bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiome interactions increase plant haplotype richness
Authors: Andersen Stig , Quilbé Johan , Mouritzen Troels , Akyol Turgut , Mustamin Yusdar , Bamba Masaru , Schierup Mikkel , Sato Shusei 
Published: October 2024

Abstract

The genetic makeup of natural plant populations often allows them to persist for many years without succumbing to disease. Transferring such properties to crops could increase resilience and reduce reliance on chemical pesticides​. However, the population genomics of plant-microbiome interactions remain poorly understood. Here, we use Lotus japonicus, which has persisted as a natural population in Japan for ~20’000 years​, to identify genomic selection signatures caused by soil microbes. We found strong genetic associations with root microbiome structure within a gene we name ROOT MICROBIOME ESTABLISHMENT 1 (ROOMIE1) located in a region with high haplotype richness. This led us to quantify haplotype richness genome-wide using a new metric, HAPk. We found haplotype-rich regions strongly enriched for microbiome genetic associations, suggesting that soil microbes were imposing negative frequency-dependent selection. We validated this hypothesis by showing increased migration rates of microbiome associated alleles and by determining that ROOMIE1 shows standing variation in local populations and impacts rhizosphere colonization in native Japanese soil. Our results indicate that interactions with soil microbes represent a major selective force in plant genome evolution and suggest that haplotype-rich regions constitute a genetic resource for improvement of crop resilience.
Evaluating In-Vitro Corrosion Testing of Lean Magnesium Alloys: The Critical Role of Degradation Media Composition, Buffering, and Volume
Authors: Raguraman Sreenivas , Ulugun Beril , Ayodeji Tunde , Chowdhury Rida , Griebel Adam , Weihs Timothy 
Published: October 2024

Abstract

Biodegradable magnesium (Mg) alloys are gaining attention for biomedical implants due to their favorable mechanical properties and safe degradation within the human body. However, the rapid corrosion of Mg remains a challenge, necessitating a deeper understanding of its behavior in physiological environments. This study examines the in-vitro corrosion performance of a lean Mg-Zn-Ca alloy in various degradation media, including Hank’s Balanced Salt Solution (HBSS), Earle’s Balanced Salt Solution (EBSS) buffered with 5% CO2, and Dulbecco’s Modified Eagle Medium (DMEM) with 10% Fetal Bovine Serum (FBS) buffered with 5% CO2. Significant differences in corrosion rates were observed across media, with HBSS exhibiting the lowest rates and EBSS the highest. DMEM with 10% FBS and corrosion conditions that most closely resemble physiological environments produced intermediate corrosion rates. The effect of CO2 buffering in HBSS was also evaluated, demonstrating enhanced pH control below 7.5, which simulates physiological pH. Additionally, increasing the volume of HBSS, both with and without CO2 buffering, led to reduced corrosion rates and greater pH stabilization. These findings shed light on how testing conditions can impact corrosion rates and pH stability.
Countering the Ideology of Consumerism in the System of Anti-Corruption Measures as a Function of State Power
Authors:   Transbaikal State University, Ivanova Maria V. 
Published: October 2024

The object of the study is corruption in the sphere of state power. The subject of the study is the role of the ideology of consumerism in the corrupt activities of representatives of the state authorities and the main directions of countering this ideology as a function of state power. Corruption in the sphere of higher authorities is considered as the main type of corruption. The study is based on the differentiation of two directions in the system of preventive anti-corruption measures: 1) intimidation by criminal punishment of persons capable of committing corruption crimes; 2) formation of a negative attitude towards corruption in society, education of people who are not capable of corrupt behavior. In the context of the second direction, the analysis of the ideology of consumerism as a subjective cause of corruption in the sphere of state power is presented. The purpose of the work is to substantiate the policy of countering the ideology of consumerism in the system of anti-corruption measures as a necessary function of state power. Research objectives are as follows: to clarify the concept of corruption in the sphere of state power and its features; to identify the normative and regulatory function of the ideology of consumerism in the corrupt activities of government officials; to identify the main directions of countering the ideology of consumerism in the anti-corruption policy of the state. The study has yielded the following results. The direct subjective cause of corruption in the sphere of state power is the ideology of consumerism, which causes a consumer race and excessive consumption among highly paid representatives of state power. The prevention of corruption in this area implies the need to combat this ideology. The main directions of the state policy of countering the ideology of consumerism are state control over the activities of the media in order to limit the propaganda of consumerism; the revival of the institute of state ideology, namely, the ideology of humanism and patriotism; the introduction of an ideological component in state educational programs, including a critical discussion of the ideology of consumerism. From these research results, it follows that there is a need for a policy of countering the ideology of consumerism in the system of anti-corruption measures as a function of state power.
Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions
Authors: Sridharan Kannan , Al Jufairi Mona 
Published: October 2024

Aims:
To explore the relationship between oxidative stress biomarkers and the occurrence of acute
kidney injury (AKI) alongside notable liver function disturbances in preterm neonates.

