bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research on quality assessment method of blockchain multi-source heterogeneous business data
Authors: Wang Junlu , Zhang Ran , Ji Wanting , Zhang Haolin , Song Baoyan 
Published: August 2022

Abstract
The application of blockchain technology in business is more and more widespread. Business data mostly come from different data sources, the information representation is inconsistent, the information ambiguity between blocks in the same blockchain is too large, resulting in information consistency, credibility and value is difficult to evaluate, and other problems, this paper proposes a multi-source heterogeneous blockchain data quality assessment method for business activities. Firstly, the entity information representation method based on CEKGRL model is proposed, and the triplet structure of related entities is introduced into the blockchain, which is associated with the business activity category. The similarity is calculated through the context information to realize the consistency evaluation of blockchain information. Secondly, a credibility representation method based on information source, information comment and information content is proposed, and the credibility assessment of business activity information is obtained by fusing the representation results. Finally, on the basis of information credibility representation, the value evaluation method is introduced to evaluate the total value of business information in the blockchain, and the blockchain quality evaluation model is constructed. Experimental results show that the proposed method is superior to the existing methods in evaluating inter-block consistency, intra-block information credibility and value.
Clinical outcomes of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for metastasised rectal or anal canal adenocarcinoma
Authors: Hasegawa Hiroshi , Matsuda Takeru , Yamashita Kimihiro , Sawada Ryuichiro , Harada Hitoshi , Urakawa Naoki , Goto Hironobu , Kanaji Shingo , Oshikiri Taro , Kakeji Yoshihiro 
Published: August 2022

Abstract
Purpose
Rectal or anal canal adenocarcinoma with inguinal lymph node metastasis (ILNM) is rare and is associated with poor prognostic outcomes. This study aimed to elucidate the clinical significance of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for rectal or anal canal adenocarcinoma with clinically suspected ILNM.
Methods
This study enrolled 15 consecutive patients who underwent neoadjuvant therapy and curative resection for rectal or anal canal adenocarcinoma with clinically suspected ILNM between 2005 and 2019 at a single institution. Inguinal lymph node dissection was selectively performed on the side of suspected metastasis before neoadjuvant therapy. Short- and long-term outcomes were retrospectively reviewed.
Results
Out of the15 patients, 11 were treated with neoadjuvant chemoradiation, three with chemotherapy, and one with chemoradiation followed by chemotherapy. Six patients had negative fluorodeoxyglucose (FDG) accumulation in inguinal lymph nodes on preoperative FDG-positron emission tomography (FDG-PET) scan, and their inguinal lymph nodes were also pathologically negative for metastasis. Of the nine patients who had positive FDG accumulation, four had pathologically positive inguinal lymph nodes. Seven patients (46.7%) had inguinal seroma postoperatively. Five-year-overall survival was 77.5%, and 5-year-relapse-free survival was 64.2%. No patient had a recurrence in the inguinal region.
Conclusion
In patients with rectal or anal canal adenocarcinoma associated with clinical ILNM, radical resection with neoadjuvant therapy provides a good long-term survival.
Investigating the Perceptions and Practices of EFL Teachers in Teaching English Vocabulary to Young Learners: The Case of Some Selected Primary Schools in Dawro Zone, Tercha Town, and its Surroundings, SWRS, Ethiopia
Authors: Bedilu Woldemariam Bezabih , Wubshet Hailu 
Published: August 2022

Abstract
The authors have requested that this preprint be removed from Research Square.
Reasons for Disagreement Between Screening and Standard Echocardiography in Primary Care: Data from the PROVAR+ Study
Authors: Galdino Bruno Fernandes , Amaral Arthur Maia , Santos Luiza Pereira Afonso , Nogueira Marcelo Augusto Almeida , Rocha Rodrigo Tavares Lanna , Nunes Maria Carmo Pereira , Beaton Andrea Zawacki , Oliveira Kaciane Krauss Bruno , Franco Juliane , Barbosa Márcia Melo , Silva Victor Raggazzi Hohne , Reese Alison Tompsett , Ribeiro Antonio Luiz P. , Sable Craig , Nascimento Bruno Ramos 
Published: August 2022

