bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Chemical Profiling of Compound Huanggen Granules and Absorbed Prototypes
in Cynomolgus Monkey Plasma by Integrating UHPLC-Q-TOF-MSE Method
and Data Post-Processing Strategy
Authors: Wei Wei , Li Siwei , Hao Erwei , Pan Xianglong , Xie Jinling , Du Zhengcai , Hou Xiaotao , Deng Jiagang 
Published: August 2022

Aims:
In this study, we aim to establish an integrated research strategy for the rapid chemical profiling of
Compound Huanggen Granules (CHG) and absorbed prototypes in plasma by integrating the UHPLC-Q-TOF-MSE
method and data post-processing strategy, to provide some valuable research basis for the further studies on the
quality control, pharmacokinetics and pharmacodynamics of CHG.

Background:
Compound Huanggen Granules (CHG), a traditional Chinese medicine (TCM) hospital preparation,
has long been used in clinical practice for the prevention and treatment of liver fibrosis. However, due to the lack of
in vitro chemical and in vivo metabolism studies, its pharmacodynamic material basis is still unrevealed.

Objective:
To simplify the mass data post-processing process and enhance the structural identification efficiency by
reducing the possibility of false positive, and rapidly identify the absorbed prototypes in plasma after oral administration
of CHG.

Method:
An analytical strategy integrating ultra high-performance liquid chromatography coupled with quadrupletime-
of-flight mass spectrometry (UHPLC-Q-TOF-MSE, E represents collision energy) method and data postprocessing
strategy based on a self-built in-house components database was established and utilized for the rapid
characterization of the multi-constituents of CHG and prototypes in cynomolgus monkey plasma after oral administration.

Result:
As a result, a total of 81 compounds, including 14 phenolic acids, 6 coumarins, 25 flavonoids, 5 anthraquinones,
5 phenylpropanoids, 15 triterpenoid saponins, and 11 others, were plausibly or unambiguously identified
based on their accurate masses, and MS/MS fragment pathways analysis, and also by comparison of retention time
and MS data with reference standards. In the in vivo study, according to the extracted ion chromatograms (EICs) of
identified components, 34 absorbed prototypical components were rapidly identified in cynomolgus monkey plasma
after oral administration.

Conclusion:
It was demonstrated that the data post-processing strategy applied in this study could greatly simplify
the data post-processing process and enhance the structural identification efficiency by reducing the possibility of
false positives, and the results obtained might be helpful for further studies on the quality control, pharmacokinetics
and pharmacodynamics of CHG.
The Role of NF-κB in Myocardial Ischemia/Reperfusion Injury
Authors: Han Hua , Dong Peiliang , Liu Kemeng 
Published: August 2022

Abstract:
Acute myocardial infarction (AMI) is a threat to human life and physical health worldwide.
Timely reperfusion is very important to limit infarct size and protect ischemic myocardium.
Unfortunately, it has also caused severer myocardial damage, which is called “myocardial ischemia/
reperfusion injury (MIRI)”. There is no effective clinical treatment for it. Over the past two decades,
biological studies of NF-κB have improved the understanding of MIRI. Nuclear Factor-κB
(NF-κB) is a major transcription factor associated with cardiovascular health and disease. It is involved
in the release of pro-inflammatory factors and apoptosis of cardiomyocytes. Recent studies
have shown that inhibition of NF-κB plays a protective role in acute hypoxia and reperfusion injury.
Here we review the molecular regulation of NF-κB in MIRI, better understanding of NF-κB signaling
mechanisms related to inflammation and crosstalk with endogenous small molecules. We hope
this review will aid in improving therapeutic approaches to clinical diagnosing. This review provides
evidence for the role of NF-κB in MIRI and supports its use as a therapeutic target.
Protective Effect of Plumeria Pudica Latex Proteins on Intestinal Mucositis
Induced by 5-Fluorouracil
Authors: de Oliveira Jefferson Soares , de Andrade Gabriella Linhares , da Silva Souza Bruna , Araújo Dakson Douglas , de Freitas Cleverson Diniz Teixeira 
Published: August 2022

