the expression of aquaporin-9 through CEBPB to enhance the cytotoxic activity of arsenic trioxide to acute myeloid leukemia cells
Authors: Fu Wanbin , Zhu Gelan , Xu Lan , Liu Jia , Han Xiaofeng , Wang Junying , Wang Xinpeng , Hou Jian , Zhao Huanbin , Zhong Hua 
Published: May 2022

Abstract
Background
Arsenic trioxide (ATO) is highly effective in acute promyelocytic leukemia (APL) patients, but it fails to show satisfactory efficacy in other acute myeloid leukemia (AML) patients with non-APL subtypes. Different from the APL cells, most non-APL AML cells express low levels of the ATO transporter Aquaporin-9 (AQP9) protein, making them less sensitive to ATO treatment. Recently, we found that granulocyte colony stimulating factor (G-CSF) can upregulate the expression of AQP9. We hypothesized that the pretreatment with G-CSF may enhance the antitumor effect of ATO in non-APL AML cells. In addition, we aimed to elucidate the underlying mechanisms by which G-CSF upregulates the expression of AQP9.

Methods
Non-APL AML cell lines including THP-1 and HL-60 were pretreated with or without G-CSF (100 ng/ml) for 24 h, followed by the treatment with ATO (2 μM) for 48 h. Cell morphology was observed under the microscope after Wright-Giemsa staining. Flow cytometry was performed to evaluate the cell apoptosis levels. The intracellular concentrations of ATO were determined by atomic fluorescence spectrometry. The mRNA and protein expression were respectively measured by quantitative reverse transcription PCR (RT-qPCR) and western blotting. Target genes were knocked down by transfection with small interfering RNA (siRNA), or overexpressed by transfection with overexpression plasmids. The cell line derived xenograft mouse model was established to confirm the results of the in vitro experiments.

Results
Compared with using ATO alone, the combination of G-CSF with ATO induced the cell apoptosis more dramatically. G-CSF upregulated the expression of AQP9 and enhanced the intracellular concentrations of ATO in AML cells. When AQP9 was overexpressed, it markedly enhanced the cytotoxic activity of ATO. On the other hand, when AQP9 was knocked down, it profoundly attenuated the combinational effect. Moreover, we found that the upregulation of AQP9 by G-CSF depends on the transcription factor CCAAT enhancer binding protein beta (CEBPB). We also demonstrated that the combination of G-CSF and ATO significantly inhibited tumor growth in the xenograft mouse model.

Conclusions
The combination of G-CSF and ATO may be a potential therapeutic strategy for AML patients.
A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease
Authors: Hu Xiaozhi , Fan Jiajun , Ma Qianqian , Han Lei , Cao Zhonglian , Xu Caili , Luan Jingyun , Jing Guangjun , Nan Yanyang , Wu Tao , Zhang Yuting , Wang Hanqi , Zhang Yuanzhen , Ju Dianwen 
Published: May 2022

AbstractBackgroundNonalcoholic fatty liver disease (NAFLD) is a metabolic disease mainly on account of hypercholesterolemia and may progress to cirrhosis and hepatocellular carcinoma. The discovery of effective therapy for NAFLD is an essential unmet need. Angiopoietin-like protein 3 (ANGPTL3), a critical lipid metabolism regulator, resulted in increased blood lipids and was elevated in NAFLD. Here, we developed a nanobody-heavy chain antibody (VHH-Fc) to inhibit ANGPTL3 for NAFLD treatment.ResultsIn this study, we retrieved an anti-ANGPTL3 VHH and Fc fusion protein, C44-Fc, which exhibited high affinities to ANGPTL3 proteins and rescued ANGPLT3-mediated inhibition of lipoprotein lipase (LPL) activity. The C44-Fc bound a distinctive epitope within ANGPTL3 when compared with the approved evinacumab, and showed higher expression yield. Meanwhile, C44-Fc had significant reduction of the triglyceride (~ 44.2%), total cholesterol (~ 36.6%) and LDL-cholesterol (~ 54.4%) in hypercholesterolemic mice and ameliorated hepatic lipid accumulation and liver injury in NAFLD mice model.ConclusionsWe discovered a VHH-Fc fusion protein with high affinity to ANGPTL3, strong stability and also alleviated the progression of NAFLD, which might offer a promising therapy for NAFLD.Graphical Abstract
Perceptions of Community Health Workers (CHW) on barriers and enablers to care for people with psychosis in rural Mozambique: findings of a focus group discussion study using the Capability, Opportunity, Motivation and Behaviour framework (COM-B framework)
Authors: Mabunda Dirceu , Oliveira Déborah , Sidat Mohsin , Cournos Francine , Wainberg Milton , Mari Jair de Jesus 
Published: May 2022

Abstract
Background
Psychotic disorders contribute significantly to the global disease burden by causing disability, impaired quality of life, and higher mortality in affected people compared with the general population. In rural settings, where there is limited or no access to healthcare, individuals living with psychotic disorders often seek support from Community Health Workers (CHWs). However, little is known about what CHWs know about psychosis and how they manage such cases. This study aimed to explore the CHWs perception of psychosis and their experiences and beliefs about the factors that might enable or hinder care-taking for patients with psychosis in rural settings in Mozambique.

