bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of disulfidptosis-related immune genes signature to boost the efficacy of prognostic prediction in gastric cancer
Authors: Li Jie , Yu Tian , Sun Juan , Ma Mingwei , Zheng Zicheng , He Yixuan , Kang Weiming , Ye Xin 
Published: March 2024

Abstract
Background
Gastric cancer (GC) remains a malignant tumor with high morbidity and mortality, accounting for approximately 1,080,000 diagnosed cases and 770,000 deaths worldwide annually. Disulfidptosis, characterized by the stress-induced abnormal accumulation of disulfide, is a recently identified form of programmed cell death. Substantial studies have demonstrated the significant influence of immune clearance on tumor progression. Therefore, we aimed to explore the intrinsic correlations between disulfidptosis and immune-related genes (IRGs) in GC, as well as the potential value of disulfidptosis-related immune genes (DRIGs) as biomarkers.

Methods
This study incorporated the single-cell RNA sequencing (scRNA-seq) dataset GSE183904 and transcriptome RNA sequencing of GC from the TCGA database. Disulfidptosis-related genes (DRGs) and IRGs were derived from the representative literature on both cell disulfidptosis and immunity. The expression and distribution of DRGs were investigated at the single-cell level in different GC cell types. Pearson correlation analysis was used to identify the IRGs closely related to disulfidptosis. The prognostic signature of DRIGs was established using Cox and LASSO analyses. We then analyzed and evaluated the differences in long-term prognosis, Gene Set Enrichment Analysis (GSEA), immune infiltration, mutation profile, CD274 expression, and response to chemotherapeutic drugs between the two groups. A tissue array containing 63 paired GC specimens was used to verify the expression of 4 DRIGs and disulfidptosis regulator SLC7A11 through immunohistochemistry staining.

Results
The scRNA-seq analysis found that SLC7A11, SLC3A2, RPN1 and NCKAP1 were enriched in specific cell types and closely related to immune infiltration. Four DIRGs (GLA, HIF-1α, VPS35 and CDC37) were successfully identified to establish a signature to potently predict the survival time of GC patients. Patients with high risk scores generally experienced worse prognoses and exhibited greater resistant to classical chemotherapy drugs. Furthermore, the expression of GLA, HIF-1α, VPS35, CDC37 and SLC7A11 were elevated in GC tissues. A high expression of GLA, HIF-1α, VPS35 or CDC37 was associated with more advanced clinical stage of GC and increased SLC7A11 expression.

Conclusion
Current study first highlights the potential value of DRIGs as biomarkers in GC. We successfully constructed a robust model incorporating four DRIGs to accurately predict the survival time and clinicopathological characteristics of GC patients.
Mg-ZIF nanozyme regulates the switch between osteogenic and lipogenic differentiation in BMSCs via lipid metabolism
Authors: Li Jinying , Chen Yongshao , Zha Dingsheng , Wu Chunhui , Li Xiaofen , Yang Li , Cao Hui , Cai Shexing , Cai Yuebo 
Published: March 2024

AbstractThe accumulation of reactive oxygen species (ROS) within the bone marrow microenvironment leads to diminished osteogenic differentiation and heightened lipogenic differentiation of mesenchymal stem cells residing in the bone marrow, ultimately playing a role in the development of osteoporosis (OP). Mitigating ROS levels is a promising approach to counteracting OP. In this study, a nanozyme composed of magnesium-based zeolitic imidazolate frameworks (Mg-ZIF) was engineered to effectively scavenge ROS and alleviate OP. The results of this study indicate that Mg-ZIF exhibits significant potential in scavenging ROS and effectively promoting osteogenic differentiation of bone mesenchymal stem cells (BMSCs). Additionally, Mg-ZIF was found to inhibit the differentiation of BMSCs into adipose cells. In vivo experiments further confirmed the ability of Mg-ZIF to mitigate OP by reducing ROS levels. Mechanistically, Mg-ZIF enhances the differentiation of BMSCs into osteoblasts by upregulating lipid metabolic pathways through ROS scavenging. The results indicate that Mg-ZIF has potential as an effective therapeutic approach for the treatment of osteoporosis.
Landet: an efficient physics-informed deep learning approach for automatic detection of anatomical landmarks and measurement of spinopelvic alignment
Authors: MohammadiNasrabadi AliAsghar , Moammer Gemah , Quateen Ahmed , Bhanot Kunal , McPhee John 
Published: March 2024

Abstract
Purpose:
An efficient physics-informed deep learning approach for extracting spinopelvic measures from X-ray images is introduced and its performance is evaluated against manual annotations.