Abstract:
Intestinal mucositis is characterized by inflammation and ulceration of the mucosa that
affects the gastrointestinal tract and is associated with administering some drugs, such as 5-
Fluorouracil (5-FU), conventional chemotherapy used in clinics for cancer therapy. Inside intestinal
mucosa, the 5-FU acts, leading to oxidative stress, stimulating the production/release of proinflammatory
cytokines, local accumulation of neutrophils and consequent tissue damage. These
alterations favor bacterial proliferation, triggering secondary infections, and are responsible for
undesired effects such as myelosuppression and diarrhea. These factors negatively impact oncological
patients' quality of life and explain why they commonly interrupt their treatment prematurely.
Currently, there is no specific drug with the ability to completely avoid this condition, so
the search for new molecules with pharmacological properties that can be used for preventing or
ameliorating intestinal mucositis is important. Plumeria pudica is a plant that produces latexcontaining
molecules with therapeutic potential. A protein fraction obtained from this latex
(LPPp), which comprises a well-defined mixture of chitinases, proteinases proteinase inhibitors,
was demonstrated to have antioxidant and anti-inflammatory activities, preserving tissue glutathione
and malondialdehyde concentration, reducing superoxide dismutase and myeloperoxidase
activity, and reducing the level of proinflammatory cytokines in different experimental models.
Given this scenario, inflammation and oxidative stress are directly involved in the pathogenesis of
intestinal mucositis promoted by 5-FU. So, the hypothesis is that LPPp could inhibit these factors
to attenuate the cytotoxicity of this pathology associated with 5-FU-treatment. This article brings
new insights into the potential of the laticifer proteins extracted from the latex of P. pudica and
opens new perspectives for the treatment of this type of intestinal mucositis with LPPp.
Lymphocytic Interstitial Pneumonia Associated with Sjögren Syndrome: Case-Based Review
Authors: de Carvalho Jozélio Freire , Gonçalves Caio Marco , Cordeiro Luísa Rodrigues , de Andrade Carlos Augusto Ferreira 
Published: August 2022

Background:
Few studies have described lymphocytic interstitial pneumonia (LIP) in
Sjögren's syndrome (SS). We aimed to analyze the clinical, therapeutic, and outcome of patients
with SS and LIP.

Methods:
We searched for articles in PubMed/MEDLINE, LILACS, SciELO, and Cochrane from
1966 to 2020, in English, Spanish, French, Chinese, and Japanese literature had an English summary
about LIP and SS. The keywords were "Sjögren syndrome" and "Lymphocytic interstitial
pneumonia." Additionally, we report a patient with SS and LIP.

Result:
27 patients with SS and LIP were found. The age range ranged from 14 to 73 years old,
with only 3 male patients, with a predominance of LIP cases in patients with primary SS (22/27). In
the following case, the LIP preceded SS by 2 years; in the other 26 patients, SS preceded it. The
majority presented dyspnea, mainly on exertion, followed by a dry cough. Lung biopsy was performed
in 10 studies. Therapy varied from the use of clinical observation, corticosteroids alone, or
associated with immunosuppressants. Most studies have shown improvement or stabilization of the
pulmonary condition after therapy (13/16 studies).

Conclusion:
This article reviews cases of lymphocytic interstitial pneumonia associated with
Sjögren syndrome and shows a good outcome with adequate treatment. It emphasizes that early LIP
diagnosis in patients with Sjogren Syndrome may be determined using lung computed tomography.
De Novo Vasculitis after COVID-19 Vaccination
Authors: Mao Jianhua , Tang Xiaoxiao , Liu Fei , Li Qiuyu , Fu Haidong , Wang Jingjing 
Published: August 2022

Background:
The coronavirus disease 2019 (COVID-19) pandemic continues to spread around the world. Vaccinations have been administered globally and have been proven to be safe and effective. However, vasculitis has been reported as an adverse event occurring after COVID-19 vaccination.

Methods:
In this review, we analyzed the literature to identify original articles that reported on pa-tients who developed vasculitis following COVID-19 vaccination and summarized their clinical manifestations. PubMed and Web of Knowledge were searched to identify relevant studies.

Results:
A total of 27 patients who developed vasculitis following COVID-19 vaccination were identified from 21 studies. The involved organs included the skin and kidney. The main clinical fea-tures of patients whose skin was affected were papules, maculopapular rashes, and plaques. Most of the patients exhibited small vessel vasculitis and single-organ vasculitis; these were resolved within one month. Patients whose kidneys were affected exhibited vasculitis, including anti-neutrophil cytoplasmic antibody glomerulonephritis and IgA nephritis. Most patients were treated with corti-costeroid, rituximab, and cyclophosphamide, and one patient needed hemodialysis. The renal func-tion of most patients was improved or recovered, but one patient needed maintenance dialysis.

