bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics Analysis Reveals shared molecular pathways for Relationship between Ulcerative Colitis and Primary Sclerosing Cholangitis
Authors: Jalali Pooya , Rezaee Malihe , Yaghoobi Alireza , Piroozkhah Moein , Zabihi Mohammad Reza , Aliyari Shahram , Salehi Zahra 
Published: October 2024

Abstract

Background
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders, including ulcerative colitis (UC) and Crohn’s disease, affecting the gastrointestinal tract and is associated with high morbidity and mortality. Accumulating evidence indicates that IBD not only impacts the gastrointestinal tract but also affects multiple extra-intestinal organs, which may manifest prior to the diagnosis of IBD. Among these extra-intestinal manifestations associated with IBD, primary sclerosing cholangitis (PSC) stands out as a prominent example. PSC is recognized as a progressive cholestatic disorder, characterized by the narrowing of bile ducts, eventual development of liver cirrhosis, end-stage liver disease, and the potential emergence of cholangiocarcinoma.
Aim of the study:
In this study, we aimed to identify the molecular contributors in UC-induced PSC by detecting the essential regulatory genes that are differentially expressed in both diseases.
Materials and Methods
We conducted a comprehensive bioinformatics analysis to detect UC and PSC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, the top module and hub genes within the protein-protein interaction network were identified. Furthermore, the co-expression network of the top module was constructed using the HIPPIE database. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. At last, we searched the DGIdb database for possible interacting drugs with UC-PSC top module genes.
Results
Our microarray dataset analysis identified 56 common DEGs between UC and PSC with significant enrichment in genes involved in mRNA processes such as mRNA splicing process, and RNA bindings. We also identified 291 common DEGs from the DisGeNET database, demonstrating only one common DEG, called PTPN2, with microarray dataset. In this study we also identified 122 common SNPs between UC and PSC. Additionally, the top cluster of PPI network analysis was consisted of PABPC1, SNRPA1, NOP56, NHP2L1, and HNRNPA2B1 genes. We constructed a ceRNA network involving 4 specific mRNAs, 94 miRNAs, and 200 selected circRNAs.
Conclusion
In conclusion, the present study provides novel potential candidate genes that may be involved in the molecular association between ulcerative colitis and primary sclerosing cholangitis, resulting in the development of diagnostic tools and therapeutic targets to prevent the progression of PSC from UC.
Synthesis and Biological Assessment of Triazolo-Quinazoline Carbothioamide Derivatives for p38 MAP Kinase Inhibition: In-Silico and In-Vitro Approaches
Authors: CH Keerthi , Kola Ramesh , Pingili Divya , Awasthi Archana , Prashanth DSNBK , Chamakuri Kantlam 
Published: October 2024

Abstract

A series of 4-Alkyl-5-oxo-N-(pyridin-3-yl)-4,5-dihydro [1,2,3] triazolo[1,5-a] quinazoline-3-carbothioamide compounds (8a-8k) were synthesized as p38 MAP kinase inhibitors, which could potentially be used as anticancer agents. The synthesized compounds were assessed for their effectiveness in inhibiting cancer using the MCF-7 cancer cell line. The results showed that compound 8a had the highest potency, with an IC50 value of 39.76 ± 0.25 µM. Compound 8f and 8d exhibited noteworthy activity, with IC50 values of 40.43 ± 2.04 µM and 42.15 ± 2.15 µM, respectively. Compound 8a was found to effectively bind with the active site of p38α MAP kinase, with the PDB ID 1W7H. The docking score was found to be -8.8 kcal/mol. The ADME experiments, following Lipinski's rule of five and Ergan's egg graph, showed that all the synthesized compounds had excellent oral bioavailability and acceptable stomach absorption. Compound 8a stood out as the most potent drug in the series, exhibiting considerable docking affinity, ADME profile, and p38 MAP kinase inhibitory action. The findings indicated that compound 8a has promising p38 kinase inhibition and can be a possible therapeutic drug for further investigation.
QSAR, Molecular Docking, MD Simulations, and ADMET Screening Identify Potential Heliotropium indicum Leads against Key Targets in Benign Prostatic Hyperplasia
Authors: Omirin Emmanuel Sunday , Aribisala Precious Oluwasanmi , Olugbogi Ezekiel Abiola , Adeniran Olawole Yakubu , Emaleku Sunday Adeola , Saliu Jamiyu Ayodeji , Fapohunda Oluwaseun , Omirin Bukunmi , Gbadamosi Mary Oyinlola , Wopara Iheanyichukwu 
Published: October 2024

