bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responses of roots and rhizosphere of female papaya to the exogenous application of GA3
Authors: Zhou Yongmei , Pang Ziqin , Jia Haifeng , Yuan Zhaonian , Ming Ray 
Published: January 2023

AbstractExogenous GAs have an indeterminate effect on root development. Our current study used female papaya to reveal how the roots and rhizosphere respond to the exogenous application of GA3 by investigating the transcriptome profile in roots, metabolic profile and microbial community in both roots and rhizosphere of GA3-treated and control female papaya. The results demonstrated that exogenous GA3 treatment enhanced female papaya lateral root development, which gave plants physical advantages of water and nutrient uptake. In addition, it was likely that GA3 spraying in papaya shoot apices increased the level of auxin, which was transported to roots by CpPIN1, where auxin upregulated CpLBD16 and repressed CpBP to promote the lateral root initiation and development. In papaya roots, corresponding transporters (CpTMT3, CpNRT1:2, CpPHT1;4, CpINT2, CpCOPT2, CpABCB11, CpNIP4;1) were upregulated and excretion transporters were downregulated such as CpNAXT1 for water and nutrients uptake with exogenous GA3 application. Moreover, in GA3-treated papaya roots, CpALS3 and CpMYB62 were downregulated, indicating a stronger abiotic resistance to aluminum toxic and phosphate starvation. On the other hand, BRs and JAs, which involve in defense responses, were enriched in the roots and rhizosphere of GA3-treated papayas. The upregulation of the two hormones might result in the reduction of pathogens in roots and rhizosphere such as Colletotrichum and Verticillium. GA3-treated female papaya increased the abundance of beneficial bacteria species including Mycobacterium, Mitsuaria, and Actinophytocola, but decreased that of the genera Candidatus and Bryobacter for that it required less nitrate. Overall, the roots and rhizosphere of female papaya positively respond to exogenous application of GA3 to promote development and stress tolerance. Treatment of female papaya with GA3 might result in the promotion of lateral root formation and development by upregulating CpLBD16 and downregulating CpBP. GA3-treated papaya roots exhibited feedback control of brassinolide and jasmonate signaling in root development and defense. These findings revealed complex response to a growth hormone treatment in papaya roots and rhizosphere and will lead to investigations on the impact of other plant hormones on belowground development in papaya.
Implication of changes in xanthine oxidase activity following hemodialysis
Authors: Fujioka Hayato , Koike Tsutomu , Imamura Teruhiko , Kakeshita Kota , Yamazaki Hidenori , Kinugawa Koichiro 
Published: January 2023

Abstract
Background
Xanthine oxidase activity has a key role in the development of oxidative stress and progression of cardiovascular diseases. However, the change of xanthine oxidase activity following hemodialysis and its prognostic impact remain uncertain.

Methods
We prospectively included hemodialysis patients who did not take any anti-hyperuricemic agents and measured their xanthine oxidase activity before and after the index hemodialysis. The impact of change in xanthine oxidase activity during hemodialysis on cardiovascular death were investigated.

Results
A total of 46 patients (median 72 years old, 29 men) were included. During hemodialysis, a common logarithm of xanthine oxidase activity decreased significantly from 1.16 (0.94, 1.27) to 1.03 (0.80, 1.20) (p < 0.01). Of them, xanthine oxidase activity remained unchanged or increased in 16 patients, who had a greater decrease in blood pressure and more hemoconcentration compared with others. Two–year survival from cardiovascular death was not significantly stratified by the changes in xanthine oxidase activity (p = 0.43).

