bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Raltitrexed on ECA109 Cellular Radiosensitivity and its Mechanism
in Esophageal Cancer
Authors: Xu Li-Ben , Wu Chao-Yang , Wang Yan , Zhou Ju-Ying 
Published: May 2024

Background:
To investigate the effect of raltitrexed + X-ray irradiation on esophageal cancer
ECA109 cells and analyze the potential action mechanism

Methods:
The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze
the inhibitory effect of raltitrexed on cell proliferation. The effect of raltitrexed on radiosensitivity was
studied through a clone-forming experiment. The scratch assay and invasion test were performed to understand
the cell migration and invasion abilities. The apoptosis rate change was measured using a flow cytometer,
and Western Blotting was used to determine the expression of B cell lymphoma-2 (Bcl-2) and Bcl2-associated
X protein (Bax) in each group.

Results:
Raltitrexed significantly inhibited ECA109 proliferation in a time-dose-dependent manner; there
were significant differences among different concentrations and times of action. The results of the clone-forming
experiment showed a sensitization enhancement ratio of 1.65, and this demonstrated a radiosensitization effect.
After the combination of raltitrexed with X-ray, the cell migration distance was shortened, and the number
of cells penetrating the membrane was reduced.

Conclusion:
Raltitrexed can inhibit the growth of esophageal cancer ECA109 cells and has a radiosensitization
effect.
One-pot Synthesis of Condensed Azepines
Authors: Bhardwaj Khushboo , Jaiswal Shivangi , Bhardwaj Annu , Kishore Dharma , Dwivedi Jaya , Sharma Swapnil 
Published: May 2024

Abstract:
Azepine is a privileged nitrogen-containing ring that has been found to display a
wide range of biological activities. Azepine is a valuable skeleton in designing novel compounds
in medicinal chemistry due to its interesting chemical and biological properties.
The study on the synthesis of this ring system engenders a fascinating area of research owing
to its potential to form an active pharmacophore for De Novo exploration. In this study,
conventional and domino results were compared to access the diverse set of azepines in
high yield. The domino approach has revolutionized the way through which the previously
impossible yet significant transformations could be conceptualized, allowing the construction
of difficult materials in one step. The aim of the present mini-review is to highlight
the importance of the one-pot domino reaction for the synthesis of condensed azepines.
This review also presents research on this subject from the past two decades.
A Review on Piezoelectric-mediated Mechanoredox Reactions by Ball Milling in
Organic Synthesis
Authors: Jiang Shan , Wang Miao 
Published: May 2024

Abstract:
Recently, the concept of mechanoredox chemistry has been proposed and welldeveloped
in organic synthesis. Mechanoredox chemistry is conceptually similar to a photocatalyst
reaction system, where piezoelectric materials are introduced to the reaction system
in a manner analogous to photoredox catalysis. These reactions feature the ability to
generate high-value radicals that do not require harsh reaction conditions of anhydrous and
anaerobic conditions, an expensive photocatalyst, and the use of solvents, which renders
these transformations highly industrially applicable. In addition, mechanoredox chemistry
is also an emerging interdisciplinary research field that combines material chemistry with
synthetic chemistry to create more useful reactions. This review provides a comprehensive
summary of progress to date in the specific transformation and related mechanisms of piezoelectric-
mediated mechanoredox reactions by ball milling in organic synthesis.
Network Pharmacology Combined with Animal Models to Investigate the Mechanism of ChangPu YuJin Tang in the Treatment of Tourette Syndrome
Authors: Lu Man-Qi , Shi Zheng-Gang , Shang Jing , Gao Lei , Gao Wei-Jiao , Gao Lu 
Published: May 2024

Background:
ChangPu YuJin Tang (CPYJT) is a Chinese herbal formula that has
been shown to be an effective therapeutic strategy for pediatric patients with Tourette Syndrome
(TS). Using an integrated strategy of network pharmacology and animal model, the aim
of this study was to investigate the mechanism of CPYJT in the treatment of TS.