Methods:
Two datasets, comprising a total of 1470 images, were collected to evaluate the model’s performance. We propose a novel method of detecting landmarks as objects, incorporating their relationships as constraints (LanDet). Using this approach, we trained our deep learning model to extract five spine and pelvis measures: Sacrum Slope (SS), Pelvic Tilt (PT), Pelvic Incidence (PI), Lumbar Lordosis (LL), and Sagittal Vertical Axis (SVA). The results were compared to manually labelled test dataset (GT) as well as measures annotated separately by three surgeons.

Results:
The LanDet model was evaluated on the two datasets separately and on an extended dataset combining both. The final accuracy for each measure is reported in terms of Mean Absolute Error (MAE), Standard Deviation (SD), and R Pearson correlation coefficient as follows: $$[SS^\circ : 3.7 (2.7), R = 0.89]$$

[
S

S
∘

:
3.7

(
2.7
)

,
R
=
0.89
]

, $$[PT^\circ : 1.3 (1.1), R = 0.98], [PI^\circ : 4.2 (3.1), R = 0.93], [LL^\circ : 5.1 (6.4), R=0.83], [SVA(mm): 2.1 (1.9), R = 0.96]$$

[
P

T
∘

:
1.3

(
1.1
)

,
R
=
0.98
]

,

[
P

I
∘

:
4.2

(
3.1
)

,
R
=
0.93
]

,

[
L

L
∘

:
5.1

(
6.4
)

,
R
=
0.83
]

,

[
S
V
A

(
m
m
)

:
2.1

(
1.9
)

,
R
=
0.96
]

. To assess model reliability and compare it against surgeons, the intraclass correlation coefficient (ICC) metric is used. The model demonstrated better consistency with surgeons with all values over 0.88 compared to what was previously reported in the literature.

Conclusion:
The LanDet model exhibits competitive performance compared to existing literature. The effectiveness of the physics-informed constraint method, utilized in our landmark detection as object algorithm, is highlighted. Furthermore, we addressed the limitations of heatmap-based methods for anatomical landmark detection and tackled issues related to mis-identifying of similar or adjacent landmarks instead of intended landmark using this novel approach.
Acceptance and utilization of web-based self-help for caregivers of children with externalizing disorders
Authors: Wähnke Laura , Plück Julia , Bodden Mikel , Ernst Angela , Klemp Marie-Theres , Mühlenmeister Judith , Döpfner Manfred 
Published: March 2024

Abstract
Background
Web-based self-help interventions for parents of children with ADHD and other externalizing disorders have been proven to be effective. In order to recommend individualized and optimized interventions, a better understanding of the acceptance and utilization of this innovative treatment approach is needed. Previous research has frequently employed subjective reports of utilization, but the validity of these studies may be limited.

Methods
Data from the German WASH study were used. Participants (n = 276) were randomly assigned to the intervention condition (a) web-based self-help or (b) web-based self-help with optional telephone-based support calls. Data collection took place at baseline (T1) and 12 weeks later (T2). Utilization data were tracked using a log file generated for each participant at T2. Prediction models were calculated using CART (Classification and Regression Trees), a method known mostly from the field of machine learning.

Results
Acceptance, of the intervention as defined in this paper was very high on objective (89.4% have taken up the intervention) and subjective measures (91.4% reported having used the intervention and 95.3% reported they would recommend the intervention to a friend). The average number of logins corresponded to recommendations. Predictors of acceptance and predictors of utilization were similar and included, e.g., child’s externalizing symptoms, parental psychopathology, and above all additional telephone-based support by counselors.

Conclusions
Through a detailed identification of acceptance and utilization, and the predictors thereof, we were able to gain a better understanding of the acceptance and utilization of web-assisted self-help for a parent management intervention in the treatment of children with ADHD and ODD. These findings can be used to recommend web-based interventions to particularly suitable families. It should be noted that some form of support is required for an intensive engagement with the content of the program.