Abstract

Steroid 5 alpha-reductase (5αR) is a membrane-embedded enzyme responsible for converting testosterone into the more potent androgen, dihydrotestosterone (DHT), within the prostate. The androgen receptor (AR), in turn, mediates DHT's effects by regulating genes critical to cell proliferation and survival. Both 5αR and AR play pivotal roles in the development and progression of Benign Prostatic Hyperplasia (BPH), making them prime therapeutic targets for drug discovery. Unfortunately, no current drugs simultaneously target both enzymes, and existing treatments for either often lead to significant side effects, emphasizing the urgent need for safer, more effective alternatives. Through in silico screening, 13 pyrrolizidine alkaloids were evaluated for their inhibitory potential against 5αR and AR. The top six alkaloids—Heliotrine, Europine-N-oxide, Heleurine-N-oxide, Lasiocarpine, Indicine, and Heliotridine-N-oxide—exhibited promising pIC50 values. Notably, Europine-N-oxide (-10.27 kcal/mol) and Heliotridine-N-oxide (-9.72 kcal/mol) demonstrated stronger binding affinities to 5αR compared to the standard drug, Finasteride (-9.66 kcal/mol). Similarly, Heliotrine (-10.09 kcal/mol) and Europine-N-oxide (-8.76 kcal/mol) outperformed the standard AR blocker, Enzalutamide (-8.21 kcal/mol). Key hydrogen bonds were revealed, with Europine-N-oxide forming interactions with residues Tyr91, Arg94, Tyr98, and Glu197 in 5αR, while Heliotrine engaged with Asn160, Asp164, Glu57, and Arg94. MD simulations confirmed more stable and favorable interactions between the ligands from Heliotropium indicum (HI) and the targets compared to the standard drugs. Furthermore, pharmacokinetic screening highlighted high solubility, strong intestinal absorption, and minimal CYP enzyme inhibition, indicating favorable drug-like profiles. In conclusion, this study identifies HI alkaloids as promising multi-target inhibitors for BPH treatment. These findings warrant further in vivo validation and structural optimization to fully unlock their therapeutic potential in managing BPH
Beyond Single Company Risk Disclosure: Event-Based Physical Risk Reporting
Authors: Håkansson Victor Wattin , Meiler Simona , Hülsen Sarah , Villiger Leonie , McCaughey Jamie , Kropf Chahan M. , Bresch David N. 
Published: October 2024

Abstract

An increasing number of countries and stakeholders now require large companies to disclose physical climate-related risks, following Task Force for Climate-related Financial Disclosures (TCFD) guidelines. However, the lack of standardization has led to the use of varied risk metrics from different data sources, making it difficult to compare physical risks across companies and preventing investors from aggregating risks at the portfolio level. To address this, we develop an approach using standardized, event-based probabilistic natural catastrophe risk assessments to improve global risk data aggregation and enable customized risk metrics. Integrating these methods into TCFD reporting would help investors align portfolios with a risk-return efficient frontier that accounts for physical risks, directing capital toward companies better equipped to manage climate impacts and promoting strategic adaptation. We propose a transparent, replicable, open-source methodology using Event-Loss Tables to present per-event impact data and construct this efficient frontier. This approach is illustrated with two fictional companies exposed to tropical cyclone risk under current and future scenarios, highlighting the potential for improved disclosure, company comparison, and portfolio risk assessment. Finally, we call on the scientific community to establish standardized hazard sets and financial loss functions to support accurate comparison and risk aggregation.
Mapping zygote-to-adult developmental cell phylogeny in Arabidopsis thaliana reveals a 3-cell rule of branching
Authors: He Xionglei , Xia Fan-Nv , Liu Kehui , Wang Jianguo , Liu Zhan , Li Ang 
Published: October 2024

