bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial Drp1 Couples VEGF-induced Redox Signaling with Glycolysis Through Cysteine Oxidation
to Drive Angiogenesis
Authors: Ushio-Fukai Masuko , Nagarkoti Sheela , Kim Young-Mee , Das Archita , Ash Dipankar , Vitriol Eric , Read Tracy-Ann , Sudhahar Varadarajan , Hossain Md. Selim , Yadav Shikha , McMenamin Malgorzata , Kelley Stephanie , Lucas Rudolf , Stepp David , de Chantemele Eric Belin , Caldwell Ruth , Fulton David , Fukai Tohru 
Published: June 2024

Abstract

Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly relies on aerobic glycolysis for ATP production. However, the connections linking redox signaling with glycolysis are not well understood. The GTPase Drp1 is a member of the dynamin superfamily that moves from cytosol to mitochondria through posttranslational modifications to induce mitochondrial fission. The role of Drp1 in ROS-dependent VEGF signaling and angiogenesis in ECs has not been previously described. Here, we identify an unexpected function of endothelial Drp1 as a redox sensor, transmitting VEGF-induced H2O2 signals to enhance glycolysis and angiogenesis. Loss of Drp1 expression in ECs inhibited VEGF-induced angiogenic responses. Mechanistically, VEGF rapidly induced the NOX4-dependent sulfenylation (CysOH) of Drp1 on Cys644, promoting disulfide bond formation with the metabolic kinase AMPK and subsequent sulfenylation of AMPK at Cys299/304 via the mitochondrial fission-mitoROS axis. This cysteine oxidation of AMPK, in turn, enhanced glycolysis and angiogenesis. In vivo, mice with EC-specific Drp1 deficiency or CRISPR/Cas9-engineered “redox-dead” (Cys to Ala) Drp1 knock-in mutations exhibited impaired retinal angiogenesis and post-ischemic neovascularization. Our findings uncover a novel role for endothelial Drp1 in linking VEGF-induced mitochondrial redox signaling to glycolysis through a cysteine oxidation-mediated Drp1-AMPK redox relay, driving both developmental and reparative angiogenesis.
LLM-A*: Large Language Model Enhanced Incremental Heuristic Search on Path Planning
Authors: Meng Silin , Wang Yiwei , Yang Cheng-Fu , Peng Nanyun , Chang Kai-Wei 
Published: June 2024

Abstract

Path planning is a fundamental scientific problem in robotics and autonomous navigation, requiring the derivation of efficient routes from starting to destination points while avoiding obstacles. Traditional algorithms like A* and its variants are capable of ensuring path validity but suffer from significant computational and memory inefficiencies as the state space grows. Conversely, large language models (LLMs) excel in broader environmental analysis through contextual understanding, providing global insights into environments. However, they fall short in detailed spatial and temporal reasoning, often leading to invalid or inefficient routes. In this work, we propose LLM-A*, an new LLM based route planning method that synergistically combines the precise pathfinding capabilities of A* with the global reasoning capability of LLMs. This hybrid approach aims to enhance pathfinding efficiency in terms of time and space complexity while maintaining the integrity of path validity, especially in large-scale scenarios. By integrating the strengths of both methodologies, LLM-A* addresses the computational and memory limitations of conventional algorithms without compromising on the validity required for effective pathfinding.
Supplementation of Antioxidants in Chronic Kidney Disease: Clinical Necessity or Wishful Thinking? A Bench to Bedside Translational Research
Authors: Roumeliotis Stefanos , Neofytou Ioannis E. , Kantartzi Konstantia , Georgianos Panagiotis I. , Liakopoulos Vassilios 
Published: June 2024