Trial Registration
The protocol of the study (German Clinical Trials Register DRKS00013456 conducted on January 3rd, 2018) was approved by the Ethics Committee of the University Hospital, Cologne.
The ARIA trial protocol: a randomised controlled trial to assess the clinical, technical, and cost-effectiveness of a cloud-based, ARtificially Intelligent image fusion system in comparison to standard treatment to guide endovascular Aortic aneurysm repair
Authors: Budge James , Carrell Tom , Yaqub Medeah , Wafa Hatem , Waltham Matt , Pilecka Izabela , Kelly Joanna , Murphy Caroline , Palmer Stephen , Wang Yanzhong , Clough Rachel E 
Published: March 2024

Abstract
Background
Endovascular repair of aortic aneurysmal disease is established due to perceived advantages in patient survival, reduced postoperative complications, and shorter hospital lengths of stay. High spatial and contrast resolution 3D CT angiography images are used to plan the procedures and inform device selection and manufacture, but in standard care, the surgery is performed using image-guidance from 2D X-ray fluoroscopy with injection of nephrotoxic contrast material to visualise the blood vessels. This study aims to assess the benefit to patients, practitioners, and the health service of a novel image fusion medical device (Cydar EV), which allows this high-resolution 3D information to be available to operators at the time of surgery.

Methods
The trial is a multi-centre, open label, two-armed randomised controlled clinical trial of 340 patient, randomised 1:1 to either standard treatment in endovascular aneurysm repair or treatment using Cydar EV, a CE-marked medical device comprising of cloud computing, augmented intelligence, and computer vision. The primary outcome is procedural time, with secondary outcomes of procedural efficiency, technical effectiveness, patient outcomes, and cost-effectiveness. Patients with a clinical diagnosis of AAA or TAAA suitable for endovascular repair and able to provide written informed consent will be invited to participate.

Discussion
This trial is the first randomised controlled trial evaluating advanced image fusion technology in endovascular aortic surgery and is well placed to evaluate the effect of this technology on patient outcomes and cost to the NHS.

Trial registration
ISRCTN13832085. Dec. 3, 2021
Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health
Authors: Smith Hannah M. , Moodie Joanna E. , Monterrubio-Gómez Karla , Gadd Danni A. , Hillary Robert F. , Chybowska Aleksandra D. , McCartney Daniel L. , Campbell Archie , Redmond Paul , Page Danielle , Taylor Adele , Corley Janie , Harris Sarah E. , Valdés Hernández Maria , Muñoz Maniega Susana , Bastin Mark E. , Wardlaw Joanna M. , Deary Ian J. , Boardman James P. , Mullin Donncha S. , Russ Tom C. , Cox Simon R. , Marioni Riccardo E. 
Published: March 2024

Abstract
Background
Epigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum of DNA methylation (DNAm) levels at CpG sites are predictive of protein levels. Here, we examine 84 previously published protein EpiScores as possible biomarkers of cross-sectional and longitudinal measures of general cognitive function and brain health, and incident dementia across three independent cohorts.

Results
Using 84 protein EpiScores as candidate biomarkers, associations with general cognitive function (both cross-sectionally and longitudinally) were tested in three independent cohorts: Generation Scotland (GS), and the Lothian Birth Cohorts of 1921 and 1936 (LBC1921 and LBC1936, respectively). A meta-analysis of general cognitive functioning results in all three cohorts identified 18 EpiScore associations (absolute meta-analytic standardised estimates ranged from 0.03 to 0.14, median of 0.04, PFDR < 0.05). Several associations were also observed between EpiScores and global brain volumetric measures in the LBC1936. An EpiScore for the S100A9 protein (a known Alzheimer disease biomarker) was associated with general cognitive functioning (meta-analytic standardised beta: − 0.06, P = 1.3 × 10−9), and with time-to-dementia in GS (Hazard ratio 1.24, 95% confidence interval 1.08–1.44, P = 0.003), but not in LBC1936 (Hazard ratio 1.11, P = 0.32).