Background:
Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative
stress poses a considerable threat to their renal and hepatic health.

Objective:
To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant
enzymes with renal and live functions.

Methods:
In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing
oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes.
Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers.
Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these
biomarkers, denoted by the area-under-the-curve (AUC).

Results:
Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal
AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical
cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC:
0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL.

Conclusions:
We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase
with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings,
with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function
abnormalities.
Screening of FDA-approved Drugs against Protein Thymidine Kinase 2
Using Machine Learning Method Validated Applying Molecular Dynamics
and Free Energy Landscape Calculation
Authors: Sameer Hayder Naji , Mohammed Samer Shukur , Oraibi Amjad Ibrahim , Al-Ibadah Mahmood , Al-Hussainy Hany Aqeel 
Published: October 2024

Background:
Thymidine kinase 2 (TK2) is a crucial enzyme in the mitochondrial pyrimidine
salvage pathway, strongly associated with several mitochondrial diseases. Current treatments
frequently damage mitochondria, leading to a decrease in cellular energy output.

Objective:
This study aimed to use computational approaches to identify inhibitors of TK2 that could
prevent these harmful consequences.

Method:
The initial screening process entailed the application of machine learning algorithms, more
particularly a Random Forest model, which was trained on 189 FDA-approved drugs and decoy datasets
obtained from the DUD-E database. Its purpose was to identify potential inhibitors. The molecular
docking technique was employed to evaluate the affinity of the chosen medicines towards
TK2. Molecular dynamics (MD) simulations lasting 100 nanoseconds were employed to conduct
additional validation by examining the dynamic interactions between the top-found compounds and
TK2.

Results:
Three hit compounds (3168, 5209502, and 135402009) were identified through the screening
process for their high affinity for TK2. Compound 5209502 had the most stable interaction with
the lowest root-mean-square deviation (RMSD) in the molecular dynamics (MD) simulations and
maintained 12 hydrogen bonds consistently. MM/GBSA computations verified that 5209502 exhibited
the strongest binding affinity with a binding free energy of -62.14 kcal/mol, which was notably
lower than that of the control ligand.

Conclusion:
Compound 5209502 is a promising candidate for additional experimental evaluation
because of its notable stability and great affinity for TK2. This chemical may provide a focused and
less harmful treatment for mitochondrial illnesses linked to TK2 malfunction.
A Groundwater Quality Index Proposed for Assessment of Groundwater Quality: A Case Study of Quang Tri Province, Central Vietnam
Authors: Trung Kien Truong , Truong Khoa Nguyen , Quy Tung Truong , Giang Chau Nguyen Dang , Van Hop Nguyen 
Published: October 2024

Background:
Water quality assessment is a crucial task to manage water sources and
control water pollution. The purpose of this study is to develop a Groundwater Quality Index
(GWQI) to assess groundwater quality.

Methods:
The GWQI was developed and functioned by weight (wi) and sub-index (qi) of ten selected
water quality parameters. Principal Component Analysis (PCA) was applied to a water quality monitoring
data set (year 2016 to 2019, 163 samples) at 27 locations in Quang Tri province, aiming to
identify the weight of each parameter. Sub-index linear function was established based on the allowable
limits for each parameter defined in the National Technical Regulation on drinking water quality.
Multiplicate (GWQIM), additive (GWQIA), and reference (GWQIRef) formulas were used to compute
the final GWQI indices. The sensitivity and suitability of the proposed GWQI in water quality
evaluation were also tested.

Results:
Among the three GWQI calculation methods, GWQIM was found to be the most suitable in
reflecting groundwater quality in the study area. From 2019 to 2022 (152 samples), in the province,
63.2% of GWQIM values were classified as EXCELLENT or GOOD, 17.1% as POOR, and 19.7% as
VERY POOR, or UNFIT FOR DRINKING.