Conclusions
During hemodialysis, xanthine oxidase activity decreased among the overall cohort, whereas some patients experienced its increases, which might be associated with hypotension and hemoconcentration during hemodialysis. Further larger-scale studies are required to validate our findings and find clinical implication of change in xanthine oxidase activity during hemodialysis.
Predictors of do-not-attempt-resuscitation decisions in patients with infratentorial or large supratentorial intracerebral hemorrhages and consequences thereafter: a register-based, longitudinal study in Sweden
Authors: Soomägi Amanda , Viktorisson Adam , Sunnerhagen Katharina S. 
Published: January 2023

Abstract
Objectives
Do-not-attempt-resuscitation (DNAR) decisions for patients with infratentorial or large supratentorial intracerebral hemorrhages (ICHs) pose clinical and ethical challenges. We aimed to investigate factors associated with DNAR decisions in patients with infratentorial or large (≥30 mL) supratentorial ICH, and differences in complications, treatment, and mortality.

Materials & methods
This longitudinal, observational study comprised all patients treated for ICH at three stroke units in Gothenburg, Sweden, between November 2014 and June 2019. Patients were identified in the local stroke register, and additional data were collected from medical records and national registries. Mortality rates were followed 1 year after incident ICHs. Factors associated with DNAR decisions, and one-year mortality were explored.

Results
Of 307 included patients, 164 received a DNAR decision. Most (75%) decisions were made within 24 h. DNAR decisions were associated with higher age, pre-stroke dependency, stroke severity, and intraventricular hemorrhage. Patients without DNAR decisions received thrombosis prophylaxis, oral antibiotics, and rehabilitative evaluations more frequently. The one-year survival probability was 0.16 (95% confidence interval [CI] 0.11–0.23) in patients with DNAR decisions, and 0.87 (95% CI 0.81–0.92) in patients without DNAR decision. DNAR decisions, higher age, stroke severity, hematoma volume, and comorbidities were associated with increased one-year mortality. Thrombosis prophylaxis and living alone were associated with a lower hazard.

Conclusion
The majority of DNAR decisions for patients with infratentorial or large supratentorial ICH were made within 48 h. Higher age, pre-stroke dependency, high stroke severity, and intraventricular hemorrhage predicted receiving a DNAR decision. DNAR decisions were strongly associated with increased short- and long-term mortality.
Carboxylated superparamagnetic Fe3O4 nanoparticles modified with 3-amino propanol and their application in magnetic resonance tumor imaging
Authors: Wang Changyuan , Wang Yang , Xiao Wangchuan , Chen Xiaohua , Li Renfu , Shen Zhiyong , Lu Fengchun 
Published: January 2023

Abstract
Background
Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are of potential magnetic resonance imaging (MRI) contrast agents for tumor diagnosis. However, ultrasmall particle size or negative surface charge lead to relative short half-life which limit the utilization of USPIO for in vivo MRI contrast agents.

Methods
Superparamagnetic Fe3O4 nanoparticles coated with polyacrylic acid (PAA)were synthetized, and modified by 3-amino propanol and 3-diethyl amino propyl amine. The characteristics of superparamagnetic Fe3O4 nanoparticles were investigated through transmission electron microscopy, X-ray diffraction analysis, Zata potential analysis, thermogravimetric analysis, and relaxation properties analysis. Magnetic resonance imaging animal experiment was performed.

Results
The synthetized nanoparticles were irregular spherical, with small particle size, few agglomeration, and good dispersion in water. After modification, the potential fluctuation of nanoparticles was small, and the isoelectric point of nanoparticles changed to high pH. After 3-amino propanol modification, the weight loss of the curve from 820 to 940 °C was attributed to the decomposition of 3-amino propanol molecules on the surface. The T1 relaxation rate of nanoparticles changed little before and after modification, which proved that the modification didn’t change the relaxation time. Brighter vascular images were observed after 3-amino propanol modification through measurement of magnetic resonance tumor imaging.