Methods:
Compound libraries of CPYJT were established using databases, such as the Traditional
Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP).
The TCMSP database and Swiss Target Prediction database were used to predict the targets.
The above results were constructed into a CPYJT-Drug-Component-Target network. Moreover,
TS targets were predicted using GeneCards and other databases. The targets corresponding
to the potential ingredients in CPYJT and the targets corresponding to TS were taken as the intersections
to construct the CPYJT-TS network. The target network was analysed by PPI using
the string database. GO and KEGG enrichment analyses were performed on the target network.
The whole process was performed using Cytoscape 3.7.2 to make visual network diagrams of
the results. CPYJT was characterised by Ultra-Performance Liquid Chromatography-Tandem
Mass Spectrometry (UHPLC-MS). Transmission Electron Microscopy (TEM) was used to observe
the structural changes of CPYJT on the neuronal cells of the IDPN model rats. RT-PCR
and Western Blot were used to analyse the changes in the mRNA and protein expression levels
of BDNF, TrkB, PI3K, and AKT in the cortex, striatum, and thalamus brain regions after
CPYJT administration in IDPN model rats.

Results:
Network pharmacology and UHPLC-MS studies revealed that CPYJT acted on the TS
through multiple neurotransmitters and the BDNF/TrkB and PI3K/AKT signalling pathways.
CPYJT ameliorated neurocellular structural damage in the cortex, striatum, and thalamus of TS
model rats. Additionally, CPYJT up-regulated the levels of BDNF, TrkB, PI3k, and AKT in
the cortex, striatum, and thalamus of TS model rats.

Conclusion:
It was found that CPYJT protected neuronal cells from structural damage in multiple
brain regions and affected the expression levels of BDNF, TrkB, PI3K, and Akt in the
cortex, striatum, and thalamus during TS treatment.
ANRIL: A Long Noncoding RNA in Age-related Diseases
Authors: Wang Rui , Yuan Qi , Wen Yuan , Zhang Yifan , Hu Yaqi , Wang Shuwen , Yuan Chengfu 
Published: May 2024

:
The intensification of the aging population is often accompanied by an increase in agerelated diseases, which impair the quality of life of the elderly. The characteristic feature of aging is
progressive physiological decline, which is the largest cause of human pathology and death worldwide. However, natural aging interacts in exceptionally complex ways within and between organs,
but its underlying mechanisms are still poorly understood. Long non-coding RNA (lncRNA) is a
type of noncoding RNA that exceeds 200 nucleotides in length and does not possess protein-coding
ability. It plays a crucial role in the occurrence and development of diseases. ANRIL, also known as
CDKN2B-AS1, is an antisense ncRNA located at the INK4 site. It can play a crucial role in agerelated disease progression by regulating single nucleotide polymorphism, histone modifications, or
post-transcriptional modifications (such as RNA stability and microRNA), such as cardiovascular
disease, diabetes, tumor, arthritis, and osteoporosis. Therefore, a deeper understanding of the molecular mechanisms of lncRNA ANRIL in age-related diseases will help provide new diagnostic and
therapeutic targets for clinical practice.
Prenatal Exposure to the 1944-45 Dutch Famine and Risk for Dementia up
to Age 75: An Analysis of Primary Care Data
Authors: Wiegersma Aline Marileen , Boots Amber , van Bussel Emma F. , Lissenberg-Witte Birgit I. , Nielen Mark M.J. , Roseboom Tessa J. , de Rooij Susanne R. 
Published: May 2024

Background:
A poor prenatal environment adversely affects brain development.
Studies investigating long-term consequences of prenatal exposure to the 1944-45 Dutch famine
have shown that those exposed to famine in early gestation had poorer selective attention, smaller
brain volumes, poorer brain perfusion, older appearing brains, and increased reporting of cognitive
problems, all indicative of increased dementia risk.

Objective:
In the current population-based study, we investigated whether dementia incidence up
to age 75 was higher among individuals who had been prenatally exposed to famine.

Methods:
We included men (n=6,714) and women (n=7,051) from the Nivel Primary Care
Database who had been born in seven cities affected by the Dutch famine. We used Cox regression
to compare dementia incidence among individuals exposed to famine during late (1,231), mid
(1,083), or early gestation (601) with those unexposed (born before or conceived after the famine).