Methods
A qualitative study was conducted in rural districts of Maputo Province, a southern region of Mozambique, using six focus group discussions with participation of 79 CHWs. Thematic analysis was used informed by the Capabilities, Opportunities, Motivation and Behaviour framework (COM-B).

Results
Nine primary themes were identified. Overall, CHWs perceived psychosis as treatable medical conditions and held a positive attitude about being part of the care-taking process of patients with psychosis in rural settings. Partnerships with key-stakeholders such as traditional healers, health care workers, and families, were perceived by CHWs as enablers to improve access to care in rural areas. However, stigma, myths, and lack of competencies to treat people with psychosis were perceived by CHWs as barriers for appropriate care.

Conclusion
CHWs, with adequate support, could play an important role in the care of patients with psychosis in rural settings, including identifying patients requiring care and referring them to appropriate healthcare professionals, and following up medicated patients with psychosis. Training of CHWs should consider inclusion of basic mental health care competencies.
Two-year intermittent exposure of a multiwalled carbon nanotube by intratracheal instillation induces lung tumors and pleural mesotheliomas in F344 rats
Authors: Hojo Motoki , Maeno Ai , Sakamoto Yoshimitsu , Ohnuki Aya , Tada Yukie , Yamamoto Yukio , Ikushima Kiyomi , Inaba Ryota , Suzuki Jin , Taquahashi Yuhji , Yokota Satoshi , Kobayashi Norihiro , Ohnishi Makoto , Goto Yuko , Numano Takamasa , Tsuda Hiroyuki , Alexander David B. , Kanno Jun , Hirose Akihiko , Inomata Akiko , Nakae Dai 
Published: May 2022

Abstract
Background
A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study.

Results
Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent.

Conclusions
Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation.
Wheat leaf area index prediction using data fusion based on high-resolution unmanned aerial vehicle imagery
Authors: Wu Shuang , Deng Lei , Guo Lijie , Wu Yanjie 
Published: May 2022

Abstract
Background
Leaf Area Index (LAI) is half of the amount of leaf area per unit horizontal ground surface area. Consequently, accurate vegetation extraction in remote sensing imagery is critical for LAI estimation. However, most studies do not fully exploit the advantages of Unmanned Aerial Vehicle (UAV) imagery with high spatial resolution, such as not removing the background (soil and shadow, etc.). Furthermore, the advancement of multi-sensor synchronous observation and integration technology allows for the simultaneous collection of canopy spectral, structural, and thermal data, making it possible for data fusion.

Methods
To investigate the potential of high-resolution UAV imagery combined with multi-sensor data fusion in LAI estimation. High-resolution UAV imagery was obtained with a multi-sensor integrated MicaSense Altum camera to extract the wheat canopy's spectral, structural, and thermal features. After removing the soil background, all features were fused, and LAI was estimated using Random Forest and Support Vector Machine Regression.

Results
The results show that: (1) the soil background reduced the accuracy of the LAI prediction of wheat, and soil background could be effectively removed by taking advantage of high-resolution UAV imagery. After removing the soil background, the LAI prediction accuracy improved significantly, R2 raised by about 0.27, and RMSE fell by about 0.476. (2) The fusion of multi-sensor synchronous observation data could achieve better accuracy (R2 = 0.815 and RMSE = 1.023), compared with using only one data; (3) A simple LAI prediction method could be found, that is, after selecting a few features by machine learning, high prediction accuracy can be obtained only by simple multiple linear regression (R2 = 0.679 and RMSE = 1.231), providing inspiration for rapid and efficient LAI prediction of wheat.

Conclusions
The method of this study can be transferred to other sites with more extensive areas or similar agriculture structures, which will facilitate agricultural production and management.
Review of outcomes of delayed chest closure following lung transplantation: a meta-analysis
Authors: Chen Cheng , Zheng Quan , Wu Dongsheng , Song Yongxiang , Xu Gang 
Published: May 2022

Abstract
Purpose
The clinical outcomes of delayed chest closure (DCC) compared with primary chest closure (PCC) following lung transplantation, including perioperative outcomes and long-term survival, remained controversial. This was the first systematic review and meta-analysis aimed to identify the short- and long-term outcomes of DCC following lung transplantation.