Conclusion
These data indicated the Fe3O4 nanoparticles modified by 3-amino propanol should be a better contrast agent in the field of magnetic resonance tumor imaging.
Notch3 signaling promotes colorectal tumor growth by enhancing immunosuppressive cells infiltration in the microenvironment
Authors: Huang Kai , Luo Wenwu , Fang Jinmei , Yu Changjun , Liu Guangjie , Yuan Xiaodong , Liu Yun , Wu Wenyong 
Published: January 2023

Abstract
Background
Macrophage infiltration in the tumor microenvironment participates in the regulation of tumor progression. Previous studies have found that Notch signaling pathway is involved in regulating the progression of colorectal cancer (CRC), however, the specific mechanism is still unclear.

Methods
The correlation between Notch signaling pathway and macrophage infiltration was investigated in TCGA database and verified in clinical samples of patients with CRC using immunohistochemistry. Gene Set Enrichment Analysis was used to find out genes related to Notch3 expression. Colony formation assay, and flow cytometry were utilized to test tumor growth and immune cell infiltration in vitro and in vivo.

Results
Using bioinformatics analysis and clinical sample validation, we found that Notch3 was highly expressed in colon tumor tissues compared to adjacent normal tissues, and it participated in regulating the recruitment of macrophages to the tumor microenvironment. Furthermore, we found that the Notch3 expression was positively correlated with the expression of macrophage recruitment-related cytokines in colon tumor tissues. Finally, we demonstrated that depletion of Notch3 had no significant effect on the growth of colon tumor cells in vitro, while, attenuated the growth of colon cancer tumors in vivo. Simultaneous, immunosuppressive cells, macrophages and myeloid-derived suppressor cell (MDSC) infiltration were dramatically reduced in the tumor microenvironment.

Conclusion
Our study illustrated that Notch3 could facilitate the progression of CRC by increasing the infiltration of macrophages and MDSCs to promote the immunosuppressive tumor microenvironment. Targeting Notch3 specifically is a potentially effective treatment for CRC.
Phosphorylation of TGIF2 represents a therapeutic target that drives EMT and metastasis of lung adenocarcinoma
Authors: Du Renle , Wang Chen , Liu Jingjing , Wang Keyan , Dai Liping , Shen Wenzhi 
Published: January 2023

Abstract
Background
TGF-β-induced factor homeobox 2 (TGIF2) is a transcription regulator that is phosphorylated by EGFR/ERK signaling. However, the functions of phosphorylated (p)-TGIF2 in cancer are largely unknown. Here, we investigated the roles of p-TGIF2 in promoting epithelial–mesenchymal transition (EMT) and metastasis in lung adenocarcinoma (LUAD).

Methods
In vitro and in vivo experiments were conducted to investigate the role of TGIF2 in LUAD EMT and metastasis. Dual-luciferase reporter and ChIP assays were employed to observe the direct transcriptional regulation of E-cadherin by TGIF2 and HDAC1. Co-immunoprecipitation was performed to identify the interaction between TGIF2 and HDAC1.

Results
Downregulating the expression of TGIF2 inhibited LUAD cell migration, EMT and metastasis in vitro and in vivo. Phosphorylation of TGIF2 by EGFR/ERK signaling was required for TGIF2-promoted LUAD EMT and metastasis since phosphorylation-deficient TGIF2 mutant lost these functions. Phosphorylation of TGIF2 was necessary to recruit HDAC1 to the E-cadherin promoter sequence and subsequently suppress E-cadherin transcription. Meanwhile, inhibition of HDAC1 repressed the TGIF2 phosphorylation-induced migration and EMT of LUAD cells. In xenograft mouse models, both inhibition of ERK and HDAC1 could significantly inhibited TGIF2-enhanced metastasis. Furthermore, TGIF2-positive staining was significantly correlated with E-cadherin-negative staining in human lung cancer specimens.

