bluuebunny/crossref_metadata_2025_split huggingface dataset:
Porphyrinuria in Autism Spectrum Disorder: A Review
Authors: Bjørklund Geir , Semenova Yuliya , El-Ansary Afaf , Al-Ayadhi Laila Youssef 
Published: November 2023

:Numerous studies demonstrated that the number of children with autism spectrum disorder (ASD) has increased remarkably in the past decade. A portion of ASD etiology, however, is attributed to environmental issues and genetic disorders. We highlighted a scoping review to principally evaluate the current information on mercury exposure in ASD children and to reveal knowledge gaps. Elevated porphyrins concentration in the urinary system related to mercury exposure, such as precoproporphyrin (prcP), coproporphyrin (cP), and pentacarboxyporphyrin (5cxP), was shown in comparison with controls. Moreover, high levels of urinary porphyrins have been elevated in response to heavy metal exposure. The related pattern (increased prcP, cP, and 5cxP) with Hg exposure may be used as biomarkers in the characteristics of ASD symptoms. However, this review highlighted the data gaps because the control groups were not genderand age-matched for ASD children.
Combining Mendelian Randomization Analysis and 3D-QSAR to
Investigate the Effectiveness of a New Series of Hydroxyquinolines in
Osteoarthritis
Authors: Lian Zheng , Su Kunpeng , Lu Hui , Qu Changpeng , Ma Xuexiao 
Published: November 2023

Background:
Osteoarthritis (OA) represents a persistent degenerative joint
ailment. As OA advances, profound joint pain coupled with diminished joint function inflicts
substantial physical distress and psychological strain on patients. Presently, pharmacological
solutions for arthritis remain limited, primarily encompassing analgesics
and joint replacement surgical procedures. Hence, non-operative strategies to mitigate
osteoarthritis progression have captured significant attention in orthopedic research.

Objective:
This study aims to discern a definitive causal linkage between ADAMTS-4/5
and osteoarthritis through Mendelian randomization analysis.

:
Moreover, it seeks to anticipate the therapeutic efficacy of a suite of emergent hydroxyquinolines
for osteoarthritis using the Quantitative Structure-Activity Relationship
(QSAR) methodology.

Methods:
Within this study, genetic variants specific to knee osteoarthritis were procured
as exposure variables from a genome-wide association study (GWAS). Genetic
variant data for ADAMTS-4/5 served as the endpoint to evaluate the causal nexus employing
univariate Mendelian randomization. This analysis underpins the hypothesis
that ADAMTS-4/5 presents a promising therapeutic target for osteoarthritis management.
The suppressive properties of novel hydroxyquinolines against ADAMTS-4/5
were subsequently examined through conformational analyses, underscoring the potential
of these compounds as therapeutic candidates for osteoarthritis.

Results:
IVW outcomes from the Mendelian randomization revealed a significant association
of KOA (OR: 1.1675, 95% CI: 1.0003-1.3627, P = 0.0495) with ADAMTS-5.
However, KOA (OR: 1.0801, 95% CI: 0.9256-1.2604, P = 0.3278) displayed no evident
connection with ADAMTS-4. Notably, the instrumental variables manifested neither
heterogeneity nor horizontal pleiotropy. In this research endeavor, 16 pharmacological
models were formulated via the CoMSIA method within 3D conformational relationship
evaluations. A synergistic interplay of hydrophobic, spatial, and hydrogen-bonded receptor
domains emerged as the most predictively potent. The cross-validation coefficient q2
for the optimum model stood at 0.716, with a principal component score of 5, a regression
coefficient r2 of 0.971, a standard estimation error of 0.351, and an f-value of
156.951. Such metrics intimate the commendable predictive prowess of our devised
CoMSIA models.