Abstract
Purpose: To evaluate the reasons for disagreement between screening echocardiography (echo), acquired by non-experts, and standard echo in the Brazilian primary care (PC). Methods: Over 20 months, 22 PC workers were trained on simplified handheld (GE VSCAN) echo protocols. Screening groups, consisting of patients aged 17-20, 35-40 and 60-65 years, and patients referred for clinical indications underwent focused echo. Studies were remotely interpreted in US and Brazil, and those diagnosed with major or severe HD were referred for standard echo performed by an expert. Major HD was defined as moderate to severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. A random sample of exams was selected for evaluation of variables accounting for disagreement.Results: A sample of 768 patients was analyzed, 651 (85%) in the referred group. Quality issues were reported in 5.8%, and the random Kappa for major HD between screening and standard echo was 0.51. The most frequent reasons for disagreement were: overestimation of mitral regurgitation (MR) (17.9%, N=138), left ventricular (LV) dysfunction (15.7%, N=121), aortic regurgitation (AR) (15.2%, N=117), LV hypertrophy (13.5%, N=104) and tricuspid regurgitation (12.7%, N=98). Misdiagnosis of mitral and aortic morphological abnormalities was observed in 12.4% and 3.0%, and underestimation of AR and MR occurred in 4.6% and 11.1%. Among 257 patients with suspected mild/moderate MR, 129 were reclassified to normal. Conclusion: Although screening echo with task-shifting in PC is a promising tool in low-income areas, estimation of valve regurgitation and LV function and size account for considerable disagreement with standard exams.
The Interaction Between Two Metabolites of Polygala tenuifolia and
Cholinesterases
Authors: Gao Chengxia , Du Huizhi 
Published: August 2022

Objective:
The work aimed to compare the binding between the two main components of
Polygala tenuifolia Willd. and two cholinesterases (ChEs) by using a variety of spectral techniques.

Methods:
Two main components of Polygala tenuifolia Willd. included Tenuifolin (Ten) and
Onjisaponin B (Onj B), and two ChEs included acetylcholinesterase (AChE) and butyrylcholinesterase
(BChE).

Results:
The UV-visible absorption spectra results showed that Ten had no effect on the structure of
ChEs, and the combination of Onj B with ChEs changed its structure. Onj B statically quenched the
endogenous fluorescence of both of ChEs, Ten dynamically quenched the endogenous fluorescence of
AChE with no effect on BChE. The fluorescence quenching rate of ChEs by Onj B was much higher
than that of AChE by Ten, and only one binding site of each protein spontaneously interacted with the
compound to bind to or collide. Synchronous fluorescence results showed that Ten and Onj B
quenched the fluorescence intensity by affecting tryptophan and tyrosine residues in cholinesterases,
respectively. Hydrophobic force played an important role in the interaction between Ten and AChE,
and van der Waals force and hydrogen bond were the main driving forces for the binding of Onj B to
ChEs. The Enzyme activity test showed that Onj B inhibited ChE activity, and Ten never inhibited
ChE activity.

Conclusion:
Onj B has the potential to inhibit ChE activity and increase the neurotransmitter
acetylcholine content in the nerve system, improving the Alzheimer's disease (AD).
Modified Levels of Renin Angiotensin Related Components in the Frontal
Cortex and Hippocampus were Associated with Neuroinflammation and
Lower Neuroprotective Effects of NGF During Acute Hepatic
Encephalopathy in Mice
Authors: Oliveira Natália Katley , de Brito Toscano Eliana Cristina , Silva Oliveira Bruna da , Dias Lima Luiza Cioglia , Simões e Silva Ana Cristina , de Miranda Aline Silva , Teixeira Antônio Lúcio , Rachid Milene Alvarenga 
Published: August 2022

Background:
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves
cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest
that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R),
which compose the classical pathway of the renin–angiotensin system (RAS), exacerbate
neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor,
which integrate the alternative RAS axis, have been shown as promising therapeutic targets in
neuropsychiatric disorders, leading to neuroprotection.

Objective:
This study aimed to investigate the potential participation of the RAS components in
thioacetamide (TAA)-induced HE in mice.

Methods:
We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and
chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute
liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS
components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF)
were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the
chemokine (CCL2) were quantified by cytometric bead array. The student’s t-test was applied for
statistical analysis.