Methods
We comprehensively searched electronic literature from 4 databases up to April 1st, 2022. Dichotomous data and continuous data were pooled with odds ratio and weighted mean difference, respectively. The quality of included studies was assessed with the Newcastle–Ottawa Scale.

Results
Ten studies were included in the systematic review and 4 studies were included in the meta-analysis. Pooled analysis showed that DCC was associated with an increased risk of surgical site infection, prolonged hospital stays, and higher risk of primary graft dysfunction compared to PCC. The 30 day and 5 year survival were higher in PCC cohort compared with DCC cohort while differences in survival at 6 months was insignificant.

Conclusion
Our findings do not support the aggressive application of DCC. DCC should be cautiously applied since its association with worse perioperative outcomes and higher mortality. But it remains the life-saving steps under dangerous circumstances.
Post-transplant cyclophosphamide alters immune signatures and leads to impaired T cell reconstitution in allogeneic hematopoietic stem cell transplant
Authors: Zhao Chenchen , Bartock Matthew , Jia Bei , Shah Neal , Claxton David F. , Wirk Baldeep , Rakszawski Kevin L. , Nickolich Myles S. , Naik Seema G. , Rybka Witold B. , Ehmann W Christopher C. , Hohl Raymond J. , Valentin Jessica , Bernas-Peterson Michelle , Gerber Emily M. , Zimmerman Michele , Mierski Joseph A. , Mineishi Shin , Zheng Hong 
Published: May 2022

AbstractDespite the increased usage of post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation (allo-HSCT), our knowledge of immune reconstitution post-allo-HSCT in the setting of PTCy is limited. Adequate immune reconstitution is the key to a successful transplant. In this study, we aim to investigate the effect of PTCy on the reconstitution of each immune component; more focus was placed on the immunophenotype and functions of T cells. Using blood samples from patients who underwent allo-HSCT under regimens containing PTCy (n = 23) versus those who received no PTCy (n = 14), we examined the impact of PTCy on the post-transplant immune response. We demonstrated a distinct T cell immune signature between PTCy versus non-PTCy group. PTCy significantly delayed T cell reconstitution and affected the T cell subsets by increasing regulatory T cells (Treg) while reducing naïve T cells. In addition, we observed remarkable enhancement of multiple inhibitory receptors (TIGIT, PD-1, TIM-3, CD38, CD39) on both CD4+ and CD8+ T cells on day 30 post-transplantation in patients who received PTCy. Importantly, upregulation of PD-1 on CD8 T cells was persistent through day 180 and these T cells were less functional, manifested by reduced cytokine production upon anti-CD3/CD28 stimulation. Furthermore, we found a significant correlation of T cell immune phenotypes to clinical outcome (disease relapse and GVHD) in patients who received PTCy. Our novel findings provide critical information to understand the mechanism of how PTCy impacts immune reconstitution in allo-HSCT and may subsequently lead to optimization of our clinical practice using this treatment.
Web-based application for predicting the potential target phenotype for recombinant human thrombomodulin therapy in patients with sepsis: analysis of three multicentre registries
Authors: Goto Tadahiro , Kudo Daisuke , Uchimido Ryo , Hayakawa Mineji , Yamakawa Kazuma , Abe Toshikazu , Shiraishi Atsushi , Kushimoto Shigeki 
Published: May 2022

AbstractA recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distinct phenotype that could be a potential target of rhTM therapy (rhTM target phenotype). However, for application in the clinical setting, a simple tool for determining this target is necessary. Thus, using three multicentre sepsis registries, we aimed to develop and validate a machine learning model for predicting presence of the target phenotype that we previously identified for targeted rhTM therapy. The predictors were platelet count, PT-INR, fibrinogen, fibrinogen/fibrin degradation products, and D-dimer. We also implemented the model as a web-based application. Two of the three registries were used for model development (n = 3694), and the remaining registry was used for validation (n = 1184). Approximately 8–9% of patients had the rhTM target phenotype in each cohort. In the validation, the C statistic of the developed model for predicting the rhTM target phenotype was 0.996 (95% CI 0.993–0.998), with a sensitivity of 0.991 and a specificity of 0.967. Among patients who were predicted to have the potential target phenotype (predicted target patients) in the validation cohort (n = 142), rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, − 31.3% [− 53.5 to − 9.1%]). The developed model was able to accurately predict the rhTM target phenotype. The model, which is available as a web-based application, could profoundly benefit clinicians and researchers investigating the heterogeneity in the treatment effects of rhTM and its mechanisms.