Conclusion:
The research unearthed a robust causal interrelation between ADAMTS-5
and osteoarthritis via Mendelian randomization. Furthermore, a credible drug model targeting
ADAMTS-5 was constructed. Collectively, these findings illuminate a path forward
in the pursuit of target-specific drugs for osteoarthritis management in subsequent
investigations.
Computational Approaches: A New Frontier in Cancer Research
Authors: Srivastava Shubham , Jain Pushpendra 
Published: November 2023

Abstract:
Cancer is a broad category of disease that can start in virtually any organ or tissue of
the body when aberrant cells assault surrounding organs and proliferate uncontrollably. According
to the most recent statistics, cancer will be the cause of 10 million deaths worldwide in 2020,
accounting for one death out of every six worldwide. The typical approach used in anti-cancer
research is highly time-consuming and expensive, and the outcomes are not particularly encouraging.
Computational techniques have been employed in anti-cancer research to advance our
understanding. Recent years have seen a significant and exceptional impact on anticancer research
due to the rapid development of computational tools for novel drug discovery, drug design,
genetic studies, genome characterization, cancer imaging and detection, radiotherapy, cancer
metabolomics, and novel therapeutic approaches. In this paper, we examined the various subfields
of contemporary computational techniques, including molecular docking, artificial intelligence,
bioinformatics, virtual screening, and QSAR, and their applications in the study of cancer.
Identification of Two Novel Pathogenic Variants of the ATM Gene in
the Iranian-Azeri Turkish Ethnic Group by Applying Whole Exome
Sequencing
Authors: Dalal Amandi Amir-Reza , Jabbarpour Neda , Shiva Shadi , Bonyadi Mortaza 
Published: November 2023

Background:
The ATM gene encodes a multifunctional kinase involved in important
cellular functions, such as checkpoint signaling and apoptosis, in response to DNA damage. Bi-allelic
pathogenic variants in this gene cause Ataxia Telangiectasia (AT), while carriers of ATM
pathogenic variants are at increased risk of cancer depending on the pathogenicity of the variant
they carry. Identifying pathogenic variants can aid in the management of the disease in carriers.

Methods:
Whole-exome sequencing (WES) was performed on three unrelated patients from the
Iranian-Azeri Turkish ethnic group referred to a genetic center for analysis. WES was also conducted
on 400 individuals from the same ethnic group to determine the frequencies of all ATM
variants. Blood samples were collected from the patients and their family members for DNA extraction,
and PCR-Sanger sequencing was performed to confirm the WES results.

Results:
The first proband with AT disease had two novel compound heterozygote variants
(c.2639-2A>T, c.8708delC) in the ATM gene revealed by WES analysis, which was potentially/-
likely pathogenic. The second proband with bi-lateral breast cancer had a homozygous pathogenic
variant (c.6067G>A) in the ATM gene identified by WES analysis. The third case with a family
history of cancer had a heterozygous synonymous pathogenic variant (c.7788G>A) in the ATM
gene found by WES analysis. Sanger sequencing confirmed the WES results, and bioinformatics
analysis of the mutated ATM RNA and protein structure added evidence for the potential pathogenicity
of the novel variants. WES analysis of the cohort revealed 38 different variants, including
a variant (rs1800057, ATM:c.3161C>G, p.P1054R) associated with prostate cancer that had a higher
frequency in our cohort.

Conclusion:
Genetic analysis of three unrelated families with ATM-related disorders discovered
two novel pathogenic variants. A homozygous missense pathogenic variant was identified in a woman
with bi-lateral breast cancer, and a synonymous but pathogenic variant was found in a family
with a history of different cancers.
Improved Transdermal Delivery of Anti-hypertensive Drug Loaded
Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction
and Pharmacokinetic Assessment
Authors: Chettupalli Ananda Kumar , Avula Purnachandra Rao , Chauhan Vivek 
Published: November 2023

Background:
The vasoselective calcium-channel blocker lercanidipine hydrochloride
(LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic
metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very
variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of
the medication is almost impossible to produce.

Objective:
The purpose of this research was to see whether an approach involving the development
of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation
of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot
homogenization-ultrasonication strategy.

Methods:
Following initial improvements with hot homogenization and ultrasonication, the LCHloaded
NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs
composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants
poloxamer 188 (1%) and Tween 80(1%), and other ingredients.

Results:
The optimized NLCs formulation was found to have mean vesicle sizes of 128.72 ± 1.59
nm, polydispersity indices of 0.169 ± 0.06, zeta potentials of -36.81 ± 0.42 mV, and entrapment efficiencies
of 79.84 ± 0.11%. The optimized NLCs formulation released much more LCH (88.74 ± 4.62)
than the LCH-suspension (36.84 ± 0.37%) in in-vitro drug release experiments lasting up to 24 hours.
Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was
much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated
that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily
over a longer time period.