Abstract

Similar to the evolutionary history of all species on Earth, the developmental lineage history of all cells in a multicellular organism is stored in a phylogenetic tree. Mapping the zygote-to-adult developmental cell phylogeny of a complex organism is of tremendous value but technically challenging. We here adapted SMALT, a powerful cell lineage tracing system developed in our laboratory, to Arabidopsis thaliana to record the zygote-to-adult developmental lineages of two plant individuals. SMALT performed efficiently in A. thaliana, with an average of ~50 barcoding mutations accumulated on the 1-kb barcode sequence of each cell in three-month-old plants. Using the barcoding mutations we reconstructed, with high statistical confidence and at single-cell resolution, the phylogenetic tree for thousands of cells sampled from various shoot branches of each plant. The cell phylogenies show cells of every shoot branch are derived from exactly three founder cells, each belonging to one of three early-determined lineages. The 3-cell pattern holds for primary, secondary and tertiary branches, and even for single leaves or flowers/siliques. Integrating SMALT with single-cell RNA sequencing revealed the three founder cells responsible for establishing three germ layers of each branch/organ, which in turn updates our understandings of plant germ layers to single-cell resolution. We further showed that the 3-cell rule represents the optimal strategy for an indeterminate plant to manage its stem cell pool, with a general analytical framework proposed to unify the distinct strategies used in plant and animal organogenesis.
Mechanisms and motivations of medicinal plant use against dysmenorrhea.
Authors: Zandstra Berber E. , Andel Tinde R. van , Geertsma Isabela Pombo 
Published: October 2024

Abstract

Background
Dysmenorrhea (painful menstruation) negatively impacts the lives of many women on a global scale. It is a major cause of absenteeism in work or school, decreases classroom performance in adolescents, and affects overall quality of life. For centuries, women across the world have relied on medicinal plants to treat dysmenorrhea. For an industrialized country like the Netherlands, however, data on such plant use is almost absent. This study aimed to document which plant taxa women in the Netherlands use to treat dysmenorrhea and their motivations behind plant choice. Furthermore, phytochemical properties of the reported species related to treating dysmenorrhea were reviewed. As people with a migration background are known to use medicinal plants, we expected a significant association between plant use prevalence and migration background.
Methods
Semi-structured interviews and online surveys were conducted among women who used and advised plants to treat dysmenorrhea. Respondents were recruited via social media and snowballing. Literature research was conducted to investigate what phytochemicals are related to alleviating dysmenorrhea in the Netherlands and abroad. A Chi-Squared test of independence was performed to determine associations between migration background and the prevalence of medicinal plant use.
Results
Our 156 respondents mentioned 87 plant taxa to treat menstrual pain. Alchemilla spp., Achillea millefolium L., Matricaria spp., Rubus idaeus L., Salix spp., Cannabis sativa L. and Zingiber officinale Roscoe were the most used and advised plant taxa. Familiarity, experienced positive effects and availability were the most important motivations reported for choosing specific plant taxa. Experienced side effects as a result of painkillers were often mentioned as a reason to use herbal medicine. No association between migration background and medicinal plant use was found.
Conclusions
This study is a valuable addition to current knowledge about medicinal plant use to alleviate dysmenorrhea in an industrialized country like the Netherlands. The reported plant taxa were similarly used in other countries, and contained a wide variety in mechanisms of action, which indicates that dysmenorrhea can have different treatments. There still were considerable gaps in knowledge concerning plant species identification and usage. Gaining more insight in women’s healthcare choices and motivations is vital in securing high-quality and suitable, personalized healthcare.
AdditiveGDL: Generative deep learning for predicting local thermal distributions in metal 3D-printed layers
Authors: Guirguis David , Tucker Conrad , Beuth Jack 
Published: October 2024

Abstract

In this paper, we propose a method that leverages constrained generative neural networks to predict the local thermal distribution given the laser toolpath. By identifying critical regions of heat accumulation, we can optimize geometry, and scan paths, ultimately enhancing the quality and reliability of 3D-printed metal components.
Thermal distribution and dynamics affect various critical aspects including microstructure and mechanical properties, fatigue life, residual stresses, dimensional accuracy, shape integrity, and surface quality. Additionally, the scan strategy significantly impacts heat accumulation, especially at geometric features with sharp corners, overhangs, and thin walls. Thus, predicting heat distribution given the scan strategy becomes crucial. While numerical simulations using finite element methods are common, they can be computationally prohibitive for complex parts. Results show that generative deep learning offers an alternative approach to predicting the thermal field of printed layers efficiently.
The First Occurence of Mafic Alkaline Rock (Lamproite) in Mamuju District, West Sulawesi, Indonesia: Implications To The REEs and Critical Elements Enrichment
Authors: Fadlin Fadlin , Godang Shaban , Idrus Arifudin , Hartono Hill Gendoet , Zaenurrohman Januar Aziz , Iswahyudi Sachrul , Asfaro Raden Muhammad , Hamzah Wildan Nur , Nhatinombe Hernani Vitorino 
Published: October 2024