Conclusion:
Vasculitis was rarely reported after COVID-19 vaccine administration. It often mani-fested as cutaneous small-vessel vasculitis or glomerulonephritis. Notably, when a patient demon-strates hematuria, proteinuria, and acute kidney injury after COVID-19 vaccination, there is a pos-sibility that the patient could have developed vasculitis. Skin-related problems were quickly re-solved, while kidney-related problems may progress to chronic kidney disease.
Modern Concepts of the Role of Fine Particles (PM 2.5) in the Genesis of
Atherosclerosis and Myocardial Damage: Clinical and Epidemiological
Data, the Main Pathophysiological Mechanisms
Authors: Chaulin Aleksey Michailovich , Sergeev Artem Konstantinovich 
Published: August 2022

Abstract:
Due to the fact that atherosclerotic cardiovascular diseases (CVDs) dominate in the structure of morbidity, disability and mortality of the population, the study of the risk factors for the development of atherosclerotic CVDs, as well as the study of the underlying pathogenetic mechanisms thereof, is the most important area of scientific research in modern medicine. Understanding these aspects will allow to improve the set of treatment and preventive measures and activities. One of the important risk factors for the development of atherosclerosis, which has been actively studied recently, is air pollution with fine particulate matter (PM 2.5). According to clinical and epidemiological data, the level of air pollution with PM 2.5 exceeds the normative indicators in most regions of the world and is associated with subclinical markers of atherosclerosis and mortality from atherosclerotic CVDs.

The aim:
of this article is to systematize and discuss in detail the role of PM 2.5 in the development of atherosclerosis and myocardial damage with consideration of epidemiological and pathogenetic aspects

Materials and method:
This narrative review is based on the analysis of publications in the Medline, PubMed, and Embase databases. The terms "fine particles" and "PM 2.5" in combination with "pathophysiological mechanisms," "cardiovascular diseases", "atherosclerosis", "cardiac troponins", "myocardial damage" and "myocardial injury" were used to search publications.

Conclusion:
. According to the conducted narrative review, PM 2.5 should be regarded as the significant risk factor for the development of atherosclerotic CVDs. The pro-atherogenic effect of fine particulate matter is based on several basic and closely interrelated pathophysiological mechanisms: endothelial dysfunction, impaired lipid metabolism, increased oxidative stress and inflammatory reactions, impaired functioning of the vegetative nervous system and increased activity of the hemostatic system. In addition, PM 2.5 causes subclinical damage of cardiac muscle cells by several mechanisms: apoptosis, oxidative stress, decreased oxygen delivery due to coronary atherosclerosis and ischemic damage of cardiomyocytes. Highly sensitive cardiac troponins are promising markers for detecting subclinical myocardial damage in people living in polluted regions.
Computational Investigations of Coumarin Derivatives as Cyclindependent Kinase 9 Inhibitors Using 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation
Authors: Li Yaxin , Liu Sisi , Wei Xilin , Zhang Ran , Zhang Yifan , Guo Chunyan 
Published: August 2022

Background:Cyclin-Dependent Kinase 9 as one of the serine/threonine protein kinases has become an important target for the treatment of cancer especially driven by transcriptional dysregulation.Objective:This thesis was conducted to elucidate the structure-activity relationship and interaction mode of coumarin compounds acting on CDK9.Methods:Three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulation were conducted to reveal the structural requirements for bioactivities. The 3D-QSAR model was constructed to find the features required for different substituents on the coumarin scaffold. Molecular docking and molecular dynamics simulation were employed to generate the binding mode and stability of CDK9.Results:The Q2 and R2 values of the CoMFA model were calculated as 0.52 and 0.999, while those for the CoMSIA model were 0.606 and 0.998. It is believed that the significant statistical parameters of CoMFA and CoMSIA models revealed high activity-descriptor relationship efficiency. Therefore, we considered the 3D-QSAR model to be robust and accurate. The contour maps provided a deep structure-activity relationship and valuable clues for rational modification. Based on the contour maps, 4 novel CDK9 inhibitors which were predicted to have satisfactory pharmacokinetic characteristics were designed and exhibited better-predicted activities. Subsequently, molecular docking was employed to generate the binding mode of CDK9. Furthermore, 50 ns MD simulation was of great help in verifying the accuracy of docking results and the stability of the complexes.Conclusion:The study is a valuable insight for further research on novel and effective inhibitors targeting CDK9.
Isoproterenol-induced Upregulation of HPSE Accelerates Triple-negative Breast
Cancer Cell Proliferation and Migration through Enhancing the Transcriptional Activity
of HIF-1α
Authors: Jiang Guoqin , Ni Qichao , Qiu Jian , Shen Zhongyi 
Published: August 2022

Backgrounds:
Triple-negative breast cancer (TNBC) is considered to be the most malignant subtype of breast cancer (BC). Heparanase (HPSE) has been reported to contribute to tumor development, but its potential function in TNBC is not clear. The intention of this study was to investigate whether HPSE affects TNBC progression and to explore the possible mechanisms.

Methods:
Bioinformatics analyses were applied to analyze the expression of HPSE in TNBC samples and normal breast samples. The mRNA and protein levels of HPSE in TNBC cells were detected by RT-qPCR and western blot. Function assays, including CCK-8 assay, colony formation assay, transwell assay and wound healing assay were conducted to validate the effects of HPSE silencing on TNBC cell proliferation and migration. Mechanism experiments were performed to explore the upstream molecular mechanism of HPSE in TNBC cells.