Conclusion:
These findings provide additional evidence that NLCs have great promise as a drug
delivery technology for the treatment of hypertension, just as they show promise as a controlled release
formulation for the treatment of LCH.
Association of Cardiovascular Events with COVID-19 Vaccines Using
Vaccine Adverse Event Reporting System (VAERS): A Retrospective
Study
Authors: Amir Mohd , Latha S. , Sharma Ruchika , Kumar Anoop 
Published: November 2023

Background::
COVID-19 vaccines have played a crucial role in reducing the burden of
the global pandemic. However, recent case reports have indicated the association of the COVID-
19 vaccines with cardiovascular events but the exact association is unclear so far.

Objective::
Therefore, the objective of the current study is to find out the association of cardiovascular
events with COVID-19 vaccines.

Methods::
The COVID-19 Vaccine Knowledge Base (Cov19VaxKB) tool was used to query the
Vaccine Adverse Event Reporting System (VAERS) database. The proportional reporting ratio
[PRR (≥2)] with associated chi-squared value (>4), and the number of cases > 0.2% of total
reports, was used to assess the association of COVID-19 vaccines with cardiovascular events.

Results::
A total of 33,754 cases of cardiovascular events associated with COVID-19 vaccines
were found in the Cov19VaxKB tool. The cases were observed in different age groups (18-64,
and 65 years and above) and gender. The disproportionality measures indicate a statistically
significant association between cardiovascular events and COVID-19 vaccines.

Conclusion::
The current study identified a signal of various cardiovascular events with the
COVID-19 vaccines. However, further causality assessment is required to confirm the association.
Regulation of ROS/inflammasome Axis is Essential for Cardiac Regeneration in Aging Rats Receiving Transplantation of Mesenchymal Stem Cells
Authors: Hu Wei-Syun , Chen Jing-Yi , Liao Wei-Yu , Chang Chin-Hsien , Chen Tung-Sheng 
Published: November 2023

Background:
Aging is a biological and gradual deterioration of function in living organisms.
Aging is one of the risk factors for heart disease.

Objective:
Although mesenchymal stem cell transplantation shows potential in heart disease treatment,
the relationship between stem cell-based therapy and oxidative stress/inflammasome axis
regulation remains unclear. This study hypothesized that intervention of stem cells showed protective
effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome
axis.

Methods:
An aging animal model was designed to test the above hypothesis. Experimental animals
were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose),
and D-gal+WJSC (aging rats receiving mesenchymal stem cells).

Results:
Compared to the Sham, the experimental results indicate that structural alteration (HE
stain and Masson’s Trichrome stain), oxidative stress elevation (increase of TBARS level, expression
of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression
of cardiogenesis marker Troponin T, and inflammasome related protein markers expression
(NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological
pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition,
migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group.

Conclusion:
These findings suggest that mesenchymal stem cell transplantation effectively ameliorates
aging hearts through oxidative stress/inflammasome axis regulation. The results from this
study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.
Study Deciphering the Crucial Involvement of Notch Signaling Pathway in
Human Cancers
Authors: Pandey Pratibha , Khan Fahad , Singh Megha , verma Aditi , Kumar Hariom , Mazumder Avijit , Rakhra Gurmeen 
Published: November 2023

:
In recent years, dysregulation of the notch pathway has been associated with the development
and progression of various cancers. Notch signaling is involved in several cellular
processes, such as proliferation, differentiation, apoptosis, and angiogenesis, and its abnormal
activation can lead to uncontrolled cell growth and tumorigenesis. In various human cancers, the
Notch pathway has been shown to have both tumor-promoting and tumor-suppressive effects,
depending on the context and stage of cancer development. Notch signaling has been implicated
in tumor initiation, cancer cell proliferation, cell migration and maintenance of cancer stem cells
in several human cancers, including leukemia, breast, pancreatic and lung cancer. Understanding
the role of the Notch pathway in cancer development and progression may provide new opportunities
for the development of potent targeted therapies for cancer treatment. Several drugs
targeting the Notch pathway are currently in preclinical or clinical development and may hold
promise for anticancer therapy in the future.
Microwave-Assisted Synthesis of Biologically Relevant Six-Membered N-Heterocycles
Authors: Kamboj Monika , Bajpai Sangeeta , Pandey Garima , Yadav Monika , Banik Bimal K. 
Published: November 2023