Results:
Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in
cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the
Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal
cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6,
IL-12, and CCL2 in the hippocampus compared with controls.

Conclusion:
This study suggested that the reduction of components of the alternative RAS axis was
associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF
during TAA-induced HE.
Elabela Peptide: An Emerging Target in Therapeutics
Authors: Bhatt Lokesh Kumar , Sharma Maneesha , Prabhavalkar Kedar S. 
Published: August 2022

Abstract:
Elabela, a bioactive micropeptide, is recognized as the second endogenous ligand for Apelin receptor and is widely distributed in different tissues and organs. Elabela plays important role in various physiological processes such blood pressure control, heart morphogenesis, apoptosis, angiogenesis, cell proliferation, migration, etc. Elabela is also implicated in pathological conditions like cardiac dysfunctions, heart failure, hypertension, kidney diseases, cancer and CNS disorders. The association of Elabela with these disease conditions makes it a potential target for their therapy. This review summarizes physiological role of Elabela peptide as well as its implication in various disease conditions.
Fibrinogen, Fibrin, and Fibrin Degradation Products in COVID-19
Authors: Flick Matthew J. , Kangro Kadri , Wolberg Alisa S. 
Published: August 2022

Abstract:Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the highly patho-genic and highly transmissible human coronavirus that is the causative agent for the worldwide COVID-19 pandemic. COVID-19 manifests predominantly as a respiratory illness with symptoms consistent with viral pneumonia, but other organ systems (e.g., kidney, heart, brain) can also be-come perturbed in COVID-19 patients. Accumulating data suggest that significant activation of the hemostatic system is a common pathological manifestation of SARS-CoV-2 infection. The clotting protein fibrinogen is one of the most abundant plasma proteins. Following activation of coagulation, the central coagulation protease thrombin converts fibrinogen to fibrin monomers, which self-assemble to form a matrix, the primary structural component of the blood clot. Severe COVID-19 is associated with a profound perturbation of circulating fibrinogen, intra- and extravascular fibrin deposition and persistence, and fibrin degradation. Current findings suggest high levels of fibrino-gen and the fibrin degradation product D-dimer are biomarkers of poor prognosis in COVID-19. Moreover, emerging studies with in vitro and animal models indicate fibrin(ogen) as an active play-er in COVID-19 pathogenesis. Here, we review the current literature regarding fibrin(ogen) and COVID-19, including possible pathogenic mechanisms and treatment strategies centered on clotting and fibrin(ogen) function.
The Dual Functions of Non-Coding RNA CRNDE in Different Tumors
Authors: Wang Zhuowei , Wu Yinxin , Du Zhuoyin , Tan Fangshun , Zhou Yunxi , Zhang Zhicheng , Yuan Chengfu 
Published: August 2022

Abstract:
Long non-coding RNA has attracted the interest of researchers as a relevant factor that can
influence human cancers. As an oncogene and suppressor gene, it has numerous pathways and is
closely related to the pathophysiology of human diseases. Meanwhile, it may become a novel treatment
option and target for tumor treatment. CRNDE is the gene symbol for Colorectal Neoplasia Differentially
Expressed (non-protein-coding) since it was found to be considerably higher in colorectal
cancer when it was first discovered. It's transcribed from human chromosome 16. Many studies have
shown that it is intimately linked to the etiology of many tumors and malignancies. According to the
paper, the biological function and pathophysiological mechanism of CRNDE in tumors have been
studied extensively in recent years. PubMed served as an essential platform for conducting literature
searches and related analyses. CRNDE, a long non-coding RNA closely related to tumors, was highly
expressed in many tumor cells. There were various underlying mechanisms affecting the progression
of CRNDE-regulated tumorigenesis, including hepatocellular carcinoma, gastric cancer, prostate carcinoma,
oral squamous cell carcinoma, breast cancer, thyroid cancer, myeloma, leukemia, melanoma,
colorectal cancer, glioblastoma, osteosarcoma, cervical cancer, intrahepatic cholangiocarcinoma, nonsmall
cell lung cancer, hepatoblastoma cell tumor, abdominal aortic aneurysm, nasopharyngeal carcinoma,
bladder cancer, Wilms tumor, medulloblastoma, pancreatic cancer, gallbladder cancer, ovarian
cancer, and renal cell carcinoma. CRNDE is involved in the processes of proliferation, migration, invasion,
and inhibition of apoptosis of various cancer cells.
RON Receptor Tyrosine Kinase in Tumorigenic Stemness as a Therapeutic
Target of Antibody-drug Conjugates for Eradication of Triple-negative
Breast Cancer Stem Cells
Authors: Wang Ming-Hai , Suthe Sreedhar Reddy , Yao Hang-Ping , Weng Tian-Hao 
Published: August 2022