Results:
We did not observe differences in dementia incidence for those exposed to famine in mid
or early gestation compared to those unexposed. Men and women exposed to famine in late gestation
had significantly lower dementia rates compared to unexposed individuals (HR 0.52 [95%CI
0.30-0.89]). Sex-specific analyses showed a lower dementia rate in women exposed to famine in
late gestation (HR 0.39 [95%CI 0.17-0.86]) but not in men (HR 0.68 [95%CI 0.33-1.41]).

Results:
We did not observe differences in dementia incidence for those exposed to famine in mid
or early gestation compared to those unexposed. Men and women exposed to famine in late gestation
had significantly lower dementia rates compared to unexposed individuals (HR 0.52 (95%CI
0.30-0.89)). Sex-specific analyses showed a lower dementia rate in women exposed to famine in
late gestation (HR 0.39 (95%CI 0.17-0.86)) but not in men (HR 0.68 (95%CI 0.33-1.41)).

Conclusion:
Although prenatal exposure to the Dutch famine has previously been associated with
measures of accelerated brain aging, the present population-based study did not show increased dementia
incidence up to age 75 in those exposed to famine during gestation.
Therapeutic Interventions for Diabetes Mellitus-associated Complications
Authors: Pradhan Dharmendra , Sahu Prafulla Kumar , Purohit Sukumar , Ranajit Santosh Kumar , Acharya Biswajeet , Sangam Shreya , Shrivastava Amit Kumar 
Published: May 2024

Background:
Diabetes Mellitus (DM) is an alarming health concern, affecting approximately
537 million people worldwide. As a leading cause of morbidity and mortality, DM demands
a comprehensive understanding of its diverse pathophysiological mechanisms and disease
progression.

Methods:
This traditional review has consolidated literature on the pathogenesis of hyperglycemia,
its progression into complications, and advances in optimal treatment strategies. The literature
in the last two decades has been reviewed using several keywords, including “diabetes,”
“diabetes-associated complications”, “novel therapeutic interventions for diabetes-associated
diseases”, “phyto-extracts as antidiabetic drugs”, etc. in prominent databases, such as PubMed,
Scopus, Google Scholar, Web of Science, and ClinicalTrials.gov.

Results:
We have discussed macrovascular and microvascular complications, such as atherosclerosis,
cardiovascular disease, Peripheral Arterial Disease (PAD), stroke, diabetic nephropathy,
retinopathy, and neuropathy, as well as various pharmacological and non-pharmacological interventions
that are currently available for the management of DM. We have also focused on the
potential of natural products in targeting molecular mechanisms involved in carbohydrate metabolism,
insulin production, repair of pancreatic cells, and reduction of oxidative stress, thereby
contributing to their antidiabetic activity. Additionally, novel therapeutic approaches, like genetic,
stem cell, and immunomodulatory therapies, have been explored. We have also discussed
the benefits and limitations of each intervention, emerging research and technologies, and precision
medicine interventions.

Conclusion:
This review has emphasized the need for an improved understanding of these advancements,
which is essential to enhance clinicians' ability to identify the most effective
therapeutic interventions.
Optimization Design of the Luffing Mechanism of Truck Crane Based on NSGA-II
Authors: Xin Yunsheng , Lv Shuyi , Dong Ruiyi 
Published: May 2024

Background:
The luffing mechanism of the truck crane is one of the key components of
the crane, which is used to control the extension and contraction of the telescopic boom to achieve
the luffing function of the crane. With the development of the engineering environment, the lifting
height of the truck crane is getting higher and higher, the lifting mass is getting bigger and bigger,
and the force situation of the crane luffing mechanism is becoming more and more complicated, in
order to improve the stability of the lifting process, it is necessary to carry out the optimization
work of the luffing mechanism.

Objective:
The purpose of this study is to optimize the luffing mechanism of the truck crane, improve
the lifting performance, and improve the stability of the lifting process.

Methods:
Inspired by the patent, this paper takes the position of the three hinge points of the luffing
mechanism of the truck crane as a research object, carrying on the force analysis, through the
mathematical model. The multi-objective optimization model is established with the maximum
force, maximum total length change rate and maximum stroke of the variable amplitude hydraulic
cylinder as the optimization objectives. The multi-objective genetic algorithm was selected to
compute the optimization model. Finally, the satisfaction function based on the robust design
method and analytic hierarchy process is established, the optimization results are sorted and
screened, and the optimal solution of the three optimization objectives is obtained.