Abstract:
Chronic Kidney Disease (CKD) patients are at increased risk for atherosclerosis,
cardiovascular disease (CVD), and progression to end-stage kidney disease (ESKD).
This heavy CVD risk cannot be solely attributed to traditional Framingham risk factors.
Oxidative stress, defined as the disruption of the balance between prooxidants and antioxidants
in favor of the former, has emerged as a novel risk factor for CVD and CKD
progression. Specifically, lipid peroxidation has been identified as a trigger for endothelial
dysfunction, the first step towards atherogenesis, and protein oxidation has been associated
with CKD progression. The oxidation of proteins and lipids starts early in
CKD, increases gradually with disease progression, and is further exacerbated in ESKD
due to dialysis-related factors. In order to counteract the deleterious effects of free radicals
and thereby ameliorate, or delay, CV disease and progression of CKD, exogenous
administration of antioxidants has been proposed. Here, we attempt to summarize existing
data from experimental and clinical studies that test antioxidants for their possible
beneficial effects against CVD and CKD progression, such as vitamins E and C, statins,
omega-3 fatty acids, trace elements, polyphenols, and N-acetylcysteine.
Exploring Anthocyanins: Unveiling Sources, Analytical Techniques, and Biological Activities
Authors: Agarwal Ashutosh , Thakor Niyatee , Manani Lata , Prajapati Parixit , Elossaily Gehan M. , Prajapati Bhupendra G. 
Published: June 2024

Abstract:
Anthocyanins (ANCs) are obtained from pigmented foods like blueberry,
strawberry, and red cabbage and are phenolic compounds belonging to the flavonoids
family. ANCs have garnered significant attention in recent years due to their diverse biological
activities and potential health benefits. This comprehensive review presents a
holistic exploration of anthocyanins, spanning from their chemical structure and biosynthesis
pathways to the myriad analytical techniques employed for their identification and
quantification. Furthermore, the rich tapestry of plant sources yields anthocyanins is
delved into, highlighting their incorporation into various pharmaceutical formulations.
This review aims to provide a comprehensive synthesis of current knowledge on anthocyanins,
spanning from their origins in nature to their multifaceted pharmacological activities
and innovative pharmaceutical applications.
Network Pharmacology, Molecular Docking, and Experimental Validation of the Mechanism of Jiedu Xiaoliu Formula against Diffuse Large B-Cell
Lymphoma
Authors: Wei Congmin , Hu Ming , Hu Qi 
Published: June 2024

Introduction:
Diffuse Large B-Cell Lymphoma (DLBCL) is the most common Bcell
lymphoma type. Detoxification and tumor elimination formula, a herbal compound, can
potentially treat lymphoma. In this study, network pharmacology and molecular docking approaches
were utilized to reveal the potential mechanism of the Jiedu Xiaoliu formula (JDXLF)
against DLBCL.

Methods:
Active compounds and targets of JDXLF were obtained from the Traditional Chinese
Medicine Systems Pharmacology (TCMSP) database. Targets related to DLBCL were retrieved
from GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Protein-
Protein Interaction (PPI) networks were established to screen core targets. Gene Ontology
(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses
were performed using R 4.2.2. Model interactions between potential disease targets and pharmacologically
active compounds were determined by molecular docking.

Results:
Screening of 14 herbal active ingredients yielded 129 active compounds and 1414 disease
targets for DLBCL. GO annotations showed that the effects of JDXLF were related to protein
phosphorylation and reactive oxygen species response. KEGG pathway enrichment analysis
indicated that the detoxification and elimination of tumors formula mainly regulated apoptosis
pathways. Nobiletin showed good interaction with AKT1, TP53, and CASP3, and the cell
counting kit-8 (CCK-8) assay confirmed that nobiletin inhibited the proliferation of SU-DHL-4
cells. Western blot analysis showed that nobiletin downregulated the expressions of p-PI3K, p-
AKT, and BCL-2 proteins and upregulated those of cleaved-caspase3 and BAX.

Conclusion:
Our findings preliminarily suggested that the active ingredient of JDXLF, nobiletin,
may induce apoptosis in Diffuse Large B-Cell Lymphoma SU-DHL-4 cells by regulating
the PI3K/AKT signaling pathway.
Evaluating the Performance of In silico Tools for PRRT2 Missense
Variants
Authors: Sun Hui , Song Wang , Li Bin 
Published: June 2024

Background:
Variants in the PRRT2 gene are associated with paroxysmal kinesigenic
dyskinesia and other episodic disorders. With the employment of variant screening in patients
with episodic dyskinesia, many PRRT2 variants have been discovered. Bioinformatics tools are
becoming increasingly important for predicting the functional significance of variants. This
study aimed to evaluate the performance of six in silico tools for PRRT2 missense variants.