Abstract

Mafic alkaline igneous rocks along with their weathering products, are a significant source of Rare Earth Elements (REEs) and critical elements. One of mafic alkaline rock related to the REE and critical elements sources is lamproite. Therefore, understanding the formation of mafic alkaline especially lamproite rocks and their role in enriching REEs and critical elements is a crucial future scientific goal. Various methods utilized in this study, including optical microscopy, X-ray diffraction (XRD), and Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS), as well as whole-rock geochemical analyses using X-ray fluorescence (XRF) and Inductively Coupled Plasma Mass Spectrometry/Optical Emission Spectroscopy (ICP-MS/OES). Based on mineralogical observations, it has been confirmed that the dykes from West Sulawesi as orendite lamproite rocks. Sanidine, phlogopite, diopside, and aegirine are the main minerals found in these rocks, including apatite and oxide minerals as an accessory mineral. The dykes' whole-rock geochemistry indicates an ultrapotassic nature with a K2O/Na2O ratio > 3. Lamproite dykes display an increase in the Large ion lithophile elements (LILEs) and a decrease in Ti, Sr, and P, with minimal Eu anomalies. They also show an increase in the Light rare earth elements (LREEs), ranging from 901 to 1558 ppm, and a significantly higher content of Zr (968–3083 ppm), Th (152–408 ppm), and U (30–37 ppm). The dykes are related to an orogenic lamproite that formed during tectonic continental extension (post collision). It contained a significant portion of REE-Zr-Th bearing minerals, such as apatite (La-Ce-Nd), zirconosilicate (Zr-Ce), and Ba-perovskite (Zr-Th-Ce-Tb). The enrichment of light rare earth elements (LREEs), thorium (Th), and zirconium (Zr) in these dykes can be attributed to both primary and secondary enrichment processes, such as metasomatism and hydrothermal alteration. This is indicated by replacement or pseudomorphs, as well as a skeletal texture resulting from rapid cooling in a hydrothermal fluid environment.
Música, Educação Permanente e Trabalho em Saúde: O que a enfermagem que atuou em tempos de Covid-19 tem a dizer?
Authors: Souza Marcone Ferreira de , Souza Ândrea Cardoso de 
Published: October 2024

Os dados do recorte desta pesquisa de mestrado possibilitaram entender ao questionamento sobre os benefícios da música terapêutica como ferramenta de cuidado de si e educação permanente em saúde para a equipe de enfermagem que atuou durante a pandemia de Covid-19. Esse período histórico ocasionou sintomas de estresse agudo e ansiedade, e exigiu recursos humanos que pudessem aliviar essas tensões. Objetivo geral: compreender como a música contribuiu para o cuidado de si das equipes de enfermagem que atenderam aos pacientes com Covid-19 na pandemia, e como pode ser utilizada como uma ferramenta da educação permanente em saúde (EPS). Pesquisa narrativa de abordagem qualitativa, com 7 enfermeiros e 9 técnicos de enfermagem, durante a performance com uma orquestra de cordas, em um concerto musical realizado na unidade de trabalho e materializado em um roteiro de entrevistas com onze perguntas transcritas e analisados em categorias temáticas conforme Bardin. Os resultados apontaram que a música foi capaz de proporcionar alívio emocional, autocuidado, facilitação da comunicação e empatia e integração na educação permanente em saúde. A música como tecnologia leve, foi utilizada com fins de produção de cuidado, acolhimento, promoção de bem-estar e propagadora de sentimentos de esperança, ofertada aos trabalhadores em situação de fragilidades. Espera-se que os achados da pesquisa contribuam para a conscientização do cuidado de si e EPS da equipe de enfermagem, e incrementados nos programas que assegurem a prática da música terapêutica em ambientes hospitalares.
Palavras chave: Música Terapêutica; Cuidado de Si; Equipe de Enfermagem; Acolhimento; Covid-19.
Regulation of Curcumin on Follicle Initiation Rate in Diminished Ovarian Reserve
Authors: Li Wanjing , Xu Jinbang , Wang Jingyi , Zhang Junxin , Deng Disi 
Published: October 2024

Aim:
To study the mechanism by which curcumin regulates ovarian primordial follicle
initiation in rats with triptolide-induced diminished ovarian reserve (DOR).