Results:
The mathematical model of the structural force was established through mathematical derivation,
and the optimization model was solved using MATLAB combined with multi-objective
genetic algorithm, and the optimization results show that the force, total length change rate and
range of amplitude of the luffing mechanism have been improved.

Conclusion:
The mathematical model, the multi-objective optimization method and the satisfaction
function method are effective for the optimization of the luffing mechanism. It can be extended and
applied to other construction machinery with boom luffing mechanisms and provide a reference for
patent application.
Drug Target to Alleviate Mitochondrial Dysfunctions in Alzheimer’s
Disease: Recent Advances and Therapeutic Implications
Authors: Rahman Md. Ataur , Rahman MD. Hasanur , Rhim Hyewhon , Kim Bonglee 
Published: May 2024

:
Alzheimer's disease (AD) is a severe progressive neurodegenerative condition associated
with neuronal damage and reduced cognitive function that primarily affects the aged worldwide.
While there is increasing evidence suggesting that mitochondrial dysfunction is one of the most significant
factors contributing to AD, its accurate pathobiology remains unclear. Mitochondrial bioenergetics
and homeostasis are impaired and defected during AD pathogenesis. However, the potential of mutations
in nuclear or mitochondrial DNA encoding mitochondrial constituents to cause mitochondrial
dysfunction has been considered since it is one of the intracellular processes commonly compromised
in early AD stages. Additionally, electron transport chain dysfunction and mitochondrial pathological
protein interactions are related to mitochondrial dysfunction in AD. Many mitochondrial parameters
decline during aging, causing an imbalance in reactive oxygen species (ROS) production, leading to
oxidative stress in age-related AD. Moreover, neuroinflammation is another potential causative factor
in AD-associated mitochondrial dysfunction. While several treatments targeting mitochondrial dysfunction
have undergone preclinical studies, few have been successful in clinical trials. Therefore, this
review discusses the molecular mechanisms and different therapeutic approaches for correcting mitochondrial
dysfunction in AD, which have the potential to advance the future development of novel
drug-based AD interventions.
Evaluating the Effects of a Self-Help Mobile Phone App on Worry and Rumination Experienced by Young Adults: Randomized Controlled Trial
Authors: Edge Daniel , Watkins Edward , Newbold Alexandra , Ehring Thomas , Frost Mads , Rosenkranz Tabea 
Published: May 2024

Background
Delivery of preventative interventions via mobile phone apps offers an effective and accessible way to address the global priority of improving the mental health of adolescents and young adults. A proven risk factor for anxiety and depression is elevated worry and rumination, also known as repetitive negative thinking (RNT).

Objective
This was a prevention mechanism trial that aimed to investigate whether an RNT-targeting self-help mobile phone app (MyMoodCoach) reduces worry and rumination in young adults residing in the United Kingdom. A secondary objective was to test whether the app reduces symptoms of anxiety and depression and improves well-being.

Methods
A web-based, single-blind, 2-arm parallel-group randomized controlled trial was conducted with 236 people aged between 16 and 24 years, who self-reported high levels of worry or rumination. Eligible participants were randomized to an active intervention group (usual practice, plus up to 6 weeks of using the RNT-targeting mobile app, n=119) or a waitlist control group (usual practice with no access to the app until after 6 weeks, n=117). The primary outcome was changes in worry and rumination 6 weeks after randomization. Secondary outcomes included changes in well-being and symptoms of anxiety and depression after 6 weeks and changes in all measures after 12 weeks.

Results
Participants randomly allocated to use the RNT-targeting self-help app showed significantly lower levels of rumination (mean difference –2.92, 95% CI –5.57 to –0.28; P=.03; ηp2=0.02) and worry (mean difference –3.97, 95% CI –6.21 to –1.73; P<.001; ηp2=0.06) at 6-week follow-up, relative to the waitlist control. Similar differences were observed for well-being (P<.001), anxiety (P=.03), and depression (P=.04). The waitlist control group also showed improvement when given access to the app after 6 weeks. Improvements observed in the intervention group after 6 weeks of using the app were maintained at the 12-week follow-up point.