Methods:
Pathogenic PRRT2 variants were retrieved from the Human Gene Mutation Database
(HGMD) and literature from the PubMed database. The benign set of non-deleterious variants
was retrieved from the Genome Aggregation Database (gnomAD). The overall accuracy, sensitivity, specificity, positive predictive values, and negative predictive values of SIFT, PolyPhen2,
MutationTaster, CADD, Fathmm, and Provean were analyzed. The MCC score and ROC curve
were calculated. The GraphPad Prism 8.0 software was used to plot ROC curves for the six bioinformatics software.

Results:
A total of 45 missense variants with confirmed pathogenicity were used as a positive
set, and 222 missense variants were used as a negative set. The top three tools in accuracy are
Fathmm, Provean, and MutationTaster. The top three predictors in sensitivity are SIFT, PolyPhen2, and CADD. Regarding specificity, the top three tools were Provean, Fathmm, and MutationTaster. In terms of the MCC and F-score, the highest degree was observed in Fathmm.
Fathmm also had the highest AUC score. The cutoff values of Fathmm, CADD, PolyPhen2, and
Provean were between the median prediction scores of the positive and negative sets. In contrast, the cutoff value of SIFT was below the median prediction score of the positive and negative sets. Fathmm had the highest accuracy.

Conclusion:
The prediction performance of six in silico tools differed among the parameters.
Fathmm had the best prediction performance, with the highest accuracy and MCC/F-score for
PRRT2 missense variants.
Targeted Treatment Strategies for Mitochondria Dysfunction: Correlation with Neurological Disorders
Authors: Sharma Rishav , Malviya Rishabha , Srivastava Saurabh , Ahmad Irfan , Rab Safia Obaidur , Uniyal Prerna 
Published: June 2024

:
Mitochondria are an essential intracellular organelle for medication targeting and delivery
since they seem to create energy and conduct many other cellular tasks, and mitochondrial dysfunctions
and malfunctions lead to many illnesses. Many initiatives have been taken to detect, diagnose,
and image mitochondrial abnormalities, and to transport and accumulate medicines precisely
to mitochondria, all because of special mitochondrial aspects of the pathophysiology of cancer.
In addition to the negative membrane potential and paradoxical mitochondrial dynamics, they
include high temperatures, high levels of reactive oxygen species, high levels of glutathione, and
high temperatures. Neurodegenerative diseases represent a broad spectrum of debilitating illnesses.
They are linked to the loss of certain groups of neurons based on an individual's physiology or
anatomy. The mitochondria in a cell are generally accepted as the authority with respect to ATP
production. Disruption of this system is linked to several cellular physiological issues. The development
of neurodegenerative disorders has been linked to mitochondrial malfunction, according
to pathophysiological studies. There seems to be substantial evidence connecting mitochondrial
dysfunction and oxidative stress to the development of neurodegenerative disorders. It has been extensively
observed that mitochondrial malfunction triggers autophagy, which plays a role in neurodegenerative
disorders. In addition, excitotoxicity and mitochondrial dysfunction have been
linked to the development of neurodegenerative disorders. The pathophysiology of neurodegenerative
illnesses has been linked to increased apoptosis and necrosis, as well as mitochondrial malfunction.
A variety of synthetic and natural treatments have shown efficacy in treating neurodegenerative
illnesses caused by mitochondrial failure. Neurodegenerative illnesses can be effectively
treated with existing drugs that target mitochondria, although their precise formulations are poorly
understood. Therefore, there is an immediate need to focus on creating drug delivery methods specifically
targeted at mitochondria in the treatment and diagnosis of neurodegenerative disorders.
The Dilemma of Insulin Delivery into the Brain: A Comprehensive Review
Authors: Hatami Hooman , Askari Vahid Reza , Rahimi Vafa Baradaran , Hasnain Md Saquib , Nayak Amit Kumar 
Published: June 2024