Conclusion:
This improved GWQI can be applied to assess groundwater quality at local or regional
scales.
Therapies Using Anti-diabetics to Prevent and Manage Progression of Parkinson's Disease
Authors: Rout Monalisa , Prusty Shakti Ketan , Kar Durga Madhab 
Published: October 2024

:
Currently, a significant proportion of older individuals have demonstrated connections
between Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM). Emerging evidence from
cohort studies, clinical data, and preclinical meta-analyses reveals that T2DM patients have an increased
risk of developing PD, often accompanied by more severe disease progression. These two
chronic conditions are believed to share common pathways. The pathways that likely connect the
neurodegenerative process of PD include autophagy, mitochondrial dysfunction, dysregulated insulin
signaling, inflammation, and insulin resistance. Preclinical PD models highlight the importance
of cerebral insulin signaling, which confers numerous neuroprotective benefits. Several ongoing
phase II and phase III trials are being conducted in PD-affected populations. These trials reflect
the potential of existing anti-diabetic medications to improve PD motor symptoms and halt
the progression of neurodegeneration. Brain insulin resistance plays a crucial role in the pathophysiology
of PD. The insulin signaling pathway represents a promising novel target for disease modification
in both diabetic and non-diabetic PD. Incretin receptors in the brain have emerged as the
most promising targets for repurposing existing drugs in PD treatment. Targeting these receptors
mitigates inflammation, apoptosis, toxic protein aggregation, long-term potentiation, autophagy,
and insulin signaling failure.

:
Presently, various novel anti-diabetic targets are available that can regulate the insulin signaling
pathway in dopaminergic neurons, suggesting improvements in cognitive function and significant
neuroprotective effects in PD. Throughout neurodegenerative processes, insulin and incretins exert
therapeutic effects in multiple manners. Preclinical studies have demonstrated that glucagon--
like peptide 1 (GLP-1) receptor agonists reduce neuroinflammation, tau phosphorylation, and amyloid
deposition while increasing synaptic function and enhancing memory formation. Incretin
mimetics may act through the restoration of insulin signaling pathways, inducing further neuroprotective
effects.

:
This review examined the reported shared cellular and molecular pathologies between PD and
T2DM, and explored the repurposing of anti-diabetic drugs for the prevention of PD progression
through the regulation of insulin signaling pathways.
Investigating Full-Length circRNA Transcripts to Reveal circRNAMediated Regulation of Competing Endogenous RNAs in Gastric Cancer
Authors: Liu Jingjing , Yuan Quan , Cai Runqiu , Zhao Jian , Chen Juan , Zhang Meng , Wang Yulan , Zhuang Minhui , Xu Tianyi , Song Xiaofeng , Wu Jing 
Published: October 2024

Background:
Circular RNAs (circRNAs) play important regulatory roles in the progression
of gastric cancer (GC), but the exact mechanisms governing their regulation remain incompletely
understood. Prior studies typically used back-spliced junctions (BSJs) to represent a range of
circRNA isoforms, overlooking the prevalence of alternative splicing (AS) events within circRNAs,
which could lead to unreliable or even incorrect conclusions in subsequent analyses, hindering our
comprehension of the specific functions of circRNAs in GC.

Objective:
This study aimed to explore the potential functional roles of the dysregulated circRNA
transcripts in GC and provide new biomarkers and effective novel therapeutic strategies for GC
treatment.

Methods:
RNA-seq data with rRNA depletion and RNase R treatment was employed to characterize
the expression profiles of circRNAs in GC, and RNA-seq data only with rRNA depletion was employed
to identify differentially expressed mRNAs in GC. Based on the full-sequence information
and accurate isoform-level quantification of circRNA transcripts calculated by the CircAST tool, we
performed a series of bioinformatic analyses. A circRNA-miRNA-hub gene regulatory network was
constructed to reveal the circRNA-mediated regulation of competing endogenous RNAs in GC, and
then the protein-protein interaction (PPI) network was built to identify hub genes.

Results:
A total of 18,398 circular transcripts were successfully reconstructed in the samples. Herein,
351 upregulated and 177 downregulated circRNA transcripts were identified. Functional enrichment
analysis revealed that their parental genes were strongly associated with GC. After several
screening steps, 19 dysregulated circRNA transcripts, 40 related miRNAs, and 65 target genes
(mRNAs) were selected to construct the ceRNA network. Through PPI analysis, five hub genes
(COL5A2, PDGFRB, SPARC, COL1A2, and COL4A1) were excavated. All these hub genes may
play vital roles in gastric cancer cell proliferation and invasion.

Conclusion:
Our study revealed a comprehensive profile of full-length circRNA transcripts in GC,
which could provide potential prognostic biomarkers and targets for GC treatment. The results
would be helpful for further studies on the biological roles of circRNAs in GC and offer new mechanistic
insights into the pathogenesis of GC.
Outcomes of Patients With Early and Locally Advanced Lung Cancer: Protocol for the Italian Lung Cancer Observational Study (LUCENT)
Authors: Bertolaccini Luca , Ciani Oriana , Lucchi Marco , Zaraca Francesco , Bertani Alessandro , Crisci Roberto , Spaggiari Lorenzo ,   LUCENT Study Group
Published: October 2024

Background
Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a formidable challenge, necessitating an in-depth understanding of evolving treatment paradigms. The Italian Lung Cancer Observational Study (LUCENT) addresses this need by investigating the outcomes of patients with early and locally advanced lung cancer in Italy.