Abstract:
One of the most efficient non-conventional heating methods is microwave irradiation. In organic synthesis, microwave irradiation has become a popular heating technique as it enhances product yields and purities, reduces reaction time from hours to minutes, and decreases unwanted side reactions. Microwave-assisted organic synthesis utilizes dielectric volumetric heating as an alternative activation method, which results in rapid and more selective transformations because of the uniform heat distribution. Heterocyclic compounds have a profound role in the drug discov-ery and development process along with their applications as agrochemicals, fungicides, herbi-cides, etc., making them the most prevalent form of biologically relevant molecules. Hence, enor-mous efforts have been made to flourish green routes for their high-yielding synthesis under mi-crowave irradiation as a sustainable tool. Among the different clinical applications, heterocyclic compounds have received considerable attention as anti-cancer agents. Heterocyclic moieties have always been core parts of the development of anti-cancer drugs, including market-selling drugs, i.e., 5-fluorouracil, doxorubicin, methotrexate, daunorubicin, etc., and natural alkaloids, such as vinblastine and vincristine. In this review, we focus on the developments in the microwave-assisted synthesis of heterocycles and the anti-cancer activities of particular heterocycles.
Tofacitinib Citrate-loaded Nanoparticle Gel for the Treatment of Alopecia
Areata: Response Surface Design, Formulation and In vitro-in Vivo
Characterization
Authors: Kuchukuntla Mounika , Palanivel Venkatesan , Madhubabu Ananthula 
Published: November 2023

Objective:
The purpose of this research was to optimize the design and construction of
nanoparticle gel (TFN-NPs) loaded with tofacitinib citrate (TFN) using poly lactic co glycolic acid
(PLGA).

Method:
PLGA (A) as the polymer, polyvinyl alcohol (PVA) (B) as the stabilizer and stirring speed
(C) as independent variables were used. TFN-NPs were prepared using single emulsion-solvent
evaporation. Box Behnken Design (BBD) was used to determine the optimal component ratio of
TFN-NPs based on point prediction.

Results:
The entrapment efficiency, particle size, and cumulative drug release of the best-composed
TFN-NPs were, respectively, 79.82±0.9%, 236.19±5.07 nm, and 82.31±1.23%; the PDI, zeta potential,
and drug loading were, respectively, 0.297±0.21, -30.21±0.94mV, and 69.81±0.16%. Gel formulation
employing Carbopol as a gelling polymer was then developed using the optimal TFN-NPs
mixture. Gel characterization, drug release, permeation studies, irritation, and pharmacokinetic
studies were also conducted. Further solid state and morphology were evaluated using FTIR, DSC,
XRD, SEM, TEM, and AFM on the developed topical gel formulation (TFN-NPG) and TFN-NPs.
The release and permeation investigations indicated that TFN was slowly released (38.42±2.87%)
and had significantly enhanced penetration into the epidermal membrane of mice. The cumulative
irritation score of 0.33 determined during testing suggested little discomfort. The generated nanogels
are stable and have a high drug penetration profile over the skin, as shown by the findings.
When compared to both pure TFN solutions, TFN-NPs and TFN-NPG demonstrated superior
pharmacokinetic properties.

Conclusion:
Based on the results, the NPs and NPG formulations were depicted to enhance the activity
of TFN compared to the free drug solution. TFN could be a safe and effective treatment for
Alopecia areata. The tofacitinib citrate NPG could be a clinically translatable, safer topical formulation
for managing Alopecia areata.
Sosialisasi Edukasi Reproduksi Wanita Berbasis Sains Teknologi Islam melalui e-Modul di Desa Sentul
Authors: Meishanti Ospa Pea Yuanita , Putra Ino Angga , Shobirin Mochammad Syafiuddin , Widianti Arina , Annas Farhani 
Published: November 2023