Methods:
An in vitro gelatin sponge culture was performed on 3-day-old rat ovaries. After the
establishment of the DOR model with triptolide, curcumin was administered for 3 days. Histological
analysis and follicle counts were performed using H&E staining. ELISA detection of
ovarian hormones in the culture medium (E2, FSH and LH), western blotting and Q-PCR for protein
and mRNA expression (LTCONS-00011173, TGF-β1, Smad1, AMH, PTEN and GDF-9).

Results:
Ovarian primordial and growing follicles increased significantly after curcumin intervention
(p < 0.05), FSH/LH and E2 levels were increased significantly (p < 0.05). Curcumin also
significantly decreased the expression of LTCONS-00011173. Meanwhile, curcumin increased
the expression of TGF-β, AMH, and GDF-9 (p < 0.05). In addition, curcumin increased Smad1
gene expression and protein phosphorylation in the ovary on the one hand (p < 0.05), but inhibited
Smad1 and p-Smad1 protein expression on the other hand (p < 0.05). Moreover, curcumin decreased
PTEN protein and mRNA expression (p < 0.05).

Conclusion:
Curcumin activates primordial follicles in DOR model rats through TGF-β1 and
downstream AMH signaling pathways and may limit follicle exhaustion through LncRNA.
In silico-driven identification of Pranlukast as a Stabilizer of PD-L1 Homodimers
Authors: Cordova-Bahena Luis , Landero-Marin Carlos , Flores-Hernandez Xcaret , Alvarez-Coronel Leonardo Daniel , Jimenez-Uribe Alexis Paulina , Salinas-Jazmin Nohemi , An Zhiqiang , Velasco-Velazquez Marco 
Published: October 2024

Introduction:
Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1)
are critical immune checkpoints in cancer biology. Multiple small-molecule drugs have been developed as inhibitors
of the PD-1/PD-L1 axis. Those drugs promote the formation of PD-L1 homodimers, causing their stabilization,
internalization, and subsequent degradation. Drug repurposing is a strategy that expedites the clinical translation
by identifying new effects of drugs with clinical use. Herein, we aimed to repurpose drugs as inductors of
PD-L1 homodimerization and, therefore, as potential inhibitors of PD-L1.

Methods:
We generated a hybrid pharmacophore model by analyzing the structures of reported ligands that induce
PD-L1 homodimerization and their target-binding mode. Pharmacophore-matching compounds were selected
from a chemical library of Food and Drug Administration (FDA)-approved drugs. Their binding modes to PDL1
homodimers were assessed by molecular docking and the stability of the complexes and the corresponding
binding energies were evaluated by molecular dynamics (MD) simulations. Finally, the activity of one drug as
promoter of PD-L1 homodimerization was assessed in protein crosslinking assays.

Results:
We identified 12 pharmacophore-matching compounds, but only 4 reproduced the binding mode of the
reference inhibitors. Further characterization by MD showed that pranlukast, an antagonist of leukotriene receptors
that is used to treat asthma, generated stable and energy-favorable interactions with PD-L1 homodimers and
induced homodimerization of recombinant PD-L1.

Conclusion:
Our results suggest that pranlukast inhibits the PD-1/PD-L1 axis, meriting its repurposing as an
antitumor drug.
Molecular Activities and Mechanisms of Action of Substances and Molecules from Medicinal Plants from Sub-Saharan Africa on Prostate and Cervical Cancer Cells
Authors: Coulibaly Liz Laetitia , Bayala Bagora , Simpore Jacques 
Published: October 2024

Background:
Despite years of medical research, cancer remains a major public health problem worldwide,
particularly in Africa. The cost, duration, and toxicity of currently available treatments are all drawbacks.
Plant secondary metabolites are significant anticancer compounds. Already used in traditional health systems,
plants are currently the subject of numerous studies to discover new anti-cancer drugs.

Objective:
This review assesses the literature on the cytotoxic effect of plant substances (extracts) and molecules
on prostate and cervical cancer cell lines.

Methods:
PubMed, Science Direct, and Google Scholar were used to find in vitro studies carried out between
2006 and 2023 related to the cytotoxicity of extracts, substances and/or molecules from plants harvested in sub-
Saharan Africa against prostate and/or cervical cancer cell lines.

Results:
A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were
extracted from the selected databases. All the plants listed had a cytotoxic effect on prostate and/or cervical cancer
cells. Some plant extracts or molecules showed significant activity with an IC50< 20 μg/ml. Burkina Faso and
South Africa had the most plant extracts tested for prostate and cervical cancer, respectively.

Conclusion:
A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were
extracted from the selected databases.