Abstract:
Insulin is a peptide hormone that is essential for regulating body homeostasis. Furthermore,
it is involved in various neurological functions such as memory, behaviors, and cognition.
The ubiquitous distribution of insulin receptors on various brain cells, such as neurons, microglia,
astrocytes, and oligodendrocytes, and their differential localization across various brain regions, including
the hippocampus, hypothalamus, and olfactory bulb, collectively underscore the crucial involvement
of insulin in the modulation of cerebral functions. Along with ageing, in some pathological
conditions such as diabetes and brain insulin resistance, the need for exogenous insulin is felt
to compensate for insulin deficiency. In these cases, the biggest obstacle to the delivery of insulin
to the brain is the blood-brain barrier (a physical barrier consisting of endothelial cells with tight
junctions), which prevents the direct entry of most substances possessing high molecular weight,
like insulin, into the brain. Therefore, different delivery methods have been proposed by researchers
for insulin delivery that directly or indirectly cause the transfer of insulin to the brain. Some of
these methods lack high efficiency and cause many side effects for the patient. In this regard,
many new technologies have come to the aid of researchers and have introduced more effective delivery
strategies, including the use of nanocarriers. Despite the promising outcomes demonstrated
in the experimental models, the utilization of these techniques in human studies remains at a nascent
stage and necessitates further comprehensive investigation. This review article aims to examine
the diverse methods of insulin administration to the brain by gathering extensive information
on insulin and its obstacles to brain delivery.
Clinical Decision Support Systems in Adults with Chronic Respiratory Disease: A Systematic Review
Authors: O'Neill Katherine , Parrott Helen , Neely Curtis , McLeese Rebecca , Fleming Glenda , Scott Mike , Bradley Judy M. 
Published: June 2024

Background:
Clinical decision support systems (CDSS) are systems which analyse and present data so that users can make decisions more easily and are suggested as part of the solution to poor adoption of guidelines.

Aims:
The aim of this review was to describe the literature on CDSS in chronic respiratory dis-ease management, their function and the features that may impact their effectiveness.

Methods:
The electronic databases PubMed, MEDLINE, EMBASE, Web of Science, the trial
registries Cochrane Central Register of Controlled Trials, EU Clinical Trial Register, ClinicalTrials.
gov and World Health Organisation (WHO) trial registry were searched with the aid of a medical
librarian. All searches began from September 2019 to March 2021.

:
Data from relevant studies were extracted independently by 2 review authors using Covidence
software and Microsoft Excel. Study quality was assessed. CDSS description and indication,
function and the theory underpinning the CDSS (e.g., guidelines, expert opinion, etc.) were
themed and summarised. The presence or absence of the important CDSS features were recorded
i.e., (i) computer-based decision support, (ii) automatic provision of decision support as part of
clinician workflow, (iiii) provision of decision support at the time and location of decisionmaking
and (iv) provision of recommendations rather than just assessments.

Results:
Of the 2647 articles screened, 27 papers or abstracts (n = 22 full text and n = 5 abstracts)
describing 26 studies met all inclusion and exclusion criteria.

:
The 26 studies evaluated asthma care (n = 16), COPD care (n = 9) and both asthma and COPD
care (n = 1). The highest level of evidence was generated by RCTs (n = 7).

:
The 26 studies described 24 different CDSS. Most were based solely or in part on clinical and
best practice guidelines. Whilst most CDSS had multiple functions, which were wide ranging,
medicines management was the most prevalent function. Most systems had 3 out of 4 of the specific
system features that have been correlated with improvements in clinical practice.

:
Generally, in both controlled studies and in other study designs, patient and process outcome
measures were commonly reported with performance outcomes measures less commonly reported.
Fewer positive effects were reported in the higher quality studies (i.e., controlled studies). The
success rate of the CDSS was higher in those studies that had 3 out of the 4 important CDSS features.

Conclusion:
This review demonstrates that CDSS can improve chronic respiratory disease management processes, performance and clinical outcomes in adult patients with asthma and COPD. Results from non-controlled study designs provided valuable information on important process and performance outcomes, including healthcare utility.
Is There an Association between 5a Reductase Inhibitors and Metabolic Syndrome? A Narrative Review of the Literature
Authors: Ziogou Afroditi , Giannakodimos Alexios , Mitakidi Evangelia , Konstantinos Tzelepis , Giannakodimos Ilias 
Published: June 2024