The people of Sentul village, especially women and teenagers, still do not really understand the problems related to women including the solutions, so the service team conducts counseling about the female reproductive system based on Islamic technology to provide knowledge, understanding, concern for and the importance of maintaining the reproductive system in women, also providing education about the development of the reproductive system in women based on Islamic science technology. The implementation method is preparation, namely making products, implementing education in the form of socialization and practice of using e-modules, evaluating implementation by providing an implementation framework and product results in the form of e-modules and analysis of sustainable programs that develop community service implementation programs in Tembelang District. The results of the program evaluation show that the education provided can increase knowledge about the importance of female reproduction, technological developments and Islam. The output product produced by the community service team is an e-module for the female reproductive system based on Islamic science and technology which can be accessed anywhere.
===
Ibu-ibu dan remaja Desa Sentul, Kecamatan Tambelang belum memahami problematika yang terkait dengan kewanitaan dan solusinya sehingga tim pengabdian kepada masyarakat melakukan edukasi tentang sistem reproduksi wanita berbasis sains teknologi Islam untuk memberikan pengetahuan, pemahaman, kepedulian dan pentingnya menjaga sistem reproduksi pada wanita, serta memberikan edukasi perkembangan sistem reproduksi kepada wanita. Tahapan pelaksanaan melalui metode persiapan, pelaksanaan, dan hasil, yakni (1) tahap persiapan: penyusunan produk; (2) pelaksanaan berupa sosialisasi edukasi praktik penggunaan; (3) tahap hasil berupa evaluasi pelaksanaan dengan memberikan angket pelaksanaan maupun hasil produk berupa e-modul dan analisis berkelanjutan program yang merupakan pengembangan program pelaksanaan pengabdian di Desa Sentul, Kecamatan Tembelang. Hasil evaluasi program menunjukkan bahwa dengan adanya edukasi yang diberikan dapat meningkatkan pengetahuan akan pentingnya reproduksi wanita, perkembangan teknologi, dan segi keagamaan. Luaran produk yang dihasilkan tim pengabdian masyarakat ini berupa e-modul sistem sistem reproduksi wanita berbasis sains teknologi Islam yang dapat diakses di mana saja.
Indigenous literacy of local knowledge about the signs of natural disaster A case of Way Ela Natural Dam - Maluku
Authors: Rizal Edwin , Nurislaminingsih Rizki 
Published: November 2023

Introduction. Various natural disasters occurred in Maluku, with one of the impacts is changing the land surface. One example is a forest has changed into a hill or a river has changed into a natural dam. In Maluku, Way Ela natural dam was formed as a resultof the disaster in 2012 and was destroyed again by the disaster in 2013. This natural event that occurred in a relatively short period of time is still remembered by the community. This study aims to explore the types of local knowledge about dam disasters based on their memories.
Data Collection Method. Data collection in this study was conducted by the interviews.
Data Analysis. Data were analyzed by grouping the themes on natural signs of the formation and of the broken of the dam.
Results and Discussion. The formation of dams begins with earthquakes, landslides, dry rivers, and strange animal behavior. Natural signs before a broken-down dam are earthquakes, heavy rain, cracked ground, strange behavior of animals, and changes in cooler air temperature.
Conclusion. This study concludes that the community is aware of three types of disaster signs including the formation of a dam, before the dam breaks, and when the dam breaks.
Effect of cognitive stimulation based on puzzle games on learning achievement in school-aged stunted children
Authors: N Nurjannah , T Taamu , D Dali , Noviawati Setya Arum Dyah 
Published: November 2023

Introduction; Stunting causes obstacles to physical development but also threatens cognitive development which has an impact on reducing children's productivity in adulthood. So efforts are needed to helpth ecognitive development of stunting children through educational games.
Objective; Effect of Puzzle Game-Based Cognitive Stimulation on Learning Achievement of Stunted Children of School Age.
Method; This type of pre-experimental research with a one group pre test-post test design. This study used measurements three times before the intervention and three times after the intervention. A sample of 36 people with the criteria of a stunted child based on BMI results according to measurements of height/age and weight/age.
Results; the average value of stunting children's learning achievement given cognitive stimulation based on a puzzle game is PreTest 1 = 70.36, Post Test 1 = 69.36; Pre Test 2 = 72.36, Post Test 2 = 69.36, and PreTest 3 = 74.63, Post Test 3 = 70.72. In the statistical test results with the paired T-Test, there is a statistically significant difference (p <0.05) significant for all puzzle game interventions given to stunting children.
Suggestion; the need for cognitive stimulus-based learning methods through puzzle games, as a learning approach technique for elementary school-age children who are stunted.