Conclusions
EpiScores might make a contribution to the risk profile of poor general cognitive function and global brain health, and risk of dementia, however these scores require replication in further studies.
Effectiveness of molecular fingerprints for exploring the chemical space of natural products
Authors: Boldini Davide , Ballabio Davide , Consonni Viviana , Todeschini Roberto , Grisoni Francesca , Sieber Stephan A. 
Published: March 2024

AbstractNatural products are a diverse class of compounds with promising biological properties, such as high potency and excellent selectivity. However, they have different structural motifs than typical drug-like compounds,e.g., a wider range of molecular weight, multiple stereocenters and higher fraction ofsp3-hybridized carbons. This makes the encoding of natural products via molecular fingerprints difficult, thus restricting their use in cheminformatics studies. To tackle this issue, we explored over 30 years of research to systematically evaluate which molecular fingerprint provides the best performance on the natural product chemical space. We considered 20 molecular fingerprints from four different sources, which we then benchmarked on over 100,000 unique natural products from the COCONUT (COlleCtion of Open Natural prodUcTs) and CMNPD (Comprehensive Marine Natural Products Database) databases. Our analysis focused on the correlation between different fingerprints and their classification performance on 12 bioactivity prediction datasets. Our results show that different encodings can provide fundamentally different views of the natural product chemical space, leading to substantial differences in pairwise similarity and performance. While Extended Connectivity Fingerprints are the de-facto option to encoding drug-like compounds, other fingerprints resulted to match or outperform them for bioactivity prediction of natural products. These results highlight the need to evaluate multiple fingerprinting algorithms for optimal performance and suggest new areas of research. Finally, we provide an open-source Python package for computing all molecular fingerprints considered in the study, as well as data and scripts necessary to reproduce the results, athttps://github.com/dahvida/NP_Fingerprints.
Large-scale next generation sequencing based analysis of SLCO1B1 pharmacogenetics variants in the Saudi population
Authors: Goljan Ewa , Abouelhoda Mohammed , Tahir Asma , ElKalioby Mohamed , Meyer Brian , Monies Dorota 
Published: March 2024

Abstract
Background
SLCO1B1 plays an important role in mediating hepatic clearance of many different drugs including statins, angiotensin-converting enzyme inhibitors, chemotherapeutic agents and antibiotics. Several variants in SLCO1B1 have been shown to have a clinically significant impact, in relation to efficacy of these medications. This study provides a comprehensive overview of SLCO1B1 variation in Saudi individuals, one of the largest Arab populations in the Middle East.

Methods
The dataset of 11,889 (9,961 exomes and 1,928 pharmacogenetic gene panel) Saudi nationals, was used to determine the presence and frequencies of SLCO1B1 variants, as described by the Clinical Pharmacogenetic Implementation Consortium (CPIC).

Results
We identified 141 previously described SNPs, of which rs2306283 (50%) and rs4149056 (28%), were the most common. In addition, we observed six alleles [*15 (24.7%) followed by *20 (8.04%), *14 (5.86%), *5 (3.84%), *31 (0.21%) and *9 (0.03%)] predicted to be clinically actionable. Allele diplotype to phenotype conversion revealed 41 OATP1B1 diplotypes. We estimated the burden of rare, and novel predicted deleterious variants, resulting from 17 such alterations.

Conclusions
The data we present, from one of the largest Arab cohorts studied to date, provides the most comprehensive overview of SLCO1B1 variants, and the subsequent OATP1B1 activity of this ethnic group, which thus far remains relatively underrepresented in available international genomic databases. We believe that the presented data provides a basis for further clinical investigations and the application of personalized statin drug therapy guidance in Arabs.
Chronic hypoxia remodels the tumor microenvironment to support glioma stem cell growth
Authors: Nicholson J. G. , Cirigliano S. , Singhania R. , Haywood C. , Shahidi Dadras M. , Yoshimura M. , Vanderbilt D. , Liechty B. , Fine H. A. 
Published: March 2024