Background:
Cancer stem-like cells in triple-negative breast cancer (TNBC-SLCs) are the
tumorigenic core for malignancy. Aberrant expression of the RON receptor tyrosine kinase has implications
in TNBC tumorigenesis and malignancy.

Objective:
In this study, we identified the RON receptor as a pathogenic factor contributing to TNBC
cell stemness and validated anti-RON antibody-drug conjugate Zt/g4-MMAE for eradication of RONexpressing
TNBC-SLCs.

Methods:
Immunofluorescence and Western blotting were used for analyzing cellular marker expression.
TNBC-SLCs were isolated by magnetic-immunofluorescence cell-sorting techniques. Spheroids
were generated using the ultralow adhesion culture methods. Levels of TNBC-SLC chemosensitivity
were determined by MTS assays. TNBC-SLC mediated tumor growth was determined in athymic nude
mice. The effectiveness of Zt/g4-induced RON internalization was measured by immunofluorescence
analysis. Efficacies of Zt/g4-MMAE in killing TNBC-SLCs in vitro and in eradicating TNBC-SLCmediated
tumors were determined in mouse models. All data were statistically analyzed using the
GraphPad Prism 7 software.

Results:
Increased RON expression existed in TNBC-SLCs with CD44+/CD24- phenotypes and ALDH
activities and facilitated epithelial to mesenchymal transition. RON-positive TNBC-SLCs enhanced
spheroid-formatting capability compared to RON-negative TNBC-SLCs, which were sensitive to small
molecule kinase inhibitor BMS-777607. Increased RON expression also promoted TNBC-SLC chemoresistance
and facilitated tumor growth at an accelerated rate. In vitro, Zt/g4-MMAE caused massive
TNBC-SLC death with an average IC50 value of ~1.56 μg per/ml and impaired TNBC cell spheroid
formation. In mice, Zt/g4-MMAE effectively inhibited and/or eradicated TNBC-SLC mediated tumors
in a single agent regimen.

Conclusions:
Sustained RON expression contributes to TNBC-SLC tumorigenesis. Zt/g4-MMAE is
found to be effective in vivo in killing TNBC-SLC-mediated xenograft tumors. Our findings highlight
the feasibility of Zt/g4-MMAE for the eradication of TNBC-SLCs in the future.
An Immune-suppressive Triterpenoid from the Stem of Kadsura coccinea
Authors: Gao Feng , Tian Jiaxin , Li Kunyu , Ma Guanghai , Cui Yong 
Published: August 2022

Abstract:
Kadsura coccinea has been used as a folk medicine in China, treating various diseases, including
chronic gastritis and rheumatoid arthritis (RA). Chemical studies have revealed that lignans
and triterpenes are the main constituents of its roots and stems. In this paper, a chemical investigation
on the stem of K. coccinea was performed and a previously undescribed 3,4-secolanostane (1) was afforded.
The structure of 1 was determined through comprehensive NMR and HRESI-MS data analysis.
The stereo-configuration of 1 was established based on a comparison of experimental and calculated
ECD spectra. Bioactivity assay carried out in immune cells indicated that 1 could show moderate
effects on ConA (5 μg/mL)-induced T-cell proliferation with an IC50 value of 13.28 μM (cyclosporine
A as the positive drug, IC50 = 0.13 μM) while the IC50 value was 23.12 μM in LPS (10 μg/mL)-induced
B cells (mycophenolate mofetil as the positive drug, IC50 = 16.71 μM).
Investigation of Therapeutic Drug Monitoring of Tacrolimus in Different
Age Groups: Results from a Turkish Nationwide Study
Authors: Caglayan Murat , Gonel Ataman , Celik Osman , Sozuer Abdulvahit , Ulgu Mustafa Mahir , Ata Naim , Birinci Suayip 
Published: August 2022

Background:
The blood level of tacrolimus (TAC) used for post-transplant immunosuppression
should be within the therapeutic index. Geriatric individuals may be at risk of organ rejection because,
in this age group, routine drug use is usually disrupted, and the bioavailability of aging-related
drugs is decreased.