Conclusions
Our study reveals the novel function of p-TGIF2 in promoting EMT and metastasis in LUAD; p-TGIF2 could be a potential therapeutic target to inhibit LUAD metastasis.
The burden of Parkinson’s disease in the Middle East and North Africa region, 1990–2019: results from the global burden of disease study 2019
Authors: Safiri Saeid , Noori Maryam , Nejadghaderi Seyed Aria , Mousavi Seyed Ehsan , Sullman Mark J. M. , Araj-Khodaei Mostafa , Singh Kuljit , Kolahi Ali-Asghar , Gharagozli Kurosh 
Published: January 2023

Abstract
Background
Parkinson’s disease (PD) remains a common disabling progressive neurodegenerative disorder. We aimed to report the prevalence, death and disability-adjusted life-years (DALYs) attributable to PD in the Middle East and North Africa (MENA) region and its 21 countries by age, sex and socio-demographic index (SDI), between 1990 and 2019.

Methods
Publicly available data on the burden of PD in the MENA countries were retrieved from the Global Burden of Disease (GBD) 2019 project. The results are presented with age-standardised numbers and rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs).

Results
In 2019, PD had an age-standardised point prevalence of 82.6 per 100,000 population in MENA and an age-standardised death rate of 5.3, which have increased from 1990 to 2019 by 15.4% and 2.3%, respectively. In 2019, the age-standardised DALY rate of PD was 84.4, which was 0.9% higher than in 1990. The highest and lowest age-standardised DALY rates of PD in 2019 were found in Qatar and Kuwait, respectively. Also in 2019, the highest number of prevalent cases and number of DALYs were found in the 75–79 age group for both sexes. In 2019, females in MENA had an overall higher DALY rate. Furthermore, from 1990 to 2019 the burden of PD generally decreased with increasing socio-economic development, up to an SDI of around 0.4, and then increased with higher levels of SDI.

Conclusion
An upward trend was observed in the point prevalence of PD over the last three decades. This highlights the need to allocate more resources for research. Furthermore, properly equipped healthcare services are needed for the increasing number of patients with PD.
Diffuse pigmented villonodular synovitis treated with arthroscopic total synovial peel
Authors: Song Hao-Qiang , Wu Guo-Feng , Qi Wei-Zhong , Lin Li-Jun 
Published: January 2023

Abstract
Background
Diffuse pigmented villonodular synovitis (PVNS) is prone to recurrence after surgery, and it is difficult to achieve a long-term complete cure.

Objective
To reduce the recurrence rate of PVNS, the author pioneered the arthroscopic total synovial peel (ATSP).

Methods
From March 2014 to July 2020, a total of 19 patients (6 males and 13 females) with diffuse PVNS of the knee were treated in our department and underwent ATSP. It’s ‘peel’ rather than simple excision. This method is similar to peeling bark. Relapse rates and functional scores were determined, with follow-ups ranging from 12 to 72 months, on average 36 months.

Results
Treatment efficacy was assessed by imaging and functional scores. Imaging results indicated a recurrence rate of 10.5%. In patients without recurrence, the visual analog score (VAS) decreased from 4.76 ± 2.02 preoperatively to 1.56 ± 1.15 postoperatively. The Tegner-Lysholm knee function score (TLS) score increased from 67.76 ± 15.64 preoperatively to 90.32 ± 8.32 postoperatively. Compared with the literature, ATSP significantly reduces the postoperative recurrence rate of diffuse PVNS. The preliminarily findings suggest that this approach could greatly reduce the recurrence rate of postoperative PVNS in follow-up studies.

Conclusion
This approach may be a viable option for treating diffuse PVNS via arthroscopy and is worthy of clinical consideration.
Exploring the mechanism of the Fructus Mume and Rhizoma Coptidis herb pair intervention in Ulcerative Colitis from the perspective of inflammation and immunity based on systemic pharmacology
Authors: Yang Yatian , Qian Chengcheng , Wu Rui , Wang Rui , Ou Jinmei , Liu Shoujin 
Published: January 2023

Abstract
Purpose
Ulcerative Colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Fructus Mume (FM) and Rhizoma Coptidis (RC) exert effects on inflammatory and immune diseases. We evaluated the hypothesis of the FM and RC (FM-RC) herb pair remedy in alleviating dextran sulfate sodium (DSS)-induced colitis, through network pharmacology-based analyses, molecular docking, and experimental validation.