Conclusions
The MyMoodCoach app had a significant positive effect on worry and rumination, well-being, anxiety, and depression in young adults, relative to waitlist controls, providing proof-of-principle that an unguided self-help app can effectively reduce RNT. This app, therefore, has potential for the prevention of anxiety and depression although longer-term effects on incidence need to be directly evaluated.

Trial Registration
ClinicalTrials.gov NCT04950257; https://www.clinicaltrials.gov/ct2/show/NCT04950257

International Registered Report Identifier (IRRID)
RR2-10.1186/s12888-021-03536-0
The tools of cognitive creativity assessment
Authors: Khramtsov D.M. , Muratova T.M. , Vikarenko M.S. , Vorokhta Yu.M. 
Published: May 2024

Background. The purpose of the study was to assess the occurrence of disorders in the field of cognitive creativity in patients with minimal manifestations of leukoencephalopathy. Materials and methods. The study was carried out in the Expert Health Center in 2021–2022. We have examined 43 patients aged 45–60 years who had hyperintense foci in the white matter of the brain on magnetic resonance imaging, meeting Fazekas 1 criteria, and preserved cognitive abilities according to the MMSE and MoCA (≥ 25 and ≥ 26 points, respectively). As a control, 20 people of the same age with Fazekas 0 were examined, including 9 people employed in the creative professions. Additionally, all participants were examined using the Divergent Association Task (DAT). Statistical processing of the obtained results was performed by methods of dispersion and correlation analysis using Statistica 14.1 software (TIBCO, USA). Results. The average age of patients in the main group was 53.1 ± 0.3 years, while in the controls, it was 52.6 ± 0.5 years. In patients with signs of minimal microangiopathy of cerebral vessels, the MMSE score was on average 26.4 ± 0.2 points, and MoCA — 27.0 ± 0.3 points, while in the control group, 27.8 ± 0.2 and 28.1 ± 0.3 points, respectively (p < 0.05). In the main group, the DAT was on average 59.0 ± 1.3 %, while in the controls, it was 81.9 ± 1.1 % (Z = 3.8; p = 0.0001). The highest indicators of DAT were found in workers of creative specialties — 85.0 ± 0.9 % (Z = 2.7; p = 0.008). Conclusions. There was demonstrated that 95.0 % of patients with minimal manifestations of leukoencephalopathy caused by microangiopathy had a decrease in creative abilities (DAT 59.0 ± 1.3 vs. 81.9 ± 1.1 %; Z = 3.8; p = 0.0001). The coefficient of internal agreement of the DAT test αk was 0.7 with a reproducibility of 85.7 %, which allows recommending the method for use in clinical practice. The method of assessing associative tasks on divergent thinking has a higher sensitivity (97.7 %) than traditional methods of evaluating cognitive abilities at subclinical stages of chronic cerebral blood flow disorders.
APRENDIZAGEM SIGNIFICATIVA E EDUCAÇÃO AMBIENTAL: DISCUTINDO E (RE)SIGNIFICANDO O GERENCIAMENTO DE RESÍDUOS SÓLIDOS URBANOS
Authors: Santos Francisco Rauzito Neris dos , Barros José Deomar de Souza 
Published: May 2024

A capacidade de transformação dos ambientes naturais realizada pelos seres humanos foi acentuada, principalmente, a partir do século XVIII marcado pela ascensão da Revolução Industrial, evidenciando os caminhos de degradação que a humanidade estava percorrendo. Por isso, a educação possui um papel crucial em contribuir para a formação de cidadãos críticos-reflexivos que possam atuar na transformação social. Assim, a presente pesquisa objetivou aplicar estratégias potencialmente significativas para a promoção da Educação Ambiental envolvendo o ensino de Ciências. Para tanto, foram realizadas intervenções pedagógicas respaldadas nos preceitos de Aprendizagem Significativa de David Paul Ausubel em uma escola municipal de Cajazeiras – PB. Os sujeitos consistiram nos alunos do 8º ano do Ensino Fundamental II. Para a análise dos resultados, foi utilizada a técnica de Análise Categorial proposta por Bardin (2016). Os resultados obtidos indicam a incipiência acerca do conhecimento das temáticas ambientais dos estudantes, contudo, as atividades de Educação Ambiental forneceram resultados exitosos e apontam a potencialidade da utilização dos preceitos da Teoria de Aprendizagem Significativa em sala de aula.