Results:
Silencing of HPSE suppressed the proliferation and migration of TNBC cells. Moreover, hypoxia inducible factor-1 alpha (HIF-1α) interacted with HPSE promoter and promoted the transcription of HPSE. Isoproterenol (ISO), a pharmacological substitute for chronic stress-induced sympathetic activation, was proven to induce HIF-1α upregulation, so as to transcriptionally activate HPSE in TNBC cells. Furthermore, it manifested that ISO facilitated TNBC cell proliferation and migration in a HPSE-dependent way.

Conclusion:
HPSE activated by ISO-induced HIF-1α promoted TNBC cell proliferation and migration, which might offer a novel sight for TNBC treatment.
O Programa Proinfância E Seus Desdobramentos Em Um Município De Minas Gerais
Authors: Araújo Víviam Carvalho de , Santos Núbia Aparecida Schaper 
Published: August 2022

Esse texto tem por objetivo apresentar os dados produzidos em uma pesquisa de Doutorado em Educação que teve como objetivo compreender o processo de implementação do Programa Proinfância no município de Juiz de Fora/MG. A base teórico-metodológica adotada fundamentou-se na perspectiva do círculo de Mikhail Bakhtin em diálogo com a proposta do ciclo de políticas (policy cycle approach), desenvolvida pelo sociólogo inglês Stephen Ball e colaboradores. As políticas públicas no campo da Educação Infantil e dos autores que as analisam constituíram-se também como parâmetro teórico importante na construção do percurso do trabalho. Como instrumentos metodológicos, foram utilizados a pesquisa bibliográfica, a análise documental e entrevistas. Os efeitos do processo de implementação do Programa Proinfância indicam uma política municipal de Educação Infantil dual, fragmentada e focalizada ao estabelecer uma política de conveniamento para a gestão das creches via terceiro setor. Conquanto o Programa tenha trazido uma expansão de vagas nas creches e, de certa forma, uma melhoria na infraestrutura, vem acarretando uma extrema desigualdade nas condições de oferta da Educação Infantil no município.
Long-term Consequences of COVID-19 and the Pandemic: Protocol for a Web-Based, Longitudinal Observational Study (DEFEAT)
Authors: Mikuteit Marie , Heinemann Stephanie , Roder Sascha , Niewolik Jacqueline , Schröder Dominik , Vahldiek Kai , Klawitter Sandra , Cossmann Anne , Bergemann Torsten , Degen Chantal , Klawonn Frank , Behrens Georg Martin Norbert , Müller Frank , Dopfer-Jablonka Alexandra , Steffens Sandra 
Published: August 2022

Background
With population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms.

Objective
In this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic.

Methods
With a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID.

Results
Recruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database.

Conclusions
This study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID.

Trial Registration
German Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt

International Registered Report Identifier (IRRID)
DERR1-10.2196/38718
A Chatbot to Support Young People During the COVID-19 Pandemic in New Zealand: Evaluation of the Real-World Rollout of an Open Trial
Authors: Ludin Nicola , Holt-Quick Chester , Hopkins Sarah , Stasiak Karolina , Hetrick Sarah , Warren Jim , Cargo Tania 
Published: August 2022

Background
The number of young people in New Zealand (Aotearoa) who experience mental health challenges is increasing. As those in Aotearoa went into the initial COVID-19 lockdown, an ongoing digital mental health project was adapted and underwent rapid content authoring to create the Aroha chatbot. This dynamic digital support was designed with and for young people to help manage pandemic-related worry.

Objective
Aroha was developed to provide practical evidence-based tools for anxiety management using cognitive behavioral therapy and positive psychology. The chatbot included practical ideas to maintain social and cultural connection, and to stay active and well.

Methods
Stay-at-home orders under Aotearoa’s lockdown commenced on March 20, 2020. By leveraging previously developed chatbot technology and broader existing online trial infrastructure, the Aroha chatbot was launched promptly on April 7, 2020. Dissemination of the chatbot for an open trial was via a URL, and feedback on the experience of the lockdown and the experience of Aroha was gathered via online questionnaires and a focus group, and from community members.

Results
In the 2 weeks following the launch of the chatbot, there were 393 registrations, and 238 users logged into the chatbot, of whom 127 were in the target age range (13-24 years). Feedback guided iterative and responsive content authoring to suit the dynamic situation and motivated engineering to dynamically detect and react to a range of conversational intents.

Conclusions
The experience of the implementation of the Aroha chatbot highlights the feasibility of providing timely event-specific digital mental health support and the technology requirements for a flexible and enabling chatbot architectural framework.