AbstractCerebral organoids co-cultured with patient derived glioma stem cells (GLICOs) are an experimentally tractable research tool useful for investigating the role of the human brain tumor microenvironment in glioblastoma. Here we describe long-term GLICOs, a novel model in which COs are grown from embryonic stem cell cultures containing low levels of GSCs and tumor development is monitored over extended durations (ltGLICOs). Single-cell profiling of ltGLICOs revealed an unexpectedly long latency period prior to GSC expansion, and that normal organoid development was unimpaired by the presence of low numbers of GSCs. However, as organoids age they experience chronic hypoxia and oxidative stress which remodels the tumor microenvironment to promote GSC expansion. Receptor-ligand modelling identified astrocytes, which secreted various pro-tumorigenic ligands including FGF1, as the primary cell type for GSC crosstalk and single-cell multi-omic analysis revealed these astrocytes were under the control of ischemic regulatory networks. Functional validation confirmed hypoxia as a driver of pro-tumorigenic astrocytic ligand secretion and that GSC expansion was accelerated by pharmacological induction of oxidative stress. When controlled for genotype, the close association between glioma aggressiveness and patient age has very few proposed biological explanations. Our findings indicate that age-associated increases in cerebral vascular insufficiency and associated regional chronic cerebral hypoxia may contribute to this phenomenon.
Experimental study of sulfate crystallization damage to glutenite rock in the Maijishan Grottoes
Authors: Sheng Yumeng , Liu Ping , Shi Wentao , Sun Bo , Peng Ningbo , Jiao Dading , Li Changqing 
Published: March 2024

Abstract
Salt crystallization is one of the most important factors causing weathering in grottoes. Cumulative crystallization of salts causes damage such as flaking and peeling of the rocks and accelerates the weathering processes of the grottoes. The accumulated crystalline salts cause spalling, skinning and other damage and accelerate the weathering process of the grotto rock body. It is necessary to study the existing glutenite rock grottoes. This paper took the glutenite rock of the Maijishan Grottoes as a case study, and Na2SO4 or MgSO4 solutions were applied to glutenite rock specimens subjected to different deterioration cycles. The crystallization patterns of the two different salts and their damage to the glutenite rock were analyzed and studied, the mechanism for salt crystallization damage to the glutenite rock was explored, and the crystallization pressures of the two salts in the glutenite rock were derived with theoretical calculations. The results showed that both Na2SO4 and MgSO4 crystallization damaged the glutenite rock, and the former different sulfate solutions changed at different rates, and the changes in the wave caused faster damage than the latter. The physical indices of the rock samples in the velocities and tensile strengths were consistent. Na2SO4 was mainly accumulated on the surface of the specimen and damaged the glutenite rock centripetally via pulverization and exfoliation. MgSO4 mainly crystallized inside the glutenite rock, which created internal fissures and reduced the strength of the rock. The theoretical maximum crystallization pressures of Na2SO4 and MgSO4 in the glutenite rock specimens reached 33.00 MPa and 9.94 MPa, respectively. This study provides a theoretical basis for studies of salt crystallization in glutenite rock grottoes and provides a method for protecting the stones in cultural heritage sites against weathering.
Bilirubin metabolism: delving into the cellular and molecular mechanisms to predict complications
Authors: Kumbhar Sadhana , Musale Manish , Jamsa Anas 
Published: March 2024

AbstractBilirubin is a metabolic product of heme, and an increase in its level may be toxic to the body. It may be conjugated or unconjugated. Encephalopathy is caused by unconjugated bilirubin has the ability to pass through the blood-brain barrier, entering the central nervous system. Conjugated forms of bilirubin result in biliary obstruction and a change in urine colour due to a decrease in excretion. Excessive hemolysis can result from hereditary and autoimmune diseases, deficient RBC membranes, enzyme deficiency, and hemoglobin structural anomalies. In this review, we summarize all the possible mechanisms and complications regarding bilirubin. Cellular and molecular functions and mechanisms of bilirubin are explained, followed by several complications viz neurotoxicity, auditory dysfunction, and nephrotoxicity. The cause of bilirubin-induced neuronal cell damage is likely due to the elevated levels of unconjugated bilirubin in plasma, mitochondrial, and endoplasmic reticulum (ER) membranes. These disruptions in the membranes could lead to harmful effects such as neuronal excitotoxicity, energy failure in mitochondria, or an increased concentration of calcium within the cells. At the cellular level, bilirubin exerts its toxic effect by disturbing the normal functioning of neuronal cells. Bilirubin's presence can cause certain inflammatory responses, resulting in the activation of proinflammatory cytokines. Additionally, research has demonstrated that bilirubin can negatively affect auditory abilities. It disrupts the integrity of auditory pathways, resulting in auditory dysfunction and potentially causing long-term hearing impairments in infants affected by it. In conclusion, a comprehensive understanding of the complications associated with unconjugated bilirubin in neonates is essential for improving clinical management and outcomes. Understanding the cellular and molecular pathophysiology of high bilirubin may lead to a new therapeutic approach.