Objective:
The aim of this study was to analyze the age-related variability of blood TAC levels in patients
in Turkey.

Methods:
In this study, 697,616 patients who underwent TAC measurement in the laboratories of public,
private, and university hospitals between 2018 and 2020 were identified from the Health-net database of
the Ministry of Health. The results of patients aged ≥65 years were compared with those of patients aged
<65 years. The differences between the sexes in the same age group were also examined. Data from the
Turkish Ministry of Health National Electronic Database were used to design a multicenter retrospective
cohort study.

Results:
The study included 697,616 patients. The mean TAC concentration was 7.2 ± 6.25 ng/mL for all
the patients, 7.13 ± 6.7 ng/mL for the female patients, and 7.24 ± 5.96 ng/mL for the male patients. A
statistically significant difference in TAC concentration was found between men and women in the general
population. Groups aged ≥65 years were compared among themselves. A statistically significant decrease
in TAC concentration was found only in the age group of 75–79 years (5.63 ± 4.09 ng/mL) of
women compared with the men. In all other age groups, the TAC levels of the men were lower.

Conclusions:
The proportion of patients with TAC concentrations lower than the therapeutic index was
higher in the groups aged ≥65 years. Thus, patients aged ≥65 years may be at risk of organ rejection, as
optimum immunosuppression cannot be achieved. In these patients, more frequent drug monitoring and
providing training to ensure the compliance of the patient and the patient's relatives in the use of TAC
may be recommended.
Implementation of the QbD Approach to the Development and Validation
of an Analytical Method for Alpha-beta Arteether
Authors: Baldi Ashish , Bajwa Neha , Mahal Shipra , Madan Jitender 
Published: August 2022

Background:
The development of effective, cost-effective, robust, sensitive, and specific analytical techniques for the analysis of drug(s), degradation product(s), and contaminants in dosage forms and biological samples is constantly required as part of the pharmaceutical product life-cycle. The adoption of systematic analytical development methodologies such as quality by design (QbD) is particularly advantageous for enhancing method performance since analytical method development encompasses a number of variables that are significant in explaining variability in method performance. Analytical Quality by Design (AQbD) is a standardised method to process validation that covers all aspects of an analytical procedure. It comprises determining the analytical target profile (ATP), identifying critical method parameters or variables, and selecting critical method attributes (CMAs) or qualities.

Objective:
Spectroscopic and chromatographic methods were developed, conferring the Quality by Design (QbD) tactic as per ICH Q8(R2) guidelines for analytical method development of α-β-arteether.

Methods:
Understanding dependent variables, various factors, and their interaction effects through a desired series of experiments on the answers to be examined is referred to as QbD. Various variable factors were detected using the Ishikawa diagram. As a result, many essential factors for chromatography methods were investigated. A desired set of experiments on the answers to be evaluated was used to comprehend dependent variables, various factors, and their interaction effects using Design-Expert software version 13. Statistical research such fractional factorial designs and Plackett-Burman were employed for this. The QbD methodology was used to establish a durable, precise, and accurate HPLC analytical method for arteether.

Result:
Using Design Expert 13's statistical software, the findings of the Plackette Burman research were studied, and the influence of each parameter on the answers was analysed using an overlay plot. Mobile phase (Acetonitrile: water), column C18250nmX4.6mm, column temperature 300 οC, wavelength: 254 nm, injection volume 20l/min, run time 10 mins, detector waters 2489 UV/Visible detector, retention time 4.149 are among the critical parameters estimated for the development of an analytical method for α,β- arteether.

Conclusion:
The analytical method developed by the QbD approach was validated according to ICH Q2(R1) guidelines, and it was found that the developed analytical method is robust and specific.