:
Finasteride and dutasteride are 5a Reductase Inhibitors (5a-RIs) and comprise the mainstay
of treatment for the management of patients with benign prostatic hyperplasia. 5a-RIs are expressed
in a variety of tissues, such as adipose tissues and liver, resulting in a reduction of glucocorticoid
levels and affecting androgen regulation and metabolic function. As a result, the administration
of these regimens may generate adverse metabolic events, such as liver disease, hyperglycemia,
hyperlipidemia, and diabetes mellitus. Although several studies have tried to record these
adverse metabolic events both in human subjects and animal models, the exact mechanisms of these
actions have not been well described yet in the literature. Further well-designed clinical trials
are needed to elucidate the exact role of 5a reductase inhibitors in the progression of the metabolic
syndrome. The aim of this study was to systematically review the literature concerning the role of
dutasteride or finasteride in the progression of metabolic adverse events and further investigate
possible pathophysiologic mechanisms.
Multinomial Logistic Regression with Adaptive Regularization for Cancer
Subtype Classification via Multi-omics Data
Authors: Wu Yingdi , Cao Fuzhen , Li Juntao 
Published: June 2024

Background:
Integrating multi-omics data for cancer classification brings complementary
biological insights while also facing challenges such as data integration, gene grouping, and
adaptive weight construction.

Objective:
This paper aims to address the challenges faced by the cancer subtype classification and
gene screening based on multi-omics data.

Methods:
Multinomial logistic regression with adaptive regularization (MLRAR) was proposed by
integrating DNA methylation, gene mutation, and RNA-seq information. A data preprocessing strategy
that effectively utilizes multi-omics information was presented, and the local maximum quasiclique
merging (lmQCM) algorithm was implemented to group genes. Biological pathway information
was utilized to evaluate the significance of gene groups, while the significance of each gene
within a group was evaluated by integrating mutation information, information theory, and methylation
information.

Results:
Compared to MRlasso, MRGL, MSGL, MROGL, AMRSOGL, and AGLRMR, the proposed
method yielded improvements in subtype classification accuracy of breast cancer by 2.6%,
2.9%, 3.5%, 2.3%, 2.0%, and 1.8%, respectively. In addition, MLRAR also achieved significant improvements
in ovarian cancer by 8.2%, 5.0%, 6.8%, 5.2%, 12.7%, and 6.3%, respectively.

Conclusion:
The proposed method can effectively deal with data integration, gene grouping, and
adaptive weight construction.
An Insight into Cubosomal Drug Delivery Approaches: An Explicative Review
Authors: Mukherjee Swarupananda , Dutta Ayon , Ash Dipanjana , Karati Dipanjan 
Published: June 2024

Abstract:
Cubosomes, a novel drug delivery system, have gained significant attention in recent
years due to their unique self-assembled structures and enhanced drug encapsulation capabilities.
They are administered by oral, ophthalmic, transdermal, and chemotherapeutic routes, to name a
few. Due to their many potential benefits—which include high drug dispersal due to the cubic structure,
a large surface area, a relatively simple manufacturing process, biodegradability, the capacity to
encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release
of bioactive agents, and the biodegradability of lipids—cubosomes show enormous promise in drug
nanoformulations for cancer therapeutics. The most common preparation method involves emulsifying
a monoglyceride with a polymer, homogenizing, and then sonicating the mixture. Two distinct
approaches to preparing are top-down and bottom-up. This evaluation will examine the materials,
methods of preparation, cubosome-related drug encapsulating techniques, drug loading, release
mechanism, and their uses. The following databases were used for literature searches: PubMed,
Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles
and contents (2015-2024), the keywords "cubosome; drug delivery systems, nano-carrier,
theranostic, drug release mechanism" and others of a similar nature were utilized. This review will
conduct a comprehensive analysis of the cubosome-related composition, production methods, drug
encapsulating strategies, drug release mechanisms, and applications. Moreover, the difficulties encountered
in fine-tuning different parameters to improve loading capabilities and prospects are also
discussed. Innovation in pharmaceutical research and development can be stimulated by the
knowledge gathered about cubosomal drug delivery methods. Through the clarification of the mechanisms
involved in drug release from cubosomes and the investigation of innovative fabrication procedures,
scientists can enhance the cubosomal formulation design for targeted therapeutic uses.