Methods
The Traditional Chinese medicine systematic pharmacology analysis platform(TCMSP) and Swiss database were used to predict potential targets of FM-RC and the GeneCards database was utilized to collect UC genes. Cytoscape software was used to construct and analyze the networks, and DAVID was utilized to perform enrichment analysis. AutoDock software was used to dock the core chemical components of the FM-RC herb pair with key UC targets. Animal experiments were performed to validate the prediction results and general conditions and body weight were observed. Pathological changes in colon tissue were observed by staining with hematoxylin and eosin. The levels of TNF-α, IL-8, IL-17, and IL-4 in serum and colon tissue were detected by ELISA.

Results
Eighteen effective components of the herb couple were screened, and their potential therapeutic targets in the treatment of UC were acquired from 110 overlapped targets. GO and KEGG analyses revealed that these targets were highly correlated with protein autophosphorylation, plasma membrane, ATP binding, cancer pathways, the PI3K-AKt signaling pathway, and the Rap1 signaling pathway. Molecular docking established the core protein interactions with compounds having a docking energy < 0 kJ·mol−1, indicating the core active components had strong binding activities with the core targets. FM-RC herb pair relieved pathological indicators and reduced the concentration of TNF-α, IL-8, and IL-17 and increased IL-4 levels in the serum and colon tissues of UC rats.

Conclusion
Collectively, FM-RC herb pair administration alleviated UC. These beneficial effects targeted MAPK1 signaling related to inflammation and immunity, which provided a basis for a better understanding of FM-RC in the treatment of UC.
Fragmented understanding: exploring the practice and meaning of informed consent in clinical trials in Ho Chi Minh City, Vietnam
Authors: Nguyen Yen Hong Thi , Dang Thuan Trong , Lam Ngoc Bao Hong , Le Phuong Thanh , Nguyen Phu Hoan , Bull Susan , Kestelyn Evelyne , Van Nuil Jennifer Ilo 
Published: January 2023

Abstract
Background
The informed consent process in clinical trials has been extensively studied to inform the development processes which protect research participants and encourage their autonomy. However, ensuring a meaningful informed consent process is still of great concern in many research settings due to its complexity in practice and interwined socio-cultural factors.

Objectives
This study explored the practices and meaning of the informed consent process in two clinial trials conducted by Oxford University Clinical Research Unit in collaboration with the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.

Methods
We used multiple data collection methods including direct observervations, in-depth interviews with study physicians and trial participants, review of informed consent documents from 2009 to 2018, and participant observation with patients’ family members. We recruited seven physicians and twenty-five trial participants into the study, of whom five physicians and thirteen trial participants completed in-depth interviews, and we held twenty-two direct observation sessions.

Results
We use the concept “fragmented understanding” to describe the nuances of understanding about the consent process and unpack underlying reasons for differing understandings.

Conclusions
Our findings show how practices of informed consent and different understanding of the trial information are shaped by trial participants’ characteristics and the socio-cultural context in which the trials take place.
Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration
Authors: Abbasizanjani Hoda , Torabi Fatemeh , Bedston Stuart , Bolton Thomas , Davies Gareth , Denaxas Spiros , Griffiths Rowena , Herbert Laura , Hollings Sam , Keene Spencer , Khunti Kamlesh , Lowthian Emily , Lyons Jane , Mizani Mehrdad A. , Nolan John , Sudlow Cathie , Walker Venexia , Whiteley William , Wood Angela , Akbari Ashley ,   CVD-COVID-UK/COVID-IMPACT Consortium
Published: January 2023

Abstract
Background
The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt.

Methods
Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer.

Results
Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information.

Conclusions
We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.