Objective
With a focus on real-world data and patient registries, this study aims to provide comprehensive insights into clinical, psychosocial, and economic impacts, contributing to informed decision-making in health care.

Methods
LUCENT is a prospective observational multicenter cohort study enrolling patients eligible for minimally invasive manual, robot-assisted, or traditional open surgery. The study will develop a web-based registry to collect longitudinal surgical, oncological, and socioeconomic outcome data. The primary objectives include performance assessment through the establishment of national benchmarks based on risk-adjusted outcomes and processes of care indicators. The secondary objectives encompass economic and psychosocial impact assessments of innovative technologies and treatment pathways. The multicenter design ensures a diverse and representative study population.

Results
The evolving landscape of NSCLC treatment necessitates a nuanced approach with consideration of the dynamic shifts in therapeutic strategies. LUCENT strives to fill existing knowledge gaps by providing a platform for collecting and analyzing real-world data, emphasizing the importance of patient-reported outcomes in enhancing the understanding of the disease. By developing a web-based registry, the study not only facilitates efficient data collection but also addresses the limitations of traditional methods, such as suboptimal response rates and costs associated with paper-and-pencil questionnaires. Recruitment will be conducted from January 01, 2024, to December 31, 2026. Follow-up will be performed for a minimum of 2 years. The study will be completed in the year 2028.

Conclusions
LUCENT’s potential implications are substantial. Establishing national benchmarks will enable a thorough evaluation of outcomes and care processes, guiding clinicians and policymakers in optimizing patient management. Furthermore, the study’s secondary objectives, focusing on economic and psychosocial impacts, align with the contemporary emphasis on holistic cancer care. Insights gained from this study may influence treatment strategies, resource utilization, and patient well-being, thereby contributing to the ongoing refinement of lung cancer management.

Trial Registration
ClinicalTrials.gov NCT05851755; https://clinicaltrials.gov/study/NCT05851755. ISRCTN 67197140; https://www.isrctn.com/ISRCTN67197140

International Registered Report Identifier (IRRID)
PRR1-10.2196/57183
Fat Distribution and Urolithiasis Risk Parameters in Uric Acid Stone Formers and Patients with Type 2 Diabetes Mellitus
Authors: Zomorodian Alireza , Li Xilong , Poindexter John , Maalouf Naim M. , Sakhaee Khashayar , Moe Orson W. 
Published: October 2024

Key Points

Under a controlled diet, uric acid stone formers (UASFs) and diabetic patients have higher endogenous net acid production.Under a controlled diet, UASFs have lower ammonium-to-net acid excretion ratio.Body fat inversely correlates with urine buffer capacity in normal individuals, but this relationship is lost in diabetic patients and UASFs.

Background
Uric acid (UA) nephrolithiasis affects approximately 10% of kidney stones, with a greater preponderance among patients with obesity and diabetes mellitus (DM). UA lithogenicity is driven by abnormally acidic urine pH. Distinguishing the contribution of intrinsic (e.g., body adiposity) versus external (e.g., dietary) factors to UA stone propensity is challenging because of uncontrolled diets in outpatients in previously published studies.

Methods
This compilation of metabolic studies with body composition examined by dual-energy x-ray absorptiometry scan and blood and urine biochemistry collected under a controlled metabolic diet was conducted across three distinct populations: 74 UA stone formers (UASF group), 13 patients with type 2 DM without kidney stones (DM group), and 51 healthy volunteers (HV group).

Results
Compared with HVs, both UASFs and patients with DM exhibited higher levels of net acid excretion (NAE) and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH4
+/NAE), all under controlled diets. UASFs exhibited significantly lower NH4
+/NAE compared with patients with DM. UASFs also showed higher total body and truncal fat compared with HVs. Among the HVs, lower NH4
+/NAE ratio correlated with higher truncal and total fat. However, this association was abolished in the UASF and DM groups who exhibit a fixed low NH4
+/NAE ratio across a range of body and truncal fat.

Conclusions
The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH4
+ excretion as major contributors to the risk of UA stone formation. There is an inverse physiologic association between body fat content and NH4
+/NAE in HVs, whereas NH4
+/NAE is persistently low in UASFs and patients with DM, regardless of body fat, representing pathophysiology.